Laboratoř molekulární terapie

Návrh a vývoj nových protirakovinných látek, zejména analogů vitaminu E, které jsou účinné a selektivní pro maligní buňky.

Vedoucí laboratoře: prof. Ing. Jiří Neužil, CSc.

Jiří Neužil je vedoucím Laboratoře molekulární terapie.  Zaměřuje její činnost, obdobně jako v sesterské australské skupině (Mitochondria, Apoptosis and Cancer Research Group, Griffith University, Southport, Qld, Austrálie), na navrhování a vývoj nových protirakovinných látek, zejména analogů vitaminu E, které jsou účinné a selektivní pro maligní buňky. Je zde zejména  vědecký zájem o molekulární mechanismy apoptózy vyvolané takovými látkami, které zahrnují dráhy mitochondriální destabilizace. Byly definovány a charakterizovány takzvané mitokany, nízkomolekulární látky vykazující protirakovinnou aktivitu prostřednictvím mitochondrií. Tyto látky jsou pozoruhodné zejména z translačního pohledu, jelikož nyní už je zřejmé, že nádory jsou vysoce heterogenní z hlediska mutací, dokonce v různých oblastech téhož nádoru. A mitochondrie mohou představovat stabilní cíl využitelný pro terapii rakoviny.

V laboratoři se zkoumají zejména  mitokany ze skupiny analogů vitaminu E, reprezentované redoxně neaktivním α-tokoferylsukcinátem (α-TOS). Tato látka vykazuje vysokou apoptogenní aktivitu v mnoha liniích rakovinných buněk, zatímco je netoxická pro normální buňky. Tato in vitro proapoptotická aktivita má obdobu v protirakovinné aktivitě in vivo u myších modelů nádorů, což bylo prokázáno pro nádory konečníku, prsu a mezoteliomy. Tímto nálezem  získává α-TOS značný translační význam a stává se  výchozí látkou pro vývoj účinnějších agens.

Ve snaze charakterizovat dráhy regulující  přenos apoptotických signálů v rakovinných buňkách spouštěný α-TOSem, objevili Neužil a spol. nový cíl protirakovinných léčiv, mitochondriální komplex II (CII). Zjistili, že α-TOS a podobné látky interagují s proximálním i distálním vazebným místem CII pro ubichinon (UbQ), a tím v CII UbQ nahrazují. CII, působením své sukcinátdehydrogenázové (SDH) aktivity, převádí sukcinát na fumarát, jakožto komponenta cyklu trikarbonových kyselin (TCA). Elektrony uvolněné touto reakcí jsou normálně  převzaty UbQ a předány na CIII elektron-transportního řetězce (ETC), součást oxidativní fosforylace. V případě, že UbQ je nahrazen α-TOSem nebo podobnými látkami, elektrony reagují s molekulárním kyslíkem a způsobí vznik superoxidu, čímž zapínají apoptotickou signální kaskádu. Jelikož geny kódující subjednotky CII mutují zcela výjimečně, komplex představuje velmi slibný cíl pro protirakovinná léčiva.

V úsilí zvýšit apoptogenní aktivitu α-TOSu byla látka modifikována připojením kationtové trifenylfosfoniové (TPP) skupiny, která způsobí akumulaci činidla (mitochondriálně zacílený sukcinát vitaminu E, MitoVES) mezi mitochondriální vnitřní membránou a mitochondriální matrix. Tím se zvýší apoptogenní aktivita rodičovské látky o 1-2 řády. Je důležité, že tento vzestup toxicity vůči rakovinným buňkám neovlivní  selektivitu látky pro maligní buňky. Přístup laboratoře k  terapii rakoviny pomocí přivěšení lipofilních kationtů (jako je TPP) k protirakovinným agens představuje nový vzor účinné léčby rakoviny. Ve skupině dále pokračují v této linii výzkumu, aby syntetizovali nové, účinnější protirakovinné látky zacílené na mitochondrie. Zejména plánují  započít translační výzkum,  na jehož základě by předali jejich nová léčiva do klinické praxe. V případě úspěchu by to mohlo úplně změnit dosavadní i budoucí terapeutické způsoby a potenciálně vést k opravdu účinné léčbě rakoviny.

video

Anděra Ladislav, RNDr., CSc.
Barzegar Yarmohammadi Arash
Benešová Simona
Boháčová Klára, Mgr.
Botsios Panagiotis
Boukalová Štěpána, Mgr., Ph.D.
Brisudová Petra, Mgr.
Brožková Andrea, Ing.
Dvořáková Šárka, RNDr., Ph.D.
Endaya Berwini Beduya
Heller Cristina-Daniela
Hrysiuk Mariia, Mgr.
Jarošová Kateřina
Le Thi Dan Diem
Lopes Oliveira Gabriela
Miklovičová Soňa, Mgr.
Nahácka Zuzana, RNDr., Ph.D.
Neřoldová Markéta, Bc.
Neužil Jiří, prof. Ing., CSc.
Novák Jaromír, Mgr.
Novotná Monika, Mgr.
Stojanović Dana
Štemberková - Hubáčková Soňa, RNDr., Ph.D.
Volpini Luca
Zobalová Renata, Mgr., Ph.D.

2024

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  • Čunátová K, Vrbacký M, Puertas-Frias G, Alán L, Vanišová M, Saucedo-Rodríguez MJ, Houštěk J, Fernández-Vizarra E, Neužil J, Pecinová A, Pecina P, Mráček T. Mitochondrial translation is the primary determinant of secondary mitochondrial complex I deficiencies. iScience. 2024 Jul 19;27(8):110560. doi: 10.1016/j.isci.2024.110560. PMID: 39184436; PMCID: PMC11342289.

  • Herst P, Carson G, Lewthwaite D, Eccles D, Schmidt A, Wilson A, Grasso C, O'Sullivan D, Neuzil J, McConnell M, Berridge M. Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model. Front Oncol. 2024 May 1;14:1362786. doi: 10.3389/fonc.2024.1362786. PMID: 38751813; PMCID: PMC11094293.

  • Jadhav SB, Vondrackova M, Potomova P, Sandoval-Acuña C, Smigova J, Klanicova K, Rosel D, Brabek J, Stursa J, Werner L, Truksa J. NDRG1 acts as an oncogene in triple-negative breast cancer and its loss sensitizes cells to mitochondrial iron chelation. Front Pharmacol. 2024 Jun 25;15:1422369. doi: 10.3389/fphar.2024.1422369. PMID: 38983911; PMCID: PMC11231402.

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  • Novotna E, Milosevic M, Prukova D, Magalhaes-Novais S, Dvorakova S, Dmytruk K, Gemperle J, Zudova D, Nickl T, Vrbacky M, Rosel D, Filimonenko V, Prochazka J, Brabek J, Neuzil J, Rohlenova K, Rohlena J. Mitochondrial HER2 stimulates respiration and promotes tumorigenicity. Eur J Clin Invest. 2024 Jun;54(6):e14174. doi: 10.1111/eci.14174. Epub 2024 Jan 30. PMID: 38291340.

  • Sharma P, Maklashina E, Voehler M, Balintova S, Dvorakova S, Kraus M, Hadrava Vanova K, Nahacka Z, Zobalova R, Boukalova S, Cunatova K, Mracek T, Ghayee HK, Pacak K, Rohlena J, Neuzil J, Cecchini G, Iverson TM. Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners. Nat Commun. 2024 Jan 11;15(1):473. doi: 10.1038/s41467-023-44563-7. PMID: 38212624; PMCID: PMC10784507.

  • Sovilj D, Kelemen CD, Dvorakova S, Zobalova R, Raabova H, Kriska J, Hermanova Z, Knotek T, Anderova M, Klener P, Filimonenko V, Neuzil J, Andera L. Cell-specific modulation of mitochondrial respiration and metabolism by the pro-apoptotic Bcl-2 family members Bax and Bak. Apoptosis. 2024 Apr;29(3-4):424-438. doi: 10.1007/s10495-023-01917-2. Epub 2023 Nov 24. PMID: 38001340.

2023

  • Amore F, Garella R, Santi A, Guasti D, Martinelli S, Canu L, Bani D, Neuzil J, Maggi M, Squecco R, Rapizzi E. The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide. Endocr Relat Cancer. 2023 Aug 25;30(10):e230167. doi: 10.1530/ERC-23-0167. PMID: 37493200.
  • Bielcikova Z, Stursa J, Krizova L, Dong L, Spacek J, Hlousek S, Vocka M, Rohlenova K, Bartosova O, Cerny V, Padrta T, Pesta M, Michalek P, Hubackova SS, Kolostova K, Pospisilova E, Bobek V, Klezl P, Zobalova R, Endaya B, Rohlena J, Petruzelka L, Werner L, Neuzil J. Mitochondrially targeted tamoxifen in patients with metastatic solid tumours: an open-label, phase I/Ib single-centre trial. EClinicalMedicine. 2023 Feb 23;57:101873. doi: 10.1016/j.eclinm.2023.101873. PMID: 37064512; PMCID: PMC10102891.
  • Dong LF, Rohlena J, Zobalova R, Nahacka Z, Rodriguez AM, Berridge MV, Neuzil J. Mitochondria on the move: Horizontal mitochondrial transfer in disease and health. J Cell Biol. 2023 Mar 6;222(3):e202211044. doi: 10.1083/jcb.202211044. Epub 2023 Feb 16. PMID: 36795453; PMCID: PMC9960264.

  • Oh S, Jo S, Bajzikova M, Kim HS, Dao TTP, Rohlena J, Kim JM, Neuzil J, Park S. Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression. Theranostics. 2023 Jan 1;13(2):438-457. doi: 10.7150/thno.75973. PMID: 36632231; PMCID: PMC9830446.
  • Oh S, Jo S, Kim HS, Mai VH, Endaya B, Neuzil J, Jung KH, Hong SS, Kim JM, Park S. Chemical Biopsy for GNMT as Noninvasive and Tumorigenesis-Relevant Diagnosis of Liver Cancer. Anal Chem. 2023 Jan 17;95(2):1184-1192. doi: 10.1021/acs.analchem.2c03944. Epub 2023 Jan 5. PMID: 36602057.

  • Qasemi M, Sur VP, Simonik O, Postlerova P, Skrobanek P, Hradec T, Boublikova L, Zamecnik L, Buchler T, Neuzil J, Komrskova K. Sperm mitochondria dysfunction in response to testicular cancer. Eur J Clin Invest. 2024 Apr;54(4):e14146. doi: 10.1111/eci.14146. Epub 2023 Dec 8. PMID: 38069497.

  • Sharma, P., Maklashina, E., Voehler, M. et al. Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners. Nat Commun 15, 473 (2024). https://doi.org/10.1038/s41467-023-44563-7

  • Tomasetti M, Monaco F, Strogovets O, Volpini L, Valentino M, Amati M, Neuzil J, Santarelli L. ATG5 as biomarker for early detection of malignant mesothelioma. BMC Res Notes. 2023 Apr 24;16(1):61. doi: 10.1186/s13104-023-06330-1. PMID: 37095543; PMCID: PMC10127310.

2022

  • Oh, S., Jo, S., Bajzikova, M., Kim, H. S., Dao, T. T. P., Rohlena, J., Kim, J. M., Neuzil, J., & Park, S. (2023). "Non-bioenergetic roles of mitochondrial GPD2 promote tumor progression." Theranostics, 13(2), 438-457. https://doi.org/10.7150/thno.75973

  • Oh, S., Jo, S., Kim, H. S., Mai, V. H., Endaya, B., Neuzil, J., Jung, K. H., Hong, S. S., Kim, J. M., & Park, S. (2023). "Chemical Biopsy for GNMT as Noninvasive and Tumorigenesis-Relevant Diagnosis of Liver Cancer." Anal Chem, 95(2), 1184-1192. https://doi.org/10.1021/acs.analchem.2c03944

2022

  • Arbon, D., Zeniskova, K., Subrtova, K., Mach, J., Stursa, J., Machado, M., Zahedifard, F., Lestinova, T., Hierro-Yap, C., Neuzil, J., Volf, P., Ganter, M., Zoltner, M., Zikova, A., Werner, L., & Sutak, R. (2022). "Repurposing of MitoTam: Novel Anti-Cancer Drug Candidate Exhibits Potent Activity against Major Protozoan and Fungal Pathogens." Antimicrob Agents Chemother, 66(8), e0072722. https://doi.org/10.1128/aac.00727-22

  • Fialova, J. L., Honigova, K., Raudenska, M., Miksatkova, L., Zobalova, R., Navratil, J., Smigova, J., Moturu, T. R., Vicar, T., Balvan, J., Vesela, K., Abramenko, N., Kejik, Z., Kaplanek, R., Gumulec, J., Rosel, D., Martasek, P., Brabek, J., Jakubek, M., Neuzil, J., & Masarik, M. (2022)."Pentamethinium salts suppress key metastatic processes by regulating mitochondrial function and inhibiting dihydroorotate dehydrogenase respiration." Biomed Pharmacother, 154, 113582. https://doi.org/10.1016/j.biopha.2022.113582

  • Gupta, P., Strange, K., Telange, R., Guo, A., Hatch, H., Sobh, A., Elie, J., Carter, A. M., Totenhagen, J., Tan, C., Sonawane, Y. A., Neuzil, J., Natarajan, A., Ovens, A. J., Oakhill, J. S., Wiederhold, T., Pacak, K., Ghayee, H. K., Meijer, L., Reddy, S., & Bibb, J. A. (2022)."Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer." Cell Rep, 40(7), 111218. https://doi.org/10.1016/j.celrep.2022.111218

  • Hadrava Vanova, K., Uher, O., Meuter, L., Ghosal, S., Talvacchio, S., Patel, M., Neuzil, J., & Pacak, K. (2022). PD-L1 expression and association with genetic background in pheochromocytoma and paraganglioma. Front Oncol, 12, 1045517. https://doi.org/10.3389/fonc.2022.1045517

  • Magalhaes-Novais, S., Blecha, J., Naraine, R., Mikesova, J., Abaffy, P., Pecinova, A., Milosevic, M., Bohuslavova, R., Prochazka, J., Khan, S., Novotna, E., Sindelka, R., Machan, R., Dewerchin, M., Vlcak, E., Kalucka, J., Stemberkova Hubackova, S., Benda, A., Goveia, J., Mracek, T., Barinka, C., Carmeliet, P., Neuzil, J., Rohlenova, K., & Rohlena, J. (2022). Mitochondrial respiration supports autophagy to provide stress resistance during quiescence. Autophagy, 1-18. https://doi.org/10.1080/15548627.2022.2038898

  • Nahacka, Z., Novak, J., Zobalova, R., & Neuzil, J. (2022). "Miro proteins and their role in mitochondrial transfer in cancer and beyond." Front Cell Dev Biol, 10, 937753. https://doi.org/10.3389/fcell.2022.937753

  • Neuzil, J. (2022). "Optimized expression of alternative oxidase." Gene Ther, 29(12), 653-654. https://doi.org/10.1038/s41434-022-00340-7

  • Stemberkova-Hubackova, S., Zobalova, R., Dubisova, M., Smigova, J., Dvorakova, S., Korinkova, K., Ezrova, Z., Endaya, B., Blazkova, K., Vlcak, E., Brisudova, P., Le, D. T., Juhas, S., Rosel, D., Daniela Kelemen, C., Sovilj, D., Vacurova, E., Cajka, T., Filimonenko, V., Dong, L., Andera, L., Hozak, P., Brabek, J., Bielcikova, Z., Stursa, J., Werner, L., & Neuzil, J. (2022, Mar). Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy. Clin Transl Med, 12(3), e645. https://doi.org/10.1002/ctm2.645

  • Vacurova, E., Trnovska, J., Svoboda, P., Skop, V., Novosadova, V., Reguera, D. P., Petrezselyova, S., Piavaux, B., Endaya, B., Spoutil, F., Zudova, D., Stursa, J., Melcova, M., Bielcikova, Z., Werner, L., Prochazka, J., Sedlacek, R., Huttl, M., Hubackova, S. S., Haluzik, M., & Neuzil, J. (2022)."Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice." Nature Communications, 13(1), 1866. https://doi.org/10.1038/s41467-022-29486-z

  • Vondrakova, J., Frolikova, M., Ded, L., Cerny, J., Postlerova, P., Palenikova, V., Simonik, O., Nahacka, Z., Basus, K., Valaskova, E., Machan, R., Pacey, A., Holubcova, Z., Koubek, P., Ezrova, Z., Park, S., Liu, R., Partha, R., Clark, N., Neuzil, J., Ikawa, M., Erickson, K., Lam, K. S., Moore, H., & Komrskova, K. (2022). "MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization. "Sci Adv, 8(36), eabn0047. https://doi.org/10.1126/sciadv.abn0047

2021

  • Boukalova, S., Ezrova, Z., & Neuzil, J. (2021). "Mechanisms of resistance to mitochondria-targeted therapy in pancreatic cancer." Oncotarget, 12(16), 1627-1628. https://doi.org/10.18632/oncotarget.27976

  • Ezrova, Z., Nahacka, Z., Stursa, J., Werner, L., Vlcak, E., Kralova Viziova, P., Berridge, M. V., Sedlacek, R., Zobalova, R., Rohlena, J., Boukalova, S., Neuzil, J. (2021). "SMAD4 loss limits the vulnerability of pancreatic cancer cells to complex I inhibition via promotion of mitophagy." Oncogene. https://doi.org/10.1038/s41388-021-01726-4

  • Gaetani, S., Galzignati, L., Marcati, M., Durazzi, P., Cianella, A., Mocheggiani, V., Monaco, F., Bracci, M., Neuzil, J., Tomasetti, M., Amati, M., & Santarelli, L. (2021)."Mitochondrial function as related to psychological distress in health care professionals." Psychosom Med. https://doi.org/10.1097/PSY.0000000000001000

  • Hadrava Vanova, K., Pang, Y., Krobova, L., Kraus, M., Nahacka, Z., Boukalova, S., Pack, S. D., Zobalova, R., Zhu, J., Huynh, T. T., Jochmanova, I., Uher, O., Hubackova, S., Dvorakova, S., Garrett, T. J., Ghayee, H. K., Wu, X., Schuster, B., Knapp, P. E., Frysak, Z., Hartmann, I., Nilubol, N., Cerny, J., Taieb, D., Rohlena, J., Neuzil, J., Yang, C., & Pacak, K. (2021). Germline SUCLG2 Variants in Patients with Pheochromocytoma and Paraganglioma. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djab158

  • Hadrava Vanova, K., Yang, C., Meuter, L., Neuzil, J., & Pacak, K. (2021). Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma. Cancers (Basel), 13(15). https://doi.org/10.3390/cancers13153769

  • Klener, P., Sovilj, D., Renesova, N., & Andera, L. (2021)." BH3 Mimetics in Hematologic Malignancies." Int J Mol Sci, 22(18). https://doi.org/10.3390/ijms221810157 (ASEP)

  • Levoux, J., Prola, A., Lafuste, P., Gervais, M., Chevallier, N., Koumaiha, Z., Kefi, K., Braud, L., Schmitt, A., Yacia, A., Schirmann, A., Hersant, B., Sid-Ahmed, M., Ben Larbi, S., Komrskova, K., Rohlena, J., Relaix, F., Neuzil, J., & Rodriguez, A. M. (2021b, Mar 2). Platelets facilitate the wound-healing capability of mesenchymal stem cells by mitochondrial transfer and metabolic reprogramming. Cell Metabolism, 33(3), 688-690. https://doi.org/10.1016/j.cmet.2021.02.003

  • Matlac, D. M., Hadrava Vanova, K., Bechmann, N., Richter, S., Folberth, J., Ghayee, H. K., Ge, G. B., Abunimer, L., Wesley, R., Aherrahrou, R., Dona, M., Martinez-Montes, A. M., Calsina, B., Merino, M. J., Schwaninger, M., Deen, P. M. T., Zhuang, Z., Neuzil, J., Pacak, K., Lehnert, H., & Fliedner, S. M. J. (2021). "Succinate Mediates Tumorigenic Effects via Succinate Receptor 1: Potential for New Targeted Treatment Strategies in Succinate Dehydrogenase Deficient Paragangliomas." Front Endocrinol (Lausanne), 12, 589451. https://doi.org/10.3389/fendo.2021.589451

  • Nahacka, Z., Zobalova, R., Dubisova, M., Rohlena, J., Neuzil, J. (2021)."Miro proteins connect mitochondrial function and intercellular transport." Crit Rev Biochem Mol Biol, 1-25. https://doi.org/10.1080/10409238.2021.1925216

  • Sandoval-Acuna, C., Torrealba, N., Tomkova, V., Jadhav, S. B., Blazkova, K., Merta, L., Lettlova, S., Adamcova, M. K., Rosel, D., Brabek, J., Neuzil, J., Stursa, J., Werner, L., Truksa, J. (2021). "Targeting mitochondrial iron metabolism suppresses tumor growth and metastasis by inducing mitochondrial dysfunction and mitophagy." Cancer Res. https://doi.org/10.1158/0008-5472.CAN-20-1628

  • Simoes, R. F., Pino, R., Moreira-Soares, M., Kovarova, J., Neuzil, J., Travasso, R., Oliveira, P. J., Cunha-Oliveira, T., & Pereira, F. B. (2021). "Quantitative analysis of neuronal mitochondrial movement reveals patterns resulting from neurotoxicity of rotenone and 6-hydroxydopamine." FASEB J, 35(12), e22024. https://doi.org/10.1096/fj.202100899R

  • Valdinocci, D., Kovarova, J., Neuzil, J., Pountney, D. L. (2021). "Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes." Neurotox Res, 39(2), 429-443. https://doi.org/10.1007/s12640-020-00285-y (ASEP)

  • Vidimce, J., Pillay, J., Shrestha, N., Dong, L. F., Neuzil, J., Wagner, K. H., Holland, O. J., Bulmer, A. C. (2021). "Mitochondrial Function, Fatty Acid Metabolism, and Body Composition in the Hyperbilirubinemic Gunn Rat." Front Pharmacol, 12, 586715. https://doi.org/10.3389/fphar.2021.586715

2020

  • Boukalova, S., S. Hubackova, M. Milosevic, Z. Ezrova, J. Neuzil and J. Rohlena (2020). "Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer." Biochim Biophys Acta Mol Basis Dis 1866(6): 165759.
  • Dong, L., Gopalan, V., Holland, O., & Neuzil, J. (2020). "Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy." Int J Mol Sci, 21(21).
  • Gaetani, S., F. Monaco, F. Alessandrini, A. Tagliabracci, A. Sabbatini, M. Bracci, M. Valentino, J. Neuzil, M. Amati, L. Santarelli and M. Tomasetti (2020). "Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy." Int J Biochem Cell Biol: 105700.

  • Grasso, C., Eccles, D. A., Boukalova, S., Fabre, M. S., Dawson, R. H., Neuzil, J., Herst, P. M., & Berridge, M. V. (2020). Mitochondrial DNA Affects the Expression of Nuclear Genes Involved in Immune and Stress Responses in a Breast Cancer Model. Front Physiol, 11, 543962.
  • Hadrava Vanova, K., Kraus, M., Neuzil, J., & Rohlena, J. (2020). "Mitochondrial complex II and reactive oxygen species in disease and therapy." Redox Rep, 25(1), 26-32.

  • Henrichs, V., Grycova, L., Barinka, C., Nahacka, Z., Neuzil, J., Diez, S., Rohlena, J., Braun, M., & Lansky, Z. (2020). "Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments." Nature Communications, 11(1), 3123.
  • Hubackova, S., E. Davidova, S. Boukalova, J. Kovarova, M. Bajzikova, A. Coelho, M. G. Terp, H. J. Ditzel, J. Rohlena and J. Neuzil (2020). "Replication and ribosomal stress induced by targeting pyrimidine synthesis and cellular checkpoints suppress p53-deficient tumors." Cell Death Dis 11(2): 110.

  • Liu, Y., Pang, Y., Zhu, B., Uher, O., Caisova, V., Huynh, T. T., Taieb, D., Hadrava Vanova, K., Ghayee, H. K., Neuzil, J., Levine, M., Yang, C., & Pacak, K. (2020). "Therapeutic Targeting of SDHB-Mutated Pheochromocytoma/Paraganglioma with Pharmacologic Ascorbic Acid." Clin Cancer Res, 26(14), 3868-3880.
  • Raninga, P. V., Lee, A., Sinha, D., Dong, L. F., Datta, K. K., Lu, X., Kalita-de Croft, P., Dutt, M., Hill, M., Pouliot, N., Gowda, H., Kalimutho, M., Neuzil, J., & Khanna, K. K. (2020). "Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition." Theranostics, 10(12), 5259-5275.
  • Valdinocci, D., Kovarova, J., Neuzil, J., & Pountney, D. L. (2020). "Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes." Neurotox Res.

2019

  • Bajzikova, M., J. Kovarova, A. R. Coelho, S. Boukalova, S. Oh, K. Rohlenova, D. Svec, S. Hubackova, B. Endaya, K. Judasova, A. Bezawork-Geleta, K. Kluckova, L. Chatre, R. Zobalova, A. Novakova, K. Vanova, Z. Ezrova, G. J. Maghzal, S. M. Novais, M. Olsinova, L. Krobova, Y. J. An, E. Davidova, Z. Nahacka, M. Sobol, T. Cunha-Oliveira, C. Sandoval-Acuna, H. Strnad, T. C. Zhang, T. Huynh, T. L. Serafim, P. Hozak, V. A. Sardao, W. J. H. Koopman, M. Ricchetti, P. J. Oliveira, F. Kolar, M. Kubista, J. Truksa, K. Dvorakova-Hortova, K. Pacak, R. Gurlich, R. Stocker, Y. Q. Zhou, M. V. Berridge, S. Park, L. F. Dong, J. Rohlena and J. Neuzil (2019). "Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells." Cell Metabolism 29(2): 399-+.

  • Hubackova, S., M. Pribyl, L. Kyjacova, A. Moudra, R. Dzijak, B. Salovska, H. Strnad, V. Tambor, T. Imrichova, J. Svec, P. Vodicka, R. Vaclavikova, L. Rob, J. Bartek and Z. Hodny (2019). "Interferon-regulated suprabasin is essential for stress-induced stem-like cell conversion and therapy resistance of human malignancies." Mol Oncol 13(7): 1467-1489.

  • Jha, A., K. de Luna, C. A. Balili, C. Millo, C. A. Paraiso, A. Ling, M. K. Gonzales, B. Viana, R. Alrezk, K. T. Adams, I. Tena, A. Chen, J. Neuzil, M. Raygada, E. Kebebew, D. Taieb, M. S. O'Dorisio, T. O'Dorisio, A. C. Civelek, C. A. Stratakis, L. Mercado-Asis and K. Pacak (2019). "Clinical, Diagnostic, and Treatment Characteristics of SDHA-Related Metastatic Pheochromocytoma and Paraganglioma." Front Oncol 9: 53.

  • Monaco, F., S. Gaetani, F. Alessandrini, A. Tagliabracci, M. Bracci, M. Valentino, J. Neuzil, M. Amati, M. Bovenzi, M. Tomasetti and L. Santarelli (2019). "Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication." Cancer Lett 463: 27-36.

  • Prukova, D., L. Andera, Z. Nahacka, J. Karolova, M. Svaton, M. Klanova, O. Havranek, J. Soukup, K. Svobodova, Z. Zemanova, D. Tuskova, E. Pokorna, K. Helman, K. Forsterova, M. Pacheco-Blanco, P. Vockova, A. Berkova, E. Fronkova, M. Trneny and P. Klener (2019). "Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma." Clin Cancer Res 25(14): 4455-4465.

  • Santarelli, L., S. Gaetani, F. Monaco, M. Bracci, M. Valentino, M. Amati, C. Rubini, A. Sabbatini, E. Pasquini, N. Zanotta, M. Comar, J. Neuzil, M. Tomasetti and M. Bovenzi (2019). "Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies." Cancer Epidemiol Biomarkers Prev 28(1): 119-126.

  • Stetka, J., P. Vyhlidalova, L. Lanikova, P. Koralkova, J. Gursky, A. Hlusi, P. Flodr, S. Hubackova, J. Bartek, Z. Hodny and V. Divoky (2019). "Addiction to DUSP1 protects JAK2V617F-driven polycythemia vera progenitors against inflammatory stress and DNA damage, allowing chronic proliferation." Oncogene 38(28): 5627-5642.

  • Tomasetti, M., S. Gaetani, F. Monaco, J. Neuzil and L. Santarelli (2019). "Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy." Front Oncol 9: 1293.

  • Valdinocci, D., R. F. Simoes, J. Kovarova, T. Cunha-Oliveira, J. Neuzil and D. L. Pountney (2019). "Intracellular and Intercellular Mitochondrial Dynamics in Parkinson's Disease." Front Neurosci 13: 930.

2018

  • Berridge, M. V., C. Crasso and J. Neuzil (2018). "Mitochondrial Genome Transfer to Tumor Cells Breaks The Rules and Establishes a New Precedent in Cancer Biology." Mol Cell Oncol 5(5): e1023929.

  • Bezawork-Geleta, A., H. Wen, L. F. Dong, B. Yan, J. Vider, S. Boukalova, L. Krobova, K. Vanova, R. Zobalova, M. Sobol, P. Hozak, S. M. Novais, V. Caisova, P. Abaffy, R. Naraine, Y. Pang, T. Zaw, P. Zhang, R. Sindelka, M. Kubista, S. Zuryn, M. P. Molloy, M. V. Berridge, K. Pacak, J. Rohlena, S. Park and J. Neuzil (2018). "Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints." Nature Communications 9.

  • Cuyas, E., S. Verdura, L. Llorach-Pares, S. Fernandez-Arroyo, F. Luciano-Mateo, N. Cabre, J. Stursa, L. Werner, B. Martin-Castillo, B. Viollet, J. Neuzil, J. Joven, A. Nonell-Canals, M. Sanchez-Martinez and J. A. Menendez (2018). "Metformin directly targets the H3K27me3 demethylase KDM6A/UTX." Aging Cell 17(4): e12772.

  • Cuyas, E., S. Fernandez-Arroyo, S. Verdura, R. A. Garcia, J. Stursa, L. Werner, E. Blanco-Gonzalez, M. Montes-Bayon, J. Joven, B. Viollet, J. Neuzil and J. A. Menendez (2018). "Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism." Oncogene 37(7): 963-970.

  • Hubackova, S., S. M. Novais, E. Davidova, J. Neuzil and J. Rohlena (2018). "Mitochondria-Driven Elimination of Cancer and Senescent Cells." Biol Chem.

  • Hubackova, S., E. Davidova, K. Rohlenova, J. Stursa, L. Werner, L. Andera, L. Dong, M. G. Terp, Z. Hodny, H. J. Ditzel, J. Rohlena and J. Neuzil (2018). "Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2." Cell Death Differ.

  • Nahacka, Z., J. Svadlenka, M. Peterka, M. Ksandrova, S. Benesova, J. Neuzil and L. Andera (2018). "TRAIL induces apoptosis but not necroptosis in colorectal and pancreatic cancer cells preferentially via the TRAIL-R2/DR5 receptor." Biochim Biophys Acta Mol Cell Res 1865(3): 522-531.

  • Pan, J., Y. Lee, G. Cheng, J. Zielonka, Q. Zhang, M. Bajzikova, D. Xiong, S. W. Tsaih, M. Hardy, M. Flister, C. M. Olsen, Y. Wang, O. Vang, J. Neuzil, C. R. Myers, B. Kalyanaraman and M. You (2018). "Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity." iScience 3: 192-207.

  • Tomasetti, M., M. Re, F. Monaco, S. Gaetani, C. Rubini, A. Bertini, E. Pasquini, C. Bersaglieri, M. Bracci, S. Staffolani, M. Colomba, A. Gregorini, M. Valentino, A. Tagliabracci, M. Bovenzi, J. Neuzil, M. Amati and L. Santarelli (2018). "MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses." BMC Cancer 18(1): 896.

2017

  • Berridge, M. V. and J. Neuzil (2017). "The mobility of mitochondria: Intercellular trafficking in health and disease." Clin Exp Pharmacol Physiol 44 Suppl 1: 15-20.

  • Bezawork-Geleta, A., J. Rohlena, L. Dong, K. Pacak and J. Neuzil (2017). "Mitochondrial Complex II: At the Crossroads." Trends Biochem Sci 42(4): 312-325.

  • Blecha, J., S. M. Novais, K. Rohlenova, E. Novotna, S. Lettlova, S. Schmitt, H. Zischka, J. Neuzil and J. Rohlena (2017). "Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death." Free Radic Biol Med 112: 253-266.

  • Dong, L. F., J. Kovarova, M. Bajzikova, A. Bezawork-Geleta, D. Svec, B. Endaya, K. Sachaphibulkij, A. R. Coelho, N. Sebkova, A. Ruzickova, A. S. Tan, K. Kluckova, K. Judasova, K. Zamecnikova, Z. Rychtarcikova, V. Gopalan, L. Andera, M. Sobol, B. Yan, B. Pattnaik, N. Bhatraju, J. Truksa, P. Stopka, P. Hozak, A. K. Lam, R. Sedlacek, P. J. Oliveira, M. Kubista, A. Agrawal, K. Dvorakova-Hortova, J. Rohlena, M. V. Berridge and J. Neuzil (2017). "Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells." Elife 6.

  • Grimolizzi, F., F. Monaco, F. Leoni, M. Bracci, S. Staffolani, C. Bersaglieri, S. Gaetani, M. Valentino, M. Amati, C. Rubini, F. Saccucci, J. Neuzil, M. Tomasetti and L. Santarelli (2017). "Exosomal miR-126 as a circulating biomarker in non-small-cell lung cancer regulating cancer progression." Sci Rep 7(1): 15277.

  • Rohlenova, K., K. Sachaphibulkij, J. Stursa, A. Bezawork-Geleta, J. Blecha, B. Endaya, L. Werner, J. Cerny, R. Zobalova, J. Goodwin, T. Spacek, E. Alizadeh Pesdar, B. Yan, M. N. Nguyen, M. Vondrusova, M. Sobol, P. Jezek, P. Hozak, J. Truksa, J. Rohlena, L. F. Dong and J. Neuzil (2017). "Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2(high) Breast Cancer." Antioxid Redox Signal 26(2): 84-103.

  • Rychtarcikova, Z., S. Lettlova, V. Tomkova, V. Korenkova, L. Langerova, E. Simonova, P. Zjablovskaja, M. Alberich-Jorda, J. Neuzil and J. Truksa (2017). "Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism." Oncotarget 8(4): 6376-6398.

  • Tomasetti, M., W. Lee, L. Santarelli and J. Neuzil (2017). "Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy." Exp Mol Med 49(1): e285.

  • Tomasetti, M., M. Amati, J. Neuzil and L. Santarelli (2017). "Circulating epigenetic biomarkers in lung malignancies: From early diagnosis to therapy." Lung Cancer 107: 65-72.

2016

  • Berridge, M. V., M. J. McConnell, C. Grasso, M. Bajzikova, J. Kovarova and J. Neuzil (2016). "Horizontal transfer of mitochondria between mammalian cells: beyond co-culture approaches." Curr Opin Genet Dev 38: 75-82.

  • Bezawork-Geleta, A., L. Dong, J. Rohlena and J. Neuzil (2016). "The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells." J Biol Chem 291(41): 21414-21420.

  • Boukalova, S., J. Stursa, L. Werner, Z. Ezrova, J. Cerny, A. Bezawork-Geleta, A. Pecinova, L. Dong, Z. Drahota and J. Neuzil (2016). "Mitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer." Mol Cancer Ther 15(12): 2875-2886.

  • Endaya, B., B. Cavanagh, F. Alowaidi, T. Walker, N. de Pennington, J. M. Ng, P. Y. Lam, A. Mackay-Sim, J. Neuzil and A. C. Meedeniya (2016). "Isolating dividing neural and brain tumour cells for gene expression profiling." J Neurosci Methods 257: 121-133.

  • Endaya, B. B., P. Y. Lam, A. C. Meedeniya and J. Neuzil (2016). "Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model." Mol Oncol 10(1): 126-137.

  • Moudra, A., S. Hubackova, V. Machalova, M. Vancurova, J. Bartek, M. Reinis, Z. Hodny and A. Jonasova (2016). "Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine." Oncoimmunology 5(10): e1183860.

  • Rohlenova, K., J. Neuzil and J. Rohlena (2016). "The role of Her2 and other oncogenes of the PI3K/AKT pathway in mitochondria." Biol Chem 397(7): 607-615.

  • Tomasetti, M., F. Monaco, N. Manzella, J. Rohlena, K. Rohlenova, S. Staffolani, S. Gaetani, V. Ciarapica, M. Amati, M. Bracci, M. Valentino, J. Goodwin, M. Nguyen, J. Truksa, M. Sobol, P. Hozak, L. F. Dong, L. Santarelli and J. Neuzil (2016). "MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma." Oncotarget 7(24): 36338-36352.

  • Tomasetti, M., M. Amati, L. Santarelli and J. Neuzil (2016). "MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis." Int J Mol Sci 17(5).

  • Vanova, K., S. Boukalova, H. Gbelcova, L. Muchova, J. Neuzil, R. Gurlich, T. Ruml and L. Vitek (2016). "Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells." BMC Cancer 16: 309.

  • Yan, B., L. Dong and J. Neuzil (2016). "Mitochondria: An intriguing target for killing tumour-initiating cells." Mitochondrion 26: 86-93.

2015

  • Berridge, M. V., L. Dong and J. Neuzil (2015). "Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer." Cancer Res 75(16): 3203-3208.

  • Khera, A., L. F. Dong, O. Holland, J. Vanderlelie, E. A. Pasdar, J. Neuzil and A. V. Perkins (2015). "Selenium supplementation induces mitochondrial biogenesis in trophoblasts." Placenta 36(8): 863-869.

  • Kluckova, K., L. F. Dong, M. Bajzikova, J. Rohlena and J. Neuzil (2015). "Evaluation of respiration of mitochondria in cancer cells exposed to mitochondria-targeted agents." Methods Mol Biol 1265: 181-194.

  • Kluckova, K., M. Sticha, J. Cerny, T. Mracek, L. Dong, Z. Drahota, E. Gottlieb, J. Neuzil and J. Rohlena (2015). "Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation." Cell Death Dis 6: e1749.

  • Koudelka, S., P. Turanek Knotigova, J. Masek, L. Prochazka, R. Lukac, A. D. Miller, J. Neuzil and J. Turanek (2015). "Liposomal delivery systems for anti-cancer analogues of vitamin E." J Control Release 207: 59-69.

  • Pasdar, E. A., M. Smits, M. Stapelberg, M. Bajzikova, M. Stantic, J. Goodwin, B. Yan, J. Stursa, J. Kovarova, K. Sachaphibulkij, A. Bezawork-Geleta, M. Sobol, A. Filimonenko, M. Tomasetti, R. Zobalova, P. Hozak, L. F. Dong and J. Neuzil (2015). "Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents." Plos One 10(5): e0119549.

  • Santarelli, L., S. Staffolani, E. Strafella, L. Nocchi, N. Manzella, P. Grossi, M. Bracci, E. Pignotti, R. Alleva, B. Borghi, C. Pompili, A. Sabbatini, C. Rubini, L. Zuccatosta, E. Bichisecchi, M. Valentino, K. Horwood, M. Comar, M. Bovenzi, L. F. Dong, J. Neuzil, M. Amati and M. Tomasetti (2015). "Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma." Lung Cancer 90(3): 457-464.

  • Tan, A. S., J. W. Baty, L. F. Dong, A. Bezawork-Geleta, B. Endaya, J. Goodwin, M. Bajzikova, J. Kovarova, M. Peterka, B. Yan, E. A. Pesdar, M. Sobol, A. Filimonenko, S. Stuart, M. Vondrusova, K. Kluckova, K. Sachaphibulkij, J. Rohlena, P. Hozak, J. Truksa, D. Eccles, L. M. Haupt, L. R. Griffiths, J. Neuzil and M. V. Berridge (2015). "Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA." Cell Metabolism 21(1): 81-94.

  • Tomasetti, M., L. Santarelli, R. Alleva, L. F. Dong and J. Neuzil (2015). "Redox-active and redox-silent compounds: synergistic therapeutics in cancer." Curr Med Chem 22(5): 552-568.

  • Truksa, J., L. F. Dong, J. Rohlena, J. Stursa, M. Vondrusova, J. Goodwin, M. Nguyen, K. Kluckova, Z. Rychtarcikova, S. Lettlova, J. Spacilova, M. Stapelberg, M. Zoratti and J. Neuzil (2015). "Mitochondrially targeted vitamin E succinate modulates expression of mitochondrial DNA transcripts and mitochondrial biogenesis." Antioxid Redox Signal 22(11): 883-900.

  • Vondrusova, M., A. Bezawork-Geleta, K. Sachaphibulkij, J. Truksa and J. Neuzil (2015). "The effect of mitochondrially targeted anticancer agents on mitochondrial (super)complexes." Methods Mol Biol 1265: 195-208.

  • Yan, B., M. Stantic, R. Zobalova, A. Bezawork-Geleta, M. Stapelberg, J. Stursa, K. Prokopova, L. Dong and J. Neuzil (2015). "Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner." BMC Cancer 15: 401.

2014

  • Dong, L. F. and J. Neuzil (2014). "Mitochondria in cancer: why mitochondria are a good target for cancer therapy." Prog Mol Biol Transl Sci 127: 211-227.

  • Hwang, M. S., J. Rohlena, L. F. Dong, J. Neuzil and S. Grimm (2014). "Powerhouse down: Complex II dissociation in the respiratory chain." Mitochondrion 19 Pt A: 20-28.

  • Kovarova, J., M. Bajzikova, M. Vondrusova, J. Stursa, J. Goodwin, M. Nguyen, R. Zobalova, E. A. Pesdar, J. Truksa, M. Tomasetti, L. F. Dong and J. Neuzil (2014). "Mitochondrial targeting of alpha-tocopheryl succinate enhances its anti-mesothelioma efficacy." Redox Rep 19(1): 16-25.

  • Stapelberg, M., R. Zobalova, M. N. Nguyen, T. Walker, M. Stantic, J. Goodwin, E. A. Pasdar, T. Thai, K. Prokopova, B. Yan, S. Hall, N. de Pennington, S. R. Thomas, G. Grant, J. Stursa, M. Bajzikova, A. C. B. Meedeniya, J. Truksa, S. J. Ralph, O. Ansorge, L. F. Dong and J. Neuzil (2014). "Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans." Free Radical Biology and Medicine 67: 41-50.

  • Tomasetti, M., L. Nocchi, S. Staffolani, N. Manzella, M. Amati, J. Goodwin, K. Kluckova, M. Nguyen, E. Strafella, M. Bajzikova, M. Peterka, S. Lettlova, J. Truksa, W. Lee, L. F. Dong, L. Santarelli and J. Neuzil (2014). "MicroRNA-126 suppresses mesothelioma malignancy by targeting IRS1 and interfering with the mitochondrial function." Antioxid Redox Signal 21(15): 2109-2125.

  • Tomasetti, M., L. Santarelli, J. Neuzil and L. Dong (2014). "MicroRNA regulation of cancer metabolism: role in tumour suppression." Mitochondrion 19 Pt A: 29-38.

  • Tomasetti, M., J. Neuzil and L. Dong (2014). "MicroRNAs as regulators of mitochondrial function: role in cancer suppression." Biochim Biophys Acta 1840(4): 1441-1453.

  • Yanamala, N., A. A. Kapralov, M. Djukic, J. Peterson, G. Mao, J. Klein-Seetharaman, D. A. Stoyanovsky, J. Stursa, J. Neuzil and V. E. Kagan (2014). "Structural re-arrangement and peroxidase activation of cytochrome c by anionic analogues of vitamin E, tocopherol succinate and tocopherol phosphate." J Biol Chem 289(47): 32488-32498.

2013

  • Kluckova, K., A. Bezawork-Geleta, J. Rohlena, L. Dong and J. Neuzil (2013). "Mitochondrial complex II, a novel target for anti-cancer agents." Biochim Biophys Acta 1827(5): 552-564.

  • Kovarova, N., T. Mracek, H. Nuskova, E. Holzerova, M. Vrbacky, P. Pecina, K. Hejzlarova, K. Kluckova, J. Rohlena, J. Neuzil and J. Houstek (2013). "High molecular weight forms of mammalian respiratory chain complex II." Plos One 8(8): e71869.

  • Moreno-Sanchez, R., L. Hernandez-Esquivel, N. A. Rivero-Segura, A. Marin-Hernandez, J. Neuzil, S. J. Ralph and S. Rodriguez-Enriquez (2013). "Reactive oxygen species are generated by the respiratory complex II--evidence for lack of contribution of the reverse electron flow in complex I." FEBS J 280(3): 927-938.

  • Neuzil, J. and R. Moreno-Sanchez (2013). "Editorial: The Bioenergetics of Cancer, the Warburg Hypothesis and the Mitochondrial Function." Curr Pharm Biotechnol 14(3): 249-250.

  • Neuzil, J., L. F. Dong, J. Rohlena, J. Truksa and S. J. Ralph (2013). "Classification of mitocans, anti-cancer drugs acting on mitochondria." Mitochondrion 13(3): 199-208.

  • Prochazka, L., S. Koudelka, L. F. Dong, J. Stursa, J. Goodwin, J. Neca, J. Slavik, M. Ciganek, J. Masek, K. Kluckova, M. Nguyen, J. Turanek and J. Neuzil (2013). "Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to alpha-tocopheryl succinate." Apoptosis 18(3): 286-299.

  • Rohlena, J., L. F. Dong and J. Neuzil (2013). "Targeting the mitochondrial electron transport chain complexes for the induction of apoptosis and cancer treatment." Curr Pharm Biotechnol 14(3): 377-389.

2012

  • Dong, L. F., G. Grant, H. Massa, R. Zobalova, E. Akporiaye and J. Neuzil (2012). "alpha-Tocopheryloxyacetic acid is superior to alpha-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability." Int J Cancer 131(5): 1052-1058.

  • Midwinter, R. G., G. J. Maghzal, J. M. Dennis, B. J. Wu, H. Cai, A. A. Kapralov, N. A. Belikova, Y. Y. Tyurina, L. F. Dong, L. Khachigian, J. Neuzil, V. E. Kagan and R. Stocker (2012). "Succinobucol induces apoptosis in vascular smooth muscle cells." Free Radic Biol Med 52(5): 871-879.

  • Neuzil, J., J. Rohlena and L.-F. Dong (2012). "K-Ras and mitochondria: Dangerous liaisons." Cell Research 22(2): 285-287.

  • Rodriguez-Enriquez, S., L. Hernandez-Esquivel, A. Marin-Hernandez, L. F. Dong, E. T. Akporiaye, J. Neuzil, S. J. Ralph and R. Moreno-Sanchez (2012). "Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue." Biochim Biophys Acta 1817(9): 1597-1607.

  • Tomasetti, M., L. Nocchi, J. Neuzil, J. Goodwin, M. Nguyen, L. Dong, N. Manzella, S. Staffolani, C. Milanese, B. Garrone, R. Alleva, B. Borghi, L. Santarelli and R. Guerrieri (2012). "Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death." Plos One 7(12): e52263.

2011

  • Dong, L. F., V. J. Jameson, D. Tilly, L. Prochazka, J. Rohlena, K. Valis, J. Truksa, R. Zobalova, E. Mahdavian, K. Kluckova, M. Stantic, J. Stursa, R. Freeman, P. K. Witting, E. Norberg, J. Goodwin, B. A. Salvatore, J. Novotna, J. Turanek, M. Ledvina, P. Hozak, B. Zhivotovsky, M. J. Coster, S. J. Ralph, R. A. Smith and J. Neuzil (2011). "Mitochondrial targeting of alpha-tocopheryl succinate enhances its pro-apoptotic efficacy: a new paradigm for effective cancer therapy." Free Radic Biol Med 50(11): 1546-1555.

  • Dong, L. F., V. J. Jameson, D. Tilly, J. Cerny, E. Mahdavian, A. Marin-Hernandez, L. Hernandez-Esquivel, S. Rodriguez-Enriquez, J. Stursa, P. K. Witting, B. Stantic, J. Rohlena, J. Truksa, K. Kluckova, J. C. Dyason, M. Ledvina, B. A. Salvatore, R. Moreno-Sanchez, M. J. Coster, S. J. Ralph, R. A. Smith and J. Neuzil (2011). "Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex II." J Biol Chem 286(5): 3717-3728.

  • Ito, K., S. A. Scott, S. Cutler, L. F. Dong, J. Neuzil, H. Blanchard and S. J. Ralph (2011). "Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress." Angiogenesis 14(3): 293-307.

  • Neuzil, J., J. Cerny, J. C. Dyason, L. F. Dong and S. J. Ralph (2011). "Affinity of vitamin E analogues for the ubiquinone complex II site correlates with their toxicity to cancer cells." Mol Nutr Food Res 55(10): 1543-1551.

  • Nocchi, L., M. Tomasetti, M. Amati, J. Neuzil, L. Santarelli and F. Saccucci (2011). "Thrombomodulin is silenced in malignant mesothelioma by a poly(ADP-ribose) polymerase-1-mediated epigenetic mechanism." J Biol Chem 286(22): 19478-19488.

  • Ralph, S. J., R. Moreno-Sanchez, J. Neuzil and S. Rodriguez-Enriquez (2011). "Inhibitors of succinate: quinone reductase/Complex II regulate production of mitochondrial reactive oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death." Pharm Res 28(11): 2695-2730.

  • Rohlena, J., L. F. Dong, K. Kluckova, R. Zobalova, J. Goodwin, D. Tilly, J. Stursa, A. Pecinova, A. Philimonenko, P. Hozak, J. Banerjee, M. Ledvina, C. K. Sen, J. Houstek, M. J. Coster and J. Neuzil (2011). "Mitochondrially targeted alpha-tocopheryl succinate is antiangiogenic: potential benefit against tumor angiogenesis but caution against wound healing." Antioxid Redox Signal 15(12): 2923-2935.

  • Rohlena, J., L. F. Dong, S. J. Ralph and J. Neuzil (2011). "Anticancer drugs targeting the mitochondrial electron transport chain." Antioxid Redox Signal 15(12): 2951-2974.

  • Santarelli, L., E. Strafella, S. Staffolani, M. Amati, M. Emanuelli, D. Sartini, V. Pozzi, D. Carbonari, M. Bracci, E. Pignotti, P. Mazzanti, A. Sabbatini, R. Ranaldi, S. Gasparini, J. Neuzil and M. Tomasetti (2011). "Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma." Plos One 6(4): e18232.

  • Tomasetti, M., M. Amati, L. Nocchi, F. Saccucci, E. Strafella, S. Staffolani, L. M. Tarquini, D. Carbonari, R. Alleva, B. Borghi, J. Neuzil, M. Bracci and L. Santarelli (2011). "Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis." Mutagenesis 26(5): 585-591.

  • Valis, K., L. Prochazka, E. Boura, J. Chladova, T. Obsil, J. Rohlena, J. Truksa, L.-F. Dong, S. J. Ralph and J. Neuzil (2011). "Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner." Cancer Research 71(3): 946-954.

  • Zobalova, R., K. Prokopova, M. Stantic, M. Stapelberg, L. F. Dong, S. J. Ralph, E. Akporiaye and J. Neuzil (2011). "The potential role of CD133 in immune surveillance and apoptosis: a mitochondrial connection?" Antioxid Redox Signal 15(12): 2989-3002.

2010

  • Biasutto, L., L. F. Dong, M. Zoratti and J. Neuzil (2010). "Mitochondrially targeted anti-cancer agents." Mitochondrion 10(6): 670-681.

  • Koudelka, S., J. Masek, J. Neuzil and J. Turanek (2010). "Lyophilised liposome-based formulations of alpha-tocopheryl succinate: preparation and physico-chemical characterisation." J Pharm Sci 99(5): 2434-2443.

  • Prochazka, L., L. F. Dong, K. Valis, R. Freeman, S. J. Ralph, J. Turanek and J. Neuzil (2010). "alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels." Apoptosis 15(7): 782-794.

  • Ralph, S. J., S. Rodriguez-Enriquez, J. Neuzil, E. Saavedra and R. Moreno-Sanchez (2010). "The causes of cancer revisited: "mitochondrial malignancy" and ROS-induced oncogenic transformation - why mitochondria are targets for cancer therapy." Mol Aspects Med 31(2): 145-170.

  • Ralph, S. J., S. Rodriguez-Enriquez, J. Neuzil and R. Moreno-Sanchez (2010). "Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger." Mol Aspects Med 31(1): 29-59.

  • Tomasetti, M., E. Strafella, S. Staffolani, L. Santarelli, J. Neuzil and R. Guerrieri (2010). "alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate." Br J Cancer 102(8): 1224-1234.

2009

  • Dong, L. F., R. Freeman, J. Liu, R. Zobalova, A. Marin-Hernandez, M. Stantic, J. Rohlena, K. Valis, S. Rodriguez-Enriquez, B. Butcher, J. Goodwin, U. T. Brunk, P. K. Witting, R. Moreno-Sanchez, I. E. Scheffler, S. J. Ralph and J. Neuzil (2009). "Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II." Clin Cancer Res 15(5): 1593-1600.

  • Morrison, B. J., L. Andera, B. A. Reynolds, S. J. Ralph and J. Neuzil (2009). "Future use of mitocans against tumour-initiating cells?" Mol Nutr Food Res 53(1): 147-153.

  • Ralph, S. J. and J. Neuzil (2009). "Mitochondria as targets for cancer therapy." Mol Nutr Food Res 53(1): 9-28.

  • Turanek, J., X. F. Wang, P. Knotigova, S. Koudelka, L. F. Dong, E. Vrublova, E. Mahdavian, L. Prochazka, S. Sangsura, A. Vacek, B. A. Salvatore and J. Neuzil (2009). "Liposomal formulation of alpha-tocopheryl maleamide: in vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice." Toxicol Appl Pharmacol 237(3): 249-257.

2008

  • Dong, L. F., P. Low, J. C. Dyason, X. F. Wang, L. Prochazka, P. K. Witting, R. Freeman, E. Swettenham, K. Valis, J. Liu, R. Zobalova, J. Turanek, D. R. Spitz, F. E. Domann, I. E. Scheffler, S. J. Ralph and J. Neuzil (2008). "Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II." Oncogene 27(31): 4324-4335.

  • Zobalova, R., M. Stantic, K. Prokopova, L. F. Dong and J. Neuzil (2008). "Cancer cells with high expression of CD133 exert FLIP upregulation and resistance to TRAIL-induced apoptosis." Biofactors 34(3): 231-235.

 Patents

  • Neuzil, J. S., J.; Werner, L. ( 2019). Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level., Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2018). Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (US), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2018). MD4626. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (CA), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2018). GEP20186868. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (JP), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2018). EA029881. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (EA), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2018). JP6375091. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (GEP), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2017). CA2909994. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (CN), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2017). US9896466. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (AU). A. P. Office, Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. S., J.; Werner, L. ( 2017). KR101764991. Tamoxifen derivatives for treatment of neoplastic diseases, especially with high HER2 protein level. (KR), Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ); KKCG, AG (CH).

  • Neuzil, J. W., L.; Stursa, J. ( 2017). CZ307146. Biguanide triphenylphosphonium analogs, process of their preparation and their use as a medicament., KKCG, SE (CY); Smart Brain s.r.o. (CZ); MitoTAX s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ).

  • Neuzil, J. S., J.; Werner, L. ( 2015). CZ305571. Tamoxifen derivatives intended for the treatment of neoplastic diseases, particularly with higher level of HER2 protein., Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ);.

  • Neuzil, J. S., J.; ( 2014). CZ304553. Tamoxifen derivatives exhibiting activity against tumors, especially tumors with higher protein level HER2., Smart Brain s.r.o. (CZ); Biotechnologický ústav AVCR, v.v.i. (CZ); Jiří Neužil (CZ);.

GAČR: GF24-10406K, R. Zobalová: Jak je důležité mýti funkční mitochondrie: cílení na mitochondriální metabolismus v glioblastomech. 2024 – 2026

GAČR: GA23-04671S, J. Neužil: Metabolický zvrat u regenerace jater. 2023 – 2025

GAČR: GA23-05303S, Š. Boukalová: Využití metabolických poruch pro léčbu karcinomů s deficitem sukcinát dehydrogenázy. 2023 – 2025

AZV: NU23-03-00226, Š. Dvořáková: Změny v respiračním komplexu II jako komplikace v mitochondriálně cílené protinádorové léčbě karcinomů ledvin. 2023 – 2026

MŠMT: LX22NPO5102, J. Neužil: Národní ústav pro výzkum rakoviny. 2022 – 2025

AZV: NU22-01-00096, S. Hubáčková: Ovlivnění senescence jako nový terapeutický cíl v léčbě metabolických onemocnění a jejich komplikací (TITAN). 2022 – 2025

AZV: NU21-03-00386, L. Anděra: Inovativní léčebné postupy a mechanismy lékové rezistence u lymfomu z plášťových buněk. 2021 – 2024

GAČR: GA21-04607X, J. Neužil: Horizontální přenos mitochondrií v biologii rakoviny, 2021-2025

AZV: NU21-03-00545,J. Neužil: Mitochondriálně cílený tamoxifen jako lék proti nádoru ledvin.  2021 - 2024

GAČR: GA20-18513S, J. Rohlena: Faktory limitující de novo syntézu pyrimidinů: úloha mitochondriální respirace. 2020-2022.

GAČR: GJ20-11724Y, Š. Boukalová: Využití mitochondriálního metabolizmu v cílené terapii rakoviny slinivky břišní. 2020-2022.

GAČR: GA20-05942S, J. Neužil: Role horizontálního transferu mitochondrií v tvorbě nádorů mozku. 2020-2022.

GAČR: GA19-08772S, L. Anděra: Rozklíčování vlivu proteinů z rodiny BCL-2 na mitochondriální bioenergetiku. 2019-2021.

GAČR: GA19-20553S, J. Rohlena: Složení a funkce CII-low, alternativní formy respiračního kompexu II. 2019-2021.

GAČR: GA18-10832S, J. Neužil: Molekulární mechanismus pohybu mitochondrií mezi buňkami. 2018-2020.

GAČR: GA18-02550S, S. Hubáčková: Specifická eliminace senescentních buněk pomocí mitochondriálně cílených látek. 2018-2020.

GAČR: GA17-07635S, S. Hubáčková: Mechanismy IFNgama-indukované buněčné senescence a fenotypové plasticity. 2017-2019.

GAČR: GA17-20904S, J. Rohlena: Poruchy mitochondriálního komplexu II při vzniku rakoviny. 2017-2019.

GAČR: GC17-01192J, J. Neužil: Role mitochondriální respirace v tvorbě nádorů: mechanistická studie. 2017-2019.

AZV: 17-30138A, J. Neužil: Adikce na oxidativní fosforylaci jako nová vlastnost nádorových onemocnění a její využití pro vývoj nových účinných protirakovinných postupů. 2017-2020.

AZV: 16-31604A, J. Neužil: Mitochondriální směrování jako účinná léčba nádoru slinivky břišní a diabetu melitu 2. typu. 2016-2019.

GAČR: GA16-12719S, J. Neužil: Úloha receptorové tyrozikinázy Her2 v mitochondriích. 2016-2018.

GAČR: GA16-22823S, J. Rohlena: Úloha mitochondriální bioenergetiky v rezistenci klidových buněk k oxidačnímu stresu. 2016-2018.

GAČR: GA15-02203S, J. Neužil: Přenos mitochondriálního genomu do buněk s poškozenou mitochondriální DNA vede k obnově mitochondriální funkce a schopnosti tvořit nádory. 2015-2017.

GAUK: 362015 Mechanismus mitochondriálního přenosu in vivo. 2015-2016.

GAUK: 98215 Role mitochondrií v citlivosti proliferujících buněk k oxidačnímu stresu a buněčné smrti. 2015-2016.

MZ: NT14078, Inhibice angiogeneze jako účinná metoda potlačení karcinomu pankreatu. 2013-2015.

GAČR: GAP301/12/1851, J. Rohlena: Indukce apoptózy v rakovinných buňkách pomocí látek cílených na mitochondrie; úloha respiračního komplexu II. 2012-2014.

GAČR: GAP305/12/1708, J. Truksa: Modulace mitochondriálních funkcí rakovinných buněk vyvolané mitochondriálně cílenými deriváty vitaminu E. 2012-2014.

GAUK: 268111 Úloha erbB-2 v rezistenci rakovinných kmenových buněk k terapii. 2011-2012.

GAČR: GAP301/10/1937, J. Neužil: Mechanismy účinného zabíjení kmenových buněk rakoviny prsu. 2010-2013.

AVČR: KJB500970904, K. Vališ: Molekulární mechanismus apoptózy indukované alfa-tokoferylsukcinátem v nádorových buňkách. 2009-2010.

GAČR: GA204/08/0811, J. Neužil: Mechanismus tvorby kyslíkových radikálů a mitochondriální permeabilizace. 2008-2010.

AVČR: KAN200520703, J. Neužil: Nanotechnologie pro společnost: Použití ultrazvuku v nanomedicině. 2007-2011.

AVČR: IAA500520702, J. Neužil: Nový model indukce apoptozy pomocí "mitokanů". 2007-2009.

GAČR: GA305/07/1008, J. Neužil: Úloha mitochondrií v apoptóze kardiomyocytů při infarktu myokardu: od buněk k celému zvířeti. 2007-2009.

AVČR: IAA500520602, J.Neužil: Signální dráhy buněčné smrti v mesotheliomálních buňkách díky účinku farmakologických a imunologických induktorů apoptosy: genomický a proteomický přístup. 2006-2008.