Explore the vast range of titles available.

A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM), a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq) performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections.

Epithelial cell adhesion molecule (EpCAM) has been used as diagnostic/prognostic marker and therapeutic target. The aim of the present study was to compare immunoreactivity of antibodies against distinct epitopes in the ectodomain of EpCAM for detection of carcinoma from different primary sites and of different histological types in effusions and peritoneal wash. Two antibodies against epitopes in the EGF-like domain I (clones Moc-31 and Ber-EP4) and one antibody against the epitope in the cysteine-poor region (158210) of EpCAM were used (all commercially available). Independently of the clone used, EpCAM overexpression was observed in almost all samples when all the adenocarcinoma samples were analyzed together. By using Moc-31, EpCAM overexpression was observed in all samples of adenocarcinoma. Absence of EpCAM overexpression was observed in a few adenocarcinoma samples at some sites of tumor origin, including ovary, breast and stomach, when Ber-EP4 and 158210 were used. Regarding carcinomas aside from adenocarcinomas, histological types, such as squamous cell, urothelial and small cell carcinoma showed different degrees of EpCAM expression according to the antibody used. In squamous cell carcinoma, overexpression was observed only with the clone 158210. It was concluded that, overall, most samples of metastatic carcinoma from effusions showed overexpression of EpCAM. However, there are significant variations in its detection according to the primary site, histological type of the carcinoma and depending on the antibody used. Thus, the use of more than one type of anti-EpCAM antibody would increase the chance of its detection in metastatic carcinoma effusion.

PurposePenile cancer is highly prevalent in low- and middle-income countries, with significant morbidity and mortality rates. The first Brazilian consensus provides support to improve penile cancer patients’ outcomes, based on expert’s opinion and evidence from medical literature.MethodsFifty-one Brazilian experts (clinical oncologists, radiation oncologists, urologists, and pathologists) assembled and voted 104 multiple-choice questions, confronted the results with the literature, and ranked the levels of evidence.ResultsHealthcare professionals need to deliver more effective communication about the risk factors for penile cancer. Staging and follow-up of patients include physical examination, computed tomography, and magnetic resonance imaging. Close monitoring is crucial, because most recurrences occur in the first 2–5 years. Lymph-node involvement is the most important predictive factor for survival, and management depends on the location (inguinal or pelvic) and the number of lymph nodes involved. Conservative treatment may be helpful in selected patients without compromising oncological outcomes; however, surgery yields the lowest rate of local recurrence.ConclusionThis consensus provides an essential decision-making orientation regarding this challenging disease.