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Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.
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Neoplasias de Cabeza y Cuello/inmunología , Interleucina-6/inmunología , Microambiente Tumoral , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inflamación , Interleucina-6/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Knowledge of the phenotypic pattern of oral squamous epithelium is important in the histopathologic evaluation of lesions including cancer. The literature on normal epithelium is controversial as the phenotype has not been evaluated in samples from completely healthy tissue donors without a history of tobacco and alcohol exposure. METHODS: In this study, we evaluated normal upper lip fornix and gingival mucosa from carefully selected young healthy donors without a history of smoking and alcohol exposure, and keratin types 8, 10, 14, and 17, filaggrin, and Ki67 were investigated in these donors. The results were compared with profile of epithelium from leukoplakia. RESULTS: The results demonstrated that the phenotypic patterns of gingiva and upper lip fornix mucosa were different. Surprisingly, a high proportion of gingival samples exhibited keratin 8 and a suprabasal signal for keratin 14. These patterns were compared with that of human oral leukoplakia, and some phenotypic similarities were noted. CONCLUSIONS: These results demonstrated oral epithelium phenotypic plasticity based on functional requirements of the microenvironment, which can be used in diagnosis.
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Mucosa Bucal/anatomía & histología , Adulto , Anciano , Femenino , Proteínas Filagrina , Humanos , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Fenotipo , Adulto JovenRESUMEN
This article presents a case of complex investigation of defects of lime mortar and plaster that have been developing over a period of 48 years in a house in Prague and are strongly influenced by thermal and salt crystallization cycles. The aim of this research was to describe the degradation phenomena of mortars and plasters observed on a narrowly limited part of the building, combining structural elements of different types and ages and to explain the mechanisms of their formation and development. The geometric characteristics of the defects were determined by non-destructive methods, especially optical interference moiré, laser profilometry, photogrammetry, and infrared thermography. Material data were determined on samples by electron microscopy, ion exchange chromatography, and direct moisture content measurements. The results supported the hypothesis of the increase in the deformation of large buckles of detached plasters by the mechanism of buckling caused by loading of the edges with compression generated by volume changes. Direct loading of the boundary surfaces causes the formation of bulges in the confined areas. This study shows the importance of failure analysis of real structures to gain knowledge about the behavior of structures and materials under long-term service conditions.
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Galectins are potent effectors of cell adhesion and growth regulation. Their expression as comples network necessitates systematic study of each member of this family. Toward this aim, we here focus on the tandem-repeat-type galectin-9. Its presence is monitored in normal squamous epithelium of the head and neck, the surgical margin, and four types of squamous cell carcinoma. Lectin presence was detected in cells of the basal layer of the epithelium. All galectin-9-negative epithelia showed aberrant positivity for keratins 14 and 19. The surgical margin presented either a normal pattern of galectin-9 and keratin presence or a mosaic-like presence/absence of galectin-9 and aberrant expression of both keratins 14 and 19. All studied specimens of squamous cell carcinoma were negative for galectin-9. When biotinylated galectin-9, or its N-terminal domain, was tested, no significant tissue reactivity for both probes was observed. Neuraminidase treatment generated reactivity to the N-domain. In conclusion, galectin-9 is expressed in the majority of samples of normal epithelium, along with regular presence of keratins 14 or 19. This lectin can represent a potential marker of normality in the cases of the studied squamous cell epithelia.
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Carcinoma de Células Escamosas/patología , Galectinas/análisis , Neoplasias de Cabeza y Cuello/patología , Actinas/análisis , Adhesión Celular , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Epitelio/patología , Femenino , Galectinas/genética , Humanos , Queratina-14/análisis , Queratina-19/análisis , Queratina-8/análisis , Neoplasias Laríngeas/patología , Antígenos Comunes de Leucocito/análisis , Leucocitos/patología , Masculino , Miofibroblastos/patología , Estadificación de Neoplasias , Neoplasias Faríngeas/patología , Secuencias Repetidas en Tándem/genética , Neoplasias de la Lengua/patología , Neoplasias Tonsilares/patologíaRESUMEN
Tumor stroma is an active part influencing the biological properties of malignancies via molecular cross-talk. Cancer-associated fibroblasts play a significant role in this interaction. These cells frequently express smooth muscle actin and can be classified as myofibroblasts. The adhesion/growth-regulatory lectin galectin-1 is an effector for their generation. In our study, we set the presence of smooth muscle actin-positive cancer-associated fibroblasts in relation to this endogenous lectin and an in vivo competitor (galectin-3). In squamous cell carcinomas of head and neck, upregulation of galectin-1 presence was highly significantly correlated to presence of smooth muscle actin-positive cancer-associated fibroblasts in the tumor (p = 4 × 10(-8)). To pinpoint further correlations on the molecular level, we applied microarray analyses to the transcription profiles of the corresponding tumors. Significant correlations of several transcripts were detected with the protein level of galectin-1 in the cancer-associated fibroblasts. These activated genes (MAP3K2, TRIM23, PTPLAD1, FUSIP1, SLC25A40 and SPIN1) are related to known squamous-cell-carcinoma poor-prognosis factors, NF-κB upregulation and splicing downregulation. These results provide new insights into the significance of presence of myofibroblasts in squamous cell carcinoma.
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Actinas/biosíntesis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Galectina 1/biosíntesis , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Actinas/genética , Actinas/metabolismo , Carcinoma de Células Escamosas/genética , Regulación hacia Abajo , Femenino , Galectina 1/genética , Galectina 1/metabolismo , Galectina 3/genética , Galectina 3/metabolismo , Neoplasias de Cabeza y Cuello/genética , Humanos , Masculino , Músculo Liso/metabolismo , Músculo Liso/patología , Miofibroblastos/metabolismo , Miofibroblastos/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Pronóstico , Empalme del ARN , Células del Estroma/metabolismo , Células del Estroma/patología , Transcripción Genética , Regulación hacia ArribaRESUMEN
A peeling test known as the "Scotch Tape test" has been used for more than 40 years in conservation practice for assessing the consolidation efficiency of degraded stone. However, the method has not been supported by any standard or reliably verified recommendations for its application. Its applicability is overestimated, and its unrestricted use without adequate knowledge and sufficient understanding can lead to non-comparable, non-reproducible and, in many cases, incorrect and severely biased results and assessments. This paper presents the results of a recent study focused on establishing limits for application, reliable procedures and a "standard" protocol for testing the cohesion characteristics of brittle and quasi-brittle materials, mainly mortars and stones. The main application strategy exploits repeated peeling in the same place on a surface in order to eliminate the effect of the natural decrease in the detached material from the subsurface layers, which might be incorrectly interpreted as a consolidation effect. There is a discussion of factors influencing the performance of the peeling test method, and examples of peeling measurements on various natural and artificial stones are presented.
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Epithelial-mesenchymal interaction between stromal fibroblasts and cancer cells influences the functional properties of tumor epithelium, including the tumor progression and spread. We compared fibroblasts prepared from stroma of squamous cell carcinoma and normal dermal fibroblasts concerning their biological activity toward normal keratinocytes assessed by immunocytochemistry and profiling of gene activation for growth factors/cytokines by microarray chip technology. IGF-2 and BMP-4 were determined as candidate factors responsible for tumor-associated fibroblast activity that influences normal epithelia. This effect was confirmed by addition of recombinant IGF-2 and BMP4, respectively, to the culture medium. This hypothesis was also verified by inhibition experiments where blocking antibodies were employed in the medium conditioned by cancer-associated fibroblast. Presence of these growth factors was also detected in tumor samples.
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Proteína Morfogenética Ósea 4/biosíntesis , Carcinoma de Células Escamosas/metabolismo , Fibroblastos/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Factor II del Crecimiento Similar a la Insulina/biosíntesis , Queratinocitos/metabolismo , Animales , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Queratinocitos/citología , Ratones , Células 3T3 NIH , Fenotipo , Análisis por Matrices de Proteínas , Proteínas Recombinantes/biosíntesisRESUMEN
BACKGROUND/AIM: Stromal cells in the tumor microenvironment are primarily considered as sources of promalignant factors. The objective of our study was to define the effect of extracellular matrix (ECM) produced by normal dermal or cancer-associated fibroblasts exposed to adhesion/growth-regulatory lectin galectin-1 on human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Fibroblasts were cultured for 10 days with lectin, followed by removing cellular constituents after an osmotic shock. Freshly-isolated HUVECs were placed on the ECM. In parallel, HUVECs were seeded on untreated and gelatin-coated surfaces as controls. A positive control for growth of HUVECs culture using medium supplemented with vascular endothelial growth factor completed the test panel. Cells were kept in contact to the substratum for two days and then processed for immunocytochemistry. RESULTS: HUVECs seeded on fibroblast-generated ECM presented a comparatively high degree of proliferation. Furthermore, contact to substratum produced by tumor-associated fibroblasts led to generation of a meshwork especially rich in fibronectin. CONCLUSION: Galectin-1 is apparently capable to trigger ECM production favorable for growth of HUVECs, prompting further work on characterizing structural features of the ECM and in situ correlation of lectin presence, ECM constitution and neoangiogenesis.
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Matriz Extracelular/metabolismo , Fibroblastos/fisiología , Galectina 1/farmacología , Microambiente Tumoral , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Factor A de Crecimiento Endotelial Vascular/farmacologíaRESUMEN
With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey's P value <0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.