• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.215-221
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• 2002

Cephradine is a first generation cephalosporin and has broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms, through inhibition of bacterial cell wall synthesis. Cephradine is useful for treatment of infections of the urinary and respiratory tract, skin and soft tissues. The purpose of the present study was to evaluate the bioequivalence of two cephradine capsules, Cefradine Yuhan (YuHan Corporation) and Broadcef (Ilsung Pharmaceuticals Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cephradine release from the two cephradine capsules in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $23.10{\pm}2.90$ years in age and $67.69{\pm}8.04\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 500 mg as cephradine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephradine in serum were determined using HPLC method with UV detector. The dissolution profiles of two cephradine capsules were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AVC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Cefradine Yuhan were -2.87%, -0.96% and -4.85%, respectively. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of 1og(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.02)\;and\;log(0.88){\sim}log(1.13)\;for \;AVC_t\;and\;C_{max},\;respectively)$. The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g., \;-17.54{\sim}7.78\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Broadcef capsule is bioequivalent to Cefradine Yuhan capsule.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10255-10262
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• 2015

High risk human papillomavirus (HR-HPV) E2 proteins play roles in transcriptional regulation and are commonly functionally disrupted when the HPV genome integrates into host chromosomes. Some 15-40% of cancer cases, however, contain an intact E2 gene or episomal HPV. In these cases, polymorphism of the E2 gene might be involved. This study aimed to determine polymorphisms of the E2 gene in episomal HPV16 detected in high grade squamous intraepithelial lesions and squamous cell carcinomas and altered functions compared to the E2 prototype. The E2 gene was amplified and sequenced. Two expression vectors containing E2 gene polymorphisms were constructed and transfected in SiHa and C33A cells, then E6 gene as well as Il-10 and TNF-${\alpha}$ expression was determined by quantitative RT-PCR. Expression vectors and reporter vectors containing the HPV16 long control region (LCR) were co-transfected and transcriptional activity was determined. The results showed that a total of 32 nucleotides and 23 amino acids were changed in all 20 cases of study, found in the transactivation (TA) domain, hinge (H) region and DNA binding (DB) domain with 14, 5 and 13 nucleotide positions. They mostly caused amino acid change. The expressing vectors containing different E2 gene polymorphisms showed E6 mRNA suppression, TNF-${\alpha}$ mRNA suppression and IL-10 induction but no statistically significant differences when compared to the E2 prototype. Moreover, promoter activity in HPV16 LCR was not affected by E2 protein with different gene polymorphisms, in contrast to nucleotide variations in LCR that showed an effect on transcription activity. These results demonstrated that E2 gene polymorphisms of episomal HPV16 did not affect transcriptional regulation and suggested that nucleotide variation as well as epigenetic modification of the LCR might play a role in inducing malignant transformation of cells containing episomal HPV16.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6789-6794
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• 2015

Background: To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. Materials and Methods: Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. Results: The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). Conclusions: Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• 대한소아치과학회지
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• 제29권4호
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• pp.581-585
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• 2002

Focal epithelial hyperplasia(FEH)는 구강편평상피의 국소적인 증식으로 사람유두종바이러스(Human papilloma virus)에 의해 유발되는 것으로 알려져 있다. 보통 어린 나이에 호발하며 종종 젊은 성인에서 발생하기도 한다. 협,순측 및 설측 점막에 호발하지만 치은이나 혀의 병소(lesions of tongue)도 보고된 바 있다. 이 병소는 전형적으로 다발성인 부드럽고 촉진 시 압통이 없는 편평한 구진이나 반의 형태를 갖는다. 종종 유두상의 표면을 보이기도 한다. 각각의 병소는 비교적 작고 분리되어 있으며 잘 경계지어진다. FEH의 조직학적 특징은 구강 상피의 유극세포증(acanthosis)이다. 그 밖에 바이러스에 의한 세포병리학적 변화를 나타내는 구멍세포(koilocyte)나 유사분열상 세포(mitosoid cell)가 관찰되기도 한다. 본 증례의 5세 여자환아는 치은의 돌기성 병소를 주소로 연세대학교 치과대학병원 소아치과에 내원하였다. 임상구강검사 결과 무경형의 유두상 구진(sessile papillary papules)이 상악 좌우측 제 2 유구치 협측 치은에서 관찰되었다. 촉진 시 동통은 없었다. 조직학적 검사를 위해 조직생검을 시행하였으며, 유극세포증이 관찰되었다. 이에 FEH로 진단되어 보고하는 바이다. FEH는 몇 달이나 몇 년 이내에 자발적으로 소멸하므로 일반적으로 치료는 불필요하다. 다만 진단적인 이유나 심미적인 이유로 보존적인 절제술을 시행하기도 한다. 이러한 치료 후 재발의 위험은 최소한이며, 악성 전이 가능성 역시 거의 없다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5013-5018
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• 2015

Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. Objective: To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. Materials and Methods: All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. Results: One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Conclusions: Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4215-4218
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• 2015

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3431-3436
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• 2016

Background: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator. Materials and Methods: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 18-70 years. Quantitative Real Time Polymerase Chain Reaction (q-RT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters. Results: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P < .05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04). Conclusions: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3101-3103
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• 2016

Background: According to the most recent estimation of GLOBOCAN, Cambodia has the highest incidence and mortality rate of cervical cancer in Southeast Asia. A screen-and-treat strategy using visual inspection with acetic acid (VIA test) and cryotherapy has been implemented in Cambodia's national cervical cancer screening program since 2013. However, where resources are available, cervical cytology with or without high-risk HPV DNA testing is the preferred screening method used in this country. Aim: This study aims to calculate the prevalence of abnormal cervical cytology and explain the possible factors contributing to a reduced quality of cervical cytology among women participating in a hospital-based cervical cancer screening program in Cambodia. Materials and Methods: A descriptive study was conducted using information from the cytology and pathology database in the Department of Pathology of Calmette Hospital between January 2012 and December 2015. Prevalence of abnormal cervical cytology, based on the Bethesda 2001 classification, was calculated. Data on the adequacy of cytological specimens were analyzed in order to explain the factors contributing to a reduced quality of cervical cytology interpretation. Results: Among 6,207 women who participated in the cervical cancer screening program at Calmette Hospital during 2012 and 2015, 388 (6.25%) had abnormal cytology, which could be classified into Atypical Squamous Cells of Undetermined Significance (92 cases; 1.48%), Atypical Squamous Cells - Cannot Exclude High-Grade Intraepithelial Lesion (13 cases; 0.21%), Atypical Glandular Cells (11 cases; 0.18%), Low-Grade Squamous Intraepithelial Lesion (221 cases; 3.56%), High-Grade Squamous Intraepithelial Lesion (26 cases; 0.42%), and Squamous Cell Carcinoma (25 cases; 0.40%). Unsatisfactory smears made up 12.2% of the total cases. The most frequently identified factor leading to unsatisfactory smears was the absence of cells from the transformation zone. Conclusions: The present study showed an overall prevalence of abnormal cervical cytology of 6.25%, which is comparable to that in many large population-based studies in the Asia Pacific region. Nevertheless, the remarkably high rate of unsatisfactory smears in this study justifies further improvement in specimen sampling among Cambodian gynecologists.

• Journal of Plant Biotechnology
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• 제43권3호
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• pp.383-390
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• 2016

본 연구에서는 국내에서 재배중인 배추 전세포 추출물의 FT-IR 스펙트럼 데이터로부터 다변량 통계분석(PCA, PLS-DA, HCA)을 이용하여 신속하고 간편한 계통 구분체계를 확립하였다. 다변량 통계분석 결과 대사체 수준에서 배추의 부계, 모계, $F_1$ 계통들이 계통에 따라 유연관계가 높음을 알 수 있었다. 아울러 본 연구에서 얻어진 대사체 정보의 유연관계분석은 $F_1$ 계통의 부계와 모계에 대한 유연관계가 교배에 따라 달라질 수 있음을 보여주었다. 따라서 FT-IR 스펙트럼 데이터의 다변량 통계분석 기술은 대사체 정보를 기반으로 한 신품종 선발방법의 간편성과 신속성을 고려할 때 배추의 계통이나 품종의 신속한 식별 수단으로 활용이 가능할 것으로 기대된다.