Background: Endobronchial ultrasound (EBUS) is a new technique that enables the assessment of bronchial wall layers. The aim of the study
was to verify the utility of EBUS for the assessment of ...bronchial wall remodeling in patients with asthma.
Methods: In 35 patients with asthma and 23 control subjects, high-resolution CT (HRCT) scanning and EBUS were used to measure bronchial
wall thickness in the 10th segment of the right lung. With a radial 20-MHz probe, EBUS identified the 5-laminar structure
of the bronchial wall. Layer 1 (L 1 ) and layer 2 (L 2 ) were analyzed separately, and layers 3 through 5 (L 3â5 ), which corresponded to cartilage, were analyzed jointly. Digitalized EBUS images were used for the quantitative assessment
of bronchial wall thickness and the wall area (WA) of the layers. Finally, bronchial biopsy specimens were taken for measuring
the thickness of the reticular basement membrane (RBM). The thickness and WA of the bronchial wall layers, which were assessed
using EBUS, were correlated with FEV 1 and RBM.
Results: There was no significant difference in the measurements of total bronchial wall thickness using EBUS and HRCT scanning. The
thickness and WA of the bronchial wall and its layers were significantly greater in patients with asthma than in the control
subjects. A negative correlation among the thicknesses of L 1 , L 2 , and L 3â5 and FEV 1 , and a positive correlation with RBM were observed only in the patients with asthma.
Conclusions: EBUS allows precise measurement of the thickness and WA of bronchial wall layers. The correlation of these parameters with
asthma severity suggests implementation of EBUS in the assessment of bronchial wall remodeling in patients with asthma.
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► Cell stiffness was determined for various cancer cells using AFM. ► The proposed methodology has been applied to tissue samples. ► The obtained results have highlighted the ...potential of AFM in cancer detection.
Currently, cancer diagnosis relies mostly on morphological examination of exfoliated, aspirated cells or surgically removed tissue. As long as standard diagnosis is concerned, this classical approach seems to be satisfactory. In the recent years, cancer progression has been shown to be accompanied by alterations in mechanical properties of cells. This offers the detection of otherwise unnoticed cancer cell disregarded by histological analysis due to insignificant manifestations. One of techniques, sensitive to changes in mechanical properties, is the atomic force microscopy, which detects cancer cells through their elastic properties. Such measurements were applied to tissue sections collected from patients suffering from various cancers. Despite of heterogeneity and complexity of cancer cell sections, the use of the Young’s modulus as an indicator of cell elasticity allow for detection of cancer cells in tissue slices.
Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote ...carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs.
Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays.
Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia.
The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results.
Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin ...superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1–expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1–positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1–positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma.
•PD-L1 and stem cell marker expressions were analyzed in malignant mesotheliomas.•PD-L1 and ALCAM were expressed in 33% and 25% of mesothelioma cases, respectively.•The Cox proportional hazards model identified these proteins as independent risk factors for death.
The mast cells participate in inflammation and possibly in carcinogenesis. The aim of the study was to study mast cells in melanocytic lesions. The material consisted of 24 pigmented nevi, 18 ...dysplastic nevi and 19 melanomas. The sections were stained immunohistochemically for tryptase and chymase. Positive cells were counted inside the lesions and at the interface between the lesion and dermis. The mean intralesional tryptase+ count was 15.75 for nevi, 21.78 for dysplastic nevi, and 8.07 for melanomas. The chymase+ intralesional count was 14.89 for nevi, 21.88 for dysplastic nevi, and 11.34 for melanomas. The tryptase+ perilesional count was 16.89 for nevi, 15.93 for dysplastic nevi, and 15.71 for melanomas. The chymase+ perilesional count was 16.52 for nevi, 16.16 for dysplastic nevi, and 14.77 for melanomas. The tryptase/chymase intralesional ratio was 0.93 for nevi, 1.05 for dysplastic nevi, and 1.67 for melanomas. The tryptase/chymase perilesional ratio was 1.02 for nevi, 1.09 for dysplastic nevi, and 1.00 for melanomas. The differences between intralesional mast cells, both tryptase+ and chymase+, were statistically significant. The intralesional tryptase+ count showed an inverse correlation to age (R = -0.42); this correlation was the strongest in melanomas. The results obtained in our study suggest a possible correlation between mast cells and the pathogenesis of cutaneous melanoma.
Markers of bladder cancer cells remain elusive, which is a major cause of the low recognition of this malignant neoplasm and its recurrence. This implies an urgent need for additional diagnostic ...tools which are based on the identification of the chemism of bladder cancer. In this study, we employed label-free techniques of molecular imaging-Fourier Transform Infrared and Raman spectroscopic imaging-to investigate bladder cancer cell lines of various invasiveness (T24a, T24p, HT-1376, and J82). The urothelial HCV-29 cell line was the healthy control. Specific biomolecules discriminated spatial distribution of the nucleus and cytoplasm and indicated the presence of lipid bodies and graininess in some cell lines. The most prominent discriminators are the total content of lipids and sugar moieties as well as the presence of glycogen and other carbohydrates, un/saturated lipids, cytochromes, and a level of S-S bridges in proteins. The combination of the obtained hyperspectral database and chemometric methods showed a clear differentiation of each cell line at the level of the nuclei and cytoplasm and pointed out spectral signals which differentiated bladder cancer cells. Registered spectral markers correlated with biochemical composition changes can be associated with pathogenesis and potentially used for the diagnosis of bladder cancer and response to experimental therapies.
Introduction: Immunoglobulin E is an important modulator of the inflammatory reaction in allergic asthma. It also contributes to airway remodeling in the course of the disease. The authors evaluated ...airway structural changes in severe allergic asthma during the omalizumab therapy. Patients and methods: The study included 13 patients with severe allergic asthma treated with omalizumab for at least one year. In each patient clinical, laboratory, and spirometry parameters were evaluated before and after the treatment. In addition, bronchoscopy with bronchial mucosa biopsy and bronchoalveolar lavage was performed. The basal lamina thickness, inflammatory cell infiltration, fibronectin, as well as type I and III collagen accumulation were assessed in bronchial mucosa specimens, together with the assessment of bronchoalveolar lavage cellularity. Results: The omalizumab therapy led to a decrease in the basal lamina thickness (p = 0.002), and to a reduction in fibronectin (p = 0.02), but not collagen deposits in the bronchial mucosa. The decrease in fibronectin accumulation was associated with an improvement in asthma control and quality of life (p = 0.01, both), and a diminished dose of systemic corticosteroids (p = 0.001). It was also associated with a tendency towards reduction of the eosinophil count in the peripheral blood, bronchoalveolar lavage fluid, and bronchial mucosa specimens. Conclusion: Our study has shown that omalizumab, effective in the treatment of severe allergic asthma, may also decrease unfavorable structural airway changes in allergic asthmatics, at least with respect to the fibronectin deposit and an increased thickness of the basal lamina. However, more extensive observational studies are needed to verify the above hypothesis.
Mast cells (MCs) are known to be regulators of inflammation and immunity, due to the released mediators and expressed cell surface molecules. Lupus erythematosus (LE) is a group of diseases which can ...be systemic or limited to the skin. Due to the fact that cytokines and chemokines produced by inflammatory cells contribute to the pathogenesis of LE, we quantified the number of mast cells present in the skin. The aim of the study was to compare the chymase-positive and tryptase-positive mast cell counts within skin biopsies from patients with systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The material consisted of 45 skin biopsies: 6 with SLE, 34 with DLE and 5 with SCLE. Chymase- and tryptase-positive cells were stained by immunohistochemistry and counted. The mean count of chymase-positive mast cells was 85.14 hpf for the whole group, 35.83 for SLE, 88.48 for DLE and 121.6 for SCLE. The mean count of tryptase-positive cells was 120.05 hpf for the entire group, 59.17 for SLE, 126.42 for DLE and 149.8 for SCLE. The differences between groups were significant for chymase- and tryptase-positive cells.
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