• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6391-6395
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• 2012

Background: Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia, it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer but its diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumor marker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposed for the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4 quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this study was to determine reference intervals for HE4 in an Asian population presenting in University Malaya Medical Centre, a tertiary reference hospital. Materials and Methods: 300 healthy women were recruited comprising 150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to a pelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levels were determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The reference intervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. Results: The upper limits of the $95^{th}$ percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L, and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was noted to increase with age especially in women who were more than 50 years old. We also noted that our proposed reference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study also showed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels of HE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between the Malays and Chinese ethnic groups. Conclusions: More data are needed to establish a reference interval that will better represent the multiethnic Malaysian population. Probably a larger sampling size of equal representation of the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidence on whether genetics plays a role in reference interval determination.

• 한국자기공명학회논문지
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• 제8권1호
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• pp.28-36
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• 2004

Authors investigated whether there is a lateral effect of $^1$H MRS observable metabolite ratios between the symptomatic and the nonsymptomatic side in the early stage of Parkinson's disease with unilateral symptom. Localized in vivo $^1$H MR spectroscopy (MRS) was used to measure the metabolite levels in the symptomatic and the nonsymptomatic sides of the lentiform nucleus in Parkinson"s disease with unilateral symptom (N=25). The metabolite ratios of NAA/Cr and Cho/Cr in the symptomatic side were compared with those in the nonsymptomatic side. Significant metabolic lateral effect of NAA/(Cho+Cr) ratio was established between the symptomatic and the nonsymptomatic side of lentiform nucleus in Parkinson's disease with unilateral symptom (p<0.05). The ratio of NAA/(Cho+Cr) homolateral to the sympatomatic side of the patient is also lower than that of the control (P<0.05). On the basis of NAA/Cr ratios of lentiform nucleus between the symptomatic and the nonsymptomatic side, the present $^1$H MRS study shows a significant neuronal laterality in Parkinson's disease with unilateral symptom. In vivo $^1$H MRS may provide a diagnostic marker for neuronal dysfunction in Parkinson's disease with unilateral symptom.

• Clinical and Experimental Pediatrics
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• 제63권8호
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• pp.329-334
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• 2020

Background: Birth asphyxia is a leading cause of neonatal mortality. Ischemia-modified albumin (IMA) levels may have a predictive role in the identification and prevention of hypoxic disorders, as they increase in cases of ischemia of the liver, heart, brain, bowel, and kidney. Purpose: This study aimed to assess the value of IMA levels as a diagnostic marker for neonatal hypoxic-ischemic encephalopathy (HIE). Methods: Sixty newborns who fulfilled 3 or more of the clinical and biochemical criteria and developed HIE as defined by Levene staging were included in our study as the asphyxia group. Neonates with congenital malformation, systemic infection, intrauterine growth retardation, low-birth weight, cardiac or hemolytic disease, family history of neurological diseases, congenital or perinatal infections, preeclampsia, diabetes, and renal diseases were excluded from the study. Sixty healthy neonates matched for gestational age and with no maternal history of illness, established respiration at birth, and an Apgar score ≥7 at 1 and 5 minutes were included as the control group. IMA was determined by double-antibody enzyme-linked immunosorbent assay of a cord blood sample collected within 30 minutes after birth. Results: Cord blood IMA levels were higher in asphyxiated newborns than in controls (250.83±36.07 pmol/mL vs. 120.24±38.9 pmol/mL). Comparison of IMA levels by HIE stage revealed a highly significant difference among them (207.3±26.65, 259.28±11.68, 294.99±4.41 pmol/mL for mild, moderate, and severe, respectively). At a cutoff of 197.6 pmol/mL, the sensitivity was 84.5%, specificity was 86%, positive predictive value was 82.8%, negative predictive value was 88.3%, and area under the curve was 0.963 (P<0.001). Conclusion: IMA levels can be a reliable marker for the early diagnosis of neonatal HIE and can be a predictor of injury severity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10501-10504
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• 2015

Background: Colon cancer is the second most common cancer in developed countries. Activated platelets play a key role in inflammation and atherothrombosis, with mean platelet volume (MPV) is an early marker of platelet activation. The aim of the study was to clarify the relevance of MPV in patients with colon cancer. Materials and Methods: We measured MPV levels in 128 patients with colon cancer before and after surgery, and 128 controls matched for age, gender, body mass index (BMI) and smoking status. The odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer were calculated using multivariate logistic regression analyses across MPV quartiles. Results: Patients with colon cancer had higher MPV compared with controls. Surgical tumor resection resulted in a significant decrease in MPV levels (11.4 fL vs 10.7 fL; p<0.001). A positive correlation between MPV and tumor-nodule-metastases (TNM) stage was found. Furthermore, after adjusting for other risk factors, the ORs (95%CIs) for colon cancer according to MPV quartiles were 1.000, 2.238 (1.014-4.943), 3.410 (1.528-7.613), and 5.379 (2.372-12.198), respectively. Conclusions: The findings show that patients with colon cancer have higher MPV levels compared with controls, and these are reduced after surgery. In addition, MPV was found to be independently associated with the presence of colon cancer. Further studies are warranted to assess the utility of MPV as a novel diagnostic screening tool for colon cancer.

• Clinical and Experimental Pediatrics
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• 제63권4호
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• pp.151-156
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• 2020

Background: Acute kidney injury (AKI) is one of the most significant postoperative complications of pediatric cardiac surgery. Because serum creatinine has limitations as a diagnostic marker of AKI, new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are being evaluated to overcome these limitations and detect AKI at an early stage after cardiac surgery. Purpose: This study aimed to investigate the clinical usefulness of these biomarkers in young children. Methods: Thirty patients with congenital heart diseases who underwent cardiac surgery using cardiopulmonary bypass (CPB) were selected, and their urine and blood samples were collected at baseline and 6, 24, and 48 hours after surgery. Serum creatinine and blood urea nitrogen levels as well as NGAL, KIM-1, and IL-18 levels in urine samples were measured, and clinical parameters were evaluated. Results: Of the 30 patients, 12 developed AKI within 48 hours after cardiac surgery. In the AKI group, 8 of 12 (66.6%) met AKI criteria after 24 hours, and urine KIM-1/creatinine (Cr) level (with adjustment of urine creatinine) peaked at 24 hours with significant difference from baseline level. Additionally, urine KIM-1/Cr level in the AKI group was significantly higher than in the non-AKI group at 6 hours. However, urine NGAL/Cr and IL-18/Cr levels showed no specific trend with time for 48 hours after cardiac surgery. Conclusion: It is suggested that urine KIM-1/Cr concentration could be considered a good biomarker for early AKI prediction after open cardiac surgery using CPB in young children with congenital heart diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.3043-3050
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• 2015

The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

• Tuberculosis and Respiratory Diseases
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• 제66권6호
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• pp.444-450
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• 2009

연구배경: 폐암은 진단 당시에 완치할 수 있는 확률이 적어 예후가 불량한 종양으로 알려져 있어, 폐암 진행을 예측할 수 있는 암 표지자(tumor marker)의 발굴이 필요한 실정이다. 그러나 폐암에서 아직까지 특이적인 항원이 없고 현재까지 알려진 많은 종양관련 항원들의 민감도가 떨어지기 때문에 보편화되지 못하고 있다. 본 연구에서는 원발성 폐암 환자에서 혈장 G-CSF를 측정하고 암의 진행 및 예후와 관련이 있는지 알아보고자 하였다. 방 법: 원발성 폐암으로 진단된 100명 환자와 건강 검진에서 이상 소견이 없는 127명 정상인을 대상으로 하였다. 결 과: 정상인에서 혈장 G-CSF 농도는 12.2$\pm$3.6 pg/mL (mean$\pm$SD), 폐암환자에서는 46.0$\pm$38.0 pg/mL였다(p<0.001). 비소세포폐암에서 G-CSF 농도는 유의하게 소세포폐암보다 높았으며(p<0.05), 비소세포 폐암중 대세포 폐암이 가장 높았고, 편평세포암, 선암, 세기관지폐포암 순이었다. G-CSF 농도는 국소형보다는 진행형 비소 세포폐암에서 증가하는 경향을 보였다. 또한 타 장기로의 전이가 있을 때 유의하게 증가하였으며(p<0.05), 다발성 전이에서는 뇌, 부신, 골 전이 순으로 혈청 G-CSF 농도가 증가하는 경향이었다. 결 론: 혈장 G-CSF 농도는 폐암이 진행한 경우, 특히 타 장기로의 전이가 있을 때 유의하게 증가하였다. 그러므로 진행형 폐암의 추적관찰에 이용할 수 있으리라 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제51권2호
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• pp.108-121
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• 2001

배 경 : p16 종양 억제 유전자 promoter의 aberrant methylation에 의한 불활성화가 비소세포 폐암이 발병하는 초기단계에 영향을 미치는 것으로 추측되며, DAP kinase 유전자 promoter의 hypermethylation은 유전자의 발현을 억제하여 폐암의 전이에 중요한 역할을 한다고 알려져 있다. 방 법 : 본 연구는 비소세포 폐암으로 근치적 절제술을 받은 환자 중에서 총 35 예를 대상으로 MSP률 이용하여 p16 유전자와 DAP kinase의 비정상적인 methylation의 양상을 조사하여, 폐암에서 두 유전자의 메틸화 빈도, 진단적 응용의 가능성 빛 임상적 유용성을 알고자 하였다. 결 과 : 전체 대상 35예중 p16 유전자의 aberrant methylation은 33예중 13예(39.4%)에서, DAP kinase 유전자 hypermethylation은 35예중 21예(60%)에서 확인할 수 있었다. 55 세 이상에서 p16의 aberrant methylation은 유의하게 증가되어 있었으며, DAP kinase는 병기의 진행도에 따라 발현 빈도가 증가하였으나, 통계학적 의미는 없었다. 또한 p16 유전자와 DAP kinase 유전자간의 메틸화 양상에서도 연관성은 관찰할 수 없었다. 결 론 : p16과 DAP kinase 유전자중 하나라도 비정상적인 메틸화가 발견된 경우는 전체 대상의 74.3% 로 비교적 높은 빈도로 관찰되어 폐암의 조기 진단을 위한 분자 생물학적 방법으로 이용될 수 있을 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제55권4호
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• pp.388-394
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• 2003

배 경 : 지금까지 폐암의 종양표지자로 알려진 것들 중에 최근에는 CK 19뿐만 아니라 폐암에서 많이 발견되는 CK 8, 18에 대해 특이적인 세가지 단클론항체를 이용한 면역방사선계수법(MonoTotal$^{TM}$)이 개발되어 폐암의 진단에 이용할 수 있는 것으로 보고되었다. 따라서 저자들은 Cyfra 21-1에 비교하여 CK 8, 18, 19의 폐암표지자로서의 진단적 가치에 대해 연구하였다. 대상 및 방법 : 2002년 5월 l일부터 2002년 9월 30일까지 서울대학교병원 내과에 입원하여 기관지내시경 또는 객담도말세포검사, 경피적 조직생검으로 확진된 원발성 폐암환자 129명을 폐암군으로 하고 폐암이 배제된 비악성 호흡기 질환자 160명을 환자 대조군으로 연구에 동의한 건강한 성인 57명을 정상 대조군으로 하여 본 연구를 시행하였다. Cyfra 21-1의 측정은 Fujibebio Diagnostics사(USA)의 immnoradiometric assay kit인 Cyfra$^{TM}$ 21-1을 사용하였고 CK 8, 18, 19의 측정은 IDL biotech사의 2-hour immunoradiometric sandwich test kit인 Monototal$^{TM}$을 사용하였다. 결 과 : 폐암의 조직학적 분류에 따른 Monototal의 혈중평균치(mean${\pm}$SD)는 비소세포폐암이 $412.47{\pm}455.45$ U/L, 소세포폐암이 $237.08{\pm}145.15$ U/L로 환자 대조군 $126.54{\pm}95.72$ U/L, 정상 대조군 $63.68{\pm}31.66$ U/L에 비해 유의하게 증가되어 있었다(p<0.01). Monotoal의 정상범위를 정상 대조군의 가장 높은 수치인 188U/L 이내로 하였을때 비소세포폐암의 민감도는 66.4%, 특이도는 81.9%였다. 병기를 I,II군(32명)과 III,IV군(84명)의 두 군으로 나누어 Monototal의 평균을 비교해 보았을 때 각각 $227.6{\pm}185.2$ U/L, $482.9{\pm}506.4$ U/L로 두 군간에 통계적으로 유의한 차이가 있었다(p<0.001). 환자대조군 세부질환별로 Monototal의 평균치를 보면 미만성폐질환 환자군(11명)에서 $298.7{\pm}210.0$ U/L로 환자 대조군 평균치인 $126.54{\pm}95.72$ U/L에 비해 통계적으로 유의하게 높게 측정되었다(p<0.001)(Table 4). 결 론 : cytokeratin 8, 18, 19의 측정은 폐암의 대표적인 종양 표지자중의 하나인 Cyfra 21-1과 비슷한 민감도와 특이도를 보이고 있어 효과적인 종양표지자로 앞으로 사용될 수 있다.