• Asian Pacific Journal of Cancer Prevention
• /
• 제15권4호
• /
• pp.1823-1829
• /
• 2014

Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to the development of acquired chemoresistance. However, the molecular mechanisms are not fully clear. Therefore, we investigated a possible correlation of mRNA expression of HIF-$1{\alpha}$ and GLUT1 with chemoresistance in acute myeloid leukemia (AML). Methods: Bone marrow samples were obtained from newly diagnosed and relapsed AML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1 or HIF-$1{\alpha}$ gene expression in an AML cell line and HIF-$1{\alpha}$ and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR). Results: High levels of HIF-$1{\alpha}$ and GLUT1 were associated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 by RNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparable with RNA interference for the HIF-$1{\alpha}$ gene. Conclusions: Our data revealed that over-expression of HIF-$1{\alpha}$ and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권3호
• /
• pp.985-989
• /
• 2012

Objective: To make sure the feasibility with $^{18F}FDG$ PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Methods: Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and $^{18F}FDG$ PET/CT). The dose distributions of the various regional were realized by SMART. Results: The absolute mean errors of interest area were $2.39%{\pm}0.66$ using 0.6cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Conclusions: Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

• 핵의학기술
• /
• 제25권1호
• /
• pp.21-28
• /
• 2021

갈색지방세포(Brown fat 또는 Brown Adipose Tissue, BAT)는 포도당 대사(glucose metabolism)와 비오한성 열생성(non-shivering thermogenesis)을 통하여 열을 발산하여 추위로부터 생명체를 보호한다. BAT의 활성화는 연령, 성별, 체질량지수(BMI) 등의 환자 내적 요인과 기온, 환경 등의 환자외적 요인에 의해 확률적으로 발생한다. 본 연구에서는 후향적, 의무기록 관찰 연구를 진행하여 여러 인자들을 추출하고 통계 분석을 실시하여 BAT 활성화와 여러 인자 간에 관련성을 확인하고자 한다. 2018년 1월부터 2019년 12월까지 2년간 국립암센터에서 PET/CT 검사를 시행한 환자의 의무기록을 수집하여 총 9155명의 환자를 추출하고 중복 검사를 포함한 13442건의 환자데이터를 대상으로 하였다. 환자데이터의 의무기록에서는 BAT 발생여부, 성별, 검사당시 나이, 영상촬영날짜, 검사장소, 주사시간, 키, 체중, 혈당, 진단명이 나오도록 조건을 설정하였다. BAT 활성화가 PET/CT 촬영 시 환경(기온, 검사장소)과 환자의 상태(혈당, BMI, 암의 종류, 성별, 나이)에 따라 영향을 받는지 확인하기 위하여 단변량 로지스틱 회귀분석을 실행한 후, P<0.1인 변수를 선택하여 BAT 활성화에 영향을 주는 다변량 회귀분석 모형을 최종적으로 분석하였다. BAT 활성화는 전체 13442건 중 93건(0.7%)이 발생되었다. 단변수 로지스틱 회귀분석 결과에서 유의한 결과는, 50세 이상인 환자보다 50세 미만인 환자에게서(P<0.001), 여성이 남성에 비해서(P<0.001), 외부기온 14.5도 미만에서(P<0.001), 정상 BMI보다 낮은 BMI에서(P<0.001), 혈당이 100mg/dl 미만에서(P<0.001), 오후 12시 30분 이전에 주사를 맞은 환자에게서(P<0.001) BAT 활성화가 증가하였다. 반면, 정상보다 높은 BMI에서(P<0.001), 폐암진단을 받은 환자에게서(P<0.05) 감소하였다. 다변수 결과에서는, 50세 미만인 환자에게서(P<0.001), 여성에게서(P<0.001), 외부기온 14.5도 미만에서(P<0.001) BAT 활성화가 유의하게 증가하였고, 정상보다 높은 BMI에서(P<0.05) 유의하게 감소하였다. 국립암센터에서 2년간 PET/CT 시행한 환자를 대상으로 BAT 활성화에 영향을 미치는 인자에 대한 후행 연구를 진행하였다. 그 결과, 외부기온 14.5도 미만의 날씨에 PET/CT 검사를 시행했던 50대 미만의 정상 체중 여성에게서 BAT가 유의하게 활성화가 되었음을 확인할 수 있었다. 이 결과를 토대로 해당 인자에 적용된 환자를 사전에 식별할 수 있으며, 앞으로 여러 연구를 통하여 BAT의 활성화를 줄이는 것에 도움이 될 수 있다고 사료된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권11호
• /
• pp.4525-4530
• /
• 2015

Background: The MTHFR C677T polymorphism is a genetic alteration affecting an enzyme involved in folate metabolism, but its relationship to host susceptibility to prostate cancer remains uncertain. The aim of this study was to investigate the association between MTHFR C677T polymorphism and prostate cancer by performing a meta-analysis. Materials and Methods: Pubmed and Web of Science databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess any link. Results: A total of 22 independent studies were identified, including 10,832 cases and 11,993 controls. Meta-analysis showed that there was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer under all five genetic models. There was also no obvious association between MTHFR C677T polymorphism and risk of prostate cancer in the subgroup analyses of Caucasians. In contrast, MTHFR C677T polymorphism was associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95 %CI =1.121-1.506, P=0.001, $P_{heterogeneity}=0.120$, $I^2=45%$), additive genetic model (CC vs TT: OR =1.925, 95 % CI= 1.340-2.265, P=0.00, $P_{heterogeneity}=0.587$, $I^2=0.00%$), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI=1.233-2.367, P=0.001, $P_{heterogeneity}=0.716$, $I^2=0.00%$), and heterozygote genetic model (CT vs TT: OR=2.193, 95 % CI =1.510-3.186, P=0.000, $P_{heterogeneity}=0.462$, $I^2=0.00%$). Conclusions: These results suggest that the MTHFR C677T polymorphism does not contribute to the risk of prostate cancer from currently available evidence in populations overall and Caucasians. However, the meta analysis indicates that it may play a role in prostate cancer development in Asians.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5921-5926
• /
• 2014

A large proportion of patients with thyroid nodules in China undergo thyroidectomy in order to get confirmatory histology diagnosis. The financial impact of this modality remains to be investigated. To evaluate rationality of performing thyroidectomy without a routine FNA preoperatively from the economic perspective, we conducted a retrospective, observational study of all archival thyroidectomies with records of cost per stay (CPS), cost per day (CPD) and length of stay (LOS) from 2008 to 2013 in the First Affiliated Hospital of Nanjing Medical University. We compared all the parameters between cancer and non-cancer thyroidectomies. We recruited 6, 140 thyroidectomies with valid records of CPS, CPD and LOS in this period. The CPS of cancer thyroidectomy was significantly higher than non-cancer thyroidectomy. The percentage of cancer thyroidectomy increased from 26.5% to 41.6%. The percentage of annual cost of cancer thyroidectomies rose from 30.2% to 45.2%. The LOS for cancer and non-cancer thyroidectomy decreased while the CPD increased in the past six years. The estimated national cost in 2012 for all thyroidectomies would be USD 1.86 billion with USD 1.09 billion for non-cancer thyroidectomies. We have witnessed great improvement in the healthcare for patients with thyroid nodules in China. However, given limited healthcare resources, currently thyroid FNA for more precise preoperative diagnosis may help to curb the rapidly increasing demand in healthcare costs in the future for nodular thyroid disease in China.

• IMMUNE NETWORK
• /
• 제11권3호
• /
• pp.135-154
• /
• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권3호
• /
• pp.1453-1461
• /
• 2016

Regarding 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South American regions), most epidemiologic studies showed positive associations with risk of some cancers, (e.g. upper aerodigestive tract), but evidence on breast cancer (BC) risk is limited to a previous multi-site study, which reported a non significant odds ratio [OR]=0.85, 95% confidence interval [95% CI] 0.67-1.09, p for trend=0.31) for the highest quartile of intake. The present study was conducted in order to further assess associations of 'mate' intake with BC risk. We combined two databases of women belonging to public and private healthcare hospitals. The sample included 572 BC incident cases and 889 controls interviewed with a specific questionnaire featured by socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, also analyzing 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit, intensity of intake). ORs and their 95%CI were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest quartile of 'mate' intake was inversely associated with BC risk (OR=0.40, 95%CI 0.26-0.57, p for trend <0.001). Stratified analyses also displayed strong significant inverse associations for 'mate' in frequent tea drinkers (OR=0.22), high energy intake (OR=0.23), high body mass index (OR=0.29) and in postmenopausal women (OR=0.36), among other results. As conclusions, we found evidence of a significant inverse association for 'mate' intake and BC risk.

• Advances in Traditional Medicine
• /
• 제7권4호
• /
• pp.357-362
• /
• 2007

Cytochrome P450 2C19 (CYP2C19) is a clinically important enzyme involved in the metabolism of therapeutic drugs, including (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals are characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2-5% of Caucasians, but in 18-23% of Asians. To clarify the association between CYP2C19 polymorphisms and gastric cancer in Koreans, we investigated CYP2C19 genotypes ($CYP2C19^*1,\;{^*2},\;and\;^*3$) in 109 patients with gastric cancer and 211 controls. Normal ($CYP2C19^*1$) and defective alleles were detected with polymerase chain reaction/restriction enzyme analysis. CYP2C19 has three hereditary genotypes: homozygous EM, with high enzymatic activity; heterozygous EM, with moderate enzymatic activity; and PM, with no enzyme activity. We found that CYP2C19 heterozygous EM is more closely associated with gastric cancer than is homozygous EM. Because the CYP2C19 genotype varies in Koreans, a genotyping test is desirable to prevent gastropathy recurrence in patients before their doses of omeprazole are reduced during maintenance therapy.

• Journal of Gastric Cancer
• /
• 제2권4호
• /
• pp.213-220
• /
• 2002

Purpose: The cDNA microarray provides a powerful alternative with an unprecedented view in monitoring geneexpression levels and leads to discoveries of regulatory pathways involved in complicated biological processes. Our aim is to explore the different gene-expression patterns in gastric adenocarcinomas. Materials and Methods: By using a cDNA microarray representing 4,600 cDNA clusters, we studied the expression profiling in 10 paired gastric adenocarcinoma samples and in adjacent noncancerous gastric tissues from the same patients. Alterations in the gene-expression levels were confirmed by Vsing Northern blots and reverse-transcription PCR (RT-PCR) in all of 4 randomly selected genes. Results: Genes those were expressed differently in cancer ous and noncancerous tissues were identified. 44 (of which 26 were known) and 92 (of which 43 were known) genes or cDNA were up- and down-regulated, respectively, in more than $80\%$ of the gastric adenocarcinoma samples. In cancer ous tissues, genes related to gene/protein expression, cellcycle regulation, and metabolism were mostly up-regulated whereas genes related to the oncogene/tumor suppressor gene, cell structure/motility, and immunology were mostly down-regulated. The semi-quantitative RT-PCR results for the four genes we tested were consistent with the array findings. Conclusions: These results provide not only a new molecular basis for understanding the biological properties of gastric adenocarcinomas but also a useful resource for future development of therapeutic targets and diagnostic markers for gastric adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권4호
• /
• pp.1851-1855
• /
• 2016

Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was $44.3{\pm}11.1years$, and they were subtyped as ER+/progesterone receptor (PR)+ (28 patients), ER+/PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.