• Title/Summary/Keyword: p63

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

  • Kim, In-Su;Kim, Chul-Hwan;Kim, Kyung-Wook
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.3
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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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    • v.14 no.12
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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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    • v.13 no.3
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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.

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

  • Akihiro, Hosoya;Lee, Jong-Min;Kim, Ji-Youn;Jung, Han-Sung;Choi, Sung-Won
    • Development and Reproduction
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    • v.13 no.2
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    • pp.89-95
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    • 2009
  • p63 has been demonstrated to localize in stem cells and precursor cells of various epithelial tissues previously, but the localization of p63 throughout tooth formation, particularly during the enamel and root formation stages, remains to be adequately characterized. Therefore, in this study, we have demonstrated, via immunohistochemical methods, that p63 is ubiquitously expressed in the dental epithelium during tooth development. p63 was detected in the basal and suprabasal layers of the epithelia, including the skin, hair follicles, oral mucosa, and submandibular ducts. However, in the tooth region, all cells of the dental lamina, enamel organ, Hertwig's epithelial root sheath (HERS), and epithelial cell rests of Malassez (ERM) evidenced immunoreactivity for p63. These results indicate that p63 may perform different roles, other than stem cell maintenance, in tooth development.

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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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    • v.43 no.5
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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.

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

  • Choi, Jae Yeong;Koo, Hyo Jin;Cho, Hyen Goo
    • Journal of the Mineralogical Society of Korea
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    • v.31 no.4
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    • pp.257-266
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    • 2018
  • East China Sea (ECS) is known to be supplied with large amounts of sediments form Huanghe, Changjiang and various rivers in Korea. Many studies have been conducted to identify the effects of rivers and deposition process of ECS, but no consensus has been reached. In this study, clay minerals, rare earth elements (REEs) and grain size were analyzed to study the provenance and sedimentation environment of core 99MAP-P63 in ECS. Clay mineral contents of 99MAP-P63 are abundant in order of illite, chlorite, kaolinite, and smectite. The provenance of 99MAP-P63 sediments using clay minerals is interpreted as the Changjiang regardless of depth. As a result of REEs analysis, 99MAP-P63 sediments are very similar to Chinese rivers sediments. Therefore, the provenance of 99MAP-P63 is Changjiang, and the influence of Korean river seems to be insignificant. 99MAP-P63 sediments are generally classified as sandy silt, but the top of the core is divided into sand with a sand contents of 85 %. Compared with surrounding cores, sandy silt sediments arecorresponded to the low stand stage when sea-level was low, and the sediments were thought to have been supplied directly through the paleo-Changjiang. Sandy sediments in uppermost of core are corresponded to transgressive stage. Although distance from estuary was increased due to sea-level rise, it was possible to supply coarse sediments due to high bottom stress, and the paleo-Changjiang sediments deposited in study area were re-deposited.

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

  • Park, Jee-Hyun;Lee, Won-Deok;Min, Chul-Gi;Kang, Jin-Han;Myung, Hoon;Lee, Jong-Ho;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.31 no.3
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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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    • v.13 no.5
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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.

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

  • 지철근;여인선
    • The Proceedings of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.1 no.1
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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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