• 제목/요약/키워드: p63

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분화도 좋은 구강 편평상피세포암종에서 Dominant Negative p63 isoform의 발현 (EXPRESSION OF DOMINANT NEGATIVE p63 ISOFORM IN WELL-DIFFERENCIATED ORAL SQUAMOUS CELL CARCINOMA)

  • 김인수;김철환;김경욱
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제33권3호
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    • pp.191-198
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    • 2007
  • The p53 which is well known as tumor suppressor gene is located at 17p13. p53 is a sequence-specific DNA binding transcription factor that responds to certain cytotoxic stresses, such as DNA damage, by enhancing the transcription of genes that regulate cell-cycle progression as well as programmed cell death. The p63 gene that is located at 3q27-29, is recognized members of the p53 family, and responsible for the transcription of 6 isoforms. Three isoforms ($TAp63{\alpha}$, $TAp63{\beta}$, $TAp63{\gamma}$) contain an N-terminal transactivation (TA) domain and can induce apoptosis. The other 3 isoforms (${\Delta}Np63{\alpha}$, ${\Delta}Np63{\beta}$, ${\Delta}Np63{\gamma}$) lack the TA domain and may function in a dominant-negative fashion by inhibiting the transactivation functions of p53 and TAp63 proteins, and thus act as oncoproteins. A number of studies have investigated the role of p63 in human squamous cell carcinomas from different organs. Only a few studies have examined ${\Delta}Np63$ isoform in oral squamous cell carcinoma including normal epithelium. This study aimed to evaluate expression of ${\Delta}Np63$ isoform in human oral squamous cell carcinoma tissue and normal mucosa. The 3 cases of well differenciated oral squamous cell carcinoma specimen including adjacent normal mucosa were examined, and immunohistochemical study with monoclonal antibody(4A4) and tumor cell apoptosis analysis with Transmission Electon Microscopy were studied. And, RT-PCR analysis was done for expression of ${\Delta}Np63$ isoform. The results were as followed. 1. Normal gingiva showed the restricted p63 expression in basal cell layer. 2. Well differentiated squamous cell carcinoma showed mainly p63 expression in overall area of malignancy, especially in basal cell layer to adjacent stromal tissue. 3. Tumor cells around keratinized area with no p63 expression disclosed less micro-organelle in decreased size cytoplasm and severe chromatin margination with nuclear destruction that means apoptosis. 4. Comparison of mRNA expression of ${\Delta}Np63$ isoform by RT-PCR showed variable expression of ${\Delta}Np63$ isoform, but ${\Delta}Np63{\alpha}$ was most highly expressed in all 3 tumor specimen. From theses results, it should be suggested that ${\Delta}Np63$ isoform expression in well differentiated squamous cell carcinoma was closely related to tumor oncogenesis, expecially overexpression of ${\Delta}Np63{\alpha}$ is a most important factor in tumor genesis of oral squamous cell carcinoma.

Clinicopathology Significance of p53 and p63 Expression in Indonesian Cervical Squamous Cell Carcinomas

  • Romus, Ilhami;Triningsih, F.X. Ediati;Mangunsudirdjo, Sagiri;Harijadi, Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권12호
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    • pp.7737-7741
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    • 2013
  • Background: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. Materials and Methods: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. Results: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. Conclusions: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.

Diagnostic Utility of p63 (Ab-1) and (Ab-4) Tumor Markers in the Squamous Cell Carcinomas of Head and Neck

  • Khan, Nauman Rauf;Khan, Amna Nauman;Bashir, Saira;Khan, Ayyaz Ali;Suleman, Bilquis A.;Chaudhry, Saima
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권3호
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    • pp.975-978
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    • 2012
  • P63 is a gene product required in cell cycle regulation which plays vital roles in tumor differentiation. Aims of the present study were to assess the frequency, pattern, sensitivity and specificity of two p63 protein clones P63 4A4 and P63 4A4+Y4A3 in squamous cell carcinomas (SCCs). Thirty cases of head and neck region SCC diagnosed on the basis of H&E staining were examined along with 60 cases of head and neck region biopsies other than squamous cell carcinoma, negative on H&E staining, were taken as control. Immunostaining was performed on slides according to the Thermo Scientific UltraVision LP detection System. P63 4A4+Y4A3 clone is more sensitive 96.6% in comparison to 86% in P63 4A4 with having greater NPV of 98.3%. The results signify the importance of P63 4A4+Y4A3 marker over the old markers and may be used as a confirmatory marker of squamous cell carcinoma.

생쥐의 초기 두개악안면 발생 중 p63의 발현 양상 (Expression of p63 during Early Craniofacial Development of the Mouse Embryo)

  • 호소야 아카히로;이종민;김지연;정한성;조성원
    • 한국발생생물학회지:발생과생식
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    • 제13권2호
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    • pp.89-95
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    • 2009
  • p63은 다양한 상피 조직의 줄기세포와 전구세포에 존재한다는 사실이 잘 알려져 있으나, 치아 형성, 특히 사기질과 뿌리 형성시기에서의 p63 위치느 ㄴ아직 연구해야 할 과제로 남아 있다. 본 연구에서는 p63이 치아 발생 동안 치아상피에 편재하여 나타나는 것을 면역조직화학 기법을 이용하여 확인하였다. p63은 피부, 모낭, 구강점막 그리고 턱밑샘 도관을 포함하는 상피의 바닥층과 바닥위층에 위치하였다. 그러나 치아 부위에서는 치아관의 모든 세포, 사기질기관, 헤르트비히 뿌리상피집 그리고 말라세쯔 상피잔사에 p63이 관찰되었다. 이 결과는 치아 발생 중 p63이 줄기세포 유지 외에도 다른 기능을 한다는 사실을 보여준다.

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Immunohistochemical evaluation of p63 and cyclin D1 in oral squamous cell carcinoma and leukoplakia

  • Patel, Sunit B.;Manjunatha, Bhari S.;Shah, Vandana;Soni, Nishit;Sutariya, Rakesh
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제43권5호
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    • pp.324-330
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    • 2017
  • Objectives: There are only a limited number of studies on cyclin D1 and p63 expression in oral squamous cell carcinoma (OSCC) and leukoplakia. This study compared cyclin D1 and p63 expression in leukoplakia and OSCC to investigate the possible correlation of both markers with grade of dysplasia and histological grade of OSCC. Materials and Methods: The study included a total of 60 cases, of which 30 were diagnosed with OSCC and 30 with leukoplakia, that were evaluated immunohistochemically for p63 and cyclin D1 expression. Protein expression was correlated based on grades of dysplasia and OSCC. Results: Out of 30 cases of OSCC, 23 cases (76.7%) were cyclin D1 positive and 30 cases (100%) were p63 positive. Out of 30 cases of leukoplakia, 21 cases (70.0%) were cyclin D1 positive and 30 (100%) were p63 positive (P<0.05). Conclusion: The overall expression of cyclin D1 and p63 correlated with tumor differentiation, and increases were correlated with poor histological grades, from well-differentiated to poorly-differentiated SCC. Increased cyclin D1 and p63 expression was associated with the severity of leukoplakia. Based on these results cyclin D1 and p63 products can be a useful tool for improved leukoplakia prognosis.

동중국해 99MAP-P63 코어 퇴적물의 기원지 연구 (Provenance Study of 99MAP-P63 Core Sediments in the East China Sea)

  • 최재영;구효진;조현구
    • 한국광물학회지
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    • 제31권4호
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    • pp.257-266
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    • 2018
  • 동중국해는 황하(Huanghe), 장강(Changjiang) 및 한국의 여러 강들로부터 많은 양의 퇴적물을 공급받는 것으로 알려져 있으며, 각 강들의 영향 및 퇴적과정을 밝혀내기 위해 많은 연구가 수행되었으나, 의견일치가 이루어지지 못하였다. 본 연구에서는 동중국해 퇴적물의 기원지 및 퇴적 환경 유추를 위해, 99MAP-P63 코어 퇴적물에 대해 입도, 점토광물 및 희토류원소 분석을 수행하였다. 점토광물 분석 결과, 일라이트(illite)의 함량이 가장 높고, 카올리나이트(kaolinite) 및 녹니석(chlorite), 스멕타이트(smectite)의 순으로 풍부하며, 점토광물을 이용한 99MAP-P63 퇴적물의 기원지는 깊이에 관계없이 모두 장강인 것으로 판단된다. 희토류원소 분석 결과, 99MAP-P63 퇴적물들은 중국 강 퇴적물의 희토류원소 함량과 매우 유사하다. 따라서 99MAP-P63 퇴적물들의 기원지는 장강이며, 한국 강의 영향은 미미하거나 없을 것으로 판단된다. 99MAP-P63 퇴적물은 대체로 사질 실트로 구분되지만, 코어의 최상부는 모래의 함량이 85 %인 사질로 구분된다. 주변 코어들과 비교한 결과, 사질 실트는 해수면이 낮았던 저수위기(lowstand stage)에 해당되며, 장강의 고수로를 통해 퇴적물들이 직접 공급되었을 것으로 판단된다. 코어 최상부의 사질 퇴적물은 해침기(transgressive stage)에 해당되며 해수면 상승으로 인해 강 하구와의 거리는 멀어졌지만, 현재보다 높은 해저면의 응력으로 인해 조립질 퇴적물들이 공급될 수 있었으며, 인근에 퇴적되었던 고 장강(paleo-Changjiang) 퇴적물들이 재동된 것으로 해석된다.

DMBA 유도 햄스터 협낭 발암모델에서 세포증식 및 사멸과 p63 발현의 관계 분석 (THE RELATIONSHIP OF P63 EXPRESSION WITH CELL PROLIFERATION AND APOPTOSIS IN DMBA-INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS)

  • 박지현;이원덕;민철기;강진한;명훈;이종호;김명진
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제31권3호
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    • pp.219-227
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    • 2005
  • Purpose: Abnormalities in the p53 gene are regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 and p63 have recently been identified. They share considerable sequence homology with p53 in the transactivation, DNA binding, and oligomerization domains, indicating possible involvement in carcinogenesis. Disruption of the homeostatic balance between proliferation and apoptosis is widely believed to contribute to human oral carcinogenesis. The aim of this study was to analyze expression of p63 in squamous cell carcinogenesis and to compare with immunochemical markers representing cell proliferation and apoptosis. Materials and Methods: Using the Syrian hamster oral cancer model, the fraction of apoptotic (apoptotic index-AI), proliferating (mitotic index-MI) and p63 expressing keratinocytes were examined at normal, dysplastic and malignant oral epithelium using the TUNEL assay, PCNA and p63 immunostaining. Results: p63 significantly increased between normal and dysplastic epithelium and between dysplastic and malignant epithelium. PCNA significantly increased between normal and dysplastic epithelium and between normal and malignant epithelium. However, increase between dysplastic and malignant epithelium, though still increasing, was not statistically significant. The percentage of TUNEL positive cells increased from normal to dysplastic epithelium and returned to normal keratinocyte level in the malignant epithelium. However, differences between tissue types were not significant. The ratio of MI:AI increased significantly only in the dysplastic-malignant epithelial transition. The increase of p63 expression closely reflected the change in the MI:AI ratio during oral carcinogenesis. Conclusion: The p63 may be associated with the regulation of epithelial proliferation and apoptosis in DMBA-induced hamster buccal pouch squamous cell carcinogenesis. Further study is required to investigate which p63 isoforms are involved in hamster buccal pouch carcinogenesis.

p63 Cytoplasmic Aberrance is Associated with High Prostate Cancer Stem Cell Expression

  • Ferronika, Paranita;Triningsih, F.X. Ediati;Ghozali, Ahmad;Moeljono, Abraham;Rahmayanti, Siti;Shadrina, Arifah Nur;Naim, Awang Emir;Wudexi, Ivan;Arnurisa, Alfa Monica;Nanwani, Sandeep Tarman;Harijadi, Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권5호
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    • pp.1943-1948
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    • 2012
  • Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

평면거울법에 의한 수은-아르곤 방전중의 $6^{3}P$ 수은원자의 농도 결정 (Determination of the Concentration of $6^{3}P$ Mercury Atoms in a Hg-Ar Discharge by the Plane-Mirror Method)

  • 지철근;여인선
    • 한국조명전기설비학회지:조명전기설비
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    • 제1권1호
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    • pp.55-60
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    • 1987
  • 본 연구의 목적은 스펙트럼의 재흡수를 이용하여, 수은-아르곤 방전중의 63P 여기원자 농도를 결정하는 데 있다. 먼저, 평면거울을 사용한 경우의 재흡수 이론을 전개한 다음, 이를 수은-아르곤 방전에 적용시켜, 복잡한 미세구조를 갖는 수은의 visible-triplet lines에 있어서의 스펙트럼의 흡수계수와 측정된 흡수율사이의 수치적 관계를 구하였다. 이와함께, 흡수계수와 흡수원자농도사이의 관계를 이용하여, 방전관의 관벽온도를 변화시킨 경우와 방전전류를 변화시킨 경우에 있어서, 측정 흡수율에 상응하는 수은의 63P 여기원자 농도를 구하였고 다음과 같은 결과를 얻었다. ⅰ) 측정범위내에서 준안정원자의 농도는 63P1 상태의 농도보다 높다. ⅱ) 방전전류를 증가시킴에 따라 435.8[nm]의 재흡수가 급격히 증가하고, 그 결과 63P1 여기상태의 농도는 준안정원자에 비해 상대적으로 높은 증가속도를 보인다. ⅲ) 방전전류 증가시 준안정원자와 전자사이의 충돌이 빈번해져서 준안정원자의 증가속도가 둔화하는 대신 축적여기 또는 전리의 확률이 높아진다.

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