• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10893-10898
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• 2015

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of $O^6$-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

• 대한수학회보
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• 제53권2호
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• pp.487-494
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• 2016

Let p be an odd prime and c be a fixed integer with (c, p) = 1. For each integer a with $1{\leq}a{\leq}p-1$, it is clear that there exists one and only one b with $0{\leq}b{\leq}p-1$ such that $ab{\equiv}c$ mod p. Let N(c, p) denote the number of all solutions of the congruence equation $ab{\equiv}c$ mod p for $1{\leq}a$, $b{{\leq}}p-1$ in which a and $\bar{b}$ are of opposite parity, where $\bar{b}$ is defined by the congruence equation $b{\bar{b}}{\equiv}1$ mod p. The main purpose of this paper is using the mean value theorem of Dirichlet L-functions and the properties of Gauss sums to study the computational problem of one kind mean value function related to $E(c,p)=N(c,p)-{\frac{1}{2}}{\phi}(p)$, and give its an exact computational formula.

• 생명과학회지
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• 제24권2호
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• pp.112-117
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• 2014

본 연구는 복분자와 쑥 추출물이 UVB (자외선-B)에 의한 유전독성의 감소에 효과를 보이는 지를 HaCaT 세포를 이용하여 분석하였다. 자외선을 조사하지 않은 정상 세포의 세포활성은 복분자와 쑥 추출물을 처리한 경우 처리하지 않은 대조군과 차이를 나타내지 않았지만, 자외선을 조사한 세포에 복분자와 쑥 추출물을 처리한 경우 처리하지 않은 대조군에 비해 농도 의존적으로 세포 활성을 증가하였다. UVB를 조사한 후 세포의 핵 분절율은 복분자와 쑥 추출물을 처리한 경우 정상 배양액으로 배양한 대조군에 비해 핵 분절율을 각각 약 20%, 15% 정도 감소하였다. DNA 상해 회복에 반응하는 cyclobutane pyrimidine dimer (CPD)의 잔여량을 확인한 결과, 복분자와 쑥 추출만 처리한 경우 처리하지 않은 대조군에 비해 차이를 나타내지 않았으나 UVB 조사한 후 복분자와 쑥추출물을 처리한 경우 정상 배양액으로 배양한 대조군에 비해 농도의존적으로 감소하였다. 세포 상해에 반응하는 유전자인 phospho-p53과 GADD45의 단백질 수준을 Western blot으로 분석한 결과, 자외선을 조사하지 않은 정상세포에 복분자와 쑥 추출물만 처리한 경우 처리하지 않은 대조군과 비교하여 유의적인 차이를 나타내지 않았지만 UVB 조사한 후 복분자와 쑥 추출물을 처리한 경우 농도 의존적으로 phospho-p53과 GADD45 단백질 발현량이 감소하였다. 위의 결과에서 복분자와 쑥 추출물은 UVB에 유도된 DNA 상해와 p53 및 GADD45와 같은 상해 반응단백질의 수준을 감소시키는 것으로 보아 UVB에 의해 손상된 세포의 유전독성을 회복하는 효능이 있다고 생각된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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• pp.337-344
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• 2000

본 연구에서는 MSI와 구강암과의 상관관계를 규명하기 위하여 17례의 구강암에 대하여 12종류의 marker를 이용하여 MSI 빈도를 조사하였으며, 동시에 p53단백의 과발현과 유전자 돌연변이 양상에 대해서도 알아보았다. 그 결과 4종류 이상의 marker에 대해서 MSI가 나타나는 widespread MSI의 경우 임상병리학적으로 뚜렷한 특징이 없었다. 또한 흡연과 MSI 빈도간에도 연관성이 없었으나 흡연은 p53 유전자의 돌연변이를 증가시켜 암화과정을 촉진하는 작용을 하는 것으로 나타났다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.419-422
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• 2013

Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP-NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (${\geq}$ 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (${\geq}$ 10% positive nuclei) in 33 (49%). High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7619-7625
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• 2015

Background: Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC). In this study, we examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five (miR-34a, miR-143, miR-373, miR-380-5p, and miR-504) regulate the tumor suppressor TP53 and one (miR-99a) is involved in AKT/mTOR signaling. Materials and Methods: Tumor tissues (punch biopsies) were collected from 52 oral cancer patients and as a control, 8 independent adjacent normal tissue samples were also obtained. After RNA isolation, we assessed the mature miRNA levels of the 6 selected candidates against RNU44 and RNU48 as endogenous controls, using specific TaqMan miRNA assays. Results: miR-34a, miR-99a, miR-143 and miR-380-5p were significantly down-regulated in tumors compared to controls. Moreover, high levels of miR-34a were associated with alcohol consumption while those of miR-99a and miR-143 were associated with advanced tumor size. No significant difference was observed in the levels of miR-504 between the tumors and controls whereas miR-373 was below the detection level in all but two tumor samples. Conclusions: Low levels of miR-380-5p and miR-504 that directly target the 3'UTR of TP53 suggest that p53 may not be repressed by these two miRNAs in OSCC. On the other hand, low levels of miR-34a or miR-143 may relieve MDM4 and SIRT1 or MDM2 respectively, which will sequester p53 indicating an indirect mode of p53 suppression in oral tumors.

• Journal of Chest Surgery
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• 제36권11호
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• pp.852-857
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• 2003

배경: 중피종은 일반적 치료에 대하여 큰 효과가 없다고 알려져 있다. 저자들은 Adenoviral p53에 민감하게 반응하는 중피종 세포주인 염증 및 표피세포 아유형(subtype)에 adenovirus유전자 핵산전달감염(transfection)으로 중피종 치료의 새로운 방법에 대하여 평가하고자 하였다. 대상 및 방법: 두 쌍의 adenoviral PTEN와 LacZ (Ad/GT-LacZ와 Ad/GV16) 매개체(vectors)에 REN (p53 sensitive)인 중피종 세포주(methothelioma cell lines)의 형질을 도입(transduction)하였으며, 단백질 함량은 Western blotting 분석을 이용하여 측정하였다. 세포사멸은 fluorescence-activated cell sorter analysis of subdiploid populations에 의하여 평가하였으며, 세포 생존력은 XTT 분석에 의하여 결정하였다. 통계 분석은 analysis of variance와 Student t test를 이용하여 하였다. 결과: Adenoviral PTEN 유전자로 처치된 세포사는 72시간 후에 MOI of 20에서 대조군 2.5%에 비하여 REN군 32.9%로 상대적으로 높게 나타났다. 또한 REN cell에서의 전구세포사멸 단백질(proapoptotic protein)인 BAX 발현 증가를, BCL-2에서 발현 감소를 나타내었으나, BCL-XL, BAK 및 BAD 단백질은 변화가 없었다. 결론: Adenovirus PTEN을 매개로 한 BAX 발현 증가는 세포사멸을 유도하고 p53에 민감한 중피종 세포들(p53-sensitive methothelioma cells)에서 세포 생존력을 감소시킨다. 이러한 결과는 PTEN 유전자 핵산전달감염하는 것은 중피종 치료의 새로운 대안적 방법이 될 수 있다는 것을 암시한다.

• 대한한방부인과학회지
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• 제23권3호
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• pp.38-55
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• 2010

Purpose: This study was designed to find out the anti-cancer effects of Samultang-Gami which was composed of Rehmanniae Radix(RR), Angelicae Gigantis Radix(AGR), Cnidii Rhizoma(CR), Paeoniae Radix(PR), Cortex Moutan Radicis(CMR), Hedyotis Diffusa(HD) and Caesalpinia Sappan on HeLa, HepG2 and AGS cells. Methods: Various cancer cell lines including HeLa, HepG2 and AGS cells, were used. In vitro anti-cancer effects were measured by MTT assay using cancer cell lines treated with various concentrations of 70% ethanol extract of Samultang-Gami. Expression of cell cycle arrest mediators including Bax, Bcl-2, p53 and DARP-1 proteins were measured by Western blot analysis. Results: 1. Samultang-Gami decreased the viability of HeLa and HepG cells in a dosedependent manner. 2. AGR, CMR, PR and HD decreased the viability of HeLa, HepG2 and AGS cells. 3. We could observe that the decreased Bax and Bcl-2 expression level and the increased PARP-1 expression level by Samultang-Gami extracts treated in HeLa cells. 4. We could observe that the decreased Bcl-2 expression level and the increased Bax, p53 and PARP-1 expression level by RR extracts treated in HeLa cells. and also could observe that the reduction of the protein level of Bcl-2, p53 and PARP-1 and the increase of the protein level of Bax by PR in HeLa cells. 5. We could observe that the increased p53 expression level, the decreased PARP-1's that and the unchanged Bax and Bcl-2's that by Samultang-Gami extracts treated in HepG2 cells. 6. We could observe that the reduced Bcl-2 expression level by each of RR extracts and PR extracts in HepG2 cells. 7. The treatment of Samultang-Gami in AGS cells didn't have any effect on the expression level of Bax, Bcl-2, p53 and PARP-1. 8. We could observe that the increased p53 and PARP-1 expression level by each of CR, RR and PR extracts in AGS cells. Conclusion: Taken together, we suggest that Samultang-Gami exhibits cytotoxic effects on HeLa, HepG2 and AGS cells, causing apoptosis. The results showed that Samultang-Gami may do so by regulating the expression of specific target molecules that promote efficient apoptotic cell death in a dose-dependent manner.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권1호
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• pp.15-21
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• 2000

저자는 국소적 재발율에 있어서 큰 차이를 보이는 두 치성종양중 대표적인 함치성 낭종과 법랑아세포종에 있어서 apoptosis 관련 단백(p53, bcl-2, bax)의 발현 양상을 관찰하기 위하여 10례의 함치성 낭종과 16례의 법랑아세포종에 대하여 면역조직화학적 연구를 실시하여 다음과 같은 결론을 얻었다. 1. p53은 함치성 낭종보다 법랑아세포종에서 강하게 발현되었고 법랑아세포종의 조직학적 분류에 따른 p53 발현의 차이를 관찰할 수 없었으며 함치성 낭종의 경우에는 p53이 거의 basal layer에서 발현되었다. 2. Bcl-2는 함치성 낭종의 경우 주로 기저층 혹은 전층에서 발현되었고 법랑아세포종에서는 바깥층 혹은 전층에서 발현되었는데 특히 종양 실질조직중 입방형 또는 주상형 세포층에 집중되어 염색되었다. 3. Bax는 함치성 낭종의 경우 법랑아세포종에 비하여 보다 강하게 발현되었고 함치성 낭종과 법랑아세포종간에 발현양상의 차이는 관찰할 수 없었다. 함치성 낭종 및 법랑아세포종에 있어서 apoptosis 관련단백의 발현양상에 관한 이러한 차이가 법랑아세포종의 독특한 공격적 성장양상과 연관이 있으리라 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.267-273
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• 2017

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colon-derived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.