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Frontiers in Neuroscience 2022Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the of the nasal mucosa. They display neurogenic and immunomodulatory properties...
BACKGROUND
Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the of the nasal mucosa. They display neurogenic and immunomodulatory properties and were shown to induce recovery in animal models of spinal cord trauma, hearing loss, Parkinsons's disease, amnesia, and peripheral nerve injury. As a step toward clinical practice, we sought to (i) devise a culture protocol that meets the requirements set by human health agencies and (ii) assess the efficacy of stem cells on neuron differentiation.
METHODS
Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a.
RESULTS
Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells.
CONCLUSION
We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.
PubMed: 36466172
DOI: 10.3389/fnins.2022.1042276 -
Indian Journal of Otolaryngology and... Oct 2022Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Olfactory neuroblastoma centered in the posterior right orbit with prominent...
Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Olfactory neuroblastoma centered in the posterior right orbit with prominent orbital protrusion is even rare. Grading ONB is extremely important as individualized treatment plans must be formulated according to tumor grade. We report the case of a 67-year-old female who presented with the chief complaints of persistent nasal congestion with intermittent epistaxis and unilateral proptosis over the past five years. Radiological imaging was suggestive of a large heterogeneous mass in the right superior nasal cavity with extensions into the right medial orbit, nasopharynx, the right maxillary sinus, the anterior cranial fossa, right ethmoidal, frontal and bilateral sphenoidal sinuses, as well as into the right frontal lobe. Assessment of the radiologic features revealed the diagnostic possibility of olfactory neuroblastoma. A nasopharyngeal biopsy confirmed an olfactory neuroblastoma. Frontal osteoplastic craniotomy and excision of the intracranial part of the tumor from above and transnasal endoscopic removal of the mass in the nasal cavities, paranasal sinuses and right medial orbit from below was done. Evaluation of histopathological characteristics and immunohistochemical findings revealed a diagnosis of WHO grade IV olfactory neuroblastoma. Because of poor economic condition, the patient did not take adjuvant radiotherapy and chemoradiation and post-operative examination. We report a huge ONB centered in the posterior right orbit with prominent orbital protrusion. Magnetic resonance image and computed tomography are helpful for evaluating the appearance and the extent of ONB, as well as grading this tumor, which may aid therapeutic decisions and improve survival.
PubMed: 36452830
DOI: 10.1007/s12070-020-02359-x -
Indian Journal of Otolaryngology and... Oct 2022Olfactory neuroblastoma (ONB) or esthesioneuroblastoma is a rare malignant intranasal tumor, commonly originated from upper part of nasal cavity. Majority of cases...
Olfactory neuroblastoma (ONB) or esthesioneuroblastoma is a rare malignant intranasal tumor, commonly originated from upper part of nasal cavity. Majority of cases presented with nasal obstruction or epistaxis. ONB is rarely reported in ectopic locations. Here we present the first-ever documented case of an olfactory neuroblastoma situated anterior to body of maxilla, presented as left sided facial swelling. This case report is aimed at achieving the consideration of this rare tumour as a differential diagnosis in the lesions of the anatomical region surrounding the commonly known site of origin i.e. the sinonasal cavity.
PubMed: 36452651
DOI: 10.1007/s12070-021-02595-9 -
Indian Journal of Otolaryngology and... Oct 2022Esthesioneuroblastoma (ENB) is a rare, aggressive and malignant sinonasal tumour. This tumour makes for a very interesting study because ever since its mention in...
Esthesioneuroblastoma (ENB) is a rare, aggressive and malignant sinonasal tumour. This tumour makes for a very interesting study because ever since its mention in medical literature, although quite a lot of research has been put into it, a lot is yet to be known about it. To summarize the available literature & document an article on the contemporary practises in the management of ENB. A comprehensive literature review was done using Google Scholar and PubMed database with the key words: "esthesioneuroblastoma", "olfactory neuroblastoma", "Kadish" and "Hyams". Articles published in English were used. Articles published till April 2021 were reviewed. ENB has a diverse histological appearance. This tumour has a bimodal age distribution without any gender predilection. Prompt identification and treatment is required for a favourable outcome and requires close collaboration of radiology, pathology, and rhinology. Staging, management and prognosis are determined by regional involvement in non-metastatic cases due to its proximity to neurological structures and locally destructive nature. Immunohistochemistry is a must for accurate diagnosis. Uni-modality of treatment has high chances of local recurrence. Multi-modality provides good results even in advanced stage. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. The exact role of chemotherapy in treatment protocols is still unclear. Cervical lymph node metastases are commonly studied, however its management in patients who present without apparent nodal involvement is not yet clear. An extended follow-up period is recommended in all patients of ENB patients.
PubMed: 36452592
DOI: 10.1007/s12070-021-02726-2 -
Cureus Oct 2022Primary desmoplastic small round cell tumor (DSRCT) in the head and neck region is extremely rare. There is limited information about its clinicopathological... (Review)
Review
Primary desmoplastic small round cell tumor (DSRCT) in the head and neck region is extremely rare. There is limited information about its clinicopathological characteristics, prognosis, and treatment modalities. The purpose of this study is to provide a comprehensive review of DSRCT occurring primarily in the head and neck, to demonstrate its peculiar morphology and immunohistochemical expression, and to address the differential diagnoses. A total of 25 cases were collected after a thorough review of the relevant literature. DSRCT was most frequently reported in the major salivary glands, followed by the eyes. Furthermore, some cases were misinterpreted as poorly differentiated carcinoma, Ewing sarcoma, and olfactory neuroblastoma. Diagnosing DSRCTs in the head and neck can be very challenging due to their rarity in this location, overlapping morphology, and immunohistochemistry. In these cases, following a systemic approach helps to solve diagnostic problems.
PubMed: 36415387
DOI: 10.7759/cureus.30475 -
The British Journal of Radiology Dec 2022To investigate the efficacy of pretreatment ADC and Ki-67 index in the prediction of the response to neoadjuvant chemotherapy (NACT) in advanced olfactory neuroblastoma...
OBJECTIVES
To investigate the efficacy of pretreatment ADC and Ki-67 index in the prediction of the response to neoadjuvant chemotherapy (NACT) in advanced olfactory neuroblastoma (ONB) patients.
METHODS
A total of 21 advanced ONB patients (mean 43.48 years ± 14.26; range 25-69 years; 13 men and 8 women) with diffusion-weighted imaging (DWI) before NACT between June 2015 and October 2021 were retrospectively analyzed. Patients were categorized into responders and non-responders according to RECIST 1.1 after two cycles of NACT. The clinical data, ADC value, and Ki-67 index were analyzed.
RESULTS
Kadish stage, ADC value, and Ki-67 index showed statistical significance between responders and non-responders. Patients with Kadish C stage were more likely to respond to platinum-based NACT ( = 0.035). Patients with the lower ADC value showed response to NACT ( = 0.002) and the cutoff point was 1.04 × 10 mm/s. Patients with the higher Ki-67 index showed response to NACT ( = 0.003) and the cutoff point was 17.5%. Predictive performance of Ki-67 index and ADC value showed no significance between responders and non-responders ( = 0.865). A significant negative correlation was found between ADC value and Ki-67 index ( = -0.539, = 0.038).
CONCLUSIONS
The pretreatment ADC value, Ki-67 index and Kadish stage have the potential to predict the response to NACT in advanced ONB patients.
ADVANCES IN KNOWLEDGE
This is the first study that investigated the feasibility of DWI in predicting the response to NACT in ONB patients and showed that Kadish stage, pretreatment ADC and Ki-67 index may play an important role in the prediction.
Topics: Male; Humans; Female; Neoadjuvant Therapy; Ki-67 Antigen; Retrospective Studies; Esthesioneuroblastoma, Olfactory; Diffusion Magnetic Resonance Imaging; Nasal Cavity; Nose Neoplasms
PubMed: 36240450
DOI: 10.1259/bjr.20220367 -
Frontiers in Neuroscience 2022Dual specificity tyrosine-phosphorylation-regulated kinases (DYRKs) are a group of conserved eukaryotic kinases phosphorylating tyrosine, serine, and threonine residues.... (Review)
Review
Dual specificity tyrosine-phosphorylation-regulated kinases (DYRKs) are a group of conserved eukaryotic kinases phosphorylating tyrosine, serine, and threonine residues. The human DYRK family comprises 5 members (DYRK1A, DYRK1B, DYRK2, DYRK3, and DYRK4). The different DYRKs have been implicated in neurological diseases, cancer, and virus infection. Specifically, DYRK2 has been mainly implicated in cancer progression. However, its role in healthy and pathological nervous system function has been overlooked. In this context, we review current available data on DYRK2 in the nervous system, where the available studies indicate that it has key roles in neuronal development and function. DYRK2 regulates neuronal morphogenesis (e.g., axon growth and branching) by phosphorylating cytoskeletal elements (e.g., doublecortin). Comparative data reveals that it is involved in the development of olfactory and visual systems, the spinal cord and possibly the cortex. DYRK2 also participates in processes such as olfaction, vision and, learning. However, DYRK2 could be involved in other brain functions since available expression data shows that it is expressed across the whole brain. High DYRK2 protein levels have been detected in basal ganglia and cerebellum. In adult nervous system, DYRK2 mRNA expression is highest in the cortex, hippocampus, and retina. Regarding nervous system disease, DYRK2 has been implicated in neuroblastoma, glioma, epilepsy, neuroinflammation, Alzheimer's disease, Parkinson's disease, spinal cord injury and virus infection. DYRK2 upregulation usually has a negative impact in cancer-related conditions and a positive impact in non-malignant conditions. Its role in axon growth makes DYRK2 as a promising target for spinal cord or brain injury and regeneration.
PubMed: 36161154
DOI: 10.3389/fnins.2022.994256 -
NMC Case Report Journal 2022Owing to recent advances in medical optical technology, a high-definition (4K) three-dimensional (3D) exoscope has been developed as an alternative tool to using...
Owing to recent advances in medical optical technology, a high-definition (4K) three-dimensional (3D) exoscope has been developed as an alternative tool to using conventional microscopes for microscopic surgery, and its efficacy for neurosurgery has been reported. We report a case who underwent simultaneous surgery aiming for en bloc resection of an anterior skull base malignancy with concurrent exoscopic transcranial and endoscopic endonasal approaches using a 4K 3D exoscope. The patient was a 76-year-old woman who underwent en bloc resection for an anterior skull base olfactory neuroblastoma 13 years ago. After confirming the recurrence of progressive olfactory neuroblastoma, tumor resection was again decided to be performed. As with the first procedure, surgery was performed in an en bloc manner, using both transcranial and endonasal approaches. Exoscope provided enough space above the surgical field to allow us to perform transcranial and endonasal surgeries simultaneously. Moreover, the surgeons could maintain a comfortable posture throughout the procedure, and total tumor removal was successfully achieved without any abnormal event. To our knowledge, this is the first report of the introduction of an exoscope aiming for en bloc resection of an anterior skull base malignancy while performing simultaneous surgery with both transcranial and endonasal approaches. We believe that the more cases are accumulated, the more efficacy of a 4K 3D exoscope will be elucidated.
PubMed: 36128056
DOI: 10.2176/jns-nmc.2022-0081 -
European Journal of Nuclear Medicine... Dec 2022
Topics: Humans; Inappropriate ADH Syndrome; Adult; Diagnostic Imaging; Esthesioneuroblastoma, Olfactory
PubMed: 36094565
DOI: 10.1007/s00259-022-05960-0