• Molecules and Cells
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• 제43권10호
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• pp.856-869
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• 2020

To elucidate the mechanism of action of HOXA11-AS in modulating the cisplatin resistance of nasopharyngeal carcinoma (NPC) cells. HOXA11-AS and miR-454-3p expression in NPC tissue and cisplatin-resistant NPC cells were measured via quantitative reverse transcriptase polymerase chain reaction. NPC parental cells (C666-1 and HNE1) and cisplatin-resistant cells (C666-1/DDP and HNE1/DDP) were transfected and divided into different groups, after which the MTT method was used to determine the inhibitory concentration 50 (IC₅₀) of cells treated with different concentrations of cisplatin. Additionally, a clone formation assay, flow cytometry and Western blotting were used to detect DDP-induced changes. Thereafter, xenograft mouse models were constructed to verify the in vitro results. Obviously elevated HOXA11-AS and reduced miR-454-3p were found in NPC tissue and cisplatin-resistant NPC cells. Compared to the control cells, cells in the si-HOXA11-AS group showed sharp decreases in cell viability and IC₅₀, and these results were reversed in the miR-454-3p inhibitor group. Furthermore, HOXA11-AS targeted miR-454-3p, which further targeted c-Met. In comparison with cells in the control group, HNE1/DDP and C666-1/DDP cells in the si-HOXA11-AS group demonstrated fewer colonies, with an increase in the apoptotic rate, while the expression levels of c-Met, p-Akt/Akt and p-mTOR/mTOR decreased. Moreover, the si-HOXA11-AS-induced enhancement in sensitivity to cisplatin was abolished by miR-454-3p inhibitor transfection. The in vivo experiment showed that DDP in combination with si-HOXA11-AS treatment could inhibit the growth of xenograft tumors. Silencing HOXA11-AS can inhibit the c-Met/AKT/mTOR pathway by specifically upregulating miR-454-3p, thus promoting cell apoptosis and enhancing the sensitivity of cisplatin-resistant NPC cells to cisplatin.

• 대한두경부종양학회지
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• 제21권1호
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8351-8359
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• 2014

Background: Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous. Materials and Methods: HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation. Results: We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status. Conclusions: Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied.

• Journal of Korean Neurosurgical Society
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• 제63권1호
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• pp.34-44
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• 2020

Objective : Despite widespread use of flow diverters (FDs) to treat aneurysms, the exact healing mechanism associated with FDs remains poorly understood. We aim to describe the healing process of aneurysms treated using FDs by demonstrating the histopathologic progression in a canine aneurysm model. Methods : Twenty-one side wall aneurysms were created in common carotid artery of eight dogs and treated with two different FDs. Angiographic follow-ups were done immediately after placement of the device, 4 weeks and 12 weeks. At last follow-up, the aneurysm and the device-implanted parent artery were harvested. Results : Histopathologic findings of aneurysms at 4 weeks follow-up showed intra-aneurysm thrombus formation in laminating fashion, and neointimal thickening at the mid-segment of aneurysm. However, there are inhomogenous findings in aneurysms treated with the same type of FD showing same angiographic outcomes. At 12 weeks, aneurysms of complete and near-complete occlusion revealed markedly shrunken aneurysm filled with organized connective tissues with thin neointima. Aneurysms of incomplete occlusion at 12 weeks showed small amount of organized thrombus around fringe neck and large empty space with thick neointmal formation. Neointimal thickness and diameter stenosis was not significantly different between the groups of FD specification and follow-up period. Conclusion : Intra-aneurysmal thrombus formation and organization seem to be an important factor for the complete occlusion of aneurysms treated using the FD. Neointimal formation could occur along the struts of the FD independently of intra-aneurysmal thrombus formation. However, neointimal formation could not solely lead to complete aneurysm healing.

• The Journal of Korean Physical Therapy
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• 제25권5호
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• pp.288-296
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• 2013

Purpose: This study was conducted in order to determine whether mechanical horseback-riding training depending on velocity can improve vestibular function and static postural balance on standing in healthy adults. Methods: For evaluation of vestibular function, electrooculography (EOG) of vertical and horizontal was performed for identification of the motion of eyes. For evaluation of static postural balance, COP distance, time spent on the sharpened Romberg test with neck extension (SRNE) were measured. Measurements were performed three times before training, three weeks after training, and six weeks after training. Participants were randomly assigned to three groups: fast velocity-mechanical horse -riding training (FV-MHRT, n=12), moderate velocity-mechanical horse-riding training (MV-MHRT, n=12), and slow velocity-mechanical horse-riding training (SV-MHRT, n=12). Results: According to the result for vertical, horizontal EOG, there was significant interaction in each group in accordance with the experiment time (p<0.05). The FV-MHRT group showed a significant decrease compared with the MV- MHRT, SV-MHRT groups (p<0.05). According to the result for static postural balance, the time spent, COP distance in SRNE showed significant interaction in each group in accordance with the experiment time (p<0.05). The time spent on the SRNE showed a significant increas in FV-MHRT, SV-MHRT (p<0.05). The COP distance of SRNE showed a significant increase in MV-MHRT (p<0.05). Conclusion: The MHRT velocity activated mechanism of vestibular spinal reflex (VSR), vestibular ocular reflex (VOR), also helped to strengthen vestibular function and static postural balance. In addition, it should be applied to different velocity of MHRT according to the specific purpose.

• Archives of Plastic Surgery
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• 제43권2호
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• pp.134-144
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• 2016

In adults, mallet finger is a traumatic zone I lesion of the extensor tendon with either tendon rupture or bony avulsion at the base of the distal phalanx. High-energy mechanisms of injury generally occur in young men, whereas lower energy mechanisms are observed in elderly women. The mechanism of injury is an axial load applied to a straight digit tip, which is then followed by passive extreme distal interphalangeal joint (DIPJ) hyperextension or hyperflexion. Mallet finger is diagnosed clinically, but an X-ray should always be performed. Tubiana's classification takes into account the size of the bony articular fragment and DIPJ subluxation. We propose to stage subluxated fractures as stage III if the subluxation is reducible with a splint and as stage IV if not. Left untreated, mallet finger becomes chronic and leads to a swan-neck deformity and DIPJ osteoarthritis. The goal of treatment is to restore active DIPJ extension. The results of a six- to eight-week conservative course of treatment with a DIPJ splint in slight hyperextension for tendon lesions or straight for bony avulsions depends on patient compliance. Surgical treatments vary in terms of the approach, the reduction technique, and the means of fixation. The risks involved are stiffness, septic arthritis, and osteoarthritis. Given the lack of consensus regarding indications for treatment, we propose to treat all cases of mallet finger with a dorsal glued splint except for stage IV mallet finger, which we treat with extra-articular pinning.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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• pp.313-317
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• 2004

The present study were designed to characterize the action mechanisms of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries precontracted with high $K^+$(70 mM). For this, we simultaneously measured both muscle tension and cytosolic free $Ca^{2+}$ concentration $([Ca^{2+}]_i)$, using fura-2, in endothelium-intact, rabbit carotid arterial strips. In the artery with endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension whereas ACh $(10{\mu}M)$ significantly relaxed the muscle and increased $[Ca^{2+}]_i$. In the presence of $N^G$-nitro-L-arginine (L-NAME, 0.1 mM), ACh increased $[Ca^{2+}]_i$ without relaxing the muscle. In the artery without endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension although ACh was ineffective. 4-DAMP (10 nM) or atropine $(0.1{\mu}M)$ abolished ACh-induced increase in $[Ca^{2+}]_i$ and relaxation. The increase of $[Ca^{2+}]_i$ and vasorelaxation by ACh was siginificantly reduced by either $3{\mu}M$ gadolinium, $10{\mu}M$ lanthanum, or by $10{\mu}M$ SKF 96365. These results suggest that in rabbit carotid artery, ACh-evoked relaxation of 70 mM $K^+$-induced contractions appears to be mediated by the release of NO. ACh-evoked vasorelaxation is mediated via the $M_3$ subtype, and activation of the $M_3$ subtype is suggested to stimulate nonselective cation channels, leading to increase of $[Ca^{2+}]_i$ in endothelial cells.

• 한국정보처리학회논문지
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• 제5권10호
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• pp.2686-2703
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• 1998

프로세서 메모리 혼합 구조는 해마다 증가하는 프로세서와 메모리간의 성능 격차를 해결하는 대안으로 연구가 활발히 진행되고 있다. 본 논문에서는 프로세서 메모리 혼합 구조의 여러 가지 설계 대안들을 고찰하였다. 이를 위해서 DRAM 접근 시간의 분석적 모델을 제안하고 성능 향상점 및 성능 병목점을 찾았다. 제안한 분석적 모델에 의하여 DRAM 페이지 적중률을 증대하여 성능을 향상시키는 구조로써 새로운 온칩 DRAM 구조인 프리차지 연기 뱅크 아키텍쳐를 제안하였다. 또한 제안한 뱅크 아키텍쳐에 효율적으로 적용할 수 있는 뱅크 인터리빙 방법을 제시하였다. 제안한 구조는 기존의 일반적 DRAM 구조 및 계층적 다중-뱅크 구조보다 우수함을 시뮬레이션을 통하여 증명하였다. 시뮬레이션은 SimpleScalar 툴을 개조하여 사용하였고, SPEC95 벤치마크에 대해서, 캐쉬 메모리의 크기, 뱅크 개수, 프리차지 연기 시간 등의 변화에 대한 성능을 분석하였다.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.72-80
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• 2020

Purpose: Proximal gastrectomy (PG) is a function-preserving surgery in cases of proximally located early-stage gastric cancer. Because gastroesophageal reflux is a major pitfall of this operation, we devised a modified esophagogastrostomy (EG) anastomosis to fix the distal part of the posterior esophageal wall to the proximal part of the anterior stomach wall to produce an anti-reflux mechanism; we named this the SPADE operation. This study aimed to show demonstrate the clinical outcomes of the SPADE operation and compare them to those of previous PG cases. Materials and Methods: Case details of 56 patients who underwent PG between January 2012 and March 2018 were retrospectively reviewed: 30 underwent conventional esophagogastrostomy (CEG) anastomosis using a circular stapler, while 26 underwent the SPADE operation. Early postoperative clinical outcome-related reflux symptoms, endoscopic findings, and postoperative complications were compared in this case-control study. Results: Follow-up endoscopy showed more frequent reflux esophagitis cases in the CEG group than in the SPADE group (30% vs. 15.3%, P=0.19). Similarly, bile reflux (26.7% vs. 7.7%, P=0.08) and residual food (P=0.01) cases occurred more frequently in the CEG group than in the SPADE group. In the CEG group, 13 patients (43.3%) had mild reflux symptoms, while 3 patients (10%) had severe reflux symptoms. In the SPADE group, 3 patients (11.5%) had mild reflux symptoms, while 1 had severe reflux symptoms (absolute difference, 31.8%; 95% confidence interval, 1.11-29.64; P=0.01). Conclusions: A novel modified EG, the SPADE operation, has the potential to decrease gastroesophageal reflux following a PG.

• 대한의생명과학회지
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• 제20권2호
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• pp.85-95
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• 2014

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the head and neck tumors. To investigate the mechanism of antiproliferation to EGFR inhibition in oral cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$). We have demonstrated that ZD1839 induces growth arrest and apotosis in oral cancer cell lines by independent of EGFR-mediated signaling. An exposure of oral cancer cells to ZD1839 resulted in a dose dependent up-regulation of the cyclin-dependent kinase inhibitor p21 and p27, down regulation of cyclin D1, inactivation of GSK-$3{\beta}$ and of active MAPK. In resistant cells, GSK-$3{\beta}$ is constitutively active and its activity is negatively regulated primarily through Ser 9 phosphorylation and further enhanced by Tyr216 phosphorylation. These results showed that the resistance to the antiproliferative effects of ZD1839, in vitro was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-$3{\beta}$ activation and degradation of its target cyclin D1 were indicators of high cell sensitivity to ZD1839. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in oral cancer.