Mast Cell Tryptase and Carboxypeptidase A3 in the Formation of Ovarian Endometrioid Cysts.

The mechanisms of ovarian endometrioid cyst formation, or cystic ovarian endometriosis, still remain to be elucidated. To address this issue, we analyzed the involvement of mast cell (MC) tryptase and carboxypeptidase A3 (CPA3) in the development of endometriomas. It was found that the formation of endometrioid cysts was accompanied by an increased MC population in the ovarian medulla, as well as by an MC appearance in the cortical substance.

Mast Cells in Regeneration of the Skin in Burn Wound with Special Emphasis on Molecular Hydrogen Effect.

The mechanisms of regeneration for the fibrous component of the connective tissue of the dermis are still insufficiently studied. The aim of this study was to evaluate the effectiveness of the use of molecular hydrogen on the local therapy of a II degree burn wound with the intensification of collagen fibrillogenesis in the skin. We analyzed the involvement of mast cells (MCs) in the regeneration of the collagen fibers of the connective tissue using water with a high content of molecular hydrogen and in a therapeutic ointment for the cell wounds.

The Remodeling of Dermal Collagen Fibrous Structures in Mice under Zero Gravity: The Role of Mast Cells.

Mechanisms of adaptive rearrangements of the fibrous extracellular matrix of connective tissues under microgravity practically remain unexplored, despite the most essential functions of the stroma existing to ensure the physiological activity of internal organs. Here we analyzed the biomaterial (the skin dermis) of C57BL/6J mice from the Rodent Research-4 experiment after a long stay in space flight. The biomaterial was fixed onboard the International Space Station.

Fluorescence in situ hybridization test for detection of endometrial carcinoma cells by non-invasive vaginal swab.

Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future.

Chloroacetate esterase reaction combined with immunohistochemical characterization of the specific tissue microenvironment of mast cells.

This study provides a combined histochemical method for detecting enzyme activity of chloroacetate esterase simultaneously with immunolabeling of the components of a specific tissue microenvironment on formalin-fixed, paraffin-embedded specimens. Chromogenic detection of the molecular targets within and outside the mast cells provides novel options in determining the histoarchitectonics of organ-specific mast cell populations, studying the functional significance of chloroacetate esterase and specifying the immune landscape of the tissue microenvironment.

Recent Advances in Castleman Disease.

Background: Castleman disease (CD) encompasses a spectrum of rare disorders with characteristic histopathological features. Unicentric CD (UCD) is a benign, local hyperplasia of lymphoid tissue that is usually curable. Multicentric CD (MCD) manifests as a potentially life-threatening systemic disease with complex symptomatology which is mostly due to an overproduction of interleukin-6 (IL-6) or dysregulation of IL-6-related signaling pathways.

Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy.

Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)/receptor tyrosine kinase inhibitor (ROS1), demonstrated efficacy in ROS1 positive (ROS1+) non-small cell lung cancer (NSCLC), although approval is currently limited to the treatment of ALK+ patients. However, lorlatinib-induced resistance mechanisms, and its efficacy against the resistance mutation G2032R in ROS1, respectively, have not yet been fully understood. Furthermore, concomitant tumor suppressor gene p53 (TP53) mutations occur in driver alteration positive NSCLC, but their prognostic contribution in the context of ROS1 inhibition remains unclear.

The ADP-Ribosylation Factor 4d Restricts Regulatory T-Cell Induction via Control of IL-2 Availability.

Interleukin-2 is central to the induction and maintenance of both natural (nT) and induced Foxp3-expressing regulatory T cells (iT). Thus, signals that modulate IL-2 availability may, in turn, also influence T homeostasis. Using global knockout and cell-specific knockout mouse models, we evaluated the role of the small GTPase ADP-ribosylation factor 4d (Arl4d) in regulatory T-cell biology.

Protease Profile of Tumor-Associated Mast Cells in Melanoma.

Mast cells (MCs) produce a variety of mediators, including proteases-tryptase, chymase, and carboxypeptidases-which are important for the immune response. However, a detailed assessment of the mechanisms of biogenesis and excretion of proteases in melanoma has yet to be carried out. In this study, we present data on phenotype and secretory pathways of proteases in MCs in the course of melanoma.

Frequent detection of functional hyposplenism via assessment of pitted erythrocytes in patients with advanced liver cirrhosis.

Background: Asplenia or functional hyposplenism are risk factors for severe infections, and vaccinations against encapsulated bacteria are advised. There are only limited data regarding the spleen function of cirrhotic patients.

Methods: We evaluated spleen function in patients with liver cirrhosis, who were prospectively enrolled in this study.

Effects of acute ischemia and hypoxia in young and adult calsequestrin (CSQ2) knock-out and wild-type mice.

Calsequestrin (CSQ2) is the main Ca-binding protein in the sarcoplasmic reticulum of the mammalian heart. In order to understand the function of calsequestrin better, we compared two age groups (young: 4-5 months of age versus adult: 18 months of age) of CSQ2 knock-out mice (CSQ2(-/-)) and littermate wild-type mice (CSQ2(+/+)). Using echocardiography, in adult mice, the basal left ventricular ejection fraction and the spontaneous beating rate were lower in CSQ2(-/-) compared to CSQ2(+/+).

Outcome of Ordinary Polymorphous Adenocarcinomas of the Salivary Glands in Comparison With Papillary and Cribriform Subtypes.

Background/aim: Polymorphous adenocarcinoma (PAC) is a low-grade salivary gland malignancy in contrast to variants with papillary (PAP) or cribriform (CASG) architecture and confers the second most common malignancy of minor salivary glands. Our study aimed to identify prognostic factors and to evaluate histomorphological and molecular diagnostic criteria of PACs.

Patients And Methods: A series of 155 PACs, including 10 PAPs and 12 CASGs from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW) and the Hamburg Salivary Gland Reference Centre (HRC) were analyzed.

Carboxypeptidase A3-A Key Component of the Protease Phenotype of Mast Cells.

Carboxypeptidase A3 (CPA3) is a specific mast cell (MC) protease with variable expression. This protease is one of the preformed components of the secretome. During maturation of granules, CPA3 becomes an active enzyme with a characteristic localization determining the features of the cytological and ultrastructural phenotype of MC.

Diagnostic Yield of Transbronchial Lung Cryobiopsy Compared to Transbronchial Forceps Biopsy in Patients with Sarcoidosis in a Prospective, Randomized, Multicentre Cross-Over Trial.

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis.

Smad7 Deficiency in Myeloid Cells Does Not Affect Liver Injury, Inflammation or Fibrosis after Chronic CCl Exposure in Mice.

Myeloid cells play an essential role in the maintenance of liver homeostasis, as well as the initiation and termination of innate and adaptive immune responses. In chronic hepatic inflammation, the production of transforming growth factor beta (TGF-β) is pivotal for scarring and fibrosis induction and progression. TGF-β signalling is tightly regulated via the Smad protein family.

Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples.

Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding DLL3 expression in relapses is not available.

Expression of CD38 in Mast Cells: Cytological and Histotopographic Features.

The biological significance of the CD38 molecule goes beyond metabolic, enzymatic, and proliferative functions. CD38 possesses the functions of an exoenzyme and receptor, and is actively involved in the mechanisms of adhesion, migration, intercellular signaling, formation of immune synapses, and modulation of the activity of a wide range of immune and non-immune cells. The aim of this study was the immunohistochemical assessment of the cytological and histotopographic characteristics of CD38 expression in mast cells.

Mechanisms of Systolic Cardiac Dysfunction in PP2A, PP5 and PP2AxPP5 Double Transgenic Mice.

As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated transgenic mice with cardiac muscle cell-specific overexpression of PP2Acα (PP2A) and PP5 (PP5). For further studies we crossbred PP2A and PP5 mice to obtain PP2AxPP5 double transgenic mice (PP2AxPP5, DT) and compared them with littermate wild-type mice (WT) serving as a control. The mortality of DT mice was greatly enhanced vs.

Deep learning approach to predict sentinel lymph node status directly from routine histology of primary melanoma tumours.

Aim: Sentinel lymph node status is a central prognostic factor for melanomas. However, the surgical excision involves some risks for affected patients. In this study, we therefore aimed to develop a digital biomarker that can predict lymph node metastasis non-invasively from digitised H&E slides of primary melanoma tumours.

Notch1 Deficiency Induces Tumor Cell Accumulation Inside the Bronchiolar Lumen and Increases TAZ Expression in an Autochthonous Driven Lung Cancer Mouse Model.

Abrogation of Notch signaling, which is pivotal for lung development and pulmonary epithelial cell fate decisions was shown to be involved in the aggressiveness and the differentiation of lung carcinomas. Additionally, the transcription factors YAP and TAZ which are involved in the Hippo pathway, were recently shown to be tightly linked with Notch signaling and to regulate the cell fate in epidermal stem cells. Thus, we aim to elucidate the effects of conditional Notch1 deficiency on carcinogenesis and TAZ expression in lung cancer.

Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping.

Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n = 167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n = 384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system).

Histamine can be Formed and Degraded in the Human and Mouse Heart.

Histamine is metabolized by several enzymes and . The relevance of this metabolism in the mammalian heart is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H-histamine receptors.

Identification of CTLA-4-Positive Cells in the Human Tonsil.

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was originally defined as a T-lymphocyte antigen and was used as a target in cancer immunotherapy. Unfortunately, the existence of CTLA-4 in cells other than T-lymphocytes is often overlooked. The goal of the present study was to analyze the distribution pattern of CTLA-4 in the human tonsils using a panel of anti-CTLA-4 antibodies of different clones.

BRAF mutations and BRAF mutation functional class have no negative impact on the clinical outcome of advanced NSCLC and associate with susceptibility to immunotherapy.

Objective: BRAF mutations have been subtyped in three functional classes with different oncogenic modes of action. The clinical impact of BRAF mutational subtypes in non-small-cell lung cancer (NSCLC) remains to be defined. So far, ambiguous results were reported from analyses of heterogeneous patient cohorts.

NOX2 Deficiency Permits Sustained Survival of in Macrophages and Contributes to Severity of Infection.

Although the crucial role of professional phagocytes for the clearance of infections is well-established, several studies indicate an adverse role of leukocytes in the dissemination of during infection. Since only little is known about macrophages in this context, we analyzed the role of macrophages, and in particular reactive oxygen species deficiency, for the seeding of metastases. Infection of bone marrow-derived macrophages (BMDM) with revealed that NADPH oxidase 2 (NOX2-) deficient, but not NOX1- or NOX4-deficient, BMDM failed to clear intracellular .