Homing Peptide-Based Targeting of Tenascin-C and Fibronectin in Endometriosis

The current diagnostic and therapeutic strategies for endometriosis are limited. Although endometriosis is a benign condition, some of its traits, such as increased cell invasion, migration, tissue inflammation, and angiogenesis are similar to cancer. Here we explored the application of homing peptides for precision delivery of diagnostic and therapeutic compounds to endometriotic lesions. First, we audited a panel of peptide phages for the binding to the cultured immortalized endometriotic epithelial 12Z and eutopic stromal HESC cell lines. The bacteriophages displaying PL1 peptide that engages with angiogenic extracellular matrix overexpressed in solid tumors showed the strongest binding to both cell lines. The receptors of PL1 peptide, tenascin C domain C (TNC-C) and fibronectin Extra Domain-B (Fn-EDB), were expressed in both cells. Silver nanoparticles functionalized with synthetic PL1 peptide showed specific internalization in 12Z and HESC cells. Treatment with PL1-nanoparticles loaded with the potent antimitotic drug monomethyl auristatin E decreased the viability of endometriotic cells in 2D and 3D cultures. Finally, PL1-nanoparticless bound to the cryosections of clinical peritoneal endometriotic lesions in the areas positive for TNC-C and Fn-EDB immunoreactivities and not to sections of normal endometrium. Our findings suggest potential applications for PL1-guided nanoparticles in precision diagnosis and therapy of endometriosis.

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Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

Molecules ◽

10.3390/molecules26144288 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4288

Author(s):

Fernanda Malhão ◽

Ana Catarina Macedo ◽

Carla Costa ◽

Eduardo Rocha ◽

Alice Abreu Ramos

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

3D Models ◽

Anticancer Activities ◽

Cytotoxic Effects ◽

3D Cultures ◽

3D Cell Cultures ◽

Tumoral Cell ◽

Microscopy Techniques ◽

2D And 3D

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.

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EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation in Ewing sarcoma

British Journal of Cancer ◽

10.1038/s41416-019-0608-1 ◽

2019 ◽

Vol 121 (11) ◽

pp. 922-933 ◽

Cited By ~ 3

Author(s):

Shaohui He ◽

Quan Huang ◽

Jinbo Hu ◽

Lei Li ◽

Yanbin Xiao ◽

...

Keyword(s):

Cell Lines ◽

Ewing Sarcoma ◽

Nuclear Translocation ◽

Tumour Progression ◽

Underlying Mechanism ◽

Integrin Α5β1 ◽

Tenascin C ◽

Tumorigenesis And Progression

Abstract Background The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear. Methods TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored. Results TNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5β1 signalling might be correlated with YAP dephosphorylation and nuclear translocation. Conclusions TNC may promote ES tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation.

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Expression Changes and Impact of the Extracellular Matrix on Etoposide Resistant Human Retinoblastoma Cell Lines

International Journal of Molecular Sciences ◽

10.3390/ijms21124322 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4322 ◽

Cited By ~ 2

Author(s):

Jacqueline Reinhard ◽

Natalie Wagner ◽

Miriam M. Krämer ◽

Marvin Jarocki ◽

Stephanie C. Joachim ◽

...

Keyword(s):

Extracellular Matrix ◽

Mrna Expression ◽

Cell Lines ◽

Cluster Formation ◽

Collagen Iv ◽

Tissue Inhibitor Of Metalloproteinase ◽

Receptor Protein ◽

Tenascin C ◽

Chemotherapy Drugs ◽

Protein Levels

Retinoblastoma (RB) represents the most common malignant childhood eye tumor worldwide. Several studies indicate that the extracellular matrix (ECM) plays a crucial role in tumor growth and metastasis. Moreover, recent studies indicate that the ECM composition might influence the development of resistance to chemotherapy drugs. The objective of this study was to evaluate possible expression differences in the ECM compartment of the parental human cell lines WERI-RB1 (retinoblastoma 1) and Y79 and their Etoposide resistant subclones via polymerase chain reaction (PCR). Western blot analyses were performed to analyze protein levels. To explore the influence of ECM molecules on RB cell proliferation, death, and cluster formation, WERI-RB1 and resistant WERI-ETOR cells were cultivated on Fibronectin, Laminin, Tenascin-C, and Collagen IV and analyzed via time-lapse video microscopy as well as immunocytochemistry. We revealed a significantly reduced mRNA expression of the proteoglycans Brevican, Neurocan, and Versican in resistant WERI-ETOR compared to sensitive WERI-RB1 cells. Also, for the glycoproteins α1-Laminin, Fibronectin, Tenascin-C, and Tenascin-R as well as Collagen IV, reduced expression levels were observed in WERI-ETOR. Furthermore, a downregulation was detected for the matrix metalloproteinases MMP2, MMP7, MMP9, the tissue-inhibitor of metalloproteinase TIMP2, the Integrin receptor subunits ITGA4, ITGA5 and ITGB1, and all receptor protein tyrosine phosphatase β/ζ isoforms. Downregulation of Brevican, Collagen IV, Tenascin-R, MMP2, TIMP2, and ITGA5 was also verified in Etoposide resistant Y79 cells compared to sensitive ones. Protein levels of Tenascin-C and MMP-2 were comparable in both WERI cell lines. Interestingly, Fibronectin displayed an apoptosis-inducing effect on WERI-RB1 cells, whereas an anti-apoptotic influence was observed for Tenascin-C. Conversely, proliferation of WERI-ETOR cells was enhanced on Tenascin-C, while an anti-proliferative effect was observed on Fibronectin. In WERI-ETOR, cluster formation was decreased on the substrates Collagen IV, Fibronectin, and Tenascin-C. Collectively, we noted a different ECM mRNA expression and behavior of Etoposide resistant compared to sensitive RB cells. These findings may indicate a key role of ECM components in chemotherapy resistance formation of RB.

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Monitoring Alveolar Ridge Remodelling Post-Extraction Using Sequential Intraoral Scanning over a Period of Four Months

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17186638 ◽

2020 ◽

Vol 17 (18) ◽

pp. 6638

Author(s):

Khaled E. Ahmed

Keyword(s):

Computer Aided Design ◽

Three Dimensional ◽

Dimensional Changes ◽

Intraoral Scanning ◽

Computer Aided ◽

Potential Applications ◽

Cad Cam ◽

Aided Design ◽

2D And 3D

The potential applications of computer-aided design/computer-aided manufacturing (CAD/CAM) and intraoral scanning exceed the delivery of standard prosthodontic interventions. The aim of this study was to clinically present a developed assessment technique, that relies on the use of sequential intraoral scanning, three-dimensional superimposition, and 2D and 3D deviation analyses based on a standardised protocol, as an auxiliary tool in monitoring dimensional changes of residual ridge post-extraction with a follow-up period of four months.

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Isolation of rabbit single domain antibodies to B7-H3 via protein immunization and phage display

Antibody Therapeutics ◽

10.1093/abt/tbaa002 ◽

2020 ◽

Vol 3 (1) ◽

pp. 10-17

Author(s):

Ruonan Feng ◽

Ruixue Wang ◽

Jessica Hong ◽

Christopher M Dower ◽

Brad St Croix ◽

...

Keyword(s):

Tumor Cell ◽

Phage Display ◽

Cell Lines ◽

Single Domain ◽

Tumor Cell Lines ◽

Positive Tumor Cell ◽

Drug Candidates ◽

Potential Applications ◽

Single Domain Antibodies ◽

Protein Immunization

Abstract Single domain antibodies have certain advantages including their small size, high stability and excellent tissue penetration, making them attractive drug candidates. Rabbit antibodies can recognize diverse epitopes, including those that are poorly immunogenic in mice and humans. In the present study, we established a method to isolate rabbit VH single domain antibodies for potential cancer therapy. We immunized rabbits with recombinant human B7-H3 (CD276) protein, made a phage-displayed rabbit VH single domain library with a diversity of 7 × 109, and isolated two binders (A1 and B1; also called RFA1 and RFB1) from phage panning. Both rabbit VH single domains exhibited antigen-dependent binding to B7-H3-positive tumor cell lines but not B7-H3 knockout tumor cell lines. Our study shows that protein immunization followed by phage display screening can be used to isolate rabbit single domain antibodies. The two single domain antibodies reported here may have potential applications in cancer immunotherapy.

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Solid State Synthesis and Characterization of Tin-Based Low-Dimensional Materials

MRS Proceedings ◽

10.1557/proc-755-dd6.19 ◽

2002 ◽

Vol 755 ◽

Cited By ~ 1

Author(s):

Tolulope O. Salami ◽

Scott R. J. Oliver

Keyword(s):

Variable Temperature ◽

Layered Compounds ◽

Layered Compound ◽

X Ray Diffraction ◽

Group 14 ◽

Potential Applications ◽

Low Dimensional ◽

2D And 3D ◽

Extended Materials

ABSTRACTWe report the synthetic conditions, physical properties and potential applications of late group 14 metal (Sn) 0D, 1D, 2D and 3D extended materials. The structures are primarily neutral chain and anionic layered compounds. The latter are charge-balanced by ammonium cations, as in and BING-7 [Sn(C2O4)F-] [NH4+] and BING-8 [Sn(PO4H)F-] [NH4+]. The neutral layered compound and chain compounds BING-1 [Na4Sn4(C2O4)F6], BING-2 [KSn(C2O4)F] and BING-4 [Sn(C2O4)(C5H5N)] have also been synthesized solvothermally. Thermogravimetric analysis (TGA) under nitrogen and in-situ variable temperature X-ray diffraction show that the materials decompose in the 200°C to 300°C range to more stable phases. Nuclear magnetic resonance (NMR) was used to monitor the ion-exchange properties of some of the materials. The intercalation properties of these materials are still being investigated.

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Nanoparticle-Aided Detection of Colorectal Cancer-Associated Glycoconjugates of Extracellular Vesicles in Human Serum

International Journal of Molecular Sciences ◽

10.3390/ijms221910329 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10329

Author(s):

Rufus Vinod ◽

Randa Mahran ◽

Erica Routila ◽

Janne Leivo ◽

Kim Pettersson ◽

...

Keyword(s):

Colorectal Cancer ◽

Human Serum ◽

Cell Lines ◽

Extracellular Vesicles ◽

Late Stage ◽

Early Stage ◽

Biological Fluids ◽

Serum Samples ◽

Benign Condition ◽

Hek 293

Extracellular vesicles (EVs) are found in all biological fluids, providing potential for the identification of disease biomarkers such as colorectal cancer (CRC). EVs are heavily glycosylated with specific glycoconjugates such as tetraspanins, integrins, and mucins, reflecting the characteristics of the original cell offering valuable targets for detection of CRC. We report here on europium-nanoparticle (EuNP)-based assay to detect and characterize different surface glycoconjugates of EVs without extensive purification steps from five different CRC and the HEK 293 cell lines. The promising EVs candidates from cell culture were clinically evaluated on small panel of serum samples including early-stage (n = 11) and late-stage (n = 11) CRC patients, benign condition (n = 11), and healthy control (n = 10). The majority of CRC cell lines expressed tetraspanin sub-population and glycovariants of integrins and conventional tumor markers. The subpopulation of CD151 having CD63 expression (CD151CD63) was significantly (p = 0.001) elevated in early-stage CRC (8 out of 11) without detecting any benign and late-stage samples, while conventional CEA detected mostly late-stage CRC (p = 0.045) and with only four early-stage cases. The other glycovariant assays such as CEACon-A, CA125WGA, CA 19.9Ma696, and CA 19.9Con-A further provided some complementation to the CD151CD63 assay. These results indicate the potential application of CD151CD63 assay for early detection of CRC patients in human serum.

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Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

10.5772/intechopen.98497 ◽

2021 ◽

Author(s):

Somi Patranabis

Keyword(s):

Tyrosine Kinases ◽

Receptor Tyrosine Kinases ◽

Therapeutic Strategies ◽

Cellular Functions ◽

Recent Advances ◽

Different Types ◽

Therapeutic Development ◽

Potential Applications ◽

Specific Ligand ◽

Novel Therapeutic

Receptor Tyrosine Kinases (RTKs) are an important class of receptors involved in regulating different cellular functions. The usual pathway of RTK activation involves specific ligand binding, dimerization and trans-autophosphorylation. Recently, RTK has been extensively studied as they have potential applications in targeted cancer therapy. RTK-based therapeutic strategies are promising because dysfunction of RTK is connected to a variety of diseases. More specifically, RTK has been widely associated with different types of cancer and related diseases. The chapter aims to cover recent advances and challenges in RTK related research, to get an overview of the problems and possibilities associated with targeted therapy. This will help in deciphering novel therapeutic applications in the future.

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Exosomes and Brain Metastases: A Review on Their Role and Potential Applications

International Journal of Molecular Sciences ◽

10.3390/ijms221910899 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10899

Author(s):

Filipa D. Oliveira ◽

Miguel A. R. B. Castanho ◽

Vera Neves

Keyword(s):

Brain Metastases ◽

Intercellular Communication ◽

Therapeutic Strategies ◽

Cancer Therapies ◽

Life Prognosis ◽

Potential Applications ◽

Advanced Stages ◽

Promising Application

Brain metastases (BM) are a frequent complication in patients with advanced stages of cancer, associated with impairment of the neurological function, quality of life, prognosis, and survival. BM treatment consists of a combination of the available cancer therapies, such as surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Even so, cancer patients with BM are still linked to poor prognosis, with overall survival being reported as 12 months or less. Intercellular communication has a pivotal role in the development of metastases, therefore, it has been extensively studied not only to better understand the metastization process, but also to further develop new therapeutic strategies. Exosomes have emerged as key players in intercellular communication being potential therapeutic targets, drug delivery systems (DDS) or biomarkers. In this Review, we focus on the role of these extracellular vesicles (EVs) in BM formation and their promising application in the development of new BM therapeutic strategies.

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