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Neuroblastoma immunotherapy

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https://www.readbyqxmd.com/read/29764159/emerging-role-of-immunotherapy-for-childhood-cancers
#1
Rupert Handgretinger, Patrick Schlegel
Recent developments in cell and gene therapy have a great impact on the new therapeutic approaches in pediatric cancers. Monoclonal antibodies for neuroblastoma and bispecific antibodies for leukemia have induced significant clinical responses for otherwise chemorefractory patients. Moreover, cellular therapeutic approaches including chimeric antigen receptor (CAR) T-cells as well as natural killer (NK) cells have the potential to cure patients with so far incurable malignancies and are the basis for future new therapies for pediatric cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29692663/uncommon-reasons-of-the-digestive-tract-related-paraneoplastic-syndromes-in-children-with-neuroblastic-tumors-three-case-reports
#2
Elżbieta Czkwianianc, Beata Zalewska-Szewczyk, Józef Kobos, Anna Socha-Banasiak, Szymon Janczar, Sylwia Prymus-Kasińska, Joanna Kazanek-Zasada, Wojciech Młynarski
Aim of the study: presentation of the uncommon paraneoplastic syndromes related to the gastrointestinal tract that may occur in children with neuroblastic tumors and their impact on the disease course. Material and methods: Retrospective analysis of three cases of patients mainly with digestive tract-related symptoms, who were originally admitted to the gastroenterology department from 2013 to 2016 and were finally diagnosed with neuroblastic tumors. Results: The clinical data analysis showed that the symptoms from gastrointestinal tract were dominant in analyzed subjects...
2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29682521/immune-escape-mechanisms-and-future-prospects-for-immunotherapy-in-neuroblastoma
#3
REVIEW
Thitinee Vanichapol, Somchai Chutipongtanate, Usanarat Anurathapan, Suradej Hongeng
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29674658/high-dose-carboplatin-etoposide-melphalan-increases-risk-of-thrombotic-microangiopathy-and-organ-injury-after-autologous-stem-cell-transplantation-in-patients-with-neuroblastoma
#4
Sonata Jodele, Christopher E Dandoy, Kasiani Myers, Gregory Wallace, Adam Lane, Ashley Teusink-Cross, Brian Weiss, Stella M Davies
Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplant that can result in multi-organ failure (MOF). Patients undergoing high-dose chemotherapy with autologous stem cell transplant (aHCT) for neuroblastoma require good organ function to receive post-transplant radiation and immunotherapy. We examined TA-TMA incidence and transplant outcomes in patients with neuroblastoma receiving different transplant preparative regimens. Sixty patients underwent aHCT using high-dose chemotherapy: 41 patients received carboplatin/etoposide/melphalan (CEM), 13 patients busulfan/melphalan (Bu/Mel) and six patients received tandem transplant (cyclophosphamide/thiotepa and CEM)...
April 19, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29574715/treatment-and-outcome-of-adult-onset-neuroblastoma
#5
Maya Suzuki, Brian H Kushner, Kim Kramer, Ellen M Basu, Stephen S Roberts, William J Hammond, Michael P LaQuaglia, Suzanne L Wolden, Nai-Kong V Cheung, Shakeel Modak
Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29572647/neuroblastoma-clinical-and-biological-approach-to-risk-stratification-and-treatment
#6
REVIEW
Vanessa P Tolbert, Katherine K Matthay
Neuroblastoma is the most common extra-cranial solid tumor of childhood and the most common in the first year of life. It is a unique malignancy in that infants often present with either localized or metastatic disease that can spontaneously regress without intervention while older children can succumb to the disease after months to years of arduous therapy. Given this wide range of outcomes, the International Neuroblastoma Risk Group was created to stratify patients based on presenting characteristics and tumor biology in order to guide intensity of treatment strategies...
March 23, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29559757/successful-use-of-extracorporeal-life-support-in-a-hematopoietic-stem-cell-transplant-patient-with-neuroblastoma
#7
Feifei Z Williams, Atul Vats, Thomas Cash, James D Fortenberry
Respiratory failure associated with hematopoietic stem cell transplantation (HSCT) has been considered a contraindication for use of extracorporeal membrane oxygenation (ECMO) at many centers. We describe a child with neuroblastoma and hypoxemic respiratory failure following HSCT who was successfully managed with veno-venous (VV) ECMO. The patient was an 18-month-old female with high-risk neuroblastoma status post tumor resection, chemotherapy, autologous HSCT, and primary site radiation. On day 113 posttransplant while receiving maintenance immunotherapy, she had an acute respiratory decompensation because of rhinovirus, aspiration pneumonia, and capillary leak syndrome...
March 2018: Journal of Extra-corporeal Technology
https://www.readbyqxmd.com/read/29554305/neuroradiological-and-neuropathological-changes-after-177lu-octreotate-peptide-receptor-radionuclide-therapy-of-refractory-esthesioneuroblastoma
#8
Julia R Schneider, Deborah R Shatzkes, Stephen C Scharf, Tristan M Tham, Kay O Kulason, François-Alexandre Buteau, Michela Del Prete, Shamik Chakraborty, Todd A Anderson, Saeed Asiry, Jean-Mathieu Beauregard, David J Langer, Peter D Costantino, John A Boockvar
BACKGROUND AND IMPORTANCE: Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors...
March 14, 2018: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/29393340/characterisation-of-the-p53-pathway-in-cell-lines-established-from-th-mycn-transgenic-mouse-tumours
#9
Lindi Chen, Arman Esfandiari, William Reaves, Annette Vu, Michael D Hogarty, John Lunec, Deborah A Tweddle
Cell lines established from the TH-MYCN transgenic murine model of neuroblastoma are a valuable preclinical, immunocompetent, syngeneic model of neuroblastoma, for which knowledge of their p53 pathway status is important. In this study, the Trp53 status and functional response to Nutlin-3 and ionising radiation (IR) were determined in 6 adherent TH-MYCN transgenic cell lines using Sanger sequencing, western blot analysis and flow cytometry. Sensitivity to structurally diverse MDM2 inhibitors (Nutlin-3, MI-63, RG7388 and NDD0005) was determined using XTT proliferation assays...
March 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29378002/neuroblastoma
#10
Akira Nakagawara, Yuanyuan Li, Hideki Izumi, Katsumi Muramori, Hiroko Inada, Masanori Nishi
Neuroblastoma is one of the most common solid tumors in children and has a diverse clinical behavior that largely depends on the tumor biology. Neuroblastoma exhibits unique features, such as early age of onset, high frequency of metastatic disease at diagnosis in patients over 1 year of age and the tendency for spontaneous regression of tumors in infants. The high-risk tumors frequently have amplification of the MYCN oncogene as well as segmental chromosome alterations with poor survival. Recent advanced genomic sequencing technology has revealed that mutation of ALK, which is present in ~10% of primary tumors, often causes familial neuroblastoma with germline mutation...
March 1, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29371588/cell-death-based-treatment-of-neuroblastoma
#11
REVIEW
Kadri Valter, Boris Zhivotovsky, Vladimir Gogvadze
Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and causes 15% of childhood cancer-related mortality. The main drivers of NB formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. Moreover, NB is a complex disease that has high heterogeneity and is therefore difficult to target for successful therapy. Thus, a better understanding of NB development helps to improve treatment and increase the survival rate. One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB...
January 25, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#12
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
April 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#13
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
April 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29274926/3-methoxytyramine-an-independent-prognostic-biomarker-that-associates-with-high-risk-disease-and-poor-clinical-outcome-in-neuroblastoma-patients
#14
I R N Verly, A B P van Kuilenburg, N G G M Abeling, S M I Goorden, M Fiocco, F M Vaz, M M van Noesel, C M Zwaan, G J L Kaspers, J H M Merks, H N Caron, G A M Tytgat
INTRODUCTION: Prognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. PATIENTS AND METHODS: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis...
February 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29225605/the-state-of-cellular-adoptive-immunotherapy-for-neuroblastoma-and-other-pediatric-solid-tumors
#15
Thanh-Phuong Le, To-Ha Thai
Research on adult cancer immunotherapy is proceeding at a rapid pace resulting in an impressive success rate exemplified by a few high profile cases. However, this momentum is not readily extended to pediatric immunotherapy, and it is not for lack of trying. Though reasons for the slower advance are not apparent, some issues can be raised. Pediatric cancer patients represent a distinct demographic group whose immune system is inherently different from that of mature adults. Treating pediatric patients with immunotherapy designed for adults may not yield objective clinical responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29221128/-mycn-amplified-stage-2-3-neuroblastoma-excellent-survival-in-the-era-of-anti-g-d2-immunotherapy
#16
Brian H Kushner, Michael P LaQuaglia, Shakeel Modak, Suzanne L Wolden, Ellen M Basu, Stephen S Roberts, Kim Kramer, Karima Yataghene, Irene Y Cheung, Nai-Kong V Cheung
High-risk neuroblastoma (HR-NB) includes MYCN -amplified stage 2/3, but reports covering anti-GD2 immunotherapy, which recently became standard for HR-NB, do not provide details on this subset. We now report on all 20 MYCN -amplified stage 2/3 patients who received induction chemotherapy at our center during the era of consolidation with anti-GD2 antibody 3F8/ granulocyte-macrophage colony-stimulating factor (GM-CSF) (2000-2015). Early in this period, consolidation included autologous stem-cell transplantation (ASCT)...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#17
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29196189/pd-l1-inflammation-non-coding-rnas-and-neuroblastoma-immuno-oncology-perspective
#18
REVIEW
Palanisamy Nallasamy, Srinivas Chava, Sumit S Verma, Shruti Mishra, Santhi Gorantla, Don W Coulter, Siddappa N Byrareddy, Surinder K Batra, Subash C Gupta, Kishore B Challagundla
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system...
November 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29191664/immune-reconstitution-following-autologous-stem-cell-transplantation-in-patients-with-high-risk-neuroblastoma-at-the-time-of-immunotherapy
#19
Michele L Nassin, Elitsa Nicolaou, Sandeep Gurbuxani, Susan L Cohn, John M Cunningham, James L LaBelle
Outcomes for patients with high-risk neuroblastoma (HR-NBL) are significantly improved with the addition of immunotherapy (dinutuximab + cytokines) following autologous hematopoietic stem cell transplantation (auto-HSCT). We hypothesized that the immune system is not fully reconstituted at the initiation of immunotherapy. To test this hypothesis, we evaluated hematologic and immune subsets in 34 patients with HR-NBL before and after auto-HSCT. We found that absolute T, B, and NK cell counts at the time of immunotherapy were below normal in 80% of patients...
March 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29189429/new-developments-in-immunotherapy-for-pediatric-solid-tumors
#20
Liora M Schultz, Robbie Majzner, Kara L Davis, Crystal Mackall
PURPOSE OF REVIEW: Building upon preclinical advances, we are uncovering immunotherapy strategies that are translating into improved outcomes in tumor subsets. Advanced pediatric solid tumors carry poor prognoses and resultant robust efforts to apply immunotherapy advances to pediatric solid tumors are in progress. Here, we discuss recent developments in the field using mAb and mAb-based therapies including checkpoint blockade and chimeric antigen receptors (CARs). RECENT FINDINGS: The pediatric solid tumor mAb experience targeting the diganglioside, GD2, for patients with neuroblastoma has been the most compelling to date...
February 2018: Current Opinion in Pediatrics
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