Skip to main content
Erschienen in: Cancer Microenvironment 3/2013

01.12.2013

Cysteine (C)-X-C Receptor 4 Regulates NADPH Oxidase-2 During Oxidative Stress in Prostate Cancer Cells

verfasst von: Kia J. Jones, Mahandranauth A. Chetram, Danaya A. Bethea, Latoya K. Bryant, Valerie Odero-Marah, Cimona V. Hinton

Erschienen in: Cancer Microenvironment | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Reactive oxygen species (ROS) are implicated in many human diseases, including cancer. We have previously demonstrated that ROS increased the expression and activity of the chemokine receptor, CXCR4, which enhanced metastatic functions in prostate cancer cells. Studies have also revealed that CXCR4 and its ligand, SDF-1α, promoted ROS accumulation; however the source of ROS was not investigated. Recent evidence suggested that ROS accumulation in prostate cancer cell lines was contributed by the NADPH oxidase (NOX) family of enzymes. Herein, we sought to determine whether the CXCR4/SDF-1α signaling axis mediates ROS production through NOX in prostate cancer. We observed an increase in intracellular ROS generation in prostate cancer cells upon SDF-1α stimulation compared to untreated samples. Conversely, lower levels of ROS were detected in cells treated with AMD3100 (CXCR4 antagonist) or the ROS scavenger, N-acetyl-cysteine (NAC). Markedly reduced levels of ROS were observed in cells treated with apocynin (NOX inhibitor) compared to rotenone (mitochondrial complex I inhibitor)-treated cells. Specifically, we determined that NOX2 responded to, and was regulated by, the SDF-1α/CXCR4 signaling axis. Moreover, chemical inhibition of the ERK1/2 and PI3K pathways revealed that PI3K/AKT signaling participated in CXCR4-mediated NOX activity, and that these collective signaling events resulted in enhanced cell movement towards a chemoattractant. Finally, NOX2 may be a potential therapeutic target, as Oncomine microarray database analysis of normal prostate, benign prostatic hyperplasia (BPH) and prostatic intraepithelial neoplasia (PIN) tissue samples determined a correlation between NOX2 expression and prostate cancer. Taken together, these results suggest that CXCR4/SDF-1α-mediated ROS production through NOX2 enzymes may be an emerging concept by which chemokine signaling progresses tumorigenesis.
Literatur
4.
Zurück zum Zitat Yang Y, Karakhanova S, Werner J, Bazhin AV (2013) Reactive oxygen species in cancer biology and anticancer therapy. Curr med chem Yang Y, Karakhanova S, Werner J, Bazhin AV (2013) Reactive oxygen species in cancer biology and anticancer therapy. Curr med chem
8.
Zurück zum Zitat Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56. doi:10.1038/35065016 PubMedCrossRef Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56. doi:10.​1038/​35065016 PubMedCrossRef
10.
Zurück zum Zitat Sutton A, Friand V, Brulé-Donneger S, Chaigneau T, Ziol M, Sainte-Catherine O, Poiré A, Saffar L, Kraemer M, Vassy J, Nahon P, Salzmann J-L, Gattegno L, Charnaux N (2007) Stromal cell–derived factor-1/chemokine (C-X-C motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion. Mol Cancer Res 5(1):21–33. doi:10.1158/1541-7786.mcr-06-0103 PubMedCrossRef Sutton A, Friand V, Brulé-Donneger S, Chaigneau T, Ziol M, Sainte-Catherine O, Poiré A, Saffar L, Kraemer M, Vassy J, Nahon P, Salzmann J-L, Gattegno L, Charnaux N (2007) Stromal cell–derived factor-1/chemokine (C-X-C motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion. Mol Cancer Res 5(1):21–33. doi:10.​1158/​1541-7786.​mcr-06-0103 PubMedCrossRef
11.
Zurück zum Zitat Block K, Gorin Y (2012) Aiding and abetting roles of NOX oxidases in cellular transformation. Nat Rev Cancer 12(9):627–637PubMedCrossRef Block K, Gorin Y (2012) Aiding and abetting roles of NOX oxidases in cellular transformation. Nat Rev Cancer 12(9):627–637PubMedCrossRef
13.
Zurück zum Zitat Juhasz A, Ge Y, Markel S, Chiu A, Matsumoto L, van Balgooy J, Roy K, Doroshow JH (2009) Expression of NADPH oxidase homologues and accessory genes in human cancer cell lines, tumours and adjacent normal tissues. Free radic res 43(6):523–532. doi:10.1080/10715760902918683 PubMedCrossRef Juhasz A, Ge Y, Markel S, Chiu A, Matsumoto L, van Balgooy J, Roy K, Doroshow JH (2009) Expression of NADPH oxidase homologues and accessory genes in human cancer cell lines, tumours and adjacent normal tissues. Free radic res 43(6):523–532. doi:10.​1080/​1071576090291868​3 PubMedCrossRef
14.
Zurück zum Zitat Urao N, Inomata H, Razvi M, Kim HW, Wary K, McKinney R, Fukai T, Ushio-Fukai M (2008) Role of Nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia. Circ Res 103(2):212–220. doi:10.1161/circresaha.108.176230 PubMedCrossRef Urao N, Inomata H, Razvi M, Kim HW, Wary K, McKinney R, Fukai T, Ushio-Fukai M (2008) Role of Nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia. Circ Res 103(2):212–220. doi:10.​1161/​circresaha.​108.​176230 PubMedCrossRef
15.
Zurück zum Zitat Wu HC, Hsieh JT, Gleave ME, Brown NM, Pathak S, Chung LW (1994) Derivation of androgen-independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells. Int j cancer 57(3):406–412PubMedCrossRef Wu HC, Hsieh JT, Gleave ME, Brown NM, Pathak S, Chung LW (1994) Derivation of androgen-independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells. Int j cancer 57(3):406–412PubMedCrossRef
19.
Zurück zum Zitat Silva A, Yunes JA, Cardoso BA, Martins LR, Jotta PY, Abecasis M, Nowill AE, Leslie NR, Cardoso AA, Barata JT (2008) PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J clin investig 118(11):3762–3774. doi:10.1172/JCI34616 PubMedCrossRef Silva A, Yunes JA, Cardoso BA, Martins LR, Jotta PY, Abecasis M, Nowill AE, Leslie NR, Cardoso AA, Barata JT (2008) PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J clin investig 118(11):3762–3774. doi:10.​1172/​JCI34616 PubMedCrossRef
20.
Zurück zum Zitat Chetram MA, Hinton CV (2012) ROS-mediated regulation of CXCR4 in cancer. Front Biol Chetram MA, Hinton CV (2012) ROS-mediated regulation of CXCR4 in cancer. Front Biol
21.
Zurück zum Zitat Lee RL, Westendorf J, Gold MR (2007) Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4. J Cell Commun Signal 1(1):33–43. doi:10.1007/s12079-007-0006-y PubMedCrossRef Lee RL, Westendorf J, Gold MR (2007) Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4. J Cell Commun Signal 1(1):33–43. doi:10.​1007/​s12079-007-0006-y PubMedCrossRef
22.
Zurück zum Zitat Lin W, Wu G, Li S, Weinberg EM, Kumthip K, Peng LF, Méndez-Navarro J, Chen WC, Jilg N, Zhao H, Goto K, Zhang L, Brockman MA, Schuppan D, Chung RT (2011) HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFkappaB. J biol chem 286(4):2665–2674. doi:10.1074/jbc.M110.168286 PubMedCrossRef Lin W, Wu G, Li S, Weinberg EM, Kumthip K, Peng LF, Méndez-Navarro J, Chen WC, Jilg N, Zhao H, Goto K, Zhang L, Brockman MA, Schuppan D, Chung RT (2011) HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFkappaB. J biol chem 286(4):2665–2674. doi:10.​1074/​jbc.​M110.​168286 PubMedCrossRef
23.
Zurück zum Zitat Dar A, Schajnovitz A, Lapid K, Kalinkovich A, Itkin T, Ludin A, Kao WM, Battista M, Tesio M, Kollet O, Cohen NN, Margalit R, Buss EC, Baleux F, Oishi S, Fujii N, Larochelle A, Dunbar CE, Broxmeyer HE, Frenette PS, Lapidot T (2011) Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. Leukemia. doi:10.1038/leu.2011.62 PubMed Dar A, Schajnovitz A, Lapid K, Kalinkovich A, Itkin T, Ludin A, Kao WM, Battista M, Tesio M, Kollet O, Cohen NN, Margalit R, Buss EC, Baleux F, Oishi S, Fujii N, Larochelle A, Dunbar CE, Broxmeyer HE, Frenette PS, Lapidot T (2011) Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. Leukemia. doi:10.​1038/​leu.​2011.​62 PubMed
28.
Zurück zum Zitat Kwon J, Lee SR, Yang KS, Ahn Y, Kim YJ, Stadtman ER, Rhee SG (2004) Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc Natl Acad Sci U S A 101(47):16419–16424. doi:10.1073/pnas.0407396101 PubMedCrossRef Kwon J, Lee SR, Yang KS, Ahn Y, Kim YJ, Stadtman ER, Rhee SG (2004) Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc Natl Acad Sci U S A 101(47):16419–16424. doi:10.​1073/​pnas.​0407396101 PubMedCrossRef
29.
Zurück zum Zitat Seo JH, Ahn Y, Lee SR, Yeol Yeo C, Chung Hur K (2005) The major target of the endogenously generated reactive oxygen species in response to insulin stimulation is phosphatase and tensin homolog and not phosphoinositide-3 kinase (PI-3 kinase) in the PI-3 kinase/Akt pathway. Mol biol cell 16(1):348–357. doi:10.1091/mbc.E04-05-0369 PubMedCrossRef Seo JH, Ahn Y, Lee SR, Yeol Yeo C, Chung Hur K (2005) The major target of the endogenously generated reactive oxygen species in response to insulin stimulation is phosphatase and tensin homolog and not phosphoinositide-3 kinase (PI-3 kinase) in the PI-3 kinase/Akt pathway. Mol biol cell 16(1):348–357. doi:10.​1091/​mbc.​E04-05-0369 PubMedCrossRef
30.
Zurück zum Zitat Dorfmuller P, Chaumais MC, Giannakouli M, Durand-Gasselin I, Raymond N, Fadel E, Mercier O, Charlotte F, Montani D, Simonneau G, Humbert M, Perros F Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension. Respir Res 12:119. doi: 10.1186/1465-9921-12-119 Dorfmuller P, Chaumais MC, Giannakouli M, Durand-Gasselin I, Raymond N, Fadel E, Mercier O, Charlotte F, Montani D, Simonneau G, Humbert M, Perros F Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension. Respir Res 12:119. doi: 10.1186/1465-9921-12-119
31.
32.
Zurück zum Zitat Brar SS, Corbin Z, Kennedy TP, Hemendinger R, Thornton L, Bommarius B, Arnold RS, Whorton AR, Sturrock AB, Huecksteadt TP, Quinn MT, Krenitsky K, Ardie KG, Lambeth JD, Hoidal JR (2003) NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol 285(2):C353–C369. doi:10.1152/ajpcell.00525.2002 PubMedCrossRef Brar SS, Corbin Z, Kennedy TP, Hemendinger R, Thornton L, Bommarius B, Arnold RS, Whorton AR, Sturrock AB, Huecksteadt TP, Quinn MT, Krenitsky K, Ardie KG, Lambeth JD, Hoidal JR (2003) NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol 285(2):C353–C369. doi:10.​1152/​ajpcell.​00525.​2002 PubMedCrossRef
33.
Zurück zum Zitat Wartenberg M, Hoffmann E, Schwindt H, Grunheck F, Petros J, Arnold JR, Hescheler J, Sauer H (2005) Reactive oxygen species-linked regulation of the multidrug resistance transporter P-glycoprotein in Nox-1 overexpressing prostate tumor spheroids. FEBS Lett 579(20):4541–4549. doi:10.1016/j.febslet.2005.06.078 PubMedCrossRef Wartenberg M, Hoffmann E, Schwindt H, Grunheck F, Petros J, Arnold JR, Hescheler J, Sauer H (2005) Reactive oxygen species-linked regulation of the multidrug resistance transporter P-glycoprotein in Nox-1 overexpressing prostate tumor spheroids. FEBS Lett 579(20):4541–4549. doi:10.​1016/​j.​febslet.​2005.​06.​078 PubMedCrossRef
34.
Zurück zum Zitat Lu JP, Monardo L, Bryskin I, Hou ZF, Trachtenberg J, Wilson BC, Pinthus JH Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase. Prostate Cancer Prostatic Dis 13 (1):39–46. doi: 10.1038/pcan.2009.24 Lu JP, Monardo L, Bryskin I, Hou ZF, Trachtenberg J, Wilson BC, Pinthus JH Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase. Prostate Cancer Prostatic Dis 13 (1):39–46. doi: 10.1038/pcan.2009.24
35.
Zurück zum Zitat Woolley JF, Corcoran A, Groeger G, Landry WD, Cotter TG Redox-Regulated Growth Factor Survival Signaling. Antioxid Redox Signal. doi:10.1089/ars.2012.5028 Woolley JF, Corcoran A, Groeger G, Landry WD, Cotter TG Redox-Regulated Growth Factor Survival Signaling. Antioxid Redox Signal. doi:10.1089/ars.2012.5028
36.
Zurück zum Zitat Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T (1995) Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270(5234):296–299PubMedCrossRef Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T (1995) Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270(5234):296–299PubMedCrossRef
37.
Zurück zum Zitat Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG (1997) Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J biol chem 272(1):217–221PubMedCrossRef Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG (1997) Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J biol chem 272(1):217–221PubMedCrossRef
38.
Zurück zum Zitat Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, Lambeth JD (1999) Cell transformation by the superoxide-generating oxidase Mox1. Nature 401(6748):79–82. doi:10.1038/43459 PubMedCrossRef Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, Lambeth JD (1999) Cell transformation by the superoxide-generating oxidase Mox1. Nature 401(6748):79–82. doi:10.​1038/​43459 PubMedCrossRef
39.
Zurück zum Zitat Weyemi U, Redon CE, Parekh PR, Dupuy C, Bonner WM NADPH Oxidases NOXs and DUPXs As Putative Targets for Cancer Therapy. Anticancer Agents Med Chem Weyemi U, Redon CE, Parekh PR, Dupuy C, Bonner WM NADPH Oxidases NOXs and DUPXs As Putative Targets for Cancer Therapy. Anticancer Agents Med Chem
40.
Zurück zum Zitat Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, Hallett M, Park M (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat med 14(5):518–527. doi:10.1038/nm1764 PubMedCrossRef Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, Hallett M, Park M (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat med 14(5):518–527. doi:10.​1038/​nm1764 PubMedCrossRef
41.
Zurück zum Zitat Ginos MA, Page GP, Michalowicz BS, Patel KJ, Volker SE, Pambuccian SE, Ondrey FG, Adams GL, Gaffney PM (2004) Identification of a gene expression signature associated with recurrent disease in squamous cell carcinoma of the head and neck. Cancer res 64(1):55–63PubMedCrossRef Ginos MA, Page GP, Michalowicz BS, Patel KJ, Volker SE, Pambuccian SE, Ondrey FG, Adams GL, Gaffney PM (2004) Identification of a gene expression signature associated with recurrent disease in squamous cell carcinoma of the head and neck. Cancer res 64(1):55–63PubMedCrossRef
42.
Zurück zum Zitat Beroukhim R, Brunet JP, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell RA, Moch H, Rubin MA, Sellers WR, Meyerson M, Linehan WM, Kaelin WG Jr, Signoretti S (2009) Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer res 69(11):4674–4681. doi:10.1158/0008-5472.CAN-09-0146 PubMedCrossRef Beroukhim R, Brunet JP, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell RA, Moch H, Rubin MA, Sellers WR, Meyerson M, Linehan WM, Kaelin WG Jr, Signoretti S (2009) Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer res 69(11):4674–4681. doi:10.​1158/​0008-5472.​CAN-09-0146 PubMedCrossRef
43.
Zurück zum Zitat Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403(6769):503–511. doi:10.1038/35000501 PubMedCrossRef Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403(6769):503–511. doi:10.​1038/​35000501 PubMedCrossRef
44.
Zurück zum Zitat Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, Kalyana-Sundaram S, Wei JT, Rubin MA, Pienta KJ, Shah RB, Chinnaiyan AM (2007) Integrative molecular concept modeling of prostate cancer progression. Nat genet 39(1):41–51. doi:10.1038/ng1935 PubMedCrossRef Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, Kalyana-Sundaram S, Wei JT, Rubin MA, Pienta KJ, Shah RB, Chinnaiyan AM (2007) Integrative molecular concept modeling of prostate cancer progression. Nat genet 39(1):41–51. doi:10.​1038/​ng1935 PubMedCrossRef
Metadaten
Titel
Cysteine (C)-X-C Receptor 4 Regulates NADPH Oxidase-2 During Oxidative Stress in Prostate Cancer Cells
verfasst von
Kia J. Jones
Mahandranauth A. Chetram
Danaya A. Bethea
Latoya K. Bryant
Valerie Odero-Marah
Cimona V. Hinton
Publikationsdatum
01.12.2013
Verlag
Springer Netherlands
Erschienen in
Cancer Microenvironment / Ausgabe 3/2013
Print ISSN: 1875-2292
Elektronische ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-013-0136-0

Weitere Artikel der Ausgabe 3/2013

Cancer Microenvironment 3/2013 Zur Ausgabe

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

03.06.2024 NSCLC Nachrichten

Wie stark Menschen mit fortgeschrittenem NSCLC von einer Therapie mit Immun-Checkpoint-Hemmern profitieren, hängt offenbar auch davon ab, wie sehr die Diagnose ihre psychische Verfassung erschüttert

Antikörper mobilisiert Neutrophile gegen Krebs

03.06.2024 Onkologische Immuntherapie Nachrichten

Ein bispezifischer Antikörper formiert gezielt eine Armee neutrophiler Granulozyten gegen Krebszellen. An den Antikörper gekoppeltes TNF-alpha soll die Zellen zudem tief in solide Tumoren hineinführen.

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.