Bassel Nazha, Cengiz Inal, Taofeek K Owonikoko
Gangliosides are carbohydrate-containing sphingolipids that are widely expressed in normal tissues, making most subtypes unsuitable as targets for cancer therapy. However, the disialoganglioside GD2 subtype has limited expression in normal tissues but is overexpressed across a wide range of tumors. Disialoganglioside GD2 can be considered a tumor-associated antigen and well-suited as a target for cancer therapy. Disialoganglioside GD2 is implicated in tumor development and malignant phenotypes through enhanced cell proliferation, motility, migration, adhesion, and invasion, depending on the tumor type...
2020: Frontiers in Oncology
Maria El Kababri, Sarra Benmiloud, Siham Cherkaoui, Jamila El Houdzi, Khadija Maani, Nawal Ansari, Nissrine Khoubila, Amina Kili, Mohammed El Khorassani, Abdellah Madani, Mohammed Adnane Tazi, Samir Ahid, Laila Hessissen, Asmaa Quessar, Mhamed Harif, Mohammed Khattab, Nicolas André
BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies...
July 13, 2020: Pediatric Blood & Cancer
Maria Łastowska, Joanna Trubicka, Anna Sobocińska, Bartosz Wojtas, Magdalena Niemira, Anna Szałkowska, Adam Krętowski, Agnieszka Karkucińska-Więckowska, Magdalena Kaleta, Maria Ejmont, Marta Perek-Polnik, Bożenna Dembowska-Bagińska, Wiesława Grajkowska, Ewa Matyja
Four molecular types of rare central nervous system (CNS) tumors have been recently identified by gene methylation profiling: CNS Neuroblastoma with FOXR2 activation (CNS NB-FOXR2), CNS Ewing Sarcoma Family Tumor with CIC alteration (CNS EFT-CIC), CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) and CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Although they are not represented in 2016 updated WHO classification of CNS tumors, their diagnostic recognition is important because of clinical consequences...
July 10, 2020: Acta Neuropathologica Communications
Loredana Amoroso, Victoria Castel, Gianni Bisogno, Michela Casanova, Catalina Marquez-Vega, Julia C Chisholm, François Doz, Lucas Moreno, Antonio Ruggiero, Nicolas U Gerber, Franca Fagioli, Pooja Hingorani, Soledad G Melcón, Ruta Slepetis, Nianhang Chen, Yvan le Bruchec, Mathew Simcock, Gilles Vassal
BACKGROUND: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study. PATIENTS AND METHODS: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m2 of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle...
June 15, 2020: European Journal of Cancer
Ardine M J Reedijk, Leontien C Kremer, Otto Visser, Valery Lemmens, Rob Pieters, Jan Willem W Coebergh, Henrike E Karim-Kos
BACKGROUND: This is the first national study on trends in cancer incidence for children and young adolescents in the Netherlands, including stage at diagnosis as a potential marker of early diagnosis and better staging. METHODS: All neoplasms in patients younger than 18 years, diagnosed between 1990 and 2017 (N = 15,233), were derived from the Netherlands Cancer Registry. Incidence rates and the average annual percentage change with 95% CIs were calculated for all cancers combined and diagnostic (sub)groups...
June 7, 2020: European Journal of Cancer
Nikki Phanhthilath, Sara Hakim, Catherine Su, Andrea Liu, Divya Subramonian, Jacqueline Lesperance, Peter E Zage
Children with aggressive pediatric solid tumors have poor outcomes and novel treatments are needed. Pediatric solid tumors demonstrate aberrant expression and activity of the fibroblast growth factor receptor (FGFR) family, suggesting FGFR inhibitors may be effective therapeutic agents. AZD4547 is a multikinase inhibitor of the FGFR1-3 kinases, and we hypothesized that AZD4547 would be effective in pediatric solid tumor preclinical models. We evaluated the effects of AZD4547 on neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma cells alone and in combination with STAT3 inhibition...
May 20, 2020: Investigational New Drugs
Olga Zajac-Spychala, Jacek Wachowiak, Olga Gryniewicz-Kwiatkowska, Aneta Gietka, Bozenna Dembowska-Baginska, Katarzyna Semczuk, Katarzyna Dzierzanowska-Fangrat, Krzysztof Czyzewski, Magdalena Dziedzic, Mariusz Wysocki, Patrycja Zalas-Wiecek, Anna Szmydki-Baran, Lukasz Hutnik, Michal Matysiak, Filip Pierlejewski, Wojciech Mlynarski, Zofia Małas, Wanda Badowska, Ninela Irga-Jaworska, Ewa Bien, Elzbieta Drozynska, Magdalena Bartnik, Tomasz Ociepa, Tomasz Urasiński, Pawel Wawrykow, Jaroslaw Peregud-Pogorzelski, Weronika Stolpa, Grazyna Sobol-Milejska, Jowita Fraczkiewicz, Malgorzata Salamonowicz, Bernarda Kazanowska, Alicja Chybicka, Liliana Chelmecka-Wiktorczyk, Walentyna Balwierz, Iwona Zak, Zuzanna Gamrot-Pyka, Mariola Woszczyk, Renata Tomaszewska, Tomasz Szczepanski, Marcin Plonowski, Maryna Krawczuk-Rybak, Agnieszka Urbanek-Dadela, Grazyna Karolczyk, Jakub Musial, Radoslaw Chaber, Jerzy Kowalczyk, Jan Styczynski
Background: Infectious complications (IC) caused by bacterial strains often impede anticancer therapy. The study aimed to retrospectively analyze bacterial IC that could help predict the risk and optimize the empirical treatment for bacterial infections in pediatric cancer patients. Patients and Methods: Over a 72-month period, all-in 5,599 children with cancer: 2,441 patients with hematological malignancy (HM including acute leukemias, Hodgkin and non-Hodgkin lymphomas [NHLs], and Langerhans cell histiocytosis) and 3,158 with solid tumors (STs including central nervous system tumors, neuroblastoma, Wilms' tumor, soft tissue sarcoma, germ cell tumors, Ewing sarcoma, osteosarcoma, hepatoblastoma, and others) were enrolled into the study...
May 20, 2020: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Özlem Tezol, Fatih Sağcan, Pınar Pelin Özcan, Elvan Çağlar Çıtak
BACKGROUND AND OBJECTIVES: The comparison of Positron emission tomography- computed tomography (PETCT) and bone marrow biopsy (BMB) modalities in detecting bone marrow disease is an up to date research topic. In this study, we aimed to compare the results of PET-CT and BMB procedures in detecting bone marrow involvement in pediatric malignancies. METHOD: At the time of diagnosis, PET-CT imaging and BMB performed patients` data were evaluated, retrospectively. Malign diagnoses were Hodgkin's lymphoma in 23 (30...
2020: Turkish Journal of Pediatrics
Jacob Pfeil, Lauren M Sanders, Ioannis Anastopoulos, A Geoffrey Lyle, Alana S Weinstein, Yuanqing Xue, Andrew Blair, Holly C Beale, Alex Lee, Stanley G Leung, Phuong T Dinh, Avanthi Tayi Shah, Marcus R Breese, W Patrick Devine, Isabel Bjork, Sofie R Salama, E Alejandro Sweet-Cordero, David Haussler, Olena Morozova Vaske
Precision oncology has primarily relied on coding mutations as biomarkers of response to therapies. While transcriptome analysis can provide valuable information, incorporation into workflows has been difficult. For example, the relative rather than absolute gene expression level needs to be considered, requiring differential expression analysis across samples. However, expression programs related to the cell-of-origin and tumor microenvironment effects confound the search for cancer-specific expression changes...
April 10, 2020: PLoS Computational Biology
Mehmet Azizoglu, Ugur Demirsoy, Ibrahim Kulac, Safiye Aktas, Funda Çorapcioglu
Background: Although neuroblastoma and Ewing sarcoma/Primitive neuroectodermal tumor are different clinical entities, they are both a member of small round blue cell tumors and can mimic each other's behavior in clinical and molecular aspects. Case report: A 3 year-old girl with an abdominal mass was found to have a small round blue cell tumor originating from the right adrenal gland. High level of neuron specific enolase, initial genetic test results (N-Myc amplification: negative, loss of 1p, 11q, and unbalanced gain of 17q) and characteristic radiological appearance of the tumor suggested a preliminary diagnosis of neuroblastoma but further analysis showed CD99 expression and presence of EWSR1 rearrangement, which are mostly observed in Ewing sarcoma...
April 3, 2020: Fetal and Pediatric Pathology
Kara L Davis, Elizabeth Fox, Melinda S Merchant, Joel M Reid, Rachel A Kudgus, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall
BACKGROUND: Immune checkpoint inhibitors targeting PD-1 have shown clinical benefit in adults with cancer, but data on these drugs in children are scarce. We did a phase 1-2 study of nivolumab, a PD-1 blocking monoclonal antibody, to determine its safety, pharmacokinetics, and antitumour activity in children and young adults with recurrent or refractory non-CNS solid tumours or lymphoma. METHODS: We did a multicentre, open-label, single-arm, dose-confirmation and dose-expansion, phase 1-2 trial in 23 hospitals in the USA...
April 2020: Lancet Oncology
Dominik Karres, Sahra Ali, Paula B van Hennik, Sabine Straus, Filip Josephson, Geanne Thole, Pieter J Glerum, Carla Herberts, Negar Babae, Ralf Herold, Irene Papadouli, Francesco Pignatti
On March 28, 2019, the Committee for Medicinal Products for Human Use adopted a positive opinion recommending the marketing authorization for the medicinal product plerixafor. The marketing authorization holder for this medicinal product is Genzyme Europe B.Th. The adoption was for an extension of the existing adult indication in combination with granulocyte colony-stimulating factor (G-CSF) to pediatric patients (aged 1 year to <18 years) to enhance mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in children with lymphoma or solid malignant tumors...
March 10, 2020: Oncologist
Sarah Kehr, Tinka Haydn, Annika Bierbrauer, Barnabas Irmer, Meike Vogler, Simone Fulda
With the development of potent and selective inhibitors of MCL-1 (S63845) and BCL-XL (A-1331852) novel cancer treatment options have emerged. BCL-2 family proteins are important regulators of apoptosis in pediatric solid tumors. In the current study, we discover that rhabdomyosarcoma, Ewing sarcoma, osteosarcoma and neuroblastoma cell lines are co-dependent on BCL-XL and MCL-1 for survival. A-1331852/S63845 co-treatment, but not combinations of either inhibitor with ABT-199, synergistically induces rapid intrinsic apoptosis in vitro and demonstrates efficiency in an in vivo embryonic chicken model of rhabdomyosarcoma...
March 4, 2020: Cancer Letters
Takashi Suzuki
Outcomes of treatment for malignant pediatric tumors including leukemia are improving by conventional multimodal treatment with strong chemotherapy, surgical resection, radiotherapy, and bone marrow transplantation. However, patients with advanced neuroblastoma, metastatic Ewing's sarcoma family of tumor (ESFT), and metastatic osteosarcoma continue to have an extremely poor prognosis. Therefore novel therapeutic strategies are urgently needed to improve their survival. Apoptotic cell death is a key mechanism for normal cellular homeostasis...
2020: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Francesco Cicone, Thibaut Denoël, Silvano Gnesin, Nicolo Riggi, Melita Irving, Gopinadh Jakka, Niklaus Schaefer, David Viertl, George Coukos, John O Prior
PURPOSE: Endosialin/tumor endothelial marker-1 (TEM1) is an attractive theranostic target expressed by the microenvironment of a wide range of tumors, as well as by sarcoma and neuroblastoma cells. We report on the radiolabeling and preclinical evaluation of the scFv78-Fc, a fully human TEM1-targeting antibody fragment cross-reactive with mouse TEM1. PROCEDURES: The scFv78-Fc was conjugated with the chelator p-SCN-Bn-CHX-A"-DTPA, followed by labeling with indium-111...
January 28, 2020: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Kristina A Cole, Sharmistha Pal, Rachel A Kudgus, Heba Ijaz, Xiaowei Liu, Charles G Minard, Bruce R Pawel, John M Maris, Daphne A Haas-Kogan, Stephan D Voss, Stacey L Berg, Joel M Reid, Elizabeth Fox, Brenda J Weigel
PURPOSE: Adavosertib (AZD1775), an inhibitor of WEE1 kinase, potentiates replicative stress induced by oncogenes or chemotherapy. Anti-tumor activity of adavosertib has been demonstrated in preclinical models of pediatric cancer. This phase I trial was performed to define dose-limiting toxicities (DLT), recommended phase 2 dose (RP2D) and pharmacokinetics of adavosertib in combination with irinotecan in children and adolescents with relapsed or refractory solid tumors or primary central nervous system tumors...
December 19, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ekrem Ünal, Ebru Yilmaz, Alper Özcan, Bilgen Işik, Musa Karakükcü, Cüneyt Turan, Hülya Akgün, Figen Öztürk, Abdulhakim Coşkun, Mehmet Akif Özdemir, Türkan Patiroğlu
BACKGROUND/AIM: Non Wilms renal tumors (NWRT) are rarely encountered in children. The aim of this study is to determine the treatment strategies, prognosis, outcomes and survival of children with NWRT at Erciyes University, Kayseri Materials and methods: Medical records of all patients (n=20) treated for NWRT over a 23-years period (1995-2018) were reviewed retrospectively. RESULTS: There was male predominance (female/male: 7/13); median age at the diagnosis was 3...
October 27, 2019: Turkish Journal of Medical Sciences
Katrin Sak
Over the past decades, studies of phytochemicals as modifiers of radiotherapeutic efficacy have become increasingly popular to improve the treatment outcome of human malignancies. In the current comprehensive review article, radiosensitizing effects of curcumin, a yellow-colored polyphenolic constituent of turmeric, in various preclinical cancer models, both In Vitro and In Vivo , are presented. Attenuation of radioadaptation and augmentation of irradiation-induced cancer cell killing are achieved through multifaceted action of curcumin on suppression of prosurvival and antiapoptotic factors...
October 24, 2019: Nutrition and Cancer
Miranda P Lawell, Daniel J Indelicato, Arnold C Paulino, William Hartsell, Nadia N Laack, Ralph P Ermoian, John P Perentesis, Ralph Vatner, Stephanie Perkins, Victor S Mangona, Christine E Hill-Kayser, Suzanne L Wolden, Young Kwok, John Han-Chih Chang, J Ben Wilkinson, Iain MacEwan, Andrew L Chang, Bree R Eaton, Matthew M Ladra, Sara L Gallotto, Elizabeth A Weyman, Benjamin V M Bajaj, Sujith Baliga, Beow Y Yeap, Amy Berrington de Gonzalez, Torunn I Yock
OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients < 22 years treated at one of 15 United States (US) participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap...
October 10, 2019: British Journal of Radiology
Katrin Menke, Melanie Schwermer, Alexander Schramm, Tycho J Zuzak
In Europe, especially in German-speaking countries, administration of mistletoe extracts is the most common and popular complementary and alternative therapy approach reported in oncology. Mistletoe therapy is applied to children with cancer for curative and palliative therapeutic regimes with increasing frequency, but at the same time, there are only a few studies on the effectiveness of this therapy. Therefore, we have investigated the response of various pediatric cell lines (acute myeloid leukemia, Ewing's sarcoma, hepatocellular carcinoma, medulloblastoma, neuroblastoma, and osteosarcoma) to mistletoe extract, abnobaVISCUM Fraxini...
October 7, 2019: Planta Medica
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