Congenital neuroblastoma with liver metastasis presenting with Hashimoto Pritzker disease

Jacob, Elliot; Varghese, Renu G'Boy; Toi, Pampa Ch; Bhaskaran, Reshma; Rai, Ramji

doi:10.4103/0377-4929.54998

Cited by 4 publications

(3 citation statements)

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“…More than 90% of the neuroblastomas are diagnosed before 5 years of age with greater occurrence of refractory and relapsed neuroblastomas in pediatric population over 18 months. Neuroblastomas metastasize to various sites like skull, bones, spine and retro-orbital tissues which lead to challenging clinical presentations like proptosis and retro-orbital ecchymosis in children (2–4). The major genetic causes for the incidence and therapeutic refractoriness of neuroblastomas include amplification of the oncogene N-Myc and loss of tumor suppressor p53 (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Didymin Induces Apoptosis by Inhibiting N-Myc and Upregulating RKIP in Neuroblastoma

Singhal

Nagaprashantha²,

Vatsyayan³

et al. 2012

Cancer Prevention Research

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Neuroblastomas arise from the neural crest cells and represent the most common solid tumors outside the nervous system in children. The amplification of N-Myc plays a primary role in the pathogenesis of neuroblastomas whereas acquired mutations of p53 lead to refractory and relapsed cases of neuroblastomas. In this regard, dietary compounds which can target N-Myc and exert anti-cancer effects independent of p53 status acquire significance in the management of neuroblastomas. Hence, we investigated the anti-cancer properties of the flavonoid didymin in neuroblastomas. Didymin effectively inhibited proliferation and induced apoptosis irrespective of p53 status in neuroblastomas. Didymin down regulated PI3K, pAkt, Akt, vimentin and up regulated RKIP levels. Didymin induced G2/M arrest along with decreasing the levels of cyclin D1, CDK4 and cyclin B1. Importantly, didymin inhibited NMyc as confirmed at protein, mRNA and transcriptional level by promoter-reporter assays. HPLC analysis of didymin (2 mg/kg b.w.) treated mice serum revealed effective oral absorption with free didymin concentration of 2.1 μM. Further in vivo mice xenograft studies revealed that didymin (2 mg/kg b.w.) treated animals had significant reductions in tumors size compared to controls. Didymin strongly inhibited the proliferation (Ki67) and angiogenesis (CD31) markers as well as N-Myc expression as revealed by the histopathological examination of paraffin embedded section of resected tumors. Collectively, our in vitro and in vivo studies elucidated the anti-cancer properties and mechanisms of action of a novel, orally active and palatable flavonoid didymin which makes it a potential new approach for neuroblastoma therapy (NANT) to target pediatric neuroblastomas.

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Section: Introductionmentioning

confidence: 99%

Didymin Induces Apoptosis by Inhibiting N-Myc and Upregulating RKIP in Neuroblastoma

Singhal

Nagaprashantha²,

Vatsyayan³

et al. 2012

Cancer Prevention Research

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“…Neuroblastomas arise from the neural crest tissue of the sympathetic ganglia. Neuroblastomas can metastasize to the liver where the metastatic tumors can be massive (2). The most common metastatic site is the skull where it metastasizes to sphenoid bone and retro bulbar tissue leading to common symptoms of proptosis and periorbital echymosis (3, 4).…”

Section: Introductionmentioning

confidence: 99%

Targeting p53-Null Neuroblastomas through RLIP76

Singhal

Yadav²,

Nagaprashantha³

et al. 2011

Cancer Prevention Research

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The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug-resistant p53-mutant as compared with drug-resistant p53 wild-type neuroblastoma revealed a novel mechanism for resistance to apoptosis: a direct role of p53 in regulating the cellular concentration of proapoptotic alkenals by functioning as a specific and saturable allosteric inhibitor of the alkenal-glutathione conjugate transporter, RLIP76. The RLIP76-p53 complex was showed by both immunoprecipitation analyses of purified proteins and immunofluorescence analysis. Drug transport studies revealed that p53 inhibited both basal and PKCa-stimulated transport of glutathione conjugates of 4HNE (GSHNE) and doxorubicin. Drug resistance was significantly greater for p53-mutant as compared with p53 wild-type neuroblastoma cell lines, but both were susceptible to depletion of RLIP76 by antisense alone. In addition, inhibition of RLIP76 significantly enhanced the cytotoxicity of cisplatin. Taken together, these studies provide powerful evidence for a novel mechanism for drug and apoptosis resistance in p53-mutant neuroblastoma, based on a model of regulation of p53-induced apoptosis by RLIP76, where p53 is a saturable and specific allosteric inhibitor of RLIP76, and p53 loss results in overexpression of RLIP76; thus, in the absence of p53, the drug and glutathione-conjugate transport activities of RLIP76 are enhanced. Most importantly, our findings strongly indicate RLIP76 as a novel target for therapy of drug-resistant and p53-mutant neuroblastoma.

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“…Extensive metastatic deposits to the liver have been observed in congenital neuroblastoma (Gupta and Bansal 2012). In one patient with congenital adrenal neuroblastoma and liver metastases, the disease process was associated with Hashimoto-Pritzker disease, a congenital self-healing cutaneous reticulohistiocytosis (Jacob et al 2009). Liver metastasis of neuroblastoma may also occur via transplacental twin-totwin metastasis in monozygotic twins (Tajiri et al 2010).…”

Section: Neuroblastoma Metastasis Of the Liver: Pepper Type Of Neurobmentioning

confidence: 99%

Undifferentiated Small Cell Tumors of the Hepatobiliary Tract

Zimmermann¹

2016

Tumors and Tumor-Like Lesions of the Hepatobiliary Tract

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A small group of primary hepatobiliary tumors is characterized by the presence of morphologically undifferentiated small cells. These small cell tumors (SCTs), which histologically appear as "small cell blue tumors" due to the dense crowding of nuclei together with poorly developed cytoplasm, have several cell lineage courses that can only be identified by means of immunohistochemistry and molecular methods. One type of hepatic SCT is a member of the complex family of neuroectodermal tumors that predominantly occur in the skeleton and soft tissues of adolescents and young adults (primitive neuroectodermal tumors or PNETs). Hepatic PNETs are very rare neoplasms with an aggressive course, and the tumor also develops in the biliary tract. Other hepatobiliary SCTs include desmoplastic small round cell tumor, NUT midline carcinoma, and hepatic neuroblastoma and its variants. As all hepatobiliary SCTs are very rare neoplasms, they have to be distinguished from the more common metastatic lesions of these tumors.

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Congenital neuroblastoma with liver metastasis presenting with Hashimoto Pritzker disease

Cited by 4 publications

References 0 publications

Didymin Induces Apoptosis by Inhibiting N-Myc and Upregulating RKIP in Neuroblastoma

Didymin Induces Apoptosis by Inhibiting N-Myc and Upregulating RKIP in Neuroblastoma

Targeting p53-Null Neuroblastomas through RLIP76

Undifferentiated Small Cell Tumors of the Hepatobiliary Tract

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