Kawasaki disease (KD) is a systemic vasculitis affecting children younger than 5 years of age. Early period in life is marked by rapid somatic growth with cell proliferation and immaturity of the immunity with dominant innate immune system. Coronary complications in KD are the most common acquired heart disease in children, yet the diagnosis of KD still depends on the clinical diagnostic criteria. Glossy red lips and conjunctival injection are characteristic signs enabling pediatricians to make the initial diagnosis of KD; however, little is known why these are so characteristic. The diagnostic criteria of KD seem to be scattered in seemingly irrelevant body systems such as the eyes, lips, skin, and heart. KD is classified as a connective tissue disease. Recently, red blood cells (RBCs) have emerged as important modulators in innate immune response. RBCs are reported to participate in extracellular matrix remodeling and upregulating matrix metalloproteinase (MMP) expression in dermal fibroblasts. Also, fibroblast growth factors and microRNAs associated with fibrosis are drawing attention in KD. The cardinal signs of KD appear at the border of muco-cutaneous junction. Head and neck regions are abundant in tissues undergoing epithelial-to-mesenchymal transition (EMT). Interstitial carditis and valve insufficiency as well as coronary arterial lesions may complicate KD, and these lesions present in tissues that originated from epicardial progenitor cells by EMT. Having reviewed the recent research on KD, we presume that the signs of KD present at borders between keratinized and non-keratinized stratified squamous epithelium where the EMT is still ongoing for the rapid somatic growth where RBCs are recruited as an innate immune response and to prevent excessive fibrosis in mucosa. KD presents scarcely in adults with somatic growth and immune maturation completed. In this review, we attempted to explain the reasons for the clinical manifestations of KD and to search for a link among the diagnostic clues in the perspective of EMT during the somatic growth and immune system maturation in children with KD.

Metaplastic breast cancer (MpBC) is an uncommon aggressive malignancy that is associated with a poor prognosis. Due to its rarity, the relationships between the clinical and pathological features of MpBC, treatment approach, and clinical outcomes remain underexplored. In the following review article, we synthesize the existing data on the clinical, pathological and genomic features, management, and outcomes of MpBC. We also identify potential targets for future clinical trials.

Sustained, transmural inflammation of the bowel wall may result in the development of a fistula in Crohn\'s disease (CD). Fistula formation is a recognized complication and cause of morbidity, occurring in 40% of patients with CD. Despite advanced treatment, one-third of patients experience recurrent fistulae. Development of targeting treatment for fistulae will be dependent on a more in depth understanding of its pathogenesis. Presently, pathogenesis of CD-associated fistulae remains poorly defined, in part due to the lack of accepted in vitro tissue models recapitulating the pathogenic cellular lesions linked to fistulae and limited in vivo models. This review provides a synthesis of the existing knowledge of the histopathological, immune, cellular, genetic, and microbial contributions to the pathogenesis of CD-associated fistulae including the widely accredited contribution of epithelial-to-mesenchymal transition, upregulation of matrix metalloproteinases, and overexpression of invasive molecules, resulting in tissue remodeling and subsequent fistula formation. We conclude by exploring how we might utilize advancing technologies to verify and broaden our current understanding while exploring novel causal pathways to provide further inroads to future therapeutic targets.

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

This review provides an overview of the current understanding of the ontogeny and biology of melanoma stem cells in cutaneous malignant melanoma. This article also summarizes and evaluates the current knowledge of the underlying epigenetic mechanisms, the regulation of melanoma progress by the tumor microenvironment as well as the therapeutic implications and applications of these novel insights, in the setting of personalized medicine. Unraveling the complex ecosystem of cutaneous malignant melanoma and the interplay between its components, aims to provide novel insights into the establishment of efficient therapeutic strategies.

In the past years, a multitude of studies has been published in the field of pancreatic organogenesis to interrogate the critical regulators of endocrine lineage segregation. Preliminary, transcription factors are guiding the transcriptional hierarchy of the endocrine specified cells, underpinning the importance of open chromatin formation. Signaling pathways either inhibit or accelerate the transcriptional landscape of pancreatic organogenesis. Thus, the fine-tuned process in the former pancreatic multipotent progenitors in the mechanism of lineage segregation needs to be elucidated more precisely for unraveling the temporal-spatial lineage-determining factors.Previously, Willmann et al. described candidate gene regulators of lineage segregation during the secondary transition of pancreatic organogenesis. At embryonic stage (E) 12.5, the former multipotent pancreatic progenitor compartmentalizes into the acinar, ductal, and endocrine lineage. In the adult pancreatic gland, acinar cells secrete enzymes that are transported by the duct to the duodenum. In contrast, the endocrine cells are clustered within the acinar tissue in the Islets of Langerhans. These Islets of Langerhans consist of a subset of α, δ, ε, and PP cells and β cells, and the function of the α and β cells is predominantly described by regulating glucose homeostasis, contrary, the function of the additional subtypes in the Islets of Langerhans remains still unclear and is rather pointing to a supportive role for the α and β cells.The essential wave of endocrine precursor cells emerges at E 14.5 out of the ductal cord-like structure in a process called epithelial-to-mesenchymal transition (EMT). This EMT is a reversible and incomplete process that includes significant intermedia states. As EMT is in focus in the field of cancer research, missense in endocrine lineage segregation is linking to a progression of pancreatic cancer, to be more precise in adenocarcinoma, e.g., meaning pancreatic ductal adenocarcinoma.Thus, the previous review will further accelerate the understanding of EMT about endocrine lineage segregation, respective pancreatic ductal adenocarcinoma, and introduces factors previously only known for either lineage segregation or related in cancer disease into a complete picture.

Inflammatory bowel disease is known as the most chronic inflammatory disorder in colon, which subsequently progresses to intestinal obstruction and fistula formation. Many studies to date for the treatment of IBD have been focused on inflammation. However, most of the anti-inflammatory agents do not have anti-fibrotic effects and could not relieve intestinal stricture in IBD patients. Because preventing or reversing intestinal fibrosis in IBD is a major therapeutic target, we analyzed the papers focusing on TGF-β signaling in intestinal fibrosis. TGF-β is a good candidate to treat the intestinal fibrosis in IBD which involves TGF-β signaling pathway, EMT, EndMT, ECM, and other regulators. Understanding the mechanism involved in TGF-β signaling will contribute to the treatment and diagnosis of intestinal fibrosis occurring in IBD as well as the understanding of the molecular mechanisms underlying the pathogenesis.

Fibroblast growth factors (FGFs) are diffusible polypeptides released by a variety of cell types. FGF8 subfamily members regulate embryonic development processes through controlling progenitor cell growth and differentiation, and are also functional in adults in tissue repair to maintain tissue homeostasis. FGF8 family members exhibit unique binding affinities with FGF receptors and tissue distribution patterns. Increasing evidence suggests that, by regulating multiple cellular signaling pathways, alterations in the FGF8 subfamily are involved in craniofacial development, odontogenesis, tongue development and salivary gland branching morphogenesis. Aberrant FGF signaling transduction, caused by mutations as well as abnormal expression or isoform splicing, plays an important role in the development of oral diseases. Targeting FGF8 subfamily members provides a new promising strategy for the treatment of oral diseases. The aim of this review was to summarize the aberrant regulations of FGF8 subfamily members and their potential implications in oral‑maxillofacial diseases.

Glioblastoma (GB) is the most aggressive primary brain tumor in adults. The aggressive nature of GB has been attributed to the presence of cancer stem cells (CSCs) which drive tumorigenesis and are thought to be the root cause of the disease. Circulating tumor stem cells (CTSCs), which can be derived from CSCs, have been identified in numerous types of cancer including GB, have been proposed to contribute to local and distant recurrence. There are many technical difficulties in studying CTSCs, therefore there is a significant gap in the literature pertaining to how they arise and function, and how the understanding of the biology of CTSCs could elucidate the underlying cause of local recurrence and metastasis. An initial epithelial-to-mesenchymal transition (EMT) followed by mesenchymal-to-epithelial transition involving these primitive cells appear to be the critical processes underpinning metastasis. This review focuses on the association between CSCs undergoing EMT to become CTSCs, and how this could arise from the CSC subpopulation in GB, and contribute to the understanding of the pathogenesis and treatment.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In spite of various attempts to ameliorate outcome by escalating treatment, significant improvement is lacking particularly in the adjuvant setting. It has been proposed that cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) are at least partially responsible for therapy resistance in CRC. The epithelial cell adhesion molecule (EpCAM) was one of the first CSC antigens to be described. Furthermore, an EpCAM-specific antibody (edrecolomab) has the merit of having launched the era of monoclonal antibody treatment in oncology in the 1990s. However, despite great initial enthusiasm, monoclonal antibody treatment has not proven successful in the adjuvant treatment of CRC patients. In the meantime, new insights into the function of EpCAM in CRC have emerged and new drugs targeting various epitopes have been developed. In this review article, we provide an update on the role of EpCAM in CSCs and EMT, and emphasize the potential predictive selection criteria for novel treatment strategies and refined clinical trial design. Stem Cells Translational Medicine 2018;7:495-501.