Cancers, Vol. 11, Pages 1818: WWOX Possesses N-Terminal Cell Surface-Exposed Epitopes WWOX7-21 and WWOX7-11 for Signaling Cancer Growth Suppression and Prevention In Vivo

Cancers, Vol. 11, Pages 1818: WWOX Possesses N-Terminal Cell Surface-Exposed Epitopes WWOX7-21 and WWOX7-11 for Signaling Cancer Growth Suppression and Prevention In Vivo Cancers doi: 10.3390/cancers11111818 Authors: Wan-Jen Wang Pei-Chuan Ho Ganesan Nagarajan Yu-An Chen Hsiang-Ling Kuo Dudekula Subhan Wan-Pei Su Jean-Yun Chang Chen-Yu Lu Katarina T. Chang Sing-Ru Lin Ming-Hui Lee Nan-Shan Chang Membrane hyaluronidase Hyal-2 supports cancer cell growth. Inhibition of Hyal-2 by specific antibody against Hyal-2 or pY216-Hyal-2 leads to cancer growth suppression and prevention in vivo. By immunoelectron microscopy, tumor suppressor WWOX is shown to be anchored, in part, in the cell membrane by Hyal-2. Alternatively, WWOX undergoes self-polymerization and localizes in the cell membrane. Proapoptotic pY33-WWOX binds Hyal-2, and TGF-β induces internalization of the pY33-WWOX/Hyal-2 complex to the nucleus for causing cell death. In contrast, when pY33 is downregulated and pS14 upregulated in WWOX, pS14-WWOX supports cancer growth in vivo. Here, we investigated whether membrane WWOX receives extracellular signals via surface-exposed epitopes, especially at the S14 area, that signals for cancer growth suppression and prevention. By using a simulated 3-dimentional structure and generated specific antibodies, WWOX epitopes were determined at amino acid #7 to 21 and #286 to 299. Synthetic WWOX7-21 peptide, or truncation to 5-amino acid WWOX7-11, s...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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ConclusionsSelPac met its primary endpoint, demonstrating a statistically significant improvement in PFS for SEL + PT without a significant increase in toxicity. No trend for a prolongation of OS was observed.Clinical trial identificationISRCTN 29621851.Legal entity responsible for the studyUniversity of Liverpool&Liverpool Cancer Trials Unit.FundingCancer Research UK and AstraZeneca.DisclosureP. Nathan: Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: AstraZeneca; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: BMS; Honoraria (self), Advisory / Consultancy, Consultancy / ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Emily Roarty Jing Wang Fei Yang Michelle Barton Jeffrey Rosen Sendurai Mani Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study was carried out in accordance with approval of the Melbourne Health and Walter and Eliza Hall Institute of Medical Research's Human Research Ethics Committee (approval number: 2013.081). All subjects gave written informed consent for participation and publication. Results and Discussion TGF-β signaling in NK cells is associated with: phosphorylation in SMAD2 and 3, inhibition of IL-15-induced metabolism/proliferation, simultaneous downregulation of CD44, CD49e, and Eomes, and upregulation of CD16 and CD49a expression (7, 10). SMAD family member 4 (SMAD4) belongs to the SMAD family of transcription...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we investigated the role of IL-19 in asthmatic animal models in order to determine the therapeutic potential of IL-19-signaling antagonists for treating allergic asthma. Materials and Methods Animals All animal experiments were done using the protocols of the National Institutes of Health standards and guidelines for the care and use of experimental animals. The research procedures were approved by the Animal Ethics Committee of National Cheng Kung University (IACUC NO. 107272 and 105077). Generating IL-20R1 Knockout Mice IL-20R1 knockout(−/−) mice were generated and maintained on a C57BL/6 ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.Tg) mouse models of PDA and investigated the associated immune responses. Treatment with TAB004 + Lip-MSA-IL-2 resulted in significantly improved survival and slower tumor growth compared to controls in MUC1.Tg mice bearing an orthotopic PDA.MUC1 tumor. Similarly, in the spontaneous model of PDA that expresses human MUC1, the combination treatment stalled the progression of pancreatic intraepithelial pre-neoplastic (PanIN) lesion to adenocarcinoma. Treatment with t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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