bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olfactory Receptor Family 7 Subfamily C Member 1 as a potential prognostic marker for pediatric T‐cell acute lymphoblastic leukemia patients
Authors: Ahmed Haidar , Espinoza Juan Silva , Jeon Dayoung , Jauregui Alexia , Bill Charles A. , Parada Zachary , Paz David , Hernandez Alice , Kirken Robert A. , Bill Colin A. , Vines Charlotte M. 
Published: June 2021

A recent study showed that self‐renewing colorectal cancer‐stem cells/cancer‐initiating cells ectopically express the olfactory receptor family 7 subfamily C member 1 (OR7C1). OR7C1, which is a G protein‐coupled receptor (GPCR) was associated with the expression of stem‐cell markers and decreased survival of colon cancer patients. We study T‐cell acute lymphoblastic leukemia (T‐ALL), a neoplasm of immature T‐cell precursors that predominately affect children with an incidence of ~20% of the overall acute lymphoblastic leukemia (ALL) cases. In a screen of 9 pediatric T‐ALL patients, we identified a single nucleotide polymorphism (SNP) in the OR7C1 gene in isolated T‐cells from all 9 patients with T‐ALL that was not present in control T‐cells. Based on published 3D structures of GPCRs we have used in silico modeling to predict the structural effects of the OR7C1 point mutation located in the second extracellular loop, which we expect will regulate downstream signaling. We hypothesize that the SNP form of OR7C1 contributes to the proliferation and aggressiveness of T‐ALL. We identified OR7C1 expression in human T‐ALL cell lines by reverse transcription PCR and western blot analysis with no expression in control peripheral blood mononuclear cells. Sequencing of amplified DNA from T‐ALL cell lines determined the same OR7C1 SNP in two of the human T‐ALL cell lines that we observed in pediatric T‐ALL patients. Using an antibody to OR7C1, we have isolated OR7C1 expressing cells by fluorescence‐activated cell sorting in T‐ALL cell line, HuT78. Currently, we are determining the stemness characteristics of our enriched OR7C1 expressing HuT78 population with the aim of defining the role of OR7C1 in T‐ALL cell proliferation and invasiveness.Support or Funding InformationResearch reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers SC1GM111172, RL5GM118969, TL4GM118971, UL1GM118970, and 5G12MD007592.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Targeting Calcium Channels to prevent EMT
Authors: Hermanson Kole J , Bhattacharya Atrayee , Dhasarathy Archana J 
Published: June 2021

Breast cancer is the most common cancer among women worldwide, with many breast cancer‐associated deaths being attributed to metastasis of the primary tumor. In a process known as Epithelial to Mesenchymal transition (EMT), normal epithelial cells lose their cell‐to‐cell adhesions, become elongated and migratory, resulting in the mesenchymal phenotype. The SNAIL protein is known to be a master regulator of EMT, serving to repress expression of genes associated with cellular adhesion and activate genes involved in chemoresistance. In vivo and in vitro studies have both indicated that high levels of SNAIL correlate with poor prognosis, increased chemoresistance, and greater probability of recurrence of the tumor.Calcium signaling in the cell is important for several biological functions, and was implicated in EMT and breast cancer. To determine which calcium channels were involved in SNAIL upregulation during TGF‐β induced EMT, we blocked store‐operated calcium entry (SOCE) with 2‐aminoethoxydiphenylborane (2APB). This reduced cell migration but, paradoxically, increased the level of TGF‐β dependent SNAIL gene activation. We determined that this increased SNAIL transcription involved signaling through the AKT pathway and subsequent binding of NF‐κB (p65) at the SNAIL promoter in response to TGF‐β. We also demonstrated that the calcium channel protein ORAI3 and the stromal interaction molecule 1 (STIM1) are required for TGF‐β dependent SNAIL transcription. These results suggest that calcium channels differentially regulate cell migration and SNAIL transcription, indicating that each of these steps could be targeted to ensure complete blockade of cancer progression. We are currently testing whether this increase in SNAIL contributes to chemoresistance, and if blockade of ORAI3 can inhibit chemoresistance.Support or Funding InformationThis work was funded by grant support from the National Institutes of Health grants P20‐GM104360 to Archana Dhasarathy and UND School of Medicine and Health Sciences.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of hypoxia and oxygen supplementation on gynecological cancer cells
Authors: Kraus Aileen Kathryn , Higgins Jillian Lee , Arruda Dominic T. , Guo Hao , Lautato Matthew , Lautato Christopher , DaCunha Eliana , Chen Ashley , Yao Ricky , Li Xaiofei , Yang Dongqin , Wan Yinsheng 
Published: June 2021

Existing data have shown that cobalt chloride or CoCl2, as well as 2% O2, introduces hypoxia and activates transcription factor HIF1‐α in ovarian cancer cells (CaOV3 cell line). We hypothesize that this transcription factor is also activated in HeLa cells in response to CoCl2. Initially, we analyzed the morphology of cultured HeLa cells with the addition of various concentrations of CoCl2 in the cultured medium. The results revealed that cells with as low as 8 μM of CoCl2 treatment differ from the untreated cells because they are less confluent and irregularly shaped. We further investigated the CoCl2 effects through Western blot analysis and confocal imaging. We found that high concentration of CoCl2 directly induces hypoxia leading to the degradation of the cytoskeleton and nuclear membrane. As the concentration of CoCl2 increases, the activities of HIF1‐α and phosphorylated S6 decrease. The cell viability with MTT assay showed that there is no significant effect of CoCl2 on HeLa cells, except at the highest concentration tested. We then tested the effect of oxygen supplement by PDMS‐CaO2 disks on HeLa cells with MTT assay as well. The data showed that the viability of HeLa cells is lower when treated with these disks as opposed to CoCl2 treatment. Finally, we analyzed the mitochondrial activity of cultured CaOV3 cells with CoCl2 as well as control and PDMS‐CaO2 disks using MitoTraker. It was clear that 400 μM CoCl2 induces maximal mitochondrial activity as Mitotraker signal is highly concentrated in the surrounding cytoskeleton of the cells. PDMS‐CaO2 disks notably reduce mitochondrial activity in CaOV3 cells, as they appear dull and darker in comparison to the untreated, control cells. Taken all together, our preliminary data suggest that the manipulation of oxygen level in gynecological cancer cells may provide insights into the understanding of the role of oxygen in solid tumors and eventually offer clinic oxygen therapy.Support or Funding InformationThe RI‐INBRE grant funded this research in addition to the Providence College Biology Department.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
γ‐Tocotrienol and α‐Tocopheryloxyacetic Acid Increase the Effectiveness of Docetaxel Treatment of PC‐3 Prostate Cancer Cells and Docetaxel‐resistant PC‐3 Cells
Authors: Asay Spencer , Graham Andrew , Oblad Richard , Kenealey Jason 
Published: June 2021

Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments such as docetaxel. Chemotherapeutic resistance is one of the greatest challenges facing successful cancer treatment, but can be ameliorated with combination chemotherapy. Vitamin E analogs, such as γ‐tocotrienol (γ‐T3) and α‐tocopheryloxyacetic acid (α‐TEA), have been proposed and studied as potential chemotherapeutics. We modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to see if combinations of three chemotherapeutic agents (γ‐T3, α‐TEA, and docetaxel) would be better than docetaxel alone in the treatment of PC‐3 human prostate cancer cells. Response surfaces were generated for cell viability and apoptotic responses and the optimal treatment combination for each response was calculated. We found that a combination of γ‐tocotrienol, α‐TEA, and docetaxel was more effective than docetaxel alone in the treatment of PC‐3 cells, and docetaxel resistant PC‐3 cells.Support or Funding InformationThis work was funded by a generous donation from the Bryant Adams Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myeloid cell‐derived IL‐6 in Chronic Lymphocytic Leukemia
Authors: McManus Sheighlah Dallas , Bertilaccio Maria Teresa Sabrina 
Published: June 2021

First‐line therapies, like chemo immunotherapy have limitation that lead patients to build resistance to mainstream treatments for chronic lymphocytic leukemia. Traditionally, the focus has been on leukemic cells. Conversely, little attention has been brought to the influence myeloid cells have on CLL progression. This study focused on the production of IL‐6 specifically by monocytes, macrophages, and myeloid‐derived suppressor cells (MDSCs) in the microenvironment of CLL cells. Experimentation revealed an increase of myeloid cell‐derived IL‐6 production in the peripheral blood and lymphoid tissues of Eμ‐TCL1 transgenic mice. Ultimately, these findings can be the basis for exploration of new treatments that target myeloid cells, and can be presented as an alternative for patients who have acquired a resistance to current therapies for CLL.Support or Funding InformationSM was supported by the CPRIT Research Training Program RP170067This study was supported by CLL Global Research Foundation (to MTSB)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Colonic Epithelial Cells Express an Oncolytic Bispecific IgA/IgG heterodimer
Authors: Nair Padmanabhan Padmanabhan 
Published: June 2021

The gastrointestinal epithelium sheds about 10(12) cells per day. Contrary to conventional wisdom a majority of these cells (>90%) are excreted into the fecal stream intact. We first demonstrated the isolation of these cells in a viable state (1991) and showed the feasibility of studying the expression of various bomarkers in health and disease. During the course of our studies mapping the expression of surface markers using flow cytometry we discovered that these cells had the ability to destroy a variety of cancer cells. These colonic cells expressed among other markers (COX‐2 during an inflammatory condition) IgA and IgG along with a subpopulation of cells co‐expressing IgA/IgG. Blocking the IgG component with anti‐IgG antibody discharged the oncolytic property of these cells. We also observed that these cells expressed Lgr5 and Musashi1, the putative markers of gastrointestinal progenitor stem cells. Long term tissue culture experiments revealed the persistence of the heterodimer. In a cohort of 80 random human samples we observed the absence of this hybrid IgA/IgG antibody in two subjects of African American origin. Lineage directed differentiation of these cells generated a progeny that secreted this chimeric antibody. This antibody was shown to arrest the growth of human colon cancer in xenotransplants in nude mice. From these observations It was concluded that this is a novel native antibody that may be absent in certain individuals as a result of a genetic aberration.Support or Funding InformationSBIR grants R43 & R44 DK‐56567 and R‐43 & R‐44 CA‐81799 from the NIDDK and NCI of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Notch, IL‐1 and Leptin (NILCO) Inhibition in Xenograft Colorectal Cancer
Authors: Ozyurt Rumeysa , Erkasap Nilufer , Ozkurt Mete , Erkasap Serdar , Ulukaya Engin , Dimas Kostantinos 
Published: June 2021

The aim of this study was to investigate the effects of inhibition of Notch, IL‐1 and leptin systems on tumorigenesis and angiogenesis in xenograft colorectal cancer model. This study was conducted with the approval of the EU/2010/63 directive and the Greek Presidential Decree 56/2013 (Approval No. 5542/228006/1). In each group, 40 scid (NOD/SCID) mice with 6–8 weeks of age were studied in 5 groups. For tumor formation 1 × 107 human colon cancer cells HCT‐15 were injected subcutaneously into the dorsal flank of the mice. When the tumor size was 100–250 mm3, treatment was started. Group 1: Leptin receptor antagonist ALLO‐aca was injected with 1mg / kg / day subcutaneously (s.c) for 15 days (n: 8). Group 2: γ‐secretase inhibitor DAPT was injected with 10 mg / kg / day subcutaneously (s.c) for 15 days (n: 8). Group 3: Recombinant human IL‐1 receptor antagonist (IL‐1Ra) was injected with 1mg / kg / day subcutaneously (s.c) for 15 days (n: 8). Group 4: 4% DMSO/Safflower Oil (DAPT solvent) was injected subcutaneously (s.c) for 15 days. (n: 8). Group 5: 10% DMSO/0,9%NaCl (Allo aca and IL‐1 iınhibitor solvent) was injected subcutaneously (s.c) for 15 days. (n: 8). After 15 days, tissues were collected and gene expression experiments were performed. mRNA abundance of leptin, leptin OB‐RL receptor, Notch1 receptor, JAGGED1 ligand, IL‐1β, IL‐1R tI, VEGF‐A, VEGFR2 conducted by qRT‐PCR. According to PCR results, leptin, its receptor Ob‐R, Notch1, JAGGED1, VEGF‐A and VEGFR1 mRNA abundance were decreased only in the DAPT group (respectively; p<0.05, p<0.05, p<0.05, p<0.01, p<0.05, p<0.01). The mRNA abundance of VEGFR2 was decreased only in the IL‐1 inhibitor group (p<0.05). According to the results, DAPT at 10 mg / kg / day dose Notch receptor and its ligand was reduced as well as decreased mRNA abundance of leptin and VEGF systems that pro‐angiogenogenic factors. The results of our study support the oncogenic role of Notch, IL‐1 and Leptin crosstalk in colorectal cancer. Inhibition of NILCO signaling could lead to the development of new adjuvant therapies to reduce or eliminate tumor angiogenesis.Support or Funding InformationThis study is supported by a grant from Eskisehir Osmangazi University Scientific Research Projects (Project no:2017‐11028)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synergistic effect of epigenetic inhibitors decitabine and suberoylanilide hydroxamic acid on colorectal cancer in vitro
Authors: Rizk Sandra , Najem Sonia Abou , Hodroj Mohammad Hassan , Khawaja Ghada 
Published: June 2021

Colorectal cancer (CRC) is major public health burden and a common cause of oncological deaths worldwide. Alterations of the epigenetic landscape are a well‐documented hallmark of CRC phenotype. Accumulation of aberrant DNA methylation and histone acetylation orchestrates to modify gene activity and drive tumor onset, progression and metastasis. In this study we evaluated the effect of suberoylanilide hydroxamic acid (SAHA), a pan histone deacetylase inhibitor, and decitabine (DAC), a DNA methyltransferase inhibitor, either alone or in combination, on Caco‐2 human colon cancer cell line in vitro. Our results showed that SAHA and DAC, separately, significantly decreased cell proliferation, induced apoptosis and cell cycle arrest of Caco‐2 cell line. On the other hand, the sequential treatment of Caco‐2 cells, first with DAC and then with SAHA, induced a synergistic anti‐tumor effect; the sequential treatment significantly enhanced growth inhibition and apoptosis of Caco‐2 cell line in comparison to cells treated with either drug alone. Furthermore, the combination therapy upregulates protein expression levels of pro‐apoptotic proteins Bax, p53 and cytochrome c, down regulates the expression of anti‐apoptotic Bcl‐2 protein and increases the cleavage of procaspases 8 and 9; this suggests that the combination activates apoptosis via both the intrinsic and extrinsic pathways. Mechanistically, we demonstrated that the synergistic anti‐neoplastic activity of combined SAHA and DAC involves an effect on PI3K/AKT and Wnt/β‐catenin signaling pathways as it down regulates p‐PI3K, p‐AKT, Wnt1, p‐GSK3, cyclin A1+A2, cyclin E1 and up regulates p‐β‐catenin protein expression levels. In conclusion, our results provide evidence for the profound anti‐tumorigenic effect of sequentially combined SAHA and DAC in CRC cell line and offer new insights into the corresponding underlined molecular mechanism.Support or Funding InformationThis work was funded by SRDC, School of Arts and Sciences, Lebanese American UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Linking microbial metabolism to antibiotic tolerance in the microbiome
Authors: Belenky Peter A 
Published: June 2021

Empirical antimicrobial therapy has saved billions of lives in the past 70 years but has also led to the development of the antimicrobial resistance crisis. Additionally, we now know that each antibiotic exposure has the potential to eliminate trillions of beneficial microbes and lead to profound complications. Thus, as we improve antibiotic therapy we must understand why and how antibiotics kill members of the microbiome. Previous data indicate that active and oxidative metabolism of bacteria is linked to antibiotic efficacy in vitro. Here we utilize a metagenomic/metatranscriptomic approach to profile the impacts of microbial metabolism on antibiotic susceptibility in the total microbiome in human subjects and murine models. We found that reduce metabolic activity of specific taxa before and during treatment is a key determinant of susceptibility to broad‐spectrum antibiotics. We found that taxa within the microbiome that direct metabolism to anabolic and fermentative pathways survive whereas taxa that utilize oxidative catabolism are eliminated. Utilizing metatranscriptomic RNAseq, at a species resolution, within our microbiome we describe the transcriptional response of the 12 most abundant species such as Akkermansia muciniphila, Bacteroides thetaiotaomicron and others to antibiotics. In the case of B. thetaiotaomicron we found that it upregulates fiber fermentation (including the sus operon) in response to amoxicillin and that polysaccharide supplementation protects this bacterium in vitro and in the microbiome. Based on these experiments we implement and report a murine study to profile the impacts of an array of purified fibers on antibiotic‐induced dysbiosis. This work indicates that host diet modulation and metabolic state may provide an important intervention to protect microbiome homeostasis and may lead to the identification of prebiotic therapy to protect the microbiome from antibiotics.Support or Funding InformationThis work was supported by funding received from the COBRE Center for Computational Biology of Human Disease (NIH P20 GM109035) and from the National Science Foundation Graduate Research Fellowship (Grant No. 1644760).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identifying Microbial Resistance of the Apis mellifera Melanization Immune Response
Authors: Knier Rochelle 
Published: June 2021

Apis mellifera, one of the most common species of honey bee, has been suffering disease and colony collapse. While there has been effort in identification and treatment of the pathogens, the study of their insufficient immunoresponse has gone under‐researched. Melanization is a common form of immune response in insects and has been seen in Apis mellifera. The goal of this study is to isolate melanin from hemolymph and conduct multiple experiments with known pathogens against it with the purpose of identifying microbial resistance and further inferring the mechanism of immunity. With this knowledge, a method of improving the Apis mellifera immune response may be found.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elucidating the effect of antibiotics on Pal's release from Escherichia coli
Authors: Bauer Morgan , Gallardo Leslie , Jackson Niaya , Michel Lea 
Published: June 2021

The clinical condition of sepsis often results from a systemic bacterial infection, followed by an over‐exuberant immune response, which leads to widespread inflammation. Severe sepsis can result in organ failure or death. Past studies have proposed a role for bacterial Peptidoglycan‐Associated Lipoprotein (Pal) in the pathogenesis of Gram‐negative sepsis. In this study, we confirmed the ability of Escherichia coli (E. coli) to release Pal under certain conditions, and we employed both in vitro and in vivo (mouse) studies and protein detection methods to determine the effect of antibiotics on Pal's release from E. coli. Results from our studies suggest that antibiotics that target peptidoglycan may enhance Pal's release more so than other antibiotics.Support or Funding InformationRochester Institute of TechnologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.