Aggressive Pattern Research Articles

Multiplatform molecular analysis of vestibular schwannoma reveals two robust subgroups with distinct microenvironment

BackgroundVestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle and poses a significant morbidity for patients. While many exhibit benign behaviour, others have a more aggressive nature and pattern of growth. Predicting who will fall into which category consistently remains uncertain. There is a need for a better understanding of the molecular landscape, and important subgroups therein, of this disease.MethodsWe select all vestibular schwannomas from our tumour bank with both methylation and RNA profiling available. Unsupervised clustering methods were used to define two distinct molecular subgroups of VS which were explored using computational techniques including bulk deconvolution analysis, gene pathway enrichment analysis, and drug repurposing analysis. Methylation data from two other cohorts were used to validate our findings, given a paucity of external samples with available multi-omic data.ResultsA total of 75 tumours were analyzed. Consensus clustering and similarity network fusion defined two subgroups (“immunogenic” and “proliferative”) with significant differences in immune, stroma, and tumour cell abundance (p < 0.05). Gene network analysis and computational drug repurposing found critical differences in targets of immune checkpoint inhibition PD-1 and CTLA-4, the MEK pathway, and the epithelial to mesenchymal transition program, suggesting a need for subgroup-specific targeted treatment/trial design in the future.ConclusionsWe leverage computational tools with multi-omic molecular data to define two robust subgroups of vestibular schwannoma with differences in microenvironment and therapeutic vulnerabilities.

S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma

BackgroundExcess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed.MethodsThe gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated.ResultsIn human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages.ConclusionS1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis.Graphical

Spatial patterns and risk of aggression of dogs and cats in a central township of Mexico City

Dog and cat aggressions are public health concerns associated with rabies transmission to the human population. The social and environmental conditions of marginalized and urban areas stand a risk due to people's contact with dogs. This study aimed to identify spatial patterns related to dog and cat aggression in a densely populated area in the center of Mexico City, analyzing the risk of aggression at the census unit level in the 2018–2020 triennium. This cross-sectional study was carried out in Coyoacán, in the south-central area of Mexico City's urbanized region. The total number of cases (n = 1,078) was obtained from monthly records of aggressions by dogs and cats, from the Control and Prevention of Zoonoses-Rabies Program of the Coyoacán Sanitary Jurisdiction. The information collected was related to the victims and the aggressors. Associations between the occurrence of bites and the characteristics of the victim were evaluated using a geographic information system (GIS), as well as the spatio-temporal distribution of the aggressions to the census unit level. Out of 1,078 cases reported, 977 (90.6%) were caused by dogs and 101 (9.4%) by cats, 55.1% (n = 587) occurred within the same household, and 13.7% (n = 148) were categorized as severe injuries. Adult men were the most affected group. Attacks on the street had a higher risk of resulting in a severe injury, compared to those that occurred at home (OR 1.63, 95CI 1.15 - 2.31, p <0.006). According to the standardized rate of the triennium, the values ​​ranged between 54.1 and 619 aggressions per 100,000 inhabitants, and summer was the season with a higher probability of occurrence. These results provide a basis for the analytical investigation of the spatial patterns of dog and cat aggression, highlighting the need to implement efficient surveillance systems and public health strategies.

Shape-based proximity effect correction method for throughput, fidelity, and contrast enhancement of electron-beam writer

Conventional shape-based proximity effect correction (PEC) methods can only improve pattern fidelity and present a risk to correction effectiveness under severe resist-contour distortions for electron-beam writers. Herein, a shape-based PEC method for effectively improving both the pattern fidelity and energy slope without the risk in realizing high throughput, fidelity, and contrast is presented. An extra-framed pattern added to the target pattern is optimized to achieve better trade-off between contrast improvement and writing-time reduction. The proposed method demonstrated significant improvements in lithographic performance compared with the conventional and dose-based PEC methods for high-numerical-aperture extreme-ultraviolet mask and aggressive patterns.

GammaTile® (GT) as a brachytherapy platform for rapidly growing brain metastasis.

A subset of brain metastasis (BM) shows rapid recurrence post-initial resection or aggressive tumor growth between interval scans. Here we provide a pilot experience in the treatment of these BM with GammaTile® (GT), a collagen tile-embedded Cesium 131 (131Cs) brachytherapy platform. We identified ten consecutive patients (2019-2023) with BM that showed either (1) symptomatic recurrence while awaiting post-resection radiosurgery or (2) enlarged by >25% of tumor volume on serial imaging and underwent surgical resection followed by GT placement. Procedural complication, 30-day readmission, local control, and overall survival were assessed. For this cohort of ten BM patients, 3 patients suffered tumor progression while awaiting radiosurgery and 7 showed >25% tumor growth prior to surgery and GT placement. There were no procedural complications or 30-day mortality. All patients were discharged home, with a median hospital stay of 2 days (range: 1-9 days). 4/10 patients experienced symptomatic improvement while the remaining patients showed stable neurologic conditions. With a median follow-up of 186 days (6.2 months, range: 69-452 days), no local recurrence was detected. The median overall survival (mOS) for the newly diagnosed BM was 265 days from the time of GT placement. No patients suffered from adverse radiation effects. Our pilot experience suggests that GT offers favorable local control and safety profile in patients suffering from brain metastases that exhibit aggressive growth patterns and support the future investigation of this treatment paradigm.

Is Problematic Media Use a Marker for Aggression in Children with Attention Deficit/Hyperactivity Disorder?

Background: Attention Deficit/Hyperactivity Disorder (ADHD) is associated with a series of problems, including aggressive behavior and problematic media use (PMU). However, the literature concerning the relationship between PMU and aggressive behavior patterns in children diagnosed with ADHD is limited. This study examines the relationships between PMU and aggression in children with ADHD. Methods: One hundred sixty-two children aged 6-12 years diagnosed with ADHD were included in the study. All participants were assessed with DSM-5-based psychiatric evaluations. Aggressive behaviors in children were evaluated using the Children’s Aggression Scale Parent Version (CAS-P). The children’s screen use was scored using the Problematic Media Use Measure Short Form (PMUM-SF). The data obtained were compared using statistical methods. Results: A significant correlation at the p&lt;.05 level was determined between PMU and the severity of ADHD (mild-moderate and severe). PMU was positively and statistically significantly correlated with verbal aggression (r = 0.422, p &lt; 0.001), aggression against objects and animals (r = 0.367, p &lt; 0.001), provoked physical aggression (r = 0.365, p &lt; 0.001) and unprovoked physical aggression (r = 0.283, p &lt; 0.001). In addition, PMU significantly (p &lt;0.001) predicted verbal aggression, aggression against objects and animals, and provoked and unprovoked physical aggression. Conclusions: A positive correlation was observed between PMU in children and the risk of aggression in this group, and PMU predicted aggression. These findings may contribute to the formation of guidelines for intervention when problematic behaviors emerge in children diagnosed with ADHD.

Abstract A080: The immunological signatures of African American prostate cancer as biological determinants of disease disparity

Abstract Background: Prostate cancer (PCa) is currently the second leading cause of cancer-related deaths among men in the United States. African American men suffer the highest incidence of disease morbidity and mortality compared to other racial groups. Although socio-economic, cultural, epidemiological, and genomic factors have been described to contribute to cancer health disparities in African American men, there is a knowledge gap regarding how the tumor immune landscape shapes aggressive disease patterns in this patient population, and whether their tumor microenvironment (TME) is amenable to immune modulation. This study aims to identify distinct and targetable immunosuppressive phenotypes and immunological signatures in prostate tumors of AA patients. Methodology: Peripheral blood from consented African American (AA) and Caucasian American (CA) patients undergoing prostatectomy at Moffitt Cancer Center were analyzed by Luminex multiplex cytokine/chemokine assay and comprehensive immune profiling via multi-parameter flow cytometry. Also, multiparameter immune profiling of freshly resected PCa specimens obtained from these same patients after prostatectomy was performed. In addition, multiplex immunohistochemical staining was performed on prostate tumor tissue microarrays to compare the proportions and phenotypes of T cells in the prostate TME of AA and CA patients. Lastly, the immunomodulatory potential of AZD5153, a bivalent Bromodomain 4 (BRD4) inhibitor was investigated on orthotopic prostate tumor-bearing humanized mouse models under racially defined settings, followed by comprehensive flow cytometry immunophenotypic profiling of tumor-infiltrating immune cells in the resected mice prostate tumors at clinical endpoints. Results: Prostate tumors of AA patients harbored higher proportions of CD4+ regulatory T cells (Tregs) and lower proportions of CD8+ T cells relative to CA patients. Furthermore, the immunophenotypic analysis of T cells showed higher expression of immune checkpoint molecules in AA compared to CA patients. Serum analysis revealed cytokine and chemokine expression signatures that are skewed towards a more immunosuppressive profile in AA compared to CA patients. Treatment with AZD5153 led to an increase in the survival time and a more striking reduction in tumor volume of AA-matched prostate tumor-bearing humanized mice relative to CA-matched prostate tumor-bearing humanized mice. A decrease in the proportion of tumor-infiltrating Tregs and a reduction in the expression of immune checkpoint molecules were also observed in prostate tumors from AA-matched humanized mice relative to CA-matched humanized mice. Conclusion: Our findings support the contributory role of racially distinct immunophenotypes and immune signatures in PCa disparity, and highlight the potential immunotherapeutic benefits of BRD4 inhibitors, such as AZD5153 in AA PCa patients. Citation Format: Saheed O. Oseni, Arup Bag, Oluwaseyi Oluwatola, Natalie DeMars, Dennis Adeegbe. The immunological signatures of African American prostate cancer as biological determinants of disease disparity [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A080.

Female Perpetrators of Ritually Motivated Pedicide and Mutilation of Children

Ritually motivated pedicide is among contemporary Africa’s most severe crimes against children. Most of these crimes involve brutal acts of violence or mutilation of the victim. While men are most often the perpetrators of violent crimes, ritually motivated pedicide and mutilation equally attract women. The role of women in these crimes is not restricted to the less violent aspects of the crimes; instead, they also extend to the most brutal elements, often involving mutilation, decapitation or outright murder of the victim. This article explored the involvement of women in these crimes that target children for mutilation and pedicide. The article draws on case examples of incidents involving brutality and murder of children by women selected from academic reports and reports by media and non-governmental organisations to demonstrate the nature of involvement in these crimes. The article demonstrates that women also engage in the most serious roles with or without the company of men in ritually motivated pedicide and mutilation. These include mutilation and violent murder of children who are used for rituals. The author argues that the high degree of violence in ritually motivated mutilation and pedicide means that these crimes against children deviate from the established female patterns of aggression that are typically less violent.

Formation-of-Arrays Antenna Technology for High-Throughput Mobile Non-Terrestrial Networks

Effective integration of terrestrial and non-terrestrial segments is one of the key research avenues in the design of current and future wireless communication networks. To this aim, modern communication-satellite constellations intend to attain sufficiently high throughput in terms of bit rate per unit area on the ground by rather aggressive patterns of spatial frequency reuse. This goal calls for on-board narrow-beam antennas, whose size turns out to be in many cases incompatible with the size/mass and accommodation constraints of the hosting satellite. This paper investigates the attainable performance of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">large distributed arrays of antennas</i> implemented as the ensemble of a few to many simpler sub-antennas of smaller sizes, carried by one (small) satellite each. The sub-antennas can in their turn be implemented like (regular) 2D arrays of simple radiating elements, realizing an overall (distributed) antenna architecture that we call “formation of arrays” (FoA). The satellites that implement this radiating architecture need to be relatively close to each other and constitute a <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">formation</i> of flying objects, to be coordinated and controlled as a whole. In this paper, we develop a theoretical analysis of an FoA antenna, and we show how to take advantage of this new technology to improve network throughput in a multi-beam S-band mobile communication network with low-earth or geostationary orbiting satellites directly providing 5G-like communication services to hand-held user terminals.

Pediatric perianal Crohn's disease behavior in the era of biologic therapy.

To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p=0.003), use of biological therapies (p=0.005), and need for second line of biologics (p=0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

여성결혼이민자 가정 유아의 또래 간 상호작용에 대한 보육교사의 경험

This study was to analyze day care center teachers’experience for peer interaction of infant from female international marriage migrant. Fourteen teachers who take care the infant in day care center were interviewed in-depth for more than an hour. The collected data were analyzed by procedures of Bogdan and Biklen(1992) after the transcription. The resulted showed that peer interaction pattern of the infant were categorized into 5 patterns, included solitary play pattern, aggressive pattern, non-dominant obey pattern, interaction with only younger pattern, and pro-social pattern. Also, the resulted showed that non-dominant obey pattern and interaction with only younger pattern were for infant from female international marriage migrant only. And the basic etiquette, speech ability, personality, and interaction with teacher were factors that influenced peer interaction. Also the basic etiquette and speech ability were for infant from female international marriage migrant only. The findings can be used to increase the positive peer interaction.

Are perceived containment and coping styles differentially associated with reactive and proactive aggression?

Studies informing ways to target aggression in youth, particularly through the identification of internal patterns predictive of concurrent and future levels of aggression, could be particularly beneficial. To this end, the current study surveyed 216 elementary-aged children on topics of perceived containment (i.e., perceived ability of authority figures to control, limit, and set consequences for one's behaviors), coping responses, and reactive (RA) and proactive aggression (PA). Using multilevel modeling, the individual and interactive effects of coping responses and perceived containment on aggression within time and across two school years were examined. Within time, lower levels of perceived containment were associated with greater RA and PA. Passive coping was also positively associated with RA. The relation between perceived containment and RA within time was dependent on humor, whereas the relation between perceived containment and PA depended on problem-solving. Across time, while T1 passive coping predicted the trajectory of both functions of aggression, a greater number of T1 coping responses predicted the slope of RA with problem-solving and friend support-seeking as well as T1 perceived containment also predicting the trajectory of RA. No coping responses moderated the relation between T1 perceived containment and the trajectory of RA. In contrast, humor moderated the influence of T1 perceived containment and the trajectory of PA. Findings give insight into the ways internal processes of perceived containment and coping are associated with patterns of aggression in elementary-aged youth. This work is valuable in identifying several potential areas for prevention and intervention research.

Crosstalk between tumor acidosis, p53 and extracellular matrix regulates pancreatic cancer aggressiveness.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy with minimal treatment options and a global rise in prevalence. PDAC is characterized by frequent driver mutations including KRAS and TP53 (p53), and a dense, acidic tumor microenvironment (TME). The relation between genotype and TME in PDAC development is unknown. Strikingly, when wild type (WT) Panc02 PDAC cells were adapted to growth in an acidic TME and returned to normal pH to mimic invasive cells escaping acidic regions, they displayed a strong increase of aggressive traits such as increased growth in 3-dimensional (3D) culture, adhesion-independent colony formation and invasive outgrowth. This pattern of acidosis-induced aggressiveness was observed in 3D spheroid culture as well as upon organotypic growth in matrigel, collagen-I and combination thereof, mimicking early and later stages of PDAC development. Acid-adaptation-induced gain of cancerous traits was further increased by p53 knockout (KO), but only in specific extracellular matrix (ECM) compositions. Akt- and Transforming growth factor-β (TGFβ) signaling, as well as expression of the Na+ /H+ exchanger NHE1, were increased by acid adaptation. Whereas Akt inhibition decreased spheroid growth regardless of treatment and genotype, stimulation with TGFβI increased growth of WT control spheroids, and inhibition of TGFβ signaling tended to limit growth under acidic conditions only. Our results indicate that a complex crosstalk between tumor acidosis, ECM composition and genotype contributes to PDAC development. The findings may guide future strategies for acidosis-targeted therapies.

Protection for Women Victims of Domestic Violence in Indonesia: A Victimology and Criminology Approach

Law No. 23 of 2004 concerning the Elimination of Domestic Violence, defines domestic violence as any act against a person, especially women, which results in physical, sexual, psychological misery or suffering, and/or neglect of the household including threats to commit acts, coercion, or unlawful deprivation of liberty within the household sphere. However, in this case the focus will be on women as victims, this also refers to the data available at the Indonesian National Commission on Human Rights. This is unfortunate because the position of women themselves is as the first and foremost educators in a family, they are expected to be able to develop values the value of cases of saying, equality, and equality, as well as concern for one and the other, so that in the future they are able to get rid of aggressive behavior patterns from children and adolescents. Because in time, the tradition of violence inherited from parenting in this family, will face problems with state law if it is maintained. This study aims to analyze the concept of protection for women in domestic violence in Indonesia. This study uses various legal comparisons related to the protection of women in Indonesia and international law.

Interdisciplinary care of children with diffuse midline glioma

Diffuse Midline Glioma (DMG) which includes Diffuse Intrinsic Pontine Glioma (DIPG) is an infiltrative tumor of the midline structures of the central nervous system that demonstrates an aggressive pattern of growth and has no known curative treatment. As these tumors progress, children experience ongoing neurological decline including inability to ambulate, swallow and communicate effectively. We propose that optimal care for patients with DMG should involve a specialized team experienced in caring for the multifaceted needs of these patients and their families. Herein we review the roles and evidence to support early involvement of a specialized interdisciplinary team and outline our views on best practices for these challenging tumors.

Quality of life in glioblastoma after the introduction of temozolomide: a systematic review

Introduction: Gliomas are primary tumors of the central nervous system with an aggressive pattern of progression with a poor prognosis in terms of survival and quality of life. The current standard treatment consists of surgery with maximum excision associated with radiotherapy and chemotherapy, based mostly on the use of temozolomide. Since its introduction, the quality of life of patients undergoing this therapy has not been widely targeted and evaluated. Objective: To verify the quality of life of patients with glioblastoma after the introduction of temozolomide in the therapeutic protocols. Methods: A systematic literature review guided by the PICO and PRISMA protocol was conducted; PubMed, Medline and Lilacs databases were consulted. Results: Initially, 77 studies were found, after selection criteria, 35 articles were analyzed. No statistically significant change was found in overall quality of life in studies that analyzed temozolomide therapy versus different control therapies. Conclusion: The association of temozolomide with surgery and radiotherapy proved to be neutral, with no significant negative or positive impacts on the quality of life of patients with glioblastoma.

Immunohistochemical expression of p53, Ki67, α-SMA, CD44 and CD31 in different histological subtypes of basal cell carcinoma.

Basal cell carcinoma (BCC) is a common, locally invasive tumor that arises within sun-damaged skin and rarely develops on the palms and soles or mucous membranes. Men generally have higher rates of BCC than women. Incidence also increases with age and the median age of diagnosis is 68 years old. Mortality from BCC is rare and cases of aggressive, local destructive, metastatic BCCs are more likely from tumors with aggressive histopathological (HP) patterns. The aim of this study was to investigate and correlate the immunohistochemical expression of p53, Ki67, alpha-smooth muscle actin (α-SMA), cluster of differentiation (CD)44 and CD31 with both aggressive and nonaggressive types of BCCs. In our study, we observed a varied staining pattern for p53, with the highest reactivity noticed in the peripheral palisading zone. The staining pattern for Ki67 was similar to p53, with a more pronounced reaction in the periphery of the tumor. We found different Ki67 and p53 expression among the various subtypes of BCC. The CD31 reactivity, mostly seen in the stroma, was positive in all BCCs and varied significantly between its different HP subtypes. Regarding stromal expression of α-SMA, the adenoid and basosquamous types had the most intense reaction in our study. The CD44 tumor expression was correlated in our study to the aggressive pattern of BCCs.

Immunohistochemical Evaluation of S100, Alpha-Smooth Muscle Actin, Podoplanin, Matrix Metalloproteinase 13, and Human Epidermal Growth Factor Receptor 2neu Markers in Basal Cell Carcinoma Variants.

Background Variants of basal cell carcinoma (BCC) appear to behave biologically differently. Several histological patterns impact the concept of low-risk (indolent) and high-risk (aggressive) types in the head and neck. This study aims to assess the biological behavior of BCC variants by immunohistochemical expression of S100, alpha-smooth muscle actin (α-SMA), podoplanin, matrix metalloproteinase 13 (MMP-13), andhuman epidermal growth factor receptor 2 (HER2)neu biomarkers. Methodology A total of 65 paraffin-embedded tissue blocks of BCC of the head and neck were retrieved from the collections of the Histopathology Department of the Medical City Teaching Complex and the Ghazi Al-Harerri Hospital at the University of Baghdad's College of Dentistry, spanning the years 2015 through 2021. S100, α-SMA, podoplanin, MMP-13, and HER2neu biomarkers were used to perform immunohistochemical analysis (Abcam). Results This study noticed different expressions of S100, α-SMA, podoplanin, MMP-13, and HER2neu between different variants. There was no immunohistochemical expression in perineural invasion with all cases of BCC variants. The highest expression was seen in HER2neu, MMP-13, and α-SMA with aggressive histological patterns. There was no podoplanin lymphatic vessel density immunoexpressing in all variants, while tumoral podoplanin showed a significant difference in all variants. HER2neu was correlated with all other biomarkers. Conclusions HER2neu, MMP-13, and α-SMA biomarkers can be used as diagnostic markers to predict the aggressive biological behavior of BCC tumors.

Transcriptomic Comparison Analysis between Ameloblastoma and AM-1 Cell Line.

Cancer initiation and progression are profoundly along with the crosstalk between cancer cells and the surrounding stroma. Accumulating evidence has shown that the therapy targeting the extracellular matrix (ECM) would regress tumor growth and invasion in the most common carcinomas. However, it remains largely unexplored in several rare tumors like odontogenic tumors. Ameloblastoma (AM) is the representative odontogenic epithelial tumor in the jawbone, and it usually infiltrates into adjacent bone marrow and has unlimited growth capacity and a high potential for recurrence. This study aims to investigate the role of collagen-rich ECM during the invasion of AM. Transcriptomic analysis revealed that ECM- and epithelial-to-mesenchymal transition (EMT)-related genes were up-regulated in AM compared to ameloblastoma cell line, AM-1. Tumoroid forming analysis showed that Collagen-rich ECM is indispensable for AM progression, especially for aggressive growth patterns and collective invasion.

Primary intracranial extraosseous Ewing's sarcoma of the skull base in an elderly adult: illustrative case.

BACKGROUNDPrimary extraosseous intracranial Ewing’s sarcoma, also known as a peripheral primitive neuroectodermal tumor or “small round blue cell tumor,” is an extremely rare entity with limited representation in the literature beyond the pediatric population.OBSERVATIONSA 67-year-old male suffering occipital headache, nausea, and gait disturbance was found to have a large, avidly contrast-enhancing cerebellopontine angle mass extending into the cervical spinal canal with associated mass effect on medulla, cerebellum, fourth ventricle, and cervical spinal cord. This mass was not present on the imaging from 8 years prior. He underwent surgical debulking and pathology results demonstrated a malignant small round cell tumor showing diffuse immunopositivity for cytokeratins, CD99 and NKX2.2 with EWRS1-FLI1 rearrangement in 84% of the nuclei confirmatory of Ewing’s sarcoma. After 14 cycles of chemotherapy and 6 weeks of radiotherapy, 22 months after discovery, the patient remains in clinical and radiographic remission with complete return to his baseline functioning.LESSONSPrimary skull base extraosseous Ewing’s sarcoma should be considered in the differential diagnosis even in the elderly population when imaging studies demonstrate aggressive tumor growth patterns. Tumor debulking to establish a diagnosis followed by adjuvant chemoradiation therapy can result in clinical improvement with remission.