Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

Roberta Sanfilippo, Francesco Pantano, Roberta Sanfilippo, Paolo Casali, Michele Iuliani, Andrea Onetti Muda, Giuseppe Perrone, Alessandro Gronchi, Silvia Stacchiotti, Carla Rabitti, Paola Collini, Bruno Vincenzi, Angelo Paolo Dei Tos, Alfonso Baldi, Giuseppe Tonini, Daniele Santini, Daniele Santini, Giuseppe Perrone

    Risultato della ricerca: Article

    2 Citazioni (Scopus)

    Abstract

    Background:The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes.Methods:We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine. All tumour samples were analysed for hENT1 expression by real-time PCR. Median 2-ÎCtvalue was used as the cutoff to dichotomise patients into high' expression and low' expression groups. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS).Results:We found a significant association between high hENT1 expression levels and favourable outcome in terms of PFS and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (PFS: 6.8 vs 3.2 months, P=0.004; OS: 14.9 vs 8.5 months, P=0.007). In addition, hENT1 overexpression correlated with a significant improvement in PFS (9.3 vs 4.5 months; P=0.02) and OS (20.6 vs 10.8 months; P=0.001) in angiosarcoma patients treated with gemcitabine.Conclusions:Our study suggests that higher hENT1 expression are associated to gemcitabine efficacy both in patients with advanced leiomyosarcoma and angiosarcoma.
    Lingua originaleEnglish
    pagine (da-a)340-346
    Numero di pagine7
    RivistaBritish Journal of Cancer
    Volume117
    Stato di pubblicazionePublished - 2017

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    gemcitabine
    Hemangiosarcoma
    Leiomyosarcoma
    Gene Expression
    Disease-Free Survival
    Biliary Tract Neoplasms
    Survival
    Sarcoma
    human SLC29A1 protein
    Kaplan-Meier Estimate
    Pancreatic Neoplasms
    Real-Time Polymerase Chain Reaction

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

    Cita questo

    Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma. / Sanfilippo, Roberta; Pantano, Francesco; Sanfilippo, Roberta; Casali, Paolo; Iuliani, Michele; Muda, Andrea Onetti; Perrone, Giuseppe; Gronchi, Alessandro; Stacchiotti, Silvia; Rabitti, Carla; Collini, Paola; Vincenzi, Bruno; Dei Tos, Angelo Paolo; Baldi, Alfonso; Tonini, Giuseppe; Santini, Daniele; Santini, Daniele; Perrone, Giuseppe.

    In: British Journal of Cancer, Vol. 117, 2017, pag. 340-346.

    Risultato della ricerca: Article

    Sanfilippo, R, Pantano, F, Sanfilippo, R, Casali, P, Iuliani, M, Muda, AO, Perrone, G, Gronchi, A, Stacchiotti, S, Rabitti, C, Collini, P, Vincenzi, B, Dei Tos, AP, Baldi, A, Tonini, G, Santini, D, Santini, D & Perrone, G 2017, 'Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma', British Journal of Cancer, vol. 117, pagg. 340-346.
    Sanfilippo, Roberta ; Pantano, Francesco ; Sanfilippo, Roberta ; Casali, Paolo ; Iuliani, Michele ; Muda, Andrea Onetti ; Perrone, Giuseppe ; Gronchi, Alessandro ; Stacchiotti, Silvia ; Rabitti, Carla ; Collini, Paola ; Vincenzi, Bruno ; Dei Tos, Angelo Paolo ; Baldi, Alfonso ; Tonini, Giuseppe ; Santini, Daniele ; Santini, Daniele ; Perrone, Giuseppe. / Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma. In: British Journal of Cancer. 2017 ; Vol. 117. pagg. 340-346.
    @article{65570353f3924f6585143b6d01b9fd78,
    title = "Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma",
    abstract = "Background:The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes.Methods:We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine. All tumour samples were analysed for hENT1 expression by real-time PCR. Median 2-{\^I}Ctvalue was used as the cutoff to dichotomise patients into high' expression and low' expression groups. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS).Results:We found a significant association between high hENT1 expression levels and favourable outcome in terms of PFS and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (PFS: 6.8 vs 3.2 months, P=0.004; OS: 14.9 vs 8.5 months, P=0.007). In addition, hENT1 overexpression correlated with a significant improvement in PFS (9.3 vs 4.5 months; P=0.02) and OS (20.6 vs 10.8 months; P=0.001) in angiosarcoma patients treated with gemcitabine.Conclusions:Our study suggests that higher hENT1 expression are associated to gemcitabine efficacy both in patients with advanced leiomyosarcoma and angiosarcoma.",
    keywords = "80 and over; Antimetabolites, Antineoplastic; Deoxycytidine; Disease-Free Survival; Equilibrative Nucleoside Transporter 1; Female; Gene Expression; Hemangiosarcoma; Humans; Kaplan-Meier Estimate; Leiomyosarcoma; Male; Middle Aged; Retrospective Studies; Survival Rate; Oncology; Cancer Research, human equilibrative nucleoside transporter 1; gemcitabine; leiomyosarcoma; angiosarcoma; Adult; Aged; Aged",
    author = "Roberta Sanfilippo and Francesco Pantano and Roberta Sanfilippo and Paolo Casali and Michele Iuliani and Muda, {Andrea Onetti} and Giuseppe Perrone and Alessandro Gronchi and Silvia Stacchiotti and Carla Rabitti and Paola Collini and Bruno Vincenzi and {Dei Tos}, {Angelo Paolo} and Alfonso Baldi and Giuseppe Tonini and Daniele Santini and Daniele Santini and Giuseppe Perrone",
    year = "2017",
    language = "English",
    volume = "117",
    pages = "340--346",
    journal = "British Journal of Cancer",
    issn = "0007-0920",
    publisher = "Nature Publishing Group",

    }

    TY - JOUR

    T1 - Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

    AU - Sanfilippo, Roberta

    AU - Pantano, Francesco

    AU - Sanfilippo, Roberta

    AU - Casali, Paolo

    AU - Iuliani, Michele

    AU - Muda, Andrea Onetti

    AU - Perrone, Giuseppe

    AU - Gronchi, Alessandro

    AU - Stacchiotti, Silvia

    AU - Rabitti, Carla

    AU - Collini, Paola

    AU - Vincenzi, Bruno

    AU - Dei Tos, Angelo Paolo

    AU - Baldi, Alfonso

    AU - Tonini, Giuseppe

    AU - Santini, Daniele

    AU - Santini, Daniele

    AU - Perrone, Giuseppe

    PY - 2017

    Y1 - 2017

    N2 - Background:The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes.Methods:We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine. All tumour samples were analysed for hENT1 expression by real-time PCR. Median 2-ÎCtvalue was used as the cutoff to dichotomise patients into high' expression and low' expression groups. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS).Results:We found a significant association between high hENT1 expression levels and favourable outcome in terms of PFS and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (PFS: 6.8 vs 3.2 months, P=0.004; OS: 14.9 vs 8.5 months, P=0.007). In addition, hENT1 overexpression correlated with a significant improvement in PFS (9.3 vs 4.5 months; P=0.02) and OS (20.6 vs 10.8 months; P=0.001) in angiosarcoma patients treated with gemcitabine.Conclusions:Our study suggests that higher hENT1 expression are associated to gemcitabine efficacy both in patients with advanced leiomyosarcoma and angiosarcoma.

    AB - Background:The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes.Methods:We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine. All tumour samples were analysed for hENT1 expression by real-time PCR. Median 2-ÎCtvalue was used as the cutoff to dichotomise patients into high' expression and low' expression groups. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS).Results:We found a significant association between high hENT1 expression levels and favourable outcome in terms of PFS and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (PFS: 6.8 vs 3.2 months, P=0.004; OS: 14.9 vs 8.5 months, P=0.007). In addition, hENT1 overexpression correlated with a significant improvement in PFS (9.3 vs 4.5 months; P=0.02) and OS (20.6 vs 10.8 months; P=0.001) in angiosarcoma patients treated with gemcitabine.Conclusions:Our study suggests that higher hENT1 expression are associated to gemcitabine efficacy both in patients with advanced leiomyosarcoma and angiosarcoma.

    KW - 80 and over; Antimetabolites

    KW - Antineoplastic; Deoxycytidine; Disease-Free Survival; Equilibrative Nucleoside Transporter 1; Female; Gene Expression; Hemangiosarcoma; Humans; Kaplan-Meier Estimate; Leiomyosarcoma; Male; Middle Aged; Retrospective Studies; Survival Rate; Oncology; Cance

    KW - human equilibrative nucleoside transporter 1; gemcitabine; leiomyosarcoma; angiosarcoma; Adult; Aged; Aged

    UR - http://hdl.handle.net/10447/246547

    UR - http://www.nature.com/bjc/index.html

    M3 - Article

    VL - 117

    SP - 340

    EP - 346

    JO - British Journal of Cancer

    JF - British Journal of Cancer

    SN - 0007-0920

    ER -