• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7045-7056
• /
• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권11호
• /
• pp.5759-5762
• /
• 2012

The objective of the study was to evaluate the efficacy of a health check-up program among Thai people at the National Cancer Institute in the years 2008-2009. The program included history taking, physical examination, chest X-ray, EKG, and laboratory tests. A total of 28,240 women and 9,665 men were included in the study, with mean ages of 44.5 and 46.9 years, respectively. The study showed that obesity, as assessed by a BMI over 25.0 kg/m2, in men and women was present in 41.4% and 30%, respectively. Biochemical study revealed that anemia was prevalent in 21.6% of men and 20.1% of women. High plasma glucose level (>115 mg/dL), cholesterol level (>200 mg/dL), triglyceride level (>190 mg/dL) in men was 13.8%, 63.8%, 22.6% and 7.7%, 61.1%, 8.9% in women. Hepatitis B virus infection was found 7.5% in men and 4.1% in women. In this study, 177 new cancer cases were detected, of which 35 were breast, 19 were cervical and 26 were colorectal, most of these cancers being detected at early stage. In addition, precancerous states was also found including 718 cases of benign and 99 cases of adenoma in situ. In conclusion, an annual check up may detect abnormalities that have no obvious clinical symptoms of disease. Early detection of asymptomatic neoplasms and precursor lesions should contribute to a prompt provision of treatment and further decline of death from cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권18호
• /
• pp.8589-8594
• /
• 2016

Background: Liver cancer is one of the most common causes of death in the world. In Korea, hepatitis B virus (HBV) is a major risk factor for liver cancer but infection rates have been declining since the implementation of the national vaccination program. In this study, we examined the secular trends in liver cancer mortality to distinguish the effects of age, time period, and birth cohort. Materials and Methods: Data for the annual number of liver cancer deaths in Korean adults (30 years and older) were obtained from the Korean Statistical Information Service for the period from 1984-2013. Joinpoint regression analysis was used to study the shapes of and to detect the changes in mortality trends. Also, an age-period-cohort model was designed to study the effect of each age, period, and birth cohort on liver cancer mortality. Results: For both men and women, the age-standardized mortality rate for liver cancer increased from 1984 to 1993 and decreased thereafter. The highest liver cancer mortality rate has shifted to an older age group in recent years. Within the same birth cohort group, the mortality rate of older age groups has been higher than in the younger age groups. Age-period-cohort analysis showed an association with a high mortality rate in the older age group and in recent years, whereas a decreasing mortality rate were observed in the younger birth cohort. Conclusions: This study confirmed a decreasing trend in liver cancer mortality among Korean men and women after 1993. The trends in mortality rate may be mainly attributed to cohort effects.

• Genomics & Informatics
• /
• 제8권1호
• /
• pp.9-18
• /
• 2010

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (${\beta}1$) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and $P^{corr}=0.05$). The minor allele frequency (MAF) of ITGB1 haplotype -2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.

• 대한불안의학회지
• /
• 제5권2호
• /
• pp.103-111
• /
• 2009

Objectives : We examined quality of life, psychosocial adjustments to illness, changes in sexual functioning, and prevalence of psychiatric disorders in AIDS patients compared to patients with chronic hepatitis B virus infection (CHB). Methods : Thirty-one men with AIDS and 50 men with CHB were enrolled. The Short-Form 12-Item Health Survey (SF-12), the Psychosocial Adjustment to Illness Scale (PAIS), and the Changes in Sexual Functioning Questionnaire short form (CSFQ-14) were administered. Results on these assessments were compared between the 31 AIDS patients and 50 CHB patients. The Structured Clinical Interview for DSMIV (SCID) was administered to determine the psychiatric diagnosis only for the AIDS patients. Results : The Physical Component Summary score (PCS) was lower in AIDS patients than in CHB patients (p<0.001). In the section examining sexual relationships, AIDS patients exhibited a lower level of adjustment (p<0.05) and had more changes in sexual function (p<0.05) than did CHB patients. Administration of the SCID to AIDS patients indicated that the lifetime prevalence of any psychiatric disorder was 56.7% ; 43.3% for mood disorders, 33.3% for alcohol use disorders, 26.7% for anxiety disorders, and 20% for adjustment disorder. Patients who had experienced any psychiatric disorder had more severe psychosocial distress (p=0.004) and evidenced a lower level of overall psychosocial adjustment (p=0.030) than patients who had not. Conclusion : We showed that AIDS patients have a high prevalence of psychiatric disorders, and that AIDS patients with psychiatric disorders were particularly low in levels of psychosocial adjustment. Thus, careful attention should be given to psychiatric aspects of AIDS patients emphasizing the early diagnosis and treatment of psychiatric disorders.

• Molecules and Cells
• /
• 제41권5호
• /
• pp.401-412
• /
• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• Journal of Yeungnam Medical Science
• /
• 제31권2호
• /
• pp.117-121
• /
• 2014

Transarterial chemoembolization (TACE) is a widely accepted nonsurgical modality used for the treatment of multinodular hepatocellular carcinoma (HCC). The careful selection of the candidate is important due to the risk of developing various side effects. Fever, nausea, abdominal pain, and liver enzyme elevation are commonly known side effects of TACE. Hepatic failure, ischemic cholecystitis, and cerebral embolism are also reported, although their incidence might be low. Pulmonary complication after TACE is rare, and the reported cases of lipiodol pneumonitis are even rarer. A 53-year-old man was treated with TACE for ruptured HCC associated with hepatitis B virus infection. On day 19 after the procedure, the patient complained of dyspnea and dry cough. Chest computed tomography showed diffuse ground glass opacities in the whole-lung fields, suggesting lipiodol-induced pneumonitis. After 2 weeks of conservative management, the clinical symptoms and radiologic abnormalities improved. Reported herein is the aforementioned case of lipiodol-induced pnemonitis after TACE, with literature review.

• 한국가금학회지
• /
• 제46권1호
• /
• pp.31-37
• /
• 2019

닭의 clathrin-associated adaptor protein $3-{\delta}$ subunit 2(AP3S2)는 clathrin-coated vesicle를 가진 표적 세포막으로 암 배양 단백질 수송에 관여한다. AP3S2는 C형 간염 바이러스 감염으로 간 섬유화를 매개하고, 2형 당뇨병과 관련이 있는 것으로 알려져 있다. 또한, AP3S2는 clathrin-dependent endocytosis를 통해 숙주 세포로의 바이러스 유입에 관련된 역할을 하는 것으로 알려져 있다. 본 연구는 기존 연구에서 닭 신장조직에서 차별 발현 유전자로 발굴된 닭 AP3S2 유전자의 분자유전학적 특성을 구명하고, 닭의 조직에서의 유전자 발현 양상을 조사하며, 톨-유사수용체 3 (Toll-like receptor 3; TLR3) 자극에 의한 전사 조절을 연구하였다. 닭 AP3S2 유전자가 코딩하는 단백질의 구조는 다른 종과 매우 보존적이고 진화적으로 제브라 피쉬와 가장 가깝고, 포유류와 가장 먼 것으로 추정되었다. 닭의 다양한 조직에서 닭 AP3S2 유전자의 전사 수준을 조사한 결과, 폐에서 가장 높게 발현되었으며, 그 다음은 비장 순이었다. 닭의 배아 섬유아세포 주인 DF-1세포에서 조사한 결과, AP3S2 유전자의 발현은 TLR3 신호자극에 의해 감소하였다. 전사조절인자인 $NF{\kappa}B$나 AP-1의 억제제를 이용하여 조사한 결과, $NF{\kappa}B$나 AP-1의 억제에 의해 유전자 발현이 영향을 받지 않았다. 이 결과는 DF-1 세포에서 닭 AP3S2 유전자의 발현은 적어도 이 두 전사조절인자와는 독립적인 경로에 의해 조절됨을 시사한다. 본 연구의 결과는 닭 AP3S2가 바이러스 감염에 역할을 하고, TLR3 신호에 관여함을 제시한다. 추가연구를 통해 닭 AP3S2의 전사 조절과 바이러스 침입 메커니즘을 구명할 필요가 있다고 사료된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권1호
• /
• pp.245-251
• /
• 2015

Objectives: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-${\alpha}$) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone. Methods: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-${\alpha}$ (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP), and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated. Results: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE-IFN-${\alpha}$ group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-${\alpha}$ group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-${\alpha}$ combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS. Conclusions: The use of the TACE and IFN-${\alpha}$ combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.

• Journal of Yeungnam Medical Science
• /
• 제4권2호
• /
• pp.121-129
• /
• 1987

만삭 임부 및 신생아에서의 B형간염 감염실태를 알아보기 위하여 1986년 1월 1일부터 1987년 6월 30일까지 영남대학교 의과대학 부속병원 산부인과에서 분만을 위해 입원한 임부 2,032명중 1,276명에 대하여 HBsAg 혈증 여부을 검사하고 혈청 HBsAg 양성으로 확인된 임부 74명중 66명과 그 신생아에서 B형간염 바이러스 표식자 검사와 함께 SGOT 및 SGPT를 측정한 결과 다음과 같은 성적을 얻었다. 1. 만삭 임부의 혈청 HBsAg 양성율은 4.7%(53/1,279) 이었다. 2. HBsAg 혈증 임부의 신생아에서의 혈청 HBsAg과 anti-HBs 양성율은 각각 12.1%(8/66)와 9.1%(6/66)이었다. 3. HBsAg 혈증 만삭 임부에서의 혈청 anti-HBc, HBeAg, 및 anti-HBe 양성율은 각각 94.0%(62/66), 45.5%(30/66), 및 50%(33/66)이었으며, 혈청 anti-HBc, HBeAg, 및 anti-HBe의 모체 - 신생아 전파율은 각각 85.5%(53/62), 90%(27/30), 및 87.9%(29/33)이었다. 혈청 anti-HBc와 anti-HBe가 신생아에서만 검출된 경우는 각각 1예와 2예가 있었으며 anti-HBe가 검출된 신생아 2명중 1예에서만 혈청 anti-HBs도 동시에 검출되었다. 4. HBsAg 혈증 만삭 임부에서 모체가 혈청 HBeAg를 보유한 경우와 혈청 anti-HBe를 보유한 경우의 신생아 혈청 HBsAg 양성율은 각각 13.3%(4/30)와 9.1%(3/33)이었으며, 모체에서 혈청 HBeAg과 anti-HBe가 모두 검출되지 않은 경우, 신생아 혈청 HBsAg 양성율은 33.3%(1/3)이었다. 이상의 검사성적으로 미루어 한국인 임부에서도 임신말기에 B형간염 바이러스 표식자검사가 routine screening으로 시행되어야 할 것으로 생각되었으며, B형간염 바이러스의 산전 태반을 통한 신생아 전파율이 본 연구에서는 24.2%로 추정되었다.