• Journal of Gastric Cancer
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• v.6 no.4
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• pp.284-290
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• 2006

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.

• Journal of Life Science
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• v.34 no.2
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• pp.128-137
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• 2024

This review discusses the pivotal role of vascular endothelial growth factors (VEGF) in angiogenesis and lymphangiogenesis, vital processes influencing vascular permeability, endothelial cell recruitment, and the maintenance of tumor-associated blood and lymphatic vessels. VEGF exerts its effects through tyrosine-kinase receptors, VEGFR-1, VEGFR-2, and VEGFR-3. This VEGF-VEGFR system is central not only to cancer but also to diseases arising from abnormal blood vessel and lymphatic vessel formation. In the context of cancer, VEGF and its receptors are essential for the development of tumor-associated vessels, making them attractive targets for therapeutic intervention. Various approaches, such as anti-VEGF antibodies, receptor antagonists, and VEGF receptor function inhibitors, are being explored to interfere with tumor growth. However, the clinical efficacy of anti-angiogenic agents remains uncertain and necessitates further refinement. The article also highlights the physiological role of VEGFs, emphasizing their involvement in endothelial cell functions, survival, and vascular permeability. The identification of five distinct VEGFs in humans (VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF) is discussed, along with the classification of VEGFRs as typical receptor tyrosine kinases with distinct signaling systems. The family includes VEGFR-1 and VEGFR-2, crucial in tumor biology and angiogenesis, and VEGFR-3, specifically involved in lymphangiogenesis. Overall, this review has provided a comprehensive overview of VEGF and VEGFR, detailing their roles in various diseases, including cancer. This is expected to further facilitate the utilization of VEGF and VEGFR as therapeutic targets.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1172-1178
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• 2008

Purpose : Congenital chylothorax is an accumulation of lymphatic fluid within the pleural space. It is a common cause of unidentified hydrops fetalis. We examined the perinatal history, clinical manifestation, diagnosis, treatment, and outcome in 6 newborns diagnosed to have congenital chylothorax with hydrops fetalis. We also studied the effect of octreotide therapy for congenital chylothorax in relation to conservative treatment. Methods : We retrospectively reviewed the medical records of 6 patients diagnosed to have congenital chylothorax with hydrops fetalis among 27,907 newborns who were born at the Cheil General Hospital and Womens Healthcare Center between January 2004 and July 2007. The diagnosis of chylothorax is based on the analysis of pleural fluid before and after milk feeding. Results : Incidence of congenital chylothorax in this study was 0.021%. All 6 cases were noted in over the 92% lymphocyte in pleural analysis. Transudate was changed into chyle with increasing triglyceride levels above 200 mg/dL after milk feeding. Three of 6 infants improved with conservative treatment, including thoracostomy and assisted ventilation. The others had persistent symptoms despite conservative treatment and responded to octreotide therapy. A complication, specifically vomiting was noted in 1 case during octreotide therapy. Conclusion : In this study, octreotide therapy resulted in a safe and excellent outcome. Therefore, octreotide therapy is considered in severe refractory congenital chylothorax in conservative treatment. Further studies are required to determine appropriate guidelines for octreotide therapy.

• Journal of the Korean Society of Radiology
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• v.81 no.5
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• pp.1260-1265
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• 2020

Kaposi's sarcoma (KS) is a multicentric human immunodeficiency virus-associated neoplasm characterized by multiple vascular nodules in the skin, mucous membranes, and viscera. Gastrointestinal acquired immunodeficiency syndrome (AIDS)-related KS is the most common visceral involvement reported in disseminated disease. Here, we present the findings of a rare case of KS involving multiple organs with abdominal pain and active bleeding in the colon. Multiple intraluminal lesions were found in the terminal ileum, sigmoid colon, and rectum by ileocolonoscopy, and in the jejunum and ileum by fluoroscopy. Abdominopelvic CT revealed multiple enhanced flat lesions in the ileum and enlarged lymph nodes. The diagnosis was confirmed by histopathology, and antiretroviral therapy was initiated as the treatment of choice for KS. Owing to the increasing number of AIDS patients, it is essential for radiologists and clinicians to be aware of the imaging characteristics of KS to protect physicians from indiscriminate exposure to AIDS.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.201-210
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• 2000

Purpose : We observed response to PPD skin test and local side reactions among subjects who received inoculation with Tokyo 172 BCG strain by percutaneous method using multiple puncture device. Methods : 138 infants and young children were enrolled at Yongdong Severance Hospital and 7 private clinics. 5TU PPD skin test were performed at 4 months after inoculation. The local reactions at multiple puncture site were observed in 3 days, 4~6 weeks, 36 weeks, and 48 weeks after inoculations and physical check up was done for evaluation of lymphadenopathy. Results : During 48 weeks of observation period, 96 subjects among 138 who were enrolled were followed up completely with records of PPD skin test and observation of local side reactions, presenting with the photos. The size of the induration after 48 hours of PPD skin test, was less than 5mm in six subjects(6.3%), greater than 10mm in sixty seven subjects(70.0%) and greater than 12mm in forty six subjects(47.9%). All subjects showed inflammatory reaction and pustules at multiple puncture sites and only just small papules, ulcer and pustules remained 4-6 weeks later. Eight to twelve weeks later, all local inflammatory skin reactions disappeared with remaining crust. After 48 weeks, 4(4.2%) subjects showed no scar with only faint stain on the puncture site. More than 70% of subjects showed more than 10 faint pin-point scars on the sites. However, the size of scar was clearly smaller compared to that of intradermal inoculation. There were no cases of lymphadenopathy. Conclusion : We observed good immune response to 5TU PPD skin test among the infant and young children who were immunized with percutanous inoculation of Tokyo 172 BCG strain. We could not find any severe local scar at inoculation sites. A degree of satisfaction of the parents whose children received the percutaneous injection was very high.