Head and Neck Neoplasms ; pathology ; Humans ; Lymphangiogenesis ; Neoplasm Metastasis

PURPOSE: To evaluate the effect of subconjunctival bevacizumab injection before conjunctival autograft for pterygium. METHODS: Twenty-five eyes (25 patients) with pterygium received a subconjunctival injection of 2.5 mg (0.1 mL) bevacizumab 1-2 weeks prior to conjunctival autograft surgery. The control group (25 eyes of 25 patients) received the same operation. Two weeks, 1 month and every month after the surgery, the vascularization of surgical site, the recurrence rate and the effect of wound healing were analyzed. RESULTS: The bevacizumab group showed a decreased conjunctival vascularity grade compared with the control group based on light microscopy. The bevacizumab group also showed lower vascular epithelial growth factor (VEGF) compared with the control group using immunohistochemical analysis and western blot. There was no recurrence in both groups, but, persistent autograft edema was observed at 8 weeks postoperatively in the bevacizumab group. CONCLUSIONS: Although preoperative injection of bevacizumab effectively reduced vascularity and VEGF concentration of pterygium tissue, prolonged autograft edema was observed. Based on these results, bevacizumab inhibits lymphangiogenesis as well as angiogenesis. Therefore, delayed wound healing should be considered when subconjunctival bevacizumab injection is administered before pterygium surgery.
Autografts* ; Blotting, Western ; Edema ; Lymphangiogenesis ; Microscopy ; Pterygium* ; Recurrence ; Vascular Endothelial Growth Factor A ; Wound Healing ; Bevacizumab

OBJECTIVES: Angiogenesis and lymphangiogenesis are correlated with tumor growth and lymph node metastasis in cases of oral squamous cell carcinoma (OSCC). Endoglin is one of the representative vascular endothelial cell markers. Podoplanin is also a representative marker used in order to detect lymphatic endothelial cells. The aim of this study was to determine the correlation between the expression of endoglin/podoplanin and clinical variables associated with OSCC progression. MATERIALS AND METHODS: Paraffin embedded tissue specimens from 21 patients diagnosed with OSCC were used in this study. Ten patients were diagnosed with early clinical stage (I or II) and 11 patients with advanced clinical stage (III or IV) OSCC. Five patients had positive lymph node involvement. Primary antibodies for endoglin and podoplanin were used to perform the immunohistochemical detection of the vascular and lymphatic endothelial cells. The expression of endoglin and podoplanin was examined by an image analysis program in the three most highly expressed regions of each specimen. RESULTS: The average endoglin expression was observed to be 1.691+/-0.920 in the advanced stage (III, IV) specimens and 0.797+/-0.583 in the early stage (I, II) specimens (P=0.020). The average expression of podoplanin was 0.286+/-0.228 in the advance stage (III, IV) specimens and 0.374+/-0.157 in the early stage (I, II) specimens (P>0.05). There was no statistically significant difference in the expression of endoglin and podoplanin, regardless of whether or not the lymph node was positive. CONCLUSION: The expression of endoglin was significantly higher in the advanced stage specimens than that in the early stage specimens. Therefore, we concluded that endoglin is a useful molecular marker for use in the evaluation of the progression of OSCC.
Antibodies ; Carcinoma, Squamous Cell ; Endothelial Cells ; Humans ; Lymph Nodes ; Lymphangiogenesis ; Neoplasm Metastasis ; Paraffin

PURPOSE: Angiogenesis and lymphangiogenesis play important roles in the growth, progression and metastasis of colon cancer. We performed this study in order to investigate the significance of the CD31 and D2-40 expressions as prognostic factors in colon cancer. METHODS: The angiogenic and lymphagiogenic microvessel density was assessed by immunohistochemical staining of CD31 and D2-40 on samples that were resected from 66 patients with colorectal cancer. RESULTS: Strong correlation was observed between the CD31 microvessel density and being positive for having tumor emboli and lymph node metastasis (P=0.001, P=0.003). The D2-40 lymphatic vessel density was correlated with being positive for having tumor emboli (P=0.0001), the depth of invasion (P=0.0001), lymph node metastasis (P= 0.0001) and the cancer stage (P=0.0001). The D2-40 lymphatic vessel density was also correlated with the CD31 count (P=0.003). CONCLUSION: These results suggested that the CD31 and D2-40 expressions are useful predictors of lymph node metastasis and they are prognostic factors for colon cancer.
Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; Humans ; Lymph Nodes ; Lymphangiogenesis ; Lymphatic Vessels ; Microvessels* ; Neoplasm Metastasis

Lymphatic vessels are routes for leukocyte migration and fluid drainage. In addition to their passive roles in migration of leukocytes, increasing evidence indicates their active roles in immune regulation. Tissue inflammation rapidly induces lymphatic endothelial cell proliferation and chemokine production, thereby resulting in lymphangiogenesis. Furthermore, lymphatic endothelial cells induce T cell tolerance through various mechanisms. In this review, we focus on the current knowledge on how inflammatory cytokines affect lymphangiogenesis and the roles of lymphatic vessels in modulating immune responses.
Cytokines ; Drainage ; Emigration and Immigration ; Endothelial Cells ; Inflammation ; Leukocytes ; Lymphangiogenesis ; Lymphatic Vessels*

BACKGROUND: Cutaneous melanoma is a malignant neoplasm that has the tendency to metastasize through lymphatic vessels. However, the mechanism of lymphatic spread in malignant melanoma is not fully understood due to lack of lymphatic-specific markers. OBJECTIVE: The purpose of this study was to determine the intra- and peritumoral lymphatic vessel density (LVD) using a novel monoclonal antibody D2-40, and whether increased expression of lymphatic vessel correlated with malignancy grading in a series of melanocytic lesions and prognosis of malignant melanoma. METHODS: The intra- and peritumoral LVD were examined by immunohistochemistry using D2-40 antibody in a series of melanocytic lesions. RESULTS: We found significantly higher intra- and peritumoral LVD in malignant melanoma as compared with either benign melanocytic nevus, dysplastic nevus, or melanoma in situ (p<0.05), and the intratumoral LVD was significantly related to Breslow depth (p<0.05) and the development of lymphatic metastasis (p<0.05). CONCLUSION: The higher intra- and peritumoral LVD in malignant melanomas suggests that melanoma cells might promote lymphangiogenesis. In addition, our data suggests that increased lymphatics in melanoma is an independent prognostic factor and important for the development of lymphatic metastasis.
Dysplastic Nevus Syndrome ; Immunohistochemistry ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels* ; Melanoma* ; Nevus, Pigmented ; Prognosis

The lymphatic vasculature has been regarded as a passive conduit for interstitial fluid and responsible for the absorption of macromolecules such as proteins or lipids and transport of nutrients from food. However, emerging data show that the lymphatic vasculature system plays an important role in immune modulation. One of its major roles is to coordinate antigen transport and immune-cell trafficking from peripheral tissues to secondary lymphoid organs, lymph nodes. This perspective was recently updated with the notion that the interaction between lymphatic endothelial cells and leukocytes controls the immune-cell migration and immune responses by regulating lymphatic flow and various secreted molecules such as chemokines and cytokines. In this review, we introduce the lymphatic vasculature networks and genetic transgenic models for research on the lymphatic vasculature system. Next, we discuss the contribution of lymphatic endothelial cells to the control of immune-cell trafficking and to maintenance of peripheral tolerance. Finally, the physiological roles and features of the lymphatic vasculature system are further discussed regarding inflammation-induced lymphangiogenesis in a pathological condition, especially in mucosal tissues such as the gastrointestinal tract and respiratory tract.
Absorption ; Chemokines ; Cytokines ; Endothelial Cells ; Endothelium ; Extracellular Fluid ; Gastrointestinal Tract ; Leukocytes ; Lymph Nodes ; Lymphangiogenesis ; Mucous Membrane ; Peripheral Tolerance ; Respiratory System

PURPOSE: Many previous studies have suggested that cyclooxygenase-2 (COX-2) over expression is closely related to angiogenesis. However, few have reported the relationship between COX-2 and lymphangiogenesis which is still unclear. The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenetic factor, VEGF-C, in human gastric cancer and to correlate COX-2 and VEGF-C expression with other clinocopathological features to investigate whether COX-2 contributes to lymphangiogenesis and enhances lymph node metastasis. MATERIALS AND METHODS: One hundred patients who underwent curative radical surgery in Hanyang University hospital from July 1998 to June 2001 were selected. The expression of COX-2 and VEGF-C were detected by using immunohistochemistry, and the relationships between these two parameters and several clinicopathological factors (gender, stage, lymph node status, tumor location, Lauren classification and angioinvasion) were determined. RESULTS: Increased COX-2 expression was found in 86 of 100 tumor samples (86%) and in 70 of 100 tumor samples (70%) with VEGF-C. A high correlation between VEGF-C expression and lymph node metastasis was observed (P=0.033) along as well as COX-2 expression (P=0.012). Also, there was a significant correlation between COX-2 and VEGF-C expression (P=0.026), yet no correlation were found between COX-2 and VEGF-C expression and other clinicopathological parameters. CONCLUSION: Our study suggests that COX-2 expression contributes to lymphangiogenesis by mediating VEGF-C and finally promoting lymph node metastasis.
Classification ; Cyclooxygenase 2* ; Humans ; Immunohistochemistry ; Lymph Nodes* ; Lymphangiogenesis* ; Negotiating ; Neoplasm Metastasis* ; Stomach Neoplasms* ; Vascular Endothelial Growth Factor C

OBJECTIVE: Vascular endothelial growth factor(VEGF)-C is involved in lymphangiogenesis and spreading of cancer cells via lymphatic vessels. The aim of the present study is to investigate the relationship between the absence of cerebral lymphatic vessels and low metastatic rate of brain tumors. METHODS: Immunohistochemical stains were performed for VEGF-C and VEGF in surgically resected specimens from 57 patients with primary(38 cases, low grade : 10 cases, high grade : 28 cases) and metastatic(19 cases) brain tumor. RESULTS: The expression of VEGF-C was higher in metastatic carcinoma(68%) than in high-grade primary tumor(29%). There was no difference for VEGF expression between high grade brain tumor (71%) and metastatic carcinoma(58%). CONCLUSION: Low VEGF-C expression of primary brain tumors may play a role in low metastatic rate of brain tumors.
Brain Neoplasms* ; Brain* ; Coloring Agents ; Humans ; Lymphangiogenesis ; Lymphatic Vessels ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C*

OBJECTIVETo investigate the expression of CXCL12, its receptor CXCR4 and its correlations with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC).

METHODSThe tissue samples were obtained from 30 patients with PAC by surgery between January 2005 and December 2007, which including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes. The patients age ranged from 35 to 78 years old (median 57.2 years old). The expressions of CXCL12 and CXCR4 in these tissues were assayed by immunohistochemical staining, RT-PCR and fluorescence quantitative real-time PCR.

RESULTSIn the immunohistochemical staining, the CXCL12 protein mainly located in the normal pancreatic cell envelopes and/or cytolymphs. In the immunohistochemical staining, the CXCR4 protein mainly located in the cell envelopes and/or cytolymphs of PAC. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CXCR4 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lympho nodes were higher than that in the normal pancreatic tissues (P < 0.01). The MLVD in PAC were detected by morphometric analysis respectively. The level of MLVD in III-IV stages was higher than I-II stages of PAC (P < 0.01), and in these cases which had lymphatic metastasis, the level of MLVD significantly increased (P < 0.01). And there was no correlation between the differentiation and histology types of PAC (P > 0.05). There was 22 samples that the CXCR4 protein was positive, and among these samples the MLVD was higher than that in negative group of CXCR4 protein (P = 0.003).

CONCLUSIONSThe expression of CXCR4 was significantly associated with lymphatic metastasis of PAC, and the higher expression of CXCR4 in PAC tissues was significantly associated with lymphangiogenesis of PAC.

Adult ; Aged ; Chemokine CXCL12 ; metabolism ; Female ; Humans ; Lymphangiogenesis ; Lymphatic Metastasis ; Male ; Middle Aged ; Pancreatic Neoplasms ; metabolism ; pathology ; Receptors, CXCR4 ; metabolism