Histology and histopathology Vol.33, nº2 (2018)
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- PublicationOpen AccessTopically applied azaphenothiazines inhibit contact sensitivity to oxazolone in mice(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Artym, Jolanta; Kocięba, Maja; Zaczyńska, Ewa; Zimecki, Michał; Jeleń, Małgorzata; Morak Młodawska, Beata; Pluta, Krystian; Kaleta Kuratewicz, Katarzyna; Madej, Jan P.; Kuropka, Piotr; Kuryszko, JanIn this work we investigated the efficacy of two topically applied azaphenothiazine derivatives, 9- c h l o r o - 6 - a c e t y l ami n o b u t y l q u i n o b e n z o [ 3 , 2 - b][1,4]thiazine (compound 4) and 6-chloroethylureidoethyldiquino[3,2-b;2’;3’-e][1,4]thiazine (compound 5), in the amelioration of inflammatory symptoms of contact sensitivity (CS) to oxazolone in mice, in relation to the commercial ointment Protopic® (tacrolimus), the reference drug. The compounds were administered 24 h following elicitation of CS and, 24 h later, the parameters of inflammation, such as ear edema, blood composition, leukocyte level, numbers of cells in the draining lymph nodes, histological picture of the inflamed tissue, and the morphometric analysis, were analyzed. The study showed that the effectiveness of the studied azaphenothiazines applied as a 0.1% ointment was comparable to the reference drug regarding suppression of the inflammatory process, when all the investigated histological parameters are taken into account.
- PublicationOpen AccessTime-dependent and lesion-dependent HMGB1-selective localization in brains of patients with cerebrovascular diseases(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Umahara, Takahiko; Uchihara, Toshiki; Hirokawa, Katsuiku; Hirao, Kentaro; Shimizu, Soichiro; Hashimoto, Takao; Terasi, Hiroo; Hanyu, HaruoHigh mobility group box 1 protein (HMGB1) has multiple functions, including the maintenance of nucleosomes and the regulation of gene transcription. HMGB1 is released from activated macrophages, resulting in the induction of inflammatory cytokines. Recently, much research about the role of HMGB1 in cerebrovascular disease (CVD) has been reported. In an animal model, HMGB1 neutralization ameliorates brain infarction, there is an early release of HMGB1 from neurons, and HMGB1 antibody attenuates delayed cerebral vasospasm in experimental subarachnoid hemorrhage. It was also reported that elevation of HMGB1 in serum correlates with severity of acute intracerebral hemorrhage. However, the evidence of HMGB1 localization in brains of patients with CVD is very limited. Therefore, we investigated at autopsy the immunolocalization of HMGB1 in brains of patients with CVD (acute and chronic cerebral infarction, acute cerebral hemorrhage, subarachnoid hemorrhage). In 3 out of 10 acute cerebral infarction cases, the cytoplasm of neurons located around the ischemic core (i.e., penumbra) was positive for HMGB1. In the chronic stage of cerebral infarction, macrophages located in some ischemic regions were positive for HMGB1. Around the hematoma in the basal ganglia, HMGB1-like immunoreactivity (IR) was intense in macrophages. However, around the subarachnoid hematoma, HMGB1- like IR was not seen in the cortex. In arteries surrounded by subarachnoid hematoma, HMGB1-like IR was located in the cytoplasm of vascular smooth muscle cells. These findings, which partially differ from animal model results, may provide translational research and a basis for understanding the role of HMGB1 in brains of patients with CVD.
- PublicationOpen AccessThe role of tumor-associated macrophage in breast cancer biology(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Choi, Junjeong; Gyamfi, Jones; Jang, Haerin; Koo, Ja SeungBreast cancer is the most commonly diagnosed malignant tumor in women worldwide and contributes significantly as the primary cause of female cancer related mortality. Hence, research is focused on discovering new and effective treatment targets. The breast tumor microenvironment (TME) comprising of recruited host stromal cells and tumor cells, has recently emerged as an important player in tumor progression, with the potential for future treatment. The TME comprises immune system elements (such as macrophages and lymphocytes), cells composing blood vessel, fibroblast, myofibroblast, mesenchymal stem cells, adipocytes and extracellular matrix (ECM). Among these cells, tumor-associated macrophages (TAM) are the prominent components of TME in breast cancers. Macrophages exhibit a high plasticity in response to various external signals and participate in innate and adoptive immune responses to control numerous factors of TME. Depending on the microenvironmental signal present, macrophages are polarized into two distinct phenotypes, the classically activated (M1) or the alternative activated (M2) macrophages. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. In human breast carcinomas, high TAM density correlates with poor prognosis. Over the years, studies into the role of TAMs in breast cancer progression have identified TAMs to be capable of inducing angiogenesis, remodelling the tumor extracellular matrix to aid invasion, modelling breast cancer cells to evade host immune system and recruiting immunosuppressive leukocytes to the tumor microenvironment. Along with these functions, the potential role for TAMs in activation of breast cancer stem cells (CSC) has also emerged. Thus, TAMs in breast cancer can enhance cancer cell invasion by degrading the ECM, stimulate tumor vascularization and angiogenesis and suppress the antitumor functions of cytotoxic T cells resulting in poor prognosis for patients. These observations make TAMs an attractive target for therapeutic intervention by targeting various aspects of their function. This review discusses the mechanisms responsible for TAM recruitment and highlights the roles of TAMs in regulating tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, the potential for TAM-targeted therapy as a promising novel strategy is also discussed.
- PublicationOpen AccessMicroRNAs regulate APOBEC gene expression(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Cao, Wei; Wu, WeiApolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) is a family of evolutionarily conserved cytidine deaminases, encoded by eleven genes located in the human genome. APOBECs play key roles in innate immunity through their ability to mutagenize viral DNA and restrict viral replication. Recent cancer genomics revealed APOBEC3 subtype-mediated APOBEC-signature mutations are common in a broad spectrum of human cancers. The pervasive APOBEC3 activation in the host genome which converts cytosine to uracile during RNA editing has been suggested to depend on ATR/chk1 pathways. In this review, we highlight how microRNAs interact with the APOBEC gene family and post-transcriptionally regulate APOBEC gene expression, and we speculate how targeting specific microRNAs may reduce host genome mutagenesis via inactivation of APOBEC deaminases.
- PublicationOpen AccessExpression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, AndrzejBackground. The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. Objective. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). Design. The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients’ age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. Results. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients’ age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinico-pathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman’s correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). Conclusions. We report a high positive immunostaining rate for p53, suggesting a role of TP53 alterations in the development of BOTs in humans. The new finding of higher topoisomerase IIα immunostaining positivity in BOTs of ≥10 cm may be clinically relevant and requires further studies on larger patient groups.