Impaired physical ability in patients with transfusion-dependent β-thalassaemia: Can regular physical activity be a countermeasure?

Transfusion-dependent β-thalassaemia (TDβT) is a genetic disorder characterised by reduced or absent β-globin chain synthesis, resulting in chronic anaemia. Treatment consists of regular blood transfusions and chelation therapy to limit iron overload and its negative effects on organs (e.g.

Sweat Gland Tumors Arising on Acral Sites: A Molecular Survey.

Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet.

Digital Papillary Adenocarcinoma in Nonacral Skin: Clinicopathologic and Genetic Characterization of 5 Cases.

Digital papillary adenocarcinoma (DPA) is a rare sweat gland neoplasm that has exceptionally been reported outside acral locations. Recently, human papillomavirus 42 was identified as the main oncogenic driver of DPA. Herein, we report 5 tumors arising in extra-acral locations predominantly in the female anogenital skin.

Distinct Regulation of EZH2 and its Repressive H3K27me3 Mark in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is an aggressive skin cancer for which Merkel cell polyomavirus integration and expression of viral oncogenes small T and Large T have been identified as major oncogenic determinants. Recently, a component of the PRC2 complex, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) that induces H3K27 trimethylation as a repressive mark has been proposed as a potential therapeutic target in MCC. Because divergent results have been reported for the levels of EZH2 and trimethylation of lysine 27 on histone 3, we analyzed these factors in a large MCC cohort to identify the molecular determinants of EZH2 activity in MCC and to establish MCC cell lines' sensitivity to EZH2 inhibitors.

Antibody-Drug Conjugates as an Emerging Therapy in Oncodermatology.

Antibody-drug conjugates (ADCs) are an emerging class of therapeutics, with twelve FDA- and EMA-approved drugs for hematological and solid cancers. Such drugs consist in a monoclonal antibody linked to a cytotoxic agent, allowing a specific cytotoxicity to tumor cells. In recent years, tremendous progress has been observed in therapeutic approaches for advanced skin cancer patients.

Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells.

Adcitmer , a new CD56-targeting monomethyl auristatin E-conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma.

Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required.

Objectives: To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer ) targeting CD56 in preclinical models of MCC.

Merkel Cell Polyomavirus‒Negative Merkel Cell Carcinoma Originating from In Situ Squamous Cell Carcinoma: A Keratinocytic Tumor with Neuroendocrine Differentiation.

Although virus-negative Merkel cell carcinoma (MCC) is characterized by a high frequency of UV-induced mutations, the expression of two viral oncoproteins is regarded as a key mechanism driving Merkel cell polyomavirus‒positive MCC. The cells in which these molecular events initiate MCC oncogenesis have yet not been identified for both MCC subsets. A considerable proportion of virus-negative MCC is found in association with squamous cell carcinoma (SCC), suggesting (i) coincidental collision, (ii) one providing a niche for the other, or (iii) one evolving from the other.

Merkel Cell Polyomavirus T Antigens Induce Merkel Cell-Like Differentiation in GLI1-Expressing Epithelial Cells.

Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). It is still under discussion, in which cells viral integration and MCC development occurs. Recently, we demonstrated that a virus-positive MCC derived from a trichoblastoma, an epithelial neoplasia bearing Merkel cell (MC) differentiation potential.

Polyomavirus-Positive Merkel Cell Carcinoma Derived from a Trichoblastoma Suggests an Epithelial Origin of this Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells. To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing.

Muscle Oxygen Supply and Use in Type 1 Diabetes, From Ambient Air to the Mitochondrial Respiratory Chain: Is There a Limiting Step?

Objective: Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach.

Research Design And Methods: We compared 16 adults with T1D with 16 strictly matched healthy control subjects.

Prion strain-dependent tropism is maintained between spleen and granuloma and relies on lymphofollicular structures.

In peripherally acquired prion diseases, prions move through several tissues of the infected host, notably in the lymphoid tissue, long before the occurrence of neuroinvasion. Accumulation can even be restricted to the lymphoid tissue without neuroinvasion and clinical disease. Several experimental observations indicated that the presence of differentiated follicular dendritic cells (FDCs) in the lymphoid structures and the strain type are critical determinants of prion extraneural replication.

Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review.

Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. This neoplasia features aggressive behavior, resulting in a 5-year overall survival rate of 40%. In 2008, Feng et al.

Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma.

In 2008, Feng et al. identified Merkel cell polyomavirus integration as the primary oncogenic event in ~80% of Merkel cell carcinoma cases. The remaining virus-negative Merkel cell carcinoma cases associated with a high mutational load are most likely caused by UV radiation.

Evaluation of mycobacteria-specific gamma interferon and antibody responses before and after a single intradermal skin test in cattle naturally exposed to M. avium subsp. paratuberculosis and experimentally infected with M. bovis.

This study reports on the diagnostic potential of IFN-γ release assays and serology for Mycobacterium bovis in six naturally M. avium subsp. paratuberculosis (Map) exposed bulls of which four were intratracheally infected with a Belgian field strain of M.

Merkel cell carcinomas infiltrated with CD33 myeloid cells and CD8 T cells are associated with improved outcome.

Background: Merkel cell carcinoma (MCC) is a rare tumor of the skin that has an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells needs better characterization.