SRC: marker or actor in prostate cancer aggressiveness.

PubMed

Vlaeminck-Guillem, Virginie; Gillet, Germain; Rimokh, Ruth

2014-01-01

A key question for urologic practitioners is whether an apparently organ-confined prostate cancer (PCa) is actually aggressive or not. The dilemma is to specifically identify among all prostate tumors the very aggressive high-grade cancers that will become life-threatening by developing extra-prostatic invasion and metastatic potential and the indolent cancers that will never modify a patient's life expectancy. A choice must be made between several therapeutic options to achieve the optimal personalized management of the disease that causes as little harm as possible to patients. Reliable clinical, biological, or pathological markers that would enable distinctions to be made between aggressive and indolent PCas in routine practice at the time of initial diagnosis are still lacking. The molecular mechanisms that explain why a PCa is aggressive or not are also poorly understood. Among the potential markers and/or actors in PCa aggressiveness, Src and other members of the Src kinase family, are valuable candidates. Activation of Src-dependent intracellular pathways is frequently observed in PCa. Indeed, Src is at the cross-roads of several pathways [including androgen receptor (AR), TGFbeta, Bcl-2, Akt/PTEN or MAPK, and ERK …], and is now known to influence some of the cellular and tissular events that accompany tumor progression: cell proliferation, cell motility, invasion, epithelial-to-mesenchymal transition, resistance to apoptosis, angiogenesis, neuroendocrine differentiation, and metastatic spread. Recent work even suggests that Src could also play a part in PCa initiation in coordination with the AR. The aim of this review is to gather data that explore the links between the Src kinase family and PCa progression and aggressiveness.

Pharmacotherapy for the treatment of aggression in pediatric and adolescent patients with autism spectrum disorder comorbid with attention-deficit hyperactivity disorder: A questionnaire survey of 571 psychiatrists.

PubMed

Yamamuro, Kazuhiko; Tsujii, Noa; Ota, Toyosaku; Kishimoto, Toshifumi; Iida, Junzo

2017-08-01

Both attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are frequently accompanied by serious aggression that requires psychiatric treatment. However, little is known about the experiences psychiatrists have had using pharmacotherapy to treat aggression in patients who have both ASD and ADHD (ASD/ADHD). The purpose of this study was to examine the experiences of Japanese child and adolescent psychiatrists in prescribing medication for aggression in patients with ASD/ADHD. A prospective questionnaire was mailed to 2001 psychiatrists affiliated with the Japanese Society for Child and Adolescent Psychiatry. Multivariate logistic regression analysis was used to identify factors predicting the outcome of pharmacotherapeutic treatment of aggression in pediatric and adolescent patients with ASD/ADHD. Of 2001 psychiatrists, 571 (28.5%) completed the full questionnaire (final sample). Of these, 488 (85.4%) prescribed psychotropic medication in treating pediatric and adolescent patients with ASD/ADHD, 299 (61.3%) of them doing so to treat aggression. Prescribers' duration of practice (odds ratio, 1.055; P = 0.038) and patient symptoms of residual impulsivity (odds ratio, 2.479; P = 0.039) increased the odds of prescribing psychotropic medications to treat aggression in these patients. The respondents reported a similar effect for patients with ADHD/ASD compared with those with ADHD only in treating aggression. Japanese psychiatrists tended to prescribe psychotropic medication for aggression in pediatric and adolescent patients with ASD/ADHD. Future studies examining aggression in pediatric and adolescent patients with ASD/ADHD should aim to accumulate evidence for the use of psychotropic medications, which could help clinicians make better decisions. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Identifying aggressive prostate cancer foci using a DNA methylation classifier.

PubMed

Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

2017-01-12

Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

Immunotherapy Targets in Pediatric Cancer

PubMed Central

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

2011-01-01

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

Chemotherapy-Induced Peripheral Neuropathy in Pediatric Cancer Patients

PubMed Central

Groninger, Hunter

2014-01-01

Chemotherapy-induced peripheral neuropathies (CIPNs) are an increasingly common neuropathic and pain syndrome in adult and pediatric cancer patients and survivors [1–69]. However, symptoms associated with CIPNs are often undiagnosed, under-assessed, and communications problems between clinicians, family members, and patients have been observed [70–73]. Less is known about the prevalence and impact of CIPNs on pediatric cancer populations [70–71]. This article aims to provide a brief understanding of CIPNs in pediatric populations, and to review the evidence for both its prevention and treatment. PMID:25144779

Assessment of sleep in pediatric cancer patients.

PubMed

İnce, Dilek; Demirağ, Bengü; Karapınar, Tuba Hilkay; Oymak, Yeşim; Ay, Yılmaz; Kaygusuz, Arife; Töret, Ersin; Vergin, Canan

2017-01-01

İnce D, Demirağ B, Karapınar TH, Oymak Y, Ay Y, Kaygusuz A, Töret E, Vergin C. Assessment of sleep in pediatric cancer patients. Turk J Pediatr 2017; 59: 379-386. The purpose of the study is to describe sleep habits, assess the prevalence of sleep disturbances in pediatric cancer patients and healthy controls, and to compare sleep patterns, sleep problems. One hundred-thirty-five patients and 190 healthy controls were evaluated. Healthy children matched for age, sex, economic status, parental education and family structure constituted the control group. Sleep was evaluated by using the Children`s Sleep Habits Questionnaire (CSHQ). Sleep problems were detected in half of patients. There were no significant differences in total sleep score and subscale scores between patients and controls. Solely the wake-time was found significantly different between patients and controls. Although our results indicated that neither childhood cancer survivors nor patients with cancer during treatment period had more sleep problems than their healthy peers, sleep problems were not uncommon in whole study group. This study underlines the need to screen, assess and manage sleep problems in children with diagnosis of cancer.

Pediatric malignancies, treatment outcomes and abandonment of pediatric cancer treatment in Zambia.

PubMed

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

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. 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. 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). 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 be adapted for pediatric cancer treatment to

Correlations of inflammatory gene pathways, corticolimbic functional activities, and aggression in pediatric bipolar disorder: a preliminary study.

PubMed

Barzman, Drew; Eliassen, Jim; McNamara, Robert; Abonia, Pablo; Mossman, Douglas; Durling, Michele; Adler, Caleb; DelBello, Melissa; Lin, Ping-I

2014-11-30

The mechanisms underlying aggression in adolescents with bipolar disorder have been poorly understood. The present study has investigated the associations among TNF gene expressions, functional brain activations under the frustrative non-reward task, and aggression in adolescents with bipolar disorder. Baseline gene expressions and aggressive tendencies were measured with the RNA-sequencing and Brief Rating of Aggression by Children and Adolescents (BRACHA), respectively. Our results show that activity levels of left subgenual anterior cingulate gyrus (ACG), right amygdala, left Brodmann area 10 (orbitofrontal cortex), and right thalamus were inversely correlated with BRACHA scores and were activated with frustrative non-reward during the affective Posner Task. In addition, 11 TNF related gene expressions were significantly correlated with activation of amygdala or ACG during the affective Posner Task. Three TNF gene expressions were inversely correlated with BRACHA score while one TNF gene (TNFAIP3) expression was positively correlated with BRACHA score. Therefore, TNF-related inflammatory cytokine genes may play a role in neural activity associated with frustrative non-reward and aggressive behaviors in pediatric bipolar disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Msi2 Regulates the Aggressiveness of Non Small Cell Lung Cancer (NSCLC)

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0192 TITLE: Msi2 Regulates the Aggressiveness of Non -Small Cell Lung Cancer (NSCLC) PRINCIPAL INVESTIGATOR: Yanis...Annual 3. DATES COVERED (From - To) 15 Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE Msi2 Regulates the Aggressiveness of Non -Small Cell Lung Cancer...in vitro and in vivo are ongoing, while immunohistochemistry studies are starting Fall 2016. 15. SUBJECT TERMS Non -small cell lung cancer

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.

Evaluation of quality improvement initiative in pediatric oncology: implementation of aggressive hydration protocol.

PubMed

Fratino, Lisa M; Daniel, Denise A; Cohen, Kenneth J; Chen, Allen R

2009-01-01

Our goal was to improve the efficiency of chemotherapy administration for pediatric oncology patients. We identified prechemotherapy hydration as the process that most often delayed chemotherapy administration. An aggressive hydration protocol, supported by fluid order sets, was developed for patients receiving planned chemotherapy. The mean interval from admission to achieving adequate hydration status was reduced significantly from 4.9 to 1.4 hours with a minor reduction in the time to initiate chemotherapy from 9.6 to 8.6 hours. Chemotherapy availability became the new rate-limiting process.

Identification and treatment of aggressive thyroid cancers. Part 2: risk assessment and treatment.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-04-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radio-iodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article, which appeared in March, described in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, treatment, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2 covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

Pediatric Cancer Survivorship Research: Experience of the Childhood Cancer Survivor Study

PubMed Central

Leisenring, Wendy M.; Mertens, Ann C.; Armstrong, Gregory T.; Stovall, Marilyn A.; Neglia, Joseph P.; Lanctot, Jennifer Q.; Boice, John D.; Whitton, John A.; Yasui, Yutaka

2009-01-01

The Childhood Cancer Survivor Study (CCSS) is a comprehensive multicenter study designed to quantify and better understand the effects of pediatric cancer and its treatment on later health, including behavioral and sociodemographic outcomes. The CCSS investigators have published more than 100 articles in the scientific literature related to the study. As with any large cohort study, high standards for methodologic approaches are imperative for valid and generalizable results. In this article we describe methodological issues of study design, exposure assessment, outcome validation, and statistical analysis. Methods for handling missing data, intrafamily correlation, and competing risks analysis are addressed; each with particular relevance to pediatric cancer survivorship research. Our goal in this article is to provide a resource and reference for other researchers working in the area of long-term cancer survivorship. PMID:19364957

Comparing catheter-related bloodstream infections in pediatric and adult cancer patients.

PubMed

Zakhour, Ramia; Hachem, Ray; Alawami, Hussain M; Jiang, Ying; Michael, Majd; Chaftari, Anne-Marie; Raad, Issam

2017-10-01

Central venous catheters (CVCs) are essential to treatment of children with cancer. There are no studies comparing catheter-related bloodstream infections (CRBSIs) in pediatric cancer patients to those in adults, although current guidelines for management of CRBSI do not give separate guidelines for the pediatric population. In this study, we compared CRBSIs in both the pediatric and adult cancer population. We retrospectively reviewed the electronic medical records of 92 pediatric and 156 adult patients with CRBSI cared for at MD Anderson Cancer Center between September 2005 and March 2014. We evaluated 248 patients with CRBSI. There was a significant difference in etiology of CRBSI between pediatric and adult patients (P = 0.002), with the former having less Gram-negative organisms (27 vs. 46%) and more polymicrobial infections (10 vs. 1%, P = 0.003). Pediatric patients had less hematologic malignancies (58 vs. 74%) and less neutropenia at presentation (40 vs. 54%) when compared with adult patients. Peripheral blood cultures were available in only 43% of pediatric cases. CVC was removed in 64% of pediatric cases versus 88% of adult cases (P < 0.0001). We found higher rates of Gram-negative organisms in adults and higher rates of polymicrobial in children. Because of the low rates of peripheral blood cultures and the low rates of CVC removal, CRBSI diagnosis could be challenging in pediatrics. A modified CRBSI definition relying more on clinical criteria may be warranted. © 2017 Wiley Periodicals, Inc.

Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

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

Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas

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 prostatemore » 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.« less

Congenital neurodevelopmental anomalies in pediatric and young adult cancer.

PubMed

Wong-Siegel, Jeannette R; Johnson, Kimberly J; Gettinger, Katie; Cousins, Nicole; McAmis, Nicole; Zamarione, Ashley; Druley, Todd E

2017-10-01

Congenital anomalies that are diagnosed in at least 120,000 US infants every year are the leading cause of infant death and contribute to disability and pediatric hospitalizations. Several large-scale epidemiologic studies have provided substantial evidence of an association between congenital anomalies and cancer risk in children, suggesting potential underlying cancer-predisposing conditions and the involvement of developmental genetic pathways. Electronic medical records from 1,107 pediatric, adolescent, and young adult oncology patients were reviewed. The observed number (O) of congenital anomalies among children with a specific pediatric cancer subtype was compared to the expected number (E) of anomalies based on the frequency of congenital anomalies in the entire study population. The O/E ratios were tested for significance using Fisher's exact test. The Kaplan-Meier method was used to compare overall and neurological malignancy survival rates following tumor diagnosis. Thirteen percent of patients had a congenital anomaly diagnosis prior to their cancer diagnosis. When stratified by congenital anomaly subtype, there was an excess of neurological anomalies among children with central nervous system tumors (O/E = 1.56, 95%CI 1.13-2.09). Male pediatric cancer patients were more likely than females to have a congenital anomaly, particularly those <5 years of age (O/E 1.35, 95%CI 0.97-1.82). Our study provides additional insight into the association between specific congenital anomaly types and pediatric cancer development. Moreover, it may help to inform the development of new screening policies and support hypothesis-driven research investigating mechanisms underlying tumor predisposition in children with congenital anomalies. © 2017 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Analyzing the differentially expressed genes and pathway cross-talk in aggressive breast cancer.

PubMed

Chen, Wen-Yan; Wu, Fang; You, Zhen-Yu; Zhang, Zhan-Min; Guo, Yu-Ling; Zhong, Lu-Xing

2015-01-01

The aim of this study was to explore the genes and pathways involved in the aggressive breast cancer cells. The gene expression profiles of GSE40057, including four aggressive breast cell lines and six less aggressive cell lines, were downloaded from the Gene Expression Omnibus (GEO) database. The gene differential expression analysis was carried out with limma software with the method of Bayes for multiple tests. The gene ontology (GO) term enrichment and pathway cross-talk analysis were performed with the online tool of DAVID and Cytoscape software. A total of 401 differentially expressed genes (DEG), such as pentraxin 3 (PTX3), snail family zinc finger 2 (SNAI2), interleukin-8/6 (IL-8/6), osteonectin (SPARC), matrix metallopeptidase-1 (MMP-1) and Ras-related protein Rab-25 (Rab 25), were identified between aggressive and less aggressive cell lines. They were mainly enriched in the GO terms of response to wounding, negative regulation of cell proliferation and calcium binding. Pathways in cancer dysfunctionally interacted with glyoxylate and dicarboxylate metabolism (P < 0.0001), basal transcription factors (P < 0.0001), tyrosine metabolism (P < 0.0001), calcium signaling pathway (P = 0.0021), FcγR-mediated phagocytosis (P = 0.0022), metabolism of xenobiotics by cytochrome P450 (P = 0.0097) and phagosome (P = 0.0102). The screened aggressive cancer-associated DEG (PTX3, SNAI2, IL-8/6, SPARC, MMP-1 and Rab25) and significant pathways (calcium signaling pathway, tyrosine metabolism, alanine, aspartate and glutamate metabolism) give us new insights into the mechanism of aggressive breast cancer cells, and these DEG may become promising target genes in the treatment of metastatic breast cancer. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

[Burden of Parents of Pediatric Cancer Patients in Pediatric-oncological Rehabilitation].

PubMed

Inhestern, Laura; Beierlein, Volker; Krauth, Konstantin A; Rolfes, Ursula; Schulte, Thomas; Berger, Dieter; Koch, Uwe; Bergelt, Corinna

2017-03-01

Burden of Parents of Pediatric Cancer Patients in Pediatric-oncological Rehabilitation All family members experience high burden in case of paediatric cancer. Family-oriented rehabilitation (FOR) aims to improve the physical and mental situation of the families. We investigated anxiety and depression (HADS) and cancer-related burden of parents (n = 69) before and after FOR and analysed its association with quality of life of the ill children. At beginning of FOR 70 % of the parents showed moderate to high anxiety scores and 47 % moderate to high depression scores. They reported cancer-related burden such as exhaustion, cancer-related fears and a burden of family's daily life due to the cancer disease. At the end of FOR 40 % of the parents showed moderate to high anxiety scores and 30 % moderate to high depression. Cancer-related burden measured with self-developed items also decreased after FOR. Compared to age- and gender-adapted norm values, mothers show significantly higher anxiety and depression scores, whereas fathers show no differences in depression scores compared to norm values at the end of FOR. Quality of life of ill children and anxiety and depression scores in the parents are significantly associated with each other. Results of the study show that parents stabilise after FOR and improve their mental situation. However, the results also underline the need for long-term psychosocial support for all family members.

The biological age linked to oxidative stress modifies breast cancer aggressiveness.

PubMed

Sáez-Freire, María Del Mar; Blanco-Gómez, Adrián; Castillo-Lluva, Sonia; Gómez-Vecino, Aurora; Galvis-Jiménez, Julie Milena; Martín-Seisdedos, Carmen; Isidoro-García, María; Hontecillas-Prieto, Lourdes; García-Cenador, María Begoña; García-Criado, Francisco Javier; Patino-Alonso, María Carmen; Galindo-Villardón, Purificación; Mao, Jian-Hua; Prieto, Carlos; Castellanos-Martín, Andrés; Kaderali, Lars; Pérez-Losada, Jesús

2018-05-20

The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Adolescent cancer survivors’ smoking intentions are associated with aggression, attention, and smoking history

PubMed Central

Tyc, Vida L.; Wilson, Stephanie J.; Nelms, Jenna; Hudson, Melissa M.; Wu, Shengjie; Xiong, Xiaoping; Hinds, Pamela S.

2011-01-01

Introduction The present study examines behavioral and psychosocial factors associated with smoking intentions and experimentation among adolescent survivors of pediatric cancer. Methods Adolescent survivors of brain tumor and acute lymphoblastic leukemia (n=99) provided information about their smoking histories and their intentions to smoke in the future. Behavior rating scales were completed by survivors, parents, and teachers. Results Past experimentation with smoking and higher levels of self-reported aggression were associated with intentions to smoke in the future (OR=4.18, 95%CI 1.02–17.04, and OR=1.08, 95% CI 1.01–1.15, respectively), while teacher-ratings of inattention in the classroom were negatively associated with intentions to smoke (OR=0.94, 95% CI.88–.99), all p<.05. Experimentation with smoking was more likely among older survivors (OR=1.76, 95% CI 1.16–2.66, p<.01) and those whose parents had divorced (OR=4.40, 95% CI 1.21–16.06, p<.05). Discussion A concerning minority of adolescent survivors have clear intentions to smoke, a behavior that adds to their overall health risk. Smoking intentions and experimentation are important precursors to regular smoking. Prevention efforts are needed to interrupt the progression from intentions and experimentation to established smoking and nicotine dependence in this medically vulnerable population. Implications for cancer survivors Assessment of an adolescent’s history of parental divorce, past experimentation with smoking, and aggressive behavior will identify those survivors who are likely to consider smoking in the future. Screening for these characteristics will allow clinicians to be more vigilant in health promotion. PMID:20922493

Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

Steck, Susan E; Omofuma, Omonefe O; Su, L Joseph; Maise, Amanda A; Woloszynska-Read, Anna; Johnson, Candace S; Zhang, Hongmei; Bensen, Jeannette T; Fontham, Elizabeth T H; Mohler, James L; Arab, Lenore

2018-05-01

Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Among both African American and European American men diagnosed with prostate cancer, a higher Ca

Spatiotemporal switching signals for cancer stem cell activation in pediatric origins of adulthood cancer: Towards a watch-and-wait lifetime strategy for cancer treatment.

PubMed

Li, Shengwen Calvin; Kabeer, Mustafa H

2018-02-26

Pediatric origin of cancer stem cell hypothesis holds great promise and potential in adult cancer treatment, however; the road to innovation is full of obstacles as there are plenty of questions left unanswered. First, the key question is to characterize the nature of such stem cells (concept). Second, the quantitative imaging of pediatric stem cells should be implemented (technology). Conceptually, pediatric stem cell origins of adult cancer are based on the notion that plasticity in early life developmental programming evolves local environments to cancer. Technologically, such imaging in children is lacking as all imaging is designed for adult patients. We postulate that the need for quantitative imaging to measure space-time changes of plasticity in early life developmental programming in children may trigger research and development of the imaging technology. Such quantitative imaging of pediatric origin of adulthood cancer will help develop a spatiotemporal monitoring system to determine cancer initiation and progression. Clinical validation of such speculative hypothesis-that cancer originates in a pediatric environment-will help implement a wait-and-watch strategy for cancer treatment.

The prevalence and use of antidepressant medication in pediatric cancer patients.

PubMed

Portteus, Andrew; Ahmad, Naveed; Tobey, Daniel; Leavey, Patrick

2006-08-01

During the period of cancer diagnosis and active treatment, several small case series have revealed high rates of psychiatric difficulty in pediatric patients. However, due to the methodological limitations in these studies, it remains impossible to determine accurately the true prevalence of mood disorders in pediatric cancer patients receiving cancer treatment. To date, no study has reported rates of antidepressant treatment in this population. The aims of this study were: (1) To determine the prevalence of the use of antidepressant medication (ADM) in children with cancer; (2) to identify a group of children being treated for cancer, that are likely to receive ADM, and who therefore may be eligible for a prospective observational or interventional clinical trial of depression during cancer therapy. We reviewed the medical records of 224 pediatric patients suspected for cancer in 2003 at the Children's Medical Center of Dallas. Of these, 6 proved non-oncologic and 2 were lost to follow up, leaving 216 charts for review. Within 1 year of diagnosis, 29 patients (13%) had received a psychiatric consultation. Twenty-two patients (10.2%) received ADM within 1 year of cancer diagnosis. Children >/= 12 years, children with acute lymphoblastic leukemia, and children receiving radiotherapy or opiate analgesics were more likely to receive ADM by multivariate analysis. Race, sex, bone marrow transplant, and surgery were not significantly associated with ADM use. The prevalence of ADM use in pediatric cancer patients (10.2%) was higher than the reported rates of depression (4-8%) and ADM treatment (1%) in the general pediatric population. Teenagers and those who received opiate analgesic medications during their cancer therapy represent a subgroup of children in whom further study of depression and cancer therapy may be valuable.

Pediatric cancer risk in association with birth defects: A systematic review

PubMed Central

Padda, Hannah; Feng, Qianxi; Partap, Sonia; Fowler, Susan A.; Druley, Todd E.

2017-01-01

Background Many epidemiological studies have examined associations between birth defects (BDs) and pediatric malignancy over the past several decades. Our objective was to conduct a systematic literature review of studies reporting on this association. Methods We used librarian-designed searches of the PubMed Medline and Embase databases to identify primary research articles on pediatric neoplasms and BDs. English language articles from PubMed and Embase up to 10/12/2015, and in PubMed up to 5/12/2017 following an updated search, were eligible for inclusion if they reported primary epidemiological research results on associations between BDs and pediatric malignancies. Two reviewers coded each article based on the title and abstract to identify eligible articles that were abstracted using a structured form. Additional articles were identified through reference lists and other sources. Results were synthesized for pediatric cancers overall and for nine major pediatric cancer subtypes. Results A total of 14,778 article citations were identified, of which 80 met inclusion criteria. Pediatric cancer risk was increased in most studies in association with BDs overall with some notable specific findings, including increased risks for CNS tumors in association with CNS abnormalities and positive associations between rib anomalies and several pediatric cancer types. Conclusions Some children born with BDs may be at increased risk for specific pediatric malignancy types. This work provides a foundation for future investigations that are needed to clarify specific BD types predisposing toward malignancy and possible underlying causes of both BDs and malignancy. PMID:28749971

Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer.

PubMed

Mills, Christopher C; Kolb, E A; Sampson, Valerie B

2017-12-01

This review describes the pivotal roles of cell-cycle and checkpoint regulators and discusses development of specific cell-cycle inhibitors for therapeutic use for pediatric cancer. The mechanism of action as well as the safety and tolerability of drugs in pediatric patients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora kinases (AT9283 and MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids), are presented. The design of mechanism-based combinations that exploit the cross-talk of signals activated by cell-cycle arrest, as well as pediatric-focused drug development, are critical for the advancement of drugs for rare childhood diseases. Cancer Res; 77(23); 6489-98. ©2017 AACR . ©2017 American Association for Cancer Research.

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

Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer

PubMed Central

Black, Amanda; Pinsky, Paul F.; Grubb, Robert L.; Falk, Roni T.; Hsing, Ann W.; Chu, Lisa; Meyer, Tamra; Veenstra, Timothy D.; Xu, Xia; Yu, Kai; Ziegler, Regina G.; Brinton, Louise A.; Hoover, Robert N.; Cook, Michael B.

2014-01-01

Background The combined action of androgens and estrogens—specifically their balance—may play a role in prostate carcinogenesis but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer. Methods In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort we measured serum estrone, estradiol and 13 estrogen metabolites, in the 2-, 4, or 16-hydroxylation pathways, using a liquid chromatography-tandem mass spectrometry assay. Cases (n=195) were non-Hispanic white men aged 55–70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n=195) were non-Hispanic white men without prostate cancer who were frequency-matched to cases by age and year at blood draw, time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st =0.27, 95% CI 0.12–0.59, p trend=0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st =2.44, 95% CI 1.34–4.45, p trend=0.001). Estradiol, estrone and estrogen metabolites were unrelated to risk. Conclusions Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer. Impact Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions. PMID:25178985

Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

PubMed

Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

2018-05-01

To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption

The Pediatric Cancer Genome Project

PubMed Central

Downing, James R; Wilson, Richard K; Zhang, Jinghui; Mardis, Elaine R; Pui, Ching-Hon; Ding, Li; Ley, Timothy J; Evans, William E

2013-01-01

The St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project (PCGP) is participating in the international effort to identify somatic mutations that drive cancer. These cancer genome sequencing efforts will not only yield an unparalleled view of the altered signaling pathways in cancer but should also identify new targets against which novel therapeutics can be developed. Although these projects are still deep in the phase of generating primary DNA sequence data, important results are emerging and valuable community resources are being generated that should catalyze future cancer research. We describe here the rationale for conducting the PCGP, present some of the early results of this project and discuss the major lessons learned and how these will affect the application of genomic sequencing in the clinic. PMID:22641210

The PedsQL in pediatric cancer: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module.

PubMed

Varni, James W; Burwinkle, Tasha M; Katz, Ernest R; Meeske, Kathy; Dickinson, Paige

2002-04-01

The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents ages 2-18 years. The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease specific modules. The PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients. The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer specific HRQOL. The PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module were administered to 339 families (220 child self-reports; 337 parent proxy-reports). Internal consistency reliability for the PedsQL Generic Core Total Scale Score (alpha = 0.88 child, 0.93 parent report), Multidimensional Fatigue Total Scale Score (alpha = 0.89 child, 0.92 parent report) and most Cancer Module Scales (average alpha = 0.72 child, 0.87 parent report) demonstrated reliability acceptable for group comparisons. Validity was demonstrated using the known-groups method. The PedsQL distinguished between healthy children and children with cancer as a group, and among children on-treatment versus off-treatment. The validity of the PedsQL Multidimensional Fatigue Scale was further demonstrated through hypothesized intercorrelations with dimensions of generic and cancer specific HRQOL. The results demonstrate the reliability and validity of the PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module in pediatric cancer. The PedsQL may be utilized as an outcome measure in clinical trials, research, and clinical practice. Copyright 2002 American Cancer Society.

Emergency Department Visits by Adolescent and Young Adult Cancer Patients Compared with Pediatric Cancer Patients in the United States.

PubMed

Kaul, Sapna; Russell, Heidi; Livingston, John A; Kirchhoff, Anne C; Jupiter, Daniel

2018-06-20

Limited information exists on emergency department (ED) visits for adolescent and young adult (AYA) patients with cancer. We examined the clinical reasons for ED visits, and outcomes, for AYAs with cancer compared to pediatric cancer patients. The 2013 Nationwide Emergency Department Sample data were used to identify 53,274 AYA (ages 15-39) and 6952 pediatric (ages 0-14) cancer ED visits. We evaluated patient (i.e., demographic and diagnosis) and hospital characteristics, and the ED event outcome (admitted to the same hospital or treated/released). Clinical reasons for visits were identified as procedures, infections, or noninfectious toxicities. Variables were compared between groups using chi-squared tests. Logistic regressions identified characteristics associated with the outcome between and within groups. AYA cancer visits were more likely to be self-paid (15.8% vs. 1.9%, p < 0.001), and be from low-income households and nonmetro counties than pediatric visits. Toxicity was the most prevalent reason for AYA visits (46.0%) and infections for pediatrics (47.3%, p < 0.001). AYA cancer visits were less likely to be admitted (OR = 0.84, 95% CI = 0.71-0.98; p = 0.03) than pediatric cancer. Among AYAs, self-paid visits were less likely to be admitted compared with privately insured visits (OR = 0.58, 95% CI: 0.52-0.66, p < 0.001). Self-pay did not affect the outcome for pediatric visits. In the United States, compared with pediatric cancer patients, AYAs with cancer visit EDs more often for toxicity-related problems, and are more often self-paid and from poorer households. These distinctive features impacting health service use should be incorporated into care plans aimed at delineating effective care for these patients.

Low-grade prostate tumors can harbor signs of aggressive cancer | Center for Cancer Research

Cancer.gov

In a new study, Center for Cancer Research investigators found that low-grade and high-grade regions of prostate tumor tissue shared mutations typically linked to aggressive cancer. Testing for mutations to specific genes could help clinicians decide whether a patient with an initial low-grade result should undergo a follow-up biopsy. Learn more...

Feasibility, reliability, and validity of the Pediatric Quality of Life Inventory ™ generic core scales, cancer module, and multidimensional fatigue scale in long-term adult survivors of pediatric cancer.

PubMed

Robert, Rhonda S; Paxton, Raheem J; Palla, Shana L; Yang, Grace; Askins, Martha A; Joy, Shaini E; Ater, Joann L

2012-10-01

Most health-related quality of life assessments are designed for either children or adults and have not been evaluated for adolescent and young adult survivors of pediatric cancer. The objective of this study was to examine the feasibility, reliability, and validity of the Pediatric Quality of Life Inventory (PedsQL ™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale in adult survivors of pediatric cancer. Adult survivors (n = 64; Mean age 35 year old; >2 years after treatment) completed the PedsQL™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale. Feasibility was examined with floor and ceiling effects; and internal consistency was determined by Cronbach's coefficient alpha calculations. Inter-factor correlations were also assessed. Significant ceiling effects were observed for the scales of social function, nausea, procedural anxiety, treatment anxiety, and communication. Internal consistency for all subscales was within the recommended ranges (α ≥ 0.70). Moderate to strong correlations between most Cancer Module and Generic Core Scales (r = 0.25 to r = 0.76) and between the Multidimensional Fatigue Scale and Generic Core Scales (r = 0.37 to r = 0.73). The PedsQL™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale appear to be feasible for an older population of pediatric cancer survivors; however, some of the Cancer Module Scales (nausea, procedural/treatment anxiety, and communication) were deemed not relevant for long-term survivors. More information is needed to determine whether the issues addressed by these modules are meaningful to long-term adult survivors of pediatric cancers. Copyright © 2012 Wiley Periodicals, Inc.

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

PubMed

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

2014-09-09

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

Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

DTIC Science & Technology

2014-08-01

contributes to PCa’s distant metastasis, which is mediated via an E- selectin ligand, ESL -1. Consequently, the interaction of E-selectin/ ESL -1 transduces...cancer cell, E-selectin, ESL -1. OVERALL PROJECT SUMMARY A. Major goals of the project: 3 Task 1: Correlation of cancers’ aggressiveness with...Determination of the aggressive/metastatic related gene I. 1. ESL -1 expression is high in rolling cells and tissue When PCa cells come in contact with

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.

2008-01-01

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

Pediatric Oncology Branch - Support Services | Center for Cancer Research

Cancer.gov

Support Services As part of the comprehensive care provided at the NCI Pediatric Oncology Branch, we provide a wide range of services to address the social, psychological, emotional, and practical facets of pediatric cancer and to support patients and families while they are enrolled in clinical research protocols.

Psychometric properties of the Chinese version of the Pediatric Quality Of Life Inventory 4.0 Generic Core scales among pediatric cancer patients.

PubMed

Yeung, Nelson C Y; Lau, Joseph T F; Yu, Xiao-nan; Chu, Yvonne; Shing, Matthew M K; Leung, Ting Fan; Li, Chi Kong; Fok, Tai Fai; Mak, Winnie W S

2013-01-01

The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales are commonly used to assess health-related quality of life of healthy children and pediatric patients. Validation of the Generic Core Scales among Chinese pediatric cancer patients has not been reported in the literature. The scales can serve to measure different quality-of-life domains that are not captured by the PedsQL Cancer Module. Psychometric properties of the Chinese version of the PedsQL 4.0 among pediatric cancer patients and their caretakers were examined. The Generic Core Scales were administered to 335 pairs of pediatric cancer patients (aged 8-18 years) and their caretakers in Hong Kong. A 5-factor structure (physical, emotional, social, school-related cognitive function, and missed school) was identified in the patient and proxy versions of the scales using confirmatory factor analysis. Both versions of the total scale reported Cronbach α's of .90 or greater, with almost all subscales reporting α's of .70 or greater. Test-retest reliability at 2 weeks was acceptable (intraclass correlations ≥0.60) for a majority of subscales. Agreement between patients' and caretakers' ratings was medium. The scales demonstrated acceptable psychometric properties and construct validity. This study validated the Chinese version of the Generic Core Scales among pediatric cancer patients and their caretakers, which supports the future use of the scales in clinical settings. The Generic Core Scales can also be supplementary to the PedsQL Cancer Module for measuring multiple domains of quality of life in cancer population.

Pediatric melanoma: incidence, treatment, and prognosis

PubMed Central

Saiyed, Faiez K; Hamilton, Emma C; Austin, Mary T

2017-01-01

The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE) criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole). Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV)-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. PMID:29388632

Incidence and case-fatality of varicella-zoster virus infection among pediatric cancer patients in developing countries.

PubMed

Ojha, Rohit P; Stallings-Smith, Sericea; Aviles-Robles, Martha J; Gomez, Sergio; Somarriba, María Mercedes; Caniza, Miguela A

2016-04-01

Limited evidence is available about varicella-zoster virus (VZV) infection among pediatric cancer patients in developing countries, which raises questions about the generalizability of VZV vaccine recommendations for pediatric cancer patients (derived from developed countries) to these settings. We assessed the incidence and case-fatality of VZV infection at three institutions in developing countries (Argentina, Mexico, and Nicaragua). Individuals eligible for our study were aged <20 years and actively receiving cancer-directed therapy. We estimated a summary incidence rate (IR) and case-fatality risk with corresponding 95 % confidence limits (CL) of VZV infection across sites using random-effects models. Our study population comprised 511 pediatric cancer patients, of whom 64 % were aged <10 years, 58 % were male, and 58 % were diagnosed with leukemia. We observed a total of 10 infections during 44,401 person-days of follow-up across the 3 sites (IR = 2.3, 95 % CL 1.2, 4.2). The summary case-fatality risk was 10 % (95 % CL 1.4, 47 %) based on one death. Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. VZV vaccine recommendations for pediatric cancer patients in developed countries may be generalizable to developing countries. • Current recommendations, based on evidence from pediatric cancer patients in developed countries, contraindicate varicella-zoster virus (VZV) vaccination until completion of cancer-directed therapy and recovery of immune function. • The generalizability of these VZV vaccine recommendations to pediatric cancer patients in developing countries is unknown because of limited information about the incidence and case-fatality of VZV in these settings. What is New: • Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. • VZV vaccine recommendations based on evidence from

MIF Drives Pancreatic Cancer Aggressiveness by Downregulating NR3C2 | Center for Cancer Research

Cancer.gov

Pancreatic cancer, while relatively rare, is an aggressive disease ranked as the fourth leading cause of cancer-related death in the US. Because most patients are diagnosed at an advanced stage and their tumors resist available treatments, novel therapeutic targets are urgently needed. Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine that is elevated

MIF Drives Pancreatic Cancer Aggressiveness by Downregulating NR3C2 | Center for Cancer Research

Cancer.gov

Pancreatic cancer, while relatively rare, is an aggressive disease ranked as the fourth leading cause of cancer-related death in the US. Because most patients are diagnosed at an advanced stage and their tumors resist available treatments, novel therapeutic targets are urgently needed. Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine that is elevated in pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, and may provide a molecular link between inflammation and cancer, though the mechanism is unknown.

Determinants of Hospital Death for Taiwanese Pediatric Cancer Decedents, 2001-2010.

PubMed

Hung, Yen-Ni; Liu, Tsang-Wu; Tang, Siew Tzuh

2015-11-01

Factors influencing pediatric cancer patients' place of death may have evolved with advances in medical and hospice care since earlier studies were done. To comprehensively analyze factors associated with hospital death in an unbiased population of pediatric cancer patients in Taiwan. This was a retrospective cohort study using administrative data for 1603 Taiwanese pediatric cancer patients who died in 2001-2010. Place of death was hypothesized to be associated with 1) patient sociodemographics and disease characteristics, 2) primary physician's specialty, 3) characteristics and health care resources at both the hospital and regional levels, and 4) historical trends. Most Taiwanese pediatric cancer patients (87.4%) died in an acute care hospital. The probability of dying in hospital increased slightly over time, reaching significance only in 2009 (adjusted odds ratio [AOR], 95% CI: 2.84 [1.32-6.11]). Children were more likely to die in an acute care hospital if they resided in the most urbanized area, were diagnosed with leukemia or lymphoma (2.32 [1.39-3.87]), and received care from a pediatrician (1.58 [1.01-2.47]) in a nonprofit proprietary hospital (1.50 [1.01-2.24]) or large hospital, reaching significance for the third quartile (2.57 [1.28-5.18]) of acute care hospital beds. Taiwanese pediatric cancer patients predominantly died in an acute care hospital with a slightly increasing trend of shifting place of death from home to hospital. Propensity for hospital death was determined by residential urbanization level, diagnosis, primary physician's specialty, and the primary hospital's characteristics and health care resources. Clinical interventions and health policies should ensure that resources are allocated to allow pediatric cancer patients to die in the place they and their parents prefer to achieve a good death and promote their parents' bereavement adjustment. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier

A basal stem cell signature identifies aggressive prostate cancer phenotypes

PubMed Central

Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

2015-01-01

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

Approaching Pediatric Cancers through a Global Lens

Cancer.gov

Since the incidence of pediatric cancer is relatively constant worldwide, strengthening population-based registries to collect data on the extent of disease at diagnosis would be helpful in determining if late diagnosis may explain difference in outcome globally.

Molecular and Clinical Predictors of Aggressive Prostate Cancer

DTIC Science & Technology

2007-09-01

AD_________________ Award Number: W81XWH-05-1-0562 TITLE: Molecular and Clinical Predictors of...DATES COVERED (From - To) 1 SEP 2006 - 31 AUG 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Molecular And Clinical Predictors Of Aggressive...course. We are evaluating molecular and clinical predictors at diagnosis to distinguish lethal and indolent prostate cancer. In a related project, we

Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers

PubMed Central

Veeraraghavan, Jamunarani; Tan, Ying; Cao, Xi-Xi; Kim, Jin-Ah; Wang, Xian; Chamness, Gary C.; Maiti, Sourindra N.; Cooper, Laurence J. N.; Edwards, Dean P.; Contreras, Alejandro; Hilsenbeck, Susan G.; Chang, Eric C.; Schiff, Rachel; Wang, Xiao-Song

2014-01-01

Characterizing the genetic alterations leading to the more aggressive forms of estrogen receptor positive (ER+) breast cancers are of critical significance in breast cancer management. Here we identify recurrent rearrangements between estrogen receptor gene ESR1 and its neighbor CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal-B tumors, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170 positive tumors. These fusions encode N-terminally truncated CCDC170 proteins (ΔCCDC170). When introduced into ER+ breast cancer cells, ΔCCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity, and enhanced xenograft tumor formation. Mechanistic studies suggest that ΔCCDC170 engages Gab1 signalosome to potentiate growth factor signaling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer. PMID:25099679

Interstitial assessment of aggressive prostate cancer by physio-chemical photoacoustics: an ex vivo study with intact human prostates.

PubMed

Huang, Shengsong; Qin, Yu; Chen, Yingna; Pan, Jing; Xu, Chengdang; Wu, Denglong; Chao, Wan-Yu; Wei, John T; Tomlins, Scott A; Wang, Xueding; Brian Fowlkes, J; Carson, Paul L; Cheng, Qian; Xu, Guan

2018-06-23

Transrectal ultrasound (TRUS) guided biopsy is the standard procedure for evaluating the presence and aggressiveness of prostate cancer. TRUS biopsy involves tissue removal, and suffers from low core yield as well as high false negative rate. A less invasive and more accurate diagnostic procedure for prostate cancer is therefore highly desired. Combining the optical sensitivity and ultrasonic resolution to resolve the spatial distribution of the major molecular components in tissue, photoacoustic (PA) technology could be an alternative approach for the diagnosis of prostate cancer. The purpose of this study is to examine the feasibility of identifying aggressive prostate cancer using interstitial PA measurements. 17 patients with pre-biopsy magnetic resonance imaging (MRI), TRUS biopsies and planned prostatectomies were enrolled in this study. The interstitial PA measurements were achieved using our recently developed needle PA probe, which was inserted into the ex vivo prostates in the fashion of a biopsy needle. A total of 70 interstitial PA measurements were acquired. The PA measurements were quantified by a previously established PA physio-chemical analysis (PAPCA) method. The histology has confirmed the nonaggressive and aggressive cancerous conditions at the insertion locations. The diagnostic accuracy was also compared to that provided by the pre-biopsy MRI. The quantitative study shows significant differences between the individual parameters of the nonaggressive and the aggressive cancerous regions (p<0.005). Multivariate analysis of the quantitative features achieved a diagnostic accuracy of 78.6% for differentiating nonaggressive and aggressive prostate cancer tissues CONCLUSIONS: The proposed procedure has shown promises in the diagnosis of aggressive prostate cancer. This article is protected by copyright. All rights reserved.

Financial Burden of Pediatric Cancer for Patients and Their Families.

PubMed

Warner, Echo L; Kirchhoff, Anne C; Nam, Gina E; Fluchel, Mark

2015-01-01

Cancer treatment may cause financial stress for pediatric oncology patients and their families. We evaluated pediatric cancer caregivers' perceived financial burden related to socioeconomic factors (eg, parental employment) and health care use factors (eg, unexpected hospitalizations). A single-site, cross-sectional survey of primary caretakers of patients with childhood cancer was performed from July 2010 to July 2012. Eligible patients were treated at a pediatric cancer hospital, diagnosed at age ≤ 21 years and were ≤ 5 years from diagnosis (N = 254). Financial burden was rated on a visual analog scale of 0 to 100. Multivariable linear regression models were used to calculate coefficients and 95% CIs of financial burden by time since diagnosis. Mean age at diagnosis was 6.8 years (SD = 5.5 years), and average time since diagnosis was 1.6 years (SD = 1.4 years). The most common diagnosis was leukemia (41.9%). When adjusted for sex, age at diagnosis, insurance status, and rural residence, caregivers whose child was 1 to 5 years from diagnosis with ≥ 5 unexpected hospitalizations experienced 24.9 (95% CI, 9.1 to 40.7; P < .01) points higher financial burden than those with no unexpected hospitalizations. In addition, when compared with families without employment disruptions, families of children 1 to 5 years from diagnosis in which a caregiver had quit or changed jobs reported 13.4 (95% CI, 3.2 to 23.6; P = .01) points higher financial burden. Efforts to reduce unexpected hospitalizations and employment disruptions by providing more comprehensive supportive care for pediatric patients with cancer could help ease families' financial burden. Copyright © 2015 by American Society of Clinical Oncology.

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...cancer (as determined by Gleason scoring) we propose to: 1) Determine the correlation between FAS expression in prostatectomy samples and the amount... FAS expression and FAS activity in prostatectomy samples, intraprostatic lipid as measured by MRSI and prostate tumor aggressiveness. 3) To quantify

Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors.

PubMed

Sherborne, Amy L; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R; Mazor, Tali; Smirnoff, Ivan V; Horvai, Andrew E; Loh, Mignon; DuBois, Steven G; Goldsby, Robert E; Neglia, Joseph P; Hammond, Sue; Robison, Leslie L; Wustrack, Rosanna; Costello, Joseph F; Nakamura, Alice O; Shannon, Kevin M; Bhatia, Smita; Nakamura, Jean L

2017-04-01

Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs. Results: WES revealed TP53 mutations involving p53's DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53- mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53- coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852-61. ©2016 AACR . ©2016 American Association for Cancer Research.

Molecular innovations towards theranostics of aggressive prostate cancer

DTIC Science & Technology

2016-09-01

Xiankai Sun, PhD CONTRACTING ORGANIZATION: University of Texas Southwestern Medical Center Dallas, TX 75390-8542 REPORT DATE : September 2016 TYPE OF...number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) September 2016 2. REPORT TYPE Annual 3. DATES COVERED (From...Partner PI’s lab for the treatment of aggressive prostate cancer. To date , we have designed and synthesized the proposed bifunctional chelator

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…

The use of zoledronic acid in pediatric cancer patients.

PubMed

August, Keith J; Dalton, Amanda; Katzenstein, Howard M; George, Bradley; Olson, Thomas A; Wasilewski-Masker, Karen; Rapkin, Louis B

2011-04-01

The third generation bisphosphonate zoledronic acid has demonstrated efficacy in reducing skeletal-related events in adult patients with multiple cancer types that have skeletal disease. The use of zoledronic acid in pediatric oncology patients with bone metastases for the purpose of reducing pain, improving bone strength and altering the progression of metastatic disease has not been thoroughly evaluated. From October 2005 to December 2008, 19 patients at the Aflac Cancer Center received one or more doses of zoledronic acid as part of their therapy. A retrospective review of these patients was performed and information was collected including indication for treatment, toxicities, and outcomes. Most patients (n = 15) received zoledronic acid following relapse of their malignancy with metastatic disease present in one or more bony sites. Hypocalcemia and hypophosphatemia were frequent, but did not result in clinical symptoms. More significant toxicities associated with zoledronic acid, including clinically apparent renal insufficiency and osteonecrosis of the jaw, were not seen. Overall, zoledronic acid was well tolerated in this population. The benefits of zoledronic acid seen in randomized trials of adults with bone metastases have sparked interest in its use for children with metastatic cancer. The administration of zoledronic acid in pediatric oncology appears safe, and may result in improved bone strength and pain control. Further evaluation is warranted to prospectively evaluate its efficacy and long-term safety in pediatric patients with cancer and skeletal metastases. Copyright © 2010 Wiley-Liss, Inc.

Pediatric Cancer Patients' Important End-of-Life Issues, Including Quality of Life: A Survey of Pediatric Oncologists and Nurses in Japan.

PubMed

Nagoya, Yuko; Miyashita, Mitsunori; Shiwaku, Hitoshi

2017-05-01

Research into the key themes and concepts of quality of life (QOL) relevant to the end-of-life (EOL) care of pediatric cancer patients in the Japanese context is imperative. This study aimed at identifying the key items and constructive concepts of QOL at EOL of pediatric cancer patients. In 2015, pediatricians and nurses were recruited from 163 pediatric oncology treatment facilities in Japan. The questionnaire was developed on the basis of a previous qualitative study. Items that were rated as "very important" or "important" by at least 80% of the respondents were considered as "common and important" QOL items. Exploratory factor analysis was performed to conceptualize QOL of the pediatric cancer patients during EOL care. A total of 157 pediatricians and 270 nurses participated in this study. Fifty-five items were refined to 35 "common and important" QOL items. On factor analysis, 12 domains (containing 29 items) were identified: playing and learning; fulfilling wishes; spending time with family; receiving relief from physical and psychological suffering; making many wonderful memories; having a good relationship with the medical staff; having a peaceful death in the presence of family; spending time with a minimum of medical treatment; living one's life as usual; spending time in a calm hospital environment; being oneself; and having a close family. Although the respondents in this study were medical care providers rather than the patients or their family members, findings should help medical staff provide better palliative care to Japanese pediatric cancer patients.

Somatic and germline TP53 alterations in second malignant neoplasms from pediatric cancer survivors

PubMed Central

Sherborne, Amy L.; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R.; Mazor, Tali; Smirnoff, Ivan; Horvai, Andrew; Loh, Mignon; DuBois, Steven G.; Goldsby, Robert E.; Neglia, Joseph; Hammond, Sue; Robison, Leslie L.; Wustrack, Rosanna; Costello, Joseph; Nakamura, Alice O.; Shannon, Kevin; Bhatia, Smita; Nakamura, Jean L.

2016-01-01

Purpose Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design We performed whole exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in thirty-seven pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without history of a familial cancer predisposition syndrome but known to have developed SMNs. Results WES revealed TP53 mutations involving p53’s DNA binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53 mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53 coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in six patients and a synonymous single nucleotide polymorphism A639G in four others, resulting in ten out of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions Currently, germline TP53 is not routinely assessed in pediatric cancer patients. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive post-treatment monitoring. PMID:27683180

PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.

PubMed

Canto, Patricia; Granados, Jesús Benítez; Feria-Bernal, Guillermo; Coral-Vázquez, Ramón Mauricio; García-García, Eduardo; Tejeda, María Elena; Tapia, André; Rojano-Mejía, David; Méndez, Juan Pablo

2017-07-04

Obesity constitutes a risk factor for the development of aggressive forms of prostate cancer. It has been proposed, that prostate cancer has a genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in the development of this condition. To analyse the association of two PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the development of aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity. Two hundred fifty seven men with prostate cancer of Mexican-Mestizo origin were included. Body mass index (BMI) was determined and the degree of prostate cancer aggressiveness by the D'Amico classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A, and rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic discrimination. Pairwise linkage disequilibrium, between single nucleotide polymorphisms was calculated and haplotype analysis was performed. A higher-risk (D'Amico classification) was observed in 21.8% of patients. An association of cancer aggressiveness with rs2970870 of PPARGC1A, and rs501299 of ADIPOQ, as well as with one haplotype of ADIPOQ was documented. This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.

Impact of pediatric cancer on family relationships.

PubMed

Erker, Craig; Yan, Ke; Zhang, Liyun; Bingen, Kristin; Flynn, Kathryn E; Panepinto, Julie

2018-05-01

Little is known about the impact of cancer on family relationships from the perspective of the pediatric cancer patient and their sibling(s). This study assessed and compared children's experiences of family relationships in patients receiving active cancer therapy, those who have completed therapy, and siblings. A cross-sectional study of children with cancer and their siblings aged 8-17 years old was conducted. Children completed the PROMIS Pediatric Family Relationships short form and the Depressive Symptoms, Anxiety, and Peer Relationships short forms. The Mann-Whitney test assessed differences in Family Relationships scores between therapy groups, while the Wilcoxon signed-rank test assessed differences between patients and siblings. An actor-partner interdependence model (APIM) was used to assess how patient and sibling variables were associated with their own and each others' family relationships. Two hundred and sixty-five children completed the assessments. Siblings of patients on-therapy had worse family relationships than patients on-therapy (P = 0.015). Family relationships of patients off-therapy did not differ from their siblings or the patients on-therapy. Family relationships scores did not differ between the sibling cohorts. The APIM found patient family relationships were impaired when their own peer relationships decreased and when either their own or their siblings had increased depressive symptoms. Sibling family relationships were impaired when their own depression increased, and when the patient counterpart was female, younger age, had less depressive symptoms, more anxiety or a diagnosis of leukemia/lymphoma (compared to solid tumor). Based on these findings, increased psychosocial resources for patients and siblings of children undergoing cancer therapy may be warranted. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Long Noncoding RNAs AC009014.3 and Newly Discovered XPLAID Differentiate Aggressive and Indolent Prostate Cancers.

PubMed

Cesnik, Anthony J; Yang, Bing; Truong, Andrew; Etheridge, Tyler; Spiniello, Michele; Steinbrink, Maisie I; Shortreed, Michael R; Frey, Brian L; Jarrard, David F; Smith, Lloyd M

2018-06-01

The molecular mechanisms underlying aggressive versus indolent disease are not fully understood. Recent research has implicated a class of molecules known as long noncoding RNAs (lncRNAs) in tumorigenesis and progression of cancer. Our objective was to discover lncRNAs that differentiate aggressive and indolent prostate cancers. We analyzed paired tumor and normal tissues from six aggressive Gleason score (GS) 8-10 and six indolent GS 6 prostate cancers. Extracted RNA was split for poly(A)+ and ribosomal RNA depletion library preparations, followed byRNA sequencing (RNA-Seq) using an Illumina HiSeq 2000. We developed an RNA-Seq data analysis pipeline to discover and quantify these molecules. Candidate lncRNAs were validated using RT-qPCR on 87 tumor tissue samples: 28 (GS 6), 28 (GS 3+4), 6 (GS 4+3), and 25 (GS 8-10). Statistical correlations between lncRNAs and clinicopathologic variables were tested using ANOVA. The 43 differentially expressed (DE) lncRNAs between aggressive and indolent prostate cancers included 12 annotated and 31 novel lncRNAs. The top six DE lncRNAs were selected based on large, consistent fold-changes in the RNA-Seq results. Three of these candidates passed RT-qPCR validation, including AC009014.3 (P < .001 in tumor tissue) and a newly discovered X-linked lncRNA named XPLAID (P = .049 in tumor tissue and P = .048 in normal tissue). XPLAID and AC009014.3 show promise as prognostic biomarkers. We discovered several dozen lncRNAs that distinguish aggressive and indolent prostate cancers, of which four were validated using RT-qPCR. The investigation into their biology is ongoing. Published by Elsevier Inc.

Quality of life in pediatric cancer survivors: contributions of parental distress and psychosocial family risk.

PubMed

Racine, N M; Khu, M; Reynolds, K; Guilcher, G M T; Schulte, F S M

2018-02-01

Pediatric survivors of childhood cancer are at increased risk of poor quality of life and social-emotional outcomes following treatment. The relationship between parent psychological distress and child adjustment in pediatric cancer survivors has been well established. However, limited research has examined the factors that may buffer this association. The current study examined the associations between psychosocial family risk factors, parental psychological distress, and health-related quality of life (hrql) in pediatric cancer survivors. Fifty-two pediatric cancer survivors (34 males, 18 females, mean age = 11.92) and their parents were recruited from a long-term cancer survivor clinic. Children and their parents who consented to participate completed the Pediatric Quality of Life Inventory 4.0. Parents completed a demographic information form, the Psychosocial Assessment Tool (pat 2.0) and the Brief Symptom Inventory (bsi). The Intensity of Treatment Rating (itr-3) was evaluated by the research team. Multiple regression analyses revealed that parental psychological distress negatively predicted parent-reported hrql, while treatment intensity, gender, and psychosocial risk negatively predicted parent and child-reported hrql. Psychosocial risk moderated the association between parent psychological distress and parent-reported child hrql ( p = 0.03), whereby parents with high psychological distress but low levels of psychosocial risk reported their children to have higher hrql. Low levels of family psychosocial risk buffer the impact of parent psychological distress on child hrql in pediatric cancer survivors. The findings highlight the importance of identifying parents and families with at-risk psychological distress and psychosocial risk in order to provide targeted support interventions to mitigate the impact on hrql.

Understanding psychological distress among pediatric cancer caregivers.

PubMed

Nam, Gina E; Warner, Echo L; Morreall, Deborah K; Kirchhoff, Anne C; Kinney, Anita Y; Fluchel, Mark

2016-07-01

Few studies have examined distress in caregivers of pediatric cancer patients. We evaluated the association of socioeconomic, demographic, and patient clinical factors on caregivers' self-reported psychological distress associated with having a child with cancer. N = 366 pediatric cancer caregivers completed a self-administered questionnaire from July 2010 to July 2012. The Impact of Event Scale (IES), along with two subscales "intrusion" and "avoidance" measured caregiver cancer-specific distress, with higher scores indicating greater distress. Multivariable linear regression models were used to calculate coefficients (β) and 95 % confidence intervals (95 % CI) of IES by socioeconomic, demographic, and clinical factors. Average caregiver IES score was 31.2 (standard deviation (SD) = 16.9, range 0-75). Mean intrusion score was 18.1 (SD 9.8, range 0-35) and avoidance score was 12.8 (SD 9.0, range 0-40). Caregivers with household incomes <$40,000 reported higher mean distress scores than those with incomes ranging from $40,000 to $79,999 (β = 4.45, 95 % CI 0.04-8.87, p = 0.05). Infrequently or never attending religious services, younger child age, and a diagnosis of AML were associated with higher intrusion (all p < 0.05). Caregivers with a child currently receiving therapy reported higher overall IES (β = 5.9, 95 % CI 2.15-9.7, p < 0.01) and intrusion (β = 4.1, 95 % CI 1.9-6.3, p < 0.001) scores compared to those off therapy (β = 3.13, 95 % CI 0.93-5.33, p < 0.01). Our findings identify socioeconomic and clinical factors that influence psychological distress for caregivers of pediatric oncology patients. These findings underscore the importance of developing and testing interventions aimed at evaluating and addressing the psychosocial needs for high-risk caregivers in addition to those of patients.

Testosterone treatment and the risk of aggressive prostate cancer in men with low testosterone levels.

PubMed

Walsh, Thomas J; Shores, Molly M; Krakauer, Chloe A; Forsberg, Christopher W; Fox, Alexandra E; Moore, Kathryn P; Korpak, Anna; Heckbert, Susan R; Zeliadt, Steven B; Kinsey, Chloe E; Thompson, Mary Lou; Smith, Nicholas L; Matsumoto, Alvin M

2018-01-01

Testosterone treatment of men with low testosterone is common and, although relatively short-term, has raised concern regarding an increased risk of prostate cancer (CaP). We investigated the association between modest-duration testosterone treatment and incident aggressive CaP. Retrospective inception cohort study of male Veterans aged 40 to 89 years with a laboratory-defined low testosterone measurement from 2002 to 2011 and recent prostate specific antigen (PSA) testing; excluding those with recent testosterone treatment, prostate or breast cancer, high PSA or prior prostate biopsy. Histologically-confirmed incident aggressive prostate cancer or any prostate cancer were the primary and secondary outcomes, respectively. Of the 147,593 men included, 58,617 were treated with testosterone. 313 aggressive CaPs were diagnosed, 190 among untreated men (incidence rate (IR) 0.57 per 1000 person years, 95% CI 0.49-0.65) and 123 among treated men (IR 0.58 per 1000 person years; 95% CI 0.48-0.69). After adjusting for age, race, hospitalization during year prior to cohort entry, geography, BMI, medical comorbidities, repeated testosterone and PSA testing, testosterone treatment was not associated with incident aggressive CaP (HR 0.89; 95% CI 0.70-1.13) or any CaP (HR 0.90; 95% CI 0.81-1.01). No association between cumulative testosterone dose or formulation and CaP was observed. Among men with low testosterone levels and normal PSA, testosterone treatment was not associated with an increased risk of aggressive or any CaP. The clinical risks and benefits of testosterone treatment can only be fully addressed by large, longer-term randomized controlled trials.

National Cancer Institute Pediatric Preclinical Testing Program: Model Description for In Vitro Cytotoxicity Testing

PubMed Central

Kang, Min H.; Smith, Malcolm A.; Morton, Christopher L.; Keshelava, Nino; Houghton, Peter J.; Reynolds, C. Patrick

2010-01-01

Background The National Cancer Institute (NCI) has established the Pediatric Preclinical Testing Program (PPTP) for testing drugs against in vitro and in vivo childhood cancer models to aid in the prioritization of drugs considered for early phase pediatric clinical trials. Procedures In vitro cytotoxicity testing employs a semi-automated fluorescence-based digital imaging cytotoxicity assay (DIMSCAN) that has a 4-log dynamic range of detection. Curve fitting of the fractional survival data of the cell lines in response to various concentrations of the agents was used to calculate relative IC50, absolute IC50, and Ymin values The panel of 23 pediatric cancer cell lines included leukemia (n=6), lymphoma (n=2), rhabdomyosarcoma (n=4), brain tumors (n=3), Ewing family of tumors (EFT, n=4), and neuroblastoma (n=4). The doubling times obtained using DIMSCAN were incorporated into data analyses to estimate the relationship between input cell numbers and final cell number. Results We report in vitro activity data for three drugs (vincristine, melphalan, and etoposide) that are commonly used for pediatric cancer and for the mTOR inhibitor rapamycin, an agent that is currently under preclinical investigation for cancer. To date, the PPTP has completed in vitro testing of 39 investigational and approved agents for single drug activity and two investigational agents in combination with various “standard” chemotherapy drugs. Conclusions This robust in vitro cytotoxicity testing system for pediatric cancers will enable comparisons to response data for novel agents obtained from xenograft studies and from clinical trials. PMID:20922763

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

PubMed

Labbé, David P; Sweeney, Christopher J; Brown, Myles; Galbo, Phillip; Rosario, Spencer; Wadosky, Kristine M; Ku, Sheng-Yu; Sjöström, Martin; Alshalalfa, Mohammed; Erho, Nicholas; Davicioni, Elai; Karnes, R Jeffrey; Schaeffer, Edward M; Jenkins, Robert B; Den, Robert B; Ross, Ashley E; Bowden, Michaela; Huang, Ying; Gray, Kathryn P; Feng, Felix Y; Spratt, Daniel E; Goodrich, David W; Eng, Kevin H; Ellis, Leigh

2017-11-15

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer-associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts ( n = 1,900), two metastatic castration-resistant prostate cancer datasets ( n = 293), and one prospective cohort ( n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients ( n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer-derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. Clin Cancer Res; 23(22); 7072-83. ©2017 AACR . ©2017 American Association for Cancer Research.

Label free aggressive prostate cancer identification with ultraviolet photoacoustic spectral analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Guan; Davis, Mandy A.; Siddiqui, Javed; Chao, Wan-yu; Tomlins, Scott A.; Wei, John T.; Wang, Xueding

2017-03-01

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men for the past decades. PCa has a relatively low progression rate but the 5 year survival rate decreases dramatically once the cancer has metastasized. Differentiating aggressive from indolent PCa is critical for improving PCa patient outcomes and preventing metastasis and death. Prostate biopsy is the standard procedure for evaluating the presence and aggressiveness of PCa. The microarchitecture of the biopsied tissues visualized by histology process is evaluated by pathologists and assigned a Gleason score as a quantification of the aggressiveness. In our previous study, we have shown that photoacoustic spectral analysis (PASA) is capable of quantifying the Gleason scores of the H&E stained human prostate tissues. In this study, we attempt to assess the Gleason scores without any staining by taking advantage of the strong optical absorption of nucleic acid at ultraviolet wavelengths. PA signals were generated by wide field illumination at 266 nm and received by a hydrophone with a bandwidth of 0-20 MHz. DU145 prostate cancer cells at the concentrations of 0.8, 0.4, 0.05, 0.025 and 0.0125 million per cm3 simulating those in cancerous and normal tissues were first attempted. The measurements were repeated for 10 times at each concentration. A correlation of 0.86 was observed between the PA signal intensities and the cell concentrations. Human PCa tissues with Gleason score 6, 7 and 8 and normal tissues were assessed. With 11 samples, a correlation of 0.89 was found between the Gleason scores and PASA slopes.

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

PubMed

Seibert, Tyler M; Fan, Chun Chieh; Wang, Yunpeng; Zuber, Verena; Karunamuni, Roshan; Parsons, J Kellogg; Eeles, Rosalind A; Easton, Douglas F; Kote-Jarai, ZSofia; Al Olama, Ali Amin; Garcia, Sara Benlloch; Muir, Kenneth; Grönberg, Henrik; Wiklund, Fredrik; Aly, Markus; Schleutker, Johanna; Sipeky, Csilla; Tammela, Teuvo Lj; Nordestgaard, Børge G; Nielsen, Sune F; Weischer, Maren; Bisbjerg, Rasmus; Røder, M Andreas; Iversen, Peter; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Cuk, Katarina; Saum, Kai-Uwe; Park, Jong Y; Sellers, Thomas A; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Karow, David S; Mills, Ian G; Andreassen, Ole A; Dale, Anders M

2018-01-10

To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. Multiple institutions that were members of international PRACTICAL consortium. All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. Prediction with hazard score of age of onset of aggressive cancer in validation set. In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10 -16 ). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa

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.

Gas gangrene secondary to Clostridium perfringens in pediatric oncology patients.

PubMed

Temple, Ana-Maria M; Thomas, Neal J

2004-07-01

To report 2 cases of severe gas gangrene secondary to Clostridium perfringens in pediatric oncology patients. We describe 2 children with acute presentations of gas gangrene secondary to C. perfringens. Both children were initially seen and treated in a community hospital emergency department and subsequently were cared for in a pediatric intensive care unit in a tertiary care, university-based children's hospital. Both children demonstrated severe and unrelenting decompensation and required operative intervention within the first hospital day, which included amputation of the infected limb. One child survived and one child expired despite heroic measures. Gas gangrene secondary to C. perfringens is an uncommon but life-threatening and limb-threatening condition in pediatric cancer patients. A high index of suspicion in a immunocompromised child with cancer who presents with extremity pain in combination with neutropenia is the key to early diagnosis and may lead to improved survival. This disease requires prompt recognition and aggressive treatment to allow any hope of recovery. Emergency medicine physicians who treat these children should be aware of this severe and potentially fatal infectious process and should not delay treatment or prompt orthopedic surgery consultation.

Hospital discharges for fever and neutropenia in pediatric cancer patients: United States, 2009.

PubMed

Mueller, Emily L; Walkovich, Kelly J; Mody, Rajen; Gebremariam, Achamyeleh; Davis, Matthew M

2015-05-10

Fever and neutropenia (FN) is a common complication of pediatric cancer treatment, but hospital utilization patterns for this condition are not well described. Data were analyzed from the Kids' Inpatient Database (KID), an all-payer US hospital database, for 2009. Pediatric FN patients were identified using: age ≤19 years, urgent or emergent admit type, non-transferred, and a combination of ICD-9-CM codes for fever and neutropenia. Sampling weights were used to permit national inferences. Pediatric cancer patients accounted for 1.5 % of pediatric hospital discharges in 2009 (n = 110,967), with 10.1 % of cancer-related discharges meeting FN criteria (n = 11,261). Two-fifths of FN discharges had a "short length of stay" (SLOS) of ≤3 days, which accounted for approximately $65.5 million in hospital charges. Upper respiratory infection (6.0 %) and acute otitis media (AOM) (3.7 %) were the most common infections associated with SLOS. Factors significantly associated with SLOS included living in the Midwest region (OR = 1.65, 1.22-2.24) or West region (OR 1.54, 1.11-2.14) versus Northeast, having a diagnosis of AOM (OR = 1.39, 1.03-1.87) or viral infection (OR = 1.63, 1.18-2.25) versus those without those comorbidities, and having a soft tissue sarcoma (OR = 1.47, 1.05-2.04), Hodgkin lymphoma (OR = 2.33, 1.62-3.35), or an ovarian/testicular tumor (OR = 1.76, 1.05-2.95) compared with patients without these diagnoses. FN represents a common precipitant for hospitalizations among pediatric cancer patients. SLOS admissions are rarely associated with serious infections, but contribute substantially to the burden of hospitalization for pediatric FN.

Benefit Finding in Maternal Caregivers of Pediatric Cancer Survivors: A Mixed Methods Approach.

PubMed

Willard, Victoria W; Hostetter, Sarah A; Hutchinson, Katherine C; Bonner, Melanie J; Hardy, Kristina K

2016-09-01

Benefit finding has been described as the identification of positive effects resulting from otherwise stressful experiences. In this mixed methods study, we examined the relations between qualitative themes related to benefit finding and quantitative measures of psychosocial adjustment and coping as reported by maternal caregivers of survivors of pediatric cancer. Female caregivers of survivors of pediatric cancer (n = 40) completed a qualitative questionnaire about their experiences caring for their child, along with several quantitative measures. Qualitative questionnaires were coded for salient themes, including social support and personal growth. Correlation matrices evaluated associations between qualitative themes and quantitative measures of stress and coping. Identified benefits included social support and personal growth, as well as child-specific benefits. Total benefits reported were significantly positively correlated with availability of emotional resources. Coping methods were also associated, with accepting responsibility associated with fewer identified benefits. Despite the stress of their child's illness, many female caregivers of survivors of pediatric cancer reported finding benefits associated with their experience. Benefit finding in this sample was associated with better adjustment. © 2016 by Association of Pediatric Hematology/Oncology Nurses.

Quality of life in pediatric cancer survivors: contributions of parental distress and psychosocial family risk

PubMed Central

Racine, N.M.; Khu, M.; Reynolds, K.; Guilcher, G.M.T.; Schulte, F.S.M.

2018-01-01

Background Pediatric survivors of childhood cancer are at increased risk of poor quality of life and social-emotional outcomes following treatment. The relationship between parent psychological distress and child adjustment in pediatric cancer survivors has been well established. However, limited research has examined the factors that may buffer this association. The current study examined the associations between psychosocial family risk factors, parental psychological distress, and health-related quality of life (hrql) in pediatric cancer survivors. Methods Fifty-two pediatric cancer survivors (34 males, 18 females, mean age = 11.92) and their parents were recruited from a long-term cancer survivor clinic. Children and their parents who consented to participate completed the Pediatric Quality of Life Inventory 4.0. Parents completed a demographic information form, the Psychosocial Assessment Tool (pat 2.0) and the Brief Symptom Inventory (bsi). The Intensity of Treatment Rating (itr-3) was evaluated by the research team. Results Multiple regression analyses revealed that parental psychological distress negatively predicted parent-reported hrql, while treatment intensity, gender, and psychosocial risk negatively predicted parent and child-reported hrql. Psychosocial risk moderated the association between parent psychological distress and parent-reported child hrql (p = 0.03), whereby parents with high psychological distress but low levels of psychosocial risk reported their children to have higher hrql. Conclusion Low levels of family psychosocial risk buffer the impact of parent psychological distress on child hrql in pediatric cancer survivors. The findings highlight the importance of identifying parents and families with at-risk psychological distress and psychosocial risk in order to provide targeted support interventions to mitigate the impact on hrql. PMID:29507482

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. PsycINFO Database Record (c) 2015 APA, all rights reserved.

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

European Union pediatric legislation jeopardizes worldwide, timely future advances in the care of children with cancer.

PubMed

Rose, Klaus

2014-02-01

Diagnosis of childhood cancer is no longer an automatic death sentence, but it has not lost all of its horror. Drugs, surgery, radiation, and clinical trials have advanced our capacity to handle these cancers, but pediatric cancers still face challenges. Pediatric pharmaceutical legislation was introduced in the United States in 1997 and has triggered many clinical trials that have helped us better understand what drugs do to a child's body and vice versa. Following the US precedence, the European Union introduced its own legislation. The US legislation was designed to generate additional pediatric data and balances between mandatory requirements and voluntary incentives. The US legislation was designed to mandate full registration of all new drugs for children whenever there is any potential pediatric use. The purpose of this article is to discuss unintended negative consequences of the legislation of the European Medicines Agency (EMA). We analyzed the effects of the EU pediatric legislation with respect to the history of the emergence of modern drugs, pediatric clinical pharmacology, and the development of drugs for pediatric malignancies. No new drug can be registered in the European Union without a detailed pediatric investigation plan (PIP) approved by the EMA's Pediatric Committee (PDCO). This has moved the discussion of the pediatric aspects of drug development to an earlier stage and has increased public awareness. It also has brought industry and pediatric oncologists closer together. However, in a review of >100 PDCO PIP decisions in childhood cancer, we found a lack of balance between the legitimate desire to include children in drug development and the common sense needed in the complex worlds of drug development and pediatric oncology. Many decisions appeared to have been based on both exaggerated assumptions about the frequency of childhood malignancies and the feasibility of the clinical trials proposed. Pharmaceutical companies are being forced

Spending on Hospital Care and Pediatric Psychology Service Use Among Adolescents and Young Adults With Cancer.

PubMed

McGrady, Meghan E; Peugh, James L; Brown, Gabriella A; Pai, Ahna L H

2017-10-01

To examine the relationship between need-based pediatric psychology service use and spending on hospital care among adolescents and young adults (AYAs) with cancer. Billing data were obtained from 48 AYAs with cancer receiving need-based pediatric psychology services and a comparison cohort of 48 AYAs with cancer not receiving services. A factorial analysis of covariance examined group differences in spending for hospital care. Pending significant findings, a multivariate analysis of covariance was planned to examine the relationship between need-based pediatric psychology service use and spending for inpatient admissions, emergency department (ED) visits, and outpatient visits. Spending for hospital care was higher among AYAs receiving need-based pediatric psychology services than in the comparison cohort (p < .001, ωPartial2 = .11). Group differences were driven by significantly higher spending for inpatient admissions and ED visits among AYAs receiving need-based pediatric psychology services. The behavioral and psychosocial difficulties warranting need-based pediatric psychology services may predict higher health care spending. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

YAP and the Hippo pathway in pediatric cancer

PubMed Central

Mohamed, Abdalla D.; Gener, Melissa; Li, Weijie; Taboada, Eugenio

2017-01-01

ABSTRACT The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell–cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation of Hippo pathway members in several pediatric cancers and may offer prognostic information on rhabdomyosarcoma, osteosarcoma, Wilms tumor, neuroblastoma, medulloblastoma, and other brain gliomas. We review the results of such published studies and highlight the potential clinical application of this pathway in pediatric oncologic and pathologic studies. These studies support targeting this pathway as a novel treatment strategy. PMID:28616573

YAP and the Hippo pathway in pediatric cancer.

PubMed

Ahmed, Atif A; Mohamed, Abdalla D; Gener, Melissa; Li, Weijie; Taboada, Eugenio

2017-01-01

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation of Hippo pathway members in several pediatric cancers and may offer prognostic information on rhabdomyosarcoma, osteosarcoma, Wilms tumor, neuroblastoma, medulloblastoma, and other brain gliomas. We review the results of such published studies and highlight the potential clinical application of this pathway in pediatric oncologic and pathologic studies. These studies support targeting this pathway as a novel treatment strategy.

Glucose-regulated protein of 94 kDa contributes to the development of an aggressive phenotype in breast cancer cells.

PubMed

Buc Calderon, Pedro; Sennesael, Anne-Laure; Glorieux, Christophe

2018-05-28

Grp94 plays an essential role in protein assembly. We previously suggested that Grp94 overexpression is involved in tumor aggressiveness. However, the underlying mechanisms remain unknown. Since many tumors display high Grp94 levels, we investigated the effects of tumor microenvironment on the regulation of this chaperone expression. First, we found out that hypoxia did not change Grp94 expression in the human tumor cell lines MCF-7 (breast cancer) and HepG2 (liver cancer). Second, glucose deprivation significantly increased Grp94 protein levels. Subsequently, we focused in the putative role of Grp94 in the acquisition of an aggressive phenotype by cancer cells. Using a more aggressive cancer cell model (MDA-MB-231 breast tumor cells), we found out that Grp94 knockdown using siRNA decreased the invasive capacity of cancer cells. Moreover, cells with decreased Grp94 levels displayed an enhanced sensitivity of tumor cells to doxorubicin, a standard drug in the treatment of breast cancer. Taken together, our results suggest that the expression of Grp94 is linked to tumor aggressiveness. Therefore, targeting Grp94 could be an effective way to inhibit tumor growth improving chemotherapy outcome. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Relationship Between Prostate Cancer Aggressiveness and Glycemic Levels in Patients Submitted to Radical Prostatectomy

PubMed Central

Goncalves, Suzana Cristina; de Moraes Siqueira, Rafael; Nogueira, Marcus Vinicius F; Pereira-Correia, Joao Antonio; Vaz, Fernando Pires; Peres, Wilza Arantes Ferreira

2013-01-01

Background The relationship between hyperglycemia and prostate cancer remains controversial. According to current hypotheses, elevated serum glucose levels may lead to disease development or disease prevention. Our study examined the potential correlation between pre-operative glycemic levels of patients with prostate cancer and the grade of tumor aggressiveness. Method We studied the case files of patients with a diagnosis of prostate cancer who had received putatively curative cancer surgery at the Urology Department of the Servidores do Estado Federal Hospital (RJ/Brazil). We transcribed information related to glycemia - collected up to 3 months before the surgery - and the histopathological grade of tumor aggressiveness (Gleason score) of the surgically removed prostates. Results We analyzed 42 people who met the inclusion criteria. Based on Gleason scores, among the normoglycemic patients, we detected low, moderate, and highly aggressive neoplasias in 13%, 53%, and 36% of the cases, respectively. For the hyperglycemic group, these rates were 30%, 60%, and 10%, respectively. Normoglycemic patients had primary Gleason grade 3 in 40% of the cases and grade 4 in 60% of the cases. For the hyperglycemic patients, these rates were 90% and 10%, respectively (P < 0.05 vs. grade 3 group). Conclusion Both Gleason score and primary Gleason grade were lower in hyperglycemic patients with prostate cancer than in normoglycemic patients, suggesting a “protective action” of hyperglycemic states. PMID:29147337

Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

PubMed

Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

2012-10-01

This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

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…

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

Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.

PubMed

Demeure, Michael J; Aziz, Meraj; Rosenberg, Richard; Gurley, Steven D; Bussey, Kimberly J; Carpten, John D

2014-06-01

Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In radioiodine resistant aggressive papillary thyroid cancers, there remain few effective therapeutic options. A 62-year-old man who underwent multiple operations for papillary thyroid cancer and whose metastases progressed despite standard treatments provided tumor tissue. We analyzed tumor and whole blood DNA by whole genome sequencing, achieving 80× or greater coverage over 94 % of the exome and 90 % of the genome. We determined somatic mutations and structural alterations. We found a total of 57 somatic mutations in 55 genes of the cancer genome. There was notably a lack of mutations in NRAS and BRAF, and no RET/PTC rearrangement. There was a mutation in the TRAPP oncogene and a loss of heterozygosity of the p16, p18, and RB1 tumor suppressor genes. The oncogenic driver for this tumor is a translocation involving the genes for anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4). The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib. This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4-ALK translocation of a TRAPP oncogene mutation. These findings suggest that this tumor has a more distinct oncogenesis than BRAF mutant papillary thyroid cancer. Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.

SERUM THYROTROPIN CONCENTRATIONS ARE NOT PREDICTIVE OF AGGRESSIVE BREAST CANCER BIOLOGY IN EUTHYROID INDIVIDUALS

PubMed Central

Villa, Natalie M.; Li, Ning; Yeh, Michael W.; Hurvitz, Sara A.; Dawson, Nicole A.; Leung, Angela M.

2015-01-01

Objective The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin [thyroid-stimulating hormone (TSH)] concentration and markers of aggressive breast cancer biology, as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. Methods This was a retrospective cohort study of patients from 2002–2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and Her2/neu) and pre-diagnosis serum TSH data (n=437) were included. All patients had one of six receptor profiles: ER+ PR+ Her2/neu −, ER+ PR− Her2/neu−, ER+ PR+ Her2/neu+, ER+ PRHer2/ neu+, ER− PR− Her2/neu+, ER− PR− Her2/neu−. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions for a potential relationship with markers of breast cancer aggressiveness. Results Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu− profile (OR=0.52, p=0.0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, or tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. Conclusions Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort. PMID:26121443

Barriers to accessing palliative care for pediatric patients with cancer: A review of the literature.

PubMed

Haines, Emily R; Frost, A Corey; Kane, Heather L; Rokoske, Franziska S

2018-06-01

Although many of the 16,000 children in the United States diagnosed who are with cancer each year could benefit from pediatric palliative care, these services remain underused. Evidence regarding the barriers impeding access to comprehensive palliative care is dispersed in the literature, and evidence specific to pediatric oncology remains particularly sparse. The purpose of the current review was to synthesize the existing literature regarding these barriers and the strategies offered to address them. The authors completed a literature search using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science databases. In total, 71 articles were reviewed. Barriers to accessing pediatric palliative care were categorized according to the 4 levels of a modified socioecological model (ie, barriers related to policy/payment, health systems, organizations, and individuals). Major themes identified at each level included: 1) the lack of consistent and adequate funding mechanisms at the policy/payment level, 2) the lack of pediatric palliative care programs and workforce at the health systems level, 3) difficulties integrating palliative care into existing pediatric oncology care models at the organizational level, and 4) the lack of knowledge about pediatric palliative care, discomfort with talking about death, and cultural differences between providers and patients and their families at the individual level. Recommendations to address each of the barriers identified in the literature are included. Cancer 2018;124:2278-88. © 2018 American Cancer Society. © 2018 American Cancer Society.

The Impact of Cancer and its Treatment on the Growth and Development of the Pediatric Patient.

PubMed

Brand, Sarah; Wolfe, Joanne; Samsel, Chase

2017-01-01

Cancer treatment can have profound effects on the growth and development of pediatric patients. Different models of psychosocial development and behavioral treatment approaches aid children receiving medical treatment. Providing education, anticipatory guidance, and individualized support to child and their families is a psychosocial standard. Clarify the different models of psychosocial development and applicable psychosocial interventions to better prepare and tailor cancer treatment to pediatric patients. Authors reviewed existing evidenced-based literature in oncology, psychology, developmental, and psychiatric while drawing on case examples and expert knowledge to illustrate the impact of cancer treatment on pediatric patients, analyze developmentally individualized needs, and describe facilitative interventions. Pediatric patients of all ages cope and adjust better to all phases of treatment when their care is delivered in a developmentally-informed and psychosocially thoughtful way. Providers can comprehensively prepare their patients and families for treatment better by utilizing a psychosocially- and developmentally-informed framework while meeting individualized unique needs of patients. An integrated multidisciplinary psychosocial support team is facilitative in anticipating and meeting the needs of pediatric cancer patients and has recently become a psychosocial standard of care. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of pediatric cancer and its treatment on nutritional status: a systematic review.

PubMed

Iniesta, Raquel Revuelta; Paciarotti, Ilenia; Brougham, Mark F H; McKenzie, Jane M; Wilson, David C

2015-05-01

Malnutrition in pediatric cancer is common worldwide, yet its prevalence and effects on clinical outcomes remain unclear. The aim of this review was to evaluate primary research reporting the prevalence of malnutrition in pediatric cancer patients and to assess the effects of pediatric cancer and its treatment on nutritional status. Electronic databases of MEDLINE, CINHAL, and PubMed were searched (January 1990-February 2013). Studies of patients aged <18 years who were diagnosed with and treated for cancer and for whom measurements of anthropometry were reported and included. The primary outcome was the prevalence of malnutrition (undernutrition and overnutrition), expressed as body mass index (BMI), in children diagnosed with and treated for cancer. Evidence was appraised critically by employing the Critical Appraisal Skills Program tool, and data was extracted from original articles. A total of 46 studies were included, most of which were considered to be of low quality on the basis of heterogeneity in both the criteria and the measurements used to define malnutrition. Undernutrition was identified by measuring BMI, weight loss, mid-upper arm circumference, and triceps skinfold thickness, while overnutrition was assessed using BMI. Overall, the prevalence of undernutrition ranged from 0% to 65% and overnutrition from 8% to 78%. Finally, undernutrition in pediatric cancer at diagnosis was associated with poor clinical outcomes in 6 of 9 studies. The possibility of a high prevalence of malnutrition in childhood cancer, indicated by the studies reviewed, highlights the need for high-quality, population-based, longitudinal studies using standard criteria to identify malnutrition. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Defining Aggressive Prostate Cancer Using a 12-Gene Model1

PubMed Central

Riva, Alberto; Kim, Robert; Varambally, Sooryanarayana; He, Le; Kutok, Jeff; Aster, Jonathan C; Tang, Jeffery; Kuefer, Rainer; Hofer, Matthias D; Febbo, Phillip G; Chinnaiyan, Arul M; Rubin, Mark A

2006-01-01

Abstract The critical clinical question in prostate cancer research is: How do we develop means of distinguishing aggressive disease from indolent disease? Using a combination of proteomic and expression array data, we identified a set of 36 genes with concordant dysregulation of protein products that could be evaluated in situ by quantitative immunohistochemistry. Another five prostate cancer biomarkers were included using linear discriminant analysis, we determined that the optimal model used to predict prostate cancer progression consisted of 12 proteins. Using a separate patient population, transcriptional levels of the 12 genes encoding for these proteins predicted prostate-specific antigen failure in 79 men following surgery for clinically localized prostate cancer (P = .0015). This study demonstrates that cross-platform models can lead to predictive models with the possible advantage of being more robust through this selection process. PMID:16533427

Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

PubMed Central

Moro, Kazuki; Kawaguchi, Tsutomu; Tsuchida, Junko; Gabriel, Emmanuel; Qi, Qianya; Yan, Li; Wakai, Toshifumi; Takabe, Kazuaki; Nagahashi, Masayuki

2018-01-01

Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients. PMID:29731990

Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition.

PubMed

Ros, Martine M; Bueno-de-Mesquita, H Bas; Kampman, Ellen; Büchner, Frederike L; Aben, Katja K H; Egevad, Lars; Overvad, Kim; Tjønneland, Anne; Roswall, Nina; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie Christine; Morois, Sophie; Kaaks, Rudolf; Teucher, Birgit; Weikert, Steffen; von Ruesten, Anne; Trichopoulou, Antonia; Naska, Androniki; Benetou, Vassiliki; Saieva, Calogero; Pala, Valeria; Ricceri, Fulvio; Tumino, Rosario; Mattiello, Amalia; Peeters, Petra H M; van Gils, Carla H; Gram, Inger T; Engeset, Dagrun; Chirlaque, Maria-Dolores; Ardanazx, Eva; Rodríguez, Laudina; Amanio, Pilar; Gonzalez, Carlos A; Sánchez, María José; Ulmert, David; Ernström, Roy; Ljungberg, Börje; Allen, Naomi E; Key, Timothy J; Khaw, Kee-Tee; Wareham, Nick; Slimani, Nadia; Romieu, Isabelle; Kiemeney, Lambertus A; Riboli, Elio

2012-11-01

Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). After 8.9 years of follow-up, 947UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95%confidence interval (CI) 0.78-1.00 and HR 0.87; 95%CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95%CI 0.77-0.98). Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ

PubMed Central

Xu, Mei; Wang, Siying; Ren, Zhenhua; Frank, Jacqueline A.; Yang, Xiuwei H.; Zhang, Zhuo; Ke, Zun-ji; Shi, Xianglin; Luo, Jia

2016-01-01

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the scattering of MCF7, BT20 and T47D cell colonies in a 3-dimension culture system. Chronic ethanol exposure also increased colony formation in an anchorage-independent condition and stimulated cell invasion/migration. Chronic ethanol exposure increased cancer stem-like cell (CSC) population by more than 20 folds. Breast cancer cells exposed to ethanol in vitro displayed a much higher growth rate and metastasis in mice. Ethanol selectively activated p38γ MAPK and RhoC but not p38α/β in a concentration-dependent manner. SP-MCF7 cells, a derivative of MCF7 cells which compose mainly CSC expressed high levels of phosphorylated p38γ MAPK. Knocking-down p38γ MAPK blocked ethanol-induced RhoC activation, cell scattering, invasion/migration and ethanol-increased CSC population. Furthermore, knocking-down p38γ MAPK mitigated ethanol-induced tumor growth and metastasis in mice. These results suggest that chronic ethanol exposure can enhance the aggressiveness of breast cancer by activating p38γ MAPK/RhoC pathway. PMID:26655092

Communication Preferences of Pediatric Cancer Patients: Talking about Prognosis and Their Future Life

PubMed Central

Brand, Sarah R; Fasciano, Karen; Mack, Jennifer W

2017-01-01

Purpose The American Academy of Pediatrics recommends that healthcare providers communicate information to patients in a truthful and developmentally appropriate manner. However there is limited guidance about how to translate these recommendations into clinical practice. The aim of this study was to explore how young cancer patients experienced communication around their illness, especially communication about possible outcomes from disease or treatment. Methods Participants included young people ages 8 to under 18 years with cancer (N=16). Semi-structured interviews focused on their expectations about the future, the process of information exchange, and their preferences for communication within the pediatric oncology setting. Results Overall, participants wanted medical information to be provided to them by their healthcare providers and wanted to be direct participants in medical conversations. However, many participants displayed some ambivalence or conveyed conflicting wishes for prognostic information. For example, some participants reported that they were satisfied with what they knew, but later raised lingering questions. While not the focus of the study, almost every participant discussed social concerns as a key concern for their present and future life. Conclusions While most pediatric cancer patients want to be involved in conversations about their cancer care, including conversations about prognosis, this is an individual and sometimes fluctuating decision, and healthcare providers should be encouraged to discuss preferences for involvement with patients and families. This study highlights the importance of understanding the developmental factors that make pediatric patients unique, especially with regards to their patterns of communication. PMID:27747479

Communication preferences of pediatric cancer patients: talking about prognosis and their future life.

PubMed

Brand, Sarah R; Fasciano, Karen; Mack, Jennifer W

2017-03-01

The American Academy of Pediatrics recommends that healthcare providers communicate information to patients in a truthful and developmentally appropriate manner. However, there is limited guidance about how to translate these recommendations into clinical practice. The aim of this study was to explore how young cancer patients experienced communication around their illness, especially communication about possible outcomes from disease or treatment. Participants included young people ages 8 to under 18 years with cancer (N = 16). Semi-structured interviews focused on their expectations about the future, the process of information exchange, and their preferences for communication within the pediatric oncology setting. Overall, participants wanted medical information to be provided to them by their healthcare providers and wanted to be direct participants in medical conversations. However, many participants displayed some ambivalence or conveyed conflicting wishes for prognostic information. For example, some participants reported that they were satisfied with what they knew, but later raised lingering questions. While not the focus of the study, almost every participant discussed social concerns as a key concern for their present and future life. While most pediatric cancer patients want to be involved in conversations about their cancer care, including conversations about prognosis, this is an individual and sometimes fluctuating decision, and healthcare providers should be encouraged to discuss preferences for involvement with patients and families. This study highlights the importance of understanding the developmental factors that make pediatric patients unique, especially with regard to their patterns of communication.

Measuring Medication Adherence in Pediatric Cancer: An Approach to Validation.

PubMed

Rohan, Jennifer M; Fukuda, Tsuyoshi; Alderfer, Melissa A; Wetherington Donewar, Crista; Ewing, Linda; Katz, Ernest R; Muriel, Anna C; Vinks, Alexander A; Drotar, Dennis

2017-03-01

This study described the prospective relationship between pharmacological and behavioral measures of 6-mercaptopurine (6MP) medication adherence in a multisite cohort of pediatric patients diagnosed with cancer ( N  = 139). Pharmacological measures (i.e., metabolite concentrations) assessed 6MP intake. Behavioral measures (e.g., electronic monitoring) described adherence patterns over time. Three metabolite profiles were identified across 15 months: one group demonstrated low levels of both metabolites (40.8%) consistent with nonadherence and/or suboptimal therapy; two other groups demonstrated metabolite clusters indicative of adequate adherence (59.2%). Those patients whose metabolite profile demonstrated low levels of both metabolites had consistently lower behavioral adherence rates. To our knowledge, this was the first study to prospectively validate a pharmacological measure of medication adherence with a behavioral adherence measure in a relatively large sample of pediatric patients with cancer. Using multiple methods of adherence measurement could inform clinical care and target patients in need of intervention. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Pediatric MATCH Infographic

Cancer.gov

Infographic explaining NCI-COG Pediatric MATCH, a cancer treatment clinical trial for children and adolescents, from 1 to 21 years of age, that is testing the use of precision medicine for pediatric cancers.

Pediatric Psychosocial Oncology: A Quick Reference on the Psychosocial Dimensions of Cancer Symptom Management | Center for Cancer Research

Cancer.gov

The 2nd Edition of the handbook, Pediatric Psycho-Oncology: A Quick Reference on the Psychosocial Dimensions of Cancer Symptom Management, by Oxford Press, 2015 fills an important niche, as it provides practical hands-on information on many aspects of psychological and psychiatric aspects of pediatric oncology care.  It is organized with sections addressing specific clinical

Impact of aggressive management and palliative care on cancer costs in the final month of life.

PubMed

Cheung, Matthew C; Earle, Craig C; Rangrej, Jagadish; Ho, Thi H; Liu, Ning; Barbera, Lisa; Saskin, Refik; Porter, Joan; Seung, Soo Jin; Mittmann, Nicole

2015-09-15

A significant share of the cost of cancer care is concentrated in the end-of-life period. Although quality measures of aggressive treatment may guide optimal care during this timeframe, little is known about whether these metrics affect costs of care. This study used population data to identify a cohort of patients who died of cancer in Ontario, Canada (2005-2009). Individuals were categorized as having received or having not received aggressive end-of-life care according to quality measures related to acute institutional care or chemotherapy administration in the end-of-life period. Costs (2009 Canadian dollars) were collected over the last month of life through the linkage of health system administrative databases. Multivariate quantile regression was used to identify predictors of increased costs. Among 107,253 patients, the mean per-patient cost over the final month was $18,131 for patients receiving aggressive care and $12,678 for patients receiving nonaggressive care (P < .0001). Patients who received chemotherapy in the last 2 weeks of life also sustained higher costs than those who did not (P < .0001). For individuals receiving end-of-life care in the highest cost quintile, early and repeated palliative care consultation was associated with reduced mean per-patient costs. In a multivariate analysis, chemotherapy in the 2 weeks of life remained predictive of increased costs (median increase, $536; P < .0001), whereas access to palliation remained predictive for lower costs (median decrease, $418; P < .0001). Cancer patients who receive aggressive end-of-life care incur 43% higher costs than those managed nonaggressively. Palliative consultation may partially offset these costs and offer resultant savings. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.

PubMed

Allen, Carl E; Laetsch, Theodore W; Mody, Rajen; Irwin, Meredith S; Lim, Megan S; Adamson, Peter C; Seibel, Nita L; Parsons, D Williams; Cho, Y Jae; Janeway, Katherine

2017-05-01

Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies. The Children's Oncology Group (COG), in partnership with the National Cancer Institute (NCI), is planning a trial entitled the COG-NCI Pediatric Molecular Analysis for Therapeutic Choice (Pediatric MATCH) protocol utilizing an umbrella design. This protocol will have centralized infrastructure and will consist of a biomarker profiling protocol and multiple single-arm phase II trials of targeted therapies. Pediatric patients with recurrent or refractory solid tumors, lymphomas, or histiocytoses with measurable disease will be eligible. The Pediatric MATCH Target and Agent Prioritization (TAP) committee includes membership representing COG disease committees, the Food and Drug Administration, and the NCI. The TAP Committee systematically reviewed target and agent pairs for inclusion in the Pediatric MATCH trial. Fifteen drug-target pairs were reviewed by the TAP Committee, with seven recommended for further development as initial arms of the Pediatric MATCH trial. The current evidence for availability, efficacy, and safety of targeted agents in children for each class of mutation considered for inclusion in the Pediatric MATCH trial is discussed in this review. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses

PubMed Central

Stefansson, Ingunn M.; Birkeland, Even; Bø, Trond Hellem; Øyan, Anne M.; Trovik, Jone; Kalland, Karl-Henning; Jonassen, Inge; Salvesen, Helga B.; Wik, Elisabeth; Akslen, Lars A.

2015-01-01

Aims Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions. Methods and Results By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB. Conclusions Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis. PMID:26485755

Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses.

PubMed

Bredholt, Geir; Mannelqvist, Monica; Stefansson, Ingunn M; Birkeland, Even; Bø, Trond Hellem; Øyan, Anne M; Trovik, Jone; Kalland, Karl-Henning; Jonassen, Inge; Salvesen, Helga B; Wik, Elisabeth; Akslen, Lars A

2015-11-24

Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions. By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB. Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis.

The Role of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Aggressive Histological Subtypes of Thyroid Cancer: An Overview

PubMed Central

Treglia, Giorgio; Annunziata, Salvatore; Muoio, Barbara; Salvatori, Massimo; Ceriani, Luca; Giovanella, Luca

2013-01-01

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis. PMID:23653645

The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview.

PubMed

Treglia, Giorgio; Annunziata, Salvatore; Muoio, Barbara; Salvatori, Massimo; Ceriani, Luca; Giovanella, Luca

2013-01-01

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis.

Confirmatory factor analysis of the Chinese version of the Pediatric Quality-of-Life Inventory Cancer Module.

PubMed

Li, Ho Cheung William; Williams, Phoebe D; Williams, Arthur R; Chung, Joyce O K; Chiu, Sau Ying; Lopez, Violeta

2013-01-01

Before the Chinese version of the Pediatric Quality-of-Life Inventory Cancer Module can be used to assess the multidimensional construct of quality of life among Hong Kong Chinese pediatric patients with cancer, its psychometric properties need to be further empirically tested. The objectives of the study were to establish the construct validity, including hypothesis testing and a confirmatory factor analysis of factor structure, of the Chinese version of the Pediatric Quality-of-Life Inventory Cancer Module. A cross-sectional study was used; 200 children hospitalized with cancer (9- to 16-year-olds) were recruited. Participants were asked to respond to the Chinese version of the Cancer Module, Therapy-Related Symptom Checklist, and Rosenberg's Self-esteem Scale. The results showed that there was a strong positive correlation between children's self-esteem and quality of life (r = 0.50) and a strong negative correlation between children's therapy-related symptoms and quality of life (r = -0.65). Confirmatory factor analysis indicated that there were 7 factors underlying the Chinese version of the Cancer Module. The study added further evidence of the construct validity of the Chinese version of the Cancer Module, patient version. The Cancer Module can be used to assess and evaluate psychological interventions directed toward promoting the quality of life of children hospitalized with cancer.

Development of a stress response therapy targeting aggressive prostate cancer.

PubMed

Nguyen, Hao G; Conn, Crystal S; Kye, Yae; Xue, Lingru; Forester, Craig M; Cowan, Janet E; Hsieh, Andrew C; Cunningham, John T; Truillet, Charles; Tameire, Feven; Evans, Michael J; Evans, Christopher P; Yang, Joy C; Hann, Byron; Koumenis, Constantinos; Walter, Peter; Carroll, Peter R; Ruggero, Davide

2018-05-02

Oncogenic lesions up-regulate bioenergetically demanding cellular processes, such as protein synthesis, to drive cancer cell growth and continued proliferation. However, the hijacking of these key processes by oncogenic pathways imposes onerous cell stress that must be mitigated by adaptive responses for cell survival. The mechanism by which these adaptive responses are established, their functional consequences for tumor development, and their implications for therapeutic interventions remain largely unknown. Using murine and humanized models of prostate cancer (PCa), we show that one of the three branches of the unfolded protein response is selectively activated in advanced PCa. This adaptive response activates the phosphorylation of the eukaryotic initiation factor 2-α (P-eIF2α) to reset global protein synthesis to a level that fosters aggressive tumor development and is a marker of poor patient survival upon the acquisition of multiple oncogenic lesions. Using patient-derived xenograft models and an inhibitor of P-eIF2α activity, ISRIB, our data show that targeting this adaptive brake for protein synthesis selectively triggers cytotoxicity against aggressive metastatic PCa, a disease for which presently there is no cure. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

KIAA0100 Modulates Cancer Cell Aggression Behavior of MDA-MB-231 through Microtubule and Heat Shock Proteins.

PubMed

Zhong, Zhenyu; Pannu, Vaishali; Rosenow, Matthew; Stark, Adam; Spetzler, David

2018-06-04

The KIAA0100 gene was identified in the human immature myeloid cell line cDNA library. Recent studies have shown that its expression is elevated in breast cancer and associated with more aggressive cancer types as well as poor outcomes. However, its cellular and molecular function is yet to be understood. Here we show that silencing KIAA0100 by siRNA in the breast cancer cell line MDA-MB-231 significantly reduced the cancer cells' aggressive behavior, including cell aggregation, reattachment, cell metastasis and invasion. Most importantly, silencing the expression of KIAA0100 particularly sensitized the quiescent cancer cells in suspension culture to anoikis. Immunoprecipitation, mass spectrometry and immunofluorescence analysis revealed that KIAA0100 may play multiple roles in the cancer cells, including stabilizing microtubule structure as a microtubule binding protein, and contributing to MDA-MB-231 cells Anoikis resistance by the interaction with stress protein HSPA1A. Our study also implies that the interaction between KIAA0100 and HSPA1A may be targeted for new drug development to specifically induce anoikis cell death in the cancer cell.

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

PubMed

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.

Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer?

PubMed

Rhana, P; Trivelato, R R; Beirão, P S L; Cruz, J S; Rodrigues, A L P

2017-06-05

Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.

Is there a role for voltage-gated Na+ channels in the aggressiveness of breast cancer?

PubMed Central

Rhana, P.; Trivelato, R.R.; Beirão, P.S.L.; Cruz, J.S.; Rodrigues, A.L.P.

2017-01-01

Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress. PMID:28591378

Pediatric stroke: clinical characteristics, acute care utilization patterns, and mortality.

PubMed

Statler, Kimberly D; Dong, Li; Nielsen, Denise M; Bratton, Susan L

2011-04-01

Acute care utilization patterns are not well described but may help inform care coordination and treatment for pediatric stroke. The Kids Inpatient Database was queried to describe demographics and clinical characteristics of children with stroke, compare acute care utilization for hemorrhagic vs. ischemic stroke and Children's vs. non-Children's Hospitals, and identify factors associated with aggressive care and in-hospital mortality. Using a retrospective cohort of children hospitalized with stroke, demographics, predisposing conditions, and intensive (mechanical ventilation, advanced monitoring, and blood product administration) or aggressive (pharmacological therapy and/or invasive interventions) care were compared by stroke and hospital types. Factors associated with aggressive care or in-hospital mortality were explored using logistic regression. Hemorrhagic stroke comprised 43% of stroke discharges, was more common in younger children, and carried greater mortality. Ischemic stroke was more common in older children and more frequently associated with a predisposing condition. Rates of intensive and aggressive care were low (30% and 15%), similar by stroke type, and greater at Children's Hospitals. Older age, hemorrhagic stroke, predisposing condition, and treatment at a Children's Hospital were associated with aggressive care. Hemorrhagic stroke and aggressive care were associated with in-hospital mortality. Acute care utilization is similar by stroke type but both intensive and aggressive care are more common at Children's Hospitals. Mortality remains relatively high after pediatric stroke. Widespread implementation of treatment guidelines improved outcomes in adult stroke. Adoption of recently published treatment recommendations for pediatric stroke may help standardize care and improve outcomes.

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

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

Mueller, Sabine, E-mail: muellers@neuropeds.ucsf.edu; Fullerton, Heather J.; Stratton, Kayla

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, 292more » 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.« less

Vitamin D and Related Genes, Race and Prostate Cancer Aggressiveness

DTIC Science & Technology

2015-12-29

currently a postdoctoral fellow at the Mayo Clinic in Minnesota. 6. Have all raw data sent to USC and to PCaP parent study a. Raw data from Roswell...completion of lab work and raw data deposit at centralized location) were completed. Data were begun to be merged and cleaned, and preliminary data...example, two SNPs in the vitamin D binding protein gene known as GC, were inversely associated with high aggressive prostate cancer (rs222054: OR

[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.

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

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.

Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia--species distribution and susceptibility patterns.

PubMed

Miedema, Karin G E; Winter, Rik H L J; Ammann, Roland A; Droz, Sara; Spanjaard, Lodewijk; de Bont, Eveline S J M; Kamps, Willem A; van de Wetering, Marianne D; Tissing, Wim J E

2013-09-01

Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of prophylactic and empirical antibiotics. We analyzed positive blood cultures of pediatric cancer patients presenting with febrile neutropenia between 2004 and 2011 in Groningen and Amsterdam (the Netherlands) and in Bern (Switzerland), using different antibiotic prophylactic and empirical regimens. A total of 156 patients with 202 bacteremias, due to 248 bacteria species, were enrolled. The majority (73%) of bacteremias were caused by Gram-positive bacteria. Gram-negative bacteria, especially Pseudomonas aeruginosa, were observed significantly more often in Bern, where no fluoroquinolone prophylaxis was used. Ciprofloxacin-resistant bacteria were cultured more often from patients who did receive ciprofloxacin prophylaxis, compared to the patients who did not (57 versus 11%, p = 0.044). Gram-positive bacteria predominated in this study. We showed that the use of prophylactic antibiotics in pediatric cancer patients was associated with increased resistance rates, which needs further study. The strategy for empiric antimicrobial therapy for febrile neutropenia should be adapted to local antibiotic resistance patterns.

Social adjustment and repressive adaptive style in survivors of pediatric cancer.

PubMed

Schulte, Fiona; Wurz, Amanda; Russell, K Brooke; Reynolds, Kathleen; Strother, Douglas; Dewey, Deborah

2018-01-01

The aim of the study was to explore the relationship between repressive adaptive style and self-reports of social adjustment in survivors of pediatric cancer compared to their siblings. We hypothesized that there would be a greater proportion of repressors among survivors of pediatric cancer compared to siblings, and that repressive adaptive style would be significantly associated with more positive self-reports of social adjustment. We utilized a cross-sectional approach. Seventy-seven families participated. Survivors of pediatric cancer (n = 77, 48% male; 8-18 years of age) and one sibling (n = 50, 48% male; 8-18 years of age) completed measures assessing repressive adaptive style and social adjustment. As well, one parent from each family completed a socio-demographic questionnaire. Questionnaire packages were mailed to eligible families who agreed to participate, and were mailed back to investigators in a pre-addressed, pre-stamped envelope. Chi-square analyses revealed there was no significant difference in the proportion of repressors among survivors and siblings. Social adjustment scores were subjected to a two (group: survivor, sibling) by two (repressor, nonrepressor) ANCOVA with gender and age as covariates. There was a significant main effect of repressive adaptive style (F = 5.69, p < .05, η 2 = 0.05) with a modest effect. Survivors and siblings with a repressive style reported significantly higher social adjustment scores (M = 106.91, SD = 11.69) compared to nonrepressors (M = 99.57, SD = 13.45). Repressive adaptive style explains some of the variance in survivors and siblings' self-reports of social adjustment. Future research should aim to better understand the role of the repressive adaptive style in survivors and siblings of children with cancer.

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.…

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

Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-12-1-0597 TITLE: Parametric PET /MR Fusion Imaging to...Parametric PET /MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies...The study investigates whether fusion PET /MRI imaging with 18F-choline PET /CT and diffusion-weighted MRI can be successfully applied to target prostate

Survival outcomes following aggressive treatment of oligometastatic breast cancer: a systematic review protocol.

PubMed

Coombe, Robyn; Lisy, Karolina; Campbell, Jared; Perry, Gajen; Prasannan, Subhita

2017-08-01

The objective of this systematic review is to assess the effectiveness of aggressive treatment of oligometastatic breast cancer (OMBC) on survival outcomes by conducting a meta-analysis of current available evidence.More specifically, the objectives are to identify the effectiveness of intensified multidisciplinary treatment with aggressive locoregional therapies on survival time, five-year survival rates and disease free survival. The population is adult women (18 years and over) with OMBC defined as single or few (five or less) metastases limited to a single organ and the comparative group is conventional palliative treatment aimed at disease control. Secondary objectives to be assessed will be adverse outcomes associated with intensified treatment regimes.

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

PubMed

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

2013-06-01

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.

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.

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.

Implementing the psychosocial standards in pediatric cancer: Current staffing and services available.

PubMed

Scialla, Michele A; Canter, Kimberly S; Chen, Fang Fang; Kolb, E Anders; Sandler, Eric; Wiener, Lori; Kazak, Anne E

2017-11-01

Fifteen evidence-based Standards for Psychosocial Care for Children with Cancer and Their Families (Standards) were published in 2015. The Standards cover a broad range of topics and circumstances and require qualified multidisciplinary staff to be implemented. This paper presents data on the availability of psychosocial staff and existing practices at pediatric oncology programs in the United States, providing data that can be used to advocate for expanded services and prepare for implementation of the Standards. Up to three healthcare professionals from 144 programs (72% response rate) participated in an online survey conducted June-December 2016. There were 99 pediatric oncologists with clinical leadership responsibility (Medical Director/Clinical Director), 132 psychosocial leaders in pediatric oncology (Director of Psychosocial Services/Manager/most senior staff member), and 58 administrators in pediatric oncology (Administrative Director/Business Administrator/Director of Operations). The primary outcomes were number and type of psychosocial staff, psychosocial practices, and identified challenges in the delivery of psychosocial care. Over 90% of programs have social workers and child life specialists who provide care to children with cancer and their families. Fewer programs have psychologists (60%), neuropsychologists (31%), or psychiatrists (19%). Challenges in psychosocial care are primarily based on pragmatic issues related to funding and reimbursement. Most participating pediatric oncology programs appear to have at least the basic level of staffing necessary to implement of some of the Standards. However, the lack of a more comprehensive multidisciplinary team is a likely barrier in the implementation of the full set of Standards. © 2017 Wiley Periodicals, Inc.

Mediterranean Dietary Pattern is Associated with Low Risk of Aggressive Prostate Cancer: MCC-Spain Study.

PubMed

Castelló, Adela; Boldo, Elena; Amiano, Pilar; Castaño-Vinyals, Gemma; Aragonés, Nuria; Gómez-Acebo, Inés; Peiró, Rosana; Jimenez-Moleón, Jose Juan; Alguacil, Juan; Tardón, Adonina; Cecchini, Lluís; Lope, Virginia; Dierssen-Sotos, Trinidad; Mengual, Lourdes; Kogevinas, Manolis; Pollán, Marina; Pérez-Gómez, Beatriz

2018-02-01

We explored the association of the previously described Western, prudent and Mediterranean dietary patterns with prostate cancer risk by tumor aggressiveness and extension. MCC-Spain (Multicase-Control Study on Common Tumors in Spain) is a population based, multicase-control study that was done in 7 Spanish provinces between September 2008 and December 2013. It collected anthropometric, epidemiological and dietary information on 754 histologically confirmed incident cases of prostate cancer and 1,277 controls 38 to 85 years old. Three previously identified dietary patterns, including Western, prudent and Mediterranean, were reconstructed using MCC-Spain data. The association of each pattern with prostate cancer risk was assessed by logistic regression models with random, province specific intercepts. Risk according to tumor aggressiveness (Gleason score 6 vs greater than 6) and extension (cT1-cT2a vs cT2b-cT4) was evaluated by multinomial regression models. High adherence to a Mediterranean dietary pattern rich not only in fruits and vegetables but also in fish, legumes and olive oil was specifically associated with a lower risk of Gleason score greater than 6 prostate cancer (quartile 3 vs 1 relative RR 0.66, 95% CI 0.46-0.96 and quartile 4 vs 1 relative RR 0.68, 95% CI 0.46-1.01, p-trend = 0.023) or with higher clinical stage (cT2b-T4 quartile 4 vs 1 relative RR 0.49, 95% CI 0.25-0.96, p-trend = 0.024). This association was not observed with the prudent pattern, which combines vegetables and fruits with low fat dairy products, whole grains and juices. The Western pattern did not show any association with prostate cancer risk. Nutritional recommendations for prostate cancer prevention should consider whole dietary patterns instead of individual foods. We found important differences between the Mediterranean dietary pattern, which was associated with a lower risk of aggressive prostate cancer, and Western and prudent dietary patterns, which had no relationship with

Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer.

PubMed

Beg, Shaham; Siraj, Abdul K; Prabhakaran, Sarita; Jehan, Zeenath; Ajarim, Dahish; Al-Dayel, Fouad; Tulbah, Asma; Al-Kuraya, Khawla S

2015-06-01

PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

PubMed

Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

2014-07-30

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Identification of Methylated Genes Associated with Aggressive Bladder Cancer

PubMed Central

Marsit, Carmen J.; Houseman, E. Andres; Christensen, Brock C.; Gagne, Luc; Wrensch, Margaret R.; Nelson, Heather H.; Wiemels, Joseph; Zheng, Shichun; Wiencke, John K.; Andrew, Angeline S.; Schned, Alan R.; Karagas, Margaret R.; Kelsey, Karl T.

2010-01-01

Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245) through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment. PMID:20808801

Identification of methylated genes associated with aggressive bladder cancer.

PubMed

Marsit, Carmen J; Houseman, E Andres; Christensen, Brock C; Gagne, Luc; Wrensch, Margaret R; Nelson, Heather H; Wiemels, Joseph; Zheng, Shichun; Wiencke, John K; Andrew, Angeline S; Schned, Alan R; Karagas, Margaret R; Kelsey, Karl T

2010-08-23

Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245) through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment.

Nestin: A biomarker of aggressive uterine cancers.

PubMed

Hope, Erica R; Mhawech-Fauceglia, Paulette; Pejovic, Tanja; Zahn, Christopher M; Wang, Guisong; Conrads, Thomas P; Larry Maxwell, G; Hamilton, Chad A; Darcy, Kathleen M; Syed, Viqar

2016-03-01

Evidence of potential prognostic and predictive value for nestin was investigated in well-annotated uterine cancers (UCs). Nestin expression and previously-published biomarkers were evaluated by immunohistochemistry (IHC) in UC tissue microarrays. Biomarkers were categorized as low vs. high, and nestin was cut at 10% positive staining. Relationship between nestin and clinicopathologic factors, biomarkers and outcome were evaluated using exact/log-rank testing or logistic/Cox modeling. There were 323 eligible cases, 34% had advanced stage disease, 37% had type II disease, and 5% were carcinosarcomas. High nestin, observed in 19% of cases, was more common in advanced vs. early stage disease, type II cancers or uterine carcinosarcoma vs. type I cancers, grade 3 disease, positive lymphovascular space invasion (LVSI) and tumors >6cm (p<0.05). Nestin was inversely correlated with ER, PR and TFF3, and correlated with p53 and IMP3. Women with high vs. low nestin had worse progression-free survival (PFS) and cancer-specific survival overall, and worse PFS in the subset who received no adjuvant therapy or radiation, or had early stage, type I disease or tumors with both low and high ER, PR, TFF3, PTEN, p53 or IMP3. The relationship between nestin and PFS was independent of stage, LVSI and risk categorization but not type of UC. High nestin was more common in UCs with aggressive features and poor outcome. Nestin may represent a predictive biomarker for treatment selection for patients previously considered to be lower risk and a candidate for no or radiation-based adjuvant therapy, and compliment ER/PR testing. Published by Elsevier Inc.

Study Finds Dual Inhibition Therapy May Lead to Better Outcomes for Aggressive Form of Breast Cancer | Poster

Cancer.gov

A collaboration between the National Cancer Institute (NCI); the Frederick National Laboratory (FNL); and the National University of Ireland, Galway, has shown that two key biomarkers are co-expressed in an aggressive subtype of breast cancer and that inhibiting those two molecules can significantly improve patient survival outcomes.

Female fertility preservation in the pediatric and adolescent cancer patient population.

PubMed

Algarroba, Gabriela N; Sanfilippo, Joseph S; Valli-Pulaski, Hanna

2018-04-01

The 5-year survival rate for childhood cancer is over 80%, thereby increasing the number of young women facing infertility in the future because of the gonadotoxic effects of chemotherapy and radiation. The gonadotoxic effects of childhood cancer treatment vary by the radiation regimen and the chemotherapeutic drugs utilized. Although the American Society of Clinical Oncology guidelines recommend fertility preservation for all patients, there are several barriers and ethical considerations to fertility preservation in the pediatric and adolescent female population. Additionally, the fertility preservation methods for pre- and postpubertal females differ, with only experimental methods available for prepubertal females. We will review the risk of chemotherapy and radiation on female fertility, the approach to fertility preservation in the pediatric and adolescent female population, methods of fertility preservation for both pre- and postpubertal females, barriers to fertility preservation, cost, and psychological and ethical considerations. Copyright © 2018 Elsevier Ltd. All rights reserved.

E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness

PubMed Central

Devis, Laura; Lapyckyj, Lara; Besso, María José; Llauradó, Marta; Abascal, María Florencia; Matos, María Laura; Lanau, Lucia; Castellví, Josep; Sánchez, José Luis; Pérez Benavente, Asunción; Gil-Moreno, Antonio; Reventós, Jaume; Santamaria Margalef, Anna; Rigau, Marina; Vazquez-Levin, Mónica Hebe

2017-01-01

Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies. Moreover, E-cadherin, Neural cadherin (N-cadherin), cytokeratins and vimentin expression was assessed in TOV-112, SKOV-3, OAW-42 and OV-90 OC cell lines grown in monolayers and under anchorage-independent conditions to mimic ovarian tumor cell dissemination, and results were associated with cell aggressiveness. According to these EMT-related markers, cell lines were classified as mesenchymal (M; TOV-112), intermediate mesenchymal (IM; SKOV-3), intermediate epithelial (IE; OAW-42) and epithelial (E; OV-90). M- and IM-cells depicted the highest migration capacity when grown in monolayers, and aggregates derived from M- and IM-cell lines showed lower cell death, higher adhesion to extracellular matrices and higher invasion capacity than E- and IE-aggregates. The analysis of E-cadherin, N-cadherin, cytokeratin 19 and vimentin mRNA levels in 20 advanced-stage high-grade serous human OC ascites showed an IM phenotype in all cases, characterized by higher proportions of N- to E-cadherin and vimentin to cytokeratin 19. In particular, higher E-cadherin mRNA levels were associated with cancer antigen 125 levels more than 500 U/mL and platinum-free intervals less than 6 months. Altogether, E-cadherin expression levels were found relevant for the assessment of OC progression and aggressiveness. PMID:28934230

Place of death of pediatric cancer patients in a single institute during 7 years.

PubMed

Yanai, Tomoko; Hirase, Satoshi; Matsunoshita, Natsuki; Yamamoto, Nobuyuki; Ninchoji, Takeshi; Kubokawa, Ikuko; Mori, Takeshi; Hayakawa, Akira; Takeshima, Yasuhiro; Iijima, Kazumoto; Matsuo, Masafumi

2012-06-27

Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.

Pediatric Genomic Data Inventory (PGDI) Overview

Cancer.gov

About Pediatric cancer is a genetic disease that can largely differ from similar malignancies in an adult population. To fuel new discoveries and treatments specific to pediatric oncologies, the NCI Office of Cancer Genomics has developed a dynamic resource known as the Pediatric Genomic Data Inventory to allow investigators to more easily locate genomic datasets. This resource lists known ongoing and completed sequencing projects of pediatric cancer cohorts from the United States and other countries, along with some basic details and reference metadata.

BRCA1-IRIS Overexpression Promotes Formation of Aggressive Breast Cancers

PubMed Central

Shimizu, Yoshiko; Luk, Hugh; Horio, David; Miron, Penelope; Griswold, Michael; Iglehart, Dirk; Hernandez, Brenda; Killeen, Jeffrey; ElShamy, Wael M.

2012-01-01

Introduction Women with HER2+ or triple negative/basal-like (TN/BL) breast cancers succumb to their cancer rapidly due, in part to acquired Herceptin resistance and lack of TN/BL-targeted therapies. BRCA1-IRIS is a recently discovered, 1399 residue, BRCA1 locus alternative product, which while sharing 1365 residues with the full-length product of this tumor suppressor gene, BRCA1/p220, it has oncoprotein-like properties. Here, we examine whether BRCA1-IRIS is a valuable treatment target for HER2+ and/or TN/BL tumors. Methodology/Principal Findings Immunohistochemical staining of large cohort of human breast tumor samples using new monoclonal anti-BRCA1-IRIS antibody, followed by correlation of BRCA1-IRIS expression with that of AKT1, AKT2, p-AKT, survivin and BRCA1/p220, tumor status and age at diagnosis. Generation of subcutaneous tumors in SCID mice using human mammary epithelial (HME) cells overexpressing TERT/LT/BRCA1-IRIS, followed by comparing AKT, survivin, and BRCA1/p220 expression, tumor status and aggressiveness in these tumors to that in tumors developed using TERT/LT/RasV12-overexpressing HME cells. Induction of primary and invasive rat mammary tumors using the carcinogen N-methyl-N-nitrosourea (NMU), followed by analysis of rat BRCA1-IRIS and ERα mRNA levels in these tumors. High BRCA1-IRIS expression was detected in the majority of human breast tumors analyzed, which was positively correlated with that of AKT1-, AKT2-, p-AKT-, survivin, but negatively with BRCA1/p220 expression. BRCA1-IRIS-positivity induced high-grade, early onset and metastatic HER2+ or TN/BL tumors. TERT/LT/BRCA1-IRIS overexpressing HME cells formed invasive subcutaneous tumors that express high AKT1, AKT2, p-AKT and vimentin, but no CK19, p63 or BRCA1/p220. NMU-induced primary and invasive rat breast cancers expressed high levels of rat BRCA1-IRIS mRNA but low levels of rat ERα mRNA. Conclusion/Significance BRCA1-IRIS overexpression triggers aggressive breast tumor formation

Challenges in managing infections among pediatric cancer patients: Suboptimal national essential medicines lists for low and middle income countries.

PubMed

Kirby, Jeannette; Ojha, Rohit P; Johnson, Kyle M; Bittner, Elizabeth C; Caniza, Miguela A

2015-02-01

Infection management for pediatric cancer patients may be compromised in low and middle income countries (LMICs) if key antimicrobials are not included in national essential medicines lists. We screened national essential medicines lists for 81 LMICs, and assessed the frequency and corresponding 95% confidence limits (CL) of countries that included the 15 International Society of Paediatric Oncology-recommended antimicrobial agents. Only 19% (95% CL: 11%, 28%) of countries included all recommended antimicrobials in their national essential medicines lists. The selection of antimicrobial agents for national essential medicines lists in LMICs warrants attention from a pediatric cancer perspective. Pediatr Blood Cancer 2015;62:204-207. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Palliative Care is Associated with Reduced Aggressive End-of-Life Care in Patients with Gastrointestinal Cancer.

PubMed

Merchant, Shaila J; Brogly, Susan B; Goldie, Craig; Booth, Christopher M; Nanji, Sulaiman; Patel, Sunil V; Lajkosz, Katherine; Baxter, Nancy N

2018-06-01

We examined the delivery of physician palliative care (PC) services and its association with aggressive end-of-life care (EOLC) in patients with gastrointestinal (GI) cancer in Ontario, Canada. All patients with primary cause of death from esophageal, gastric, colon, and anorectal cancer from January 2003 to December 2013 were identified. PC services within 2 years of death were classified: (1) any PC; (2) timing of first PC (≤ 7, 8-90, 91-180, and 181-730 days before death); and (3) intensity of PC measured by number of days used (1st-25th, 26th-50th, 51st-75th, and 76th-100th percentiles). Aggressive EOLC was defined as any of the following: chemotherapy, emergency department visits, hospital or intensive care unit (ICU) admissions (all ≤ 30 days of death), and death in hospital and in the ICU; these were combined as a composite outcome (any aggressive EOLC). The cohort included 34,630 patients, of whom 74% had at least one PC service. Timing of the first PC service varied: ≤ 7 (12%), 8-90 (42%), 91-180 (16%), and 181-730 (30%) days before death. Compared with patients not receiving PC, any PC was associated with a reduction in any aggressive EOLC (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.74-0.76); this association was similar regardless of timing of the first PC service. The most dramatic reduction in aggressive EOLC occurred in patients who received the greatest number of days of PC (RR 0.65, 95% CI 0.63-0.67). The majority of patients received PC within 2 years of death. A larger number of days of PC was associated with a greater reduction in aggressive EOLC.

Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

PubMed Central

Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

2016-01-01

As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

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. 2010 APA, all rights reserved

Interaction of mammographic breast density with menopausal status and postmenopausal hormone use in relation to the risk of aggressive breast cancer subtypes.

PubMed

Yaghjyan, Lusine; Tamimi, Rulla M; Bertrand, Kimberly A; Scott, Christopher G; Jensen, Matthew R; Pankratz, V Shane; Brandt, Kathy; Visscher, Daniel; Norman, Aaron; Couch, Fergus; Shepherd, John; Fan, Bo; Chen, Yunn-Yi; Ma, Lin; Beck, Andrew H; Cummings, Steven R; Kerlikowske, Karla; Vachon, Celine M

2017-09-01

We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy. This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ≥2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy. Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (≥51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (≥51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant. Our findings suggest that associations of mammographic

Creation and evaluation of a cancer survivorship curriculum for pediatric resident physicians.

PubMed

Schwartz, Lindsay F; Braddock, Clarence H; Kao, Roy L; Sim, Myung-Shin; Casillas, Jacqueline N

2018-06-25

There is a paucity of formal clinician education concerning cancer survivorship care, which produces care barriers and poorer outcomes for survivors of childhood cancer. To address this, we implemented a curriculum in childhood cancer survivorship care for pediatric residents at the University of California, Los Angeles (UCLA). We examined the efficacy of this curriculum following program completion. A case-based curriculum was created and integrated within existing educational structures using Kern's model. We utilized the retrospective pre-posttest method to evaluate participating residents' knowledge, clinical skills, and attitudes towards cancer survivorship topics before and after receiving the curriculum. Pre-posttest items were compared using paired t tests and one-sided binomial tests. We analyzed free-response question items for major themes using constant comparative methods. Thirty-four residents completed the curriculum and its evaluation. Each assessment item significantly increased from pre- to post-curriculum; p < 0.05. Greater than 40% of residents improved in all but one assessment item post-curriculum; p < 0.05. Residents reported the curriculum enhanced their pediatric knowledge base (M = 3.24; SD = 0.65) and would recommend it to other residency programs; M = 3.24; SD = 0.69. Major themes included residents' request for additional oncofertility information, training in counseling survivors, and cancer survivorship training opportunities. A cancer survivorship curriculum can successfully increase trainees' knowledge, clinical skills, and comfort in discussing topics relevant to survivorship care. With increasing numbers of childhood cancer survivors living into adulthood, residents will likely treat this population regardless of intended career path. This curriculum represents one method to deliver formal cancer survivorship training.

Investigating the Role of NOS2 in Breast Cancer | Center for Cancer Research

Cancer.gov

Inducible nitric oxide synthase (NOS2) is often elevated in breast tumors that lack expression of the estrogen receptor (ER) and predicts a poor prognosis for patients with these tumors. However, it is unclear whether NOS2 directly contributes to ER-negative breast cancer aggressiveness or how NOS2 expression is controlled within the tumor microenvironment. To tease apart the regulatory pathways upstream and downstream of NOS2, David Wink, Jr., Ph.D., Senior Investigator in CCR’s Radiation Biology Branch, along with colleagues from CCR’s Pediatric Oncology Branch, Laboratory of Human Carcinogenesis, and Laboratory of Experimental Immunology and from the Prostate Cancer Institute in Ireland, carried out studies in cell culture and mouse models.

Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy.

PubMed

Renard Penna, Raphaele; Cancel-Tassin, Geraldine; Comperat, Eva; Mozer, Pierre; Léon, Priscilla; Varinot, Justine; Roupret, Morgan; Bitker, Marc-Olivier; Lucidarme, Olivier; Cussenot, Olivier

2016-10-01

To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 × 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 × 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

PubMed

de Ridder, Lissy; Turner, Dan; Wilson, David C; Koletzko, Sibylle; Martin-de-Carpi, Javier; Fagerberg, Ulrika L; Spray, Christine; Sladek, Malgorzata; Shaoul, Ron; Roma-Giannikou, Eleftheria; Bronsky, Jiri; Serban, Daniela E; Cucchiara, Salvatore; Veres, Gabor; Ruemmele, Frank M; Hojsak, Iva; Kolho, Kaija L; Davies, Ieuan H; Aloi, Marina; Lionetti, Paolo; Veereman-Wauters, Gigi; Braegger, Christian P; Trindade, Eunice; Wewer, Anne V; Hauer, Almuthe; Levine, Arie

2014-02-01

The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes

PubMed Central

Lauvrak, S U; Munthe, E; Kresse, S H; Stratford, E W; Namløs, H M; Meza-Zepeda, L A; Myklebost, O

2013-01-01

Background: Osteosarcoma is the most common primary malignant bone tumour, predominantly affecting children and adolescents. Cancer cell line models are required to understand the underlying mechanisms of tumour progression and for preclinical investigations. Methods: To identify cell lines that are well suited for studies of critical cancer-related phenotypes, such as tumour initiation, growth and metastasis, we have evaluated 22 osteosarcoma cell lines for in vivo tumorigenicity, in vitro colony-forming ability, invasive/migratory potential and proliferation capacity. Importantly, we have also identified mRNA and microRNA (miRNA) gene expression patterns associated with these phenotypes by expression profiling. Results: The cell lines exhibited a wide range of cancer-related phenotypes, from rather indolent to very aggressive. Several mRNAs were differentially expressed in highly aggressive osteosarcoma cell lines compared with non-aggressive cell lines, including RUNX2, several S100 genes, collagen genes and genes encoding proteins involved in growth factor binding, cell adhesion and extracellular matrix remodelling. Most notably, four genes—COL1A2, KYNU, ACTG2 and NPPB—were differentially expressed in high and non-aggressive cell lines for all the cancer-related phenotypes investigated, suggesting that they might have important roles in the process of osteosarcoma tumorigenesis. At the miRNA level, miR-199b-5p and mir-100-3p were downregulated in the highly aggressive cell lines, whereas miR-155-5p, miR-135b-5p and miR-146a-5p were upregulated. miR-135b-5p and miR-146a-5p were further predicted to be linked to the metastatic capacity of the disease. Interpretation: The detailed characterisation of cell line phenotypes will support the selection of models to use for specific preclinical investigations. The differentially expressed mRNAs and miRNAs identified in this study may represent good candidates for future therapeutic targets. To our knowledge, this is

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

conjugating enzymes . J. Biol. Chem. 270, 30408-30414. [66] Bertone-Johnson, E. R. (2009) Vitamin D and breast cancer . Ann. Epidemiol. 19, 462-467... cancer growth in a murine model of bone metastasis. Cancer Res. 70, 1835- 1844. 22 [68] Ohyama, Y., and Yamasaki, T. (2004) Eight cytochrome ...0697 TITLE: Enhancement of the efficacy of conventional anticancer compounds through the repression of SNAI proteins in aggressive breast cancer

Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues.

PubMed

Majzner, Robbie G; Simon, Jason S; Grosso, Joseph F; Martinez, Daniel; Pawel, Bruce R; Santi, Mariarita; Merchant, Melinda S; Geoerger, Birgit; Hezam, Imene; Marty, Virginie; Vielh, Phillippe; Daugaard, Mads; Sorensen, Poul H; Mackall, Crystal L; Maris, John M

2017-10-01

Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers. Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression. Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P < .001). A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017;123:3807-3815. © 2017 American Cancer Society. © 2017 American Cancer Society.

Outpatient Palliative Care and Aggressiveness of End-of-Life Care in Patients with Metastatic Colorectal Cancer.

PubMed

Lee, Si Won; Jho, Hyun Jung; Baek, Ji Yeon; Shim, Eun Kyung; Kim, Hyun Mi; Ku, Ji Yeon; Nam, Eun Jung; Chang, Yoon-Jung; Choi, Hye Jin; Kim, Sun Young

2018-01-01

Palliative care in outpatient setting has been shown to promote better symptom management and transition to hospice care among patients with advanced cancer. Nevertheless, specialized palliative care is rarely provided at cancer centers in Korea. Herein, we aimed to assess aggressiveness of end-of-life care for patients with metastatic colorectal cancer according to the use of outpatient palliative care (OPC) at a single cancer center in Korea. We performed a retrospective medical record review for 132 patients with metastatic colorectal cancer who died between 2011 and 2014. Fifty patients used OPC (OPC group), while 82 patients did not (non-OPC group). Indicators of aggressiveness of end-of-life care including chemotherapy use, emergency department visits, hospitalization, and utilization of hospice care were analyzed according to the use of OPC. More patients in the OPC group were admitted to hospice than those in the non-OPC group (32% vs 17%, P = .047). The mean of inpatient days within 30 days of death was shorter for the OPC group than the non-OPC group (4.02 days vs 7.77 days, respectively, P = .032). There were no differences in the proportions of patients who received chemotherapy and visited the emergency department within 30 days from death. Among patients with metastatic colorectal cancer, OPC was associated with shorter inpatient days near death and greater hospice utilization. Further prospective studies are needed to evaluate the impact of OPC on end-of-life care in Korea.

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

Cancer of the nasal cavity in the pediatric population.

PubMed

Benoit, Margo McKenna; Bhattacharyya, Neil; Faquin, William; Cunningham, Michael

2008-01-01

The purpose of this work was to investigate the clinical manifestations and diagnostic range of malignant entities presenting as a nasal mass in the pediatric population. A retrospective cohort analysis was conducted at a specialty hospital and a tertiary care university hospital. Patients aged between birth and 18 years and diagnosed with a malignancy that arose within the nasal cavity between the years 1991 and 2006 were included. This institution-specific patient group was compared with a similar cohort of patients extracted from the national Surveillance Epidemiology and End Results database. The main outcome measures were the incidence, presentation, and diagnoses of nasal cancer presenting in this population. Sixteen patients with nasal malignancies presented institutionally in the defined pediatric age group. Patient age at the time of diagnosis ranged from 7 months to 17 years, with a slight male predominance. The main presenting symptoms were unilateral nasal congestion and ophthalmologic complaints. The median time from presentation to diagnosis was 7 weeks; patients who presented with nonspecific complaints, such as nasal obstruction, headache, and fatigue, were given a diagnosis, on average, later than those who presented with focal manifestations. Nationwide, 47 patients were identified from the Surveillance Epidemiology and End Results database. In both subject groups, the most common diagnoses were rhabdomyosarcoma (37.5% institutionally and 23% in the Surveillance Epidemiology and End Results group) and esthesioneuroblastoma (25% institutionally and 28% Surveillance Epidemiology and End Results). In the Surveillance Epidemiology and End Results cohort, the overall mean survival rate was 188 months. Nasal cancer in the pediatric population often presents with nonspecific signs and symptoms, and a high index of suspicion is necessary for a timely diagnosis. Soft tissue sarcomas are expectedly common. The relative high frequency of

Comprehensive Evaluation of the Role of EZH2 in the Growth, Invasion, and Aggression of a Panel of Prostate Cancer Cell Lines

PubMed Central

Karanikolas, Breanne D.W.; Figueiredo, Marxa L.; Wu, Lily

2010-01-01

Background Although most prostate cancers respond well to initial treatments, a fraction of prostate cancers are more aggressive and will recur and metastasize. At that point, there are few treatment options available. Significant efforts have been made to identify biomarkers that will identify these more aggressive cancers to tailor a more vigorous treatment in order to improve outcome. Polycomb Group protein Enhancer of Zeste 2 (EZH2) was found to be overexpressed in metastatic prostate tumors, and is considered an excellent candidate for such a biomarker. Scattered studies have found that EZH2 overexpression causes neoplastic transformation, invasion, and growth of prostate cells. However, these studies utilized different systems and cell lines, and so are difficult to correlate with one another. Methods In this study, a comprehensive evaluation of the phenotypic effects of EZH2 in a panel of five prostate cancer cell lines was performed. By using multiple cell lines, and examining overexpression and knockdown of EZH2 concurrently, a broad view of EZH2's role in prostate cancer was achieved. Results Overexpression of EZH2 led to more aggressive behaviors in all prostate cell lines tested. In contrast, downregulation of EZH2 reduced invasion and tumorigenicity of androgen-independent cell lines CWR22Rv1, PC3, and DU145, but not of androgen-dependent cell lines LAPC4 and LNCaP. Conclusions Findings from this study suggest androgen-independent prostate tumors are more dependent on EZH2 expression than androgen-dependent tumors. Our observations provide an explanation for the strong correlation between EZH2 overexpression and advanced stage, aggressive prostate cancers. PMID:20087897

Association between aggressive care and bereaved families' evaluation of end-of-life care for veterans with non-small cell lung cancer who died in Veterans Affairs facilities.

PubMed

Ersek, Mary; Miller, Susan C; Wagner, Todd H; Thorpe, Joshua M; Smith, Dawn; Levy, Cari R; Gidwani, Risha; Faricy-Anderson, Katherine; Lorenz, Karl A; Kinosian, Bruce; Mor, Vincent

2017-08-15

To the authors' knowledge, little is known regarding the relationship between patients' and families' satisfaction with aggressive end-of-life care. Herein, the authors examined the associations between episodes of aggressive care (ie, chemotherapy, mechanical ventilation, acute hospitalizations, and intensive care unit admissions) within the last 30 days of life and families' evaluations of end-of-life care among patients with non-small cell lung cancer (NSCLC). A total of 847 patients with NSCLC (34% of whom were aged <65 years) who died in a nursing home or intensive care, acute care, or hospice/palliative care (HPC) unit at 1 of 128 Veterans Affairs Medical Centers between 2010 and 2012 were examined. Data sources included Veterans Affairs administrative and clinical data, Medicare claims, and the Bereaved Family Survey. The response rate for the Bereaved Family Survey was 62%. Greater than 72% of veterans with advanced lung cancer who died in an inpatient setting had at least 1 episode of aggressive care and 31% received chemotherapy within the last 30 days of life. For all units except for HPC, when patients experienced at least 1 episode of aggressive care, bereaved families rated care lower compared with when patients did not receive any aggressive care. For patients dying in an HPC unit, the associations between overall ratings of care and ≥2 inpatient admissions or any episode of aggressive care were not found to be statistically significant. Rates of aggressive care were not associated with age, and family ratings of care were similar for younger and older patients. Aggressive care within the last month of life is common among patients with NSCLC and is associated with lower family evaluations of end-of-life care. Specialized care provided within an HPC unit may mitigate the negative effects of aggressive care on these outcomes. Cancer 2017;123:3186-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

Kilovoltage Imaging Doses in the Radiotherapy of Pediatric Cancer Patients

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

Deng Jun, E-mail: jun.deng@yale.edu; Chen Zhe; Roberts, Kenneth B.

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,more » 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.« less

Strategies facilitating practice change in pediatric cancer: a systematic review.

PubMed

Robinson, Paula D; Dupuis, Lee L; Tomlinson, George; Phillips, Bob; Greenberg, Mark; Sung, Lillian

2016-09-01

By conducting a systematic review, we describe strategies to actively disseminate knowledge or facilitate practice change among healthcare providers caring for children with cancer and we evaluate the effectiveness of these strategies. We searched Ovid Medline, EMBASE and PsychINFO. Fully published primary studies were included if they evaluated one or more professional intervention strategies to actively disseminate knowledge or facilitate practice change in pediatric cancer or hematopoietic stem cell transplantation. Data extracted included study characteristics and strategies evaluated. In studies with a quantitative analysis of patient outcomes, the relationship between study-level characteristics and statistically significant primary analyses was evaluated. Of 20 644 titles and abstracts screened, 146 studies were retrieved in full and 60 were included. In 20 studies, quantitative evaluation of patient outcomes was examined and a primary outcome was stated. Eighteen studies were 'before and after' design; there were no randomized studies. All studies were at risk for bias. Interrupted time series was never the primary analytic approach. No specific strategy type was successful at improving patient outcomes. Literature describing strategies to facilitate practice change in pediatric cancer is emerging. However, major methodological limitations exist. Studies with robust designs are required to identify effective strategies to effect practice change. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A prospective multicenter study of microbiologically defined infections in pediatric cancer patients with fever and neutropenia: Swiss Pediatric Oncology Group 2003 fever and neutropenia study.

PubMed

Agyeman, Philipp; Kontny, Udo; Nadal, David; Leibundgut, Kurt; Niggli, Felix; Simon, Arne; Kronenberg, Andreas; Frei, Reno; Escobar, Hugo; Kühne, Thomas; Beck-Popovic, Maja; Bodmer, Nicole; Ammann, Roland A

2014-09-01

Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multicenter study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared with patients without MDI, fever [median, 5 (interquartile range: 3-8) vs. 2 (interquartile range: 1-3) days, P < 0.001] and hospitalization [10 (6-14) vs. 5 (3-8) days, P < 0.001] lasted longer, transfer to the intensive care unit was more likely [13 of 95 (14%) vs. 7 of 346 (2.0%), P < 0.001], and antibiotics were given longer [10 (7-14) vs. 5 (4-7) days, P < 0.001]. Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but also the purposeful omission of coverage for coagulase-negative staphylococci and enterococci was taken into account [81% (95% confidence interval: 68-90) vs. 96.6% (95% confidence interval: 87-99.4), P = 0.004]. MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

Pediatric quality of life in long-term survivors of childhood cancer treated with anthracyclines.

PubMed

Ryerson, A Blythe; Wasilewski-Masker, Karen; Border, William L; Goodman, Michael; Meacham, Lillian; Austin, Harland; Marchak, Jordan Gilleland; Mertens, Ann C

2016-12-01

Anthracyclines are a common class of drugs used to treat pediatric cancer. While much attention is given to their cardiotoxicity, little is known about the relationship between the use of anthracyclines and health-related quality-of-life (HRQoL) outcomes. This study examines the association of anthracycline cardiotoxicity risk status and Pediatric Quality-of-Life (PedsQL) Inventory TM scores in childhood cancer METHODS: Pediatric cancer survivors aged 8-21 who were at least 5 years posttreatment were recruited from a Cancer Survivor Clinic. Participants completed the PedsQL 4.0 Generic Core Scales and a health behavior survey. Linear regression was used to evaluate the association between PedsQL scores and anthracycline cardiotoxicity risk status and to assess whether self-reported physical activity modified the association. Eighty survivors participated and were characterized by cardiotoxicity risk status (high: 12; moderate: 23, low: 24, no risk: 21) as defined by the Children's Oncology Group (COG). Measures in all PedsQL domains tended to be slightly lower for survivors exposed to anthracyclines as compared to the unexposed. The largest difference in unadjusted mean scores was for social functioning (96.0% for unexposed vs. 91.3% for exposed, P = 0.0068). There was also an inverse dose-response relation between adjusted PedsQL scores and increasing anthracycline cardiotoxicity risk; this association was not modified by physical activity level. These data indicate that regular psychosocial assessments, such as those currently recommended by the COG, may be especially important for survivors treated with anthracyclines. © 2016 Wiley Periodicals, Inc.

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.

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

PubMed

Le Pennec, Soazig; Konopka, Tomasz; Gacquer, David; Fimereli, Danai; Tarabichi, Maxime; Tomás, Gil; Savagner, Frédérique; Decaussin-Petrucci, Myriam; Trésallet, Christophe; Andry, Guy; Larsimont, Denis; Detours, Vincent; Maenhaut, Carine

2015-04-01

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer. © 2015 Society for Endocrinology.

Specific deficit analyses in motor performance and quality of life of pediatric cancer patients--a cross-sectional pilot study.

PubMed

Beulertz, Julia; Bloch, Wilhelm; Prokop, Aram; Baumann, Freerk T

2013-05-01

Although survival rates in childhood cancer have distinctly improved, pediatric cancer patients often experience various disease- and treatment-related side effects with long-term consequences. Despite current studies investigating inactivity and limitations in physical functioning and quality of life in pediatric cancer patients, only little information regarding specific deficits in physical functioning and quality of life has been available until now. No study has yet analyzed these parameters from a global perspective and then identified specific deficits in a mixed childhood cancer population. Within this cross-sectional pilot study, motor performance and quality of life of 26 pediatric cancer patients were assessed after inpatient medical treatment, using standardized motor test batteries (MOT 4-6; DMT 6-18) and a quality of life questionnaire (KINDL®). Reference data have been mainly provided by the German "Children and Young People Health Survey" (KiGGS). Patients achieved lower motor performance scores (p = .000) (more than 27% below the average of healthy peers). Specific deficits were identified in motor speed and motor control (4-6 years), as well as in endurance, strength and coordination under time pressure (6-17 years). In terms of quality of life, no significant differences were examined compared to healthy children of the same age. The results of this study confirm that children with oncological diseases frequently have specific motor problems. Future research in pediatric oncology must investigate the impact of targeted, individualized exercise interventions addressing these specific deficits.

Turkish validity and reliability of a pediatric quality of life cancer module for children aged 8-12 and parents.

PubMed

Tanir, Meltem Kurtuncu; Kuguoglu, Sema

2011-01-01

This descriptive study was conducted to determine the validity and reliability in Turkey of the Pediatric Quality of Life Inventory Cancer Module (PedsQL 3.0) for children aged 8-12 in the hematology-oncology polyclinics of two university hospitals in Istanbul during the period 2006-2007. The data collection instruments were the Pediatric Quality of Life Inventory (PedsQL 4.0), the Pediatric Quality of Life Inventory Cancer Module (PedsQL 3.0) and a socio-demographic questionnaire, applied for 146 children diagnosed with cancer and 146 parents. Cronbach's alpha coefficients for the PedsQL 3.0 were found to be 0.602-0.982 for sub-groups with the children's form, 0.644-0.966 with the parents' form. The scale was found to give a significantly high level of reliability (0.60 ≤ ± < 0.80). Significant and directly proportional correlations were demonstrated between the forms for children and parents. It was concluded that the PedsQL 3.0 cancer module is a valid and reliable tool for assessing the quality of life of Turkish children, aged 8-12, diagnosed with cancer.

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

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

PubMed

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

2016-04-19

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.

Phospho-TCTP as a therapeutic target of dihydroartemisinin for aggressive breast cancer cells

PubMed Central

Lucibello, Maria; Adanti, Sara; Antelmi, Ester; Dezi, Dario; Ciafrè, Stefania; Carcangiu, Maria Luisa; Zonfrillo, Manuela; Nicotera, Giuseppe; Sica, Lorenzo; De Braud, Filippo; Pierimarchi, Pasquale

2015-01-01

Upregulation of Translationally Controlled Tumor Protein (TCTP) is associated with poorly differentiated aggressive tumors, including breast cancer, but the underlying mechanism(s) are still debated. Here, we show that in breast cancer cell lines TCTP is primarily localized in the nucleus, mostly in the phosphorylated form. The effects of Dihydroartemisinin (DHA), an anti-malaria agent that binds TCTP, were tested on breast cancer cells. DHA decreases cell proliferation and induces apoptotic cell death by targeting the phosphorylated form of TCTP. Remarkably, DHA enhances the anti-tumor effects of Doxorubicin in triple negative breast cancer cells resulting in an increased level of apoptosis. DHA also synergizes with Trastuzumab, used to treat HER2/neu positive breast cancers, to induce apoptosis of tumor cells. Finally, we present new clinical data that nuclear phospho-TCTP overexpression in primary breast cancer tissue is associated with high histological grade, increase expression of Ki-67 and with ER-negative breast cancer subtypes. Notably, phospho-TCTP expression levels increase in trastuzumab-resistant breast tumors, suggesting a possible role of phospho-TCTP as a new prognostic marker. In conclusion, the anti-tumor effect of DHA in vitro with conventional chemotherapeutics suggests a novel therapeutic strategy and identifies phospho-TCTP as a new promising target for advanced breast cancer. PMID:25779659

Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001-2010.

PubMed

Brecht, Ines B; Bremensdorfer, Claudia; Schneider, Dominik T; Frühwald, Michael C; Offenmüller, Sonja; Mertens, Rolf; Vorwerk, Peter; Koscielniak, Ewa; Bielack, Stefan S; Benesch, Martin; Hero, Barbara; Graf, Norbert; von Schweinitz, Dietrich; Kaatsch, Peter

2014-07-01

The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients. © 2014 Wiley Periodicals, Inc.

Infancy and pediatric cancer: an exploratory study of parent psychological distress.

PubMed

Vernon, L; Eyles, D; Hulbert, C; Bretherton, L; McCarthy, M C

2017-03-01

Research on the psychological experiences of parents of infants within pediatric oncology is sparse. This study examined rates and indicative risk factors for psychological distress in parents where there is either an infant patient or infant sibling of a patient. Participants were mothers (n = 41) and fathers (n = 25) of infants under 2 years who either had a cancer diagnosis (n = 37; infant patients) or was an infant sibling of an older child with cancer (n = 29; infant siblings) recruited from a single oncology center. There were 21 couple dyads. Parents completed the Depression Anxiety Stress Scales short form and the Posttraumatic Stress Disorder Checklist. Mothers (47.5%) and fathers (37.5%) reported elevated, cancer-related posttraumatic stress symptoms. Rates of depression (12.2% of mothers and 12.0% of fathers) and anxiety symptoms (17.1% of mothers and 8.0% of fathers) were lower. Compared with parents of infant patients, parents of infant siblings reported significantly higher rates of depressive symptoms and trends toward higher rates of posttraumatic stress symptoms and anxiety symptoms. Parent anxiety was higher with increased time post diagnosis. No demographic or illness-related variables were associated with psychological distress, with the exception of the number of children in the family. Parent-child relationships are of fundamental importance during infancy. This study provides novel data highlighting the psychological impact for parents when a cancer diagnosis is made during this critical developmental period, including the contribution of family structure to parental distress. Results provide further support for applying a traumatic stress framework when exploring parent experiences of pediatric cancer. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Pediatric Brain Tumor Foundation

MedlinePlus

... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

Facading in transcultural interactions: examples from pediatric cancer care in Sweden.

PubMed

Pergert, Pernilla

2017-07-01

The aims of the study were to generate a grounded theory explaining the latent pattern of behavior in transcultural care interactions in the context of pediatric cancer care and to unify previously performed studies. The basic tenets of classic grounded theory were applied on a theoretical sample of data from previous studies that included 5 focus group interviews with health care professionals (n = 35) and individual interviews with nurses (n = 12) and foreign-born parents (n = 11). Facading emerged as the core category and is the act of showing an outer appearance that will influence other people's interpretations. In transcultural interactions, facading might be misinterpreted related to different obstacles. Examples are given of different facades explored in pediatric cancer care including strength facading. Facading is a strategy aiming to protect oneself and others emotionally in care and includes: emotional facading and facading-sensitive issues. This grounded theory could help make health care professionals aware of different meanings of facading across cultures in health care. Also, awareness is needed of different views on emotional facading and facading-sensitive issues to provide a congruent care. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical research participation among adolescent and young adults at an NCI-designated Comprehensive Cancer Center and affiliated pediatric hospital.

PubMed

Sanford, Stacy D; Beaumont, Jennifer L; Snyder, Mallory A; Reichek, Jennifer; Salsman, John M

2017-05-01

Minimal clinical trial participation among adolescents and young adults (AYAs) with cancer limits scientific progress and ultimately their clinical care and outcomes. These analyses examine the current state of AYA clinical research participation at a Midwestern comprehensive cancer center and affiliated pediatric hospital to advise program development and increase availability of trials and AYA participation. Enrollment is examined across all diagnoses, the entire AYA age spectrum (15-39), and both cancer therapeutic and supportive care protocols. his study was a retrospective review of electronic medical records via existing databases and registries for all AYAs. Data were collected for AYAs seen by an oncologist at the adult outpatient cancer center or at the pediatric hospital between the years 2010 and 2014. Descriptive statistics and logistic regression analyses were conducted to characterize this sample. In the pediatric setting, 42.3% of AYAs were enrolled in a study compared to 11.2% in the adult setting. Regression analyses in the pediatric setting revealed that AYAs with private insurance or Caucasian race were more likely to participate. Within the adult setting, ethnicity, race, insurance, and diagnosis were associated with study participation; 54.8% of study enrollments were for cancer therapeutic and 43.4% for supportive care studies. These results are comparable to previously published data and support the need for new local and national AYA initiatives to increase the availability of and enrollment in therapeutic clinical trials. The same is true for supportive care studies which play a crucial role in improving quality of life.

Fertility preservation in pediatric and adolescent cancer patients in Switzerland: A qualitative cross-sectional survey.

PubMed

Diesch, Tamara; von der Weid, Nicolas Xavier; Szinnai, Gabor; Schaedelin, Sabine; De Geyter, Christian; Rovó, Alicia

2016-10-01

Fertility preservation (FP) is an important topic of discussion in the field of oncology, particularly in pediatric oncology. Despite the awareness of severe impact of infertility on quality of life and different guidelines available in this area, the options in FP are not routinely discussed with the pediatric cancer patients and their parents. To the best of our knowledge, this is the first survey report concerned to FP counseling and procedures in pediatric and adolescent cancer patients in Switzerland. This survey was conducted from June 2014 to October 2014 on the counseling and procedures performed between 2009 and 2013; the questionnaire was completed by one of the professional from hematology/oncology centers in Switzerland. Currently, only four out of nine centers have a program for FP. In 2013, 45/301 (15%) patients received FP counseling and 36/301 (12%) underwent an FP procedure. The most commonly performed procedures from 2009 to 2013 were administration of gonadotropin releasing hormone agonist (3%) and cryopreservation of ovarian tissue in females (3%) and cryopreservation of sperms in males (6%); the most frequently cited reason for the absence of FP counseling was lack of time (55%). Therefore, this survey should help to develop and harmonize practices with respect to FP counseling and procedures in Switzerland, and to establish FP as a standard of care during cancer treatment. Copyright © 2016. Published by Elsevier Ltd.

Non-invasive estimation of prostate cancer aggressiveness using diffusion-weighted MRI and 3D proton MR spectroscopy at 3.0 T.

PubMed

Thörmer, Gregor; Otto, Josephin; Horn, Lars-Christian; Garnov, Nikita; Do, Minh; Franz, Toni; Stolzenburg, Jens-Uwe; Moche, Michael; Kahn, Thomas; Busse, Harald

2015-01-01

Clinical management of prostate cancer increasingly aims to distinguish aggressive types that require immediate and radical treatment from indolent tumors that are candidates for watchful waiting. This requires reliable and reproducible parameters to effectively control potential cancer progression. Magnetic resonance imaging (MRI) may provide a non-invasive means for this purpose. To assess the value of diffusion-weighted imaging and proton MR spectroscopy for the prediction of prostate cancer (PCa) aggressiveness. In 39 of 64 consecutive patients who underwent endorectal 3-T MRI prior to radical prostatectomy, prostate specimens were analyzed as whole-mount step sections. Apparent diffusion coefficient (ADC), normalized ADC (nADC: tumor/healthy tissue), choline/citrate (CC), and (choline + creatine)/citrate (CCC) ratios were correlated with Gleason scores (GS) from histopathological results. The power to discriminate low (GS ≤ 6) from higher-risk (GS ≥ 7) tumors was assessed with receiver operating characteristics (area under the curve [AUC]). Resulting threshold values were used by a blinded reader to distinguish between aggressive and indolent tumors. Ninety lesions (1 × GS = 5, 41 × GS = 6, 36 × GS = 7, 12 × GS = 8) were considered. nADC (AUC = 0.90) showed a higher discriminatory power than ADC (AUC = 0.79). AUC for CC and CCC were 0.73 and 0.82, respectively. Using either nADC < 0.46 or CCC > 1.3, as well as both criteria for aggressive PCa, the reader correctly identified aggressive and indolent tumors in 31 (79%), 28 (72%), and 33 of 39 patients (85%), respectively. Predictions of tumor aggressiveness from TRUS-guided biopsies were correct in 27 of 36 patients (75%). The combination of a highly sensitive normalized ADC with a highly specific CCC was found to be well suited to prospectively estimate PCa aggressiveness with a similar diagnostic accuracy as biopsy results. © The Foundation

Historical trends in the use of radiation therapy for pediatric cancers: 1973-2008.

PubMed

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

2013-03-01

This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. 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. 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. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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

Jairam, Vikram; Roberts, Kenneth B.; Yale Cancer Center, New Haven, Connecticut

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 whomore » 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.« less

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

PubMed

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

2016-12-08

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.

Disparities in pediatric oncology patient education and linguistic resources: results of a national survey of pediatric oncologists.

PubMed

Slone, Jeremy S; Self, Elizabeth; Friedman, Debra; Heiman, Harry

2014-02-01

Extensive patient and family education is required at the time of a new diagnosis of pediatric cancer yet little data exist regarding the availability and linguistic competency of new cancer diagnosis education provided by pediatric oncology institutions. Using the American Society of Pediatric Hematology/Oncology (ASPHO) membership list, a web-based survey was conducted among a cohort of pediatric oncologists to determine pediatric oncologists' assessment of institutional resources for new cancer diagnosis education and the availability of linguistically appropriate education. Of 1,294 ASPHO members sent email survey invitations, 573 (44.3%) responded with 429 meeting eligibility criteria. Oncologists at academic institutions reported their institutions had more availability of resources for new diagnosis education compared with those from non-academic institutions (mean 78.6 vs. 74.3; 0 [not at all]-100 [well equipped]; P = 0.05). The mean score increased with volume of new cancer diagnoses/year: small (<75) = 73.4; medium (75-149) = 76.7; large (>150) = 84.5 (P < 0.001). Oncologists at large volume institutions reported more availability of an established patient education protocol (50.8% vs. 38.1%, P < 0.001) and increased use of dedicated non-physician staff (79.9% vs. 66.1%, P = 0.02), but less use of websites for patient education (17.2% vs. 33.3%, P = 0.001). Availability of linguistically appropriate education improved with increasing institution size: small (76.4), medium (82.3), and large (84.0) patient volume (P < 0.011). According to pediatric oncologists, a disparity in educational and linguistic resources for new pediatric cancer diagnosis education exists depending on institution type and size. © 2013 Wiley Periodicals, Inc.

Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation Patients Despite Both Standard and Aggressive Supplementation.

PubMed

Wallace, Gregory; Jodele, Sonata; Myers, Kasiani C; Dandoy, Christopher E; El-Bietar, Javier; Nelson, Adam; Taggart, Cynthia B; Daniels, Pauline; Lane, Adam; Howell, Jonathan; Teusink-Cross, Ashley; Davies, Stella M

2016-07-01

We recently reported that more than 70% of pediatric and young adult patients had a vitamin D (VD) deficiency at the time of their hematopoietic stem cell transplantation (HSCT). Moreover, VD deficiency was associated with inferior survival at 100 days after transplantation. The goal of the present study was to evaluate the VD requirements needed to maintain an optimal VD level (30 to 60 ng/mL) during the first 3 months after transplantation using real-time VD monitoring and personalized VD supplementation. We examined 2 cohorts in this study: cohort 1, the "preintervention" cohort (n = 35), who were treated according to National Kidney Foundation guidelines for VD therapy, and cohort 2, the "intervention" cohort (n = 25) who were treated with high-dose VD with an aggressive dosage increase in those who remained VD-insufficient. Results from cohort 1 showed that despite aggressive monitoring and VD supplementation, therapeutic vitamin D levels were difficult to achieve and maintain in HSCT recipients during the early post-transplantation period. Only 43% of cohort 1 achieved a therapeutic VD level, leading to our intervention in cohort 2. Outcomes improved in cohort 2, but still only 64% of cohort 2 patients achieved a therapeutic VD level despite receiving >200 IU/kg/day of VD enterally. The median VD level in patients who did achieve sufficient levels was 40 ng/mL, with only 1 patient in each cohort achieving a supratherapeutic but nontoxic level. These data indicate that standard guidelines for VD replacement are inadequate in HSCT recipients, and further work is needed to define more appropriate dosing in this clinical setting. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A cross-sectional study of carnitine deficiency and fatigue in pediatric cancer patients.

PubMed

Lai, Jin-Shei; Haertling, Tracy; Weinstein, Joanna; Rademaker, Alfred W; Goldman, Stewart

2016-03-01

Carnitine deficiency has been found in cancer patients and has been associated with fatigue. This study aimed to explore the prevalence of carnitine deficiency in pediatric cancer patients and its relationship with fatigue and other potential contributing factors. Children with cancer or Langerhans cell histiocytosis who were receiving treatment or had completed therapy were eligible. Patients completed the Pediatric Functional Assessment of Chronic Illness-Fatigue, the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, a numeric fatigue rating, and had carnitine levels obtained. Carnitine deficiency was defined as a total and/or free carnitine level less than normal for age or an acylcarnitine value higher than normal for age. Data from 142 children aged 8-17 were analyzed. Twenty-eight of 142 (19.7 %) had decreased total and 42.8 % (12/28) had decreased free carnitine levels. No patients had elevated acylcarnitine levels or elevated ratios. Patients with versus without carnitine deficiency differed by age (p = 0.043), treatment (p = 0.037), duration since last chemotherapy (p = 0.020), and body mass index (p = 0.010), but not fatigue, when all data were analyzed together. Yet, a negative relationship between fatigue and carnitine levels was found on a subgroup (off-therapy; fatigue worse than the norm). No significant association between fatigue and carnitine level was demonstrated when data from all patients were analyzed together; however, a significant yet unexpected relationship was found for patients who completed therapy and reported elevated fatigue. Given the small sample size, these results should be interpreted with caution. Future studies to explore impact upon excessive carnitine levels are warranted.

Diagnostic accuracy of prostate health index to identify aggressive prostate cancer. An Institutional validation study.

PubMed

Morote, J; Celma, A; Planas, J; Placer, J; Ferrer, R; de Torres, I; Pacciuci, R; Olivan, M

2016-01-01

New generations of tumor markers used to detect prostate cancer (PCa) should be able to discriminate men with aggressive PCa of those without PCa or nonaggressive tumors. The objective of this study has been to validate Prostate Health Index (PHI) as a marker of aggressive PCa in one academic institution. PHI was assessed in 357 men scheduled to prostatic biopsy between June of 2013 and July 2014 in one academic institution. Thereafter a subset of 183 men younger than 75 years and total PSA (tPSA) between 3.0 and 10.0 ng/mL, scheduled to it first prostatic biopsy, was retrospectively selected for this study. Twelve cores TRUS guided biopsy, under local anaesthesia, was performed in all cases. Total PSA, free PSA (fPSA), and [-2] proPSA (p2PSA) and prostate volume were determined before the procedure and %fPSA, PSA density (PSAd) and PHI were calculated. Aggressive tumors were considered if any Gleason 4 pattern was found. PHI was compared to %fPSA and PSAd through their ROC curves. Thresholds to detect 90%, 95% of all tumors and 95% and 100% of aggressive tumors were estimated and rates of unnecessary avoided biopsies were calculated and compared. The rate of PCa detection was 37.2% (68) and the rate of aggressive tumors was 24.6% (45). The PHI area under the curve was higher than those of %fPSA and PSAd to detect any PCa (0.749 vs 0.606 and 0.668 respectively) or to detect only aggressive tumors (0.786 vs 0.677 and 0.708 respectively), however, significant differences were not found. The avoided biopsy rates to detect 95% of aggressive tumors were 20.2% for PHI, 14.8% for %fPSA, and 23.5% for PSAd. Even more, to detect all aggressive tumors these rates dropped to 4.9% for PHI, 9.3% for %fPSA, and 7.9% for PSAd. PHI seems a good marker to PCa diagnosis. However, PHI was not superior to %fPSA and PSAd to identify at least 95% of aggressive tumors. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Who is a survivor? Perceptions from individuals who experienced pediatric cancer and their primary support persons.

PubMed

Molinaro, Monica L; Fletcher, Paula C

2018-04-01

The purpose of this research was to examine the lived experiences of individuals who had cancer as children, as well as lived experiences of their current primary support persons. Based on van Manen's "new" interpretive phenomenology, interviews were conducted with ten pediatric cancer survivors and nine of their support persons to gain a more holistic understanding of the pediatric cancer experiences of children and their families. Four themes emerged from the data; however, only the topic of the use of the term "survivor" and identification with the term will be discussed. All participants in the study described their personal definition of the term survivor and what it meant to be a survivor. Additionally, all individuals in the study discussed the concept of being a survivor and if they would consider themselves, or their loved ones, to be "survivors." The results of this study provide health care professionals, family members, and individuals fundraising or advocating for cancer causes with insights on how the term survivor may be interpreted. This study may provide insight to individuals who had cancer as children, in showing that their personal perspective shapes their identity; although "survivor" is common cancer vernacular, individuals can choose not to identify with their illness experiences.

Acute loss of TET function results in aggressive myeloid cancer in mice

PubMed Central

An, Jungeun; González-Avalos, Edahí; Chawla, Ashu; Jeong, Mira; López-Moyado, Isaac F.; Li, Wei; Goodell, Margaret A.; Chavez, Lukas; Ko, Myunggon; Rao, Anjana

2015-01-01

TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumour suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. Here we show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice, pointing to a causative role for TET loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling shows aberrant differentiation of haematopoietic stem/progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observe progressive accumulation of phospho-H2AX and strong impairment of DNA damage repair pathways, suggesting a key role for TET proteins in maintaining genome integrity. PMID:26607761

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

PubMed Central

Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C.; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M.; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid

2014-01-01

The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA. PMID:24742583

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication.

PubMed

Forster, Tobias; Rausch, Vanessa; Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid

2014-03-30

The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA.

Exercise interventions for patients with pediatric cancer during inpatient acute care: A systematic review of literature.

PubMed

Rustler, Vanessa; Hagerty, Meaghan; Daeggelmann, Julia; Marjerrison, Stacey; Bloch, Wilhelm; Baumann, Freerk T

2017-11-01

Physical inactivity has been shown to exacerbate negative side effects experienced by pediatric patients undergoing cancer therapy. Exercise interventions are being created in response. This review summarizes current exercise intervention data in the inpatient pediatric oncology setting. Two independent reviewers collected literature from three databases, and analyzed data following the PRISMA statement for systematic reviews and meta-analyses. Ten studies were included, representing 204 patients. Good adherence, positive trends in health status, and no adverse events were noted. Common strategies included individual, supervised, combination training with adaptability to meet fluctuating patient abilities. We recommend that general physical activity programming be offered to pediatric oncology inpatients. © 2017 Wiley Periodicals, Inc.

Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

PubMed

Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

2017-04-01

Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

Expression screening of cancer/testis genes in prostate cancer identifies NR6A1 as a novel marker of disease progression and aggressiveness.

PubMed

Mathieu, Romain; Evrard, Bertrand; Fromont, Gaëlle; Rioux-Leclercq, Nathalie; Godet, Julie; Cathelineau, Xavier; Guillé, François; Primig, Michael; Chalmel, Frédéric

2013-07-01

Cancer/Testis (CT) genes are expressed in male gonads, repressed in most healthy somatic tissues and de-repressed in various somatic malignancies including prostate cancers (PCa). Because of their specific expression signature and their associations with tumor aggressiveness and poor outcomes, CT genes are considered to be useful biomarkers and they are also targets for the development of new anti-cancer immunotherapies. The aim of this study was to identify novel CT genes associated with hormone-sensitive prostate cancer (HSPC), and castration-resistant prostate cancer (CRPC). To identify novel CT genes we screened genes for which transcripts were detected by RNA profiling specifically in normal testis and in either HSPC or CRPC as compared to normal prostate and 44 other healthy tissues using GeneChips. The expression and clinicopathological significance of a promising candidate--NR6A1--was examined in HSPC, CRPC, and metastatic site samples using tissue microarrays. We report the identification of 98 genes detected in CRPC, HSPC and testicular samples but not in the normal controls. Among them, cellular levels of NR6A1 were found to be higher in HSPC compared to normal prostate and further increased in metastatic lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly associated with a high Gleason score, advanced pT stage and cancer cell proliferation. Our results show that cellular levels of NR6A1 are correlated with disease progression in PCa. We suggest that this essential orphan nuclear receptor is a potential therapeutic target as well as a biomarker of PCa aggressiveness. Copyright © 2013 Wiley Periodicals, Inc.

Event-related potentials in impulsively aggressive juveniles: a retrospective chart-review study.

PubMed

Fisher, William; Ceballos, Natalie; Matthews, Dan; Fisher, Larry

2011-05-30

The assessment, treatment and management of aggressive youth represent a major clinical challenge facing pediatric mental health professionals today. Although a number of studies have examined physiological differences among aggressive patients vs. controls, the current literature lacks a comprehensive examination of the electroencephalographic activity of impulsively aggressive juveniles. The current study was designed to fill this void in the literature via a retrospective chart review of 80 male and female juveniles undergoing inpatient treatment for pathologically impulsive aggression. Clinical reports for mid- and late-latency event-related potentials (ERPs) were examined to determine their correlations with aggression characteristics, as well as any differential predictive utility of hemispheric differences and auditory vs. visual potentials. Results indicated that decrements of mid-latency potentials and ERPs evoked by auditory stimuli (vs. late-latency components and visual ERPs) were more highly predictive of aggressive behavior. No significant hemispheric differences were noted. Taken together, these results have theoretical significance for the etiology of impulsive aggression, and perhaps also clinical relevance for the treatment of this condition. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Pediatric oncology nurses' attitudes related to discussing fertility preservation with pediatric cancer patients and their families.

PubMed

Vadaparampil, Susan T; Clayton, Heather; Quinn, Gwendolyn P; King, Lindsey M; Nieder, Michael; Wilson, Crystal

2007-01-01

This study explores nurses' attitudes toward the discussion of fertility preservation (FP) with pediatric cancer patients and their families. A cross-sectional survey was administered to attendees of a pediatric oncology conference. Of the 115 nurses who responded and comprised the study sample, most reported discussing risks of infertility or FP

The Immunohistochemical Analysis of SOCS3 Protein Identifies a Subgroup of Prostatic Cancer Biopsies With Aggressive Behavior.

PubMed

Pierconti, Francesco; Martini, Maurizio; Cenci, Tonia; Larocca, Luigi M

Recently, we demonstrated that hypermethylation of SOCS3 determines a significant reduction of its mRNA and protein expression and identifies a subgroup of prostate cancer with aggressive behavior. In this paper, our objective was to investigate whether the immunohistochemical expression of the SOCS3 protein could represent an alternative method to molecular analysis for the individualization of aggressive prostate carcinoma. We analyzed the SOCS3 immunohistochemical expression in 65 patients undergoing biopsies at the Institute of Urology of our hospital between September 2011 and October 2011 (median age, 66.4 y; range, 50 to 73 y), and in 35 cases, a subset of 65 cases originally used for the immunohistochemical study, we studied the methylation status of the SOCS3 promoter. We found that the percentage of cases with SOCS3 negativity (-) or with SOCS3 weak staining in <50% of the neoplastic glands (+/-) correlated to the worst prognosis in terms of the Gleason score (P=0.0001; Fisher's exact test), the pT stage (P=0.012; Fisher's exact test), and progression-free survival (P=0.0334; hazard ratio, 0.34; and 95% confidence interval, from 0.1261 to 0.9188). Moreover, some cases with an SOCS3 unmethylated pattern showed SOCS3-negative immunostaining (-) or SOCS3-negative glands with weak cytoplasmatic staining in <50% of the neoplastic glands (+/-). Our data suggest that in prostatic cancer biopsies, the immunohistochemical analysis of SOCS3 protein expression may provide a method that is less expensive and easier to apply than SOCS3 methylation analysis for the distinction of a subgroup of prostate cancer with a more aggressive behavior.

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

Geography and the burden of care in pediatric cancers.

PubMed

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

2014-11-01

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. 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. Of the 29% of caregivers who reported moving residences as 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 6 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. 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. © 2014 Wiley Periodicals, Inc.

Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject.

PubMed

Scollon, Sarah; Bergstrom, Katie; McCullough, Laurence B; McGuire, Amy L; Gutierrez, Stephanie; Kerstein, Robin; Parsons, D Williams; Plon, Sharon E

2015-01-01

The return of genetic research results after death in the pediatric setting comes with unique complexities. Researchers must determine which results and through which processes results are returned. This paper discusses the experience over 15 years in pediatric cancer genetics research of returning research results after the death of a child and proposes a preventive ethics approach to protocol development in order to improve the quality of return of results in pediatric genomic settings. © 2015 American Society of Law, Medicine & Ethics, Inc.

Epidemiology of bacterial isolates among pediatric cancer patients from a tertiary care oncology center in North India.

PubMed

Kapoor, G; Sachdeva, N; Jain, S

2014-01-01

Infections are a major cause of morbidity and mortality in pediatric oncology. Resistance pattern of bacterial isolates determine empiric antibiotic therapy and influence outcome. This study was planned to determine profile of bacterial isolates and their antibiotic resistance pattern among pediatric cancer patients. It was a retrospective, single institutional study. The study was carried out in the department of pediatric hematology-oncology of a tertiary care cancer centre in north India over a period of 24 months (2012-2014). Microbiological data pertaining to pediatric cancer patients, less than 18 yrs of age was analysed. Hence, 238 bacterial isolates were cultured from among 1757 blood, urine and other specimens. Gram negative bacteria were the most common (74%) pathogens identified and E. coli and Klebsiella comprised 80% of them. A high incidence of extended spectrum beta lactamase producing organisms (84%), beta-lactam beta-lactamase inhibitor (78%) and carbapenem resistance was observed (29%). Blood stream infection with multi-drug resistant Klebsiella was associated with high mortality. The gram positive bacteria isolated were predominantly staphylococcus aureus and were antibiotic sensitive. Reduction in the number of culture positive isolates in the second year of our study was probably due to rigorous implementation of infection control measures. These results on microbiologic profile and antibiotic sensitivity pattern of the isolates will be extremely helpful in revision of antibiotic guidelines for our patients and in developing strategies for coping with high prevalence of multi-drug resistance. Antibiotic stewardship and strict implementation of infection control practices will be important components of this effort.

A Summary of Pediatric Palliative Care Team Structure and Services as Reported by Centers Caring for Children with Cancer.

PubMed

Weaver, Meaghann S; Rosenberg, Abby R; Tager, Julia; Wichman, Christopher S; Wiener, Lori

2018-04-01

Little is known about the composition, availability, integration, communication, perceived barriers, and work load of pediatric palliative care (PPC) providers serving children and adolescents with cancer. To summarize the structure and services of programs to better understand successes and gaps in implementing palliative care as a standard of care. Cross-sectional online survey about the palliative care domains determined by the Psychosocial Care of Children with Cancer and Their Families Workgroup. A total of 142 surveys were completed with representation from 18 countries and 39 states. Three-fourths of sites reported having a PPC program available for the pediatric cancer population at their center. Over one-fourth (28%) have been in existence less than five years. Fewer than half of sites (44%) offered 24/7 access to palliative care consultations. Neither hospital-based nor local community hospice services were available for pediatric patients at 24% of responding sites. A specific inpatient PPC unit was available at 8% of sites. Criteria for automatic palliative referrals ("trigger" diagnoses) were reported by 44% respondents. The presence of such "triggers" increased the likelihood of palliative principle introduction 3.41 times (p < 0.003). Six percent of respondents perceived pediatric oncology patients and their families "always" were introduced to palliative care concepts and 17% reported children and families "always" received communication about palliative principles. The most prevalent barriers to palliative care were at the provider level. Children and adolescents with cancer do not yet receive concurrent palliative care as a universal standard.

Communicating and understanding the purpose of pediatric phase I cancer trials.

PubMed

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

2012-12-10

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. 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. 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. 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.

RANK-c attenuates aggressive properties of ER-negative breast cancer by inhibiting NF-κB activation and EGFR signaling.

PubMed

Sirinian, Chaido; Papanastasiou, Anastasios D; Schizas, Michail; Spella, Magda; Stathopoulos, Georgios T; Repanti, Maria; Zarkadis, Ioannis K; King, Tari A; Kalofonos, Haralabos P

2018-05-29

The RANK/RANKL axis emerges as a key regulator of breast cancer initiation, progression, and metastasis. RANK-c is a RANK receptor isoform produced through alternative splicing of the TNFRSF11A (RANK) gene and a dominant-negative regulator of RANK-induced nuclear factor-κB (NF-κB) activation. Here we report that RANK-c transcript is expressed in 3.2% of cases in The Cancer Genome Atlas breast cancer cohort evenly between ER-positive and ER-negative cases. Nevertheless, the ratio of RANK to RANK-c (RANK/RANK-c) is increased in ER-negative breast cancer cell lines compared to ER-positive breast cancer cell lines. In addition, forced expression of RANK-c in ER-negative breast cancer cell lines inhibited stimuli-induced NF-κB activation and attenuated migration, invasion, colony formation, and adhesion of cancer cells. Further, RANK-c expression in MDA-MB-231 cells inhibited lung metastasis and colonization in vivo. The RANK-c-mediated inhibition of cancer cell aggressiveness and nuclear factor-κB (NF-κB) activation in breast cancer cells seems to rely on a RANK-c/TNF receptor-associated factor-2 (TRAF2) protein interaction. This was further confirmed by a mutated RANK-c that is unable to interact with TRAF2 and abolishes the ability to attenuate NF-κB activation, migration, and invasion. Additional protein interaction characterization revealed epidermal growth factor receptor (EGFR) as a novel interacting partner for RANK-c in breast cancer cells with a negative effect on EGFR phosphorylation and EGF-dependent downstream signaling pathway activation. Our findings further elucidate the complex molecular biology of the RANKL/RANK system in breast cancer and provide preliminary data for RANK-c as a possible marker for disease progression and aggressiveness.

Childhood cancer survivorship educational resources in North American pediatric hematology/oncology fellowship training programs: a survey study.

PubMed

Nathan, Paul C; Schiffman, Joshua D; Huang, Sujuan; Landier, Wendy; Bhatia, Smita; Eshelman-Kent, Debra; Wright, Jennifer; Oeffinger, Kevin C; Hudson, Melissa M

2011-12-15

Childhood cancer survivors require life-long care by clinicians with an understanding of the specific risks arising from the prior cancer and its therapy. We surveyed North American pediatric hematology/oncology training programs to evaluate their resources and capacity for educating medical trainees about survivorship. An Internet survey was sent to training program directors and long-term follow-up clinic (LTFU) directors at the 56 US and Canadian centers with pediatric hematology/oncology fellowship programs. Perceptions regarding barriers to and optimal methods of delivering survivorship education were compared among training program and LTFU clinic directors. Responses were received from 45/56 institutions of which 37/45 (82%) programs require that pediatric hematology/oncology fellows complete a mandatory rotation focused on survivorship. The rotation is 4 weeks or less in 21 programs. Most (36/45; 80%) offer didactic lectures on survivorship as part of their training curriculum, and these are considered mandatory for pediatric hematology/oncology fellows at 26/36 (72.2%). Only 10 programs (22%) provide training to medical specialty trainees other than pediatric hematology/oncology fellows. Respondents identified lack of time for trainees to spend learning about late effects as the most significant barrier to providing survivorship teaching. LTFU clinic directors were more likely than training program directors to identify lack of interest in survivorship among trainees and survivorship not being a formal or expected part of the fellowship training program as barriers. The results of this survey highlight the need to establish standard training requirements to promote the achievement of basic survivorship competencies by pediatric hematology/oncology fellows. Copyright © 2011 Wiley Periodicals, Inc.

Bridging Adult Experience to Pediatrics in Oncology Drug Development.

PubMed

Leong, Ruby; Zhao, Hong; Reaman, Gregory; Liu, Qi; Wang, Yaning; Stewart, Clinton F; Burckart, Gilbert

2017-10-01

Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population. Therefore, the development of drug dosing in pediatric oncology patients represents a special challenge. Potential approaches to pediatric dosing in oncology patients include extrapolation of efficacy from adult studies in those few cases where the disease is similar, inclusion of adolescent patients in adult trials when possible, and bridging the adult dose to the pediatric dose. An analysis of the recommended phase 2 dose for 40 molecularly targeted agents in pediatric patients provides some insight into current practices. Increased knowledge of tumor biology and efforts to identify and validate molecular targets and genetic abnormalities that drive childhood cancers can lead to increased opportunities for precision medicine in the treatment of pediatric cancers. © 2017, The American College of Clinical Pharmacology.

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

PubMed Central

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

2015-01-01

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. PMID:26436135

A Jagged road to lymphoma aggressiveness

PubMed Central

Radojcic, Vedran; Maillard, Ivan

2014-01-01

In this issue of Cancer Cell, Cao and colleagues identifyanFGF4/Jagged1-driven crosstalk between tumor cells and their vascular niche that activates Notch signaling, sustaining the aggressiveness of certain mouse and human B cell lymphomas. These findings identify new therapeutic opportunities to target pathogenic angiocrine functions in cancer. PMID:24651005

Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions.

PubMed

Richardson, Janet; Smith, Joanna E; McCall, Gillian; Pilkington, Karen

2006-01-01

The aim of this study was to systematically review and critically appraise the evidence on the effectiveness of hypnosis for procedure-related pain and distress in pediatric cancer patients. A comprehensive search of major biomedical and specialist complementary and alternative medicine databases was conducted. Citations were included from the databases' inception to March 2005. Efforts were made to identify unpublished and ongoing research. Controlled trials were appraised using predefined criteria. Clinical commentaries were obtained for each study. Seven randomized controlled clinical trials and one controlled clinical trial were found. Studies report positive results, including statistically significant reductions in pain and anxiety/distress, but a number of methodological limitations were identified. Systematic searching and appraisal has demonstrated that hypnosis has potential as a clinically valuable intervention for procedure-related pain and distress in pediatric cancer patients. Further research into the effectiveness and acceptability of hypnosis for pediatric cancer patients is recommended.

Patient-specific radiation dose and cancer risk estimation in pediatric chest CT: a study in 30 patients

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2010-04-01

Radiation-dose awareness and optimization in CT can greatly benefit from a dosereporting system that provides radiation dose and cancer risk estimates specific to each patient and each CT examination. Recently, we reported a method for estimating patientspecific dose from pediatric chest CT. The purpose of this study is to extend that effort to patient-specific risk estimation and to a population of pediatric CT patients. Our study included thirty pediatric CT patients (16 males and 14 females; 0-16 years old), for whom full-body computer models were recently created based on the patients' clinical CT data. Using a validated Monte Carlo program, organ dose received by the thirty patients from a chest scan protocol (LightSpeed VCT, 120 kVp, 1.375 pitch, 40-mm collimation, pediatric body scan field-of-view) was simulated and used to estimate patient-specific effective dose. Risks of cancer incidence were calculated for radiosensitive organs using gender-, age-, and tissue-specific risk coefficients and were used to derive patientspecific effective risk. The thirty patients had normalized effective dose of 3.7-10.4 mSv/100 mAs and normalized effective risk of 0.5-5.8 cases/1000 exposed persons/100 mAs. Normalized lung dose and risk of lung cancer correlated strongly with average chest diameter (correlation coefficient: r = -0.98 to -0.99). Normalized effective risk also correlated strongly with average chest diameter (r = -0.97 to -0.98). These strong correlations can be used to estimate patient-specific dose and risk prior to or after an imaging study to potentially guide healthcare providers in justifying CT examinations and to guide individualized protocol design and optimization.

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…

Thyroid Cancer in the Pediatric Age in Sicily: Influence of the Volcanic Environment.

PubMed

Russo, Marco; Malandrino, Pasqualino; Moleti, Mariacarla; D'Angelo, Antonio; Tavarelli, Martina; Sapuppo, Giulia; Giani, Fiorenza; Richiusa, Pierina; Squatrito, Sebastiano; Vigneri, Riccardo; Pellegriti, Gabriella

2017-03-01

Pediatric thyroid cancer (TC) is rare but its incidence is increasing. We analyzed incidence and characteristics of pediatric TC in Sicily and comparatively evaluated data from the volcanic and non-volcanic areas. All incident pediatric (0-19 years) TCs in Sicily between 2002-2009 were analyzed for the area of residence and compared to data for adults. A total of 54 differentiated TCs (DTC) and nine medullary TCs were diagnosed in Sicily in children between 2002-2009. DTC age standardized rate for the world population (ASRw) was 0.8/10 5 in females and 0.2/10 5 in males, with a higher incidence in the volcanic area (ASRw=1.4/10 5 in females, 0.5/10 5 in males) vs. the rest of Sicily (ASRw=0.6/10 5 in females, 0.1/10 5 in males). Pediatric TCs were larger in size and more frequently with extrathyroid extension and lymph-node involvement in comparison to TCs in adults. In the volcanic environment of Sicily, TC incidence is markedly increased in children, suggesting a short-term effect of unidentified carcinogens of volcanic origin. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Coping with pediatric cancer: strategies employed by children and their parents to manage cancer-related stressors during treatment.

PubMed

Hildenbrand, Aimee K; Clawson, Kathleen J; Alderfer, Melissa A; Marsac, Meghan L

2011-01-01

Pediatric cancer patients and their families face significant physical, emotional, and psychosocial challenges. Few studies have investigated how children manage these challenges and how parents may help in the process. This qualitative study aimed to explore common cancer-related stressors for children and to examine child coping and parental assistance in coping with these stressors during treatment. Fifteen children undergoing cancer treatment and their parents participated in semistructured interviews. Four themes emerged capturing cancer-related stressors: cancer treatment/side effects, distressing emotions, disruption in daily routines, and social challenges. Six themes emerged regarding child coping strategies that were classified within an approach/avoidance coping framework. Approach coping strategies included the following: cognitive restructuring, relaxation, practical strategies, seeking social support, and emotional expression. Distraction was the only avoidant coping strategy. Parents tended to encourage approach coping strategies (eg, cognitive restructuring, social support). Within families, few coping strategies were reported (child: M = 1.47, SD = 0.99; parent: M = 3.33, SD = 1.18), suggesting that early family-based interventions teaching coping techniques for cancer-related stressors may be beneficial.

Pediatric Psycho-oncology Care: Standards, Guidelines and Consensus Reports

PubMed Central

Wiener, Lori; Viola, Adrienne; Koretski, Julia; Perper, Emily Diana; Patenaude, Andrea Farkas

2014-01-01

Objective To identify existing guidelines, standards, or consensus-based reports for psychosocial care of children with cancer and their families. Purpose Psychosocial standards of care for children with cancer can systematize the approach to care and create a replicable model that can be utilized in pediatric hospitals around the world. Determining gaps in existing standards in pediatric psycho-oncology can guide development of useful evidence- and consensus-based standards. Methods The MEDLINE and PubMed databases were searched by investigators at two major pediatric oncology centers for existing guidelines, consensus-based reports, or standards for psychosocial care of pediatric cancer patients and their families published in peer-reviewed journals in English between 1980 and 2013. Results We located 27 articles about psychosocial care that met inclusion criteria: 5 set forth standards, 19 guidelines and 3 were consensus-based reports. None were sufficiently up-to-date, significantly evidence-based, comprehensive and specific enough to serve as a current standard for psychosocial care for children with cancer and their families. Conclusion Despite calls by a number of international pediatric oncology and psycho-oncology professional organizations about the urgency of addressing the psychosocial needs of the child with cancer in order to reduce suffering, there remains a need for development of a widely acceptable, evidence- and consensus-based, comprehensive standard of care to guide provision of essential psychosocial services to all pediatric cancer patients. PMID:24906202

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

PubMed

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

2016-12-01

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.

Use of Patient Registries and Administrative Datasets for the Study of Pediatric Cancer

PubMed Central

Rice, Henry E.; Englum, Brian R.; Gulack, Brian C.; Adibe, Obinna O.; Tracy, Elizabeth T.; Kreissman, Susan G.; Routh, Jonathan C.

2015-01-01

Analysis of data from large administrative databases and patient registries is increasingly being used to study childhood cancer care, although the value of these data sources remains unclear to many clinicians. Interpretation of large databases requires a thorough understanding of how the dataset was designed, how data were collected, and how to assess data quality. This review will detail the role of administrative databases and registry databases for the study of childhood cancer, tools to maximize information from these datasets, and recommendations to improve the use of these databases for the study of pediatric oncology. PMID:25807938

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 ...

Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders.

PubMed

Gupta, Saurabh; Gersing, Kenneth Ronald; Erkanli, Alaattin; Burt, Tal

2016-06-01

In 2004 the Food and Drug Administration issued a warning on the risk of suicidality in children and adolescents receiving antidepressants. This was followed by reports of changes in antidepressant prescription patterns, suicidality and other aggressive behaviors, but debate is continuing regarding the nature and magnitude of these changes. We examined a large physician database for impact of the warning on antidepressant prescriptions, suicidality and other aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in adult and pediatric patients. We analyzed electronic database covering over 100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning periods. We compared strength of the association between the measures and the time period with two tests. Multivariate logistic regression analyses were performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0 %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant prescription and 16.1 % were pediatric patients. In post-warning period, there was a greater reduction in adult versus pediatric antidepressant prescription rates. Logistic modeling showed greater likelihood of antidepressant prescription in MDD as compared with anxiety disorders in post-warning period. Pediatric patients were more likely than adults to receive fluoxetine during the post-warning period. There was an overall reduction in suicidality and other aggressive behaviors in the post-warning period. Regulatory warnings may have had an impact on antidepressant benefit/risk assessment and consequent utilization, therapeutic effects, and adverse events. Our observations suggest that psychiatrists may heed regulatory warnings, but may also exert professional independence and discrimination in their application.

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

Overcoming autopsy barriers in pediatric cancer research.

PubMed

Alabran, Jennifer L; Hooper, Jody E; Hill, Melissa; Smith, Sandra E; Spady, Kimberlee K; Davis, Lara E; Peterson, Lauren S; Malempati, Suman; Ryan, Christopher W; Acosta, Rae; Spunt, Sheri L; Keller, Charles

2013-02-01

More than 13,000 children annually in the United States and Canada under the age of 20 will be diagnosed with cancer at a mortality approaching 20% 1,2. Tumor samples obtained by autopsy provide an innovative way to study tumor progression, potentially aiding in the discovery of new treatments and increased survival rates. The purpose of this study was to identify barriers to autopsies and develop guidelines for requesting autopsies for research purposes. Families of children treated for childhood cancer were referred by patient advocacy groups and surveyed about attitudes and experiences with research autopsies. From 60 interviews, barriers to autopsy and tumor banking were identified. An additional 14 interviews were conducted with medical and scientific experts. Ninety-three percent of parents of deceased children did or would have consented to a research autopsy if presented with the option; however, only half of these families were given the opportunity to donate autopsy tissue for research. The most significant barriers were the physicians' reluctance to ask a grieving family and lack of awareness about research opportunities. The value of donating tumor samples to research via an autopsy should be promoted to all groups managing pediatric cancer patients. Not only does autopsy tumor banking offer a potentially important medical and scientific impact, but the opportunity to contribute this Legacy Gift of autopsy tumor tissue also creates a positive outlet for the grieving family. Taking these findings into account, our multidisciplinary team has developed a curriculum addressing key barriers. Copyright © 2012 Wiley Periodicals, Inc.

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

MeSS: A novel prognostic scale specific for pediatric well-differentiated thyroid cancer: a population-based, SEER outcomes study.

PubMed

Shayota, Brian J; Pawar, Shonali C; Chamberlain, Ronald S

2013-09-01

High-risk prognostic factors for adults with well-differentiated thyroid cancer (WDTC) have been well established, but the same is not true for pediatric patients. This study sought to determine whether validated adult prognostic systems are applicable to pediatric patients and to develop a novel prognostic scale that may better reflect outcomes in pediatric subgroups. We queried 62,007 cases of WDTC from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2009) to identify 895 patients <20 years of age with WDTC. Data abstracted included age, gender, race, histology type, primary tumor size, cancer stage, and mortality. Odds ratio and 95% confidence intervals were set and data were analyzed with SAS version 9.2. Among 895 pediatric WDTC patients, the overall cause-specific mortality was 0.8%. The presence of distant metastasis was associated with the worst prognosis (P = .0045) followed by larger primary tumor size (P = .0135) and male gender (P = .0162). When classified into low-, moderate-, and high-risk categories according to the distant metastasis (Me), larger primary tumor size (S), and male sex (S) (MeSS) algorithm, mortality rates were 0%, 2.7%, and 23%, respectively. Commonly used prognostic indices for WDTC in adults do not reliably predict poor outcomes among pediatric patients. Rather, a system based on MeSS is more applicable to pediatric patients. Patients who exhibit a high MeSS score have a significantly worse overall survival than those who do not express any MeSS characteristics. Copyright © 2013 Mosby, Inc. All rights reserved.

Endometrial cancer

MedlinePlus

... aggressive, and grade 3 is the most aggressive. Aggressive means that the cancer grows and spreads quickly. Treatment Treatment options include surgery, radiation therapy , and chemotherapy . Surgery to remove the uterus ( hysterectomy ) may be done in women with early stage 1 cancer. The doctor may ...

Experimental drug STA-8666 causes complete tumor regression in animal models of pediatric sarcomas | Center for Cancer Research

Cancer.gov

New studies from scientists in the NCI Center for Cancer Research’s (CCR) Pediatric Oncology Branch suggest that an experimental drug called STA-8666 could be an effective treatment for the childhood cancers Ewing sarcoma and rhabdomyosarcoma. In mouse models of these diseases, STA-8666 eliminated tumors and prolonged survival beyond that of animals treated with a related

Systematic review of antimicrobial lock therapy for prevention of central-line-associated bloodstream infections in adult and pediatric cancer patients.

PubMed

Norris, LeAnn B; Kablaoui, Farah; Brilhart, Maggie K; Bookstaver, P Brandon

2017-09-01

Central venous catheter (CVC) use is commonplace in cancer patients. Antimicrobial lock therapy (ALT), the instillation of a concentrated antimicrobial solution into the catheter lumen, is one method for preventing infection among CVCs. This systematic review discusses the effectiveness and safety of prophylactic ALT in cancer patients with CVCs. A literature search was performed using the Medline database and Google Scholar from inception until April 2016. The following terms were used: 'antimicrobial lock solution', 'antibiotic lock solution', 'oncology', 'hematology', 'pediatrics', 'prevention', 'cancer', 'catheter related bloodstream infections', 'central-line associated bloodstream infection' (CLABSI) and 'central venous catheter'. Studies evaluating prophylactic ALT in cancer patients alone were eligible for inclusion. Case reports, case series and in-vitro studies were excluded. In total, 78 articles were identified. Following all exclusions, 13 articles (three adult and 10 pediatric) were selected for evaluation. The most common agents utilized were vancomycin with heparin; ethanol; taurolidine; and minocycline with EDTA. Quality of evidence was moderate to high in adult studies and low to moderate in pediatric studies. Use of ALT decreased the incidence of CLABSI in the majority of studies; however, there were significant differences in definitions of CVC-related infection, dwell times and lock solutions. Lock therapy may be an adjunct in high-risk cancer patients for the prevention of CLABSI; higher quality evidence is needed for specific ALT recommendations. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Central Nervous System Disease, Education, and Race Impact Radiation Refusal in Pediatric Cancer Patients.

PubMed

Patel, Chirayu G; Stavas, Mark; Perkins, Stephanie; Shinohara, Eric T

2017-07-01

To investigate the determinants of radiation therapy refusal in pediatric cancer, we used the Surveillance, Epidemiology, and End Results registry to identify 24,421 patients who met the eligibility criteria, diagnosed between 1974 and 2012. Patients had any stage of cancer, were aged 0 to 19, and received radiation therapy or refused radiation therapy when it was recommended. One hundred twenty-eight patients (0.52%) refused radiation therapy when it was recommended. Thirty-two percent of patients who refused radiation therapy ultimately died from their cancer, at a median of 7 months after diagnosis (95% confidence interval, 3-11 mo), as compared with 29.0% of patients who did not refuse radiation therapy died from their cancer, at a median of 17 months after diagnosis (95% confidence interval, 17-18 mo). On multivariable analysis, central nervous system (CNS) site, education, and race were associated with radiation refusal. The odds ratio for radiation refusal for patients with CNS disease was 1.62 (P=0.009) as compared with patients without CNS disease. For patients living in a county with ≥10% residents having less than ninth grade education, the odds ratio for radiation refusal was 1.71 (P=0.008) as compared with patients living in a county with <10% residents having less than ninth grade education. Asian, Pacific Islander, Alaska Native, and American Indian races had an odds ratio of 2.12 (P=0.002) for radiation refusal as compared with black or white race. Although the radiation refusal rate in the pediatric cancer population is low, we show that CNS site, education level, and race are associated with a significant difference in radiation refusal.

MO-D-BRB-02: Pediatric Treatment Planning II: Applications of Proton Beams for Pediatric Treatment

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

Hua, C.

Most Medical Physicists working in radiotherapy departments see few pediatric patients. This is because, fortunately, children get cancer at a rate nearly 100 times lower than adults. Children have not smoked, abused alcohol, or been exposed to environmental carcinogens for decades, and of course, have not fallen victim to the aging process. Children get very different cancers than adults. Breast or prostate cancers, typical in adults, are rarely seen in children but instead a variety of tumors occur in children that are rarely seen in adults; examples are germinomas, ependymomas and primitive neuroectodermal tumors, which require treatment of the child’smore » brain or neuroblastoma, requiring treatment in the abdomen. The treatment of children with cancer using radiation therapy is one of the most challenging planning and delivery problems facing the physicist. This is because bones, brain, breast tissue, and other organs are more sensitive to radiation in children than in adults. Because most therapy departments treat mostly adults, when the rare 8 year-old patient comes to the department for treatment, the physicist may not understand the clinical issues of his disease which drive the planning and delivery decisions. Additionally, children are more prone than adults to developing secondary cancers after radiation. For bilateral retinoblastoma for example, an irradiated child has a 40% chance of developing a second cancer by age 50. The dosimetric tradeoffs made during the planning process are complex and require careful consideration for children treated with radiotherapy. In the first presentation, an overview of childhood cancers and their corresponding treatment techniques will be given. These can be some of the most complex treatments that are delivered in the radiation therapy department. These cancers include leukemia treated with total body irradiation, medulloblastoma, treated with craniospinal irradiation plus a conformal boost to the posterior

Examination of Aggression and Self Injury in Children with Autism Spectrum Disorders and Serious Behavioral Problems

PubMed Central

Carroll, Devon; Hallett, Victoria; McDougle, Christopher J.; Aman, Michael G.; McCracken, James T.; Tierney, Elaine; Arnold, L. Eugene; Sukhodolsky, Denis G.; Lecavalier, Luc; Handen, Benjamin; Swiezy, Naomi; Johnson, Cynthia; Bearss, Karen; Vitiello, Benedetto; Scahill, Lawrence

2014-01-01

Synopsis This study identified subtypes of aggression in a sample of 206 children (174 boys, 32 girls) with autism spectrum disorder (ASD) who participated in two risperidone trials conducted by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. The classification of aggression subtypes was based on a review of brief narratives documented at baseline. The narratives were derived from a parent interview about the child’s two most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and non-aggressive. The aggression and SIB group had the highest proportion of children with IQ below 70. Children in the hot aggression group were slightly younger and had higher scores on the ABC-Irritability subscale than the non-aggression group. The SIB only group had the highest ABC-Irritability score. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend our understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD. PMID:24231167

MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness.

PubMed

Planells-Ferrer, L; Urresti, J; Soriano, A; Reix, S; Murphy, D M; Ferreres, J C; Borràs, F; Gallego, S; Stallings, R L; Moubarak, R S; Segura, M F; Comella, J X

2014-09-04

Neuroblastoma (NBL) is the most common solid tumor in infants and accounts for 15% of all pediatric cancer deaths. Several risk factors predict NBL outcome: age at the time of diagnosis, stage, chromosome alterations and MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-Derived Homolog) amplification, which characterizes the subset of the most aggressive NBLs with an overall survival below 30%. MYCN-amplified tumors develop exceptional chemoresistance and metastatic capacity. These properties have been linked to defects in the apoptotic machinery, either by silencing components of the extrinsic apoptotic pathway (e.g. caspase-8) or by overexpression of antiapoptotic regulators (e.g. Bcl-2, Mcl-1 or FLIP). Very little is known on the implication of death receptors and their antagonists in NBL. In this work, the expression levels of several death receptor antagonists were analyzed in multiple human NBL data sets. We report that Lifeguard (LFG/FAIM2 (Fas apoptosis inhibitory molecule 2)/NMP35) is downregulated in the most aggressive and undifferentiated tumors. Intringuingly, although LFG has been initially characterized as an antiapoptotic protein, we have found a new association with NBL differentiation. Moreover, LFG repression resulted in reduced cell adhesion, increased sphere growth and enhanced migration, thus conferring a higher metastatic capacity to NBL cells. Furthermore, LFG expression was found to be directly repressed by MYCN at the transcriptional level. Our data, which support a new functional role for a hitherto undiscovered MYCN target, provide a new link between MYCN overexpression and increased NBL metastatic properties.

MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness

PubMed Central

Planells-Ferrer, L; Urresti, J; Soriano, A; Reix, S; Murphy, D M; Ferreres, J C; Borràs, F; Gallego, S; Stallings, R L; Moubarak, R S; Segura, M F; Comella, J X

2014-01-01

Neuroblastoma (NBL) is the most common solid tumor in infants and accounts for 15% of all pediatric cancer deaths. Several risk factors predict NBL outcome: age at the time of diagnosis, stage, chromosome alterations and MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-Derived Homolog) amplification, which characterizes the subset of the most aggressive NBLs with an overall survival below 30%. MYCN-amplified tumors develop exceptional chemoresistance and metastatic capacity. These properties have been linked to defects in the apoptotic machinery, either by silencing components of the extrinsic apoptotic pathway (e.g. caspase-8) or by overexpression of antiapoptotic regulators (e.g. Bcl-2, Mcl-1 or FLIP). Very little is known on the implication of death receptors and their antagonists in NBL. In this work, the expression levels of several death receptor antagonists were analyzed in multiple human NBL data sets. We report that Lifeguard (LFG/FAIM2 (Fas apoptosis inhibitory molecule 2)/NMP35) is downregulated in the most aggressive and undifferentiated tumors. Intringuingly, although LFG has been initially characterized as an antiapoptotic protein, we have found a new association with NBL differentiation. Moreover, LFG repression resulted in reduced cell adhesion, increased sphere growth and enhanced migration, thus conferring a higher metastatic capacity to NBL cells. Furthermore, LFG expression was found to be directly repressed by MYCN at the transcriptional level. Our data, which support a new functional role for a hitherto undiscovered MYCN target, provide a new link between MYCN overexpression and increased NBL metastatic properties. PMID:25188511

Parental spirituality in life-threatening pediatric cancer.

PubMed

Nicholas, David B; Barrera, Maru; Granek, Leeat; D'Agostino, Norma Mammone; Shaheed, Jenny; Beaune, Laura; Bouffet, Eric; Antle, Beverley

2017-01-01

This study addressed parental spirituality in the context of pediatric cancer with a poor prognosis. Drawing upon previous research implementing a longitudinal grounded theory design examining parental hope, 35 parents were interviewed regarding their experiences with an emergent description of the role of spirituality in parents' daily lives. Spirituality included religious beliefs and practices, notions of a higher force or cosmos, relationship with a divine being, as well as elements emerging from meaning-making and relationships. Parental expectations of spirituality remained relatively constant across data collection time points (3-9 months postdiagnosis), although limited variation occurred relative to shifting circumstance (e.g., deterioration of the child's condition). Spirituality appeared to offer: greater acceptance of parents' inability to protect their child from harm related to her/his life-threatening illness, guidance and emotion decompression, and support from one's faith community. Recommendations for integrating spiritual assessment in clinical care practice are offered.

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

Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial.

PubMed

Marous, Miguelle; Huang, Wen-Yi; Rabkin, Charles S; Hayes, Richard B; Alderete, John F; Rosner, Bernard; Grubb, Robert L; Winter, Anke C; Sutcliffe, Siobhan

2017-08-01

Results from previous sero-epidemiologic studies of Trichomonas vaginalis infection and prostate cancer (PCa) support a positive association between this sexually transmitted infection and aggressive PCa. However, findings from previous studies are not entirely consistent, and only one has investigated the possible relation between T. vaginalis seropositivity and PCa in African-American men who are at highest risk of both infection and PCa. Therefore, we examined this possible relation in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, including separate analyses for aggressive PCa and African-American men. We included a sample of participants from a previous nested case-control study of PCa, as well as all additional Caucasian, aggressive, and African-American cases diagnosed since the previous study (total n = 438 Gleason 7 Caucasian cases, 487 more advanced Caucasian cases (≥Gleason 8 or stage III/IV), 201 African-American cases, and 1216 controls). We tested baseline sera for T. vaginalis antibodies. No associations were observed for risk of Gleason 7 (odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.55-1.37) or more advanced (OR = 0.90, 95% CI 0.58-1.38) PCa in Caucasian men, or for risk of any PCa (OR = 1.06, 95% CI 0.67-1.68) in African-American men. Our findings do not support an association between T. vaginalis infection and PCa.

Presentation of suspected pediatric uveitis.

PubMed

Saeed, Muhammad Usman; Raza, Syed Hamid; Goyal, Sudeshna; Cleary, Gavin; Newman, William David; Chandna, Arvind

2014-01-01

Presentation of suspected pediatric uveitis: Pediatric uveitis is usually managed in specialized ophthalmic centers in the UK. Meaningful data acquisition in these clinics may be helpful in clinical governance, and healthcare planning in a specialty that is gradually changing due to changes in treatment choices. Retrospective analysis of prospectively acquired data in the Liverpool pediatric uveitis database was performed. Analysis of our data, based on 147 patients, with a mean age of 10 years, indicated a female to male ratio of 2:1. 99% of patients were Caucasian. Our data indicates 86% of all patients attending the uveitis clinic were diagnosed with juvenile idiopathic arthritis, followed by intermediate uveitis 5% and idiopathic uveitis 4%. 46% of patients required treatment. Systemic treatment included methotrexate (34%), prednisolone (14%), etanercept (6%), ciclosporin (6%), mycophenolate (3%), and infliximab (1%). Severe visual loss (defined by counting fingers or below vision) was seen in 10 eyes despite appropriately treated chronic uveitis. Our data shows uveitis-related ocular morbidity in a predominantly pediatric Caucasian population. Patients with severe and chronic uveitis may experience significant uveitis-related complications and subsequent visual loss despite aggressive treatment.

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. © 2013.

Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model

PubMed Central

Zhou, Kejin; Nguyen, Liem H.; Miller, Jason B.; Yan, Yunfeng; Kos, Petra; Xiong, Hu; Li, Lin; Hao, Jing; Minnig, Jonathan T.; Siegwart, Daniel J.

2016-01-01

RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC50 < 0.02 mg/kg siRNA against FVII (siFVII)] in dose–response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors (>75 mg/kg dendrimer repeated dosing). Delivery of let-7g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer’s own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs. PMID:26729861

Timing of palliative care needs reporting and aggressiveness of care near the end of life in metastatic lung cancer: A national registry-based study.

PubMed

Goldwasser, François; Vinant, Pascale; Aubry, Régis; Rochigneux, Philippe; Beaussant, Yvan; Huillard, Olivier; Morin, Lucas

2018-05-09

Early integration of palliative care for patients with metastatic lung cancer improves their quality of life and survival and reduces the aggressiveness of care near the end of life. This study examined the association between the timing of palliative care needs reporting and the aggressiveness of end-of-life care. This retrospective cohort study used the French National Hospital Registry to identify all hospitalized adults (≥20 years old) who died of metastatic lung cancer in France between 2010 and 2013. It compared the use of care and treatments near the end of life as a function of the timing of the first reporting of palliative care needs. The use of chemotherapy and the use of invasive ventilation were defined as primary outcomes. Propensity score weighting was used to control for potential confounders. Among a total of 64,950 deceased patients with metastatic lung cancer, the reporting of palliative care needs was characterized as timely (from 91 to 31 days before death) for 26.3%, late (from 30 to 8 days before death) for 31.5%, and very late (from 7 to 0 days before death) for 12.8%. Palliative care needs were not reported for 19,106 patients (29.4%). Patients with timely reporting of palliative care needs had the earliest and most progressive decrease in the use of anticancer therapy. The use of invasive ventilation also increased with a delay in palliative care needs reporting. There is a clear association between the timing of palliative care needs reporting and the aggressiveness of care near the end of life. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

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. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

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

Relilgious beliefs and practices of Taiwanese parents of pediatric patients with cancer.

PubMed

Yeh, C H

2001-12-01

The aim of this study was to increase understanding of religious beliefs and practices among Taiwanese parents of pediatric patients. Parents of 63 pediatric patients with cancer were interviewed to explore their related religious beliefs and practices, ie, worship at temple, drawing Chien, and divinations. Rituals were used to diminish the harmful effects of the child's disease, such as temple ceremonies, changing the child's name, and taking "Fu" water. Such practices were generally undertaken with a lack of medical guidance from oncologists largely because of poor interactions between parents and oncologists. The findings suggest that discovering a caregiver's worldview and cultural values is important to establish holistic nursing practices. Because immigrants increasingly move around the world, Taiwanese parents become a culturally diverse clientele for healthcare professionals who have to be aware of the existing cultural differences in healthcare values, patterns, and practices, particularly between Western and Eastern cultures.

Experimental drug STA-8666 causes complete tumor regression in animal models of pediatric sarcomas | Center for Cancer Research

Cancer.gov

New studies from scientists in the NCI Center for Cancer Research’s (CCR) Pediatric Oncology Branch suggest that an experimental drug called STA-8666 could be an effective treatment for the childhood cancers Ewing sarcoma and rhabdomyosarcoma. In mouse models of these diseases, STA-8666 eliminated tumors and prolonged survival beyond that of animals treated with a related drug, irinotecan. Read more…

On complexity and homogeneity measures in predicting biological aggressiveness of prostate cancer; Implication of the cellular automata model of tumor growth.

PubMed

Tanase, Mihai; Waliszewski, Przemyslaw

2015-12-01

We propose a novel approach for the quantitative evaluation of aggressiveness in prostate carcinomas. The spatial distribution of cancer cell nuclei was characterized by the global spatial fractal dimensions D0, D1, and D2. Two hundred eighteen prostate carcinomas were stratified into the classes of equivalence using results of ROC analysis. A simulation of the cellular automata mix defined a theoretical frame for a specific geometric representation of the cell nuclei distribution called a local structure correlation diagram (LSCD). The LSCD and dispersion Hd were computed for each carcinoma. Data mining generated some quantitative criteria describing tumor aggressiveness. Alterations in tumor architecture along progression were associated with some changes in both shape and the quantitative characteristics of the LSCD consistent with those in the automata mix model. Low-grade prostate carcinomas with low complexity and very low biological aggressiveness are defined by the condition D0 < 1.545 and Hd < 38. High-grade carcinomas with high complexity and very high biological aggressiveness are defined by the condition D0 > 1.764 and Hd < 38. The novel homogeneity measure Hd identifies carcinomas with very low aggressiveness within the class of complexity C1 or carcinomas with very high aggressiveness in the class C7. © 2015 Wiley Periodicals, Inc.

Epidemiologic, Racial and Healthographic Mapping of Delaware Pediatric Cancer: 2004–2014

PubMed Central

Holmes, Laurens; Vandenberg, Jonathan; McClarin, Lavisha; Dabney, Kirk

2015-01-01

Childhood cancer remains the leading cause of disease-related death among children 0 to 14 years and incidence varies by race, ethnicity, sex, geographic locale, and age at onset. However, data are unavailable in some regions, indicative of a need for such information for cancer awareness, education and prevention program. We utilized retrospective epidemiologic design to assess and characterize pediatric tumors in the Nemours Electronic Medical Records, between 2004 and 2014. Tumor frequency and children population size were used to determine the period prevalence as cumulative incidence (CI) proportion, as well as chi-square and Poisson Regression. The CI for overall childhood cancer in Delaware was 234 per 100,000 children, and varied by race, black (273 per 100,000), white (189 per 100,000). Similarly, sex variability was observed in CI, boys (237 per 100,000) and girls (230 per 100,000). The most commonly diagnosed malignancies were acute lymphoblastic leukemia (ALL), Central Nervous System (CNS)/brain and renal cancer. The geographic locales with relatively higher cancer CI in the state of DE were zip codes 19804 and 19960, but this does not imply cancer clustering. Differences in overall childhood cancer distribution occurred by race, sex, geography, and age. These findings are indicative of the need for cancer-specific health education, awareness and prevention programs in reducing the observed disparities in Delaware. PMID:26703649

Positive schemas, psychopathology, and quality of life in children with pediatric cancer: A pilot study.

PubMed

McArthur, Brae Anne; Strother, Douglas; Schulte, Fiona

2017-01-01

Research in the area of pediatric oncology has shown that although some children and youth diagnosed with this disease cope adaptively after their diagnosis, others continue to have long-term psychosocial difficulties. The potential mechanisms that may protect against the experience of psychopathology and poor quality of life within this population are not well known. The purpose of this pilot study was to utilize a new comprehensive measure of positive schemas to better understand the relationship between positive schemas, quality of life, and psychopathology, for children on active treatment for cancer. Participants were 22 patients, aged 8-18 years, being treated in a pediatric oncology clinic. Patients and parents completed measures of positive schemas, quality of life, and psychopathology. The mean age at time of initial diagnosis of the patient sample was 11.6 years. Child-reported positive schemas were significantly related to child-reported child quality of life (r = 0.46, p = 0.03). This is the first study to examine positive schemas within a pediatric oncology sample. Future research is needed to further explore facets of positive schemas that may be particularly relevant to child psychological functioning in a pediatric oncology population.

A20 promotes metastasis of aggressive basal-like breast cancers through multi-monoubiquitylation of Snail1.

PubMed

Lee, Ji-Hyung; Jung, Su Myung; Yang, Kyung-Min; Bae, Eunjin; Ahn, Sung Gwe; Park, Jin Seok; Seo, Dongyeob; Kim, Minbeom; Ha, Jihoon; Lee, Jaewon; Kim, Jun-Hyeong; Kim, Jun Hwan; Ooshima, Akira; Park, Jinah; Shin, Donghyuk; Lee, Youn Sook; Lee, Sangho; van Loo, Geert; Jeong, Joon; Kim, Seong-Jin; Park, Seok Hee

2017-10-01

Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.

A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease.

PubMed

Kaur, Punit; Nagaraja, Ganachari M; Zheng, Hongying; Gizachew, Dawit; Galukande, Moses; Krishnan, Sunil; Asea, Alexzander

2012-03-27

Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems. To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER), progesterone receptor (PgR) or the gene for human epidermal growth factor receptor 2 (HER2). As a control, we produced a stable triple-positive breast cancer (TPBC) cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis. We isolated tumor-initiating cells (TICs) by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1) and seventy-two kDa heat shock protein (Hsp72/HspA1A). Taken together, we have developed a TNBC-TICs model system

A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease

PubMed Central

2012-01-01

Background Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems. Methods To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER), progesterone receptor (PgR) or the gene for human epidermal growth factor receptor 2 (HER2). As a control, we produced a stable triple-positive breast cancer (TPBC) cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis. Results We isolated tumor-initiating cells (TICs) by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1) and seventy-two kDa heat shock protein (Hsp72/HspA1A). Conclusions Taken together, we

Conditional Survival in Pediatric Malignancies: Analysis of data from the Childhood Cancer Survivor Study and the Surveillance, Epidemiology and End Results Program

PubMed Central

Mertens, Ann C; Yong, Jian; Dietz, Andrew; Kreiter, Erin; Yasui, Yutaka; Bleyer, Archie; Armstrong, Gregory T; Robison, Leslie L; Wasilewski-Masker, Karen

2015-01-01

Background Long-term survivors of pediatric cancer are at risk for life-threatening late effects of their cancer. Previous studies have shown excesses in long-term mortality within high-risk groups defined by demographic and treatment characteristics. Methods To investigate conditional survival in a pediatric cancer population, we performed an analysis of conditional survival in the original Childhood Cancer Survivor Study (CCSS) cohort and the Surveillance, Epidemiology and End Results (SEER) database registry. The overall probability of death for patients in 5 years and 10 years after they survived 5, 10, 15, and 20 years since cancer diagnosis, and cause-specific death in 10 years for 5-year survivors were estimated using the cumulative incidence method. Results Among CCSS and SEER patients who were alive 5 years post cancer diagnosis, within each diagnosis group at least 92% are alive in the subsequent 5 years, except leukemia patients of whom only 88% of 5-year survivors remain alive in the subsequent 5 years. The probability of all-cause mortality in the next 10 years on patients who survived at least 5 years after diagnosis, was 8.8% in CCSS and 10.6% in SEER, approximately three quarter of which were due to neoplasms as causes of death. Conclusion The risk of death of pediatric cancer survivors in 10 years can vary between diagnosis groups by at most 12% even up to 20 years post diagnosis. This information is clinically important in counseling patients on their conditional survival, particularly when survivors are seen in long-term follow-up. PMID:25557134

CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

PubMed

Taghizadeh, Rouzbeh; Noh, Minsoo; Huh, Yang Hoon; Ciusani, Emilio; Sigalotti, Luca; Maio, Michele; Arosio, Beatrice; Nicotra, Maria R; Natali, PierGiorgio; Sherley, James L; La Porta, Caterina A M

2010-12-22

A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone. The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

[Difficulties in communication with parents of pediatric cancer patients during the transition to palliative care].

PubMed

Nyirő, Judit; Hauser, Péter; Zörgő, Szilvia; Hegedűs, Katalin

2017-07-01

Adequate communication by medical personnel is especially important at certain points during the treatment of childhood cancer patients. To investigate the timing and manner of communication with parents concerning the introduction of palliative care in pediatric oncology. Structured interviews, containing 14 questions, were carried out with physicians working in pediatric oncology (n = 22). Codes were generated inductively with the aid of Atlas.ti 6.0 software. Interviews show a tendency of a one-step transition to palliative care following curative therapy. Another expert is usually involved in communication, most likely a psychologist. Regarding communication, there are expressions utilized or avoided, such as expressing clarity, self-defense and empathy. The communication of death and dying was the most contradictory. This was the first investigation regarding communication in pediatric palliative care in Hungary. Our results show that a modern perspective of palliative communication is present, but necessitates more time to become entrenched. Orv Hetil. 2017; 158(30): 1175-1181.

Expression between African American and Caucasian Prostate Cancer Tissue Reveals that Stroma is the Site of Aggressive Changes

PubMed Central

Kinseth, Matthew A.; Jia, Zhenyu; Rahmatpanah, Farahnaz; Sawyers, Anne; Sutton, Manuel; Wang-Rodriguez, Jessica; Mercola, Dan; McGuire, Kathleen L.

2013-01-01

In prostate cancer, race/ethnicity is the highest risk factor after adjusting for age. African Americans have more aggressive tumors at every clinical stage of the disease, resulting in poorer prognosis and increased mortality. A major barrier to identifying crucial gene activity differences is heterogeneity, including tissue composition variation intrinsic to the histology of prostate cancer. We hypothesized differences in gene expression in specific tissue types would reveal mechanisms involved in the racial disparities of prostate cancer. We examined seventeen pairs of arrays for African Americans and Caucasians that were formed by closely matching the samples based on the known tissue type composition of the tumors. Using pair wise T-test we found significantly altered gene expression between African Americans and Caucasians. Independently, we performed multiple linear regression analyses to associate gene expression with race considering variation in percent tumor and stroma tissue. The majority of differentially expressed genes were associated with tumor-adjacent stroma rather than tumor tissue. Extracellular matrix, Integrin family and signaling mediators of the epithelial-to-mesenchymal transition pathways were all down regulated in stroma of African Americans. Using MetaCore (GeneGo Inc.) analysis, we observed that 35% of significant (p < 10-3) pathways identified EMT and 25% identified immune response pathways especially for Interleukins -2, -4, -5, -6, -7, -10, -13, -15 and -22 as the major changes. Our studies reveal that altered immune and EMT processes in tumor-adjacent stroma may be responsible for the aggressive nature of prostate cancer in African Americans. PMID:23754304

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion

PubMed Central

Hussein, Deema; Punjaruk, Wiyada; Storer, Lisa C.D.; Shaw, Lucy; Ottoman, Ramadan; Peet, Andrew; Miller, Suzanne; Bandopadhyay, Gagori; Heath, Rachel; Kumari, Rajendra; Bowman, Karen J.; Braker, Paul; Rahman, Ruman; Jones, George D.D.; Watson, Susan; Lowe, James; Kerr, Ian D.; Grundy, Richard G.; Coyle, Beth

2011-01-01

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3–4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents. PMID:20978004

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion.

PubMed

Hussein, Deema; Punjaruk, Wiyada; Storer, Lisa C D; Shaw, Lucy; Othman, Ramadhan; Ottoman, Ramadan; Peet, Andrew; Miller, Suzanne; Bandopadhyay, Gagori; Heath, Rachel; Kumari, Rajendra; Bowman, Karen J; Braker, Paul; Rahman, Ruman; Jones, George D D; Watson, Susan; Lowe, James; Kerr, Ian D; Grundy, Richard G; Coyle, Beth

2011-01-01

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3-4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents.

Quality of life among pediatric patients with cancer: Contributions of time since diagnosis and parental chronic stress.

PubMed

Hamner, Taralee; Latzman, Robert D; Latzman, Natasha E; Elkin, T David; Majumdar, Suvankar

2015-07-01

Pediatric cancer is associated with a host of negative psychosocial consequences; however, outcomes vary extensively suggesting a need to better understand this variation. Empirical research suggests a positive association between time since diagnosis (TSD) and Quality of Life (QoL). In addition to TSD, family stressors have been found to be particularly important in predicting QoL among children. The current study examined parental chronic stress beyond TSD in explanation of QoL functioning among a sample of pediatric patients with cancer. Participants included 43 pediatric patients aged 5-18 years (M(age) = 10.2 ± 3.6) who were undergoing oncological treatment. Parents reported on TSD, child's QoL, and their own chronic stress. TSD was associated with greater physical functioning (r = 0.30, P < 0.05). Parental chronic stress was associated with poorer emotional (r = -0.54, P < 0.01), physical (r = -0.41, P < 0.01), and social functioning (r = -0.44, P < 0.01). Further, hierarchal linear regression analyzes indicated parental chronic stress contributed incrementally beyond TSD in the explanation of physical (β = -0.37, t = -2.58, P < 0.01), emotional (β = -0.47, t = -3.51, P < 0.00), and social functioning (β = -0.38, t = -2.67, P < 0.01). Parental chronic stress is associated with reduced levels of emotional, physical, and social functioning among pediatric patients. Future research is needed to further investigate the process by which chronic stress within the family interferes with adaptive coping among pediatric patients. In addition, clinical services may benefit from increased consideration of family factors, such as parental chronic stress, during oncological treatment. © 2015 Wiley Periodicals, Inc.

NCI, FNLCR Help Launch Pediatric MATCH Precision Medicine Trial | Poster

Cancer.gov

The National Cancer Institute and Children’s Oncology Group recently opened enrollment for a new Phase II trial of personalized precision cancer therapies. Called the Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH), the trial seeks to treat children and adolescents aged 1­–21 whose solid tumors have failed to respond to or re-emerged after traditional cancer

NCI, FNLCR Help Launch Pediatric MATCH Precision Medicine Trial | Poster

Cancer.gov

The National Cancer Institute and Children’s Oncology Group recently opened enrollment for a new Phase II trial of personalized precision cancer therapies. Called the Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH), the trial seeks to treat children and adolescents aged 1­–21 whose solid tumors have failed to respond to or re-emerged after traditional cancer treatments.

Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells.

PubMed

Peak, Taylor C; Praharaj, Prakash P; Panigrahi, Gati K; Doyle, Michael; Su, Yixin; Schlaepfer, Isabel R; Singh, Ravi; Vander Griend, Donald J; Alickson, Julie; Hemal, Ashok; Atala, Anthony; Deep, Gagan

2018-05-23

The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSC Exo ) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ± 0.9 nm) and concentration of exosomes (5.23 × 10 10 ±1.99 × 10 9 per ml) secreted by PLSC. PLSC Exo treatment strongly inhibited the viability of enzalutamide-sensitive and -resistant PCa cell lines (C4-2B, CWR-R1, and LNCaP cells). Interestingly, PLSC Exo treatment had no effect on the viability of a non-neoplastic human prostate cell line (PREC-1). Mass spectrometry (MS) analyses showed that PLSC Exo are loaded with 241 proteins and mainly with saturated fatty acids. Further, Ingenuity Pathway Analysis analyses of proteins loaded in PLSC Exo suggested the role of retinoic acid receptor/liver x receptor pathways in their biological effects. Together, these results suggest the novel selective anti-cancer effects of PLSC Exo against aggressive PCa cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Vocal Cord Palsy in Children With Cancer: A 10-Year Analysis of UK Pediatric Intensive Care Admissions.

PubMed

Capsomidis, Anna; Hall, Andrew; Daya, Hamid; Round, Jonathan; Lancaster, Donna; Bate, Jessica

2017-05-01

Vocal cord palsy (VCP) is a rare but potentially life-threatening complication in children with cancer. This study reviews UK Intensive Care admissions for children with cancer and VCP using data obtained from the Pediatric Intensive Care Audit Network (PICANet) database. 26 children with cancer and VCP were admitted to intensive care from 2002 to 2012. The majority of admissions (23/26) required respiratory intervention (17 invasive ventilation, 8 noninvasive ventilation, and 5 tracheostomy). VCP should be considered early in children with cancer who present with signs of upper airway obstruction, especially in those receiving vinca-alkaloids as VCP is likely to be reversible.

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Evaluating Early Case Capture of Pediatric Cancers in Seven Central Cancer Registries in the United States, 2013

PubMed Central

Neri, Antonio; Rohan, Elizabeth; Clerkin, Castine; Underwood, J. Michael; Ryerson, A. Blythe; Stewart, Sherri L.

2016-01-01

Objective Cancer is the second-leading cause of death in children, but incidence data are not available until two years after diagnosis, thereby delaying data dissemination and research. An early case capture (ECC) surveillance program was piloted in seven state cancer registries to register pediatric cancer cases within 30 days of diagnosis. We sought to determine the quality of ECC data and understand pilot implementation. Methods We used quantitative and qualitative methods to evaluate ECC. We assessed data quality by comparing demographic and clinical characteristics from the initial ECC submission to a resubmission of ECC pilot data and to the most recent year of routinely collected cancer data for each state individually and in aggregate. We conducted telephone focus groups with registry staff to determine ECC practices and difficulties in August and September 2013. Interviews were recorded, transcribed, and coded to identify themes. Results Comparing ECC initial submissions with submissions for all states, ECC data were nationally representative for age (9.7 vs. 9.9 years) and sex (673 of 1,324 [50.9%] vs. 42,609 of 80,547 [52.9%] male cases), but not for primary site (472 of 1,324 [35.7%] vs. 27,547 of 80,547 [34.2%] leukemia/lymphoma cases), behavior (1,219 of 1,324 [92.1%] vs. 71,525 of 80,547 [88.8%] malignant cases), race/ethnicity (781 of 1,324 [59.0%] vs. 64,518 of 80,547 [80.1%] white cases), or diagnostic confirmation (1,233 of 1,324 [93.2%] vs. 73,217 of 80,547 [90.9%] microscopically confirmed cases). When comparing initial ECC data with resubmission data, differences were seen in race/ethnicity (808 of 1,324 [61.1%] vs. 1,425 of 1,921 [74.2%] white cases), primary site (475 of 1,324 [35.9%] vs. 670 of 1,921 [34.9%] leukemia/lymphoma cases), and behavior (1,215 of 1,324 [91.8%] vs. 1,717 of 1,921 [89.4%] malignant cases). Common themes from focus group analysis included implementation challenges and facilitators, benefits of ECC, and utility of

Evaluating Early Case Capture of Pediatric Cancers in Seven Central Cancer Registries in the United States, 2013.

PubMed

Puckett, Mary; Neri, Antonio; Rohan, Elizabeth; Clerkin, Castine; Underwood, J Michael; Ryerson, A Blythe; Stewart, Sherri L

2016-01-01

Cancer is the second-leading cause of death in children, but incidence data are not available until two years after diagnosis, thereby delaying data dissemination and research. An early case capture (ECC) surveillance program was piloted in seven state cancer registries to register pediatric cancer cases within 30 days of diagnosis. We sought to determine the quality of ECC data and understand pilot implementation. We used quantitative and qualitative methods to evaluate ECC. We assessed data quality by comparing demographic and clinical characteristics from the initial ECC submission to a resubmission of ECC pilot data and to the most recent year of routinely collected cancer data for each state individually and in aggregate. We conducted telephone focus groups with registry staff to determine ECC practices and difficulties in August and September 2013. Interviews were recorded, transcribed, and coded to identify themes. Comparing ECC initial submissions with submissions for all states, ECC data were nationally representative for age (9.7 vs. 9.9 years) and sex (673 of 1,324 [50.9%] vs. 42,609 of 80,547 [52.9%] male cases), but not for primary site (472 of 1,324 [35.7%] vs. 27,547 of 80,547 [34.2%] leukemia/lymphoma cases), behavior (1,219 of 1,324 [92.1%] vs. 71,525 of 80,547 [88.8%] malignant cases), race/ethnicity (781 of 1,324 [59.0%] vs. 64,518 of 80,547 [80.1%] white cases), or diagnostic confirmation (1,233 of 1,324 [93.2%] vs. 73,217 of 80,547 [90.9%] microscopically confirmed cases). When comparing initial ECC data with resubmission data, differences were seen in race/ethnicity (808 of 1,324 [61.1%] vs. 1,425 of 1,921 [74.2%] white cases), primary site (475 of 1,324 [35.9%] vs. 670 of 1,921 [34.9%] leukemia/lymphoma cases), and behavior (1,215 of 1,324 [91.8%] vs. 1,717 of 1,921 [89.4%] malignant cases). Common themes from focus group analysis included implementation challenges and facilitators, benefits of ECC, and utility of ECC data. ECC provided data

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study.

PubMed

Ahmed, Nabil; El-Mahallawy, Hadir A; Ahmed, Ibrahim A; Nassif, Shimaa; El-Beshlawy, Aamal; El-Haddad, Alaa

2007-11-01

Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care. Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control). Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization, and cost between both groups. A prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated on an outpatient basis. We found a statistically significant difference between the duration of hospitalization of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P < 0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications. We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization. (c) 2007 Wiley-Liss, Inc.

Chemotherapy versus supportive care alone in pediatric palliative care for cancer: comparing the preferences of parents and health care professionals.

PubMed

Tomlinson, Deborah; Bartels, Ute; Gammon, Janet; Hinds, Pamela S; Volpe, Jocelyne; Bouffet, Eric; Regier, Dean A; Baruchel, Sylvain; Greenberg, Mark; Barrera, Maru; Llewellyn-Thomas, Hilary; Sung, Lillian

2011-11-22

The choice between palliative chemotherapy (defined as the use of cytotoxic medications delivered intravenously for the purpose of our study) and supportive care alone is one of the most difficult decisions in pediatric oncology, yet little is known about the preferences of parents and health care professionals. We compared the strength of these preferences by considering children's quality of life and survival time as key attributes. In addition, we identified factors associated with the reported preferences. We included parents of children whose cancer had no reasonable chance of being cured and health care professionals in pediatric oncology as participants in our study. We administered separate interviews to parents and to health care professionals. Visual analogue scales were shown to respondents to illustrate the anticipated level of the child's quality of life, the expected duration of survival and the probability of cure (shown only to health care professionals). Respondents were then asked which treatment option they would favour given these baseline attributes. In addition, respondents reported what factors might affect such a decision and ranked all factors identified in order of importance. The primary measure was the desirability score for supportive care alone relative to palliative chemotherapy, as obtained using the threshold technique. A total of 77 parents and 128 health care professionals participated in our study. Important factors influencing the decision between therapeutic options were child quality-of-life and survival time among both parents and health care professionals. Hope was particularly important to parents. Parents significantly favoured chemotherapy (42/77, 54.5%) compared with health care professionals (20/128, 15.6%; p < 0.0001). The opinions of the physician and child significantly influenced the parents' desire for supportive care; for health care professionals, the opinions of parents and children were significant factors

Hypercalcemia and hypophosphatemia among preterm infants receiving aggressive parenteral nutrition.

PubMed

Brener Dik, Pablo H; Galletti, María F; Bacigalupo, Leticia T; Fernández Jonusas, Silvia; L Mariani, Gonzalo

2018-06-01

Aggressive parenteral nutrition is the standard of care among very-low-birth weight preterm infants. However, in recent studies, its impact on short-term outcomes, has been evaluated. The objective was to compare the prevalence of hypercalcemia and hypophosphatemia among preterm infants receiving aggressive or standard parenteral nutrition. Observational, retrospective study comparing a group of preterm infants weighing less than 1250 grams who received aggressive parenteral nutrition with a historical control group. The prevalence of hypercalcemia was estimated and its association with aggressive parenteral nutrition was searched adjusting by confounders. The mean phosphate level was estimated for the control group by linear regression and was compared to the value in the other group. Forty patients per group were included. The prevalence of hypercalcemia was higher in the group who received aggressive parenteral nutrition (87.5% versus 35%, p= 0.001). Aggressive parenteral nutrition was associated with hypercalcemia when adjusting by birth weight, intrauterine growth restriction, amino acid, and calorie intake (adjusted odds ratio: 21.8, 95% confidence interval [CI]: 3.7-128). The mean calcium level was different between both groups (p= 0.002). Infants who received aggressive parenteral nutrition had more sepsis without reaching statistical significance and the mean phosphate level was lower than that estimated for the control group (p= 0.04). The prevalence of hypophosphatemia in this group was 90% (95% CI: 76-97%). Our data show an association between hypercalcemia/hypophosphatemia and aggressive parenteral nutrition. It is recommended to frequently monitor calcium and phosphate levels since they might be associated with adverse clinical outcomes. Sociedad Argentina de Pediatría.

Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology.

PubMed

Fenger, Joelle M; London, Cheryl A; Kisseberth, William C

2014-01-01

Osteosarcoma (OSA) is the most common form of malignant bone cancer in children and dogs, although the disease occurs in dogs approximately 10 times more frequently than in people. Multidrug chemotherapy and aggressive surgical techniques have improved survival; however, new therapies for OSA are critical, as little improvement in survival times has been achieved in either dogs or people over the past 15 years, even with significant efforts directed at the incorporation of novel therapeutic approaches. Both clinical and molecular evidence suggests that human and canine OSA share many key features, including tumor location, presence of microscopic metastatic disease at diagnosis, development of chemotherapy-resistant metastases, and altered expression/activation of several proteins (e.g. Met, ezrin, phosphatase and tensin homolog, signal transducer and activator of transcription 3), and p53 mutations, among others. Additionally, canine and pediatric OSA exhibit overlapping transcriptional profiles and shared DNA copy number aberrations, supporting the notion that these diseases are similar at the molecular level. This review will discuss the similarities between pediatric and canine OSA with regard to histology, biologic behavior, and molecular genetic alterations that indicate canine OSA is a relevant, spontaneous, large animal model of the pediatric disease and outline how the study of naturally occurring OSA in dogs will offer additional insights into the biology and future treatment of this disease in both children and dogs. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pediatric Supportive Care (PDQ®)—Patient Version

Cancer.gov

Pediatric supportive care is an important aspect of cancer care as children and adolescents face unique challenges compared to adult patients. Learn more about supportive care for pediatric patients during and after treatment in this expert-reviewed summary.

Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

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

2015-09-01

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. 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. 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), P(trend)  = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend)  = 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), P(trend)  = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend)  = 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)]. 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. © 2015 Wiley Periodicals, Inc.

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

Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells.

PubMed

Saha, Subbroto Kumar; Kim, Kyeongseok; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2018-05-09

Cytokeratin 19 ( KRT19 ) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1 , CXCR4 , and CD133 , but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers ( ALDH1 , CXCR4 , and CD133 ), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment.

Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells

PubMed Central

Kim, Kyeongseok; Yang, Gwang-Mo; Choi, Hye Yeon

2018-01-01

Cytokeratin 19 (KRT19) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1, CXCR4, and CD133, but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers (ALDH1, CXCR4, and CD133), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment. PMID:29747452

Promoting innovation in pediatric nutrition.

PubMed

Bier, Dennis M

2010-01-01

Truly impactful innovation can only be recognized in retrospect. Moreover, almost by definition, developing algorithmic paths on roadmaps for innovation are likely to be unsuccessful because innovators do not generally follow established routes. Nonetheless, environments can be established within Departments of Pediatrics that promote innovating thinking. The environmental factors necessary to do so include: (1) demand that academic Pediatrics Departments function in an aggressively scholarly mode; (2) capture the most fundamental science in postnatal developmental biology; (3) focus education and training on the boundaries of our knowledge, rather than the almost exclusive attention to what we think we already know; (4) devote mentoring, time and resources to only the most compelling unanswered questions in the pediatric sciences, including nutrition; (5) accept only systematic, evidence-based answers to clinical questions; (6) if systematic, evidence-based data are not available, design the proper studies to get them; (7) prize questioning the answers to further move beyond the knowledge limit; (8) support the principle that experiments in children will be required to convincingly answer clinical questions important to children, and (9) establish the multicenter resources in pediatric scientist training, clinical study design and implementation, and laboratory and instrument technologies required to answer today's questions with tomorrow's methods. Copyright © 2010 S. Karger AG, Basel.

Evaluating a 4-marker signature of aggressive prostate cancer using time-dependent AUC.

PubMed

Gerke, Travis A; Martin, Neil E; Ding, Zhihu; Nuttall, Elizabeth J; Stack, Edward C; Giovannucci, Edward; Lis, Rosina T; Stampfer, Meir J; Kantoff, Phillip W; Parmigiani, Giovanni; Loda, Massimo; Mucci, Lorelei A

2015-12-01

We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer. Using data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n = 276). Based on these models, we generated prognostic risk scores in an independent population, the Health Professionals Follow-up Study (HPFS; n = 347) to evaluate external validity. In each cohort, men were followed prospectively from cancer diagnosis through 2011 for development of distant metastasis or cancer mortality. We measured protein tumor expression of PTEN, SMAD4, SPP1, and CCND1 on tissue microarrays. During a median of 11.9 and 14.3 years follow-up in the PHS and HPFS cohorts, 24 and 32 men (9%) developed lethal disease. When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. Although the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in aggressive prostate tumors and highlight the challenges that may result from overfitting in discovery-based research. © 2015 Wiley Periodicals, Inc.

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

Developing a healthy web-based cookbook for pediatric cancer patients and survivors: rationale and methods.

PubMed

Li, Rhea; Raber, Margaret; Chandra, Joya

2015-03-31

Obesity has been a growing problem among children and adolescents in the United States for a number of decades. Childhood cancer survivors (CCS) are more susceptible to the downstream health consequences of obesity such as cardiovascular disease, endocrine issues, and risk of cancer recurrence due to late effects of treatment and suboptimal dietary and physical activity habits. The objective of this study was to document the development of a Web-based cookbook of healthy recipes and nutrition resources to help enable pediatric cancer patients and survivors to lead healthier lifestyles. The Web-based cookbook, named "@TheTable", was created by a committee of researchers, a registered dietitian, patients and family members, a hospital chef, and community advisors and donors. Recipes were collected from several sources including recipe contests and social media. We incorporated advice from current patients, parents, and CCS. Over 400 recipes, searchable by several categories and with accompanying nutritional information, are currently available on the website. In addition to healthy recipes, social media functionality and cooking videos are integrated into the website. The website also features nutrition information resources including nutrition and cooking tip sheets available on several subjects. The "@TheTable" website is a unique resource for promoting healthy lifestyles spanning pediatric oncology prevention, treatment, and survivorship. Through evaluations of the website's current and future use, as well as incorporation into interventions designed to promote energy balance, we will continue to adapt and build this unique resource to serve cancer patients, survivors, and the general public.

Malnutrition in pediatric patients with cancer at diagnosis and throughout therapy: A multicenter cohort study.

PubMed

Zimmermann, Karin; Ammann, Roland A; Kuehni, Claudia E; De Geest, Sabina; Cignacco, Eva

2013-04-01

Malnutrition is a common problem in pediatric patients with cancer. Reported prevalence varies widely and has often been assessed only in a subset of childhood types of cancer. This study aimed to describe the prevalence of malnutrition among pediatric patients newly diagnosed with cancer, to describe the occurrence and course of malnutrition during therapy and to identify factors associated with malnutrition during therapy. In a retrospective cohort study of 327 patients diagnosed from 2003 to 2006 in three Swiss tertiary care hospitals, weight and height measures together with patient-, disease-, and treatment-related characteristics were assessed. Malnutrition was defined as body mass index (BMI) below -2 standard deviation scores (SDS) or a weight loss >10% from diagnosis. Malnutrition was assessed at diagnosis and continuously during anticancer therapy. At diagnosis, 5.8% of the patients (19) were malnourished based on BMI. During anticancer therapy, the cumulative incidence of malnutrition rose to 22% (70 patients) after 30 days, to 36% (116 patients) after 60 days, and finally to 47% (155 patients). In these 155 patients, the median duration of malnutrition was 60 days (interquartile range, 21-122). Age above 10 years at diagnosis, BMI ≤ -1.0 SDS at diagnosis, and a diagnosis of medulloblastoma were positively associated with a higher proportion of malnutrition time during therapy. The rapid increase of malnutrition after the start of treatment underlines the need to develop evidence-based and efficient methods to provide nutritional support for children with cancer. Copyright © 2012 Wiley Periodicals, Inc.

Developing a Healthy Web-Based Cookbook for Pediatric Cancer Patients and Survivors: Rationale and Methods

PubMed Central

Raber, Margaret

2015-01-01

Background Obesity has been a growing problem among children and adolescents in the United States for a number of decades. Childhood cancer survivors (CCS) are more susceptible to the downstream health consequences of obesity such as cardiovascular disease, endocrine issues, and risk of cancer recurrence due to late effects of treatment and suboptimal dietary and physical activity habits. Objective The objective of this study was to document the development of a Web-based cookbook of healthy recipes and nutrition resources to help enable pediatric cancer patients and survivors to lead healthier lifestyles. Methods The Web-based cookbook, named “@TheTable”, was created by a committee of researchers, a registered dietitian, patients and family members, a hospital chef, and community advisors and donors. Recipes were collected from several sources including recipe contests and social media. We incorporated advice from current patients, parents, and CCS. Results Over 400 recipes, searchable by several categories and with accompanying nutritional information, are currently available on the website. In addition to healthy recipes, social media functionality and cooking videos are integrated into the website. The website also features nutrition information resources including nutrition and cooking tip sheets available on several subjects. Conclusions The “@TheTable” website is a unique resource for promoting healthy lifestyles spanning pediatric oncology prevention, treatment, and survivorship. Through evaluations of the website’s current and future use, as well as incorporation into interventions designed to promote energy balance, we will continue to adapt and build this unique resource to serve cancer patients, survivors, and the general public. PMID:25840596

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. Copyright © 2017 by the American Academy of Pediatrics.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

PubMed

Bernatsky, Sasha; Clarke, Ann E; Zahedi Niaki, Omid; Labrecque, Jeremy; Schanberg, Laura E; Silverman, Earl D; Hayward, Kristen; Imundo, Lisa; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; Oen, Kiem; Wagner-Weiner, Linda; Rosenberg, Alan M; O'Neil, Kathleen M; Duffy, Ciarán M; von Scheven, Emily; Joseph, Lawrence; Lee, Jennifer L; Ramsey-Goldman, Rosalind

2017-10-01

To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Genetic polymorphism and prostate cancer aggressiveness: A case-only study of 1536 GWAS and candidate SNPs in African Americans and European Americans

PubMed Central

Bensen, Jeannette T.; Xu, Zongli; Smith, Gary J.; Mohler, James L.; Fontham, Elizabeth T.H.; Taylor, Jack A.

2012-01-01

BACKGROUND Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men. METHODS A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable. RESULTS 4 GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and 7 flanking SNPs were associated with CaP aggressiveness (P<0.05) in 3 genomic regions: one at 3p12 (EA), 7 at 8q24 (5 AA, 2 EA), and 3 at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (2 AA, 1 AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (p < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons. CONCLUSIONS Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. PMID:22549899

The YAP1/SIX2 axis is required for DDX3-mediated tumor aggressiveness and cetuximab resistance in KRAS-wild-type colorectal cancer

PubMed Central

Wu, De-Wei; Lin, Po-Lin; Wang, Lee; Huang, Chi-Chou; Lee, Huei

2017-01-01

The mechanism underlying tumor aggressiveness and cetuximab (CTX) resistance in KRAS-wild-type (KRAS -WT) colorectal cancer remains obscure. We here provide evidence that DDX3 promoted soft agar growth and invasiveness of KRAS-WT cells, as already confirmed in KRAS-mutated cells. Mechanistically, increased KRAS expression induced ROS production, which elevated HIF-1α and YAP1 expression. Increased HIF-1α persistently promoted DDX3 expression via a KRAS/ROS/HIF-1α feedback loop. DDX3-mediated aggressiveness and CTX resistance were regulated by the YAP1/SIX2 axis in KRAS-WT cells and further confirmed in animal models. Kaplan-Meier and Cox regression analysis indicated that DDX3, KRAS, and YAP1 expression had prognostic value for OS and RFS in KRAS-WT and KRAS-mutated tumors, but SIX2 and YAP1/SIX2 were prognostic value only in KRAS-WT patients. The observation from patients seemed to support the mechanistic action of cell and animal models. We therefore suggest that combining YAP1 inhibitors with CTX may therefore suppress DDX3-mediated tumor aggressiveness and enhance CTX sensitivity in KRAS-WT colorectal cancer. PMID:28435452

Gabriella Miller Kids First (GMKF/Kids First) Pediatric Research Program | Office of Cancer Genomics

Cancer.gov

The Gabriella Miller Kids First initiative is a trans-NIH effort to increase understanding of genetic changes associated with certain devastating pediatric conditions. The initiative will develop a centralized database of well-curated clinical and genetic sequence data from childhood cancer and structural birth defects cohorts comprising thousands of patients and their families. To learn more about the initiative and the data available, please visit https://commonfund.nih.gov/kidsfirst

Pediatric Supportive Care (PDQ®)—Health Professional Version

Cancer.gov

Pediatric supportive care includes managing issues from the cancer diagnosis, through treatment, and into adult survivorship. Get detailed information addressing pediatric supportive care including psychologic, family, and end-of-life concerns in this clinician summary.

Assessment of family psychosocial functioning in survivors of pediatric cancer using the PAT2.0.

PubMed

Gilleland, Jordan; Reed-Knight, Bonney; Brand, Sarah; Griffin, Anya; Wasilewski-Masker, Karen; Meacham, Lillian; Mertens, Ann

2013-09-01

This study aimed to examine clinical validity and utility of a screening measure for familial psychosocial risk, the Psychosocial Assessment Tool 2.0 (PAT2.0), among pediatric cancer survivors participating in long-term survivorship care. Caregivers (N=79) completed the PAT2.0 during their child's survivorship appointment. Caregivers also reported on family engagement in outpatient mental health treatment. Medical records were reviewed for treatment history and oncology provider initiated psychology consults. The internal consistency of the PAT2.0 total score in this survivorship sample was strong. Psychology was consulted by the oncology provider to see 53% of participant families, and families seen by psychology had significantly higher PAT2.0 total scores than families without psychology consults. PAT2.0 total scores and corresponding subscales were higher for patients, parents, and siblings enrolled in outpatient mental health services since treatment completion. Results were consistent with psychosocial risk categories presented within the Pediatric Psychosocial Preventative Health Model. Fifty-one percent of families presenting for survivorship care scored in the "universal" category, 34% scored in the "targeted" category, and 15% scored in the "clinical" category. Data indicate that the overall proportions of families experiencing "universal", "targeted", and "clinical" levels of familial distress may be constant from the time of diagnosis into survivorship care. Overall, the PAT2.0 demonstrated strong psychometric properties among survivors of pediatric cancer and shows promise as a psychosocial screening measure to facilitate more effective family support in survivorship care. Copyright © 2013 John Wiley & Sons, Ltd.

Barriers and Facilitators of Transition from Pediatric to Adult Long-Term Follow-Up Care in Childhood Cancer Survivors.

PubMed

Rosenberg-Yunger, Zahava R S; Klassen, Anne F; Amin, Leila; Granek, Leeat; D'Agostino, Norma M; Boydell, Katherine M; Greenberg, Mark; Barr, Ronald D; Nathan, Paul C

2013-09-01

Despite the risk for late effects in adult survivors of cancer in childhood or adolescence, many survivors fail to transition from pediatric to adult long-term follow-up (LTFU) care. The purpose of this study was to identify the barriers and facilitators of transition from pediatric to adult LTFU care. In this qualitative study, 38 Canadian survivors of cancer in childhood or adolescence, currently aged 15-26 years, were interviewed using semi-structured, open-ended questions. Participants belonged to one of four groups: pre-transition (n=10), successful transition (n=11), failed to transition (n=7), and transitioned to an adult center but then dropped out of adult care (n=10). A constructivist grounded theory approach was used to analyze the interview data. This approach consisted of coding transcripts line by line to develop categories and using constant comparison to examine relationships within and across codes and categories. Interviewing continued until saturation was reached. Three interrelated themes were identified that affected the transition process: micro-level patient factors (e.g., due diligence, anxiety), meso-level support factors (e.g., family, friends), and macro-level system factors (e.g., appointments, communication, healthcare providers). Factors could act as facilitators to transition (e.g., family support), barriers to transition (e.g., difficulty booking appointments), or as both a barrier and a facilitator (e.g., anxiety). This study illustrates the interaction between multiple factors that facilitate and/or prevent transition from pediatric to adult LTFU cancer care. A number of recommendations are presented to address potential macro-level system barriers to successful transition.

Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

PubMed

Rava, Marta; Czachorowski, Maciej J; Silverman, Debra; Márquez, Mirari; Kishore, Sirish; Tardón, Adonina; Serra, Consol; García-Closas, Montse; Garcia-Closas, Reina; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Kogevinas, Manolis; Malats, Núria

2018-02-01

Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis. © 2017 UICC.

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

Surgical care of the pediatric Crohn's disease patient.

PubMed

Stewart, Dylan

2017-12-01

Despite the significant advances in the medical management of inflammatory bowel disease over the last decade, surgery continues to play a major role in the management of pediatric Crohn's disease (CD). While adult and pediatric Crohn's disease may share many clinical characteristics, pediatric Crohn's patients often have a more aggressive phenotype, and the operative care given by the pediatric surgeon to the newly diagnosed Crohn's patient is very different in nature to the surgical needs of adult patients after decades of disease progression. Children also have the unique surgical indication of growth failure to consider in the overall clinical decision making. While surgery is never curative in CD, it has the ability to transform the disease process in children, and appropriately timed operations may have tremendous impact on a child's physical and mental maturation. This monograph aims to address the surgical care of Crohn's disease in general, with a specific emphasis on the surgical treatment of small intestinal and ileocecal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

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 ...

Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient

NASA Astrophysics Data System (ADS)

Zhang, Rui; Howell, Rebecca M.; Giebeler, Annelise; Taddei, Phillip J.; Mahajan, Anita; Newhauser, Wayne D.

2013-02-01

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

Genetic polymorphism and prostate cancer aggressiveness: a case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans.

PubMed

Bensen, Jeannette T; Xu, Zongli; Smith, Gary J; Mohler, James L; Fontham, Elizabeth T H; Taylor, Jack A

2013-01-01

Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men. A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable. Four GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and seven flanking SNPs were associated with CaP aggressiveness (P < 0.05) in three genomic regions: One at 3p12 (EA), seven at 8q24 (5 AA, 2 EA), and three at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (two AA, one AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (P < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons. Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. Copyright © 2012 Wiley Periodicals, Inc.

Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins

PubMed Central

Vainio, Paula; Lehtinen, Laura; Mirtti, Tuomas; Hilvo, Mika; Seppänen-Laakso, Tuulikki; Virtanen, Johannes; Sankila, Anna; Nordling, Stig; Lundin, Johan; Rannikko, Antti; Orešič, Matej; Kallioniemi, Olli; Iljin, Kristiina

2011-01-01

Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50% of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management. PMID:22202492

Management of Herpes Simplex Virus Keratitis in the Pediatric Population.

PubMed

Vadoothker, Saujanya; Andrews, Laura; Jeng, Bennie H; Levin, Moran Roni

2018-05-14

Herpes simplex virus (HSV) keratitis is a highly prevalent and visually-disabling disease in both the pediatric and adult population. While many studies have investigated the treatment of HSV keratitis in adult patients, few have focused on managing this condition in children. Children are at particularly high risk for visual morbidity due to unique challenges in diagnosis and treatment, and the often more aggressive disease course that results in corneal scarring, and subsequently amblyopia. This review presents the pathogenesis and most current recommendations for the medical and surgical management of HSV keratitis in the pediatric population.

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

Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival.

PubMed

Moore, Lauren M; England, Allison; Ehrlich, Barbara E; Rimm, David L

2017-07-01

Neuronal Calcium Sensor 1 (NCS-1) is a multi-functional Ca 2+ -binding protein that affects a range of cellular processes beyond those related to neurons. Functional characterization of NCS-1 in neuronal model systems suggests that NCS-1 may influence oncogenic processes. To this end, the biological role of NCS-1 was investigated by altering its endogenous expression in MCF-7 and MB-231 breast cancer cells. Overexpression of NCS-1 resulted in a more aggressive tumor phenotype demonstrated by a marked increase in invasion and motility, and a decrease in cell-matrix adhesion to collagen IV. Overexpression of NCS-1 was also shown to increase the efficacy of paclitaxel-induced cell death in a manner that was independent of cellular proliferation. To determine the association between NCS-1 and clinical outcome, NCS-1 expression was measured in two independent breast cancer cohorts by the Automated Quantitative Analysis method of quantitative immunofluorescence. Elevated levels of NCS-1 were significantly correlated with shorter survival rates. Furthermore, multivariate analysis demonstrated that NCS-1 status was prognostic, independent of estrogen receptor, progesterone receptor, HER2, and lymph node status. These findings indicate that NCS-1 plays a role in the aggressive behavior of a subset of breast cancers and has therapeutic or biomarker potential. Implications: NCS-1, a calcium-binding protein, is associated with clinicopathologic features of aggressiveness in breast cancer cells and worse outcome in two breast cancer patient cohorts. Mol Cancer Res; 15(7); 942-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Economic Analysis of Neoadjuvant Chemotherapy Versus Primary Debulking Surgery for Advanced Epithelial Ovarian Cancer Using an Aggressive Surgical Paradigm.

PubMed

Cole, Ashley L; Barber, Emma L; Gogate, Anagha; Tran, Arthur-Quan; Wheeler, Stephanie B

2018-04-21

Neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced epithelial ovarian cancer (AEOC) remains controversial in the United States. Generalizability of existing trial results has been criticized because of less aggressive debulking procedures than commonly used in the United States. As a result, economic evaluations using input data from these trials may not accurately reflect costs and outcomes associated with more aggressive primary surgery. Using data from an ongoing trial performing aggressive debulking, we investigated the cost-effectiveness and cost-utility of NACT versus PDS for AEOC. A decision tree model was constructed to estimate differences in short-term outcomes and costs for a hypothetical cohort of 15,000 AEOC patients (US annual incidence of AEOC) treated with NACT versus PDS over a 1-year time horizon from a Medicare payer perspective. Outcomes included costs per cancer-related death averted, life-years and quality-adjusted life-years (QALYs) gained. Base-case probabilities, costs, and utilities were based on the Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasms trial. Base-case analyses assumed equivalent survival; threshold analysis estimated the maximum survival difference that would result in NACT being cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds. Probabilistic sensitivity analysis was used to characterize model uncertainty. Compared with PDS, NACT was associated with $142 million in cost savings, 1098 fewer cancer-related deaths, and 1355 life-years and 1715 QALYs gained, making it the dominant treatment strategy for all outcomes. In sensitivity analysis, NACT remained dominant in 99.3% of simulations. Neoadjuvant chemotherapy remained cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds if survival differences were less than 2.7 and 1.4 months, respectively. In the short term, NACT is cost-saving with improved outcomes

Validation of a pediatric early warning system for hospitalized pediatric oncology patients in a resource-limited setting.

PubMed

Agulnik, Asya; Méndez Aceituno, Alejandra; Mora Robles, Lupe Nataly; Forbes, Peter W; Soberanis Vasquez, Dora Judith; Mack, Ricardo; Antillon-Klussmann, Federico; Kleinman, Monica; Rodriguez-Galindo, Carlos

2017-12-15

Pediatric oncology patients are at high risk of clinical deterioration, particularly in hospitals with resource limitations. The performance of pediatric early warning systems (PEWS) to identify deterioration has not been assessed in these settings. This study evaluates the validity of PEWS to predict the need for unplanned transfer to the pediatric intensive care unit (PICU) among pediatric oncology patients in a resource-limited hospital. A retrospective case-control study comparing the highest documented and corrected PEWS score before unplanned PICU transfer in pediatric oncology patients (129 cases) with matched controls (those not requiring PICU care) was performed. Documented and corrected PEWS scores were found to be highly correlated with the need for PICU transfer (area under the receiver operating characteristic, 0.940 and 0.930, respectively). PEWS scores increased 24 hours prior to unplanned transfer (P = .0006). In cases, organ dysfunction at the time of PICU admission correlated with maximum PEWS score (correlation coefficient, 0.26; P = .003), patients with PEWS results ≥4 had a higher Pediatric Index of Mortality 2 (PIM2) (P = .028), and PEWS results were higher in patients with septic shock (P = .01). The PICU mortality rate was 17.1%; nonsurvivors had higher mean PEWS scores before PICU transfer (P = .0009). A single-point increase in the PEWS score increased the odds of mechanical ventilation or vasopressors within the first 24 hours and during PICU admission (odds ratio 1.3-1.4). PEWS accurately predicted the need for unplanned PICU transfer in pediatric oncology patients in this resource-limited setting, with abnormal results beginning 24 hours before PICU admission and higher scores predicting the severity of illness at the time of PICU admission, need for PICU interventions, and mortality. These results demonstrate that PEWS aid in the identification of clinical deterioration in this high-risk population, regardless of a hospital

Impact of cachexia on outcomes in aggressive lymphomas.

PubMed

Karmali, Reem; Alrifai, Taha; Fughhi, Ibtihaj A M; Ng, Ronald; Chukkapalli, Vineela; Shah, Palmi; Basu, Sanjib; Nathan, Sunita; Szymanski-Grant, Kelly; Gordon, Leo I; Venugopal, Parameswaran; Penedo, Frank J; Borgia, Jeffrey A

2017-06-01

Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87-93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into "non-cachectic" (CXI ≥49.8, n = 41) and "cachectic" (CXI <49.8, n = 40) groups. Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR = 4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

Applications of Genomic Sequencing in Pediatric CNS Tumors.

PubMed

Bavle, Abhishek A; Lin, Frank Y; Parsons, D Williams

2016-05-01

Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient-matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers.

Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

PubMed

Verner, Emma; Forsyth, Cecily; Grigg, Andrew

2014-05-01

Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

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

PubMed Central

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. PMID:25602521

Quality improvement in pediatric sepsis.

PubMed

Melendez, Elliot; Bachur, Richard

2015-06-01

Although there is abundant literature detailing the impact of quality improvement in adult sepsis, the pediatric literature is lacking. Despite consensus definitions for sepsis, which patients along the sepsis spectrum should receive aggressive management and the exact onset of sepsis ('time zero') are not clearly established. In the adult emergency department (ED), sepsis onset is defined as the time of entry into the ED; however, this definition cannot be applied to hospitalized patients or patients who evolve during their ED course. Since the time of sepsis onset will dictate the timeliness of subsequent process measures, the variable definitions in the literature make it difficult to generalize findings among prior studies. Despite the variation in defining time zero, aggressive fluid administration, timely antibiotics, and compliance with sepsis bundles have been shown to improve mortality and to reduce hospital and intensive care length of stay. In addition, early identification tools show promise in beginning to define sepsis onset and retrospective search tools may allow improved case finding of those children of concern for sepsis. Quality improvement in pediatric sepsis is evolving. As we continue to define quality measures, we must standardize the definition of sepsis onset. This definition should be applicable to any treatment venue to ensure measures can be evaluated across all settings. In addition, we must delineate which patients along the sepsis spectrum should be candidates for timely interventions and standardize other outcome measures beyond mortality.

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

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

PubMed

Gibbons, Kathleen; DeMonbrun, Andrea; Beckman, Elizabeth J; Keefer, Patricia; Wagner, Deb; Stewart, Margaret; Saul, D'Anna; Hakel, Stephanie; Liu, My; Niedner, Matthew

2016-07-01

Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children. © 2016 Wiley Periodicals, Inc.

Variation in Management of Fever and Neutropenia Among Pediatric Patients with Cancer: A Survey of Providers in Michigan

PubMed Central

Mueller, Emily L.; Walkovich, Kelly J.; Yanik, Gregory A.; Clark, Sarah J.

2016-01-01

Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An on-line survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for “Decreased” and “Increased” risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%), the majority defined a febrile event as temperature >38.3°C and/or two events > 38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) <500/μL. Majority of respondents recommended “Decreased” and “Increased” patients present to a local emergency department (ED) if they live >2 hours away. Respondents were significantly more likely to have a “Decreased Risk” patient travel over 2 hours if they rated the local ED as “Poor to Fair” on ability to access Port-a-caths (p 0.048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL. 40% preferred discharge on oral antibiotics when the ANC<500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers’ perceptions of local EDs. Future investigation of local hospitals’ ability to provide urgent evaluation, combined with parental perspectives could lead to improvements in timely and effective management. PMID:26086779

Variation in Management of Fever and Neutropenia Among Pediatric Patients With Cancer: A Survey of Providers in Michigan.

PubMed

Mueller, Emily L; Walkovich, Kelly J; Yanik, Gregory A; Clark, Sarah J

2015-01-01

Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An online survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for "Decreased" and "Increased" risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%); the majority defined a febrile event as temperature >38.3°C and/or 2 events >38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) <500/μL. Majority of respondents recommended "Decreased" and "Increased" patients present to a local emergency department (ED) if they live >2 hours away. Respondents were significantly more likely to have a "Decreased Risk" patient travel over 2 hours if they rated the local ED as "Poor to Fair" on ability to access Port-a-caths (P = .048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL; 40% preferred discharge on oral antibiotics when the ANC <500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers' perceptions of local EDs. Future investigation of local hospitals' ability to provide urgent evaluation, combined with parental perspectives, could lead to improvements in timely and effective management.

Risk Factors for Hospital-acquired Clostridium difficile Infection Among Pediatric Patients With Cancer.

PubMed

Daida, Atsuro; Yoshihara, Hiroki; Inai, Ikuko; Hasegawa, Daisuke; Ishida, Yasushi; Urayama, Kevin Y; Manabe, Atsushi

2017-04-01

Hospital-acquired Clostridium difficile infection (CDI) may cause life-threatening colitis for children with cancer, making identification of risk factors important. We described characteristics of pediatric cancer patients with primary and recurring CDI, and evaluated potential risk factors. Among 189 cancer patients, 51 cases (27%) of CDI and 94 matched controls of cancer patients without CDI were analyzed. Multivariable logistic regression was used to evaluate the association between CDI and several potential risk factors. Median age of CDI cases was lower (3.3 y; 0.60 to 16.2) than controls (7.7 y; 0.4 to 20.5). Median duration of neutropenia before CDI was longer for CDI cases (10.0 d; 0.0 to 30.0) compared with duration calculated from reference date in controls (6.0 d; 0.0 to 29.0). Multivariable analysis showed that older age was associated with reduced risk (≥7 vs. 0 to 3 y, odds ratio=0.11; 95% confidence interval, 0.02-0.54), and prolonged neutropenia was associated with increased risk (odds ratio=1.11; 95% confidence interval, 1.01-1.22). CDI recurred in 26% of cases. Younger age and prolonged neutropenia were risk factors for CDI in children with cancer. Increasing awareness to these risk factors will help to identify opportunities for CDI prevention in cancer patients.

Nonmelanoma Skin Cancer With Aggressive Subclinical Extension in Immunosuppressed Patients.

PubMed

Song, Silvia Soohyun; Goldenberg, Alina; Ortiz, Arisa; Eimpunth, Sasima; Oganesyan, Gagik; Jiang, Shang I Brian

2016-06-01

Immunosuppression (IS), such as in solid-organ transplant recipients (SOTRs) and patients with human immunodeficiency virus (HIV) or hematologic malignant neoplasms, increases the risk of developing nonmelanoma skin cancers (NMSCs). However, it is unknown whether IS patients are at increased risk of developing NMSCs with aggressive subclinical extensions (NMSC-ASE), which may extend aggressively far beyond conventional surgical margins. To study clinical characteristics of NMSC-ASE among immunocompetent (IC) and various subgroups of IS patients and to suggest a predictive model for NMSC-ASE lesions. A 6-year retrospective review of 2998 NMSC cases between February 26, 2007, and February 17, 2012, at the Dermatologic and Mohs Micrographic Surgery Unit of the University of California, San Diego, Medical Center. Nonmelanoma skin cancers that required at least 3 Mohs micrographic surgery stages with final surgical margins of at least 10 mm were defined as ASE lesions. All cases were categorized into 1 of 2 groups, IS or IC. Immunosuppressed cases were further subcategorized into 3 subgroups: SOTRs and patients with HIV or hematologic malignant neoplasm. The data were analyzed in December 2012. We evaluated the odds ratio of having NMSC-ASE lesions in IS patients (SOTRs, HIV, hematologic malignant neoplasm) compared with IC patients. Other clinical characteristics and preoperative risks were analyzed and compared. Of all 2998 cases, we identified 805 NMSC-ASE cases: 137 IS and 668 IC. Immunosuppressed patients had an odds ratio of 1.94 of having ASE lesions compared with IC patients (95% CI, 1.54-2.44; P < .001). Additionally, the SOTR subgroup was associated with a 2.74 odds of having NSMC-ASE compared with non-SOTRs (95% CI, 2.00-3.76; P < .001), and the presence of hematologic malignant neoplasm was associated with 1.74 times the odds compared with IC patients (95% CI, 1.04-2.90; P = .04). Multivariate analysis found older age (P < .001), lesion

Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians

PubMed Central

Kato, Taku; Yamamura, Soichiro; Tanaka, Yuichiro; Majid, Shahana; Saini, Sharanjot; Varahram, Shahryari; Kulkarni, Priyanka; Dasgupta, Pritha; Mitsui, Yozo; Sumida, Mitsuho; Tabatabai, Laura; Deng, Guoren; Kumar, Deepak; Dahiya, Rajvir

2017-01-01

African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. miR-34b functions as a tumor suppressor and has a multi-functional role, through regulation of cell proliferation, cell cycle and apoptosis. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians. DNA hypermethylation of the miR-34b-3p promoter region showed significantly higher methylation in prostate cancer compared to normal samples. We then sequenced the promoter region of miR-34b-3p and found a chromosomal deletion in miR-34b in African-American prostate cancer cell line (MDA-PCA-2b) and not in Caucasian cell line (DU-145). We found that AR and ETV1 genes are differentially expressed in MDA-PCa-2b and DU-145 cells after overexpression of miR-34b. Direct interaction of miR-34b with the 3’ untranslated region of AR and ETV1 was validated by luciferase reporter assay. We found that miR-34b downregulation in African-Americans is inversely correlated with high AR levels that lead to increased cell proliferation. Overexpression of miR-34b in cell lines showed higher inhibition of cell proliferation, apoptosis and G1 arrest in the African-American cells (MDA-PCa-2b) compared to Caucasian cell line (DU-145). Taken together, our results show that differential expression of miR-34b and AR are associated with prostate cancer aggressiveness in African-Americans. PMID:28039468

Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis

PubMed Central

Suh, Yun-Suhk; Yu, Jieun; Kim, Byung Chul; Choi, Boram; Han, Tae-Su; Ahn, Hye Seong; Kong, Seong-Ho; Lee, Hyuk-Joon; Kim, Woo Ho; Yang, Han-Kwang

2015-01-01

Purpose The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. Materials and Methods Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients. Results CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393). Conclusion DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC. PMID:25687870

What You Need to Know about Cervical Cancer

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

What You Need to Know about Kidney Cancer

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

What You Need to Know about Breast Cancer

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

What You Need to Know about Liver Cancer

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

What You Need to Know about Thyroid Cancer

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

Patient-specific Radiation Dose and Cancer Risk for Pediatric Chest CT

PubMed Central

Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2011-01-01

Purpose: To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. Materials and Methods: The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0–16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDIvol) or dose–length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Results: Organ dose normalized by tube current–time product or CTDIvol decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current–time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current–time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). Conclusion: The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1 PMID:21467251

Patient-specific radiation dose and cancer risk for pediatric chest CT.

PubMed

Li, Xiang; Samei, Ehsan; Segars, W Paul; Sturgeon, Gregory M; Colsher, James G; Frush, Donald P

2011-06-01

To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1. RSNA, 2011

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

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.

Improved outcomes after successful implementation of a pediatric early warning system (PEWS) in a resource-limited pediatric oncology hospital.

PubMed

Agulnik, Asya; Mora Robles, Lupe Nataly; Forbes, Peter W; Soberanis Vasquez, Doris Judith; Mack, Ricardo; Antillon-Klussmann, Federico; Kleinman, Monica; Rodriguez-Galindo, Carlos

2017-08-01

Hospitalized pediatric oncology patients are at high risk of clinical decline and mortality, particularly in resource-limited settings. Pediatric early warning systems (PEWS) aid in the early identification of clinical deterioration; however, there are limited data regarding their feasibility or impact in low-resource settings. This study describes the successful implementation of PEWS at the Unidad Nacional de Oncología Pediátrica (UNOP), a pediatric oncology hospital in Guatemala, resulting in improved inpatient outcomes. A modified PEWS was implemented at UNOP with systems to track errors, transfers to a higher level of care, and high scores. A retrospective cohort study was used to evaluate clinical deterioration events in the year before and after PEWS implementation. After PEWS implementation at UNOP, there was 100% compliance with PEWS documentation and an error rate of <10%. Implementation resulted in 5 high PEWS per week, with 30% of patients transferring to a higher level of care. Among patients requiring transfer to the pediatric intensive care unit (PICU), 93% had an abnormal PEWS before transfer. The rate of clinical deterioration events decreased after PEWS implementation (9.3 vs 6.5 per 1000-hospitalpatient-days, p = .003). Despite an 18% increase in total hospital patient-days, PICU utilization for inpatient transfers decreased from 1376 to 1088 PICU patient-days per year (21% decrease; P<.001). This study describes the successful implementation of PEWS in a pediatric oncology hospital in Guatemala, resulting in decreased inpatient clinical deterioration events and PICU utilization. This work demonstrates that PEWS is a feasible and effective quality improvement measure to improve hospital care for children with cancer in hospitals with limited resources. Cancer 2017;123:2965-74. © 2017 American Cancer Society. © 2017 American Cancer Society.

End-of-life chemotherapy is associated with poor survival and aggressive care in patients with small cell lung cancer.

PubMed

Zhu, Yingming; Tang, Ke; Zhao, Fen; Zang, Yuanwei; Wang, Xiaodong; Li, Zhenxiang; Sun, Xindong; Yu, Jinming

2018-05-29

Concerns regarding end-of-life (EOL) chemotherapy are being increasingly raised. Tumor chemosensitivity may influence the decision for aggressive chemotherapy near the EOL. Data on EOL chemotherapy in highly chemosensitive tumors, such as small cell lung cancer (SCLC), are scarce. A total of 143 SCLC decedents were consecutively included. Data about clinical factors and treatment modalities were obtained from the electronic medical records. The relationships among EOL chemotherapy, clinical features, overall survival (OS), and aggressive care were investigated. About 64% of patients had chemosensitive disease. In total, 30.8 and 16.1% of patients received EOL chemotherapy within the last 1 and 2 months of life, respectively. Younger age was associated with a higher rate of EOL chemotherapy. We determined that EOL chemotherapy was related to inferior OS not only in the entire group, but also in the chemosensitive subgroup. Furthermore, more intensive care was observed among patients who underwent EOL chemotherapy compared with those who did not. EOL chemotherapy was correlated with shorter survival and more aggressive care in patients with SCLC. More research is needed to develop indications for terminating palliative chemotherapy, to help physicians and patients with their difficult choices.

Overview of pediatric oncology and hematology in Myanmar

PubMed Central

Halbert, Jay; Khaing, Aye Aye

2014-01-01

Myanmar is a country in southeast Asia in political, economic and healthcare transition. There are currently only two pediatric oncology centers serving a population of almost 19 million children. An estimated 85-92% of children with cancer are undiagnosed or not receiving treatment. Abandonment of treatment is as high as 60%. Although a number of chemotherapy agents are available, difficulties remain concerning treatment costs, quality control and the availability of supportive care. Radiotherapy services are also limited and not usually included in pediatric protocols. Healthcare professional training, improved diagnostics, strategies to tackle abandonment of treatment and the development of a parents’ support group are major priorities. Local and international partnerships including a recent partnership with world child cancer are essential in the interim to support the development of pediatric oncology and hematology in Myanmar. A unique opportunity exists to support the development of preventive, diagnostic, curative and palliative care for children's cancer in Myanmar from the outset. PMID:24665454

Overview of pediatric oncology and hematology in Myanmar.

PubMed

Halbert, Jay; Khaing, Aye Aye

2014-01-01

Myanmar is a country in southeast Asia in political, economic and healthcare transition. There are currently only two pediatric oncology centers serving a population of almost 19 million children. An estimated 85-92% of children with cancer are undiagnosed or not receiving treatment. Abandonment of treatment is as high as 60%. Although a number of chemotherapy agents are available, difficulties remain concerning treatment costs, quality control and the availability of supportive care. Radiotherapy services are also limited and not usually included in pediatric protocols. Healthcare professional training, improved diagnostics, strategies to tackle abandonment of treatment and the development of a parents' support group are major priorities. Local and international partnerships including a recent partnership with world child cancer are essential in the interim to support the development of pediatric oncology and hematology in Myanmar. A unique opportunity exists to support the development of preventive, diagnostic, curative and palliative care for children's cancer in Myanmar from the outset.

Scattered dose to radiosensitive organs and associated risk for cancer development from head and neck radiotherapy in pediatric patients.

PubMed

Kourinou, Kalliopi M; Mazonakis, Michalis; Lyraraki, Efrosini; Stratakis, John; Damilakis, John

2013-11-01

The purpose of this study was to measure the scattered dose to out-of-field organs from head and neck radiotherapy in pediatric patients and to estimate the risk for second cancer induction to individual organs. Radiotherapy for thalamic tumor, brain tumor, acute leukemia and Hodgkin's disease in the neck region was simulated on 5 and 10-year-old pediatric phantoms with a 6 MV photon beam. The radiation dose to thyroid, breast, lung, stomach, ovaries, bladder, liver, uterus, prostate and colon was measured using thermoluminescent dosimeters. The methodology, provided by the BEIR VII report was used for the second cancer risk estimations. Peripheral dose range for a simulated 5-year-old patient was 0.019%-1.572% of the given tumor dose. The corresponding range at the advanced patient age was reduced to 0.018%-1.468%. The second cancer risk per fraction for male patients varied from 3 to 215 per 1,000,000 patients depending upon the age at the time of exposure, primary cancer site and organ scattered dose. The corresponding risk for females was 1-1186 per 1,000,000 patients. The higher risk values were found for breast, thyroid and lung cancer development. The current data concerning the risk magnitude for developing subsequent neoplasms to various out-of-field organs may be of value for health care professionals in the follow-up studies of childhood cancer survivors. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

Cumulative effective dose and cancer risk for pediatric population in repetitive full spine follow-up imaging: How micro dose is the EOS microdose protocol?

PubMed

Law, Martin; Ma, Wang-Kei; Lau, Damian; Cheung, Kenneth; Ip, Janice; Yip, Lawrance; Lam, Wendy

2018-04-01

To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol. Organ absorbed doses of full spine exposed scoliotic pediatric patients have been simulated with the use of EOS microdose protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and age specific effective dose has been calculated with the simulated organ absorbed dose using the ICRP-103 approach. The associated radiation induced cancer risk, expressed as lifetime attributable risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Values of LAR have been estimated for scoliotic patients exposed repetitively during their follow up period at different age for US and Hong Kong population. The effective doses of full spine imaging with simultaneous posteroanterior and lateral projection for patients exposed at the age between 5 and 18 years using the EOS microdose protocol have been calculated within the range of 2.54-14.75 μSv. The corresponding LAR for US and Hong Kong population was ranged between 0.04 × 10 -6 and 0.84 × 10 -6 . Cumulative effective dose and cancer risk during follow-up period can be estimated using the results and are of information to patients and their parents. With the use of computer simulation and analytic formulation, we obtained the cumulative effective dose and cancer risk at any age of exposure for pediatric patients of US and Hong Kong population undergoing repetitive

Frequency, characteristics and management of adolescent inpatient aggression.

PubMed

Baeza, Immaculada; Correll, Christoph U; Saito, Ema; Amanbekova, Dinara; Ramani, Meena; Kapoor, Sandeep; Chekuri, Raja; De Hert, Marc; Carbon, Maren

2013-05-01

Inpatient aggression is a serious challenge in pediatric psychiatry. A chart review study in adolescent psychiatric inpatients consecutively admitted over 24 months was conducted, to describe aggressive events requiring an intervention (AERI) and to characterize their management. AERIs were identified based on specific institutional event forms and/or documentation of as-needed (STAT/PRN) medication administration for aggression, both recorded by nursing staff. Among 408 adolescent inpatients (age: 15.2±1.6 years, 43.9% male), 1349 AERIs were recorded, with ≥1 AERI occurring in 28.4% (n=116; AERI+). However, the frequency of AERIs was highly skewed (median 4, range: 1-258). In a logistical regression model, the primary diagnosis at discharge of disruptive behavior disorders and bipolar disorders, history of previous inpatient treatment, length of hospitalization, and absence of a specific precipitant prior to admission were significantly associated with AERIs (R(2)=0.32; p<0.0001). The first line treatment of patients with AERIs (AERI+) was pharmacological in nature (95.6%). Seclusion or restraint (SRU) was used at least once in 59.4% of the AERI+ subgroup (i.e., in 16.9% of all patients; median within-group SRU frequency: 3). Treatment and discharge characteristics indicated a poorer prognosis in the AERI+ (discharge to residential care AERI+: 22.8%, AERI-: 5.6%, p<0.001) and a greater need for psychotropic polypharmacy (median number of psychotropic medications AERI+: 2; AERI-: 1, p<0.001). Despite high rates of pharmacological interventions, SRU continue to be used in adolescent inpatient care. As both of these approaches lack a clear evidence base, and as adolescents with clinically significant inpatient aggression have increased illness acuity/severity and service needs, structured research into the most appropriate inpatient aggression management is sorely needed.

PERSPECTIVES ON CANCER STEM CELLS IN OSTEOSARCOMA

PubMed Central

Basu-Roy, Upal; Basilico, Claudio; Mansukhani, Alka

2012-01-01

Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. These mesenchymal tumors are derived from progenitor cells in the osteoblast lineage that have accumulated mutations to escape cell cycle checkpoints leading to excessive proliferation and defects in their ability to differentiate appropriately into mature bone-forming osteoblasts. Like other malignant tumors, osteosarcoma is often heterogeneous, consisting of phenotypically distinct cells with features of different stages of differentiation. The cancer stem cell hypothesis posits that tumors are maintained by stem cells and it is the incomplete eradication of a refractory population of tumor-initiating stem cells that accounts for drug resistance and tumor relapse. In this review we present our current knowledge about the biology of osteosarcoma stem cells from mouse and human tumors, highlighting new insights and unresolved issues in the identification of this elusive population. We focus on factors and pathways that are implicated in maintaining such cells, and differences from paradigms of epithelial cancers. Targeting of the cancer stem cells in osteosarcoma is a promising avenue to explore to develop new therapies for this devastating childhood cancer. PMID:22659734

Global challenges in pediatric oncology.

PubMed

Rodriguez-Galindo, Carlos; Friedrich, Paola; Morrissey, Lisa; Frazier, Lindsay

2013-02-01

Reduction of child mortality is one of the Millennium Development Goals; as low-income and middle-income countries (LMICs) advance toward the achievement of this goal, initiatives aimed at reducing the burden of noncommunicable diseases, including childhood cancer, need to be developed. Approximately 200 000 children and adolescents are diagnosed with cancer every year worldwide; of those, 80% live in LMICs, which account for 90% of the deaths. Lack of quality population-based cancer registries in LMICs limits our knowledge of the epidemiology of pediatric cancer; however, available information showing variations in incidence may indicate unique interactions between environmental and genetic factors that could provide clues to cause. Outcome of children with cancer in LMICs is dictated by late presentation and underdiagnosis, high abandonment rates, high prevalence of malnutrition and other comorbidities, suboptimal supportive and palliative care, and limited access to curative therapies. Initiatives integrating program building with education of healthcare providers and research have proven to be successful in the development of regional capacity. Intensity-graduated treatments adjusted to the local capacity have been developed. Childhood cancer burden is shifted toward LMICs; global initiatives directed at pediatric cancer care and control are urgently needed. International partnerships facilitating stepwise processes that build capacity while incorporating epidemiology and health services research and implementing intensity-graduated treatments have been shown to be effective.

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

PubMed Central

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

2014-01-01

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. PMID:19305045

Response to a Treatment Summary and Care Plan Among Adult Survivors of Pediatric and Young Adult Cancer

PubMed Central

Spain, Peter D.; Oeffinger, Kevin C.; Candela, Joanne; McCabe, Mary; Ma, Xiaomei; Tonorezos, Emily S.

2012-01-01

Purpose: Survivors of pediatric and young adult cancer are at increased risk for treatment-related problems. Yet, few survivors receive risk-based care. The treatment summary and care plan are recommended to improve understanding of cancer treatment, potential late effects, and recommended screening. It is unknown whether survivors retain, understand, value, and disseminate the document, and whether it causes worry. Methods: We surveyed 111 adult survivors of pediatric and young adult cancer 1 to 6 weeks after receipt of a one-page treatment summary and care plan (response rate, 96%). Participants answered questions regarding retention, understanding, value, dissemination, concern, and preferences. Results: Participants were majority female (58%), college-educated (60%), diagnosed with cancer before age 21 (76%), on average 18 years from diagnosis (range, 2 to 50 years), and treated with radiation and chemotherapy (61%). Median age was 30 years (range, 18 to 65 years). A majority of participants stated that they understood the treatment summary (95%), retained the document (95%), and valued it (92%). A minority reported that the document caused concern (14%) or wanted more information than the form provided (20%). Although the time between receipt of the document and survey was brief, many described dissemination of the document to their personal circle (44%) or an outside provider (10 [33%] of 30 who saw an outside doctor). Conclusion: A one-page treatment summary and care plan was well-received and did not cause report of undue concern. Additional health-related information was requested by some, and dissemination to outside providers could be improved. PMID:22942816

Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.

PubMed

Winter, Jean M; Curry, Natasha L; Gildea, Derek M; Williams, Kendra A; Lee, Minnkyong; Hu, Ying; Crawford, Nigel P S

2018-06-11

It is well known that development of prostate cancer (PC) can be attributed to somatic mutations of the genome, acquired within proto-oncogenes or tumor-suppressor genes. What is less well understood is how germline variation contributes to disease aggressiveness in PC patients. To map germline modifiers of aggressive neuroendocrine PC, we generated a genetically diverse F2 intercross population using the transgenic TRAMP mouse model and the wild-derived WSB/EiJ (WSB) strain. The relevance of germline modifiers of aggressive PC identified in these mice was extensively correlated in human PC datasets and functionally validated in cell lines. Aggressive PC traits were quantified in a population of 30 week old (TRAMP x WSB) F2 mice (n = 307). Correlation of germline genotype with aggressive disease phenotype revealed seven modifier loci that were significantly associated with aggressive disease. RNA-seq were analyzed using cis-eQTL and trait correlation analyses to identify candidate genes within each of these loci. Analysis of 92 (TRAMP x WSB) F2 prostates revealed 25 candidate genes that harbored both a significant cis-eQTL and mRNA expression correlations with an aggressive PC trait. We further delineated these candidate genes based on their clinical relevance, by interrogating human PC GWAS and PC tumor gene expression datasets. We identified four genes (CCDC115, DNAJC10, RNF149, and STYXL1), which encompassed all of the following characteristics: 1) one or more germline variants associated with aggressive PC traits; 2) differential mRNA levels associated with aggressive PC traits; and 3) differential mRNA expression between normal and tumor tissue. Functional validation studies of these four genes using the human LNCaP prostate adenocarcinoma cell line revealed ectopic overexpression of CCDC115 can significantly impede cell growth in vitro and tumor growth in vivo. Furthermore, CCDC115 human prostate tumor expression was associated with better survival

Pediatric cervicofacial necrotizing fasciitis: a case report and review of a 10-year national pediatric database.

PubMed

King, Ericka; Chun, Robert; Sulman, Cecille

2012-04-01

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. Case report and review. Pediatric intensive care unit. 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. 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). 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.

Bacteremia and fungemia in pediatric versus adult cancer patients after chemotherapy: comparison of etiology, risk factors and outcome.

PubMed

Krupova, I; Kaiserova, E; Foltinova, A; Kovacicova, G; Kiskova, M; Krchnakova, A; Kunova, A; Trupl, J; West, D; Krcmery, V

1998-06-01

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

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

Psychological and Physical Interventions for 
the Management of Cancer-Related Pain in Pediatric and Young Adult Patients: An Integrative Review.

PubMed

Jibb, Lindsay A; Nathan, Paul C; Stevens, Bonnie J; Seto, Emily; Cafazzo, Joseph A; Stephens, Nisha; Yohannes, Liza; Stinson, Jennifer N

2015-11-01

To identify and appraise current evidence related to the effectiveness of psychological and physical (nonpharmacologic) pain management modalities for children and young adults with cancer
. Electronic searches in MEDLINE, EMBASE, CINAHL, PsycINFO, and Web of Science (from database inception to June 2013) for clinical trials. A total of 32 unique studies were identified. Substantial heterogeneity existed across identified studies, precluding meta-analysis. Therefore, a narrative review of included studies is presented. Studies featured psychological and/or physical pain interventions for children and young adults (N = 1,171) aged 1-21 years with a variety of cancer diagnoses. Interventions included aromatherapy, art therapy, distraction, hypnosis, physical activity, physical positioning, touch therapy, and multimodal cognitive-behavior therapy. Twenty-two studies (69%) reported success in preventing or reducing pain intensity. The level of evidence and methodologic quality of studies were generally low
. Current nonpharmacologic pain interventions for pediatric and young adult patients with cancer are diverse. Several modalities significantly decreased pain intensity, suggesting that these strategies may be effective methods of pain treatment, particularly in the case of painful medical procedures. Future well-designed, multicenter, randomized, controlled trials are needed to further discern treatment effects on pain and other health outcomes in this population and to compare the relative effectiveness of different modalities. Nurses play a key role in pain assessment and management in pediatric and young adult patients with cancer. The studies included in this review constitute the beginnings of an evidence base that supports the need to implement psychological and physical interventions to improve pain outcomes in pediatric and young adult patients with cancer.

The impact of language barriers and immigration status on the care experience for Spanish-speaking caregivers of patients with pediatric cancer.

PubMed

Zamora, Eduardo R; Kaul, Sapna; Kirchhoff, Anne C; Gwilliam, Vannina; Jimenez, Ornella A; Morreall, Deborah K; Montenegro, Roberto E; Kinney, Anita Y; Fluchel, Mark N

2016-12-01

An increasing proportion of pediatric cancer patients in the United States are Latino and many have Spanish-speaking immigrant parents with limited English proficiency (LEP). Little is known about how language or undocumented immigration status impacts their care experience. A cross-sectional survey was administered to English (N = 310) and Spanish-speaking LEP (N = 56) caregivers of pediatric cancer patients. To assess differences in healthcare experiences between the language groups, t-tests and chi-square statistics were used. Multivariable logistic regression evaluated associations between primary language and knowledge of clinical trial status. Spanish-speaking caregivers were more likely to report higher rates of quitting or changing jobs as a direct result of their child's cancer, and their children were more likely to experience a delay in education. Although Spanish-speaking caregivers reported higher satisfaction with care, 32% reported feeling that their child would have received better care if English was their primary language. Spanish-speaking caregivers were more likely to incorrectly identify whether their child was on a clinical trial compared with English-speaking caregivers. The majority of Spanish-speaking caregivers reported at least one undocumented caregiver in the household and 11% of them avoided or delayed medical care for their child due to concerns over their undocumented immigration status. Language barriers and undocumented immigration status may negatively impact the quality of informed decision-making and the care experience for Spanish-speaking LEP caregivers of pediatric cancer patients. These families may benefit from culturally appropriate Spanish language resources to improve communication and open a dialogue regarding undocumented immigration status. © 2016 Wiley Periodicals, Inc.

Comparability of the Patient-Reported Outcomes Measurement Information System Pediatric short form symptom measures across culture: examination between Chinese and American children with cancer.

PubMed

Liu, Yanyan; Yuan, Changrong; Wang, Jichuan; Brown, Jeanne Geiger; Zhou, Fen; Zhao, Xiufang; Shen, Min; Hinds, Pamela S

2016-10-01

Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric forms measure symptoms and function of pediatric patients experiencing chronic disease by using the same measures. Comparability is one of the most important purposes of the PROMIS initiative. This study aimed to test the factorial structures of four symptom measures (i.e., Anxiety, Depression, Fatigue, and Pain Interference) in the original English and the Chinese versions and examine the measurement invariance of the measures across two cultures. Four PROMIS Pediatric measures were used to assess symptoms, respectively, in Chinese (n = 232) and American (n = 200) children and adolescents (8-17 years old) in treatment for cancer or in survivorship. The categorical confirmatory factor analysis (CCFA) model was used to examine factorial structures, and multigroup CCFA was applied to test measurement invariance of these measures between the Chinese and American samples. The CCFA models of the four PROMIS Pediatric symptom measures fit the data well for both the Chinese and American children and adolescents. Minor partial measurement invariance was identified. Factor means and factor variances of the four PROMIS measures were not significantly different between the two populations. Our results provide evidence that the four PROMIS Pediatric symptom measures have valid factorial structures and a statistical property of measurement invariance across American and Chinese children and adolescents with cancer. This means that the items of these measures were interpreted in a conceptually similar manner by two groups. They could be readily used for meaningful cross-cultural comparisons involving pediatric oncology patients in these two countries.

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.

Satisfaction with support versus size of network: differential effects of social support on psychological distress in parents of pediatric cancer patients.

PubMed

Harper, Felicity W K; Peterson, Amy M; Albrecht, Terrance L; Taub, Jeffrey W; Phipps, Sean; Penner, Louis A

2016-05-01

This study examined the direct and buffering effects of social support on longer-term global psychological distress among parents coping with pediatric cancer. In both sets of analyses, we examined whether these effects depended on the dimension of social support provided (i.e., satisfaction with support versus size of support network). Participants were 102 parents of pediatric cancer patients. At study entry, parents reported their trait anxiety, depression, and two dimensions of their social support network (satisfaction with support and size of support network). Parents subsequently reported their psychological distress in 3- and 9-month follow-up assessments. Parents' satisfaction with support had a direct effect on longer-term psychological distress; satisfaction was negatively associated with distress at both follow-ups. In contrast, size of support network buffered (moderated) the impact of trait anxiety and depression on later distress. Parents with smaller support networks and higher levels of trait anxiety and depression at baseline had higher levels of psychological distress at both follow-ups; for parents with larger support networks, there was no relationship. Social support can attenuate psychological distress in parents coping with pediatric cancer; however, the nature of the effect depends on the dimension of support. Whereas interventions that focus on increasing satisfaction with social support may benefit all parents, at-risk parents will likely benefit from interventions that ensure they have an adequate number of support resources. Copyright © 2015 John Wiley & Sons, Ltd.

Satisfaction with support versus size of network: Differential effects of social support on psychological distress in parents of pediatric cancer patients

PubMed Central

Harper, Felicity W. K.; Peterson, Amy M.; Albrecht, Terrance L.; Taub, Jeffrey W.; Phipps, Sean; Penner, Louis A.

2016-01-01

Objective This study examined the direct and the buffering effects of social support on longer-term global psychological distress among parents coping with pediatric cancer. In both sets of analyses we examined whether these effects depended on the dimension of social support provided (i.e., satisfaction with support versus size of support network). Method Participants were 102 parents of pediatric cancer patients. At study entry, parents reported their trait anxiety, depression, and two dimensions of their social support network (satisfaction with support and size of support network). Parents subsequently reported their psychological distress in 3- and 9-month follow-up assessments. Results Parents’ satisfaction with support had a direct effect on longer-term psychological distress; satisfaction was negatively associated with distress at both follow-ups. In contrast, size of support network buffered (moderated) the impact of trait anxiety and depression on later distress. Parents with smaller support networks and higher levels of trait anxiety and depression at baseline had higher levels of psychological distress at both follow-ups; for parents with larger support networks, there was no relationship. Conclusion Social support can attenuate psychological distress in parents coping with pediatric cancer; however, the nature of the effect depends on the dimension of support. Whereas, interventions that focus on increasing satisfaction with social support may benefit all parents, at-risk parents will likely benefit from interventions that ensure they have an adequate number of support resources. PMID:27092714

Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive, behavioral, and emotional outcomes.

PubMed

Marusak, Hilary A; Iadipaolo, Allesandra S; Harper, Felicity W; Elrahal, Farrah; Taub, Jeffrey W; Goldberg, Elimelech; Rabinak, Christine A

2018-06-01

Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine's true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent "cure" that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer - namely, the presence of a life-threatening disease and endurance of invasive medical procedures - has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for

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

Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.

PubMed

Fisher, Brian T; Robinson, Paula D; Lehrnbecher, Thomas; Steinbach, William J; Zaoutis, Theoklis E; Phillips, Bob; Sung, Lillian

2017-05-26

Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Parents’ Aggressive Influences and Children's Aggressive Problem Solutions with Peers

PubMed Central

Duman, Sarah; Margolin, Gayla

2009-01-01

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 9−10 year old children, and their mothers and fathers. Children's aggressive solutions correlated with same-sex parents’ actual marital aggression. For children with mothers who exhibit low actual marital aggression, mothers’ aggressive solutions to hypothetical situations corresponded with children's tendencies to propose aggressive but not assertive solutions. In a 3-way interaction, fathers’ aggressive solutions to peer scenarios and marital aggression, combined, exacerbated girls’ aggressive problem solving, but had the opposite effect for boys. Discussion addresses the complexity, particularly with respect to parent and child gender combinations, in understanding parents’ aggressive influences on children's peer relationships. PMID:17206880

Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses.

PubMed

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

2016-02-01

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. 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. 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. Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Strategies to improve success of pediatric cancer cooperative group quality of life studies: a report from the Children's Oncology Group.

PubMed

Whitlow, Puja G; Caparas, Mae; Cullen, Patricia; Trask, Christine; Schulte, Fiona; Embry, Leanne; Nagarajan, Rajaram; Johnston, Donna L; Sung, Lillian

2015-06-01

Quality of life (QoL) has been increasingly emphasized in National Cancer Institute (NCI)-sponsored multisite clinical trials. Little is known about the outcomes of these trials in pediatric cancer. Objectives were to describe the proportion of Children's Oncology Group (COG) QoL studies that successfully accrued subjects and were analyzed, presented or published. We conducted a survey to describe outcomes of COG QoL studies. We included studies that contained at least one QoL assessment and were closed to patient accrual at the time of survey dissemination. Respondents were the investigators most responsible for the QoL aim. Sixteen studies were included; response rate was 100%. Nine (56%) studies were embedded into a cancer treatment trial. Only 3 (19%) studies accrued their intended sample size. Seven (44%) studies were analyzed, 9 (56%) were presented, and 6 (38%) were published. NCI-sponsored pediatric QoL studies have high rates of failure to accrue. Many were not analyzed or disseminated. Using these data, strategies have been implemented to improve conduct in future trials. Monitoring of QoL studies is important to maximize the chances of study success.

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

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

2016-09-01

Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from 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. 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 (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. 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. 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 observed racial differences in associations. Prostate 76:1053-1066, 2016. © 2016 Wiley Periodicals, Inc. © 2016

A Prototype Exercise-Empowerment Mobile Video Game for Children With Cancer, and Its Usability Assessment: Developing Digital Empowerment Interventions for Pediatric Diseases.

PubMed

Bruggers, Carol S; Baranowski, Sabrina; Beseris, Mathew; Leonard, Rachel; Long, Derek; Schulte, Elizabeth; Shorter, Ashton; Stigner, Rowan; Mason, Clinton C; Bedrov, Alisa; Pascual, Ian; Bulaj, Grzegorz

2018-01-01

Medical advances continue to improve morbidity and mortality of serious pediatric diseases, including cancer, driving research addressing diminished physical and psychological quality of life in children with these chronic conditions. Empowerment enhances resilience and positively influences health, disease, and therapy understanding. We describe the development and usability assessment of a prototype Empower Stars! mobile video game grounded in behavioral and exercise theories with the purpose of coupling physical exercise with empowerment over disease in children with cancer. Academic faculty, health-care providers, and community video game developers collaborated in this project. The iPadAir was selected as a delivery platform for its accelerometer and gyroscope features facilitating exercise design. Unity multiplatform technology provided animation and audiovisual features for immediate player feedback. Javascript, C#, Photoshop, Flash, and SketchUp were used for coding, creating graphical assets, Sprite sheets, and printing files, respectively. 3D-printed handles and case backing were used to adapt the iPad for physical exercise. Game usability, engagement, and enjoyment were assessed via a multilevel study of children undergoing cancer chemotherapy, their parents, and pediatric cancer health-care providers. Feedback crucial for ongoing game development was analyzed. A prototype Empower Stars! mobile video game was developed for children 7-14 years old with cancer. Active, sedentary, educational, and empowerment-centered elements intermix for 20 min of exercise within a 30 min "one-day treatment" gameplay session involving superheroes, space exploration, metaphorical cancer challenges, life restoration on a barren planet, and innumerable star rewards. No player "dies." Usability assessment data analyses showed widespread enthusiasm for integrating exercise with empowerment over cancer and the game itself. Favorite elements included collecting star

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

Pediatric Oncology Branch - training- resident electives | Center for Cancer Research

Cancer.gov

Resident Electives Select pediatric residents may be approved for a 4-week elective rotation at the Pediatric Oncology Branch. This rotation emphasizes the important connection between research and patient care in pediatric oncology. The resident is supervised directly by the Branch’s attending physician and clinical fellows. Residents attend daily in-patient and out-patient

IQGAP1 Is Involved in Enhanced Aggressive Behavior of Epithelial Ovarian Cancer Stem Cell-Like Cells During Differentiation.

PubMed

Huang, Lu; Xu, Shanshan; Hu, Dongxiao; Lu, Weiguo; Xie, Xing; Cheng, Xiaodong

2015-05-01

Wide metastasis is one of characteristics of ovarian cancer. Cancer stem cells, as a source in cancer invasion and metastasis, possess powerful potential of differentiation. Scaffolding IQ domain GTPase-activating protein 1 (IQGAP1) plays a key role in the invasion and metastasis of cancer cells, but IQGAP1's role in cancer stem cells including ovarian cancer was unclear. Spheroid culture with serum-free medium was used for enriching ovarian cancer stem cell-like cells (CSC-LCs) from 3AO cell line, and a medium with 10% fetal bovine serum was used to induce the differentiation of CSC-LCs. Immunofluorescence was for detecting the stem markers OCT4 and SOX2. The quantitative real-time-polymerase chain reaction and Western blotting were performed to determine the messenger RNA and protein expression of IQGAP1, respectively. The capacity of cell invasion was evaluated by transwell chamber assay. Ovarian CSC-LCs obtained through spheroid culture showed irregularly elongated appearance, CD24 negative, and OCT4 and SOX2 positive. IQGAP1 expression was decreased in ovarian CSC-LCs compared with parental 3AO cells, but increased de novo during the differentiation of CSC-LCs. Knockdown of IQGAP1 by specific small interfering RNA remarkably weakened invasion capacity of 2-day differentiated ovarian CSC-LCs. Increased IQGAP1 expression during the differentiation of CSC-LCs is involved in an aggressive cell behavior, which may contribute to metastasis of ovarian cancer.

Global Pediatric Oncology: Lessons From Partnerships Between High-Income Countries and Low- to Mid-Income Countries

PubMed Central

Antillon, Federico; Pedrosa, Francisco; Pui, Ching-Hon

2016-01-01

Partnerships between medical institutions in high-income countries (HICs) and low- to mid-income countries (LMICs) have succeeded in initiating and expanding pediatric cancer control efforts. The long-term goal is consistently a sustainable national pediatric cancer program. Here, we review the elements required for successful implementation, development, and long-term sustainability of pediatric cancer programs in LMICs that first arise as partnerships with institutions in HICs. Although plans must be adapted to each country's resources, certain components are unfailingly necessary. First, an essential step is provision of treatment regardless of ability to pay. Second, financial support for program development and long-term sustainability must be sought from sources both international and local, public and private. A local leader, typically a well-trained pediatric oncologist who devotes full-time effort to the project, should direct medical care and collaborate with hospital, governmental, and community leadership and international agencies. Third, nurses must be trained in pediatric cancer care and allowed to practice this specialty full-time. It is also essential to develop a grassroots organization, such as a foundation, dedicated solely to pediatric oncology. Its members must be trained and educated to provide pediatric cancer advocacy, fundraising, and (in concert with government) program sustainability. Finally, a project mentor in the HIC is crucial and should explore the possibility of collaborative research in the LMIC, which may offer significant opportunities. Relationships between the partnership's leaders and influential individuals in the community, hospital, grassroots foundation, and government will lay the foundation for productive collaboration and a sustainable pediatric oncology program. PMID:26578620

The Effect of Cancer Therapies on Pediatric Anophthalmic Sockets

PubMed Central

Shildkrot, Yevgeniy; Kirzhner, Maria; Haik, Barrett G.; Qaddoumi, Ibrahim; Rodriguez-Galindo, Carlos; Wilson, Matthew W.

2012-01-01

Purpose To determine the impact of chemotherapy or external beam radiotherapy (EBRT) on pediatric anophthalmic sockets. Design A retrospective, nonrandomized, interventional cohort study. Participants A total of 135 sockets of 133 children undergoing enucleation from late 1999 to early 2009 at the St. Jude Children’s Research Hospital were included. Methods A retrospective chart review of outcomes after enucleation in patients treated with systemic chemotherapy or orbital EBRT either before or after removal of the eye compared with patients who received no other treatment. Main Outcome Measures Incidence of implant exposure, migration, extrusion, socket contracture, and pyogenic granuloma formation. Results Retinoblastoma was the primary diagnosis in 128 eyes (95%). Median follow-up was 3.6 years (range, 0.1–9.3 years). Event-free course was observed in 94 sockets (69.6%). Complications included implant exposure (n = 28, 20.7%), socket contracture (n = 16, 11.9%), pyogenic granuloma (n = 9, 6.7%), implant extrusion (n = 3, 2.2%), and migration (n = 2, 1.5%). Exposure resolved in 21 sockets (77.8%) and improved in 2 sockets (11.1%); 1 patient with exposure died. Use of prior, adjuvant, or subsequent chemotherapy increased the long-term risk of exposure (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.4–9.4), and contracture (OR could not be calculated, P<0.0001). External beam radiotherapy greatly increased the risk of contracture (OR 24.0; 95% CI, 6.9–82.8) and exposure (OR 2.89; 95% CI, 1.1–7.9). Conclusions In this unique pediatric population with cancer, chemotherapy and EBRT had an additive effect, significantly increasing the incidence of exposure and socket contracture. PMID:21856015

Plasma cell leukaemia and other aggressive plasma cell malignancies

PubMed Central

Sher, Taimur; Miller, Kena C.; Deeb, George; Lee, Kelvin; Chanan-Khan, Asher

2014-01-01

Summary Extramedullary plasma cell cancers, such as plasma cell leukemia (PCL) and multiple extramedullary plasmacytomas (MEP) are very aggressive malignancies. These can be primary (de-novo) or secondary due to progressive prior multiple myeloma (MM). Recent reports suggest an increase in incidence of these disorders. Compared to MM, organ invasion is common in PCL, while soft tissue tumors involving the head, neck or paraspinal area are common sites for MEP. Markers of poor prognosis are frequently observed in these extramedullary forms of plasma cell cancers, and survival is significantly inferior compared to patients with MM. Conventional chemotherapeutic and radiotherapy approaches have been employed with variable results. Even high dose chemotherapy with autologous stem cell rescue has not been able to demonstrate consistent improvement in survival outcome. Although not specifically evaluated, novel anti-plasma cell agents, such as the proteasome inhibitor bortezomib, and immunomodulatory drugs, such as lenalidomide, appear to be active against these aggressive cancers. Clinical and translational research directed at improved understanding of disease biology and development of novel therapeutics is urgently needed. PMID:20701603

What You Need to Know about Cancer of the Uterus

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

What You Need to Know about Cancer of the Esophagus

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

What You Need to Know about Cancer of the Larynx

MedlinePlus

... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

A genome-wide pleiotropy scan for prostate cancer risk.

PubMed

Panagiotou, Orestis A; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R; Siddiq, Afshan; Papatheodorou, Stefania I; Stanford, Janet L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J; Diver, W Ryan; Gapstur, Susan M; Stevens, Victoria L; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Barricarte Gurrea, Aurelio; Kaaks, Rudolf; Khaw, Kay-Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J Michael; Hunter, David J; Koutros, Stella; Yeager, Meredith; Hoover, Robert N; Chanock, Stephen J; Wacholder, Sholom; Key, Timothy J; Tsilidis, Konstantinos K

2015-04-01

No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. SNPs implicated in any phenotype other than prostate cancer (p≤10(-7)) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24,534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p=1.6×10(-6)), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p=3.22×10(-18)). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p=2.5×10(-6)). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p=4.67×10(-5)); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in

Adolescents’ Aggression to Parents: Longitudinal Links with Parents’ Physical Aggression

PubMed Central

Margolin, Gayla; Baucom, Brian R.

2014-01-01

Purpose To investigate whether parents’ previous physical aggression (PPA) exhibited during early adolescence is associated with adolescents’ subsequent parent-directed aggression even beyond parents’ concurrent physical aggression (CPA); to investigate whether adolescents’ emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. Methods Adolescents (N = 93) and their parents participated in a prospective, longitudinal study. Adolescents and parents reported at waves 1–3 on four types of parents’ PPA (mother-to-adolescent, father-to-adolescent, mother-to-father, father-to-mother). Wave 3 assessments also included adolescents’ emotion dysregulation, attitudes condoning aggression, and externalizing behaviors. At waves 4 and 5, adolescents and parents reported on adolescents’ parent-directed physical aggression, property damage, and verbal aggression, and on parents’ CPA Results Parents’ PPA emerged as a significant indicator of adolescents’ parent-directed physical aggression (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.0–1.55; p = .047), property damage (OR: 1.29, 95% CI: 1.1–1.5, p = .002), and verbal aggression (OR: 1.35, 95% CI: 1.15–1.6, p < .001) even controlling for adolescents’ sex, externalizing behaviors, and family income. When controlling for parents’ CPA, previous mother-to-adolescent aggression still predicted adolescents’ parent-directed physical aggression (OR: 5.56, 95% CI: 1.82–17.0, p = .003), and father-to-mother aggression predicted adolescents’ parent-directed verbal aggression (OR: 1.86, 95% CI: 1.0–3.3, p = .036). Emotion dysregulation and attitudes condoning aggression did not produce direct or moderated effects. Conclusions Adolescents’ parent-directed aggression deserves greater attention in discourse about lasting, adverse effects of even minor forms of parents’ physical aggression. Future research should investigate parent-directed aggression as

An Aggressive Surgical Approach Leads to Improved Survival in Patients With Gallbladder Cancer

PubMed Central

Dixon, Elijah; Vollmer, Charles M.; Sahajpal, Ajay; Cattral, Mark; Grant, David; Doig, Christopher; Hemming, Al; Taylor, Bryce; Langer, Bernard; Greig, Paul; Gallinger, Steven

2005-01-01

Objective: To determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Summary Background Data: Many physicians express a relatively nihilistic approach to the treatment of gallbladder cancer; consensus among surgeons regarding the indications for a radical surgical approach has not been reached. Methods: A retrospective review of all patients with gallbladder cancer admitted during the past 12 years was conducted. Ninety-nine patients were identified. Cases treated during the 12-year period 1990 to 2002 were divided into 2 time-period (TP) cohorts, those treated in the first 6 years (TP1, N = 35) and those treated in the last 6 years (TP2, N = 64). Results: Disease stratification by stage and other demographic features were similar in the 2 time periods. An operation with curative intent was performed on 38 patients. Nine (26%) R0 resections were performed in TP1 and 24 (38%) in TP2. The number of liver resections, as well as the frequency of extrahepatic biliary resections, was greater in TP2 (P < 0.04). In both time periods, an R0 resection was associated with improved survival (P < 0.02 TP1, P < 0.0001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.03), with a median survival of 9 months in TP1 and 17 months in TP2. The median 5-year survival in TP1 was 7%, and 35% in TP2. The surgical mortality rate for the entire cohort was 2%, with a 49% morbidity rate. Conclusions: A margin-negative, R0 resection leads to improved survival in patients with gallbladder cancer. PMID:15729060

Rhabdomyosarcoma treatment and outcome at a multidisciplinary pediatric cancer center in Lebanon.

PubMed

Salman, Maysaa; Tamim, Hani; Medlej, Fouad; El-Ariss, Tarek; Saad, Fatima; Boulos, Fouad; Eid, Toufic; Muwakkit, Samar; Khoury, Nabil; Abboud, Miguel; Saab, Raya

2012-05-01

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Outcome of patients treated on standard protocols, in a multidisciplinary cancer center setting outside of clinical trials, is not well reported. We reviewed characteristics and outcome of 23 pediatric patients treated at a single, multidisciplinary cancer center in Lebanon, between April 2002 and December 2010. Median follow-up was 41 months. The most commonly affected primary site was the head and neck (48%, n = 11). Nineteen tumors (82.6%) were of embryonal histology. Tumor size was ≥5 cm in eight (34.8%) patients. Sixteen patients (69.6%) had localized disease, and one (4.4%) had metastatic disease. Fifteen (65.2%) had Group III tumors. All patients received chemotherapy, for a duration ranging 21-51 weeks. Upfront surgical resection was performed in 10 patients (43.5%). Eighteen patients (78.3%) received radiation therapy. The 5-year overall and disease-free survival rates were 83% and 64%, respectively. Relapse correlated with absence of surgery. Treatment of childhood RMS in a multidisciplinary cancer center in Lebanon results in similar survival to that in developed countries when similar protocols are applied. There was a higher incidence of local relapse, but those were salvageable with further therapy and surgical local control.

Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study.

PubMed

Harris, Marian H; DuBois, Steven G; Glade Bender, Julia L; Kim, AeRang; Crompton, Brian D; Parker, Erin; Dumont, Ian P; Hong, Andrew L; Guo, Dongjing; Church, Alanna; Stegmaier, Kimberly; Roberts, Charles W M; Shusterman, Suzanne; London, Wendy B; MacConaill, Laura E; Lindeman, Neal I; Diller, Lisa; Rodriguez-Galindo, Carlos; Janeway, Katherine A

2016-01-28

Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit. To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors. Clinical sequencing study at 4 academic medical centers enrolling patients between September 5, 2012, and November 19, 2013, with 1 year of clinical follow-up. Participants were 30 years or younger with high-risk, recurrent, or refractory extracranial solid tumors. The data analysis was performed October 28, 2014. Tumor profiling performed on archived clinically acquired specimens consisted of mutation detection by a Sequenom assay or targeted next-generation sequencing and copy number assessment by array comparative genomic hybridization. Results were reviewed by a multidisciplinary expert panel, and iCat recommendations were made if an actionable alteration was present, and an appropriate drug was available. Feasibility was assessed using a 2-stage design based on the proportion of patients with recommendations. Of 100 participants (60 male; median [range] age, 13.4 [0.8-29.8] years), profiling was technically successful in 89 (89% [95% CI, 83%-95%]). Median (range) follow-up was 6.8 (2.0-23.6) months. Overall, 31 (31% [95% CI, 23%-41%]) patients received an iCat recommendation and 3 received matched therapy. The most common actionable alterations leading to an iCat recommendation were cancer-associated signaling pathway gene mutations (n = 10) and copy number alterations in MYC/MYCN (n = 6) and cell cycle genes (n = 11). Additional alterations with implications for clinical care but not resulting in iCat recommendations were identified, including mutations indicating the possible presence of a cancer predisposition syndrome

Media violence exposure and physical aggression in fifth-grade children.

PubMed

Coker, Tumaini R; Elliott, Marc N; Schwebel, David C; Windle, Michael; Toomey, Sara L; Tortolero, Susan R; Hertz, Marci F; Peskin, Melissa F; Schuster, Mark A

2015-01-01

To examine the association of media violence exposure and physical aggression in fifth graders across 3 media types. We analyzed data from a population-based, cross-sectional survey of 5,147 fifth graders and their parents in 3 US metropolitan areas. We used multivariable linear regression and report partial correlation coefficients to examine associations between children's exposure to violence in television/film, video games, and music (reported time spent consuming media and reported frequency of violent content: physical fighting, hurting, shooting, or killing) and the Problem Behavior Frequency Scale. Child-reported media violence exposure was associated with physical aggression after multivariable adjustment for sociodemographics, family and community violence, and child mental health symptoms (partial correlation coefficients: TV, 0.17; video games, 0.15; music, 0.14). This association was significant and independent for television, video games, and music violence exposure in a model including all 3 media types (partial correlation coefficients: TV, 0.11; video games, 0.09; music, 0.09). There was a significant positive interaction between media time and media violence for video games and music but not for television. Effect sizes for the association of media violence exposure and physical aggression were greater in magnitude than for most of the other examined variables. The association between physical aggression and media violence exposure is robust and persistent; the strength of this association of media violence may be at least as important as that of other factors with physical aggression in children, such as neighborhood violence, home violence, child mental health, and male gender. Copyright © 2015 Academic Pediatric Association. All rights reserved.

Breast Cancer Following Spinal Irradiation for a Childhood Cancer: A Report from the Childhood Cancer Survivor Study

PubMed Central

Moskowitz, Chaya S.; Malhotra, Jyoti; Chou, Joanne F.; Wolden, Suzanne L.; Weathers, Rita E.; Stovall, Marilyn; Armstrong, Gregory T.; Leisenring, Wendy M.; Neglia, Joseph P.; Robison, Leslie L.; Oeffinger, Kevin C.

2015-01-01

Summary It has been suggested that pediatric patients treated with spinal irradiation may have an elevated risk of breast cancer. Among a cohort of 363 long-term survivors of a pediatric central nervous system tumor or leukemia treated with spinal irradiation, there was little evidence of an increased breast cancer risk. PMID:26391961

A mindfulness-based intervention for self-management of verbal and physical aggression by adolescents with Prader-Willi syndrome.

PubMed

Singh, Nirbhay N; Lancioni, Giulio E; Myers, Rachel E; Karazsia, Bryan T; Courtney, Theresa M; Nugent, Kristen

2017-07-01

There is a dearth of clinical and research literature on the treatment of maladaptive behaviors in adolescents with Prader-Willi syndrome (PWS). The purpose of this study was to evaluate the effectiveness of a mindfulness-based intervention, Meditation on the Soles of the Feet (SoF), to facilitate self-management of verbal and physical aggression. We utilized a multiple-baseline design across participants to test the intervention with three adolescents diagnosed with PWS. Relative to baseline, verbal aggression decreased to minimal levels following mindfulness-based practice and physical aggression was nearly eliminated. Intervention effects were maintained at 12-month follow-up. Quantitative analytics confirmed statistically significant outcomes. The SoF mindfulness intervention was effective in reducing verbal and physical aggression in three adolescents with PWS. Future research should test the SoF intervention with this clinical population in a larger clinical trial, and the SoF intervention may be applicable to other pediatric populations.

Development and Implementation of a Pediatric Palliative Care Program in a Developing Country.

PubMed

Doherty, Megan; Thabet, Chloé

2018-01-01

Palliative care is recognized as an important component of care for children with cancer and other life-limiting conditions. In resource limited settings, palliative care is a key component of care for children with cancer and other life-limiting conditions. Globally, 98% of children who need palliative care live in low- or middle-income countries, where there are very few palliative care services available. There is limited evidence describing the practical considerations for the development and implementation of sustainable and cost-effective palliative care services in developing countries. Our aim is to describe the key considerations and initiatives that were successful in planning and implementing a hospital-based pediatric palliative care service specifically designed for a resource-limited setting. Bangabandu Sheikh Mujib Medical University (BSMMU) is a tertiary referral hospital in Bangladesh. Local palliative care services are very limited and focused on adult patients. In partnership with World Child Cancer, a project establishing a pediatric palliative care service was developed for children with cancer at BSMMU. We describe four key elements which were crucial for the success of this program: (1) raising awareness and sensitizing hospital administrators and clinical staff about pediatric palliative care; (2) providing education and training on pediatric palliative care for clinical staff; (3) forming a pediatric palliative care team; and (4) collecting data to characterize the need for pediatric palliative care. This model of a hospital-based pediatric palliative care service can be replicated in other resource-limited settings and can be expanded to include children with other life-limiting conditions. The development of pilot programs can generate interest among local physicians to become trained in pediatric palliative care and can be used to advocate for the palliative care needs of children.

Aggression Can be Contagious: Longitudinal Associations between Proactive Aggression and Reactive Aggression Among Young Twins

PubMed Central

Dickson, Daniel J.; Richmond, Ashley; 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. PMID:25683448

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. © 2015 Wiley Periodicals, Inc.

Endothelin-1 Expression in Prostate Needle Biopsy Specimens Correlated With Aggressiveness of Prostatic Cancer

PubMed Central

Asgari, Mojgan; Eftekhar, Elham; Abolhasani, Maryam; Shahrokh, Hossein

2017-01-01

Background & Objective: As the prostate adenocarcinoma is one of the most common malignant tumors in males, looking for a marker to effectively predict aggressiveness and metastatic potential in an apparently localized cancer in initial needle biopsy specimens can help the clinicians to make more appropriate decision for treatment, planning, and choosing appropriate targeted therapy. The present study assessed the value of Endothelin-1 expression to predict prognosis of prostatic cancer Methods: In a cross sectional study, 83 patients who underwent radical prostatectomy in Hasheminejad Kidney Center in 2008 through 2012 were assigned to two groups including 43 with and 40 without extra-prostatic extension (EPE). Endothelin-1 staining was performed on Paraffin Embedded blocks of preoperative needle biopsies. Results: The expression of Endothelin-1 increased in 72% of patients in the group with EPE (P<0.001). The group with Endothelin-1 positivity showed higher serum level of prostate specific antigen (PSA) (p = 0.039). Endothelin-1 expression was positive in 67% of patients with perineurial invasion (P<0.001). Adjusting the baseline variables of PSA and PN in a multivariable logistic regression model, the Endothelin-1 positivity could effectively predict EPE in patients with prostatic cancer (OR: 5.46, p = 0.010). Conclusion: Correlation of Endothelin-1 expression in needle biopsy specimens in expected with extra-prostatic extension of tumor in radical prostatectomy specimens, perineurial invasion and serum PSA level at the time of diagnosis. PMID:29515640

A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM).

PubMed

González, A; Lluch, A; Aba, E; Albanell, J; Antón, A; Álvarez, I; Ayala, F; Barnadas, A; Calvo, L; Ciruelos, E; Cortés, J; de la Haba, J; López-Vega, J M; Martínez, E; Muñoz, M; Peláez, I; Redondo, A; Rodríguez, Á; Rodríguez, C A; Ruíz, A; Llombart, A

2017-05-01

To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.

Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group.

PubMed

Bock, Matthew J; Pahl, Elfriede; Rusconi, Paolo G; Boyle, Gerard J; Parent, John J; Twist, Clare J; Kirklin, James K; Pruitt, Elizabeth; Bernstein, Daniel

2017-08-01

We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post-HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post-HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post-HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

School Aggression and Dispositional Aggression among Middle School Boys

ERIC Educational Resources Information Center

Ballard, Mary E.; Rattley, Kelvin T.; Fleming, Willie C.; Kidder-Ashley, Pamela

2004-01-01

We examined the relationship between dispositional (trait) aggression and administrative reports of school aggression among 100 adolescent male participants from an urban middle school. Aggression was fairly common among the sample; 58 boys had a record of school aggression, and many of those were repeat offenders. Our hypothesis that those higher…

Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women.

PubMed

Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

2017-01-01

Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p -value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young (<35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade ( r  = 0.696, p  < 0.05) but weakly correlated with tumour stage ( r  = 0.420, p  < 0.05). Patient's age correlated with DAPK1 concentration ( r  = 0

Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

PubMed

Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

2017-07-01

Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p < 0.01; respectively). Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

CONCEPT ANALYSIS: AGGRESSION

PubMed Central

Liu, Jianghong

2006-01-01

The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

Impact of attention on social functioning in pediatric medulloblastoma survivors.

PubMed

Holland, Alice Ann; Colaluca, Beth; Bailey, Laurie; Stavinoha, Peter L

2018-02-01

Parent-reported attention problems have been associated with social functioning in a broad sample of pediatric cancer survivors. The present study focused on a more homogeneous sample (pediatric medulloblastoma survivors), with the novel inclusion of self-reported attention ratings. Thirty-three pediatric medulloblastoma survivors, ages 7-18 years, completed a brief IQ measure and self-report of attentional and social functioning. Parents rated patients' attentional and social functioning. Mean attention ratings were average based on both parent- and self-report, though parent ratings were significantly discrepant from normative means. No significant demographic or treatment-related predictors of self-reported attention problems were identified, whereas female gender was associated with greater parent-reported attention problems. Canonical correlation analysis revealed a significant association between parent-reported attention difficulties and social functioning in pediatric medulloblastoma survivors, but there was no association between self-reported attention problems and measures of social functioning. Consistent with existing literature in broader samples of pediatric cancer survivors, the present study further affirms attention deficits as an underlying contributor to social deficits in pediatric medulloblastoma survivors while also finding little relationship between self-reports of attention and social performance. Notably, present findings provide additional support suggesting that attention functioning is a more significant contributor to social outcomes for pediatric medulloblastoma survivors than the level of cognitive ability.

The effect of cancer therapies on pediatric anophthalmic sockets.