Search results for "Histochemistry"

Protein tyrosine phosphatase 1b deficiency protects against hepatic fibrosis by modulating nadph oxidases

2019

Inflammation is typically associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. The key role of protein tyrosine phosphatase 1B (PTP1B) in inflammatory responses has focused this study in understanding its implication in liver fibrosis. Here we show that hepatic PTP1B mRNA expression increased after bile duct ligation (BDL), while BDL-induced liver fibrosis was markedly reduced in mice lacking Ptpn1 (PTP1B−/−) as assessed by decreased collagen deposition and α-smooth muscle actin (α-SMA) expression. PTP1B−/− mice also showed a significant increase in mRNA levels of key markers of monocytes recruitment (Cd68, Adgre1 and Ccl2) compared to their wild-type (PTP1B+…

Modeling of Hepatocytes Proliferation Isolated from Proximal and Distal Zones from Human Hepatocellular Carcinoma Lesion

2016

Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liv…

mTOR inhibition in diffuse large B-cell lymphoma: new hope?

2016

Molecular similarities and differences from human pulmonary fibrosis and corresponding mouse model: MALDI imaging mass spectrometry in comparative me…

2017

Animal models can reproduce some model-specific aspects of human diseases, but some animal models translate poorly or fail to translate to the corresponding human disease. Here, we develop a strategy to systematically compare human and mouse tissues, and conduct a proof-of-concept experiment to identify molecular similarities and differences using patients with idiopathic pulmonary fibrosis and a bleomycin-induced fibrosis mouse model. Our novel approach employs high-throughput tissue microarrays (TMAs) of humans and mice, high-resolution matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance-mass spectrometry imaging (MALDI-FT-ICR-MSI) to spatially resolve ma…

Cutaneous manifestations associated with anosmia, ageusia and enteritis in SARS-CoV-2 infection - a possible pattern? Observational study and review …

2021

BACKGROUND: The cutaneous manifestations of coronavirus disease 2019 (COVID-19) have been covered insufficiently in the literature. METHODS: Thirty-nine patients admitted to the study hospital with confirmed COVID-19 who experienced various skin manifestations during hospitalization or in the convalescence period, were analysed retrospectively. RESULTS: Thirty-nine patients with COVID-19, admitted to the study hospital between 23 March and 12 September 2020, had intra-infectious rash or lesions of cutaneous vasculitis during convalescence. The most common cutaneous manifestations of COVID-19 were erythematous and erythematous papular rash. Twenty-seven of the 39 patients had anosmia (69.2%)…

p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging.

2017

[Background]: Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. [Methods]: Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. [Results]: We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M…

Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.

2016

The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.

Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

2019

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…

Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade

2019

Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutat…

Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors

2014

Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in m…