Cavit O.Tütengil üzerine

Taha Toros Arşivi, Dosya No: 200-Cavit Orhan Tütengil. Not: Gazetenin "Olaylar ve Görüşler" köşesinde yayımlanmıştır.Unutma İstanbul projesi İstanbul Kalkınma Ajansı'nın 2016 yılı "Yenilikçi ve Yaratıcı İstanbul Mali Destek Programı" kapsamında desteklenmiştir. Proje No: TR10/16/YNY/010

A New Wrinkle on Topical Vitamin E and Photo-inflammation: Mechanistic Studies of a Hydrophilic γ-Tocopherol Derivative Compared with α-Tocopherol

The antioxidant function of vitamin E is thought to mediate its photo-protective effects. Cyclooxygenase-2 (COX-2) is an important mediator of early photo-inflammation. Thus, the ability of γ-tocopherol to inhibit COX-2 activity independently of its antioxidant function raises important questions regarding potential roles that this form of vitamin E plays in photo-protection and skin cancer chemoprevention

The Rosenberg Case: Touchstone of a Changing America

Ted Konger is a senior at IPFW, majoring in Secondary Education-Social Studies with a minor in mathematics. He worked as a merchandiser/buyer for SuperValu Corp. for twenty-nine years before returning to school. He is a member of the Phi Kappa Phi Honor Society. In 2010 he received the Sharon Alt Piepenbrink Award for his paper “The Rosenberg Case: Touchstone of a Changing America.

The PPARγ Agonist Rosiglitazone Suppresses Syngeneic Mouse SCC (Squamous Cell Carcinoma) Tumor Growth through an Immune-Mediated Mechanism

Recent evidence suggests that PPARγ agonists may promote anti-tumor immunity. We show that immunogenic PDV cutaneous squamous cell carcinoma (CSCC) tumors are rejected when injected intradermally at a low cell number (1 × 106) into immune competent syngeneic hosts, but not immune deficient mice. At higher cell numbers (5 × 106 PDV cells), progressively growing tumors were established in 14 of 15 vehicle treated mice while treatment of mice with the PPARγ agonist rosiglitazone resulted in increased tumor rejection (5 of 14 tumors), a significant decrease in PDV tumor size, and a significant decrease in tumor cell Ki67 labeling. Rosiglitazone treatment had no effect on tumor rejection, tumor volume or PDV tumor cell proliferation in immune deficient NOD.CB17-PrkdcSCID/J mice. Rosiglitazone treatment also promoted an increase in tumor infiltrating CD3+ T-cells at both early and late time points. In contrast, rosiglitazone treatment had no significant effect on myeloid cells expressing either CD11b or Gr-1 but suppressed a late accumulation of myeloid cells expressing both CD11b and Gr-1, suggesting a potential role for CD11b+Gr-1+ myeloid cells in the late anti-tumor immune response. Overall, our data provides evidence that the PPARγ agonist rosiglitazone promotes immune-mediated anti-neoplastic activity against tumors derived from this immunogenic CSCC cell line

Growth regulation of primary human keratinocytes by prostaglandin E receptor EP2 and EP3 subtypes

AbstractWe examined the contribution of specific EP receptors in regulating cell growth. By RT–PCR and northern hybridization, adult human keratinocytes express mRNA for three PGE2 receptor subtypes associated with cAMP signaling (EP2, EP3, and small amounts of EP4). In actively growing, non-confluent primary keratinocyte cultures, the EP2 and EP4 selective agonists, 11-deoxy PGE1 and 1-OH PGE1, caused complete reversal of indomethacin-induced growth inhibition. The EP3/EP2 agonist (misoprostol), and the EP1/EP2 agonist (17-phenyl trinor PGE2), showed less activity. Similar results were obtained with agonist-induced cAMP formation. The ability of exogenous dibutyryl cAMP to completely reverse indomethacin-induced growth inhibition support the conclusion that growth stimulation occurs via an EP2 and/or EP4 receptor-adenylyl cyclase coupled response. In contrast, activation of EP3 receptors by sulprostone, which is virtually devoid of agonist activity at EP2 or EP4 receptors, inhibited bromodeoxyuridine uptake in indomethacin-treated cells up to 30%. Although human EP3 receptor variants have been shown in other cell types to markedly inhibit cAMP formation via a pertussis toxin sensitive mechanism, EP3 receptor activation and presumably growth inhibition was independent of adenylyl cyclase, suggesting activation of other signaling pathways

Platelet-Activating Factor-Receptor and Tumor Immunity

First described in 1972 by Benveniste and colleagues, platelet-activating factor (PAF) remains one of the potent phospholipid known to date. The role of PAF produced enzymatically in mediating diverse biological and pathophysiological processes including inflammatory and allergic diseases and cancers in response to various stimuli has been extensively studied. However, little is known about the role of non-enzymatically-generated PAF-like lipids produced in response to pro-oxidative stressors, particularly in modulating the host immune responses to tumor immunity, which is the focus of this review

Large area, label-free imaging of extracellular matrix using telecentricity

Subtle alterations in stromal tissue structures and organizations within the extracellular matrix (ECM) have been observed in several types of tissue abnormalities, including early skin cancer and wounds. Current microscopic imaging methods often lack the ability to accurately determine the extent of malignancy over a large area, due to their limited field of view. In this research we focus on the development of simple mesoscopic (i.e. between microscopic and macroscopic) biomedical imaging device for non-invasive assessment of ECM alterations over a large, heterogeneous area. In our technology development, a telecentric lens, commonly used in machine vision systems but rarely used in biomedical imaging, serves as a key platform to visualize alterations in tissue microenvironments in a label-free manner over a clinically relevant area. In general, telecentric imaging represents a simple, alternative method for reducing unwanted scattering or diffuse light caused by the highly anisotropic scattering properties of biological tissue. In particular, under telecentric imaging the light intensity backscattered from biological tissue is mainly sensitive to the scattering anisotropy factor, possibly associated with the ECM. We demonstrate the inherent advantages of combining telecentric lens systems with hyperspectral imaging for providing optical information of tissue scattering in biological tissue of murine models, as well as light absorption of hemoglobin in blood vessel tissue phantoms. Thus, we envision that telecentric imaging could potentially serve for simple site-specific, tissue-based assessment of stromal alterations over a clinically relevant field of view in a label-free manner, for studying diseases associated with disruption of homeostasis in ECM

Ultraviolet B radiation mediated generation of Platelet-activating factor agonists augments melanoma tumor growth

poster abstractPlatelet-activating factor (1-alkyl-2-acetyl-glycerophosphocholine; PAF) is a potent lipid mediator with diverse activities. Our previous studies have demonstrated that oxidized glycerophosphocholines (OxGPCs) that act as agonists for the Platelet-activating factor receptor (PAF-R) mediate ultraviolet B radiation (UVB) induced systemic immunosuppression in a process involving IL-10. However, the exact role of UVB-mediated systemic immunosuppression in pathophysiological processes remains unclear. The current studies sought to define whether UVB-induced systemic immunosuppression could modulate experimental murine melanoma tumor growth. Using a murine UVB model of systemic immunosuppression, we demonstrate that UVB exposure to a remote site from skin implanted with subcutaneous B16F10 melanoma results in enhanced tumor growth in C57BL/6 (wild-type) mice but not in PAF-R-deficient mice. We further show that intraperitoneal injection of the PAF agonist carbamoylPAF (CPAF) mimicked the UVB effect. Interestingly, neutralizing antibody against IL-10 blocked both CPAF- and UVB-mediated augmentation of B16F10 tumor growth. The next studies were designed to define whether the PAF-R effect was due to direct effects on B16F10 cells. Of note, B16F10 cells lack functional PAF-R expression. To address this question, we first generated PAF-R expressing B16F10 (B16-PAFR) and its vector control B16-MSCV cells by retroviral transduction and confirmed the presence of PAF-R in B16-PAF-R cells by intracellular Ca2+ flux in response to CPAF and qRT-PCR. Transplantation of B16-PAFR cells into mice did not result in an increased rate of tumor growth over control B16-MSCV cells either alone, or in response to UVB or CPAF. These studies provide a novel unreported effect of UVB-mediated PAF agonists, namely, that they can augment melanoma tumor growth via IL-10

Cigarette smoke exposure mediated generation of Platelet-activating factor agonists induces systemic immunosuppression

poster abstractThe ubiquitous environmental pollutant cigarette smoke (CS) is known to exert immodulatory effects. CS also acts as a potent pro-oxidative stressor. Several studies including ours have characterized the importance of various pro-oxidative stressors including UVB to inhibit host immunity and an importance of the platelet-activating factor (1-alkyl-2-acetyl-glycerophosphocholine; PAF), a potent lipid mediator in this process. PAF is produced enzymatically in a tightly-controlled process. In addition, oxidative stressors can act directly on glycerophosphocholines (GPC) to produce oxidized GPC which are potent PAF-R agonists. The present studies employed model systems consisting of PAF-receptor (PAF-R)-expressing (KBP) and–deficient (KBM) cells and mice (wild type [WT] and Pafr-/-) to determine whether CS exposure could generate PAF-R agonists in blood and whether it could suppress contact hypersensitivity reactions in a PAF-R-dependent manner. We show that lipid extracts derived from the blood of CS-treated WT mice resulted in immediate intracellular calcium (Ca2+2+mice. This inhibitory effect of CS in WT mice were similar to those induced by a PAF-R agonist, CPAF or histamine. Furthermore, this inhibition of CHS by CS in WT mice was blocked by antioxidants vitamin C and N-acetyl cysteine. These findings indicate that CS exposure induces systemic immunosuppression in a PAF-R-dependent manner. These studies provide the first evidence that the pro-oxidative stressor CS can modulate cutaneous immunity via the generation of PAF agonists through lipid oxidation.) mobilization response only in KBP cells. However, no Camobilization response was detected with lipid extracts from non-smoked (sham) mice both in KBP and KBM cells. In addition, lipid extracts only from CS-treated mice induced an increase in IL-8 secretion in KBP cells indicating that CS generates systemic PAF-R agonists. CS exposure also inhibited contact hypersensitivity to the allergen dinitrofluorobenzene (DNFB) selectively in WT but not inPafr-/

Data-driven imaging of tissue inflammation using RGB-based hyperspectral reconstruction toward personal monitoring of dermatologic health

Sensitive and accurate assessment of dermatologic inflammatory hyperemia in otherwise grossly normal-appearing skin conditions is beneficial to laypeople for monitoring their own skin health on a regular basis, to patients for looking for timely clinical examination, and to primary care physicians or dermatologists for delivering effective treatments. We propose that mathematical hyperspectral reconstruction from RGB images in a simple imaging setup can provide reliable visualization of hemoglobin content in a large skin area. Without relying on a complicated, expensive, and slow hyperspectral imaging system, we demonstrate the feasibility of determining heterogeneous or multifocal areas of inflammatory hyperemia associated with experimental photocarcinogenesis in mice. We envision that RGB-based reconstructed hyperspectral imaging of subclinical inflammatory hyperemic foci could potentially be integrated with the built-in camera (RGB sensor) of a smartphone to develop a simple imaging device that could offer affordable monitoring of dermatologic health