Browsing by Subject "Mechanisms"

Now showing 1 - 4 of 4

Open Access
Feedforward and feedback processes in vision
(Frontiers Research Foundation, 2015) Kafalıgönül, Hulusi; Breitmeyer, Buruno G.; Öğmen, Haluk
[No abstract available]
Open Access
Induction of ROS, p53, p21 in DEHP-and MEHP-exposed LNCaP cells-protection by selenium compunds
(Elsevier, 2011-07) Erkekoglu, P.; Rachidi, W.; Yazgullu, O. G.; Giray, B.; Ozturk, M.; Favier, A.; Hincal, F.
This study was designed to investigate the hypothesis that the toxic effects of di(2-ethylhexyl)phthalate (DEHP), the most abundantly used plasticizer and ubiquitous environmental contaminant that cause alterations in endocrine and spermatogenic functions in animals is mediated through the induction of reactive oxygen species (ROS) and activation of nuclear p53 and p21 proteins in LNCaP human prostate adenocarcinoma cell line. Protective effects of two selenocompounds, sodium selenite (SS) and selenomethionine (SM) were also examined. It was demonstrated that 24. h exposure of the cells to 3. mM DEHP or its main metabolite, mono(2-ethylhexyl)phthalate (MEHP, 3 μM) caused strongly amplified production of ROS. Both SS (30. nM) and SM (10 μM) supplementations reduced ROS production, and p53 and p21 activation that induced significantly only by MEHP-exposure. The overall results of this study indicated that the induction of oxidative stress is one of the important mechanisms underlying the toxicity of DEHP and this is mainly through the effects of the metabolite, MEHP. Generated data also emphasized the critical role of Se in modulation of intracellular redox status, implicating the importance of the appropriate Se status in cellular response against testicular toxicity of phthalates. © 2011 Elsevier Ltd.
Open Access
Targeting TACC3 induces immunogenic cell death and enhances T-DM1 Response in HER2-positive breast cancer
(American Association for Cancer Research, 2024-05-02) Gedik, Mustafa Emre; Saatçi, Özge; Oberholtzer, Nathaniel; Üner, Meral; Akbulut Çalışkan, Özge; Çetin, Metin; Aras, Mertkaya; İbiş, Kübra; Çalışkan, Burcu; Banoğlu, Erden; Wiemann, Stefan; Üner, Ayşegül; Aksoy, Sercan; Mehrotra, Shikhar; Şahin, Özgür
Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2 alpha phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance. Accordingly, ICD-related gene signatures in pretreatment samples correlated with clinical response to T-DM1-containing therapy, and increased infiltration of antitumor CD8(+) T cells in posttreatment samples was correlated with better T-DM1 response. Transforming acidic coiled-coil containing 3 (TACC3) was overexpressed in T-DM1-resistant cells, and T-DM1 responsive patients had reduced TACC3 protein expression whereas nonresponders exhibited increased TACC3 expression during T-DM1 treatment. Notably, genetic or pharmacologic inhibition of TACC3 restored T-DM1-induced SAC activation and induction of ICD markers in vitro. Finally, TACC3 inhibition in vivo elicited ICD in a vaccination assay and potentiated the antitumor efficacy of T-DM1 by inducing dendritic cell maturation and enhancing intratumoral infiltration of cytotoxic T cells. Together, these results illustrate that ICD is a key mechanism of action of T-DM1 that is lost in resistance and that targeting TACC3 can restore T-DM1-mediated ICD and overcome resistance.
Open Access
Three-dimensional motion and dense-structure estimation using convex projections
(SPIE, 1997-02) Alatan, A. Aydın; Erdem, A. Tanju; Onural, Levent
We propose a novel method for estimating the 3D motion and dense structure of an object form its two 2D images. The proposed method is an iterative algorithm based on the theory of projections onto convex sets (POCS) that involves successive projections onto closed convex constraint sets. We seek a solution for the 3D motion and structure information that satisfies the following constraints: (i) rigid motion - the 3D motion parameters are the same for each point on the object. (ii) Smoothness of the structure - depth values of the neighboring points on the object vary smoothly. (iii) Temporal correspondence - the intensities in the given 2D images match under the 3D motion and structure parameters. We mathematically derive the projection operators onto these sets and discuss the convergence properties of successive projections. Experimental results show that the proposed method significantly improves the initial motion and structure estimates.