• Archives of Plastic Surgery
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• 제36권1호
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• pp.1-10
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• 2009

Purpose: Partial necrosis of skin flaps remains a substantial problem in reconstructive surgery. We investigated the potential use of an adenovirus vector encoding the VEGF, COMP-angiopoietin-1 gene in an attempt to promote the viability of the inferior epigastric artery flap in a rat model. Methods: Three by six cm lower abdominal transverse skin flaps, supplied only by the left inferior epigastric artery, were designed. After skin flap elevation, the adenovirus VEGF and adenovirus COMP-angiopoietin-1 were injected into the distal portion of the flap, which has a high tendency of developing flap ischemia. Control animals were injected with the same volume of normal saline. On 3, 7 and 14 days after the flap elevation, the flap survival and vascularization were assessed using Visitrak digital$^{(R)}$, CD31 immunohistochemistry in addition to evaluating the general histological characteristics. Results: There was a significant increase in the mean percentage of flap viability by 89.8%, 91.1% and 94.8% in flaps transfected with adenovirus VEGF, COMP-angiopoietin-1, coadministraion of VEGF and COMP-angiopoietin-1 at seven days, and by 95.6%, 94.8% and 96.3% at 14 days. Histological assessment revealed that there were more blood vessels formed after adenovirus with VEGF, COMP-angiopoietin-1 or VEGF plus COMP-angiopoietin-1 than with adenovirus Lac Z. Conclusion: The results of this study suggest that adenovirus-mediated VEGF, COMP-angiopoietin-1 gene therapy, promote therapeutic angiogenesis in patients that undergo reconstructive procedures.

• Biomolecules & Therapeutics
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• 제26권5호
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• pp.464-473
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• 2018

Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

• Archives of Reconstructive Microsurgery
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• 제16권2호
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• pp.57-62
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• 2007

Non-vascularized free composite graft is one of the simple and effective reconstructive options, but its clinical use has been limited due to questionable survival rate. Early vascularization is essential for graft survival and is mainly carried out via recipient bed or repaired sites. This study was designed to investigate the effect of the lateral marginal approximations on the survival of the free composite flap using a model of skin-subcutaneous composite graft in rats. Thirty 1.5 ${\times}$ 1.5 $cm^2$ sized square shape composite flaps were elevated freely and reposed in place immediately on the dorsum of five Sprague-Dawley rats, and divided into five groups of six flaps. In all groups, graft bed was isolated with silastic sheet. In the group I, all sides of flap were repaired with blockage of silastic sheet insertion. Three, two, and one sides of flap were treated with same method in the group II, III, and IV respectively. Other sides of flaps were repaired without blockage, so all sides of flap were repaired in the group V. At 14 days later, the survived rate of each flap was evaluated according to the numbers of the repair sites. Histological examination was done for the evaluation of new vessel development quantitatively. Overall survived rates were increased with the number of repaired sites, but the group V only showed increased survival rate up to more than fifty percentile of the flap size with a significant difference statistically. New vessels were also increased in proportion with the number of repaired sites, and the repair site more than two had significant effect on the increased number of new vessels. In conclusion, at least more than three-fourth of flap circumference should be repaired in order to increase flap survival effectively under the condition of bed isolation.

• 대한두경부종양학회지
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• 제14권2호
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• pp.191-198
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• 1998

Objectives: We performed an immunohistochemical study to examine the place of neovascularization in the tumorigenic process of follicular thyroid carcinoma and to determine whether tumor angiogenic activity in follicular carcinoma plays a role in tumor aggression. Materials & Methods: We studied 63 follicular thyroid carcinomas and compared with 22 follicular adenomas. The areas of capsular invasion, vascular invasion and cellular atypism of the tumor were confimed on H & E stains. The paraffin embedded tissues were stained by the use of monoclonal antibodies against Ag CD34. Microvesseles were counted in the area of highest vascular density at 200 times magnification. The microvessel densities(MVD) were analized in relation to histologic type and location of the tumors. Results: There were 59 minimal invasive types and 4 widely invasive types of carcinoma. In the histologic specimens of carcinomas, capsular invasion was identified in all the cases, vascular invasion in 46 and cellular atypism in 24. Mean values of the MVDs of the minimal invasive carcinomas, the widely invasive carcinomas and the adenomas were $263.8{\pm}69.2,\;256.l{\pm}49.3\;and\;241.5{\pm}159.4$, respectively and there was no significant difference between each group. In follicular carcinomas, there was a regional difference of the MVDs. The areas of tumor showing cellular atypism and adjacent to or penetrating the capsule, in which represents the tumorigenic process of carcinoma, had a higher rate of vascularization, than other areas of the tumor(p<0.05). However, these features were not noted in the follicular adenomas. Conclusion: Although there was no significant difference of the MVD between follicular carcinomas and adenomas, there was a regional difference of the MVD within the carcinomas and the values were significantly higher in the more malignant areas, as indicated by cellular atypism and capsular invasion. Therefore, tumor angiogenic activity measured by MVD may play a role in tumor aggression in follicular thyroid carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제46권4호
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• pp.266-274
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• 2020

Objectives: Melatonin induces human stem cells, converts pre-osteoblasts to mature osteoblasts, and reduces the duration of this transition. However, melatonin itself prevents activation of osteoclasts. Here, we evaluate the role of melatonin in prevention of bisphosphonate-related osteonecrosis of the jaw. Materials and Methods: In this experimental-interventional study, 30 rats were evaluated in 3 groups. The first and second groups received saline and zoledronic acid, respectively, for 4 weeks and the third group received 4 weeks of zoledronic acid and 3 weeks of melatonin simultaneously. First-right-maxillary-molar extraction was performed for all animals, which were sacrificed after 4 weeks of recovery. The extraction sockets were examined histologically for the presence of osteonecrosis, number of osteoclasts and fibroblasts, severity of inflammation, and vascularization. Data were analyzed by chi-square, one-way ANOVA, Tukey, Kruskal-Wallis and Fisher's exact statistical tests (α=0.05). Results: Osteonecrosis was observed in 20%, 90%, and 70% of the first, second and third groups, respectively (P=0.008). The lowest number of osteoclasts and fibroblasts was seen in the third group. Conclusion: Melatonin may effectively prevent some undesirable side effects of bisphosphonates. However, further studies are required to confirm the results of this study.

• 한국임상수의학회지
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• 제25권5호
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• pp.424-428
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• 2008

A 10-year-old castrated male Schnauzer (case 1) and a 13-year-old intact male Schnauzer (case 2) was referred with mass of left hind limb. We performed hemogram, serum chemistry, radiography, ultrasonography, computed tomography, fine needle aspiration and histopathology. The complete blood counts and serum biochemistry results were within the reference range. Radiography showed cutaneous mass with soft tissue density. The lesions of two dogs were revealed a definite marginated hyperechoic mass with vascularization in ultrasonography. Computed tomography showed an isodense mass in the left hind limb region with minimal contrast enhancing in case 1 and heterogenous enhancement in case 2. Cytology from ultrasonographic guided aspiration of the mass was suspected fibrous tissue-derived benign cell in two dogs. A surgical excision was performed in two dogs. In histological examination of the resected mass, cutaneous fibroma was revealed. The two patients were successfully treated by surgery and postoperative care. This report decribes and compares radiographic, ultrasonographic, computed tomographic, cytologic and histopathologic features of the cutaneous fibroma of two schnauzer dogs.

• Journal of Gastric Cancer
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• 제4권2호
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• pp.121-125
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• 2004

Purpose: Esophagojejunal anastomotic complications after a total gastrectomy include leakage, stenosis, bleeding, and abscess formation. Especially, the mortality rate for esophagojejunal anastomotic leakage is $80\%$. Although these complications hare been reduced by the usage of the EEA stapler, they are still serious and depend on various factors: the surgeon's experience, the stage of disease, the extent of surgical intervention, the method of operation, and the patient. Some local factors, such as vascularization of the graft, traction on the anastomosis suture line, and local infections, have been implicated as contributing to these complications. Materials and Methods: During the period $1995\∼2003$, of the 850 gastrectomies for gastric carcinomas, 171 were intra-abdominal total gastrectomies. All of these 171 operations were performed by one surgeon using a routine D2 lymph-node dissection and a 25-mm EEA stapler on an antecolic end-to-side esophagojejunostomy. In the 77 cases a seromuscular reinforced suture at the esophagojejunostomy site was performed, and in 94 cases, a whole layer reinforced suture with absorbible materials was used. We evaluated the incidence of complications according to age, sex, stage of patients, and combined resection. Also, we compared the incidences of complications for seromuscular and whole layer reinforced sutures. Results: The complications are major leaks ($2.9\%$), minor leaks ($3.5\%$), stenosis, bleeding ($1.8\%$), and abscess formation formation ($1.8\%$). In the five cases of major leaks, there were four mortalities with operative methods. The other patients with stenosis, bleeding, and abscess formation were treated conservatively with success. The incidences of complications were not related with age, sex, stages, and combined resection. The incidences of complications for the whole layer reinforced suture group ($2.9\%$) were less than those for the seromuscular reinforced group ($8.8\%$, P=0.04). Conclusion: The most serious complication of esophagojejunal anastomosis is major leakage with an $80\%$ mortality. The other complications are stenosis, bleeding, and abscess formation, for which no mortalities occurred during this study. Whole layer suture of the esophagojejunal anastomotic site is an important method for preventing leakage.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.32.1-32.8
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• 2018

Background: The free vascularized fibula flap presents many advantages such as sufficient length of the bony segment, good vascularization, better quality of the bone, and a long vascular pedicle, but it is also associated with some disadvantages with regard to prosthetic rehabilitation because of its limited height. Improvement in bone height is necessary for ideal dental implant treatment of reconstructed mandibles. Case presentation: For two squamous cell carcinoma patients, mandibular bone reconstruction was performed secondarily with the peroneal flap after tumor resection. Since the bone height was insufficient at the time of implant treatment, occlusion reconstruction by dental implant was performed after vertical distraction osteogenesis. Conclusions: Vertical distraction osteogenesis is a suitable treatment option for alveolar ridge deficiency resulting from fibula transplantation for mandibular reconstruction following tumor surgery.

• Molecules and Cells
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• 제43권9호
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• pp.763-773
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• 2020

Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

• Journal of Yeungnam Medical Science
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• 제35권1호
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• pp.130-134
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• 2018

Heterotopic ossification (HO) around the hip joint is not uncommon following neurological injury. Often, surgical treatment is performed in patients with restricted motion and/or refractory pain due to grade III or IV HO according to Brooker classification. The major complication that occurs as a result of surgical HO removal is perioperative bleeding due to hyper-vascularization of the lesion. Here, we report a case of preoperative embolization in a 51-year-old male patient presenting with restricted bilateral hip range of motion (ROM) due to HO following a spinal cord injury. In the right hip without preoperative arterial embolization, massive bleeding occurred during surgical removal of HO. Thus, the patient received a transfusion postoperatively due to decreased serum hemoglobin levels. For surgery of the left hip, preoperative embolization of the arteries supplying HO was performed. Surgical treatment was completed without bleeding complications, and the patient recovered without a postoperative transfusion. This case highlights that, while completing surgical removal for ROM improvements, orthopedic surgeons should consider preoperative arterial embolization in patients with hip HO.