scholarly journals Immunohistochemical Markers for Prospective Studies in Neurofibromatosis-1 Porcine Models

2017 ◽  
Vol 65 (10) ◽  
pp. 607-618 ◽  
Author(s):  
David K. Meyerholz ◽  
Georgina K. Ofori-Amanfo ◽  
Mariah R. Leidinger ◽  
J. Adam Goeken ◽  
Rajesh Khanna ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Malignant Tumors ◽  
Neurofibromatosis Type ◽  
Nuclear Antigen ◽  
Inflammatory Factor ◽  
Glucose Transporter 1 ◽  
Peripheral Nerve Sheath Tumors ◽  
Immunohistochemical Markers ◽  
Increased Risk ◽  
Calbindin D

Neurofibromatosis type 1 (NF1) is a common, cancer-predisposing disease caused by mutations in the NF1 tumor gene. Patients with NF1 have an increased risk for benign and malignant tumors of the nervous system (e.g., neurofibromas, malignant peripheral nerve sheath tumors, gliomas) and other tissues (e.g., leukemias, rhabdomyosarcoma, etc.) as well as increased susceptibility to learning disabilities, chronic pain/migraines, hypertension, pigmentary changes, and developmental lesions (e.g., tibial pseudoarthrosis). Pigs are an attractive and upcoming animal model for future NF1 studies, but a potential limitation to porcine model research has been the lack of validated reagents for direct translational study to humans. To address that issue, we used formalin-fixed tissues (human and pigs) to evaluate select immunohistochemical markers (activated caspase-3, allograft inflammatory factor-1, beta-tubulin III, calbindin D, CD13, CD20, desmin, epithelial membrane antigen, glial fibrillary acidic protein, glucose transporter-1, laminin, myelin basic protein, myoglobin, proliferating cell nuclear antigen, S100, vimentin, and von Willebrand factor). The markers were validated by comparing known expression and localization in human and pig tissues. Validation of these markers on fixed tissues will facilitate prospective immunohistochemical studies of NF1 pigs, as well as other pig models, in a more efficient, reproducible, and translationally relevant manner.

scholarly journals Oral Metastasis of Metaplastic Breast Carcinoma in a Patient with Neurofibromatosis 1

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Paula Molina Vivas ◽  
Luana Eschholz Bomfin ◽  
Clovis Antonio Lopes Pinto ◽  
Ulisses Ribaldo Nicolau ◽  
Fabio Abreu Alves
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
English Literature ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Increased Risk ◽  
Multiple Metastases ◽  
Metaplastic Breast Carcinoma ◽  
Oral Metastasis

Neurofibromatosis type 1 (NF1) has been associated with an increased risk for development of malignancy, especially malignant peripheral nerve sheath tumors. In addition, recently, literature has demonstrated an increased risk of breast cancer in women with NF1. The present paper shows a 53-year-old woman with NF1 who presented with metaplastic breast carcinoma and developed multiple metastases, including mandible. Furthermore, we reviewed the English literature, found 63 cases showing the association between NF1 and breast cancer, and added one more case. The present study demonstrated an important association between NF1 and breast cancer. Until the present time, there has been only one case of metaplastic breast carcinoma associated with NF1. Curiously, in our case the oral metastasis corresponded to sarcomatous component of metaplastic breast carcinoma.

scholarly journals Glioblastoma in the Cerebellopontine Angle in a Patient with Neurofibromatosis Type I: A Case Report and Review of the Literature

2019 ◽  
Vol 2 (02) ◽  
pp. 72-75
Author(s):  
Mohammad Kareem Shukairy ◽  
Andrea M. Ziegler ◽  
Douglas E. Anderson ◽  
John P. Leonetti
Keyword(s):  
Case Report ◽  
Cerebellopontine Angle ◽  
Malignant Tumors ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Increased Risk ◽  
Facial Numbness ◽  
History Of ◽  
Pain Patients

Abstract Introduction Glioblastoma multiforme (GBM) is the most common primary brain malignancy in adults and is typically in the supratentorial cerebral hemispheres. It has been reported to occur in the posterior fossa at the cerebellopontine angle (CPA), but the incidence is extremely rare. Case Report We report a case of a patient with a history of neurofibromatosis type I (NFI) diagnosed with a GBM arising in the CPA after presenting with facial numbness and pain. Patients with NFI are known to have an increased risk of developing both benign and malignant tumors, including a propensity for brainstem gliomas. However, there is no known association between NFI and tumors of the CPA. We believe this is the first reported case of a GBM of the CPA in a patient with NFI. Conclusion Although rare, GBM should be included in the differential diagnosis of a patient with a CPA tumor, especially in patients with increased risk of malignant pathology.

scholarly journals Malignant Peripheral Nerve Sheath Tumors in Children with Neurofibromatosis Type 1

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Apostolos Pourtsidis ◽  
Dimitrios Doganis ◽  
Margarita Baka ◽  
Despina Bouhoutsou ◽  
Maria Varvoutsi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Soft Tissue Sarcomas ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Increased Risk

Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5–10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department.Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them.Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear.

scholarly journals A Case Report of a Malignant Peripheral Nerve Sheath Tumor of the Oral Cavity in Neurofibromatosis Type 1

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Özmen Öztürk ◽  
Alper Tutkun
Keyword(s):  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Malignant Tumors ◽  
Rapid Change ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Adjacent Structures

Patients with neurofibromatosis type 1 develop both benign and malignant tumors at an increased frequency. Most of the malignant peripheral nerve sheath tumors (MPNSTs) are considered as high-grade sarcomas originating from tissues of mesenchymal origin. It is generally accepted that MPNSTs occur in about 2% to 5% of neurofibromatosis patients. In this paper, we present a 16-year-old male patient with neurofibromatosis who developed MPNST of the retromolar area. The mass enlarged rapidly in a period of 6 weeks. The patient was treated surgically, and a tumor mass with a diameter of  cm was excised, but after 8 months a recurrence was observed at the same site. The sarcomatous change in a neurofibroma has an extremely poor prognosis, so patients with neurofibromatosis should be closely monitored for a possible malignancy. A rapid change in size of a preexisting neurofibroma, infiltration of the adjacent structures, intralesional hemorrhage, and pain indicate a possible malignant transformation to MPNST.

scholarly journals Malignant tumors in children with neurofibromatosis Type 1

2021 ◽  
Vol 67 (3) ◽  
pp. 421-429
Author(s):  
Svetlana Mikhailova ◽  
Valentina Kozlova ◽  
Tatiana Kazubskay ◽  
Elena Sharapova ◽  
Mariia Iurchenko ◽  
...  
Keyword(s):  
Clinical Data ◽  
Malignant Tumors ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Neurofibromatosis Type ◽  
Clinical Aspects ◽  
Benign Tumors ◽  
Type I ◽  
Embryonal Tumors ◽  
Peripheral Nerve Sheath Tumors

Neurofibromatosis type I (NF1) is the monogenic inherited syndrome with established variability of clinical manifestations and the predisposition to the development of malignant tumors. Studying NF1 association with different types of cancers in children is necessary to understand the risk of their occurrence and the prognosis of the disease as well as subsequent studies of this predisposition. Aim. Analysis the clinical data of patients with NF1 and malignant and benign tumors arisen in them. Methods. A retrospective analysis of clinical data of 19 patients from 0 to 18 years old with a malignant tumor, carried out in N.N. Blokhin NMRCO from 1997 to 2018. Results. The clinical signs of NF1 showed an age-dependent timing of their onset. Embryonal tumors were the most common and occurred in 11 out of 19 patients (57.9%), embryonal rhabdomyosarcoma predominated (42.1%), more often affecting the urogenital tract. Familial NF1 was found in 31.6% of patients. NF1 disease of the parents of these children (in four mothers and two fathers) was limited to pigmented skin lesions and multiple neurofibromas. Genetic testing of NF1 gene in three families of children with embryonal tumors revealed 2 de novo mutations — p.V2635FS & p.W1314X and one inherited from father to son (p.2363_2365del). Malignant peripheral nerve sheath tumors developed in 15.8% of patients by puberty. Soft tissue sarcomas and hematopoietic tumors occurred in 10.5% of patients, respectively. Melanoma was found in one patient (5.3%). Conclusion. The data obtained make it possible to supplement the diapason of types of malignant tumors in children associated with NF1 and the possibility of their use in clinical practice for a more rational and targeted observation for patients. Further study of the molecular genetics and clinical aspects of NF1 is necessary for the development of promising therapies for NF1.

scholarly journals Chitosan-Based Glycolipid Conjugated siRNA Delivery System for Improving Radiosensitivity of Laryngocarcinoma

Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 2929
Author(s):  
Jing Miao ◽  
Liwen Zhang ◽  
Peng Gao ◽  
Huawei Zhao ◽  
Xianji Xie ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Glucose Transporter ◽  
Malignant Tumors ◽  
Sirna Delivery ◽  
Survival Rates ◽  
Chitosan Oligosaccharide ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Intrinsic Marker ◽  
Sirna Delivery System

Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector LipofectamineTM2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.

scholarly journals Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 762
Author(s):  
Verena Staedtke ◽  
Tyler Gray-Bethke ◽  
Gregory J. Riggins ◽  
Ren-Yuan Bai
Keyword(s):  
Malignant Tumors ◽  
Neurofibromatosis 1 ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Extracellular Signal ◽  
Solid Malignancies ◽  
Increased Risk ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Patients with RASopathy Neurofibromatosis 1 (NF1) are at a markedly increased risk of the development of benign and malignant tumors. Malignant tumors are often recalcitrant to treatments and associated with poor survival; however, no chemopreventative strategies currently exist. We thus evaluated the effect of mebendazole, alone or in combination with cyclooxygenase-2 (COX-2) inhibitors, on the prevention of NF1-related malignancies in a cis Nf1+/−;Tp53+/− (NPcis) mouse model of NF1. Our in vitro findings showed that mebendazole (MBZ) inhibits the growth of NF1-related malignant peripheral nerve sheath tumors (MPNSTs) through a reduction in activated guanosine triphosphate (GTP)-bound Ras. The daily MBZ treatment of NPcis mice dosed at 195 mg/kg daily, initiated 60 days after birth, substantially delayed the formation of solid malignancies and increased median survival (p < 0.0001). Compared to placebo-treated mice, phosphorylated extracellular signal-regulated kinase (pERK) levels were decreased in the malignancies of MBZ-treated mice. The combination of MBZ with COX-2 inhibitor celecoxib (CXB) further enhanced the chemopreventative effect in female mice beyond each drug alone. These findings demonstrate the feasibility of a prevention strategy for malignancy development in high-risk NF1 individuals.

scholarly journals Association between Neurofibromatosis Type 1 and Breast Cancer: A Report of Two Cases with a Review of the Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yoon Nae Seo ◽  
Young Mi Park
Keyword(s):  
Breast Cancer ◽  
Neurofibromatosis Type 1 ◽  
Malignant Tumors ◽  
Genetic Diseases ◽  
Neurofibromatosis Type ◽  
Review Of The Literature ◽  
Increased Risk

Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and is associated with various benign and malignant tumors, including breast cancer. However, an increased risk of breast cancer in NF1 patients has not been widely recognized or accepted. Here, we report two cases of breast cancer in NF1 patients and review the literature on the association between NF1 and breast cancer.

Malignant Peripheral Nerve Sheath Tumor With Divergent Glandular Differentiation

2017 ◽  
Vol 25 (4) ◽  
pp. 310-313 ◽  
Author(s):  
Yurina Miki ◽  
Khin Thway
Keyword(s):  
Differential Diagnosis ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Histologic Diagnosis ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Immunohistochemical Markers ◽  
Nerve Sheath ◽  
Divergent Differentiation

Malignant peripheral nerve sheath tumors (MPNST) are soft tissue neoplasms with evidence of nerve sheath differentiation. They usually arise from peripheral nerves or from preexisting benign nerve sheath neoplasms, often in patients with neurofibromatosis type 1 (NF1). The histologic diagnosis of MPNST is challenging as their morphology is highly variable, and there has been a lack of routine diagnostic immunohistochemical markers and specific genetic aberrations. Although divergent differentiation is well documented in MPNST, it is most frequently toward mesenchymal elements. Differentiation toward epithelial elements is very rare, and we illustrate a case of MPNST with glandular differentiation, comprising prominent well-formed glands, with a brief discussion of biphasic (spindle and glandular) neoplasms in the differential diagnosis. An index of suspicion for MPNST is necessary, due to the differing management from tumors in its differential diagnosis, and because of the potential for therapies toward molecular targets in future.

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