Diagnostic and prognostic value of cancer stem cell marker CD44 and soluble CD44 in the peripheral Blood of patients with oral Squamous cell carcinoma

BackgroundHead and neck cancer is a major health problem. Recent studies on the pathobiology of oral squamous cell carcinoma (OSCC) have led to the discovery of a small population of cancer cells with a consistent behavior with the features of cancer stem cells (CSCs).  CSCs are required and responsible for initiation, maintenance and recurrence of disease. Molecular markers are commonly used for the identification of CSCs. CD44 is the most reported CSC marker in OSCC.The aim of the study was to evaluate and correlate the expression of CD44 in different histopathological grades of OSCC, as well as to assess the diagnostic and prognostic value of soluble CD44 (CD44sol) in peripheral blood of patients.Materials and methodsFifteen patients with OSCC were included; biopsies were histologically evaluated using haematoxylin and eosin. Serial sections were immunohistochemically stained by monoclonal antibody to CD44. The intensity of immunostaining of CD44 was calculated. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the concentration of CD44sol in the blood serum.ResultsAll grades of OSCC showed membranous immunosignaling of CD44. The well, moderately and poorly differentiated OSCC cases showed weak, moderate and intense positive membranous immunosignaling of CD44 respectively.CD44sol levels were significantly higher in OSCC patients than they were in control groups. Soluble CD44 serum levels were significantly higher in poorly differentiated than they were in moderately and well differentiated.ConclusionCSCs detection in fixed human tissue and CD44sol detection in peripheral blood using ELISA seemed to be a promising method and may have a diagnostic and prognostic value in management of OSCC

The effect of structural composion on self _ cleaning property of hand tuft carpet.

Here in we present a self cleaning properties of carpet. TiO2 NPs is used to impart carpet material self-cleaning characteristics. When TiO2NPs is coated on carpet polymers, its inherent photo-catalytic activity decomposes the polymeric carpet materials, as well as the contaminants. Fabric material and its weaving construction are expected factors that able to mitigate the deterioration of mechanical strength of the treated fabrics under the photocatalytic activity of TiO2NPs. The present work aims at investigating the effect of self-cleaning treatment on some physico-mechanical properties of woven carpet by hand tuft method we were chosen three kind of woven constructions were namely, wool 3/1,polyester 1600 and wool/polyester blend. All this constructions have different intensity, hight of pile and number of line pile /cm. The three kinde of carpet were treated with TiO2 NPs in presences of sodium hypophsifite as cross liking agent and citric acid as activating agent the studies appear that the best results: The polyester samples is the best one and when the number of line /cm increase the self cleaning increase but the reverse happen with intensity of carpets.Statement problem:Woven floor furnishings, especially lintels, are a suitable place for dust accumulation and adhesion to stains, and this may cause the urgent need for frequent washing and cleaning of these furnishings, which affects the appearance of the rug and reduces its consumption life, so it is a scientific study to adjust the elements of the structural composition of the carpet and treat it using technology Nanoscale to achieve self- cleaning of carpets is an important study, the impact of which is reflected on the audience of carpets and rugs.Significance:1. Providing the carpet with the self-cleaning feature, in order to increase the carpet life and maintain its elegance.2. Finding the most appropriate structural elements that achieve the highest cleaning with the best functional and mechanical properties

The Vitamin D Receptor–BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer

Treatment success of head and neck squamous cell carcinoma (HNSCC) is often hindered by cisplatin resistance. As inherent and acquired therapy resistance counteracts improvement in long-term survival, novel multi-targeting strategies triggering cancer cell apoptosis are urgently required. Here, we identify the vitamin D receptor (VDR) as being significantly overexpressed in tumors of HNSCC patients (n = 604; p = 0.0059), correlating with tumor differentiation (p = 0.0002), HPV status (p = 0.00026), and perineural invasion (p = 0.0087). The VDR, a member of the nuclear receptor superfamily, is activated by its ligand vitamin D (VitD) and analogs, triggering multiple cellular responses. As we found that the VDR was also upregulated in our cisplatin-resistant HNSCC models, we investigated its effect on overcoming cisplatin resistance. We discovered that VitD/cisplatin combinations synergistically killed even cisplatin-resistant cells at clinically achievable levels. Similar results were obtained for the clinically used VitD analog Maxacalcitol. Moreover, VitD/cisplatin combinations inhibited tumor cell migration by E-cadherin upregulation. Signaling pathway analyses revealed that VitD co-treatments triggered cancer cell death by increasing the expression of the pro-apoptotic BCL-2 family protein BIM. BIM’s pro-apoptotic activity in HNSCC cells was confirmed by ectopic overexpression studies. Importantly, BIM expression is positively associated with HNSCC patients’ (n = 539) prognosis, as high expression correlated with improved survival (p = 0.0111), improved therapy response (p = 0.0026), and remission (p = 0.004). Collectively, by identifying, for the first time, the VDR/BIM axis, we here provide a molecular rationale for the reported anti-cancer activity of VitD/analogs in combination therapies. Our data also suggest its exploitation as a potential strategy to overcome cisplatin resistance in HNSCC and other malignancies by inducing additional pro-apoptotic pathways

Impact of Secretion-Active Osteoblast-Specific Factor 2 in Promoting Progression and Metastasis of Head and Neck Cancer

Treatment success of head and neck cancer (HNC) is still hampered by tumor relapse due to metastases. Our study aimed to identify biomarkers by exploiting transcriptomics profiles of patient-matched metastases, primary tumors, and normal tissue mucosa as well as the TCGA HNC cohort data sets. Analyses identified osteoblast-specific factor 2 (OSF-2) as significantly overexpressed in lymph node metastases and primary tumors compared to normal tissue. High OSF-2 levels correlate with metastatic disease and reduced overall survival of predominantly HPV-negative HNC patients. No significant correlation was observed with tumor localization or therapy response. These findings were supported by the fact that OSF-2 expression was not elevated in cisplatin-resistant HNC cell lines. OSF-2 was strongly expressed in tumor-associated fibroblasts, suggesting a tumor microenvironment-promoting function. Molecular cloning and expression studies of OSF-2 variants from patients identified an evolutionary conserved bona fide protein secretion signal (1MIPFLPMFSLLLLLIVNPINA21). OSF-2 enhanced cell migration and cellular survival under stress conditions, which could be mimicked by the extracellular administration of recombinant protein. Here, OSF-2 executes its functions via ß1 integrin, resulting in the phosphorylation of PI3K and activation of the Akt/PKB signaling pathway. Collectively, we suggest OSF-2 as a potential prognostic biomarker and drug target, promoting metastases by supporting the tumor microenvironment and lymph node metastases survival rather than by enhancing primary tumor proliferation or therapy resistance

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy (p = 0.042). Other drug import/export transporters, such as CTR1, OCT1, or MRP1, were found to be less relevant. To experimentally verify VRAC’s critical role for cisplatin resistance, we used CRISPR/Cas9 knockout resulting in cisplatin-resistant HNSCC cells, which could be resensitized by VRAC expression. Next-generation sequencing further underlined VRAC’s importance and identified VRAC-regulated signaling networks, potentially also contributing to cisplatin resistance. CTR1, OCT1, or MRP1 did not contribute to increased cisplatin resistance. In addition to two-dimensional HNSCC models, three-dimensional tumor spheroid cultures confirmed VRAC’s unique role for cisplatin sensitivity. Here, resistance correlated with DNA damage and downstream apoptosis. The cisplatin specificity of the identified VRAC pathway was verified by testing paclitaxel and doxorubicin. Our results were independently confirmed in naturally occurring, cisplatin-resistant HNSCC cancer cell models. Collectively, we here demonstrate VRAC’s role for cisplatin resistance in HNSCC and its relevance as a potential drug target and/or prognostic biomarker for chemotherapy resistance

β-Cell Autophagy Pathway and Endoplasmic Reticulum Stress Regulating-Role of Liposomal Curcumin in Experimental Diabetes Mellitus: A Molecular and Morphometric Study

Background: Autophagy can confer protection to pancreatic β-cells from the harmful effects of metabolic stress by delaying apoptosis. Curcumin (CUR) alleviates oxidative and endoplasmic reticulum (ER) stress, activates autophagy, reduces inflammation, and decreases β-cell damage in type I diabetes. Liposomal CUR (LPs-CUR) has a higher therapeutic value and better pharmacokinetics than CUR. Objectives: We determined LPs-CUR’s ability to alleviate stress, reduce β-cell damage and unraveled the mechanism underlying its protective effect using a streptozotocin (STZ)-induced type I diabetic rat model. Methods: Sprague–Dawley rats were grouped into vehicle control, STZ-diabetic (STZ 65 mg/kg), STZ-diabetic-3-MA (3-methyladenine [3-MA] 10 mg/kg b.wt), STZ. diabetic-LPs-CUR (LPs-CUR 10 mg/kg b.wt), and STZ diabetic-LPs-CUR-3-MA (LPs-CUR 10 mg/kg b.wt; 3-MA 10 mg/kg b.wt). Results: LPs-CUR significantly reduced blood glucose, oxidative stress, and cellular inflammation in the pancreatic tissue (p < 0.001). ER stress-dependent genes included ATF-6, eIF-2, CHOP, JNK, BiP, and XBP LPs-CUR significantly suppressed fold changes, while it upregulated the autophagic markers Beclin-1 and LC3-II. Conclusions: LP-CUR ameliorates β-cell damage by targeting the autophagy pathway with the regulatory miRNAs miR-137 and miR-29b, which functionally abrogates ER stress in β-cells. This study presents a new therapeutic target for managing type I diabetes using miR-137 and miR-29b