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Origin and regenerative potential of vertebrate mechanoreceptor-associated stem cells
Widera D, Hauser S, Kaltschmidt C, Kaltschmidt B. Origin and regenerative potential of vertebrate mechanoreceptor-associated stem cells. Anatomy Research International. 2012;2012:1-9.Meissner corpuscles and Merkel cell neurite complexes are highly specialized mechanoreceptors present in the hairy and glabrous skin, as well as in different types of mucosa. Several reports suggest that after injury, such as after nerve crush, freeze injury, or dissection of the nerve, they are able to regenerate, particularly including reinnervation and repopulation of the mechanoreceptors by Schwann cells. However, little is known about mammalian cells responsible for these regenerative processes. Here we review cellular origin of this plasticity in the light of newly described adult neural crest-derived stem cell populations. We also discuss further potential multipotent stem cell populations with the ability to regenerate disrupted innervation and to functionally recover the mechanoreceptors. These capabilities are discussed as in context to cellularly reprogrammed Schwann cells and tissue resident adult mesenchymal stem cells
Immunohistochemical characterization of normal canine Merkel cells
Cutaneous Merkel cells (MCs) have been well documented in humans, but less in other mammals. In dogs, there are only a few references about immunohistochemical characterization of MCs. We present the immunohistochemical profile of MCs in the dog for the most reliable antibodies used in human medicine. Tissue samples from several locations were obtained from five adult dogs of both sexes and different age and breed, fixed in 10% buffered formalin, embedded in paraffin wax and cut in 3-mum tissue sections. The ABC method was used with different poly- and monoclonal antibodies. Positive immunoreaction was found in MCs of hair follicles, skin and mucosae of several locations in each dog studied for anticytokeratins 8, 18 and 20, anti-neurofilaments, anti-chromogranin A, anti-neuron-specific enolase, and anti-synaptophysin. Immunoreaction was always cytoplasmic with differences in intensity, pattern of intracytoplasmic distribution and reaction type. Other cytokeratins, anti-S100 protein, anti-vimentin and anti-glial fibrillary acid protein were absent in canine normal MCs.5549
Integration and democracy in the European Community: the contours of a dilemma
Wolfgang Merkel. 30 cm. He presented this paper at a seminar held at the Center for Advanced Study in the Social Sciences of the Juan March Institute in Madrid, on December 4, 1992. - T.p. Bibliography: p. 38-41
Merkel Cell Carcinoma
Merkel cell carcinoma is a rare, highly aggressive primary cutaneous tumor, predominantly affecting older patients. The pathogenesis is associated with either Merkel cell polyomavirus infection or UV-mediated damage caused by chronic sun exposure: virus-positive and virus-negative Merkel cell tumors are characterized by two different patterns of multiple DNA mutations. Virus-positive tumors are mainly diffuse in the Northern hemisphere, while virus-negative tumors have higher incidence in Australia with a predilection of fair-skinned population. Merkel cell tumor presents with asymptomatic, rapidly growing, red or violet cutaneous nodule. Histology and immunohistochemistry are necessary to confirm the diagnosis. The management of Merkel cell tumors requires a multidisciplinary approach. Surgery or definitive radiotherapy of the primary Merkel cell tumors are either treatment options for patients with localized MCC. Immune checkpoint inhibitors represent the preferred treatment option for metastatic tumors
Merkel Cell Polyomavirus and Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer. More than 80% of MCC have Merkel cell polyomavirus (MCPyV) clonally integrated into the human genome (VP-MCC) while the remaining 20% are virus negative (VN-MCC) but linked with chronic exposure to UV sunlight. MCC is particularly associated with immune suppression with 8-48 folds increase in incidence in immunosuppressive conditions. Another hallmark of VPMCC is expression of a truncated variant of one of MCPyV’s oncoproteins, i.e. large T-antigen. This thesis aims to study the role of the oncoproteins of MCPyV on inflammatory mediator regulation contributing to MCC development and on non-MCC tumor initiation and/or development. This knowledge will provide a better understanding of MCPyV-induced MCC, a prerequisite for developing novel therapeutic approaches. We have found that MCPyV fulllength large T-antigen inhibited while truncated large T antigen stimulated both early and late promoters activities of MCPyV. We have also observed that MCPyV oncoproteins upregulated CCL17/TARC and IL-33 expression in MCC. CCL17/TARC is a chemokine that helps in recruitment of regulatory T cells while IL-33 is IL-1 family member cytokine that creates immunosuppressive and pro-tumorigenic microenvironment, respectively. Human MCC tissues showed a strong staining of CCL17/TARC, CCR4, IL-33, ST2/IL1RL1 and IL1RAcP in both VP- and VN-MCC. Recent findings reported MCPyV co-infection with high-risk human papilloma virus (HR-HPV) -positive cervical cancers. We demonstrated that MCPyV oncoproteins also increase expression of HPV16/18 E6 and E7 expression that are linked with cervical cancer. Taken together, our studies have highlighted critical role of inflammatory mediators associated with MCC development. So, targeting inflammatory signaling pathways could be a better option for treating MCC
Molecular expression associated with vibrissa follicle development and differentiation
The hair follicle is a complex mini-organ formed as a result of epithelial mesenchymal interactions, provided by three different stem cell sources: epithelial, neural crest and mesenchymal. Hair follicle morphogenesis is directed by a distinct set of molecular signals which are unique to each stage of development. These interactions continue into the adult cycle, represented by periods of rapid growth (anagen), apoptosis driven regression (catagen), a period of relative quiescence (telogen) and shedding of the club hair (exogen). Many of the molecules involved have been elucidated such as Wnts, Bmps, Fgfs, TGF-ßs and Shh amongst others. However, the nature of their regulation and effect on gene expression is still unclear. Id proteins are emerging as powerful players in the transcriptional control of many fundamental biological processes, such as the cell cycle, proliferation and differentiation, apoptosis and lineage commitment. As a result, the expression patterns of Id2 and Ids were investigated by immunocytochemistry in developing and adult vibrissae. Wistar rats aged E14toP4 were used to cover all stages of vibrissae development (stages 0-6+) and 3-6 month old rats for the adult stages. This thesis reports that high Id2 expression was seen in specialised neuroendocrine cells (Merkel cells) of the hair follicle and basal epidermis, confirmed by co-expression of the Merkel cell marker, cytokeratin-20. This post-mitotic Id2 expression continued through postnatal ages and into the adult follicle. Staining with Id3 was characterised by cytoplasmic, basally polarised expression in the epithelia of stage 1-4 follicles. After this stage, expression switched to being nuclear with high levels in many different cell types including the dermal papilla, dermal sheath and outer root sheath, ш and Id3 expression was also investigated in retinole acid induced differentiation of E13.5 and E14 mystacial pads, studying the glandular morphogenesis of vibrissae and the effect on Id protein expression. Ш and Id3 immunoreactivity was cytoplasmic and polarised but no evidence of nuclear staining was seen.Id2 and ИЗ expression in developing vibrissae is reported here for the first time, describing the profiles of these proteins during hair follicle development and differentiation. These findings highlight an important cytoplasmic role for Id proteins in development and may have implications for reciprocal epithelial- mesenchymal interactions, pattern formation and stem cells in the hair follicle
Merkel cell carcinoma
Merkel cell carcinoma is a neuroendocrine skin carcinoma caused by the Merkel cell virus and ultraviolet radiation. Approximately 25 Danish patients are diagnosed each year. Merkel cell carcinoma is often located on the sun-exposed areas of the skin and definitive diagnosis is made by the pathologist. Patients are treated at the department of plastic surgery and oncology with treatment modalities including surgery, radiotherapy, immunotherapy and chemotherapy as summarised in this review.</p
Merkel cell carcinoma and Merkel cell polyomavirus: A systematic review and meta-analysis
Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first author's last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle-Ottawa scale. Crude RR was calculated from the data provided in each article. Meta-analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta-regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random-effects analysis was determined to be 6·32 (95% CI, 4·02-9·93). Global proportions of positive samples were 0·79 (95% CI, 0·72-0·84) and 0·12 (95% CI, 0·08-0·19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non-negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found. What's already known about this topic? Several studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with inconsistent results. What does study add? A systematic review and a meta-analysis including all studies from January 2008 to August 2014. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. © 2015 British Association of Dermatologists.Universidad Autónoma de Chil
Merkel Cell Carcinoma: An Immunotherapy Fairy-Tale?
Merkel cell carcinoma (MCC) is a rare, highly aggressive, neuroendocrine cutaneous tumor. The incidence of MCC is growing worldwide, and the disease-related mortality is about three-fold higher than melanoma. Since a few years ago, very little has been known about this disease, and chemotherapy has been the standard of care. Nowadays, new discoveries about the pathophysiology of this neoplasm and the introduction of immunotherapy allowed to completely rewrite the history of these patients. In this review, we provide a summary of the most important changes in the management of Merkel cell carcinoma, with a focus on immunotherapy and a landscape of future treatment strategies
Glabrous skin Merkel cell innervation at P0.
<p>Glabrous skin Merkel cell innervation at P0.</p
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