Science.gov

Sample records for aggressive pediatric cancer

  1. Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer.

    PubMed

    Scursoni, Alejandra M; Galluzzo, Laura; Camarero, Sandra; Lopez, Jessica; Lubieniecki, Fabiana; Sampor, Claudia; Segatori, Valeria I; Gabri, Mariano R; Alonso, Daniel F; Chantada, Guillermo; de Dávila, María Teresa G

    2011-01-01

    The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.

  2. Leptin increases prostate cancer aggressiveness.

    PubMed

    López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

    2011-12-01

    Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

  3. Snapshot of Pediatric Cancers

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  4. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

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

  5. Pediatric aggressive giant cell granuloma of nasal cavity

    PubMed Central

    Seo, Sung Tae; Kwon, Ki Ryun; Rha, Ki-Sang; Kim, Seon-Hwan; Kim, Yong Min

    2015-01-01

    Introduction Giant cell granuloma (GCG) is a non-neoplastic osseous proliferative lesion of unknown etiology. Although a benign disease process, GCG can be locally destructive. It is extremely rare to have a pediatric case of GCG occurring in the nasal cavity with intracranial invasion. Presentation of case We report a case of an aggressive and recurrent giant cell granuloma with intracranial invasion in a 10 years old female patient which was completely excised with endoscopic craniofacial resection. Discussion A literature review on pathogenesis, diagnosis and management is also performed. Conclusion The most common treatment for giant cell granuloma is surgery, ranging from simple curettage to resection. However, it must be completely excised in cases of aggressive and extensive lesion because of the high recurrence rate after incomplete removal. PMID:26433924

  6. Precision Medicine for Pediatric Cancer.

    PubMed

    2015-11-01

    In a recent study, whole-exome and transcriptome sequencing identified potentially actionable findings that led to effective treatments for some children with advanced and rare cancers. The findings demonstrate that genomic sequencing data can be effectively integrated into the clinical management of pediatric patients.

  7. Pediatric Cancer Recognition Training in Botswana.

    PubMed

    Slone, Jeremy S; Ishigami, Elise; Mehta, Parth S

    2016-01-01

    Delayed presentation of children with cancer is a significant barrier to improving the survival from children's cancer in low- and middle-income countries (LMICs). Botswana, a country of approximately 2 million people in southern Africa, has only 1 pediatric cancer treatment program, based at Princess Marina Hospital (PMH) in the capital of Gaborone. A pediatric cancer recognition training program was developed that reached 50% of the government hospitals in Botswana teaching 362 health care workers how to recognize and refer children with cancer to PMH. Through evaluation of attendees, limitations in pediatric cancer training and general knowledge of pediatric cancer were identified. Attendees demonstrated improvement in their understanding of pediatric cancer and the referral process to PMH following the workshop. PMID:27336006

  8. Neuroendocrine aspects of pediatric aggression: Can hormone measures be clinically useful?

    PubMed

    Barzman, Drew H; Patel, Avni; Sonnier, Loretta; Strawn, Jeffrey R

    2010-01-01

    Pediatric aggression is common in human societies, mainly presenting as impulsive aggression or predatory aggression. Numerous psychiatric disorders can contain aggression as a symptom, leading to difficulties in diagnosis and treatment. This review focuses on the biological systems that affect pediatric aggression. We review the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and the mechanisms by which these axes influence the body and mind of aggressive children and adolescents. Although this review focuses on the HPA and HPG axes, it is important to note that other biological systems have relationships with these two axes. Based on the results of the studies reviewed, elevated cortisol concentrations were associated with impulsive aggression, whereas, low levels of cortisol were associated with callous-unemotional traits similar to predatory aggression. Higher levels of dehydroepiandrosterone were correlated with higher levels of aggression as were higher levels of testosterone. However, there have been discrepancies in the results between various studies, indicating the need for more research on hormonal levels and pediatric aggression. In the future, hormonal levels may be useful in determining what treatments will work best for certain pediatric patients.

  9. 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

  10. Complications of tracheal intubation in critically ill pediatric cancer patients

    PubMed Central

    Siddiqui, Suhail Sarwar; Janarthanan, S.; Harish, M. M.; Chaudhari, Harish; Prabu, R. Natesh; Divatia, Jigeeshu V.; Kulkarni, Atul Prabhakar

    2016-01-01

    Background and Aims: The oncologists are treating cancer more aggressively, leading to increase in number of pediatric admissions to the ICU. Due to anatomical and physiological differences, pediatric patients are at high risk of complications during intubation. We evaluated the incidence of complications during intubations in pediatric patients in our ICU. Subjects and Methods: We performed retrospective analysis of complications occurring during intubation in 42 pediatric patients. All intubations were orotracheal. We recorded number of attempts at intubation, need for use of intubation adjuncts and complications during laryngoscopy and intubation. The incidence of difficult intubation, hypoxia, and severe cardiovascular collapse was also noted. Results: Complications occurred during 13 (31%) intubations. Hypoxia and severe cardiovascular collapse occurred in during 7 (16.7%) intubations each, while 4 patients (9.5%) (n=4) had cardiac arrest during intubation. Thirty three (78.6%) intubations were successful in first attempt and difficult intubation was recorded in 4 patients. Conclusion: Critically ill pediatric cancer patients have a high rate of complications during intubation. PMID:27555695

  11. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  12. Update on pediatric cancer predisposition syndromes.

    PubMed

    Schiffman, Joshua D; Geller, James I; Mundt, Erin; Means, Anthony; Means, Lindsey; Means, Von

    2013-08-01

    Hereditary cancer syndromes in children and adolescents are becoming more recognized in the field of pediatric hematology/oncology. A recent workshop held at the American Society of Pediatric Hematology/Oncology (ASPHO) 2012 Annual Meeting included several interactive sessions related to specific familial cancer syndromes, genetic testing and screening, and ethical issues in caring for families with inherited cancer risk. This review highlights the workshop presentations, including a brief background about pediatric cancer predisposition syndromes and the importance of learning about them for the practicing pediatric hematologists/oncologists. This is followed by a brief summary of the newly described cancer predisposition syndromes including Rhabdoid Tumor Predisposition Syndrome, Hereditary Paragangliomas and Pheochromocytoma Syndrome, and Familial Pleuropulmonaryblastoma Tumor Predisposition (DICER1) Syndrome. The next section covers genetic testing and screening for pediatric cancer predisposition syndromes. Ethical issues are also discussed including preimplantation genetic diagnosis or testing (PGD/PGT), suspicious lesions found on tumor screening, and incidental mutations discovered by whole genome sequencing. Finally, the perspective of a family with Li-Fraumeni Syndrome is shared.

  13. Update on pediatric cancer predisposition syndromes.

    PubMed

    Schiffman, Joshua D; Geller, James I; Mundt, Erin; Means, Anthony; Means, Lindsey; Means, Von

    2013-08-01

    Hereditary cancer syndromes in children and adolescents are becoming more recognized in the field of pediatric hematology/oncology. A recent workshop held at the American Society of Pediatric Hematology/Oncology (ASPHO) 2012 Annual Meeting included several interactive sessions related to specific familial cancer syndromes, genetic testing and screening, and ethical issues in caring for families with inherited cancer risk. This review highlights the workshop presentations, including a brief background about pediatric cancer predisposition syndromes and the importance of learning about them for the practicing pediatric hematologists/oncologists. This is followed by a brief summary of the newly described cancer predisposition syndromes including Rhabdoid Tumor Predisposition Syndrome, Hereditary Paragangliomas and Pheochromocytoma Syndrome, and Familial Pleuropulmonaryblastoma Tumor Predisposition (DICER1) Syndrome. The next section covers genetic testing and screening for pediatric cancer predisposition syndromes. Ethical issues are also discussed including preimplantation genetic diagnosis or testing (PGD/PGT), suspicious lesions found on tumor screening, and incidental mutations discovered by whole genome sequencing. Finally, the perspective of a family with Li-Fraumeni Syndrome is shared. PMID:23625733

  14. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

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

    2015-01-01

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

  15. Targeting pediatric cancer stem cells with oncolytic virotherapy.

    PubMed

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

    2012-04-01

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

  16. Targeting Pediatric Cancer Stem Cells with Oncolytic Virotherapy

    PubMed Central

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

    2013-01-01

    Cancer stem cells (CSC), also termed “cancer initiating cells” or “cancer progenitor cells”, which have the ability to self-renew, proliferate, and maintain the neoplastic clone, have recently been discovered in a wide variety of pediatric tumors. These CSC are thought to be responsible for tumorigenesis, tumor maintenance, aggressiveness and recurrence due to inherent resistance to current treatment modalities such as chemotherapy and radiation. Oncolytic virotherapy offers a novel, targeted approach for eradicating pediatric CSC by utilizing mechanisms of cell killing that differ from conventional therapies. Moreover, oncolytic viruses have the ability to target specific features of CSC such as cell surface proteins, transcription factors, and the CSC microenvironment. Through genetic engineering, a wide variety of foreign genes may be expressed by oncolytic viruses to augment the oncolytic effect. We review the current data regarding the ability of several types of oncolytic viruses (herpes simplex virus-1 (HSV-1), adenovirus, reovirus, Seneca Valley virus, vaccinia virus, Newcastle disease virus, myxoma virus, vesicular stomatitis virus) to target and kill both CSC and tumor cells in pediatric tumors. We highlight advantages and limitations of each virus and potential ways next-generation engineered viruses may target resilient CSC. PMID:22430386

  17. Facilitating the Pediatric Cancer Patient's Return to School.

    ERIC Educational Resources Information Center

    Ross, Judith W.; Scarvalone, Susan A.

    1982-01-01

    Describes the educational needs of the pediatric cancer patient in returning to school. Discusses attitudes of parents and school personnel. Presents a seminar for teachers and school nurses of elementary pupils treated at a cancer center. (RC)

  18. Two Susceptibility Loci Identified for Prostate Cancer Aggressiveness

    PubMed Central

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

    2015-01-01

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

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

    Cancer.gov

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

  20. Targeted immunotherapy for pediatric solid tumors

    PubMed Central

    Kopp, Lisa M.; Katsanis, Emmanuel

    2016-01-01

    ABSTRACT Metastatic and refractory pediatric solid tumor malignancies continue to have a poor outcome despite the > 80% cure rates appreciated in many pediatric cancers. Targeted immunotherapy is impacting treatment and survival in these aggressive tumors. We review current promising immunotherapeutic approaches in the pediatric oncology solid tumor setting. PMID:27141344

  1. Src: Marker or Actor in Prostate Cancer Aggressiveness

    PubMed Central

    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. PMID:25184116

  2. Multimodal treatment of aggressive forms of breast cancer

    PubMed Central

    Mihai, D; Voiculescu, S; Cristian, D; Constantinescu, F; Popa, E; Burcos, T

    2014-01-01

    Abstract Aggressive breast cancer is an invasive form with G3, G4 differentiation degree, the absence of receptors for estrogen and progesterone and the absence or presence of HER2 (+ or 3+) gene. The final diagnosis is established by cumulating the clinical, paraclinical, histopathological and immunohistochemical diagnosis. Material and method: 84 out of 268 aggressive breast cancer cases were presented in the study, which were operated in October 2011-September 2013. The inclusion and exclusion criteria are exposed in the study lot and the treatment schemes. Results: For the study lot (lot A made up of 36 cases, lot B made up of 41 cases, lot C made up of 7 cases) the distribution was presented on age groups, histopathological and immunohistochemical classification, etiologic factors, type of surgery, postoperative staging and complications. Conclusions: The treatment of aggressive breast cancer depends on the level of the aggressiveness of the disease, the biologic status and the age that imposes the order of chemotherapy, radiotherapy, surgical treatment and target therapy. PMID:25408768

  3. Natural compounds for pediatric cancer treatment.

    PubMed

    Ferrucci, Veronica; Boffa, Iolanda; De Masi, Gina; Zollo, Massimo

    2016-02-01

    There is a tremendous need in clinics to impair cancer progression through noninvasive therapeutic approaches. The use of natural compounds to achieve this is of importance to improve the quality of life of young patients during their treatments. This review will address the "status of the art" related to the potential of natural compounds that are undergoing investigation in combination with standard therapeutic protocols in preclinical and clinical studies and their importance for pediatric cancer treatment. The early studies of drug discovery of these natural compounds discussed here include the main targets, the cellular signaling pathways involved, and the potential modes of action. We also focus on some promising natural compounds that have shown excellent results in vitro and in vivo: Chebulagic acid, Apigenin, Norcantharidin, Saffron/Crocin, Parthenolide, Longikaurin E, Lupeol, Spongistatin 1, and Deoxy-variolin B. Additionally, we introduce the effects of several compounds from nutraceutical and functional foods, to underline their potential use as adjuvant therapies to improve therapeutic benefits. For this purpose, we have selected several compounds: Agaritine, Ganoderma and GL6 peptide, Diallyl trisulfide and Ajoene from garlic, Epigallocatechin gallate from green tea, Curcumin, Resveratrol, and Quercetin. PMID:26650503

  4. Reality of pediatric cancer in Iraq.

    PubMed

    Al-Hadad, Salma Abbass; Al-Jadiry, Mazin Faisal; Al-Darraji, Amir Fadhil; Al-Saeed, Raghad Majid; Al-Badr, Safaa Faraj; Ghali, Hasanein Habeeb

    2011-10-01

    This brief report displays comprehensive details of health services provided by Children's Welfare Teaching Hospital, medical city, Baghdad. In 2010; 366 children with newly diagnosed cancer were admitted for treatment, two thirds were leukemia and lymphoma cases followed by other solid tumors except brain tumors. With this large number of patients; there are shortcomings in provision of health services in many aspects including professional manpower, infrastructure, diagnostic and therapeutic facilities, supportive and palliative care. The previous wars and sanction and the current instability of the country added to the socioeconomic difficulties of the families jeopardizing the appropriate therapy and ultimately the poor treatment outcome. Since 2003 an international collaboration had a major contribution in many aspects like provision of drugs and medical supplies, attendance of scientific workshops, and updating doctor's knowledge and experience through telemedicine programs which resulted in decreasing the induction mortality in acute lymphoblastic leukemia from 24% in the year 2007% to 10% in 2010 after introduction of pre-phase steroids and in acute promyelocytic leukemia from 95% to 5% after introduction of all trans-retinoic acid. A collaborative work with Rome University resulted in changing diagnosis of 20% of pathological samples sent there for reevaluation. Iraqi pediatric oncologists still need real attempts to improve infrastructure and human resources in addition to twinning programs with internationally recognized cancer centers to face these management challenges.

  5. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

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

    2012-07-15

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

  6. Overcoming Autopsy Barriers in Pediatric Cancer Research

    PubMed Central

    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

    2012-01-01

    BACKGROUND 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 twenty percent [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. PROCEDURE 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. RESULTS 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. CONCLUSIONS 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. PMID:23015377

  7. Tryptophan content for monitoring breast cancer cell aggressiveness by native fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Lin; Pu, Yang; Xue, Jianpeng; Pratavieira, Sebastião.; Xu, Baogang; Achilefu, Samuel; Alfano, R. R.

    2014-03-01

    This study shows tryptophan as the key native marker in cells to determine the level of aggressive cancer in breast cell lines using native fluorescence spectroscopy. An algorithm based on the ratio of tryptophan fluorescence intensity at 340 nm to intensity at 460 nm is associated with aggressiveness of the cancer cells. The higher the ratio is, the more aggressive the tumor towards metastasis.

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

    PubMed

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

    2015-05-10

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

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

    PubMed Central

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

    2015-01-01

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

  10. [Measures of parental stress in cases of pediatric cancer].

    PubMed

    Labrell, Florence; Chevignard, Mathilde; Câmara Costa, Hugo

    2016-01-01

    This paper aims firstly to introduce a definition of parental stress (PS) and to detail the criteria of PS in case of pediatric cancers. Several reports have shown that pediatric cancers lead to posttraumatic stress symptoms (PTSS) for all parents and induce stress trajectories throughout diagnosis, treatment and recovery or relapse. Secondly, several predictors of SP are presented, such as parent's perceptions of children's medical treatment, psychological characteristics (e.g. anxiety) and sociodemographic factors. Lastly, several measures of PS are reviewed, which underline the existence of specific tools aimed at evaluating PS in pediatric cancers; however, the availability of a French version of these tools remains scarce. This review advocates systematic measures of PS in order to provide better care for children with cancer through the improvement of their family's feelings about the injury. PMID:27291717

  11. 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…

  12. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods

    PubMed Central

    Moyad, Mark A

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin). PMID:26112486

  13. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.

    PubMed

    Moyad, Mark A

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin).

  14. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.

    PubMed

    Moyad, Mark A

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin). PMID:26112486

  15. Receipt of Life-Sustaining Treatments for Taiwanese Pediatric Patients Who Died of Cancer in 2001 to 2010

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  17. Glucose promotes breast cancer aggression and reduces metformin efficacy.

    PubMed

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

    2013-12-15

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

  18. International pediatric liver cancer pathological classification: current trend.

    PubMed

    Tanaka, Yukichi; Inoue, Takeshi; Horie, Hiroshi

    2013-12-01

    This review describes the pathological classification of pediatric liver cancer types and subtypes proposed at the recent international symposium (March 2011, Los Angeles, USA) and meetings involving pathologists serving as central reviewers for the Children's Oncology Group, Société Internationale d'Oncologie Pédiatrique, Gesellschaft für Pädiatrische Onkologie und Hämatologie, or Japanese Study Group for Pediatric Liver Tumors, and pediatric oncologists/surgeons specializing in liver cancers, as well as immunohistochemical panels, recommendations for submission, sampling and evaluation of diagnostic specimens. The pathological classification is intended to be standardized and clinically meaningful, thus improving future patient management and prognosis. The most common pediatric liver cancer is hepatoblastoma (HBL). HBL has two types, the wholly epithelial type and the mixed epithelial and mesenchymal (MEM) type. The wholly epithelial type was subdivided into well-differentiated fetal (pure fetal with low mitotic activity), crowded fetal (mitotically active), embryonal, epithelial mixed, small cell undifferentiated, and cholangioblastic. A macrotrabecular pattern and a pleomorphic epithelial pattern were recognized as supplemental features of epithelial components. The MEM type was subdivided into MEM without teratoid features and MEM with teratoid features. Other liver cancers in children were divided into hepatocellular carcinoma (classic hepatocellular carcinoma and fibrolamellar carcinoma) and hepatocellular malignant tumor not otherwise specified. This classification is basically applied to pretreatment specimens; the evaluation of post-chemotherapy specimens will be the subject of further studies.

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

    ERIC Educational Resources Information Center

    Friedrich, William N.; Copeland, Donna R.

    1983-01-01

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

  20. 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…

  1. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    PubMed Central

    IFERE, GODWIN O.; DESMOND, RENEE; DEMARK-WAHNEFRIED, WENDY; NAGY, TIM R.

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggressive) prostate cancer cell lines were characterized, and we explored whether the ApoE variants were associated with tumor aggressiveness generated by intra cellular cholesterol imbalance, using the expression of caveolin-1 (cav-1), a pro-malignancy surrogate of cholesterol overload. Restriction isotyping of ApoE isoforms revealed that the non-aggressive cell lines carried ApoE ε3/ε3 or ε3/ε4 alleles, while the aggressive cell lines carried the Apoε2/ε4 alleles. Our data suggest a contrast between the non-aggressive and the aggressive prostate cancer cell lines in the pattern of cholesterol efflux and cav-1 expression. Our exploratory results suggest a relationship between prostate aggressiveness, ApoE isoforms and cholesterol imbalance. Further investigation of this relationship may elucidate the molecular basis for considering cholesterol as a risk factor of aggressive prostate tumors, and underscore the potential of the dysfunctional ApoE2/E4 isoform as a biomarker of aggressive disease. PMID:23934233

  2. Pediatric Nasopharyngeal Cancer: Case Report and Review of the Literature

    PubMed Central

    González, Garvin; Bermudéz, Yurany; Maldonado, Maria C; Castañeda, Javier M; Lopéz, David; Cotes-Mestre, Martha

    2016-01-01

    Pediatric nasopharyngeal carcinoma, also referred to as cavum carcinoma, is a rare pediatric disease with an infrequent incidence rate. We present the case of a pediatric patient with nasopharyngeal cancer who received an adult schedule of concomitant chemotherapy and conformal radiotherapy with a brachytherapy boost. Adult protocols with high radiotherapy doses are not commonly used in pediatric patients due to the high comorbidity associated with this practice. In this case, the patient displayed excellent overall survival, a longer disease-free period, and fewer side effects and comorbidities, even in the absence of interferon therapy, which is not easily available in low-income countries. In addition, this case shows that conformal radiotherapy and brachytherapy are options that can be used to escalate the radiotherapy dose and decrease side effects. A 12-year-old female pediatric patient presented to our outpatient clinic with an eight-month history of moderate-to-severe otalgia, intermittent hyaline rhinorrhea, asthenia, adynamia, nasal congestion, epistaxis in the previous months, and local pruritus. Upon physical examination, a 60x60 mm mass was detected at level II of the neck, and a biopsy of the lesion confirmed a histopathological diagnosis of undifferentiated carcinoma compatible with nasopharyngeal carcinoma. The patient was considered to have clinical Stage III cancer, and she received an adult Al-Sarraf protocol with chemoradiotherapy and an intracavitary brachytherapy boost. The patient had a complete response, and she remains without local or distance relapse. Treating pediatric nasopharyngeal carcinoma patients with the Al-Sarraf protocol could be a feasible modality, as observed in this clinical case, despite the elevated cost of using interferon-beta in low-income countries when using more advanced radiotherapy techniques such as conformal radiotherapy and now, modulated intensity radiotherapy. It should be noted that brachytherapy boosts

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

    SciTech Connect

    Kassambara, Alboukadel; Klein, Bernard Moreaux, Jerome

    2009-02-20

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

  4. PBX3 is a putative biomarker of aggressive prostate cancer.

    PubMed

    Ramberg, Håkon; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Ögren, Olov; Zhao, Sen; Løvf, Marthe; Katz, Betina; Skotheim, Rolf I; Bjartell, Anders; Eri, Lars Magne; Berge, Viktor; Svindland, Aud; Taskén, Kristin Austlid

    2016-10-15

    There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer. PMID:27273830

  5. PBX3 is a putative biomarker of aggressive prostate cancer.

    PubMed

    Ramberg, Håkon; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Ögren, Olov; Zhao, Sen; Løvf, Marthe; Katz, Betina; Skotheim, Rolf I; Bjartell, Anders; Eri, Lars Magne; Berge, Viktor; Svindland, Aud; Taskén, Kristin Austlid

    2016-10-15

    There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer.

  6. 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

  7. Nanomedicine as an innovative therapeutic strategy for pediatric cancer.

    PubMed

    Aleassa, Essa Mohd; Xing, Malcolm; Keijzer, Richard

    2015-07-01

    Childhood cancer is the leading cause of mortality in children between 1 and 14 years of age. Malignancy accounts for 18 % of overall childhood mortality. Therapeutic advances in the field of pediatric oncology have helped to increase survival. Nanotechnology is the modification of materials at a nanoscale and can be used to deliver therapeutic agents. Examples of nanotechnology applications are organic self-assembled amphiphilic polymers, non-organic nanocarriers such as nanotubes and quantum dots. Each of these has their own utility in different settings. Application of nanotechnology in medicine has been extensively studied. Examples of pediatric tumors that received special attention are: neuroblastoma, retinoblastoma, central nervous system tumors and musculoskeletal tumors. This review will summarize the application of nanomedicine as an innovative management strategy in pediatric oncology.

  8. Basic Research and Progress against Pediatric Cancer

    Cancer.gov

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

  9. Screening for Vitamin D Insufficiency in Pediatric Cancer Survivors

    PubMed Central

    Esbenshade, Adam J.; Sopfe, Jenna; Zhao, Zhiguo; Li, Zeda; Campbell, Kristin; Simmons, Jill H.; Friedman, Debra L.

    2013-01-01

    Background Corticosteroids increase risk for decreased bone mineral density, which can be worsened by vitamin D insufficiency (VDI) or deficiency (VDD). Procedure In the Vanderbilt cancer survivorship clinic, we obtained screening total 25-hydroxy vitamin D levels (VDL) in 171 cancer survivors <23 years old who were treated with prolonged corticosteroids for their cancer, and compared this group to a control group of 97 healthy pediatric patients. Results VDD was diagnosed in 15.8% and VDI in 34.5% of cancer survivors and VDD/VDI combined was associated with body mass index (BMI) >85th percentile (Odds ratio (OR) = 5.4; p<0.001), older age (OR = 2.2; p=0.012), non-Caucasian or Hispanic race (OR = 4.5 p = 0.008) and summer versus winter season (OR= 0.12, p<0.001). In multivariable analysis, VDI/VDD prevalence did not differ from the control group (VDI/VDD (43.3%). In the combined survivor/control group multivariable analysis, cancer diagnosis did not increase VDI/VDD risk, but significant associations persisted with elevated BMI (p <0.001), age (p=0.004), non-Caucasian or Hispanic race (p<0.001), and seasonality (p<0.001). Conclusion VDD/VDI is equally common in pediatric cancer survivors treated with corticosteroids and healthy children. The impact of VDD/VDI in cancer survivors may be greater due to risk for impaired bone health superimposed on that conferred from corticosteroid exposure. Thus, screening VDLs should be obtained in pediatric cancer survivors treated with corticosteroids, particularly in those with elevated BMI, older age, or non-Caucasian race. Prospective studies evaluating the impact of interventions to minimize VDD/VDI on long-term bone health in survivors are required. PMID:24194420

  10. Financial Burden of Pediatric Cancer for Patients and Their Families

    PubMed Central

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

    2015-01-01

    Purpose: 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). Methods: 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. Results: 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. Conclusions: 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. PMID:25316026

  11. Glucose promotes breast cancer aggression and reduces metformin efficacy

    PubMed Central

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

    2013-01-01

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

  12. Psychosocial Assessment as a Standard of Care in Pediatric Cancer.

    PubMed

    Kazak, Anne E; Abrams, Annah N; Banks, Jaime; Christofferson, Jennifer; DiDonato, Stephen; Grootenhuis, Martha A; Kabour, Marianne; Madan-Swain, Avi; Patel, Sunita K; Zadeh, Sima; Kupst, Mary Jo

    2015-12-01

    This paper presents the evidence for a standard of care for psychosocial assessment in pediatric cancer. An interdisciplinary group of investigators utilized EBSCO, PubMed, PsycINFO, Ovid, and Google Scholar search databases, focusing on five areas: youth/family psychosocial adjustment, family resources, family/social support, previous history/premorbid functioning, and family structure/function. Descriptive quantitative studies, systematic reviews, and meta-analyses (n = 149) were reviewed and evaluated using grading of recommendations, assessment development, and evaluation (GRADE) criteria. There is high quality evidence to support a strong recommendation for multifaceted, systematic assessments of psychosocial health care needs of youth with cancer and their families as a standard of care in pediatric oncology.

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

    PubMed Central

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

    2012-01-01

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

  14. Epidemiologic findings of cancer detected in a pediatric emergency department.

    PubMed

    Kundra, Manu; Stankovic, Curt; Gupta, Nimisha; Thomas, Ronald; Hamre, Merlin; Mahajan, Prashant

    2009-05-01

    This study describes epidemiologic findings of pediatric cancer diagnosed in the emergency department (ED) setting. Medical records are retrospectively reviewed on all patients in the hospital's cancer database between 2000 and 2004 who were diagnosed as having cancer or whose oncologic diagnosis was missed during their ED presentation. Of 427 patients identified in the cancer database, 18% (77 of 427) are analyzed. Oncologic diagnosis was missed in 5% (4 of 77) of the eligible patients initially presenting to the ED. The incidence of cancer in the ED is 22.8 cases per 100,000 ED visits. The most prevalent cancer is related to the hematologic system (37.7%), followed by the central nervous system (31.2%) and the abdomen (22.1%). Hematologic, central nervous system, and abdominal cancers constitute approximately 90% of all childhood cancers. Cancer is diagnosed frequently in our ED patient population. Based on the prevalence of certain tumors, the diagnostic approach to children with hematologic, neurologic, or abdominal complaints should include evaluation for any underlying cancer.

  15. Geographic and environmental factors in pediatric cancer

    SciTech Connect

    Gordis, L.

    1986-07-15

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

  16. Multiple aggressive squamous skin cancers in association with nonbullous congenital ichthyosiform erythroderma.

    PubMed

    Brown, V L; Farrant, P B J; Turner, R J; Price, M L; Burge, S M

    2008-05-01

    Nonbullous congenital ichthyosiform erythroderma (NBCIE) is one of the autosomal recessive inherited non-syndromic ichthyoses and is currently diagnosed on clinical grounds alone. Skin cancer is not a recognized complication of NBCIE. We report here two NBCIE patients who have developed multiple aggressive nonmelanoma skin cancers, predominantly cutaneous squamous cell carcinoma. NBCIE may be a risk factor for skin cancer development.

  17. Cadmium Status Among Pediatric Cancer Patients in Egypt

    PubMed Central

    Sherief, Laila M.; Abdelkhalek, Elhamy R.; Gharieb, Amal F.; Sherbiny, Hanan S.; Usef, Doaa M.; Almalky, Mohamed A.A.; Kamal, Naglaa M.; Salama, Mostafa A.; Gohar, Wafaa

    2015-01-01

    Abstract Cadmium (Cd) is a toxic, nonessential, and bio-accumulating heavy metal widely used in industry. Several studies have suggested a positive association between Cd exposure and risks of several cancers. However, data from general population, especially children are sparse. In the current cross-sectional case–control study, we aimed to assess the association between Cd exposure, as expressed by Cd body status (blood, urine, scalp hair, and nails) and cancer among Egyptian children. Three hundred and fifty pediatric cancer cases aged 3 to 14-years old were enrolled in our study. Their body Cd levels were evaluated using Atomic Absorption Spectrophometer and were compared with Cd levels of 350 healthy children. Significantly higher Cd levels (blood, urine, scalp hair, and nails) were documented in cancer cases when compared with control (P < 0.001). Such difference was still detected when comparing each malignant type separately, with controls. Tobacco smoke exposure, rural residence, and low socioeconomic status were reported more frequently among cases than comparisons. Positive association between Cd exposure and pediatric malignancy may be present. PMID:25997039

  18. Art Therapy with Pediatric Cancer Patients: Helping Normal Children Cope with Abnormal Circumstances.

    ERIC Educational Resources Information Center

    Councill, Tracy

    1993-01-01

    Notes that art therapy with pediatric cancer patients addresses emotional and developmental needs of normal population under extreme stress. Reviews literature on the problems likely to be encountered by pediatric cancer patient and presents case examples to illustrate the emergence of these issues and their management in art therapy. (Author/NB)

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

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

  1. Biologic response modifiers in pediatric cancer.

    PubMed

    Worth, L L; Jeha, S S; Kleinerman, E S

    2001-08-01

    Biologic response modifiers are becoming an important addition to surgery, chemotherapy, and radiotherapy in the management of cancer. As this field of research grows and expands, more biologic response modifiers will be incorporated into therapeutic regimens. By stimulating the immune system to eradicate minimal residual disease, these agents may improve the disease-free and long-term survival rates of patients with a variety of malignancies. The challenge is to incorporate biologic response modifiers into the treatment armamentarium in ways that will maximize their tumorigenicity.

  2. CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response.

    PubMed

    Chan, Kannie W Y; Jiang, Lu; Cheng, Menglin; Wijnen, Jannie P; Liu, Guanshu; Huang, Peng; van Zijl, Peter C M; McMahon, Michael T; Glunde, Kristine

    2016-06-01

    Chemical exchange saturation transfer (CEST) is an MRI contrast mechanism that detects the exchange of protons from distinct hydroxyl, amine, and amide groups to tissue water through the transfer of signal loss, with repeated exchange enhancing their effective signal. We applied CEST to detect systematically 15 common cellular metabolites in a panel of differentially aggressive human breast cancer cell lines. The highest CEST contrast was generated by creatine, myo-inositol, glutamate, and glycerophosphocholine, whose cellular concentrations decreased with increasing breast cancer aggressiveness. These decreased metabolite concentrations resulted in turn in a decreased CEST profile with increasing breast cancer aggressiveness in water-soluble extracts of breast cell lines. Treatment of both breast cancer cell lines with the chemotherapy drug doxorubicin resulted in increased metabolic CEST profiles, which correlated with significant increases in creatine, phosphocreatine, and glycerophosphocholine. CEST can detect breast cancer aggressiveness and response to chemotherapy in water-soluble extracts of breast cell lines. The presented results help shed light on possible contributions from CEST-active metabolites to the CEST contrast produced by breast cancers. The metabolic CEST profile may improve detection sensitivity over conventional MRS, and may have the potential to assess breast cancer aggressiveness and response to chemotherapy non-invasively using MRI if specialized metabolic CEST profile detection can be realized in vivo. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27100284

  3. 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.

  4. 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

  5. Psychosocial support of the pediatric cancer patient: lessons learned over the past 50 years.

    PubMed

    Askins, Martha A; Moore, Bartlett D

    2008-11-01

    Advances in pediatric cancer treatment over the past 50 years have dramatically improved survival rates. Once considered almost uniformly fatal, pediatric cancer's overall survival rates now approach 85%. Formerly, little psychosocial support existed for the child with cancer other than that provided by nurses and family. The prospect for long-term survival was so remote that plans for the future (eg, school, social relationships, late effects of treatment, and emotional adjustment) were abandoned. As the survival rate for children with cancer improved, so did the need for and quality of psychosocial care, largely because of hope for a cure. Today children with cancer benefit from comprehensive behavioral pediatric psychosocial support programs in psychiatry, psychology, neuropsychology, child life, education (school), creative arts, chaplaincy, social work, and career and vocational counseling. Pediatric psycho-oncology research has provided insights into clinical care and the psychosocial adaptation of children and families to cancer treatment and survivorship.

  6. USP44+ Cancer Stem Cell Subclones Contribute to Breast Cancer Aggressiveness by Promoting Vasculogenic Mimicry.

    PubMed

    Liu, Tieju; Sun, Baocun; Zhao, Xiulan; Li, Yanlei; Zhao, Xueming; Liu, Ying; Yao, Zhi; Gu, Qiang; Dong, Xueyi; Shao, Bing; Lin, Xian; Liu, Fang; An, Jindan

    2015-09-01

    Vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, describes the functional plasticity of aggressive cancer cells that form vascular networks. In our previous study, breast cancer stem cells (CSC) were shown to potentially participate in VM formation. In this study, breast CSCs presented centrosome amplification (CA) phenotype and ubiquitin-specific protease 44 (USP44) upregulation. USP44 expression contributed to the establishment of bipolar spindles in breast CSCs with supernumerary centrosomes by localizing at pole-associated centrosomes. The bipolar spindle patterns of breast CSCs with CA, including planar-like and apico-basal-like, functioned differently during the VM process of CSCs. Moreover, the ability of transendothelial migration in VM-forming cells was increased. In vivo experiment results showed that CSC xenografts presented linearly patterned programmed cell necrosis, which provided a spatial foundation for VM formation as well as angiogenesis. Breast CSCs further showed increased levels of IL6 and IL8. However, USP44 silencing induced spindle multipolarity, abated VM, reduced transendothelial migration, and consequently decreased IL6 and IL8 levels in breast CSCs. Finally, USP44(+) CSC subclones (ALDH1(+)/USP44(+)/IL6(+)/IL8(+)) were identified in breast cancer specimens through consecutive sections scanning. The subclones were related not only to CA, but also to VM. Statistical analysis suggested that USP44(+) CSC subclones could be used as an independent prognostic biomarker of poor clinical outcomes in patients with breast cancer. Collectively, the identification of USP44(+) CSC subclones may contribute to the prediction of VM formation and aggressive behavior. This study provides novel insights into the therapy for advanced breast cancer.

  7. Evaluation of pediatric oncology objectives developed by the American Association for Cancer Education.

    PubMed

    Bertolone, S; Teller, D N; Bell, R A

    1986-01-01

    Educational objectives in pediatric oncology for medical students developed at the Fall, 1981 meeting of the American Association for Cancer Education (AACE) were reviewed. These six terminal (general) and 40 enabling (specific) objectives were converted into 130 statements which were ranked from essential (rank 5) to not required (rank 0). The 58 pediatric oncology respondents gave broad support to the AACE pediatric oncology objectives. Primary importance was given to medical students knowing to refer pediatric malignancies. Principles of therapy, psychosocial management, management of infection, and complications during long term surveillance ranked high. Objectives were not ranked differently when related to number of new pediatric patients seen, type of hospital, or whether the institution had a core undergraduate pediatric training site. The list of terminal, enabling and supplemental pediatric oncology objectives developed by AACE appears valid for inclusion in the core curriculum of medical students.

  8. BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization.

    PubMed

    Orvis, Tess; Hepperla, Austin; Walter, Vonn; Song, Shujie; Simon, Jeremy; Parker, Joel; Wilkerson, Matthew D; Desai, Nisarg; Major, Michael B; Hayes, D Neil; Davis, Ian J; Weissman, Bernard

    2014-11-15

    SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non-small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes.

  9. Economic Impact of Advanced Pediatric Cancer on Families

    PubMed Central

    Bona, Kira; Dussel, Veronica; Orellana, Liliana; Kang, Tammy; Geyer, Russ; Feudtner, Chris; Wolfe, Joanne

    2013-01-01

    Context Despite emerging evidence of substantial financial distress in families of children with complex illness, little is known about economic hardship in families of children with advanced cancer. Objectives To describe perceived financial hardship, work disruptions, income losses and associated economic impact in families of children with advanced cancer stratified by federal poverty level (FPL). Methods This is a cross-sectional survey of 86 parents of children with progressive, recurrent or non-responsive cancer at three children’s hospitals. Seventy-one families with complete income data (82%) are included in this analysis. Results Parental work disruptions were prevalent across all income levels, with 67 (94%) families reporting some disruption. At least one parent quit a job because of the child’s illness in 29 (42%) families. Nineteen (27%) families described their child’s illness as a great economic hardship. Income losses due to work disruptions were substantial for all families; families at or below 200% FPL, however, were disproportionately affected. Six (50%) of the poorest families lost more than 40% of their annual income as compared with two (5%) of the wealthiest families (P=0.006). As a result of income losses, nine (15%) previously non-poor families fell from above to below the 200% FPL. Conclusion The economic impact of pediatric advanced cancer on families is significant at all income levels, although poorer families suffer disproportionate losses. Development of ameliorative intervention strategies is warranted. PMID:23870843

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

    PubMed

    Temkin, Sarah M; Seibel, Nita L

    2015-10-01

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

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

    SciTech Connect

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

    2012-04-01

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

  12. Pediatrics

    NASA Technical Reports Server (NTRS)

    Spackman, T. J.

    1978-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

    PubMed

    Mimeault, M; Hauke, R; Mehta, P P; Batra, S K

    2007-01-01

    Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival. PMID:17979879

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

    SciTech Connect

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

    2013-07-15

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

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

    PubMed Central

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

    2015-01-01

    Pediatric cancer (PC), that is cancer occurring in children, is the leading cause of death among children worldwide, with an incidence of 175,000 per year. Elucidating the genetic abnormalities and underlying cellular mechanisms may provide less toxic curative treatments. Therefore, it is important to understand the pathology of pediatric cancer at the genetic, genomic and epigenetic level. To unveil the cellular complexity of PC, we have developed a database of pediatric cancers (Pedican), the first literature-based pediatric gene data resource by comprehensive literature curation and data integration. In the current release, Pedican contains 735 human genes, 88 gene fusion and 24 chromosome abnormal events curated from 2245 PubMed abstracts. Pedican provides detailed annotations for each gene, such as Entrez gene information, involved pathways, protein–protein interactions, mutations, gene expression, methylation sites, TF regulation, and post-translational modification. Additionally Pedican has a user-friendly web interface, which allows sophisticated text query, sequence searches, and browsing by highlighted literature evidence and hundreds of cancer types. Overall, our curated pediatric cancer-related gene list maps the genomic and cellular landscape for various pediatric cancers, providing a valuable resource for further experiment design. The Pedican is available at http://pedican.bioinfo-minzhao.org/. PMID:26073932

  17. Neuropathic pain referrals to a multidisciplinary pediatric cancer pain service.

    PubMed

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

    2014-03-01

    Neuropathic pain (NP) in children with cancer is not well characterized. In a retrospective review of patient data from a 3.5-year period, we describe the prevalence of NP and the characteristics, duration of follow-up, and interventions provided for NP among patients referred to a pediatric oncology center's pain management service. Fifteen percent (66/439) of all referrals to our pain service were for NP (56/323 patients [17%]; 34 male, 22 female). The NP patient group had 1,401 clinical visits (778 inpatient visits [55.5%] and 623 outpatient visits [44.5%]). Patients with NP had a significantly greater mean number of pain visits per consultation (p = .008) and significantly more days of pain service follow-up (p < .001) than did other patients. The most common cause of NP was cancer treatment rather than the underlying malignancy. Pharmacologic management of NP was complex, often comprising three medications. Nonpharmacologic approaches were used for 57.6% of NP referrals. Neuropathic pain is less frequently encountered than non-NP in children with cancer; nevertheless, it is more difficult to treat, requiring longer follow-up, more clinical visits, complex pharmacologic management, and the frequent addition of nonpharmacologic interventions.

  18. Fine Mapping of Prostate Cancer Aggressiveness Loci on Chromosome 7q22-35

    PubMed Central

    Liu, Xin; Cheng, Iona; Plummer, Sarah J; Suarez, Brian; Casey, Graham; Catalona, William J.; Witte, John S.

    2010-01-01

    Background Deciphering the genetic basis of prostate cancer aggressiveness could provide valuable information for the screening and treatment of this common but complex disease. We previously detected linkage between a broad region on chromosome 7q22-35 and Gleason score—a strong predictor of prostate cancer aggressiveness. To further clarify this finding and focus on the potentially causative gene, we undertook a fine-mapping study across the 7q22-35 region. Methods Our study population encompassed 698 siblings diagnosed with prostate cancer. 3,072 single nucleotide polymorphisms (SNPs) spanning the chromosome 7q22-35 region were genotyped using the Illumina GoldenGate assay. The impact of SNPs on Gleason scores were evaluated using affected sibling pair linkage and family-based association tests. Results We confirmed the previous linkage signal and narrowed the 7q22-35 prostate cancer aggressiveness locus to a 370 kb region. Centered under the linkage peak is the gene KLRG2 (killer cell lectin-like receptor subfamily G, member 2). Association tests indicated that the potentially functional non-synonymous SNP rs17160911 in KLRG2 was significantly associated with Gleason score (p = 0.0007). Conclusions These findings suggest that genetic variants in the gene KLRG2 may affect Gleason score at diagnosis and hence the aggressiveness of prostate cancer. PMID:20945404

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

    PubMed Central

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

    2015-01-01

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

  20. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

    PubMed

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, Y Y; Liphardt, J; Hwang, E S; Weaver, V M

    2015-10-01

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

  1. 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

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

    PubMed Central

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

    2015-01-01

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

  3. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    PubMed Central

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers. In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future. PMID:25501061

  4. New targets and targeted drugs for the treatment of cancer: an outlook to pediatric oncology.

    PubMed

    Rossig, Claudia; Juergens, Heribert; Berdel, Wolfgang E

    2011-10-01

    Novel drugs and treatment modalities are urgently needed to further improve survival of children with cancer. In medical oncology, an increased understanding of the molecular basis of cancer is driving the development of new drugs that target relevant signaling pathways in cancer cells and tumor microenvironment. Small-molecule modulators of signal transduction and monoclonal antibodies against various cellular targets have been approved in adult cancers in recent years. These drugs are now starting to be considered for the use in children. Despite the biological differences between adult and pediatric cancers, common cellular pathways have emerged from experimental research. Thus, insights into clinical experience with molecular targeted drugs in adults may help to accelerate progress in pediatric oncology. Here, the authors review molecules and pathways for which drugs are approved for adult cancer treatment and provide links to existing and potential applications in pediatric oncology.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. HES6 promotes prostate cancer aggressiveness independently of Notch signalling

    PubMed Central

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

    2015-01-01

    Notch signalling is implicated in the pathogenesis of a variety of cancers, but its role in prostate cancer is poorly understood. However, selected Notch pathway members are overrepresented in high-grade prostate cancers. We comprehensively profiled Notch pathway components in prostate cells and found prostate cancer-specific up-regulation of NOTCH3 and HES6. Their expression was particularly high in androgen responsive lines. Up- and down-regulating Notch in these cells modulated expression of canonical Notch targets, HES1 and HEY1, which could also be induced by androgen. Surprisingly, androgen treatment also suppressed Notch receptor expression, suggesting that androgens can activate Notch target genes in a receptor-independent manner. Using a Notch-sensitive Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) reporter assay, we found that basal levels of Notch signalling were significantly lower in prostate cancer cells compared to benign cells. Accordingly pharmacological Notch pathway blockade did not inhibit cancer cell growth or viability. In contrast to canonical Notch targets, HES6, a HES family member known to antagonize Notch signalling, was not regulated by Notch signalling, but relied instead on androgen levels, both in cultured cells and in human cancer tissues. When engineered into prostate cancer cells, reduced levels of HES6 resulted in reduced cancer cell invasion and clonogenic growth. By molecular profiling, we identified potential roles for HES6 in regulating hedgehog signalling, apoptosis and cell migration. Our results did not reveal any cell-autonomous roles for canonical Notch signalling in prostate cancer. However, the results do implicate HES6 as a promoter of prostate cancer progression. PMID:25864518

  8. Paper Highlight: Biomarker Identified for Predicting Early Prostate Cancer Aggressiveness — Site

    Cancer.gov

    A team led by Cory Abate-Shen, Michael Shen, and Andrea Califano at Columbia University found that measuring the expression levels of three genes associated with aging can be used to predict the aggressiveness of seemingly low-risk prostate cancer.

  9. IL-8 secretion in primary cultures of prostate cells is associated with prostate cancer aggressiveness

    PubMed Central

    Neveu, Bertrand; Moreel, Xavier; Deschênes-Rompré, Marie-Pier; Bergeron, Alain; LaRue, Hélène; Ayari, Cherifa; Fradet, Yves; Fradet, Vincent

    2014-01-01

    Background Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness. Materials and methods Short-term primary cell cultures of normal epithelial prostate cells were derived from prostate biopsies from 25 men undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded viral RNA and a potent inducer of the inflammatory response. Secretion of interleukin (IL)-8 in the cell culture medium by untreated and treated cells was measured and we determined the association between IL-8 levels in these primary cell cultures and prostate cancer characteristics. The Fligner–Policello test was used to compare the groups. Results Baseline and induced IL-8 secretion were highly variable between cultured cells from different patients. This variation was not related to drug use, past medical history, age, or preoperative prostate-specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal cultured epithelial cells was associated with prostate cancer aggressiveness (P=0.0005). Conclusion The baseline secretion of IL-8 from normal prostate epithelial cells in culture is strongly correlated with cancer aggressiveness and may drive prostate cancer carcinogenesis. A better characterization of individual prostate microenvironment may provide a basis for personalized treatment and for monitoring the effects of strategies aimed at preventing aggressive prostate cancer. PMID:24892030

  10. Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers.

    PubMed

    Pannu, Vaishali; Mittal, Karuna; Cantuaria, Guilherme; Reid, Michelle D; Li, Xiaoxian; Donthamsetty, Shashikiran; McBride, Michelle; Klimov, Sergey; Osan, Remus; Gupta, Meenakshi V; Rida, Padmashree C G; Aneja, Ritu

    2015-04-30

    Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients. PMID:25868856

  11. Whole exome sequencing of rare aggressive breast cancer histologies.

    PubMed

    Dieci, Maria Vittoria; Smutná, Veronika; Scott, Véronique; Yin, Guangliang; Xu, Ran; Vielh, Philippe; Mathieu, Marie-Christine; Vicier, Cécile; Laporte, Melanie; Drusch, Francoise; Guarneri, Valentina; Conte, Pierfranco; Delaloge, Suzette; Lacroix, Ludovic; Fromigué, Olivia; André, Fabrice; Lefebvre, Celine

    2016-02-01

    Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression. PMID:26907767

  12. 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

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

    PubMed

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

    2016-01-19

    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

  14. 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.…

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

    PubMed

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

    2015-08-01

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

  16. Inositol Phosphate Recycling Regulates Glycolytic and Lipid Metabolism That Drives Cancer Aggressiveness

    PubMed Central

    2015-01-01

    Cancer cells possess fundamentally altered metabolism that supports their pathogenic features, which includes a heightened reliance on aerobic glycolysis to provide precursors for synthesis of biomass. We show here that inositol polyphosphate phosphatase 1 (INPP1) is highly expressed in aggressive human cancer cells and primary high-grade human tumors. Inactivation of INPP1 leads to a reduction in glycolytic intermediates that feed into the synthesis of the oncogenic signaling lipid lysophosphatidic acid (LPA), which in turn impairs LPA signaling and further attenuates glycolytic metabolism in a feed-forward mechanism to impair cancer cell motility, invasiveness, and tumorigenicity. Taken together these findings reveal a novel mode of glycolytic control in cancer cells that can serve to promote key oncogenic lipid signaling pathways that drive cancer pathogenicity. PMID:24738946

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

    PubMed Central

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

    2016-01-01

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

  18. 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.

  19. Overexpression of Mucin 13 due to Promoter Methylation Promotes Aggressive Behavior in Ovarian Cancer Cells

    PubMed Central

    Sung, Hye Youn; Park, Ae Kyung

    2014-01-01

    Purpose Recent discoveries suggest that aberrant DNA methylation provides cancer cells with advanced metastatic properties. However, the precise regulatory mechanisms controlling metastasis genes and their role in metastatic transformation are largely unknown. To address epigenetically-regulated gene products involved in ovarian cancer metastasis, we examined the mechanisms regulating mucin 13 (MUC13) expression and its influence on aggressive behaviors of ovarian malignancies. Materials and Methods We injected SK-OV-3 ovarian cancer cells peritoneally into nude mice to mimic human ovarian tumor metastasis. Overexpression of MUC13 mRNA was detected in metastatic implants from the xenografts by expression microarray analysis and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The DNA methylation status within the MUC13 promoter region was determined using bisulfite sequencing PCR and quantitative methylation-specific PCR. We evaluated the effects of exogenous MUC13 on cell invasion and migration using in vitro transwell assays. Results MUC13 mRNA expression was up-regulated, and methylation of specific CpG sites within the promoter was reduced in the metastatic implants relative to those in wild-type SK-OV-3 cells. Addition of a DNA methyltransferase inhibitor to SK-OV-3 cells induced MUC13 expression, thereby implying epigenetic regulation of MUC13 by promoter methylation. MUC13 overexpression increased migration and invasiveness, compared to control cells, suggesting aberrant up-regulation of MUC13 is strongly associated with progression of aggressive behaviors in ovarian cancer. Conclusion We provide novel evidence for epigenetic regulation of MUC13 in ovarian cancer. We suggest that the DNA methylation status within the MUC13 promoter region may be a potential biomarker of aggressive behavior in ovarian cancer. PMID:25048476

  20. Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis.

    PubMed

    Goh, Y I; Bollano, E; Einarson, T R; Koren, G

    2007-05-01

    Prenatal supplementation of folic acid has been shown to decrease the risk of several congenital malformations. Several studies have recently suggested a potential protective effect of folic acid on certain pediatric cancers. The protective role of prenatal multivitamins has not been elucidated. We conducted a systematic review and meta-analysis to assess the potential protective effect of prenatal multivitamins on several pediatric cancers. Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases were searched for studies published in all languages from 1960 to July 2005 on multivitamin supplementation and pediatric cancers. References from all articles collected were reviewed for additional articles. Two blinded independent reviewers assessed the articles for inclusion and exclusion. Rates of cancers in women supplemented with multivitamins were compared with unsupplemented women using a random effects model. Sixty-one articles were identified in the initial search, of which, seven articles met the inclusion criteria. There was an apparent protective effect for leukemia (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.50-0.74), pediatric brain tumors (OR=0.73, 95% CI=0.60-0.88) and neuroblastoma (OR=0.53, 95% CI=0.42-0.68). In conclusion, maternal ingestion of prenatal multivitamins is associated with a decreased risk for pediatric brain tumors, neuroblastoma, and leukemia. Presently, it is not known which constituent(s) among the multivitamins confer this protective effect. PMID:17314929

  1. Targeting uPAR with Antagonistic Recombinant Human Antibodies in Aggressive Breast Cancer

    PubMed Central

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

    2013-01-01

    Components of the plasminogen activation system (PAS) which are overexpressed in aggressive breast cancer subtypes offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared (NIR) imaging and 111In single-photon emission computed tomography (SPECT). Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard 18F-fluorodeoxyglucose (FDG) at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. Additionally, a radioimmunotherapy (RIT) study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope 177Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology. PMID:23400595

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

    PubMed Central

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

    2014-01-01

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

  3. T2 Gallbladder Cancer-Aggressive Therapy Is Warranted.

    PubMed

    Sheikh, Mohd Raashid; Osman, Houssam; Cheek, Susannah; Hunter, Shenee; Jeyarajah, Dhiresh Rohan

    2016-06-01

    Treatment of gall bladder cancer (GBC) has traditionally been viewed with pessimism and lymph node positivity has been associated with worse prognosis. The aim of this study is to analyze the role of radical cholecystectomy in T2 tumors. All patients who underwent surgery for GBC between September 2005 and June 2014 were identified retrospectively. Data collected included clinical presentation, operative findings, and histopathological data. Twenty-five patients had incidental GBC diagnosis after cholecystectomy. Ten patients were T2 on initial cholecystectomy pathology and all underwent radical resection. Two patients were N1 on initial cholecystectomy pathology. Four were upstaged to N1 and two patients were upstaged to T3 after further surgery. Overall, 60 per cent patients with T2 disease had node positivity and 60 per cent were upstaged by further surgery. Eleven patients were diagnosed on imaging. Four of these patients were unresectable and six were either stage T3 or higher or node positive. Sixty per cent of T2 GBC was node positive and 60 per cent were upstaged with radical cholecystectomy. This finding supports the call for radical resection in patients with incidental diagnosis of T2 tumor on cholecystectomy. This study also emphasizes the role of radical surgery in accurate T staging. PMID:27305883

  4. 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.

  5. Highly Aggressive HPV-related Oropharyngeal Cancer: Clinical, Radiologic, and Pathologic Characteristics

    PubMed Central

    Kaka, Azeem S.; Kumar, Bhavna; Kumar, Pawan; Wakely, Paul E.; Kirsch, Claudia M.; Old, Matthew O.; Ozer, Enver; Agrawal, Amit; Carrau, Ricardo E.; Schuller, David E.; Siddiqui, Farzan; Teknos, Theodoros N.

    2013-01-01

    Objectives While the majority of HPV+ oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly-aggressive cases. Study Design Seven patients with HPV+ oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis post-treatment were identified. Eight control cases were chosen which responded well to treatment. Pathology and radiological studies were reviewed and compared. Results Two cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (p=0.04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread and central tumor necrosis. Conclusion While most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behave more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior. PMID:23770280

  6. Hypoxia and Prostate Cancer Aggressiveness: A Tale With Many Endings.

    PubMed

    Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lopes, Carlos; Medeiros, Rui

    2015-08-01

    Angiogenesis, increased glycolysis, and cellular adaptation to hypoxic microenvironment are characteristic of solid tumors, including prostate cancer. These representative features are the cornerstone of cancer biology, which are well correlated with invasion, metastasis, and lethality, as well as likely with the success of prostate cancer treatment (eg, tumor hypoxia has been associated with resistance to chemotherapy and radiotherapy). It is well established that prostate cancer cells also metabolically depend on enhanced glucose transport and glycolysis for expansion, whereas growth is contingent with neovascularization to permit diffusion of oxygen and glucose. While hypoxia inducible factor 1 alpha (HIF-1α) remains the central player, the succeeding activated molecules and pathways track distinct branches, all positively correlated with the degree of intratumoral hypoxia. Among these, the vascular endothelial growth factor axis as well as the lysyl oxidase and carbonic anhydrase IX activities are notable in prostate cancer and merit further study. Here, we demonstrate their linkage with HIF-1α as a tentative explanatory mechanism of prostate cancer aggressiveness. Hypoxia drives a tale where HIF-1α-dependent effects lead to many influences in distinct key cancer biology features, rendering targeted therapies toward targets at the endings less efficient. The most appropriate approach will be to inhibit the upstream common driver (HIF-1α) activity. Additional translational and clinical research initiatives in prostate cancer are required to prove its usefulness.

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

    PubMed

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

    2016-05-01

    Since their discovery in 2008, cell-free circulating microRNAs have been considered potential biomarkers for various conditions, including pediatric cancer. Diagnosis of pediatric cancer still relies on clinical signs, which sometimes may be non-specific or appear at later stages. Thus, there is a need for a better understanding of molecules that allow a less invasive, early and effective method of cancer diagnosis. Despite the efforts of many researches to set specific miRNAs to be routinely used as diagnostic molecules, no miR has been currently utilized so far. In this study, we review the recent discoveries on circulating miRNAs in blood of patients suffering from the following pediatric cancers: osteosarcoma, rhabdomyosarcoma, Wilms tumor, acute myeloid leukemia, acute lymphocytic leukemia, retinoblastoma and neuroblastoma. We also focus on the roles of circulating miRs in tumorigenesis pathways, the methodological approaches used to detect and quantify circulating miRs, and discuss the challenges in using them routinely as biomarkers for pediatric cancers. PMID:27085875

  8. ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients.

    PubMed

    Baena, Esther; Shao, Zhen; Linn, Douglas E; Glass, Kimberly; Hamblen, Melanie J; Fujiwara, Yuko; Kim, Jonghwan; Nguyen, Minh; Zhang, Xin; Godinho, Frank J; Bronson, Roderick T; Mucci, Lorelei A; Loda, Massimo; Yuan, Guo-Cheng; Orkin, Stuart H; Li, Zhe

    2013-03-15

    Distinguishing aggressive from indolent disease and developing effective therapy for advanced disease are the major challenges in prostate cancer research. Chromosomal rearrangements involving ETS transcription factors, such as ERG and ETV1, occur frequently in prostate cancer. How they contribute to tumorigenesis and whether they play similar or distinct in vivo roles remain elusive. Here we show that in mice with ERG or ETV1 targeted to the endogenous Tmprss2 locus, either factor cooperated with loss of a single copy of Pten, leading to localized cancer, but only ETV1 appeared to support development of invasive adenocarcinoma under the background of full Pten loss. Mechanistic studies demonstrated that ERG and ETV1 control a common transcriptional network but largely in an opposing fashion. In particular, while ERG negatively regulates the androgen receptor (AR) transcriptional program, ETV1 cooperates with AR signaling by favoring activation of the AR transcriptional program. Furthermore, we found that ETV1 expression, but not that of ERG, promotes autonomous testosterone production. Last, we confirmed the association of an ETV1 expression signature with aggressive disease and poorer outcome in patient data. The distinct biology of ETV1-associated prostate cancer suggests that this disease class may require new therapies directed to underlying programs controlled by ETV1.

  9. 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

  10. 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

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

    PubMed

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

    2015-12-15

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

  12. 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

  13. A novel role for flotillin-1 in H-Ras-regulated breast cancer aggressiveness.

    PubMed

    Koh, Minsoo; Yong, Hae-Young; Kim, Eun-Sook; Son, Hwajin; Jeon, You Rim; Hwang, Jin-Sun; Kim, Myeong-Ok; Cha, Yujin; Choi, Wahn Soo; Noh, Dong-Young; Lee, Kyung-Min; Kim, Ki-Bum; Lee, Jae-Seon; Kim, Hyung Joon; Kim, Haemin; Kim, Hong-Hee; Kim, Eun Joo; Park, So Yeon; Kim, Hoe Suk; Moon, Woo Kyung; Choi Kim, Hyeong-Reh; Moon, Aree

    2016-03-01

    Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H-Ras, but not N-Ras, induces breast cell invasion. A crucial link between lipid rafts and H-Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible for H-Ras-induced tumorigenicity and invasiveness of breast cancer. We conducted a comparative proteomic analysis of lipid raft proteins from invasive MCF10A human breast epithelial cells engineered to express active H-Ras and non-invasive cells expressing active N-Ras. Here, we identified a lipid raft protein flotillin-1 as an important regulator of H-Ras activation and breast cell invasion. Flotillin-1 was required for epidermal growth factor-induced activation of H-Ras, but not that of N-Ras, in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Flotillin-1 knockdown inhibited the invasiveness of MDA-MB-231 and Hs578T TNBC cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell lines, we showed that flotillin-1 played a critical role in tumor growth. Using human breast cancer samples, we provided clinical evidence for the metastatic potential of flotillin-1. Membrane staining of flotillin-1 was positively correlated with metastatic spread (p = 0.013) and inversely correlated with patient disease-free survival rates (p = 0.005). Expression of flotillin-1 was associated with H-Ras in breast cancer, especially in TNBC (p < 0.001). Our findings provide insight into the molecular basis of Ras isoform-specific interplay with flotillin-1, leading to tumorigenicity and aggressiveness of breast cancer.

  14. Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study.

    PubMed

    Vance, Terrence M; Wang, Ying; Su, L Joseph; Fontham, Elizabeth T H; Steck, Susan E; Arab, Lenore; Bensen, Jeannette T; Mohler, James L; Chen, Ming-Hui; Chun, Ock K

    2016-01-01

    The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms. PMID:26847416

  15. 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…

  16. 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

  17. Pediatric cancer genetics research and an evolving preventive ethics approach for return of results after death of the subject

    PubMed Central

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

    2015-01-01

    Précis 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. PMID:26479562

  18. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion

    PubMed Central

    Roselli, Séverine; Pundavela, Jay; Demont, Yohann; Faulkner, Sam; Keene, Sheridan; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M.; Hondermarck, Hubert

    2015-01-01

    The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion. PMID:25871389

  19. The phytoalexin camalexin mediates cytotoxicity towards aggressive prostate cancer cells via reactive oxygen species

    PubMed Central

    Smith, Basil A.; Neal, Corey L.; Chetram, Mahandranauth; Vo, BaoHan; Mezencev, Roman; Hinton, Cimona

    2013-01-01

    Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. Besides moderate antibacterial and antifungal activity, camalexin was reported to also exhibit antiproliferative and cancer chemopreventive effects in breast cancer and leukemia. We studied the cytotoxic effects of camalexin treatment on prostate cancer cell lines and whether this was mediated by reactive oxygen species (ROS) generation. As models, we utilized LNCaP and its aggressive subline, C4-2, as well as ARCaP cells stably transfected with empty vector (Neo) control or constitutively active Snail cDNA that represents an epithelial to mesenchymal transition (EMT) model and displays increased cell migration and tumorigenicity. We confirmed previous studies showing that C4-2 and ARCaP-Snail cells express more ROS than LNCaP and ARCaP-Neo, respectively. Camalexin increased ROS, decreased cell proliferation, and increased apoptosis more significantly in C4-2 and ARCaP-Snail cells as compared to LNCaP and ARCaP-Neo cells, respectively, while normal prostate epithelial cells (PrEC) were unaffected. Increased caspase-3/7 activity and increased cleaved PARP protein shown by Western blot analysis was suggestive of increased apoptosis. The ROS scavenger N-acetyl cysteine (NAC) antagonized the effects of camalexin, whereas the addition of exogenous hydrogen peroxide potentiated the effects of camalexin, showing that camalexin is mediating its effects through ROS. In conclusion, camalexin is more potent in aggressive prostate cancer cells that express high ROS levels, and this phytoalexin has a strong potential as a novel therapeutic agent for the treatment of especially metastatic prostate cancer. PMID:23179315

  20. 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

  1. Internet-based psychotherapy in young adult survivors of pediatric cancer: feasibility and participants' satisfaction.

    PubMed

    Seitz, Diana C M; Knaevelsrud, Christine; Duran, Gabriele; Waadt, Sabine; Goldbeck, Lutz

    2014-09-01

    Abstract The Internet-based psychotherapeutic intervention Onco-STEP for adolescent and young adult (AYA)-aged survivors of pediatric cancer was developed, implemented, and participants' satisfaction was evaluated by use of questionnaires. The intervention consisted of two modules: "Looking Back," aimed to reduce posttraumatic stress symptoms, and "Looking Ahead," supported coping with cancer-related fears of relapse and progression. The writing program was fully completed by 20 participants (Mage=27.3±4.8 years at study; 70% female). The majority was satisfied and perceived the treatment components as helpful. Results demonstrate that an Internet-based psychotherapeutic intervention for AYA-aged survivors of pediatric cancer is feasible and accepted by the target population.

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

    PubMed Central

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

    2016-01-01

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

  3. Stratification of the aggressiveness of prostate cancer using pre-biopsy multiparametric MRI (mpMRI).

    PubMed

    Dwivedi, Durgesh Kumar; Kumar, Rajeev; Bora, Girdhar S; Thulkar, Sanjay; Sharma, Sanjay; Gupta, Siddhartha Datta; Jagannathan, Naranamangalam R

    2016-03-01

    Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision-making tool in prostate cancer management. As low-grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre-biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty-six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25-45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low-grade, intermediate-grade and high-grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively (p = 0.004). The corresponding mean ADCs (×10(-3) mm(2) /s) for low-grade, intermediate-grade and high-grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively (p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre-biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Vayalil, Praveen K.; Landar, Aimee

    2015-01-01

    Mitochondrial function is influenced by alterations in oncogenes and tumor suppressor genes and changes in the microenvironment occurring during tumorigenesis. Therefore, we hypothesized that mitochondrial function will be stably and dynamically altered at each stage of the prostate tumor development. We tested this hypothesis in RWPE-1 cells and its tumorigenic clones with progressive malignant characteristics (RWPE-1 < WPE-NA22 < WPE-NB14 < WPE-NB11 < WPE-NB26) using high-throughput respirometry. Our studies demonstrate that mitochondrial content do not change with increasing malignancy. In premalignant cells (WPE-NA22 and WPE-NB14), OXPHOS is elevated in presence of glucose or glutamine alone or in combination compared to RWPE-1 cells and decreases with increasing malignancy. Glutamine maintained higher OXPHOS than glucose and suggests that it may be an important substrate for the growth and proliferation of prostate epithelial cells. Glycolysis significantly increases with malignancy and follow a classical Warburg phenomenon. Fatty acid oxidation (FAO) is significantly lower in tumorigenic clones and invasive WPE-NB26 does not utilize FAO at all. In this paper, we introduce for the first time the mitochondrial oncobioenergetic index (MOBI), a mathematical representation of oncobioenergetic profile of a cancer cell, which increases significantly upon transformation into localized premalignant form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell lines and MOBI appears to be not related to androgen dependence or mitochondrial content, but rather dependent on the stage of the cancer. Altogether, we propose that MOBI could be a potential biomarker to distinguish aggressive cancer from that of indolent disease. PMID:26515588

  6. End-of-life management in pediatric cancer.

    PubMed

    Epelman, Claudia L

    2012-04-01

    Pediatric palliative care at the end-of-life is focused on ensuring the best possible quality of life for patients with life-threatening illness and their families. To achieve this goal, important needs include: engaging with patients and families; improving communication and relationships; relieving pain and other symptoms, whether physical, psychosocial, or spiritual; establishing continuity and consistency of care across different settings; considering patients and families in the decision-making process about services and treatment choices to the fullest possible and desired degree; being sensitive to culturally diverse beliefs and values about death and dying; and responding to suffering, bereavement, and providing staff support. Any effort to improve quality of palliative and end-of-life care in pediatric oncology must be accompanied by an educational strategy to enhance the level of competence among health care professionals with regard to palliative care and end-of-life management skills as well as understanding of individualized care planning and coordination processes.

  7. Pediatric cancer epigenome and the influence of folate

    PubMed Central

    Yiu, Teresa T; Li, Wei

    2015-01-01

    Despite improvement in clinical treatment of childhood cancer, it remains the leading cause of disease-related mortality in children with survivors often suffering from treatment-related toxicity and premature death. Because childhood cancer is vastly different from cancer in adults, a thorough understanding of the underlying molecular mechanisms specific to childhood cancer is essential. Although childhood cancer contains much fewer mutations, a subset of cancer subtypes has a higher frequency of mutations in gene encoding epigenetic regulators. Thus, in this review, we will focus on epigenetic deregulations in childhood cancers, the use of genome-wide analysis for cancer subtype classification, prediction of clinical outcomes and the influence of folate on epigenetic mechanisms. PMID:25950259

  8. 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

  9. Identification of cell surface proteins as potential immunotherapy targets in 12 pediatric cancers.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-04-01

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

  12. ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer.

    PubMed

    Zhang, Feng; Zhang, Xutao; Meng, Jin; Zhao, Yong; Liu, Xinli; Liu, Yanxia; Wang, Yukun; Li, Yuhua; Sun, Yang; Wang, Zhipeng; Mei, Qibing; Zhang, Tao

    2015-06-30

    The proteins of the Inhibitor of Growth (ING) candidate tumor suppressor family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is the new member of the family whose actual role in tumor suppression is not known. Here we show that ING5 overexpression in lung cancer A549 cells inhibited cell proliferation and invasiveness, while ING5 knockdown in lung cancer H1299 cells promoted cell aggressiveness. ING5 overexpression also abrogated tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. Further study showed that ING5 overexpression inhibited EMT indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT (epithelial to mesenchymal transition)-inducing genes including CEACAM6, BMP2 and CDH11. Clinical study by tissue microarray showed that nuclear ING5 negatively correlated with clinical stages and lymph node metastasis of lung cancer. Furthermore, high level of nuclear ING5 was associated with a better prognosis. Taken together, these findings uncover an important role for ING5 as a potent tumor suppressor in lung cancer growth and metastasis.

  13. ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer

    PubMed Central

    Zhao, Yong; Liu, Xinli; Liu, Yanxia; Wang, Yukun; Li, Yuhua; Sun, Yang; Wang, Zhipeng; Mei, Qibing; Zhang, Tao

    2015-01-01

    The proteins of the Inhibitor of Growth (ING) candidate tumor suppressor family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is the new member of the family whose actual role in tumor suppression is not known. Here we show that ING5 overexpression in lung cancer A549 cells inhibited cell proliferation and invasiveness, while ING5 knockdown in lung cancer H1299 cells promoted cell aggressiveness. ING5 overexpression also abrogated tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. Further study showed that ING5 overexpression inhibited EMT indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT (epithelial to mesenchymal transition)-inducing genes including CEACAM6, BMP2 and CDH11. Clinical study by tissue microarray showed that nuclear ING5 negatively correlated with clinical stages and lymph node metastasis of lung cancer. Furthermore, high level of nuclear ING5 was associated with a better prognosis. Taken together, these findings uncover an important role for ING5 as a potent tumor suppressor in lung cancer growth and metastasis. PMID:25938545

  14. FRZB knockdown upregulates β-catenin activity and enhances cell aggressiveness in gastric cancer.

    PubMed

    Qin, Shuai; Zhang, Zhuo; Li, Jianfang; Zang, Lu

    2014-05-01

    Studies have shown that FRZB correlates with gastric tumorigenicity and may play role in regulating the Wnt/β‑catenin signaling pathway. In the present study, we investigated the correlation between FRZB and the Wnt/β‑catenin signaling pathway using gastric cancer tissues and an FRZB‑knockdown gastric cancer cell line model. The protein levels of FRZB and β‑catenin were examined using immunohistochemical staining. FRZB-specific shRNAs were used to generate FRZB‑knockdown MKN45 gastric cancer cells. Cell proliferation assay, suspending culture and Annexin V/PI double staining analysis were used to investigate the role of FRZB knockdown in cell growth. In vitro migration/invasion assays were performed. The expression of Wnt/β‑catenin downstream targets was analyzed by RT-PCR. FRZB mRNA levels showed negative correlation with β‑catenin levels in paired non-tumor and tumor tissues. FRZB protein levels were negatively correlated with β‑catenin levels analyzed by IHC staining. Furthermore, high FRZB protein levels were correlated with membrane localization of β‑catenin. FRZB knockdown increased gastric cancer cell growth in monolayer and soft agar culture; it increased cell aggregates in suspending culture and rendered less apoptosis which indicated increased anti-anoikis growth. FRZB knockdown increased cell migration and invasion and increased the expression of Wnt/β‑catenin downstream targets such as MMP7 and cyclin D1. Our studies revealed that FRZB levels were correlated with β‑catenin subcellular localization. Knockdown of FRZB in gastric cancer cells increased cell growth and migration/invasion which was also accompanied by activation of Wnt/β‑catenin downstream targets. FRZB knockdown may upregulate the Wnt/β‑catenin pathway and promote aggressiveness in gastric cancer. PMID:24676361

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

    SciTech Connect

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

    2013-03-01

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

  16. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

    PubMed Central

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R.; Wiklund, Fredrik; Berndt, Sonja I.; Benlloch, Sara; Giles, Graham G.; Severi, Gianluca; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Hunter, David J.; Henderson, Brian E.; Thun, Michael J.; Gaziano, Michael; Giovannucci, Edward L.; Siddiq, Afshan; Travis, Ruth C.; Cox, David G.; Canzian, Federico; Riboli, Elio; Key, Timothy J.; Andriole, Gerald; Albanes, Demetrius; Hayes, Richard B.; Schleutker, Johanna; Auvinen, Anssi; Tammela, Teuvo L.J.; Weischer, Maren; Stanford, Janet L.; Ostrander, Elaine A.; Cybulski, Cezary; Lubinski, Jan; Thibodeau, Stephen N.; Schaid, Daniel J.; Sorensen, Karina D.; Batra, Jyotsna; Clements, Judith A.; Chambers, Suzanne; Aitken, Joanne; Gardiner, Robert A.; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Brenner, Hermann; Habuchi, Tomonori; Ingles, Sue; John, Esther M.; Dickinson, Joanne L.; Cannon-Albright, Lisa; Teixeira, Manuel R.; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Park, Jong Y.; Cooney, Kathleen A.; Muir, Kenneth R.; Leongamornlert, Daniel A.; Saunders, Edward; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Guy, Michelle; Govindasami, Koveela; O'Brien, Lynne T.; Wilkinson, Rosemary A.; Hall, Amanda L.; Sawyer, Emma J.; Dadaev, Tokhir; Morrison, Jonathan; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Dudderidge, Tim; Ogden, Chris; Cooper, Colin S.; Lophatonanon, Artitaya; Southey, Melissa C.; Hopper, John L.; English, Dallas; Virtamo, Jarmo; Le Marchand, Loic; Campa, Daniele; Kaaks, Rudolf; Lindstrom, Sara; Diver, W. Ryan; Gapstur, Susan; Yeager, Meredith; Cox, Angela; Stern, Mariana C.; Corral, Roman; Aly, Markus; Isaacs, William; Adolfsson, Jan; Xu, Jianfeng; Zheng, S. Lilly; Wahlfors, Tiina; Taari, Kimmo; Kujala, Paula; Klarskov, Peter; Nordestgaard, Børge G.; Røder, M. Andreas; Frikke-Schmidt, Ruth; Bojesen, Stig E.; FitzGerald, Liesel M.; Kolb, Suzanne; Kwon, Erika M.; Karyadi, Danielle M.; Orntoft, Torben Falck; Borre, Michael; Rinckleb, Antje; Luedeke, Manuel; Herkommer, Kathleen; Meyer, Andreas; Serth, Jürgen; Marthick, James R.; Patterson, Briony; Wokolorczyk, Dominika; Spurdle, Amanda; Lose, Felicity; McDonnell, Shannon K.; Joshi, Amit D.; Shahabi, Ahva; Pinto, Pedro; Santos, Joana; Ray, Ana; Sellers, Thomas A.; Lin, Hui-Yi; Stephenson, Robert A.; Teerlink, Craig; Muller, Heiko; Rothenbacher, Dietrich; Tsuchiya, Norihiko; Narita, Shintaro; Cao, Guang-Wen; Slavov, Chavdar; Mitev, Vanio; Chanock, Stephen; Gronberg, Henrik; Haiman, Christopher A.; Kraft, Peter; Easton, Douglas F.; Eeles, Rosalind A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03–1.21), P = 1.4 × 10−8]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis. PMID:23065704

  17. A mixed methods assessment of coping with pediatric cancer

    PubMed Central

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

    2014-01-01

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

  18. Epstein-Barr virus as a marker of biological aggressiveness in breast cancer

    PubMed Central

    Mazouni, C; Fina, F; Romain, S; Ouafik, L; Bonnier, P; Brandone, J-M; Martin, P-M

    2011-01-01

    Purpose: Although a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation. Methods: In this study, we established the frequency of EBV-infected BC using real-time quantitative PCR (RT–PCR) in 196 BC specimens. Biological and pathological characteristics according to EBV status were evaluated. Results: EBV DNA was present in 65 of the 196 (33.2%) cases studied. EBV-positive BCs tended to be tumours with a more aggressive phenotype, more frequently oestrogen receptor negative (P=0.05) and with high histological grade (P=0.01). Overexpression of thymidine kinase activity was higher in EBV-infected BC (P=0.007). The presence of EBV was weakly associated with HER2 gene amplification (P=0.08). Conclusion: Our study provides evidence for EBV-associated BC undergoing distinct carcinogenic processes, with more aggressive features. PMID:21179039

  19. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    PubMed

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology.

  20. Differentiated pediatric thyroid cancer: correlates with adult disease, controversies in treatment.

    PubMed

    Parisi, Marguerite T; Mankoff, David

    2007-09-01

    The biologic behavior of differentiated thyroid cancer can differ between adults and children, especially in those children younger than 10 years of age. Unlike adults, young children typically present with advanced disease at diagnosis. Despite this, children respond rapidly to therapy and have an excellent prognosis that is significantly better than that of their adult counterparts with advanced disease. In contradistinction to adults, children with thyroid cancer also have higher local and distant disease recurrences with progression-free survival of only 70% at 5 years, mandating life-long surveillance. Although thyroid cancer is the most common carcinoma in children, overall incidence is low, a factor that has prevented performance of a controlled, randomized, prospective study to determine the most efficacious treatment regimen in this age group. So, although extensively investigated, treatment of pediatric patients with differentiated thyroid cancer remains controversial. This article reviews the current controversies in the treatment of pediatric differentiated thyroid cancer, focusing on issues of optimal initial and subsequent therapy as well as that of long-term follow-up. Our approach to treatment is presented. In so doing, similarities and differences between adults and children with differentiated thyroid cancer as regards unique considerations in epidemiology, diagnosis, staging, treatment, therapy-related late effects, and disease surveillance are presented. The expanding use of and appropriate roles for thyrogen and fluorine-18-fluorodeoxyglucose positron emission tomography in disease evaluation and surveillance will be addressed.

  1. Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness

    PubMed Central

    Wu, Xiao Yu; Liu, Wen Tao; Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang

    2016-01-01

    Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment. PMID:27725900

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.

    PubMed

    Marsh, Timothy; Wong, Irene; Sceneay, Jaclyn; Barakat, Amey; Qin, Yuanbo; Sjödin, Andreas; Alspach, Elise; Nilsson, Björn; Stewart, Sheila A; McAllister, Sandra S

    2016-05-15

    Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932-43. ©2016 AACR. PMID:27197230

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Trends in the Aggressiveness of End-of-Life Care for Advanced Stomach Cancer Patients

    PubMed Central

    Hong, Ji Hyung; Rho, Sang-Young

    2013-01-01

    Purpose It is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients. Materials and Methods We retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death. Results During the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death. Conclusion Our results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives. PMID:24453999

  8. Use of patient registries and administrative datasets for the study of pediatric cancer.

    PubMed

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

    2015-09-01

    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.

  9. 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

  10. DNMT3B7 Expression Promotes Tumor Progression to a More Aggressive Phenotype in Breast Cancer Cells

    PubMed Central

    Brambert, Patrick R.; Kelpsch, Daniel J.; Hameed, Rabia; Desai, Charmi V.; Calafiore, Gianfranco; Godley, Lucy A.; Raimondi, Stacey L.

    2015-01-01

    Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics. PMID:25607950

  11. Emerging Immunotherapies for Cancer and Their Potential for Application in Pediatric Oncology.

    PubMed

    Orentas, Rimas J; Mackall, Crystal L

    2015-01-01

    After decades of basic research, immune-based therapeutics for the treatment of cancer are showing evidence of efficacy in clinical trials; several immunotherapeutics already incorporated into standard treatment regimens. Intensive research is underway to improve the efficacy of immunotherapeutics and to expand the application of immunotherapy to a wider array of cancers. The therapeutic options that comprise immunotherapy for cancer are vast and span monoclonal antibodies, tumor vaccines, adoptive cellular therapies, as well as therapies aimed at reversing immunosuppression and enhancing immune reactivity globally and/or locally within the tumor microenvironment. In pediatric cancer, monoclonal antibodies have demonstrated efficacy in hematologic malignancies, and neuroblastoma and bispecific antibodies that activate resident T cells, as well as adoptive cell therapy, have shown recent exciting results for the treatment of acute lymphoblastic leukemia in childhood. This review discusses the basic principles of tumor immunology driving clinical development of new immunotherapies, describes immunotherapeutics with demonstrated efficacy and several currently in clinical trials, and highlight agents that seem to be most promising for the treatment of pediatric cancer.

  12. Subsequent malignant neoplasms in pediatric cancer patients treated with and without hematopoietic SCT.

    PubMed

    Pole, J D; Darmawikarta, D; Gassas, A; Ali, M; Egler, M; Greenberg, M L; Doyle, J; Nathan, P C; Schechter, T

    2015-05-01

    Pediatric cancer patients are at increased risk of subsequent malignant neoplasms (SMNs). However, little is known about the contribution of hematopoietic SCT (HSCT) to the development of SMNs. The objective of this study was to compare the incidence of SMNs in a population cohort of childhood cancer survivors treated with and without HSCT. A cohort of 7986 children (age 0-14 years) diagnosed with cancer in the province of Ontario, Canada between 1985 and 2009 was identified in POGONIS (Pediatric Oncology Group of Ontario Networked Information System), a population-based active cancer registry, and linked to a clinical HSCT database. Among this cohort, 796 patients had an HSCT as part of their primary treatment. Of the 375 allogeneic HSCT patients, 14 (3.7%) developed a SMN at a median follow-up of 12.3 years (range: 2.0-22.9 years). Of the 421 autologous HSCT patients, 8 (1.9%) developed a SMN at a median of 4.5 years (range: 1.3-14.3 years). Of the 7190 patients who did not receive an HSCT, 160 (2.2%) developed a SMN at a median follow-up of 6.8 years (range: 0.0-24.9 years). The 15-year cumulative incidence of SMN was 3.1% among the allogeneic HSCT group, 2.5% among the autologous group and 2.3% in the non-HSCT group. The cumulative incidence curves for the allogeneic HSCT and non-transplant groups only diverged after ~15 years from primary diagnosis. Our findings further corroborate the observation that children who undergo allogeneic HSCT are at a significantly increased risk of developing SMN compared with pediatric cancer survivors treated without HSCT.

  13. microRNA Profiling Identifies Cancer-Specific and Prognostic Signatures in Pediatric Malignancies

    PubMed Central

    Wei, Jun S; Johansson, Peter; Chen, Qing-Rong; Song, Young K; Durinck, Steffen; Wen, Xinyu; Cheuk, Adam TC; Smith, Malcolm A.; Houghton, Peter; Morton, Christopher; Khan, Javed

    2009-01-01

    Purpose microRNAs have been shown to be involved in different human cancers. We therefore have performed expression profiles on a panel of pediatric tumors to identify cancer-specific microRNAs. We also investigated if microRNAs are co-regulated with their host gene. Experimental Design We performed parallel microRNAs and mRNA expression profiling on 57 tumor xenografts and cell lines representing 10 different pediatric solid tumors using microarrays. For those microRNAs that map to their host mRNA, we calculated correlations between them. Results We found that the majority of cancer types clustered together based on their global microRNA expression profiles by unsupervised hierarchical clustering. Fourteen microRNAs were significantly differentially expressed between rhabdomyosarcoma and neuroblastoma, and 8 of them were validated in independent patient tumor samples. Exploration of the expression of microRNAs in relationship with their host genes demonstrated that the expression for 43 (63%) of 68 microRNAs located inside known coding genes were significantly correlated with that of their host genes. Among these 43 microRNAs, 5 out of 7 microRNAs in the OncomiR-1 cluster correlated significantly with their host gene MIRHG1 (P<0.01). In addition, high expression of MIRHG1 was significantly associated with high stage and MYCN-amplification in neuroblastoma tumors; and the expression level of MIRHG1 could predict the outcome of neuroblastoma patients independently from the current neuroblastoma risk-stratification in two independent patient cohorts. Conclusion Pediatric cancers express cancer-specific microRNAs. The high expression of the OncomiR-1 host gene MIRHG1 correlates with poor outcome for patients with neuroblastoma, indicating important oncogenic functions of this microRNA cluster in neuroblastoma biology. PMID:19706822

  14. Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging

    PubMed Central

    Tieu, Minh Thi; Cigsar, Candemir; Ahmed, Sameera; Ng, Andrea; Diller, Lisa; Millar, B-A; Crystal, Pavel; Hodgson, David C

    2014-01-01

    BACKGROUND Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL. METHODS We evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy. RESULTS Median age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS Screening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations. Cancer 2014;120:2507–2513. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Screening female survivors of pediatric Hodgkin Lymphoma for breast cancer with MRI and mammography detected tumors at an earlier stage than prior studies of mammography alone, although a substantial proportion of

  15. Germline Mutations in Predisposition Genes in Pediatric Cancer

    PubMed Central

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

    2016-01-01

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

  16. 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

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

    PubMed

    Domínguez, Martí; Sapiña, Lucía

    2015-03-01

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

  18. 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.

  19. 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. PMID:26287927

  20. Social Support and Parental Adjustment to Pediatric Cancer.

    ERIC Educational Resources Information Center

    Morrow, Gary R.; And Others

    1981-01-01

    Assessed the psychosocial adjustment of (N=107) parents whose children had cancer. Different patterns of association between 11 sources of social support and adjustment were found among groups of parents. Psychosocial adjustment of parents with a child in treatment was correlated more frequently with perceived social support. (Author)

  1. 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

  2. Epidemiologic, Racial and Healthographic Mapping of Delaware Pediatric Cancer: 2004-2014.

    PubMed

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

    2016-01-01

    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.

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

    ClinicalTrials.gov

    2016-06-09

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

  4. Genetic Variation in Myeloperoxidase Modifies the Association of Serum α-Tocopherol with Aggressive Prostate Cancer among Current Smokers12

    PubMed Central

    Cheng, Ting-Yuan David; Barnett, Matt J.; Kristal, Alan R.; Ambrosone, Christine B.; King, Irena B.; Thornquist, Mark D.; Goodman, Gary E.; Neuhouser, Marian L.

    2011-01-01

    We investigated associations of serum α- and γ-tocopherols and their effect modification by polymorphisms in oxidative stress regulatory enzymes in relation to prostate cancer risk. In a nested case-control study in the Carotene and Retinol Efficacy Trial, prerandomized serum α- and γ-tocopherol were assayed among 684 men with incident prostate cancer [375 nonaggressive and 284 aggressive cancer (stage III/IV or Gleason score ≥7)] and 1441 controls. Manganese superoxide dismutase Ala-16Val (rs4880), glutathione peroxidase 1 Pro200Leu (rs1050450), catalase −262 C > T (rs1001179), and myeloperoxidase (MPO) G–463A (rs2333227) were genotyped. A multivariate-adjusted inverse association of serum α-tocopherol with total prostate cancer risk was observed in current smokers (OR = 0.62, 95% CI = 0.40–0.96, 4th vs. 1st quartiles). High (≥median) compared to low serum concentrations of α- and γ-tocopherol were inversely associated with aggressive prostate cancer in current smokers (OR = 0.50, 95% CI = 0.32–0.78 and OR = 0.64, 95% CI = 0.43–0.95, respectively). The association was stronger among those with MPO G/A+A/A genotypes. Among current smokers with low serum α-tocopherol concentrations, MPO G/A+A/A, the genotypes downregulating oxidative stress, were associated with an increased risk for aggressive prostate cancer (OR = 2.06, 95% CI = 1.22–3.46). Conversely, current smokers with these genotypes who had high α-tocopherol concentrations had a reduced risk for aggressive prostate cancer (OR = 0.34, 95% CI = 0.15–0.80; P-interaction = 0.001). In conclusion, among current smokers, both high serum α- and γ-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer. The α-tocopherol–associated risks are modified by polymorphism in MPO G–463A. PMID:21795425

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

    PubMed

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

    2013-04-01

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

  6. Historical Trends in the use of radiation for pediatric cancers: 1973–2008

    PubMed Central

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

    2013-01-01

    Purpose This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. Methods The National Cancer Institute’s Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER9) was queried to identify patients aged 0–19 years with acute lympholytic leukemia (ALL), acute myeloid leukemia (AML), bone and joint, brain and other nervous system, Hodgkin’s lymphoma (HL), neuroblastoma, non-Hodgkin’s lymphoma (NHL), soft tissue, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4 year time epochs. Number and percentage of patients who received RT as a part of initial treatment were calculated per epoch by each diagnosis group from 1973–2008. Results RT usage for ALL, NHL, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973–76 to 11%, 15%, and 2% in 2005–08, respectively. Similarly, smaller declines in RT usage were also seen in brain (70% to 39%), bone (41% to 21%), Wilms tumors (75% to 53%), and neuroblastoma (60% to 25%). RT usage curves for Wilms tumors and neuroblastoma were nonlinear with nadirs in 1993–96 at 39% and 19%, respectively. There were minimal changes in RT use for HL, soft tissue cancers, or AML, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given exclusively external beam radiation therapy (EBRT). However, from 1985–2008, 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 seven out of ten pediatric cancer categories. A limitation of this study is a potential underascertainment of radiotherapy usage in the SEER9 database including the delayed use of RT. PMID:23273995

  7. Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells.

    PubMed

    Hardwick, Matthew; Cavalli, Luciane R; Barlow, Keith D; Haddad, Bassem R; Papadopoulos, Vassilios

    2002-11-01

    Recent studies using human breast cancer cell lines, animal models, and human tissue biopsies have suggested a close correlation between the expression of the peripheral-type benzodiazepine receptor (PBR) and the progression of breast cancer. This study investigates the genetic status of the PBR gene in two human breast cancer cell lines: MDA-MB-231 cells, which are an aggressive breast cancer cell line that contains high levels of PBR, and MCF-7 cells, which are a nonaggressive cell line that contains low levels of PBR. Both DNA (Southern) blot and fluorescence in situ hybridization analyses indicate that the PBR gene is amplified in MDA-MB-231 relative to MCF-7 cells. These data suggest that PBR gene amplification may be an important indicator of breast cancer progression.

  8. Cancer-germline gene expression in pediatric solid tumors using quantitative real-time PCR.

    PubMed

    Jacobs, Joannes F M; Brasseur, Francis; Hulsbergen-van de Kaa, Christina A; van de Rakt, Mandy W M M; Figdor, Carl G; Adema, Gosse J; Hoogerbrugge, Peter M; Coulie, Pierre G; de Vries, I Jolanda M

    2007-01-01

    Cancer-germline genes (CGGs) code for immunogenic antigens that are present on various human tumors but not on normal tissues. The importance of CGGs in cancer immunotherapy has led to detailed studies of their expression in a range of human tumors. We measured the levels of expression of 12 CGGs in various pediatric solid tumors to identify targets for therapeutic cancer vaccines. Quantitative real-time PCR (qPCR) was used to measure the expression of 8 MAGE genes and of genes LAGE-2/NY-ESO-1 and GAGE-1, 2, 8 in 9 osteosarcomas, 10 neuroblastomas, 12 rhabdomyosarcomas and 18 Ewing's sarcomas. Nine tumors were also examined by immunohistochemistry with monoclonal antibodies specific for the MAGE-A1, MAGE-A4 and NY-ESO-1 proteins. All osteosarcoma and 80% of neuroblastoma samples expressed several CGGs at high levels. Six of 12 rhabdomyosarcomas and 11 of 18 Ewing's sarcomas expressed at least one CGG. Immunohistochemistry data correlated well with qPCR results and showed a homogeneous protein distribution pattern in most positive tumors. No correlation was found between the levels of CGG expression in the tumors and clinicopathological parameters of the patients. Pediatric solid tumors express several CGGs, which encode antigens that could be targeted in therapeutic vaccination trials. Several CGGs of the MAGE, GAGE and LAGE families are coexpressed in a large proportion of osteosarcoma and neuroblastoma samples. Some rhabdomyosarcomas express several of these genes at high levels. Ewing's sarcomas have an overall low CGG expression.

  9. Parent perspectives on family-based psychosocial interventions in pediatric cancer: a mixed-methods approach.

    PubMed

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

    2014-05-01

    Family-based interventions in pediatric cancer face challenges associated with integrating psychosocial care into a period of intensive treatment and escalating stress. Little research has sought input from parents on the role of interventions delivered shortly after diagnosis. This mixed-methods study obtained parents' perspectives on the potential role of family-based interventions. Twenty-five parents provided feedback on the structure and timing of psychosocial interventions via focus groups and a questionnaire. Qualitative analyses resulted in three themes that were illustrative of a traumatic stress framework: (1) tension between focusing on child with cancer and addressing other family needs, (2) factors influencing parents' perception of a shared experience with other parents, and (3) the importance of matching interventions to the trajectory of parent adjustment. Quantitative data indicated that parents preferred intervention within 6 months of diagnosis, with almost half favoring within 2 months of diagnosis, and the majority wanted interventions targeted to parents only. Qualitative themes highlight the importance of using a traumatic stress framework to inform the development of family-based interventions for those affected by pediatric cancer.

  10. Parent perspectives on family-based psychosocial interventions in pediatric cancer: a mixed-methods approach.

    PubMed

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

    2014-05-01

    Family-based interventions in pediatric cancer face challenges associated with integrating psychosocial care into a period of intensive treatment and escalating stress. Little research has sought input from parents on the role of interventions delivered shortly after diagnosis. This mixed-methods study obtained parents' perspectives on the potential role of family-based interventions. Twenty-five parents provided feedback on the structure and timing of psychosocial interventions via focus groups and a questionnaire. Qualitative analyses resulted in three themes that were illustrative of a traumatic stress framework: (1) tension between focusing on child with cancer and addressing other family needs, (2) factors influencing parents' perception of a shared experience with other parents, and (3) the importance of matching interventions to the trajectory of parent adjustment. Quantitative data indicated that parents preferred intervention within 6 months of diagnosis, with almost half favoring within 2 months of diagnosis, and the majority wanted interventions targeted to parents only. Qualitative themes highlight the importance of using a traumatic stress framework to inform the development of family-based interventions for those affected by pediatric cancer. PMID:24337762

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

    PubMed

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

    2015-01-01

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

  12. 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

  13. Acquisition of Paclitaxel Resistance Is Associated With a More Aggressive and Invasive Phenotype in Prostate Cancer

    PubMed Central

    Kim, John J.; Yin, Bo; Christudass, Christhunesa S.; Terada, Naoki; Rajagopalan, Krithika; Fabry, Ben; Lee, Danielle Y.; Shiraishi, Takumi; Getzenberg, Robert H.; Veltri, Robert W.; An, Steven S.; Mooney, Steven M.

    2014-01-01

    Drug resistance is a major limitation to the successful treatment of advanced prostate cancer (PCa). Patients who have metastatic, castration-resistant PCa (mCRPC) are treated with chemotherapeutics. However, these standard therapy modalities culminate in the development of resistance. We established paclitaxel resistance in a classic, androgen-insensitive mCRPC cell line (DU145) and, using a suite of molecular and biophysical methods, characterized the structural and functional changes in vitro and in vivo that are associated with the development of drug resistance. After acquiring paclitaxel-resistance, cells exhibited an abnormal nuclear morphology with extensive chromosomal content, an increase in stiffness, and faster cytoskeletal remodeling dynamics. Compared with the parental DU145, paclitaxel-resistant (DU145-TxR) cells became highly invasive and motile in vitro, exercised greater cell traction forces, and formed larger and rapidly growing tumors in mouse xenografts. Furthermore, DU145-TxR cells showed a discrete loss of keratins but a distinct gain of ZEB1, Vimentin and Snail, suggesting an epithelial-to-mesenchymal transition. These findings demonstrate, for the first time, that paclitaxel resistance in PCa is associated with a trans-differentiation of epithelial cell machinery that enables more aggressive and invasive phenotype and portend new strategies for developing novel biomarkers and effective treatment modalities for PCa patients. PMID:23192682

  14. Plasminogen activator inhibitor-1 enhances radioresistance and aggressiveness of non-small cell lung cancer cells

    PubMed Central

    Youn, HyeSook; Kim, Joong Sun; Youn, BuHyun

    2016-01-01

    Acquired resistance of tumor cells during treatment limits the clinical efficacy of radiotherapy. Recent studies to investigate acquired resistance under treatment have focused on intercellular communication because it promotes survival and aggressiveness of tumor cells, causing therapy failure and tumor relapse. Accordingly, a better understanding of the functional communication between subpopulations of cells within a tumor is essential to development of effective cancer treatment strategies. Here, we found that conditioned media (CM) from radioresistant non-small cell lung cancer (NSCLC) cells increased survival of radiosensitive cells. Comparative proteomics analysis revealed plasminogen activator inhibitor-1 (PAI-1) as a key molecule in the secretome that acts as an extracellular signaling trigger to strengthen resistance to radiation. Our results revealed that expression and secretion of PAI-1 in radioresistant cells was increased by radiation-induced transcription factors, including p53, HIF-1α, and Smad3. When CM from radioresistant cells was applied to radiosensitive cells, extracellular PAI-1 activated the AKT and ERK1/2 signaling pathway and inhibited caspase-3 activity. Our study also proposed that PAI-1 activates the signaling pathway in radiosensitive cells via extracellular interaction with its binding partners, not clathrin-mediated endocytosis. Furthermore, secreted PAI-1 increased cell migration capacity and expression of EMT markers in vitro and in vivo. Taken together, our findings demonstrate that PAI-1 secreted from radioresistant NSCLC cells reduced radiosensitivity of nearby cells in a paracrine manner, indicating that functional inhibition of PAI-1 signaling has therapeutic potential because it prevents sensitive cells from acquiring radioresistance. PMID:27004408

  15. Occurrence of Breast Cancer After Chest Wall Irradiation for Pediatric Cancer, as Detected by a Multimodal Screening Program

    SciTech Connect

    Terenziani, Monica; Casalini, Patrizia; Scaperrotta, Gianfranco; Gandola, Lorenza; Trecate, Giovanna; Catania, Serena; Cefalo, Graziella; Conti, Alberto; Massimino, Maura; Meazza, Cristina; Podda, Marta; Spreafico, Filippo; Suman, Laura; Gennaro, Massimiliano

    2013-01-01

    Purpose: To assess the occurrence of breast cancer (BC) after exposure to ionizing radiation for pediatric cancer, by means of a multimodal screening program. Patients and Methods: We identified 86 patients who had received chest wall radiation therapy for pediatric cancer. Clinical breast examination (CBE), ultrasound (US), and mammography (MX) were performed yearly. Magnetic resonance imaging (MRI) was added as of October 2007. We calculated the risk of developing BC by radiation therapy dose, patient age, and menarche before or after primary treatment. Results: Eleven women developed a BC from July 2002-February 2010. The sensitivity of the screening methods was 36% for CBE, 73% for MX, 55% for US, and 100% for MRI; the specificity was 91%, 99%, 95%, and 80% for CBE, MX, US, and MRI, respectively. The annual BC detection rate was 2.9%. The median age at BC diagnosis was 33 years. Although age had no influence, menarche before as opposed to after radiation therapy correlated significantly with BC (P=.027): the annual BC detection rate in the former subgroup was 5.3%. Conclusions: Mammography proved more sensitive and specific in our cohort of young women than CBE or US. Magnetic resonance imaging proved 100% sensitive (but this preliminary finding needs to be confirmed). Our cohort of patients carries a 10-fold BC risk at an age more than 20 years younger than in the general population.

  16. DNA Hypomethylation-Mediated Overexpression of Carbonic Anhydrase 9 Induces an Aggressive Phenotype in Ovarian Cancer Cells

    PubMed Central

    Sung, Hye Youn

    2014-01-01

    Purpose Both genetic and epigenetic alterations can lead to abnormal expression of metastasis-regulating genes in tumor cells. Recent studies suggest that aberrant epigenetic alterations, followed by differential gene expression, leads to an aggressive cancer cell phenotype. We examined epigenetically regulated genes that are involved in ovarian cancer metastasis. Materials and Methods We developed SK-OV-3 human ovarian carcinoma cell xenografts in mice. We compared the mRNA expression and DNA methylation profiles of metastatic tissues to those of the original SK-OV-3 cell line. Results Metastatic implants showed increased mRNA expression of the carbonic anhydrase 9 (CA9) gene and hypomethylation at CpG sites in the CA9 promoter. Treatment of wild-type SK-OV-3 cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reduced methylation of the CA9 promoter and increased CA9 mRNA expression. Eight CpGs, which were located at positions -197, -74, -19, -6, +4, +13, +40, and +86, relative to the transcription start site, were hypomethylated in metastatic tumor implants, compared to that of wild-type SK-OV-3. Overexpression of CA9 induced an aggressive phenotype, including increased invasiveness and migration, in SK-OV-3 cells. Conclusion Alterations in the DNA methylation profile of the CA9 promoter were correlated with a more aggressive phenotype in ovarian cancer cells. PMID:25323905

  17. Building a National Pediatric Cancer Center and Network in Paraguay: Lessons for Addressing Challenges in a Low-income Country.

    PubMed

    Samudio, Angélica; Figueredo, Diego; Lassaletta, Alvaro; Zelada, Ofelia; Peris, Aníbal; Bogado Yinde, Luis; Relyea, George; Pérez, Antonio; Madero, Luis; Ribeiro, Raul; Masera, Giuseppe; Caniza, Miguela A

    2015-07-01

    In Paraguay, cancer is among the leading causes of death among children. We report challenges and solutions for building the country's first pediatric cancer center at the National University School of Medicine (PCC-SM) and describe the outcomes of the National Network for Pediatric Cancer. We found that children with acute lymphoblastic leukemia treated between 2008 and 2012 had higher 3-year survival rates and lower treatment abandonment rates than did children treated between 2000 and 2007 before the network was established. This improvement directly coincided with the increased treatment capacity of the PCC-SM. Herein, we describe the role of local, national, and international contributors in improving the health care at Paraguay's PCC-SM and discuss how expediting access to specialized cancer diagnosis and care and implementing a system for referral and follow-up visits can improve cancer outcomes in other low-resource countries.

  18. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  19. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-01-01

    Abstract A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414–13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674–18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292–13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097–14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects. GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new

  20. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  1. Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness

    NASA Astrophysics Data System (ADS)

    Vignati, A.; Mazzetti, S.; Giannini, V.; Russo, F.; Bollito, E.; Porpiglia, F.; Stasi, M.; Regge, D.

    2015-04-01

    To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean) -0.522, 0.821 (median) -0.569, 0.854 (10th percentile) -0.556, 0.854 (25th percentile) -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

  2. NEDD9 Is a Positive Regulator of Epithelial-Mesenchymal Transition and Promotes Invasion in Aggressive Breast Cancer

    PubMed Central

    Kong, Chenfei; Wang, Changqing; Wang, Liping; Ma, Musong; Niu, Chunbo; Sun, Xiaoqian; Du, Juan; Dong, Zhixiong; Zhu, Shan; Lu, Jun; Huang, Baiqu

    2011-01-01

    Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes. The latest studies revealed that aggressive breast cancer, especially the triple-negative breast cancer (TNBC) subtype was frequently associated with apparent EMT, but the mechanisms are still unclear. NEDD9/HEF1/Cas-L is a member of the Cas protein family and was identified as a metastasis marker in multiple cancer types. In this study, we wished to discern the role of NEDD9 in breast cancer progression and to investigate the molecular mechanism by which NEDD9 regulates EMT and promotes invasion in triple-negative breast cancer. We showed that expression of NEDD9 was frequently upregulated in TNBC cell lines, and in aggressive breast tumors, especially in TNBC subtype. Knockdown of endogenous NEDD9 reduced the migration, invasion and proliferation of TNBC cells. Moreover, ectopic overexpression of NEDD9 in mammary epithelial cells led to a string of events including the trigger of EMT, activation of ERK signaling, increase of several EMT-inducing transcription factors and promotion of their interactions with the E-cadherin promoter. Data presented in this report contribute to the understanding of the mechanisms by which NEDD9 promotes EMT, and provide useful clues to the evaluation of the potential of NEDD9 as a responsive molecular target for TNBC chemotherapy. PMID:21829474

  3. 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

  4. 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. PMID:27274442

  5. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    PubMed

    McCabe, Martin G; Valteau-Couanet, Dominique

    2016-01-01

    Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors. PMID:27595358

  6. A Family History of Lethal Prostate Cancer and Risk of Aggressive Prostate Cancer in Patients Undergoing Radical Prostatectomy.

    PubMed

    Raheem, Omer A; Cohen, Seth A; Parsons, J Kellogg; Palazzi, Kerrin L; Kane, Christopher J

    2015-01-01

    We investigated whether a family history of lethal prostate cancer (PCa) was associated with high-risk disease or biochemical recurrence in patients undergoing radical prostatectomy. A cohort of radical prostatectomy patients was stratified into men with no family history of PCa (NFH); a first-degree relative with PCa (FH); and those with a first-degree relative who had died of PCa (FHD). Demographic, operative and pathologic outcomes were analyzed. Freedom from biochemical recurrence was examined using Kaplan-Meier log rank. A multivariate Cox logistic regression analysis was also performed. We analyzed 471 men who underwent radical prostatectomy at our institution with known family history. The three groups had: 355 patients (75%) in NFH; 97 patients (21%) in FH; and 19 patients (4%) in FHD. The prevalence of a Gleason score ≥8, higher pathologic T stage, and biochemical recurrence (BCR) rates did not significantly differ between groups. On Kaplan-Meier analysis there were no differences in short-term BCR rates (p = 0.212). In this cohort of patients undergoing radical prostatectomy, those with first-degree relatives who died of PCa did not have an increased likelihood of high-risk or aggressive PCa or shorter-term risk of BCR than those who did not.

  7. A Family History of Lethal Prostate Cancer and Risk of Aggressive Prostate Cancer in Patients Undergoing Radical Prostatectomy

    PubMed Central

    Raheem, Omer A.; Cohen, Seth A.; Parsons, J. Kellogg; Palazzi, Kerrin L.; Kane, Christopher J.

    2015-01-01

    We investigated whether a family history of lethal prostate cancer (PCa) was associated with high-risk disease or biochemical recurrence in patients undergoing radical prostatectomy. A cohort of radical prostatectomy patients was stratified into men with no family history of PCa (NFH); a first-degree relative with PCa (FH); and those with a first-degree relative who had died of PCa (FHD). Demographic, operative and pathologic outcomes were analyzed. Freedom from biochemical recurrence was examined using Kaplan-Meier log rank. A multivariate Cox logistic regression analysis was also performed. We analyzed 471 men who underwent radical prostatectomy at our institution with known family history. The three groups had: 355 patients (75%) in NFH; 97 patients (21%) in FH; and 19 patients (4%) in FHD. The prevalence of a Gleason score ≥8, higher pathologic T stage, and biochemical recurrence (BCR) rates did not significantly differ between groups. On Kaplan-Meier analysis there were no differences in short-term BCR rates (p = 0.212). In this cohort of patients undergoing radical prostatectomy, those with first-degree relatives who died of PCa did not have an increased likelihood of high-risk or aggressive PCa or shorter-term risk of BCR than those who did not. PMID:26112134

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

    PubMed

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

    2015-12-01

    Current guidelines recommend all pediatric cancer survivors receive a survivor care plan (SCP) for optimal health management, yet clinical delivery of SCPs varies. We evaluated oncology providers' familiarity with and preferences for delivering SCPs to inform the implementation of a future SCP program at our institution. From November 2013 to April 2014, oncology providers from the Primary Children's Hospital in Salt Lake City, UT, completed a survey (n=41) and a 45-min focus group (n=18). Participants reported their familiarity with and training in SCP guidelines, opinions on SCPs, and barriers to delivering SCPs. As a secondary analysis, we examined differences in survey responses between physicians and nurses with Fisher's exact tests. Focus group transcripts and open-ended survey responses were content analyzed. Participants reported high familiarity with late effects of cancer treatment (87.8%) and follow-up care that cancer survivors should receive (82.5%). Few providers had delivered an SCP (oncologists 35.3% and nurses 5.0%; p=0.03). Barriers to providing SCPs included lack of knowledge (66.7%), SCP delivery is not expected in their clinic (53.9%), and no champion (48.7%). In qualitative comments, providers expressed that patient age variation complicated SCP delivery. Participants supported testing an SCP intervention program (95.1%) and felt this should be a team-based approach. Strategies for optimal delivery of SCPs are needed. Participants supported testing an SCP program to improve the quality of patient care. Team-based approaches, including nurses and physicians, that incorporate provider training on and support for SCP delivery are needed to improve pediatric cancer care. PMID:25893925

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

    PubMed

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

    2015-12-01

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

  10. 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

  11. LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer.

    PubMed

    Sas-Chen, Aldema; Aure, Miriam R; Leibovich, Limor; Carvalho, Silvia; Enuka, Yehoshua; Körner, Cindy; Polycarpou-Schwarz, Maria; Lavi, Sara; Nevo, Nava; Kuznetsov, Yuri; Yuan, Justin; Azuaje, Francisco; Ulitsky, Igor; Diederichs, Sven; Wiemann, Stefan; Yakhini, Zohar; Kristensen, Vessela N; Børresen-Dale, Anne-Lise; Yarden, Yosef

    2016-01-01

    Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal-like subtype associates with increased EGFR signaling, while another, the HER2-enriched subtype, engages a kin of EGFR Based on the premise that EGFR-regulated lncRNAs might control the aggressiveness of basal-like tumors, we identified multiple EGFR-inducible lncRNAs in basal-like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers. PMID:27485121

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

    Cancer.gov

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

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

    ERIC Educational Resources Information Center

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

    2003-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  17. 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

  18. 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. PMID:27009842

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

    SciTech Connect

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

    2008-09-01

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

  20. miR-126-3p Inhibits Thyroid Cancer Cell Growth and Metastasis, and Is Associated with Aggressive Thyroid Cancer

    PubMed Central

    Xiong, Yin; Kotian, Shweta; Zeiger, Martha A.; Zhang, Lisa; Kebebew, Electron

    2015-01-01

    Background Previous studies have shown that microRNAs are dysregulated in thyroid cancer and play important roles in the post-transcriptional regulation of target oncogenes and/or tumor suppressor genes. Methodology/Principal Findings We studied the function of miR-126-3p in thyroid cancer cells, and as a marker of disease aggressiveness. We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort. In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas. Mechanistically, ectopic overexpression of miR-126-3p significantly inhibited thyroid cancer cell proliferation, in vitro (p<0.01) and in vivo (p<0.01), colony formation (p<0.01), tumor spheroid formation (p<0.05), cellular migration (p<0.05), VEGF secretion and endothelial tube formation, and lung metastasis in vivo. We found 14 predicted target genes, which were significantly altered upon miR-126-3p transfection in thyroid cancer cells, and which are involved in cancer biology. Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p. Conclusions/Significance To our knowledge, this is the first study to demonstrate that miR-126-3p has a tumor-suppressive function in thyroid cancer cells, and is associated with aggressive disease phenotype. PMID:26244545

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

    PubMed

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

    2011-01-01

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

  2. Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines.

    PubMed

    Parisi, Marguerite T; Eslamy, Hedieh; Mankoff, David

    2016-03-01

    First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association.

  3. The seroprevalence of Kaposi's sarcoma associated herpes virus and human herpes virus-6 in pediatric patients with cancer and healthy children in a Turkish pediatric oncology center

    PubMed Central

    Tacyildiz, Nurdan; Dincaslan, Handan Ugur; Ozdemir, Halil; Yavuz, Gulsan; Unal, Emel; Ikinciogullari, Aydan; Dogu, Figen; Guloglu, Deniz; Suskan, Emine; Kose, Kenan

    2014-01-01

    Background: Many studies have tried to be establish a pathogenic role for human herpesvirus-6 and -8 (HHV-6, HHV-8) in malignant diseases, but whether these viruses plays a role in these pathologies remains unclear. HHV-6 and HHV-8 seropositivity were shown in a healthy population. There is no published data in Turkey about seroprevalence of these viruses. We aimed to determine the seroprevalence of HHV-6 and HHV-8 in pediatric cancer patients and to compare with healthy Turkish children's viral seroprevalence. Patients and Methods: Ninety-three pediatric cancer patients and 43 age-matched healthy children were included in the study. All sera were screened for antibodies to HHV-6 and HHV-8 by ELISA. Results: HHV-8 immunoglobulin G (IgG) was positive in 3.3% of lymphoma patients, in 4.8% of acute lymphoblastic leukemia (ALL) patients, in 4.8% of retinoblastoma patients and in 7% of healthy children. There was no significant difference in HHV-8 seroprevelance between these groups. HHV-6 seroprevalence was 81% in ALL patients, 70% in lymphoma group, 81% in retinoblastoma patients and 69.8% in healthy children. Although there was no significant difference in HHV-6 prevalence between healthy children and pediatric cancer patients, HHV-6 seropositivity tended to be higher in retinoblastoma patients under age of 4 years (odds ratio: 2.925). Conclusion: HHV-6 seroprevalence was higher than HHV-8 seropositivity in our study. Viral studies related HHV-6 seroprevelance in retinoblastoma patients would be useful to clarify if there is any etiological association between HHV-6 and retinoblastoma. PMID:25336794

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

    PubMed

    Götte, Miriam; Taraks, Silke; Boos, Joachim

    2014-03-01

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

  5. Long Noncoding RNA MALAT1 Promotes Aggressive Pancreatic Cancer Proliferation and Metastasis via the Stimulation of Autophagy.

    PubMed

    Li, Le; Chen, Hua; Gao, Yue; Wang, Yong-Wei; Zhang, Guang-Quan; Pan, Shang-Ha; Ji, Liang; Kong, Rui; Wang, Gang; Jia, Yue-Hui; Bai, Xue-Wei; Sun, Bei

    2016-09-01

    Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is increased in pancreatic cancer and is identified as a diagnostic biomarker. Nonetheless, the molecular mechanism of elevated MALAT1 levels and tumor aggressiveness remains unknown. In this study, MALAT1 was found to be highly expressed in PDAC tissues, and elevated expression was associated with poorer prognoses. In addition, MALAT1 was positively linearly correlated with the expression of LC3B mRNA. Furthermore, several molecules involved in cellular autophagic flux were modulated following the downregulation of MALAT1, including LC3, P62, and LAMP-2. Mechanistically, we found that MALAT1 interacted with RNA binding protein HuR, and silencing of MALAT1 greatly enhanced the posttranscriptional regulation of TIA-1 and had further effects on inhibiting autophagy. MALAT1 was speculated to regulate tumorigenesis via HuR-TIA-1-mediated autophagic activation. Hence, we investigated the biological properties of MALAT1 in terms of tumor proliferation and metastasis by promoting autophagy in vitro In brief, these data demonstrate that MALAT1 could facilitate the advanced progression of tumors in vivo Our study highlights the new roles of MALAT1 on protumorigenic functioning and anticancer therapy via activating autophagy in pancreatic cancer. Mol Cancer Ther; 15(9); 2232-43. ©2016 AACR.

  6. Mutational Analysis in Pediatric Thyroid Cancer and Correlations with Age, Ethnicity, and Clinical Presentation

    PubMed Central

    Nikita, Maria Eleni; Jiang, Wen; Cheng, Shih-Min; Hantash, Feras M.; McPhaul, Michael J.; Newbury, Robert O.; Phillips, Susan A.; Reitz, Richard E.; Waldman, Frederic M.

    2016-01-01

    Background: Well-differentiated thyroid cancer (WDTC) incidence in pediatrics is rising, most being papillary thyroid carcinoma (PTC). The objective of the study was to assess the prevalence of different mutations in pediatric WDTC and correlate the genotype with the clinical phenotype. Methods: This is a single-center retrospective study. Thyroid tissue blocks from 42 consecutive pediatric WDTC patients who underwent thyroidectomy between 2001 and 2013 were analyzed at Quest Diagnostics for BRAFV600E, RAS mutations (N,K,H), and RET/PTC and PAX8/PPARγ rearrangements, using validated molecular methods. Thyroid carcinomas included PTC, follicular thyroid carcinoma (FTC), and follicular variant of PTC (FVPTC). Results: Thirty-nine samples (29 females) were genotyped. The mean age at diagnosis was 14.7 years (range 7.9–18.4 years), and most were Hispanic (56.4%) or Caucasian (35.9%). The mean follow-up period was 2.9 years. Mutations were noted in 21/39 (53.8%), with both BRAFV600E (n = 9), and RET/PTC (n = 6) detected only in PTC. Mutations were detected in 2/5 FTC (PAX8/PPARγ and NRAS) and 3/6 FVPTC cases (PAX8/PPARγ). Of 28 PTC patients, 57.1% had mutations: 32.1% with BRAFV600E, 21.4% with RET/PTC, and 3.6% with NRAS. Of patients with BRAFV600E, 77.8% were Hispanic and 88.9% were >15 years, while all RET/PTC-positive patients were ≤15 years (p = 0.003). Tumor size, lymph node involvement, and distant metastasis at diagnosis (or soon after 131I ablation) did not vary significantly based on the mutation. Conclusions: BRAFV600E was the most common mutation, especially in older and Hispanic adolescents. A larger, ethnically diverse pediatric cohort followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed. PMID:26649796

  7. 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.

  8. Supporting pediatric cancer survivors with neurocognitive late effects: a model of care.

    PubMed

    Northman, Lisa; Ross, Sarah; Morris, Marybeth; Tarquini, Sarah

    2015-01-01

    Educational difficulties are common for childhood survivors of central nervous system (CNS) cancers. Children who have been treated for brain tumors and those who have received treatments involving the CNS are at increased risk of developing neurocognitive late effects including difficulties with attention, executive functioning, speed of processing, and academic functioning. These children are also at risk for difficulties with social functioning and social isolation. This hospital's School Liaison Program (SLP) provides ongoing psychoeducation, advocacy, and consultation services for parents, schools, and medical staff to address the educational needs associated with the late effects of treatment for pediatric CNS-involved patients. This article provides an overview of the SLP model of care and discusses parent-perceived quality and program effectiveness. In general, parents attributed SLP involvement to improved academic performance, home-school communication, and school-level understanding of unique student cognitive profiles and learning needs. PMID:25416520

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

    PubMed Central

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

    2015-01-01

    Reduced expression of both classical and desmosomal cadherins has been associated with different types of carcinomas, including prostate cancer. This study aims to provide a comprehensive view of the role and regulation of cell–cell adhesion in prostate cancer aggressiveness by examining the functional implications of both E-cadherin and Desmoglein 2 (DSG2). E-cadherin expression was first examined using immunofluorescence in 50 normal prostate tissues and in a cohort of 414 prostate cancer patients. Correlation and survival analyses were performed to assess its clinical significance. In primary prostate cancer patients, reduced expression of both E-cadherin and DSG2 is significantly associated with an earlier biochemical recurrence. Transgenic DU145 E-cadherin knockdown and constitutively active AKT overexpression lines were generated. Functional implications of such genetic alterations were analyzed in vitro and in vivo, the latter by using tumorigenesis as well as extravasation and metastatic tumor formation assays. We observed that loss of E-cadherin leads to impaired primary and metastatic tumor formation in vivo, suggesting a tumor promoter role for E-cadherin in addition to its known role as a tumor suppressor. Activation of AKT leads to a significant reduction in E-cadherin expression and nuclear localization of Snail, suggesting a role for the PI3K/AKT signaling pathway in the transient repression of E-cadherin. This reduced expression may be regulated by separate mechanisms as neither the loss of E-cadherin nor activation of AKT significantly affected DSG2 expression. In conclusion, these findings illustrate the critical role of cell–cell adhesion in the progression to aggressive prostate cancer, through regulation by the PI3K pathway. PMID:26033689

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

    PubMed

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

    2013-11-15

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

  11. NIH Scientists Map Genetic Changes That Drive Tumors in a Common Pediatric Soft-Tissue Cancer

    MedlinePlus

    ... Press Releases NCI Press Release NIH scientists map genetic changes that drive tumors in a common pediatric ... Office 301-496-6641 Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric ...

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

    PubMed

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

    2014-06-01

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

  13. Routine use of recombinant human bone morphogenetic protein-2 in posterior fusions of the pediatric spine and incidence of cancer.

    PubMed

    Sayama, Christina; Willsey, Matthew; Chintagumpala, Murali; Brayton, Alison; Briceño, Valentina; Ryan, Sheila L; Luerssen, Thomas G; Hwang, Steven W; Jea, Andrew

    2015-07-01

    OBJECT The aim of this study was to determine the safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in posterior instrumented fusions in the pediatric population, focusing on cancer risk. In a previous study, the authors reported the short-term (mean follow-up of 11 months) safety and efficacy of rhBMP-2 in the pediatric age group. The present study reports their results with a minimum of 24 months' follow-up. METHODS The authors retrospectively reviewed 57 consecutive cases involving pediatric patients who underwent posterior occiptocervical, cervical, thoracic, lumbar, or lumbosacral spine fusion from October 1, 2007, to June 30, 2011, at Texas Children's Hospital. Seven cases were excluded from further analysis because of loss to follow-up. Three patients died during the follow-up period and were placed in a separate cohort. RESULTS The patients' average age at the time of surgery was 11 years, 4 months (range 9 months to 20 years). The mean duration of follow-up was 48.4 months (range 24-70 months). Cancer status was determined at the most recent encounter with the patient and/or caretaker(s) in person, or in telephone follow-up. Twenty-four or more months after administration of rhBMP-2, there were no cases of new malignancy, degeneration, or metastasis of existing tumors. The cause of death of the patients who died during the study period was not related to BMP or to the development, degeneration, or metastasis of cancer. CONCLUSIONS Despite the large number of adult studies reporting increased cancer risk associated with BMP use, the authors' outcomes with rhBMP-2 in the pediatric population suggest that it is a safe adjunct to posterior spine fusions of the occipitocervical, cervical, thoracic, lumbar, and lumbosacral spine. There were no new cases of cancer, or degeneration or metastasis of existing malignancies in this series.

  14. Long-term follow-up for incident cirrhosis among pediatric cancer survivors with hepatitis C virus infection

    PubMed Central

    Stallings-Smith, Sericea; Krull, Kevin R.; Brinkman, Tara M.; Hudson, Melissa M.; Ojha, Rohit P.

    2015-01-01

    Background Pediatric cancer patients who received blood transfusions were potentially exposed to hepatitis C virus (HCV) prior to second-generation HCV screening of blood products in 1992. Limited evidence is available about long-term incident cirrhosis in this population. Objectives We aimed to estimate the overall and sex-specific incidence of cirrhosis among HCV-seropositive survivors of pediatric cancer. Study design We identified 113 HCV-seropositive pediatric cancer patients treated at St. Jude Children’s Research Hospital between 1962 and 1997, who survived ≥5 years post-diagnosis, and were followed through 2014. Our outcome was cirrhosis determined by liver biopsy or diagnostic imaging. We used a competing-risk framework to estimate the overall and sex-specific cumulative incidence and 95% confidence limits (CL) of cirrhosis at 10-year follow-up intervals. Results The median duration of follow-up was 30 years (interquartile range=28 – 36) post-cancer diagnosis. Cumulative incidence of cirrhosis increased at each 10-year interval from 0% after 10 years to 13% after 40 years (Ptrend<0.001). The median age at diagnosis of cirrhosis was 30 years (interquartile range=24 – 38). We observed a linear trend in incidence for males (Ptrend<0.001), with a cumulative incidence of 18% (95% CL: 6.1%, 34%) after 40 years. The cumulative incidence for females was 6.5% (95% CL: 0.42%, 26%) after 40 years, but we did not observe a linear trend (Ptrend=0.99). Conclusion Our results suggest that the incidence of cirrhosis is similar between HCV-seropositive pediatric cancer survivors and the general population given similar duration of follow-up, but survivors may be diagnosed with cirrhosis at an earlier age. PMID:26370309

  15. Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.

    PubMed

    Murase, Ryuichi; Sumida, Tomoki; Kawamura, Rumi; Onishi-Ishikawa, Akiko; Hamakawa, Hiroyuki; McAllister, Sean D; Desprez, Pierre-Yves

    2016-07-10

    Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix-loop-helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC. PMID:27087608

  16. Implantable Port Devices, Complications and outcome in Pediatric Cancer, a Retrospective Study

    PubMed Central

    Esfahani, H; Ghorbanpor, M; Tanasan, A

    2016-01-01

    Background Peripheral blood vessels, due to availability are used for many years in cancer patients, however in patients with potentially harmful drugs to skin (vesicant drugs) or difficult accessibility to vessels, the use of implantable port (totally implantable venous access port-TIVAP) devices with central vascular access are important. Materials and Methods In this retrospective study, 85 pediatric cancer patients younger than 16 years, with TIVAP implantation, were followed for their complications and outcome. In addition to demographic data, patients’ port complications were assessed and compared with published articles. Results Mean days of implanted port usage were 531 ± 358 days in all patients. This period was 287 ±194 days in complicated patients. Complications included as infection (tunnel infection and catheter related blood-stream infection), malfunction and thrombosis, skin erosion, tube avulsion, and tube adhesion to the adjacent vessels were seen in 30.6% of patients. Conclusion According to the published data and this experience, the most common complications in TIVAP are infection and catheter malfunction. It is important to notice that in order to prolong its efficacious life, effective sterilization methods, prevention of clot formation and trauma, are the most useful measures. PMID:27222696

  17. Identifying aggressive forms of endometrioid-type endometrial cancer: new insights into molecular subtyping

    PubMed Central

    Liu, Yuexin; Broaddus, Russell R.; Zhang, Wei

    2015-01-01

    Summary Clinical heterogeneity represents a great challenge for cancer therapeutics. Molecular classification of patients into different subtypes based on genetic or epigenetic characteristics has the potential to revolutionize the clinical care and mechanistic understanding of a wide spectrum of cancers, including endometrial carcinoma, the most common gynecological cancer affecting women. PMID:25494844

  18. Glycoproteomic Analysis of Prostate Cancer Tissues by SWATH Mass Spectrometry Discovers N-acylethanolamine Acid Amidase and Protein Tyrosine Kinase 7 as Signatures for Tumor Aggressiveness*

    PubMed Central

    Liu, Yansheng; Chen, Jing; Sethi, Atul; Li, Qing K.; Chen, Lijun; Collins, Ben; Gillet, Ludovic C. J.; Wollscheid, Bernd; Zhang, Hui; Aebersold, Ruedi

    2014-01-01

    The identification of biomarkers indicating the level of aggressiveness of prostate cancer (PCa) will address the urgent clinical need to minimize the general overtreatment of patients with non-aggressive PCa, who account for the majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16), and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH mass spectrometry, an emerging data-independent acquisition method that generates a single file containing fragment ion spectra of all ionized species of a sample. The resulting datasets were searched using a targeted data analysis strategy in which an a priori spectral reference library representing known N-glycosites of the human proteome was used to identify groups of signals in the SWATH mass spectrometry data. On average we identified 1430 N-glycosites from each sample. Out of those, 220 glycoproteins showed significant quantitative changes associated with diverse biological processes involved in PCa aggressiveness and metastasis and indicated functional relationships. Two glycoproteins, N-acylethanolamine acid amidase and protein tyrosine kinase 7, that were significantly associated with aggressive PCa in the initial sample cohort were further validated in an independent set of patient tissues using tissue microarray analysis. The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive PCa. PMID:24741114

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

    PubMed Central

    2016-01-01

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

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

    PubMed

    ElShamy, Wael M; Sinha, Abhilasha; Said, Neveen

    2016-01-01

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

  1. Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases.

    PubMed

    Helfand, Brian T; Roehl, Kimberly A; Cooper, Phillip R; McGuire, Barry B; Fitzgerald, Liesel M; Cancel-Tassin, Geraldine; Cornu, Jean-Nicolas; Bauer, Scott; Van Blarigan, Erin L; Chen, Xin; Duggan, David; Ostrander, Elaine A; Gwo-Shu, Mary; Zhang, Zuo-Feng; Chang, Shen-Chih; Jeong, Somee; Fontham, Elizabeth T H; Smith, Gary; Mohler, James L; Berndt, Sonja I; McDonnell, Shannon K; Kittles, Rick; Rybicki, Benjamin A; Freedman, Matthew; Kantoff, Philip W; Pomerantz, Mark; Breyer, Joan P; Smith, Jeffrey R; Rebbeck, Timothy R; Mercola, Dan; Isaacs, William B; Wiklund, Fredrick; Cussenot, Olivier; Thibodeau, Stephen N; Schaid, Daniel J; Cannon-Albright, Lisa; Cooney, Kathleen A; Chanock, Stephen J; Stanford, Janet L; Chan, June M; Witte, John; Xu, Jianfeng; Bensen, Jeannette T; Taylor, Jack A; Catalona, William J

    2015-04-01

    Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤ 6, 7, ≥ 8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.

  2. 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.

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

    PubMed Central

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

    2013-01-01

    Pediatric patients who received radiation therapy are at risk of developing side effects like 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 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 risks of the incidence of second cancer considered after proton CSI and photon CSI were 7.7% and 92%, respectively, and the ratio of lifetime risk was 0.083. 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. PMID:23322160

  4. Thrombin stimulation of inflammatory breast cancer cells leads to aggressiveness via the EGFR-PAR1-Pak1 pathway.

    PubMed

    Ohshiro, Kazufumi; Bui-Nguyen, Tri M; Divijendra Natha, Reddy S; Schwartz, Arnold M; Levine, Paul; Kumar, Rakesh

    2012-12-27

    Inflammatory breast cancer (IBC) accounts for a small fraction but aggressive form of epithelial breast cancer. Although the role of thrombin in cancer is beginning to be unfolded, its impact on the biology of IBC remains unknown. The purpose of this study was to establish the role of thrombin on the invasiveness of IBC cells. The IBC SUM149 cell line was treated with thrombin in the absence or presence of the epidermal growth factor receptor (EGFR) inhibitor erlotinib and protease-activated receptor 1 (PAR1) inhibitor. The effects of pharmacological inhibitors on the ability of thrombin to stimulate the growth rate and invasiveness were examined. We found that the inhibition of putative cellular targets of thrombin action suppresses both the growth and invasiveness of SUM149 cells in a concentration-dependent manner. In addition, thrombin-mediated increased invasion of SUM149 cells was routed through EGFR phosphorylation, and in turn, stimulation of the p21-activated kinase (Pak1) activity in a EGFR-sensitive manner. Interestingly, thrombin-mediated activation of the Pak1 pathway stimulation was blocked by erlotinib and PAR1 inhibitor. For proof-of-principle studies, we found immunohistochemical evidence of Pak1 activation as well as expression of PAR1 in IBC. Thrombin utilizes EGFR to relay signals promoting SUM149 cell growth and invasion via the Pak1 pathway. The study provides the rationale for future therapeutic approaches in mitigating the invasive nature of IBC by targeting Pak1 and/or EGFR.

  5. Gender differences in psychological adaptation and coping in parents of pediatric cancer patients.

    PubMed

    Hoekstra-Weebers, J E; Jaspers, J P; Kamps, W A; Klip, E C

    1998-01-01

    This study investigated differences in psychological distress and coping styles between fathers and mothers of pediatric cancer patients, over a 1-year time period. Also examined were (dis)similarities in couples in distress and coping, and the relationship between (dis)similarities in coping and psychological functioning of both members of a couple. Parents (n = 124, 62 couples) were assessed at diagnosis, at 6 and 12 months. Fathers and mothers experienced higher levels of psychiatric symptomatology and psychological distress at diagnosis than men and women of a normgroup. Distress declined significantly with time. Although parents did not report more symptoms than the normgroup 12 months post-diagnosis, they still were psychologically out of balance. Contrary to findings in the general population, no differences were found between fathers and mothers in psychiatric symptoms or psychological distress on any of the measurements. Only a few gender differences in coping were found. Fathers used more active-problem focusing at diagnosis and a less palliative reaction pattern at 12 months than did mothers. Mothers used more social-support seeking on all measurements. A tendency for similarity in the use of the coping styles within couples was found. Discrepancies in coping in couples were positively related to distress in fathers at diagnosis. However, 12 months later, the more discrepant the couples were in their coping preferences the more distress the mothers indicated.

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-03-01

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

  8. Proton Therapy in Children: A Systematic Review of Clinical Effectiveness in 15 Pediatric Cancers.

    PubMed

    Leroy, Roos; Benahmed, Nadia; Hulstaert, Frank; Van Damme, Nancy; De Ruysscher, Dirk

    2016-05-01

    Because it spares many normal tissues and reduces the integral dose, proton therapy (PT) is the preferred tumor irradiation technique for treating childhood cancer. However, to the best of our knowledge, no systematic review of the clinical effectiveness of PT in children has been reported in the scientific literature. A systematic search for clinical outcome studies on PT published between 2007 and 2015 was performed in Medline (through OVID), EMBASE, and the Cochrane Library. Twenty-three primary studies were identified, including approximately 650 patients overall. The median/mean follow-up times were limited (range, 19-91 months). None of the studies were randomized, 2 were comparative, and 20 were retrospective. Most suffered from serious methodologic limitations, yielding a very low level of clinical evidence for the outcomes in all indications. For example, for retinoblastoma, very low-level evidence was found that PT might decrease the incidence of second malignancies. For chondrosarcoma, chordoma, craniopharyngioma, ependymoma, esthesioneuroblastoma, Ewing sarcoma, central nervous system germinoma, glioma, medulloblastoma, osteosarcoma, and rhabdomyosarcoma, there was insufficient evidence to either support or refute PT in children. For pelvic sarcoma (ie, nonrhabdomyosarcoma and non-Ewing sarcoma), pineal parenchymal tumor, primitive neuroectodermal tumor, and "adult-type" soft tissue sarcoma, no studies were identified that fulfilled the inclusion criteria. Although there is no doubt that PT reduces the radiation dose to normal tissues and organs, to date the critical clinical data on the long-term effectiveness and harm associated with the use of PT in the 15 pediatric cancers under investigation are lacking. High-quality clinical research in this area is needed. PMID:27084646

  9. Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer

    PubMed Central

    Calmon, Marilia Freitas; Jeschke, Jana; Zhang, Wei; Dhir, Mashaal; Siebenkäs, Cornelia; Herrera, Alexander; Tsai, Hsing-Chen; O'Hagan, Heather M; Pappou, Emmanouil P; Hooker, Craig M; Fu, Tao; Schuebel, Kornel E; Gabrielson, Edward; Rahal, Paula; Herman, James G; Baylin, Stephen B; Ahuja, Nita

    2015-01-01

    Neurofilament heavy polypeptide (NEFH) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of NEFH, NEFL, and NEFM in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes NEFH, NEFM, and NEFL are frequent events that may contribute to the progression of breast cancer and possibly other malignancies. PMID:25985363

  10. Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer.

    PubMed

    Calmon, Marilia Freitas; Jeschke, Jana; Zhang, Wei; Dhir, Mashaal; Siebenkäs, Cornelia; Herrera, Alexander; Tsai, Hsing-Chen; O'Hagan, Heather M; Pappou, Emmanouil P; Hooker, Craig M; Fu, Tao; Schuebel, Kornel E; Gabrielson, Edward; Rahal, Paula; Herman, James G; Baylin, Stephen B; Ahuja, Nita

    2015-01-01

    Neurofilament heavy polypeptide (NEFH) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of NEFH, NEFL, and NEFM in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes NEFH, NEFM, and NEFL are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.

  11. Guidelines for assistance to siblings of children with cancer: report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

    PubMed

    Spinetta, J J; Jankovic, M; Eden, T; Green, D; Martins, A G; Wandzura, C; Wilbur, J; Masera, G

    1999-10-01

    This is the seventh official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. This document develops an additional topic discussed and approved by the SIOP Committee, "Assistance to siblings of children with cancer. " It is addressed to the pediatric oncology community and outlines general principles for helping siblings throughout phases of treatment: at diagnosis, during treatment, in the event of relapse, during bone marrow transplantation, after completion of therapy, during palliative care and the terminal phase.

  12. Vasectomy and Risk of Aggressive Prostate Cancer: A 24-Year Follow-Up Study

    PubMed Central

    Siddiqui, Mohummad Minhaj; Wilson, Kathryn M.; Epstein, Mara M.; Rider, Jennifer R.; Martin, Neil E.; Stampfer, Meir J.; Giovannucci, Edward L.; Mucci, Lorelei A.

    2014-01-01

    Purpose Conflicting reports remain regarding the association between vasectomy, a common form of male contraception in the United States, and prostate cancer risk. We examined prospectively this association with extended follow-up and an emphasis on advanced and lethal disease. Patients and Methods Among 49,405 US men in the Health Professionals Follow-Up Study, age 40 to 75 years at baseline in 1986, 6,023 patients with prostate cancer were diagnosed during the follow-up to 2010, including 811 lethal cases. In total, 12,321 men (25%) had vasectomies. We used Cox proportional hazards models to estimate the relative risk (RR) and 95% CIs of total, advanced, high-grade, and lethal disease, with adjustment for a variety of possible confounders. Results Vasectomy was associated with a small increased risk of prostate cancer overall (RR, 1.10; 95% CI, 1.04 to 1.17). Risk was elevated for high-grade (Gleason score 8 to 10; RR, 1.22; 95% CI, 1.03 to 1.45) and lethal disease (death or distant metastasis; RR, 1.19; 95% CI, 1.00 to 1.43). Among a subcohort of men receiving regular prostate-specific antigen screening, the association with lethal cancer was stronger (RR, 1.56; 95% CI, 1.03 to 2.36). Vasectomy was not associated with the risk of low-grade or localized disease. Additional analyses suggested that the associations were not driven by differences in sex hormone levels, sexually transmitted infections, or cancer treatment. Conclusion Our data support the hypothesis that vasectomy is associated with a modest increased incidence of lethal prostate cancer. The results do not appear to be due to detection bias, and confounding by infections or cancer treatment is unlikely. PMID:25002716

  13. Targeting GRB7/ERK/FOXM1 Signaling Pathway Impairs Aggressiveness of Ovarian Cancer Cells

    PubMed Central

    Chan, David W.; Hui, Winnie W. Y.; Cai, Patty C. H.; Liu, Michelle X.; Yung, Mingo M. H.; Mak, Celia S. L.; Leung, Thomas H. Y.; Chan, Karen K. L.; Ngan, Hextan Y. S.

    2012-01-01

    Ovarian cancer is a highly lethal disease with poor prognosis and especially in high-grade tumor. Emerging evidence has reported that aberrant upregulation and activation of GRB7, ERK as well as FOXM1 are closely associated with aggresivenesss of human cancers. However, the interplay between these factors in the pathogenesis of human cancers still remains unclear. In this study, we found that GRB7 (P<0.0001), ERK phosphorylation (P<0.0001) and FOXM1 (P = 0.001) were frequently increased and associated with high-grade tumors, as well as a high tendency in association with advanced stage ovarian cancer by immunohistochemical analysis. Intriguingly, the expressions of GRB7 (P<0.0001), ERK phosphorylation (P<0.001) and FOXM1 (P<0.001) showed a significant stepwise increase pattern along Grade 1 to Grade 3 ovarian cancers. Biochemical studies using western blot analysis demonstrated that enforced expression or knockdown of GRB7 showed GRB7 could elevate the levels of ERK phosphorylation and FOXM1, whereas enforced expression of FOXM1 could not alter levels of GRB7 and ERK phosphorylation. But inhibition of ERK signaling by U0126 or PD98059 could reduce the level of FOXM1 in GRB7-overexpressing ovarian cancer cells, suggesting that GRB7, ERK and FOXM1 are regulated orderly. Moreover, inhibition of ERK activity by U0126 or PD98059, or decreased FOXM1 expression by Thiostrepton significantly inhibited cell migration/invasion, tumor growth in vitro and in vivo. Collectively, our findings confer that targeting GRB7/ERK/FOXM1 signaling cascade may be a promising molecular therapeutic choice in combating ovarian cancer. PMID:23285101

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

    The aim of the project was to evaluate the clinical value of a computer analysis of cytological specimen images obtained from urine and bladder washing samples. Three sample types (voided urine, catheterized urine and bladder washing) from 59 patients with primary or recurrent tumor were analyzed. All patients underwent cystoscopy and biopsy or resection. The histological results were compared with the results of the image analyzing computer system of collected urine samples. The consistency between the computer diagnosis and the clinical or histological diagnosis both in the presence and absence of cancer was as follows: 77% for voided urine samples, 72.5% for catheterized urine samples and 78% for bladder washing samples. The specificity of the method at the standard pathology level was 71%, and the sensitivity was 83%. The positive and negative predictive values (PPV and NPV) were 87.5% and 63% respectively. The sensitivity for G3 or CIS or T2 or T3 tumors reached nearly 100%. Computer analysis of urine provided correct diagnoses in cancer and control patients with the sensitivity of 83% and specificity of 71% and gave excellent results in aggressive tumors such as T2, T3, G3 and in CIS. PMID:27543866

  18. Why did the Nazis have the world's most aggressive anti-cancer campaign?

    PubMed

    Proctor, R N

    1999-01-01

    Recent historical work has shown that while certain kinds of science were destroyed under the Nazi regime, other kinds flourished. Sciences of an applied nature were especially encouraged, as were sciences that fit within the larger program of Nazi segregation and extermination. Little attention, though, has been given to Nazi cancer theory and policy. That is curious, given that the Nazi regime launched one of the most comprehensive and successful cancer prevention programs of the century, involving bans on smoking, restrictions on carcinogenic food dyes, new steps to limit exposure to asbestos and radiation, and much else as well. PMID:10451929

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

    PubMed Central

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

    2016-01-01

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

  20. 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. PMID:16442484

  1. Progranulin stimulated by LPA promotes the migration of aggressive breast cancer cells.

    PubMed

    Swamydas, Muthulekha; Nguyen, Do; Allen, Lauren D; Eddy, Jill; Dréau, Didier

    2011-12-01

    Activator and inhibitor roles for the 88-kDa-secreted glycoprotein progranulin (PGRN) have been demonstrated in ovarian cancer cells. Here, we investigated the effects of PGRN in breast cancer migration. Testing MCF7, MDA-MB-453, and MDA-MB-231 human breast cancer cells and the MCF10A breast epithelial cell line, we demonstrate that LPA-induced PGRN stimulation led to a significant increase in cell invasion of MDA-MB-453 and MDA-MB-231 cells only (p<0.05). Moreover, incubation with an anti-PGRN antibody, an inhibitor of the ERK pathway (PD98059) or both in combination inhibited the ability of MDA-MB-231 cells to invade. Furthermore, the expression of focal adhesion kinases promoted by LPA-induced PGRN was also inhibited by PD98059 alone or in combination with an anti-PGRN antibody (p<0.05). Taken together, these results suggest that the LPA activation of PGRN involving the ERK pathway is critical to promote MDA-MB-231 breast cancer cell invasion.

  2. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    PubMed Central

    Freund, Derek; Zhang, Rui; Sanders, Mary; Newhauser, Wayne

    2015-01-01

    Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis. PMID:25866999

  3. 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.

  4. Physician preferences and knowledge gaps regarding the care of childhood cancer survivors: a mailed survey of pediatric oncologists.

    PubMed

    Henderson, Tara O; Hlubocky, Fay J; Wroblewski, Kristen E; Diller, Lisa; Daugherty, Christopher K

    2010-02-10

    PURPOSE Little is known about physicians' attitudes and knowledge regarding the health care needs of childhood cancer survivors (CCS). We sought to obtain pediatric cancer physicians' self-reported attitudes and knowledge regarding this population. METHODS A mailed survey was sent to 1,159 pediatric oncologists in the United States. Results A total of 655 surveys were returned (ie, 57% response rate). Median age of respondents was 47 years (range, 31 to 82 years); 57% were men. Respondents practiced for a median 14 years (range, 1 to 50 years) and reported seeing a median of 21 patients per week (range, 0 to 250 patients per week). When comfort levels in caring for CCS were described (ie, 1 = very uncomfortable; 7 = very comfortable), respondents were most comfortable with survivors < or = 21 years (mean +/- standard deviation, 6.2 +/- 1.3 level), were less comfortable (5.0 +/- 1.5 level) with those older than 21 years but less than 30 years old, and were uncomfortable with CCS > or = 30 years (2.9 +/- 1.7 level). In response to a clinical vignette of a 29-year-old woman treated with mantle radiation for Hodgkin's lymphoma at 16 years of age, and on the basis of available guidelines, 34% of respondents did not appropriately recommend yearly breast cancer surveillance; 43% of respondents did not appropriately recommend cardiac surveillance; and 24% of respondents did not appropriately recommend yearly thyroid surveillance. Those with greater self-reported familiarity with available long-term follow-up (LTFU) guidelines (odds ratio [OR], 1.33; 95% CI, 1.15 to 1.54) and with receipt of training in the care of CCS (OR, 1.73; 95% CI, 1.18 to 2.52) were more likely to have answered all three questions correctly. CONCLUSION Pediatric oncologists express a range of preferences with regard to LTFU of CCS. Many appear unfamiliar with LTFU surveillance guidelines.

  5. Assessment of apparent diffusion coefficient values as predictor of aggressiveness in peripheral zone prostate cancer: comparison with Gleason score.

    PubMed

    Anwar, Shayan Sirat Maheen; Anwar Khan, Zahid; Shoaib Hamid, Rana; Haroon, Fahd; Sayani, Raza; Beg, Madiha; Khattak, Yasir Jamil

    2014-01-01

    Purpose. To determine association between apparent diffusion coefficient value on diffusion-weighted imaging and Gleason score in patients with prostate cancer. Methods. This retrospective case series was conducted at Radiology Department of Aga Khan University between June 2009 and June 2011. 28 patients with biopsy-proven prostate cancer were included who underwent ultrasound guided sextant prostate biopsy and MRI. MRI images were analyzed on diagnostic console and regions of interest were drawn. Data were entered and analyzed on SPSS 20.0. ADC values were compared with Gleason score using one-way ANOVA test. Results. In 28 patients, 168 quadrants were biopsied and 106 quadrants were positive for malignancy. 89 lesions with proven malignancy showed diffusion restriction. The mean ADC value for disease with a Gleason score of 6 was 935 mm(2)/s (SD = 248.4 mm(2)/s); Gleason score of 7 was 837 mm(2)/s (SD = 208.5 mm(2)/s); Gleason score of 8 was 614 mm(2)/s (SD = 108 mm(2)/s); and Gleason score of 9 was 571 mm(2)/s (SD = 82 mm(2)/s). Inverse relationship was observed between Gleason score and mean ADC values. Conclusion. DWI and specifically quantitative ADC values may help differentiate between low-risk (Gleason score, 6), intermediate-risk (Gleason score, 7), and high-risk (Gleason score 8 and 9) prostate cancers, indirectly determining the aggressiveness of the disease. PMID:24967293

  6. The effect of massage therapy on chemotherapy-induced nausea and vomiting in pediatric cancer

    PubMed Central

    Mazlum, Seyedreza; Chaharsoughi, Narges Toghian; Banihashem, Abdolah; Vashani, Hamidreza Behnam

    2013-01-01

    Background: Nausea and vomiting are the most common and unpleasant side effects of chemotherapy, and they may prevent successful treatment completion. Antiemetics not only cannot control nausea and vomiting completely but also have numerous side effects. So it is necessary to find other methods for a better control. This study aimed to assess the effect of massage therapy on chemotherapy-induced nausea and vomiting in pediatric cancer. Materials and Methods: In this randomized controlled clinical trial study, 70 patients (4-18 years of age) under chemotherapy were divided into two (massage therapy and control) groups randomly. In the massage group at 0.5 h and 24 h before and 24 h after chemotherapy, the patients were massaged (Swedish massage) for 20 min, respectively. All indices of nausea and vomiting (incidence, severity, time, and length) were assessed by Visual Analogue Scale (VAS) and BARF scales and other questionnaires and documented. Results: The results of Mann–Whitney and chi-squire tests indicated that in the massage group, the incidence of nausea was 25.7%, the severity, length, and times of nausea were 20%, 54 min, and 0.35 times, respectively, and the severity and times of vomiting were 0.24 scores and 0.31 times lower than those of the control group (P < 0.05), respectively. But vomiting incidence in the two groups showed no significant difference (P = 0.192). Conclusions: Massage therapy reduced chemotherapy-induced nausea and vomiting. So, nurses can use it and educate it to the patients’ families. Nurses, besides using it clinically, can provide instructions to families for involving them in the treatment process and they feel they are more efficate in care of their suffering children. PMID:24403922

  7. Immunological evaluation of pediatric cancer patients receiving recombinant interleukin-2 in a phase I trial.

    PubMed

    Truitt, R L; Piaskowski, V; Kirchner, P; McOlash, L; Camitta, B M; Casper, J T

    1992-05-01

    Immunological evaluations were performed on 14 pediatric cancer patients who received human recombinant interleukin-2 (rIL-2) as a bolus intravenous infusion every 8 h for 5 consecutive days in a phase I trial. Three-to-four patients were treated at dose levels of 10, 30, 60, and 100 x 10(3) Cetus U/kg. Six of the patients had stage D neuroblastoma; the remainder had other solid tumors or leukemias. Infusion of rIL-2 was associated with a rapid margination of IL-2-responsive cells followed by demargination and heightened proliferative and cytotoxic activity after therapy was completed. The predominant phenotypic change in circulating peripheral blood mononuclear cells (PBMC) was an increase in CD2 expression by CD56+ natural killer (NK) cells. Appearance of CD2+ CD56+ cells in the circulation correlated with increased lymphokine-activated killer (LAK) cell activity as defined by the ability to kill NK-resistant Daudi tumor cells in vitro. Sustained LAK activity appeared to be dependent on the bioavailability of rIL-2 in vivo as well as in vitro. After rIL-2 therapy, PBMC that were highly responsive to rIL-2 (activated and "poised" LAK cells) persisted for at least 72 h. In the patients tested, increased lysis of autologous and/or allogeneic, histologically similar tumor cell lines was also observed after therapy. The immunoenhancing effects of rIL-2 occurred even at the lower doses used in this study. However, an objective tumor response was not observed in any of the patients.

  8. Working Memory Training in Survivors of Pediatric Cancer: A Randomized Pilot Study

    PubMed Central

    Hardy, Kristina K.; Willard, Victoria W.; Allen, Taryn M.; Bonner, Melanie J.

    2012-01-01

    Objectives Survivors of pediatric brain tumors and acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive deficits, but few empirically-supported treatment options exist. We examined the feasibility and preliminary efficacy of a home-based, computerized working memory training program, CogmedRM, with survivors of childhood cancer. Methods Survivors of brain tumors or ALL (n = 20) with identified deficits in attention and/or working memory were randomized to either the success-adapted computer intervention or a non-adaptive, active control condition. Specifically, children in the adaptive condition completed exercises that became more challenging with each correct trial, whereas those in the non-adaptive version trained with exercises that never increased in difficulty. All participants were asked to complete 25 training sessions at home, with weekly, phone-based coaching support. Brief assessments were completed pre- and post-intervention; outcome measures included both performance-based and parent-report measures of working memory and attention. Results Eighty-five percent of survivors were compliant with the intervention, with no adverse events reported. After controlling for baseline intellectual functioning, survivors who completed the intervention program evidenced significant post-training improvements in their visual working memory and in parent-rated learning problems compared with those in the active control group. No differences in verbal working memory functioning were evident between groups, however. Conclusions Home-based, computerized cognitive training demonstrates good feasibility and acceptability in our sample. Children with higher intellectual functioning at baseline appeared to benefit more from the training, though further study is needed to clarify the strength, scope, and particularly the generalizability of potential treatment effects. PMID:23203754

  9. First-in-human uPAR PET: Imaging of Cancer Aggressiveness

    PubMed Central

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene; Christensen, Camilla; Madsen, Jacob; Nielsen, Carsten H.; Thurison, Tine; Klausen, Thomas Levin; Holm, Søren; Loft, Annika; Berthelsen, Anne Kiil; Ploug, Michael; Pappot, Helle; Brasso, Klaus; Kroman, Niels; Højgaard, Liselotte; Kjaer, Andreas

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with 64Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of 64Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of 64Cu-DOTA-AE105 for uPAR PET imaging in cancer patients. PMID:26516369

  10. First-in-human uPAR PET: Imaging of Cancer Aggressiveness.

    PubMed

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene; Christensen, Camilla; Madsen, Jacob; Nielsen, Carsten H; Thurison, Tine; Klausen, Thomas Levin; Holm, Søren; Loft, Annika; Berthelsen, Anne Kiil; Ploug, Michael; Pappot, Helle; Brasso, Klaus; Kroman, Niels; Højgaard, Liselotte; Kjaer, Andreas

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of (64)Cu-DOTA-AE105 for uPAR PET imaging in cancer patients.

  11. First-in-human uPAR PET: Imaging of Cancer Aggressiveness.

    PubMed

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene; Christensen, Camilla; Madsen, Jacob; Nielsen, Carsten H; Thurison, Tine; Klausen, Thomas Levin; Holm, Søren; Loft, Annika; Berthelsen, Anne Kiil; Ploug, Michael; Pappot, Helle; Brasso, Klaus; Kroman, Niels; Højgaard, Liselotte; Kjaer, Andreas

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of (64)Cu-DOTA-AE105 for uPAR PET imaging in cancer patients. PMID:26516369

  12. Genetic variants of the Wnt signaling pathway as predictors of aggressive disease and reclassification in men with early stage prostate cancer on active surveillance.

    PubMed

    Shu, Xiang; Ye, Yuanqing; Gu, Jian; He, Yonggang; Davis, John W; Thompson, Timothy C; Logothetis, Christopher J; Kim, Jeri; Wu, Xifeng

    2016-10-01

    Little is known about the genetic predictors of prostate cancer aggressiveness and reclassification in men with localized prostate cancer undergoing active surveillance. The Wnt signaling pathway is important for prostate cancer development and progression. Identifying genetic variants associated with prostate cancer aggressiveness and reclassification may have a potential role in the management of localized patients. In this study, we used a three-phase design. In phases I and II prostate cancer patient cohort, 578 single nucleotide polymorphisms (SNPs) from 45 genes of the Wnt signaling pathway were analyzed in 1762 localized prostate cancer patients. Twelve SNPs from four regions were significantly associated with aggressive disease, among which, three linked SNPs in CSNK1A1 at 5q32 (represented by rs752822) may differentiate GS 4+3 from GS 3+4 patients (OR = 1.44, 95% CI = 1.12-1.87, P = 4.76×10(-3)). In phase III active surveillance (AS) cohort, genotyping of rs752822 (candidate from phases I and II) and previously identified rs2735839 were determined in 494 GS ≤7 patients. We found a significant association between rs2735839 and prostate cancer reclassification in the AS cohort (AG + AA versus GG, HR = 1.59, 95% CI = 1.11-2.28, P = 0.012) and a suggestive association of rs752822. Jointly, rs752822 and rs2735839 showed good potentials in risk-stratifying GS 7 patients and predicting disease reclassification (OR = 2.71, 95% CI = 1.62-4.51, P = 1×10(-4) in phase II; HR = 1.89, 95% CI = 1.13-3.18, P = 0.016 in phase III). In summary, rs752822 and rs2735839 may assist in risk-stratifying GS 7 patients and predict prostate cancer reclassification. The significant associations were independent from GS, T stage and PSA levels at baseline. PMID:27515962

  13. Genetic variants of the Wnt signaling pathway as predictors of aggressive disease and reclassification in men with early stage prostate cancer on active surveillance.

    PubMed

    Shu, Xiang; Ye, Yuanqing; Gu, Jian; He, Yonggang; Davis, John W; Thompson, Timothy C; Logothetis, Christopher J; Kim, Jeri; Wu, Xifeng

    2016-10-01

    Little is known about the genetic predictors of prostate cancer aggressiveness and reclassification in men with localized prostate cancer undergoing active surveillance. The Wnt signaling pathway is important for prostate cancer development and progression. Identifying genetic variants associated with prostate cancer aggressiveness and reclassification may have a potential role in the management of localized patients. In this study, we used a three-phase design. In phases I and II prostate cancer patient cohort, 578 single nucleotide polymorphisms (SNPs) from 45 genes of the Wnt signaling pathway were analyzed in 1762 localized prostate cancer patients. Twelve SNPs from four regions were significantly associated with aggressive disease, among which, three linked SNPs in CSNK1A1 at 5q32 (represented by rs752822) may differentiate GS 4+3 from GS 3+4 patients (OR = 1.44, 95% CI = 1.12-1.87, P = 4.76×10(-3)). In phase III active surveillance (AS) cohort, genotyping of rs752822 (candidate from phases I and II) and previously identified rs2735839 were determined in 494 GS ≤7 patients. We found a significant association between rs2735839 and prostate cancer reclassification in the AS cohort (AG + AA versus GG, HR = 1.59, 95% CI = 1.11-2.28, P = 0.012) and a suggestive association of rs752822. Jointly, rs752822 and rs2735839 showed good potentials in risk-stratifying GS 7 patients and predicting disease reclassification (OR = 2.71, 95% CI = 1.62-4.51, P = 1×10(-4) in phase II; HR = 1.89, 95% CI = 1.13-3.18, P = 0.016 in phase III). In summary, rs752822 and rs2735839 may assist in risk-stratifying GS 7 patients and predict prostate cancer reclassification. The significant associations were independent from GS, T stage and PSA levels at baseline.

  14. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    PubMed Central

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  15. PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer.

    PubMed

    Ramos, F S; Serino, L T R; Carvalho, C M S; Lima, R S; Urban, C A; Cavalli, I J; Ribeiro, E M S F

    2015-01-01

    Changes in the expression of the protein disulfide isomerase genes PDIA3 and PDIA6 may increase endoplasmic reticulum stress, leading to cellular instability and neoplasia. We evaluated the expression of PDIA3 and PDIA6 in invasive ductal carcinomas. Using reverse transcription-quantitative polymerase chain reaction, we compared the mRNA expression level in 45 samples of invasive ductal carcinoma with that in normal breast samples. Increased expression of the PDIA3 gene in carcinomas (P = 0.0009) was observed. In addition, PDIA3 expression was increased in tumors with lymph node metastasis (P = 0.009) and with grade III (P < 0.02). The PDIA6 gene showed higher expression levels in the presence of lymph node metastasis (U = 99.00, P = 0.0476) and lower expression for negative hormone receptors status (P = 0.0351). Our results suggest that alterations in PDIA3/6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness. PMID:26125904

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

    PubMed Central

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

    2015-01-01

    Oncolytic engineered herpes simplex viruses (HSVs) possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy. PMID:26436134

  17. Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment

    PubMed Central

    Taira, Al V.; Butler, Wayne M.; Galbreath, Robert W.; Fiano, Ryan; Wallner, Kent E.; Adamovich, Edward

    2013-01-01

    Purpose To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. Material and methods Two thousand two hundred and thirty four patients were treated with prostate brachytherapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D90 was 119% and V100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non-prostate death as a competing risk. Results For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. Conclusions With the dose escalation achieved by high quality brachytherapy dosimetry, even high-risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the presence of micrometastatic disease prior to treatment is rare, even in high risk patients. PMID:24474970

  18. Identification of targeted therapy for an aggressive subgroup of muscle-invasive bladder cancers.

    PubMed

    Lebret, Thierry; Neuzillet, Yann; Houede, Nadine; Rebouissou, Sandra; Bernard-Pierrot, Isabelle; De Reynies, Aurélien; Benhamou, Simone; Allory, Yves; Radvanyi, François

    2015-01-01

    Rebouissou et al. recently provided preclinical evidence that a subset of patients with muscle-invasive bladder cancer might benefit from anti-epidermal growth factor receptor (EGFR) therapy and reported diagnostic tools for identifying these patients in the clinical setting. This work also identified relevant experimental models that may be useful for future basic and clinical research on this subgroup of tumors. PMID:27308521

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed

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

    2015-05-10

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

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

    PubMed Central

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

    2015-01-01

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

  2. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Cancer Foundation joins the PBTF Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  3. Circulating tumor cells exhibit a biologically aggressive cancer phenotype accompanied by selective resistance to chemotherapy.

    PubMed

    Pavese, Janet M; Bergan, Raymond C

    2014-10-01

    With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions.

  4. Upregulation of RASGRP3 expression in prostate cancer correlates with aggressive capabilities and predicts biochemical recurrence after radical prostatectomy

    PubMed Central

    Zeng, X; Hu, Z; Wang, Z; Tao, J; Lu, T; Yang, C; Lee, B; Ye, Z

    2014-01-01

    Background: This study was undertaken to investigate the expression of guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) in the cell lines and tissues in BPH and prostate cancer (PCa), as well as its associations with cancer invasion and prognosis in prostate carcinomas. Methods: Expression analysis of RasGRP3 was accomplished using immunohistochemical staining of PCa and BPH tissues. Pearson's χ2 test was used to analyze the association between RasGRP3 expression and specific clinical parameters. Survival and PSA relapse curves were evaluated using the Kaplan–Meier curves and log-rank tests, and the differences were assessed using the Cox regression methods. In addition, human PCa cell lines PC-3, DU145, LNCaP, PC3M-1E8, PC3M-2B4 and BPH-1 were examined for expression of RasGRP3 using western blot and quantitative polymerase chain reaction (Q-PCR) analysis. After PC-3 cells were transfected by small interfering RNA targeting RasGRP3, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and migratory assays were employed to determine the vitality and aggressive capability of tumor cell in vitro. Results: Expression of RasGRP3 was significantly correlated (P=0.038 and P=0.021) with Gleason score (⩽6 versus ⩾7) and T stage (T1–T2 versus T3–T4), respectively. PCa with RasGRP3-positive expression may increase the risk of PSA recurrence and decrease cancer-specific survival (P=0.0291 and P=0.0044). The expression of RasGRP3 was also associated with PSA recurrence and cancer-specific survival in univariate (P<0.001 and P<0.001) and multivariate analyses (P<0.001 and P=0.003). RasGRP3 mRNA and proteins were found to be positively expressed in PCa cell lines. There was higher expression of RasGRP3 in PC-3, DU145 and PC3M-1E8 than in LNCaP, PC3M-2B4 and BPH-1. Knockdown of RasGRP3 inhibited the proliferation, migration and invasion capabilities of PC-3 cells. Conclusions: These data suggested that elevated RasGRP3 expression may play a key role in

  5. Finding the Wolf in Sheep's Clothing: The 4Kscore Is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate Cancer.

    PubMed

    Punnen, Sanoj; Pavan, Nicola; Parekh, Dipen J

    2015-01-01

    Better biomarkers that can discriminate between aggressive and indolent phenotypes of prostate cancer are urgently needed. In the first 20 years of the prostate-specific antigen (PSA) era, screening for prostate cancer has successfully reduced prostate cancer mortality, but has led to significant problems with overdiagnosis and overtreatment. As a result, many men are subjected to unnecessary prostate biopsies and overtreatment of indolent cancer in order to save one man from dying of prostate cancer. A novel blood test known as the 4Kscore® Test (OPKO Lab, Nashville, TN) incorporates a panel of four kallikrein protein biomarkers (total PSA, free PSA, intact PSA, and human kallikrein-related peptidase 2) and other clinical information in an algorithm that provides a percent risk for a high-grade (Gleason score ≥ 7) cancer on biopsy. In 10 peer-reviewed publications, the four kallikrein biomarkers and algorithm of the 4Kscore Test have been shown to improve the prediction not only of biopsy histopathology, but also surgical pathology and occurrence of aggressive, metastatic disease. Recently, a blinded prospective trial of the 4Kscore Test was conducted across the United States among 1012 men. The 4Kscore Test replicated previous European results showing accuracy in predicting biopsy outcome of Gleason score ≥ 7. In a recent case-control study nested within a population-based cohort from Västerbotten, Sweden, the four kallikrein biomarkers of the 4Kscore Test also predicted the risk for aggressive prostate cancer that metastasized within 20 years after the test was administered. These results indicate that men with an abnormal PSA or digital rectal examination result, and for whom an initial or repeat prostate biopsy is being considered, would benefit from a reflex 4Kscore Test to add important information to the clinical decision-making process. A high-risk 4Kscore Test result may be used to select men with a high probability of aggressive prostate cancer who

  6. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.

    PubMed

    O'Brien, Keith; Lowry, Michelle C; Corcoran, Claire; Martinez, Vanesa G; Daly, Melissa; Rani, Sweta; Gallagher, William M; Radomski, Marek W; MacLeod, Roderick A F; O'Driscoll, Lorraine

    2015-10-20

    Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer. PMID:26416415

  7. Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer

    PubMed Central

    Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

    2014-01-01

    Background: Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). Methods: To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments. Results: In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by 1H-magnetic spectroscopy analysis; (III) a 35–36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context. Conclusion: We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with

  8. Prognostic Significance of Tag SNP rs1045411 in HMGB1 of the Aggressive Gastric Cancer in a Chinese Population

    PubMed Central

    He, Li; Zhao, Huadong; Wang, Nan; Ji, Gang; He, Xianli

    2016-01-01

    Compelling evidences have suggested that high mobility group box-1 (HMGB1) gene plays a crucial role in cancer development and progression. This study aimed to evaluate the effects of single nucleotide polymorphisms (SNPs) in HMGB1 gene on the survival of gastric cancer (GC) patients. Three tag SNPs from HMGB1 gene were selected and genotyped using Sequenom iPEX genotyping system in a cohort of 1030 GC patients (704 in training set, 326 in validation set). Multivariate Cox proportional hazard model and Kaplan-Meier Curve were used for prognosis analysis. AG/AA genotypes of SNP rs1045411 in HMGB1 gene were significantly associated with better overall survival (OS) in a set of 704 GC patients when compared with GG genotypes (HR = 0.77, 95% CI: 0.60–0.97, P = 0.032). This prognostic effect was verified in an independent validation set and pooled analysis (HR = 0.80, 95% CI: 0.62–0.99, P = 0.046; HR = 0.78, 95% CI: 0.55–0.98, P = 0.043, respectively). In stratified analysis, the protective effect of rs1045411 AG/AA genotypes was more prominent in patients with adverse strata, compared with patients with favorable strata. Furthermore, strong joint predictive effects on OS of GC patients were noted between rs1045411 genotypes and Lauren classification, differentiation, stage or adjuvant chemotherapy. Additionally, functional assay indicated a significant effect of rs1045411 on HMGB1 expression. Our results suggest that rs1045411 in HMGB1 is significantly associated with clinical outcomes of Chinese GC patients after surgery, especially in those with aggressive status, which warrants further validation in other ethnic populations. PMID:27116470

  9. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.

    PubMed

    O'Brien, Keith; Lowry, Michelle C; Corcoran, Claire; Martinez, Vanesa G; Daly, Melissa; Rani, Sweta; Gallagher, William M; Radomski, Marek W; MacLeod, Roderick A F; O'Driscoll, Lorraine

    2015-10-20

    Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer.

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

    PubMed Central

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

    2015-01-01

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

  11. 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 ...

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

    PubMed

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

    2010-11-11

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

  13. Prevalence and characteristics of complementary medicine used by pediatric cancer patients in a mixed western and middle-eastern population.

    PubMed

    Weyl Ben Arush, Myriam; Geva, Hana; Ofir, Ruth; Mashiach, Tania; Uziel, Rachel; Dashkovsky, Zana

    2006-03-01

    Complementary alternative medicine (CAM) usage and physicians' attitude was evaluated by interviewing all 100 pediatric cancer patients' parents and adolescents seen in the last half of 2003 at Meyer Children's Hospital in Israel. Sixty-one percent of the patients used CAM, an average of 3 different treatments per patient. CAM use was higher: among parents having previous CAM experience (85% vs. 51%, P=0.001) and higher education (79% vs. 50%, P=0.024), and in nonreligious families (71% vs. 50%). Jews and Arabs had similar CAM use rates as with different types of therapies. Socioeconomic status does not affect the rate of CAM use (P=0.9) but does affect the type of treatments used: patients of the higher socioeconomic level mainly used chemi-biological remedies and homeopathy (24% and 28% of interviewees; P=0.002). Middle or lower socioeconomic patients mostly used traditional Arab treatments (32% and 54%, respectively; P=0.012). Only 36% discussed it with their physicians, and most discussions were initiated by parents (79%). Beneficial effect was reported by 69% of CAM users. Most interviewees were interested in getting CAM information and availability in the hospital. Most pediatric cancer patients, regardless of their ethnic origin, use CAM without informing their physicians. Physicians should be aware and know more about it, to be advisors for better integrated care.

  14. Ancestral links of Chesapeake Bay region African Americans to specific Bight of Bonny (West Africa) microethnic groups and increased frequency of aggressive breast cancer in both regions.

    PubMed

    Jackson, Fatimah L C

    2008-01-01

    The high frequency of aggressive, early onset, and highly fatal breast cancer among Chesapeake Bay region African Americans suggests that there may be a contributing ancestral component. This study identifies the region's founding African, European, and Native American Indian populations using ethnogenetic layering and identifies the microethnic substructure of each founding continental aggregate. The largest component (38%) of the enslaved Africans brought to the Chesapeake Bay originally came from the coastal and hinterlands of the Bight of Bonny, a region with very high rates of aggressive, early onset breast cancer. Ethnogenetic layering is applied a second time to reveal the microethnic groups of the Bight of Bonny hinterlands with historical links to the Chesapeake Bay region. These analyses identify the specific microethnic groups within this region of Africa that may be the sources of relevant polymorphisms contributing to the etiology of aggressive breast cancer in the Chesapeake Bay. This report suggests a historical link between specific African microethnic groups and a US health disparity.

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

    PubMed

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

    2013-12-01

    Pancreatic cancer ranks fourth among cancer-related causes of death in North America. Minimal progress has been made in the diagnosis and treatment of patients with late-stage tumors. Moreover, pancreatic cancer aggressiveness is closely related to high levels of pro-survival mediators, which can ultimately lead to rapid disease progression, resistance and metastasis. The main goal of this study was to define the mechanisms by which calix[6]arene, but not other calixarenes, efficiently decreases the aggressiveness of a drug resistant human pancreas carcinoma cell line (Panc-1). Calix[6]arene was more potent in reducing Panc-1 cell viability than gemcitabine and 5-fluorouracil. In relation to the underlying mechanisms of cytotoxic effects, it led to cell cycle arrest in the G0/G1 phase through downregulation of PIM1, CDK2, CDK4 and retinoblastoma proteins. Importantly, calix[6]arene abolished signal transduction of Mer and AXL tyrosine kinase receptors, both of which are usually overexpressed in pancreatic cancer. Accordingly, inhibition of PI3K and mTOR was also observed, and these proteins are positively modulated by Mer and AXL. Despite decreasing the phosphorylation of AKT at Thr308, calix[6]arene caused an increase in phosphorylation at Ser473. These findings in conjunction with increased BiP and IRE1-α provide a molecular basis explaining the capacity of calix[6]arene to trigger endoplasmic reticulum stress and autophagic cell death. Our findings highlight calix[6]arene as a potential candidate for overcoming pancreatic cancer aggressiveness. Importantly, we provide evidence that calix[6]arene affects a broad array of key targets that are usually dysfunctional in pancreatic cancer, a highly desirable characteristic for chemotherapeutics. PMID:23872419

  16. 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.

  17. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-20

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. Signaling aggression.

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. 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

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

    PubMed

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

    2015-01-01

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

  8. Pediatric Extranodal Lymphoma.

    PubMed

    Chung, Ellen M; Pavio, Michael

    2016-07-01

    Lymphoma is the third most common pediatric neoplasm. Non-Hodgkin lymphoma (NHL) accounts for nearly half of cases and commonly involves extranodal sites. Compared with adults, this histologic spectrum of pediatric NHL is very narrow and consists of aggressive tumors. Patients typically present with widespread disease. Generally, NHL occurring in children includes Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma. Staging and assessment of therapeutic response are usually based on FDG-PET/CT. Due to the increased susceptibility of young patients to the effects of ionizing radiation, alternative methods of imaging are being explored.

  9. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Chronic oxidative stress causes estrogen-independent aggressive phenotype, and epigenetic inactivation of estrogen receptor alpha in MCF-7 breast cancer cells.

    PubMed

    Mahalingaiah, Prathap Kumar S; Ponnusamy, Logeswari; Singh, Kamaleshwar P

    2015-08-01

    The role of chronic oxidative stress in the development and aggressive growth of estrogen receptor (ER)-positive breast cancer is well known; however, the mechanistic understanding is not clear. Estrogen-independent growth is one of the features of aggressive subtype of breast cancer. Therefore, the objective of this study was to evaluate the effect of oxidative stress on estrogen sensitivity and expression of nuclear estrogen receptors in ER-positive breast cancer cells. MCF-7 cells chronically exposed to hydrogen peroxide were used as a cell model in this study, and their growth in response to 17-β estradiol was evaluated by cell viability, cell cycle, and cell migration analysis. Results were further confirmed at molecular level by analysis of gene expressions at transcript and protein levels. Histone H3 modifications, expression of epigenetic regulatory genes, and the effect of DNA demethylation were also analyzed. Loss of growth in response to estrogen with a decrease in ERα expression was observed in MCF-7 cells adapted to chronic oxidative stress. Increases in mtTFA and NRF1 in these cells further suggested the role of mitochondria-dependent redox-sensitive growth signaling as an alternative pathway to estrogen-dependent growth. Changes in expression of epigenetic regulatory genes, levels of histone H3 modifications as well as significant restorations of both ERα expression and estrogen response by 5-Aza-2'-deoxycytidine further confirmed the epigenetic basis for estrogen-independent growth in these cells. In conclusion, results of this study suggest that chronic oxidative stress can convert estrogen-dependent nonaggressive breast cancer cells into estrogen-independent aggressive form potentially by epigenetic mechanism.

  13. Pediatric Injury

    MedlinePlus

    ... common causes, which are 1 , 2 , 3 : Motor vehicle accidents Suffocation (being unable to breathe) Drowning Poisoning ... gov/safechild [top] American Academy of Pediatrics. (2008). Management of pediatric trauma. Pediatrics, 121 , 849–854. [top] ...

  14. Pediatric MS

    MedlinePlus

    ... of the oral medications in the pediatric population. Network of Pediatric MS Centers The National MS Society ... MS Study Group (2004) and established a nationwide network of six Pediatric MS Centers of Excellence (2006) ...

  15. 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

  16. New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort

    PubMed Central

    Zhang, William; Siminovitch, Katherine; Shlien, Adam; Kattan, Michael W.; Klotz, Laurence H.; Trachtenberg, John; Lu, Yan; Zhang, Jinyi; Yu, Changhong; Toi, Ants; Loblaw, D. Andrew; Venkateswaran, Vasundara; Stanimirovic, Aleksandra; Sugar, Linda; Malkin, David; Narod, Steven A.

    2011-01-01

    Purpose: To identify and examine polymorphisms of genes associated with aggressive and clinical significant forms of prostate cancer among a screening cohort.     Experimental Design: We conducted a genome-wide association study among patients with aggressive forms of prostate cancer and biopsy-proven normal controls ascertained from a prostate cancer screening program. We then examined significant associations of specific polymorphisms among a prostate cancer screened cohort to examine their predictive ability in detecting prostate cancer. Results: We found significant associations between aggressive prostate cancer and five single nucleotide polymorphisms (SNPs) in the 10q26 (rs10788165, rs10749408, and rs10788165, p value for association 1.3 × 10−10 to 3.2 × 10−11) and 15q21 (rs4775302 and rs1994198, p values for association 3.1 × 10−8 to 8.2 × 10−9) regions. Results of a replication study done in 3439 patients undergoing a prostate biopsy, revealed certain combinations of these SNPs to be significantly associated not only with prostate cancer but with aggressive forms of prostate cancer using an established classification criterion for prostate cancer progression (odds ratios for intermediate to high-risk disease 1.8–3.0, p value 0.003–0.001). These SNP combinations were also important clinical predictors for prostate cancer detection based on nomogram analysis that assesses prostate cancer risk. Conclusions: Five SNPs were found to be associated with aggressive forms of prostate cancer. We demonstrated potential clinical applications of these associations. PMID:22130093

  17. Overshadowing as prevention of anticipatory nausea and vomiting in pediatric cancer patients: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Emesis and nausea are side effects induced by chemotherapy. These effects lead to enormous stress and strain on cancer patients. Further consequences may include restrictions in quality of life, cachexia or therapy avoidance. Evidence suggests that cancer patients develop the side effects of nausea and vomiting in anticipation of chemotherapy. Contextual cues such as smell, sounds or even the sight of the clinic may evoke anticipatory nausea and vomiting prior to infusion. Anticipatory nausea and vomiting are problems that cannot be solved by administration of antiemetica alone. The purpose of the proposed randomized placebo-controlled trial is to use an overshadowing technique to prevent anticipatory nausea and vomiting and to decrease the intensity and duration of post-treatment nausea and vomiting. Furthermore, the effect on anxiety, adherence and quality of life will be evaluated. Methods/Design Fifty-two pediatric cancer patients will be evenly assigned to two groups: an experimental group and a control group. The participants, hospital staff and data analysts will be kept blinded towards group allocation. The experimental group will receive during three chemotherapy cycles a salient piece of candy prior to every infusion, whereas the control group will receive flavorless placebo tablets. Discussion If an effectiveness of the overshadowing technique is proven, implementation of this treatment into the hospitals’ daily routine will follow. The use of this efficient and economic procedure should aid a reduced need for antiemetics. Trial registration Current Controlled Trials ISRCTN30242271/ PMID:23782493

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

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo.

    PubMed

    Xu, Jiao; Yong, Min; Li, Jia; Dong, Xiaojing; Yu, Tinghe; Fu, Xiao; Hu, Lina

    2015-05-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the ATP-binding cassette (ABC) transporter family, members of which are involved in various types of cancer. The relationship between CFTR and ovarian cancer remains to be elucidated. The aim of the present study was to investigate the expression of CFTR in human ovarian cancer tissues and its clinical significance in the progression of ovarian cancer. The role of CFTR in the malignant invasion, migration and proliferation of ovarian cancer in vitro and in vivo was also investigated. Immunohistochemical staining analysis was performed to detect the expression of CFTR in 83 cases of human epithelial ovarian cancer specimens. Moreover, SKOV3 and A2780 stable cell lines containing shRNA gene specific for CFTR were established. Cell proliferation and motility were observed and compared with CFTR-RNAi cells. Tumorigenicity of CFTR-RNAi cells was investigated by tumor xenograft experiments conducted subcutaneously in nude mice. The expresssion of CFTR in ovarian cancer was significantly higher than that in benign ovarian tumor and normal ovaries (P<0.05). In ovarian cancer, CFTR expression was significantly associated with advanced FIGO stage, poor histopathological grade and serum Ca-125 (P<0.05). Furthermore, we observed that CFTR staining was stronger in the serous type as compared to the other types (P<0.05). Compared with the negative control, decreased cell invasion, migration, proliferation, adhesion and colony formation were observed in CFTR-RNAi cells in vitro. In vivo, tumorigenic abilities of CFTR-RNAi cells were significantly repressed compared with that of the control groups. CFTR overexpression may play an important role in the development and progression of ovarian cancer. Additionally, the downregulation of CFTR suppresses aggressive malignant biological behaviors of ovarian cancer cells in vitro and in vivo. PMID:25738998

  1. Hypofractionated Boost With High-Dose-Rate Brachytherapy and Open Magnetic Resonance Imaging-Guided Implants for Locally Aggressive Prostate Cancer: A Sequential Dose-Escalation Pilot Study

    SciTech Connect

    Ares, Carmen; Popowski, Youri; Pampallona, Sandro; Nouet, Philippe; Dipasquale, Giovanna; Bieri, Sabine; Ozsoy, Orhan; Rouzaud, Michel; Khan, Haleem; Miralbell, Raymond

    2009-11-01

    Purpose: To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. Methods and Materials: After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided {sup 192}Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. Results: All 77 patients completed treatment as planned. Only 2 patients presented with Grade >=3 acute urinary toxicity. The 3-year probability of Grade >=2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +- 3.4% and 94.4% +- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +- 4.1% and 100%, respectively. Conclusions: Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

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

    ERIC Educational Resources Information Center

    Ullrich, Nicole J.

    2008-01-01

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

  3. 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

  4. Understanding Aggression.

    ERIC Educational Resources Information Center

    Scott, J. P.

    Research in many fields of the social and biological sciences indicates that there are ecological, cultural, social, psychological, physiological, and genetic causes of aggression. The agonistic behavior system, which adapts to situations of social conflict, includes several patterns of conduct ranging from overt fighting to complete passivity. In…

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

    PubMed

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

    2015-05-10

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

  6. The Challenge of Access to Care for Adolescents with Cancer in Italy: National and Local Pediatric Oncology Programs. International Perspectives on AYAO, Part 2.

    PubMed

    Ferrari, Andrea

    2013-09-01

    This paper, summarizing the March 2012 presentation at the second international workshop of the Canadian Task Force on Adolescents and Young Adults with Cancer, describes the situation in Italy concerning the inadequate access to optimal cancer services for adolescents, and the need to improve the quality of care for these patients while investing in more research on the diseases that afflict them. National actions to bridge the gap in care and implement specific programs tailored to these patients arose from the pediatric oncology community. These actions include creation of the national Committee on Adolescents of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), founded with the mission of ensuring that Italian adolescents with cancer have prompt, adequate, and equitable access to the best care to optimize their treatment outcome and quality of life. Also developed was the Youth Project of the pediatric oncology unit at the Istituto Nazionale Tumori in Milan, which is currently dedicated to adolescents aged 15-19 years old and may eventually serve young adults up to the age of 25 that are affected by pediatric-type tumors.

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

    PubMed

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

    2016-06-01

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

  8. IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production

    PubMed Central

    Serret, Julien; Bièche, Ivan; Brigitte, Madly; Caicedo, Andres; Sanchez, Elodie; Vacher, Sophie; Vignais, Marie-Luce; Bourin, Philippe; Geneviève, David; Molina, Franck; Jorgensen, Christian; Lazennec, Gwendal

    2015-01-01

    The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs. PMID:26362269

  9. IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production.

    PubMed

    Escobar, Pauline; Bouclier, Céline; Serret, Julien; Bièche, Ivan; Brigitte, Madly; Caicedo, Andres; Sanchez, Elodie; Vacher, Sophie; Vignais, Marie-Luce; Bourin, Philippe; Geneviève, David; Molina, Franck; Jorgensen, Christian; Lazennec, Gwendal

    2015-10-01

    The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs.

  10. Oral complications of cancer therapies. Oral complications in the pediatric population

    SciTech Connect

    Leggott, P.J. )

    1990-01-01

    A number of acute oral complications may be associated with cancer therapy in children, but the extent and duration of these complications, and the most effective management techniques. have not been well described. The few studies differ in design, making comparisons difficult. Well-controlled, prospective clinical studies are needed to define the most effective strategies for the management of acute oral complications in children. However, it is clear that dental intervention prior to cancer therapy is an important factor in the optimal preparation of the patient. During cancer therapy, intensive supervised oral preventive protocols appear to be of benefit to the child's oral health, overall comfort, and well-being. Furthermore, the prevention of oral infection may significantly reduce the morbidity associated with cancer therapy. Long-term preventive oral care may help prevent dental disease and infection in medically compromised children and contribute to improving the quality of life. 41 references.

  11. Differential protein expression and oncogenic gene network link tyrosine kinase ephrin B4 receptor to aggressive gastric and gastroesophageal junction cancers.

    PubMed

    Liersch-Löhn, Britta; Slavova, Nadia; Buhr, Heinz J; Bennani-Baiti, Idriss M

    2016-03-01

    Transmembrane tyrosine-kinase Ephrin receptors promote tumor progression and/or metastasis of several malignancies including leukemia, follicular lymphoma, glioma, malignant pleural mesothelioma, papillary thyroid carcinoma, sarcomas and ovarian, breast, bladder and non-small cell lung cancers. They also drive intestinal stem cell proliferation and positioning, control intestinal tissue boundaries and are involved in liver, pancreatic and colorectal cancers, indicating involvement in additional digestive system malignancies. We investigated the role of Ephrin-B4 receptor (EPHB4), and its ligand EFNB2, in gastric and gastroesophageal junction cancers in patient cohorts through computational, mathematical, molecular and immunohistochemical analyses. We show that EPHB4 is upregulated in preneoplastic gastroesophageal lesions and its expression further increased in gastroesophageal cancers in several independent cohorts. The closely related EPHB6 receptor, which also binds EFNB2, was downregulated in all tested cohorts, consistent with its tumor-suppressive properties in other cancers. EFNB2 expression is induced in esophageal cells by acidity, suggesting that gastroesophageal reflux disease (GERD) may constitute an early triggering event in activating EFNB2-EPHB4 signaling. Association of EPHB4 to both Barrett's esophagus and to advanced tumor stages, and its overexpression at the tumor invasion front and vascular endothelial cells intimate the notion that EPHB4 may be associated with multiple steps of gastroesophageal tumorigenesis. Analysis of oncogenomic signatures uncovered the first EPHB4-associated gene network (false discovery rate: 7 × 10(-90) ) composed of a five-transcription factor interconnected gene network that drives proliferation, angiogenesis and invasiveness. The EPHB4 oncogenomic network provides a molecular basis for its role in tumor progression and points to EPHB4 as a potential tumor aggressiveness biomarker and drug target in gastroesophageal

  12. High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer

    PubMed Central

    LEBOK, PATRICK; ÖZTÜRK, MELIKE; HEILENKÖTTER, UWE; JAENICKE, FRITZ; MÜLLER, VOLKMAR; PALUCHOWSKI, PETER; GEIST, STEFAN; WILKE, CHRISTIAN; BURANDT, EICKE; LEBEAU, ANNETTE; WILCZAK, WALDEMAR; KRECH, TILL; SIMON, RONALD; SAUTER, GUIDO; QUAAS, ALEXANDER

    2016-01-01

    Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer. PMID

  13. Pediatric Stroke

    PubMed Central

    Jeong, Goun; Lim, Byung Chan

    2015-01-01

    Pediatric stroke is relatively rare but may lead to significant morbidity and mortality. Along with the advance of brain imaging technology and clinical awareness, diagnosis of pediatric stroke is increasing wordwide. Pediatric stroke differs from adults in variable risk factor/etiologies, diverse and nonspecific clinical presentation depending on ages. This review will be discussed pediatric stroke focusing on their clinical presentations, diagnosis and etiologies/risk factors. PMID:26180605

  14. Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer

    NASA Astrophysics Data System (ADS)

    Burfeindt, Matthew J.; Zastrow, Earl; Hagness, Susan C.; Van Veen, Barry D.; Medow, Joshua E.

    2011-05-01

    We present a numerical study of an array-based microwave beamforming approach for non-invasive hyperthermia treatment of pediatric brain tumors. The transmit beamformer is designed to achieve localized heating—that is, to achieve constructive interference and selective absorption of the transmitted electromagnetic waves at the desired focus location in the brain while achieving destructive interference elsewhere. The design process takes into account patient-specific and target-specific propagation characteristics at 1 GHz. We evaluate the effectiveness of the beamforming approach using finite-difference time-domain simulations of two MRI-derived child head models from the Virtual Family (IT'IS Foundation). Microwave power deposition and the resulting steady-state thermal distribution are calculated for each of several randomly chosen focus locations. We also explore the robustness of the design to mismatch between the assumed and actual dielectric properties of the patient. Lastly, we demonstrate the ability of the beamformer to suppress hot spots caused by pockets of cerebrospinal fluid (CSF) in the brain. Our results show that microwave beamforming has the potential to create localized heating zones in the head models for focus locations that are not surrounded by large amounts of CSF. These promising results suggest that the technique warrants further investigation and development.

  15. Vaccine therapies for pediatric malignancies.

    PubMed

    Rousseau, Raphaël F; Brenner, Malcolm K

    2005-01-01

    Cancer vaccines are examples of active immunotherapy. In pediatric malignancy such active strategies may be particularly problematic because of immune suppression produced by the tumor or its intensive treatment with combined chemotherapy. Nonetheless, the expression of tumor-specific and tumor-associated antigens on a range of pediatric tumors has encouraged investigation of the approach in patients with either bulky or minimal residual disease. Here we describe promising results in neuroblastoma and acute leukemia, suing genetically modified whole cell vaccines, peptides, and dendritic cells. The difficulties of conducting and evaluating such studies in a pediatric population are also described, and a strategy for cancer vaccine development is outlined.

  16. Psychoeducational Interventions with Pediatric Cancer Patients: Part I. Patient Information and Knowledge

    ERIC Educational Resources Information Center

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

    2003-01-01

    We present a systematic review of published research on psychoeducational interventions for children with cancer. The current lack of an organizational model for this literature makes it difficult to form a coherent picture of the scattered literature and draw nomothetic conclusions. A model is described that is based on functional concepts from…

  17. [Aggressive fibromatoses].

    PubMed

    Döhler, J R; Hamelmann, H; Lasson, U

    1984-03-01

    Benign by nature, aggressive fibromatoses (desmoid fibromas) may represent as difficult therapeutic problems as malignant tumours. When subtotally resected they tend to recur. But spontaneous regression is possible. Expense and limits of their surgical treatment are discussed with reference to seven patients. In five cases primary affliction of bone was evident. There are three reports given in detail: In the first, malignant transformation may be due to radiation therapy and hemipelvectomy could not prevent recurrence. In the second, spontaneous regression of untreated pelvic affection may have occurred. In the third, several resections and amputation of the leg failed to cure congenital infantile fibromatosis.

  18. Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol.

    PubMed

    Hardwick, M; Fertikh, D; Culty, M; Li, H; Vidic, B; Papadopoulos, V

    1999-02-15

    Aberrant cell proliferation and increased invasive and metastatic behavior are hallmarks of the advancement of breast cancer. Numerous studies implicate a role for cholesterol in the mechanisms underlying cell proliferation and cancer progression. The peripheral-type benzodiazepine receptor (PBR) is an Mr 18,000 protein primarily localized to the mitochondria. PBR mediates cholesterol transport across the mitochondrial membranes in steroidogenic cells. A role for PBR in the regulation of tumor cell proliferation has also been shown. In this study, we examined the expression, characteristics, localization, and function of PBR in a battery of human breast cancer cell lines differing in their invasive and chemotactic potential as well as in several human tissue biopsies. Expression of PBR ligand binding and mRNA was dramatically increased in the highly aggressive cell lines, such as MDA-231, relative to nonaggressive cell lines, such as MCF-7. PBR was also found to be expressed at high levels in aggressive metastatic human breast tumor biopsies compared with normal breast tissues. Subcellular localization with both antibodies and a fluorescent PBR drug ligand revealed that PBR from the MDA-231 cell line as well as from aggressive metastatic human breast tumor biopsies localized primarily in and around the nucleus. This localization is in direct contrast to the largely cytoplasmic localization seen in MCF-7 cells, normal breast tissue, and to the typical mitochondrial localization seen in mouse tumor Leydig cells. Pharmacological characterization of the receptor and partial nucleotide sequencing of PBR cDNA revealed that the MDA-231 PBR is similar, although not identical, to previously described PBR. Addition of high affinity PBR drug ligands to MDA-231 cells increased the incorporation of bromodeoxyuridine into the cells in a dose-dependent manner, suggesting a role for PBR in the regulation of MDA-231 cell proliferation. Cholesterol uptake into isolated MDA-231

  19. [Endocrine sequelae after treatment of pediatric cancer: From childhood to adulthood].

    PubMed

    Thomas-Teinturier, Cécile; Salenave, Sylvie

    2015-01-01

    Endocrine sequelae are among the most frequently reported complications in childhood cancer survivors, affecting 40 to 60% of these patients during adult life. Most of these complications are the result of cranial radiation therapy for brain or facial tumor, lymphoma or leukemia. The present review describes the main endocrine disturbances observed in this population, including disorders of hypothalamic-pituitary axis, especially the frequently observed growth hormone deficiency and disorders of puberty, thyroid and parathyroid dysfunction, obesity and metabolic syndrome, alterations in glucose metabolism and decreased bone mineral density. Gonadal dysfunction is not described, since it is detailed in another chapter. During childhood, prompt diagnosis and management of endocrine complications allow improvement of final height outcome and body composition (lean body mass and bone mass), reducing morbidity and impaired quality of life later in adulthood. Risk of developing a second neoplasm after growth hormone therapy in cancer survivors is also addressed. Life-long follow-up and management of endocrine deficiencies are essential to reduce late morbidity especially cardiovascular risk, and to diagnose late-onset deficiencies as well as radiation-induced thyroid nodules and cancer.

  20. Long-term efficacy and downstream mechanism of anti-annexinA2 monoclonal antibody (anti-ANX A2 mAb) in a pre-clinical model of aggressive human breast cancer.

    PubMed

    Sharma, Mahesh C; Tuszynski, George P; Blackman, Marc R; Sharma, Meena

    2016-04-01

    There is considerable direct evidence that calcium binding protein ANX A2 is a potential target for treating aggressive breast cancer. The most compelling data are based on the finding of ANX A2 overexpression in aggressive triple negative human breast cancer (TNBC) cell lines and in human breast cancer tissues. Previously, we and others reported a unique role of ANX A2 in cancer invasion, including breast cancer. Moreover, we demonstrated that anti-ANX A2 mAb-mediated immunoneutralization of ANX A2 inhibited invasive human breast cancer growth in a xenograft model. We further evaluated the long-term effects of multiple treatments with anti-ANX A2 mAb and its mechanism of inhibition on human breast tumor growth. We now demonstrate that three treatments with anti-ANX A2 mAb led to significant inhibition of breast tumor growth in immunodeficient mice, and that the anti-tumor response was demonstrable from day 94. After treatment, we followed tumor growth for 172 days and demonstrated 67% inhibition of tumor growth without detectable adverse effects. Biochemical analysis demonstrated that anti-ANX A2 mAb treatment caused significant inhibition of conversion of tissue plasminogen activator (tPA) in the tumor microenvironment. This led to disruption of plasmin generation that consequently inhibited activation of MMP-9 and MMP-2. These results suggest that ANX A2 plays an important role in aggressive breast tumor growth by regulating proteolytic pathways in the tumor microenvironment. ANX A2 may represent a new target for the development of therapeutics for treatment of aggressive breast cancer.

  1. Engineering functionalized multi-phased silicon/silicon oxide nano-biomaterials to passivate the aggressive proliferation of cancer.

    PubMed

    Premnath, P; Tan, B; Venkatakrishnan, K

    2015-07-20

    Currently, the use of nano silicon in cancer therapy is limited as drug delivery vehicles and markers in imaging, not as manipulative/controlling agents. This is due to limited properties that native states of nano silicon and silicon oxides offers. We introduce nano-functionalized multi-phased silicon/silicon oxide biomaterials synthesized via ultrashort pulsed laser synthesis, with tunable properties that possess inherent cancer controlling properties that can passivate the progression of cancer. This nanostructured biomaterial is composed of individual functionalized nanoparticles made of a homogenous hybrid of multiple phases of silicon and silicon oxide in increasing concentration outwards from the core. The chemical properties of the proposed nanostructure such as number of phases, composition of phases and crystal orientation of each functionalized nanoparticle in the three dimensional nanostructure is defined based on precisely tuned ultrashort pulsed laser-material interaction mechanisms. The amorphous rich phased biomaterial shows a 30 fold (95%) reduction in number of cancer cells compared to bulk silicon in 48 hours. Further, the size of the cancer cells reduces by 76% from 24 to 48 hours. This method exposes untapped properties of combination of multiple phases of silicon oxides and its applications in cancer therapy.

  2. Engineering functionalized multi-phased silicon/silicon oxide nano-biomaterials to passivate the aggressive proliferation of cancer

    PubMed Central

    Premnath, P.; Tan, B.; Venkatakrishnan, K.

    2015-01-01

    Currently, the use of nano silicon in cancer therapy is limited as drug delivery vehicles and markers in imaging, not as manipulative/controlling agents. This is due to limited properties that native states of nano silicon and silicon oxides offers. We introduce nano-functionalized multi-phased silicon/silicon oxide biomaterials synthesized via ultrashort pulsed laser synthesis, with tunable properties that possess inherent cancer controlling properties that can passivate the progression of cancer. This nanostructured biomaterial is composed of individual functionalized nanoparticles made of a homogenous hybrid of multiple phases of silicon and silicon oxide in increasing concentration outwards from the core. The chemical properties of the proposed nanostructure such as number of phases, composition of phases and crystal orientation of each functionalized nanoparticle in the three dimensional nanostructure is defined based on precisely tuned ultrashort pulsed laser-material interaction mechanisms. The amorphous rich phased biomaterial shows a 30 fold (95%) reduction in number of cancer cells compared to bulk silicon in 48 hours. Further, the size of the cancer cells reduces by 76% from 24 to 48 hours. This method exposes untapped properties of combination of multiple phases of silicon oxides and its applications in cancer therapy. PMID:26190009

  3. Engineering functionalized multi-phased silicon/silicon oxide nano-biomaterials to passivate the aggressive proliferation of cancer

    NASA Astrophysics Data System (ADS)

    Premnath, P.; Tan, B.; Venkatakrishnan, K.

    2015-07-01

    Currently, the use of nano silicon in cancer therapy is limited as drug delivery vehicles and markers in imaging, not as manipulative/controlling agents. This is due to limited properties that native states of nano silicon and silicon oxides offers. We introduce nano-functionalized multi-phased silicon/silicon oxide biomaterials synthesized via ultrashort pulsed laser synthesis, with tunable properties that possess inherent cancer controlling properties that can passivate the progression of cancer. This nanostructured biomaterial is composed of individual functionalized nanoparticles made of a homogenous hybrid of multiple phases of silicon and silicon oxide in increasing concentration outwards from the core. The chemical properties of the proposed nanostructure such as number of phases, composition of phases and crystal orientation of each functionalized nanoparticle in the three dimensional nanostructure is defined based on precisely tuned ultrashort pulsed laser-material interaction mechanisms. The amorphous rich phased biomaterial shows a 30 fold (95%) reduction in number of cancer cells compared to bulk silicon in 48 hours. Further, the size of the cancer cells reduces by 76% from 24 to 48 hours. This method exposes untapped properties of combination of multiple phases of silicon oxides and its applications in cancer therapy.

  4. Engineering functionalized multi-phased silicon/silicon oxide nano-biomaterials to passivate the aggressive proliferation of cancer.

    PubMed

    Premnath, P; Tan, B; Venkatakrishnan, K

    2015-01-01

    Currently, the use of nano silicon in cancer therapy is limited as drug delivery vehicles and markers in imaging, not as manipulative/controlling agents. This is due to limited properties that native states of nano silicon and silicon oxides offers. We introduce nano-functionalized multi-phased silicon/silicon oxide biomaterials synthesized via ultrashort pulsed laser synthesis, with tunable properties that possess inherent cancer controlling properties that can passivate the progression of cancer. This nanostructured biomaterial is composed of individual functionalized nanoparticles made of a homogenous hybrid of multiple phases of silicon and silicon oxide in increasing concentration outwards from the core. The chemical properties of the proposed nanostructure such as number of phases, composition of phases and crystal orientation of each functionalized nanoparticle in the three dimensional nanostructure is defined based on precisely tuned ultrashort pulsed laser-material interaction mechanisms. The amorphous rich phased biomaterial shows a 30 fold (95%) reduction in number of cancer cells compared to bulk silicon in 48 hours. Further, the size of the cancer cells reduces by 76% from 24 to 48 hours. This method exposes untapped properties of combination of multiple phases of silicon oxides and its applications in cancer therapy. PMID:26190009

  5. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.

    PubMed

    Gruber, Tanja A; Larson Gedman, Amanda; Zhang, Jinghui; Koss, Cary S; Marada, Suresh; Ta, Huy Q; Chen, Shann-Ching; Su, Xiaoping; Ogden, Stacey K; Dang, Jinjun; Wu, Gang; Gupta, Vedant; Andersson, Anna K; Pounds, Stanley; Shi, Lei; Easton, John; Barbato, Michael I; Mulder, Heather L; Manne, Jayanthi; Wang, Jianmin; Rusch, Michael; Ranade, Swati; Ganti, Ramapriya; Parker, Matthew; Ma, Jing; Radtke, Ina; Ding, Li; Cazzaniga, Giovanni; Biondi, Andrea; Kornblau, Steven M; Ravandi, Farhad; Kantarjian, Hagop; Nimer, Stephen D; Döhner, Konstanze; Döhner, Hartmut; Ley, Timothy J; Ballerini, Paola; Shurtleff, Sheila; Tomizawa, Daisuke; Adachi, Souichi; Hayashi, Yasuhide; Tawa, Akio; Shih, Lee-Yung; Liang, Der-Cherng; Rubnitz, Jeffrey E; Pui, Ching-Hon; Mardis, Elaine R; Wilson, Richard K; Downing, James R

    2012-11-13

    To define the mutation spectrum in non-Down syndrome acute megakaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL samples. Our analysis identified a cryptic chromosome 16 inversion (inv(16)(p13.3q24.3)) in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.

  6. Barriers to cure for children with cancer in India and strategies to improve outcomes: a report by the Indian Pediatric Hematology Oncology Group.

    PubMed

    Yadav, Satya Prakash; Rastogi, Neha; Kharya, Gaurav; Misra, Ruchira; Ramzan, Mohammed; Katewa, Satyendra; Dua, Vikas; Bhat, Sunil; Kellie, Stewart J; Howard, Scott C

    2014-04-01

    The survival of children with cancer in India is inferior to that of children in high-income countries. The Indian Pediatric Hematology Oncology Group (IPHOG) held a series of online meetings via www.Cure4kids.org to identify barriers to cure and develop strategies to improve outcomes. Five major hurdles were identified: delayed diagnosis, abandonment, sepsis, lack of co-operative groups, and relapse. Development of regional networks like IPHOG has allowed rapid identification of local causes of treatment failure for children with cancer in India and identification of strategies likely to improve care and outcomes in the participating centers. Next steps will include interventions to raise community awareness of childhood cancer, promote early diagnosis and referral, and reduce abandonment and toxic death at each center. Starting of fellowship programs in pediatric hemato-oncology, short training programs for pediatricians, publishing outcome data, formation of parent and patient support groups, choosing the right and effective treatment protocol, and setting up of bone marrow transplant services are some of the effective steps taken in the last decade, which needs to be supported further. PMID:24673115

  7. Barriers to cure for children with cancer in India and strategies to improve outcomes: a report by the Indian Pediatric Hematology Oncology Group.

    PubMed

    Yadav, Satya Prakash; Rastogi, Neha; Kharya, Gaurav; Misra, Ruchira; Ramzan, Mohammed; Katewa, Satyendra; Dua, Vikas; Bhat, Sunil; Kellie, Stewart J; Howard, Scott C

    2014-04-01

    The survival of children with cancer in India is inferior to that of children in high-income countries. The Indian Pediatric Hematology Oncology Group (IPHOG) held a series of online meetings via www.Cure4kids.org to identify barriers to cure and develop strategies to improve outcomes. Five major hurdles were identified: delayed diagnosis, abandonment, sepsis, lack of co-operative groups, and relapse. Development of regional networks like IPHOG has allowed rapid identification of local causes of treatment failure for children with cancer in India and identification of strategies likely to improve care and outcomes in the participating centers. Next steps will include interventions to raise community awareness of childhood cancer, promote early diagnosis and referral, and reduce abandonment and toxic death at each center. Starting of fellowship programs in pediatric hemato-oncology, short training programs for pediatricians, publishing outcome data, formation of parent and patient support groups, choosing the right and effective treatment protocol, and setting up of bone marrow transplant services are some of the effective steps taken in the last decade, which needs to be supported further.

  8. Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients’ Outcome in Basal-Like Breast Cancer

    PubMed Central

    Gasthaus, Janina; Tiedemann, Janina; Mijnes, Jolein; Heide, Timon; Braunschweig, Till; Knüchel, Ruth; Dahl, Edgar

    2016-01-01

    NDRG2, a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro, we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P<0.001) expression loss of NDRG2 in breast tumors. Of interest, basal-like tumors more frequently retained abundant NDRG2 expression concordant with a lower CpG-hypermethylation. Unexpectedly, basal-like breast cancer revealed an association of NDRG2 expression with unfavorable patients’ outcome. In line with this observation, in vitro experiments demonstrated reduced proliferation and migration rates (~20%) in HCC1806 cells following NDRG2 silencing. In contrast, NDRG2 over-expressing luminal-type MCF7 cells demonstrated a 26% decreased proliferation rate. Until now, this is the first study investigating the putative role of NDRG2 in depth in basal-type breast cancer. Our data indicate that the described putative tumor suppressive function of NDRG2 may be confined to luminal- and basal B-type breast cancers. PMID:27400234

  9. 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.

  10. [Survivors of pediatric cancer. Developmental paths and outcomes between trauma and resilience].

    PubMed

    Noeker, M

    2012-04-01

    In Europe and North America, about 80% of all patients with cancer in childhood and adolescence survive their leukemia, lymphomas or tumors. Therefore, neuropsychological impairments, psychopathological comorbidity and health-related quality of life become relevant parameters for treatment evaluation and conceptualization of future therapy protocols. During the last decade, a number of patient registries, multicenter studies and meta-analyses have analyzed the interaction of disease- and treatment-associated risk factors with pre-existing socio-demographic and psychosocial vulnerability factors. Brain tumors and treatment strategies including CNS surgery, cranial radiotherapy and intrathecal chemotherapy carry an increased risk for neurological and neuropsychological long-term outcomes, which in turn also threatens the patients' psychosocial and vocational participation. In the area of psychosocial adaptation, a wide range of developmental paths results, ranging from increased psychological comorbidity, to subclinical impairments in quality of life, to normal courses to resilient outcomes, even with a developmental benefit. A hypothetical model is presented to explain this enormous variance in outcomes. Protective cognitive-emotional schemata already established at the premorbid stage predispose patients to be able to cope successfully with cancer-related challenges and thus further enhance the patients' future adaptability. In contrast, dysfunctional schemata at the premorbid level increase risks of coping failure and thus intensify the long-term risk for psychopathological comorbidity in terms of post-traumatic stress disorder, anxiety disorder or depression.

  11. Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid.

    PubMed

    Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello

    2015-09-22

    In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression. PMID:26312765

  12. Oxidative Stress in Cancer-Prone Genetic Diseases in Pediatric Age: The Role of Mitochondrial Dysfunction

    PubMed Central

    Longini, Mariangela; Buonocore, Giuseppe

    2016-01-01

    Oxidative stress is a distinctive sign in several genetic disorders characterized by cancer predisposition, such as Ataxia-Telangiectasia, Fanconi Anemia, Down syndrome, progeroid syndromes, Beckwith-Wiedemann syndrome, and Costello syndrome. Recent literature unveiled new molecular mechanisms linking oxidative stress to the pathogenesis of these conditions, with particular regard to mitochondrial dysfunction. Since mitochondria are one of the major sites of ROS production as well as one of the major targets of their action, this dysfunction is thought to be the cause of the prooxidant status. Deeper insight of the pathogenesis of the syndromes raises the possibility to identify new possible therapeutic targets. In particular, the use of mitochondrial-targeted agents seems to be an appropriate clinical strategy in order to improve the quality of life and the life span of the patients. PMID:27239251

  13. PEDIATRIC PANCREATITIS

    PubMed Central

    Pohl, John F.; Uc, Aliye

    2015-01-01

    Purpose of Review The purpose of this review is to describe recent developments in pediatric pancreatitis and to discuss etiologies and current management. Recent Findings Although recent studies have estimated the annual incidence of pediatric acute pancreatitis approaching that of adults, there are no established guidelines about its diagnosis and treatment in children. Genetic and structural/congenital abnormalities are emerging as the primary risk factors for pediatric acute recurrent and chronic pancreatitis. Specifically, chronic pancreatitis is associated with a significant socioeconomic burden in children. Both medical and surgical therapies are proposed for pediatric chronic pancreatitis, but there is little evidence that they are beneficial. Summary Acute, acute recurrent and chronic pancreatitis create significant health issues in the pediatric population. Medical and surgical therapies exist to potentially treat these conditions, but the pediatric data is limited and the cohorts are small. A multidisciplinary and multicenter approach is necessary to better determine pancreatic disease processes and treatment options in children. PMID:26181572

  14. 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.

  15. 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

  16. Prostate Cancer Prevention

    MedlinePlus

    ... finasteride who did have prostate cancer had more aggressive tumors . The number of deaths from prostate cancer ... men that did not. The number of less aggressive prostate cancers was lower, but the number of ...

  17. Desmoid Tumors in the Pediatric Population

    PubMed Central

    Honeyman, Joshua N.; La Quaglia, Michael P.

    2012-01-01

    Desmoid tumors are benign soft tissue tumors associated with locally aggressive growth and high rates of morbidity, but they do not metastasize via lymphatic or hematogenous routes. While most of the data on desmoid tumors originates in the adult literature, many of the findings have been applied to the management of pediatric patients. This article discusses the epidemiology, etiology, clinical presentation, pathology, and treatment of this rare tumor in the pediatric population and includes a literature review of the most recent large series of pediatric patients with desmoid tumors. PMID:24213241

  18. Are the Psychological Needs of Adolescent Survivors of Pediatric Cancer Adequately Identified and Treated?

    PubMed Central

    Kahalley, Lisa S.; Wilson, Stephanie J.; Tyc, Vida L.; Conklin, Heather M.; Hudson, Melissa M.; Wu, Shengjie; Xiong, Xiaoping; Stancel, Heather H.; Hinds, Pamela S.

    2012-01-01

    Objectives To describe the psychological needs of adolescent survivors of acute lymphoblastic leukemia (ALL) or brain tumor (BT), we examined: (a) the occurrence of cognitive, behavioral, and emotional concerns identified during a comprehensive psychological evaluation, and (b) the frequency of referrals for psychological follow-up services to address identified concerns. Methods Psychological concerns were identified on measures according to predetermined criteria for 100 adolescent survivors. Referrals for psychological follow-up services were made for concerns previously unidentified in formal assessment or not adequately addressed by current services. Results Most survivors (82%) exhibited at least one concern across domains: behavioral (76%), cognitive (47%), and emotional (19%). Behavioral concerns emerged most often on scales associated with executive dysfunction, inattention, learning, and peer difficulties. CRT was associated with cognitive concerns, χ2(1,N=100)=5.63, p<0.05. Lower income was associated with more cognitive concerns for ALL survivors, t(47)=3.28, p<0.01, and more behavioral concerns for BT survivors, t(48)=2.93, p<0.01. Of survivors with concerns, 38% were referred for psychological follow-up services. Lower-income ALL survivors received more referrals for follow-up, χ2(1,N=41)=8.05, p<0.01. Referred survivors had more concerns across domains than non-referred survivors, ALL: t(39)=2.96, p<0.01, BT: t(39)=3.52, p<0.01. Trends suggest ALL survivors may be at risk for experiencing unaddressed cognitive needs. Conclusions Many adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long-term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors’ needs, particularly for lower-income survivors and those treated with CRT. PMID:22278930

  19. Diabetes and Its Link with Cancer: Providing the Fuel and Spark to Launch an Aggressive Growth Regime

    PubMed Central

    2015-01-01

    Diabetes is a disease involving metabolic derangements in multiple organs. While the spectrum of diabetic complications has been known for years, recent evidence suggests that diabetes could also contribute to the initiation and propagation of certain cancers. The mechanism(s) underlying this relationship are not completely resolved but likely involve changes in hormone and nutrient levels, as well as activation of inflammatory and stress-related pathways. Interestingly, some of the drugs used clinically to treat diabetes also appear to have antitumour effects, further highlighting the interaction between these two conditions. In this contribution we review recent literature on this emerging relationship and explore the potential mechanisms that may promote cancer in diabetic patients. PMID:25961014

  20. Lowering Whole-Body Radiation Doses in Pediatric Intensity-Modulated Radiotherapy Through the Use of Unflattened Photon Beams;Flattening filter; Pediatric; Intensity-modulated radiotherapy; Second cancers; Radiation-induced malignancies

    SciTech Connect

    Cashmore, Jason; Ramtohul, Mark; Ford, Dan

    2011-07-15

    Purpose: Intensity modulated radiotherapy (IMRT) has been linked with an increased risk of secondary cancer induction due to the extra leakage radiation associated with delivery of these techniques. Removal of the flattening filter offers a simple way of reducing head leakage, and it may be possible to generate equivalent IMRT plans and to deliver these on a standard linear accelerator operating in unflattened mode. Methods and Materials: An Elekta Precise linear accelerator has been commissioned to operate in both conventional and unflattened modes (energy matched at 6 MV) and a direct comparison made between the treatment planning and delivery of pediatric intracranial treatments using both approaches. These plans have been evaluated and delivered to an anthropomorphic phantom. Results: Plans generated in unflattened mode are clinically identical to those for conventional IMRT but can be delivered with greatly reduced leakage radiation. Measurements in an anthropomorphic phantom at clinically relevant positions including the thyroid, lung, ovaries, and testes show an average reduction in peripheral doses of 23.7%, 29.9%, 64.9%, and 70.0%, respectively, for identical plan delivery compared to conventional IMRT. Conclusions: IMRT delivery in unflattened mode removes an unwanted and unnecessary source of scatter from the treatment head and lowers leakage doses by up to 70%, thereby reducing the risk of radiation-induced second cancers. Removal of the flattening filter is recommended for IMRT treatments.

  1. Future of clinical genomics in pediatric oncology.

    PubMed

    Janeway, Katherine A; Place, Andrew E; Kieran, Mark W; Harris, Marian H

    2013-05-20

    The somatic genomic alterations in pediatric cancers to some extent overlap with those seen in adult cancers, but the exact distribution throughout the genome and the types and frequency of alterations differ. The ultimate goal of genomic research in children, as with adults, is translation to the clinic to achieve more accurate diagnosis, more precise risk stratification, and more effective, less toxic therapy. The genomic features of pediatric malignancies and pediatric-specific issues in clinical investigation may make translating genomic discoveries to the clinic more difficult. However, through large-scale molecular profiling of pediatric tumors, continued coordinated efforts to evaluate novel therapies in the pediatric population, thoughtful phase II and III trial design, and continued drug development, genomically based therapies will become more common in the pediatric oncology clinic in the future.

  2. A novel breast cancer cell line initially established from pleural effusion: evolution towards a more aggressive phenotype.

    PubMed

    Schmidt, Melanie; Khan, Ashraf; Schmidt, André Michael; Heinze, Barbara; Hack, Eva; Waltenberger, Johannes; Kreienberg, Rolf

    2007-03-01

    Many human breast cancer cell lines have been in culture for several years, serving as model systems for studying aspects of breast cancer biology. Molecular alterations might occur in these cells during cultivation, and it remains unknown to which extent findings in these cell lines can be related to human disease. Hereby, we describe the establishment of a breast cancer cell line, MW1, from malignant pleural effusion. We compare expression patterns of several molecular markers in breast biopsy tissue, in cultivated tumor cells derived from pleural effusion reflecting the metastatic state, and in late passages of a lineage derived from the pleural culture. Our data show that expression of estrogen and progesterone receptors was lost in the cultivated tumor cells derived from pleural effusion as shown by immunohistochemical staining. Cytokeratin expression patterns remained luminal. During cultivation, the growth rate of MW1 cells increased dramatically and the morphology underwent alterations. As shown by Western blotting, E-cadherin expression remained unchanged whereas P-cadherin expression had increased after 4 years of cultivation of the cell line. Integrin beta4 expression was low in early passages of the pleural effusion whereas the cell line exhibited high expression levels of beta4. HGF receptor (c-Met), EGF receptor, VEGF and VEGF receptor-2 (KDR) expression was detectable by semiquantitative RT-PCR and remained unchanged during cultivation. In contrast, VEGF receptor-1 (flt-1) expression showed lower expression after 4 years of cultivation. The cell line migrated towards HGF, but not towards VEGF. This study provides exemplary insight into the molecular metamorphosis tumor cells undergo in vivo or in vitro on their way from the primary tumor via an equivalent of the metastatic state and during the development of a clonal cell line.

  3. Protease Activated Receptors 1 and 2 Correlate Differently with Breast Cancer Aggressiveness Depending on Tumor ER Status

    PubMed Central

    Lidfeldt, Jon; Bendahl, Pär-Ola; Forsare, Carina; Malmström, Per; Fernö, Mårten; Belting, Mattias

    2015-01-01

    Experimental models implicate protease activated receptors (PARs) as important sensors of the proteolytic tumor microenvironment during breast cancer development. However, the role of the major PARs, PAR-1 and PAR-2, in human breast tumors remains to be elucidated. Here, we have investigated how PAR-1 and PAR-2 protein expression correlate with established clinicopathological variables and patient outcome in a well-characterized cohort of 221 breast cancer patients. Univariable and multivariable hazard ratios (HR) were estimated by the Cox proportional hazards model, distant disease-free survival (DDFS) and overall survival by the Kaplan–Meier method, and survival in different strata was determined by the log-rank test. Associations between PARs and clinicopathological variables were analyzed using Pearson’s χ2-test. We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6). Interestingly, the effect of PAR-2 was confined to the ER-positive sub-group (HR = 5.5, P = 0.003 vs. HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045). On the contrary, PAR-1 correlated with worse prognosis specifically in the ER-negative group (HR = 2.6, P = 0.069 vs. HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect). This study provides novel insight into the respective roles of PAR-1 and PAR-2 in human breast cancer and suggests a hitherto unknown association between PARs and ER signaling that warrants further investigation. PMID:26244666

  4. Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism

    PubMed Central

    Benlloch, María; Obrador, Elena; Valles, Soraya L.; Rodriguez, María L.; Sirerol, J. Antoni; Alcácer, Javier; Pellicer, José A.; Salvador, Rosario; Cerdá, Concha; Sáez, Guillermo T.

    2016-01-01

    Abstract Aims: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol). Results: Intravenous administration of Pter decreased human melanoma growth in vivo. However, Pter, at levels measured within the tumors, did not affect melanoma growth in vitro. Pter inhibited pituitary production of the adrenocorticotropin hormone (ACTH), decreased plasma levels of corticosterone, and thereby downregulated the glucocorticoid receptor- and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent antioxidant defense system in growing melanomas. Exogenous corticosterone or genetically induced Nrf2 overexpression in melanoma cells prevented the inhibition of tumor growth and decreased antioxidant defenses in these malignant cells. These effects and mechanisms were also found in mice bearing different human pancreatic cancers. Glutathione depletion (selected as an antimelanoma strategy) facilitated the complete elimination by chemotherapy of melanoma cells isolated from mice treated with Pter. Innovation: Although bioavailability-related limitations may preclude direct anticancer effects in vivo, natural polyphenols may also interfere with the growth and defense of cancer cells by downregulating the pituitary gland-dependent ACTH synthesis. Conclusions: Pter downregulates glucocorticoid production, thus decreasing the glucocorticoid receptor and Nrf2-dependent signaling/transcription and the antioxidant protection of melanoma and pancreatic cancer cells

  5. Androgen Receptor Splice Variants Contribute to Prostate Cancer Aggressiveness through Induction of EMT and Expression of Stem Cell Marker Genes

    PubMed Central

    Kong, Dejuan; Sethi, Seema; Li, Yiwei; Chen, Wei; Sakr, Wael A.; Heath, Elisabeth; Sarkar, Fazlul H.

    2014-01-01

    Background The mechanism(s) by which androgen receptor (AR) splice variants contribute to castration-resistant prostate cancer (CRPC) is still lacking. Methods Expressions of Epithelial-to-Mesenchymal Transition (EMT) and stem cell markers were molecularly tested using prostate cancer (PCa) cells transfected with AR and AR3 (also known as AR-V7) plasmids or siRNA, and also cultured cells under androgen deprivation therapy (ADT) condition. Cell migration, clonogenicity, sphere forming capacity was assessed using PCa cells under all experimental conditions and 3, 3′-diindolylmethane (DIM; BR-DIM) treatment. Human PCa samples from BR-DIM untreated or treated patients were also used for assessing the expression of AR3 and stem cell markers. Results Overexpression of AR led to the induction of EMT phenotype, while overexpression of AR3 not only induced EMT but also led to the expression of stem cell signature genes. More importantly, ADT enhanced the expression of AR and AR3 concomitant with up-regulated expression of EMT and stem cell marker genes. Dihydrotestosterone (DHT) treatment decreased the expression of AR and AR3, and reversed the expression of these EMT and stem cell marker genes. BR-DIM administered to PCa patients prior to radical prostatectomy inhibited the expression of cancer stem cell markers consistent with inhibition of self-renewal of PCa cells after BR-DIM treatment. Conclusion AR variants could contribute to PCa progression through induction of EMT and acquisition of stem cell characteristics, which could be attenuated by BR-DIM, suggesting that BR-DIM could become a promising agent for the prevention of CRPC and/or for the treatment of PCa PMID:25307492

  6. IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis.

    PubMed

    Isla Larrain, M T; Rabassa, M E; Lacunza, E; Barbera, A; Cretón, A; Segal-Eiras, A; Croce, M V

    2014-07-01

    Indoleamine-2,3-dioxygenase (IDO) has been established as a normal mechanism of peripheral tolerance and immunosuppression. Besides, malignant tumors release microvesicles (MV) related with tumor dissemination. The aims of this study were to determine the expression of IDO in breast cancer and circulating microvesicles from breast cancer patients and to perform an in silico analysis to find genes co-expressed to IDO. One hundred and twenty-two tissue and serum breast samples (91 malignant, 21 benign, and 10 normal), and MCF7, MDA-MB-231, and T47D breast cancer cell lines were included. Standard immunohistochemistry (IHC), immunocytochemistry (ICC), Western blot (WB), and RT-PCR were employed. Microvesicle isolation from plasma samples was obtained by serial centrifugation and ultracentrifugation. By IHC, 60 % breast cancer, 43 % benign, and 20 % normal samples were positive. Significant differences were found among normal, benign, and malignant samples. Breast cancer stages I, II, and III expressed IDO in 42, 66, and 71 % of samples, respectively, while breast cancer cell lines also reacted; by WB, 9/25 microvesicles fractions showed bands at 42 kD. In silico analysis of IDO 1 gene expression in breast cancer showed its association with several genes related to immune response and apoptosis. Moreover, IDO and co-expressed genes were found predominately in basal and erbB2 subtypes. The cumulative data indicate a high expression of IDO in breast cancer which increased with higher stages. Furthermore, IDO was found in association with circulating breast cancer MV, while experimental and in silico gene expression revealed that IDO was mainly expressed in a triple-negative subgroup.

  7. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning.

    PubMed

    Geng, Changran; Moteabbed, Maryam; Xie, Yunhe; Schuemann, Jan; Yock, Torunn; Paganetti, Harald

    2016-01-01

    The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from  -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains

  8. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning.

    PubMed

    Geng, Changran; Moteabbed, Maryam; Xie, Yunhe; Schuemann, Jan; Yock, Torunn; Paganetti, Harald

    2016-01-01

    The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from  -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains

  9. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning

    NASA Astrophysics Data System (ADS)

    Geng, Changran; Moteabbed, Maryam; Xie, Yunhe; Schuemann, Jan; Yock, Torunn; Paganetti, Harald

    2016-01-01

    The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from  -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains

  10. Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: Cancer and Leukemia Group B study 10002

    PubMed Central

    Rizzieri, David A.; Johnson, Jeffrey L.; Byrd, John C.; Lozanski, Gerard; Blum, Kristie A.; Powell, Bayard L.; Shea, Thomas C.; Nattam, Sreenivasa; Hoke, Eva; Cheson, Bruce D.; Larson, Richard A.

    2014-01-01

    Summary To improve long-term outcomes for Burkitt leukaemia/lymphoma (BL) or aggressive lymphomas in adults, we assessed the benefit of adding rituximab and filgrastim support to a dose-dense modified chemotherapy regimen from the Cancer and Leukemia Group B (CALGB) 9251 trial. One hundred and five patients (aged 19–79 years) were enrolled; 27% were >60 years old; 47% had high or high-intermediate risk by International Prognostic Index (IPI) criteria. Common severe toxicities included stomatitis/upper gastrointestinal toxicity (69%), renal insufficiency (10%), neurological events (25%) and pulmonary events (18%). Seven died from treatment-related causes (1 central nervous system bleed, 4 infections, 2 respiratory failure); 5 were > 60 years old. Results in this adult population are encouraging as complete response (CR) was observed in 83% and 4-year event-free (EFS) and overall survivals (OS) were 74% and 78%, respectively. Results compare favourably to our prior chemotherapy alone study (CALGB 9251) but despite this, high-risk patients still had worse outcomes. In conclusion, short duration, intensive chemo-immunotherapy is feasible and should be considered in adults with BL as it results in high remission rates and durable remissions. PMID:24428673

  11. Down-regulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype

    PubMed Central

    Roy, Srirupa; Singh, Rana P.; Agarwal, Chapla; Siriwardana, Sunitha; Sclafani, Robert; Agarwal, Rajesh

    2009-01-01

    Roles of cyclin dependent kinase inhibitors, p21/Cip1 (p21) and p27/Kip1 (p27) in prostate cancer (PCa) progression is still not clear. Lower p27 protein expression in PCa tissues is often associated with poor prognosis, but prognostic significance of p21 is still controversial. Herein, we investigated the role of these molecules in determining PCa growth characteristics. We generated human PCa DU145 cell variants with knocked down levels of p21 (DU-p21) or p27 (DU-p27), or both (DU-p21+p27) via retroviral transduction of respective shRNAs and compared their various characteristics with empty vector-transduced DU145 (DU-EV) cells in vitro as well as in vivo. Knocking down either p21 or p27 did not show any significant change in doubling time, clonogenicity and cell cycle progression in DU145 cells, but simultaneous knock-down of both p21 and p27 significantly enhanced these parameters. In athymic mice, DU-p21+p27 tumors showed higher growth rate than the comparable growth of DU-EV, DU-p21 and DU-p27 tumors. Concurrently, DU-p21+p27 tumors had significantly higher proliferation rate, showing 54% and 48% increase in proliferating cell nuclear antigen (PCNA) and Ki-67-positive cells, respectively, compared to DU-EV tumors. DU-p21+p27 tumors also showed higher microvessel density and increased expression of vascular endothelial growth factor (VEGF). Proliferation and angiogenic status of DU-p21 and DU-p27 tumors was comparable to DU-EV tumors. Both in vitro and in vivo results implicate that p21 and p27 have compensatory roles in advanced prostate cancer cells, and ablation or down-modulation of both these molecules essentially enhances the aggressive prostate carcinoma phenotype. PMID:18583941

  12. Association of RNASEL and 8q24 variants with the presence and aggressiveness of hereditary and sporadic prostate cancer in a hispanic population

    PubMed Central

    San Francisco, Ignacio F; Rojas, Pablo A; Torres-Estay, Verónica; Smalley, Susan; Cerda-Infante, Javier; Montecinos, Viviana P; Hurtado, Claudia; Godoy, Alejandro S

    2014-01-01

    To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05–18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96–13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis. PMID:24224612

  13. Aggressive behavior problems.

    PubMed

    Beaver, B V

    1986-12-01

    Accurate diagnosis of the cause of aggression in horses is essential to determining the appropriate course of action. The affective forms of aggression include fear-induced, pain-induced, intermale, dominance, protective, maternal, learned, and redirected aggressions. Non-affective aggression includes play and sex-related forms. Irritable aggression and hypertestosteronism in mares are medical problems, whereas genetic factors, brain dysfunction, and self-mutilation are also concerns. PMID:3492250

  14. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    SciTech Connect

    Fang, Zejun; Gong, Chaoju; Liu, Hong; Zhang, Xiaomin; Mei, Lingming; Song, Mintao; Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian; Chen, Xiang

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  15. Introduction to pediatric oncology

    SciTech Connect

    McWhirter, W.R.; Masel, J.P.

    1987-01-01

    This book covers the varied and complex aspects of management in pediatric oncology. Emphasis is placed on a team approach and on establishing and maintaining an individualized, humanistic relationships with the patient. Numerous illustrations show modern imaging techniques that are proving most valuable in the investigation of suspected or confirmed childhood cancer. Physical and psychological side effects of short-term and long-term treatment are also discussed.

  16. Immune Adjuvant Activity of Pre-Resectional Radiofrequency Ablation Protects against Local and Systemic Recurrence in Aggressive Murine Colorectal Cancer

    PubMed Central

    Ito, Fumito; Ku, Amy W.; Bucsek, Mark J.; Muhitch, Jason B.; Vardam-Kaur, Trupti; Kim, Minhyung; Fisher, Daniel T.; Camoriano, Marta; Khoury, Thaer; Skitzki, Joseph J.; Gollnick, Sandra O.; Evans, Sharon S.

    2015-01-01

    Purpose While surgical resection is a cornerstone of cancer treatment, local and distant recurrences continue to adversely affect outcome in a significant proportion of patients. Evidence that an alternative debulking strategy involving radiofrequency ablation (RFA) induces antitumor immunity prompted the current investigation of the efficacy of performing RFA prior to surgical resection (pre-resectional RFA) in a preclinical mouse model. Experimental Design Therapeutic efficacy and systemic immune responses were assessed following pre-resectional RFA treatment of murine CT26 colon adenocarcinoma. Results Treatment with pre-resectional RFA significantly delayed tumor growth and improved overall survival compared to sham surgery, RFA, or resection alone. Mice in the pre-resectional RFA group that achieved a complete response demonstrated durable antitumor immunity upon tumor re-challenge. Failure to achieve a therapeutic benefit in immunodeficient mice confirmed that tumor control by pre-resectional RFA depends on an intact adaptive immune response rather than changes in physical parameters that make ablated tumors more amenable to a complete surgical excision. RFA causes a marked increase in intratumoral CD8+ T lymphocyte infiltration, thus substantially enhancing the ratio of CD8+ effector T cells: FoxP3+ regulatory T cells. Importantly, pre-resectional RFA significantly increases the number of antigen-specific CD8+ T cells within the tumor microenvironment and tumor-draining lymph node but had no impact on infiltration by myeloid-derived suppressor cells, M1 macrophages or M2 macrophages at tumor sites or in peripheral lymphoid organs (i.e., spleen). Finally, pre-resectional RFA of primary tumors delayed growth of distant tumors through a mechanism that depends on systemic CD8+ T cell-mediated antitumor immunity. Conclusion Improved survival and antitumor systemic immunity elicited by pre-resectional RFA support the translational potential of this neoadjuvant

  17. Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124

    PubMed Central

    Dong, Peixin; Xiong, Ying; Watari, Hidemichi; Hanley, Sharon JB; Konno, Yosuke; Ihira, Kei; Suzuki, Fumihiko; Yamada, Takahiro; Kudo, Masataka; Yue, Junming; Sakuragi, Noriaki

    2016-01-01

    Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels. Moreover, we demonstrate that miR-124, directly targeting iASPP, reduces expression of iASPP and attenuates CC cell growth and invasiveness. Low miR-124 expression is inversely correlated with increased expression of iASPP mRNA in CC tissues. In a cohort of 40 patients with CC, the low miR-124 expression was correlated with poor 5-year overall survival (P = 0.0002) and shorter disease-free survival 5-year (P = 0006). Treatment with the DNA methyltransferase inhibitor Zebularine increases miR-124 expression and retards CC cell growth and invasion with minimal toxicity to normal cells. Even at a non-toxic concentration, Zebularine was effective in suppressing CC cell invasion and migration. Altogether, the restoration of miR-124 reduces iASPP expression and leads to p53-dependent tumor suppression, suggesting a therapeutic strategy to treat iASPP-associated CC. PMID:27765948

  18. Regional Deprivation and Non-Cancer Related Computed Tomography Use in Pediatric Patients in Germany: Cross-Sectional Analysis of Cohort Data

    PubMed Central

    Dreger, Steffen; Krille, Lucian; Maier, Werner; Pokora, Roman; Blettner, Maria; Zeeb, Hajo

    2016-01-01

    Background Conflicting findings were observed in recent studies assessing the association between patients’ area-level socio-economic status and the received number of computed tomography (CT) examinations in children. The aim was to investigate the association between area-level socio-economic status and variation in CT examination practice for pediatric patients in Germany. Methods Data from Radiology Information Systems for children aged 0 to < 15 years without cancer who had at least one CT examination between 2001 and 2010 were extracted in 20 hospitals across Germany. The small-area German Index of Multiple Deprivation (GIMD) was used to assess regional deprivation. The GIMD scores were classified into least, medium and most deprived areas and linked with the patient’s last known postal code. A multinomial logistic regression model was used to assess the association between patients’ CT numbers and regional deprivation adjusting for age, sex, and location of residence (urban/rural). Results A total of 37,810 pediatric patients received 59,571 CT scans during the study period. 27,287 (72%) children received only one CT, while n = 885 (2.3%) received six or more. Increasing numbers of CT examinations in non-cancer patients were significantly associated with higher regional deprivation, which increased, although CI overlap, for higher CT categories: ‘2–3 CT’ odds ratio (OR) = 1.45, 95%CI: 1.40–1.50; ‘4–5 CT’ OR = 1.48, 95%CI: 1.38–1.59; ‘6+CT’ OR = 1.54, 95%CI: 1.41–1.69. In addition, male sex, higher age categories, and specific body regions were positively associated with increased numbers of CT examinations. Conclusion We observed a positive association between regional deprivation and CT numbers in non-cancer pediatric patients. Limitations of the ecological approach and the lack of differentiation of CT details have to be acknowledged. More information on CT indications is necessary for a full assessment of this finding. In

  19. siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer

    PubMed Central

    Bee, Alix; Brewer, Daniel; Beesley, Carol; Dodson, Andrew; Forootan, Shiva; Dickinson, Timothy; Gerard, Patricia; Lane, Brian; Yao, Sheng; Cooper, Colin S.; Djamgoz, Mustafa B. A.; Gosden, Christine M.; Ke, Youqiang; Foster, Christopher S.

    2011-01-01

    We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected. PMID:21799931

  20. Pediatric Terminology

    Cancer.gov

    The National Institute of Child Health and Human Development (NICHD) is working with NCI Enterprise Vocabulary Services (EVS) to provide standardized terminology for coding pediatric clinical trials and other resea

  1. Pediatric Specialists

    MedlinePlus

    ... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... Life Medical Home Health Insurance Pediatric Specialists Family Dynamics Media Work & Play Getting Involved in Your Community ...

  2. Virtual Pediatric Hospital

    MedlinePlus

    ... Assistant™ Last revised on February 12, 2016 Related Digital Libraries Pediatric GeneralPediatrics.com - the general pediatrician's view of the Internet PediatricEducation.org - a pediatric digital library and learning collaboratory intended to serve as a ...

  3. Pediatric Thyroid Cancer

    MedlinePlus

    ... isthmus). The thyroid secretes three main hormones: 1) Thyroxine, that contains iodine, needed for growth and metabolism; ... also contains iodine and similar in function to Thyroxine; and 3) Calcitonin, which decreases the concentration of ...

  4. Pediatric Anthropometry

    NASA Astrophysics Data System (ADS)

    Klinich, Kathleen D.; Reed, Matthew P.

    Anthropometry is the measurement of human size, shape, and physical capabilities. Most pediatric anthropometry data are gathered to describe child growth patterns, but data on body size, mass distribution, range of motion, and posture are used to develop crash test dummies and computational models of child occupants. Pediatric anthropometry data are also used to determine child restraint dimensions, so they will accommodate the applicable population of child occupants.

  5. Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants.

    PubMed

    Chowdhury, Subrata; Veyhl, Joe; Jessa, Fatima; Polyakova, Olena; Alenzi, Ahmed; MacMillan, Christina; Ralhan, Ranju; Walfish, Paul G

    2016-05-31

    Programmed death-ligand 1(PD-L1) expression on tumor cells is emerging as a potential predictive biomarker in anti-PD-L1 directed cancer immunotherapy. We analyzed PD-L1 expression in papillary thyroid carcinoma (PTC) and its variants and determined its prognostic potential to predict clinical outcome in these patients. This study was conducted at an academic oncology hospital which is a prime referral centre for thyroid diseases. Immunohistochemical subcellular localization (IHC) analyses of PD-L1 protein was retrospectively performed on 251 archived formalin fixed and paraffin embedded (FFPE) surgical tissues (66 benign thyroid nodules and 185 PTCs) using a rabbit monoclonal anti-PD-L1 antibody (E1L3N, Cell Signaling Technology) and detected using VECTASTAIN rapid protocol with diaminobenzidine (DAB) as the chromogen. The clinical-pathological factors and disease outcome over 190 months were assessed; immunohistochemical subcellular localization of PD-L1 was correlated with disease free survival (DFS) using Kaplan Meier survival and Cox multivariate regression analysis. Increased PD-L1 immunostaining was predominantly localized in cytoplasm and occasionally in plasma membrane of tumor cells. Among all combined stages of PTC, patients with increased PD-L1 membrane or cytoplasmic positivity had significantly shorter median DFS (36 months and 49 months respectively) as compared to those with PD-L1 negative tumors (DFS, both 186 months with p < 0.001 and p < 0.01 respectively). Comparison of PD-L1+ and PD-L1- patients with matched staging showed increased cytoplasmic positivity in all four stages of PTC that correlated with a greater risk of recurrence and a poor prognosis, but increased membrane positivity significantly correlated with a greater risk of metastasis or death only in Stage IV patients. In conclusion, PD-L1 positive expression in PTC correlates with a greater risk of recurrence and shortened disease free survival supporting its potential application as

  6. Survivin Expression and Prognostic Significance in Pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST)

    PubMed Central

    Boldrin, Daniela; Merlo, Anna; Gambini, Claudio; Ferrari, Andrea; Dall'Igna, Patrizia; Coffin, Cheryl M.; Martines, Annalisa; Bonaldi, Laura; De Salvo, Gian Luca; Zanovello, Paola; Rosato, Antonio

    2013-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies comprising approximately 5–10% of all soft tissue sarcomas. In this study, we focused on pediatric MPNST arising in the first 2 decades of life, as they represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in children. In MPNST, several genetic alterations affect the chromosomal region 17q encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin has been found to be an effective marker for cancer detection and outcome prediction, we analyzed survivin expression in 35 tumor samples derived from young patients affected by sporadic and neurofibromatosis type 1-associated MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and immunohistochemical staining, respectively, while gene amplification was analyzed by FISH. Data were correlated with the clinicopathological characteristics of patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a copy number gain of BIRC5; furthermore, increased levels of transcripts correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067), and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these data support the concept that survivin can be regarded as a useful prognostic marker for pediatric MPNST and a promising target for therapeutic interventions. PMID:24303016

  7. Acquired resistance to zoledronic acid and the parallel acquisition of an aggressive phenotype are mediated by p38-MAP kinase activation in prostate cancer cells

    PubMed Central

    Milone, M R; Pucci, B; Bruzzese, F; Carbone, C; Piro, G; Costantini, S; Capone, F; Leone, A; Di Gennaro, E; Caraglia, M; Budillon, A

    2013-01-01

    The nitrogen-containing bisphosphonates (N-BP) zoledronic acid (ZOL) inhibits osteoclast-mediated bone resorption, and it is used to prevent skeletal complications from bone metastases. ZOL has also demonstrated anticancer activities in preclinical models and, recently, in cancer patients, highlighting the interest in determining eventual mechanisms of resistance against this agent. In our study, we selected and characterised a resistant subline of prostate cancer (PCa) cells to better understand the mechanisms, by which tumour cells can escape the antitumour effect of ZOL. DU145R80-resistant cells were selected in about 5 months using stepwise increasing concentrations of ZOL from DU145 parental cells. DU145R80 cells showed a resistance index value of 5.5 and cross-resistance to another N-BP, pamidronate, but not to the non-nitrogen containing BP clodronate. Notably, compared with DU145 parental cells, DU145R80 developed resistance to apoptosis and anoikis, as well as overexpressed the anti-apoptotic protein Bcl-2 and oncoprotein c-Myc. Moreover, DU145R80 cells underwent epithelial to mesenchymal transition (EMT) and showed increased expression of the metalloproteases MMP-2/9, as well as increased invading capability. Interestingly, compared with DU145, DU145R80 cells also increased the gene expression and protein secretion of VEGF and the cytokines Eotaxin-1 and IL-12. At the molecular level, DU145R80 cells showed strong activation of the p38-MAPK-dependent survival pathway compared with parental sensitive cells. Moreover, using the p38-inhibitor SB203580, we completely reversed the resistance to ZOL, as well as EMT marker expression and invasion. Furthermore, SB203580 treatment reduced the expression of VEGF, Eotaxin-1, IL-12, MMP-9, Bcl-2 and c-Myc. Thus, for the first time, we demonstrate that the p38-MAPK pathway can be activated under continuous extensive exposure to ZOL in PCa cells and that the p38-MAPK pathway has a critical role in the induction of

  8. Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011).

    PubMed

    Lau, Christine S M; Mahendraraj, Krishnaraj; Chamberlain, Ronald S

    2015-01-01

    Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973-2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival.

  9. Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973–2011)

    PubMed Central

    Lau, Christine S. M.; Mahendraraj, Krishnaraj; Chamberlain, Ronald S.

    2015-01-01

    Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973–2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival. PMID:26663981

  10. Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity.

    PubMed

    Bamodu, Oluwaseun Adebayo; Huang, Wen-Chien; Tzeng, David T W; Wu, Alexander; Wang, Liang Shun; Yeh, Chi-Tai; Chao, Tsu-Yi

    2015-08-10

    Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 µM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 µM) compared to simultaneous treatment with Doxo ( IC50 1.8 µM), or Doxo alone (IC50 9.2 µM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 µM Ova and 1.25 µM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.

  11. What Is Endometrial Cancer?

    MedlinePlus

    ... endometrial adenocarcinomas. These types tend to be more aggressive than most endometrial cancers. They tend to grow ... forming glands. Grade 3 cancers tend to be aggressive and have a poorer outlook than lower-grade ...

  12. 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 ...

  13. Acupuncture for Pediatric Pain

    PubMed Central

    Golianu, Brenda; Yeh, Ann Ming; Brooks, Meredith

    2014-01-01

    Chronic pain is a growing problem in children, with prevalence as high as 30.8%. Acupuncture has been found to be useful in many chronic pain conditions, and may be of clinical value in a multidisciplinary treatment program. The basic principles of acupuncture are reviewed, as well as studies exploring basic mechanisms of acupuncture and clinical efficacy. Conditions commonly treated in the pediatric pain clinic, including headache, abdominal pain, fibromyalgia, juvenile arthritis, complex regional pain syndrome, cancer pain, as well as perioperative pain studies are reviewed and discussed. Areas in need of further research are identified, and procedural aspects of acupuncture practice and safety studies are reviewed. Acupuncture can be an effective adjuvant in the care of pediatric patients with painful conditions, both in a chronic and an acute setting. Further studies, including randomized controlled trials, as well as trials of comparative effectiveness are needed. PMID:27417472

  14. Relational aggression in marriage.

    PubMed

    Carroll, Jason S; Nelson, David A; Yorgason, Jeremy B; Harper, James M; Ashton, Ruth Hagmann; Jensen, Alexander C

    2010-01-01

    Drawing from developmental theories of relational aggression, this article reports on a study designed to identify if spouses use relationally aggressive tactics when dealing with conflict in their marriage and the association of these behaviors with marital outcomes. Using a sample of 336 married couples (672 spouses), results revealed that the majority of couples reported that relationally aggressive behaviors, such as social sabotage and love withdrawal, were a part of their marital dynamics, at least to some degree. Gender comparisons of partner reports of their spouse's behavior revealed that wives were significantly more likely to be relationally aggressive than husbands. Structural equation modeling demonstrated that relational aggression is associated with lower levels of marital quality and greater marital instability for both husbands and wives. Implications are drawn for the use of relational aggression theory in the future study of couple conflict and marital aggression.

  15. Pediatric Sarcomas.

    PubMed

    Williams, Regan F; Fernandez-Pineda, Israel; Gosain, Ankush

    2016-10-01

    Pediatric sarcomas are a heterogeneous group of tumors accounting for approximately 10% of childhood solid tumors. Treatment is focused on multimodality therapy, which has improved the prognosis over the past two decades. Current regimens focus on decreasing treatment for low-risk patients to decrease the long-term side effects while maximizing therapy for patients with metastatic disease to improve survival. Pediatric sarcomas can be divided into soft tissue sarcomas and osseous tumors. Soft tissue sarcomas are further delineated into rhabdomyosarcomas, which affect young children and nonrhabdomyosarcomas, which are most common in adolescents. The most common bone sarcomas are osteosarcomas and Ewing's sarcoma. PMID:27542645

  16. Pediatric rosacea.

    PubMed

    Kellen, Roselyn; Silverberg, Nanette B

    2016-07-01

    Because rosacea is uncommon in the pediatric population, care must be taken to exclude other papulopustular disorders. Children can present with vascular, papulopustular, and/or ocular findings. Importantly, ocular symptoms can appear before the cutaneous symptoms of rosacea, leading to misdiagnosis. Rosacea is a clinical diagnosis, but histopathologic examination typically reveals dilated vessels, perivascular lymphohistiocytic infiltrates in the upper dermis, elastosis, and disorganization of the upper dermal connective tissue. Treatment involves avoiding known triggers and utilizing topical and/or systemic therapies. Although treatment can control flares, pediatric rosacea often persists into adulthood. PMID:27529708

  17. 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.

  18. MO-E-17A-09: Has Cancer Risk for Pediatric CT Increased Or Decreased? An Analysis of Cohort Data From 2004-2013

    SciTech Connect

    Brady, S; Kaufman, R

    2014-06-15

    Purpose: To analyze CT radiation dosimetry trends in a pediatric population imaged with modern (2004-2013) CT technology Methods: The institutional review board approved this retrospective review. Two cohorts of pediatric patients that received CT scans for treatment or surveillance for Wilms tumor (n=73) or Neuroblastoma (n=74) from 2004–2013 were included in this study. Patients were scanned during this time period on a GE Ultra (8 slice; 2004–2007), a GE VCT (2008–2011), or a GE VCT-XTe (2011–2013). Each patient's individual or combined chest, abdomen, and pelvic CT exams (n=4138) were loaded onto a PACS workstation (Intelerad, Canada) and measured to calculate their effective diameter and SSDE. Patient SSDE was used to estimate patient organ dosimetry based on previously published data. Patient's organ dosimetry were sorted by gender, weight, age, scan protocol (i.e., chest, abdomen, or pelvis), and CT scanner technology and averaged accordingly to calculate population averaged absolute and effective dose values. Results: Patient radiation dose burden calculated for all genders, weights, and ages decreased at a rate of 0.2 mSv/year (4.2 mGy/year; average organ dose) from 2004–2013; overall levels decreased by 50% from 3.0 mSv (60.0 mGy) to 1.5 mSv (25.9 mGy). Patient dose decreased at equal rates for both male and female, and for individual scan protocols. The greatest dose savings was found for patients between 0–4 years old (65%) followed by 5-9 years old (45%), 10–14 years old (30%), and > 14 years old (21%). Conclusion: Assuming a linear-nothreshold model, there always will be potential risk of cancer induction from CT. However, as demonstrated among these patient populations, effective and organ dose has decreased over the last decade; thus, potential risk of long-term side effects from pediatric CT examinations has also been reduced.

  19. Improving Pediatric Cancer Care Disparities Across the United States–Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana

    PubMed Central

    Aristizabal, Paula; Fuller, Spencer; Rivera, Rebeca; Beyda, David; Ribeiro, Raul C.; Roberts, William

    2015-01-01

    In 2007, the 5-year survival rate for children with acute leukemia in Baja California, Mexico was estimated at 10% (vs. 88% in the United States). In response, stakeholders at St. Jude Children’s Research Hospital, Rady Children’s Hospital San Diego, and the Hospital General de Tijuana (HGT) implemented a transcultural partnership to establish a pediatric oncology program. The aim was to improve clinical outcomes and overall survival for children in Baja California. An initial needs assessment evaluation was performed and a culturally sensitive, comprehensive, 5-year plan was designed and implemented. After six years, healthcare system accomplishments include the establishment of a fully functional pediatric oncology unit with 60 new healthcare providers (vs. five in 2007). Patient outcome improvements include a rise in 5-year survival for leukemia from 10 to 43%, a rise in new cases diagnosed per year from 21 to 70, a reduction in the treatment abandonment rate from 10% to 2%, and a 45% decrease in the infection rate. More than 600 patients have benefited from this program. Knowledge sharing has taken place between teams at the HGT and Rady Children’s Hospital San Diego. Further, one of the most significant outcomes is that the HGT has transitioned into a regional referral center and now mentors other hospitals in Mexico. Our results show that collaborative initiatives that implement long-term partnerships along the United States–Mexico border can effectively build local capacity and reduce the survival gap between children with cancer in the two nations. Long-term collaborative partnerships should be encouraged across other disciplines in medicine to further reduce health disparities across the United States–Mexico border. PMID:26157788

  20. Improving Pediatric Cancer Care Disparities Across the United States-Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana.

    PubMed

    Aristizabal, Paula; Fuller, Spencer; Rivera, Rebeca; Beyda, David; Ribeiro, Raul C; Roberts, William

    2015-01-01

    In 2007, the 5-year survival rate for children with acute leukemia in Baja California, Mexico was estimated at 10% (vs. 88% in the United States). In response, stakeholders at St. Jude Children's Research Hospital, Rady Children's Hospital San Diego, and the Hospital General de Tijuana (HGT) implemented a transcultural partnership to establish a pediatric oncology program. The aim was to improve clinical outcomes and overall survival for children in Baja California. An initial needs assessment evaluation was performed and a culturally sensitive, comprehensive, 5-year plan was designed and implemented. After six years, healthcare system accomplishments include the establishment of a fully functional pediatric oncology unit with 60 new healthcare providers (vs. five in 2007). Patient outcome improvements include a rise in 5-year survival for leukemia from 10 to 43%, a rise in new cases diagnosed per year from 21 to 70, a reduction in the treatment abandonment rate from 10% to 2%, and a 45% decrease in the infection rate. More than 600 patients have benefited from this program. Knowledge sharing has taken place between teams at the HGT and Rady Children's Hospital San Diego. Further, one of the most significant outcomes is that the HGT has transitioned into a regional referral center and now mentors other hospitals in Mexico. Our results show that collaborative initiatives that implement long-term partnerships along the United States-Mexico border can effectively build local capacity and reduce the survival gap between children with cancer in the two nations. Long-term collaborative partnerships should be encouraged across other disciplines in medicine to further reduce health disparities across the United States-Mexico border.

  1. Pediatric trichotillomania.

    PubMed

    Harrison, J P; Franklin, M E

    2012-06-01

    Trichotillomania (TTM) is an impulse control disorder characterized by chronic hair-pulling, distress, and impairment. Although the negative effects of TTM are documented and often readily evident, there remains a paucity of psychopathology and treatment research on this disorder, particularly in pediatric populations. In an effort to improve assessment of pediatric TTM, several TTM-specific instruments for youth have now been developed to reliably identify symptoms and examine related phenomenology. Instrument development has now yielded instruments to evaluate TTM and related symptoms in the context of clinical trials of youth, and the first randomized controlled trial of any treatment for pediatric TTM was recently published. Using the initial pediatric TTM studies as building blocks, future research is now needed to create a stronger body of knowledge about the relative and combined efficacy of potential interventions for TTM in youth, as well as to examine the effects of TTM phenomenology and comorbidity on treatment outcome. Dissemination efforts must also be heightened for this knowledge to best reach these vulnerable populations. PMID:22437627

  2. 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

  3. Improving outcomes for children with cancer in low-income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)-Part I.

    PubMed

    Howard, Scott C; Marinoni, Marco; Castillo, Luis; Bonilla, Miguel; Tognoni, Gianni; Luna-Fineman, Sandra; Antillon, Federico; Valsecchi, Maria Grazia; Pui, Ching-Hon; Ribeiro, Raul C; Sala, Alessandra; Barr, Ronald D; Masera, Giuseppe

    2007-03-01

    The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociación de Hemato-Oncología Pediátrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research. PMID:16883601

  4. Improving outcomes for children with cancer in low-income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)-Part I.

    PubMed

    Howard, Scott C; Marinoni, Marco; Castillo, Luis; Bonilla, Miguel; Tognoni, Gianni; Luna-Fineman, Sandra; Antillon, Federico; Valsecchi, Maria Grazia; Pui, Ching-Hon; Ribeiro, Raul C; Sala, Alessandra; Barr, Ronald D; Masera, Giuseppe

    2007-03-01

    The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociación de Hemato-Oncología Pediátrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research.

  5. Pediatric solid tumor genomics and developmental pliancy

    PubMed Central

    Chen, Xiang; Pappo, Alberto; Dyer, Michael A.

    2014-01-01

    Pediatric solid tumors are remarkably diverse in their cellular origins, developmental timing, and clinical features. Over the last 5 years, there have been significant advances in our understanding of the genetic lesions that contribute to the initiation and progression of pediatric solid tumors. To date, over 1,000 pediatric solid tumors have been analyzed by Next-Generation Sequencing. These genomic data provide the foundation to launch new research efforts to address one of the fundamental questions in cancer biology—why are some cells more susceptible to malignant transformation by particular genetic lesions at discrete developmental stages than others? Because of their developmental, molecular, cellular, and genetic diversity, pediatric solid tumors provide an ideal platform to begin to answer this question. In this review, we highlight the diversity of pediatric solid tumors and provide a new framework for studying the cellular and developmental origins of pediatric cancer. We also introduce a new unifying concept called cellular pliancy as a possible explanation for susceptibility to cancer and the developmental origins of pediatric solid tumors. PMID:25639868

  6. Punishment of elicited aggression.

    PubMed

    Azrin, N H

    1970-07-01

    Aversive shocks are known to produce aggression when the shocks are not dependent on behavior and to suppress behavior when the shocks are arranged as a dependent punisher. These two processes were studied by presenting non-dependent shock to monkeys at regular intervals, thereby producing biting attacks on a pneumatic tube. Immediate shock punishment was stimultaneously delivered for each biting attack. The attacks were found to decrease as a function of increasing punishment intensity. These results show that aggression is eliminated by direct punishment of the aggression even when the stimulus that is used as a punisher otherwise causes the aggression. PMID:4988590

  7. The role of thoracoscopic surgery in pediatric oncology.

    PubMed

    Malkan, Alpin D; Loh, Amos H P; Fernandez-Pineda, Israel; Sandoval, John A

    2014-11-01

    The application of thoracoscopic surgical techniques to pediatric solid tumors represents an important adjunctive tool for the surgical management of childhood cancer. Nearly four decades has passed since the introduction of minimally invasive chest surgery in children, and although the adoption of minimally invasive surgery in general pediatric surgical practice is better recognized, its role in pediatric oncology is still considered a developing field. As no consensus exists regarding the use of thoracoscopy for pediatric thoracic solid tumors, the purpose of this article is to review the current literature surrounding the use of thoracoscopic interventions in pediatric oncology and examine established indications, procedures, and technologic advances.

  8. Pediatric sleep apnea

    MedlinePlus

    Sleep apnea - pediatric; Apnea - pediatric sleep apnea syndrome; Sleep-disordered breathing - pediatric ... During sleep, all of the muscles in the body become more relaxed. This includes the muscles that help keep ...

  9. Survival with concurrent temozolomide and radiotherapy in pediatric brainstem glioma with relation to the tumor volume

    PubMed Central

    Taran, Shachi Jain; Taran, Rakesh; Batra, Manika; Ladia, Deah Deepak; Bhandari, Virendra

    2015-01-01

    Background: Brainstem gliomas account for approximately 25% of all posterior fossa tumors. In pediatric age group, it constitutes about 10% of all brain tumors. Brainstem glioma is an aggressive and lethal type of malignancy with poor outcome despite all treatments. Aim: We studied the incidence and treatment outcome in pediatric patients with brainstem glioma depending on their tumor volume presenting in our institution in last 5 years. Brain tumors comprised 2.95% of all cancers and brainstem gliomas were 8% of all brain tumors. Materials and Methods: Nine pediatric patients were included in this analysis, who were treated with localized external radiotherapy 54–59.4 Gy along with temozolomide 75 mg/m2 during the whole course of radiotherapy. Results: The median survival in all these patients was 20 months and the overall 2 years survival is 44.4% (4/9). The median survival of patients with primary disease volume <40cc is 26 months whereas when the volume is more than 40cc the median survival is 13.5 months as calculated by Chi-square test. Conclusion: As this study includes a small number of patients with unknown histology and treated on the basis of magnetic resonance imaging findings, no definite opinion can be given as some patients may have a low-grade tumor. More studies are required to establish the relation of size of the tumor with survival. PMID:26962339

  10. Pediatric Neurotrauma

    PubMed Central

    Kannan, Nithya; Ramaiah, Ramesh; Vavilala, Monica S.

    2014-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in children over 1 year of age. Knowledge about the age-specific types of injury and how to manage children with neurotrauma is essential to understanding and recognizing the extent and degree of injury and to optimize outcomes. In this article, we review the epidemiology, pathophysiology, and clinical management of pediatric neurotrauma. PMID:25024940

  11. Pediatric nutrition.

    PubMed

    Greco, Deborah S

    2014-03-01

    This article discusses pediatric nutrition in puppies and kittens. Supplementation of basic nutrients such as fat, protein, minerals, vitamins, and essential fatty acids of the bitch is essential for the proper growth and development of puppies during the lactation period. Milk replacers are compared for use in puppies and kittens. Supplements such as colostrum and probiotics for promotion of a healthy immune system and prevention or treatment of stress-induced and weaning diarrhea are also discussed. PMID:24580990

  12. Pediatric nutrition.

    PubMed

    Greco, Deborah S

    2014-03-01

    This article discusses pediatric nutrition in puppies and kittens. Supplementation of basic nutrients such as fat, protein, minerals, vitamins, and essential fatty acids of the bitch is essential for the proper growth and development of puppies during the lactation period. Milk replacers are compared for use in puppies and kittens. Supplements such as colostrum and probiotics for promotion of a healthy immune system and prevention or treatment of stress-induced and weaning diarrhea are also discussed.

  13. Psychopharmacology in pediatric critical care.

    PubMed

    Stoddard, Frederick J; Usher, Craigan T; Abrams, Annah N

    2006-07-01

    Psychopharmacologic treatment in pediatric critical care requires a careful child or adolescent psychiatric evaluation, including a thorough review of the history of present illness or injury, any current or pre-existing psychiatric disorder, past history, and laboratory studies. Although there is limited evidence to guide psychopharmacologic practice in this setting, psychopharmacologic treatment is increasing in critical care, with known indications for treatment, benefits, and risks; initial dosing guidelines; and best practices. Treatment is guided by the knowledge bases in pediatric physiology, psycho-pharmacology, and treatment of critically ill adults. Pharmacologic considerations include pharmacokinetic and pharmcodynamic aspects of specific drugs and drug classes, in particular elimination half-life, developmental considerations, drug interactions, and adverse effects. Evaluation and management of pain is a key initial step, as pain may mimic psychiatric symptoms and its effective treatment can ameliorate them. Patient comfort and safety are primary objectives for children who are acutely ill and who will survive and for those who will not. Judicious use of psychopharmacolgic agents in pediatric critical care using the limited but growing evidence base and a clinical best practices collaborative approach can reduce anxiety,sadness, disorientation, and agitation; improve analgesia; and save lives of children who are suicidal or delirious. In addition to pain, other disorders or indications for psychopharmacologic treatment are affective disorders;PTSD; post-suicide attempt patients; disruptive behavior disorders (especially ADHD); and adjustment, developmental, and substance use disorders. Treating children who are critically ill with psychotropic drugs is an integral component of comprehensive pediatric critical care in relieving pain and delirium; reducing inattention or agitation or aggressive behavior;relieving acute stress, anxiety, or depression; and

  14. A Strategic Approach to Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    2001-01-01

    Discusses two issues raised by Underwood et al.: the distinction between indirect and relational forms of aggression, and implications of indirect aggression for definitions of aggression; and the normative view of aggression that indicates that aggressive individuals may be socially skilled. Suggests that both issues lead to the conclusion that…

  15. Girls' Aggressive Behavior

    ERIC Educational Resources Information Center

    Owens, Larry; Shute, Rosalyn; Slee, Phillip

    2004-01-01

    In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

  16. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

    Since many acts of aggression in society are more than simply an aggressor-victim encounter, the role played by third person instigated aggression also needs examination. The purpose of this study was to develop a laboratory procedure to systematically investigate instigation. In a competitive reaction time task, high and low Machiavellian Males…

  17. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy through…

  18. FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway.

    PubMed

    Asad, M; Wong, M K; Tan, T Z; Choolani, M; Low, J; Mori, S; Virshup, D; Thiery, J P; Huang, R Y-J

    2014-01-01

    Ovarian cancer (OC) can be classified into five biologically distinct molecular subgroups: epithelial-A (Epi-A), Epi-B, mesenchymal (Mes), Stem-A and Stem-B. Among them, Stem-A expresses genes relating to stemness and is correlated with poor clinical prognosis. In this study, we show that frizzled family receptor 7 (FZD7), a receptor for Wnt signalling, is overexpressed in the Stem-A subgroup. To elucidate the functional roles of FZD7, we used an RNA interference gene knockdown approach in three Stem-A cell lines: CH1, PA1 and OV-17R. Si-FZD7 OC cells showed reduced cell proliferation with an increase in the G0/G1 sub-population, with no effect on apoptosis. The cells also displayed a distinctive morphologic change by colony compaction to become more epithelial-like and polarised with smaller internuclear distances and increased z-axis height. Immunofluorescence (IF) staining patterns of pan-cadherin and β-catenin suggested an increase in cadherin-based cell-cell adhesion in si-FZD7 cells. We also observed a significant rearrangement in the actin cytoskeleton and an increase in tensile contractility in si-FZD7 OC cells, as evident by the loss of stress fibres and the redistribution of phospho-myosin light chain (pMLC) from the sites of cell-cell contacts to the periphery of cell colonies. Furthermore, there was reciprocal regulation of RhoA (Ras homolog family member A) and Rac1 (Ras-related C3 botulinum toxin substrate 1 (Rho family, small GTP-binding protein Rac1)) activities upon FZD7 knockdown, with a significant reduction in RhoA activity and a concomitant upregulation in Rac1 activity. These changes in pMLC and RhoA, as well as the increased TopFlash reporter activities in si-FZD7 cells, suggested involvement of the non-canonical Wnt/planar cell polarity (PCP) pathway. Selected PCP pathway genes (cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3), prickle homolog 4 (Drosophila) (PRICKLE4), dishevelled-associated activator of morphogenesis 1 (DAAM1

  19. Pediatric radiation oncology

    SciTech Connect

    Halperin, E.C.; Kun, L.E.; Constine, L.S.; Tarbell, N.J.

    1989-01-01

    This text covers all aspects of radiation therapy for treatment of pediatric cancer. The book describes the proper use of irradiation in each of the malignancies of childhood, including tumors that are rarely encountered in adult practice. These include acute leukemia; supratentorial brain tumors; tumors of the posterior fossa of the brain and spinal canal; retinoblastoma and optic nerve glioma; neuroblastoma; Hodgkin's disease; malignant lymphoma; Ewing's sarcoma; osteosarcoma; rhabdomyosarcoma; Desmoid tumor; Wilms' tumor; liver and biliary tumors; germ cell and stromal cell tumors of the gonads; endocrine, aerodigestive tract, and breast tumors; Langerhans' cell histiocytosis; and skin cancer and hemangiomas. For each type of malignancy, the authors describe the epidemiology, common presenting signs and symptoms, staging, and proper diagnostic workup. Particular attention is given to the indications for radiation therapy and the planning of a course of radiotherapy, including the optimal radiation dose, field size, and technique.

  20. Pediatric oncology in Morocco: achievements and challenges.

    PubMed

    Hessissen, Laila; Madani, Abdellah

    2012-03-01

    Cancer in children is quickly becoming one of the leading causes of non traumatic death among children. In pediatric oncology, palliative care is a primary component of the cancer control plan. In low income countries also known as emerging nations or developing countries access to adequate care remains a challenge for most pediatric oncology patients. In Morocco the situation has dramatically improved in the last few years as both the government and NGOs have become more aware of the importance and urgency of the issue. The incidence of cancer in patients under 15 years of age in Morocco is estimated to be 1000 new cases per year and the incidence of leukemia to be 100 new cases diagnosed per year. Pediatric cancer patients are mostly managed by public hospitals. Thus they are highly influenced by the Moroccan public health system, which is now considering cancer management a priority. Since health cover is very limited, most chemotherapy drugs were purchased by local parent associations. Recently, a new large Moroccan NGO (ALSC) provides anti-cancer drugs to all government-run oncology units. Despite all the progress, Morocco has witnessed in the pediatric oncology field, the palliative aspect of the care is not yet organized. Pediatric oncology is supported by the work of the National Society of Pediatric Oncolgy. The opioide therapy is available. However its use is strongly limited by the current restrictive and obsolete legislation which represents a major barrier to care. Despite the latest progress, pediatric oncology in Morocco still needs to improve in order to achieve performances comparable to those of the developed world. These improvements include better survival rates, less treatment abandonment, developing new techniques, improving quality of life and creating data collection teams. In order for this action to succeed all the stakeholders (government, NGOs, medical societies, oncology teams) must work together and coordinate their efforts.

  1. Guidelines for the recognition, prevention, and remediation of burnout in health care professionals participating in the care of children with cancer: report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

    PubMed

    Spinetta, J J; Jankovic, M; Ben Arush, M W; Eden, T; Epelman, C; Greenberg, M L; Gentils Martins, A; Mulhern, R K; Oppenheim, D; Masera, G

    2000-08-01

    This is the eighth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. It deals with a topic discussed and approved by the SIOP Committee; namely, "Recognition, prevention, and remediation of burnout in health care professionals participating in the care of children with cancer." It is addressed to the Pediatric Oncology community and outlines: 1) the general definition of burnout as mental and physical exhaustion, indifference, sense of failure as a professional, and sense of failure as a person; 2) the causes of burnout from the nature of the work itself, the work environment, and the characteristics of the individual; 3) the prevention of burnout, changing the detrimental aspects of one's work environment and modifying one's own behavior; and accepting methods to remediate burnout when it occurs.

  2. Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers

    PubMed Central

    Emadali, Anouk; Rousseaux, Sophie; Bruder-Costa, Juliana; Rome, Claire; Duley, Samuel; Hamaidia, Sieme; Betton, Patricia; Debernardi, Alexandra; Leroux, Dominique; Bernay, Benoit; Kieffer-Jaquinod, Sylvie; Combes, Florence; Ferri, Elena; McKenna, Charles E; Petosa, Carlo; Bruley, Christophe; Garin, Jérôme; Ferro, Myriam; Gressin, Rémy; Callanan, Mary B; Khochbin, Saadi

    2013-01-01

    Immuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma. The nuclear factor CYCLON is a new MYC cooperating factor that drives tumor growth and Rituximab resistance in lymphoma. This resistance mechanism can be targeted by next-generation epigenetic therapy by BET bromodomain inhibition downstream of MYC. PMID:23828858

  3. Pediatric vitiligo.

    PubMed

    Silverberg, Nanette B

    2014-04-01

    Vitiligo is a disease of pigment loss. Most investigators currently consider vitiligo to be a disorder that occurs as a result of autoimmune destruction of melanocytes, supported by identification of antimelanocyte antibodies in many patients, and the presence of comorbid autoimmune disease in patients with and family members of individuals with vitiligo. One-half of vitiligo cases are of childhood onset. This article presents a current overview of pediatric vitiligo including comorbidities of general health, psychological factors, therapeutic options, and long-term health considerations.

  4. 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

  5. Family impact of neurodevelopmental late effects in survivors of pediatric cancer: review of research, clinical evidence, and future directions.

    PubMed

    Peterson, Catherine Cant; Drotar, Dennis

    2006-07-01

    Children and adolescents who have survived childhood cancer are vulnerable to late effects of their disease and treatment experience, including both physical and psychological sequelae. The neurodevelopmental (ND) sequelae (e.g., difficulties with attention, memory, information processing, and other executive functions) faced by children surviving central nervous system (CNS) cancers or CNS treatments can have a range of effects on their psychological adjustment and quality of life as they reintegrate into school and social settings. Survivors facing such difficulties may be influenced by their family environment, and these struggles may in turn impact the perceived burden of their parents and family system, suggesting a bidirectional framework for understanding the impact of ND late effects within the family. The current study summarizes the following: Findings of family outcomes in children with ND late effects of cancer treatment; evaluation of methodological and measurement issues; the importance of examining bidirectional family-child influences; and implications for future survivorship research and clinical care addressing the role of ND late effects from a systems perspective.

  6. Aggression in Pretend Play and Aggressive Behavior in the Classroom

    ERIC Educational Resources Information Center

    Fehr, Karla K.; Russ, Sandra W.

    2013-01-01

    Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…

  7. Personalized Assessment of kV Cone Beam Computed Tomography Doses in Image-guided Radiotherapy of Pediatric Cancer Patients

    SciTech Connect

    Zhang Yibao; Yan Yulong; Nath, Ravinder; Bao Shanglian; Deng Jun

    2012-08-01

    Purpose: To develop a quantitative method for the estimation of kV cone beam computed tomography (kVCBCT) doses in pediatric patients undergoing image-guided radiotherapy. Methods and Materials: Forty-two children were retrospectively analyzed in subgroups of different scanned regions: one group in the head-and-neck and the other group in the pelvis. Critical structures in planning CT images were delineated on an Eclipse treatment planning system before being converted into CT phantoms for Monte Carlo simulations. A benchmarked EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions of kVCBCT scans with full-fan high-quality head or half-fan pelvis protocols predefined by the manufacturer. Based on planning CT images and structures exported in DICOM RT format, occipital-frontal circumferences (OFC) were calculated for head-and-neck patients using DICOMan software. Similarly, hip circumferences (HIP) were acquired for the pelvic group. Correlations between mean organ doses and age, weight, OFC, and HIP values were analyzed with SigmaPlot software suite, where regression performances were analyzed with relative dose differences (RDD) and coefficients of determination (R{sup 2}). Results: kVCBCT-contributed mean doses to all critical structures decreased monotonically with studied parameters, with a steeper decrease in the pelvis than in the head. Empirical functions have been developed for a dose estimation of the major organs at risk in the head and pelvis, respectively. If evaluated with physical parameters other than age, a mean RDD of up to 7.9% was observed for all the structures in our population of 42 patients. Conclusions: kVCBCT doses are highly correlated with patient size. According to this study, weight can be used as a primary index for dose assessment in both head and pelvis scans, while OFC and HIP may serve as secondary indices for dose estimation in corresponding regions. With the proposed empirical functions, it is possible

  8. Effects of Time since Diagnosis on the Association between Parent and Child Distress in Families with Pediatric Cancer

    PubMed Central

    Okado, Yuko; Tillery, Rachel; Sharp, Katianne Howard; Long, Alanna M.; Phipps, Sean

    2015-01-01

    Although parental distress and child distress have been linked in families of children with cancer, how these associations change over time is unknown. The present study examined how the amount of time elapsed since the child’s diagnosis moderates the associations between self-reported parent and child symptoms of depression, anxiety, and post-traumatic stress in 255 parent-child dyads. Time since diagnosis moderated the associations between parental symptoms and child-reported anxiety and post-traumatic stress. Dyads farther out from diagnosis exhibited stronger associations between parental and child symptoms. Findings suggest the importance of monitoring the psychological adjustment of parents and children over time. PMID:27630380

  9. Pediatric cavernous sinus thrombosis

    PubMed Central

    Vossough, Arastoo; Vorona, Gregory A.; Beslow, Lauren A.; Ichord, Rebecca N.; Licht, Daniel J.

    2015-01-01

    Objective: To describe clinical characteristics, imaging findings, morbidity, and mortality in a single-center cohort of 12 pediatric cavernous sinus thrombosis cases and to review all cases available in recent English literature. Methods: Clinical data and radiographic studies on 12 cases from our institution were analyzed retrospectively. A literature search and review was conducted, with additional cases pooled with the new cohort for an aggregate analysis. Results: Twelve cases of cavernous sinus thrombosis in children from the Children's Hospital of Philadelphia between January 1, 2000, and December 31, 2013, were reviewed. All patients survived to discharge; 3 of 12 (25%) experienced neurologic morbidity. Contrast-enhanced MRI and contrast-enhanced head CT were 100% sensitive for detecting cavernous sinus thrombosis, while noncontrast time-of-flight magnetic resonance venography (TOF MRV) and noncontrast head CT were 0% sensitive. Literature review produced an additional 40 cases, and the aggregate mortality rate was 4 of 52 (8%) and morbidity rate was 10 of 40 (25%). Outcomes did not vary by treatment or with unilateral vs bilateral cavernous sinus involvement. There was a trend toward worse outcomes with fungal infections. Conclusion: Our case series demonstrates low morbidity and mortality with early, aggressive surgical, antimicrobial, and anticoagulation therapies. Although anticoagulation and surgery were not associated with significantly different outcomes, more study is needed. PMID:26231260

  10. Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail.

    PubMed

    Fontebasso, Adam M; Liu, Xiao-Yang; Sturm, Dominik; Jabado, Nada

    2013-03-01

    Primary brain tumors occur in 8 out of 100 000 people and are the leading cause of cancer-related death in children. Among brain tumors, high-grade astrocytomas (HGAs) including glioblastoma multiforme (GBM) are aggressive and are lethal human cancers. Despite decades of concerted therapeutic efforts, HGAs remain essentially incurable in adults and children. Recent discoveries have revolutionized our understanding of these tumors in children and young adults. Recurrent somatic driver mutations in the tail of histone 3 variant 3 (H3.3), leading to amino acid substitutions at key residues, namely lysine (K) 27 (K27M) and glycine 34 (G34R/G34V), were identified as a new molecular mechanism in pediatric GBM. These mutations represent the pediatric counterpart of the recurrent mutations in isocitrate dehydrogenases (IDH) identified in young adult gliomas and provide a much-needed new pathway that can be targeted for therapeutic development. This review will provide an overview of the potential role of these mutations in altering chromatin structure and affecting specific molecular pathways ultimately leading to gliomagenesis. The distinct changes in chromatin structure and the specific downstream events induced by each mutation need characterizing independently if progress is to be made in tackling this devastating cancer. PMID:23432647

  11. Pediatric anklebot.

    PubMed

    Krebs, Hermano I; Rossi, Stefano; Kim, Seung-Jae; Artemiadis, Panagiotis K; Williams, Dustin; Castelli, Enrico; Cappa, Paolo

    2011-01-01

    In this paper we present the alpha-prototype of a novel pediatric ankle robot. This lower-extremity robotic therapy module was developed at MIT to aid recovery of ankle function in children with cerebral palsy ages 5 to 8 years old. This lower-extremity robotic module will commence pilot testing with children with cerebral palsy at Blythedale Childrens Hospital (Valhalla, NY), Bambino Gesu Children's Hospital (Rome, Italy), Riley Children's Hospital (Indianapolis, IN). Its design follows the same guidelines as our upper-extremity robots and adult anklebot designs, i.e. it is a low friction, backdriveable device with intrinsically low mechanical impedance. We show the ankle robot characteristics and stability range. We also present pilot data with healthy children to demonstrate the potential of this device. PMID:22275613

  12. Pediatric tracheomalacia.

    PubMed

    Fraga, Jose Carlos; Jennings, Russell W; Kim, Peter C W

    2016-06-01

    Tracheomalacia (TM) is defined as an increased collapsibility of the trachea due to structural anomalies of the tracheal cartilage and/or posterior membrane. Tracheomalacia has a wide range of etiologies but is most commonly present in children born with esophageal atresia and tracheal esophageal fistula. Clinical symptoms can range from minor expiratory stridor with typical barking cough to severe respiratory distress episodes to acute life-threatening events (ALTE). Although the majority of children have mild-to-moderate symptoms and will not need surgical intervention, some will need life-changing surgical treatment. This article examines the published pediatric literature on TM, discusses the details of clinical presentation, evaluation, diagnosis, and a variety of treatments. PMID:27301602

  13. Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project | Office of Cancer Genomics

    Cancer.gov

    TARGET researchers sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with activated kinase signaling, including Ph-like ALL, to establish the incidence of tyrosine kinase mutations in this cohort. The study confirmed previously identified somatic mutations in JAK and FLT3, but did not find novel alterations in any additional tyrosine kinases or downstream genes. The mechanism of kinase signaling activation in this high-risk subgroup of pediatric ALL remains largely unknown.

  14. Aggression in Drosophila.

    PubMed

    Kravitz, Edward A; Fernandez, Maria de la Paz

    2015-10-01

    Aggression is used by essentially all species of animals to gain access to desired resources, including territory, food, and potential mates: Fruit flies are no exception. In Drosophila, both males and females compete in same sex fights for resources, but only males establish hierarchical relationships. Many investigators now study aggression using the fruit fly model, mainly because (a) aggression in fruit flies is a quantifiable well-defined and easily evoked behavior; (b) powerful genetic methods allow investigators to manipulate genes of interest at any place or time during embryonic, larval, pupal or adult life, and while flies are behaving; (c) the growth of the relatively new field of optogenetics makes physiological studies possible at single neuron levels despite the small sizes of neurons and other types of cells in fly brains; and (d) the rearing of fly stocks with their short generation times and limited growth space requirements can easily be performed at relatively low cost in most laboratories. This review begins with an examination of the behavior, both from a historical perspective and then from the birth of the "modern" era of studies of aggression in fruit flies including its quantitative analysis. The review continues with examinations of the roles of genes, neurotransmitters and neurohormones, peptides, nutritional and metabolic status, and surface cuticular hydrocarbons in the initiation and maintenance of aggression. It concludes with suggestions for future studies with this important model system.

  15. Nuclear Medicine in Thyroid Diseases in Pediatric and Adolescent Patients

    PubMed Central

    Volkan-Salancı, Bilge; Özgen Kıratlı, Pınar

    2015-01-01

    Both benign and malignant diseases of the thyroid are rare in the pediatric and adolescent population, except congenital hypothyroidism. Nuclear medicine plays a major role, both in the diagnosis and therapy of thyroid pathologies. Use of radioactivity in pediatric population is strictly controlled due to possible side effects such as secondary cancers; therefore, management of pediatric patients requires detailed literature knowledge. This article aims to overview current algorithms in the management of thyroid diseases and use of radionuclide therapy in pediatric and adolescent population. PMID:26316469

  16. MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple negative MDA-MB-231 human breast cancer cells

    PubMed Central

    Browne, Gillian; Dragon, Julie A.; Hong, Deli; Messier, Terri L.; Gordon, Jonathan A. R.; Farina, Nicholas H.; Boyd, Joseph R.; VanOudenhove, Jennifer J.; Perez, Andrew W.; Zaidi, Sayyed K.; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.

    2016-01-01

    The Runx1 transcription factor, known for its essential role normal hematopoiesis, was reported in limited studies to be mutated or associated with human breast tumor tissues. Runx 1 increases concomitant with disease progression in the MMTV-PyMT transgenic mouse model of breast cancer. Compelling questions relate to mechanisms that regulate Runx1 expression in breast cancer. Here, we tested the hypothesis that dysregulation of Runx1-targeting microRNAs (miRNAs) allows for pathologic increase of Runx1 during breast cancer progression. Microarray profiling of the MMTV-PyMT model revealed significant down-regulation of numerous miRNAs predicted to target Runx1. One of these, miR-378, was inversely correlated with Runx1 expression during breast cancer progression in mouse, and in human breast cancer cell lines MCF7 and triple negative MDA-MB-231 that represent early and late stage disease, respectively. MiR-378 is nearly absent in MDA-MB-231 cells. Luciferase reporter assays revealed that miR-378 binds the Runx1 3′UTR and inhibits Runx1 expression. Functionally, we demonstrated that ectopic expression of miR-378 in MDA-MB-231 cells inhibited Runx1 and suppressed migration and invasion; while inhibition of miR-378 in MCF7 cells increased Runx1 levels and cell migration. Depletion of Runx1 in late stage breast cancer cells resulted in increased expression of both the miR-378 host gene PPARGC1B and pre-miR-378, suggesting a feedback loop. Taken together, our study identifies a novel and clinically relevant mechanism for regulation of Runx1 in breast cancer that is mediated by a PPARGC1B-miR-378-Runx1 regulatory pathway. Our results highlight the translational potential of miRNA replacement therapy for inhibiting Runx1 in breast cancer. PMID:26749280

  17. Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases

    PubMed Central

    dos Santos, Gilson Costa; de Souza Góes, Andréa Carla; de Vitto, Humberto; Moreira, Carla Cristina; Avvad, Elizabeth; Rumjanek, Franklin David; de Moura Gallo, Claudia Vitoria

    2012-01-01

    OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data. METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions. RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p = 0.0207). CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness. PMID:23070345

  18. Brief Assessment of Parents’ Attitudes Toward Testing Minor Children for Hereditary Breast/Ovarian Cancer Genes: Development and Validation of the Pediatric BRCA1/2 Testing Attitudes Scale (P-TAS)

    PubMed Central

    Peshkin, Beth N.; DeMarco, Tiffani A.; Garber, Judy E.; Valdimarsdottir, Heiddis B.; Patenaude, Andrea F.; Schneider, Katherine A.; Schwartz, Marc D.

    2009-01-01

    Objective Predictive genetic testing for hereditary breast/ovarian cancer risk (BRCA1/2 testing) is not recommended for minor children due to its lack of immediate medical benefit and potential psychological risk. Yet, tested mothers are often interested in learning about their children's cancer risks via pediatric BRCA1/2 testing, raising a host of bioethical concerns. However, no reliable or valid tool exists to formally gauge parents’ interest in such testing. The aim of this study was to develop and evaluate a new measure for use in genetic research and consultation, known as the Pediatric BRCA1/2 Testing Attitudes Scale (P-TAS). Methods After pretest genetic counseling and provision of a blood sample for BRCA1/2 testing, the P-TAS was administered to 187 mothers of children between 8- and 21-years-old. The measure was also given to 96 of the mothers’ nontested co-parents. Analyses of the factor structure and psychometric properties of the measure were performed in mothers and confirmed in their co-parents. Results The two factors of the P-TAS, labeled Attitudes and Beliefs (Factor 1) and Decision Making and Communication (Factor 2), accounted for 62.9% of the variance and were reliable (Cronbach's coefficient αs =.70 and.90, respectively); the structure and properties were largely confirmed among co-parents. Validity was indicated through its convergence with related constructs. Conclusions This new tool may be integrated into genetic counseling research to better assess parents’ attitudes and interests in pediatric BRCA1/2 testing. Such information may help guide ongoing discussions about the appropriateness of testing in adolescent or young adult children. PMID:18385162

  19. The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors

    NASA Astrophysics Data System (ADS)

    Moteabbed, Maryam; Yock, Torunn I.; Paganetti, Harald

    2014-06-01

    The incidence of second malignant tumors is a clinically observed adverse late effect of radiation therapy, especially in organs close to the treatment site, receiving medium to high doses (>2.5 Gy). For pediatric patients, choosing the least toxic radiation modality is of utmost importance, due to their high radiosensitivity and small size. This study aims to evaluate the risk of second cancer incidence in the vicinity of the primary radiation field, for pediatric patients with brain/head and neck tumors and compare four treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). For a cohort of six pediatric patients originally treated with PPT, additional PBS, IMRT and VMAT plans were created. Dose distributions from these plans were used to calculate the excess absolute risk (EAR) and lifetime attributable risk (LAR) for developing a second tumor in soft tissue and skull. A widely used risk assessment formalism was employed and compared with a linear model based on recent clinical findings. In general, LAR was found to range between 0.01%-2.8% for PPT/PBS and 0.04%-4.9% for IMRT/VMAT. PBS was associated with the lowest risk for most patients using carcinoma and sarcoma models, whereas IMRT and VMAT risks were comparable and the highest among all modalities. The LAR for IMRT/VMAT relative to PPT ranged from 1.3-4.6 for soft tissue and from 3.5-9.5 for skull. Larger absolute LAR was observed for younger patients and using linear risk models. The number of fields used in proton therapy and IMRT had minimal effect on the risk. When planning treatments and deciding on the treatment modality, the probability of second cancer incidence should be carefully examined and weighed against the possibility of developing acute side effects for each patient individually.

  20. The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors.

    PubMed

    Moteabbed, Maryam; Yock, Torunn I; Paganetti, Harald

    2014-06-21

    The incidence of second malignant tumors is a clinically observed adverse late effect of radiation therapy, especially in organs close to the treatment site, receiving medium to high doses (>2.5 Gy). For pediatric patients, choosing the least toxic radiation modality is of utmost importance, due to their high radiosensitivity and small size. This study aims to evaluate the risk of second cancer incidence in the vicinity of the primary radiation field, for pediatric patients with brain/head and neck tumors and compare four treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). For a cohort of six pediatric patients originally treated with PPT, additional PBS, IMRT and VMAT plans were created. Dose distributions from these plans were used to calculate the excess absolute risk (EAR) and lifetime attributable risk (LAR) for developing a second tumor in soft tissue and skull. A widely used risk assessment formalism was employed and compared with a linear model based on recent clinical findings. In general, LAR was found to range between 0.01%-2.8% for PPT/PBS and 0.04%-4.9% for IMRT/VMAT. PBS was associated with the lowest risk for most patients using carcinoma and sarcoma models, whereas IMRT and VMAT risks were comparable and the highest among all modalities. The LAR for IMRT/VMAT relative to PPT ranged from 1.3-4.6 for soft tissue and from 3.5-9.5 for skull. Larger absolute LAR was observed for younger patients and using linear risk models. The number of fields used in proton therapy and IMRT had minimal effect on the risk. When planning treatments and deciding on the treatment modality, the probability of second cancer incidence should be carefully examined and weighed against the possibility of developing acute side effects for each patient individually. PMID:24828559

  1. 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

  2. Find a Pediatric Dentist

    MedlinePlus

    ... Litch's Law Log HIPAA Forms Practice Management and Marketing Newsletter Webinar Materials Member Resources Membership Directory Awards ... Archives Access Pediatric Dentistry Today Practice Management and Marketing Newsletter Pediatric Dentistry Journal Open Access Articles Policies & ...

  3. Nuances in pediatric trauma.

    PubMed

    Kenefake, Mary Ella; Swarm, Matthew; Walthall, Jennifer

    2013-08-01

    Pediatric trauma evaluation mimics adult stabilization in that it is best accomplished with a focused and systematic approach. Attention to developmental differences, anatomic and physiologic nuances, and patterns of injury equip emergency physicians to stabilize and manage pediatric injury.

  4. 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.

  5. 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

  6. Strong Expression of Hypoxia-Inducible Factor-1α (HIF-1α) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer

    PubMed Central

    Nalwoga, Hawa; Ahmed, Lavina; Arnes, Jarle B.; Wabinga, Henry; Akslen, Lars A.

    2016-01-01

    Purpose Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1α and Axl influence tumor growth and metastatic potential, and they have been linked to treatment failure in many cancers. However, there is a lack of reports on HIF-1α expression in African breast cancer, which has a poor prognosis, and novel treatment targets must therefore be established. Here, we aimed to evaluate HIF-1α in relation to Axl expression, angiogenesis markers, and other tumor characteristics in a series of African breast cancer. Methods Using immunohistochemistry, we examined 261 invasive breast cancers on tissue microarrays for HIF-1α and Axl as well as several other markers, and a subset of 185 cases had information on VEGF (vascular endothelial growth factor) expression, microvessel density (MVD), proliferating microvessel density (pMVD) and vascular proliferation index (VPI) for important comparisons. Results Strong HIF-1α expression was associated with increased Axl (p = 0.007), VEGF (p<0.0005), and p53 (p = 0.032) expression, as well as high tumor cell proliferation by Ki-67 (p = 0.006), and high tumor grade (p = 0.003). Tumors with strong HIF-1α expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression. Conclusions High HIF-1α expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1α and Axl as potential therapeutic targets in African breast cancer. PMID:26760782

  7. Overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) correlates with cell aggressiveness and poor survival in gastric cancer.

    PubMed

    Meng, Qing-Bin; Kang, Wei-Ming; Yu, Jian-Chun; Liu, Yu-Qin; Ma, Zhi-Qiang; Zhou, Li; Cui, Quan-Cai; Zhou, Wei-Xun

    2015-01-01

    Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A

  8. Prostate Cancer Screening (Beyond the Basics)

    MedlinePlus

    ... complications of advanced disease. ● For men with an aggressive prostate cancer, the best chance for curing it ... body. However, many early-stage cancers are not aggressive, and the five-year survival will be nearly ...

  9. Aggressiveness and Disobedience

    ERIC Educational Resources Information Center

    Vaaland, Grete Sorensen; Idsoe, Thormod; Roland, Erling

    2011-01-01

    This study aims to conceptualize disobedient pupil behavior within the more general framework of antisocial behavior and to reveal how two forms of aggressiveness are related to disobedience. Disobedience, in the context of this article, covers disruptive pupil behavior or discipline problems when the pupil is aware of breaking a standard set by…

  10. Neuroimaging and Aggression.

    ERIC Educational Resources Information Center

    Mills, Shari; Raine, Adrian

    1994-01-01

    Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

  11. Intellectual Competence and Aggression.

    ERIC Educational Resources Information Center

    Huesmann, L. Rowell; Yarmel, Patty Warnick

    Using data from a broader longitudinal study, this investigation explores within-subject and cross-generational stability of intellectual competence and the relationship of such stability to aggressive behavior. Data were gathered three times (when subjects' modal age was 8, 19, and 30 years). Initially, subjects included the entire population…

  12. Stability of Aggressive Behavior.

    ERIC Educational Resources Information Center

    Eron, Leonard D.; Huesmann, L. Rowell

    As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…

  13. Relational Aggression among Students

    ERIC Educational Resources Information Center

    Young, Ellie L.; Nelson, David A.; Hottle, America B.; Warburton, Brittney; Young, Bryan K.

    2011-01-01

    "Relational aggression" refers to harm within relationships caused by covert bullying or manipulative behavior. Examples include isolating a youth from his or her group of friends (social exclusion), threatening to stop talking to a friend (the silent treatment), or spreading gossip and rumors by email. This type of bullying tends to be…

  14. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  15. Parents' Aggressive Influences and Children's Aggressive Problem Solutions with Peers

    ERIC Educational Resources Information Center

    Duman, Sarah; Margolin, Gayla

    2007-01-01

    This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with…

  16. Relational Aggression and Physical Aggression among Adolescent Cook Islands Students

    ERIC Educational Resources Information Center

    Page, Angela; Smith, Lisa F.

    2016-01-01

    Both physical and relational aggression are characterised by the intent to harm another. Physical aggression includes direct behaviours such as hitting or kicking; relational aggression involves behaviours designed to damage relationships, such as excluding others, spreading rumours, and delivering threats and verbal abuse. This study extended…

  17. Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species.

    PubMed

    Cheng, C-W; Kuo, C-Y; Fan, C-C; Fang, W-C; Jiang, S S; Lo, Y-K; Wang, T-Y; Kao, M-C; Lee, A Y-L

    2013-06-20

    Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial-mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally, in silico and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.

  18. Reverse Discrimination and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Johnson, Stephen D.

    1980-01-01

    White subjects were aggressive toward Black opponents when contest results appeared to reflect elements of reverse discrimination; but they showed less aggressive behavior toward Black opponents when they thought their loss was due to their opponents' superior ability. (RL)

  19. Pediatric obesity epidemic: treatment options.

    PubMed

    Kirk, Shelley; Scott, Barbara J; Daniels, Stephen R

    2005-05-01

    The increasing prevalence of overweight youth in the United States and the associated increase in medical comorbidities has created a growing need for effective weight-management interventions. The recommended treatment for an overweight child to achieve a more healthful weight uses four primary behavioral strategies: (a) reduce energy intake while maintaining optimal nutrient intake to protect growth and development, (b) increase energy expenditure by promoting more physical movement and less sedentary activity, (c) actively engage parents and primary caretakers as agents of change, and (d) facilitate a supportive family environment. Although this approach has the most empirical support, the impact on the pediatric obesity epidemic has been limited, particularly for adolescents with more severe obesity and for African-American, Native-American, and Hispanic children. This has prompted efforts to adapt strategies that have been effective in adult weight management for use in pediatric behavioral intervention programs. These include using motivational interviewing to increase readiness for health behavior changes, modifying the carbohydrate content of children's diets, using culturally appropriate messages and materials, improving cultural competency of health care providers, and using computer-based strategies. Randomized, controlled clinical trials are needed to test the safety and efficacy of these approaches before they can be recommended for clinical practice. Pharmacotherapy and bariatric surgery are more aggressive and historically adult interventions with greater risk that are being considered for severely obese adolescents who have serious obesity-related medical complications and who have failed other more conventional methods. PMID:15867895

  20. [Management of pediatric status epilepticus].

    PubMed

    Vargas L, Carmen Paz; Varela E, Ximena; Kleinsteuber S, Karin; Cortés Z, Rocío; Avaria B, María de Los Ángeles

    2016-01-01

    Pediatric Status Epilepticus (SE) is an emergency situation with high morbidity and mortality that requires early and aggressive management. The minimum time criterion to define SE was reduced from 30 to 5 minutes, defined as continuous seizure activity or rapidly recurrent seizures without resumption of consciousness for more than 5 minutes. This definition considers that seizures that persist for > 5 minutes are likely to do so for more than 30 min. Those that persist for more than 30 minutes are more difficult to treat. Refractory SE is the condition that extends beyond 60-120 minutes and requires anesthetic management. Super-refractory SE is the state of no response to anesthetic management or relapse during withdrawal of these drugs. The aim of this review is to provide and update on convulsive SE concepts, pathophysiology, etiology, available antiepileptic treatment and propose a rational management scheme. A literature search of articles published between January 1993 and January 2013, focused on pediatric population was performed. The evidence about management in children is limited, mostly corresponds to case series of patients grouped by diagnosis, mainly adults. These publications show treatment alternatives such as immunotherapy, ketogenic diet, surgery and hypothermia. A 35% mortality, 26% of neurological sequelae and 35% of recovery to baseline condition is described on patient’s evolution. PMID:26998986

  1. Lessons from the Past: Opportunities to Improve Childhood Cancer Survivor Care through Outcomes Investigations of Historical Therapeutic Approaches for Pediatric Hematological Malignancies

    PubMed Central

    Hudson, Melissa M.; Neglia, Joseph P.; Woods, William G.; Sandlund, John T.; Ching-Hon, Pui; Kun, Larry E.; Robison, Leslie L.; Green, Daniel M.

    2011-01-01

    Investigations of long-term outcomes have been instrumental in designing safer and more effective contemporary therapies for pediatric hematological malignancies. Despite the significant therapeutic changes that have occurred over the last five decades, therapy modifications largely represent refinements of treatment protocols using agents and modalities that have been available for more than 30 years. This review summarizes major trends in the evolution of treatment of pediatric hematological malignancies since 1960 to support the relevance of the study of late effects of historical therapeutic approaches to the design and evaluation of contemporary treatment protocols and the follow-up of present-day survivors. PMID:22038641

  2. "Ladettes," Social Representations, and Aggression.

    ERIC Educational Resources Information Center

    Muncer, Steven; Campbell, Anne; Jervis, Victoria; Lewis, Rachel

    2001-01-01

    Examined the relationship among "laddishness" (traditionally working-class, youthful, male social behavior by young women), social representations, and self-reported aggression among English college students. Measures of aggression correlated with holding more instrumental representations of aggression. Females indicated no relationship between…

  3. Resources for pediatric drug information.

    PubMed

    Zenk, K E

    1990-10-01

    Finding information on the use of drugs fro infants and children is becoming easier with the publication of excellent resources for pediatric and neonatal drug information. Useful pediatric texts and journals are listed. Texts are graded A and B. Category A books would be useful to include in a basic pharmacy library; Category B books are more comprehensive but expensive, or texts that are not as highly recommended as those in Category A. Some of the resources listed include: (1) Pediatrics--Nelson Textbook of Pediatrics, Rudolph's Pediatrics, Current Pediatric Diagnosis and Treatment, Manual of Pediatric Therapeutics; (2) Dosage Guides--The Pediatric Drug Handbook, Harriet Lane Handbook, Problems in Pediatric Drug THerapy; (3) Intensive Care--Textbook of Pediatric Intensive Care; (4) Infectious Disease--Report of the Committee on Infectious Diseases, Pocketbook of Pediatric Antimicrobial Therapy; (5) Poisoning--Handbook of Poisoning, Medical Toxicology; (6) Parenteral Nutrition--Manual of Pediatric Parenteral Nutrition; (7) Pregnancy and Lactation--Drugs in Pregnancy and Lactation; (8) Compounding--Handbook on Extemporaneous Formulation; (9) IV Administration--Guidelines for Administration of Intravenous Medications to Pediatric Patients; (1) Neonatology--Schaffers Diseases of the Newborn, Neonatology, Basic Management, On-Call Problems, Diseases, Drugs, Drug Therapy in Infants; (11) Pediatric Journals--Pediatrics, Journal of Pediatrics, American Journal of Diseases of Children, Pediatric Infectious Disease Journal, Pediatric Alert, Clinics in Perinatology, Pediatric Clinics of North America, Pediatric Clinical Oncology Journal, and Pediatric Surgery.

  4. Refeeding syndrome in hospitalized pediatric patients.

    PubMed

    Dunn, Rebecca L; Stettler, Nicolas; Mascarenhas, Maria R

    2003-08-01

    Refeeding syndrome has been well documented over the years, primarily through case reports and literature reviews. Awareness of refeeding syndrome is crucial in preventing the occurrence of, and the metabolic and physiologic complications associated with, aggressive nutrition support in malnourished populations. Once compromised patients have been identified to be at risk of refeeding syndrome, nutrition rehabilitation should be cautiously initiated. We have found a lack of clinical validation for instituting nutrition support in high-risk pediatric patients who may develop refeeding syndrome. The purposes of our investigation were to determine the incidence of refeeding syndrome in pediatric hospitalized patients beginning on parenteral nutrition and to determine how consistently the Department of Clinical Nutrition standards of care for screening and prevention were followed at our institution.

  5. Radiation-induced osteosarcomas in the pediatric population

    SciTech Connect

    Koshy, Matthew; Paulino, Arnold C. . E-mail: apaulino@tmh.tmc.edu; Mai, Wei Y.; Teh, Bin S.

    2005-11-15

    Purpose: Radiation-induced osteosarcomas (R-OS) have historically been high-grade, locally invasive tumors with a poor prognosis. The purpose of this study was to perform a comprehensive literature review and analysis of reported cases dealing with R-OS in the pediatric population to identify the characteristics, prognostic factors, optimal treatment modalities, and overall survival of these patients. Methods and Materials: A MEDLINE/PubMed search of articles written in the English language dealing with OSs occurring after radiotherapy (RT) in the pediatric population yielded 30 studies from 1981 to 2004. Eligibility criteria included patients <21 years of age at the diagnosis of the primary cancer, cases satisfying the modified Cahan criteria, and information on treatment outcome. Factors analyzed included the type of primary cancer treated with RT, the radiation dose and beam energy, the latency period between RT and the development of R-OS, and the treatment, follow-up, and final outcome of R-OS. Results: The series included 109 patients with a median age at the diagnosis of primary cancer of 6 years (range, 0.08-21 years). The most common tumors treated with RT were Ewing's sarcoma (23.9%), rhabdomyosarcoma (17.4%), retinoblastoma (12.8%), Hodgkin's disease (9.2%), brain tumor (8.3%), and Wilms' tumor (6.4%). The median radiation dose was 47 Gy (range, 15-145 Gy). The median latency period from RT to the development of R-OS was 100 months (range, 36-636 months). The median follow-up after diagnosis of R-OS was 18 months (1-172 months). The 3- and 5-year cause-specific survival rate was 43.6% and 42.2%, respectively, and the 3- and 5-year overall survival rate was 41.7% and 40.2%, respectively. Variables, including age at RT, primary site, type of tumor treated with RT, total radiation dose, and latency period did not have a significant effect on survival. The 5-year cause-specific and overall survival rate for patients who received treatment for R-OS involving

  6. Cancer immunotherapy in children

    Cancer.gov

    More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient

  7. Children's normative beliefs about aggression and aggressive behavior.

    PubMed

    Huesmann, L R; Guerra, N G

    1997-02-01

    Normative beliefs have been defined as self-regulating beliefs about the appropriateness of social behaviors. In 2 studies the authors revised their scale for assessing normative beliefs about aggression, found that it is reliable and valid for use with elementary school children, and investigated the longitudinal relation between normative beliefs about aggression and aggressive behavior in a large sample of elementary school children living in poor urban neighborhoods. Using data obtained in 2 waves of observations 1 year apart, the authors found that children tended to approve more of aggression as they grew older and that this increase appeared to be correlated with increases in aggressive behavior. More important, although individual differences in aggressive behavior predicted subsequent differences in normative beliefs in younger children, individual differences in aggressive behavior were predicted by preceding differences in normative beliefs in older children. PMID:9107008

  8. Aggressive drowsy cache cells

    NASA Astrophysics Data System (ADS)

    Shawkey, H. A.; El-Dib, D. A.; Abid, Z.

    2010-01-01

    An aggressive drowsy cache block management, where the cache block is forced into drowsy mode all the time except during write and read operations, is proposed. The word line (WL) is used to enable the normal supply voltage (V DD_high) to the cache line only when it is accessed for read or write whereas the drowsy supply voltage (V DD_low) is enabled to the cache cell otherwise. The proposed block management neither needs extra cycles nor extra control signals to wake the drowsy cache cell, thereby reducing the performance penalty associated with traditional drowsy caches. In fact, the proposed aggressive drowsy mode can reduce the total power consumption of the traditional drowsy mode by 13% or even more, depending on the cache access rate, access frequency and the CMOS technology used.

  9. [Aggressive fibromatoses in orthopedics].

    PubMed

    Adler, C P; Stock, D

    1986-01-01

    Aggressive fibromatoses which may develop either in soft tissue or in the bone present considerable problems for the pathologist trying to establish a diagnosis as well as for the radiologist and surgeon. In radiographs, a destruction of the soft and osseous tissue is seen which suggests a malignant tumor. Histologically a monomorphic connective tissue prevails in the biopsy showing no essential signs of malignancy. Under pathoanatomical aspects often a benign proliferation of the connective tissue is assumed. Surgically the tumor may either be removed in a too radical and mutilating way, or the excision may remain incomplete. Two cases of desmoplastic bone fibroma (aggressive fibromatosis in the ulna and in the sacrum) are described in which the complete tumor removal led to healing, whereas the incomplete excision of the tumor resulted in recurrences. Aggressive fibromatosis represents a semimalignant tumor which has a locally destructive and invasive growth tendency but does not metastasize. The various fibromatoses are defined with regard to their biological growth tendency and the therapeutic consequences are discussed.

  10. Frequent amplification of ORAOV1 gene in esophageal squamous cell cancer promotes an aggressive phenotype via proline metabolism and ROS production

    PubMed Central

    Togashi, Yosuke; Arao, Tokuzo; Kato, Hiroaki; Matsumoto, Kazuko; Terashima, Masato; Hayashi, Hidetoshi; de Velasco, Marco A; Fujita, Yoshihiko; Kimura, Hideharu; Yasuda, Takushi; Shiozaki, Hitoshi; Nishio, Kazuto

    2014-01-01

    Chromosomal band 11q13 seems to be one of the most frequently amplified lesions in human cancer, including esophageal squamous cell cancer (ESCC). The oral cancer overexpressed 1 (ORAOV1) gene has been identified within this region, but its detailed biological function in human ESCC remains largely unclear. In our clinical samples of stage III ESCC, ORAOV1 amplification was observed in 49 of 94 cases (53%). ORAOV1 amplification was significantly associated with a poorly differentiated histology and tumors located in the upper or middle esophagus. Patients with ORAOV1 amplification tended to have a shorter survival period, although the difference was not significant. To investigate the function of ORAOV1, we created ORAOV1-overexpressed ESCC cell lines that exhibited increased cellular proliferation and colony formation, compared with in vitro controls. In vivo, ORAOV1-overexpressed cells exhibited a significantly increased tumorigenicity and a significantly larger tumor volume and poorer differentiation than controls. The peptide mass fingerprinting technique demonstrated that ORAOV1 bound to pyrroline-5-carboxylate reductase (PYCR), which is associated with proline metabolism and reactive oxygen species (ROS) production. Then, ORAOV1-overexpressed cell lines were resistant to stress treatment, which was cancelled by PYCR-knockdown. In addition, the ORAOV1-overexpressed cell line had a higher intracellular proline concentration and a lower ROS level. Our findings indicate that the ORAOV1 gene is frequently amplified in ESCC, enhances tumorigenicity and tumor growth, and is associated with a poorly differentiated tumor histology via proline metabolism and ROS production. ORAOV1 could be a novel target for the treatment of ESCC. PMID:24930674

  11. Proteomic characterization of peroxisome proliferator-activated receptor-γ (PPARγ) overexpressing or silenced colorectal cancer cells unveils a novel protein network associated with an aggressive phenotype.

    PubMed

    Milone, Maria Rita; Pucci, Biagio; Colangelo, Tommaso; Lombardi, Rita; Iannelli, Federica; Colantuoni, Vittorio; Sabatino, Lina; Budillon, Alfredo

    2016-10-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor of the nuclear hormone receptor superfamily implicated in a wide range of processes, including tumorigenesis. Its role in colorectal cancer (CRC) is still debated; most reports support that PPARγ reduced expression is associated with poor prognosis. We employed 2-Dimensional Differential InGel Electrophoresis (2-D DIGE) followed by Liquid Chromatography (LC)-tandem Mass Spectrometry (MS/MS) to identify differentially expressed proteins and the molecular pathways underlying PPARγ expression in CRC progression. We identified several differentially expressed proteins in HT29 and HCT116 CRC cells and derived clones either silenced or overexpressing PPARγ, respectively. In Ingenuity Pathway Analysis (IPA) they showed reciprocal relation with PPARγ and a strong relationship with networks linked to cell death, growth and survival. Interestingly, five of the identified proteins, ezrin (EZR), isoform C of prelamin-A/C (LMNA), alpha-enolase (ENOA), prohibitin (PHB) and RuvB-like 2 (RUVBL2) were shared by the two cell models with opposite expression levels, suggesting a possible regulation by PPARγ. mRNA and western blot analysis were undertaken to obtain a technical validation and confirm the expression trend observed by 2-D DIGE data. We associated EZR upregulation with increased cell surface localization in PPARγ-overexpressing cells by flow cytometry and immunofluorescence staining. We also correlated EZR and PPARγ expression in our series of CRC specimens and the expression profiling of all five proteins levels in the publicly available colon cancer genomic data from Oncomine and Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) datasets. In summary, we identified a panel of proteins correlated with PPARγ expression that could be associated with CRC unveiling new pathways to be investigated for the selection of novel potential prognostic/predictive biomarkers and/or therapeutic

  12. Transitional care in pediatric urology.

    PubMed

    Lambert, Sarah M

    2015-04-01

    The transition from childhood to adolescence and into adulthood occurs as a natural component of human development. As children progress through school and gain independence, health care practitioners must facilitate a parallel transition from pediatric to adult providers. Modern medicine has succeeded in extending the life expectancy for many children with complex conditions, and adult providers are participating in their medical care through adulthood. Transitioning pediatric urology care to adult urology care is unique to every individual and his or her underlying condition, while the transition process is universal. The objectives of all pediatric urologists include preservation of the kidneys and lower urinary tracts, safe urine storage, safe urine drainage, urinary continence, fertility, sexual function, and genital cosmesis. For some children, these objectives can be attained during childhood, while other children require lifelong maintenance and management. Children with posterior urethral valves, exstrophy-epispadias complex, cloaca, vesicoureteral reflux, neurogenic bladder, disorders of sex development, cancer, hypospadias, nephrolithiasis, undescended testes, varicoceles, ureteropelvic junction obstruction, solitary kidney, and upper tract anomalies all require long-term evaluation and management. The obstacles of altering a patient and caregiver paradigm, locating adult urologists with special expertise, coordinating care with other adult specialties such as nephrology, and navigating the adult health care environment can impede the transition process.

  13. Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer

    PubMed Central

    Scorilas, A; Kyriakopoulou, L; Katsaros, D; Diamandis, E P

    2001-01-01

    By using the positional cloning gene approach, we were able to identify a novel gene encoding for a serine/arginine-rich protein, which appears to be the human homologue of the rat A1 gene. We named this new gene SR-A1. Members of the SR family of proteins have been shown to interact with the C-terminal domain (CTD) of the large subunit of RNA polymerase II and participate in pre-mRNA splicing. We have localized the SR-A1 gene between the known genes IRF3 and RRAS on chromosome 19q13.3. The novel gene spans 16.7 kb of genomic sequence and it is formed of 11 exons and 10 intervening introns. The SR-A1 protein is composed of 1312 amino acids, with a molecular mass of 139.3 kDa and a theoretical isoelectric point of 9.31. The SR-A1 protein contains an SR-rich domain as well as a CTD-binding domain present only in a subset of SR-proteins. Through interactions with the pre-mRNA and the CTD domain of the Polymerase II, SR proteins have been shown to regulate alternative splicing. The SR-A1 gene is expressed in all tissues tested, with highest levels found in fetal brain and fetal liver. Our data suggest that this gene is overexpressed in a subset of ovarian cancers which are clinically more aggressive. Studies with the steroid hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT-474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed. Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase by estrogens, androgens and glucocorticoids, and to a lesser extend by progestins. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11461075

  14. CCR9/CCL25 expression in non-small cell lung cancer correlates with aggressive disease and mediates key steps of metastasis

    PubMed Central

    Gupta, Pranav; Sharma, Praveen K.; Mir, Hina; Singh, Rajesh; Singh, Nalinaksha; Kloecker, Goetz H.; Lillard, James W.; Singh, Shailesh

    2014-01-01

    Poor clinical outcome of lung cancer (LuCa) is primarily due to lack of knowledge about specific molecules involved in its progression and metastasis. In this study, we for the first time show the clinical and biological significance of CC chemokine receptor-9 (CCR9) in non-small cell lung cancer (NSCLC). Expression of CCR9 and CCL25, the only natural ligand of CCR9, was significantly higher (p < 0.0001) in NSCLC tissues and serum respectively, compared to their respective controls. Interestingly, expression of both CCR9 and CCL25 was significantly higher in adenocarcinomas (ACs) compared to squamous cell carcinomas (SCCs) (p = 0.04, and p < 0.0001). Similar to tissues, AC and SCC cell lines were positive for CCR9 expression. Despite of marginal difference in CCR9 expression, AC cells showed higher migratory and invasive potential in response to CCL25, compared to SCC cells. This differential biological response of AC cells was primarily due to differential expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases under the influence of CCL25. Our results suggest CCR9 as a potential target for developing new treatment modality for NSCLC. Additionally, differential serum CCL25 level in ACs and SCCs, two NSCLC subtypes, suggest its potential as a non-invasive diagnostic/prognostic biomarker. PMID:25296976

  15. CCR9/CCL25 expression in non-small cell lung cancer correlates with aggressive disease and mediates key steps of metastasis.

    PubMed

    Gupta, Pranav; Sharma, Praveen K; Mir, Hina; Singh, Rajesh; Singh, Nalinaksha; Kloecker, Goetz H; Lillard, James W; Singh, Shailesh

    2014-10-30

    Poor clinical outcome of lung cancer (LuCa) is primarily due to lack of knowledge about specific molecules involved in its progression and metastasis. In this study, we for the first time show the clinical and biological significance of CC chemokine receptor-9 (CCR9) in non-small cell lung cancer (NSCLC). Expression of CCR9 and CCL25, the only natural ligand of CCR9, was significantly higher (p<0.0001) in NSCLC tissues and serum respectively, compared to their respective controls. Interestingly, expression of both CCR9 and CCL25 was significantly higher in adenocarcinomas (ACs) compared to squamous cell carcinomas (SCCs) (p = 0.04, and p< 0.0001). Similar to tissues, AC and SCC cell lines were positive for CCR9 expression. Despite of marginal difference in CCR9 expression, AC cells showed higher migratory and invasive potential in response to CCL25, compared to SCC cells. This differential biological response of AC cells was primarily due to differential expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases under the influence of CCL25. Our results suggest CCR9 as a potential target for developing new treatment modality for NSCLC. Additionally, differential serum CCL25 level in ACs and SCCs, two NSCLC subtypes, suggest its potential as a non-invasive diagnostic/prognostic biomarker.

  16. Quantitative Analysis of Prostate Multiparametric MR Images for Detection of Aggressive Prostate Cancer in the Peripheral Zone: A Multiple Imager Study.

    PubMed

    Hoang Dinh, Au; Melodelima, Christelle; Souchon, Rémi; Lehaire, Jérôme; Bratan, Flavie; Mège-Lechevallier, Florence; Ruffion, Alain; Crouzet, Sébastien; Colombel, Marc; Rouvière, Olivier

    2016-07-01

    Purpose To assess the intermanufacturer variability of quantitative models in discriminating cancers with a Gleason score of at least 7 among peripheral zone (PZ) lesions seen at 3-T multiparametric magnetic resonance (MR) imaging. Materials and Methods An institutional review board-approved prospective database of 257 patients who gave written consent and underwent T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging before prostatectomy was retrospectively reviewed. It contained outlined lesions found to be suspicious for malignancy by two independent radiologists and classified as malignant or benign after correlation with prostatectomy whole-mount specimens. One hundred six patients who underwent imaging with 3-T MR systems from two manufacturers were selected (data set A, n = 72; data set B, n = 34). Eleven parameters were calculated in PZ lesions: normalized T2-weighted signal intensity, skewness and kurtosis of T2-weighted signal intensity, T2 value, wash-in rate, washout rate, time to peak (TTP), mean apparent diffusion coefficient (ADC), 10th percentile of the ADC, and skewness and kurtosis of the histogram of the ADC values. Parameters were selected on the basis of their specificity for a sensitivity of 0.95 in diagnosing cancers with a Gleason score of at least 7, and the area under the receiver operating characteristic curve (AUC) for the models was calculated. Results The model of the 10th percentile of the ADC with TTP yielded the highest AUC in both data sets. In data set A, the AUC was 0.90 (95% confidence interval [CI]: 0.85, 0.95) or 0.89 (95% CI: 0.82, 0.94) when it was trained in data set A or B, respectively. In data set B, the AUC was 0.84 (95% CI: 0.74, 0.94) or 0.86 (95% CI: 0.76, 0.95) when it was trained in data set A or B, respectively. No third variable added significantly independent information in any data set. Conclusion The model of the 10th percentile of the ADC with TTP yielded accurate results in

  17. Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

    PubMed Central

    2010-01-01

    significantly correlated with positive Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters. The presence of CTC in peripheral blood was significantly associated with methylated APC (p = 0.012) and methylated GSTP1 (p = 0.001). Conclusion The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients. Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease. PMID:20696638

  18. Does Aggressive Surgery Improve Outcomes? Interaction Between Preoperative Disease Burden and Complex Surgery in Patients With Advanced-Stage Ovarian Cancer: An Analysis of GOG 182

    PubMed Central

    Horowitz, Neil S.; Miller, Austin; Rungruang, Bunja; Richard, Scott D.; Rodriguez, Noah; Bookman, Michael A.; Hamilton, Chad A.; Krivak, Thomas C.; Maxwell, G. Larry

    2015-01-01

    Purpose To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction. Patients and Methods Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis. Results Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS. Conclusion In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD. PMID:25667285

  19. Challenging issues in pediatric oncology

    PubMed Central

    Pui, Ching-Hon; Gajjar, Amar J.; Kane, Javier R.; Qaddoumi, Ibrahim A.; Pappo, Alberto S.

    2011-01-01

    Improvements in protocol-driven clinical trials and supportive care for children and adolescents with cancer have reduced mortality rates by more than 50% over the past three decades. Overall, the 5-year survival rate for pediatric cancer patients has increased to approximately 80%. Recognition of the biological heterogeneity within specific subtypes of cancer, the discovery of genetic lesions that drive malignant transformation and cancer progression, and improved understanding of the basis of drug resistance will undoubtedly catalyze further advances in risk-directed treatments and the development of targeted therapies, boosting the cure rates further. Emerging new treatments include novel formulations of existing chemotherapeutic agents, monoclonal antibodies against cancer-associated antigens, and molecular therapies that target genetic lesions and their associated signaling pathways. Recent findings that link pharmacogenomic variations with drug exposure, adverse effects, and efficacy should accelerate efforts to develop personalized therapy for individual patients. Finally, palliative care should be included as an essential part of cancer management to prevent and relieve the suffering and to improve the quality of life of patients and their families. PMID:21709698

  20. Pediatric facial nerve rehabilitation.

    PubMed

    Banks, Caroline A; Hadlock, Tessa A

    2014-11-01

    Facial paralysis is a rare but severe condition in the pediatric population. Impaired facial movement has multiple causes and varied presentations, therefore individualized treatment plans are essential for optimal results. Advances in facial reanimation over the past 4 decades have given rise to new treatments designed to restore balance and function in pediatric patients with facial paralysis. This article provides a comprehensive review of pediatric facial rehabilitation and describes a zone-based approach to assessment and treatment of impaired facial movement.

  1. Pediatric Hand Injuries.

    PubMed

    Sullivan, Matthew A; Cogan, Charles J; Adkinson, Joshua M

    2016-01-01

    Pediatric hand injuries are extremely common. Although many hand injuries are adequately managed in the emergency department, some may need evaluation and treatment by a pediatric hand surgeon to ensure a good functional outcome. This article discusses the diagnosis and management of the most common pediatric hand maladies: fingertip injuries/amputation, tendon injuries, and phalangeal and metacarpal fractures. The plastic surgery nurse should be familiar with hand injuries that require intervention to facilitate efficient management and optimal postoperative care. PMID:27606586

  2. Assessment of Financial Burden as a Standard of Care in Pediatric Oncology.

    PubMed

    Pelletier, Wendy; Bona, Kira

    2015-12-01

    Family financial hardship has emerged as a burden of pediatric cancer treatment with negative implications for family well-being. As part of an extensive project to create evidence-based standards for the psychosocial care of children with cancer, we performed a literature review of pediatric cancer-associated financial hardship utilizing six databases, and identified 24 publications for incorporation into this review. Financial hardship during childhood cancer was found to affect a significant proportion of the population and to negatively impact family well-being. Existing literature supports a strong recommendation for assessment of financial hardship as a component of comprehensive psychosocial care in pediatric oncology.

  3. Girls, aggression, and emotion regulation.

    PubMed

    Conway, Anne M

    2005-04-01

    Many studies have demonstrated that boys are more aggressive than girls (see J. D. Coie & K. Dodge, 1997, for a review) and that emotion regulation difficulties are associated with problematic behaviors (N. Eisenberg & R. A. Fabes, 1999; M. Gilliom, D. S. Shaw, J. E. Beck, M. A. Schonberg, & J. L. Lukon, 2002). However, recent findings indicate that gender differences in aggressive behaviors disappear when assessments are broadened to include relational aggression--behaviors designed to harm the relationship goals of others by spreading rumors, gossiping, and eliciting peer rejection of others. Moreover, although difficulties regulating emotions have been reported for physically aggressive children, little research has examined these processes in relationally aggressive children. This article argues that investigation into the associations between emotion regulation and relational aggression is a critical direction for future research on the etiology and prevention of mental health problems in girls. PMID:15839769

  4. [The aggressive child (author's transl)].

    PubMed

    Harbauer, H

    1978-08-01

    In children a "normal" aggressiveness should be distinguished from "hostile" and "inhibited" aggression; the latter usually become apparent as heteroaggressive or autoaggressive behaviour. Autoaggression is more common with younger children. Different hypotheses about the origin of aggressiveness are discussed. In the younger child nail biting, trichotillomania, rocking, an intensified phase of contrariness and enkopresis may have components of aggressiveness. In older children and adolescents dissocial forms of development, drug taking, attempted suicid, and anorexia nervosa may be parts of aggressive behaviour. Minimal brain dysfunction, autism, and postencephalitic syndromes predominate amongst organic alterations of the brain as causes for aggressive behaviour. Particularly the Lesch-Nyhan-syndrome, but equally the Cornelia de Lange-syndrome show autoaggressive tendencies.

  5. VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer.

    PubMed

    Goel, Hira Lal; Chang, Cheng; Pursell, Bryan; Leav, Irwin; Lyle, Stephen; Xi, Hualin Simon; Hsieh, Chung-Cheng; Adisetiyo, Helty; Roy-Burman, Pradip; Coleman, Ilsa M; Nelson, Peter S; Vessella, Robert L; Davis, Roger J; Plymate, Stephen R; Mercurio, Arthur M

    2012-10-01

    We show that the VEGF receptor neuropilin-2 (NRP2) is associated with high-grade, PTEN-null prostate cancer and that its expression in tumor cells is induced by PTEN loss as a consequence of c-Jun activation. VEGF/NRP2 signaling represses insulin-like growth factor-1 receptor (IGF-IR) expression and signaling, and the mechanism involves Bmi-1-mediated transcriptional repression of the IGF-IR. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-IR therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-IR. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-IR signaling. Inhibition of both NRP2 and IGF-IR, however, completely blocks tumor growth in vivo.

  6. Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: potential role in therapy.

    PubMed

    Shimizu, Tomohiro; Torres, María P; Chakraborty, Subhankar; Souchek, Joshua J; Rachagani, Satyanarayana; Kaur, Sukhwinder; Macha, Muzafar; Ganti, Apar K; Hauke, Ralph J; Batra, Surinder K

    2013-08-19

    There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum ("Holy Basil") has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future. PMID:23523869

  7. Aggressive fibromatosis of anterior maxilla

    PubMed Central

    Shetty, Devi C; Urs, Aadithya B; Ahuja, Puneet; Sikka, Seema

    2011-01-01

    Aggressive fibromatosis is a comparitively rare tumor with unpredictable growth and varying local recurrence rates. It does not develop distant metastases but locally it shows an aggressive and infiltrative behavior. Clinically, aggressive fibromatosis manifests as a painless, firm, often rapidly enlarging mass, fixed to underlying bone or soft tissue. It is never encapsulated. Histologically, it is rich in collagen and fibroblastic cells that are devoid of hyperchromatic or atypical nuclei, but with more variable cellularity in different tumor sections. PMID:21731285

  8. Palliative Care as a Standard of Care in Pediatric Oncology.

    PubMed

    Weaver, Meaghann S; Heinze, Katherine E; Kelly, Katherine P; Wiener, Lori; Casey, Robert L; Bell, Cynthia J; Wolfe, Joanne; Garee, Amy M; Watson, Anne; Hinds, Pamela S

    2015-12-01

    The study team conducted a systematic review of pediatric and adolescent palliative cancer care literature from 1995 to 2015 using four databases to inform development of a palliative care psychosocial standard. A total of 209 papers were reviewed with inclusion of 73 papers for final synthesis. Revealed topics of urgent consideration include the following: symptom assessment and intervention, direct patient report, effective communication, and shared decision-making. Standardization of palliative care assessments and interventions in pediatric oncology has the potential to foster improved quality of care across the cancer trajectory for children and adolescents with cancer and their family members.

  9. Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients

    PubMed Central

    Alford, Elizabeth L.; Wheless, James W.

    2015-01-01

    Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients. PMID:26380568

  10. Imaging features of Burkitt lymphoma in pediatric patients

    PubMed Central

    Derinkuyu, Betül Emine; Boyunağa, Öznur; Öztunalı, Çiğdem; Tekkeşin, Funda; Damar, Çağrı; Alımlı, Ayşe Gül; Okur, Arzu

    2016-01-01

    Burkitt lymphoma is an aggressive and rapidly growing tumor that is curable and highly sensitive to chemotherapy. It can affect almost every tissue in the body, producing various clinical presentations and imaging appearances, according to the predilection of the different subtypes for certain sites. Awareness of its diagnostically specific imaging appearances plays an important role in rapid detection and treatment. In this pictorial review, we aimed to identify the most common imaging features of Burkitt lymphoma in pediatric patients. PMID:26611257

  11. Rethinking Aggression: A Typological Examination of the Functions of Aggression.

    ERIC Educational Resources Information Center

    Little, Todd D.; Brauner, Jessica; Jones, Stephanie M.; Nock, Matthew K.; Hawley, Patricia H.

    2003-01-01

    Compared five subgroups of aggressive children and adolescents on several adjustment correlates. Found that the reactive group and the group high on both instrumental and reactive reasons for aggression showed consistent maladaptive patterns across the adjustment correlates. The instrumental and typical groups (moderate on instrumental and…

  12. Pediatric mania: a developmental subtype of bipolar disorder?

    PubMed

    Biederman, J; Mick, E; Faraone, S V; Spencer, T; Wilens, T E; Wozniak, J

    2000-09-15

    Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards.

  13. Pediatric Endocrinology Nurses Society

    MedlinePlus

    ... for PENS Minneapolis 2017! Wednesday, April 26, 2017 ​​​​​​​​​​​​​​​​​​​​​​​​​​​ Journal of Pediatric Nursing The Journal of Pediatric Nursing provides original, peer-reviewed research ...

  14. Pediatric Salivary Gland Malignancies.

    PubMed

    Ord, Robert A; Carlson, Eric R

    2016-02-01

    Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children.

  15. Pediatric Odontogenic Tumors.

    PubMed

    Abrahams, Joshua M; McClure, Shawn A

    2016-02-01

    Pediatric odontogenic tumors are rare, and are often associated with impacted teeth. Although they can develop anywhere in the jaws, odontogenic tumors mainly occur in the posterior mandible. This article discusses the diagnosis and treatment of the most common pediatric odontogenic tumors, such as ameloblastoma, keratocystic odontogenic tumor, odontoma, and cementoblastoma.

  16. Teaching Prevention in Pediatrics.

    ERIC Educational Resources Information Center

    Cheng, Tina L.; Greenberg, Larrie; Loeser, Helen; Keller, David

    2000-01-01

    Reviews methods of teaching preventive medicine in pediatrics and highlights innovative programs. Methods of teaching prevention in pediatrics include patient interactions, self-directed learning, case-based learning, small-group learning, standardized patients, computer-assisted instruction, the Internet, student-centered learning, and lectures.…

  17. [Research in pediatrics].

    PubMed

    Herrera-Márquez, Julia Rocío; González-Cabello, Héctor Jaime

    2015-01-01

    In the interest of encouraging the promotion of research done by physicians of the Instituto Mexicano del Seguro Social, in this supplement we publish articles written by residents of different specialties related to critical themes on pediatrics. These residents are guided by affiliated physicians from the Hospital de Pediatría del Centro Médico Nacional Siglo XXI.

  18. THE IMPACT OF AGGRESSION IN THE CLASSROOM.

    ERIC Educational Resources Information Center

    MCNEIL, ELTON B.; AND OTHERS

    IN THIS INVESTIGATION, AGGRESSION WAS MEASURED FROM FOUR PERSPECTIVES--(1) THE PERCEPTION THAT THE SUBJECT HAD OF HIS AGGRESSION, (2) HIS SATISFACTION, AS HE VIEWED IT, WITH HIS OWN AGGRESSION, (3) THE PERCEPTION THAT THE TEACHER HAD OF THE SUBJECT'S AGGRESSIVENESS, AND (4) THE PERCEPTION OF THE SUBJECT'S AGGRESSIVENESS HELD BY HIS CLASSMATES. IN…

  19. The Effects of Pornography on Aggressive Behavior.

    ERIC Educational Resources Information Center

    Stacy, Lauri L.

    This document reviews existing empirical research on the effect of pornography on aggressive behavior. Two types of pornography are distinguished: aggressive pornography and non-aggressive pornography. Conclusions drawn from the research review are presented, including: (1) aggressive pornograpy consistently increases aggressive attitudes and…

  20. Psychological Research on Human Aggressiveness

    ERIC Educational Resources Information Center

    Hamburg, D. A.; Brodie, H. K. H.

    1973-01-01

    Discusses research relating to the effects of hormones, neurophysiology, and the environment on animal and human aggression. Indicates that the interactions of biological, psychological and social processes in the development of human aggressiveness should constitute one of the principal frontiers for science in the next two decades. (JR)