LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 50

Search options

  1. Article: Alternative models of cancer stem cells: The stemness phenotype model, 10 years later.

    Kaushik, Vivek / Kulkarni, Yogesh / Felix, Kumar / Azad, Neelam / Iyer, Anand Krishnan V / Yakisich, Juan Sebastian

    World journal of stem cells

    2021  Volume 13, Issue 7, Page(s) 934–943

    Abstract: The classical cancer stem cell (CSCs) theory proposed the existence of a rare but constant subpopulation of CSCs. In this model cancer cells are organized hierarchically and are responsible for tumor resistance and tumor relapse. Thus, eliminating CSCs ... ...

    Abstract The classical cancer stem cell (CSCs) theory proposed the existence of a rare but constant subpopulation of CSCs. In this model cancer cells are organized hierarchically and are responsible for tumor resistance and tumor relapse. Thus, eliminating CSCs will eventually lead to cure of cancer. This simplistic model has been challenged by experimental data. In 2010 we proposed a novel and controversial alternative model of CSC biology (the Stemness Phenotype Model, SPM). The SPM proposed a non-hierarchical model of cancer biology in which there is no specific subpopulation of CSCs in tumors. Instead, cancer cells are highly plastic in term of stemness and CSCs and non-CSCs can interconvert into each other depending on the microenvironment. This model predicts the existence of cancer cells ranging from a pure CSC phenotype to pure non-CSC phenotype and that survival of a single cell can originate a new tumor. During the past 10 years, a plethora of experimental evidence in a variety of cancer types has shown that cancer cells are indeed extremely plastic and able to interconvert into cells with different stemness phenotype. In this review we will (1) briefly describe the cumulative evidence from our laboratory and others supporting the SPM; (2) the implications of the SPM in translational oncology; and (3) discuss potential strategies to develop more effective therapeutic regimens for cancer treatment.
    Language English
    Publishing date 2021-03-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2583482-4
    ISSN 1948-0210
    ISSN 1948-0210
    DOI 10.4252/wjsc.v13.i7.934
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article: Selective and Irreversible Induction of Necroptotic Cell Death in Lung Tumorspheres by Short-Term Exposure to Verapamil in Combination with Sorafenib.

    Yakisich, Juan Sebastian / Kulkarni, Yogesh / Azad, Neelam / Iyer, Anand Krishnan V

    Stem cells international

    2017  Volume 2017, Page(s) 5987015

    Abstract: The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation ...

    Abstract The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100
    Language English
    Publishing date 2017-10-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2573856-2
    ISSN 1687-9678 ; 1687-966X
    ISSN (online) 1687-9678
    ISSN 1687-966X
    DOI 10.1155/2017/5987015
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Antitumor effects of naturally occurring cardiac glycosides convallatoxin and peruvoside on human ER+ and triple-negative breast cancers.

    Kaushik, Vivek / Azad, Neelam / Yakisich, Juan Sebastian / Iyer, Anand Krishnan V

    Cell death discovery

    2017  Volume 3, Page(s) 17009

    Abstract: Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal ... ...

    Abstract Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal growth factor receptor 2 (HER2). Hormone receptor-positive and HER2-enriched cancers can be targeted using hormone and HER2-targeting therapies such as trastuzumab or lapatinib. However, triple-negative breast cancers (TNBCs) do not express any of the receptors and therefore are resistant to most targeted therapies, and cytotoxic chemotherapies are the only viable option available for the treatment of TNBCs. Recently, cardiac glycosides (CGs) have emerged as potential anticancer agents that impart their antiproliferative effect by targeting multiple pathways. In this study our aim was to evaluate anticancer effects of two naturally occurring CGs, Convallatoxin (CT) and Peruvoside (PS), on ER+ and TNBCs cells. CT and PS demonstrated dose- and time-dependent cytotoxic effect on MCF-7 cells, which was further supported by loss of colony formation on drug treatment. CT and PS arrested MCF-7 cells in the G0/G1 phase and reduced the viability of MCF-7-derived mammospheres (MMs). Interestingly, while CT and PS imparted cell death in TNBCs cells from both Caucasians (MDA-MB-231 cells) and African Americans (MDA-MB-468 cells) in a dose- and time-dependent manner, the drugs were much more potent in MDA-MB-468 as compared with TNBC MDA-MB-231 cells. Both drugs significantly inhibited migration and invasion of both MCF-7 and MDA-MB-468 cells. An assessment of intracellular pathways indicated that both drugs were able to modulate several key cellular pathways such as EMT, cell cycle, proliferation and cell death in both cell types. Our data suggest a promising role for CGs in breast cancer treatment specifically in targeting TNBCs derived from African Americans, and provides impetus for further investigation of the anticancer potential of this class of drugs.
    Language English
    Publishing date 2017-02-27
    Publishing country United States
    Document type Journal Article
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/cddiscovery.2017.9
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article: A novel resveratrol-salinomycin combination sensitizes ER-positive breast cancer cells to apoptosis.

    Venkatadri, Rajkumar / Iyer, Anand Krishnan V / Kaushik, Vivek / Azad, Neelam

    Pharmacological reports : PR

    2017  Volume 69, Issue 4, Page(s) 788–797

    Abstract: Background: Resveratrol is a dietary compound that has been widely reported for its anticancer activities. However, successful extrapolation of its effects to pre-clinical studies is met with limited success due to inadequate bioavailability. We ... ...

    Abstract Background: Resveratrol is a dietary compound that has been widely reported for its anticancer activities. However, successful extrapolation of its effects to pre-clinical studies is met with limited success due to inadequate bioavailability. We investigated the potential of combination therapy to improve the efficacy of resveratrol in a more physiologically relevant dose range.
    Methods: The effect of resveratrol on canonical Wnt signaling was evaluated by Western blotting. Wnt modulators HLY78 (activator) and salinomycin (inhibitor) were evaluated in combination with resveratrol for their effect on breast cancer cell viability (MTT assay), cell cycle progression and apoptosis (Western blotting). Bliss independency model was used to evaluate combinatorial effects of resveratrol-salinomycin combination.
    Results: Resveratrol downregulated canonical Wnt signaling proteins in treated breast cancer cells (MCF-7, MDA-MB-231 and MDA-MB-468) in the dose range of 50-200μM, which also affected cellular viability. However, at very low doses (0-50μM), resveratrol exhibited no cellular toxicity. Co-treatment with salinomycin significantly potentiated the anti-cancer effects of resveratrol, whereas HLY78 co-treatment had minimal effect. Bliss independency model revealed that Wnt inhibition synergistically potentiates the effects of resveratrol in MCF-7 and BT474 cells. Significantly downregulated canonical Wnt signaling proteins and marker of epithelial-mesenchymal transition (EMT), vimentin were observed in cells treated with resveratrol-salinomycin combination. Cell cycle arrest, caspase activation and apoptosis induction in cells treated with resveratrol-salinomycin combination further confirmed the efficacy of the combination.
    Conclusion: We report a novel resveratrol-salinomycin combination for targeting ER-positive breast cancer cells and present evidence for successful pre-clinical implementation of resveratrol.
    MeSH term(s) Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Agents, Phytogenic/therapeutic use ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy ; Cell Line, Tumor ; Drug Therapy, Combination ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Pyrans/administration & dosage ; Pyrans/therapeutic use ; Receptors, Estrogen/metabolism ; Resveratrol ; Signal Transduction ; Stilbenes/administration & dosage ; Stilbenes/therapeutic use ; Wnt Proteins/genetics ; Wnt Proteins/metabolism
    Chemical Substances Anti-Bacterial Agents ; Antineoplastic Agents, Phytogenic ; Pyrans ; Receptors, Estrogen ; Stilbenes ; Wnt Proteins ; salinomycin (62UXS86T64) ; Resveratrol (Q369O8926L)
    Language English
    Publishing date 2017-04-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2186248-5
    ISSN 1734-1140
    ISSN 1734-1140
    DOI 10.1016/j.pharep.2017.03.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Cancer Cell Plasticity: Rapid Reversal of Chemosensitivity and Expression of Stemness Markers in Lung and Breast Cancer Tumorspheres.

    Yakisich, Juan Sebastian / Azad, Neelam / Kaushik, Vivek / Iyer, Anand Krishnan V

    Journal of cellular physiology

    2017  Volume 232, Issue 9, Page(s) 2280–2286

    Abstract: In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated one cycle of environmental conditions to study such reversibility by first generating floating ... ...

    Abstract In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated one cycle of environmental conditions to study such reversibility by first generating floating tumorspheres (FTs) from lung and breast cancer cells by culturing them in serum-free media without the addition of any external mitogenic stimulation, and subsequently (after 2 weeks) re-incubating them back in serum-containing media to simulate routine culture conditions (RCCs). We found that cancer cells are extremely plastic: cells grown under RCCs become multidrug-resistant when grown as FTs, but upon re-incubation under RCCs quickly re-attach and lose the acquired resistance. These phenotypic changes are accompanied by concomitant changes in the expression of key proteins associated with multiple pathways important for chemoresistance, survival, and stemness maintenance. Therefore, our strategy provides an excellent experimental model to study environmental factors that modulate the plasticity of cancer cells. J. Cell. Physiol. 232: 2280-2286, 2017. © 2016 Wiley Periodicals, Inc.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Adhesion ; Cell Plasticity/drug effects ; Cell Proliferation ; Culture Media, Serum-Free/metabolism ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Epidermal Growth Factor/pharmacology ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/metabolism ; Female ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; MCF-7 Cells ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Phenotype ; Protein Kinase Inhibitors/pharmacology ; Signal Transduction/drug effects ; Spheroids, Cellular ; Time Factors
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Culture Media, Serum-Free ; Protein Kinase Inhibitors ; Epidermal Growth Factor (62229-50-9) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2017-03-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.25725
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Anti-Tumorigenic Potential of a Novel Orlistat-AICAR Combination in Prostate Cancer Cells.

    Wright, Clayton / Iyer, Anand Krishnan V / Kaushik, Vivek / Azad, Neelam

    Journal of cellular biochemistry

    2017  Volume 118, Issue 11, Page(s) 3834–3845

    Abstract: Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various ...

    Abstract Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti-obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell-lines (DU145, PC3, and LNCaP). We show that Orlistat and 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) (AMP-activated protein kinase [AMPK] activator) co-treatment induces significant downregulation of two key fatty acid synthesis regulatory proteins (FASN, Sterol regulatory element-binding protein 1 [SREBP-1c]) as compared to control and Orlistat alone. Orlistat and AICAR co-treatment induced a significant decrease in cell viability and proliferation, and a significant increase in apoptosis in all three PCa cell-lines. Apoptosis induction was preceded by a marked increase in reactive oxygen species (ROS) production followed by G0/G1 cell cycle arrest and activation of pro-apoptotic caspases. We also observed a significant decrease in migration potential and VEGF expression in Orlistat and AICAR co-treated samples in all three PCa cell-lines. Compound C (AMPK inhibitor) negatively affected some of the enhanced anti-cancer effects observed with Orlistat treatment. We conclude that AICAR co-treatment potentiates the anti-proliferative effects of Orlistat at a low dose (100 µM), and this combination has the potential to be a viable and effective therapeutic option in PCa treatment. J. Cell. Biochem. 118: 3834-3845, 2017. © 2017 Wiley Periodicals, Inc.
    MeSH term(s) Aminoimidazole Carboxamide/analogs & derivatives ; Aminoimidazole Carboxamide/metabolism ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; G1 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Lactones/pharmacology ; Male ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/metabolism ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Reactive Oxygen Species/metabolism ; Resting Phase, Cell Cycle/drug effects ; Ribonucleotides/metabolism
    Chemical Substances Lactones ; Neoplasm Proteins ; Reactive Oxygen Species ; Ribonucleotides ; Aminoimidazole Carboxamide (360-97-4) ; orlistat (95M8R751W8) ; AICA ribonucleotide (F0X88YW0YK)
    Language English
    Publishing date 2017-05-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 392402-6
    ISSN 1097-4644 ; 0730-2312
    ISSN (online) 1097-4644
    ISSN 0730-2312
    DOI 10.1002/jcb.26033
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Translational gap in ongoing clinical trials for glioma.

    Guishard, Alecia Florence / Yakisich, Juan Sebastian / Azad, Neelam / Iyer, Anand Krishnan V

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

    2017  Volume 47, Page(s) 28–42

    Abstract: Despite the vast amounts of information gathered about gliomas, the overall survival of glioma patients has not improved in the last four decades. This could partially be due to an apparent failure to include basic concepts of glioma biology into ... ...

    Abstract Despite the vast amounts of information gathered about gliomas, the overall survival of glioma patients has not improved in the last four decades. This could partially be due to an apparent failure to include basic concepts of glioma biology into clinical trials. Specifically, attempts to overcome the limitations of the blood brain barrier (BBB) and the chemoresistance of glioma stem cells (GSCs) were seldom included (a phenomenon known as the translational gap, TG) in a study involving 29 Phase I/II clinical trials (P2CT) published in 2011. The aim of this study was to re-evaluate this finding with a new series of 100 ongoing, but still unpublished, P2CT in order to determine if there is a TG reduction. As indicators, we evaluated in each P2CT the number of drugs tested, concomitant radiotherapy, and the ability of drugs to pass the BBB and to target GSCs. Compared to clinical trials published in 2011, we found that while in OCT there is an increase in the number of P2CT using two drugs (from 24.1% to 44.9%), and an increase in the number of drugs able to pass the BBB (7.14% versus 64.29%) and target GSCs (0% versus 16.3%), there was a decrease in the number of P2CT using concomitant radiotherapy (34.5% versus 18.37%). Overall our results suggest that there is only a modest improvement regarding reducing the TG because the vast majority of ongoing P2CT are still not including well known concepts of glioma biology important for a successful treatment.
    MeSH term(s) Blood-Brain Barrier/drug effects ; Brain Neoplasms/drug therapy ; Clinical Trials, Phase II as Topic ; Glioma/drug therapy ; Humans ; Neoplastic Stem Cells/drug effects
    Language English
    Publishing date 2017-10-21
    Publishing country Scotland
    Document type Journal Article ; Review
    ZDB-ID 1193674-5
    ISSN 1532-2653 ; 0967-5868
    ISSN (online) 1532-2653
    ISSN 0967-5868
    DOI 10.1016/j.jocn.2017.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Anti-Tumorigenic Effects of Resveratrol in Lung Cancer Cells Through Modulation of c-FLIP.

    Wright, Clayton / Iyer, Anand Krishnan V / Yakisich, Juan S / Azad, Neelam

    Current cancer drug targets

    2017  Volume 17, Issue 7, Page(s) 669–680

    Abstract: Background: Resveratrol has been shown to have antioxidant and anti-proliferative properties in multiple cancer types. Here we demonstrate that H460 lung cancer cells are more susceptible to resveratrol treatment in comparison to human bronchial ... ...

    Abstract Background: Resveratrol has been shown to have antioxidant and anti-proliferative properties in multiple cancer types. Here we demonstrate that H460 lung cancer cells are more susceptible to resveratrol treatment in comparison to human bronchial epithelial Beas-2B cells. Resveratrol decreases cell viability and proliferation, and induces significant apoptosis in H460 cells. The apoptosis observed was accompanied by an increase in hydrogen peroxide (H2O2) production, Bid, PARP and caspase 8 activation, and downregulation of pEGFR, pAkt, c-FLIP and NFkB protein expression. Furthermore, treatment with HH2O2 scavenger catalase significantly inhibited resveratrol-induced c-FLIP downregulation, caspase-8 activation and apoptosis. Overexpression of c-FLIP in H460 cells (FLIP cells) resulted in the inhibition of resveratrol-induced HH2O2 production, and a significant increase in resveratrolinduced apoptosis in comparison to H460 cells. In FLIP cells, catalase treatment did not rescue cells from a decrease in cell viability and apoptosis induction by resveratrol as compared to H460 cells. Resveratrol treatment also led to VEGF downregulation in FLIP cells. Furthermore, inhibition of pEGFR or pAkt using erlotinib and LY294002 respectively, enhanced the negative effect of resveratrol on FLIP cell viability and apoptosis. The reverse was observed when FLIP cells were supplemented with EGF, or transfected with WT-AKT plasmid; resulting in a 20% decrease in resveratrol-induced apoptosis. In addition, transfection with WT-AKT plasmid resulted in the inhibition of pro-apoptotic protein activation, and c-FLIP and pAkt downregulation.
    Conclusion: Overall, resveratrol induced apoptosis in H460 lung cancer cells by specifically targeting pAkt and c-FLIP dowregulation by proteasomal degradation in a EGFR-dependent manner.
    MeSH term(s) Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/metabolism ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics ; CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism ; Cell Line, Tumor ; Humans ; Hydrogen Peroxide/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; Reactive Oxygen Species/metabolism ; Resveratrol ; Stilbenes/pharmacology
    Chemical Substances Antineoplastic Agents, Phytogenic ; Apoptosis Regulatory Proteins ; CASP8 and FADD-Like Apoptosis Regulating Protein ; CFLAR protein, human ; Reactive Oxygen Species ; Stilbenes ; Hydrogen Peroxide (BBX060AN9V) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Resveratrol (Q369O8926L)
    Language English
    Publishing date 2017-03-11
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2064824-8
    ISSN 1873-5576 ; 1568-0096
    ISSN (online) 1873-5576
    ISSN 1568-0096
    DOI 10.2174/1568009617666170315162932
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Chemoresistance of Lung and Breast Cancer Cells Growing Under Prolonged Periods of Serum Starvation.

    Yakisich, Juan Sebastian / Venkatadri, Rajkumar / Azad, Neelam / Iyer, Anand Krishnan V

    Journal of cellular physiology

    2017  Volume 232, Issue 8, Page(s) 2033–2043

    Abstract: The efficacy of chemotherapy is hindered by both tumor heterogeneity and acquired or intrinsic multi-drug resistance caused by the contribution of multidrug resistance proteins and stemness-associated prosurvival markers. Therefore, targeting multi-drug ... ...

    Abstract The efficacy of chemotherapy is hindered by both tumor heterogeneity and acquired or intrinsic multi-drug resistance caused by the contribution of multidrug resistance proteins and stemness-associated prosurvival markers. Therefore, targeting multi-drug resistant cells would be much more effective against cancer. In this study, we characterized the chemoresistance properties of adherent (anchorage-dependent) lung H460 and breast MCF-7 cancer cells growing under prolonged periods of serum starvation (PPSS). We found that under PPSS, both cell lines were highly resistant to Paclitaxel, Colchicine, Hydroxyurea, Obatoclax, Wortmannin, and LY294002. Levels of several proteins associated with increased stemness such as Sox2, MDR1, ABCG2, and Bcl-2 were found to be elevated in H460 cells but not in MCF-7 cells. While pharmacological inhibition of either MDR1, ABCG2, Bcl-2 with Verapamil, Sorafenib, or Obatoclax, respectively decreased the levels of their target proteins under routine culture conditions as expected, such inhibition did not reverse PX resistance in PPSS conditions. Paradoxically, treatment with inhibitors in serum-starved conditions produced an elevation of their respective target proteins. In addition, we found that Digitoxin, an FDA approved drug that decrease the viability of cancer cells growing under PPSS, downregulates the expression of Sox2, MDR1, phospho- AKT, Wnt5a/b, and β-catenin. Our data suggest that PPSS-induced chemoresistance is the result of extensive rewiring of intracellular signaling networks and that multi-resistance can be effectively overcome by simultaneously targeting multiple targets of the rewired network. Furthermore, our PPSS model provides a simple and useful tool to screen drugs for their ability to target multiple pathways of cancer resistance. J. Cell. Physiol. 232: 2033-2043, 2017. © 2016 Wiley Periodicals, Inc.
    MeSH term(s) ATP Binding Cassette Transporter, Sub-Family B/genetics ; ATP Binding Cassette Transporter, Sub-Family B/metabolism ; ATP Binding Cassette Transporter, Sub-Family G, Member 2/genetics ; ATP Binding Cassette Transporter, Sub-Family G, Member 2/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Culture Techniques ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Culture Media, Serum-Free/metabolism ; Digitoxin/pharmacology ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Multiple/genetics ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Drug Screening Assays, Antitumor ; Energy Metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; MCF-7 Cells ; Models, Biological ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Paclitaxel/pharmacology ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction/drug effects ; Time Factors
    Chemical Substances ABCB1 protein, human ; ABCG2 protein, human ; ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; Antineoplastic Agents ; BCL2 protein, human ; Culture Media, Serum-Free ; Neoplasm Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Digitoxin (E90NZP2L9U) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2017-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.25514
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article: Characterizing COPD Symptom Variability in the Stable State Utilizing the Evaluating Respiratory Symptoms in COPD Instrument.

    Krishnan, Jamuna K / Ancy, Kayley M / Oromendia, Clara / Hoffman, Katherine L / Easthausen, Imaani / Leidy, Nancy K / Han, MeiLan K / Bowler, Russell P / Christenson, Stephanie A / Couper, David J / Criner, Gerard J / Curtis, Jeffrey L / Dransfield, Mark T / Hansel, Nadia N / Iyer, Anand S / Paine Iii, Robert / Peters, Stephen P / Wedzicha, Jadwiga A / Woodruff, Prescott G /
    Ballman, Karla V / Martinez, Fernando J

    Chronic obstructive pulmonary diseases (Miami, Fla.)

    2022  Volume 9, Issue 2, Page(s) 195–208

    Abstract: Rationale: It has been suggested that patients with chronic obstructive pulmonary disease (COPD) experience considerable daily respiratory symptom fluctuation. A standardized measure is needed to quantify and understand the implications of day-to-day ... ...

    Abstract Rationale: It has been suggested that patients with chronic obstructive pulmonary disease (COPD) experience considerable daily respiratory symptom fluctuation. A standardized measure is needed to quantify and understand the implications of day-to-day symptom variability.
    Objectives: To compare standard deviation with other statistical measures of symptom variability and identify characteristics of individuals with higher symptom variability.
    Methods: Individuals in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Exacerbations sub-study completed an Evaluating Respiratory Symptoms in COPD (E-RS) daily questionnaire. We calculated within-subject standard deviation (WS-SD) for each patient at week 0 and correlated this with measurements obtained 4 weeks later using Pearson's r and Bland Altman plots. Median WS-SD value dichotomized participants into higher versus lower variability groups. Association between WS-SD and exacerbation risk during 4 follow-up weeks was explored.
    Measurements and main results: Diary completion rates were sufficient in 140 (68%) of 205 sub-study participants. Reproducibility (r) of the WS-SD metric from baseline to week 4 was 0.32. Higher variability participants had higher St George's Respiratory Questionnaire (SGRQ) scores (47.3 ± 20.3 versus 39.6 ± 21.5,
    Conclusions: WS-SD of the E-RS can be used as a measure of symptom variability in studies of patients with COPD. Patients with higher variability have worse health-related quality of life. WS-SD should be further validated as a measure to understand the implications of symptom variability.
    Language English
    Publishing date 2022-04-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2771715-X
    ISSN 2372-952X
    ISSN 2372-952X
    DOI 10.15326/jcopdf.2021.0263
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top