• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권3호
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• pp.209-215
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• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• 한국수산과학회지
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• 제28권1호
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• pp.114-122
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• 1995

B 세포가 다양화되어 가는 기작을 규명한다는 것은 면역 반응의 조절이 생체 내에서 어떻게 이루어지고 있는 가를 이해하는데 가장 기본이 되는 것이다. 본 연구는 기 확립한 in situ hybridization 기법을 이용하여 항체의 항원 결합 부위 유전자가 B 세포의 발달 과정 중 어떻게 조절이 되고 있으며 이것은 B 세포의 다양화라는 측면과 어떻게 연관이 되어 있는 지를 분석하였다. Gestation 시기가 16일, 18일, 19일, 20일 되었을 때간에 있는 B 세포는 $V_H7183$와 $V_HQ52$두개의 $V_H$ 유전자군을 가장 많이 이용하고 있었으며 이러한 경향은 gestation 기간 전체를 통하여 변화 없이 일정하게 나타났다. 간에 있는 fetal B 세포를 differentiation 단계별로 구분하기 위하여 표면 항체를 갖고 있는 집단과, 갖고 있지 않은 두 집단으로 나눈 후 각 집단이 발현하는 $V_H$ 유전자를 분석하였을 때 뚜렷한 차이를 나타냄이 없이 양쪽 집단 모두 fetus의 특징적 $V_H$ 이용양식을 보여주었다. 또 다른 조혈 기능 임파 기관인 fetal spleen에 있는 B 세포 또한 fetal liver의 B 세포와 동일한 양상의 $V_H$ 유전자 이용 양식을 보여 주어 각 임파 기관별 B 세포의 다양성 차이를 발견 할 수 없었다. 이와 같이 adult의 B 세포에 대비하여 독특한 $V_H$ 유전자 이용 양상을 보이는 fetal B 세포의 전구 세포를 4주 이상 미리 형성시킨 adult 골수 세포와 직접 접촉시키면서 발달, 성숙시킨 후 다시 나타난 B 세포를 분석하여도 여전히 fetal B 세포로서의 $V_H$ 유전자 이용 양상을 보이는 것은 fetal B세포의 전구 세포가 갖고 있는 유전적 잠재력에 의한 것이지 환경이나 B 세포의 differentiation 단계 또는 B 세포가 머무르고 있는 특수 임파 장기의 생리적 환경 등에 좌우되는 것이 아니라는 것이 확인되었다.

• 대한약리학회지
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• 제24권1호
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• pp.43-52
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• 1988

국소마취제의 약리학적 작용기전을 탐구키 위하여 소의 신선한 대뇌피질로부터 synaptosomal plasma membrane vesicles(SPMV)를 분리한 후 그 소수성 중심부의 microviscosity에 미치는 국소마취제의 영향을 pyrene 형광 probe법으로 측정한 결과 lidocaine HCI과 procaine HCI이 microviscosity를 낮춘다는 것을 알았고 그 정도는 procaine HCI에 비하여 tidocaine.HCI이 더욱 컸다. 또 국소마취 제 가 dimyristoylphosphatidylcholine (DMPC) multilamellar liposomes의 상전 이온도를 낮추며 cooperative unit크기를 감소시킨다는 것도 시차 열량분석법으로 알게 되었다. 상전이온도와 cooperative unit 크기의 감소 정도는 dibucaine HCI>tetracaine HCI>lidocaine HCI > procaine HCI의 순이었다.

• Journal of Korean Neurosurgical Society
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• 제61권5호
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• pp.592-599
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• 2018

Objective : Metastatic brain tumors (MBTs) often present with intracerebral hemorrhage. Although Gamma Knife surgery (GKS) is a valid treatment option for hemorrhagic MBTs, its efficacy is unclear. To achieve oncologic control and reduce radiation toxicity, we used a radiosurgical targeting technique that confines the tumor core within the hematoma when performing GKS in patients with such tumors. We reviewed our experience in this endeavor, focusing on local tumor control and treatment-associated morbidities. Methods : From 2007 to 2014, 13 patients with hemorrhagic MBTs were treated via GKS using our targeting technique. The median marginal dose prescribed was 23 Gy (range, 20-25). GKS was performed approximately 2 weeks after tumor bleeding to allow the patient's condition to stabilize. Results : The primary sites of the MBTs included the liver (n=7), lung (n=2), kidney (n=1), and stomach (n=1); in two cases, the primary tumor was a melanoma. The mean tumor volume was $4.00cm^3$ (range, 0.74-11.0). The mean overall survival duration after GKS was 12.5 months (range, 3-29), and three patients are still alive at the time of the review. The local tumor control rate was 92% (tumor disappearance 23%, tumor regression 46%, and stable disease 23%). There was one (8%) instance of local recurrence, which occurred 11 months after GKS in the solid portion of the tumor. No GKS-related complications were observed. Conclusion : Our experience shows that GKS performed in conjunction with our targeting technique safely and effectively treats hemorrhagic MBTs. The success of this technique may reflect the presence of scattered metastatic tumor cells in the hematoma that do not proliferate owing to the inadequate microenvironment of the hematoma. We suggest that GKS can be a useful treatment option for patients with hemorrhagic MBTs that are not amenable to surgery.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2953-2958
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• 2015

Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. In addition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia on TXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained. Evaluation of TXNIP and hypoxia inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$) protein expression in FFPE samples was made by immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated a significantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level was also identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with $HIF-1{\alpha}$ expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumor cell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression in NSCLC and high TXNIP expression could be a poor prognostic marker.

• International Journal of Oral Biology
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• 제30권1호
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• pp.23-30
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• 2005

Bone remodeling is a process controlled by the action of two major bone cells; the bone forming osteoblast and the bone resorbing osteoclast. In the process of osteoclastogenesis, stromal cells and osteoblast produce RANKL, OPG, and M-CSF, which in turn regulate the osteoclastogenesis. During the bone resorption by activated osteoclasts, extracellular $Ca^{2+}/{PO_4}^{2-}$ concentration and degraded organic materials goes up, providing the hypertonic microenvironment. In this study, we tested the effects of hypertonicity due to the degraded organic materials on osteoclastogenesis in co-culture system. It was examined the cellular response of osteoblastic cell in terms of osteoclastogenesis by applying the sucrose, and mannitol, as a substitute of degraded organic materials to co-culture system. Apart from the sucrose, mannitol, and NaCl was tested to be compared to the effect of organic osmotic particles. The addition of sucrose and mannitol (25, 50, 100, 150, or 200 mM) to co-culture medium inhibited the number of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells induced by 10 nM $1{\alpha},25(OH)_2vitaminD_3$ ($1{\alpha},25(OH)_2D_3$). However, NaCl did exert harmful effect upon the cells in this co-culture system, which is attributed to DNA damage in high concentration of NaCl. To further investigate the mechanism by which hypertonicity inhibits $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis, the mRNA expressions of receptor activator of nuclear factor (NF)-kB ligand (RANKL) and osteoprotegerin (OPG) were monitored by RT-PCR. In the presence of sucrose (50 mM), RANKL mRNA expression was decreased in a dose-dependent manner, while the change in OPG and M-CSF mRNA were not occurred in significantly. The RANKL mRNA expression was inhibited for 48 hours in the presence of sucrose (50 mM), but such a decrement recovered after 72 hours. However, there were no considerable changes in the expression of OPG and M-CSF mRNA. Conclusively, these findings strongly suggest that hypertonic stress down-regulates $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis via RANKL signal pathway in osteoblastic cell, and may playa pivotal role as a regulator that modulates osteoclastogenesis.

• 생명과학회지
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• 제28권1호
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• pp.116-129
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• 2018

생물체는 스트레스에 대처하기 위한 항상성 유지 기작을 가지고 있으나, 만성적이고 반복적인 스트레스는 카테콜아민과 같은 스트레스 호르몬의 과도한 방출로 인해 인체에 해로운 영향을 미친다. 교감신경계와 암과의 관련성을 분석하는 연구는 스트레스가 암을 악화시킬 수 있다는 오랜 가설을 바탕으로 이루어졌다. 다수의 전임상연구와 역학 연구결과는 교감신경계의 주요 신호전달경로인 ${\beta}$-adrenergic signaling을 조절하는 것이 암의 진행을 억제할 수 있음을 보여주고 있다. 교감신경계의 활성화는 암세포의 oncogene과 DNA repair 유전자 조절, 생존과 사멸 조절, EMT 및 전이 조절, 면역계와 혈관신생 조절, 세포외기질과 간엽세포 조절, 지방세포 조절 등을 통해 암세포와 종양미세환경에 광범위하게 영향을 미칠 수 있다. 오늘날 암의 성장과 관련된 분자적 기전을 차단하는 표적항암치료가 각광받고 있으나, 보상경로의 활성화와 항암제 내성 출현 및 여러 부작용으로 말미암아 임상적 실패를 거듭하면서 암의 생병리를 다방면에서 조절하는 전략이 새로운 치료법으로 대두되고 있다. 본 총설에서는 이러한 암의 전신적 조절인자로서 교감신경계가 암의 형성과 발전에 미치는 영향을 요약하고, 향후 새로운 암 치료전략으로서 ${\beta}$-adrenergic signaling을 조절하는 약물의 임상적 활용가능성에 대해 논의하고자 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4031-4036
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• 2012

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

• 대한화장품학회지
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• 제45권4호
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• pp.415-422
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• 2019

피부 기저막에 위치하고 있는 인간 상피 줄기 세포는 피부상피층의 항상성 유지에 중요한 역할을 담당하고 있다. 비록 상피 줄기 세포가 조직손상에 대한 반응으로 상처 회복에 필요한 새로운 세포들을 공급하고 있지만 일부 세포는 정지 상태로 남아 생존을 위해 분화와 노화로부터 보호된다. 이러한 관점에서 적소세포와 외부세포기질 단백질로 구성된 특정 미세환경인 줄기세포 적소는 줄기세포를 보호하기 위해 적절한 자극을 제공해 준다. 줄기세포 마커는 상피 줄기세포의 표면에 발현되며, 기저막의 세포외기질과 부착하여 장기간의 성장 잠재력을 가지며 외부 자극에 대한 세포 사멸의 저항성을 가진다. 본 연구에서는 외부자극의 주요 인자로써 자외선 조사가 인테그린 α2, β1 와 α6 의 발현을 저하시킴을 확인하였으며 붉나무 추출물이 자외선에 의해 유도되어지는 인테그린 발현 저하를 억제하는 것을 확인 할 수 있었다. 또한 붉나무 추출물은 콜라겐 IV와 라미닌과 같은 상피 줄기세포의 부착과 연관된 분자들의 발현을 상향조절 하였다. 이러한 결과는 붉나무 추출물이 줄기세포 표면의 인테그린의 발현을 증가시키고 적소에서의 세포외기질 성분의 발현을 증가시킴으로써 자외선 조사에 대한 보호효과가 있음을 확인하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권9호
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• pp.1239-1246
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• 2016

The breeding of yaks is highly seasonal, there are many crucial proteins involved in the reproduction control program, especially in follicular development. In order to isolate differential proteins between mature and immature follicular fluid (FF) of yak, the FF from yak follicles with different sizes were sampled respectively, and two-dimensional gel electrophoresis (2-DE) of the proteins was carried out. After silver staining, the Image Master 2D platinum software was used for protein analysis and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was performed for differential protein identification. The expression level of transferrin and enolase superfamily member 1 (ENOSF1) was determined by Western blotting for verification analysis. The results showed that 2-DE obtained an electrophoresis map of proteins from mature and immature yak FF with high resolution and repeatability. A comparison of protein profiles identified 12 differently expressed proteins, out of which 10 of them were upregulated while 2 were downregulated. Western blotting showed that the expression of transferrin and ENOSF1 was enhanced with follicular development. Both the obtained protein profiles and the differently expressed proteins identified in this study provided experimental data related to follicular development during yak breeding seasons. This study also laid the foundation for understanding the microenvironment during oocyte development.