Search Results (25)

Essential oils (EOs) are natural mixtures of volatile compounds characterized by beneficial pharmacological effects. The repeated inhalation of EOs in olfactory training (OT) has been demonstrated to improve the sense of smell in patients with olfactory deficits. We conducted a conjunct evaluation of the chemical composition, sensory profile, and bioactivity in cell models of commercial EOs of rose (EO1), eucalyptus (EO2), lemon (EO3), and clove (EO4) used for OT (StimuScent^®, Dos Medical, Sense Trading BV, Groningen, The Netherlands). Citronellol, 1,8-cineole, limonene, and eugenol emerged as the most abundant volatile compounds in EO1, EO2, EO3, and EO4, respectively, by GC-MS analysis. Some differences emerged (using a Likert-type scale) in the perception of EO’s odor dimensions (pleasantness, intensity, and familiarity in subjects with hyposmia (n = 8) compared to controls (n = 22). Cytotoxicity assays (24 h of incubation) demonstrated the anticancer effects of EOs (5–100 μg/mL) on SH-SY5Y neuroblastoma cells (the order of potency was EO3 > EO4 > EO2 > EO1), while all EOs showed lower effects on the viability/morphology of human skin HaCaT keratinocytes. SH-SY5Y cancer cells grown for six days with different EOs (at 50 μg/mL) showed evident signs of toxicity and apoptosis. Marked changes in cell morphology (structure/number of processes) were evidenced in clove EO-treated cells. EO’s sensory properties/bioactivity were also related to the in silico physicochemical/pharmacokinetic properties of the main EO components. Our results provide new insights into a more targeted EO application for OT. Full article

Background/Objectives: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare neuroectodermal malignancy of the nasal cavity characterized by aggressive local invasion and variable metastatic potential, with diverse clinical behavior, often presenting at advanced stages. ONB poses challenges for targeted therapeutic strategies, despite advances in surgical and multimodal treatment strategies, because of the rarity of this disease and the limited understanding of its molecular pathophysiology. Methods: A comprehensive review of genomic, multi-omic, and molecular studies was performed to integrate known targeted sites in ONB with the current understanding of its pathophysiology. Results: Recent genetic and molecular studies have identified significant epigenetic and signaling pathway alterations that are critical in pathogenesis and treatment resistance and may serve as potential therapeutic targets. Additionally, novel discovered immunohistochemical and transcriptomic markers, such as IDH2, NEUROD1, and OTX2, offer improved diagnostic specificity and prognostication. Multi-genomic platforms (i.e., multi-omics), involving the combined integration of transcriptomics, epigenetics, and proteomics findings, have led to several recent insights, including the subclassification of neural and basal genomic subtypes, the identification of key driver mutations, and new insights into disease development. This review synthesizes current knowledge on the molecular landscape of ONB, including its tumor origin, immune microenvironment, genetic alterations, and key molecular pathways involved in its pathogenesis. Conclusions: Future research may benefit from integrating these findings into precision medicine approaches, enabling earlier diagnosis and more accurate prognosis. Full article

Introduction: Meningeal metastasis (MM) from naso-ethmoidal malignancies (NEMs) is rare, its metastatic route is still debated, and its prognostic impact remains unclear. Our aim is to analyze a retrospective series of NEMs with non-contiguous MM to study the possible route of spread and the prognostic value of MM. Materials and methods: The institutional database of SNC treated at the University of Brescia between 1995 and 2021 was reviewed. Clinical–pathological data were collected, and survivals were estimated with Kaplan–Meier. Univariate and multivariate logistic regression analysis were run to identify predictors of MM. Results: Among 296 patients, 17 experienced non-contiguous MM, all located along the dura. Intestinal-type adenocarcinoma (10/17) and olfactory neuroblastoma (3/17) were the most frequent histologies. At univariate analysis, brain edema (p < 0.0001), resection (p = 0.026) or invasion (p = 0.006) of brain parenchyma, and local (p = 0.0004) and nodal (p = 0.021) recurrence were predictors of MM. At multivariate analysis, local recurrence was confirmed as an independent factor (odds ratio: 11.88, p = 0.0005). Dural surgical resection was not a risk factor. The five-year disease-specific survival was longer in patients with exclusive MM compared with patients with distant metastasis at other sites (64.3% vs. 30.1% p = 0.046). Conclusions: Dural venous shunt is the most likely pathway of spread of MM. Local recurrence is the only independent risk factor. Exclusive MM has a better prognosis than extrameningeal metastasis. Full article

Abstract: Background/Objectives: Sinonasal malignancies are rare and highly diverse cancers that pose significant diagnostic challenges due to their variable histological features and complex anatomical locations. Accurate diagnosis is critical for guiding treatment, yet conventional methods often require multiple biopsies. This study aimed to evaluate the potential of confocal laser endomicroscopy (CLE) for real-time imaging of sinonasal tumors to characterize specific features of different entities and improve diagnostic precision. Methods: Ten patients with various sinonasal malignancies, including squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, olfactory neuroblastoma, sinonasal mucosal melanoma, and endonasal lymphoma, were examined using CLE during diagnostic endoscopy. CLE images were compared descriptively with histopathological cross-sections to identify unique imaging patterns for each tumor type. Results: CLE was feasible across all cases, with high-quality images obtained despite anatomical challenges in some cases. Characteristic features, such as vascular clusters in undifferentiated carcinoma, mucin-filled bubbles in adenocarcinoma, and small round cells in neuroblastoma, were identified and corresponded well with histopathological findings. CLE also helped guide biopsies by revealing areas with diagnostic relevance. Conclusions: CLE demonstrates promise as an adjunct diagnostic tool in sinonasal malignancies, offering real-time imaging that correlates with histopathological findings and aids in targeted biopsies. While this study provides preliminary insights into the utility of CLE, further research with larger cohorts and statistical validation is necessary to establish its diagnostic reliability and broader clinical application. Full article

Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene (SSTR2), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzed SSTR2 gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database. SSTR2 gene expression was high in neural-type ONB and low in basal-type ONB and in most of the SNUC and SNEC cases; there was no difference in expression between primary and metastatic tumors. The T cell-inflamed (TCI) score analysis classified 38.5% of SNUC cases as T cell-inflamed compared to only 3.9% of ONB and 0% of SNEC cases; 26.9% of ONB cases were classified as intermediate TCI; and SNEC had the lowest relative immune cell infiltration by deconvolution. In high SSTR2-expressing ONB, there was a higher proportion of infiltrating of Natural Killer cells and dendritic cells by deconvolution. Additionally, high SSTR2-expressing ONB was enriched for proliferation pathways, including E2F and Myc targets and G2M checkpoints. In conclusion, our findings delineate significant differences between these three types of sinonasal malignancies that were examined. In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies. Full article

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis. Full article

Mitochondria, the energy hubs of the cell, are progressively becoming attractive targets in the search for potent therapeutics against neurodegenerative diseases. The pivotal role of mitochondrial dysfunction in the pathogenesis of various diseases, including Parkinson’s disease (PD), underscores the urgency of discovering novel therapeutic strategies. Given the limitations associated with available treatments for mitochondrial dysfunction-associated diseases, the search for new potent alternatives has become imperative. In this report, we embarked on an extensive screening of 4224 fractions from 384 Australian marine organisms and plant samples to identify natural products with protective effects on mitochondria. Our initial screening using PD patient-sourced olfactory neurosphere-derived (hONS) cells with rotenone as a mitochondria stressor resulted in 108 promising fractions from 11 different biota. To further assess the potency and efficacy of these hits, the 11 biotas were subjected to a subsequent round of screening on human neuroblastoma (SH-SY5Y) cells, using 6-hydroxydopamine to induce mitochondrial stress, complemented by a mitochondrial membrane potential assay. This rigorous process yielded 35 active fractions from eight biotas. Advanced analysis using an orbit trap mass spectrophotometer facilitated the identification of the molecular constituents of the most active fraction from each of the eight biotas. This meticulous approach led to the discovery of 57 unique compounds, among which 12 were previously recognized for their mitoprotective effects. Our findings highlight the vast potential of natural products derived from Australian marine organisms and plants in the quest for innovative treatments targeting mitochondrial dysfunction in neurodegenerative diseases. Full article

Nowadays, there is considerable attention toward the use of food waste from food processing as possible sources of compounds with health properties, such as anticancer activity. An example is tomato processing, which is responsible for generating a remarkable amount of waste (leaves, peel, seeds). Therefore, our goal was to evaluate the potential anticancer property of tomato extracts, in particular “Datterino” tomato (DT) and “Piccadilly” tomato (PT), and to study their phytochemical composition. Liquid chromatography with tandem mass spectrometry (LC/MS-MS) results showed that these extracts are rich in alkaloids, flavonoids, fatty acids, lipids, and terpenes. Furthermore, their potential anticancer activity was evaluated in vitro by MTT assay. In particular, the percentage of cell viability was assessed in olfactory ensheathing cells (OECs), a particular glial cell type of the olfactory system, and in SH-SY5Y, a neuroblastoma cell line. All extracts (aqueous and ethanolic) did not lead to any significant change in the percentage of cell viability on OECs when compared with the control. Instead, in SH-SY5Y we observed a significant decrease in the percentage of cell viability, confirming their potential anticancer activity; this was more evident for the ethanolic extracts. In conclusion, tomato leaves extracts could be regarded as a valuable source of bioactive compounds, suitable for various applications in the food, nutraceutical, and pharmaceutical fields. Full article

Tomato by-products represent a good source of phytochemical compounds with health properties, such as the steroidal glycoalkaloid α-tomatine (α-TM) and its aglycone tomatidine (TD). Both molecules have numerous beneficial properties, such as potential anticancer activity. Unfortunately, their therapeutic application is limited due to stability and bioavailability issues. Therefore, a valid strategy seems to be their encapsulation into Solid Lipid Nanoparticles (SLN). The nanoformulations containing α-TM (α-TM-SLN) and TD (TD-SLN) were prepared by solvent-diffusion technique and subsequently characterized in terms of technological parameters (particle size, polydispersity index, zeta potential, microscopy, and calorimetric studies). To assess the effect of α-TM and TD on the percentage of cellular viability in Olfactory Ensheathing Cells (OECs), a peculiar glial cell type of the olfactory system used as normal cells, and in SH-SY5Y, a neuroblastoma cancer cell line, an MTT test was performed. In addition, the effects of empty, α-TM-SLN, and TD-SLN were tested. Our results show that the treatment of OECs with blank-SLN, free α-TM (0.25 µg/mL), and TD (0.50 µg/mL) did not induce any significant change in the percentage of cell viability when compared with the control. In contrast, in SH-SY5Y-treated cells, a significant decrease in the percentage of cell viability when compared with the control was found. In particular, the effect appeared more evident when SH-SY5Y cells were exposed to α-TM-SLN and TD-SLN. No significant effect in blank-SLN-treated SH-SY5T cells was observed. Therefore, SLN is a promising approach for the delivery of α-TM and TD. Full article

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility. Full article

Developing in a limited space, rare tumors located at the nose and paranasal sinuses are sometimes difficult to diagnose due to their modest clinical presentation, which is uncorrelated with anatomopathological diversity. This limits the preoperative diagnosis without added immune histochemical study; for that reason, we present our experience with these tumors with the intention of raising awareness. The patient included in our study was investigated by our department through clinical and endoscopic examination, imaging investigations, and an anatomic-pathological study. The selected patient gave consent for participation and inclusion in this research study in compliance with the 1964 Declaration of Helsinki. Full article

Non-squamous cell carcinoma-related malignant sinonasal tract tumors (non-SCC MSTT) are rare and diverse malignancies. In this study, we report our experience in the management of this group of patients. The treatment outcome has been presented, involving both primary treatment and salvage approaches. Data from 61 patients treated radically due to non-SCC MSTT between 2000 and 2016 at the National Cancer Research Institute, Gliwice branch, were analyzed. The group consisted of the following pathological subtypes of MSTT: adenoid cystic carcinoma (ACC), undifferentiated sinonasal carcinoma (USC), sarcoma, olfactory neuroblastoma (ONB), adenocarcinoma, small cell neuroendocrine carcinoma (SNC), mucoepidermic carcinoma (MEC), and acinic cell carcinoma, which were found in nineteen (31%), seventeen (28%), seven (11.5%), seven (11.5%), five (8%), three (5%), two (3%) and one (2%) of patients, respectively. There were 28 (46%) males and 33 (54%) females at the median age of 51 years. Maxilla was the primary tumor localization followed by the nasal cavity and ethmoid sinus in thirty-one (51%), twenty (32.5%), and seven (11.5%) patients, respectively. In 46 (74%) patients, an advanced tumor stage (T3 or T4) was diagnosed. Primary nodal involvement (N) was found in three (5%) cases, and all patients underwent radical treatment. The combined treatment consisted of surgery and radiotherapy (RT) and was given to 52 (85%) patients. The probabilities of overall survival (OS), locoregional control (LRC), metastases-free survival (MFS), and disease-free survival (DFS) were assessed in pathological subtypes and grouped together, along with the ratio and effectiveness of salvage. Locoregional treatment failure was seen in 21 (34%) patients. Salvage treatment was performed in fifteen (71%) patients and was effective in nine (60%) cases. There was a significant difference in OS between patients who underwent salvage and those who did not (median: 40 months vs. 7 months, p = 0.01). In the group of patients who underwent salvage, OS was significantly longer when the procedure was effective (median: 80.5 months) than if it failed (median: 20.5 months), p < 0.0001. OS in patients after effective salvage was the same as in patients who were primary cured (median: 80.5 months vs. 88 months, p = 0.8). Distant metastases developed in ten (16%) patients. Five and ten year LRC, MFS, DFS, and OS were 69%, 83%, 60%, 70%, and 58%, 83%, 47%, 49%, respectively. The best treatment results were observed for patients with adenocarcinoma and sarcoma, while USC gave the poorest results in our set of patients. In this study, we indicate that salvage is possible in most patients with non-SCC MSTT with locoregional failure and that it may significantly prolong their overall survival. Full article

Introduction: Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. Although survival is excellent with a reported 5-year overall survival (OS) of 82%, recurrence is frequent and occurs in 40–50% of cases. This study investigates the characteristics of ENB recurrence and the subsequent prognosis of patients with recurrence. Methods: The clinical records of all patients diagnosed as having ENB with subsequent recurrence at a tertiary hospital from 1 January 1960 to 1 January 2020 were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were reported. Results: A total of 64 out of 143 ENB patients had recurrences. In total, 45 out of 64 recurrences met the inclusion criteria and were included in this study. From these, 10 (22%) had a sinonasal recurrence, 14 (31%) had an intracranial recurrence, 15 (33%) had a regional recurrence, and 6 (13%) had a distal recurrence. The average interval from initial treatment to recurrence was 4.74 years. There were no differences in rates of recurrence with respect to age, sex, or types of surgery (endoscopic, transcranial, lateral rhinotomy, and combined). The time to recurrence was shorter for Hyams grades 3 and 4 compared to Hyams grades 1 and 2 (3.75 years vs. 5.70 years, p < 0.05). Patients with recurrence limited to the sinonasal region had a lower overall primary Kadish stage compared to recurrences beyond the sinonasal region (2.60 vs. 3.03, p < 0.05). A total of 9 (20%) out of 45 patients developed secondary recurrence. Following recurrence, the subsequent 5-year OS and PFS were 63 and 56%, respectively. The mean time to secondary recurrence after treatment of the primary recurrence was 32 months, which was significantly shorter than the time to primary recurrence (32 months vs. 57 months, p = 0.048). The mean age of the secondary recurrence group is significantly older than the primary recurrence group (59.78 years vs. 50.31 years, p = 0.02). No statistically significant differences were observed between the secondary recurrence group and the recurrence group in terms of their overall Kadish stages or Hyams grades. Conclusions: Following an ENB recurrence, salvage therapy appears to be an effective therapeutic option with a subsequent 5-year OS of 63%. However, subsequent recurrences are not infrequent and may require additional therapy. Full article

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers. Full article

Posterior reversible encephalopathy syndrome (PRES) is a rare but severe neurological syndrome that may stem from the use of some medications. Although its mechanism is not well-known, hypertension and endothelial dysfunction have been mentioned in previous literature as being related. Lenvatinib serves as a neoplastic agent that inhibits the tyrosine kinase of vascular endothelial growth factor receptors (VEGFR). VEGFR inhibitors result in endothelial dysfunction and consequent hypertension by nitric oxide pathway suppression and endothelin (ET)-1 stimulation. We hypothesized that VEGFR inhibitors would cause PRES. Herein, we report the case of a 40-year-old man with olfactory neuroblastoma who developed PRES while undergoing treatment with lenvatinib, 7 months after initiation. The symptoms included loss of consciousness and seizures. Fortunately, the symptoms and presence of PRES in imaging resolved, 7 days and 1 month, respectively, after cessation of lenvatinib. Full article