Intratumoral neovascularization and growth pattern in early gastric carcinoma

Tomoda, Masashi; Maehara, Yoshihiko; Kakeji, Yoshihiro; Ohno, Shinji; Ichiyoshi, Yuji; Sugimachi, Keizō

doi:10.1002/(sici)1097-0142(19990601)85:11<2340::aid-cncr7>3.0.co;2-i

Cited by 54 publications

(40 citation statements)

References 35 publications

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“…[13][14][15][16][17]36,37 In addition, the assessment of MVD in a primary tumor ultimately may prove to be a significant and independent prognostic parameter related to tumor recurrence, metastasis, and overall patient survival. [37][38][39][40][41][42] The prognostic significance of angiogenesis has been confirmed in different types of brain tumors, e.g., diffuse astrocytomas of varying grade. In all of these tumors, angiogenesis correlates with tumor behavior and altered function of the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis in patients with craniopharyngiomas

Vidal

Kovács

Lloyd

et al. 2002

Cancer

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The functional single‐coordinate phosphine oxide ligands (4‐diphenylaminophenyl)diphenylphosphine oxide (TAPO), (4‐naphthalen‐1‐yl‐phenylaminophenyl)diphenylphosphine oxide (NaDAPO), and 9‐[4‐(diphenylphosphinoyl)phenyl]‐9H‐carbazole (CPPO), as the direct combinations of hole‐transporting moieties, and electron‐transporting triphenylphosphine oxide (TPPO) were designed and synthesized (amines or carbazole), together with their EuIII complexes [Eu(tapo)2(tta)3] (1), [Eu(nadapo)2(tta)3] (2), and [Eu(cppo)2(tta)3] (3; TTA: 2‐thenoyltrifluoroacetonate). The investigation indicated that by taking advantage of the modification inertia of the phosphine oxide ligands, the direct introduction of the hole‐transport groups as chromophore made TAPO, NaDAPO, and CPPO obtain the most compact structure and mezzo S1 and T1 energy levels, which improved the intramolecular energy transfer in their EuIII complexes. The amorphous phase of 1–3 proved the weak intermolecular interaction, which resulted in extraordinarily low self‐quenching of the complexes. The excellent double‐carrier transport ability of the ligands was studied with Gaussian calculations, and the bipolar structure of TAPO and CPPO was proved. The great improvement of the double‐carrier transport ability of 1–3 was shown by cyclic voltammetry. Their HOMO and LUMO energy levels of around 5.3 and 3.0 eV, respectively, are the best results for EuIII complexes reported so far. A single‐layer organic light‐emitting diode of 2 had the impressive brightness of 59 cd m−2 which, to the best of our knowledge, is the highest reported so far. Both of the four‐layer devices based on pure 1 and 2 had a maximum brightness of more than 1000 cd m−2, turn‐on voltages lower than 5 V, maximum external quantum yields of more than 3 % and excellent spectral stability.

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Section: Discussionmentioning

confidence: 99%

Angiogenesis in patients with craniopharyngiomas

Vidal

Kovács

Lloyd

et al. 2002

Cancer

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“…38) VEGF overexpression was significantly associated with liver metastasis and was the most significant among the clinicopathological factors by univariate analysis. Several previous studies have indicated that VEGF overexpression in a primary tumor is significantly associated with hematogenous metastasis 39,40) and is correlated with relapse 41) or poor outcome in various tumors including colorectal cancer. [20][21][22][23][24] It has also been reported that VEGF mRNA expression is high in cancer tissue with vascular involvement, and the VEGF protein has been strongly detected in cancer cells invading blood vessels.…”

Section: Discussionmentioning

confidence: 99%

“…In some studies, a positive correlation between MVD and VEGF expression has been reported using an immunohistochemical analysis with antibody to Factor VIII associated antigen, CD31 or CD34. 40,44) However, conflicting results in breast or ovarian cancer regarding the correlation between MVD, and VEGF expression or clinicopathologic factors in tumor tissue have been reported. 45,46) Particularly since specific antigens localized in the tumor vessels have not been identified, MVD measured by antibody to Factor VIII associated antigen in the present study did not necessarily reflect all tumor vasculature.…”

Section: Discussionmentioning

confidence: 99%

Urokinase Receptor and Vascular Endothelial Growth Factor Are Synergistically Associated with the Liver Metastasis of Colorectal Cancer

Konno¹,

Abe²,

Kaneko³

et al. 2001

Japanese Journal of Cancer Research

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Considering recent findings that the urokinase plasminogen activation (PA) system is involved in invasion and vascular endothelial growth factor (VEGF) is involved in angiogenesis of colorectal cancer, we evaluated these factors in the liver metastasis of primary colorectal cancer. Cancer tissues from 71 colorectal cancer patients were assayed quantitatively for antigen levels of urokinase type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1, PAI-2), and were also assayed immunohistochemically for expression of VEGF protein. Among the PA system factors, both the levels of uPAR and PAI-1 were significantly higher in larger tumors than in smaller ones, and were also significantly higher in tumors that invaded subserosa, serosa or adjacent organs than in mucosal, submucosal tumors or in tumors that invaded the muscle layer. The uPAR levels were significantly higher in tumors with liver metastasis than in those without. VEGF overexpression was significantly more frequent in tumors with lymph node involvement or liver metastasis than in those without. Among the PA system factors, the uPAR levels were significantly higher in tumors with VEGF overexpression and a multivariate analysis revealed that high uPA level and VEGF overexpression were independent risk factors for liver metastasis. The combination of high uPAR level and overexpression of VEGF was associated with the worst prognosis in patients with colorectal cancer. These results suggest that uPAR and VEGF might contribute synergistically to the liver metastasis of colorectal cancer.

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“…30 The microvessel "density" (MVD) of a tumor, or number of microvessels per unit area, is a quantitative measure of the angiogenesis process. A positive relationship between primary tumor microvessel density and risk of metastasis, tumor recurrence, and death has been widely observed [31][32][33][34][35] and high MVD in metastases is a negative prognostic factor. [36][37][38][39][40] There is, however, a paucity of studies comparing MVD in primary tumors and metastatic lesions.…”

Section: Introductionmentioning

confidence: 99%

The Natural Progression of Microvasculature in Primary Tumor and Lymph Node Metastases in a Breast Carcinoma Model: Relationship between Microvessel Density, Vascular Endothelial Growth Factor Expression and Metastatic Invasion

Rowe

Tomoda

Strebel

et al. 2004

Cancer Biology & Therapy

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The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and metastatic axillary (ALN) and inguinal lymph node (ILN) tumors over 5-6 tumor doublings. Excised tumors were examined for (i) MVD assessed by immunostaining with anti-CD31 antibody, (ii) VEGF expression assessed by immunostaining with anti-VEGF antibody, and (iii) histopathologic extent of metastatic lymph node invasion. MVD and VEGF scores rose asymptotically with increasing tumor weight in both primary and metastatic tumors. The MVD saturation level was significantly greater for primary tumors (MVD = 22) than for ALNs or ILNs (MVD = 14). Maximal VEGF score was not statistically different between the three kinds of tumors, however the rate of rise in VEGF expression was different. Near-maximal VEGF expression occurred early in tumor growth, preceding microvessel development. Both MVD and VEGF expression in lymph nodes were proportional to the pathology score characterizing increasing metastatic invasion. LNMs limited to the subcapsular sinus had the lowest MVD, indicating an ability to survive without significant vasculature. These findings underscore the differences in angiogenesis between primary tumors and LNMs and have implications for therapy of metastatic cancer. INTRODUCTIONThe development of new blood vessels, a multi-step process known as angiogenesis, is required for both tumor growth and metastatic spread of tumor cells. 1,2 Angiogenesis is initiated by tumor cell-secreted angiogenic factors, particularly members of the vascular endothelial growth factor (VEGF) family. 3 VEGF-A is essential for the normal development and differentiation of the vascular system 4,5 and also induces pathological endothelial cell proliferation and angiogenesis. 3,4,6 VEGF-C and VEGF-D are important in lymphangiogenesis and lymphatic metastasis. [7][8][9] Blocking VEGF ligand-receptor interactions significantly inhibits tumor growth 10-16 thus providing a promising target for therapeutic intervention. [17][18][19] Hypoxia is an important regulator of VEGF. [20][21][22] Since hypoxic areas are commonly present in tumors, upregulation of VEGF leads to angiogenesis and provides a mechanism for tumors to maintain a vascular supply insuring oxygen and nutrients. 23 The transition from a quiescent tumor to an invasive tumor, reflecting a change in the balance between cell death and proliferation, is accompanied by the acquisition of angiogenic properties. 24 This so-called angiogenic switch requires not only upregulation of promoters of angiogenesis, but also downregulation of suppressors. 25 Thus, tumor dormancy and control may be achieved by endogenous angiogenesis inhibitors such as angiostatin, 26 endostatin, 27 and metronomic chemotherapy. 28 Tumor cells can also be stimulated in a paracrine manner by growth factors and other cytokines produced by stromal cells, particula...

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Intratumoral neovascularization and growth pattern in early gastric carcinoma

Cited by 54 publications

References 35 publications

Angiogenesis in patients with craniopharyngiomas

Angiogenesis in patients with craniopharyngiomas

Urokinase Receptor and Vascular Endothelial Growth Factor Are Synergistically Associated with the Liver Metastasis of Colorectal Cancer

The Natural Progression of Microvasculature in Primary Tumor and Lymph Node Metastases in a Breast Carcinoma Model: Relationship between Microvessel Density, Vascular Endothelial Growth Factor Expression and Metastatic Invasion

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