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The Journal of Pediatrics Oct 2017
Topics: Biopsy, Needle; Bone Marrow Transplantation; Chemoradiotherapy; Child, Preschool; Combined Modality Therapy; Conjunctiva; Contrast Media; Ecchymosis; Eye Hemorrhage; Follow-Up Studies; Humans; Immunohistochemistry; Male; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Multiple Primary; Neuroblastoma; Orbital Neoplasms; Retroperitoneal Neoplasms; Risk Assessment; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 28651799
DOI: 10.1016/j.jpeds.2017.05.069 -
Japanese Journal of Clinical Oncology Sep 1985We have experienced 30 patients with neuroblastoma since 1975. Disseminated intravascular coagulation (DIC) developed in six of these patients. They were all in stage...
We have experienced 30 patients with neuroblastoma since 1975. Disseminated intravascular coagulation (DIC) developed in six of these patients. They were all in stage IV, namely disseminated neuroblastoma. These six cases with DIC proved that some advanced neuroblastomas have the potential to cause coagulopathy in the process of the disease. The plasma concentration of heparin was measured in some patients who were treated with heparin. The data revealed that the conventionally used intravenous heparin dose is not appropriate in the case of DIC. Effective treatment requires monitoring of the plasma concentration of heparin.
Topics: Abdominal Neoplasms; Adrenal Gland Neoplasms; Antithrombin III; Child, Preschool; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heparin; Humans; Infant; Male; Neoplasm Metastasis; Neuroblastoma; Partial Thromboplastin Time; Prothrombin Time
PubMed: 4057631
DOI: No ID Found -
Scientific Reports Oct 2017Anti-PD-1 or anti-PD-L1 blocking monoclonal antibodies (mAbs) have shown potent anti-tumor effects in adult cancer patients and clinical studies have recently been...
Anti-PD-1 or anti-PD-L1 blocking monoclonal antibodies (mAbs) have shown potent anti-tumor effects in adult cancer patients and clinical studies have recently been started in pediatric cancers, including high-risk/relapsing neuroblastoma (NB). Therefore, we studied the effects of anti-PD-1/PD-L1 mAbs in two syngeneic models of disseminated NB generated by the injection of either Neuro2a or NXS2 cells, which express PD-L1. In addition, we tested the combination of these agents with the immune-enhancing cytokine IL-21, the Ecto-NTPDase inhibitor POM-1, an anti-CD25 mAb targeting Treg cells, or an anti-CD4 mAb. We previously showed that CD4-transient depletion removes CD4CD25 Treg cells and other CD4CD25 regulatory subsets. Here we show that mono-therapy with anti-PD-1/PD-L1 mAbs had no effect on systemic NB progression in vivo, and also their combination with IL-21, POM-1 or anti-CD25 mAb was ineffective. The combined use of anti-PD-1 with an anti-CD4 mAb mediated a very potent, CD8-dependent, synergistic effect leading to significant elongation of tumor-free survival of mice, complete tumor regression and durable anti-NB immunity. Similar results were obtained by combining the anti-PD-L1 and anti-CD4 mAbs. These findings indicate that both PD-1/PD-L1 and CD4 T cell-related immune-regulatory mechanisms must be simultaneously blocked to mediate therapeutic effects in these models.
Topics: Animals; Antibodies, Monoclonal; Apoptosis; B7-H1 Antigen; CD4 Antigens; Cell Proliferation; Cytotoxicity, Immunologic; Female; Immunologic Factors; Immunotherapy; Interleukins; Lymphocyte Depletion; Mice; Mice, Inbred A; Neuroblastoma; Programmed Cell Death 1 Receptor; T-Lymphocytes, Regulatory; Tumor Cells, Cultured
PubMed: 29070883
DOI: 10.1038/s41598-017-14417-6 -
Cancer Sep 1974
Topics: Animals; Autopsy; Brain Neoplasms; Child, Preschool; Humans; Hypothalamus; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Metastasis; Neuroblastoma; Optic Chiasm; Orbital Neoplasms; Osteitis Fibrosa Cystica; Scalp
PubMed: 4859280
DOI: 10.1002/1097-0142(197409)34:3<786::aid-cncr2820340339>3.0.co;2-9 -
Genes, Chromosomes & Cancer Oct 2000Neuroblastoma has a broad spectrum of clinical behavior, ranging from spontaneous regression to dissemination and fatality. The heterogeneity that has long puzzled many... (Review)
Review
Neuroblastoma has a broad spectrum of clinical behavior, ranging from spontaneous regression to dissemination and fatality. The heterogeneity that has long puzzled many investigators has been shown by more recent studies to be closely correlated with various clinical and genetic factors. Tumor cell ploidy is one of the factors; diploid and near-triploid neuroblastomas show poor and excellent clinical outcomes, respectively. We offer a hypothesis that explains how the ploidy state of the tumor plays a fundamental role in this heterogeneity, and why various prognostic factors are correlated with each other. This hypothesis may be applicable to tumors other than neuroblastoma.
Topics: Humans; Neuroblastoma; Ploidies
PubMed: 10959087
DOI: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1021>3.0.co;2-y -
Journal of Cancer Research and Clinical... Sep 2010Most neuroblastoma patients over 18 months of age at diagnosis present disseminated disease. The presence of neuroblastoma cells in bone marrow can be used to evaluate...
PURPOSE
Most neuroblastoma patients over 18 months of age at diagnosis present disseminated disease. The presence of neuroblastoma cells in bone marrow can be used to evaluate the response to treatment. It is possible that alterations in certain tumour cells might confer a selective advantage over tumour dissemination process, and probably be helpful in the clonal selection of tumour-specific cells that could originate metastasis.
METHODS
We performed real-time quantitative PCR to identify the presence of disseminated tumour cells in bone marrow samples, and we used MSP to analyse the methylation profile of 20 genes putatively implied in dissemination.
RESULTS
We described epigenetic alterations in the methylated status of certain genes in disseminated tumour cells from bone marrow. Those cases with high rate of hypermethylation showed an increased probability of relapse during or after treatment. We found significantly poor prognosis in event-free survival in cases with hypermethylation of TMS1, MGMT and RARbeta2 genes.
CONCLUSION
We could not confirm the presence of a specific methylation profile in disseminated neuroblastoma tumour cells, but a high accumulation of epigenetic events in those cells is associated with a high risk of relapse, independently of MYCN amplification.
Topics: Bone Marrow Neoplasms; CARD Signaling Adaptor Proteins; Cytoskeletal Proteins; DNA Methylation; Disease-Free Survival; Epigenesis, Genetic; Gene Expression Profiling; Humans; Neoplasm Staging; Neuroblastoma; Prognosis; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors
PubMed: 20140741
DOI: 10.1007/s00432-010-0796-9 -
Anales de Pediatria (Barcelona, Spain :... Jul 2005NB is the most frequent pediatric cancer arising in the sympathetic nervous system and represents a serious healthcare challenge because: 1) it is the most frequent... (Review)
Review
INTRODUCTION
NB is the most frequent pediatric cancer arising in the sympathetic nervous system and represents a serious healthcare challenge because: 1) it is the most frequent neoplasm in the first decades of life; 2) it biological behavior is unpredictable (spontaneous regression, maturation to ganglioneuroma, and localized and metastasized variants); and 3) little is known about most of the risk factors involved in its etiopathogenesis. The objective of this study was to disseminate knowledge of constitutional and environmental (physical, chemical, biological and social) risk factors linked to the development of neuroblastoma (NB), with various levels of scientific evidence. To seek collaboration among pediatricians in the research project "Environment and Pediatric Cancer".
MATERIAL AND METHODS
We performed a systematic review of the literature published in the previous 25 years on risk factors for NB diagnosed in the first two decades of life, using Medline, the Science Citation Index and Embase. Search profiles were: "neuroblastoma/childhood sympathetic nervous system neoplasms and risk factors/etiology/epidemiology". The most interesting articles and the most relevant references contained therein were selected.
RESULTS
With greater or lesser scientific evidence, the following risk factors increase the risk of developing NB: genetic factors; geographic factors; ethnic factors; socioeconomic factors; infectious factors; physical factors; parental occupational exposure; gestational factors; and perinatal and maternal factors. Preventive factors associated with a lower risk of developing NB are breastfeeding and intake of vitamin supplements during pregnancy.
CONCLUSIONS
The main barriers to the identification of evidence-based risk factors involved in the development of NB are its complex biology and clinical course, its relative rarity and the difficulty of performing epidemiological studies. Research on constitutional and environmental factors involved in its etiopathogenesis should be stimulated. The best preventive strategy is to recommend breastfeeding for more than 6 months.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Neuroblastoma; Risk Factors
PubMed: 15989872
DOI: 10.1157/13076768 -
European Journal of Cancer (Oxford,... 1995Retinoic acid has considerable potential for the chemoprevention and chemotherapy of cancer. Neuroblastoma cells differentiate in response to retinoic acid in vitro, an... (Review)
Review
Retinoic acid has considerable potential for the chemoprevention and chemotherapy of cancer. Neuroblastoma cells differentiate in response to retinoic acid in vitro, an observation that has led to clinical trials using either the 13-cis or all-trans isomers of retinoic acid. We review the effects of retinoic acid on neuroblastoma, and the potential involvement of nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). 9-cis retinoic acid is a ligand for RXRs, and we review recent data on the differential effects of 9-cis and all-trans retinoic acid on neuroblastoma differentiation and proliferation in vitro, and possible mechanisms of action via hetero- and homodimers of RARs and RXRs. Although there is uncertainty whether or not 9-cis retinoic acid produces its biological effects primarily via RXR homodimers, in vitro data suggest that this isomer of retinoic acid or stable analogues may have considerable potential for the treatment of resistant, disseminated neuroblastoma.
Topics: Antineoplastic Agents; Cell Differentiation; Cell Division; Gene Expression Regulation, Neoplastic; Humans; Neuroblastoma; Phenotype; Tretinoin; Tumor Cells, Cultured
PubMed: 7576951
DOI: 10.1016/0959-8049(95)00066-r -
Surgery Oct 2018Advanced-stage neuroblastoma patients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease...
BACKGROUND
Advanced-stage neuroblastoma patients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease orthotopic neuroblastoma tumor growth in mice. We hypothesize that injecting vincristine-loaded silk gel into 8 locations within the tumor, instead of only centrally, decreases the diffusion distance and improves tumor growth suppression.
METHODS
Human neuroblastoma cells, KELLY, were injected into mouse adrenal glands to create orthotopic tumors. After the tumors reached 100 mm by ultrasound, silk gels loaded with 50 µg vincristine were injected centrally or in 8 areas throughout the tumor. Drug-release profile was measured in vitro. Endpoints were tumor size >1,000 mm and histologic examination.
RESULTS
Vincristine-loaded silk gels suppressed tumor growth up to an inflection point (458.7 ± 234.4 mm for central, 514.3 ± 165.8 mm for 8-point injection) before tumor growth accelerated >200 mm over 3 days. The time to inflection point was 6.6 days for central, 13.3 days for 8-point injection (P < .05). Using the sphere volume equation to approximate tumor volume, splitting the volume into 1/8 decreased the diffusion radius by 1/2. Histologic examination confirmed tumor necrosis adjacent to vincristine-loaded silk gel.
CONCLUSION
Injecting vincristine-loaded sustained release silk gel at 8 separate locations halved the diffusion distance and doubled the time for the tumor to reach the growth inflexion point.
Topics: Animals; Antineoplastic Agents; Biocompatible Materials; Cell Line, Tumor; Diffusion; Drug Delivery Systems; Gels; Humans; Injections, Intralesional; Mice; Neuroblastoma; Silk; Tissue Extracts; Tumor Burden; Vincristine; Xenograft Model Antitumor Assays
PubMed: 30061039
DOI: 10.1016/j.surg.2018.06.017 -
Cancer Letters Jul 2003The detection of disseminated tumor cells (DTCs) in the hematopoetic system is important for various reasons. It is essential for tumor staging. According to the... (Review)
Review
The detection of disseminated tumor cells (DTCs) in the hematopoetic system is important for various reasons. It is essential for tumor staging. According to the International Neuroblastoma Staging System (INSS) only the cytomorphological examination of bone marrow smears is accepted despite the fact that an infiltrate below 0.1%, can hardly be detected and even infiltrates of more than 10% are sometimes overlooked. Another important aspect is the monitoring of the disease response to cytotoxic drugs by quantifying DTCs. Moreover, bone marrow aspirates represent an ideal source to determine the genetic and biological make up of DTCs at diagnosis and during follow up. Key issues that can be tested on DTCs are: determination of the proliferation capacity, the apoptotic rate, the drug sensitivity etc. The prerequisite for such a bone-marrow diagnosis, however, is the unequivocal identification of disseminated tumor cells. Thus, in order to avoid false positive and false negative results, which are a risk in bone-marrow diagnostics, a system was developed to distinguish tumor cells from non-neoplastic cells and to facilitate the gain of insights into the biological make-up of tumor cells more easily.
Topics: Bone Marrow Cells; Bone Marrow Neoplasms; False Negative Reactions; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Microscopy, Fluorescence; Neoplasm Staging; Neuroblastoma
PubMed: 12880956
DOI: 10.1016/s0304-3835(03)00078-8