Nai Kong V Cheung

..We hypothesized that patients with a "missing ligand" KIR-HLA compound genotype may uniquely benefit from autologous hematopoietic stem cell transplantation (HSCT)...

..Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored...

..CHD5 gene and protein expression was reexamined after induction chemotherapy in a subset of high risk tumors to identify potential changes reflecting tumor response...

..The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups...

..To measure the sensitivity of histologic examination in detecting metastatic solid tumor in bone marrow...

..Anti-idiotypic antibody may provide a useful tool for optimizing gene transduction of CIR fusion constructs into primary human lymphocytes and their continual expansion in vitro...

..Granulocyte macrophage colony-stimulating factor (GM-CSF) enhances phagocyte-mediated ADCC. The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy...

..The reduced size resulted in a shorter half-life in vivo, while achieving comparable tumor to nontumor ratio as the native antibody 8H9. However, its in vitro activity in antibody-dependent cell-mediated cytotoxicity was modest...

..Given the favorable efficacy and toxicity profile of oral beta- D-glucan treatment, the role of natural products that contain beta-glucan in cancer treatment as an enhancer of the effect of mAb therapy deserves further study...

..We tested if (1-->3),(1-->4)-beta-D-glucan (beta-glucan) can synergize with anti-GD2 monoclonal antibody (MoAb) 3F8 (mouse IgG3) in therapy of human neuroblastoma xenografts...

..Ongoing strategies to modify or reconstruct mAbs, to engage them with cytokines, or to unite them with T cells open new avenues for harnessing the unique forces of the immune system against some of the most deadly pediatric cancers...

..To eradicate minimal residual disease with anti-G(D2) monoclonal antibody 3F8 in stage 4 neuroblastoma (NB) diagnosed at more than 1 year of age...

..We examined whether the chance of a positive IC from a single marrow site was comparable to an IC of pooled marrow from multiple sites...

..Neuroblastoma is uniquely suited for such investigations because of its abundance of surface ganglioside GD2...

..Ab3 and Ab3' antibody response correlated with prolonged PFS and survival. We postulate that successful induction of an idiotype network in patients may be responsible for long-term tumor control...

..1998): J Clin Oncol 16:3053] following antibody 3F8 (Ab1) treatment. We postulate that the induction of an idiotype network which included anti-anti-idiotypic (Ab3) and anti-G(D2) (Ab3') responses is associated with tumor control...

..Experience with metastatic neuroblastoma has provided proof of this principle. It is likely that other tumors will fall...

....

....

..Because therapy (myeloablation, immunotherapy, or differentiation) for MRD is applied at the time of clinical remission, objective surrogate markers are needed to gauge treatment efficacy...

..The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life...

..We assessed the impact on rapid HAMA formation of prior chemotherapy in NB patients...

..The falx cerebri probably does not represent an atypical site for stage 4S NB, but stage 4 NB with favorable biology is sometimes curable with minimal therapy...

..5 MBq (131)I-8H9 were significantly suppressed compared to controls. Radiolabeled 8H9 effectively targeted RMS xenografts and may have a potential clinical role in radioimmunotherapy...

..Its utility in bone marrow (BM) purging is evaluated by a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to quantify the mRNA of GD2 synthase, the key enzyme in GD2 synthesis...

..We now describe similar results with changes that reduce toxicity (fewer cycles, less vincristine, use of granulocyte colony-stimulating factor)...

..067 mg/kg was injected on day 1. With C/I, irinotecan, 50 mg/m(2) was infused i.v. (1 h) on days 1-5 (total, 250 mg/m(2)). Mesna and granulocyte colony-stimulating factor were used...

..The molecular mechanisms driven by overexpression of the MYCN gene in neuroblastoma are not well known. Whether MYCN overexpression in the absence of genomic amplification, or ID2 overexpression has prognostic value remains controversial...

..We present the first report on the effect of MIBG scans on the classification of response to dose-intensive induction therapy...

..We report a retrospective study of a novel regimen for neuroblastoma (NB) resistant to standard induction or salvage chemotherapy which now routinely includes topotecan...

..We conclude that CCND1 has potential clinical utility as a novel molecular marker of MRD in the bone marrow of patients with metastatic NB...

..To determine the prevalence of and risk factors for primary hypothyroidism following treatment with a radiolabeled monoclonal antibody ((131)I-3F8) in children with neuroblastoma...

..We report a prospective study of secondary leukemia (SL)/myelodysplastic syndrome (MDS) in neuroblastoma (NB) patients treated with > or =5 cycles of dose-intensive chemotherapy...

..The (225)Ac-3F8 treatment improved survival 2-fold from 16 to 34 days (P = 0.01). In conclusion, in vivo alpha generators targeted by 3F8 warrant additional study as a possible new approach to the treatment of carcinomatous meningitis...

..To use early marrow response as a prognostic marker is particularly relevant for patients not likely to benefit from this therapy...

..We now describe a two-compartment model to account for the ventricular reservoir of (131)I-3F8 and to identify limiting factors that may impact therapeutic ratio...

....

..These results indicate that unlicensed NK cells play a key antitumor role in patients undergoing mAb therapy via antibody-dependent cell-mediated cytotoxicity, thus explaining the potent "missing KIR ligand" benefit in patients with NB...

..We describe a single centre approach at Memorial Sloan-Kettering Cancer Centre (MSKCC) from 1991 to 2007 that minimises therapy except for those patients with MYCN-amplified NB...

..This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT)...

..No clinical toxicity was observed. The therapeutic efficacy and lack of toxicity of this combination supports further investigation into its clinical utility...

..Few studies have assessed late effects in neuroblastoma (NB) survivors, particularly those with advanced stage disease...

..We tested the toxicity, pharmacokinetics, and dosimetry of intraventricular iodine-131-labeled monoclonal antibody 3F8 (131I-3F8) targeting GD2-positive CNS/LM disease in a phase I clinical trial...

..We reviewed the utility of different treatment modalities in a large series of adolescents/adults with neuroblastoma (NB)...

..However, the 3 alpha-emitting daughter elements generated have the potential for significant toxicity as these nuclides are no longer bound to the carrier IgG...

..We reviewed clinical and biologic findings in a series of infants with neuroblastoma (NB) in liver. The aim was to gain insights into improving therapy...

..To present a large experience (73 patients) using a standard radiotherapy (RT) protocol to prevent relapse in cranial sites where measurable metastatic neuroblastoma (NB), an adverse prognostic marker, is common...

..A major reason for using this regimen was the long time since patients received previous treatment with a platinum compound. The authors also summarized the published experience on ICE in patients with NB...

..To report on an irinotecan and temozolomide regimen for neuroblastoma (NB). Quality of life and minimizing toxicity were major considerations...

..Relapse-free survival (RFS) is a powerful measure of treatment efficacy. We describe the sensitivity of standard surveillance studies for detecting relapse of neuroblastoma (NB)...

..This case illustrates that some infants with favorable-biology neuroblastoma may be observed without treatment despite the advanced INSS stage...

..Salvage therapy featured 11 cycles of temozolomide. She developed myelodysplastic syndrome with 45,XX,der(7)t(7;21) (p15;q11),-21 at age 24 and refused treatment; 19 months later she was transfusion-dependent but her NB remained in CR...

..We used a novel regimen for neuroblastoma (NB) that had responded inadequately to standard chemotherapy which now includes topotecan in induction or second-line therapy...

..Genome-wide expression arrays can uncover novel genes differentially expressed in tumors over normal marrow/blood, which may have potentials as markers of subclinical disease...

..The authors report on a series of patients who had distant recurrences after surgery alone for local-regional neuroblastoma...

..Similarly, the STX transcript level of posttreatment marrows was also highly prognostic of outcome (PFS, p = 0.001; OS, p < 0.0005). We conclude that STX mRNA has potential clinical utility as a molecular marker of metastatic NB...

....

..Although toxicity was generally thought to be mild, the efficacy of such an approach remains unproven...

..We hypothesized that 3F8 dose escalation is possible without increased analgesic requirements in patients pretreated with HM3F8...

....

....

..An indolent course is associated with neuroblastoma (NB) in adolescents and adults. In the current study, the authors analyzed this phenomenon in a large series of children with metastatic NB...

..The purpose of this study was to describe the technique, outcome and toxicities in patients with high risk NB metastatic to the skull treated with brain-sparing skull radiotherapy (BSRT)...

..5] days. Serum lipase remained normal. Patients did not develop subsequent dry mouth or dysphagia...

..We review the current status of anti-GD2 clinical trials for neuroblastoma and novel preclinical GD2-targeted strategies for this rare but often lethal childhood cancer...

....

..Without substantial policy changes in drug development for orphan indications, however, these agents are not likely to be widely available in the near future...

..Quality of life was a major issue in choosing this regimen for patients whose disease was resistant to standard anti-NB therapies...

..It is likely that a combination of therapeutic modalities will be required to improve survival and cure rates...

..Gross total resection should be part of the management of stage 4 neuroblastoma in patients greater than 1 year of age...

..03). CONCLUSIONS: BM monitoring should continue to be an integral part of disease follow-up for patients with Stage 4 NB. PB monitoring to complement tumor surveillance in the BM can be informative...

..We conclude that epitope spread during affinity maturation can be reduced by negative selection. Furthermore, efficiency of the negative selector depends on its cross-reactive affinity with the matured scFv...

..rMETase synergized with microtubule depolymerization agents. Moreover, synergism between rMETase and DNA damaging agents was dependent on whether cell lines were established at diagnosis or at relapse...

..Some patients classified as having high-risk neuroblastoma might actually do well with no cytotoxic therapy...

..Because of tumor heterogeneity, no single marker will likely be adequate. Genome-wide expression profiling can uncover potential MRD markers differentially expressed in tumors over normal marrow/blood...

..We report a retrospective study of a novel regimen for neuroblastoma (NB) resistant to standard induction or salvage chemotherapy which now routinely includes topotecan...

..CONCLUSIONS: G(D2) and the novel tumor antigen recognized by 8H9 are potential targets for immunodiagnosis and antibody-based therapy of DSRCT. Med Pediatr Oncol 2002;39:547-551...

..Differential modulation of this key immunoinhibitory molecule in tumor versus normal tissues may advance both cell-mediated immunotherapy and antibody-based targeted strategies using the B7-H3-specific mAb 8H9...

....

..Interstitial delivery of murine immunoglobulin G1 monoclonal antibody (MAb) 8H9 was investigated in a rodent model for the potential treatment of infiltrative gliomas...

..Chemotherapy may be avoided in low-risk patients who are offered potentially curative operations. Patients treated with operations for epidural disease are at high risk of subsequently developing spinal deformity...

..Currently, there are four monoclonal antibodies that have been approved by the FDA for the treatment of solid tumor malignancies. Over 100 other antibodies are in early- and late-phase clinical testing...

..Spontaneously remitting or quiescent tumors were intact at all of the regions described above...

..Transcriptional silencing of tumor suppressor genes mediated by hypermethylation of promoter CpG islands is a hallmark of human tumors. We addressed the clinical relevance of promoter hypermethylation in neuroblastoma...

..These results make 8H9(dsFv)-PE38 a candidate for further development as a therapeutic agent for breast cancers, osteosarcomas, and neuroblastomas...

..Thus, I-type stem cells may be instrumental in the genesis and growth of tumors in the patient. Their unique biology deserves attention and further investigation...

..The effects of complement can be supplemental to other antibody-mediated mechanisms and likely have increased significance at limiting antibody concentration or low antigen density...

..Distinct gene expression patterns between metastatic and non-metastatic NB tumors have been identified. Validation of these results and further mechanistic studies may shed new light on the biology of metastasis in human NB...

..These granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb...

..03) and death of disease (Kendall tau, P = 0.03; r = 0.19). Thus, EMP3 is a good candidate for being the long-sought tumor suppressor gene located at 19q13 in gliomas and neuroblastomas...

..MLL-FRYL did not increase MEIS1 expression, conferred a proliferative advantage without altering differentiation, and had protracted latency to disease...

..02; progression-free survival, P = 0.01). These results provide strong evidence for clonal ploidy heterogeneity in LR NB and clonal evolution toward diploidy in progressing LR NB...

..The sequences in these three cases show additional MLL genomic breakpoint heterogeneity. Each breakpoint junction suggests nonhomologous end joining and is consistent with DNA damage and repair. CDK6-MLL is a new fusion of both genes...

..These findings will have general implications for antibody and vaccine strategies in human cancer models, and the role of polysaccharides as complementary/herbal medicine in immune-based therapies. ..

..Armed with the tools to collect samples expeditiously and to measure MRD accurately, the paradigm of treating subclinical NB can then be tested in multicenter randomized studies. ..