bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morpho‐structural Peculiarities of Blood Formed Elements and Clinic‐pathological Characteristics in Women with Uterine (Benign, Malignant) Tumors in Menopausal Age
Authors: Kotrikadze Nanuli , Tufinashvili Tamar , Nakashidze Irina , Ramishvili Liana , Alibegashvili Manana , Gordeziani Manana , Sepiashvilli Bela , Ahmad Sarfraz 
Published: June 2021

ObjectiveTo evaluate ongoing alterations that reflect on the structural characteristics of blood formed elements based on the hormonal imbalance and to investigate the ABO system antigens among menopausal women with uterine (benign & malignant) tumors.MethodsBlood specimens from women with benign (n=15), malignant (n=15) uterine tumors, & healthy menopausal women (control, n=15) were used. ELISA kits were used for the quantitative determination of hormones. The blood formed elements ultrastructure observations were conducted by electronic microscope.ResultsCompared to control (33.8±0.7 pg/mL), estradiol level was higher in benign (45.7±0.9 pg/mL) & malignant (70.7±3.7 pg/mL) cases (p<0.001). Similar pattern was noted in testosterone levels [control=0.38±0.03 ng/mL, benign=0.55±0.04 ng/mL (p<0.01), malignant=1.56±0.14 ng/mL (p<0.001)] was higher in malignant cases. In contrast, progesterone levels were decreased in the disease cases [control=0.93±0.05 ng/mL, benign=0.44±0.003 ng/mL, 0.31±0.02 ng/ml (p<0.001)]. The percent ABO system antigens distributions were: O(I) (control=60±10.9, benign=40±10.2, malignant=25±10.2), A(II) (control=30±10.2, benign=55±11.1, malignant=70±10.6), B(III) (control=5±4.8, benign=0±0, malignant=0±0), and AB(IV) (control=5±4.8, benign=5±4.8, malignant=5±4.8) percent. Assessments of morphologic structure of erythrocytes revealed numerous pathological form erythrocytes (Poikilocytosis) as benign, also in case of malignant tumors, particularly target cell (codocytes), hamlet cell, Teardrop cells (dacrocytes), Sickle cells (Drepanocytes) erythrocytes.ConclusionsUsing ELISA and transmembrane electron microscopy, our results demonstrate that in the malignant uterine tumor of menopausal women, quantitative/structural changes occur in blood formed elements indicating ongoing alterations in hormonal imbalance. Assessing these changes in structural characteristics would be useful in examining uterine pathologies and subsequent treatment plans.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Combination of Ionizing Radiation with Glutaminase Inhibition Improves Treatment Response in Head and Neck Squamous Cell Carcinoma
Authors: Wicker Christina Ann , Mills Gordon , Wise‐Draper Trisha , Takiar Vinita 
Published: June 2021

Head and neck cancer is the 6th most common cancer worldwide. Ionizing radiation (IR) is an important aspect of cancer treatment, however its efficacy is limited by radioresistance, resulting in locoregional failure rates as high as 50%. The pathways used by cells to evade the cellular damage caused by IR are poorly understood. Initial Reverse Phase Protein Array analyses in our laboratory demonstrated that IR induced metabolic pathways, including those involving the TCA cycle. Glutamate is a key substrate of the TCA cycle, and essential for the production of biomolecules necessary for tumor proliferation. Glutaminase is the enzyme that converts glutamine to glutamate. Analysis of The Cancer Genome Atlas's transcriptome database revealed that glutaminase overexpression (upper 25%) in patients with head and neck squamous cell cancer (HNSCC) was associated with significantly reduced patient survival (p<0.03) . In this study, we aimed to identify whether glutaminase inhibition with CB‐839 (Caymen Chemical) could enhance the cellular response to IR. To do this, we used three representative human‐derived HNSCC cell lines: CAL‐27, FaDu, and HN5. We first established that proliferation of all three HNSCC cell lines was glutamine dependent by Dojindo CCK‐8 cell proliferation assay (20–50% increase, n=3 per line, p<0.01). Moreover, a synergistic decrease in cell survival was observed in clonogenic assays with HNSCC cell lines treated with IR and CB‐839 relative to either treatment alone (n=3 per line, p<0.05). In 3D cell culture, which better represents the host microenvironment, combinatorial treatment significantly reduced HNSCC spheroid size (11–26% decrease, n=3 per line, p<0.0001). To further understand the mechanism behind this reduced cell growth and survival, we examined CB‐839's effect on cellular metabolism using Seahorse MitoStress test assays. CB‐839 significantly reduced spare respiratory capacity and OCR/ECAR rate in HNSCC cell lines examined (p<0.001, p< 2.0×10−6,n>3). Mims et al. 2015 previously demonstrated that suppressing spare respiratory capacity enhances radiation sensitivity, which may explain the observed synergistic effects of CB‐839 in combination with IR. In summary, radiation resistance and locoregional failure is a major hurdle in the successful treatment of HNSCC. Combinatorial treatment with IR and the glutaminase inhibitor, CB‐839, led to an enhanced response over IR alone in HNSCC. These results support glutaminase as a possible target to overcome radiation related treatment resistance in patients with HNSCC.Support or Funding InformationPathways to Cancer Therapeutics Training Grant (CMP & SW T32CA117846‐11A1)VA Career Development Award (V.T. IK2 BX004360‐01A1)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cell Strains Derived from Long‐term 3D Tumor Models of MCF‐7 Display Characteristics and Phenotypes Consistent with Stem‐cell Populations
Authors: Topel Samantha , Lyden Timothy 
Published: June 2021

In a continuing series of studies, our laboratory has been examining the cell populations associated with long‐term 3‐D artificial tumor models generated using standard MCF‐7 breast ductal adenocarcinoma cells. In these studies we have developed long‐term cultures and grown them out to 1, 2, 3 and 4 years respectively. This report focuses on MCF‐7 tumors developed on de‐cellularized and de‐calcified bovine trabecular bone scaffolds. These long‐term cultures generate populations of cells throughout the entire culture period by shedding both individual cells and cell clusters, often in the form of spheroids. These various shed cell populations then form colonies and eventually monolayers of cells, from which the scaffold must be removed to new wells as a form of “passage”. This entire process of monolayer formation then repeats itself again within a week in the new wells. In addition to shed cells we have also harvested cell strains directly from the scaffolds by standard trypsinization for 15 minutes followed by a second trypsinization of an addition 15 minutes. The paired cultures of rapidly released and slowly released cells display significantly different phenotypes and present with differential marker patterns as well. In addition, we have also established cell strains from both explanting cells directly associated with the artificial tumors and colonies which establish themselves at a distance from the original tumor. These distinct populations also display unique phenotypes and marker patterns by flow cytometry. In these analyses it is clear that at least two major populations occur in both types of monolayer, but that the relative proportion is distinctly different, with a much increased stem‐like cell population being observed in released and floating cells from the colony strain but far less so from the explanting strain. Based on both size and CD44/CD24 immunophenotyping, we have established that this distinct cell population is mainly associated with distant colonies. It is our working hypothesis that these respective populations represent differential metastatic states in artificial tumor‐derived cell strains. Furthermore, we contend that this work characterizing cell populations derived from long‐term tumor models further confirms our overall conclusion that these artificial tumor tissues provide an effective model of tumor development including progression and metastasis in‐vitro.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Choline acetyltransferase: A novel molecular target in lung adenocarcinoma therapy
Authors: Richbart Stephen D , Akers Austin T , Friedman Jamie R , Bow Eric W , Rimoldi John M , Hardman Elaine W. , Dasgupta Piyali 
Published: June 2021

The clinicopathological properties of lung adenocarcinoma (LAC) in smokers is divergent from LAC in non‐smokers. One of the distinctive features of LAC in smokers is that the disease is relatively resistant to targeted molecular therapies. For example, targeted therapeutic agents like EGFR‐inhibitors (erlotinib and gefitinib) are highly effective in LACs in non‐smokers. However, these agents display much lower anti‐tumor activity in LACs in patients who are active smokers. Similarly, lung cancer patients (who are active smokers) show a lower response to chemotherapy than those who are non‐smokers. However, the majority of LAC patients are smokers. This underlines the need to identify viable drug targets for LAC therapy in patients who are exposed to cigarette smoke. A survey of literature reveals that nicotine (the addictive component of cigarette smoke) accelerates the growth of lung cancers, as well as confers resistance to chemotherapy. One of the mechanisms underlying the mitogenic activity of nicotine is that it promotes the production of the neurotransmitter acetylcholine (ACh) from LAC cells. ACh is known to be an autocrine growth factor for LAC cells and is synthesized by the enzyme choline acetyltransferase (ChAT). The present study investigates the feasibility of ChAT as a molecular target for LAC in smokers. We find that ChAT levels are upregulated in human LAC cell lines and tissues in analogous to their smoking history. Finally, the ChAT inhibitor BW813U causes robust apoptosis in human LAC cell lined and LAC cell lines isolated from patients. The magnitude of BW813U‐induced apoptosis is similar across LAC cell lines irrespective of smoking history; however, the concentration of BW813U which causes apoptosis is lower in LAC cell lines belonging to heavy smokers. The anti‐tumor activity of BW813U is also observed in H838 cells (belonging to an 80 pack‐year smoker) xenografted on athymic mice. Our studies show that antagonists of ChAT like BW813U may have therapeutic applications in the majority of the population of LAC who are smokers.Support or Funding InformationFunding for our study was supported by a NIH R15‐AREA Grant (2R15CA161491‐02). Furthermore, this study was supported in part by an Institutional Development Award (IDeA) Grant number P20GM104932 from the National Institute of General Medical Sciences (NIGMS) and the Research Core B of COBRE, a component of the National Institutes of Health (NIH).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
BCL6 inhibits CD4+Foxp3+ regulatory T cell trans‐differentiation into macrophage‐like cells via modulation of chromatin long‐range interactions
Authors: Mastascusa Kevin , Lai Bin , Wang Jiwei , Yang William , Sun Yu , Fagenson Alexander , Yu Daohai , Saaoud Fatma , Shao Ying , Cueto Ramon , Wu Susu , Fu Hangfei , Li Honglang , Zhu Peiqian , Wang Hong , Yang Xiaofeng 
Published: June 2021

The mechanisms underlying macrophage (Mϕ) heterogeneity and regulatory T cell (Treg) plasticity remain poorly determined. Here, we determined the mRNA expressions of 208 macrophage subset markers, Mϕ transcription factors (TFs) and other regulators in microarray data. We made the following findings: 1) Tissue Mϕ from lung, liver, spleen and intestine (LLSI) express higher M1 markers than adipose tissues (AT); the markers of Mϕ subsets such as MHb, Mhem, and HA‐Mac are AT‐enriched; and the markers of Mox are bone marrow (BM)‐specific; 2) Proadipogenic TFs C/EBPα, PPARγ and proinflamamtory adipokine leptin upregulate M1 markers; 3) Tissue Mϕ from LLSI and BM express higher levels of T cell co‐inhibition receptor CD274 than that of AT, have higher levels of glycolysis, fatty acid pathway, and fatty acid β‐oxidation pathway than that of AT, and prefer using RAB27A, STX3 to RAB31 and YKT6 in mediating exosome biogenesis and docking; 4) The expressions of 31 markers from 10 Mϕ subsets are modulated in eight groups of total 34 diseases; and a wide spectrum of pathological Mϕ pathways are identified from high hierarchical shared pathways to disease‐specific ones; 5) BCL6 inhibits Treg trans‐differentiation into Mϕ‐like cells; 6) BCL6 expression in Treg determines the status of BCL6 high stable Treg and BCL6 low plastic Treg potentially by exosomes generated from tumor cells and other cell types, respectively; and 7) BCL6 deficiency in Treg upregulates Mϕ TFs via increasing the ratio of upstream chromatin long‐range interaction sites (CLRISs) over downstream CLRISs. Our finding identified pathways underlying Mϕ heterogeneity in pathophysiological conditions and Treg plasticity, which serves as novel therapeutic targets for cancers and inflammation.Support or Funding InformationThis work was supported by NIH grant to Drs. XF. Yang, H. Wang.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glypican 3 (GPC3) cross talks with HGF/c‐Met axis in hepatocytes and hepatocellular carcinoma (HCC) by modulating p‐Ezrin (Thr567) dependent Yap activity
Authors: Xue Yuhua , Mars Wendy Michelle , Bowen William C , Tao Junyan , Orr Anne V , Stoops John W , Michalopoulos George 
Published: June 2021

The experiments that integrate different pathways in normal and abnormal circumstances will help us to develop optimum targeted therapies because of multiple pathways involved in the solid tumor carcinogenesis. We have shown that activation of CD81 is associated with phosphorylation of Ezrin, which is overexpressed in many types of solid tumors and has been identified as metastasis related protein for many years. We have also shown that GPC3 binds to the membrane tetraspanin CD81, which is one of the portals of entry of hepatitis C virus (HCV). Previous studies have shown that GPC3 is associated with inhibition of hepatocyte growth and liver regeneration by inhibiting CD81‐mediated p‐Ezrin/Hippo/Yap pathway. It also has been shown that HGF/Met axis which promotes growth in HCC can phosphorylate Ezrin as well, by different kinases. Since we have demonstrated the predominant GPC3+++/CD81− pattern in HCC, the purpose of this study is to explore the regulation of expression and phosphorylation of Ezrin in normal hepatocytes and HCC. We have found that CD81 expression could be detected in membrane fraction in human hepatoma cell lines HepG2, Huh7 and Hep3B, but immunoprecipitation suggests that CD81 from latter two human hepatoma cell lines has lost association with GPC3. Human hepatoma cell lines have dramatically up regulated Ezrin expression and Yap activity. We found that treatment of primary rat hepatocytes with CD81 agonist antibody or HGF led to higher levels of phosphorylated Ezrin and lower Hippo activity. Mice over‐expressing GPC3 had decreased p‐Ezrin but increased Hippo activity. Rat hepatoma cell lines JM1 and JM2 had dramatically down regulated CD81 expression and Hippo activity, and up regulated p‐Ezrin. In mice with post‐natal Met knock‐out, there was less Yap expression in normal liver. Force expression mutant Ezrin suppressed Hippo activity and activated Yap signaling in vitro and in vivo.ConclusionsBoth HGF/Met and CD81 mediate p‐Ezrin activity and enhance nuclear Yap levels. These pathways in normal hepatocytes are inhibited by GPC3 and low HGF/Met activity. In human hepatocytes, GPC3 inhibits the CD81‐mediated p‐Ezrin effect on Hippo pathway and cause a decrease in nuclear Yap. The different distribution pattern of HGF/Met and GPC3/CD81 between normal hepatocytes and HCC cells provides the chance to develop precise anti‐HCC therapies. And Ezrin is a promising target of anti‐HCC therapies including primary lesion and metastasis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sirtuin 1 (SIRT1) Content and Angiotensin II Receptor Type I (AT1) Expression in Human Umbilical Vein Endothelial Cells (HUVECs) in Response to Resveratrol: Pregnancy Induced Hypertension (PIH) vs Normotensive pregnancy (NTP)
Authors: Szukiewicz Dariusz , Watroba Mateusz 
Published: June 2021

Oxidative stress and endothelial dysfunction within uteroplacental unit are inherent components initiating PIH. The normal decrease of vascular angiotensin II sensitivity is lost in PIH. The polyphenol stilbene compound resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) boosts endothelium‐dependent vasorelaxation enhancing endothelial nitrix oxide synthase (eNOS) production. In fact, resveratrol acts as a secondary regulator influencing more complex biological response that includes the sirtuin system. SIRT1 is highly expressed in endothelial cells and activated/modulated by resveratrol has been shown to target eNOS for deacetylation resulting in enhanced NO‐dependent vascular relaxation. Moreover, anti‐hypertensive effects of resveratrol may be a consequence of the angiotensin II receptor type I (AT1) modulation by SIRT1. The aim of the study was to examine comparatively the effect of resveratrol on SIRT level in HUVECs isolated after PIH vs. NTP. In addition, AT1 expressions were compared. HUVECs were isolated immediately after cesarean section delivery from PIH (N = 24) and NTP (N = 24) patients (group I and group II, respectively). The umbilical cord segments was subjected to collagenase digestion and the HUVECs were cultured in vitro under normoxia. After achieving the confluence, HUVECs were exposed to resveratrol (50, 100 and 250 μM) administered into the culture media in the respective subgroups A, B and C during the 7 day period. SIRT1 levels were determined in HUVECs culture lysates obtained in the days 1,3 and 7, using ELISA. After termination of the cultures AT1 were immunostained in formalin fixed and paraffin embedded sections. To estimate the mean expression of AT1, quantitative immunohostochemistry was applied. The initial AT1 expression was estimated in the respective controls. After 3 and 7 days of the culture, in both groups the mean SIRT1 levels were significantly (p < 0.05) higher in the subgroups B and C, compared to the initial levels at day 1. However, the mean SIRT1 levels in group I were 4.6‐fold and 2.4‐fold lower (the subgroups B and C, respectively) than observed in normotensive group II. The initial expression of AT1 was significantly higher in group I and amounted to 170% of the average value in the normotensive group II. The mean expression of AT1 was significantly (p < 0.05) downregulated in group I (the subgroups B and C), while in group II was nearly unaffected. These results may suggest potential beneficial effect of SIRT1 activation by resveratrol with regard to antihypertensive therapy in PIH.Support or Funding InformationWUM grant: 2M2‐W1‐17This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Analysis of the Effect of Phototherapy on the Inflammatory Mediators in an Experimental Model of Ischemic Vascular Accident
Authors: Albertini Regiane , Vogel Debora , Villatoro Nancy , Araújo Noemi , Marques Marcia , Scorza Carla , Aimbire Flavio , Scorza Fulvio , Cavalheiro Esper 
Published: June 2021

Cerebral Vascular Accident (CVA) is a sudden neurological condition, which mostly results from cerebral ischemia. Responsible for a large number of deaths and functional disability worldwide, it is extremely important to implement preventive strategies and identify new therapies. Phototherapy has been an excellent therapeutic modality for several diseases, few studies have explored this therapeutic modality for the treatment of stroke. The aim of this study was to analyze whether the treatment with LLLT is able to modulate the inflammatory mediators in the experimental model of ischemic stroke (AVCI). The study was approved by the Ethics Committee on Animal Use of the Federal University of São Paulo (CEUA / UNIFESP) under the number 3316110516. The investigation was conducted in conformance with the FASEB Statement of Principles for the use of Animals in Research and Education. The AVC was induced by the photothrombosis method in 8 male Wistar rats (230 ± 20g) randomly assigned to two experimental groups: Group AVC Control (AVCC) and Group AVC Laserterapia (AVCL). The application of transcranial LLLT was done using a laser diode (MM Optics), with wavelength of 780 ± 5nm, power density of 10 mW / cm2, for 2 minutes, 3× / week for a period of 2 months . The animals were euthanized with anesthetic overdoses of Barbituric / Thiopental Sodium (Cristália) at a dose of 80 mg / kg intraperitoneally; transcardiac perfusion was performed and then the biological tissue (brain) was extracted. The tissues were frozen in liquid nitrogen. The levels of TNF‐α, IL‐1β, IL‐6, IL‐10, VEGFA, BDNF, IGF1, TGFB1 and ANGIOTENSIN II in the samples were determined by the enzyme‐linked immunosorbent assay (ELISA), following commercial kit instructions (R & D System, USA). ). Data were analyzed by the Shapiro‐Wilk normality test in order to verify that the samples come from populations with normal distribution; then the variance test was performed using the Snedecor F test, and then the unpaired T‐test was used; for all tests was considered α = 5%. Our results indicate that there was modulation of the IL1‐b mediators (AVCC 0.4075 ± 0.156659 × AVCL 0.232091 ± 0.083417 p <0.01); IL‐6 (AVCC 180.5753 ± 49.70076 × AVCL 25.47956 ± 15.58209; p <0.001); TNF (40.06277 ± 17.23243 × AVCL 18.2546 ± 5.8065; p <0.01), and in relation to IL‐10 and TGF‐β there were no significant changes. We can conclude that phototherapy modulates the inflammatory response , This result may indicate that the area of shadow of the lesion could be smaller favoring recovery after AVC.Support or Funding InformationFinancial Support: Foundation for Research Support of the State of São Paulo (FAPESP) 2016 / 10286‐7This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.