LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Zurück zur letzten Suche Suchhistorie
Erweiterte Suche

Ihre letzten Suchen

  1. AU="Debasis Mondal"
  2. AU="Hollingsworth, Neal A"
  3. AU=Restifo Nicholas P AU=Restifo Nicholas P
  4. AU="Farmer, Claire"
  5. AU="Hyeong, Seok-Ki"
  6. AU=Sathananthan A Henry
  7. AU="Ross D. Pollock"
  8. AU="Abouelkhair, Mohamed A"
  9. AU="Draia, Ahmed N"
  10. AU="Martins, Paulo"
  11. AU=Elliott P
  12. AU="Gill, J L"
  13. AU="Marmé, Dieter"
  14. AU=St John Ashley L
  15. AU="Macpherson, Catherine Fiona"
  16. AU=Malloy Giovanni S P
  17. AU="Bovino, Antonio"
  18. AU="Deseri, Luca"
  19. AU="Cunningham, C W"
  20. AU="Haas, Brian"
  21. AU="Raia, Anais"
  22. AU=Gollin Susanne M
  23. AU="Xie, Hong-Guang"
  24. AU="Ford, Paul Leicester"
  25. AU="Garver-Daniels, N. E."
  26. AU="De Pisapia, Nicola"
  27. AU="Inoue, Kazunori"
  28. AU="Tüzün, Funda"
  29. AU="McDonough, John"
  30. AU="Puche-Cañas, Emilio"
  31. AU="Rahim, Faraan O"
  32. AU="Barritt, Andrew W"

Suchergebnis

Treffer 1 - 10 von insgesamt 11

Suchoptionen

  1. Artikel ; Online: Osteopathic Manipulative Medicine

    Ashley Roberts / Kaylee Harris / Bethany Outen / Amar Bukvic / Ben Smith / Adam Schultz / Stephen Bergman / Debasis Mondal

    Medicines, Vol 9, Iss 33, p

    A Brief Review of the Hands-On Treatment Approaches and Their Therapeutic Uses

    2022  Band 33

    Abstract: Osteopathic manipulative medicine (OMM) is an emerging practice in the healthcare field with increasing popularity and evidence-based therapy. Osteopathic manipulative treatments (OMT) include hands-on manipulations of different body structures to ... ...

    Abstract Osteopathic manipulative medicine (OMM) is an emerging practice in the healthcare field with increasing popularity and evidence-based therapy. Osteopathic manipulative treatments (OMT) include hands-on manipulations of different body structures to increase systemic homeostasis and total patient well-being. Indeed, this new realm of the whole patient-based approach is being taught in osteopathic schools around the country, and the osteopathic principles of a mind-body-spirit-based treatment are being instilled in many new Doctor of Osteopathy (D.O.) students. However, despite their proven therapeutic value, there are still many individuals, both in and outside the medical profession, who are unaware (or misinformed) of the therapeutic uses and potential benefits of OMT. Here, we provide a brief introduction to this osteopathic therapeutic approach, focusing on the hands-on techniques that are regularly implemented in the clinical setting. It is becoming increasingly evident that different OMTs can be implemented to enhance patient recovery, both alone and in conjunction with the targeted therapies used in allopathic regimens. Therefore, it may be beneficial to inform the general medical community and educate the public and those associated with the healthcare field about the benefits of using OMT as a treatment modality. OMT is lower-cost, noninvasive, and highly effective in promoting full-body healing by targeting the nervous, lymphatic, immune, and vascular systems. There is a growing body of literature related to osteopathic research and the possible molecular pathways involved in the healing process, and this burgeoning field of medicine is expected to increase in value in the healthcare field. This brief review article explains the frequently utilized OMT modalities and their recognized therapeutic benefits, which underscore the need to understand the possible molecular mechanisms and circulating biomarkers linked to the systemic benefits of osteopathic medicine.
    Schlagwörter osteopathy ; muscle energy ; myofascial release ; balanced ligamentous tension ; diaphragm ; HVLA (High-velocity low amplitude) ; Medicine ; R
    Thema/Rubrik (Code) 360
    Sprache Englisch
    Erscheinungsdatum 2022-04-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  2. Artikel ; Online: The bountiful biological activities of cyclotides

    Samantha L Gerlach / Debasis Mondal

    Chronicles of Young Scientists, Vol 3, Iss 3, Pp 169-

    2012  Band 177

    Abstract: Cyclotides are exceptionally stable circular peptides (28-37 amino acid residues) with a unique cyclic cystine knot (CCK) motif that were originally discovered through ethnobotanical investigations and bioassay-directed natural products screenings. They ... ...

    Abstract Cyclotides are exceptionally stable circular peptides (28-37 amino acid residues) with a unique cyclic cystine knot (CCK) motif that were originally discovered through ethnobotanical investigations and bioassay-directed natural products screenings. They have been isolated from four angiosperm families (Violaceae, Rubiaceae, Curcurbitaceae, and Fabaceae), and they exhibit a wide range of bioactivities including antibacterial/antimicrobial, nematocidal, molluscicidal, antifouling, insecticidal, antineurotensin, trypsin inhibiting, hemolytic, cytotoxic, antitumor, and anti-HIV properties. Reports indicate that the mechanism of cyclotide bioactivity is the ability to target and interact with lipid membranes via the development of pores. Additionally, the nature of their surface-exposed hydrophobic patch and CCK play integral roles in the potency of cyclotides. Their extraordinary stability and flexibility have recently allowed for the successful grafting of analogs with therapeutic properties onto their CCK framework. This achievement, coupled with the myriad of useful naturally occurring bioactivities displayed by cyclotides, makes them appealing candidates in drug design and crop management.
    Schlagwörter Bioactivity ; cancer ; cyclotides ; HIV ; host defense ; Therapeutics. Pharmacology ; RM1-950 ; Medicine ; R
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Medknow Publications Pvt Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  3. Artikel ; Online: The Membrane-Active Phytopeptide Cycloviolacin O2 Simultaneously Targets HIV-1-infected Cells and Infectious Viral Particles to Potentiate the Efficacy of Antiretroviral Drugs

    Samantha L. Gerlach / Partha K. Chandra / Upal Roy / Sunithi Gunasekera / Ulf Göransson / William C. Wimley / Stephen E. Braun / Debasis Mondal

    Medicines, Vol 6, Iss 1, p

    2019  Band 33

    Abstract: Background: Novel strategies to increase the efficacy of antiretroviral (ARV) drugs will be of crucial importance. We hypothesize that membranes of HIV-1-infected cells and enveloped HIV-1 particles may be preferentially targeted by the phytopeptide, ... ...

    Abstract Background: Novel strategies to increase the efficacy of antiretroviral (ARV) drugs will be of crucial importance. We hypothesize that membranes of HIV-1-infected cells and enveloped HIV-1 particles may be preferentially targeted by the phytopeptide, cycloviolacin O2 (CyO2) to significantly enhance ARV efficacy. Methods: Physiologically safe concentrations of CyO2 were determined via red blood cell (RBC) hemolysis. SYTOX-green dye-uptake and radiolabeled saquinavir ( 3 H-SQV) uptake assays were used to measure pore-formation and drug uptake, respectively. ELISA, reporter assays and ultracentrifugation were conducted to analyze the antiviral efficacy of HIV-1 protease and fusion inhibitors alone and co-exposed to CyO2. Results: CyO2 concentrations below 0.5 μM did not show substantial hemolytic activity, yet these concentrations enabled rapid pore-formation in HIV-infected T-cells and monocytes and increased drug uptake. ELISA for HIV-1 p24 indicated that CyO2 enhances the antiviral efficacy of both SQV and nelfinavir. CyO2 (< 0.5 μM) alone decreases HIV-1 p24 production, but it did not affect the transcription regulatory function of the HIV-1 long terminal repeat (LTR). Ultracentrifugation studies clearly showed that CyO2 exposure disrupted viral integrity and decreased the p24 content of viral particles. Furthermore, direct HIV-1 inactivation by CyO2 enhanced the efficacy of enfuvirtide. Conclusions: The membrane-active properties of CyO2 may help suppress viral load and augment antiretroviral drug efficacy.
    Schlagwörter cyclotides ; cycloviolacin O2 ; CyO2 ; HIV-1 ; protease inhibitors ; fusion inhibitors ; antiretroviral drugs ; Medicine ; R
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2019-02-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  4. Artikel ; Online: Specific increase in MDR1 mediated drug-efflux in human brain endothelial cells following co-exposure to HIV-1 and saquinavir.

    Upal Roy / Christine Bulot / Kerstin Honer zu Bentrup / Debasis Mondal

    PLoS ONE, Vol 8, Iss 10, p e

    2013  Band 75374

    Abstract: Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) ...

    Abstract Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [(3)H-] SQV. The crucial role of MDR1 in (3)H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2013-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  5. Artikel ; Online: The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells

    Michelle A. Schultz / Asim B. Abdel-Mageed / Debasis Mondal

    Cancers, Vol 2, Iss 2, Pp 1354-

    2010  Band 1378

    Abstract: Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles ... ...

    Abstract Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in modulating AR expression and signaling in aggressive prostate cancer (PCa) cells. In androgen independent (AI) C4-2B cells, in comparison to the parental androgen dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1 correlated with enhanced AR transactivation. Our findings implicate a crucial balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells. Here we will discuss how understanding the mechanisms by which oxidative stress may affect AR signaling may aid in developing novel therapies for AI-PCa.
    Schlagwörter Nrf1 (NF-E2 related factor-1) ; Nrf2 (NF-E2 related factor-2) ; prostate cancer ; oxidative stress ; androgen independence ; androgen deprivation therapy ; reactive oxygen species (ROS) ; androgen receptor (AR) ; di-hydrotestosterone (DHT) ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2010-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  6. Artikel ; Online: Mesenchymal stem cells are attracted to latent HIV-1-infected cells and enable virus reactivation via a non-canonical PI3K-NFκB signaling pathway

    Partha K. Chandra / Samantha L. Gerlach / Chengxiang Wu / Namrata Khurana / Lauren T. Swientoniewski / Asim B. Abdel-Mageed / Jian Li / Stephen E. Braun / Debasis Mondal

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Band 17

    Abstract: Abstract Persistence of latent HIV-1 in macrophages (MACs) and T-helper lymphocytes (THLs) remain a major therapeutic challenge. Currently available latency reversing agents (LRAs) are not very effective in vivo. Therefore, understanding of physiologic ... ...

    Abstract Abstract Persistence of latent HIV-1 in macrophages (MACs) and T-helper lymphocytes (THLs) remain a major therapeutic challenge. Currently available latency reversing agents (LRAs) are not very effective in vivo. Therefore, understanding of physiologic mechanisms that dictate HIV-1 latency/reactivation in reservoirs is clearly needed. Mesenchymal stromal/stem cells (MSCs) regulate the function of immune cells; however, their role in regulating virus production from latently-infected MACs & THLs is not known. We documented that exposure to MSCs or their conditioned media (MSC-CM) rapidly increased HIV-1 p24 production from the latently-infected U1 (MAC) & ACH2 (THL) cell lines. Exposure to MSCs also increased HIV-1 long terminal repeat (LTR) directed gene expression in the MAC and THL reporter lines, U937-VRX and J-Lat (9.2), respectively. MSCs exposed to CM from U1 cells (U1-CM) showed enhanced migratory ability towards latently-infected cells and retained their latency-reactivation potential. Molecular studies showed that MSC-mediated latency-reactivation was dependent upon both the phosphatidyl inositol-3-kinase (PI3K) and nuclear factor-κB (NFκB) signaling pathways. The pre-clinically tested inhibitors of PI3K (PX-866) and NFκB (CDDO-Me) suppressed MSC-mediated HIV-1 reactivation. Furthermore, coexposure to MSC-CM enhanced the latency-reactivation efficacy of the approved LRAs, vorinostat and panobinostat. Our findings on MSC-mediated latency-reactivation may provide novel strategies against persistent HIV-1 reservoirs.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2018-10-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  7. Artikel ; Online: High-throughput screening identified selective inhibitors of exosome biogenesis and secretion

    Amrita Datta / Hogyoung Kim / Lauren McGee / Adedoyin E. Johnson / Sudha Talwar / Juan Marugan / Noel Southall / Xin Hu / Madhu Lal / Debasis Mondal / Marc Ferrer / Asim B. Abdel-Mageed

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    A drug repurposing strategy for advanced cancer

    2018  Band 13

    Abstract: Abstract Targeting exosome biogenesis and release may have potential clinical implications for cancer therapy. Herein, we have optimized a quantitative high throughput screen (qHTS) assay to identify compounds that modulate exosome biogenesis and/or ... ...

    Abstract Abstract Targeting exosome biogenesis and release may have potential clinical implications for cancer therapy. Herein, we have optimized a quantitative high throughput screen (qHTS) assay to identify compounds that modulate exosome biogenesis and/or release by aggressive prostate cancer (PCa) CD63-GFP-expressing C4-2B cells. A total of 4,580 compounds were screened from the LOPAC library (a collection of 1,280 pharmacologically active compounds) and the NPC library (NCGC collection of 3,300 compounds approved for clinical use). Twenty-two compounds were found to be either potent activators or inhibitors of intracellular GFP signal in the CD63-GFP-expressing C4-2B cells. The activity of lead compounds in modulating the secretion of exosomes was validated by a tunable resistive pulse sensing (TRPS) system (qNano-IZON) and flow cytometry. The mechanism of action of the lead compounds in modulating exosome biogenesis and/or secretion were delineated by immunoblot analysis of protein markers of the endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways. The lead compounds tipifarnib, neticonazole, climbazole, ketoconazole, and triademenol were validated as potent inhibitors and sitafloxacin, forskolin, SB218795, fenoterol, nitrefazole and pentetrazol as activators of exosome biogenesis and/or secretion in PC cells. Our findings implicate the potential utility of drug-repurposing as novel adjunct therapeutic strategies in advanced cancer.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2018-05-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  8. Artikel ; Online: An ex vivo model for anti-angiogenic drug testing on intact microvascular networks.

    Mohammad S Azimi / Leann Myers / Michelle Lacey / Scott A Stewart / Qirong Shi / Prasad V Katakam / Debasis Mondal / Walter L Murfee

    PLoS ONE, Vol 10, Iss 3, p e

    2015  Band 0119227

    Abstract: New models of angiogenesis that mimic the complexity of real microvascular networks are needed. Recently, our laboratory demonstrated that cultured rat mesentery tissues contain viable microvascular networks and could be used to probe pericyte- ... ...

    Abstract New models of angiogenesis that mimic the complexity of real microvascular networks are needed. Recently, our laboratory demonstrated that cultured rat mesentery tissues contain viable microvascular networks and could be used to probe pericyte-endothelial cell interactions. The objective of this study was to demonstrate the efficacy of the rat mesentery culture model for anti-angiogenic drug testing by time-lapse quantification of network growth. Mesenteric windows were harvested from adult rats, secured in place with an insert, and cultured for 3 days according to 3 experimental groups: 1) 10% serum (angiogenesis control), 2) 10% serum + sunitinib (SU11248), and 3) 10% serum + bevacizumab. Labeling with FITC conjugated BSI-lectin on Day 0 and 3 identified endothelial cells along blood and lymphatic microvascular networks. Comparison between day 0 (before) and 3 (after) in networks stimulated by 10% serum demonstrated a dramatic increase in vascular density and capillary sprouting. Growing networks contained proliferating endothelial cells and NG2+ vascular pericytes. Media supplementation with sunitinib (SU11248) or bevacizumab both inhibited the network angiogenic responses. The comparison of the same networks before and after treatment enabled the identification of tissue specific responses. Our results establish, for the first time, the ability to evaluate an anti-angiogenic drug based on time-lapse imaging on an intact microvascular network in an ex vivo scenario.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  9. Artikel ; Online: Subverting ER-stress towards apoptosis by nelfinavir and curcumin coexposure augments docetaxel efficacy in castration resistant prostate cancer cells.

    Aditi Mathur / Zakaria Y Abd Elmageed / Xichun Liu / Mikhail L Kostochka / Haitao Zhang / Asim B Abdel-Mageed / Debasis Mondal

    PLoS ONE, Vol 9, Iss 8, p e

    2014  Band 103109

    Abstract: Despite its side-effects, docetaxel (DTX) remains a first-line treatment against castration resistant prostate cancer (CRPC). Therefore, strategies to increase its anti-tumor efficacy and decrease its side effects are critically needed. Targeting of the ... ...

    Abstract Despite its side-effects, docetaxel (DTX) remains a first-line treatment against castration resistant prostate cancer (CRPC). Therefore, strategies to increase its anti-tumor efficacy and decrease its side effects are critically needed. Targeting of the constitutive endoplasmic reticulum (ER) stress in cancer cells is being investigated as a chemosensitization approach. We hypothesized that the simultaneous induction of ER-stress and suppression of PI3K/AKT survival pathway will be a more effective approach. In a CRPC cell line, C4-2B, we observed significant (p<0.005) enhancement of DTX-induced cytotoxicity following coexposure to thapsigargin and an AKT-inhibitor. However, since these two agents are not clinically approved, we investigated whether a combination of nelfinavir (NFR) and curcumin (CUR), known to target both these metabolic pathways, can similarly increase DTX cytotoxicity in CRPC cells. Within 24 hrs post-exposure to physiologic concentrations of NFR (5 µM) and CUR (5 µM) a significantly (p<0.005) enhanced cytotoxicity was evident with low concentration of DTX (10 nM). This 3-drug combination rapidly increased apoptosis in aggressive C4-2B cells, but not in RWPE-1 cells or in primary prostate epithelial cells (PrEC). Comparative molecular studies revealed that this 3-drug combination caused a more pronounced suppression of phosphorylated-AKT and higher induction in phosphorylated-eIF2α in C4-2B cells, as compared to RWPE-1 cells. Acute exposure (3-9 hrs) to this 3-drug combination intensified ER-stress induced pro-apoptotic markers, i.e. ATF4, CHOP, and TRIB3. At much lower concentrations, chronic (3 wks) exposures to these three agents drastically reduced colony forming units (CFU) by C4-2B cells. In vivo studies using mice containing C4-2B tumor xenografts showed significant (p<0.05) enhancement of DTX's (10 mg/kg) anti-tumor efficacy following coexposure to NFR (20 mg/kg) & CUR (100 mg/kg). Immunohistochemical (IHC) analyses of tumor sections indicated decreased Ki-67 staining and ...
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  10. Artikel ; Online: Nrf1 and Nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells.

    Michelle A Schultz / Sharika S Hagan / Amrita Datta / Yiguo Zhang / Michael L Freeman / Suresh C Sikka / Asim B Abdel-Mageed / Debasis Mondal

    PLoS ONE, Vol 9, Iss 1, p e

    2014  Band 87204

    Abstract: Despite androgen deprivation therapy (ADT), persistent androgen receptor (AR) signaling enables outgrowth of castration resistant prostate cancer (CRPC). In prostate cancer (PCa) cells, ADT may enhance AR activity through induction of oxidative stress. ... ...

    Abstract Despite androgen deprivation therapy (ADT), persistent androgen receptor (AR) signaling enables outgrowth of castration resistant prostate cancer (CRPC). In prostate cancer (PCa) cells, ADT may enhance AR activity through induction of oxidative stress. Herein, we investigated the roles of Nrf1 and Nrf2, transcription factors that regulate antioxidant gene expression, on hormone-mediated AR transactivation using a syngeneic in vitro model of androgen dependent (LNCaP) and castration resistant (C4-2B) PCa cells. Dihydrotestosterone (DHT) stimulated transactivation of the androgen response element (ARE) was significantly greater in C4-2B cells than in LNCaP cells. DHT-induced AR transactivation was coupled with higher nuclear translocation of p65-Nrf1 in C4-2B cells, as compared to LNCaP cells. Conversely, DHT stimulation suppressed total Nrf2 levels in C4-2B cells but elevated total Nrf2 levels in LNCaP cells. Interestingly, siRNA mediated silencing of Nrf1 attenuated AR transactivation while p65-Nrf1 overexpression enhanced AR transactivation. Subsequent studies showed that Nrf1 physically interacts with AR and enhances AR's DNA-binding activity, suggesting that the p65-Nrf1 isoform is a potential AR coactivator. In contrast, Nrf2 suppressed AR-mediated transactivation by stimulating the nuclear accumulation of the p120-Nrf1 which suppressed AR transactivation. Quantitative RT-PCR studies further validated the inductive effects of p65-Nrf1 isoform on the androgen regulated genes, PSA and TMPRSS2. Therefore, our findings implicate differential roles of Nrf1 and Nrf2 in regulating AR transactivation in PCa cells. Our findings also indicate that the DHT-stimulated increase in p65-Nrf1 and the simultaneous suppression of both Nrf2 and p120-Nrf1 ultimately facilitates AR transactivation in CRPC cells.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

Zum Seitenanfang