Epigenetic modulation in sensitizing metastatic sarcomas to therapies and overcoming resistance

Sarcomas are a class of rare malignancies of mesenchymal origin with a heterogeneous histological spectrum. They are classically associated with poor outcomes, especially once metastasized. A path to improving clinical outcomes may be made through modifying the epigenome, where a variety of sarcomas demonstrate changes that contribute to their oncogenic phenotypes. This Perspective article identifies and describes changes in the sarcoma genome, while discussing specific epigenetic changes and their effect on clinical outcomes. Clinical attempts at modulating epigenetics in sarcoma are reviewed, as well as potential implications of these studies. Epigenetic targets to reverse and delay chemotherapy resistance are discussed. Future directions with primary next steps are proposed to invigorate the current understanding of epigenetic biomarkers to enact targeted therapies to epigenetic phenotypes of sarcoma subtypes. Modifications to prior studies, as well as proposed clinical steps, are also addressed.

An aggressive fibromatosis in the palm of a female child: A rare case

Aggressive fibromatosis is the locally aggressive benign tumor of mesenchymal origin. It can be found in any part of the body. However, abdomen is the most common site of this lesion. It has a predilection to females between 15 and 60 years. We report the case of a 16-month-old female child with an aggressive fibromatosis in her right palm. The location and age of presentation make this a rare case. She was diagnosed by histopathological examination and the mass was excised. The patient was advised for follow-up examination due to the high degree of recurrence of this tumor.

Injection site sarcomas in other species than the domestic cat

Injection site sarcomas (ISS) are tumours of tissues of mesenchymal origin that occur at an injection site. These tumours have been mainly described in cats as Feline injection-site sarcoma (FISS), but suspected cases have also been described in other species such as dogs. In other species than the domestic cat, these tumours are however much rarer. As a result, the body of literature is limited. This review aims to summarize the knowledge regarding ISS in species other than the domestic cat. In general, it seems that ISS can occur in a wide range of animals and that similar treatment strategies are employed as in cats. Like in cats, it seems that the benefit of the reasons for injection (such as vaccination and microchip implantation) could outweigh the risk of ISS development in other species.

PAX2+ Mesenchymal Origin of Gonadal Supporting Cells Is Conserved in Birds

During embryonic gonadal development, the supporting cell lineage is the first cell type to differentiate, giving rise to Sertoli cells in the testis and pre-granulosa cells in the ovary. These cells are thought to direct other gonadal cell lineages down the testis or ovarian pathways, including the germline. Recent research has shown that, in contrast to mouse, chicken gonadal supporting cells derive from a PAX2/OSR1/DMRT1/WNT4 positive mesenchymal cell population. These cells colonize the undifferentiated genital ridge during early gonadogenesis, around the time that germ cells migrate into the gonad. During the process of somatic gonadal sex differentiation, PAX2 expression is down-regulated in embryonic chicken gonads just prior to up-regulation of testis- and ovary-specific markers and prior to germ cell differentiation. Most research on avian gonadal development has focused on the chicken model, and related species from the Galloanserae clade. There is a lack of knowledge on gonadal sex differentiation in other avian lineages. Comparative analysis in birds is required to fully understand the mechanisms of avian sex determination and gonadal differentiation. Here we report the first comparative molecular characterization of gonadal supporting cell differentiation in birds from each of the three main clades, Galloanserae (chicken and quail), Neoaves (zebra finch) and Palaeognathe (emu). Our analysis reveals conservation of PAX2+ expression and a mesenchymal origin of supporting cells in each clade. Moreover, down-regulation of PAX2 expression precisely defines the onset of gonadal sex differentiation in each species. Altogether, these results indicate that gonadal morphogenesis is conserved among the major bird clades.

Inflammatory Myofibroblastic Tumor of the Larynx: Case Report

Inflammatory Myofibroblastic Tumor is usually a benign tumor of mesenchymal origin that is rarely found in the larynx. This case explores the unique laryngeal location and presentation of this tumor as well as the challenging radiographic and histologic findings.

Mammoth Lipoma of the Back - A Case Report

Lipomas are very common benign tumours of mesenchymal origin. Lipomas occur with an estimated prevalence rate of 2.1 per 1000 amongst all tumours that can involve in the human body. There have been only 5 cases of giant lipomas published to date.1-5 This case report describes a unique giant lipoma located in the upper back with 30 x 30 cm in measurement and weighing 3800 grams.

Treatment Strategies for Metastatic Soft Tissue Sarcomas

Soft tissue sarcomas (STS) are a diverse group of rare tumors of mesenchymal origin with different clinical, histologic and molecular characteristics [...]

The Viscous Juncture-Juxta Articular Myxoma

Juxta-articular myxoma is an uncommon, benign, hypocellular, bland, myxoid neoplasm of mesenchymal origin occurring within the vicinity of a large joint such as the knee. The neoplasm is exemplified within 16 years to 83 years with a median age at 43 years. A male predominance is observed with a male to a female proportion of nearly 3:1. Localized tissue destruction arising on account of the neoplasm can engender pain or nerve palsy. The minimally cellular tumefaction depicts an abundant, myxoid stroma admixed with a non-malignant proliferation of spindle-shaped cells. Juxta-articular myxoma is immune reactive to vimentin and CD34.

Metabolic Heterogeneity of Brain Tumor Cells of Proneural and Mesenchymal Origin

Background: Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. Methods: BTICs of different subtypes representing tumor heterogeneity were challenged with OXPHOS (oxidative phosphorylation) inhibition to assess the differential effects of metabolic intervention on key resistance features. Results: Whereas mesenchymal BTICs were more invasive, more glycolytic and less responsive to OXPHOS-inhibition, proneural BTICs were less invasive, catabolized glucose more via the pentose phosphate pathways, and responded better to OXPHOS inhibition. Conclusion: Targeting glycolysis may be a promising approach to inhibit highly invasive tumor cells of mesenchymal origin, whereas proneural cells are more responsive to OXPHOS inhibition. Future clinical trials exploring metabolic interventions should account for metabolic heterogeneity of brain tumors to overcome resistance to current treatments.