Serum Neuron-Specific Enolase as a Marker Useful for Monitoring the Effectiveness of Therapy in Patients with Neuroblastoma

Serum Neuron-Specific Enolase as a Marker Useful for Monitoring the Effectiveness of Therapy in Patients with Neuroblastoma as Compared with Urinary Catecholamine Metabolites

KUMIKO HASHIMOTO1), YOH-ICHI GOTOH1) and KEIYA TADA1)

1) Department of Pediatrics, Tohoku University School of Medicine


HASHIMOTO, K., GOTOH, Y. and TADA, K. Serum Neuron-Specific Enolase as a Marker Useful for Monitoring the Effectiveness of Therapy in Patients with Neuroblastoma-as Compared with Urinary Catecholamine Metabolites. Tohoku J. exp. Med., 1986, 149 (1), 25-30-Neuron-specific enolase (NSE) in sera of 3 patients with neuroblastoma (Stage IV) were measured by radioimmunoassay, as compared with urinary catecholamine metabolites (vanillyl-mandelic acid (VMA) and homovanillic acid (HVA)) during the course of chemotherapy, radiation, and second look operation. In Case 1(Stage IV B) and Case 3 (Stage IV A), NSE level on admission was found to be elevated to 51.0ng/ml and 25.5ng/ml, respectively. VMA and HVA were also elevated. In Case 2 (Stage IV A), NSE on admission was elevated to 128.0ng/ml., HVA was high, but VMA was within normal range. From 1 to 3 weeks after chemotherapy and radiation, high levels of urinary VMA and/or HVA in patients promptly decreased within normal range. The size of primary tumor masses either showed no marked change or slightly decreased by radiological examinations. After intensive chemotherapy, high levels of serum NSE decreased within normal range. At that time, second look operations were carried out. The size of primary tumors was reduced (3.6×2.7×2.1cm in average) and almost all masses had scarred over. These data suggest that serum NSE levels correlate very well with residual tumor burdens.


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Children's Cancer Institute Australia for Medical Research, "Scientists find cancer causing protein", Tuesday, 13 November 2007

A team of researchers have discovered a completely new pathway in which a cell protein causes two common forms of cancer, neuroblastoma and breast cancer.
In neuroblastoma, the most common tumour of infants, and breast cancer, levels of the Myc proteins are commonly elevated in tumour cells. High levels of the protein are also associated with poor treatment outcomes. However, the way in which these proteins cause cancer has remained unknown.
For the first time, researchers at Children’s Cancer Institute Australia for Medical Research (CCIA), and collaborators in Italy, describe how the Myc proteins lead to tumour formation.
"Our results show that Myc proteins cause cancer by switching off genes involved in cancer prevention, such as transglutaminase 2 (TG2)," says Professor Glenn Marshall, Head of CCIA’s Molecular Carcinogenesis Program and Director of the Centre for Children’s Cancer and Blood Disorders at Sydney Children's Hospital.
"In addition to this, we have also shown that when the neuroblastoma and breast cancer cells are treated with a new class of anti-cancer drugs called histone deacetylase inhibitors (HDACIs), they are able to turn the TG2 gene back on, which then inhibits tumour growth."
The results, which will be published in the prestigious Proceedings of the National Academy of Science USA journal, describe in detail the complex interaction between the Myc protein, TG2 gene and HDACI drug within tumour cells.
"This work highlights the importance of HDACIs for the treatment of cancers caused by the high levels of Myc proteins," says Professor Marshall.
"More importantly, we identify TG2 as a potential drug development target for the treatment of these cancers.
"We believe that TG2 mimetics, combined with HDACIs in cancer therapy, will have potent anticancer effects in cells driven by Myc proteins."

Source: Ellen, Sat 3/29/2008 9:01 PM, The Neuroblastoma (Cancer) Online Support Group Mailing List[N-BLASTOMA@LISTSERV.ACOR.ORG]

Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse

In spite of the satisfactory frequency of clinical response to first-line therapy in neuroblastoma (NB), complete eradication of NB cells is rarely achieved. As a consequence, the majority of patients with advanced stage NB undergo relapse, which is often resistant to conventional treatment and rapidly overwhelming. Thus, after induction of the apparent remission, new therapeutic strategies are needed to completely eradicate the small number of surviving NB cells and to prevent relapse. We explored the potential of different doses of the anti-GD2 monoclonal antibody (mAb) 14G2a in an experimental metastatic model where a limited number of HTLA-230 human NB cells are injected i.v. into nude mice, leading to extensive metastases and death of animals within 7–8 weeks. Treatment with 14G2a mAb (1–4 mg/kg cumulative dose given as five i.v. daily administrations) dramatically reduced the metastatic spread of NB cells and prolonged the long-term survival of treated mice in a dose-dependent manner. Neither macrophages nor NK cells appeared to contribute to the protective effect of antibody treatment in vivo, suggesting either an involvement of granulocytes or a complement-mediated cytotoxicity towards NB cells. Whatever the effecting mechanism(s) involved, these results strongly support the clinical use of anti-GD2 mAbs after first-line induction regimens.

Reference: Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse