MedWorm: Neurofibromatosis

Running in your undies for a cause

CNN.com - Health — Mon, 25 Feb 2013 17:53:15 +0100

The Cupid's Undie Run has raised over $1.3 million for neurofibromatosis research. Who would have thought that running around in your underwear could do such good? (Source: CNN.com - Health)

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Globus pallidus high-signal lesions: A predominant MRI finding in children with neurofibromatosis type 1

Annals of Indian Academy of Neurology — Mon, 25 Feb 2013 05:00:00 +0100

Conclusion and Discussion: We have shown that UBOs are a common finding in children with NF1, and are most prevalent between the ages of 4 and 12 years. Many sites of the brain are affected by these lesions, most notably the globus pallidus and the cerebellum. Further research must be conducted to elucidate the significance of UBOs in patients with NF1 and whether these lesions have any utility in the clinical detection of NF1. (Source: Annals of Indian Academy of Neurology)

What Causes Constipation?

PediatricEducation.org — Mon, 25 Feb 2013 00:32:39 +0100

Discussion Constipation generally is defined as infrequent or painful defecation. Constipation can be very disturbing to the patient and family who believe the stools are too infrequent, too hard or too difficult to pass. Most children develop constipation after the child begins to associate pain (e.g. a hard bowel movement) with defecation. The child then begins to withhold the stools trying to decrease the defecation discomfort. As stool withholding continues, the rectum dilates and gradually accommodates with the normal defecation urge disappearing. Passing large hard stools infrequently reinforces the defecation pain. The cycle continues. If the cycling is severe enough, worsening stool retention and more abnormal defecation dynamics occurs. Chronic rectal distension results in both lo...

GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype-phenotype correlations and functional impact

Brain — Sun, 24 Feb 2013 05:00:00 +0100

Alterations in the balance between excitatory and inhibitory neurotransmission have been implicated in several neurodevelopmental disorders. Neurofibromatosis type 1 is one of the most common monogenic disorders causing cognitive deficits for which studies on a mouse model (Nfl+/–) proposed increased -aminobutyric acid-mediated inhibitory neurotransmission as the neural mechanism underlying these deficits. To test whether a similar mechanism translates to the human disorder, we used magnetic resonance spectroscopy to measure -aminobutyric acid levels in the visual cortex of children and adolescents with neurofibromatosis type 1 (n = 20) and matched control subjects (n = 26). We found that patients with neurofibromatosis type 1 have significantly lower -aminobutyric acid levels than c...

Running in your underwear to make a difference

CNN.com - Health — Thu, 21 Feb 2013 19:30:51 +0100

The Cupid's Undie Run has raised over $1.3 million for neurofibromatosis research. Who would have thought that running around in your underwear could do such good? (Source: CNN.com - Health)

Cupid's Undie Run for research

CNN.com - Health — Thu, 21 Feb 2013 15:59:40 +0100

The Cupid's Undie Run has raised over $1.3 million for neurofibromatosis research. Who would have thought that running around in your underwear could do such good? (Source: CNN.com - Health)

MedWorm Sponsor Message: Have a look at The Cancer and Oncology Daily, the new cancer portal with all the latest cancer news and research powered by MedWorm, updated daily.

Living with a rare disease, making a difference

CNN.com - Health — Thu, 21 Feb 2013 15:52:14 +0100

The Cupid's Undie Run has raised over $1.3 million for neurofibromatosis research. Who would have thought that running around in your underwear could do such good? (Source: CNN.com - Health)

Development of the adult PedsQLTM neurofibromatosis type 1 module: initial feasibility, reliability and validity

BioMed Central — Thu, 21 Feb 2013 05:00:00 +0100

Conclusions: The results demonstrate the initial feasibility, reliability and validity of the PedsQLTM NF1 module in adult patients. The PedsQLTM NF1 Module can be used to understand the multidimensional nature of NF1 on the HRQOL patients with this disorder. (Source: BioMed Central)

Young Australian adults with NF1 have poor access to health care, high complication rates, and limited disease knowledge

American Journal of Medical Genetics Part A — Wed, 20 Feb 2013 05:00:00 +0100

Abstract Neurofibromatosis type 1 (NF1) is a multisystem disease associated with a lifelong risk of debilitating and potentially life‐limiting complications, however many adults with NF1 have no regular health surveillance. We interviewed and examined 17 young adults with NF1 between the ages of 25 and 33. Most had not been assessed for NF1‐related complications within the previous 8 years, including patients with known serious vascular complications, for example, renal artery stenosis. Acute and/or chronic pain, particularly back and plexiform‐related pain were common symptoms, and despite a significant impact on quality of life, was untreated in most instances. Symptom and examination‐directed imaging revealed serious complications in 41% of the cohort. These included severe spin...

Caucasian Familial Moyamoya Syndrome With Rare Multisystemic Malformations

Pediatric Neurology — Mon, 18 Feb 2013 17:41:23 +0100

Abstract: Moyamoya disease is an idiopathic progressive steno-occlusive disorder of the intracranial arteries located at the base of the brain. It is associated with the development of compensatory extensive network of fine collaterals. Moyamoya disease is considered syndromic when certain genetic or acquired disorders such as polycystic kidney disease, neurofibromatosis, or meningitis are also present. Although the genetic contribution in moyamoya is indisputable, its cause and pathogenesis remain under discussion. Herein, we report a rare occurrence of moyamoya syndrome in two European Caucasian siblings in association with unusual multisystemic malformations (polycystic kidney disease in one, and intestinal duplication cyst in the other). The karyotype was normal. No mutation in the RFN...

What is the Differential Diagnosis of Multiple Fractures?

PediatricEducation.org — Mon, 18 Feb 2013 00:42:51 +0100

Discussion Bone mass, size and strength is at its peak in early adulthood. Multiple factors contribute to bone health including bone mass, hormonal balance, nutrition and weight bearing physical activity. Fractures are basically caused by too much force to be withstood by the bone. Abnormal momentary forces commonly occur in sports injuries such as this patient. When a child or young adult has several fractures, particularly clinically significant fractures, the possibility of an unidentified, underlying cause should be considered. According to the International Society for Clinical Densitometry, clinically significant fractures that clinicians should consider for a DXA scan includes fracture of long bones in the lower extremities, vertebral compression fractures, or two or more long-bone...

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Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model

Cell Death and Differentiation — Fri, 15 Feb 2013 05:00:00 +0100

Authors: N Sanchez-Macedo, J Feng, B Faubert, N Chang, A Elia, E J Rushing, K Tsuchihara, D Bungard, S L Berger, R G Jones, T W Mak & K Zaugg (Source: Cell Death and Differentiation)

Prolonged Survival in Adult Patients with Neurofibromatosis Type I and Recurrent High Grade Gliomas Treated with Bevacizumab (P01.098)

Neurology — Thu, 14 Feb 2013 05:00:00 +0100

CONCLUSIONS: In this case series, adult patients with recurrent HGGs had prolonged overall and post-recurrence survival. These results suggest bevacizumab may be an effective therapy in NF1 patients with recurrent HGGs. Based on these observations, evaluation of bevacizumab responses in sporadic glioblastomas with NF1 mutations is warranted.Disclosure: Dr. Theeler has nothing to disclose. Dr. Ellezam has nothing to disclose. Dr. Slopis has nothing to disclose. Dr. Loghin has nothing to disclose. Dr. De Groot has received personal compensation for activities with Genentech, Inc., VBL Therapeutics, and Merck & Co., Inc. Dr. De Groot has received research support from Sanofi-Aventis Pharmaceuticals, Inc., AstraZeneca Pharmaceuticals, and EMD Serono. (Source: Neurology)

Meningioangiomatosis: A Rare Presentation with Progressive Cortical Blindness and Encephalopathy (P01.111)

Neurology — Thu, 14 Feb 2013 05:00:00 +0100

CONCLUSIONS: MA is an extremely rare entity which is generally associated with neurofibromatosis and resolves after resection. This case is unique for four reasons; the patient does not have NF-2, never had seizures, symptoms are permanent and the disease is progressive.Disclosure: Dr. Shah has nothing to disclose. Dr. Korya has nothing to disclose. Dr. Larsen has nothing to disclose. Dr. Torres has nothing to disclose. Dr. Drake has nothing to disclose. Dr. LaWall has nothing to disclose. (Source: Neurology)

Loss of SOX10 function contributes to the phenotype of human Merlin-null schwannoma cells

Brain — Wed, 13 Feb 2013 05:00:00 +0100

Loss of the Merlin tumour suppressor causes abnormal de-differentiation and proliferation of Schwann cells and formation of schwannoma tumours in patients with neurofibromatosis type 2. Within the mature peripheral nerve the normal development, differentiation and maintenance of myelinating and non-myelinating Schwann cells is regulated by a network of transcription factors that include SOX10, OCT6 (now known as POU3F1), NFATC4 and KROX20 (also known as Egr2). We have examined for the first time how their regulation of Schwann cell development is disrupted in primary human schwannoma cells. We find that induction of both KROX20 and OCT6 is impaired, whereas enforced expression of KROX20 drives both myelin gene expression and cell cycle arrest in Merlin-null cells. Importantly, we show that...

Four-year follow-up study in a NF1 Boy with a focal pontine hamartoma

Italian Journal of Pediatrics — Mon, 11 Feb 2013 05:00:00 +0100

We describe a family affected by NF1 in whom genetic molecular analysis identified the same mutation in the son and father. Routine MRI showed pontine focal lesions in the eight-year-old son, though not in the father. We performed a four years follow-up study and at follow-up pontine hamartoma size remained unchanged in the son, and the father showed still no brain lesions, confirming thus an intra-familial phenotype variability. (Source: Italian Journal of Pediatrics)

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Piebaldism and neurofibromatosis: State of knowledge.

Dermatol Online J — Sun, 10 Feb 2013 10:20:02 +0100

Authors: Duarte A, Mota A, Baudrier T, Morais P, Santos A, Cerqueira R, Tavares P, Azevedo F Abstract Despite progress in understanding the molecular basis, the diagnosis of neurofibromatosis 1 (NF 1) is based on clinical criteria, established by the National Institute of Health (NIH) Consensus Conference in 1987. The association of NF1 and piebaldism has been reported, but some authors disagree with this co-occurrence. In the light of present knowledge, we highlight that both entities might co-exist in the same patient. PMID: 23374959 [PubMed - in process] (Source: Dermatol Online J)

A cost savings approach to SPRED1 mutational analysis in individuals at risk for neurofibromatosis type 1

American Journal of Medical Genetics Part A — Thu, 07 Feb 2013 05:00:00 +0100

Abstract Neurofibromatosis type 1 (NF1) is a clinically diagnosed autosomal dominant disorder requiring routine clinical management, particularly during the pediatric years. An overlapping disorder, Legius syndrome, at times is clinically indistinguishable from NF1 and results in a small percentage of individuals being mischaracterized. Distinguishing these two entities is increasingly important for prognosis, reproductive planning, and clinical management. The goal of our study was to evaluate the cost impact of genetic testing for patients with solely pigmentary findings. The costs of genetic testing in patients aged 1.5–18 years were modeled using a simulated population, assuming the clinical management approach of a single NF1 clinic. Two genetic testing algorithms (SPRED1 testing al...

Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria

American Journal of Medical Genetics Part A — Thu, 07 Feb 2013 05:00:00 +0100

This article summarizes the highlights presented at the Conference and represents the “state‐of‐the‐field” in 2011. Genetic studies indicate that constitutional mutations in the SMARCB1 tumor suppressor gene occur in 40–50% of familial cases and in 8–10% of sporadic cases of schwannomatosis. Tumorigenesis is thought to occur through a four‐hit, three‐step model, beginning with a germline mutation in SMARCB1 (hit 1), followed by loss of a portion of chromosome 22 that contains the second SMARCB1 allele and one NF2 allele (hits 2 and 3), followed by mutation of the remaining wild‐type NF2 allele (hit 4). Insights from research on HIV and pediatric rhabdoid tumors have shed light on potential molecular pathways that are dysregulated in schwannomatosis‐related schwannomas...

Researchers Hail Gene Breakthrough In Bid To Prevent Spinal Tumours

Health News from Medical News Today — Wed, 06 Feb 2013 10:00:00 +0100

Medical researchers have discovered a gene that is responsible for causing an inherited form of tumour known as spinal meningioma. Meningiomas are the commonest form of tumour affecting the brain and spine and are common in people who are affected by the genetic disorder Neurofibromatosis 2 (NF2). NF2 patients are more susceptible to meningiomas because they have inherited a gene with the potential to cause normal cells to become cancerous... (Source: Health News from Medical News Today)

NF1 gene deletions and mutations in de novo adult acute myeloid leukemia

American Journal of Hematology — Wed, 06 Feb 2013 05:00:00 +0100

In conclusion, direct NF1 inactivation is infrequent in de novo AML and may be a secondary event probably involved in leukemic progression. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc. (Source: American Journal of Hematology)

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How Common Are Skeletal Problems in Neurofibromatosis Patients?

PediatricEducation.org — Mon, 04 Feb 2013 00:46:33 +0100

Discussion Neurofibromatosis Type 1 (NF1) is one of many neurocutaneous diseases. Also called phacomatosis, a review can be found at: What is the Epidemiology and Genetics of the Major Phacomatoses? The key elements of NF1 and 2 are: Neurofibromatosis Type 1 Epidemiology: 1:2500-3000 – most common phacomatosis Genetics: autosomal dominant with variable penetrance, associated with chromosome 17 Neurological: various central nervous system tumors especially neurofibromas (often benign but may act malignant because of location or size, tumors may also degenerate into a malignant variant or cause other problems such as hypothalamic problems secondary to an optic chiasm tumor ), optic nerve tumors, pheochromocytomas, mental retardation Dermatological: neurofibromas, cafe-au-lait spots ...

Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas

Nature Genetics — Sun, 03 Feb 2013 05:00:00 +0100

Nature Genetics 45, 295 (2013). doi:10.1038/ng.2552 Authors: Miriam J Smith, James O'Sullivan, Sanjeev S Bhaskar, Kristen D Hadfield, Gemma Poke, John Caird, Saba Sharif, Diana Eccles, David Fitzpatrick, Daniel Rawluk, Daniel du Plessis, William G Newman & D Gareth Evans One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spin...

The Genetics of Neuroendocrine Tumors

Seminars in Oncology — Fri, 01 Feb 2013 05:00:00 +0100

Neuroendocrine tumors (NETs) present a wide spectrum of malignant diseases from rather benign to very malignant variants. The majority of these tumors are sporadic, but there are several familial (inherited) syndromes to consider, such as multiple endocrine neoplasia type 1 and type 2 (MEN-1 and MEN-2), von Hippel-Lindau syndrome (VHL), tuberosclerosis, and neurofibromatosis syndromes. The MEN-1 gene is mutated not only in MEN-1 families, but a recent study shows that more than 40% of sporadic pancreatic NETs (PNETs) harbor MEN-1 gene mutations. The same study reported that ATRX/DAXX genes are mutated in a significant number of tumors, as are genes encoding components of the mammalian target of rapamycin (mTOR) signal transduction pathway. These findings have implications for the new thera...

Malignancies in Chinese patients with neurofibromatosis type 1.

Hong Kong Med J — Fri, 01 Feb 2013 05:00:00 +0100

CONCLUSION. Chinese patients with neurofibromatosis type 1 are susceptible to different malignancies which contribute to mortality. These findings are similar to reports from overseas. Outcomes were unfavourable, except in patients having low-grade gliomas. Surveillance imaging may help early detection of deep-seated malignancies but the benefits accruing from such monitoring warrants prospective evaluation. PMID: 23378354 [PubMed - in process] (Source: Hong Kong Med J)

NF1 gene silencing induces upregulation of VEGF expression in both Schwann and non‐Schwann cells

Experimental Dermatology — Fri, 01 Feb 2013 05:00:00 +0100

Abstract Neurofibromatosis type I (NF1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors (MPNST), and glomus tumors. Previously, we and other groups reported that neurofibromas showed high‐level expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of VEGF in neurofibromas remains unclear. In the present study, we examined the effects of Nf1 gene silencing on VEGF expression in Schwann cell and non‐Schwann cell line and the upstream mTOR‐HIF‐1α – VEGF pathway in Schwann cell line. The results indicated that Nf1 gene silencing by lentiviral‐mediated RNAi resulted in elevated expres...

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Retinal vasoproliferative tumors in patients with neurofibromatosis: An analysis of 5 patients

Journal of AAPOS — Fri, 01 Feb 2013 05:00:00 +0100

Most patients with neurofibromatosis type 1 (NF1) have no major fundus manifestations. However, rare findings include multiple choroidal nevi, myelinated nerve fibers, combined hamartoma, choroidal schwannoma and choroidal melanoma. Another fundus lesion, retinal vasoproliferative tumor, (RVPT) has recently been recognized with NF1. (Source: Journal of AAPOS)

Neurofibromatosis Type 1

Springer Biomedical Sciences titles — Thu, 31 Jan 2013 22:48:42 +0100

Molecular and Cellular BiologyNeurofibromatosis type 1 (NF1), caused by mutational inactivation of the NF1 tumour suppressor gene, is one of the most common dominantly inherited human disorders, affecting 1 in 3000 individuals worldwide. This book presents in concise fashion, but as comprehensively as possible, our current state of knowledge on the molecular genetics, molecular biology and cellular biology of this tumour ... (Source: Springer Biomedical Sciences titles)

NF1 deficiency causes Bcl-xL upregulation in Schwann cells derived from neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.

International Journal of Oncology — Thu, 31 Jan 2013 08:30:08 +0100

NF1 deficiency causes Bcl-xL upregulation in Schwann cells derived from neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Int J Oncol. 2013 Feb;42(2):657-66 Authors: Park HJ, Lee SJ, Sohn YB, Jin HS, Han JH, Kim YB, Yim H, Jeong SY Abstract Since the bi-allelic inactivation of both neurofibromin 1 (NF1) gene alleles (NF1-/-) in Schwann cells (SCs) is common in both benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) in patients with neurofibromatosis type 1 (NF1), other genetic alterations in SCs may be required for tumor progression of PNs to MPNSTs. We found that the anti-apoptotic Bcl-xL protein is upregulated in MPNST tissues compared to PN tissues from patients with...

A novel neurofibromin (NF1) interaction with the leucine‐rich pentatricopeptide repeat motif‐containing protein links neurofibromatosis type 1 and the french canadian variant of leigh's syndrome in a common molecular complex

Journal of Neuroscience Research — Wed, 30 Jan 2013 05:00:00 +0100

Abstract Loss‐of‐function mutations and deletions in the neurofibromin tumor suppressor gene (NF1) cause neurofibromatosis type 1 (NF‐1), the most common inherited syndrome of the nervous system in humans, with a birth incidence of 1:3,000. The most visible features of NF‐1 are the neoplastic manifestations caused by the loss of Ras‐GTPase‐activating protein (Ras‐GAP) activity mediated through the GAP‐related domain (GRD) of neurofibromin (NF1), the protein encoded by NF1. However, the syndrome is also characterized by cognitive dysfunction and a number of developmental abnormalities. The molecular etiology of many of these nonneoplastic phenotypes remains unknown. Here we show that the tubulin‐binding domain (TBD) of NF1 is a binding partner of the leucine‐rich pentatr...

Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in NF1 disease model cells.

Molecular and Cellular Proteomics : MCP — Mon, 28 Jan 2013 05:00:00 +0100

Authors: Hirayama M, Kobayashi D, Mizuguchi S, Morikawa T, Nagayama M, Midorikawa U, Wilson MM, Nambu AN, Yoshizawa AC, Kawano S, Araki N Abstract Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein/gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differ...

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Experimental therapy for neurofibromatosis I shows promise

American Journal of Medical Genetics Part A — Thu, 24 Jan 2013 05:00:00 +0100

(Source: American Journal of Medical Genetics Part A)

Pheochromocytoma and Gastrointestinal Stromal Tumors in Patients With Neurofibromatosis Type I

The American Journal of Medicine — Thu, 17 Jan 2013 00:01:17 +0100

Conclusions: The simultaneous occurrence of pheochromocytoma and gastrointestinal stromal tumor should be considered in all patients with neurofibromatosis I presenting with an abdominal mass with symptoms suggestive of pheochromocytoma. Therefore, a pheochromocytoma should be excluded before a patient with neurofibromatosis I undergoes surgery for a gastrointestinal stromal tumor because an undiagnosed pheochromocytoma carries a high risk of life-threatening cardiovascular complications during surgery. Finally, this combination may be associated with an increased risk for thromboembolic events, but more studies are necessary to confirm this. (Source: The American Journal of Medicine)

AR-42 as a Potential Treatment for NF2-Deficient Meningioma

Cancer Research — Wed, 16 Jan 2013 05:00:00 +0100

Meningiomas constitute about 34% of primary intracranial tumors and are associated with increased mortality in patients with neurofibromatosis type 2 (NF2). To evaluate potential medical therapies for these tumors, we have established a quantifiable orthotopic model for NF2-deficient meningiomas. We showed that telomerase-immortalized Ben-Men-1 benign meningioma cells harbored a single nucleotide deletion in NF2 exon 7 and did not express the NF2 protein, merlin. We also showed that AR-42, a pan-histone deacetylase inhibitor, inhibited proliferation of both Ben-Men-1 and normal meningeal cells by increasing expression of p16INK4A, p21CIP1/WAF1, and p27KIP1. In addition, AR-42 increased proapoptotic Bim expression and decreased anti-apoptotic BclXL levels. However, AR-42 predominantly arres...

Autism spectrum disorder symptomatology in children with neurofibromatosis type 1

Developmental Medicine and Child Neurology — Wed, 16 Jan 2013 05:00:00 +0100

This commentary is on the original articles by Walsh et al. and Garg et al. on pages 131–138 and 139–145 of this issue (Source: Developmental Medicine and Child Neurology)

Potential Non-Surgical Therapy For Neurofibromatosis Type 2 Brain Tumors

Health News from Medical News Today — Tue, 15 Jan 2013 10:00:00 +0100

One in 25,000 people worldwide is affected by neurofibromatosis type 2 (NF2), a condition where the loss of a tumour suppressor called Merlin results in multiple tumours in the brain and nervous system. Sufferers may experience 20 to 30 tumours at any one time and such numbers often lead to hearing loss, disability and eventually death. Currently, the only available effective therapies are repeated invasive surgery or radiotherapy aimed at one tumour at a time and which are unlikely to eradicate all the tumours in one go... (Source: Health News from Medical News Today)

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Abdominal Manifestations of Neurologic Disorders [Multisystem Radiology]

Radiographics recent issues — Tue, 15 Jan 2013 05:00:00 +0100

A variety of disorders—including infectious, inflammatory, hereditary, and metabolic diseases—may affect both the brain and abdominal cavity, and the findings in one region may help establish the diagnosis or limit the differential diagnosis. Establishing an accurate early diagnosis enables clinicians to adequately manage these unusual diseases and potentially avert life-threatening complications. For example, an early diagnosis of Gardner syndrome enables annual sigmoid- or colonoscopy and ultrasonography. In many conditions, abdominal manifestations precede neurologic manifestations and may have prognostic significance. Patients with celiac disease more often present with abdominal manifestations such as duodenitis, slow transit time, reversal of the jejunal-ileal fold patter...

Neurofibromatosis type 2 in the elderly population: Clinical and molecular features

American Journal of Medical Genetics Part A — Tue, 15 Jan 2013 05:00:00 +0100

Abstract Neurofibromatosis type 2 (NF2) is rare genetic disorder characterized by the development of multiple benign tumors of the nervous system. The majority of people with NF2 are diagnosed in the second or third decade of life with bilateral vestibular schwannomas. Among NF2 patients followed up in our NF2 clinic, seven patients have been diagnosed with NF2 after the age of 70 years. Bilateral vestibular schwannomas were present in 4/7 patients. No NF2 mutation was identified by blood screening, suggesting a high prevalence of NF2 somatic mosaicism. During a mean follow‐up of 96 months, 8/11 vestibular schwannomas demonstrated no tumor growth, and only one patient required treatment. Other tumors, including meningiomas and other schwannomas, remained stable. One patient required shun...

Delayed primary diagnosis of LEOPARD syndrome type 1

Journal of the American Academy of Dermatology — Mon, 14 Jan 2013 15:39:41 +0100

To the Editor: LEOPARD syndrome (LS) is a rare autosomal dominant genodermatosis. It is characterized by multiple Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary valve stenosis, Abnormal genitals, Retarded growth, and Deafness. Like neurofibromatosis type 1, Noonan syndrome, Costello syndrome, and cardiofaciocutaneous syndrome, it belongs to the group of neurocardiofaciocutaneous diseases. Zeisler and Becker reported the first case of LS in 1936, and later the acronym of the syndrome was coined because of the multiple lentigines that resemble the fur pattern of a leopard. The acronym has been widely used ever since. (Source: Journal of the American Academy of Dermatology)

Café-au-lait macules and enlarging papules on the face

Journal of the American Academy of Dermatology — Mon, 14 Jan 2013 15:39:33 +0100

A 2-year-old girl was referred by her pediatrician for the evaluation of several lesions on her face and scalp. They were asymptomatic, and the patient's mother indicated that they were slowly enlarging. She was otherwise healthy with normal development. Her father had a diagnosis of neurofibromatosis. The physical examination revealed a well-appearing girl with several 4- to 5-mm light orange macules on the scalp and 2 small orange-tan papules on the right cheek (). She had numerous café-au-lait macules scattered on her trunk and 1 soft dermal nodule on the right labia (). (Source: Journal of the American Academy of Dermatology)

Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma [RESEARCH]

Genome Research — Mon, 14 Jan 2013 05:00:00 +0100

Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify ...

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NG2-cells are not the cell of origin for murine neurofibromatosis-1 (Nf1) optic glioma

Oncogene — Mon, 14 Jan 2013 05:00:00 +0100

Authors: A C Solga, S M Gianino & D H Gutmann (Source: Oncogene)

Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis.

The American Journal of Pathology — Sun, 13 Jan 2013 05:00:00 +0100

Authors: Kazmi SJ, Byer SJ, Eckert JM, Turk AN, Huijbregts RP, Brossier NM, Grizzle WE, Mikhail FM, Roth KA, Carroll SL Abstract Patients with neurofibromatosis type 1 (NF1) develop benign plexiform neurofibromas that frequently progress to become malignant peripheral nerve sheath tumors (MPNSTs). A genetically engineered mouse model that accurately models plexiform neurofibroma-MPNST progression in humans would facilitate identification of somatic mutations driving this process. We previously reported that transgenic mice overexpressing the growth factor neuregulin-1 in Schwann cells (P(0)-GGFβ3 mice) develop MPNSTs. To determine whether P(0)-GGFβ3 mice accurately model human neurofibroma-MPNST progression, cohorts of these animals were monitored through death and were necropsie...

Proteus: Mythology to modern times

Indian Journal of Urology — Thu, 10 Jan 2013 05:00:00 +0100

Conclusions: Thus proteus, true to its name, has had a myriad of connotations over the centuries. (Source: Indian Journal of Urology)

Exercise capacity impairment in individuals with neurofibromatosis type 1

American Journal of Medical Genetics Part A — Thu, 10 Jan 2013 05:00:00 +0100

(Source: American Journal of Medical Genetics Part A)

Polarity: Merlin and ezrin get organized

Nature Reviews Cancer — Thu, 10 Jan 2013 05:00:00 +0100

Nature Reviews Cancer 13, 76 (2013). doi:10.1038/nrc3453 Author: Sarah Seton-Rogers The tumour suppressor neurofibromatosis type 2 (NF2) restricts ezrin localization to establish cortical asymmetry and correctly position centrosomes and spindles during cell division in polarized epithelial cells. (Source: Nature Reviews Cancer)

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Modeling cognitive dysfunction in neurofibromatosis-1.

Trends in Neurosciences — Tue, 08 Jan 2013 05:00:00 +0100

Authors: Diggs-Andrews KA, Gutmann DH Abstract Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and dissect mechanistically the molecular and cellular bases underlying cognitive dysfunction. In this review, we discuss Nf1 fly and mouse systems that mimic many of the cognitive abnormalities seen in children with NF1. Further, we describe discoveries from these models that have uncovered defects in the regulation of Ras activity, cAMP generation, and dopam...

Genetics and molecular pathogenesis of pheochromocytoma and paraganglioma

Clinical Endocrinology — Mon, 07 Jan 2013 05:00:00 +0100

Summary Although most pheochromocytomas (PCCs) and paragangliomas (PGLs) are sporadic, molecular genetic medicine has revealed that a considerable number of patients with apparently sporadic PCC actually have a genetic predisposition to the development of these tumors. After decades of intensive research, several genes are now known to play an important role in the pathogenesis of PCC. At present, these are RET proto‐oncogene, von Hippel–Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes. I...

Surgical correction of severe cervical kyphosis in patients with neurofibromatosis Type 1.

Journal of Neurosurgery.Spine — Fri, 04 Jan 2013 05:00:00 +0100

Authors: Kawabata S, Watanabe K, Hosogane N, Ishii K, Nakamura M, Toyama Y, Matsumoto M Abstract Severe cervical kyphosis requiring surgical treatment is rare in patients with neurofibromatosis Type 1 (NF1). When it occurs, however, dystrophic changes in the vertebrae make surgical correction and fusion of the deformity extremely difficult. The authors report on 3 cases of severe cervical kyphosis associated with NF1 that were successfully treated with combined anterior and posterior correction and fusion. All patients underwent halo-gravity traction for approximately 1 month prior to surgery to correct the deformity gradually. Posterior correction and fusion were performed with segmental spinal instrumentation consisting of lateral mass screws, lamina screws, pedicle screws, and ...

In Tumor Disorder There Are Many Causes For Learning Lags

Health News from Medical News Today — Thu, 03 Jan 2013 08:00:00 +0100

The causes of learning problems associated with an inherited brain tumor disorder are much more complex than scientists had anticipated, researchers at Washington University School of Medicine in St. Louis report. The disorder, neurofibromatosis 1 (NF1), is among the most common inherited pediatric brain cancer syndromes. Children born with NF1 can develop low-grade brain tumors, but their most common problems are learning and attention difficulties... (Source: Health News from Medical News Today)

A 17-year-old with neurofibromatosis and spontaneous coronary artery dissection [CASE STUDIES]

Asian Cardiovascular and Thoracic Annals — Wed, 02 Jan 2013 05:00:00 +0100

A 17-year-old girl with neurofibromatosis type 1 presented with unstable angina. Cardiac catheterization revealed an aneurysm with thrombus in the left anterior descending coronary artery. She was discharged on medical treatment but returned 2 months later with severe chest pains. Angiography revealed an increase in the size of the aneurysm in the left anterior descending coronary artery, with thrombus and dissection. The patient underwent coronary artery bypass surgery. Follow-up after 1 year revealed no problems. (Source: Asian Cardiovascular and Thoracic Annals)

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[Partial unilateral lentiginosis and segmental neurofibromatosis: A nosologic problem].

Archives de Pediatrie — Tue, 01 Jan 2013 05:00:00 +0100

Authors: Amouri M, Chaaben H, Meziou TJ, Mseddi M, Masmoudi A, Boudaya S, Turki H PMID: 23266173 [PubMed - in process] (Source: Archives de Pediatrie)

Neurofibromatosis type 1 and pregnancy: Maternal complications and attitudes about prenatal diagnosis

American Journal of Medical Genetics Part A — Tue, 01 Jan 2013 05:00:00 +0100

(Source: American Journal of Medical Genetics Part A)

Spontaneous massive hemothorax in a patient with neurofibromatosis type 1 with successful transarterial embolization.

Korean J Radiol — Tue, 01 Jan 2013 05:00:00 +0100

We report a case of a patient with spontaneous rupture of a left intercostal artery aneurysm, which presented as a massive left hemothorax and was successfully treated by transarterial coil embolization. PMID: 23323035 [PubMed - in process] (Source: Korean J Radiol)

Corrigendum to “The Learning Disabilities Network (LeaDNet): Using Neurofibromatosis Type 1 [NF1] as a Paradigm for Translational Research”

American Journal of Medical Genetics Part A — Mon, 24 Dec 2012 05:00:00 +0100

(Source: American Journal of Medical Genetics Part A)

Reply

The Journal of Pediatrics — Sat, 22 Dec 2012 02:32:05 +0100

We appreciate the comments of Nicita et al. The index patient we reported did not have a family history of neurofibromatosis (NF) and, thus, was a sporadic case. In consequence, we could not strictly diagnose him with familial spinal NF. However, his presentation was very similar to that of patients with this entity despite the lack of family history. In fact, he also had evident stigmata of NF type 1, as portrayed in Figure 1, A of our report. This highlights the fact expressed by Nicita et al that severe spinal NF can present in the context of “classic” NF type 1 and must be considered in such patients with neurologic deficits and/or musculoskeletal pain. The patient we reported had normal brain magnetic resonance imaging, but we agree that it is necessary to evaluate brain str...

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Malignant peripheral nerve sheath tumor of the trigeminal nerve: Clinicopathologic features in a young adult patient

Neuropathology — Fri, 21 Dec 2012 05:00:00 +0100

Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves are rare and usually affect adults. Here we report the clinicopathologic features of a young adult patient with a trigeminal nerve MPNST, in whom another tumor involving the oculomotor nerve on the contralateral side was evident. The patient, an 18‐year‐old woman, had suffered recurrent paroxysmal sharp stabbing pain over her cheek and forehead on the right side for 1 month. A brain MRI study disclosed a mass, 35 mm in diameter, in the right Meckel's cave, and another mass, 10 mm in diameter, involving the intracranial portion of the left oculomotor nerve. Following gadolinium administration, the former and latter tumors exhibited strong and weak enhancement, respectively. The patient had no clinical stig...

Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study

British Journal of Cancer AOP — Thu, 20 Dec 2012 05:00:00 +0100

Authors: O O Seminog & M J Goldacre (Source: British Journal of Cancer AOP)

Diffusion-Tensor Imaging Derived Metrics of the Corpus Callosum in Children With Neurofibromatosis Type I

American Journal of Roentgenology — Wed, 19 Dec 2012 05:00:00 +0100

CONCLUSION. Children with NF-1 have abnormal DTI metrics, particularly in the genu, and elevated whole-brain mean diffusivity. NF-1–related microstructural abnormalities of the corpus callosum are detectable in childhood and likely persist through myelination maturation. (Source: American Journal of Roentgenology)

Plasma S100β is not a useful biomarker for tumor burden in neurofibromatosis.

Clinical Biochemistry — Wed, 19 Dec 2012 05:00:00 +0100

CONCLUSIONS: Plasma S100β is not a useful biomarker for tumor burden in the neurofibromatoses. Further work is needed to identify a reliable biomarker of tumor burden in NF patients. PMID: 23261835 [PubMed - as supplied by publisher] (Source: Clinical Biochemistry)

Molecular Diagnosis of Genodermatoses

Springer protocols feed by Molecular Medicine — Wed, 19 Dec 2012 05:00:00 +0100

The progress of molecular genetics helps clinicians to prove or exclude a suspected diagnosis for a vast and yet increasing number of genodermatoses. This leads to precise genetic counselling, prenatal diagnosis and preimplantation genetic haplotyping for many inherited skin conditions. It is also helpful in such occasions as phenocopy, late onset and incomplete penetrance, uniparental disomy, mitochondrial inheritance and pigmentary mosaicism. Molecular methods of two genodermatoses are explained in detail, i.e. genodermatoses with skin fragility and neurofibromatosis type 1. (Source: Springer protocols feed by Molecular Medicine)

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Clinical and Pathological Characteristics of Breast Cancer in Women with Neurofibromatosis Type 1

Cancer Research — Mon, 17 Dec 2012 05:00:00 +0100

Conclusion: Our findings suggest that NF1-associated breast cancer tends to be more aggressive, with a higher frequency of grade 3 and HER2 positive tumours compared to sporadic breast cancer. Further genomic profiling of these tumours (in progress) may elucidate the role of NF1 in breast cancer. This may also have implications for sporadic tumours with somatic NF1 mutations in individuals without NF1.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-09. (Source: Cancer Research)

Radiation-Induced Neoplasms Share Nf1 Loss

Cancer Research — Sun, 16 Dec 2012 05:00:00 +0100

Second malignant neoplasms (SMN) are therapy-induced malignancies and a growing problem in cancer survivors, particularly survivors of childhood cancers. The lack of experimental models of SMNs has limited understanding of their pathogenesis. It is currently not possible to predict or prevent this devastating late complication. Individuals with neurofibromatosis I (NF1) are at increased risk of developing therapy-induced cancers for unclear reasons. To model SMNs, we replicated clinical radiotherapy and delivered fractionated abdominal irradiation to Nf1+/− and wild-type mice. Similar to irradiated cancer survivors, irradiated wild-type and Nf1+/− mice developed diverse in-field malignancies. In Nf1+/− mice, fractionated irradiation promoted both classical NF1-associated malignancies...

The Neediest Cases: Disabled Young Man and His Protective Mother Deal With Life’s Challenges

NYT Health — Sat, 15 Dec 2012 04:32:32 +0100

Joann West, whose son, Zaquan, 25, has a genetic disorder that causes tumors on his skin, offers him unflagging support while trying to let him be as independent as he wants to be. (Source: NYT Health)

L5–S1 extraforaminal intraneural disc herniation mimicking a malignant peripheral nerve sheath tumor

The Spine Journal — Thu, 13 Dec 2012 05:00:00 +0100

Conclusions: Several pitfalls exist in establishing the uncommon diagnosis of an extraforaminal disc herniation. This entity occurs ventrally and must remain a consideration when elaborating the differential diagnosis of a retroperitoneal mass in close proximity to the vertebral column. (Source: The Spine Journal)

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice.

Behavior Genetics — Wed, 12 Dec 2012 05:00:00 +0100

Authors: Tsai PT, Greene-Colozzi E, Goto J, Anderl S, Kwiatkowski DJ, Sahin M Abstract Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders-such as Tuberous Sclerosis Complex-can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral e...

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MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors

Journal of Clinical Investigation — Tue, 11 Dec 2012 00:30:01 +0100

Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK si...

Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice

Journal of Clinical Investigation — Tue, 11 Dec 2012 00:30:01 +0100

Children with neurofibromatosis type 1 (NF1) are predisposed to juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative neoplasm (MPN) that is refractory to conventional chemotherapy. Conditional inactivation of the Nf1 tumor suppressor in hematopoietic cells of mice causes a progressive MPN that accurately models JMML and chronic myelomonocytic leukemia (CMML). We characterized the effects of Nf1 loss on immature hematopoietic populations and investigated treatment with the MEK inhibitor PD0325901 (hereafter called 901). Somatic Nf1 inactivation resulted in a marked expansion of immature and lineage-committed myelo-erythroid progenitors and ineffective erythropoiesis. Treatment with 901 induced a durable drop in leukocyte counts, enhanced erythropoietic function, and mar...

Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk

Journal of Clinical Investigation — Tue, 11 Dec 2012 00:30:01 +0100

Neurofibromatosis type 1 (NF1) predisposes individuals to the development of juvenile myelomonocytic leukemia (JMML), a fatal myeloproliferative disease (MPD). In genetically engineered murine models, nullizygosity of Nf1, a tumor suppressor gene that encodes a Ras-GTPase–activating protein, results in hyperactivity of Raf/Mek/Erk in hematopoietic stem and progenitor cells (HSPCs). Activated Erk1/2 phosphorylate kinases and transcription factors with myriad mitogenic roles in diverse cell types. However, genetic studies examining Erk1/2’s differential and/or combined control of normal and Nf1-deficient myelopoiesis are lacking. Moreover, prior studies relying on chemical Mek/Erk inhibitors have reached conflicting conclusions in normal and Nf1-deficient mice. Here, we show ...

Targeted molecular therapy for untreatable neurofibroma tumors

ScienceDaily Headlines — Mon, 10 Dec 2012 17:45:45 +0100

Researchers conducting a preclinical study in mice successfully used targeted molecular therapy to block mostly untreatable nerve tumors that develop in people with the genetic disorder Neurofibromatosis 1 (NF1). Scientists say the data provide strong rationale for testing the therapy in clinical trials for NF1. (Source: ScienceDaily Headlines)

Study Identifies Targeted Molecular Therapy For Untreatable NF1 Tumors

Health News from Medical News Today — Mon, 10 Dec 2012 17:00:00 +0100

Researchers conducting a preclinical study in mice successfully used targeted molecular therapy to block mostly untreatable nerve tumors that develop in people with the genetic disorder Neurofibromatosis 1 (NF1). Scientists from Cincinnati Children's Hospital Medical Center report their findings online Dec. 10 in the Journal of Clinical Investigation... (Source: Health News from Medical News Today)

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Alternative splicing of the neurofibromatosis type 1 pre-mRNA is regulated by the muscleblind-like proteins and the CUG-BP and ELAV-like factors

BioMed Central — Mon, 10 Dec 2012 05:00:00 +0100

Conclusion: This study along with our previous work that demonstrated roles for Hu, CELF, and TIA-1 and TIAR proteins in the regulation of NF1 exon 23a establish that this exon is under tight, complex control. (Source: BioMed Central)

Study identifies targeted molecular therapy for untreatable NF1 tumors

EurekAlert! - Cancer — Mon, 10 Dec 2012 05:00:00 +0100

(Cincinnati Children's Hospital Medical Center) Researchers conducting a preclinical study in mice successfully used targeted molecular therapy to block mostly untreatable nerve tumors that develop in people with the genetic disorder Neurofibromatosis 1 (NF1). Scientists from Cincinnati Children's Hospital Medical Center report their findings online Dec. 10 in the Journal of Clinical Investigation, and say the data provide strong rationale for testing the therapy in clinical trials for NF1. (Source: EurekAlert! - Cancer)

JCI early table of contents for Dec. 10, 2012

EurekAlert! - Cancer — Mon, 10 Dec 2012 05:00:00 +0100

(Journal of Clinical Investigation) This release contains summaries, links to PDFs, and contact information for the following newsworthy papers to be published online, Dec. 10, 2012, in the JCI: Brown fat transplants help mice lose weight; Researchers identify therapeutic targets in neurofibromatosis; Gene regulatory network links obesity and inflammation; research identify inflammatory mediators associated with kidney stones; and many more. (Source: EurekAlert! - Cancer)

Researchers identify therapeutic targets in neurofibromatosis

EurekAlert! - Cancer — Mon, 10 Dec 2012 05:00:00 +0100

(Journal of Clinical Investigation) In this issue of the Journal of Clinical Investigation, three independent groups of researchers report that MAPK hyperactivation is a critical mediator of disease pathogenesis in neurofibromatosis. (Source: EurekAlert! - Cancer)

Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma [RESEARCH]

Genome Research — Wed, 05 Dec 2012 05:00:00 +0100

Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically-engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify ...

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Understanding relationships between autism, intelligence, and epilepsy: a cross‐disorder approach

Developmental Medicine and Child Neurology — Tue, 04 Dec 2012 05:00:00 +0100

Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood‐onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were complet...

Congenital pseudarthrosis of the tibia: Management and complications

Table of Contents : Indian Journal of Orthopaedics : 2007 - 41(1) — Mon, 03 Dec 2012 05:00:00 +0100

Hitesh Shah, Marie Rousset, Federico CanaveseIndian Journal of Orthopaedics 2012 46(6):616-626Congenital pseudarthrosis of the tibia (CPT) is a rare pathology, which is usually associated with neurofibromatosis type I. The natural history of the disease is extremely unfavorable and once a fracture occurs, there is a little or no tendency for the lesion to heal spontaneously. It is challenging to treat effectively this difficult condition and its possible complications. Treatment is mainly surgical and it aims to obtain a long term bone union, to prevent limb length discrepancies, to avoid mechanical axis deviation, soft tissue lesions, nearby joint stiffness, and pathological fracture. The key to get primary union is to excise hamartomatous tissue and pathological periosteum. Age at surger...

Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors.

Clinical Cancer Research — Mon, 03 Dec 2012 05:00:00 +0100

CONCLUSION: mTOR inhibition is a potential treatment option for both NF1-related and sporadic MPNSTs. PMID: 23209032 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Nonunion of forearm fracture: a rare instance in a toddler.

Chinese Journal of Traumatology — Sat, 01 Dec 2012 05:00:00 +0100

We report here a case of an eighteen-month-old child who developed nonunion following treatment of fracture of both forearm bones with cast and was successfully treated with plating. To the best of our knowledge, this is the youngest reported case of nonunion following conservative management of closed diaphyseal pediatric fracture. PMID: 23186933 [PubMed - in process] (Source: Chinese Journal of Traumatology)

Long-term follow-up studies of Gamma Knife surgery with a low margin dose for vestibular schwannoma.

Journal of Neurosurgery — Sat, 01 Dec 2012 05:00:00 +0100

Conclusions With a low prescribed margin dose of 14 Gy or less, GKS was confirmed to provide long-term tumor control for small to medium-sized VSs and largely to prevent cranial nerves from iatrogenic injury. Based on the findings of this study, GKS is also a reasonable option for the treatment of large, heterogeneously enhancing tumors without symptomatic brainstem compression. Gamma Knife surgery can preserve a high quality of life for most patients with VS who do not have symptomatic brainstem compression. Long-term follow-up is required because of the risk of delayed recurrence of VS. PMID: 23205790 [PubMed - in process] (Source: Journal of Neurosurgery)

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Link Between Gene That Causes Tumor Disorder And Increased Breast Cancer Risk

Health News from Medical News Today — Wed, 28 Nov 2012 09:00:00 +0100

New Johns Hopkins research showing a more than four-fold increase in the incidence of breast cancer in women with neurofibromatosis-1 (NF1) adds to growing evidence that women with this rare genetic disorder may benefit from early breast cancer screening with mammograms beginning at age 40, and manual breast exams as early as adolescence. In a small study of 126 women with NF1 at the Johns Hopkins Comprehensive Neurofibromatosis Center, the Johns Hopkins scientists identified four cases of breast cancer... (Source: Health News from Medical News Today)

In vitro antisense therapeutics for a deep intronic mutation causing Neurofibromatosis type 2

European Journal of Human Genetics — Wed, 28 Nov 2012 05:00:00 +0100

Authors: Elisabeth Castellanos, Imma Rosas, Ares Solanes, Isabel Bielsa, Conxi Lázaro, Cristina Carrato, Cristina Hostalot, Pepe Prades, Francesc Roca-Ribas, Ignacio Blanco & Eduard Serra (Source: European Journal of Human Genetics)

Gene that Causes Tumor Disorder Linked to Increased Breast Cancer Risk - 11/27/12

Johns Hopkins Medicine News — Tue, 27 Nov 2012 12:00:00 +0100

New Johns Hopkins research showing a more than four-fold increase in the incidence of breast cancer in women with neurofibromatosis-1 (NF1). (Source: Johns Hopkins Medicine News)

Gene that causes tumor disorder linked to increased breast cancer risk

EurekAlert! - Medicine and Health — Tue, 27 Nov 2012 05:00:00 +0100

(Johns Hopkins Medicine) New Johns Hopkins research showing a more than four-fold increase in the incidence of breast cancer in women with neurofibromatosis-1 adds to growing evidence that women with this rare genetic disorder may benefit from early breast cancer screening with mammograms beginning at age 40, and manual breast exams as early as adolescence. (Source: EurekAlert! - Medicine and Health)

[Articles] Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial

The Lancet Oncology — Sat, 24 Nov 2012 13:04:53 +0100

Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results. (Source: The Lancet Oncology)

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[Comment] Treatment for plexiform neurofibromas in patients with NF1

The Lancet Oncology — Sat, 24 Nov 2012 13:04:38 +0100

Plexiform neurofibromas are congenital lesions associated with neurofibromatosis type 1 (NF1). They grow at variable rates, particularly in childhood, and can result in substantial morbidity and early mortality. Tumours can be multiple and extensive, and cause differing symptoms depending on their location, including pain and disfigurement, functional impairment of vision, mobility, bladder and bowel function, and respiratory compromise. (Source: The Lancet Oncology)

[Tongue base schwannoma in a child.]

Revue de Stomatologie et de Chirurgie Maxillo-Faciale — Thu, 22 Nov 2012 05:00:00 +0100

DISCUSSION: The particularities of this report are the patient's very young age and the tumor's tongue base location. The prognosis is usually good after complete excision, if there is only one tumor. Type 2 neurofibromatosis should be excluded, given the risk of malignant degeneration. PMID: 23182691 [PubMed - as supplied by publisher] (Source: Revue de Stomatologie et de Chirurgie Maxillo-Faciale)

Anuric Acute Kidney Injury in Neurofibromatosis 1

American Journal of Kidney Diseases — Thu, 22 Nov 2012 05:00:00 +0100

We present a unique case of a man with neurofibromatosis 1 presenting with anuric acute kidney injury, followed by a brief discussion of neurofibromatosis 1 and its association with renovascular disease. (Source: American Journal of Kidney Diseases)

The 'hobbit boy' with feet so big he can barely walk will soon be able to play again after groundbreaking treatment

the Mail online | Health — Wed, 21 Nov 2012 13:21:26 +0100

Teenager Xiao Meng, who has been nicknamed Hobbit by schoolmates, was born with congenital neurofibromatosis - a genetic condition which causes the feet to swell abnormally. (Source: the Mail online | Health)

Clues To Cause Of Pediatric Brain Tumors

Health News from Medical News Today — Tue, 20 Nov 2012 08:00:00 +0100

Insights from a genetic condition that causes brain cancer are helping scientists better understand the most common type of brain tumor in children. In new research, scientists at Washington University School of Medicine in St. Louis have identified a cell growth pathway that is unusually active in pediatric brain tumors known as gliomas. They previously identified the same growth pathway as a critical contributor to brain tumor formation and growth in neurofibromatosis-1 (NF1), an inherited cancer predisposition syndrome... (Source: Health News from Medical News Today)

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Key features of neurofibromatoses 1 and 2

Archives of Disease in Childhood - Education and Practice — Tue, 20 Nov 2012 05:00:00 +0100

Conclusions NF1 and NF2 are clinically distinct syndromes that should not be confused. Neurofibromas are indicative of NF1 and schwannomas of NF2. Vestibular schwannomas and meningiomas do not occur in NF1 so screening for these in NF1 would be inappropriate. Cutaneous or... (Source: Archives of Disease in Childhood - Education and Practice)

Increased risk of breast cancer in women with NF1

American Journal of Medical Genetics Part A — Mon, 19 Nov 2012 05:00:00 +0100

Abstract Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with increased risk for neoplasms. Two studies in the United Kingdom have indicated that women with NF1 (particularly women under 50) may also be at increased risk of breast cancer. No such study has been done to date in the United States. Chart review for breast cancer diagnoses was undertaken for 126 women with NF1 followed at Johns Hopkins who were 20 years of age or older. Four of 126 women who met eligibility criteria were diagnosed with breast cancer (3.2% over 15 years). The unadjusted standardized incidence ratio (SIR) for breast cancer in the NF1 population between the ages of 20 and 49 was 2.68 (P = 0.076, 95% CI 0.68–7.29) based on incidence rates of breast cancer in the general popu...

Bilateral Mediastinal Neurofibroma of the Vagus Nerves in a Patient with Neurofibromatosis Type 1.

Annals of Thoracic and Cardiovascular Surgery — Sat, 17 Nov 2012 05:00:00 +0100

Authors: Kanzaki R, Inoue M, Minami M, Sawabata N, Shintani Y, Nakagiri T, Okumura M Abstract Bilateral mediastinal vagus neurogenic tumors are very rare. We herein report the case of Neurofibromatosis type 1 (NF-1) patient with bilateral neurofibromas originating from the mediastinal vagus just distal site of the recurrent nerve, who underwent two-staged extirpations that successfully preserved both recurrent nerves. A 31-yearold female with a history of NF-1 was admitted to our hospital under a diagnosis of multiple tumors in the upper mediastinum. First, the tumor at the right paratracheal to precarinal site was completely resected through a median sternotomy, preserving the right recurrent nerve. After confirming no right recurrent nerve paralysis, thoracoscopic resection of th...

Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population‐based study

Developmental Medicine and Child Neurology — Fri, 16 Nov 2012 05:00:00 +0100

Aim To investigate psychopathology in children with neurofibromatosis type 1 (NF1), particularly the prevalence of autism spectrum disorder (ASD) and attention‐deficit–hyperactivity disorder (ADHD) symptomatology, using a population‐based sampling approach. Method Standard questionnaire screen reports were analysed for ASD (Social Responsiveness Scale, SRS), ADHD (Conners’ Parent Rating Scale‐ Revised, CPRS‐R), and other psychiatric morbidity (Strengths and Difficulties Questionnaire, SDQ) from parents and teachers of children aged from 4 to 16 years (112 females, 95 males) on the UK North West Regional Genetic Service register for NF1. Results Parental response rate was 52.7% (109/207 children; 59 females, 50 males, mean age 9y 11mo, SD 3y 3mo). The SRS showed that ...

Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1

Developmental Medicine and Child Neurology — Fri, 16 Nov 2012 05:00:00 +0100

We present a retrospective, cross‐sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. Results Sixty‐six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T ≥ 60), and 14% reached levels consistent with those seen in children with ASDs (T ≥ 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral di...

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Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen's disease): clinicopathological spectrum with pathogenetic considerations.

International Journal of Clinical and Experimental Pathology — Thu, 15 Nov 2012 23:15:03 +0100

Authors: Agaimy A, Vassos N, Croner RS Abstract Neurofibromatosis type 1 (NF-1, Recklinghausen disease) is the most common hereditary multitumor syndrome with an incidence at birth of approximately 1:3000. However, the significant variation in the expression of the disease not infrequently precludes early diagnosis. As a consequence of non-familiarity with their frequency and wide clinicopathological spectrum, gastrointestinal manifestations of NF-1 are seldom thought of in routine clinical practice and might thus be significantly under-recognized. Their heterogeneous spectrum ranges from localized microscopic proliferative lesions of autonomic nerves and interstitial cells of Cajal and diffuse microscopic ganglio/neuro/fibromatosis to grossly recognizable mass-forming neurofibroma...

Cancer: Neurons and astrocytes can make gliomas

Nature Reviews Neuroscience — Thu, 15 Nov 2012 05:00:00 +0100

Nature Reviews Neuroscience 13, 812 (2012). doi:10.1038/nrn3387 Author: Rachel Jones The origins of gliomas are not well understood. Here, oncogenic lentiviral vectors targeting the genes that encode tumour protein 53 (also known as p53) and neurofibromatosis type 1 (which are often mutated in gliomas) were used to transduce stem cells, astrocytes and mature neurons in (Source: Nature Reviews Neuroscience)

Use of supramaximal stimulation to predict facial nerve outcomes following vestibular schwannoma microsurgery: results from a decade of experience.

Journal of Neurosurgery — Fri, 09 Nov 2012 05:00:00 +0100

Conclusions In a large cohort of patients, the authors found that interrogating intraoperative FN function with SMS is safe and technically simple. It is useful for predicting which patients will ultimately have good facial function, but is very limited in identifying patients destined for long-term facial weakness. This test may prove helpful in the future in tailoring less than gross-total tumor removal to limit postoperative facial weakness. PMID: 23140153 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery.

Journal of Neurosurgery — Fri, 09 Nov 2012 05:00:00 +0100

Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs. PMID: 23140152 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

Spinal neurofibromatosis in children

The Journal of Pediatrics — Fri, 09 Nov 2012 05:00:00 +0100

We have read with great interest the paper by Nuñez-Farías et al. The authors report on a child with a rare and severe form of neurofibromatosis (NF) type 1 (NF1), familial spinal NF, which is characterized by multiple, histologically proven, neurofibromas of the spinal roots and major peripheral nerves, associated or not with multiple cafè-au-lait spots, and without any other typical NF1 or NF type 2 stigmata. The authors did not describe the genetic features of the child (eg, sporadic or familial case, NF1 gene mutation), but named the case as “spinal NF,” probably suggesting a sporadic nature. They also underlined the importance of considering the spinal NF in patients with NF1 features, neurologic deficits, and musculoskeletal pain. (Source: The Journal of Pediatrics)

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Indiana University Researchers Report First Effective Treatment Of Tumors Arising From Common Genetic Disease NF1

Health News from Medical News Today — Sat, 03 Nov 2012 07:00:00 +0100

Physician-researchers at Indiana University School of Medicine have reported the first effective therapy for a class of previously untreatable and potentially life-threatening tumors often found in children. Announcing their findings in the online first edition of Lancet Oncology, the researchers said the drug imatinib mesylate, marketed as Gleevec as a treatment for chronic myeloid leukemia, provided relief to a significant number of patients with plexiform neurofibromas, tumors caused by neurofibromatosis type 1, or NF1... (Source: Health News from Medical News Today)

A-Z of malignant peripheral nerve sheath tumors.

Cancer Imaging — Sat, 03 Nov 2012 00:15:02 +0100

This article reviews the typical and atypical locations, imaging findings, local recurrence, and metastatic pattern of malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are rare soft tissue sarcomas, commonly occur in extremities, and are often associated with neurofibromatosis. Distinction between benign and malignant tumors can be challenging on imaging. MPNSTs have a poor prognosis; however, rhabdomyoblastic differentiation (malignant triton tumor), which has imaging features similar to MPNSTs, is associated with even more aggressive behavior. PMID: 23108260 [PubMed - in process] (Source: Cancer Imaging)

Neurofibromatosis 1 and breast cancer: be alert.

The American Surgeon — Thu, 01 Nov 2012 04:00:00 +0100

Authors: Zagouri F, Sergentanis TN, Domeyer P, Zografos GC PMID: 23089412 [PubMed - in process] (Source: The American Surgeon)

[Corpus callosum tumor as the presenting symptom of neurofibromatosis type 1 in a patient and literature review].

Revista de Neurologia — Thu, 01 Nov 2012 04:00:00 +0100

CONCLUSIONS. We present a new case with tumor of the corpus callosum and NF1. The imaging characteristics and the clinical course were in favour of the benign nature of this type of tumor. PMID: 23111991 [PubMed - in process] (Source: Revista de Neurologia)

Dopamine deficiency underlies learning deficits in Neurofibromatosis‐1 mice

Annals of Neurology — Tue, 30 Oct 2012 04:00:00 +0100

Abstract Children with neurofibromatosis type 1 (NF1) are prone to learning and behavioral abnormalities, including problems with spatial learning and attention. The molecular etiology for these deficits is unclear, as previous studies have implicated defective dopamine, cAMP and Ras homeostasis. Using behavioral, electrophysiological and primary culture, we now demonstrate that reduced dopamine signaling is responsible for cAMP‐dependent defects in neuron function and learning. Collectively, these results establish defective dopaminergic function as one contributing factor underlying impaired spatial learning and memory in children and adults with NF1, and support the use of treatments that restore normal dopamine homeostasis for select individuals. ANN NEUROL 2010 (Source: Annals of Ne...

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Neurofibromatosis 1-Related Osteopenia Often Progresses to Osteoporosis in 12 Years

Calcified Tissue International — Mon, 29 Oct 2012 20:15:50 +0100

Abstract The current study is based on our earlier investigation carried out in 1999, where bone mineral density (BMD) of 35 neurofibromatosis type 1 (NF1) patients was measured and osteoporosis was shown to be common in NF1. The findings have been confirmed by a number of later publications. The purpose of the current longitudinal study was to assess the bone health of these 35 NF1 patients 12 years after the initial study. A total of 28 patients were reached, and BMD of 19 patients was subsequently remeasured. Fracture history of 28/35 NF1 patients who were reached was verified from the medical records. Six NF1 patients had osteoporosis in 1999, and three of them had an osteoporotic fracture between 1999 and 2011, showing an increased fracture risk compared to NF1 p...

Management of glioblastoma in an NF1 patient with moyamoya syndrome: a case report

Child's Nervous System — Mon, 29 Oct 2012 20:12:18 +0100

Discussion Glioblastoma is a fatal disease in children, and our patient successfully received chemoradiotherapy with temozolomide despite the diagnoses of NF1 and moyamoya syndrome. Although radiotherapy or chemotherapy potentially causes cerebrovascular complications, chemoradiotherapy might be feasible for glioblastoma treatment in patients with moyamoya syndrome and NF1. The following issues are discussed in the management of the present case: the indication of biopsy in NF1 cases, the method of surgery, and the treatment protocol for tumors concomitant with moyamoya disease or syndrome. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s00381-012-1948-9Authors Hideyuki Arita, Department of Neurosurgery and Neuro-Oncology, National Cancer Cen...

Pathological and Molecular Advances in Pediatric Low-Grade Astrocytoma.

Annual Review of Pathology — Mon, 29 Oct 2012 04:00:00 +0100

Authors: Rodriguez FJ, Lim KS, Bowers D, Eberhart CG Abstract Pediatric low-grade astrocytomas are the most common brain tumors in children. They can have similar microscopic and clinical features, making accurate diagnosis difficult. For patients whose tumors are in locations that do not permit full resection, or those with an intrinsically aggressive biology, more effective therapies are required. Until recently, little was known about the molecular changes that drive the initiation and growth of pilocytic and other low-grade astrocytomas beyond the association of a minority of cases, primarily in the optic nerve, with neurofibromatosis type 1. Over the past several years, a wide range of studies have implicated the BRAF oncogene and other members of this signaling cascade in the...

Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition

Acta Neuropathologica — Fri, 26 Oct 2012 12:22:48 +0100

Abstract Neurofibromatosis type 1 (NF1) is a common genetic disease that predisposes 30–50 % of affected individuals to develop plexiform neurofibromas. We found that macrophage infiltration of both mouse and human neurofibromas correlates with disease progression. Macrophages accounted for almost half of neurofibroma cells, leading us to hypothesize that nerve macrophages are inflammatory effectors in neurofibroma development and/or growth. We tested the effects of PLX3397, a dual kit/fms kinase inhibitor that blocks macrophage infiltration, in the Dhh-Cre; Nf1 flox/flox mouse model of GEM grade I neurofibroma. In mice aged 1–4 months, prior to development of nerve pathology and neurofibroma formation, PLX3397 did not impair tumor initiation and increased...

Scientists Identify Brain Mechanism for Learning Disabilities

About.com Mental Health — Fri, 26 Oct 2012 04:00:00 +0100

UCLA scientists have discovered the brain mechanism that causes learning disabilities in neurofibromatosis 1, an inherited disease marked by disfiguring tumors. The discovery will lead to new treatments for the disease, which affects nearly one million people worldwide. (Nature, 16-Jan-2002) (Source: About.com Mental Health)

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Non-coding RNA ANRIL and the number of plexiform neurofibromas in patients with NF1 microdeletions

BMC Medical Genetics - Latest articles — Fri, 26 Oct 2012 04:00:00 +0100

Conclusion: Our findings imply that, at least in patients with NF1 microdeletions, PNF susceptibility is not associated with rs2151280. Although somatic inactivation of the NF1 wild-type allele is considered to be the PNF-initiating event in NF1 patients with intragenic mutations and patients with NF1 microdeletions, both patient groups may differ with regard to tumour progression because of the heterozygous constitutional deletion of SUZ12 present only in patients with NF1 microdeletions. (Source: BMC Medical Genetics - Latest articles)

Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis Type 1.

Journal of Neurosurgery — Fri, 26 Oct 2012 04:00:00 +0100

Conclusions These findings suggest that GTR offers significant long-term benefit on survival in patients with NF1. Benefit on survival occurred independently of all other covariates, suggesting that complete resection should be the principal goal of treatment in this patient population. PMID: 23101443 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

Diffuse cystic lung disease as a manifestation of neurofibromatosis.

Radiologia — Thu, 25 Oct 2012 04:00:00 +0100

Authors: Fernández Plaza A, Sánchez González A PMID: 23102517 [PubMed - as supplied by publisher] (Source: Radiologia)

Horizon scanning: Phase II trial of imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1

NeLM - News — Tue, 23 Oct 2012 04:00:00 +0100

Source: Lancet Oncology Area: News The Lancet Oncology has featured the results of a phase II study evaluating the use of imatinib mesylate for the treatment of plexiform neurofibromas in patients with neurofibromatosis type 1 (NF1). The study involved 36 patients aged between 3 and 65 years who had been diagnosed with NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m2 twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. The following results were reported: . Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% o...

Microsurgical management of non-neurofibromatosis spinal schwannoma.

Neurocirugia — Tue, 23 Oct 2012 04:00:00 +0100

CONCLUSION: Spinal schwannomas may occur at any level of the spinal axis and are most frequently intradural-extramedullary. The most common clinical presentation is pain. Most of the spinal schwannomas in non-NF patients can be resected completely without or with minor post-operative deficits. This knowledge may help us to create a strategy for total resection of a spinal schwannomas. PMID: 23102980 [PubMed - as supplied by publisher] (Source: Neurocirugia)

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Phalanges deformity associated with neurofibromatosis-1: a case report.

Hand Surgery — Sat, 20 Oct 2012 22:45:02 +0100

We present a case of phalangeal deformity in a 17-year-old boy. The deformity was caused by a neurofibroma associated with neurofibromatosis type 1, affecting the left ring finger. The mass was surgically resected. Recurrence had not occurred at three-year follow-up. PMID: 23061950 [PubMed - in process] (Source: Hand Surgery)

The Endovascular Management of a Neurofibromatosis Vasculopathy: A Case Report

Vascular and Endovascular Surgery — Thu, 18 Oct 2012 04:00:00 +0100

We describe the management of a 30-year-old male with type I neurofibromatosis who required an above-knee amputation for bleeding, infection, swelling, and multiple severe joint instability. Postoperatively, he continued to bleed from the stump site. Angiography revealed multiple small distal bleeding aneurysms. Hemostasis was eventually achieved with standard microcoil embolization. (Source: Vascular and Endovascular Surgery)

Diagnosis and Treatment of Osteopenic Fractures in Children

Current Osteoporosis Reports — Wed, 17 Oct 2012 05:49:09 +0100

Abstract Osteopenic fractures occur in children every day. At times the osteopenic nature of these fractures is painfully obvious, as in neurofibromatosis and osteogenesis imperfecta, while in many other situations overt osteopenia does not declare itself, such as in normal and obese children. Normal pediatric bone growth commonly involves periods of relative bone weakness. Childhood obesity creates a situation where bone is unable to fully adapt to the stresses placed upon it. Conditions like neurofibromatosis and osteogenesis imperfecta place pediatric bone at a distinct genetic disadvantage. This review will highlight recent research in these areas and provide radiographic examples of the treatment of osteopenic fractures in children. Content Type Journal ArticleCat...

Genetics and Molecular Pathogenesis of Phaeochromocytoma and Paraganglioma

Clinical Endocrinology — Sat, 13 Oct 2012 04:00:00 +0100

Abstract Although most phaeochromocytomas (PCCs) and paragangliomas (PGLs) are sporadic, molecular genetic medicine has revealed that a considerable number of patients with apparently sporadic PCC actually have a genetic predisposition to the development of these tumours. After decades of intensive research, several genes are now known to play an important role in the pathogenesis of PCC. At present these are RET proto‐oncogene, von Hippel‐Lindau disease tumour suppressor gene (VHL), neurofibromatosis type 1 tumour suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumour suppressor gene...

Anti-nociceptive Ca2+ Channel Peptides [Neurobiology]

Journal of Biological Chemistry — Fri, 12 Oct 2012 04:00:00 +0100

This study suggests that CaV peptides, by perturbing interactions with the neuromodulator CRMP2, contribute to suppression of neuronal hypersensitivity and nociception. (Source: Journal of Biological Chemistry)

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Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: a novel genotype–phenotype correlation

European Journal of Human Genetics — Wed, 10 Oct 2012 04:00:00 +0100

Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: a novel genotype–phenotype correlation European Journal of Human Genetics advance online publication, October 10 2012. doi:10.1038/ejhg.2012.221 Authors: Shay Ben-Shachar, Shlomi Constantini, Hen Hallevi, Emma K Sach, Meena Upadhyaya, Gareth D Evans & Susan M Huson (Source: European Journal of Human Genetics)

Auditory Brainstem Implants: How Do They Work?

Mon, 08 Oct 2012 04:00:00 +0100

Abstract This review covers the design, structure, and function of auditory brainstem implants. Auditory brainstem implants (ABIs) are auditory prostheses initially designed to treat deafness in patients with neurofibromatosis type 2 (NF2). NF2 typically results in deafness due to disruption of the cochlear nerves. When the tumors are removed the auditory nerve is usually cut or nonfunctional anymore. In these cases, patients cannot benefit from peripheral devices such as cochlear implants (CI). Another cause of VIII nerve loss is bilateral temporal bone fracture. Worldwide, more than 500 persons have received an ABI after removal of the tumors that occur with NF2. More recently, some extensions of indications have been proposed to include subjects who would not benefit enough from a cochl...

What Causes Scoliosis?

PediatricEducation.org — Mon, 08 Oct 2012 00:15:38 +0100

Discussion Alignment of the spine is measured from a plumbline dropped from C7 vertebrae as the line of reference. Lordosis is anterior curving, kyphosis is posterior curving and scoliosis is lateral curving relative to this line. Scoliosis has a large differential diagnosis with neuromuscular and spinal abnormalities being the most common as groups. Adolescent idiopathic scoliosis is the most common type of idiopathic scoliosis and the most common type of scoliosis (as a distinct entity) overall. By mid- to late- adolescence, 2-3% will have a 10-degree angle or more. The Cobb angle measures the degree of curvature and its determination can be seen here. Treatment for scoliosis consists of 3 O’s – observation, orthosis (bracing) and operation. Learning Point The differential ...

Ganglioneuroma in the papilla of Vater with neurofibromatosis type 1: report of a case

Surgery Today — Sun, 07 Oct 2012 05:41:01 +0100

We report in this article the case of a young woman, subjected to diagnostic work-up because of abdominal pain. Endoscopy and histology revealed not only a GN in the papilla of Vater, but also NF-1. Because of the size and macroscopic features of the lesion, we performed pancreatoduodenectomy, from which she recovered uneventfully. Histological examination of the resected tumor confirmed a diagnosis of GN. Content Type Journal ArticleCategory Case ReportPages 1-3DOI 10.1007/s00595-012-0367-6Authors Róbert Papp, Department of Surgery, Medical Faculty of Pécs University, Rákóczi u. 2, 7623 Pécs, HungaryJózsef Baracs, Department of Surgery, Medical Faculty of Pécs University, Rákóczi u. 2, 7623 Pécs, HungaryAndrás Papp, Department of Surgery, Medical Faculty of Pécs Univ...

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Cervical myelopathy caused by bilateral C1–2 dumbbell ganglioneuromas and C2–3 and C3–4 neurofibromas associated with neurofibromatosis type 1

Journal of Orthopaedic Science — Fri, 05 Oct 2012 17:08:54 +0100

Content Type Journal ArticleCategory Case ReportPages 1-6DOI 10.1007/s00776-012-0315-8Authors Kei Ando, Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ward, Nagoya, Aichi 466-8550, JapanShiro Imagama, Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ward, Nagoya, Aichi 466-8550, JapanZenya Ito, Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ward, Nagoya, Aichi 466-8550, JapanKenichi Hirano, Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ward, Nagoya, Aichi 466-8550, JapanRyoji Tauchi, Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai Sh...

Dental age in patients with neurofibromatosis 1

European Journal of Oral Sciences — Thu, 04 Oct 2012 04:00:00 +0100

In this study the dental age of 34 Finnish NF1 patients, 8–17 yr of age, was estimated using the Demirjian & Goldstein method. The dental age of children with NF1 was similar to that of a Finnish control population. The findings suggest that NF1 does not affect the timing of tooth development. (Source: European Journal of Oral Sciences)

Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1

Orphanet Journal of Rare Diseases — Thu, 04 Oct 2012 04:00:00 +0100

Background: To examine the natural growth dynamics of internal plexiform neurofibromas (PNs) in patients with neurofibromatosis 1 (NF1). Methods: Two hundred and one NF1 patients underwent whole body MRI (WBMRI). Tumour burden was estimated volumetrically. Non-parametric Spearman's rho correlation coefficients were used to analyse the relationship of growth rate to tumour volume and age. Chi-squared and Mann--Whitney U tests were used for analysing the association of tumour occurrence with sex or age. Chi-squared tests were used to analyse the association of tumour growth to age group. Results: Seventy-one of 171 patients with serial WBMRI exams had internal PNs (median follow up 2.2 years [1.1 to 4.9 years]). Median whole body tumour volume was 86.4 mL [5.2 to 5878.5 mL]) with a median gr...

Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum

Cancer Genetics and Cytogenetics — Thu, 04 Oct 2012 04:00:00 +0100

This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy. A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene. Furthermore, SNP analyses determined that LOH was observed in the IL17RA (22q11.1), CHECK2 (22q12.1), and SHANK3 (22q13.3) genes, thus suggesting that NF2 loss occurred through 22q deletions or monosomy 22. The LOH of the NF2 gene was observed in an early stage of WDPMP, thus indicating that LOH of the NF2 gene is an early molecular alteration, and NF2 loss is a molecular mechanism associ...

Neuropsychological profile in adults with neurofibromatosis type 1 compared to a control group

Journal of Intellectual Disability Research — Mon, 01 Oct 2012 04:00:00 +0100

ConclusionTaking into account that primary visual perception problems could be part of a more general central coherence deficit while interpreting auditory memory problems as possibly related to deficits in language use and comprehension, this idea also fits with the observation of several problems in social information processing and functioning of NF1 persons. (Source: Journal of Intellectual Disability Research)

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Tumors at the lateral portion of the C1-2 interlaminar space compressing the spinal cord by rotation of the atlantoaxial joint: new aspects of spinal cord compression.

Journal of Neurosurgery.Spine — Fri, 28 Sep 2012 04:00:00 +0100

Authors: Ozawa H, Kusakabe T, Aizawa T, Nakamura T, Ishii Y, Itoi E Abstract The authors describe 2 patients with C-2 nerve root tumors in whom the lesions were located bilaterally in the lateral portions of the C1-2 interlaminar space and compressed the spinal cord when the atlantoaxial joint was rotated. The patients were adult men with neurofibromatosis. Each presented with clumsiness of both hands and motor weakness of the extremities accompanied by spastic gait. Magnetic resonance imaging of the cervical spine performed with the neck in the neutral position showed tumors at the bilateral lateral portion of the C1-2 interlaminar space without direct compression of the spinal cord. The spinal cord exhibited an I-shaped deformity at the same level as the tumors in one case and a...

Plexiform perineurioma of the lip: A case report and review of literature

Pathology International — Mon, 24 Sep 2012 04:00:00 +0100

We describe a plexiform perineurioma, which is an extremely rare variant of soft tissue perineurioma. A 43‐year‐old Japanese man presented with a painless, well‐demarcated, elastic, soft tumor measuring 2.0 × 1.9 cm on the upper lip that had persisted for three years. Microscopically, a plexiform tumor composed of minimally atypical spindle cells with wavy nuclei was located in the lamina propria of the oral mucosa. Tumor cells were concentrically arranged around small vessels and aligned in parallel with delicate collagen fibers on a fibromyxoid background in the hypocellular area. Tumor cells were immunohistochemically positive for EMA, GLUT‐1, claudin‐1, and CD34 and negative for S‐100 protein. The histopathological and immunohistochemical profiles of the excised tumo...

Neurofibromatosis type 1 (NF1) associated with tumor of the corpus callosum

Child's Nervous System — Fri, 21 Sep 2012 16:12:10 +0100

Conclusions Tumors of corpus callosum in patients with NF1 are very uncommon. The patient presented in this paper consulted due to family history of NF1, progressive hyperactivity, and below average school performance. The MR study showed tumor in the corpus callosum. Tumor histology was not investigated. Content Type Journal ArticleCategory Case ReportPages 1-4DOI 10.1007/s00381-012-1903-9Authors Ignacio Pascual-Castroviejo, Pediatric Neurology Service, University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, SpainSamuel-Ignacio Pascual-Pascual, Pediatric Neurology Service, University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain Journal Child's Nervous SystemOnline ISSN 1433-0350Print ISSN 0256-7040 (Source: Child's Nervous S...

Children's Tumor Foundation and Cenix BioScience Sign Framework...

PRWeb: Medical Pharmaceuticals — Fri, 21 Sep 2012 03:20:06 +0100

The Children's Tumor Foundation (CTF), a nonprofit medical foundation dedicated to improving the health and well being of individuals and families affected by neurofibromatosis (NF), and Cenix...(PRWeb September 20, 2012)Read the full story at http://www.prweb.com/releases/2012/9/prweb9924672.htm (Source: PRWeb: Medical Pharmaceuticals)

Neurofibromatosis type 1 associated with central giant cell lesion of the maxilla and mandible

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics — Tue, 18 Sep 2012 00:01:50 +0100

Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder affecting approximately 1 in 3500 people, caused by a spectrum of mutations affecting the Nf1 gene. Central giant cell lesion affects fewer than 7% of all benign tumor of the jaws and can develop in patients with neurofibromatosis. It is benign but sometimes aggressive osteolytic proliferation consisting of fibrous tissue with hemorrhage and hemosiderin deposits, presence of osteoclast-like giant cells and reactive bone formation is present. A 39 years old, female, NF1 patient, revealed, in both maxilla and mandible, a sessile nodule of 5 cm in length, it also demonstrated to be painful and bleeding to the touch. In the panoramic radiography, an intra-osseous mass could be notice. The serum levels of calcium and ...

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Aggressive Leptomeningeal Gliomatosis in Neurofibromatosis Type 1 [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Mon, 17 Sep 2012 04:00:00 +0100

(Source: Journal of Clinical Oncology)

Hybrid peripheral nerve sheath tumor.

Journal of Neurosurgery — Fri, 14 Sep 2012 04:00:00 +0100

Authors: Lang SS, Zager EL, Coyne TM, Nangunoori R, Kneeland JB, Nathanson KL Abstract In recent literature, there have been case reports of an extremely rare entity characterized by hybrid peripheral nerve tumors consisting of elements of neurofibroma, schwannoma, and/or perineurioma. The authors present a unique case of a patient with multiple painful hybrid tumors with negative genetic testing for neurofibromatosis Type 1 and no clinical evidence of neurofibromatosis Type 2 or schwannomatosis. A 28-year-old woman presented with tentatively diagnosed schwannomatosis. She had painful bilateral retromastoid scalp tumors as well as multiple other painful tumors in the distribution of the saphenous, femoral, and sciatic nerves. Her family history was significant for a paternal grand...

The Effect of Apamin, a Small Conductance Calcium Activated Potassium (SK) Channel Blocker, on a Mouse Model of Neurofibromatosis 1.

Behavioural Brain Research — Thu, 13 Sep 2012 04:00:00 +0100

In this study we demonstrate a possible mechanism for the learning deficits seen in Nf1(+/-) mice and a possible drug therapy for rescuing these deficits. PMID: 22983217 [PubMed - as supplied by publisher] (Source: Behavioural Brain Research)

Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1

Human Brain Mapping — Tue, 11 Sep 2012 04:00:00 +0100

Abstract Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model‐driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data‐driven classification approach. We...

A new nonsense mutation in the NF1 gene with neurofibromatosis–Noonan syndrome phenotype

Child's Nervous System — Mon, 10 Sep 2012 15:56:32 +0100

Conclusion We report the case of a 14-year-old boy with neurofibromatosis type 1 with Noonan-like features, who complained of headache with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549C>T in exon 51. Content Type Journal ArticleCategory Case ReportPages 1-3DOI 10.1007/s00381-012-1905-7Authors Sevgi Yimenicioğlu, Department of Pediatric Neurology, Osmangazi University Medical Faculty, Eskisehir, TurkeyAyten Yakut, Department of Pediatric Neurology, Osmangazi University Medical Faculty, Eskisehir, TurkeyKadri Karaer, Department of Medical Genetics, Osmangazi University Medical Faculty, Eskisehir, TurkeyMartin Zenker, Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, GermanyArzu Ekici, Department of Pediatric Neurolog...

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Breast cancer and other neoplasms in women with neurofibromatosis type 1: A retrospective review of cases in the Detroit metropolitan area

American Journal of Medical Genetics Part A — Mon, 10 Sep 2012 04:00:00 +0100

Abstract Neurofibromatosis type 1 (NF1) is one of the most common cancer predisposing syndromes with an incidence of 1 in 3,500 worldwide. Certain neoplasms or malignancies are over‐represented in individuals with NF1; however, an increased risk of breast cancer has not been widely recognized or accepted. We identified 76 women with NF1 seen in the Henry Ford Health System (HFHS) from 1990 to 2009, and linked them to the Surveillance Epidemiology and End Results (SEER) registry covering the metropolitan Detroit area. Fifty‐one women (67%) were under age 50 years at the time of data analysis. Six women developed invasive breast cancer before age 50, and three developed invasive breast cancer after age 50. Using standardized incidence ratios (SIRs) calculated based on the SEER age‐adju...

MRI in hypertrophic mono- and polyneuropathies

Clinical Radiology — Mon, 10 Sep 2012 04:00:00 +0100

Different conditions that may lead to enlarged nerves or nerve roots include hereditary motor and sensory neuropathy (HMSN), neurofibromatosis (NF) type 1, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and intraneural perineurioma. Differential diagnosis of hypertrophic mono- and polyradiculopathies remains challenging but is important because of different treatments and prognosis. Magnetic resonance imaging (MRI) can identify the hypertrophic nerve segments and guide a fascicular biopsy. A fascicular biopsy will often be necessary for precise diagnosis. (Source: Clinical Radiology)

Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas

Pediatric Blood and Cancer — Fri, 07 Sep 2012 04:00:00 +0100

ConclusionsChildren with NF1 and PN did not tolerate sorafenib at doses substantially lower than the MTD in children and adults with malignant solid tumors. Future trials with targeted agents for children with NF1 may require a more conservative starting dose and separate definitions of dose limiting toxicities (DLT) than children with cancer. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis

Journal of Clinical Investigation — Tue, 04 Sep 2012 17:01:21 +0100

Intrinsic stress response pathways are frequently mobilized within tumor cells. The mediators of these adaptive mechanisms and how they contribute to carcinogenesis remain poorly understood. A striking example is heat shock factor 1 (HSF1), master transcriptional regulator of the heat shock response. Surprisingly, we found that loss of the tumor suppressor gene neurofibromatosis type 1 (Nf1) increased HSF1 levels and triggered its activation in mouse embryonic fibroblasts. As a consequence, Nf1–/– cells acquired tolerance to proteotoxic stress. This activation of HSF1 depended on dysregulated MAPK signaling. HSF1, in turn, supported MAPK signaling. In mice, Hsf1 deficiency impeded NF1-associated carcinogenesis by attenuating oncogenic RAS/MAPK signaling. In cell lines from ...

Giant cell glioblastoma with unique bilateral cerebellopontine angle localization considered as extraaxial tumor growth in a patient with neurofibromatosis Type 1.

Clinical Neuropathology — Tue, 04 Sep 2012 04:00:00 +0100

We report a case of GCGBM presenting primarily as an extraaxial bilateral CPA tumor in a 29-year-old woman with neurofibromatosis Type 1 (NF1). The patient died shortly after surgery of the right CPA tumor. Postmortem study of the brain revealed large tumor masses, located in the CPA bilaterally, encasing the brainstem base and cisternal portions of the cranial nerves. Tumor masses were demarcated from the brainstem and cerebellum and covered by leptomeninges. Microscopically, a slight subpial tumor seeding from the leptomeninges into the brain parenchyma was observed in the right CPA region. The tumor showed highly pleomorphic, giant and multinucleated cells, densely cellular sheets of poorly differentiated cells and pseudopalisading necroses. Tumor cells were positive for GFAP, S-100 pro...

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Clinical characteristics predicting internal neurofibromas in 357 children with neurofibromatosis-1: results from a cross-selectional study

Orphanet Journal of Rare Diseases — Mon, 03 Sep 2012 04:00:00 +0100

Conclusions: Several easily recognizable clinical characteristics indicate a high risk of internal neurofibromas in children with NF1 and, therefore, a need for very close monitoring. (Source: Orphanet Journal of Rare Diseases)

Jelly Belly trans‐synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture

Journal of Neurobiology — Sat, 01 Sep 2012 04:00:00 +0100

Abstract In Drosophila the secreted signaling molecule Jelly Belly (Jeb) activates AnaplasticLymphoma Kinase (Alk), a receptor tyrosine kinase, in multiple developmental and adultcontexts. We have shown previously that Jeb and Alk are highly enriched at Drosophilasynapses within the CNS neuropil and neuromuscular junction (NMJ) and postulated a conservedintercellular signaling function. At the embryonic and larval NMJ Jeb is localized in the motorneuron presynaptic terminal whereas Alk is concentrated in the muscle postsynaptic domainsurrounding boutons, consistent with anterograde trans‐synaptic signaling. Here, we show byfunctional inhibition of Jeb‐Alk signaling that neurotransmission is regulated by Jeb secretion.Jeb is a novel negative regulator of neuromuscular transmission. Redu...

The impact of comorbidities, regional trends, and hospital factors on discharge dispositions and hospital costs after acoustic neuroma microsurgery: a United States nationwide inpatient data sample study (2005-2009).

Neurosurgical Focus — Sat, 01 Sep 2012 04:00:00 +0100

Conclusions The authors' study shows that several factors can affect patient outcome and hospital charges for patients who have undergone acoustic neuroma surgery. Factors such as younger age, higher ZIP code income, less comorbidity, private insurance, elective surgery, and the West region predicted for better disposition outcome. However, the West region, higher comorbidities, and weekend admissions were associated with higher hospitalization costs. PMID: 22937854 [PubMed - in process] (Source: Neurosurgical Focus)

Association of Piebaldism, Multiple Café‐au‐lait Macules, and Intertriginous Freckling: Clinical Evidence of a Common Pathway between KIT and Sprouty‐Related, Ena/Vasodilator‐Stimulated Phosphoprotein Homology‐1 Domain Containing Protein 1 (SPRED1)

Pediatric Dermatology — Sat, 01 Sep 2012 04:00:00 +0100

We report the case of a 5‐year‐old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café‐au‐lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty‐related, Ena/vasodilator‐stimulated phosphoprotein homology‐1 domain containing protein 1 (SPRED1) mutations that also has multiple café‐au‐lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café‐au‐lait macules and freckling may be seen in some patie...