Epithelial-mesenchymal transition (EMT) is involved in physiologic processes such as embryogenesis and wound healing. A similar mechanism occurs in some tumors where cells leave the epithelial layer and gain mesenchymal particularities in order to easily migrate to other tissues. This process can explain the invasiveness and aggressiveness of these tumors which metastasize, by losing the epithelial phenotype (loss of E-cadherin, desmoplakin, and laminin-1) and acquiring mesenchymal markers (N-cadherin). Complex changes and interactions happen between the tumor cells and the microenvironment involving different pathways, transcription factors, altered expression of adhesion molecules, reorganization of cytoskeletal proteins, production of ECM-degrading enzymes, and changes in specific microRNAs. The purpose of this review is to determine particularities of the EMT process in the most common malignant cutaneous tumors (squamous cell carcinoma, basal cell carcinoma, and melanoma) which still have an increasingly high incidence. More studies are required on this topic in order to establish clear correlations. High costs related to skin cancer therapies in general as well as high impact on patients’ quality of life demand finding new, reliable prognostic and therapeutic markers with significant public health impact.
(1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.
Mycobacteria identification is crucial to diagnose tuberculosis. Since the bacillus is very small, finding it in Ziehl–Neelsen (ZN)-stained slides is a long task requiring significant pathologist’s effort. We developed an automated (AI-based) method of identification of mycobacteria. We prepared a training dataset of over 260,000 positive and over 700,000,000 negative patches annotated on scans of 510 whole slide images (WSI) of ZN-stained slides (110 positive and 400 negative). Several image augmentation techniques coupled with different custom computer vision architectures were used. WSIs automatic analysis was followed by a report indicating areas more likely to present mycobacteria. Our model performs AI-based diagnosis (the final decision of the diagnosis of WSI belongs to the pathologist). The results were validated internally on a dataset of 286,000 patches and tested in pathology laboratory settings on 60 ZN slides (23 positive and 37 negative). We compared the pathologists’ results obtained by separately evaluating slides and WSIs with the results given by a pathologist aided by automatic analysis of WSIs. Our architecture showed 0.977 area under the receiver operating characteristic curve. The clinical test presented 98.33% accuracy, 95.65% sensitivity, and 100% specificity for the AI-assisted method, outperforming any other AI-based proposed methods for AFB detection.
12 September 2018 in Journal of Immunology Research
Introduction. The clinical use of bioactive materials for bone augmentation has remained a challenge because of predictability and effectiveness concerns, as well as increased costs. The purpose of this study was to analyse the ability to integrate bone substitutes by evaluating the immunohistochemical expression of the platelet endothelial cell adhesion molecules, vascular endothelial growth factor, collagen IV, laminin, and osteonectin, in the vicinity of bone grafts, enabling tissue revascularization and appearance of bone lamellae. There is a lack of in vivo studies of inflammatory-driven angiogenesis in bone engineering using various grafts. Methods. The study was performed in animal experimental model on the standardized monocortical defects in the tibia of 20 New Zealand rabbits. The defects were augmented with three types of bone substituents. The used bone substituents were beta-tricalcium phosphate, bovine hydroxyapatite, and bioactive glasses. After a period of 6 months, bone fragments were harvested for histopathologic examination. Endothelial cell analysis was done by analysing vascularization with PECAM/CD31 and VEGF and fibrosis with collagen IV, laminin, and osteonectin stains. Statistical analysis was realized by descriptive analysis which was completed with the kurtosis and skewness as well as the Kruskal-Wallis and Mann-Whitney statistical tests. Results. The discoveries show that the amount of bone that is formed around beta-tricalcium phosphate and bovine hydroxyapatite is clearly superior to the bioactive glasses. Both the lumen diameter and the number of vessels were slightly increased in favor of beta-tricalcium phosphate. Conclusion. We can conclude that bone substitutes as bovine bone and beta-tricalcium phosphate have significant increased angiogenesis (and subsequent improved osteogenesis) compared to the bioactive glass. In our study, significant angiogenesis is linked with a greater tissue formation, indicating that in bone engineering with the allografts we used, inflammation has more benefic effects, the catabolic action being exceeded by the tissue formation.
23 March 2021 in Experimental and Therapeutic Medicine
Skin endometriosis is a rare disease with variable clinical and histopathological characteristics that depend on hormonal stimuli. The skin is not a common location, as most cases of endometriosis involve pelvic sites, such as the ovaries, peritoneum and bowel. However, the most common extrapelvic site affected is the abdominal wall and this location of the disease is frequently associated with obstetric and gynecologic surgery. Here we report a case of skin endometriosis emerged as a painful subcutaneous nodule located near to the left side of an obstetrical surgery procedure scar. The patient affected was a woman in her reproductive age, with a history of right ovary endometriotic cyst laparoscopically removed and histologically confirmed as a primary endometriosis. Dermatologists should be aware of this condition in any woman with a painful lump located in the proximity of a pelvic surgery‑induced scar. Its non‑specific clinical appearance may confuse the clinician and may delay the diagnosis and management.
Dendritic cells (DCs) are antigen-presenting cells with an important role in the innate and adaptive immune system. In skin lesions, cutaneous DCs (Langerhans cells, dermal DCs and plasmacytoid DCs) are involved in immune activation in inflammatory benign lesions, as well as in malignant lymphoid proliferations. Density and distribution of DCs in the dermal infiltrate can be helpful to differentiate benign, reactive infiltrate from malignant nature of the lymphoid population. We performed a retrospective study including 149 patients: 35 with mycosis fungoides, 35 with spongiotic dermatitis, 35 with psoriasis, 35 with lupus and 9 with cutaneous T-cell lymphomas (other than mycosis fungoides), diagnosed using histopathological and immunohistochemical stains. Density and distribution of DCs were evaluated using specific markers (CD1a, CD11c and langerin). In all cases, numerous DCs were identified in the dermal infiltrate. Their number was significantly increased in mycosis fungoides and T-cell lymphomas and moderately increased in inflammatory lesions. Variable patterns of distribution were identified such as clusters of DCs with arachnoid extension in mycosis fungoides, nodular pattern in inflammatory lesions and dispersed distribution with peripheric accumulation in T-skin lymphomas. Therefore, immunohistochemical characterization of DC distribution can be an adjuvant tool in differential diagnosis in inflammatory dermatosis and skin lymphomas.