• BMB Reports
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• v.54 no.6
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• pp.285-294
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• 2021

The lymphatic vasculature plays important role in regulating fluid homeostasis, intestinal lipid absorption, and immune surveillance in humans. Malfunction of lymphatic vasculature leads to several human diseases. Understanding the fundamental mechanism in lymphatic vascular development not only expand our knowledge, but also provide a new therapeutic insight. Recently, Hippo-YAP/TAZ signaling pathway, a key mechanism of organ size and tissue homeostasis, has emerged as a critical player that regulate lymphatic specification, sprouting, and maturation. In this review, we discuss the mechanistic regulation and pathophysiological significant of Hippo pathway in lymphatic vascular development.

• BMB Reports
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• v.49 no.8
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• pp.403-404
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• 2016

The Wnt/β-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/β-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/β-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). β-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of β-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/β-catenin signaling is a mechanotransducer that links fluid force with lymphatic vascular development.

• Archives of Plastic Surgery
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• v.49 no.6
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• pp.773-781
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• 2022

Anatomies of the vascular and lymphatic systems have been vital research topics in reconstructive surgery. Harvey was a pioneer who provided the earliest descriptions of the cutaneous vasculature in the 17th century. The concept of vascular territories of the skin was first described by Manchot. The radiographic injection method in cadavers was developed by Salman, who defined more than 80 vascular territories. The arterial system has been thoroughly investigated with the development of regional and free flaps. The concept of axial and random pattern flaps was introduced by McGregor and Morgan. Manchot's vascular territories were refined by Taylor and Palmer as the angiosome concept. Detailed information about the venous circulation is essential for reconstructive surgeries. The concept of intrinsic and extrinsic venocutaneous vascular systems was introduced by Nakajima and led to the development of the venoadipofascial flap. The importance of venous augmentation in flap survival was emphasized by Chang. The lymphatic system was discovered much later than the arterial and venous systems. Aselli was credited for discovering the lacteal vessels in the 17th century; mercury was popularly used as a contrast agent to distinguish lymphatic vessels for the next three centuries. A radiographic method in cadavers was developed by Suami. Lymphatic imaging devices are constantly upgrading, and photoacoustic imaging was recently introduced for three-dimensional visualization of architecture of superficial layers of the lymphatic and venous systems.

• Animal Bioscience
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• v.34 no.4
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• pp.533-538
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• 2021

Objective: Pluripotent stem cell-derived lymphatic endothelial cells (LECs) show great promise in their therapeutic application in the field of regenerative medicine related to lymphatic vessels. We tested the approach of forced differentiation of mouse embryonal stem cells into LECs using biodegradable poly lactic-co-glycolic acid (PLGA) nanospheres in conjugation with growth factors (vascular endothelial growth factors [VEGF-A and VEGF-C]). Methods: We evaluated the practical use of heparin-conjugated PLGA nanoparticles (molecular weight ~15,000) in conjugation with VEGF-A/C, embryoid body (EB) formation, and LEC differentiation using immunofluorescence staining followed by quantification and quantitative real-time polymerase chain reaction analysis. Results: We showed that formation and differentiation of EB with VEGF-A/C-conjugated PLGA nanospheres, compared to direct supplementation of VEGF-A/C to the EB differentiation media, greatly improved yield of LYVE1(+) LECs. Our analyses revealed that the enhanced potential of LEC differentiation using VEGF-A/C-conjugated PLGA nanospheres was mediated by elevation of expression of the genes that are important for lymphatic vessel formation. Conclusion: Together, we not only established an improved protocol for LEC differentiation using PLGA nanospheres but also provided a platform technology for the mechanistic study of LEC development in mammals.

• Kosin Medical Journal
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• v.33 no.3
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• pp.289-296
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• 2018

Objectives: In these days, patients with stage I breast cancer have increased by regular health examination and diagnostic tool development. The aim of this retrospective study is to identify systemic recurrence related factors after breast conserving surgery (BCS) for stage I breast cancer. Methods: In this study, we analyzed the correlation between systemic recurrence and pathologic factors. We reviewed 223 patients who underwent BCS for stage I breast cancer. Postoperative pathologic factors, recurrent rates and sites were studied. In addition, preoperative patients'data were also collected. Statistical analysis was done by using PASW 16.0 (SPSS Inc., Chicago, IL, USA). Results: Systemic recurrence was found in 16 patients (7.17%) within 5 years after primary surgery. 5 patients had lymphatic invasion and 6 patients had vascular invasion. Lymphatic and vascular invasion had statistical correlation with systemic recurrence (P = 0.004, P = 0.001). Conclusions: In this retrospective study, we can conclude that vascular invasion and lymphatic invasion are related systemic recurrence after BCS for stage I patients. Further studies with large cohort will be required to fully understand the risk factors of systemic recurrence for stage I breast cancer patients.

• Korean Journal of Cleft Lip And Palate
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• v.13 no.2
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• pp.85-92
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• 2010

Vascular malformations (VMs) in the head and neck region are present at birth and grow commensurately with the child, they can result in significant cosmetic problems for the patient, and some may lead to even serious life threatening hemorrhage. Although the molecular mechanisms underlying the formation of these VMs remain unclear, lesions are known to result from abnormal development and morphogenesis. Histologically, there are no evidence of cellular proliferation, but rather progressive dilatation of abnormal channels, which VMs are designated to their prominent channel types such as capillary, venous, lymphatic, arterial, and combined malformations. VMs with an arterial component are rheologically fast-flow, whereas capillary, lymphatic, and venous components are slow-flow. In this article, we review the clinical presentations, diagnosis, and management of VMs of facial regions with author's embolization and surgical treatment cases.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7149-7153
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• 2015

Background: Inflammation plays a major role in the development and progression of gastric and other gastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy. Materials and Methods: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients with gastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. Results: In only 5 (8.8%) of the patients' sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximum concentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in one of the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen between age and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in the same population. Conclusions: It is possible that the inflammopathology of CRC and GC are rather different, at least in Fars, a southern province of Iran.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.197-207
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• 2024

The potential of tivozanib as a treatment for oral squamous cell carcinoma (OSCC) was explored in this study. We investigated the effects of tivozanib on OSCC using the Ca9-22 and CAL27 cell lines. OSCC is a highly prevalent cancer type with a significant risk of lymphatic metastasis and recurrence, which necessitates the development of innovative treatment approaches. Tivozanib, a vascular endothelial growth factor receptor inhibitor, has shown efficacy in inhibiting neovascularization in various cancer types but has not been thoroughly studied in OSCC. Our comprehensive assessment revealed that tivozanib effectively inhibited OSCC cells. This was accompanied by the suppression of Bcl-2, a reduction in matrix metalloproteinase levels, and the induction of intrinsic pathway-mediated apoptosis. Furthermore, tivozanib contributed to epithelial-to-mesenchymal transition (EMT) inhibition by increasing E-cadherin levels while decreasing N-cadherin levels. These findings highlight the substantial anticancer potential of tivozanib in OSCC and thus its promise as a therapeutic option. Beyond reducing cell viability and inducing apoptosis, the capacity of tivozanib to inhibit EMT and modulate key proteins presents the possibility of a paradigm shift in OSCC treatment.

• Advances in pediatric surgery
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• v.7 no.2
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• pp.142-146
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• 2001

Lymphangioma is a congenital malformation of the lymphatic system, commonly seen in the neck. Operation was the treatment of choice but it is difficult to resect the lymphangiomas completely. The aim of this study is to evaluate the result of intralesional injection of OK-432 as a treatment strategy of lymphangioma in children. Medical records of 51 cases of lymphangioma from March 1996 to February 2001 were reviewed retrospectively. Intralesional injection of 0.1mg OK-432 in 10ml normal saline was performed after the aspiration of as much fluid as possible. The location of the lesion was the face and neck in 26 patients, the chest wall in 14, the extremities in 9, and the abdominal wall in 2. The cystic type was present in 45 patients and the cavernous type in 6. Four postoperative recurrent cases were included. Fluid aspiration from the lesion was impossible in 5 patients. Development of fever after injection was observed in 27 patients and local inflammatory reaction was in 5 patients. There was no scar formation at injection sites. Complete shrinkage was observed in 20 patients, remarkable shrinkage in 23, slight shrinkage in 3, and no response in 5. Cystic type or aspiration-possible cases showed better outcome than cavernous type or aspiration-impossible cases. All of four recurrent cases after surgical excision showed at least remarkable shrinkage. These results indicate that intralesional injection of OK-432 is a safe and satisfactory treatment modality of lymphangiomas in children and might be considered as a treatment of choice, even in recurrent cases.