• Title/Summary/Keyword: p53-independent p21

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Comparative Outcome of Thai Pediatric Osteosarcoma Treated with Two Protocols: the Role of High-Dose Methotrexate (HDMTX) in a Single Institute Experience

  • Choeyprasert, Worawut;Pakakasama, Samart;Sirachainan, Nongnuch;Songdej, Duantida;Chuansumrit, Ampaiwan;Anurathapan, Usanarat;Hongeng, Suradej;Nartthanarung, Adisak
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9823-9829
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    • 2014
  • Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

Apoptotic Cell Death by Methanol Extract of Phellinus linteus-Barley Corn in Human Leukemic U937 Cells through Induction of p21 and Bax, and Activation of Caspase-3 (상황보리 추출물에 의한 p21 및 Bax 발현 증가와 caspase 활성화를 통한 U937 인체백혈병 세포의 apoptosis 유발)

  • Park, Cheol;Kim, Hyun-Joog;Chung, Kyung-Tae;Yoon, Tae-Kyung;Choi, Byung-Tae;Lee, Yong-Tae;Park, Dong-Il;Choi, Yung-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1226-1232
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    • 2007
  • Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the anti-proliferative activity of the methanol extract of P. linteus-Barley corn (MEPLB) in human lekemic U937 cells. It was found that exposure of U937 cells to MEPLB resulted morphological change and growth inhibition in a dose-dependent manner as measured by trypan blue count and MTT assay. Upon treatment with MEPLB, U937 cells developed many of the hallmark features of apoptosis, including condensation of chromatin and an increase in the sub-G1 population suggesting that the anti-proliferative effect of MEPLB is associated with the induction of apoptosis. The anti-proliferative and apoptotic effects of MEPLB were connected with a marked induction of the pro-apoptotic Bax and cyclin-dependent kinase (Cdk) inhibitor p21 in a p53-independent manner. Additionally, MEPLB treatment significantly induced the caspase-3 activity in U937 cells. Taken together, the present results suggest that apoptotic signals evoked by MEPLB in human leukemic U937 cells may converge caspase-3 activation through an up-regulation of Bax rather than a down-regulation of Bcl-2 or Bel-xL.

Comparison of General Composition of Cooked Krill and Alcalase Optimization for Maximum Antioxidative Activity by Using Response Surface Methodology (자숙크릴의 일반성분 분석과 항산화 활성을 위한 반응표면법에 의한 알카라제 가수분해 최적화)

  • Kim, Kyoung-Myo;Cho, Yong-Bum;Hwang, Young-Jeong;Lee, Da-Sun;Lee, Yang-Bong
    • Culinary science and hospitality research
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    • v.18 no.1
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    • pp.15-26
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    • 2012
  • The objective of this study is to optimize enzymatic hydrolysis of cooked krill by using Alcalase. To optimize krill hydrolysis on such dependent variables as TCA, DPPH-scavenging, and Fe-chelating activities by using Alcalase, independent variables of hydrolysis pH and temperature were investigated Their formulas and three dimensional graphs were obtained by using SAS and Maple softwares, respectively. For comparison of general composition of raw krill, its contents of moisture, crude protein, crude fat, and ash were 17.48%, 53.74%, 15.66%, and 10.21%, respectively, and for cooked krill, its contents were 4.80%, 71.84%, 5.26%, and 15.09%, respectively. The composition of fatty acids for cooked krill was similar to that of raw krill. The most abundant fatty acid was palmitic acid(16:0) and the following order was oleic acid(18:1), eicosapentaenoic acid (20:5), palmitoleic acid(16:1), and docosahexaenoic acid(22:6). For DH optimization of hydrolysates from cooked krill, its result was pH 8.5 and $66.6^{\circ}C$ hydrolysis temperature for the maximum DH of 29.4% For DPPH-antioxidative optimization of hydrolysates from raw krill, its maximum result of 27.1% was obtained in the hydrolysis condition of pH 7.4 and $67.5^{\circ}C$. For Fe-chelating optimization of hydrolysates from cooked krill, its maximum result of 24.9% was in the condition of pH 8.7 and $65.5^{\circ}C$. These results can be used for basic data for using krill products and other fish products as bioactive ingredients.

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Analysis of Risk factors & Morphological Ultrasound Image for Gallbladder Polyp in Adults Living in Busan and Gyeongnam Provinces (부산·경남 지역 성인의 담낭용종 위험인자 및 초음파 영상의 형태학적 분석)

  • An, Hyeon;Hwang, Chul-Hwan;Ko, Sung-Jin;Kim, Chang-Soo
    • Journal of radiological science and technology
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    • v.39 no.3
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    • pp.353-359
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    • 2016
  • This study were to evaluate risk factors of GB polpy in Busan and Gyeongnam area. This study was performed with patients by abdominal ultrasonography among the patients who came to the P hospital from January to May 2016. Among them, risk factors were analyzed on 399 people at the same time when abdominal ultrasonography and hematological test. The statistical analysis of risk factors related to the GB ployp was performed by independent t-test and chi-square test. In consider of difference verification result for calculations odds ratio about independent variables, multiple logistic regression analysis to conduct verify adequacy by calculating forecasting model from variable. As a result, GB polyp risk factors have relevance to male, HBsAg positive, triglyceride. GB polyp risk factors confirmed to male, HBsAg positive, triglyceride were calculated forecasting model and forecasting probability value. Forecasting probability sensitivity 61.0%, specificity 76.8%, ROC area under curve 0.735 showed, it confirmed validity of forecasting model. When analyzing the GB polyps morphologically, among the GB polyp types observed from abdominal ultrasonography, the hyperechoic and homogeneous pattern with neck was the largest as shown from 27.5% and two GB polyps were shown most from 38%, sizes were shown most by maximum diameter, 5 to 10mm from 53%. As a disease accompany with GB polyp showed mild fatty liver(23%), diffuse hepatopathy(21%).

Anti-proliferative Effects by Aqueous Extract of Cordyceps Militaris in Human Leukemic U937 Cells (동충하초 추출물에 의한 U937 인체 백혈병 세포의 성장억제 효과)

  • Park, Dong-Il;Seo, Sang-Ho;Choi, Yung-Hyun;Hong, Sang-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.2
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    • pp.452-458
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    • 2005
  • Cordyceps militaris is a medicinal fungus, which has been used for patient suffering from cancer in Oriental medicine. It was reported previously that C. militaris extracts are capable of inhibiting tumor growth, however, the anti-poliferative effects of human cancer cells have not been poorly understood. In this study, to elucidate the growth inhibitory mechanisms of human cancer cells by treatment of aqueous extract of C. militaris (AECM) we investigated the anti-proliferative effects of AECM in human leukemia U937 cell line. AECM treatment inhibited the growth of U937 cells and induced the apoptotic cell death in a concentration-dependent manner, which was associated with morphological changes. We observed the up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) by p53-independent manner and activation of caspase-3 in AECM-treated U937 cells, however, the activity of caspase-9 was remained unchanged. Additionally, AECM treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1). Taken together, these findings suggest that AECM-induced inhibition of human leukemic cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and C. militaris may have therapeutic potential in human lung cancer.

Objective Quantitation of EGFR Protein Levels using Quantitative Dot Blot Method for the Prognosis of Gastric Cancer Patients

  • Xin, Lei;Tang, Fangrong;Song, Bo;Yang, Maozhou;Zhang, Jiandi
    • Journal of Gastric Cancer
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    • v.21 no.4
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    • pp.335-351
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    • 2021
  • Purpose: An underlying factor for the failure of several clinical trials of anti-epidermal growth factor receptor (EGFR) therapies is the lack of an effective method to identify patients who overexpress EGFR protein. The quantitative dot blot method (QDB) was used to measure EGFR protein levels objectively, absolutely, and quantitatively. Its feasibility was evaluated for the prognosis of overall survival (OS) of patients with gastric cancer. Materials and Methods: Slices of 2×5 ㎛ from formalin-fixed paraffin-embedded gastric cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for the Kaplan-Meier OS analysis. Results: EGFR protein levels ranged from 0 to 772.6 pmol/g (n=246) for all gastric cancer patients. A poor correlation was observed between quantitated EGFR levels and immunohistochemistry scores with ρ=0.024 and P=0.717 in Spearman's correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric cancer patients only through absolute quantitation, with a hazard ratio of 1.92 (95% confidence interval, 1.05-3.53; P=0.034) in multivariate Cox regression OS analysis. A cutoff of 208 pmol/g was proposed to stratify patients with a 3-year survival probability of 44% for patients with EGFR levels above the cutoff versus 68% for those below the cutoff based on Kaplan-Meier OS analysis (log rank test, P=0.002). Conclusions: A QDB-based assay was developed for gastric cancer specimens to measure EGFR protein levels absolutely, quantitatively, and objectively. This assay should facilitate clinical trials aimed at evaluation of anti-EGFR therapies retrospectively and prospectively for gastric cancer.

Effect of Strength Coaching Program for First Clinical Experience of Nursing Students (강점코칭 프로그램이 간호대학생의 첫 임상실습에 미치는 효과)

  • Hong, Ju-Young;Lee, So-Young
    • The Journal of the Convergence on Culture Technology
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    • v.6 no.2
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    • pp.139-143
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    • 2020
  • Purpose: This study was conducted to examine the effects of a strength coaching program on nursing students' clinical competence, self esteem, and practice satisfaction. The study was designed using a nonequivalent control group pretest-post test design, and data were collected between January 7 and February 1, 2019. The participants consisted of 41, 3-year nursing students in G City who were assigned to an experimental group (n=21) or a control group (n=20). The data were analyzed using descriptive analysis, a t-test, χ2 test, and paired t-test with the SPSS/WIN 21.0 program. After receiving the strength coaching program, a difference was observed in self esteem(t=5.53, p<0.038), and practice satisfaction (t=7.66, p<0.019) of the experimental group. The results of this study indicate that the strength coaching program was effective at increasing self esteem and practice satisfaction in nursing students.

Clinical significance of loss of p16 protein by immunohistochemical staining in acute lymphoblastic leukemia (급성림프구성백혈병에서 면역조직화학염색에 의한 p16 단백질 소실의 의의)

  • Jin, Hye Young;Kang, Kyoung In;Kim, Sun Young;Youn, You Sook;Kang, Joon Won;Jo, Deog Yeon;Kwon, Kye Chul;Park, Kyung Duk
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.73-77
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    • 2008
  • Purpose : p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acute lymphoblastic leukemia (ALL), deletion and/or mutation of the p16 gene has been found. Despite their high frequency, the prognostic importance of p16 alterations is still controversial in ALL and has been reported to be either unfavorable or similar to that of other patients. We studied the correlation between loss of p16 protein confirmed by immunohistochemical staining and clinical outcomes of patients diagnosed as ALL. Methods : We performed an immunohistochemical staining for p16 protein in 74 cases of bone marrow biopsy slide initially diagnosed as ALL between January 1998 and December 2006. We reviewed the clinical manifestations, laboratory findings, treatment outcomes retrospectively. Results : Of 74 slides, 12 were negative for p16 protein. Seven were males and 5 were females with a median age at diagnosis was 5.8 (1.3-18.8) years. Initial WBC were 17,225 $(500-403,300)/{\mu}L$. By immunologic surface marker analysis, 7 patients were early pre-B CALLA (+) and 5 patients were T-cell ALL. Two patients of intermediate risk group had relapsed and died. Three patients had family history of breast cancer. Four patients died and overall survival rates were $53.5{\pm}18.7%$. Conclusion : Loss of p16 protein is supposed to be an independent risk factor of childhood ALL associated with poor outcomes. In clinical setting, the clinician must take into account p16 status, not only at the genomic but also at the protein level. Further clinical experience on thoroughly investigated cases will help a better understanding between p16 status and clinical outcomes.

The effect of clinical dental hygienist psychological well-being on emotional intelligence in an area (임상치과위생사의 심리적 안녕감이 감성지능에 미치는 영향)

  • Kim, Young-im
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.7
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    • pp.504-509
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    • 2020
  • This study analyzed the factors that affect the emotional intelligence of clinical dental hygienists' psychological well-being. The study was conducted from September 1, 2019 to November 30, 2019 with 180 dental hygienists living in Jeollabuk-do province. The data was analyzed by independent t-tests, one-way ANOVA, Scheffé test, Pearson's correlation coefficient, and stepwise multiple regression using SPSS 18.0. Psychological well-being has a significant correlation with emotional intelligence (r=.596, p<.001). Emotional intelligence of clinical dental hygienists was found to be significant in a suitable regression model (F=116.575, p<.05), and the explanatory power was 53.6%. The higher the psychological well-being was, the higher the emotional intelligence was. The factors related to emotional intelligence of clinical dental hygienists were psychological well-being, self-acceptance, positive relations to others, personal growth, environmental mastery and clinical experience. The results of this study show that psychological well-being is related to emotional intelligence. It is necessary to establish an effective strategy to enhance the psychological well-being of clinical dental hygienists and strengthen their emotional intelligence.

Dichloroacetate Inhibits the Proliferation of a Human Anaplastic Thyroid Cancer Cell Line via a p53-independent Pathway (Dichloroacetate의 p53 비의존적 경로를 통한 인간 역분화 갑상선 암세포주의 성장억제 효과)

  • KC, Yam Bahadur;Poudel, Sunil;Jeon, Eon Ju;Shon, Ho Sang;Byun, Sung June;Jeoung, Nam Ho
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1469-1476
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    • 2018
  • Occurrence of the Warburg effect in solid tumors causes resistance to cancer chemotherapy, and targeting energy metabolisms such as aerobic glycolysis is a potential strategy for alternative treatment. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), shifts glucose metabolism from aerobic glycolysis to oxidative phosphorylation (OxPhos) in many cancers. In this study, we investigated the anticancer effect of DCA on a human anaplastic thyroid cancer (ATC) cell line, 8505C. We found that DCA selectively inhibits cell proliferation of the 8505C line but not of a normal thyroid line. In 8505C, the cell cycle was arrested at the G1/S phase with DCA treatment as a result of decreased antiapoptotic proteins such as $HIF1{\alpha}$, PDK1, and Bcl-2 and increased proapoptotic proteins such as Bax and p21. DCA treatment enhanced the production of reactive oxygen species which consequently induced cell cycle arrest and apoptosis. Interestingly, DCA treatment not only reduced lactate production but also increased the expression of sodium-iodine symporter, indicating that it restores the OxPhos of glucose metabolism and the iodine metabolism of the ATC. Taken together, our findings suggest that PDK inhibitors such as DCA could be useful anticancer drugs for the treatment of ATC and may also be helpful in combination with chemotherapy and radiotherapy.