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S. Schoppmann, A. Fenzl, K. Nagy, Sandra Unger, G. Bayer, S. Geleff, M. Gnant, R. Horvat, R. Jakesz, P. Birner (2006)
VEGF-C expressing tumor-associated macrophages in lymph node positive breast cancer: impact on lymphangiogenesis and survival.Surgery, 139 6
T. Padera, A. Kadambi, E. Tomaso, C. Carreira, E. Brown, Y. Boucher, N. Choi, D. Mathisen, J. Wain, E. Mark, L. Munn, R. Jain (2002)
Lymphatic Metastasis in the Absence of Functional Intratumor LymphaticsScience, 296
S. Tsutsui, K. Yasuda, Kosuke Suzuki, K. Tahara, H. Higashi, S. Era (2005)
Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density.Oncology reports, 14 2
V. Joukov, K. Pajusola, A. Kaipainen, D. Chilov, I. Lahtinen, E. Kukk, O. Saksela, N. Kalkkinen, K. Alitalo (1996)
A novel vascular endothelial growth factor, VEGF‐C, is a ligand for the Flt4 (VEGFR‐3) and KDR (VEGFR‐2) receptor tyrosine kinases.The EMBO Journal, 15
B. Jiang, Ling-Zhi Liu (2008)
PI3K/PTEN signaling in tumorigenesis and angiogenesis.Biochimica et biophysica acta, 1784 1
S. Tsutsui, M. Kume, S. Era (2003)
Prognostic value of microvessel density in invasive ductal carcinoma of the breastBreast Cancer, 10
Soichi Kobayashi, T. Kishimoto, S. Kamata, M. Otsuka, M. Miyazaki, H. Ishikura (2007)
Rapamycin, a specific inhibitor of the mammalian target of rapamycin, suppresses lymphangiogenesis and lymphatic metastasisCancer Science, 98
H. Kahn, Alexander Marks (2002)
A New Monoclonal Antibody, D2-40, for Detection of Lymphatic Invasion in Primary TumorsLaboratory Investigation, 82
V. Schacht, S. Dadras, L. Johnson, D. Jackson, Young-Kwon Hong, M. Detmar (2005)
Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors.The American journal of pathology, 166 3
N. Mazure, E. Chen, K. Laderoute, A. Giaccia (1997)
Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element.Blood, 90 9
Zongxian Cao, Jing Fang, Chang Xia, Xianglin Shi, B. Jiang (2004)
trans-3,4,5′-Trihydroxystibene Inhibits Hypoxia-Inducible Factor 1α and Vascular Endothelial Growth Factor Expression in Human Ovarian Cancer CellsClinical Cancer Research, 10
Yasushi Nakamura, H. Yasuoka, M. Tsujimoto, Qifeng Yang, A. Tsukiyama, S. Imabun, M. Nakahara, K. Nakao, Misa Nakamura, I. Mori, K. Kakudo (2003)
Clinicopathological Significance of Vascular Endothelial Growth Factor-C in Breast Carcinoma with Long-Term Follow-UpModern Pathology, 16
J. Jacquemier, M. Mathoulin-Portier, R. Valtola, E. Charafe-Jauffret, J. Geneix, G. Houvenaeghel, B. Puig, V. Bardou, J. Hassoun, P. Viens, D. Birnbaum (2000)
Prognosis of breast‐carcinoma lymphagenesis evaluated by immunohistochemical investigation of vascular‐endothelial‐growth‐factor receptor 3International Journal of Cancer, 89
K. Schmitz, F. Otterbach, R. Callies, B. Levkau, M. Hölscher, O. Hoffmann, F. Grabellus, R. Kimmig, K. Schmid, H. Baba (2004)
Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 casesModern Pathology, 17
R. Mohammed, A. Green, S. Elshikh, E. Paish, Ian Ellis, Stewart Martin (2007)
Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesisBritish Journal of Cancer, 96
F. Rényi-Vámos, J. Tóvári, J. Fillinger, J. Tímár, S. Paku, I. Kenessey, G. Ostoros, L. Agócs, I. Soltész, B. Dome (2005)
Lymphangiogenesis Correlates with Lymph Node Metastasis, Prognosis, and Angiogenic Phenotype in Human Non–Small Cell Lung CancerClinical Cancer Research, 11
Yasushi Nakamura, H. Yasuoka, M. Tsujimoto, S. Imabun, M. Nakahara, K. Nakao, Misa Nakamura, I. Mori, K. Kakudo (2005)
Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancerBreast Cancer Research and Treatment, 91
I. Auwera, Yihai Cao, J. Tille, M. Pepper, D. Jackson, Stephen Fox, A. Harris, L. Dirix, Peter Vermeulen (2006)
First international consensus on the methodology of lymphangiogenesis quantification in solid human tumoursBritish Journal of Cancer, 95
Yihai Cao, P. Linden, J. Farnebo, R. Cao, A. Eriksson, Vijay Kumar, J. Qi, L. Claesson-Welsh, K. Alitalo (1998)
Vascular endothelial growth factor C induces angiogenesis in vivo.Proceedings of the National Academy of Sciences of the United States of America, 95 24
J. Kinoshita, K. Kitamura, A. Kabashima, H. Saeki, Shinji Tanaka, K. Sugimachi (2001)
Clinical significance of vascular endothelial growth factor‐C (VEGF‐C) in breast cancerBreast Cancer Research and Treatment, 66
Y. Kitadai, M. Kodama, Songde Cho, Tsuyoshi Kuroda, T. Ochiumi, Shigeru Kimura, Shinji Tanaka, Shunji Matsumura, W. Yasui, K. Chayama (2005)
Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodesInternational Journal of Cancer, 115
H. Zhong, K. Chiles, D. Feldser, E. Laughner, C. Hanrahan, M. Georgescu, J. Simons, G. Semenza (2000)
Advances in Brief Modulation of Hypoxia-inducible Factor 1 a Expression by the Epidermal Growth Factor / Phosphatidylinositol 3-Kinase / PTEN / AKT / FRAP Pathway in Human Prostate Cancer Cells : Implications for Tumor Angiogenesis and Therapeutics 1
B. Agarwal, R. Saxena, A. Morimiya, S. Mehrotra, S. Badve (2005)
Lymphangiogenesis Does Not Occur in Breast CancerThe American Journal of Surgical Pathology, 29
E. Mylona, P. Alexandrou, A. Mpakali, I. Giannopoulou, G. Liapis, S. Markaki, A. Keramopoulos, L. Nakopoulou (2007)
Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma.European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 33 3
Jo Forsythe, B. Jiang, N. Iyer, F. Agani, S. Leung, R. Koos, G. Semenza (1996)
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1Molecular and Cellular Biology, 16
S. Tsutsui, S. Ohno, S. Murakami, Y. Hachitanda, S. Oda (2004)
Prognostic value of epidermal growth factor receptor (EGFR) and its relationship to the estrogen receptor status in 1029 patients with breast cancerBreast Cancer Research and Treatment, 71
A. Franchi, O. Gallo, D. Massi, G. Baroni, M. Santucci (2004)
Tumor lymphangiogenesis in head and neck squamous cell carcinomaCancer, 101
M. Skobe, T. Hawighorst, D. Jackson, R. Prevo, L. Janes, P. Velasco, L. Riccardi, K. Alitalo, K. Claffey, M. Detmar (2001)
Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasisNature Medicine, 7
S. Tsutsui, H. Inoue, K. Yasuda, Kosuke Suzuki, H. Takeuchi, T. Nishizaki, H. Higashi, S. Era, M. Mori (2006)
Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel densityBreast Cancer Research and Treatment, 98
Terhi Karpanen, M. Egeblad, M. Karkkainen, Hajime Kubo, Seppo Ylä-Herttuala, Marja Jäättelä, Kari Alitalo (2001)
Advances in Brief Vascular Endothelial Growth Factor C Promotes Tumor Lymphangiogenesis and Intralymphatic Tumor Growth 1
Claudio Scavelli, A. Vacca, G. Pietro, F. Dammacco, D. Ribatti (2004)
Crosstalk between angiogenesis and lymphangiogenesis in tumor progressionLeukemia, 18
M. Mattila, J. Ruohola, Terhi Karpanen, D. Jackson, K. Alitalo, P. Härkönen (2002)
VEGF‐C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF‐7 tumorsInternational Journal of Cancer, 98
T. Hachisuka, M. Narikiyo, Yukishige Yamada, H. Ishikawa, M. Ueno, H. Uchida, R. Yoriki, Yuichiro Ohigashi, Katsuhiko Miki, H. Tamaki, T. Mizuno, Y. Nakajima (2005)
High lymphatic vessel density correlates with overexpression of VEGF-C in gastric cancer.Oncology reports, 13 4
Jing Fang, Chang Xia, Zongxian Cao, Jenny Zheng, E. Reed, B. Jiang (2005)
Apigenin inhibits VEGF and HIF‐1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathwaysThe FASEB Journal, 19
H. Skinner, Jenny Zheng, Jing Fang, F. Agani, B. Jiang (2004)
Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated by Hypoxia-inducible Factor 1α, HDM2, and p70S6K1 in Response to Phosphatidylinositol 3-Kinase/AKT Signaling*Journal of Biological Chemistry, 279
R. Saad, Lana Kordunsky, Yulin Liu, K. Denning, Hosam Kandil, J. Silverman (2006)
Lymphatic microvessel density as prognostic marker in colorectal cancerModern Pathology, 19
H. Bando, H. Weich, S. Horiguchi, N. Funata, Taeko Ogawa, M. Toi (2006)
The association between vascular endothelial growth factor-C, its corresponding receptor, VEGFR-3, and prognosis in primary breast cancer: a study with 193 cases.Oncology reports, 15 3
W. Thiele, J. Sleeman (2006)
Tumor-induced lymphangiogenesis: a target for cancer therapy?Journal of biotechnology, 124 1
D. Hanahan, J. Folkman (1996)
Patterns and Emerging Mechanisms of the Angiogenic Switch during TumorigenesisCell, 86
S. Hirakawa, S. Kodama, R. Kunstfeld, K. Kajiya, L. Brown, M. Detmar (2005)
VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasisThe Journal of Experimental Medicine, 201
F. Hoar, S. Chaudhri, M. Wadley, P. Stonelake (2003)
Co-expression of vascular endothelial growth factor C (VEGF-C) and c-erbB2 in human breast carcinoma.European journal of cancer, 39 12
M. Ueda, Y. Hung, Y. Terai, K. Kanda, M. Kanemura, H. Futakuchi, H. Yamaguchi, Daisuke Akise, M. Yasuda, M. Ueki (2005)
Vascular Endothelial Growth Factor-C Expression and Invasive Phenotype in Ovarian CarcinomasClinical Cancer Research, 11
Yucheng Tang, Donglei Zhang, L. Fallavollita, P. Brodt (2003)
Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor.Cancer research, 63 6
B. Jiang, Guoqiang Jiang, Jenny Zheng, Zhimin Lu, T. Hunter, P. Vogt (2000)
Phosphatidylinositol 3-Kinase Signaling Controls Levels of Hypoxia-inducible Factor 11
R. Sedivy, J. Beck-Mannagetta, C. Haverkampf, W. Battistutti, S. Hönigschnabl (2003)
Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 32 8
M. Ohno, Takeshi Nakamura, Y. Kunimoto, K. Nishimura, Cheng Chung-Kang, Y. Kuroda (2003)
Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer.Oncology reports, 10 4
Koichiro Okada, M. Osaki, Kunio Araki, K. Ishiguro, Hisao Ito, S. Ohgi (2005)
Expression of hypoxia-inducible factor (HIF-1alpha), VEGF-C and VEGF-D in non-invasive and invasive breast ductal carcinomas.Anticancer research, 25 4
B. Manning, L. Cantley (2007)
AKT/PKB Signaling: Navigating DownstreamCell, 129
S. Schoppmann, A. Fenzl, M. Schindl, T. Bachleitner-Hofmann, K. Nagy, M. Gnant, R. Horvat, R. Jakesz, P. Birner (2006)
Hypoxia inducible factor-1α correlates with VEGF-C expression and lymphangiogenesis in breast cancerBreast Cancer Research and Treatment, 99
S. Gunningham, M. Currie, Cheng Han, B. Robinson, P. Scott, A. Harris, Stephen Fox (2000)
The short form of the alternatively spliced flt-4 but not its ligand vascular endothelial growth factor C is related to lymph node metastasis in human breast cancers.Clinical cancer research : an official journal of the American Association for Cancer Research, 6 11
E. Ogawa, K. Takenaka, Kazuhiro Yanagihara, M. Kurozumi, Toshiaki Manabe, Hiromi Wada, F. Tanaka (2004)
Clinical significance of VEGF-C status in tumour cells and stromal macrophages in non-small cell lung cancer patientsBritish Journal of Cancer, 91
M. Volm, R. Koomägi, J. Mattern (1997)
Prognostic value of vascular endothelial growth factor and its receptor Flt‐1 in squamous cell lung cancerInternational Journal of Cancer, 74
J. Kurebayashi, T. Otsuki, H. Kunisue, Y. Mikami, Katsuhiko Tanaka, S. Yamamoto, H. Sonoo (1999)
Expression of Vascular Endothelial Growth Factor (VEGF) Family Members in Breast CancerJapanese Journal of Cancer Research : Gann, 90
Y. Miyata, S. Kanda, K. Ohba, Koichiro Nomata, Y. Hayashida, J. Eguchi, Tomayoshi Hayashi, H. Kanetake (2006)
Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -DClinical Cancer Research, 12
J. Nagy, E. Vasile, Dian Feng, C. Sundberg, L. Brown, M. Detmar, J. Lawitts, L. Benjamin, X. Tan, E. Manseau, A. Dvorak, H. Dvorak (2002)
Vascular Permeability Factor/Vascular Endothelial Growth Factor Induces Lymphangiogenesis as well as AngiogenesisThe Journal of Experimental Medicine, 196
S. Tsutsui, K. Yasuda, Kosuke Suzuki, H. Takeuchi, T. Nishizaki, H. Higashi, S. Era (2006)
A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancerBritish Journal of Cancer, 94
O. Watanabe, Jun Kinoshita, Tadao Shimizu, Hiroshi Imamura, A. Hirano, Toshihiro Okabe, M. Aiba, Kenji Ogawa (2005)
Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer.Journal of experimental & clinical cancer research : CR, 24 1
S. Schoppmann, G. Bayer, K. Aumayr, S. Taucher, S. Geleff, M. Rudas, E. Kubista, H. Hausmaninger, H. Samonigg, M. Gnant, R. Jakesz, R. Horvat (2004)
Prognostic Value of Lymphangiogenesis and Lymphovascular Invasion in Invasive Breast CancerAnnals of Surgery, 240
N. Beasley, R. Prevo, Suneale Banerji, R. Leek, John Moore, P. Trappen, G. Cox, A. Harris, D. Jackson (2002)
Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer.Cancer research, 62 5
A. Bellacosa, J. Testa, S. Staal, P. Tsichlis (1991)
A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region.Science, 254 5029
I. Auwera, P. Vermeulen, E. Marck, L. Dirix (2004)
Lack of lymphangiogenesis during breast carcinogenesis.Journal of clinical pathology, 57 12
P. Bono, V. Wasenius, P. Heikkilä, J. Lundin, D. Jackson, H. Joensuu (2004)
High LYVE-1–Positive Lymphatic Vessel Numbers Are Associated with Poor Outcome in Breast CancerClinical Cancer Research, 10
Francis Hall, J. Freeman, S. Asa, D. Jackson, N. Beasley (2003)
Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma.Archives of otolaryngology--head & neck surgery, 129 7
W. Choi, M. Lewis, D. Lawson, Q. Yin-Goen, G. Birdsong, G. Cotsonis, C. Cohen, A. Young (2005)
Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expressionModern Pathology, 18
S. Tsutsui, H. Inoue, K. Yasuda, Kosuke Suzuki, K. Tahara, H. Higashi, S. Era, M. Mori (2005)
Inactivation of PTEN is associated with a low p27Kip1 protein expression in breast carcinomaCancer, 104
Cory Williams, R. Leek, A. Robson, Suneale Banerji, R. Prevo, A. Harris, D. Jackson (2003)
Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancerThe Journal of Pathology, 200
Yasushi Nakamura, H. Yasuoka, M. Tsujimoto, Qifeng Yang, S. Imabun, M. Nakahara, K. Nakao, Misa Nakamura, I. Mori, K. Kakudo (2003)
Flt-4-positive vessel density correlates with vascular endothelial growth factor-d expression, nodal status, and prognosis in breast cancer.Clinical cancer research : an official journal of the American Association for Cancer Research, 9 14
I. Auwera, C. Colpaert, E. Marck, P. Vermeulen, L. Dirix (2006)
Lymphangiogenesis in breast cancer.The American journal of surgical pathology, 30 8
B. Jiang, Guoqiang Jiang, Jenny Zheng, Zhimin Lu, T. Hunter, P. Vogt (2001)
Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1.Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 12 7
G. Pérez-Tenorio, O. Stål, A. Group (2002)
Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patientsBritish Journal of Cancer, 86
P. Maxwell, G. Dachs, J. Gleadle, L. Nicholls, A. Harris, I. Stratford, O. Hankinson, C. Pugh, P. Ratcliffe (1997)
Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth.Proceedings of the National Academy of Sciences of the United States of America, 94 15
Xin-hua Liang, Dajiang Yang, Jing Hu, Xiaoming Hao, Jiarang Gao, Z. Mao (2008)
Hypoxia inducible factor-alpha expression correlates with vascular endothelial growth factor-C expression and lymphangiogenesis/angiogenesis in oral squamous cell carcinoma.Anticancer research, 28 3A
Y. Koyama, K. Kaneko, K. Akazawa, C. Kanbayashi, T. Kanda, K. Hatakeyama (2003)
Vascular endothelial growth factor-C and vascular endothelial growth factor-d messenger RNA expression in breast cancer: association with lymph node metastasis.Clinical breast cancer, 4 5
Akt activation has been found in various human cancers, while experimental studies have suggested that Akt plays an important role in the development of tumor angiogenesis and lymphangiogenesis. Immunohistochemical analyses for VEGF-C and Akt and the lymphatic endothelial specific marker D2-40 were performed on a series of 242 invasive ductal carcinomas of the breast, in which VEGF-A expression and microvessel density (MVD) had been determined previously. Lymphatic vessel density (LVD) was estimated in three hot spots. A significant correlation was observed between the VEGF-C expression and LVD (p=0.0026) and between LVD and the lymph node status (p<0.0001). The VEGF-C expression, however, did not correlate significantly with the lymph nodes status, while a high VEGF-C expression was associated with a smaller tumor size (p=0.0188). There was a significant correlation between VEGF-C and VEGF-A expression (p=0.0079) and between LVD and MVD (p=0.0008). The VEGF-C expression correlated with MVD (p<0.0001), while the VEGF-A expression correlated with LVD (p=0.0155). The Akt expression correlated with VEGF-A (p=0.0173) and -C expression (p=0.0056) as well as MVD (p=0.0482) and LVD (p=0.0012), while the correlation of Akt expression to VEGF-C expression and LVD was stronger than that to VEGF-A expression and MVD. Although the patients with a high LVD have a poorer disease-free survival than those with a low LVD (p=0.0005), a multivariate analysis determined the lymph node status and MVD to be independently significant factors for the disease-free survival. In conclusion, the correlation of both VEGF-C and VEGF-A to LVD and MVD suggested the two growth factors to be involved in both angiogenesis and lymphangiogenesis in breast cancer. The correlation of the Akt expression to the VEGF-A and -C expression as well as MVD and LVD, thus, suggested Akt activation to contribute to both angiogenesis and lymphangiogenesis via VEGF-A and -C expression in breast cancer.
Oncology Reports – Spandidos Publications
Published: Mar 1, 2010
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