• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5165-5169
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• 2013

Background: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. Materials and Methods: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. Results: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). Conclusions: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권1호
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• pp.1-8
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• 2005

This study was aimed to characterize osteogenic potential of rat bone marrow stromal cells (BMSC) isolated with standard flushing method and investigate the plasticity of transdifferentiation between osteoblastic and adipocytic lineage of cultured BMSC. Unlike aspiration method in human, rat bone marrow was extracted by means of irrigation with culture media that elevates the possibility of co-extraction of committed osteoprogenitor, or preosteoblast or other progenitor cells of several types present inside bone marrow. The cultured stromal cells showed high ALP activity which is representative marker of osteoblast without any treatment. Osteogenic inducers such as Dex and BMP-2 were examined for the evaluation of their effect on osteogenic and adipocytic differentiation of stromal cells, because they function as osteoinductive agent in stromal cells, but simultaneously induce adipogenic differentiation. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity or mRNA expression of osteoblast markers such as osteopontin, bone sialoprotein, collagen type I and CbfaI, and in vitro matrix mineralization by von Kossa staining. Oil red staining method was used to detect adipocyte and adipocytic marker, aP2 and $PPAR{\gamma}2$ expression was examined using RT-PCR. It can be supposed that irrigation procedure resulted in high portion of already differentiation-committed osteoprogenitor cell showing elevated ALP activity and strong mineralization only under the supplement of $100{\mu}M$ ascorbic 2-phosphate and 10mM ${\beta}$-glycerophosphate without any treatment of osteogenic inducers such as Dex and BMP-2. Dex and BMP-2 seemed to transdifferentiate osteoprogenitor cells having high ALP activity into adipocytes temporarily, but continuous treatment redifferentiated into osteoblast and developed in vitro matrix mineralization. This property must be considered either in tissue engineering for bone regeneration, or in research of characterization of osteogenic differentiation, with rat BMSC isolated by the standard irrigation method.

• Tuberculosis and Respiratory Diseases
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• 제49권1호
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• pp.60-71
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• 2000

배경 및 목적 : Cathepsin D는 리소솜에 위치하는 단백분해효소로서 종양의 침윤, 전이, 증식에 관여할 것으로 생각되며, 이러한 작용을 통해 예후에도 중요한 역할을 할 것으로 추정된다. 폐암에서의 Cathepsin D의 예후인자로서의 역할은 아직 확립되지 않고 논란이 많은 실정이다. 이 연구의 목적은 비소세포폐암에서 Cathepsin D 발현의 예후적인 중요성을 알고자 하였다. 방법 : 비소세포 폐암환자 중 치료 목적으로 수술적 처치를 시행한 총 54명의 환자를 대상으로 하여 적출한 폐조직의 면역조직화학적 염색으로 Cathepsin D의 발현을 관찰하고 생존기간 및 TNM 병기와의 관계를 보았다. 결과 : 종양세포에서의 Cathepsin D의 발현은 총 54례 중 18례에서 관찰되어 33.3%의 발현율을 보였으나, 발현군과 비발현군 사이에 조직학적 분화도, 암의 크기. 영역 림프절 침범, 병리조직적 병기(surgical-pathologic stage, p-stage)는 통계적인 유의한 차이를 보이지 않았다. 간질세포에서는 29례(53.7%)에서 중둥도에서 다량(moderate to massive)의 Cathepsin D가 발현되는 것이 관찰되었고, 발현양상과 병리조직적 병기사이에 통계적으로 유의한 관련성이 있었으나(p=0.031), 각각의 조직학적 분화도, 암의 크기, 영역 림프절 침범과는 관계가 없었다. 종양세포와 세포에서의 Cathepsin D 의 발현은 생존율로 표현한 예후와의 유의한 관련성이 없었다. 예후와 관련된 변수를 사용한 다변량 분석결과 영역림프절 침범이 유일한 독립적 예후인자가 되었으며 Cathepsin D는 예후 인자로서의 의미는 없었다. 결론 : 비소세포폐암의 간질세포내 Cathepsin D 발현양상은 병리조직적 병기와 유의한 관련성을 나타내어 종양 진행과의 관련 가능성을 제사하였으나, 다른 임상병리인자들 및 예후와의 관련성은 없었다. 종양세포내에서의 Cathepsin D 발현은 병리조직적 병기를 포함한 임상병리 인자들 및 예후와 관계가 없었다.

• Bulletin of the Korean Chemical Society
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• 제31권2호
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• pp.281-285
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• 2010

Hemodialysis vascular access dysfunction (HVAD) due to the aggressive development of venous neointimal hyperplasia remains a major complication for patients with synthetic arteriovenous grafts. Paclitaxel-coated expanded polytetrafluoroethylene (ePTFE) grafts effectively prevent neointimal hyperplasia and stenosis. However, perigraft inflammation or edema can be another complication of ePTFE grafts, preventing early cannulation. Three different types of ePTFE grafts, including grafts without paclitaxel coating (control group, n = 12), grafts with paclitaxel coating at a dose density of $0.61ug/mm^2$ (low concentration group, n = 12), and grafts with paclitaxel coating at a dose density of $1.15ug/mm^2$ (high concentration group, n = 12) were placed in the backs of 12 rabbits, simultaneously. Six rabbits were euthanized after one week and the remaining six were euthanized two weeks after implantation. Perigraft inflammation, graft wall inflammation, stromal cell proliferation, blood vessel formation, tissue necrosis and edema were analyzed for the grafts in each animal. Inflammation surrounding the paclitaxel-coated grafts was significantly reduced compared to the control group. Stromal cell layers were detected at the interface between the graft and the surrounding tissue in the control group, infiltrated into the graft interstices, and differentiated into myofibroblasts for graft healing. Paclitaxel-coated grafts inhibited stromal cell proliferation and infiltration into the graft wall. Tissue necrosis and edema were not detected in either of the paclitaxel-coated graft groups.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4187-4192
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• 2014

Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9 expression in EGIST tissue samples for association with clinicopathological data from the patients. Twenty-one surgical EGIST tissue specimens were collected for analysis of MMP-2 and MMP-9 expression using immunohistochemistry. MMP-2 and MMP-9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas they were only expressed in 75% of the spindle cell type, although there was no statistically significant difference (p>0.05). Expression of MMP-2 and MMP-9 proteins was associated with tumor size, mitotic rate, tumor necrosis, and distant metastasis (p<0.05). MMP-2 expression was linked with MMP-9 levels (p<0.05). However, there was no correlation between MMP-9 expression and age, sex, primary site, or cell morphology in any of these 21 EGIST patients (p>0.05). Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9 expression with advanced EGIST behavior.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권4호
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• pp.352-359
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• 2006

MMP-2 and MMP-9, type IV collagenases which degrade basement membrane, have been known to play important roles in invasion and metastasis of tumor cells, In addition, they seem to be involved in cell differentiation, apoptosis, angiogenesis and immunity, etc. We immunohistochemically examined epithelial and stromal expressions of MMP-2 and MMP-9 in irritation fibroma, oral leukoplakia, and oral squamous cell carcinoma (OSCC) and have some results as follows: 1. Irritation fibromas, oral leukoplakias and OSCCs mostly showed increased expression of MMP-2 and MMP-9 in the epithelium and connective tissue compared with normal mucosa. 2. There was a significant difference in the epithelial expression of MMP-2 and MMP-9 between irritation fibroma and oral leukoplakia. 3. There was a significant difference in the epithelial and stromal expression of MMP-2 and MMP-9 between irritation fibroma and OSCC. 4. There was a significant difference in the stromal expression of MMP-9 between oral leukoplakia and OSCC. We concluded that rritation fibroma, oral leukoplakia and OSCC have somewhat different characteristics of MMP-2 and MMP-9 expressions, which perhaps result from different pathogenesis.

• Macromolecular Research
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• 제13권4호
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• pp.285-292
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• 2005

We developed alginate beads loaded with transforming growth $factor-{\beta}_{1}(TGF-{\beta}_{1})$ to examine the possible application of the scaffold and cytokine carrier in tissue engineering. In this study, bone marrow stromal cells (BMSCs) and $TGF{\beta}_{1}$ were uniformly encapsulated in the alginate beads and then cultured in vitro. The cell morphology and shape of the alginate beads were observed using inverted microscope, scanning electron microscope (SEM), histological staining and RT-PCR to confirm chondrogenic differentiation. The amount of the $TGF{\beta}_{1}$ released from the $TGF-{\beta}_{1}$ loaded alginate beads was analyzed for 28 days in vitro in a phosphate buffered saline (pH 7.4) at $37^{\circ}C$. We observed the release profile of $TGF-{\beta}_{1}$ from $TGF-{\beta}_{1}$ loaded alginate beads with a sustained release pattern for 35 days. Microscopic observation showed the open cell pore structure and abundant cells with a round morphology in the alginate beads. In addition, histology and RT-PCR results revealed the evidence of chondrogenic differentiation in the beads. In conclusion, these results confirmed that $TGF-{\beta}_{1}$ loaded alginate beads provide excellent conditions for chondrogenic differentiation.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.263-275
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• 2019

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

• 대한골관절종양학회지
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• 제10권1호
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• pp.13-21
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• 2004

목적: 골수에서 분리한 기질 세포를 단독으로 또는 동종 망상골과 함께 이식하여 치료했던 양성 골 병변 소파 후 발생한 골 결손에 대한 치료 결과를 보고 하고자 한다. 대상 및 방법: 1996년 7월 이래 장관골 양성 골 병변에 대해 병변이 작거나 소아여서 소파술과 함께 자가 골수 기질 세포를 단독으로 이식하였던 2명 3례와, 자가 골수 기질 세포와 동종 망상골 이식을 병행하여 치료하였던 6명 6례 등 총 8명 9례를 대상으로 수술 후 임상증상의 해소, 신생 골 형성 및 주변 정상골과의 유합 과정을 추시하였다. 남자가 6례, 여자가 2례였으며 평균 연령은 24세(8세~47세)였다. 조직학적 진단은 섬유성 골 이형성증이 5례로 많았고, 단순 골 낭종 2례, 연골모세포종과 섬유성 피질 결손이 각각 1례씩 이었다. 수술 후 평균 추시기간은 16.3개월(3개월~84개월) 이었다. 결과: 수술 전 병소 부위에 통증을 호소했던 4례 모두에서 술 후 2주 이내에 증상이 소실되었으며, 수술 후 촬영한 단순 방사선 사진 상 약 4주경부터 병변 부위에 신생 골 형성이 관찰되고 약 8주경에는 골 결손 부위가 신생 골로 충전되고 주변 정상골과 유합된 소견을 보였다. 합병증으로는 1례에서 술 후 3주에 병소 부위를 통과하는 골절이 발생했으며, 단순 골 낭종 1례에서 술 후 5개월에 병소가 재발하였다. 결론: 장관골 양성 골 병변에 대해 소파 후 골수에서 분리한 골수 기질 세포를 단독으로 또는 동종 망상골과 함께 이식할 때 빠른 치유과정을 보여, 비록 단 기간의 추시 결과이기는 하나 골수 기질 세포 이식술이 향후 골 낭종이나 양성 골 병변의 치료에 크게 이용될 수 있을 것으로 보인다. 골 낭종 수술 후 재발 원인은 낭종내벽 섬유조직의 불완전 소파의 결과로 보이며, 골절 발생 가능성이 높은 대퇴골 전자간 골 낭종 등에 대하여는 금속판 등을 이용한 예방적인 고정이 필요할 것으로 판단되었다.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.