Biological Behavior Research Articles

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

BANF1 is a novel prognostic biomarker linked to immune infiltration in head and neck squamous cell carcinoma.

Barrier-to-autointegration factor 1 (BANF1) is an abundant and ubiquitously expressed postnatal mammalian protein that is overexpressed in numerous human cancers and can promote cancer cell proliferation. However, the role of BANF1 in prognosis remains unclear in head and neck squamous cell carcinoma (HNSCC). BANF1 expression data were obtained from the GEO and TCGA databases. We used Cox regression and Kaplan-Meier curves to assess the prognostic potential of BANF1. The role of BANF1-related genes was investigated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. In addition, we explored the link between BANF1, drug sensitivity, and the tumor immune microenvironment. Finally, functional in vitro and in vivo assays were used to explore the effects of BANF1 on tumor growth and metastasis of HNSCC. BANF1 was markedly overexpressed in HNSCC and was correlated with clinicopathological characteristics. According to survival analysis, BANF1 can be inversely correlated with patient survival and can act as a prognostic risk indicator. IC50 values for chemotherapeutic treatments indicated that the group with high BANF1 expression was more responsive to most antitumor treatments. Furthermore, higher TIDE scores were observed in the low BANF1 expression group, indicating a decline in the efficacy of immune checkpoint inhibitor therapy. Functionally, the malignant biological behavior of HNSCC cell lines was inhibited when BANF1 expression was knocked down. BANF1 can promote tumor progression in patients with HNSCC. BANF1 shows great promise as a potential biomarker to assess the prognosis.

GAS5 promotes glucose metabolism reprogramming and resistance to ferroptosis of endothelial progenitor cells through the miR-495-3p/SIX1 and IGF2BP2/NRF2 dual-regulatory pathways in coronary heart disease.

We aimed to explore the potential along with mechanism of lncRNA growth arrest-specific 5 (GAS5) in modulating glucose metabolism and ferroptosis of endothelial progenitor cells (EPCs) in coronary heart disease (CHD). CCK-8, flow cytometry, EdU, colony formation, scratch test as well as transwell assays were implemented to assess cell biological behaviors. Glucose uptake testing, lactic acid production assay, and detection of extracellular acidification rate (EACR) together with oxygen consumption rate (OCR) were used to assess glucose metabolism. Iron, GSH and MDA detection were used to measure ferroptosis. Besides, a series of mechanical experiments were implemented to clarify the modulatory relationship between GAS5 and nuclear factor erythroid 2-related factor 2 (NRF2) as well as sine oculis homeobox 1 (SIX1). We found that GAS5 was down-regulated in CHD patients relative to healthy controls. GAS5 depletion repressed EPCs proliferation, migration along with invasion while elevated cell apoptosis. GAS5 promoted the reprogramming of glucose metabolism and inhibited ferroptosis in EPCs. GAS5 affected glycometabolic reprogramming and ferroptosis resistance through regulating SIX1 and NRF2. On the one hand, GAS5 promoted NRF2 mRNA stability through IGF2BP2. On the other hand, GAS5 regulated the miR-495-3p/SIX1 axis in EPCs. To sum up, GAS5 promotes glucose metabolism reprogramming and resistance to ferroptosis of EPCs through the miR-495-3p/SIX1 and IGF2BP2/NRF2 dual-regulatory pathways in CHD.

Comprehensive treatment strategy for improving surgical resection rate of retroperitoneal sarcomas: a histology-specific approach narrative review.

Retroperitoneal sarcoma (RPS) represents a rare and heterogeneous group of malignancies, posing significant challenges in evaluation and management. Surgery, the cornerstone of RPS treatment, critically depends on complete resection for a favorable prognosis. The extent of resection is a crucial determinant of local control and survival. This review delves into the evolution of multidisciplinary management of localized RPS, highlighting the imperative to adapt surgical strategies to tumor histology, location, and patient functional status. We explore the principles of compartmental surgery-an extended first-line approach that involves resecting adjacent viscera for wide negative margins-and its effectiveness across different histological subtypes of RPS and more limited resections for other types. Particular emphasis is placed on the heterogeneity of the disease, as various histological subtypes exhibit distinct biological behaviors. This necessitates a shift away from a one-size-fits-all treatment approach. The review analyzes the role of different surgical strategies, focusing on histological type and location. Additionally, the potential benefits of (neo)adjuvant treatments, such as radiotherapy and chemotherapy, are examined, recognizing their specific histological indications and limitations. This comprehensive review consolidates recent data on surgical strategies and complementary therapies, advocating for a personalized approach tailored to histology. As understanding of the molecular and genetic underpinnings of RPS continues to evolve, so will strategies for its effective management, underscoring the need for global collaboration among specialists in this field to enhance our collective knowledge and treatment methodologies.

Stable or at least once HER2-low status during neoadjuvant chemotherapy confers survival benefit in patients with breast cancer

Background Temporal heterogeneity in human epidermal growth factor receptor 2 (HER2) status may be associated with the prognosis of breast cancer. We aimed to clarify the relationship of HER2-low transition during neoadjuvant therapy with survival outcomes under the new classification of HER2 status. Methods This retrospective study was conducted based on the prospective database of breast cancer patients treated with neoadjuvant therapy from September 2013 to August 2020. Results This analysis enrolled 185 patients, including 44 patients with HER2-zero tumours, 93 patients with HER2-low tumours and 48 patients with HER2-positive tumours after neoadjuvant therapy. Nearly, 57.6% of HER2-zero tumours turned into HER2-low tumours after neoadjuvant therapy, while 25.0% of HER2-low patients changed to HER2-zero or HER2-positive tumours. We found that at least once diagnosis as HER2-low breast cancer was related to hormone receptor status (p < .001) and Ki-67 expression (p = .036). Patients ever diagnosed as HER2-low tumours had favourable clinicopathological features (less Ki-67 expression, lower pathological staging, etc.) as well as significantly better locoregional relapse-free survival (LRFS; p = .007) and overall survival (OS; p = .026) compared with those never exhibiting HER2-low expression. Furthermore, the 6-year OS rates were 94.2% (95% confidence interval (CI) 83.1–98.1), 88.7% (74.4–95.2) and 78.1% (65.4–86.6) for patients with stable, once and none HER2-low expression, respectively (adjusted HR, 0.514 [95%CI, 0.294–0.897], p = .019). Conclusions Our study first indicated in patients across all expression levels of HER2 that stable or at least once HER2-low status may confer favourable attributes including less malignant biological behaviour and long-term survival benefit for breast cancer receiving neoadjuvant therapy.

Lidocaine inhibits the lung cancer progression through decreasing the HIST1H2BL levels via SIRT5 mediated succinylation

Lung cancer is a malignant tumor originating from the bronchial mucosa or gland of the lung. Recently, lidocaine, a widely used amide local anesthetic, was demonstrated to inhibit many cancer progression. This research was performed to explore the specific mechanism of lidocaine in the lung cancer progression. The human normal lung epithelial cells (BEAS-2B), and NSCLC cell lines (A549 and H1299) were used and treated with lidocaine in this study. The cell biological behaviors were detected by CCK-8, wound healing and transwell assay. Besides, the mRNA and protein levels of related genes were detected by western blot. The results showed that lidocaine treatment significantly decreased the cell viability and migration of the A549 and H1299 cells. Furthermore, the lidocaine treatment significantly decreased the succinylation and protein levels of HIST1H2BL, which was reversed after SIRT5 knockdown. Additionally, HIST1H2BL knockdown decreased the cell viability and migration of the A549 and H1299 cells, while HIST1H2BL overexpression reversed the effects of lidocaine on the cell viability and migration of the A549 and H1299 cells. In conclusion, lidocaine treatment might inhibited the lung cancer progression through decreasing the SIRT5 mediated succinylation of HIST1H2BL.

Evaluation of prognostic factors for late recurrence in clear cell renal carcinoma: an institutional study.

Following nephrectomy with curative intent, a subset of patients diagnosed with non-metastatic renal cell carcinoma (nmRCC) will present late recurrences, with metastatic relapses after 5 years from the surgical intervention. The aim of this study is to evaluate the prevalence of late recurrences in Romanian patients with nmRCC that have undergone surgery and to assess the clinicopathological characteristics prognostic for late-relapse RCC. This is a single-center, retrospective and observational study that analyzed patients with nmRCC with clear cell histology who underwent surgical resection of the primary tumor with curative intent. The patients included in the study were treated and further surveilled according to a personalized follow-up plan between January 2011 and December 2012 in The Oncology Institute "Prof. Dr. Ion Chiricuţă", Cluj-Napoca, Romania. Study endpoints included median disease-free survival (DFS), median overall survival (OS), as well as evaluation of possible prognostic factors indicative of late relapse. In the study cohort (n=51), the median DFS was 46 months and median OS was 130 months. DFS was significantly correlated with the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (p=0.04, HR=2.48; 95% CI [1.02, 6.01]), neutrophil to lymphocyte ratio (NLR) (a higher NLR value was associated with a poorer DFS, p=0.035), tumor size (T4 tumors vs. T1 p<0.05, HR=9,81; 95% CI [2.65, 36.27]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=4,16; 95% CI = [1.13,15.22]). Fifty one percent of the patients included experienced disease relapse. From this subgroup, a significant percentage of 42% patients presented disease recurrence after 60 months from nephrectomy. OS was correlated to IMDC score (p=0.049, HR=2.36; 95% CI [1, 5.58]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=3,97; 95% CI [1.08, 14.54]). The results of this study support the previously presented biological behavior of RCC, demonstrating that late recurrences in RCC are not uncommon occurrences and patients with localized RCC should be followed up for a longer interval after the surgery for the primary tumor. In addition, the study strengthens the data supporting certain biomarkers as valuable prognostic factors determining survival outcomes of patients with RCC.

The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer.

Short-chain fatty acids (SCFAs), which are saturated fatty acids consisting of six or fewer carbon atoms, have been found to be closely associated with the biological behavior of malignant tumors. This manuscript provides a comprehensive review on the role of SCFAs in regulating cell cycle, apoptosis, tumor angiogenesis, epithelial-mesenchymal transition, protein regulatory pathways, and histone regulation in promoting the development of malignant tumors. Furthermore, we discuss the potential therapeutic strategies targeting SCFAs for treating malignant tumors. This review offers a theoretical foundation for investigating the mechanisms by which SCFAs impact malignant tumors and provides insights into developing novel treatment targets.

The impact of cryopreservation on cytokine secretion and polyfunctionality in human PBMCs: a comparative study.

Human peripheral blood mononuclear cells (hPBMCs) are widely used in fundamental research and clinical applications as studying their responses to in vitro activation is an effective way to uncover functional alterations and disease associated phenotypes. However, the availability of samples in large numbers at a specific time and location remains challenging, hence they often might preferably be collected and cryopreserved for later analysis. While the effect of cryopreservation on viability and cell surface expression is well established, changes in activity and cytokine secretion still lead to conflicting results as it is often measured in bulk or within the cells. Here, we used our platform for dynamic single-cell multiplexed cytokine secretion measurement and compared it to a traditional intracellular cytokine staining to quantify the effect of cryopreservation on cytokine secretion and expression of individual hPBMCs. Following stimulation with LPS or anti-CD3/CD28 antibodies for up to 36 or 72 h incubation, we observed distinct alterations in cytokine responses due to cryopreservation when comparing to fresh samples, but also remarkable consistencies for some cytokines and parameters. In short, the frequencies of cytokine-secreting cells in cryopreserved samples were lower for IL-6 (LPS), IL1-β (CD3/CD28) and IFN-γ (CD3/CD28), while the frequency and dynamics of IL-8 secretion were strongly impacted in all cases. We observed a large disconnect between cytokine expression and secretion for TNF-α, where the expression dramatically increased after cryopreservation, but actual secretion was, in comparison, remarkably stable. The polyfunctionality of single cells was altered by cryopreservation in specific co-secreting populations led by the effects on IL-6 or IL-8 secretion. Among immune cells, cryopreservation seemed to affect lymphocytes and monocytes differently as effects appeared early on in lymphocytes while generally observed in later time points in monocytes. Together, this study offers an in-depth quantitative insight into the biological behavior of immune cells in response to cryopreservation and stimulation, further providing some insights into conflicting results in theliterature as well as guidelines for researchers planning to assess cytokine-secreting from frozen hPBMCs in immunological research or clinical applications.

Chaotic self-beating of left ventricle modeled by liquid crystal elastomer

Self-vibration systems using active materials generate sustained vibrations spontaneously through synergistic actions between internal structure and external environment. Therefore, the self-vibration systems have a wide application prospect in bionic design and soft robots. Inspired by the human left ventricle, a novel chaotic self-beating system modeled by an electrothermal responsive liquid crystal elastomer balloon is proposed. To study the self-beating characteristics of the liquid crystal elastomer left ventricle, a simplified theoretical framework is formed by combining the electric joule heat conduction model, the left ventricle circulatory system model and the dynamic principle. The numerical results show that the left ventricle has two typical self-beating modes: periodic beating and chaotic beating. The mechanisms of periodic beating and chaotic beating are elucidated by analyzing the balance between the work done by each force on the left ventricle. In addition, the effects of key system parameters on self-beating behavior are investigated in detail. This research will promote the application of chaotic dynamics in artificial hearts and medical devices, while providing a new perspective for the study of chaotic behavior and mechanism in biology.

Biological role of Semaphorin 6D in the proliferation, migration and invasion of gastric cancer

Background: To analyse how Semaphorin 6D (SEMA6D) expression and extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathways are activated and how they influence gastric cancer proliferation, migration, and invasion. Methodology: SEMA6D expression was knocked down in human gastric cancer cells using RNA interference technology. In vitro assays were used to analyse how SEMA6D knockdown affects clone formation, migration, and invasion. ERK and PI3K/ AKT/mTOR signaling pathway related proteins were detected by immunoblotting. Results: In the si-NC group, Sema6D protein levels were higher than those in the si-1 and si-2 groups after knockdown of Sema6D, while in the si-1 group, Sema6D protein levels were higher than those in the si-2 group (P&lt;0.05). P-PI3K, ERK/p-ERK, AKT/p-AKT, and mTOR/p-mTOR levels in the si-NC group were significantly higher than those in the si-1 and si-2 groups after knockdown of Sema6D (P &lt; 0.05). It was found that scratch healing rate of SGC-7901 cells in si-NC group was higher than that in si-1 and si-2 groups, and the difference was statistically significant (P &lt; 0.05). Conclusion: SEMA6D expression level can affect the biological behavior of gastric cancer cells. Keywords: Gastric cancer; extracellular signal-regulated kinase; semaphorin 6D; ERK and PI3K/AKT/mTOR; cell proliferation.

Expression of histone methyltransferase WHSC1 in invasive breast cancer and its correlation with clinical and pathological data

BackgroundThe WHSC1 protein facilitates specific dimethylation of histone H3 at the K36 position, enhancing gene transcription and expression. Studies have confirmed its high expression in diverse malignant tumors. We aimed to identify novel molecular markers to assess the biological behavior of breast cancer cells. MethodsWe conducted a comprehensive analysis of mRNA expression in breast cancer and adjacent tissues based on TCGA data. We enrolled 141 breast cancer patients treated at the First Affiliated Hospital of Fujian Medical University between 2012 and 2016. Patient clinical information and pathological specimens were obtained. We utilized tissue microarray (TMA) technology. We employed the chi-square test for between-group comparisons, with p < 0.05 indicating statistical significance. Furthermore, we analyzed the associations between WHSC1 expression and clinical or pathological data. ResultsWHSC1 mRNA expression was significantly higher in breast cancer tissues than in adjacent tissues (p < 0.001). Moreover, high WHSC1 protein expression in breast cancer was associated with several important clinical parameters, such as pathological type (p = 0.007), high Ki67 expression(Ki67＞20 %) (p < 0.001), lymph node metastasis (p < 0.001), T stage (p = 0.011), N stage (p < 0.001), postoperative pathological stage (p < 0.001), premenopausal status (p = 0.004), and positive HER2 status (p < 0.001). Multivariate regression analysis showed that high WHSC1 expression, elevated Ki67 levels, and positive HER2 status were independent risk factors for axillary lymph node metastasis in breast cancer patients. ConclusionWHSC1 protein expression is upregulated in breast cancer patients and represents an independent risk factor influencing axillary lymph node metastasis, highlighting its potential significance as a strong candidate biomarker.

Proteomic analysis of HeLa cells after stable transfection with the Chlamydia trachomatis CT143 gene

BackgroundThe CT143 protein of Chlamydia trachomatis (Ct) is a key immunodominant antigen and candidate type-III secretion substrate. Although CT143 expression has not been detected in the cytosol of infected cells, it is known to interfere with the physiological behavior of HeLa cells. This study aims to investigate how the CT143 protein affects the protein expression profile of HeLa cells, providing a basis for further research into Ct’s pathogenic mechanisms. MethodsWe constructed a stably transfected HeLa cell line, pCD513B-1-CT143-HeLa, and a control cell line, pCD513B-1-HeLa. Protein expression profiles of these cell lines were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins were identified, constructed into a database, and verified using parallel reaction monitoring (PRM). Bioinformatics software facilitated the preliminary analysis of the biological functions of these differential proteins. ResultsA total of 221 host proteins were differentially expressed, with 68 upregulated and 153 downregulated. These variations influence the regulation of peptidase activity and are crucial in biological processes such as cell secretion and protease activity. Significant changes were noted in protein processing, alcohol dehydrogenase activity, Aldo-Keto reductase activity, and peptidase regulator activity. Furthermore, alterations were observed in cellular components like the plasma membrane and cell periphery. Pathways involving the hematopoietic system, glycosaminoglycan degradation, retinol metabolism, and cytochrome P450-mediated exogenous drug metabolism were notably affected. Indirect interactions among differentially expressed proteins included three key nodal proteins: C3, IFIT3, and IFIT1. ConclusionThe successful construction of a host differential protein expression profile was achieved through stable transfection of HeLa cells with the CT143 gene. The differential proteins identified are implicated in regulating various biological processes such as intracellular signal transduction, cell secretion, protein processing, hydrolysis, and enzyme activity. These findings suggest that the CT143 protein may influence the host cell’s biological behavior by altering host protein expression, potentially hindering Ct growth and development.

MicroRNA-503 Suppresses Oral Mucosal Fibroblast Differentiation by Regulating RAS/RAF/MEK/ERK Signaling Pathway.

The abnormal proliferation and differentiation of oral mucosal fibroblasts (FBs) is the key to the progression of oral submucosal fibrosis. To clarify the mechanism of platelet-derived growth factor (PDGF-BB)-induced FBs fibrosis in oral mucosa, real-time quantitative polymerase chain reaction and Western blot were used in this study to detect the expression of miR-503 and the expression of p-MEK, p-ERK, miR-503, RAF, smooth actin and type I collagen under different time and concentration stimulation of PDGF-BB. The effects of overexpression of miR-503 or RAF on the proliferation and migration of FBs were detected by cell counting kit 8 and cell scratch assay, respectively. A dual luciferase reporter gene assay was used to verify the targeting effect of miR-503 on RAF. The results showed that miR-503 was downregulated in a dose- and time-dependent manner in PDGF-BB-induced FBs. In addition, RAF is a direct target of miR-503 and can be negatively regulated. Overexpression of RAF can promote FB proliferation, migration, differentiation, collagen synthesis, and activation of downstream molecules (MEK/ERK), while overexpression of miR-503 can partially reverse the effects of RAF. Therefore, miR-503 regulates the biological behavior of PDGF-BB-induced oral mucosal FBs by influencing the activation of the RAS/RAF/MEK/ERK signaling pathway.

Methacrylated chitosan/jellyfish collagen membranes as cell instructive platforms for liver tissue engineering

Although the multidisciplinary area of liver tissue engineering is in continuous progress, research in this field is still focused on developing an ideal liver tissue template. Innovative strategies are required to improve membrane stability and bioactivity.In our study, sustainable biomimetic membranes were developed by blending methacrylated chitosan (CSMA) with jellyfish collagen (jCol) for liver tissue engineering applications.The in vitro biological behaviour demonstrated the capability of the developed membranes to create a suitable milieu to enable hepatocyte growth and differentiation. The functionalization of chitosan together with the biocompatibility of marine collagen and the intrinsic membrane properties offered the ideal biochemical, topographical, and mechanical cues to the cells. Thanks to the enhanced CSMA/jCol membranes' characteristics, hepatocytes on such biomaterials exhibited improved growth, viability, and active liver-specific functions when compared to the cell fate achieved on CSMA membranes. Our study provides new insights about the influence of membrane properties on liver cells behaviour for the design of novel instructive biomaterials. The enrichment of functionalized chitosan with marine collagen represents a promising and innovative approach for the development of an appropriate platform for hepatic tissue engineering.

Anorectal melanoma: systematic review of the current literature of an aggressive type of melanoma.

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM's diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma.

Atypical Presentation of Dysembryoplastic Neuroepithelial Tumor

Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm, usually found in children and adolescents, in the vast majority of cases associated with drug-resistant epilepsy. Typically, epileptic seizures are the main, and in most cases, their only clinical manifestation. Although DNET is a benign, biologically stable tumor with few reports of malignancy, it is one of the most common reasons for epileptic surgery. The epileptogenic potential of this tumor is so high that DNET s, along with ganglioglioma, have received the informal term “epileptomas” and are by far the leaders in the group of low-grade tumors associated with long-term epilepsy-associated tumors (LEAT). It is believed that this epileptogenicity is due to localization in the neocortex and frequent association with focal cortical dysplasias (FCD). In the world literature, there are only a few mentions of DNET s not associated with epilepsy. The article presents the experience of complex, interdisciplinary diagnosis of DNET in a child without epilepsy who complained of frequent headaches. During a comprehensive MRI examination, a cortical-subcortical pathological substrate was discovered in the left temporal lobe with radiological signs of DNET. During video-EEG monitoring of night sleep, no epileptiform signs were recorded. There was no history of epileptic seizures or other paroxysms. A control MRI revealed a slight increase in the size of the pathological substrate, which was the reason for surgical treatment. Pathological examination revealed microscopic features of DNET. This case of absence of epilepsy in a child with cortical DNET in the temporal lobe cortex suggests that the spectrum of its clinical manifestations and biological behavior is not fully understood and requires further comprehensive study.

Cancer-associated fibroblast-secreted exosomes promote prostate cancer cell migration and invasion by the FGL1/SOX5 axis.

Exosomes secreted by cancer-associated fibroblasts (CAFs) play a critical role in cancer progression. This study aimed to explore the effects of CAF exosomes on prostate cancer (PC) cell metastasis. PC cells were treated with these exosomes, and their processes were evaluated using cell-counting kit-8 and Transwell assays. Exosome-regulated mRNAs were explored using quantitative real-time PCR. The relationship between FGL1 and SOX5 was analyzed using co-immunoprecipitation and fluorescence in situ hybridization (FISH) assays. The results of this study showed that exosomes derived from CAFs promoted PC cell viability, migration, and invasion. CAFs promoted PC cell viability and metastasis by releasing exosomes. Exosome treatment increased the levels of FGL1, which interacted with SOX5 and negatively regulated its expression. Rescue experiments demonstrated that CAF exosomes promoted the biological behaviors of PC cells by upregulating FGL1 and downregulating SOX5. Moreover, exosomes accelerated tumor growth by regulating the FGL1 level. In conclusion, CAF-derived exosomes promoted PC cell viability, migration, and invasion by elevating the FGL1/SOX5 axis, suggesting a novel strategy for the treatment of metastatic PC.

Clinical-proteomic classification and precision treatment strategy of chordoma

Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.

Concomitant melanoma and keratoma affecting the equine digit: clinical, pathological, and long-term follow-up findings

BackgroundThis case report details a long-term follow-up of a hoof melanoma with dermo-epidermal activity (resembling Spreading Superficial Melanoma (SSM)) in a bay horse with a history of a right front hoof keratoma. Melanomas involving the horse's foot are seldom reported and usually diagnosed as anaplastic melanomas based on signalment and post-mortem examination. The clinical-pathological characteristics of the foot melanoma in this bay horse are consistent with SSM-like described in humans, which is considered an intermediate malignant tumour attending their biological behaviour. However, a definitive diagnosis is limited by the single case and the lack of references in horses.Case presentationA 12-year-old bay Andalusian gelding underwent keratoma removal on the lateral aspect of the hoof wall. A partial resection of the hoof wall was performed for this purpose. Additionally, a plaque-like, hyperkeratotic pigmented lesion, 2 × 2X0,4 cm in size, was observed at the lateral aspect of the coronary band and was also resected for histopathological examination. Microscopically, a melanocytic tumour, characterised by small nests of large polygonal or epithelioid cells infiltrating the basal and suprabasal epidermis, the dermo – epidermal junction, and the superficial dermis, was observed. The neoplastic cells exhibited large euchromatic nuclei, prominent nucleoli, moderate pleomorphism and 4 mitotic figures per 2,37mm2; variable amounts of dark granules (melanin) were present in the cytoplasm, as well as in numerous peritumoral macrophages. The immunophenotype of the tumour cells was PNL2 + + + , S100 + + , AE1/AE3-. A diagnosis of melanoma with dermo-epidermal junction and marked intraepidermal activity (consistent with superficial spreading melanoma) was made.A magnetic resonance imaging (MRI) performed, revealed no further invasion into surrounding structures. Treatment was based on surgical resection and multiple local chemotherapy sessions with cisplatin were applied. The biopsies obtained after treatment showed partial regression of the tumour and different stages of healing. After 26 months of follow-up, there was no signs of malignant spreading into surrounding structures including the pedal bone and distal metastasis but a dark – coloured area persists over the lateral aspect of the coronary band.ConclusionsThis case presents a concomitant keratoma and melanoma with dermo – epidermal activity, resembling a spreading superficial melanoma. After a follow – up of 26 months the horse remains healthy and sound providing new information for clinicians and pathologists. Despite the poor prognosis associated with foot malignant melanocytic tumours, it is important that an early and accurate diagnosis is reached through different diagnostic modalities such as advanced imaging techniques and histopathology. Additionally, these findings demonstrate that the current classification and prognosis for equine foot melanomas are insufficient.