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References
1.
Rockson
SG
. The lymphatic continuum: the past, present, and exciting future of lymphatic research . Ann N Y Acad Sci. , 2002 ; 979 :1 –4 discussion 35–38.
2.
Sabin
F
. On the origin of the lymphatic system from the veins and the development of the lymph hearts and thoracic duct in the pig . Am J Anat. , 1901 ; 4 :367 –389 .
3.
Rafii
S
,
Skobe
M
. Splitting vessels: keeping lymph apart from blood . Nat Med. , 2003 ; 9 :166 –168 .
4.
Folkman
J
,
Kaipainen
A
. Genes tell lymphatics to sprout or not . Nat Immunol. , 2004 ; 5 :11 –12 .
5.
Zawieja
DC
. Contractile physiology of lymphatics . Lymphat Res Biol. , 2009 ; 7 :87 –96 .
6.
Rockson
SG
. The lymphatic continuum revisited . Ann N Y Acad Sci. , 2008 ; 1131 :ix–x.
7.
Al-Rawi
M
,
Mansel
R
,
Jiang
W
. Molecular and cellular mechanisms of lymphangiogenesis . EJSO. , 2005 ; 31 :117 –121 .
8.
Al-Adnani
M
,
Williams
S
,
Rampling
D
,
Ashworth
M
,
Malone
M
,
Sebire
NJ
. Histopathological reporting of paediatric cutaneous vascular anomalies in relation to proposed multidisciplinary classification system . J Clin Pathol. , 2006 ; 59 :1278 –1282 .
9.
Alitalo
K
,
Tammela
T
,
Petrova
TV
. Lymphangiogenesis in development and human disease . Nature , 2005 ; 438 :946 –953 .
10.
Karpanen
T
,
Alitalo
K
. Molecular biology and pathology of lymphangiogenesis . Annu Rev Pathol. , 2008 ; 3 :367 –397 .
11.
Baluk
P
,
McDonald
DM
. Markers for microscopic imaging of lymphangiogenesis and angiogenesis . Ann N Y Acad Sci. , 2008 ; 1131 :1 –12 .
12.
Stacker
SA
,
Achen
MG
. From anti-angiogenesis to anti-lymphangiogenesis: emerging trends in cancer therapy . Lymphat Res Biol. , 2008 ; 6 :165 –172 .
13.
Nakamura
K
,
Rockson
SG
. Molecular targets for therapeutic lymphangiogenesis in lymphatic dysfunction and disease . Lymphat Res Biol. , 2008 ; 6 :181 –189 .
14.
Bruyere
F
,
Noe
A
. Lymphangiogenesis: in vitro and in vivo models . Faseb J. Sep , 2 . 2009 .
15.
Baldwin
M
,
Stacker
S
,
Achen
M
. Molecular control of lymphangiogenesis . Bioessays. , 2002 ; 24 :1030 –1040 .
16.
Shin
WS
,
Rockson
SG
. Animal models for the molecular and mechanistic study of lymphatic biology and disease . Ann N Y Acad Sci. , 2008 ; 1131 :50 –74 .
17.
Kim
H
,
Dumont
D
. Molecular mechanisms in lymphangiogenesis: model systems and implications in human disease . Clinical Genetics. , 2003 ; 64 :282 –292 .
18.
Karkkainen
MJ
,
Ferrell
RE
,
Lawrence
EC
,
Kimak
MA
,
Levinson
KL
,
McTigue
MA
,
Alitalo
K
,
Finegold
DN
. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema . Nat Genet. , 2000 ; 25 :153 –159 .
19.
Irrthum
A
,
Karkkainen
MJ
,
Devriendt
K
,
Alitalo
K
,
Vikkula
M
. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase . Am J Hum Genet. , 2000 ; 67 :295 –301 .
20.
Noguchi
T
,
Takeno
S
,
Shibata
T
,
Uchida
Y
,
Yokoyama
S
,
Muller
W
. VEGF-C expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus . Oncol Rep. , 2002 ; 9 :995 –999 .
21.
Amioka
T
,
Kitadai
Y
,
Tanaka
S
,
Haruma
K
,
Yoshihara
M
,
Yasui
W
,
Chayama
K
. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa . Eur J Cancer. , 2002 ; 38 :1413 –1419 .
22.
Dadras
SS
,
Paul
T
,
Bertoncini
J
,
Brown
LF
,
Muzikansky
A
,
Jackson
DG
,
Ellwanger
U
,
Garbe
C
,
Mihm
MC
,
Detmar
M
. Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival . Am J Pathol. , 2003 ; 162 :1951 –1960 .
23.
Arinaga
M
,
Noguchi
T
,
Takeno
S
,
Chujo
M
,
Miura
T
,
Uchida
Y
. Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma . Cancer. , 2003 ; 97 :457 –464 .
24.
Stacker
SA
,
Caesar
C
,
Baldwin
ME
,
Thornton
GE
,
Williams
RA
,
Prevo
R
,
Jackson
DG
,
Nishikawa
S
,
Kubo
H
,
Achen
MG
. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics . Nat Med. , 2001 ; 7 :186 –191 .
25.
Skobe
M
,
Hawighorst
T
,
Jackson
DG
,
Prevo
R
,
Janes
L
,
Velasco
P
,
Riccardi
L
,
Alitalo
K
,
Claffey
K
,
Detmar
M
. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis . Nat Med. , 2001 ; 7 :192 –198 .
26.
Mandriota
SJ
,
Jussila
L
,
Jeltsch
M
,
Compagni
A
,
Baetens
D
,
Prevo
R
,
Banerji
S
,
Huarte
J
,
Montesano
R
,
Jackson
DG
,
Orci
L
,
Alitalo
K
,
Christofori
G
,
Pepper
MS
. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis . Embo J. , 2001 ; 20 :672 –682 .
27.
Karkkainen
MJ
,
Saaristo
A
,
Jussila
L
,
Karila
KA
,
Lawrence
EC
,
Pajusola
K
,
Bueler
H
,
Eichmann
A
,
Kauppinen
R
,
Kettunen
MI
,
Yla-Herttuala
S
,
Finegold
DN
,
Ferrell
RE
,
Alitalo
K
. A model for gene therapy of human hereditary lymphedema . Proc Natl Acad Sci USA. , 2001 ; 98 :12677 –12682 .
28.
Szuba
A
,
Skobe
M
,
Karkkainen
MJ
,
Shin
WS
,
Beynet
DP
,
Rockson
NB
,
Dakhil
N
,
Spilman
S
,
Goris
ML
,
Strauss
HW
,
Quertermous
T
,
Alitalo
K
,
Rockson
SG
. Therapeutic lymphangiogenesis with human recombinant VEGF-C . FASEB J. , 2002 ; 16 :U114 –U130 .
29.
Yoon
YS
,
Murayama
T
,
Gravereaux
E
,
Tkebuchava
T
,
Silver
M
,
Curry
C
,
Wecker
A
,
Kirchmair
R
,
Hu
CS
,
Kearney
M
,
Ashare
A
,
Jackson
DG
,
Kubo
H
,
Isner
JM
,
Losordo
DW
. VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema . J Clin Invest. , 2003 ; 111 :717 –725 .
30.
Cheung
L
,
Han
J
,
Beilhack
A
,
Joshi
S
,
Wilburn
P
,
Dua
A
,
An
A
,
Rockson
SG
. An experimental model for the study of lymphedema and its response to therapeutic lymphangiogenesis . BioDrugs. , 2006 ; 20 :363 –370 .
31.
Jin
DP
,
An
A
,
Liu
J
,
Nakamura
K
,
Rockson
SG
. Therapeutic Responses to Exogenous VEGF-C Administration in Experimental Lymphedema: Immunohistochemical and Molecular Characterization . Lymphat Res Biol. , 2009 ; 7 :47 –57 .
32.
Karpanen
T
,
Egeblad
M
,
Karkkainen
MJ
,
Kubo
H
,
Yla-Herttuala
S
,
Jaattela
M
,
Alitalo
K
. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth . Cancer Res. , 2001 ; 61 :1786 –1790 .
33.
Van der Auwera
I
,
Cao
Y
,
Tille
JC
,
Pepper
MS
,
Jackson
DG
,
Fox
SB
,
Harris
AL
,
Dirix
LY
,
Vermeulen
PB
. First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours . Br J Cancer. , 2006 ; 95 :1611 –1625 .
34.Executive Summary. Lymphatic Research . Trans-NIH Working Group Meeting , 2007 . http://www.nhlbi.nih.gov/meetings/workshops/lymph-res.htm.
