Pathobiology
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Long-Term NO<sub>2</sub> Exposure Induces Pulmonary Inflammation and Progressive Development of Airflow Obstruction in C57BL/6 Mice: A Mouse Model for Chronic Obstructive Pulmonary Disease? Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, development of emphysema and irreversible airway obstruction. Macrophages, neutrophils and CD8+ T cells and their products have been shown to play an important role in the initiation and maintenance of these processes. In contrast, the mechanisms underlying COPD pathogenesis still remain uncertain. This article focuses on the generation of an animal model that mirrors some features of human COPD in association with a progredient airflow limitation.
Pathobiology - Tập 70 Số 5 - Trang 284-286 - 2002
<i>SOX</i> Gene Expression in Human Osteoarthritic Cartilage <i>Objective:</i> While the developmental role of the SOX transcription factors in fetal chondrocyte differentiation is well documented, much less is known about the expression of SOX family members in normal and osteoarthritic adult cartilage. Therefore, the aim of the present study was to present a thorough analysis of <i>SOX</i> gene expression in normal and osteoarthritic human adult cartilage. <i>Methods:</i> RNA from normal and osteoarthritic knee cartilage from human adults was analyzed by gene expression profiling using GeneChip technology (Affymetrix) and quantitative real time PCR. <i>Results:</i> Most members of the SOX transcription factor family showed no or very low expression levels in normal and osteoarthritic cartilage from adults. In contrast, <i>SOX9</i> expression was fairly high in normal cartilage, amounting to approximately 20% of GAPDH levels. <i>SOX9</i> transcript levels were substantially reduced in osteoarthritis. <i>SOX6</i> levels were reduced, albeit starting from a low basis expression in normal tissue. <i>Conclusion:</i> The presented data indicate that the role of the SOX transcription factor family in adult human cartilage is most probably restricted to a few members, with SOX9 being the most prominent. Furthermore, the reduction of <i>SOX9</i> and <i>SOX6</i> transcript levels in osteoarthritic chondrocytes might be responsible for the loss of phenotypic stability of osteoarthritic chondrocytes.
Pathobiology - Tập 75 Số 3 - Trang 195-199 - 2008
Microbiome: A Supportive or a Leading Actor in Lung Cancer? Lung cancer is still the leading cause of cancer death worldwide. Despite the major diagnostic and therapeutic innovations, the effect on mortality has been modest and the overall survival is still poor. Better understanding of the pathology of these tumors is necessary in order to develop personalized therapeutic strategies in lung cancer patients. Human microbiome has been associated with normal physiology and function, and increasing evidence points towards a key role of the microbiome in promoting the progression of lung disease. Studies have shown that although poorly understood, lung has a distinctive microbiome that may an important role in lung cancer development and progression, and interactions between microbial populations have the potential to influence disease, suggesting that microbiome can be an emerging target in cancer therapeutics. We will review mechanisms how the lung microbiota influences carcinogenesis, focusing on the bacterial dysbiosis and inflammation. Moreover, we will discuss the link between the microbiome and cancer and the consequences induced by the immune system, as the host microbiota plays an essential role in activating and modulating the immune response. We summarize current research advances in the lung microbiome and demonstrate the potential to exploit microbiome as a mechanism to prevent carcinogenesis and modulate therapeutic strategy, suggesting microbiome as a valuable approach in lung cancer patients.
Pathobiology - Tập 88 Số 2 - Trang 198-207 - 2021
Overexpression of Fatty Acid Synthase in Oesophageal Squamous Cell Dysplasia and Carcinoma <i>Objective:</i> The expression of fatty acid synthase (FAS), an enzyme necessary for de novo fatty acid synthesis, has been examined in several types of tumours so far, but not in oesophageal cancer and dysplasia. <i>Methods:</i> We examined the immunohistochemical reactivity of FAS in 4 normal adult oesophagi, 14 dysplastic oesophageal lesions, and 80 squamous cell carcinomas and 6 cases with 4 special types of malignancies of the oesophagus. We also analysed the correlation between FAS expression and various clinicopathological features and long-term survival in patients with oesophageal cancer. <i>Results:</i> In the normal oesophagus, only faint cytoplasmic FAS expression was observed in cells of the basal layer. In contrast, FAS-positive cells were found in 92.9% of cases of dysplasia and 96.5% of cases of carcinoma including 6 cases with a specific histological subtype. However, high expression of FAS did not correlate with either clinicopathological features or prognosis of patients with oesophageal cancer. <i>Conclusion:</i> Our results demonstrate that FAS is expressed in almost all oesophageal carcinomas of both usual and special types and dysplastic lesions, suggesting that FAS may be upregulated continuously from the early stage of oesophageal squamous cell carcinogenesis to established carcinoma.
Pathobiology - Tập 69 Số 6 - Trang 297-303 - 2001
The Impact of COVID-19 Disease on Platelets and Coagulation Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.
Pathobiology - Tập 88 Số 1 - Trang 15-27 - 2021
Reconstructed Human Cornea Produced in vitro by Tissue Engineering The aim of the present study was to produce a reconstructed human cornea in vitro by tissue engineering and to characterize the expression of integrins and basement membrane proteins in this reconstructed cornea. Epithelial cells and fibroblasts were isolated from human corneas (limbus or centre) and cultured on plastic substrates in vitro. Reconstructed human corneas were obtained by culturing epithelial cells on collagen gels containing fibroblasts. Histological (Masson’s trichrome staining) and immunohistological (laminin, type VII collagen, fibronectin as well as β<sub>1</sub>, α<sub>3</sub>, α<sub>4</sub>, α<sub>5</sub>, and α<sub>6</sub> integrin subunits) studies were performed. Human corneal epithelial cells from the limbus yielded colonies of small fast-growing cells when cultured on plastic substrates. They could be subcultured for several passages in contrast to central corneal cells. In reconstructed cornea, the epithelium had 4–5 cell layers by the third day of culture; basal cells were cuboidal. The basement membrane components were already detected after 3 days of culture. Integrin stainings, except for the α<sub>4</sub> integrin, were also positive after 3 days. They were mostly detected at the epithelium-stroma junction. Such in vitro tissue-engineered human cornea, which shows appropriate histology and expression of basement membrane components and integrins, provides tools for further physiological, toxicological and pharmacological studies as well as being an attractive model for gene expression studies.
Pathobiology - Tập 67 Số 3 - Trang 140-147 - 1999
Pathobiological Implications of MUC16/CA125 Expression in Intrahepatic Cholangiocarcinoma-Mass Forming Type <i>Objectives:</i> MUC16 carries the peptide epitope CA125, which is well known as a marker of ovarian cancer. High serum levels of MUC16 (CA125) have been reported not only in patients with ovarian cancer but also in patients with liver diseases. We evaluated the expression of MUC16 in intrahepatic cholangiocarcinoma-mass forming type (ICC-MF) tissues. <i>Methods:</i> We examined the expression of MUC16 by immunohistochemical analyses using the monoclonal antibody M11 in ICC-MF tissues from 63 patients. To compare the prevalence of each mucin expression by clinicopathological features, appropriate statistical analysis was performed. <i>Results:</i> MUC16 was detected in 48% of samples (30/63). After adjusting for the effects of other prognostic factors, multivariate survival analysis revealed that MUC16 expression is a significant independent factor of poor prognosis (p = 0.005). <i>Conclusion:</i> The current results indicate that MUC16 expression is a prognostic factor of poor survival in ICC-MF.
Pathobiology - Tập 79 Số 2 - Trang 101-106 - 2012
Circulating Neutrophil Extracellular Trap Levels in Well-Controlled Type 2 Diabetes and Pathway Involved in Their Formation Induced by High-Dose Glucose <b><i>Objectives:</i></b> Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. <b><i>Methods:</i></b> Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. <b><i>Results:</i></b> Serum MPO-DNA complex levels were<b> </b>significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. <b><i>Conclusions:</i></b> Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose.
Pathobiology - Tập 83 Số 5 - Trang 243-251 - 2016
Role of the Tumor Microenvironment in Breast Cancer In recent years, it has been shown that breast cancer consists not only of neoplastic cells, but also of significant alterations in the surrounding stroma or tumor microenvironment. These alterations are now recognized as a critical element for breast cancer development and progression, as well as potential therapeutic targets. Various components of the breast cancer microenvironment, such as suppressive immune cells, soluble factors and altered extracellular matrix, act together to impede effective antitumor immunity and promote breast cancer progression and metastasis. Stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, some of which are prognostic of clinical outcome. Several new therapies targeting stromal components are in development or undergoing clinical trials. We focus herein on the composition of the breast cancer microenvironment and concomitant molecular alterations, the specific interplay between various cell types and cancer cells, and the clinical implications of these findings.
Pathobiology - Tập 82 Số 3-4 - Trang 142-152 - 2015
The Role of Micro-CT in 3D Histology Imaging <b><i>Objectives:</i></b> 3D histology tissue modeling is a useful analytical technique for understanding anatomy and disease at the cellular level. However, the current accuracy of 3D histology technology is largely unknown, and errors, misalignment and missing information are common in 3D tissue reconstruction. We used micro-CT imaging technology to better understand these issues and the relationship between fresh tissue and its 3D histology counterpart. <b><i>Methods:</i></b> We imaged formalin-fixed and 2% Lugol-stained mouse brain, human uterus and human lung tissue with micro-CT. We then conducted image analyses on the tissues before and after paraffin embedding using 3D Slicer and ImageJ software to understand how tissue changes between the fixation and embedding steps. <b><i>Results:</i></b> We found that all tissue samples decreased in volume by 19.2-61.5% after embedding, that micro-CT imaging can be used to assess the integrity of tissue blocks, and that micro-CT analysis can help to design an optimized tissue-sectioning protocol. <b><i>Conclusions:</i></b> Micro-CT reference data help to identify where and to what extent tissue was lost or damaged during slide production, provides valuable anatomical information for reconstructing missing parts of a 3D tissue model, and aids in correcting reconstruction errors when fitting the image information in vivo and ex vivo.
Pathobiology - Tập 83 Số 2-3 - Trang 140-147 - 2016
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