1. Recent Articles

    1. Risk and impact of pulmonary complications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

      "By the age of 45 years, the cumulative incidence of any pulmonary condition was 29.6% (95% CI, 29.1%-30.0%) for cancer survivors and 26.5% (95% CI, 24.9%-28.0%) for siblings. Fewer survivors reported ever smoking (23.6% vs 36.4%, P < .001), but survivors were more likely to report chronic cough (rate ratio [RR], 1.6; 95% CI, 1.4-1.9), oxygen need (RR, 1.8; 95% CI, 1.5-2.2), lung fibrosis (RR, 3.5; 95% CI, 2.3-5.4), and recurrent pneumonia (RR, 2.0; 95% CI, 1.4-3.0). The SMR ...

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    2. SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR‑410 in human neuroblastoma cells.

      "In the present study, we demonstrate that overexpression of secreted protein acidic and rich in cysteine (SPARC) suppresses radiation induced angiogenesis in SK-N‑BE(2) and NB1691 neuroblastoma cells. We observed that overexpression of SPARC in SK-N-BE(2) and NB1691 cells reduced radiation induced angiogenesis in an in vivo mouse dorsal skin model and an ex vivo chicken CAM (chorioallantoic-membrane) model and also reduced tumor size in subcutaneous mouse tumor models of NB. We also observed that SPARC overexpression reduces VEGF-A expression, in SK-N-BE(2) and NB1691 NB cells via miR-410, a VEGF-A targeting microRNA. SPARC overexpression alone or in ...

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    3. Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy.

      "Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the clinic, becoming an important approach for cancer immunotherapy. Due to its limited expression on normal tissue, the GD2 disialogangloside expressed on neuroblastoma cells is an excellent candidate for mAb therapy. In 2015, dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in a combination immunotherapeutic regimen for the treatment of children with high-risk neuroblastoma. Here, we review the extensive preclinical and clinical development of anti-GD2 mAbs and the different mechanisms by which they mediate tumor cell killing. In addition, we discuss different mAb-based strategies that capitalize ...

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      Mentions: Immunotherapy
    4. The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.

      "The first-in class ALK/c-MET/ROS1 inhibitor crizotinib (Xalkori) has shown remarkable clinical efficacy in treatment of ALK-positive NSCLC. In neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma models in vitro and in vivo In vitro kinase assays and cell-based experiments examining ALK mutations of increasing potency show that PF-06463922 is an effective inhibitor of ALK with greater activity towards ALK neuroblastoma mutants ...

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      Mentions: ALK MYCN
    5. Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

      "All patients had a stage 4 neuroblastoma. NMYC amplification was displayed in 24% of the tumors. The hematopoietic support consisted of bone marrow or PBSCs in 46% and 49% of patients, respectively. The 5-year event-free survival and overall survival rates of the whole cohort were 35.1% and 40%, respectively. Age at diagnosis, bone marrow involvement and tumor response after induction chemotherapy were significant prognostic factors. Toxicity was manageable and decreased over time, owing to both PBSC administration and better supportive care. Based on this experience, HD Bu–melphalan (Mel) has been implemented in Europe and compared with Carboplatin–Etoposide ...

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      Mentions: Bone Marrow
    6. Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma.

      "Targeted therapy using histone deacetylase inhibitors (HDACi) is currently being explored in cancer treatment and already shows promising results. Using our recently developed transplantable TH-MYCN NBL model, we here report that the HDAC inhibitor Vorinostat synergizes with anti-GD2 mAb therapy in reducing NBL tumor growth. Further mechanistic studies uncovered multiple mechanisms for the observed synergy, including Vorinostat-induced specific NBL cell death and upregulation of the tumor antigen GD2 on the cell surface of surviving NBL cells. Moreover, Vorinostat created a permissive tumor microenvironment (TME) for tumor-directed mAb therapy by increasing macrophage effector cells expressing high levels of Fc-receptors (FcR) and ...

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      Mentions: Treatment MYCN
    7. Heterogeneity of MYCN Amplification in Neuroblastoma at Diagnosis, Treatment, Relapse and Metastasis.

      "Nineteen cases (63%) showed diffuse MYCN amplification in all samples tested. Nine cases (30%) showed a reduction in MYCN copy number: five cases with diffuse amplification subsequently showed focal amplification, one case with diffuse MYCN amplification showed MYCN gain after treatment, and three focally amplified cases were non-amplified in later specimens. In two cases (7%), focal amplification became diffuse in subsequent samples. Histology was not predictive of the temporal or spatial pattern of MYCN amplification for a particular tumour. If extent of amplification (focal vs. diffuse) is not considered, 26/30 (87%) of cases were consistently MYCN-amplified. However, our data ...

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    8. Challenge To Denial Of Children’S Cancer Treatment

      Challenge To Denial Of Children’S Cancer Treatment

      "A children’s cancer charity will today appeal against a National Institute for Health and Care Excellence (NICE) decision on dinutuximab, a drug that would give a greater chance of survival to children in the UK diagnosed with an aggressive childhood cancer. The appeal challenges the decision on the grounds that NICE failed to act fairly, exceeded its powers and that the recommendation is unreasonable in light of the evidence submitted."

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      Mentions: Treatment
    9. Researchers describe a new type of cancer therapy

      Researchers describe a new type of cancer therapy

      "We tested RCn's tumour killing efficacy in cell lines of numerous cancers, including sarcomas, lymphoma and neuroblastoma," said Timothy Cripe, MD, PhD, principal investigator in the Center for Childhood Cancer and Blood Disease in The Research Institute at Nationwide Children's and senior author on the paper. "We observed anticancer activity of the RCn amines in all the cancer cell lines analysed."  Researchers found that RCn, and RC16 in particular, is 10 times more effective in harming tumour cells than regular cells. That means the low dose needed to kill cancer will have minimal effect on normal cells."

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      Mentions: Chemotherapy
    10. MYCN promotes neuroblastoma malignancy by establishing a regulatory circuit with transcription factor AP4.

      "We show for the first time that high expression of TFAP4 in primary neuroblastoma patients is associated with poor clinical outcome. siRNA-mediated suppression of TFAP4 in MYCN-expressing neuroblastoma cells led to inhibition of cell proliferation and migration. Chromatin immunoprecipitation assay demonstrated that TFAP4 expression is positively regulated by MYCN. Microarray analysis identified genes regulated by both MYCN and TFAP4 in neuroblastoma cells, including Phosphoribosyl-pyrophosphate synthetase-2 (PRPS2) and Syndecan-1 (SDC1), which are involved in cancer cell proliferation and metastasis. Overall this study suggests a regulatory circuit in which MYCN by elevating TFAP4 expression, cooperates with it to control a specific set ...

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      Mentions: MYCN
    11. Transition and transfer of childhood cancer survivors to adult care: A national survey of pediatric oncologists

      "Of 347 respondents, 50% are male, median years in practice 10 (range 5–22), 37% practice in freestanding children's hospitals. Almost all care for survivors up to age 21 years (96%), 42% care for survivors over age 25 years, and only 16% over age 30 years. While 66% of oncologists reported providing transition education to their patients, very few (8%) reported using standardized transition assessments. The most frequent barriers to transfer were perceived attachment to provider (91%), lack of adult providers with cancer survivor expertise (86%), patient's cognitive delay (81%), or unstable social situation (80%). Oncologists who continue ...

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      Mentions: COG
    12. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients.

      "The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an ...

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      Mentions: Relapse PHOX2B
    13. Advancing clinicopathologic diagnosis of high-risk neuroblastoma using computerized image analysis and proteomic profiling.

      "After expert pathologist review of tumor sections to ensure quality and representative material input, we evaluated multiple regions of single slides as well as multiple sections from different patients' tumors using computational histologic analysis and semi-quantitative proteomic profiling. We found that both approaches determined that intertumor heterogeneity was greater than intratumor heterogeneity. Unbiased clustering of samples was greatest within a tumor, suggesting a single section can be representative of the tumor as a whole. There is expected heterogeneity between tumor samples from different individuals with a high degree of similarity among specimens derived from the same patient. Both techniques are ...

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  2. Topics in the News

    1. (5 articles) MYCN
    2. (4 articles) Treatment
    3. (2 articles) Immunotherapy
    4. (2 articles) Relapse
    5. (1 articles) COG
  3. Recent Quotes

    1. We wanted to remove an important barrier in using B cells as an antigen-presenting cell population, helping them complement or replace dendritic cells.
      By Gregory Szeto
    2. The antigen-presenting capabilities of B cells have often been underestimated, but they are being increasingly appreciated for their practical advantages in therapies.
      By Gail Bishop
    3. Our dream is to spawn out a whole class of therapies which involve taking out your own cells, telling them what to do, and putting them back into your body to fight your disease, whatever that may be.
      By Armon Sharei
    4. We envision a future system, if we can take advantage of its microfluidic nature, as a bedside or field-deployable device.
      By Armon Sharei
    5. Down the road, you could potentially get enough cells from just a normal syringe-based blood draw, run it through a bedside device that has the antigen you want to vaccinate against, and then you'd have the vaccine.
      By Gregory Szeto
    6. The problem is that unlike blood, a skin sample or even a tissue biopsy, you can't take a piece of a patient's neural system. It runs like complex wiring throughout the body and portions cannot be sampled for study.
      By Mick Bhatia
    7. Now we can take easy to obtain blood samples, and make the main cell types of neurological systems - the central nervous system and the peripheral nervous system - in a dish that is specialized for each patient.
      By Mick Bhatia
    8. If I was a patient and I was feeling pain or experiencing neuropathy, the prized pain drug for me would target the peripheral nervous system neurons, but do nothing to the central nervous system, thus avoiding non-addictive drug side effects.
      By Mick Bhatia
    9. This bench to bedside research is very exciting and will have a major impact on the management of neurological diseases, particularly neuropathic pain.
      By Akbar Panju
    10. The dBET1 and the dFKBP12 compounds are presently in a late stage of lead optimization for therapeutic development in both cancer and non-malignant diseases, Composition-of-matter and method-of-use patent applications have been filed on these and other additional targeted agents, as well as on the chemistry platform.
      By Prem Das