• 대한두경부종양학회:학술대회논문집
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• 대한두경부종양학회 1995년도 제12차 학술대회 연제순서 및 초록집
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• pp.201-202
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• 1995

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2385-2390
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• 2015

Background: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC. Objectives: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC. Materials and Methods: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records. Results: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC. Conclusions: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5033-5036
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• 2012

Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.

• Nuclear Medicine and Molecular Imaging
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• 제43권1호
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• pp.26-34
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• 2009

목적: 원발성 위암 환자의 PET/CT 스캔에서 FDG 섭취에 영향을 주는 임상병리학적 및 면역조직화학적 지표들이 있는지 알아보고자 하였다. 대상 및 방법: 본원에 내원하여 수술 전 FDG PET/CT 스캔을 시행한 89명의 위암환자들을 대상으로 하였다. PET/CT 영상에서 원발 종양의 SUVmax를 구한 후 침범 깊이(T기),종양 크기, 림프절전이, 종양 분화, Lauren의 분류, Ki-67 지수, p53, EGFR, Cathepsin D, c-erb-B2. COX-2의 발현과 같은 임상병리학적 및 면역조직화학적 지표들과의 상관 관계를 분석하였다. 결과: 89예의 위암 중 19예에서는 PET/CT 영상에서 인지 가능한 FDG 섭취가 없었는데, 이 19예 중 16예는 원발 종양의 침범 깊이가 점막하 이내에 국한된 경우였다. 위암의 FDG섭취 정도는 T기가 T2 이상일 때가 T1일 때보다 유의하게 높았고($5.8{\pm}3.1$ vs. $3.7{\pm}2.1$, p=0.002), 위암의 크기가 3 cm 이상일 경우가 3 cm 미만일 경우보다 유의하게 높았다($5.7{\pm}3.2$ vs. $3.7{\pm}2.0$, p=0.002) Lauren의 분류에 따른 장형 위암에서 장형이 아닐 때보다 높은 SUVmax를 보였다($5.4{\pm}2.8$ vs. $3.7{\pm}1.3$, p=0.003). 원발 종양의 SUVmax는 p53 양성인 경우가 음성인 경우보다 의미 있게 높았다($6.0{\pm}2.8$ vs. $4.4{\pm}3.0$, p=0.035). 그 외 림프절 전이 유무, 종양 분화, Ki-67 지수, EGFR, Cathepsin D, c-erb-B2 그리고 COX-2 같은 다른 지표들은 원발성 위암의 SUVmax와 의미 있는 상관 관계가 없었다. 결론: 원발성 위암의 침범 깊이(T기)는 FDG PET/CT 스캔에서의 위암 발견율에 영향을 주었다. 위암이 PET/CT스캔에서 인지 가능한 FDG 섭취를 보일 경우 T기, 종양의 크기, Lauren의 분류에 따른 조직형, 그리고 p53의 발현 정도는 원발성 위암의 FDG 섭취와 유의한 상관 관계가 있었다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권6호
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• pp.421-433
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• 2002

In order to elucidate the pathogenesis of cleft lip and palate, first of all, it is necessary to understand the developmental mechanisms of growth factors and extracellular matrix proteins in the tissues of cleft lip and palate. We have performed immunohistochemical studies on human cleft lip and palate tissues to elucidate the pathogenetic implications of cleft lip and palate. 16 specimens from postnatal human cleft lip and palate subjects and 17 specimens from autopsy of prenatal human cleft lip and palate were fixed in 10% buffered formalin, embedded in paraffin. The sections were routinely stained by hematoxylin and eosin, also stained by PAS, and followed by immunohistochemical stainings using the antiseras of growth factors and extracellular matrix proteins such as PCNA, S-100, c-erb-B2, MMP-3, MMP-10, HSP-70, transglutaninase-C, E-cadherin, VEGF, vWF. Both the prenatal and postnatal specimens of cleft lip and palate showed dysplastic proliferation of the basal cell layer, increased infiltration of melanocytes into mucosal epithelium, sebaceous gland hyperplasia ingrowing into the muscular tissue of lip and palate, and fatty infiltration into the submucosal deep connective tissue. The strong reactions of MMP-3 and HSP-70 were detected in the tissues of cleft lip and palate, especially increased in degenerating muscle bundles, while the immunostainings of PCNA and c-erb-B2 were weakly positive in the tissues of cleft lip and palate. These data suggest that the retrogressive tissue degeneration around the cleft areas persistently exist during the prenatal and postnatal period after cleft formation, and the sebaceous gland hyperplasia and fatty infiltration with the intense expression of MMP-3 and HSP-70 is closely related to the muscular degeneration around the cleft area.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권3호
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• pp.193-201
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• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• Applied Microscopy
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• 제31권2호
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• pp.185-197
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• 2001

여러 가지 장점이 있음에도 일정성이 유지되지 않는 다는 단점이 있는 마이크로파 고정 효과를 "저에너지 마이크로파"를 사용하여 보완하고자 하였다. 이를 위해 사람 위선암(gastric adenocarcinoma)을 저 에너지 마이크로파(low energy of microwave, LEM)로 고정하여 미세구조와 항원-항체반응 수준에서 그 효과를 관찰하고자 하였다. LEM으로 고정한 시료에서 항원-항체반응은 monoclonal 생쥐-항-사람-p53 (IgG2b, kappa)과 토끼-항-사람-c-erbB-2로 처리하여 결과를 냉동 절편과 비교하였다. 암세포 특이 항원은 LEM으로 처리한 시료에서 발색반응 산물의 확산이 적은 것으로 관찰되었고 보다 쉽게 인지될 수 있었다. LEM으로 고정한 위선암 조직의 미세구조는 보존된 것으로 보였으나 그 고정효과는 2차 원인에 의해 손상되는 것으로 보였으므로 이를 보상하기 위해서 LEM 고정 후 저농도 화학 고정액으로 재차 처리하여 다소의 일정성을 유지할 수 있었으나 위선암 조직은 더 낮은 마이크로파 에너지 요구성이 있는 것으로 생각할 수 있었다. 따라서 암세포가 요구하는 "최소 마이크로파 요구 범위"를 밝히기 위해서 배양 HeLa 세포를 더 낮은 에너지의 마이크로파와 저농도 화학고정액으로 처리한 결과 HeLa세포 미세구조가 보존되는 등 비교적 좋은 효과를 볼 수 있었다. 이 결과로 보면 LEM 조사(照射)로서 생체 저분자 및 수용성 단백질이 crosslink되는 효과가 있는 것으로 보았고 이를 저농도 화학 고정액으로 재차 고정하는 방법으로서 미세구조 및 항원성 보존 효과가 있는 것으로 사료되었으므로 이에 대하여 논의하고자 하였다.

• Parasites, Hosts and Diseases
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• 제54권1호
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• pp.31-38
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• 2016

Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked $IFN-{\gamma}$. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, $5{\mu}M$) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine ($5{\mu}M$) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, $20{\mu}M$) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, $10{\mu}M$) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.

• Molecules and Cells
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• 제43권1호
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• pp.34-47
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• 2020

The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Reverbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Rev-erbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo. Taken together, our results demonstrate a molecular mechanism of Rev-erbs in the bone remodeling, and provide a molecular basis for a potential therapeutic target for treatment of bone disease characterized by excessive bone resorption.

• 한국표면공학회:학술대회논문집
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• 한국표면공학회 2003년도 추계학술발표회초록집
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• pp.54-54
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• 2003

DLC films were deposited on Si(100) substrates by inductively coupled plasma (ICP) assisted chemical vapor deposition (CVD). A mixture of acetylene (C$_2$H$_2$) and argon (Ar) gases was used as the precursor and plasma source, respectively. The structure of the films was characterized by the Raman spectroscopy. Results from the Raman spectroscopy analysis indicated that the property change of the DLC films is due to the sp$^3$ and sp$^2$ ratio in the films under various conditions such as ICP power, working pressure and RF substrate bias. The hydrogen content in the DLC films was determined by an electron recoil detector (ERB). The roughness of the films was measured by atomic force microscope (Am). A microhardness tester was used for the hardness and elastic modulus measurement. The DLC film showed a maximum hardness of 37㎬. In this work, the relationship between deposition parameters and mechanical properties were discussed.