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1.  MYCN-mediated transcriptional repression in neuroblastoma: the other side of the coin 
Neuroblastoma is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during the infancy. MYCN amplification and overexpression occur in about 25% of total neuroblastoma cases and this percentage increases at 30% in advanced stage neuroblastoma. So far, MYCN expression profile is still one of the most robust and significant prognostic markers for neuroblastoma outcome. MYCN is a transcription factor that belongs to the family of MYC oncoproteins, comprising c-MYC and MYCL genes. Deregulation of MYC oncoprotein expression is a crucial event involved in the occurrence of different types of malignant tumors. MYCN, as well as c-MYC, can heterodimerize with its partner MAX and activate the transcription of several target genes containing E-Box sites in their promoter regions. However, recent several lines of evidence have revealed that MYCN can repress at least as many genes as it activates, thus proposing a novel function of this protein in neuroblastoma biology. Whereas the mechanism by which MYCN can act as a transcriptional activator is relatively well known, very few studies has been done in the attempt to explain how MYCN can exert its transcription repression function. Here, we will review current knowledge about the mechanism of MYCN-mediated transcriptional repression and will emphasize its role as a repressor in the recruitment of a precise set of proteins to form complexes capable of down-regulating specific subsets of genes whose function is actively involved in apoptosis, cell differentiation, chemosensitivity, and cell motility. The finding that MYCN can also act as a repressor has widen our view on its role in oncogenesis and has posed the bases to search for novel therapeutic drugs that can specifically target its transcriptional repression function.
doi:10.3389/fonc.2013.00042
PMCID: PMC3593680  PMID: 23482921
MYCN; neuroblastoma; transcriptional repression; cell differentiation; apoptosis; cell cycle
2.  Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma 
Molecular cancer therapeutics  2009;8(8):2461-2469.
We studied expression of the Aurora A gene and its clinical significance in a cohort of neuroblastoma patients. In addition, we investigated the antitumor activity of MLN8054, a novel small-molecule inhibitor of Aurora A kinase, on cultured NB cell lines in vitro. Aurora A mRNA expression was assessed by quantitative real-time PCR in tumor tissue specimens from 67 patients at diagnosis and in 9 human neuroblastoma cell lines. Western blot assays for Aurora A protein were done on tumor tissue of 53 patients. The results were correlated with various prognostic factors of neuroblastoma. Aurora A mRNA and protein expression were identified in 9 of 9 neuroblastoma cell lines. Overexpression of Aurora A mRNA in neuroblastoma tumor tissue is associated with high risk (P = 0.019), high-stage (International Neuroblastoma Staging System III and IV) tumors (P = 0.007), unfavorable histology (P = 0.007), MYCN amplification (P = 0.017), disease relapse (P = 0.019), and decreased progression-free survival (P < 0.0001) but not correlated with the age at diagnosis (P = 0.877). Similarly, Aurora A protein expression also significantly correlated with high risk (P = 0.011), high stage (P = 0.0028), unfavorable histology (P = 0.0006), MYCN amplification (P = 0.0029), and disease relapse (P = 0.044). Small interfering RNA–mediated knockdown of the endogenous Aurora A gene causes a proliferation defect and enhances chemosensitivity in human neuroblastoma cell lines. In support of these observations, the Aurora A kinase inhibitor, MLN8054, markedly inhibited growth of cultured neuroblastoma cell lines through an apoptosis-dependent pathway. Overexpression of Aurora A is associated with disease progression in neuroblastoma. Inhibition of this kinase is a promising modality for neuroblastoma treatment.
doi:10.1158/1535-7163.MCT-08-0857
PMCID: PMC3966113  PMID: 19671766
3.  Extra luminal colonic gastrointestinal stromal tumor: a case report 
Cases Journal  2009;2:7525.
Introduction
Gastrointestinal stromal tumors are the commonest mesenchymal tumors of the gastrointestinal tract, the stomach and small intestine are the favored sites of occurrence. They rarely occur in the colon, rectum and esophagus. GIST is neoplasm of mesenchymal origin originating from precursors of the interstitial cells of cajal. The symptoms of gastrointestinal stromal tumor depend on the site and size of the tumor, and may include abdominal pain, gastrointestinal bleeding or signs of obstruction; small tumors may, however, be asymptomatic. Majority of the patients with gastrointestinal stromal tumor have bloody stools and abdominal pain as the commonest manifestation. We describe a young female with extra luminal colonic gastrointestinal stromal tumor presenting as mass abdomen.
Case presentation
We describe 34-year-old female from north Indian state of Jammu and Kashmir who had presented with history of slowly increasing epigastric lump associated with abdominal discomfort of 4 months duration. She had no features of luminal obstruction. Her contrast enhanced computed tomography abdomen revealed a large extra-colonic mass in relation to transverse colon. The tumor was resected and histology was suggestive of gastrointestinal stromal tumor.
Conclusion
Extra luminal colonic gastrointestinal stromal tumors are very rare and can present as mass abdomen. Resection is the treatment of choice.
doi:10.1186/1757-1626-2-7525
PMCID: PMC2740148  PMID: 19829995
4.  Biochemical parameters in neuroblastoma 
Apart from the biochemical parameters routinely used like Vanillyl Mandellic Acid for the patients with neuroblastoma the parameters like neuron specific enolase, ferritin, lactate dehydrogenase, gamma glutamyl transferase were also studied to assess the utility in diagnosing the patients with neuroblastoma. The study involved 40 healthy ambulatory subjects and 30 untreated cases of histologically proved neuroblastoma referred to the Tata Memorial Hospital for further management and treatment. The urinary Vanillyl Mandellic Acid levels and the serum levels of neuron specific enolase, ferritin, lactate dehydrogenase had increased significantly, p<0.001 whereas the gamma glutamyl transferase had decreased significantly p<0.001, as compared to the normal. Serum neuron specific enolase, ferritin, lactate dehydrogenase alongwith urinary Vanillyl Mandellic Acid could be of help in diagnosing the patients with neuroblastoma.
doi:10.1007/s12291-008-0066-7
PMCID: PMC3453444  PMID: 23105774
Biochemical Parameters; Neuroblastoma; Vanillyl Mandellic Acid; Neuron Specific Enolase
5.  Neuroblastoma occurring in a 38-year old Nigerian man: a rare finding 
Rare Tumors  2009;1(1):e15.
Neuroblastoma (NB) is a common malignancy in children, but rarely occurs in adults. Accepted unfavorable prognostic factors include age over one year, low histological grade and advanced stage, MYCN amplification, chromosomal aberrations, elevations of neuron specific enolase and lactate dehydrogenase, and increased catecholamine metabolites in urine or serum. In adults, abdomen/retroperitoneum are the primary sites and in children the adrenal gland. We report a 38-year old civil servant who presented at our urology clinic on the 21st of December 2007 with a six month history of right flank dull pain which was worse on walking and relieved by rest, hypertension and a large right retroperitoneal mass. Tumor resection revealed a grade III NB. Chemotherapy using a combination of vincristine, adriamycin and cyclophosphamide was started. Follow-up showed regression of the mass initially with a relapse after patient absconded for three months. He resurfaced with new masses and he had a repeat chemotherapy with disappearance of the masses and is currently undergoing further treatment. To our knowledge this is the only report of NB in an adult registered so far in Nigeria and perhaps the whole of Africa. Currently, there are no standard treatment guidelines for patients with NB in adulthood. This study emphasizes the need for a standard treatment regime for adult onset neuroblastoma and its recognition as a possible differential in intra-abdominal mass in adults.
doi:10.4081/rt.2009.e15
PMCID: PMC2994447  PMID: 21139886
neuroblastoma; adult.
6.  Primary Intrarenal Neuroblastoma with Hypertension and Disseminated Intravascular Coagulation 
The primary intrarenal neuroblastoma (IRNB) is a rare condition. Intrarenal neuroblastoma typically results from direct renal invasion from an adrenal neuroblastoma, but true intrarenal neuroblastoma originates either sequestered adrenal rests during the fetal life or intrarenal sympathetic ganglia. Clinical, radiological, and pathological correlation is very essential for diagnosis and appropriate management of this type of unusual cases. The distinction of this rare tumor from Wilms' tumor is an important challenge since both tumors have major differences in prognostic and therapeutic response. We present a 3-year-old boy of primary intrarenal neuroblastoma with extensive abdominal and mediastinal mass, persistent hypertension, and disseminated intravascular coagulation (DIC).
doi:10.1155/2013/684939
PMCID: PMC3876591  PMID: 24416605
7.  Lung Metastases in Neuroblastoma at Initial Diagnosis: A Report from the International Neuroblastoma Risk Group (INRG) Project 
Pediatric blood & cancer  2008;51(5):589-592.
Background
Neuroblastoma is the most common extracranial pediatric solid cancer. Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma. We aimed to describe the incidence, clinical characteristics, and outcome of patients with lung metastasis at initial diagnosis using a large international database.
Procedure
The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis. Clinical and biological characteristics were compared between patients with and without lung metastasis. Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods. Cox proportional hazards methods were used to determine the independent prognostic value of lung metastasis at diagnosis.
Results
Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis. Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (p < 0.02 in each case). Five-year overall survival ± standard error for patients with lung metastasis was 34.5% ± 6.8% compared to 44.7% ± 1.3% for patients without lung metastasis (p=0.0002). However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome.
Conclusions
Lung metastasis at initial diagnosis of neuroblastoma is associated with MYCN amplification and elevated LDH levels. Although lung metastasis at diagnosis was not independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome.
doi:10.1002/pbc.21684
PMCID: PMC2746936  PMID: 18649370
Neuroblastoma; Lung Metastases; Pulmonary; MYCN
8.  Immature extragastric teratoma of infancy: a rare tumour with review of the literature 
BMJ Case Reports  2011;2011:bcr1220103674.
A full term otherwise healthy, 4-months-old male infant presented with progressive distension of abdomen from 2 months. The clinical examination showed shifting dullness only but no definite lump palpable. The abdominal radiography revealed calcification in right hypochondrium. Serum α-feto protein (AFP), neuron specific enolase, β human chorionic gonadotrophin and urinary vanillymandelic acid (VMA) were appropriate for age-range. Contrast enhanced abdominal CT showed predominantly multicystic lesion in right hypochondrium with central solid component and calcification, but no definite organ of origin determined. The exploratory laparotomy showed extra gastric multilobulated cystic mass sized 23×15×8 cm lesion arising from the lesser curvature of body of stomach. The tumour was feeding through short pedicle based on left gastric artery. There was no infiltration to adjacent areas. Histopathology of excised specimen showed immature teratoma. The child was discharged with appropriate advice and had no recurrence in 1 year of follow-up.
doi:10.1136/bcr.12.2010.3674
PMCID: PMC3070927  PMID: 22700350
9.  Significance of MYCN Amplification in International Neuroblastoma Staging System Stage 1 and 2 Neuroblastoma: A Report From the International Neuroblastoma Risk Group Database 
Journal of Clinical Oncology  2009;27(3):365-370.
Purpose
Treatment of patients with localized neuroblastoma with unfavorable biologic features is controversial. To evaluate the outcome of children with low-stage MYCN-amplified neuroblastoma and develop a rational treatment strategy, data from the International Neuroblastoma Risk Group (INRG) database were analyzed.
Patients and Methods
The database is comprised of 8,800 patients. Of these, 2,660 patients (30%) had low-stage (International Neuroblastoma Staging System stages 1 and 2) neuroblastoma, known MYCN status, and available follow-up data. Eighty-seven of these patients (3%) had MYCN amplified tumors.
Results
Patients with MYCN-amplified, low-stage tumors had less favorable event-free survival (EFS) and overall survival (OS) than did patients with nonamplified tumors (53% ± 8% and 72% ± 7% v 90% ± 1% and 98% ± 1%, respectively). EFS and OS were statistically significantly higher for patients whose tumors were hyperdiploid rather than diploid (EFS, 82% ± 20% v 37% ± 21%; P = .0069; OS, 94% ± 11% v 54% ± 15%; P = .0056, respectively). No other variable had prognostic significance. Initial treatment consisted of surgery alone for 29 (33%) of 87 patients. Details of additional therapy were unknown for 14 patients. Twenty-two patients (25%) underwent surgery and moderate-intensity chemotherapy; another 22 underwent surgery, intensive chemotherapy, and radiation therapy. Nine of the latter 22 underwent stem cell transplantation. Survival in patients who received transplantation did not differ from survival in those who did not receive transplantation.
Conclusion
Among patients with low-stage, MYCN-amplified neuroblastoma, outcomes of patients with hyperdiploid tumors were statistically, significantly better than those with diploid tumors. The data suggest that tumor cell ploidy could potentially be used to identify candidates for reductions in therapy. Further study of MYCN-amplified, low-stage neuroblastoma is warranted.
doi:10.1200/JCO.2008.17.9184
PMCID: PMC2651034  PMID: 19047282
10.  Excision of N-myc from chromosome 2 in human neuroblastoma cells containing amplified N-myc sequences. 
Molecular and Cellular Biology  1990;10(2):823-829.
Amplification of one of three growth-stimulating myc genes is a common method by which many tumor types gain a proliferative advantage. In metastatic human neuroblastoma, the amplification of the N-myc locus, located on chromosome 2, is a dominant feature of this usually fatal pediatric cancer. Of the many models proposed to explain this amplification, all incorporate as the initial step either disproportionate overreplication of the chromosomal site or recombination across a loop structure. The original locus is retained within the chromosome in the overreplication models but is excised in the recombination models. To test these models, we have used somatic cell hybrids to separate and analyze the chromosomes 2 from a neuroblastoma cell line containing in vivo amplified N-myc. Our results demonstrate that N-myc is excised from one of the chromosomes, suggesting that deletion is a requisite part of gene amplification in a naturally occurring system.
Images
PMCID: PMC360884  PMID: 2405257
11.  Transcribed-ultra conserved region expression is associated with outcome in high-risk neuroblastoma 
BMC Cancer  2009;9:441.
Background
Neuroblastoma is the most common, pediatric, extra-cranial, malignant solid tumor. Despite multimodal therapeutic protocols, outcome for children with a high-risk clinical phenotype remains poor, with long-term survival still less than 40%. Hereby, we evaluated the potential of non-coding RNA expression to predict outcome in high-risk, stage 4 neuroblastoma.
Methods
We analyzed expression of 481 Ultra Conserved Regions (UCRs) by reverse transcription-quantitative real-time PCR and of 723 microRNAs by microarrays in 34 high-risk, stage 4 neuroblastoma patients.
Results
First, the comparison of 8 short- versus 12 long-term survivors showed that 54 UCRs were significantly (P < 0.0491) over-expressed in the former group. For 48 Ultra Conserved Region (UCRs) the expression levels above the cut-off values defined by ROC curves were strongly associated with good-outcome (OS: 0.0001

Conclusions
Our pilot study suggests that a deregulation of the microRNA/T-UCR network may play an important role in the pathogenesis of neuroblastoma. After further validation on a larger independent set of samples, such findings may be applied as the first T-UCR prognostic signature for high-risk neuroblastoma patients.
doi:10.1186/1471-2407-9-441
PMCID: PMC2804711  PMID: 20003513
California Medicine  1953;78(4):263-266.
A study was undertaken to determine whether there are any features of retroperitoneal tumors in children that might be demonstrated on roentgenograms to aid in identifying them preoperatively. Study was limited to Wilms' tumor of the kidney and neuroblastoma.
Calcification was found in 57 per cent of the neuroblastomas and in only 12 per cent of Wilms' tumors. Calcifications in neuroblastomas differed from those in Wilms' tumors. Calcification in neuroblastoma was more frequent in older children than in the younger ones.
The kidney was frequently displaced by both types of tumor. However, the neuroblastoma always displaced the kidney downward, or downward and slightly outward.
In most instances, the Wilms' tumor also displaced the kidney downward and outward, but in some instances upward and medially. This, of course, depended upon the site of origin of the tumor.
There was a distortion of the intrarenal structures in 75 per cent of the cases of neuroblastoma and in 71 per cent of the cases of Wilms' tumor.
Images
PMCID: PMC1521811  PMID: 13042655
Obstetrics & Gynecology Science  2013;56(6):412-415.
Extra-ovarian yolk sac tumor arising in the omentum is extremely rare. As yolk sac tumor originated from the omentum has been rarely reported, its clinical information is very limited. The authors encountered a case of yolk sac tumor originated from the omentum, and reported the case herein. A 32-year-old woman was presented with developed low abdominal distension for a month. Magnetic resonance imaging findings were suggestive of ovarian malignancy with ascites and peritoneal seeding nodules. Explorative laparotomy was performed and then the findings from frozen biopsy of omentum were suggestive of poorly differentiated tumor though whether it was primary or metastatic was uncertain. Thus, staging laparotomy were performed. Histopathology confirmed that the tumor was a yolk sac tumor of omentum origin. Then, 6 cycles of postoperative adjuvant chemotherapy at intervals of 3 weeks were performed using bleomycin, etoposide, and cisplatin regimen. Four-year outpatient follow-up thereafter showed no relapse.
doi:10.5468/ogs.2013.56.6.412
PMCID: PMC3859011  PMID: 24396822
Bleomycin, etoposide, and cisplatin regimen; Chemotherapy, Omentum; Yolk sac tumor
Genome Biology  2008;9(10):R150.
Differences in MYCN/c-MYC target gene expression are associated with distinct neuroblastoma subtypes and clinical outcome.
Background
Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype. In MYCN single-copy neuroblastomas, elevated MYCN mRNA and protein levels are paradoxically associated with a more favorable clinical phenotype, including disseminated tumors that subsequently regress spontaneously (stage 4s-non-amplified). In this study, we asked whether distinct transcriptional MYCN or c-MYC activities are associated with specific neuroblastoma phenotypes.
Results
We defined a core set of direct MYCN/c-MYC target genes by applying gene expression profiling and chromatin immunoprecipitation (ChIP, ChIP-chip) in neuroblastoma cells that allow conditional regulation of MYCN and c-MYC. Their transcript levels were analyzed in 251 primary neuroblastomas. Compared to localized-non-amplified neuroblastomas, MYCN/c-MYC target gene expression gradually increases from stage 4s-non-amplified through stage 4-non-amplified to MYCN amplified tumors. This was associated with MYCN activation in stage 4s-non-amplified and predominantly c-MYC activation in stage 4-non-amplified tumors. A defined set of MYCN/c-MYC target genes was induced in stage 4-non-amplified but not in stage 4s-non-amplified neuroblastomas. In line with this, high expression of a subset of MYCN/c-MYC target genes identifies a patient subtype with poor overall survival independent of the established risk markers amplified MYCN, disease stage, and age at diagnosis.
Conclusions
High MYCN/c-MYC target gene expression is a hallmark of malignant neuroblastoma progression, which is predominantly driven by c-MYC in stage 4-non-amplified tumors. In contrast, moderate MYCN function gain in stage 4s-non-amplified tumors induces only a restricted set of target genes that is still compatible with spontaneous regression.
doi:10.1186/gb-2008-9-10-r150
PMCID: PMC2760877  PMID: 18851746
Nucleic Acids Research  1994;22(2):187-193.
In order to elucidate the initiation of the N-myc gene amplification, we have analyzed the original structures of the N-myc amplicons among 38 human neuroblastomas. Nineteen DNAs isolated from the N-myc amplicons recognized a continuous stretch totally encompassing a 5.5 megabase region spanning the normal N-myc gene. The co-amplification profiles with these DNAs showed that two of them, which mapped into a 300 kb region flanking the N-myc gene, were commonly amplified in most specimens, while others were differentially amplified among various subsets. These profiles enabled us to divide the N-myc amplicons into several groups and outline their original domains as a continuous stretches, pointing to the existence of 'consensus sites' for the ends of the initial domains in the original region. In one cell line, the domain was found to be several times larger than that of the derivative amplicon; and the rearranged sites identified within the amplicons, which showed no site specificity, were consistent with those deduced from the domain structure. These results lead to a model in which N-myc gene amplification is initiated at some consensus sites by a preferential mechanism and followed by a random loss of the domain structures during subsequent stages.
Images
PMCID: PMC307770  PMID: 8121803
Extra-abdominal desmoid tumors are known as aggressive fibromatosis (AFM). Synchronous and metachronous multicentric aggressive fibromatosis are rare lesions and pose dilemma in diagnosis and management. A rare and interesting case of recurrent multicentric, synchronous AFM is presented which to the best of our knowledge has not been reported earlier. A young male presented with well defined, hard, fixed swelling on the thigh. Resected tumor mass on histopathology was diagnosed as an extra abdominal fibromatosis. He presented again after two months with swelling at the same site; and two more swellings on the foot. Fine needle aspiration cytology (FNAC) from all three sites was performed; and was suggestive of benign spindle cell lesion of fibrogenic origin with the possibility of multicentric synchronous recurrent aggressive fibromatosis.
doi:10.4103/0970-9371.93227
PMCID: PMC3307455  PMID: 22438620
Aggressive fibromatosis; cytology; desmoid tumor; synchronous multicentric tumors
Gynecological Surgery  2012;9(3):237-245.
The aim of this study was to provide a single site resource for investigators, clinicians, and others seeking preclinical, animal, and human investigational studies concerning the postsurgical, anti-adhesion barrier Seprafilm™ (Genzyme Corporation, Cambridge, MA). All published preclinical, animal, human extra-abdominal research as of July 2011 have been summarized and included in this document. Searches of Medline and EMBASE Drugs and Pharmaceuticals databases were conducted for original preclinical, animal, and human extra-abdominal studies involving Seprafilm. Preclinical, animal, and extra-abdominal human investigational studies are the study selection for this manuscript. Intraabdominal use is discussed in the accompanying manuscript. Data extraction includes systematic manuscript review. Summary of preclinical, animal, and extra-abdominal human investigational use of Seprafilm by surgical discipline were gathered for data synthesis. The clinical use of Seprafilm, which was approved by the FDA for intra-abdominal procedures, is supported by preclinical and animal studies relating to general surgical and obstetrical/gynecological applications. Findings from preclinical, animal, and human investigational studies at other sites throughout the body raises the potential for additional human clinical trials to assess efficacy and safety following surgical procedures at non-abdominal locations.
doi:10.1007/s10397-012-0741-9
PMCID: PMC3401296  PMID: 22837732
Postoperative adhesions; Seprafilm; Anti-adhesion adjuvant; Adhesiolysis
Cell Death & Disease  2014;5(3):e1100-.
Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting.
doi:10.1038/cddis.2014.68
PMCID: PMC3973198  PMID: 24603328
neuroblastoma; schwannian stroma; neural cell differentiation; neuroblastoma prognostic factor
Background
Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site.
Case presentation
A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma.
Methods and results
We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors.
Conclusion
Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed.
doi:10.1186/1477-7819-7-47
PMCID: PMC2691402  PMID: 19454018
Journal of Oncology  2011;2012:782020.
Neuroblastoma, a progressive solid tumor in childhood, continues to be a clinical challenge. It is highly vascular, heterogeneous, and extracranial tumor that originates from neural crest. Angiogenesis, genetic abnormalities, and oncogene amplification are mainly responsible for malignant phenotype of this tumor. Survivability of malignant neuroblastoma patients remains poor despite the use of traditional therapeutic strategies. Angiogenesis is a very common and necessary pre-requisite for tumor progression and metastasis. Angiogenesis is also a major factor in making malignant neuroblastoma. Thus, prevention of angiogenesis can be a highly significant strategy in the treatment of malignant neuroblastoma. Here, we summarize our current understanding of angiogenesis in malignant neuroblstoma and describe the use of experimental anti-angiogenic agents either alone or in combination therapy. This review will clearly indicate the importance of angiogenesis in the pathogenesis of malignant neuroblastoma, its prevention as a promising therapy in preclinical models of malignant neuroblastoma, and prospective clinical trials.
doi:10.1155/2012/782020
PMCID: PMC3163143  PMID: 21876694
Journal of Korean Medical Science  2003;18(4):618-620.
Neuroblastomas are derived from the neural crest ectoderm, and are the most common solid abdominal masses of infancy. Congenital neuroblastoma, however, is rare. We report a rare case of congenital neuroblastoma with multiple metastases found at autopsy, performed at 2 days after birth. He was born by cesarian section and weighed 2,350 g. His respiration was weak and abdomen was distended. The patient died 2 days after birth. Postmortem examination revealed a relatively well demarcated ovoid mass, in the left adrenal, with necrosis and hemorrhage. Multiple small metastatic tumor nodules in the liver, lung, kidney, brain, rib, thyroid glands, and spleen, were noted. The histopathological pictures confirmed the diagnosis of neuroblastoma of the adrenal with multiple metastasis.
PMCID: PMC3055087  PMID: 12923347
Neuroblastoma is a common pediatric solid tumor that exhibits a striking clinical bipolarity favorable and unfavorable. The survival rate of children with unfavorable neuroblastoma remains low among all childhood cancers. MYCN and MYC play a crucial role in determining the malignancy of unfavorable neuroblastomas, whereas high-level expression of the favorable neuroblastoma genes is associated with a good disease outcome and confers growth suppression of neuroblastoma cells. A small fraction of neuroblastomas harbors TP53 mutations at diagnosis, but a higher proportion of the relapse cases acquire TP53 mutations. In this study, we investigated the effect of S(+)-ibuprofen on neuroblastoma cell lines, focusing on the expression of the MYCN, MYC, AKT, p53 proteins and the favorable neuroblastoma genes in vitro as biomarkers of malignancy. Treatment of neuroblastoma cell lines with S(+)-ibuprofen resulted in a significant growth suppression. This growth effect was accompanied by a marked decrease in the expression of MYC, MYCN, AKT and an increase in p53 expression in neuroblastoma cell lines without TP53 mutation. In addition, S(+)-ibuprofen enhanced the expression of some favorable neuroblastoma genes (EPHB6, CD44) and genes involved in growth suppression and differentiation (EGR1, EPHA2, NRG1 and SEL1L). Gene expression profile and Ingenuity pathway analyses using TP53-mutated SKNAS cells further revealed that S(+)-ibuprofen suppressed molecular pathways associated with cell growth and conversely enhanced those of cell cycle arrest and the unfolded protein response. Collectively, these results suggest that S(+)-ibuprofen or its related compounds may have the potential for therapeutic and/or palliative use for unfavorable neuroblastoma.
doi:10.3892/ijo.2013.2148
PMCID: PMC3867363  PMID: 24173829
neuroblastoma; MYCN; MYC; p53; favorable neuroblastoma genes
Molecular and Cellular Biology  1989;9(11):4903-4913.
Human neuroblastoma cells often carry amplified DNA encompassing the gene N-myc. Amplified N-myc has been found localized in "double minutes" in direct tumor cell preparations. In contrast, later passages carried amplified N-myc almost exclusively within a single homogeneously staining chromosomal region located at a chromosomal site different from the normal location of N-myc. We used pulsed field gel electrophoresis to define the structural arrangement of the amplified DNA. Long-range mapping was facilitated by the presence of several sites for rare cutting restriction endonucleases in the 5' region of N-myc. Amplified DNAs of different neuroblastoma cell lines were heterogeneous in size and had undergone recombination at various distances from N-myc. N-myc occupied a central position within the amplified DNA, and in no case was the coding region affected by recombination. Among neuroblastoma cells, varying proportions of amplified DNA (in some instances close to 100%) consisted of multiple tandem arrays of DNA segments ranging in size from 100 to 700 kilobase pairs. Tumor cells with low degrees of amplification revealed regions of amplified DNA in excess of 1,500 kilobase pairs without apparent rearrangement. Our observations, in concert with the cytogenetic findings, suggest a model of gene amplification which involves unscheduled DNA replication, recombination, and formation of extrachromosomal DNA followed by integration into a chromosome and subsequent in situ multiplication. The central position which N-myc occupies within the amplified sequences and the lack of recombination within the coding region of N-mc indicate that N-myc rather than other genetic information provides the selective advantage for retention of the amplified DNA.
Images
PMCID: PMC363641  PMID: 2601700
Introduction
Retroperitoneal neoplasms are rare and easily misdiagnosed. These tumors are often discovered incidentally during imaging studies performed for other reasons. Paragangliomas are tumors that arise from extra-adrenal medullary neural crest derivatives. They are usually located in the head and neck but can be found in various body sites, including the chest cavity, abdomen, pelvis and bladder. We report the case of a patient who had a retroperitoneal paraganglioma manifested as paralytic ileus, which is an unusual presentation of a paraganglioma.
Case presentation
A 63-year-old Taiwanese woman was admitted to the emergency department of our hospital with progressive abdominal fullness for two days. Her medical history included medically controlled hypertension for 10 years and type 2 diabetes mellitus. Plain abdominal radiography showed a solitary loop of the air-filled dilated small bowel. Abdominal computed tomography did not show a mechanical obstruction; however, a retroperitoneal mass was incidentally detected. Histological analysis of the mass led to a diagnosis of a paraganglioma.
Conclusions
In cases of patients with hypertension presenting with an intestinal pseudo-obstruction, a paraganglioma may be considered as a possible differential diagnosis of retroperitoneal tumors to avoid risky therapeutic procedures or medication that may produce severe adverse effects.
doi:10.1186/1752-1947-6-158
PMCID: PMC3441355  PMID: 22716303
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that arise from the gastrointestinal tract. In rare cases, these tumors are found in intra-abdominal sites unrelated to the gastrointestinal tract, such as the mesentery, omentum and retroperitoneum. However, pancreatic extra-gastrointestinal stromal tumors are extremely rare, with only 14 previous cases reported. A 61-year-old man with no clinical symptoms had a routine check-up, during which an abdominal mass located in the pancreas tail was detected. Abdominal surgery was performed with resection of the pancreas tail and the spleen, and he was diagnosed with low-risk GISTs. Another 60-year-old man with no clinical symptoms underwent Computed tomography which revealed a well-demarcated tumor, 6 cm in diameter, in the head of the pancreas. He was diagnosed with pancreatic GISTs. Here, we describe two rare cases of pancreatic GISTs and review the cases previously reported in the literature.
doi:10.3748/wjg.v20.i3.863
PMCID: PMC3921496  PMID: 24574760
Gastrointestinal Stromal tumors; Extra-gastrointestinal Stromal Tumors; Pancreatic gastrointestinal stromal tumors

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