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Background: Spindle cell carcinoma is a rare biphasic malignancy consisting of epithelial and mesenchymal components. It is a poorly differentiated variant of squamous cell carcinoma accounting for less than 2% of intraoral tumours, with only 69 cases reported in the literature. Clinical presentation may vary from exophytic tumours to infiltrating ulceration in the oral mucosa. Atypical presentation and erractic behaviour of these tumours mean management can be challenging, therefore prompt diagnosis and treatment are required to address the significant morbidity and mortality associated with this disease. Case Presentation: A 49‐year‐old patient presented to the oral medicine clinic reporting pain affecting the left side of their palate and cheek. Prior to their attendance, they were assessed by their general medical practitioner and neurologist; however, a trial of various medications resulted in no improvement in their symptoms. Intra‐oral examination revealed an ulcer in the left hard palate with underlying visible maxillary bone. A subsequent biopsy confirmed the diagnosis of spindle cell carcinoma, and the patient received radiotherapy with adjuvant chemotherapy. Further imaging revealed distant metastasis in the right lung and treatment was changed to palliative immunotherapy. Follow‐up imaging has shown lung nodules to be stable, and the patient remains under review with the regional head and neck cancer team. Conclusions: We report a rare case of intra‐oral spindle cell carcinoma diagnosed from a palatal lesion, which has only been reported in four cases previously at this site. Despite preceding encounters with multiple medical professionals, it is not clear whether an intra‐oral examination was carried out which may have established the diagnosis earlier. It emphasizes the importance of full head & neck examination, including intraoral examination in presentations of unexplained and intractable orofacial pain. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies. [ABSTRACT FROM AUTHOR]

Quiescence promotes resilience of neural stem cells to cellular stress and aging. Likewise, in glioma tumour/glioma stem cell populations, quiescent/slow-cycling states impart resistance to cellular stress and chemoradiation. Emerging evidence suggests that the molecular signatures of quiescent neural stem cells correlates with the molecular signatures of quiescent glioma stem cells. The few signals that have been experimentally interrogated, suggest these pathways are also functionally conserved. There are multiple challenges in identifying and tracking quiescent neural stem cells and glioma stem cells. Recent advances in methodologies such as intravital imaging, electroporation models of brain cancer and single-cell data tools are overcoming these challenges, which may accelerate the development of targeted therapeutics. Quiescence is a prolonged but reversible state of cell-cycle arrest that is an adaptive feature of most adult stem cell populations. In the brain, quiescence helps to protect adult neural stem cells from stress and supports lifelong neurogenesis. Unfortunately however, entry into a quiescent or a slow-cycling state is also a malignant feature of brain cancer stem cells. In glioblastoma, where the process has been best characterised, quiescent glioma stem cells preferentially survive chemoradiation, and after therapy, reactivate to regrow the tumour and drive recurrence. In this Review, we discuss the in vitro and in vivo models that have been developed for studying neural stem cell quiescence and how these tools may be used to deepen biological understanding and to develop novel therapies targeting quiescent glioma stem cells. [ABSTRACT FROM AUTHOR]

Simple Summary: High levels of the transcription factor Grainyhead-like protein 2 (GRHL2) contribute to worse outcomes for patients with breast cancer tumors that express estrogen receptor (ER). Using multiple methods to increase GRHL2 expression in breast cancer cells, we found that high GRHL2 promotes both epithelial and mesenchymal phenotypes. This is indicative of an intermediate state between epithelial and mesenchymal cells, which is associated with metastasis. We also observed that elevated GRHL2 stimulates properties characteristic of cellular plasticity, including a decrease in cellular proliferation with a reciprocal increase in dormancy and stem cell markers. Elevated levels of GRHL2 broadly changed its control of gene expression at the level of DNA and shifted nearby transcription factor binding sites from those associated with development to those associated with disease progression. These results provide a possible explanation for how elevated GRHL2 levels could contribute to poorer prognosis in ER-positive breast cancer. Estrogen receptor (ER)-positive breast cancer is characterized by late recurrences following initial treatment. The epithelial cell fate transcription factor Grainyhead-like protein 2 (GRHL2) is overexpressed in ER-positive breast cancers and is linked to poorer prognosis as compared to ER-negative breast cancers. To understand how GRHL2 contributes to progression, GRHL2 was overexpressed in ER-positive cells. We demonstrated that elevated GRHL2 imparts plasticity with stem cell- and dormancy-associated traits. RNA sequencing and immunocytochemistry revealed that high GRHL2 not only strengthens the epithelial identity but supports a hybrid epithelial to mesenchymal transition (EMT). Proliferation and tumor studies exhibited a decrease in growth and an upregulation of dormancy markers, such as NR2F1 and CDKN1B. Mammosphere assays and flow cytometry revealed enrichment of stem cell markers CD44 and ALDH1, and increased self-renewal capacity. Cistrome analyses revealed a change in transcription factor motifs near GRHL2 sites from developmental factors to those associated with disease progression. Together, these data support the idea that the plasticity and properties induced by elevated GRHL2 may provide a selective advantage to explain the association between GRHL2 and breast cancer progression. [ABSTRACT FROM AUTHOR]

Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule‐associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient‐derived glioma stem‐like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST. [ABSTRACT FROM AUTHOR]

Microfluidic devices serve as essential tools across diverse fields like medicine, biotechnology, and chemistry, enabling advancements in analytical techniques, point‐of‐care diagnostics, microfluidic cell cultures, and organ‐on‐chip models. While polymeric microfluidics are favoured for their cost‐effectiveness and ease of fabrication, their inherent hydrophobic properties necessitate surface functionalization, often post‐sealing. Here, we introduce a versatile apparatus for functionalizing sealed microfluidic devices using atmospheric plasma processing, with a focus on PDMS (polydimethylsiloxane) microfluidics. Through meticulous analysis of surface properties and capillary speed, before and after plasma treatment, along with a comparison between vacuum and atmospheric plasma functionalization methods, we demonstrate the efficacy of our approach. Subsequent experimentation within 3D PDMS microfluidic chambers, combining atmospheric pressure plasma treatment with collagen coating to facilitate mesenchymal stem cells (MSCs) growth over five days, reveals enhanced initial cell adhesion and proliferation, highlighting the potential of our method for improving cell‐based applications within microfluidic systems. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin (DOX) is a potent chemotherapy widely used in treating various neoplastic diseases. However, the clinical use of DOX is limited due to its potential toxic effect on the cardiovascular system. Thus, identifying the pathway involved in this toxicity may help minimize chemotherapy risk and improve cancer patients' quality of life. Recent studies suggest that Endothelial-to-Mesenchymal transition (EndMT) and endothelial toxicity contribute to the pathogenesis of DOX-induced cardiovascular toxicity. However, the molecular mechanism is yet unknown. Given that arachidonic acid and associated cytochrome P450 (CYP) epoxygenase have been involved in endothelial and cardiovascular function, we aimed to examine the effect of suppressing CYP epoxygenases on DOX-induced EndMT and cardiovascular toxicity in vitro and in vivo. Methods and Results: To test this, human endothelial cells were treated with DOX, with or without CYP epoxygenase inhibitor, MSPPOH. We also investigated the effect of MSPPOH on the cardiovascular system in our zebrafish model of DOX-induced cardiotoxicity. Our results showed that MSPPOH exacerbated DOX-induced EndMT, inflammation, oxidative stress, and apoptosis in our endothelial cells. Furthermore, we also show that MSPPOH increased cardiac edema, lowered vascular blood flow velocity, and worsened the expression of EndMT and cardiac injury markers in our zebrafish model of DOX-induced cardiotoxicity. Conclusion: Our data indicate that a selective CYP epoxygenase inhibitor, MSPPOH, induces EndMT and endothelial toxicity to contribute to DOX-induced cardiovascular toxicity. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells are considered potent sources that can be used for tissue regeneration and treatment of various diseases and syndromes. Among the mesenchymal stem cells, amniotic fluid-derived stem cells come forward as they possess some pluripotent properties and there are no serious ethical concerns upon their derivation. Therefore, gaining a better understanding of the nature of amniotic fluid stem cells is important. Although it is known that stem cells show slightly different characteristics between passages, scientists often consider only cell numbers and the proliferation pattern of the cells when deciding the passage to use in their studies. In this study, it was aimed to characterize rat amniotic fluid-derived stem cells for their mesenchymal and pluripotent features and make inter-passage comparisons by real-time qPCR to reveal their distinctions between different passages, and eventually help decide the appropriate passage numbers to be used in future research. The outcomes of the study showed that using rat amniotic fluid-derived stem cells at P5 could be beneficial for mesodermal differentiation studies and using them in earlier passages may be more favorable for the studies requiring better ectodermal differentiation properties. [ABSTRACT FROM AUTHOR]

Primary mesenchymal tumours of the thorax are rare lesions that can pose significant diagnostic difficulties, particularly given the morphological overlap with carcinomas and mesotheliomas that occur much more commonly at these sites. In this article we will discuss a morphology-based approach to assist pathologists when confronted with a possible mesenchymal neoplasm. This will be combined with an overview of the key immunohistochemical and molecular studies that aid diagnosis of the more commonly encountered neoplasms that arise in the thorax. [ABSTRACT FROM AUTHOR]

Glioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized to re‐populate the tumor milieu due to selection following conventional therapies. Here, we show that 5‐aminolevulinic acid (ALA) treatment—a pro‐fluorophore used for fluorescence‐guided cancer surgery—leads to elevated levels of fluorophore conversion in patient‐derived GSC cultures, and subsequent red light‐activation induces apoptosis in both intrinsically temozolomide chemotherapy‐sensitive and ‐resistant GSC phenotypes. Red light irradiation of ALA‐treated cultures also exhibits the ability to target mesenchymal GSCs (Mes–GSCs) with induced temozolomide resistance. Furthermore, sub‐lethal light doses restore Mes–GSC sensitivity to temozolomide, abrogating GSC‐acquired chemoresistance. These results suggest that ALA is not only useful for fluorescence‐guided glioblastoma tumor resection, but that it also facilitates a GSC drug‐resistance agnostic, red light‐activated modality to mop up the surgical margins and prime subsequent chemotherapy. [ABSTRACT FROM AUTHOR]

A scoping review of published literature found 108 articles related to mesenchymal stem or stromal cell (MSC) use in cats. Twenty-four of the publications summarized the treatment of 192 cats with MSC products for 12 naturally occurring and induced diseases. These trials used a variety of cell sources, administration routes, delivery vehicles, and dosages. The majority of studies did not have a control group. The disease with the largest number of cats administered MSCs thus far is chronic kidney disease (n = 59 cats). The majority of cats had no adverse events associated with treatment, which supports continued interest in the potential use of MSC products to address unmet medical needs. Treatment outcomes of the 192 cats have ranged from no response to long-term cure, depending on the disease being treated and the particularstudy. Some of these early studiesshow promiseand providesignificant information to direct both the design and focus of larger clinical trials investigating the safety and efficacy of MSC treatment for veterinary and human applications. [ABSTRACT FROM AUTHOR]

Despite a pressing need for new therapies to address unmet veterinary medical need, no approved stem cell products are available for use in cats in the US. To evaluate the current state of mesenchymal stem or stromal cell (MSC) research in cats, a scoping review of published literature was performed, which identified 108 publications related to feline MSCs. Twenty-six of the articles described administration of MSC products to a total of 215 cats. Twelve of the studies included a control group. These experimental and clinical trials used 7 cell sources, 9 administration routes, 12 delivery vehicles, and a 300-fold range in dosages for initial studies in healthy cats and cats with 12 naturally occurring and induced diseases. The majority of studies administered 2 doses of allogeneic, adipose-derived MSC IV and monitored a median of 6.5 treated cats for a median of 90 days. The majority (150/215 [69.8%]) of cats had no reported adverse events associated with treatment. Although an increase in feline MSC publications in the past 10 years indicates progress, the wide variety and small number of studies using MSCs and MSC products in cats demonstrates that current evaluations are mostly still in the discovery phase, and several issues remain related to larger scale trials using MSC products in cats. The current available publications provide information to direct further clinical study development and informed owner consent for study enrollment. [ABSTRACT FROM AUTHOR]

Ependymal tumors are classified based on their location, histology, and molecular characteristics. Supratentorial ependymomas (ST‐EPNs) are a group of circumscribed supratentorial gliomas, which usually have pathogenic fusions involving either zinc finger translocation associated (ZFTA) (formerly C11orf95) or YAP1. A subtype of ependymoma was recently described and labeled ependymoma‐like tumors with mesenchymal differentiation (ELTMDs). We describe a case of a 5‐year‐old boy who presented with a right frontal tumor. The diagnosis was challenging, and a correct diagnosis could only be reached after reanalysis of methylation data with a more recent version of the classifier and RNA fusion testing, which revealed ZFTA:NCOA1 (nuclear receptor coactivator 1) fusion. There are only a handful of cases of this entity, which is being reported for its rarity and the diagnostic challenge it poses. [ABSTRACT FROM AUTHOR]

Phosphaturic mesenchymal tumours (PMT) are rare, benign lesions and the most common tumour to cause tumour-induced osteomalacia (TIO), a paraneoplastic syndrome. Patients frequently exhibit severe osteomalacia, accompanied by multiple fractures, which significantly impair their quality of life. Complete surgical resection is curative. Contribution: A rare case of sinonasal PMT is presented, with a focus on the imaging findings and role of the radiologist and nuclear physician.

Background: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer known for its challenging survival rates; it is characterized by distinct subtypes, such as the proneural and mesenchymal states. The development of targeted therapies is critically dependent on a thorough understanding of these subtypes. Advances in single-cell RNA-sequencing (scRNA-seq) have opened new avenues for identifying subtype-specific gene biomarkers, which are essential for innovative treatments. Methods: This study introduces a genetic optimization algorithm designed to select a precise set of genes that clearly differentiate between the proneural and mesenchymal GBM subtypes. By integrating differential gene expression analysis with gene variability assessments, our dual-criterion strategy ensures the selection of genes that are not only differentially expressed between subtypes but also exhibit consistent variability patterns. This approach enhances the biological relevance of identified biomarkers. We applied this algorithm to scRNA-seq data from GBM samples, focusing on the discovery of subtype-specific gene biomarkers. Results: The application of our genetic optimization algorithm to scRNA-seq data successfully identified significant genes that are closely associated with the fundamental characteristics of GBM. These genes show a strong potential to distinguish between the proneural and mesenchymal subtypes, offering insights into the molecular underpinnings of GBM heterogeneity. Conclusions: This study introduces a novel approach for biomarker discovery in GBM that is potentially applicable to other complex diseases. By leveraging scRNA-seq data, our method contributes to the development of targeted therapies, highlighting the importance of precise biomarker identification in personalized medicine.

Soft tissue myxomas are extremely rare benign soft tissue tumors of the oral cavity. They comprise of myxoid ground substance and often present as painless, slow-growing masses. Their differential diagnosis is challenging due to their non-specific clinical features and histopathologic similarities with other tumors of myxoid stroma. In this communication, diagnosis and management of soft tissue myxoma in the anterior palatal gingiva of a 22-year-old male patient is reported which clinically appeared as a routine hyperplastic growth. Both the incidence and location of this tumor was rare and has been sparsely reported in the literature.

This case highlights a primary cutaneous rhabdomyoma presenting as a slowly enlarging subcutaneous nodule on the mentum of an 82-year-old White man with a medical history of two intracranial rhabdomyomas. Although they are rarely syndromic, it is important to note that the most common demographic for presentation of rhabdomyomas includes older males presenting as a subcutaneous nodule on the head, neck, or oral cavity. They are most often seen in isolation but can be multifocal in up to 25% of all cases. Being a rare entity, there is no generally recognized treatment consensus; however, complete surgical excision is recommended to prevent recurrence and morbidity from local tissue destruction.

Purpose: This article aims to provide a comprehensive review of the management challenges associated with Spinal Phosphaturic Mesenchymal tumors (PMTs) and evaluates the surgical management outcomes for this rare entity linked to Tumor-induced osteolysis. The primary objective of this study is to enhance the familiarity of treating physicians with the clinical features, diagnosis, and treatment options for Spinal PMTs. Methods: A retrospective analysis was conducted, reviewing electronic medical records of patients diagnosed with spinal PMTs at our hospital between January 2019 and December 2022. The data collected included demographic information, clinical presentation, radiological findings, surgical details, and follow-up outcomes. Results: A total of three cases of Spinal PMTs causing Tumor-induced osteomalacia were identified. The diagnosis of Spinal PMTs presented challenges, with incidental detection often occurring during routine imaging. Surgical management was undertaken, resulting in successful symptom resolution and normalization of phosphate levels. The application of 68 Ga-DOTA-TATE PET/CT scans facilitated tumor localization, aiding in surgical planning. Spinal PMTs demonstrated a favorable response to surgical intervention. Conclusion: Spinal PMTs play a significant role in Tumor-induced osteolysis, warranting timely and accurate diagnosis. Although diagnosing Spinal PMTs presents challenges, surgical management has proven to yield favorable outcomes, effectively alleviating symptoms and restoring phosphate levels. A multidisciplinary approach and continued vigilance are essential in ensuring early diagnosis, effective treatment, and long-term monitoring for patients affected by spinal PMTs. [ABSTRACT FROM AUTHOR]

Quantitative studies of mesenchymal cell motion are important to elucidate cytoskeleton function and mechanisms of cell migration. To this end, confinement of cell motion to one dimension (1D) significantly simplifies the problem of cell shape in experimental and theoretical investigations. Here we review 1D migration assays employing micro-fabricated lanes and reflect on the advantages of such platforms. Data are analyzed using biophysical models of cell migration that reproduce the rich scenario of morphodynamic behavior found in 1D. We describe basic model assumptions and model behavior. It appears that mechanical models explain the occurrence of universal relations conserved across different cell lines such as the adhesion-velocity relation and the universal correlation between speed and persistence (UCSP). We highlight the unique opportunity of reproducible and standardized 1D assays to validate theory based on statistical measures from large data of trajectories and discuss the potential of experimental settings embedding controlled perturbations to probe response in migratory behavior. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer known for its challenging survival rates; it is characterized by distinct subtypes, such as the proneural and mesenchymal states. The development of targeted therapies is critically dependent on a thorough understanding of these subtypes. Advances in single-cell RNA-sequencing (scRNA-seq) have opened new avenues for identifying subtype-specific gene biomarkers, which are essential for innovative treatments. Methods: This study introduces a genetic optimization algorithm designed to select a precise set of genes that clearly differentiate between the proneural and mesenchymal GBM subtypes. By integrating differential gene expression analysis with gene variability assessments, our dual-criterion strategy ensures the selection of genes that are not only differentially expressed between subtypes but also exhibit consistent variability patterns. This approach enhances the biological relevance of identified biomarkers. We applied this algorithm to scRNA-seq data from GBM samples, focusing on the discovery of subtype-specific gene biomarkers. Results: The application of our genetic optimization algorithm to scRNA-seq data successfully identified significant genes that are closely associated with the fundamental characteristics of GBM. These genes show a strong potential to distinguish between the proneural and mesenchymal subtypes, offering insights into the molecular underpinnings of GBM heterogeneity. Conclusions: This study introduces a novel approach for biomarker discovery in GBM that is potentially applicable to other complex diseases. By leveraging scRNA-seq data, our method contributes to the development of targeted therapies, highlighting the importance of precise biomarker identification in personalized medicine. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood to the tumor, GBM vessels also provide trophic support to glioma cells and serve as conduits for migration into the surrounding brain, promoting recurrence. Here, we enrich CD31-expressing glioma vascular cells (GVCs) and A2B5-expressing glioma tumor cells (GTCs) from primary GBM and use RNA sequencing to create a comprehensive molecular interaction map of the secreted and extracellular factors elaborated by GVCs that can interact with receptors and membrane molecules on GTCs. To validate our findings, we utilize functional assays, including a hydrogel-based migration assay and in vivo mouse models to demonstrate that one identified factor, the little-studied integrin binding sialoprotein (IBSP), enhances tumor growth and promotes the migration of GTCs along the vasculature. This perivascular niche interactome will serve as a resource to the research community in defining the potential functions of the GBM vasculature.

Leiomyomas, originating from smooth muscle cells, are common in the uterus but rare in the scrotum, presenting a clinical challenge. Scrotal leiomyomas, first described in the 19th century, are characterized by benign pathology from the subcutaneous dartos muscle. We present two cases of middle-aged males with scrotal leiomyomas, detailing clinical presentations, histopathological findings, and immunohistochemistry results. The first involved a 48-year-old with a painless scrotal lump, excised to reveal well-circumscribed smooth muscle bundles. Immunohistochemistry confirmed vimentin, desmin, and smooth muscle actin (SMA) positivity, consistent with scrotal leiomyoma. The second case featured a 25-yearold with a painless scrotal swelling, histologically matching the features of scrotal leiomyoma. Accurate diagnosis is crucial for guiding appropriate management strategies. Clinicians often employ a combination of clinical evaluation, imaging studies, and histopathological examination to confirm the presence of scrotal leiomyomas. Ultrasound remains a valuable tool for assessing the size, location, and vascularity of the tumor, aiding in the formulation of a differential diagnosis. Definitive diagnosis, however, relies on histological examination, which typically reveals spindle-shaped smooth muscle cells arranged in interlacing bundles.

Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation.

Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies.

Epithelial-mesenchymal transition (EMT) and its reverse mechanism, mesenchymal-epithelial transition (MET), are evolutionarily conserved mechanisms initially identified in studies of early metazoan development. EMT may even have been established in choanoflagellates, the closest unicellular relative of Metazoa. These crucial morphological transitions operate during body plan formation and subsequently in organogenesis. These findings have prompted an increasing number of investigators in biomedicine to assess the importance of such mechanisms that drive epithelial cell plasticity in multiple diseases associated with congenital disabilities and fibrosis, and, most importantly, in the progression of carcinoma. EMT and MET also play crucial roles in regenerative medicine, notably by contributing epigenetic changes in somatic cells to initiate reprogramming into stem cells and their subsequent differentiation into distinct lineages. [ABSTRACT FROM AUTHOR]

Background: The GL261 and CT2A syngeneic tumor lines are frequently used as immunocompetent orthotopic mouse models of human glioblastoma (huGBM) but demonstrate distinct differences in their responses to immunotherapy. Methods: To decipher the cell-intrinsic mechanisms that drive immunotherapy resistance in CT2A-luc and to define the aspects of human cancer biology that these lines can best model, we systematically compared their characteristics using whole exome and transcriptome sequencing, and protein analysis through immunohistochemistry, Western blot, flow cytometry, immunopeptidomics, and phosphopeptidomics. Results: The transcriptional profiles of GL261-luc2 and CT2A-luc tumors resembled those of some huGBMs, despite neither line sharing the essential genetic or histologic features of huGBM. Both models exhibited striking hypermutation, with clonal hotspot mutations in RAS genes (Kras p.G12C in GL261-luc2 and Nras p.Q61L in CT2A-luc). CT2A-luc distinctly displayed mesenchymal differentiation, upregulated angiogenesis, and multiple defects in antigen presentation machinery (e.g. Tap1 p.Y488C and Psmb8 p.A275P mutations) and interferon response pathways (e.g. copy number losses of loci including IFN genes and reduced phosphorylation of JAK/STAT pathway members). The defect in MHC class I expression could be overcome in CT2Aluc by interferon-g treatment, which may underlie the modest efficacy of some immunotherapy combinations. Additionally, CT2A-luc demonstrated substantial baseline secretion of the CCL-2, CCL-5, and CCL-22 chemokines, which play important roles as myeloid chemoattractants. Conclusion: Although the clinical contexts that can be modeled by GL261 and CT2A for huGBM are limited, CT2A may be an informative model of immunotherapy resistance due to its deficits in antigen presentation machinery and interferon response pathways. [ABSTRACT FROM AUTHOR]

Primary mesenchymal tumours of the pleura are uncommon and can be diagnostically challenging due to their overlapping histopathologic and immunophenotypic features. Herein we discuss selected mesenchymal tumours of the pleura, including solitary fibrous tumour, calcifying fibrous tumour, desmoid fibromatosis, synovial sarcoma, schwannoma, malignant peripheral nerve sheath tumour, inflammatory myofibroblastic tumour, follicular dendritic cell sarcoma, epithelioid hemangioendothelioma, and desmoplastic small round cell tumour. We review their clinicopathologic characteristics, along with an update on the relevant immunohistochemical and molecular features. [ABSTRACT FROM AUTHOR]

Odontogenic myxomas (OMs) represent asymptomatic, slowly expanding gnathic lesions with aggressive biological behaviour. Though the spectrum of OMs remains classical with multilocular radiolucency and presentation of stellate-shaped cells embedded in a mucoid stroma, they may mimic many other lesions radiographically or histopathologically. We hereby discuss a case of OM in a 28-year-old woman with special emphasis on pathogenesis and differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Gastric staple line leak treatment after laparoscopic sleeve gastrectomy (LSG) remains challenging. Regenerative medicine is gaining place in the accelerated treatment of damaged tissues. This study presents the first series of gastric leak treatment after LSG using endoscopic intragastric administration of combined autologous mesenchymal stem cells (MSC) and platelet-rich plasma (PRP). Methods: MSC-PRP harvesting and endoscopic administration techniques are described in detail. Data were prospectively gathered and analyzed. Primary endpoints were morbidity/mortality rates and fistula closure time. Results: Twelve patients (9 women, 3 men) were included. Median age was 41.5 years, median weight 105.5 kg and median BMI 38.9 kg/m2. Median time to gastric staple line leak detection was 10 days post-LSG. Median time between re-laparoscopy and MSC-PRP administration was 5 days. MSC-PRP endoscopic administration was successfully performed and tolerated by all patients, with median procedure duration of 27 min and minimal blood loss. Four postoperative complications were noted: two patients with increased tibial pain at tibial puncture site, one with tibial hematoma, and one with epigastric pain/dysphagia. Median length of hospital stay was 1 day. Gastric leak healing occurred after a median of 14 days, only two patients requiring a second MSC-PRP endoscopic injection. Median follow-up was 19 months, all patients being in good health at last contact. Conclusion: Endoscopic administration of combined autologous MSC-PRP seems to be a good option for treatment of gastric leaks after sleeve gastrectomy. It is a challenging procedure that should be performed in specialized bariatric centers by expert bariatric surgeons and endoscopists after meticulous patient selection. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite an in-depth understanding of Epstein–Barr virus-associated epithelial and lymphoid tumors, there is a paucity of knowledge concerning mesenchymal tumors associated with the Epstein–Barr virus. Our objective with this review article is to provide a comprehensive reference, offering current insights into the clinical features, pathological characteristics, pathophysiology, prognostic factors, and current therapeutic approaches of Epstein–Barr virus-associated mesenchymal tumors. The Epstein–Barr virus (EBV) is associated with various tumor types, including nasopharyngeal carcinoma and lymphoproliferative disorders. While much is known about EBV-related epithelial and lymphoid tumors, there is a paucity of knowledge concerning EBV-associated mesenchymal tumors. This review aims to provide a comprehensive overview of EBV-associated mesenchymal tumors, encompassing their clinical features, pathological characteristics, pathophysiology, prognostic factors, and current treatment approaches. Through an extensive literature search using the PubMed database, we were able to identify three distinct EBV-associated mesenchymal tumors: EBV-associated smooth muscle tumors, inflammatory pseudotumor-like follicular dendritic cell sarcomas, and EBV-associated osteosarcomas. Although this review extensively explored the different aspects of these mesenchymal tumors, our comprehension of the underlying pathophysiology in this context is still incomplete. Therefore, we hope that this review paper will not only serve as a valuable repository of information but also serve as a catalyst for prospective in vitro and in vivo research studies to bridge the existing knowledge gap surrounding pathophysiology, ultimately making an important contribution to shaping future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC) pre-conditioning with interleukin-1 alpha (IL-1ɑ) drives MSCs toward a potent anti-inflammatory phenotype. The aim of this study was to assess the therapeutic potential of intra-arterially administered IL-1ɑ preconditioned MSCs, after experimental cerebral ischaemia in mice. After 3 h from the start of middle cerebral artery occlusion, animals were treated with vehicle, 9.1 × 104 non-conditioned or IL-1ɑ preconditioned MSCs by intra-arterial administration. Animals were allowed to recover for 1.5 h after treatment to measure cerebral blood flow (CBF), and 3 days or 14 days post-stroke to evaluate lesion volume and functional outcomes. At 3-days post-stroke preconditioned MSCs reduced (by 67%) lesion volume and increased CBF (by 32%) compared to vehicle, while non-conditioned MSCs had no effect. A separate cohort of animals recovered to 14 days post-stroke also showed reduced infarct volume (by 51%) at 48 h (assessed by MRI) and better functional recovery at 14 days when treated with preconditioned MSCs when compared to vehicle. Preconditioning MSCs with IL-1α increases their neuroprotective capability and improves functional recovery after delayed intra-arterial administration. With increasing use of thrombectomy, the adjunct use of preconditioned MSCs therefore represents a highly relevant therapy to improve outcomes in ischemic stroke. [ABSTRACT FROM AUTHOR]

Visceral leiomyosarcoma is well described in dogs, but information about non-visceral locations and prevalence is lacking. The diagnosis of leiomyosarcoma is challenging without a gold standard, and often includes the use of immunohistochemical (IHC) stains. We used defined histopathologic patterns, histochemical staining, and IHC staining for smooth muscle actin (SMA), desmin, and laminin to characterize suspected non-visceral leiomyosarcoma in dogs at a single academic institution. In a retrospective search, we identified 24 dogs with a definitive or suspected histologic diagnosis of leiomyosarcoma in a non-visceral location. Histopathology results and clinical details were obtained. Biopsy sections were reviewed by a single pathologist using standardized histologic criteria, including light microscopic appearance, immunohistochemistry (more than two-thirds of neoplastic cells labeled with SMA and desmin or laminin), and histochemical staining (minimal-to-mild matrix deposition by Masson trichrome). Of the 24 cases of possible non-visceral leiomyosarcomas, 4 were consistent with a definitive diagnosis of non-visceral leiomyosarcoma (3) or leiomyoma (1) based on the established criteria. Only the leiomyoma had more than two-thirds of neoplastic cells label with all 3 markers; all 3 leiomyosarcomas had more than two-thirds of neoplastic cells label with SMA and laminin. Our data highlight the uncommon nature of non-visceral leiomyosarcoma and the importance of IHC for their diagnosis. A definitive diagnosis could not be made based on SMA alone, and desmin was not useful in this cohort. Further studies are needed to clarify the histopathologic, IHC, and clinical features of canine non-visceral SMA-positive mesenchymal tumors.

Abstract Background Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that are supported by a complex extracellular matrix and immunosuppressive microenvironment. To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen. A top hit was the cancer-associated, proteoglycan subunit synthesis enzyme UDP-glucose dehydrogenase (UGDH). Methods Immunohistochemistry was used to characterize UGDH expression in histological and molecular subtypes of EOC. EOC cell lines were subtyped according to the molecular subtypes and the functional effects of modulating UGDH expression in vitro and in vivo in C1/Mesenchymal and C4/Differentiated subtype cell lines was examined. Results High UGDH expression was observed in high-grade serous ovarian cancers and a distinctive survival prognostic for UGDH expression was revealed when serous cancers were stratified by molecular subtype. High UGDH was associated with a poor prognosis in the C1/Mesenchymal subtype and low UGDH was associated with poor prognosis in the C4/Differentiated subtype. Knockdown of UGDH in the C1/mesenchymal molecular subtype reduced spheroid formation and viability and reduced the CD133 + /ALDH high TIC population. Conversely, overexpression of UGDH in the C4/Differentiated subtype reduced the TIC population. In co-culture models, UGDH expression in spheroids affected the gene expression of mesothelial cells causing changes to matrix remodeling proteins, and fibroblast collagen production. Inflammatory cytokine expression of spheroids was altered by UGDH expression. The effect of UGDH knockdown or overexpression in the C1/ Mesenchymal and C4/Differentiated subtypes respectively was tested on mouse intrabursal xenografts and showed dynamic changes to the tumor stroma. Knockdown of UGDH improved survival and reduced tumor burden in C1/Mesenchymal compared to controls. Conclusions These data show that modulation of UGDH expression in ovarian cancer reveals distinct roles for UGDH in the C1/Mesenchymal and C4/Differentiated molecular subtypes of EOC, influencing the tumor microenvironmental composition. UGDH is a strong potential therapeutic target in TICs, for the treatment of EOC, particularly in patients with the mesenchymal molecular subtype.

Glioblastoma (GBM) is one of the most aggressive types of cancer and exhibits profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of patients with GBM has led to an improved categorization into various tumour subtypes with different prognoses and disease management. In this work, we have exploited the benefits of genome‐wide multi‐omic approaches to identify potential molecular vulnerabilities existing in patients with GBM. Integration of gene expression and DNA methylation data from both bulk GBM and patient‐derived GBM stem cell lines has revealed the presence of major sources of GBM variability, pinpointing subtype‐specific tumour vulnerabilities amenable to pharmacological interventions. In this sense, inhibition of the AP‐1, SMAD3 and RUNX1/RUNX2 pathways, in combination or not with the chemotherapeutic agent temozolomide, led to the subtype‐specific impairment of tumour growth, particularly in the context of the aggressive, mesenchymal‐like subtype. These results emphasize the involvement of these molecular pathways in the development of GBM and have potential implications for the development of personalized therapeutic approaches.

The term fibroblast has been used generally to describe spindle-shaped stromal cells of mesenchymal origin that produce extracellular matrix, establish tissue structure, and form scar. Current evidence has found that cells with this morphology are highly heterogeneous with some fibroblastic cells actively participating in both innate and adaptive immune defense. Detailed analysis of barrier tissues such as skin, gut, and lung now show that some fibroblasts directly sense pathogens and other danger signals to elicit host defense functions including antimicrobial activity, leukocyte recruitment, and production of cytokines and lipid mediators relevant to inflammation and immunosuppression. This review will synthesize current literature focused on the innate immune functions performed by fibroblasts at barrier tissues to highlight the previously unappreciated importance of these cells in immunity.

Abstract Background The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1 + stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfra low stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. Results We show here that a Twist2 stromal lineage, which constitutes the Pdgfra low stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2 + subpopulations also play a role in crypt regeneration but not homeostasis. Conclusions These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration.

Background: Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that are supported by a complex extracellular matrix and immunosuppressive microenvironment. To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen. A top hit was the cancer-associated, proteoglycan subunit synthesis enzyme UDP-glucose dehydrogenase (UGDH). Methods: Immunohistochemistry was used to characterize UGDH expression in histological and molecular subtypes of EOC. EOC cell lines were subtyped according to the molecular subtypes and the functional effects of modulating UGDH expression in vitro and in vivo in C1/Mesenchymal and C4/Differentiated subtype cell lines was examined. Results: High UGDH expression was observed in high-grade serous ovarian cancers and a distinctive survival prognostic for UGDH expression was revealed when serous cancers were stratified by molecular subtype. High UGDH was associated with a poor prognosis in the C1/Mesenchymal subtype and low UGDH was associated with poor prognosis in the C4/Differentiated subtype. Knockdown of UGDH in the C1/mesenchymal molecular subtype reduced spheroid formation and viability and reduced the CD133 + /ALDH high TIC population. Conversely, overexpression of UGDH in the C4/Differentiated subtype reduced the TIC population. In co-culture models, UGDH expression in spheroids affected the gene expression of mesothelial cells causing changes to matrix remodeling proteins, and fibroblast collagen production. Inflammatory cytokine expression of spheroids was altered by UGDH expression. The effect of UGDH knockdown or overexpression in the C1/ Mesenchymal and C4/Differentiated subtypes respectively was tested on mouse intrabursal xenografts and showed dynamic changes to the tumor stroma. Knockdown of UGDH improved survival and reduced tumor burden in C1/Mesenchymal compared to controls. Conclusions: These data show that modulation of UGDH expression in ovarian cancer reveals distinct roles for UGDH in the C1/Mesenchymal and C4/Differentiated molecular subtypes of EOC, influencing the tumor microenvironmental composition. UGDH is a strong potential therapeutic target in TICs, for the treatment of EOC, particularly in patients with the mesenchymal molecular subtype. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Desmoplastic round cell tumor, though rare, must be taken into consideration as a differential diagnosis, thus aiding in early evaluation and changing the trajectory of the natural history of the disease condition, and improving the prognosis of patients. Desmoplastic small round cell tumor is a rare, aggressive tumor of mesenchymal origin with an incidence of 0.74 cases per million. We present a young adult with a periumbilical mass who was diagnosed as a desmoplastic round cell tumor and later was treated with exploratory laparotomy and resection of the tumor with no recurrence during a 6‐month follow‐up period. [ABSTRACT FROM AUTHOR]

Objectives: Fine needle aspiration cytology (FNAC) is a minimally invasive method for sampling a heterogenous lesion. It is one of the first-line investigations in the evaluation of soft tissue tumours. However, the heterogeneity of mesenchymal lesions pose a challenge to the cytological diagnosis. The present study aims at evaluation of the cytomorphological findings of mesenchymal lesions on FNAC along with their histopathological correlation. Material and Methods: This was a retrospective study conducted over a period of 1 year from January 2021 to January 2022. All the patients of cytologically diagnosed mesenchymal lesions on their FNA aspirates were included in the study. Cytomorphology of the May Grunwald Giemsa and Papanicolaou stained slides were examined and correlated with clinical and histopathological details wherever available. Results: Out of the 90 patients, 69 (76.7%) were males and 21 (23.3%) were females. Maximum number of cases were in 4--5th decade of life. The lower limb was found to be the most common site (57.8%) for the mesenchymal lesions. Majority of the cases on FNA in our study were found to be benign -- 79 (87.8%), while only 11 cases were malignant (12.2%). On cytological examination, spindle cell lesions were most common followed by adipocytic lesions. Based on the cyto-histological correlation, sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of FNAC in diagnosis of mesenchymal lesion was 78.6%, 100%, 92.5%, 100% and 94.1% respectively. Conclusion: FNAC is a simple and minimally invasive tool that plays an important role in triaging patients with good specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stem cells (MSCs) are considered to be the most promising stem cell type for cell-based therapies in regenerative medicine. Based on their potential to home to diseased body sites following a therapeutically application, these cells could (i) differentiate then into organspecific cell types to locally restore injured cells or, most prominently, (ii) foster tissue regeneration including immune modulations more indirectly by secretion of protective growth factors and cytokines. As tissue-resident stem cells of mesenchymal origin, these cells are morphologically and even molecularly-at least concerning the classical marker genes-indistinguishable from similar lineage cells, particularly fibroblasts. Methods: Here we used microarray-based gene expression and global DNA methylation analyses as well as accompanying computational tools in order to specify differences between MSCs and fibroblasts, to further unravel potential identity genes and to highlight MSC signaling pathways with regard to their trophic and immunosuppressive action. Results: We identified 1352 differentially expressed genes, of which in the MSCs there is a strong signature for e.g., KRAS signaling, known to play essential role in stemness maintenance, regulation of coagulation and complement being decisive for resolving inflammatory processes, as well as of wound healing particularly important for their regenerative capacity. Genes upregulated in fibroblasts addressed predominately transcription and biosynthetic processes and mapped morphological features of the tissue. Concerning the cellular identity, we specified the already known HOX code for MSCs, established a potential HOX code for fibroblasts, and linked certain HOX genes to functional cell-type-specific properties. Accompanied methylation profiles revealed numerous regions, especially in HOX genes, being differentially methylated, which might provide additional biomarker potential. Discussion: Conclusively, transcriptomic together with epigenetic signatures can be successfully be used for the definition (cellular identity) of MSCs versus fibroblasts as well as for the determination of the superior functional properties of MSCs, such as their immunomodulatory potential. [ABSTRACT FROM AUTHOR]