共 171 条
Acute lymphoblastic leukaemia
被引:1155
作者:

Pui, Ching-Hon
论文数: 0 引用数: 0
h-index: 0
机构:
St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

Robison, Leslie L.
论文数: 0 引用数: 0
h-index: 0
机构:
St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

Look, A. Thomas
论文数: 0 引用数: 0
h-index: 0
机构:
Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USA St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA
机构:
[1] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA
[3] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA USA
来源:
关键词:
D O I:
10.1016/S0140-6736(08)60457-2
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Acute lymphoblastic leukaemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-firee survival while reducing the toxic side-effects of current intensive regimens. Advances in our understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease. Meanwhile, studies are underway to ascertain the precise events that take place in the genesis of acute lymphoblastic leukaemia, to enhance the clinical application of known risk factors and antileukaemic agents, and to identify treatment regimens that might boost the generally low cure rates in adults and subgroups of children with high-risk leukaemia.
引用
收藏
页码:1030 / 1043
页数:14
相关论文
共 171 条
[1]
A pooled analysis of magnetic fields and childhood leukaemia
[J].
Ahlbom, A
;
Day, N
;
Feychting, M
;
Roman, E
;
Skinner, J
;
Dockerty, J
;
Linet, M
;
McBride, M
;
Michaelis, J
;
Olsen, JH
;
Tynes, T
;
Verkasalo, PK
.
BRITISH JOURNAL OF CANCER,
2000, 83 (05)
:692-698

Ahlbom, A
论文数: 0 引用数: 0
h-index: 0
机构:
Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Day, N
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Feychting, M
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

论文数: 引用数:
h-index:
机构:

Skinner, J
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Dockerty, J
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Linet, M
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

McBride, M
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Michaelis, J
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Olsen, JH
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Tynes, T
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden

Verkasalo, PK
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Div Epidemiol, Natl Inst Environm Med, S-10401 Stockholm, Sweden
[2]
Zebrafish as a cancer model system
[J].
Amatruda, JF
;
Shepard, JL
;
Stern, HM
;
Zon, LI
.
CANCER CELL,
2002, 1 (03)
:229-231

Amatruda, JF
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp, Howard Hughes Med Inst, Dept Hematol Oncol, Boston, MA 02115 USA

Shepard, JL
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp, Howard Hughes Med Inst, Dept Hematol Oncol, Boston, MA 02115 USA

Stern, HM
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp, Howard Hughes Med Inst, Dept Hematol Oncol, Boston, MA 02115 USA

Zon, LI
论文数: 0 引用数: 0
h-index: 0
机构:
Childrens Hosp, Howard Hughes Med Inst, Dept Hematol Oncol, Boston, MA 02115 USA Childrens Hosp, Howard Hughes Med Inst, Dept Hematol Oncol, Boston, MA 02115 USA
[3]
Outcome of treatment in children with philadelphia chromosome-positive acute lymphoblastic leukemia
[J].
Aricò, M
;
Valsecchi, MG
;
Camitta, B
;
Schrappe, M
;
Chessells, J
;
Baruchel, A
;
Gaynon, P
;
Silverman, L
;
Janka-Schaub, G
;
Kamps, W
;
Pui, CH
;
Masera, G
.
NEW ENGLAND JOURNAL OF MEDICINE,
2000, 342 (14)
:998-1006

Aricò, M
论文数: 0 引用数: 0
h-index: 0
机构:
Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Valsecchi, MG
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Camitta, B
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Schrappe, M
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Chessells, J
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Baruchel, A
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Gaynon, P
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

论文数: 引用数:
h-index:
机构:

Janka-Schaub, G
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Kamps, W
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Pui, CH
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy

Masera, G
论文数: 0 引用数: 0
h-index: 0
机构: Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy
[4]
Molecular genetics of acute lymphoblastic leukemia
[J].
Armstrong, SA
;
Look, AT
.
JOURNAL OF CLINICAL ONCOLOGY,
2005, 23 (26)
:6306-6315

Armstrong, SA
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Karp Res Labs, Boston, MA 02115 USA

Look, AT
论文数: 0 引用数: 0
h-index: 0
机构: Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Karp Res Labs, Boston, MA 02115 USA
[5]
MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia
[J].
Armstrong, SA
;
Staunton, JE
;
Silverman, LB
;
Pieters, R
;
de Boer, ML
;
Minden, MD
;
Sallan, SE
;
Lander, ES
;
Golub, TR
;
Korsmeyer, SJ
.
NATURE GENETICS,
2002, 30 (01)
:41-47

Armstrong, SA
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Staunton, JE
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Silverman, LB
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Pieters, R
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

de Boer, ML
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Minden, MD
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Sallan, SE
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Lander, ES
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Golub, TR
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

Korsmeyer, SJ
论文数: 0 引用数: 0
h-index: 0
机构:
Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
[6]
A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia:: a Children's Cancer Group study
[J].
Avramis, VI
;
Sencer, S
;
Periclou, AP
;
Sather, H
;
Bostrom, BC
;
Cohen, LJ
;
Ettinger, AG
;
Ettinger, LJ
;
Franklin, J
;
Gaynon, PS
;
Hilden, JM
;
Lange, B
;
Majlessipour, F
;
Mathew, P
;
Needle, M
;
Neglia, J
;
Reaman, G
;
Holcenberg, JS
.
BLOOD,
2002, 99 (06)
:1986-1994

Avramis, VI
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Sencer, S
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Periclou, AP
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Sather, H
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Bostrom, BC
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Cohen, LJ
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Ettinger, AG
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Ettinger, LJ
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Franklin, J
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Gaynon, PS
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Hilden, JM
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Lange, B
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Majlessipour, F
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Mathew, P
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Needle, M
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Neglia, J
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Reaman, G
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

Holcenberg, JS
论文数: 0 引用数: 0
h-index: 0
机构: Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA
[7]
Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study
[J].
Balduzzi, A
;
Valsecchi, MG
;
Uderzo, C
;
De Lorenzo, P
;
Klingebiel, T
;
Peters, C
;
Stary, J
;
Felice, MS
;
Magyarosy, E
;
Conter, V
;
Reiter, A
;
Messina, C
;
Gadner, H
;
Schroppe, M
.
LANCET,
2005, 366 (9486)
:635-642

Balduzzi, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Valsecchi, MG
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Uderzo, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

De Lorenzo, P
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Klingebiel, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Peters, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Stary, J
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Felice, MS
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Magyarosy, E
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Conter, V
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Reiter, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Messina, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Gadner, H
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy

Schroppe, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Osped San Gerardo, Pediat Clin, I-20052 Milan, Italy
[8]
Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: A pediatric oncology group study
[J].
Barredo, Julio C.
;
Devidas, Meenakshi
;
Lauer, Stephen J.
;
Billett, Amy
;
Marymont, MaryAnne
;
Pullen, Jeanette
;
Camitta, Bruce
;
Winick, Naomi
;
Carroll, William
;
Ritchey, A. Kim
.
JOURNAL OF CLINICAL ONCOLOGY,
2006, 24 (19)
:3142-3149

Barredo, Julio C.
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Devidas, Meenakshi
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Lauer, Stephen J.
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Billett, Amy
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Marymont, MaryAnne
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Pullen, Jeanette
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Camitta, Bruce
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Winick, Naomi
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Carroll, William
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA

Ritchey, A. Kim
论文数: 0 引用数: 0
h-index: 0
机构: Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA
[9]
Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols
[J].
Barry, Elly
;
DeAngelo, Daniel J.
;
Neuberg, Donna
;
Stevenson, Kristen
;
Loh, Mignon L.
;
Asselin, Barbara L.
;
Barr, Ronald D.
;
Clavell, Luis A.
;
Hurwitz, Craig A.
;
Moghrabi, Albert
;
Samson, Yvan
;
Schorin, Marshall
;
Cohen, Harvey J.
;
Sallan, Stephen E.
;
Silverman, Lewis B.
.
JOURNAL OF CLINICAL ONCOLOGY,
2007, 25 (07)
:813-819

Barry, Elly
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

DeAngelo, Daniel J.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Neuberg, Donna
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Stevenson, Kristen
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Loh, Mignon L.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Asselin, Barbara L.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Barr, Ronald D.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Clavell, Luis A.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Hurwitz, Craig A.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Moghrabi, Albert
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Samson, Yvan
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Schorin, Marshall
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Cohen, Harvey J.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Sallan, Stephen E.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

Silverman, Lewis B.
论文数: 0 引用数: 0
h-index: 0
机构: Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[10]
Biological and therapeutic aspects of infant leukemia
[J].
Biondi, A
;
Cimino, G
;
Pieters, R
;
Pui, CH
.
BLOOD,
2000, 96 (01)
:24-33

论文数: 引用数:
h-index:
机构:

Cimino, G
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Pediat Clin, Ctr Ric M Tettamanti, Monza, MI, Italy

Pieters, R
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Pediat Clin, Ctr Ric M Tettamanti, Monza, MI, Italy

Pui, CH
论文数: 0 引用数: 0
h-index: 0
机构: Univ Milano Bicocca, Pediat Clin, Ctr Ric M Tettamanti, Monza, MI, Italy