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E6 inhibitor

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https://www.readbyqxmd.com/read/28521396/inhibition-of-mmp-9-expression-by-ritonavir-or-saquinavir-is-associated-with-inactivation-of-the-akt-fra-1-pathway-in-cervical-intraepithelial-neoplasia-cells
#1
Ilaria Bacigalupo, Clelia Palladino, Patrizia Leone, Elena Toschi, Cecilia Sgadari, Barbara Ensoli, Giovanni Barillari
A reduced incidence and decreased clinical progression of uterine cervical intraepithelial neoplasia (CIN) has been observed in women infected with human immunodeficiency virus (HIV) treated with HIV-protease inhibitors (PIs). The HIV-PIs saquinavir (SQV) and ritonavir (RTV) have been demonstrated to efficiently inhibit invasion of human primary CIN cells by downregulating the expression of matrix metalloproteinase (MMP)-9. The present study further investigated the molecular mechanisms underlying the activity of SQV and RTV in CIN...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521287/5azadc-treatment-upregulates-mir-375-level-and-represses-hpv16-e6-expression
#2
Adrien Morel, Aurélie Baguet, Jérôme Perrard, Caroline Demeret, Elise Jacquin, David Guenat, Christiane Mougin, Jean-Luc Prétet
High risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28508744/overexpression-of-human-papillomavirus-type-16-oncoproteins-enhances-epithelial-mesenchymal-transition-via-stat3-signaling-pathway-in-non-small-cell-lung-cancer-cells
#3
Wenzhang Zhang, Xin Wu, Liang Hu, Yuefan Ma, Zihan Xiu, Bingyu Huang, Yun Feng, Xudong Tang
Human papillomavirus (HPV) infection may be associated with the development and progression of non-small cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial-mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here, we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with EGFP-N1-HPV-16 E6 or E7 plasmid...
December 15, 2016: Oncology Research
https://www.readbyqxmd.com/read/28487025/mouse-prolyl-oligopeptidase-plays-a-role-in-trophoblast-stem-cell-differentiation-into-trophoblast-giant-cell-and-spongiotrophoblast
#4
Yuki Maruyama, Shin Matsubara, Atsushi P Kimura
INTRODUCTION: Prolyl oligopeptidase (prolyl endopeptidase, Prep), a multifunctional protease hydrolyzing -Pro-X- peptide bonds, is highly expressed in the mouse placenta, but the function during development is not known. We explored the possibility of Prep's involvement in placental differentiation. METHODS: We cultured trophoblast stem cells (TSCs) derived from the E6.5 mouse embryo and investigated the detailed expression pattern of Prep during their differentiation...
May 2017: Placenta
https://www.readbyqxmd.com/read/28477016/e6ap-promotes-prostate-cancer-by-reducing-p27-expression
#5
Dinesh Raghu, Piotr Jan Paul, Twishi Gulati, Siddhartha Deb, Christine Khoo, Andrea Russo, Enzo Gallo, Giovanni Blandino, Ai-Leen Chan, Elena Takano, Shahneen K Sandhu, Stephen B Fox, Scott Williams, Sue Haupt, Cristina Gamell, Ygal Haupt
Prostate cancer (PC) is the most common cancer in men. Elevated levels of E3 ligase, E6-Associated Protein (E6AP) were previously linked to PC, consistent with increased protein expression in a subset of PC patients. In cancers, irregular E3 ligase activity drives proteasomal degradation of tumor suppressor proteins. Accordingly, E3 ligase inhibitors define a rational therapy to restore tumor suppression. The relevant tumor suppressors targeted by E6AP in PC are yet to be fully identified. In this study we show that p27, a key cell cycle regulator, is a target of E6AP in PC...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403145/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection
#6
Elizabeth A Nelson, Julie Dyall, Thomas Hoenen, Alyson B Barnes, Huanying Zhou, Janie Y Liang, Julia Michelotti, William H Dewey, Lisa Evans DeWald, Richard S Bennett, Patrick J Morris, Rajarshi Guha, Carleen Klumpp-Thomas, Crystal McKnight, Yu-Chi Chen, Xin Xu, Amy Wang, Emma Hughes, Scott Martin, Craig Thomas, Peter B Jahrling, Lisa E Hensley, Gene G Olinger, Judith M White
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM)...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28368541/interferon-beta-and-interferon-gamma-are-weak-inhibitors-of-ebola-virus-in-cell-based-assays
#7
Julie Dyall, Brit J Hart, Elena Postnikova, Yu Cong, Huanying Zhou, Dawn M Gerhardt, Denise Freeburger, Julia Michelotti, Anna N Honko, Lisa Evans DeWald, Richard S Bennett, Gene G Olinger, Peter B Jahrling, Lisa E Hensley
Previous studies demonstrated little efficacy of interferons (IFNs) in animal models of Ebola virus disease. However, these studies were limited to a small number of Type I IFNs and, during the most recent outbreak of Ebola virus, questions regarding the suitability of the animal models to evaluate IFNs were raised. To address the potential that anti-Ebola virus activity was overlooked, Type I and Type II IFNs (α-2a, α-2b, -β, -γ, and -universal) were tested in a variety of cell types (Vero E6, Huh 7 cells, and human macrophages)...
March 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28235572/role-of-akt-pkb-and-pfkfb-isoenzymes-in-the-control-of-glycolysis-cell-proliferation-and-protein-synthesis-in-mitogen-stimulated-thymocytes
#8
Amina Houddane, Laurent Bultot, Laura Novellasdemunt, Manuel Johanns, Marie-Agnès Gueuning, Didier Vertommen, Pierre G Coulie, Ramon Bartrons, Louis Hue, Mark H Rider
Proliferating cells depend on glycolysis mainly to supply precursors for macromolecular synthesis. Fructose 2,6-bisphosphate (Fru-2,6-P2) is the most potent positive allosteric effector of 6-phosphofructo-1-kinase (PFK-1), and hence of glycolysis. Mitogen stimulation of rat thymocytes with concanavalin A (ConA) led to time-dependent increases in lactate accumulation (6-fold), Fru-2,6-P2 content (4-fold), 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase isoenzyme 3 and 4 (PFKFB3 and PFKFB4) protein levels (~2-fold and ~15-fold, respectively) and rates of cell proliferation (~40-fold) and protein synthesis (10-fold) after 68h of incubation compared with resting cells...
February 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28043143/effects-of-ala-pdt-on-hpv16-immortalized-cervical-epithelial-cell
#9
S X Wu, X Y Ren, Y L Pan, D D Guan, S Liu, X Y Zou, C G Shi, Y Z Li, Y Z Zhang
Current treatments for high-grade cervical intraepithelial neoplasia (CIN) and persistent infection with high-risk human papillomavirus (HR-HPV) type are mainly surgical interventions. However, such treatments are associated with adverse side effects and pose risks for future pregnancies. In order to reduce the requirement for excisional procedures, an effective and noninvasive therapy is needed for women at reproductive age. ALA-PDT has proved to be effective in the treatment of HPV-associated disease in several clinical investigations...
2017: Neoplasma
https://www.readbyqxmd.com/read/27822180/axonal-cleaved-caspase-3-regulates-axon-targeting-and-morphogenesis-in-the-developing-auditory-brainstem
#10
Sarah E Rotschafer, Michelle R Allen-Sharpley, Karina S Cramer
Caspase-3 is a cysteine protease that is most commonly associated with cell death. Recent studies have shown additional roles in mediating cell differentiation, cell proliferation and development of cell morphology. We investigated the role of caspase-3 in the development of chick auditory brainstem nuclei during embryogenesis. Immunofluorescence from embryonic days E6-13 revealed that the temporal expression of cleaved caspase-3 follows the ascending anatomical pathway. The expression is first seen in the auditory portion of VIIIth nerve including central axonal regions projecting to nucleus magnocellularis (NM), then later in NM axons projecting to nucleus laminaris (NL), and subsequently in NL dendrites...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27678330/cross-talk-between-human-papillomavirus-oncoproteins-and-hedgehog-signaling-synergistically-promotes-stemness-in-cervical-cancer-cells
#11
Kanchan Vishnoi, Sutapa Mahata, Abhishek Tyagi, Arvind Pandey, Gaurav Verma, Mohit Jadli, Tejveer Singh, Sukh Mahendra Singh, Alok C Bharti
Viral oncoproteins E6/E7 play key oncogenic role in human papillomavirus (HPV)-mediated cervical carcinogenesis in conjunction with aberrant activation of cellular signaling events. GLI-signaling has been implicated in metastasis and tumor recurrence of cervical cancer. However, the interaction of GLI-signaling with HPV oncogenes is unknown. We examined this relationship in established HPV-positive and HPV-negative cervical cancer cell lines using specific GLI inhibitor, cyclopamine and HPVE6/E7 siRNAs. Cervical cancer cell lines showed variable expression of GLI-signaling components...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650607/the-braf-inhibitor-vemurafenib-enhances-uv-induced-skin-carcinogenesis-in-beta-hpv38-e6-and-e7-transgenic-mice
#12
Daniele Viarisio, Karin Müller-Decker, Jessica C Hassel, Jean-Claude Alvarez, Christa Flechtenmacher, Michael Pawlita, Lutz Gissmann, Massimo Tommasino
No abstract text is available yet for this article.
January 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27635203/effects-of-valproic-acid-and-pioglitazone-on-cell-cycle-progression-and-proliferation-of-t-cell-acute-lymphoblastic-leukemia-jurkat-cells
#13
Marie Saghaeian Jazi, Saeed Mohammadi, Yaghoub Yazdani, Sima Sedighi, Ali Memarian, Mehrdad Aghaei
OBJECTIVES: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies...
July 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27624132/tandemly-integrated-hpv16-can-form-a-brd4-dependent-super-enhancer-like-element-that-drives-transcription-of-viral-oncogenes
#14
Katharine E Dooley, Alix Warburton, Alison A McBride
UNLABELLED: In cancer cells associated with human papillomavirus (HPV) infections, the viral genome is very often found integrated into the cellular genome. The viral oncogenes E6 and E7 are transcribed from the viral promoter, and integration events that alter transcriptional regulation of this promoter contribute to carcinogenic progression. In this study, we detected highly enriched binding of the super-enhancer markers Brd4, MED1, and H3K27ac, visible as a prominent nuclear focus by immunofluorescence, at the tandemly integrated copies of HPV16 in cells of the cervical neoplasia cell line W12 subclone 20861...
2016: MBio
https://www.readbyqxmd.com/read/27599897/stat3-activity-regulates-sensitivity-to-tumor-necrosis-factor-related-apoptosis-inducing-ligand-induced-apoptosis-in-cervical-cancer-cells
#15
Hiroe Nakamura, Ayumi Taguchi, Kei Kawana, Akira Kawata, Mitsuyo Yoshida, Asaha Fujimoto, Juri Ogishima, Masakazu Sato, Tomoko Inoue, Haruka Nishida, Hitomi Furuya, Kensuke Tomio, Satoko Eguchi, Mayuyo Mori-Uchino, Aki Yamashita, Katsuyuki Adachi, Takahide Arimoto, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Yutaka Osuga, Tomoyuki Fujii
In cervical cancer, p53-induced apoptosis is abrogated by human papilloma virus (HPV)-derived oncoprotein E6. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) provides tumor-specific apoptosis in various cancers, including cervical cancer, the sensitivity differs depending on the cell lines. Signal transducer and activator of transcription 3 (STAT3) is a hub molecule that shifts the cellular fate to apoptosis or survival in response to cellular stresses. However, the contribution of STAT3 activity to TRAIL-induced apoptosis in cervical cancer remains unknown...
November 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27538837/mtor-inhibition-prevents-rapid-onset-of-carcinogen-induced-malignancies-in-a-novel-inducible-hpv-16-e6-e7-mouse-model
#16
Juan Luis Callejas-Valera, Ramiro Iglesias-Bartolome, Panomwat Amornphimoltham, Julia Palacios-Garcia, Daniel Martin, Joseph A Califano, Alfredo A Molinolo, J Silvio Gutkind
The rising incidence of human papillomavirus (HPV)-associated malignancies, especially for oropharyngeal cancers, has highlighted the urgent need to understand how the interplay between high-risk HPV oncogenes and carcinogenic exposure results in squamous cell carcinoma (SCC) development. Here, we describe an inducible mouse model expressing high risk HPV-16 E6/E7 oncoproteins in adults, bypassing the impact of these viral genes during development. HPV-16 E6/E7 genes were targeted to the basal squamous epithelia in transgenic mice using a doxycycline inducible cytokeratin 5 promoter (cK5-rtTA) system...
October 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27508098/mir-153-promotes-breast-cancer-cell-apoptosis-by-targeting-hectd3
#17
Xiaowei Wu, Lin Li, Yi Li, Zhihua Liu
Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) is an E3 ubiquitin ligase which ubiquitinates caspase-8, caspase-9 and promotes cancer cell survival. Aberrant HECTD3 expression is frequently involved in various types of cancer progression. However, to date, the regulation of HECTD3 remains unclear. Here, we demonstrated that miR-153 functions as a negative regulator of HECTD3 and sensitizes cisplatin-induced apoptosis in triple-negative breast cancer cells MDA-MB-231 and BT-549...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27489353/hpv16-e6-e7-induces-cancer-stem-like-cells-phenotypes-in-esophageal-squamous-cell-carcinoma-through-the-activation-of-pi3k-akt-signaling-pathway-in-vitro-and-in-vivo
#18
Ruxing Xi, Shupei Pan, Xin Chen, Beina Hui, Li Zhang, Shenbo Fu, Xiaolong Li, Xuanwei Zhang, Tuotuo Gong, Jia Guo, Xiaozhi Zhang, Shaomin Che
High-risk human papillomavirus (HPV), especially HPV16, correlates with cancerogenesis of human esophageal squamous cell carcinoma (ESCC) and we have reported that HPV16 related with a poor prognosis of ESCC patients in China. We aim to investigate the potential role and mechanism of HPV16 in ESCC development and progress. Our following researches demonstrated that ESCC cells which were stably transfected by HPV16 E6-E7 lentiviral vector showed a remarkable cancer stem-like cells (CSCs) phenotype, such as: migration, invasion, spherogenesis, high expression of CSCs marker in ESCC---p75NTR, chemoresistance, radioresistance, anti-apoptosis ability in vitro and cancerogenesis in vivo...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27466989/the-expression-of-inhibitor-of-growth-4-is-reduced-in-cervical-cancer-tissues
#19
J Yuan, Y-L Han, T-Y Wang, S Wu, L Tong, L-X Lin, M Li, L-L Wei, Z-H Zhong, G-M Zhang, Y Wang
OBJECTIVE: Inhibitor of growth 4 (ING4) is a candidate tumor suppressor which plays an important role in multiple processes including DNA repair, apoptosis, cell cycle control, tumor metastasis and angiogenesis. However, clinical data about the role of ING4 in the development and progression of cervical cancer are still limited. This study aimed to examine ING4 expression in cervical cancer and analyze its correlation with the progression of the malignancy. PATIENTS AND METHODS: RT-PCR, Western blot and immunohistochemistry analysis were performed to determine ING4 expression in 18 clinical specimens from cervical cancer patients...
July 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27364951/vitamin-e-synthetic-derivate-tpgs-selectively-induces-apoptosis-in-jurkat-t-cells-via-oxidative-stress-signaling-pathways-implications-for-acute-lymphoblastic-leukemia
#20
Cristian Ruiz-Moreno, Marlene Jimenez-Del-Rio, Ligia Sierra-Garcia, Betty Lopez-Osorio, Carlos Velez-Pardo
D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of natural vitamin E commonly used as a drug delivery agent. Recently, TPGS alone has been reported to induce cell death in lung, breast and prostate cancer. However, the effect of TPGS on cancer cell viability remains unclear. Thus, this study was aimed to evaluate the cytotoxic effect of TPGS on human periphral blood lymphocytes (PBL) and on T cell acute lymphocytic leukemia (ALL) Jurkat clone E6-1 cells and its possible mechanism of action...
September 2016: Apoptosis: An International Journal on Programmed Cell Death
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