Human Endogenous Retroviruses
Buket Çakmak Güner & Nermin Gözükırmızı
pp. 1-8 | DOI: 10.29329/ijiasr.2018.132.1 | MID: MANU-1712-30-0001.R1
Manuscript Views: 18 | Manuscript Download: 34
Human Endogenous retroviruses (HERVs) occupy nearly 8% of human genome. They are thought to be remnants of retroviruses. These integrated elements have gag, pol and env coding regions. The genome order of 5 ’LTR-gag-pro-pol-env-LTR 3’ is completely conserved among known retroviruses and endogenous retroviruses. A complete LTRs consists of untranslated 5’ (U5), repeat (R) and untranslated 3’ (U3) regions. ERVs have the potential to proliferate within a genome. Due to the nonsense mutations, methylations and deletions, most families of HERV lost their coding regions and therefore could not produce functional proteins. Most of HERVs are structurally incomplete with deletions and insertions. Although human genomehave many protective mechanisms, there are many transcriptionally active transposons and endogenous retroviruses in the human genome. Given their nature within the genome, HERVs have potential for genetic disorders, cancer, autoimmunity and neurological diseases. There are many studies investigating the association ofHERVs with diseases. In this review, we give a short summary from a few of of these studies.
Keywords: Human endogenous retroviruses, human diseases, HERV-K, HERV-E, HERV-W.
- Bannert N, Kurth R, 2004, Retroelements and the human genome: new perspectives on an old relation, Proc Natl Acad Sci. 101, 14572–14579.
- Belshaw R, Pereira V, Katzourakis A, Talbot G, Paces J, Burt, A, et al., 2004, Long-term reinfection of the human genome by endogenous retroviruses. Proc. Natl. Acad. Sci. 101, 4894–4899.
- Best S, Le Tissier P, Towers G, Stoye JP, 1996, Positional cloning of the mouse retrovirus restriction gene Fv1, Nature, 382:826829.
- Blanco P, Shlumukova M, Sargent CA, et al, 2002, Divergent outcomes of intra-chromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism, J Med Genet; 37:752–8.
- Blikstad V, Benachenhou F, Sperber GO, Blomberg J, 2008, Evolution of human endogenous retroviral sequences: a conceptual account, Cellular and Molecular Life Sciences, 65:3348-65.
- Buzdin A, 2007, Human-specific endogenous retroviruses, Scientific World Journal 7, 1848–1868.
- Buzdin A, Kovalskaya-Alexandrova E, Gogvadze E, and Sverdlov E, 2006, At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo as active promoters for host nonrepetitive DNA transcription, J. Virol. 80, 10752–10762.
- Buzdin AA, Prassolov V, Garazha AV, 2017, Friends-Enemies: Endogenous retroviruses are major trascriptional regulators of human DNA, Front in Chem 5.
- Cakmak B, Marakli S, Gözükirmizi N, 2017, Sukkula retrotransposon movements in the human genome, Biotechnology & Biotechnological Equipment 31, 900-905.
- Denner, J, 2016, Expression and function of endogenous retroviruses in the placenta. APMIS Acta Pathol. Microbiol. Immunol. Scand, 124, 31–43.
- Douville R, Liu J, Rothstein J, Nath A, 2011, Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis, Ann. Neurol. 69 (1), 577-587.
- Downey R.F, Sullivan FJ, Wang-Johanning F, Ambs S, Giles FJ, Glynn SA, 2015, Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice? Int. J. Cancer 137, 1249–1257.
- Elkina MA, Erkenov TA, Glazko VI, 2015, Mobile genetic elements as a tool for the analysis of genetic differentiation of varieties of cultivated plants and breeds of farm animals. IJRSR 6:5893-5900.
- Gonzalez-Cao M, Iduma P, Karachaliou N, Santarpia M, Blanco J, Rosell R, 2016, Human endogenous retroviruses and cancer. Cancer Biol. Med. 13, 483–488.
- Griffiths DJ, 2001, Endogenous retroviruses in the human genome sequence, Genome Biology 2 (6).
- Guliev M, Yilmaz S, Sahin K, et al, 2013, Human endogenous retrovirus H (Herv-H) genome insertion variations in humans, Mol Med Rep. 7:1305-1309.
- Hayward A, Cornwallis CK, Jern P, 2015, Pan-vertebrate comparative genomics unmasks retrovirus macroevolution. Proc Natl Acad Sci, 112:464–9.
- Hohn O, Hanke K, Bannert N, 2013, HERV-K(HML-2), the best preserved family of HERVs: endogenization, expression, and implications in health and disease, Front Oncol 3:246.
- Hurst TP, and Magiorkinis G, 2017, Epigenetic control of human endogenous retrovirus expression: Focus on Regulation of Long-Terminal Repeats (LTRs), Viruses 9, 130.
- Jern P, Coﬃn JM, 2008, Eﬀects of retroviruses on host genome function. Annu Rev Genet. 42:709–32.
- Jern P, Sperber GO, Blomberg J, 2005, Definition and variation of human endogenous retrovirus. H Virology, 327:93-110.
- Kremer D, Glanzman R, Traboulsee A, Nath A, Groc L, Horwitz M, Göttle P et al, 2017, Prehistoric enemies within: The contribution of human endogenous retroviruses to neurological diseases. Meeting report: “Second International Workshop on Human Endogenous Retroviruses and Disease. Mult Scler Relat Disord 15: 18-23.
- Lenasi T, Contreras X, and Peterlin BM, 2010, Transcription, splicing and transport of retroviral RNA. In: BANNERT, N. & KURTH, R. (eds.) Retroviruses. Molecular Biology, Genomics and Pathogenesis. Norforlk: Caister Academic Press.
- Lerat E, Semon M,2007, Influence of the transposable element neighborhood on human gene expression in normal and tumor tissue, Gene 396, pp.303–11.
- Lettini AA, Guidoboni M, Fonsatti E, Anzalone L, Cortini E, Maio M et al, 2007, Epigenetic remodelling of DNA in cancer, Histology and Histopathology 22:1413-24.
- Li M, Radvanyi LG, Yin B, Li J, Chivukula R, Lin K, Lu Y, et al, 2017, Down-regulation of human endogenous retrovirus type K (HERV-K) viral env RNA in pancreatic cancer cells decreases cell proliferation and tumor growth. AACR.
- Mamedov I, Lebedev Y, Hunsmann G, Khusnutdinova E, and Sverdlova E, 2004, A rare event of insertion polymorphism of a HERV-K LTR in the human genome, Genomics 84: 596-599.
- Mariani-Costantini R, Horn TM, Callahan R, 1989, Ancestry of a human endogenous retrovirus family. J Virol 63:4982–5.
- Mayer J, Blomberg J, and Seal R, 2011, A revised nomenclature for transcribed human endogenous retroviral loci, Mobile DNA.
- Menendez L, Benigno BB, McDonald JF,2004, L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas. Mol. Cancer 3, 12.
- Nelson PN, Roden D, Nevill A, Freimanis GL, Trela M, Ejtehadi HD, Bowman S, Axford J, Veitch AM, Tugnet N, Rylance PB, 2014, Rheumatoid arthritis is associated with IgG antibodies to human endogenous retrovirus gag matrix: a potential pathogenic mechanism of disease? J Rheumatol 41(10): 1952–1960.
- Ohnuki M, Tanabe K, Sutou K, Teramoto I, Sawamura Y, Narita M, et al, 2014, Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential, Proc. Natl. Acad. Sci 111, 12426–12431.
- Paces J, Huang YT, Paces V, Ridl Y, and Chang CM, 2013, New insight into transcription of human endogenous retroviral elements, N Biotechnol 30 (3): 314-318.
- Perron H, Garson JA, Bedin F, Beseme F, Paranhos-Baccala G, Komurian-Pradel F, Mallet F, Tuke PW, Voisset C, Blond JL, et al, 1997, molecular identification of a novel retrovirus repeatedly isolted from patients with multiple sclerosis, Proc Natl Acad Sci, 7583-7588.
- Reis BS, Jungbluth AA, Frosina D, Holz M, Ritter E, Nakayama E, Ishida T, Obata Y, Carver B, Scher H, Scardino PT et al, 2013, Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein, Clin Cancer Res 19(22):6112–6125.
- Schumann GG, Gogvadze EV, Osanai-Futahashi M, Kuroki A, Münk C, Fujiwara H, et al, 2010, Unique functions of repetitive transcriptomes, Int. Rev. Cell Mol. Biol. 115–188.
- Seal RL, Gordon SM, Lush MJ, Wright MW, Bruford EA, 2011, genenames.org: the HGNC resources in 2011. Nucleic Acids Res 39.
- Sotgiu S, Mameli G, Serra C, Zarbo IR, Arru G, Dolei A, 2010, Multiple sclerosis-associated retrovirus and progressive disability of multiple sclerosis, Mult. Scler. 16, 1248-1251.
- Stengel S, Fiebig U, Kurth R, Denner J, 2010, Regulation of human endogenous retrovirus-K expression in melanomas by CpG methylation. Genes. Chromosomes Cancer 49, 401–411.
- Stoye JP, 2001, Endogenous retroviruses: still actie all these years? Current Biology 11: R914-6.
- Suntsova M, Garazha A, Ivanova A, Kaminsky D, Zhavoronkov A, and Buzdin A, 2015, Molecular functions of human endogenous retroviruses in health and disease, Cell. Mol. Life Sci. 72, 3653–3675.
- Suntsova M, Gogvadze EV, Salozhin S, Gaifullin N, Eroshkin F, Dmitriev SE, et al, 2013, Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene PRODH. Proc. Natl. Acad. Sci 110, 19472–19477.
- Takahashi Y, Harashima N, Kajigaya S, Yokoyama H, Cherkasova E, McCoy JP et al, 2008, Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells, J Clin Investig 118(3):1099–1109.
- Van Horssen J, van der Pol S, Nijland P, Amor S, Perron H, 2016, Human endogenous retrovirus W in brain lesions: rationale for targeted therapy in multiple sclerosis, Mult. Scler. Relat. Disord. 8, 11-18.
- Volkman, HE, Stetson DB, 2014, The enemy within: Endogenous retroelements and autoimmune disease Nat. Immunol 15, 415–42.
- Yi JM, Kim HM, Kim HS, 2004, Expression of the human endogenous retrovirus HERVW family in various human tissues and cancer cells. Journal of General Virology 85, pp.1203–10
DSSC’ler için NNN ligantlar ile kararlaştırılmış Rutenyum malzemeler
Osman Dayan, Namık Özdemir, Fahrettin Yakuphanoğlu, Zafer Şerbetci & Ali Bilici
pp. 9-24 | DOI: 10.29329/ijiasr.2018.132.2 | MID: MANU-1803-19-0003.R2
Manuscript Views: 11 | Manuscript Download: 29
Bu çalışmada 2,6-bis(benzimidazol)piridinil (NNN) ligantlar ile kararlaştırılmış yeni rutenyum nano partüküllerin üretildi. Malzemeler NMR, IR, SEM-EDX, TEM ve XRD gibi teknikler kullanılarak yapıları hakkında bilgi edinildi ve boya duyarlı güneş hücrelerinin hazırlanmasında kullanıldı.
Keywords: Boya duyarlı güneş hücresi, Rutenyum, I-V karakteristiği
-  B. Oregan, M. Gratzel, A Low-Cost, High-Efficiency Solar-Cell Based on Dye-Sensitized Colloidal Tio2 Films, Nature, 353 (1991) 737-740.
-  S.M. Feldt, E.A. Gibson, E. Gabrielsson, L. Sun, G. Boschloo, A. Hagfeldt, Design of Organic Dyes and Cobalt Polypyridine Redox Mediators for High-Efficiency Dye-Sensitized Solar Cells, J Am Chem Soc, 132 (2010) 16714-16724.
-  K.R. Seddon, Ruthenium, Coordin Chem Rev, 41 (1982) 79-157.
-  H.N. Yi, J.A. Crayston, J.T.S. Irvine, Ruthenium complexes of 2-(2 '-pyridyl) benzimidazole as photosensitizers for dye-sensitized solar cells, Dalton T, DOI 10.1039/b208289f(2003) 685-691.
-  D.B. Kuang, C. Klein, S. Ito, J.E. Moser, R. Humphry-Baker, S.M. Zakeeruddin, M. Gratzel, High molar extinction coefficient ion-coordinating ruthenium sensitizer for efficient and stable mesoscopic dye-sensitized solar cells, Adv Funct Mater, 17 (2007) 154-160.
-  M.K. Nazeeruddin, A. Kay, I. Rodicio, R. Humphrybaker, E. Muller, P. Liska, N. Vlachopoulos, M. Gratzel, Conversion of Light to Electricity by Cis-X2bis(2,2'-Bipyridyl-4,4'-Dicarboxylate)Ruthenium(Ii) Charge-Transfer Sensitizers (X = Cl-, Br-, I-, Cn-, and Scn-) on Nanocrystalline Tio2 Electrodes, J Am Chem Soc, 115 (1993) 6382-6390.
-  X.M. Xiao, M.A. Haga, T. Matsumurainoue, Y. Ru, A.W. Addison, K. Kano, Synthesis and Proton Transfer-Linked Redox Tuning of Ruthenium(Ii) Complexes with Tridentate 2,6-Bis(Benzimidazol-2-Yl)Pyridine Ligands, J Chem Soc Dalton, DOI Doi 10.1039/Dt9930002477(1993) 2477-2484.
-  O. Kohle, S. Ruile, M. Gratzel, Ruthenium(II) charge-transfer sensitizers containing 4,4'-dicarboxy-2,2'-bipyridine. Synthesis, properties, and bonding mode of coordinated thio- and selenocyanates, Inorg Chem, 35 (1996) 4779-4787.
-  S. Ruile, O. Kohle, P. Pechy, M. Gratzel, Novel sensitisers for photovoltaic cells. Structural variations of Ru(II) complexes containing 2,6-bis(1-methylbenzimidazol-2-yl)pyridine, Inorg Chim Acta, 261 (1997) 129-140.
-  M.K. Nazeeruddin, E. Muller, R. Humphry-Baker, N. Vlachopoulos, M. Gratzel, Redox regulation in ruthenium(II) polypyridyl complexes and their application in solar energy conversion, J Chem Soc Dalton, DOI Doi 10.1039/A704242f(1997) 4571-4578.
-  S.C. Yu, S.J. Hou, W.K. Chan, Synthesis, metal complex formation, and electronic properties of a novel conjugate polymer with a tridentate 2,6-bis(benzimidazol-2-yl)pyridine ligand, Macromolecules, 32 (1999) 5251-5256.
-  M.A. Haga, K. Wang, N. Kato, H. Monjushiro, Electrochemical properties of dinuclear Ru complex Langmuir-Blodgett films towards molecular electronics, Mol Cryst Liq Crys A, 337 (1999) 89-92.
-  K.Z. Wang, M.A. Haga, Chemical transformation of amphiphilic Ru complexes containing 2,6-pyridinedicarboxylate at the air-water interface, Mol Cryst Liq Cryst, 342 (2000) 225-230.
-  L. Mishra, R. Sinha, Mononuclear and binuclear ruthenium(III) polypyridyl complexes containing 2,6-bis(2 '-benzimidazyl)-pyridine as co-ligand: Synthesis, spectroscopic properties and redox activity, Indian J Chem A, 39 (2000) 1131-1139.
-  V.G. Vaidyanathan, B.U. Nair, Synthesis, characterization and DNA binding studies of a ruthenium(II) complex, J Inorg Biochem, 91 (2002) 405-412.
-  M. Haga, T. Takasugi, A. Tomie, M. Ishizuya, T. Yamada, M.D. Hossain, M. Inoue, Molecular design of a proton-induced molecular switch based on rod-shaped Ru dinuclear complexes with bis-tridentate 2,6-bis(benzimidazol-2-yl) pyridine derivatives, Dalton T, DOI 10.1039/b300130j(2003) 2069-2079.
-  V.G. Vaidyanathan, B.U. Nair, Synthesis, characterization and electrochemical studies of mixed ligand complexes of ruthenium(II) with DNA, Dalton T, DOI 10.1039/b502917a(2005) 2842-2848.
-  D. Mishra, A. Barbieri, C. Sabatini, M.G.B. Drew, H.M. Figgle, W.S. Sheldrick, S.K. Chattopadhyay, Tuning of redox potential and visible absorption band of ruthenium(II) complexes of (benzimidazolyl) derivatives: Synthesis, characterization, spectroscopic and redox properties, X-ray structures and DFT calculations, Inorg Chim Acta, 360 (2007) 2231-2244.
-  A. Singh, B. Chetia, S.M. Mobin, G. Das, P.K. Iyer, B. Mondal, Ruthenium monoterpyridine complexes with 2,6-bis(benzimidazol-2-yl)pyridine: Synthesis, spectral properties and structure, Polyhedron, 27 (2008) 1983-1988.
-  J.J. Concepcion, J.W. Jurss, P.G. Hoertz, T.J. Meyer, Catalytic and Surface-Electrocatalytic Water Oxidation by Redox Mediator-Catalyst Assemblies, Angewandte Chemie-International Edition, 48 (2009) 9473-9476.
-  C. Bhaumik, S. Das, D. Saha, S. Dutta, S. Baitalik, Synthesis, Characterization, Photophysical, and Anion-Binding Studies of Luminescent Heteroleptic Bis-Tridentate Ruthenium(II) Complexes Based on 2,6-Bis(Benzimidazole-2-yl)Pyridine and 4'-Substituted 2,2 ':6 ',2 '' Terpyridine Derivatives, Inorg Chem, 49 (2010) 5049-5062.
-  Q.Y. Yu, B.X. Lei, J.M. Liu, Y. Shen, L.M. Xiao, R.L. Qiu, D.B. Kuang, C.Y. Su, Ruthenium dyes with heteroleptic tridentate 2,6-bis(benzimidazol-2-yl)-pyridine for dye-sensitized solar cells: Enhancement in performance through structural modifications, Inorg Chim Acta, 392 (2012) 388-395.
-  A.W. Addison, P.J. Burke, Synthesis of Some Imidazole-Derived and Pyrazole-Derived Chelating-Agents, J Heterocyclic Chem, 18 (1981) 803-805.
-  D. Gonzalez-Galvez, P. Lara, O. Rivada-Wheelaghan, S. Conejero, B. Chaudret, K. Philippot, P.W.N.M. van Leeuwen, NHC-stabilized ruthenium nanoparticles as new catalysts for the hydrogenation of aromatics, Catal Sci Technol, 3 (2013) 99-105.
Effects of Salinomycin and Everolimus on Breast Cancer Stem Cells in Hypoxia
Hatice Pilevneli & Mehtap Kılıç Eren
pp. 25-40 | DOI: 10.29329/ijiasr.2018.132.3 | MID: MANU-1803-26-0008.R2
Manuscript Views: 21 | Manuscript Download: 32
Cancer stem cells (CSCs) are a collection of small numbers of cells that have the potential to induce all cell types within the tumor mass and have self-renewal capacity. Today, the reasons for the failure of conventional cancer therapies lie in the fact that they are unable to target cancer stem cells. Targeting the cancer stem cell is thought to provide a very important and revolutionary advance in cancer cell targeting and therapy.
Tumor hypoxia is a characteristic of solid tumors and has been associated with poor prognosis and resistance to radiotherapy and chemotherapy. HIF-1 (Hypoxia Inducible Factor-1) is the major transcription factor activated in hypoxic conditions and allows transcriptional activation of various genes that are effective for the adaptation of the cell to the hypoxic condition. Experimental studies have provided evidence that also hypoxia and HIF-1α promote the cancer stem cell phenotype and targeting of HIF-1α may reduce or eliminate cancer stem cells.
Breast cancer is the most common form of cancer in women worldwide and affects 10% of the world's female population. 25% to 30% of patients with invasive breast cancer still die from this disease. The recurrence frequency of the disease varies between 60% and 80% within the first 3 years after treatment. In order to target breast cancer stem cells more effectively, in this study we aimed to reveal whether the hypoxic conditions in the tumor, which act as the stem cell production area, at the same time creates resistance to therapy. Thus, we evaluated effect of CSCs targeting agent Salinomycin alone or in combination with Everolimus which is an m-TOR and HIF-1α inhibitor on parental MCF-7 and MDA-231 breast cancer cells and their isolated CSCs in hypoxic conditions.
Here it is presented that starting with 2 mM, increased concentrations of salinomycin significantly inhibits proliferation and induce apoptosis in hypoxia, in both parental MCF-7 and MDA-231 breast cancer cells and in their isolated CSCs. The most effective concentration of salinomycin was 10 mM and induced around 35% and 45% of apoptosis in both parental MCF-7 and MDA-231 and their isolated CSCs, respectively. Whereas everolimus alone was not as effective as salinomycin, as 25 mM everolimus induced 30% and 15% of growth inhibition or apoptosis in both parental and CSCs of MCF-7 and MDA-231 cellsin hypoxia, respectively. When lower concentrations of salinomycin (2mM) and everolimus (5mM) was used in combination they show synergistic effect and able to inhibit proliferation at least 35% and 45% in both parental and CSCs of MCF-7 and MDA-231 cells in hypoxia, respectively. Similar results were also obtained for induction of apoptosis in response to salinomycin + everolimus treatment in hypoxia in both parental and CSCs of MCF-7 and MDA-231 cells. Hence using lower concentrations of salinomycin and everolimus together may provide an effective targeting strategy for hypoxic CSCs and may contribute to the development of novel strategies for therapeutic intervention in breast cancer.
Keywords: MCF-7,MDA-231, cancer stem cell, Salinomycin, Everolimus, hypoxia
- Al Dhaheri Y., Attoub S., Arafat K., Abuqamar S., Eid A, Al Faresi N, Iratni R., 2013, Salinomycin induces apoptosis and senescence in breast cancer: upregulation of p21, downregulation of survivin and histone H3 and H4 hyperacetylation, Biochim Biophys Acta. Apr;1830(4):3121-35. 22.
- Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., and Clarke, M. F., 2003, Prospective identification of tumorigenic breast cancer cells, Proc Natl Acad Sci U S A 100(7):3983-8.
- Alison, M. R., Murphy, G., and Leedham, S., 2008, Stem cells and cancer: a deadly mix, Cell Tissue Res 331(1):109-24.
- Conley, S. J., Gheordunescu, E., Kakarala, P., Newman, B., Korkaya, H., Heath, A. N., Clouthier, S. G., and Wicha, M. S., Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia, Proc Natl Acad Sci U S A 109(8):2784-9.
- Dewangan Jayant, Srivastava Sonal, Rath Srikanta Kumar., 2017, Salinomycin: A new paradigm in cancer therapy. Tumor Biology 39 (3): 1-12
- Ercan, C., van Diest, P. J., and Vooijs, M., 2011, Mammary development and breast cancer: the role of stem cells, Curr Mol Med 11(4):270-85.
- Gil, J., Stembalska, A., Pesz, K. A., and Sasiadek, M. M., 2008, Cancer stem cells: the theory and perspectives in cancer therapy, J Appl Genet 49(2):193-9.
- Gupta, P. B., Onder, T. T., Jiang, G., Tao, K., Kuperwasser, C., Weinberg, R. A., and Lander, E. S., 2009, Identification of selective inhibitors of cancer stem cells by high-throughput screening, Cell 138(4):645-59.
- Hambardzumyan, D., Becher, O. J., and Holland, E. C., 2008, Cancer stem cells and survival pathways, Cell Cycle 7(10):1371-8.
- Hu, Y., and Fu, L., 2012, Targeting cancer stem cells: a new therapy to cure cancer patients, Am J Cancer Res 2(3):340-56.
- Iida, H., Suzuki, M., Goitsuka, R., and Ueno, H., 2011, Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of OCT3/4 and SOX2, Int J Oncol 40(1):71
- Keith, B., and Simon, M. C., 2007, Hypoxia-inducible factors, stem cells, and cancer, Cell 129(3):465-72.
- Kilic M., Kasperczyk H., Fulda S., Debatin KM., 2007, Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance, Oncogene 26 (14), 2027-2038.
- Kilic-Eren M., Boylu T., Tabor V., 2013, Targeting PI3 K/Akt represses hypoxia inducible factor-1alpha activation and sensitizes Rhabdomyosarcoma and Ewing's sarcoma cells for apoptosis, Cancer Cell Int 13 (1), 36.
- Klonisch, T., Wiechec, E., Hombach-Klonisch, S., Ande, S. R., Wesselborg, S., Schulze-Osthoff, K., and Los, M., 2008, Cancer stem cell markers in common cancers - therapeutic implications, Trends Mol Med 14(10):450-60.
- Liang, D., Ma, Y., Liu, J., Trope, C. G., Holm, R., Nesland, J. M., and Suo, Z., 2012, The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells, BMC Cancer 12:201.
- Liu, S., and Wicha, M. S., 2010, Targeting breast cancer stem cells, J Clin Oncol 28(25):4006-12.
- Oak PS1, Kopp F, Thakur C, Ellwart JW, Rapp UR, Ullrich A, Wagner E, Knyazev P, Roidl A., 2012, Combinatorial treatment of mammospheres with trastuzumab and salinomycin efficiently targets HER2-positive cancer cells and cancer stem cells. Int J Cancer, 15;131(12):2808-19.
- Pires BR, DE Amorim ÍS, Souza LD, Rodrigues JA, Mencalha AL., 2016 Targeting Cellular Signaling Pathways in Breast Cancer Stem Cells and it’s Implication for CancerTreatment, Anticancer Res. ;36(11):5681-5691.
- Schwab, L. P., Peacock, D. L., Majumdar, D., Ingels, J. F., Jensen, L. C., Smith, K. D., Cushing, R. C., and Seagroves, T. N., 2012, Hypoxia-inducible factor 1alpha promotes primary tumor growth and tumor-initiating cell activity in breast cancer, Breast Cancer Res 14(1):R6.
- Semenza G. L., 2015, Regulation of the breast cancer stem cell phenotype by hypoxia-inducible factors, Clinical Science Sep 24, 129 (12) 1037-1045.
- Semenza, G. L., 2009, HIF-1 inhibitors for cancer therapy: from gene expression to drug discovery, Curr Pharm Des 15(33):3839-43.
- Skog S, He Q, Khoshnoud R, Fornander T, Rutqvist LE. . 2004, Genes related to growth regulation, DNA repair and apoptosis in an oestrogen receptor-negative (MDA-231) versus an oestrogen receptor-positive (MCF-7) breast tumour cell line. Tumour BiolJan-Apr;25(1-2):41-7.