Extracellular Vesicle - MDM2-DNA as a Potential Liquid Biopsy Biomarker for Disease Identification in Retroperitoneal Liposarcoma.

OBJECTIVE: We aimed to assess the levels of MDM2-DNA within extracellular vesicles (EVs) isolated from the serum of retroperitoneal liposarcoma (RLS) patients versus healthy donors, as well as within the same patients at the time of surgery versus post-operative surveillance visits. To determine whether EV-MDM2 may serve as a possible first-ever biomarker of liposarcoma recurrence. BACKGROUND: A hallmark of well-differentiated and de-differentiated (WD/DD) retroperitoneal liposarcoma is elevated MDM2 due to genome amplification, with recurrence rates of >50% even after complete resection. Imaging technologies frequently cannot resolve recurrent WD/DD-RLS versus postoperative scarring. Early detection of recurrent lesions, for which biomarkers are lacking, would guide surveillance and treatment decisions. METHODS: WD/DD-RLS serum samples were collected both at the time of surgery and during follow-up visits from 42 patients, along with sera from healthy donors (n=14). EVs were isolated, DNA purified and MDM2-DNA levels determined through q-PCR analysis. Non-parametric tests were employed to compare EV-MDM2 DNA levels from patients versus control group, as well as the time of surgery versus post-surgery conditions. RESULTS: EV-MDM2 levels were significantly higher in WD/DD-RLS than controls (P= 0.00085). Moreover, EV-MDM2 levels were remarkably decreased in WD/DD-RLS patients after resection (P=0.00036), reaching values comparable to control group (P=0.124). During post-operative surveillance, significant increases of EV-MDM2 was observed in some patients, correlating with CT scan evidence of recurrent or persistent post-resection disease. CONCLUSIONS: Serum EV-MDM2 may serve as a potential biomarker of early recurrent or post-operatively persistent WD/DD-RLS, a disease currently lacking such determinants.

Clinical biomarkers in soft tissue sarcoma A comprehensive review of current soft tissue sarcoma biomarkers.

Soft tissue sarcomas (STS) are a heterogeneous group of tumors that arise from mesenchymal tissue. Investigation at the molecular level has been challenging due to the rarity of STS and the number of histologic subtypes. However, recent research has provided new insight into potential genomic, proteomic, and immunological biomarkers of STS. The identification of biomarkers can improve diagnosis, prognosis, and prediction of recurrence and treatment response. This review provides an understanding of biomarkers, discussing the current status of biomarker research in STS.

Entomopathogenic fungi and Schinus molle essential oil: The combination of two eco-friendly agents against Aedes aegypti larvae.

Aedes aegypti transmits arbovirus, which is a public health concern. Certain filamentous fungi have the potential to control the disease. Here, the effects of Metarhizium anisopliae s.l. CG 153, Beauveria bassiana s.l. CG 206 and Schinus molle L. were investigated against Aedes aegypti larvae. In addition, the effect of essential oil on fungal development was analyzed. Fungal germination was assessed after combination with essential oil at 0.0025 %, 0.0075 %, 0.005 %, or 0.01 %; all of the oil concentrations affected germination except 0.0025 % (v/v). Larvae were exposed to 0.0025 %, 0.0075 %, 0.005 %, or 0.01 % of the essential oil or Tween 80 at 0.01 %; however, only the essential oil at 0.0025 % achieved similar results as the control. Larvae were exposed to fungi at 107 conidia mL-1 alone or in combination with the essential oil at 0.0025 %. Regardless of the combination, M. anisopliae reduced the median survival time of mosquitoes more than B. bassiana. The cumulative survival of mosquitoes exposed to M. anisopliae alone or in combination with essential oil was 7.5 % and 2 %, respectively, and for B. bassiana, it was 75 % and 71 %, respectively. M. anisopliae + essential oil had a synergistic effect against larvae, whereas B. bassiana + essential oil was antagonistic. Scanning and transmission electron microscopy, and histopathology confirmed that the interaction of M. anisopliae was through the gut and hemocoel. In contrast, the mosquito's gut was the main route for invasion by B. bassiana. Results from gas chromatography studies demonstrated sabinene and bicyclogermacrene as the main compounds of S. molle, and the in-silico investigation found evidence that both compounds affect a wide range of biological activity. For the first time, we demonstrated the potential of S. molle and its interaction with both fungal strains against A. aegypti larvae. Moreover, for the first time, we reported that S. molle might be responsible for significant changes in larval physiology. This study provides new insights into host-pathogen interplay and contributes to a better understanding of pathogenesis in mosquitoes, which have significant consequences for biological control strategies.

Insights into the Role of Tick Salivary Protease Inhibitors during Ectoparasite-Host Crosstalk.

Protease inhibitors (PIs) are ubiquitous regulatory proteins present in all kingdoms. They play crucial tasks in controlling biological processes directed by proteases which, if not tightly regulated, can damage the host organism. PIs can be classified according to their targeted proteases or their mechanism of action. The functions of many PIs have now been characterized and are showing clinical relevance for the treatment of human diseases such as arthritis, hepatitis, cancer, AIDS, and cardiovascular diseases, amongst others. Other PIs have potential use in agriculture as insecticides, anti-fungal, and antibacterial agents. PIs from tick salivary glands are special due to their pharmacological properties and their high specificity, selectivity, and affinity to their target proteases at the tick-host interface. In this review, we discuss the structure and function of PIs in general and those PI superfamilies abundant in tick salivary glands to illustrate their possible practical applications. In doing so, we describe tick salivary PIs that are showing promise as drug candidates, highlighting the most promising ones tested in vivo and which are now progressing to preclinical and clinical trials.

Association of Lifestyle and Body Composition on Risk Factors of Cardiometabolic Diseases and Biomarkers in Female Adolescents.

BACKGROUND: Female adolescents are considered a risk group for cardiometabolic disease due to their lifestyle (LS). OBJECTIVE: To evaluate the association between LS classes and body composition groups with cardiometabolic disease risk factors and pro- and anti-inflammatory biomarkers in female adolescents. METHODS: This cross-sectional study was carried out with female adolescents aged 14 to 19 years, from Viçosa-MG, Brazil. Latent class analysis assessed LS classes. Kinanthropometric measurements were taken together with the body fat percentage (BF%), being analyzed by the Dual Energy X-ray Absorptiometry (DEXA) equipment. Blood pressure and biochemical parameters were analyzed in the Health Division of the Federal University of Viçosa. The pro- and anti-inflammatory biomarkers were analyzed using Luminex technology. Associations with biomarkers were estimated by multiple linear regression. RESULTS: 405 female adolescents were evaluated. The majority, 82.57%, 72.90%, and 65.31%, were classified as inactive by the number of steps, with high screen and cell phone time, respectively. Furthermore, 41.55% did meet the minimum of 60 minutes of moderate-to-vigorous physical activity (MVPA) and 54.69% had high values of BF% (DEXA). The "Sedentary & Inactive LS" class together with the high levels of weight and BF% were associated with increased levels of blood pressure, lipid profile, and uric acid. It was also found that "Inactive & Sedentary LS", high BF%, insulin resistance, and ultra-sensitive C-reactive protein were associated with the concentrations of proinflammatory biomarkers of tumor necrosis factor-α, interleukin-6, and leptin. CONCLUSION: We concluded that female adolescents with overweight/obese and high BF% presented higher values of anthropometric indicators, levels of blood pressure, concentration of uric acid and hs-CRP, and lower concentration of HDL. Inactive and Sedentary lifestyle of these girls, along with excess body fat, insulin resistance, and higher concentrations of hs-CRP were associated with the higher concentration proinflammatory markers.

Proteomic informed by transcriptomic for salivary glands components of the camel tick Hyalomma dromedarii.

BACKGROUND: The hard tick Hyalomma dromedarii is one of the most injurious ectoparasites affecting camels and apparently best adapted to deserts. As long-term blood feeders, ticks are threatened by host defense system compounds that can cause them to be rejected and, ultimately, to die. However, their saliva contains a cocktail of bioactive molecules that enables them to succeed in taking their blood meal. A recent sialotranscriptomic study uncovered the complexity of the salivary composition of the tick H. dromedarii and provided a database for a proteomic analysis. We carried out a proteomic-informed by transcriptomic (PIT) to identify proteins in salivary glands of both genders of this tick species. RESULTS: We reported the array of 1111 proteins identified in the salivary glands of H. dromedarii ticks. Only 24% of the proteins were shared by both genders, and concur with the previously described sialotranscriptome complexity. The comparative analysis of the salivary glands of both genders did not reveal any great differences in the number or class of proteins expressed their enzymatic composition or functional classification. Indeed, few proteins in the entire proteome matched those predicted from the transcriptome while others corresponded to other proteins of other tick species. CONCLUSION: This investigation represents the first proteomic study of H. dromedarii salivary glands. Our results shed light on the differences between the composition of H. dromedarii male and female salivary glands, thus enabling us to better understand the gender-specific strategy to feed successfully.

Costs analysis of surgical treatment of stress urinary incontinence in a brazilian public hospital, comparing burch and synthetic sling techniques.

INTRODUCTION: Surgical treatment of urinary incontinence progressed significantly with the introduction of synthetic slings. However, in some public Brazilian hospitals, the costs of these materials prevent their routine use. OBJECTIVE: To compare the costs of ambulatory synthetic sling surgery with an historical series of patients submitted to Burch surgery in a Brazilian public hospital. MATERIALS AND METHODS: Twenty nine incontinent patients were selected to synthetic sling surgery. Demographic data were prospectively collected and also the costs of the procedure, including drugs and materials, use of surgical and recovery wards, medical staff and hospitalization. These data were compared to the costs of 29 Burch surgeries performed before the introduction of synthetic slings. RESULTS: Demographic data were similar, although median age was lower in the group submitted to Burch surgery (46.3±8.6 versus 56.2±11.3 (p<0.001)). Cost was significantly lower in patients submitted to sling in all items, except for time spent in recovery ward. Total value of 29 Burch surgeries was R$ 217.766.12, and of R$ 68.049.92 of 29 patients submitted to sling surgery (p<0.001). CONCLUSION: Burch surgery was more expensive than ambulatory synthetic transobturator sling surgery, even when the cost of the synthetic sling was considered.

Clinical and sociodemographic characteristics of patients with epilepsy attended at a regional reference psychiatric emergency unit.

OBJECTIVE: Epilepsy is one of the most prevalent chronic neurological diseases, presenting a high frequency of psychiatric disorders (PD). This study sought to evaluate the clinical and sociodemographic profile of patients with epilepsy (PWE) attended at a regional reference psychiatric emergency unit. METHODS: A retrospective, cross-sectional, and descriptive observational study was conducted utilizing a patient record database of individuals with epilepsy who were attended in a regional reference psychiatric emergency unit between January 2018 and August 2022. RESULTS: Out of the 31,800 psychiatric emergency visits, 260 (0.8 %) were of patients with epilepsy (ICD-10: G40). The majority were males (63.5 %) with a mean age of 42.11±15.39 years, single marital status (154; 59.25 %) and elementary education (75; 28.9 %). Most of them (203; 78.1 %) presented at least one psychiatric comorbidity at the emergency visit, but 109 (41.9 %) were not receiving any psychiatric follow-up. A total of 106 patients (40.8 %) had experienced at least one past psychiatric hospitalization. CONCLUSIONS: The occurrence of PD is highly prevalent in PWE, and probably with a high frequency of psychiatric emergencies occurring among them. Further studies are needed to assess such patient profile, particularly involving data from psychiatric emergency units.

Comparison of three-dimensional cell culture techniques of dedifferentiated liposarcoma and their integration with future research.

Background: Dedifferentiated liposarcoma is a formidable sarcoma subtype due to its high local recurrence rate and resistance to medical treatment. While 2D cell cultures are still commonly used, 3D cell culture systems have emerged as a promising alternative, particularly scaffold-based techniques that enable the creation of 3D models with more accurate cell-stroma interactions. Objective: To investigate how 3D structures with or without the scaffold existence would affect liposarcoma cell lines growth morphologically and biologically. Methods: Lipo246 and Lipo863 cell lines were cultured in 3D using four different methods; Matrigel® ECM scaffold method, Collagen ECM scaffold method, ULA plate method and Hanging drop method, in addition to conventional 2D cell culture methods. All samples were processed for histopathological analysis (HE, IHC and DNAscope™), Western blot, and qPCR; moreover, 3D collagen-based models were treated with different doses of SAR405838, a well-known inhibitor of MDM2, and cell viability was assessed in comparison to 2D model drug response. Results: Regarding morphology, cell lines behaved differently comparing the scaffold-based and scaffold-free methods. Lipo863 formed spheroids in Matrigel® but not in collagen, while Lipo246 did not form spheroids in either collagen or Matrigel®. On the other hand, both cell lines formed spheroids using scaffold-free methods. All samples retained liposarcoma characteristic, such as high level of MDM2 protein expression and MDM2 DNA amplification after being cultivated in 3D. 3D collagen samples showed higher cell viability after SAR40538 treatment than 2D models, while cells sensitive to the drug died by apoptosis or necrosis. Conclusion: Our results prompt us to extend our investigation by applying our 3D models to further oncological relevant applications, which may help address unresolved questions about dedifferentiated liposarcoma biology.

Civil liability of orthodontists and aligner manufacturers in the treatment with orthodontic aligners.

INTRODUCTION: The use of clear aligners as an alternative to fixed orthodontic appliances has become popular due to the aesthetic demands of adult patients seeking orthodontic treatment. However, orthodontists' lack of knowledge about the legal consequences of their activities, and the lack of solid scientific evidence raise concerns regarding civil liability in this type of treatment. Marketing campaigns of manufacturing companies often exaggerate promises of results, and ignore the lack of scientific evidence. Patients, as consumers, are protected by the Consumer Protection Code, whereas orthodontists are considered treatment providers. Therefore, they can be held liable for damage caused to patients, whether by subjective or objective fault. OBJECTIVE: This article aims to identify the civil responsibilities of orthodontists and aligner manufacturing companies, by means of a literature review, providing basic legal guidance to help professionals protect themselves from possible lawsuits related to treatment with orthodontic aligners. CONCLUSIONS: The study highlights the importance of knowledge of legal notions in treatments with orthodontic aligners by orthodontists, who should legally safeguard themselves through individual written contracts, avoiding obligation of results. In addition, in cases of legal claims, it is possible that the manufacturing companies are jointly and severally liable for possible damages claimed by the patient.

Three dimensional models of dedifferentiated liposarcoma cell lines: scaffold-based and scaffold-free approaches.

Sarcomas are rare malignancies, the number of reports is limited, and this rarity makes further research difficult even though liposarcoma is one of major sarcomas. 2D cell culture remains an important role in establishing basic tumor biology research, but its various shortcomings and limitations are still of concern, and it is now well-accepted that the behavior of 3D-cultured cells is more reflective of in vivo cellular responses compared to 2D models. This study aimed to establish 3D cell culture of liposarcomas using two different methods: scaffold-based (Matrigel extracellular matrix [ECM] scaffold method) and scaffold-free (Ultra-low attachment [ULA] plate). Lipo246, Lipo224 and Lipo863 cell lines were cultured, and distinctive differences in structures were observed in Matrigel 3D model: Lipo224 and Lipo863 formed spheroids, whereas Lipo246 grew radially without forming spheres. In ULA plate approaches, all cell lines formed spheroids, but Lipo224 and Lipo863 spheroids showed bigger size and looser aggregation than Lipo246. Formalin fixed, paraffin embedded (FFPE) blocks were obtained from all 3D models, confirming the spheroid structures. The expression of MDM2, Ki-67 positivity and MDM2 amplification were confirmed by IHC and DNAscope™, respectively. Protein and DNA were extracted from all samples and MDM2 upregulation was confirmed by western blot and qPCR analysis. After treatment with MDM2 inhibitor SAR405838, DDLPS spheroids demonstrated different sensitivity patterns from 2D models. Taken together, we believed that 3D models would have a possibility to provide us a new predictability of efficacy and toxicity, and considered as one important process in in vitro pre-clinical phase prior to moving forward to clinical trials.

Fractal dimension, lacunarity, and cortical thickness in the mandible: Analyzing differences between healthy men and women with cone-beam computed tomography.

Purpose: The objective of this study was to assess the fractal dimension, lacunarity, trabecular microarchitecture parameters, and cortical linear measurements in the mandibles of male and female individuals to identify differences between them. Materials and Methods: In total, 116 cone-beam computed tomography scans of healthy individuals of different ages (57 men and 59 women, aged between 20 and 60 years) were selected. The following bone parameters were measured: 1) buccal, lingual, and basal cortical bone thickness in 5 standard parasagittal sections (the midline, the left and right sides of the lower lateral incisors, and the left and right sides of the lower canines); 2) the bone volume fraction of 10 sequential axial sections from each patient by creating a volume of interest in the area between the lower canines; and 3) fractal dimension and lacunarity using grayscale images of the same region of the volume of interest in the anterior mandible. Spearman correlation coefficients and the Mann-Whitney test were used. Results: A significant and positive correlation was found between age and cortical thickness, especially in the region of the central incisors. Significant differences between sexes in terms of fractal dimension, lacunarity, and bone volume were found. Women revealed lower fractal dimension values and higher lacunarity and bone volume ratio values than men. Conclusion: Fractal dimension, lacunarity, trabecular bone volume, and cortical thickness were different between men and women of different ages.

Lower incisor inclination and thickness of the alveolar process and mandibular symphysis in the development of gingival recession: A retrospective cohort study.

Introduction: Retrospective studies have found conflicting results regarding the relationship between lower incisor inclination and the development of gingival recession (GR) after orthodontic treatment. Objective: This study aimed to investigate the relationship between lower incisor inclination and alveolar process (AP) and mandibular symphysis (MS) thickness in the development of GR. Materials and Methods: Frontal intraoral photography and cephalometric radiography were conducted before (T0) and after (T1) orthodontic treatment of 62 subjects. The presence of GR was considered when the cementoenamel junction was visible in the lower incisor on the frontal intraoral photograph. The circumstances for improvement, stability, and worsening of the gingival situation were based on the reduction, maintenance, and increase in the number of lower incisors with GR before and after treatment. To measure the incisor-mandibular plane angle (IMPA) and the thickness of the AP and the MS were used the cephalometric radiographs. Results: Men had a significantly thicker MS than women at T0 and T1 (p < 0.0004). There was a significant reduction of approximately 10% in AP between T0 and T1 (p < 0.0001). Among subjects without GR at T0, 70.4% presented a stable gingival situation at T1. For subjects with 1 lower incisor with GR at T0, 50% showed improvement in the gingival situation at T1, 21.4% remained stable, and 28.6% experienced worsening. Sixteen lateral incisors presented a worsening gingival situation, representing an increase of 129% compared to the central incisors. Conclusion: No relationship was found between lower incisor inclination and the thickness of the AP and MS in the development of GR.

Evaluation of functionality and socioeconomic status of patients with chronic pain.

OBJECTIVE: This study aimed to evaluate the influence of chronic pain on functionality and its consequences on work and patient income. METHODS: A total of 103 patients from the Multidisciplinary Pain Center of the Clinics Hospital of Universidade Federal de Minas Gerais were interviewed between January 2020 and June 2021, applying questionnaires on mobile devices. Socioeconomic data, multidimensional characterization of pain, and instruments for assessing pain functionality and intensity were analyzed. Pain intensity was categorized as mild, moderate, or intense for comparative analysis. Ordinal logistic regression was used to identify risk factors and variables that jointly influence the outcome of pain intensity. RESULTS: The patients had a median age of 55 years, were predominantly female, married or in a stable relationship, white race, and completed high school. The median family income was R$2,200. Most patients were retired due to disability and pain-related causes. Functionality analysis showed severe disability directly associated with pain intensity. The financial impacts observed were correlated with the pain intensity of the patients. Age was a risk factor for pain intensity, while sex, family income, and duration of pain served as protective factors. CONCLUSION: Chronic pain was associated with severe disability, decreased productivity, and exit from the labor market, with a negative impact on financial condition. Age, sex, family income, and duration of pain were directly associated with pain intensity.

Targetable Pathways in the Treatment of Retroperitoneal Liposarcoma.

Liposarcoma (LPS) is the most prevalent soft tissue sarcoma histological subtype. When it occurs in the abdomen the overall survival rate is as low as 10% at 10 years and is fraught with high rates of recurrence, particularly for the more aggressive dedifferentiated subtype. Surgery remains the mainstay of treatment. Systemic therapies for the treatment of metastatic or unresectable disease have low response rates. Deep understanding of well-differentiated and de-differentiated LPS (WDLPS and DDLPS, respectively) oncologic drivers is necessary for the development of new efficacious targeted therapies for the management of this disease. This review discusses the current treatments under evaluation for retroperitoneal DDLPS and the potential targetable pathways in DDLPS.

Sleep, sedentary behavior, and physical activity in Brazilian adolescents: Achievement recommendations and BMI associations through compositional data analysis.

Physical activity, sedentary behavior (SB), and sleep are habitual human behaviors (HHB) which are modifiable throughout the different life phases. Therefore, it is necessary to analyze how the time distribution throughout the day among HHB may be associated with body mass index (BMI). These results could provide inferences which can guide interventions that trigger changes in adolescent behaviors in favor of their health. The objective of this study was to verify the proportion of adolescents who meet the recommendation of sleep, moderate to vigorous physical activity (MVPA), and screen time (ST); to analyze the associations between HHB and BMI, and to determine possible changes in BMI associated with time reallocation between different HHB. Daily HHB recommendations (yes/no) were analyzed by frequency distribution. Compositional data analyses were used to examine the association between HHB and the BMI z-score (zBMI) with covariates (sex, age, and socioeconomic status). Compositional isotemporal substitution models estimated the change in zBMI associated with HHB reallocations from 15 to 120 minutes. A total of 185 adolescents were included (15 to 18 years, 50.8% boys). Thus, total sleep time, SB, light physical activity (LPA) and MVPA were measured by 24-hour accelerometry for seven consecutive days. ST, demographic characteristics, and socioeconomic status were assessed using a questionnaire. Sleep, MVPA, and ST recommendations were achieved by 32.97%, 8.10%, and 1.08% of the sample, respectively. No adolescent was able to achieve all of the daily recommendations. Age was significantly and positively associated with zBMI (p<0.001). Simply replacing 75, 90, and 120 minutes of MVPA by LPA led to an estimated significant increase in zBMI (95CI% z-value, 0.01 to 1.49). The HHB relocation estimates in 24h did not show positive effects on zBMI, nor did it increase the time engaged in MVPA, which may raise the hypothesis that other parameters related to obesity and their related interactions need to be better understood.

Time-use movement behaviors are associated with scores of depression/anxiety among adolescents: A compositional data analysis.

Movement behaviors have been associated with mental health. The purposes of this study were to examine the association between movement behaviors and scores of depression/anxiety among adolescents and to determine the difference in depression/anxiety associated with reallocating time between different movement behaviors. This cross-sectional study included 217 Brazilian adolescents (15 to 18 years old, 49.3% female). Adolescents wore an accelerometer for one week to assess the four-movement behaviors which include sleep, sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). The depression/anxiety score was calculated by factor analysis using the 12-item General Health Questionnaire. Compositional data analyses were used to examine the association between movement behavior and the depression/anxiety score. Compositional isotemporal substitution models estimated the change in depression/anxiety score associated with reallocating 10, 30, and 60 min between movement behaviors. The composition of movement behaviors was significantly associated with depression/anxiety scores (p < 0.05). Replacing time from SB to LPA was associated with improvement in the depression/anxiety score, while the inverse was associated with an increase in this score. Replacing time of LPA with MVPA was associated with worsening in the depression/anxiety score. The 24-h time distribution of the day may play a crucial role in mental health. Compositions with more time spent in LPA at the expense of less SB are associated with improvement in the scores of depression/anxiety. The type of MVPA may moderate its effects on depression/anxiety in adolescents. Holistic interventions including the full range of movement behaviors may be a gateway to reduce the levels of depression/anxiety in adolescence.

Preclinical efficacy of the Wnt/ß-catenin pathway inhibitor BC2059 for the treatment of desmoid tumors.

Mutation in the CTNNB1 gene, leading to a deregulation of the WTN/ß-catenin pathway, is a common feature of desmoid tumors (DTs). Many ß-catenin inhibitors have recently been tested in clinical studies; however, BC2059 (also referred as Tegavivint), a selective inhibitor of nuclear ß-catenin that works through binding TBL-1, is the only one being evaluated in a clinical study, specifically for treatment of desmoid tumor patients. Preclinical studies on BC2059 have shown activity in multiple myeloma, acute myeloid leukemia and osteosarcoma. Our preclinical studies provide data on the efficacy of BC2059 in desmoid cell lines, which could help provide insight regarding antitumor activity of this therapy in desmoid tumor patients. In vitro activity of BC2059 was evaluated using desmoid tumor cell lines. Ex vivo activity of BC2059 was assessed using an explant tissue culture model. Pharmacological inhibition of the nuclear ß-catenin activity using BC2059 markedly inhibited cell viability, migration and invasion of mutated DT cells, but with lower effect on wild-type DTs. The decrease in cell viability of mutated DT cells caused by BC2059 was due to apoptosis. Treatment with BC2059 led to a reduction of ß-catenin-associated TBL1 in all mutated DT cells, resulting in a reduction of nuclear ß-catenin. mRNA and protein levels of AXIN2, a ß-catenin target gene, were also found to be downregulated after BC2059 treatment. Taken together, our results demonstrate that nuclear ß-catenin inhibition using BC2059 may be a novel therapeutic strategy for desmoid tumor treatment, especially in patients with CTNNB1 mutation.