Top

Journal of Cancer Research and Clinical Oncology

Published in:

Open Access 01-11-2020 | Glioblastoma | Original Article – Cancer Research

Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres

Authors: Hyeong-Cheol Oh, Jin-Kyoung Shim, Junseong Park, Ji-Hyun Lee, Ran Joo Choi, Nam Hee Kim, Hyun Sil Kim, Ju Hyung Moon, Eui Hyun Kim, Jong Hee Chang, Jong In Yook, Seok-Gu Kang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2020

Abstract

Purpose

Glioblastoma (GBM) is the most aggressive type of brain tumor and has poor survival outcomes, even after a combination of surgery, radiotherapy, and chemotherapy. Temozolomide is the only agent that has been shown to be effective against GBM, suggesting that combination of temozolomide with other agents may be more effective. Niclosamide, an FDA approved anthelmintic agent, has shown anti-cancer effects against human colon, breast, prostate cancers as well as GBM. However, the efficacy of the combination of niclosamide with temozolomide against GBM tumorspheres (TSs) has not been determined. We hypothesized that the combined treatment could effectively suppress GBM TSs.

Methods

GBM TSs (TS15-88, GSC11) were treated with niclosamide and/or temozolomide. Combined effects of two drugs were evaluated by measuring viability, neurosphere formation, and 3D-invasion in collagen matrix. Transcriptional profiles of GBM TS were analyzed using RNA sequencing. In vivo anticancer efficacy of combined drugs was tested in a mouse orthotopic xenograft model.

Results

Combination treatment of niclosamide and temozolomide significantly inhibited the cell viability, stemness, and invasive properties of GBM TSs. This combined treatment significantly down-regulated the expression of epithelial mesenchymal transition-related markers, Zeb1, N-cadherin, and β-catenin. The combined treatment also significantly decreased tumor growth in orthotopic xenograft models.

Conclusion

The combination of niclosamide and temozolomide effectively decreased the stemness and invasive properties of GBM TSs, suggesting that this regimen may be therapeutically effective in treating patients with GBM.

Available only for authorised users

Ahn SY, Kim NH, Lee K, Cha YH, Yang JH, Cha SY, Cho ES, Lee Y, Cha JS, Cho HS, Jeon Y, Yuk YS, Cho S, No KT, Kim HS, Lee H, Choi J, Yook JI (2017) Niclosamide is a potential therapeutic for familial adenomatosis polyposis by disrupting Axin-GSK3 interaction. Oncotarget 8(19):31842–31855. https://doi.org/10.18632/oncotarget.16252CrossRefPubMedPubMedCentral

Balgi AD, Fonseca BD, Donohue E, Tsang TC, Lajoie P, Proud CG, Nabi IR, Roberge M (2009) Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. PLoS ONE 4(9):e7124. https://doi.org/10.1371/journal.pone.0007124CrossRefPubMedPubMedCentral

Barrallo-Gimeno A, Nieto MA (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132(14):3151–3161. https://doi.org/10.1242/dev.01907CrossRefPubMed

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25(8):1091–1093. https://doi.org/10.1093/bioinformatics/btp101CrossRefPubMedPubMedCentral

Cheng B, Morales LD, Zhang Y, Mito S, Tsin A (2017) Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line. PLoS ONE 12(9):e0184324. https://doi.org/10.1371/journal.pone.0184324CrossRefPubMedPubMedCentral

Chien MH, Ho YC, Yang SF, Yang YC, Lai SY, Chen WS, Chen MJ, Yeh CB (2018) Niclosamide, an oral antihelmintic drug, exhibits antimetastatic activity in hepatocellular carcinoma cells through downregulating twist-mediated CD10 expression. Environ Toxicol 33(6):659–669. https://doi.org/10.1002/tox.22551CrossRefPubMed

Choi J, Lee JH, Koh I, Shim JK, Park J, Jeon JY, Yun M, Kim SH, Yook JI, Kim EH, Chang JH, Kim SH, Huh YM, Lee SJ, Pollak M, Kim P, Kang SG, Cheong JH (2016) Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A). Oncotarget 7(40):65643–65659. https://doi.org/10.18632/oncotarget.11595CrossRefPubMedPubMedCentral

Chong CR, Sullivan DJ Jr (2007) New uses for old drugs. Nature 448(7154):645–646. https://doi.org/10.1038/448645aCrossRefPubMed

D'Alessandris QG, Biffoni M, Martini M, Runci D, Buccarelli M, Cenci T, Signore M, Stancato L, Olivi A, De Maria R, Larocca LM, Ricci-Vitiani L, Pallini R (2017) The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response. Neuro Oncol 19(8):1097–1108. https://doi.org/10.1093/neuonc/now304CrossRefPubMedPubMedCentral

Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275–284. https://doi.org/10.1038/nrc1590CrossRefPubMed

Flicek P, Ahmed I, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S, Gil L, Garcia-Giron C, Gordon L, Hourlier T, Hunt S, Juettemann T, Kahari AK, Keenan S, Komorowska M, Kulesha E, Longden I, Maurel T, McLaren WM, Muffato M, Nag R, Overduin B, Pignatelli M, Pritchard B, Pritchard E, Riat HS, Ritchie GR, Ruffier M, Schuster M, Sheppard D, Sobral D, Taylor K, Thormann A, Trevanion S, White S, Wilder SP, Aken BL, Birney E, Cunningham F, Dunham I, Harrow J, Herrero J, Hubbard TJ, Johnson N, Kinsella R, Parker A, Spudich G, Yates A, Zadissa A, Searle SM (2013) Ensembl 2013. Nucleic Acids Res 41(Database issue):D48–55. https://doi.org/10.1093/nar/gks1236CrossRefPubMed

Garin JP, Despeignes J, Billerau M (1964) Present treatment of taeniasis with niclosamide. Lyon Med 212:1581–1588PubMed

Gyamfi J, Lee YH, Min BS, Choi J (2019) Niclosamide reverses adipocyte induced epithelial-mesenchymal transition in breast cancer cells via suppression of the interleukin-6/STAT3 signalling axis. Sci Rep 9(1):11336. https://doi.org/10.1038/s41598-019-47707-2CrossRefPubMedPubMedCentral

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003. https://doi.org/10.1056/NEJMoa043331CrossRefPubMed

Jin B, Wang C, Li J, Du X, Ding K, Pan J (2017) Anthelmintic niclosamide disrupts the interplay of p65 and FOXM1/beta-catenin and eradicates leukemia stem cells in chronic myelogenous leukemia. Clin Cancer Res 23(3):789–803. https://doi.org/10.1158/1078-0432.CCR-16-0226CrossRefPubMed

Kang SG, Cheong JH, Huh YM, Kim EH, Kim SH, Chang JH (2015) Potential use of glioblastoma tumorsphere: clinical credentialing. Arch Pharm Res 38(3):402–407. https://doi.org/10.1007/s12272-015-0564-0CrossRefPubMed

Kim BS, Seol HJ, Nam DH, Park CK, Kim IH, Kim TM, Kim JH, Cho YH, Yoon SM, Chang JH, Kang SG, Kim EH, Suh CO, Jung TY, Lee KH, Kim CY, Kim IA, Hong CK, Yoo H, Kim JH, Kang SH, Kang MK, Kim EY, Kim SH, Chung DS, Hwang SC, Song JH, Cho SJ, Lee SI, Lee YS, Ahn KJ, Kim SH, Lim DH, Gwak HS, Lee SH, Hong YK (2017a) Concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for newly diagnosed glioblastoma patients: a retrospective multicenter observation study in Korea. Cancer Res Treat 49(1):193–203. https://doi.org/10.4143/crt.2015.473CrossRefPubMed

Kim EH, Lee JH, Oh Y, Koh I, Shim JK, Park J, Choi J, Yun M, Jeon JY, Huh YM, Chang JH, Kim SH, Kim KS, Cheong JH, Kim P, Kang SG (2017b) Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin. Neuro Oncol 19(2):197–207. https://doi.org/10.1093/neuonc/now174CrossRefPubMed

Kohsaka S, Wang L, Yachi K, Mahabir R, Narita T, Itoh T, Tanino M, Kimura T, Nishihara H, Tanaka S (2012) STAT3 inhibition overcomes temozolomide resistance in glioblastoma by downregulating MGMT expression. Mol Cancer Ther 11(6):1289–1299. https://doi.org/10.1158/1535-7163.MCT-11-0801CrossRefPubMed

Kokkinakis DM, Bocangel DB, Schold SC, Moschel RC, Pegg AE (2001) Thresholds of O6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea or temozolomide. Clin Cancer Res 7(2):421–428PubMed

Kong BH, Shin HD, Kim SH, Mok HS, Shim JK, Lee JH, Shin HJ, Huh YM, Kim EH, Park EK, Chang JH, Kim DS, Hong YK, Kim SH, Lee SJ, Kang SG (2013a) Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma. Int J Oncol 42(5):1754–1762. https://doi.org/10.3892/ijo.2013.1856CrossRefPubMed

Kong BH, Park NR, Shim JK, Kim BK, Shin HJ, Lee JH, Huh YM, Lee SJ, Kim SH, Kim EH, Park EK, Chang JH, Kim DS, Kim SH, Hong YK, Kang SG, Lang FF (2013b) Isolation of glioma cancer stem cells in relation to histological grades in glioma specimens. Childs Nerv Syst 29(2):217–229. https://doi.org/10.1007/s00381-012-1964-9CrossRefPubMed

Kwak J, Shin HJ, Kim SH, Shim JK, Lee JH, Huh YM, Kim EH, Park EK, Chang JH, Kim SH, Hong YK, Kim DS, Lee SJ, Kang SG (2013) Isolation of tumor spheres and mesenchymal stem-like cells from a single primitive neuroectodermal tumor specimen. Childs Nerv Syst 29(12):2229–2239. https://doi.org/10.1007/s00381-013-2201-xCrossRefPubMed

Lal S, Lacroix M, Tofilon P, Fuller GN, Sawaya R, Lang FF (2000) An implantable guide-screw system for brain tumor studies in small animals. J Neurosurg 92(2):326–333. https://doi.org/10.3171/jns.2000.92.2.0326CrossRefPubMed

Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, Um JY, Kim WK, Lee JK, Park J, Kim EH, Lee JH, Lee JH, Chung WS, Ju YS, Park SH, Chang JH, Kang SG, Lee JH (2018) Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 560(7717):243–247. https://doi.org/10.1038/s41586-018-0389-3CrossRefPubMed

Li R, Hu Z, Sun SY, Chen ZG, Owonikoko TK, Sica GL, Ramalingam SS, Curran WJ, Khuri FR, Deng X (2013) Niclosamide overcomes acquired resistance to erlotinib through suppression of STAT3 in non-small cell lung cancer. Mol Cancer Ther 12(10):2200–2212. https://doi.org/10.1158/1535-7163.MCT-13-0095CrossRefPubMedPubMedCentral

Li Y, Li PK, Roberts MJ, Arend RC, Samant RS, Buchsbaum DJ (2014) Multi-targeted therapy of cancer by niclosamide: a new application for an old drug. Cancer Lett 349(1):8–14. https://doi.org/10.1016/j.canlet.2014.04.003CrossRefPubMedPubMedCentral

Lim E-J, Kim S, Oh Y, Suh Y, Kaushik N, Lee J-H, Lee H-J, Kim M-J, Park M-J, Kim R-K, Cha J, Kim SH, Shim J-K, Choi J, Chang JH, Hong YK, Huh YM, Kim P, Kang S-G, Lee S-J (2020) Crosstalk between GBM cells and mesenchymal stemlike cells promotes the invasiveness of GBM through the C5a/p38/ZEB1 axis. Neuro Oncol. https://doi.org/10.1093/neuonc/noaa064CrossRefPubMedPubMedCentral

Liu X, Wang L, Cui W, Yuan X, Lin L, Cao Q, Wang N, Li Y, Guo W, Zhang X, Wu C, Yang J (2016) Targeting ALDH1A1 by disulfiram/copper complex inhibits non-small cell lung cancer recurrence driven by ALDH-positive cancer stem cells. Oncotarget 7(36):58516–58530. https://doi.org/10.18632/oncotarget.11305CrossRefPubMedPubMedCentral

Londono-Joshi AI, Arend RC, Aristizabal L, Lu W, Samant RS, Metge BJ, Hidalgo B, Grizzle WE, Conner M, Forero-Torres A, Lobuglio AF, Li Y, Buchsbaum DJ (2014) Effect of niclosamide on basal-like breast cancers. Mol Cancer Ther 13(4):800–811. https://doi.org/10.1158/1535-7163.MCT-13-0555CrossRefPubMedPubMedCentral

Lu W, Lin C, Roberts MJ, Waud WR, Piazza GA, Li Y (2011) Niclosamide suppresses cancer cell growth by inducing Wnt co-receptor LRP6 degradation and inhibiting the Wnt/beta-catenin pathway. PLoS ONE 6(12):e29290. https://doi.org/10.1371/journal.pone.0029290CrossRefPubMedPubMedCentral

Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4CrossRefPubMed

Natale CA, Li J, Zhang J, Dahal A, Dentchev T, Stanger BZ, Ridky TW (2018) Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade. Elife. https://doi.org/10.7554/eLife.31770CrossRefPubMedPubMedCentral

Osada T, Chen M, Yang XY, Spasojevic I, Vandeusen JB, Hsu D, Clary BM, Clay TM, Chen W, Morse MA, Lyerly HK (2011) Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Cancer Res 71(12):4172–4182. https://doi.org/10.1158/0008-5472.CAN-10-3978CrossRefPubMedPubMedCentral

Park J, Shim JK, Kang JH, Choi J, Chang JH, Kim SY, Kang SG (2018) Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres. Neuro Oncol 20(7):954–965. https://doi.org/10.1093/neuonc/nox243CrossRefPubMed

Ren X, Duan L, He Q, Zhang Z, Zhou Y, Wu D, Pan J, Pei D, Ding K (2010) Identification of niclosamide as a new small-molecule inhibitor of the STAT3 signaling pathway. ACS Med Chem Lett 1(9):454–459. https://doi.org/10.1021/ml100146zCrossRefPubMedPubMedCentral

Roh TH, Park HH, Kang SG, Moon JH, Kim EH, Hong CK, Ahn SS, Choi HJ, Cho J, Kim SH, Lee SK, Kim DS, Kim SH, Suh CO, Lee KS, Chang JH (2017) Long-term outcomes of concomitant chemoradiotherapy with temozolomide for newly diagnosed glioblastoma patients: a single-center analysis. Medicine (Baltimore) 96(27):e7422. https://doi.org/10.1097/MD.0000000000007422CrossRef

Roh TH, Kang SG, Moon JH, Sung KS, Park HH, Kim SH, Kim EH, Hong CK, Suh CO, Chang JH (2020) Survival benefit of lobectomy over gross-total resection without lobectomy in cases of primary glioblastoma in non-eloquent area: a retrospective study. J Neurosurg 132(3):895–901. https://doi.org/10.3171/2018.12.JNS182558CrossRef

Sack U, Walther W, Scudiero D, Selby M, Kobelt D, Lemm M, Fichtner I, Schlag PM, Shoemaker RH, Stein U (2011) Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer. J Natl Cancer Inst 103(13):1018–1036. https://doi.org/10.1093/jnci/djr190CrossRefPubMed

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303CrossRefPubMedPubMedCentral

Stewart RL, Carpenter BL, West DS, Knifley T, Liu L, Wang C, Weiss HL, Gal TS, Durbin EB, Arnold SM, O'Connor KL, Chen M (2016) S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide. Oncotarget 7(23):34630–34642. https://doi.org/10.18632/oncotarget.8969CrossRefPubMedPubMedCentral

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. https://doi.org/10.1056/NEJMoa043330CrossRefPubMed

Trapnell C, Pachter L, Salzberg SL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25(9):1105–1111. https://doi.org/10.1093/bioinformatics/btp120CrossRefPubMedPubMedCentral

Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7(3):562–578. https://doi.org/10.1038/nprot.2012.016CrossRefPubMedPubMedCentral

Trivedi RN, Almeida KH, Fornsaglio JL, Schamus S, Sobol RW (2005) The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death. Cancer Res 65(14):6394–6400. https://doi.org/10.1158/0008-5472.CAN-05-0715CrossRefPubMed

Wang AM, Ku HH, Liang YC, Chen YC, Hwu YM, Yeh TS (2009) The autonomous notch signal pathway is activated by baicalin and baicalein but is suppressed by niclosamide in K562 cells. J Cell Biochem 106(4):682–692. https://doi.org/10.1002/jcb.22065CrossRefPubMedPubMedCentral

Wang YC, Chao TK, Chang CC, Yo YT, Yu MH, Lai HC (2013) Drug screening identifies niclosamide as an inhibitor of breast cancer stem-like cells. PLoS ONE 8(9):e74538. https://doi.org/10.1371/journal.pone.0074538CrossRefPubMedPubMedCentral

Wang Y, Xu H, Fu W, Lu Z, Guo M, Wu X, Sun M, Liu Y, Yu X, Sui D (2019) 20(S)-Protopanaxadiol inhibits angiotensin II-induced epithelial- mesenchymal transition by downregulating SIRT1. Front Pharmacol 10:475. https://doi.org/10.3389/fphar.2019.00475CrossRefPubMedPubMedCentral

Wieland A, Trageser D, Gogolok S, Reinartz R, Hofer H, Keller M, Leinhaas A, Schelle R, Normann S, Klaas L, Waha A, Koch P, Fimmers R, Pietsch T, Yachnis AT, Pincus DW, Steindler DA, Brustle O, Simon M, Glas M, Scheffler B (2013) Anticancer effects of niclosamide in human glioblastoma. Clin Cancer Res 19(15):4124–4136. https://doi.org/10.1158/1078-0432.CCR-12-2895CrossRefPubMed

Xia W, Lo CM, Poon RYC, Cheung TT, Chan ACY, Chen L, Yang S, Tsao GSW, Wang XQ (2017) Smad inhibitor induces CSC differentiation for effective chemosensitization in cyclin D1- and TGF-beta/Smad-regulated liver cancer stem cell-like cells. Oncotarget 8(24):38811–38824. https://doi.org/10.18632/oncotarget.16402CrossRefPubMedPubMedCentral

Ye T, Xiong Y, Yan Y, Xia Y, Song X, Liu L, Li D, Wang N, Zhang L, Zhu Y, Zeng J, Wei Y, Yu L (2014) The anthelmintic drug niclosamide induces apoptosis, impairs metastasis and reduces immunosuppressive cells in breast cancer model. PLoS ONE 9(1):e85887. https://doi.org/10.1371/journal.pone.0085887CrossRefPubMedPubMedCentral

Yoon SJ, Park J, Jang DS, Kim HJ, Lee JH, Jo E, Choi RJ, Shim JK, Moon JH, Kim EH, Chang JH, Lee JH, Kang SG (2020) Glioblastoma cellular origin and the firework pattern of cancer genesis from the subventricular zone. J Korean Neurosurg Soc 63(1):26–33. https://doi.org/10.3340/jkns.2019.0129CrossRefPubMed

Zuo Y, Yang D, Yu Y, Xiang M, Li H, Yang J, Li J, Jiang D, Zhou H, Xu Z, Yu Z (2018) Niclosamide enhances the cytotoxic effect of cisplatin in cisplatin-resistant human lung cancer cells via suppression of lung resistance-related protein and c-myc. Mol Med Rep 17(3):3497–3502. https://doi.org/10.3892/mmr.2017.8301CrossRefPubMed

Title: Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres
Authors: Hyeong-Cheol Oh
Jin-Kyoung Shim
Junseong Park
Ji-Hyun Lee
Ran Joo Choi
Nam Hee Kim
Hyun Sil Kim
Ju Hyung Moon
Eui Hyun Kim
Jong Hee Chang
Jong In Yook
Seok-Gu Kang
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Keywords: Glioblastoma
Glioblastoma
Niclosamide
Glioblastoma
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03330-7

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2020

DNA CpG methylation in sequential glioblastoma specimens

Chemosaturation with percutaneous hepatic perfusion is effective in patients with ocular melanoma and cholangiocarcinoma

Risk factors and treatment outcomes of 239 patients with testicular granulosa cell tumors: a systematic review of published case series data

Lysine-specific histone demethylase 1A (LSD1) in cervical cancer

Gastric cancer in young patients: a separate entity with aggressive features and poor prognosis

Ruxolitinib combined with doxorubicin, etoposide, and dexamethasone for the treatment of the lymphoma-associated hemophagocytic syndrome

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials