• 핵의학기술
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• 제22권1호
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• pp.80-83
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• 2018

Purpose Assessment of Serum Thyroglobulin (sTg) value in total thyroidectomy patients having an ablation dose of radioactive iodine indicates remaining cancer or metastasis. Especially, sTg in patients on withdrawal thyroxine or thyrogen administration for radioiodine ablation is an important indicator to determine the direction of further treatment and prognosis. Current guidelines suggest measurement of sTg is performed at 72 hours after the last injection of thyrogen. and assumes that sTg reaches maximum serum levels at that time. The purpose of this study is to evaluate the variation of sTg measured after thyrogen administration. Materials and Methods We compared with sTg performed at 24hours(D0) and 72hours(D2) after the last injection of thyrogen. We reviewed D0 and D2 from 276 patients were divided them into three groups according to ablation dose of radioactive iodine, 5mCi(A group), 30~80mCi(B group) and 100~200mCi(C group). We used T-test for comparison between D0 and D2. sTg was measured in serum using immunoradiometric assay (Tg-plus RIA; BRAHMS, Berlin, Germany). Results There is no critical variation between D0 and D2 in A group(n=100)(P=0.32), The case of increase(D2>D0) is 45, no change(D2=D0) is 23, decrease(D2D0 is 91, D2=D0 is 28, D2D0 is 19, D2=D0 is 2. The biggest increase is 143.6 ng/mL from 98.4 to 242. Conclusion There was a significant difference in the group over 30mCi. and the case of D2>D0 is 45%, 58.7%, 90.5% for each group. therefore, D2 increased as the dose of radioactive iodine increased. Furthermore, the most sTg values of D0 and D2 are variation under 2.0 ng/mL, so reproducibility as well as sensitivity of sTg will be important at values below 2ng/mL.

• Radiation Oncology Journal
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• 제10권2호
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• pp.187-192
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• 1992

영남대학교 의료원 치료방사선과에서 1988년 6월 15일에 위암 환자의 수술중 방사선치료를 시작한 이래 1992년 8월 30일까지 총 58예에서 시도하여 그중 53예에서 IORT를 실시하였으며, 정기적인 추적 검사에서 한명의 국소재발 환자도 보고되지 않고 있다. 출혈(3예), 장관폐쇄(3예), 폐혈증(2예), 골수기능저하(1예)를 포함한 총 9예($17\%$)의 합병증이 보고되었고, 이중 6예 ($13\%$)가 사망하였다. IORT(1500 cGy), 외부 방사선치료(-4500 cGy)와 강한 항암제를 병합치료 하였음에도 불구하고 주등(수술과 항암제 치료)의 $25.2\%$, 김등(수술 불가능한 환자에서 항암제 투여)의 $18\%$, 리등(수술)의 $18.5\%$, Kramling등(IORT 2800-3500 cGy)의 $35.3\%$에 비해 낮은 합병증을 보여 IORT가 위암의 치료에 공헌할 수 있음을 시사하였다. 그러나 비교적 높은 치사율($11.3\%$)은 더욱 세심한 수술수기 및 수술 후 환자의 치료가 필요하며 외부 방사선치료와 항암제치료의 적절한 시기 조절 및 치료선량의 가감이 필요할 것으로 생각된다.

• 대한핵의학회지
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• 제22권1호
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• pp.83-92
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• 1988

The cocktails of two $^{131}I$ labeled Monoclonal antibody (MCAB) (Anti CA 19-9 F$(ab')_2$ + Anti CEA $F(ab')_2$ fragment), which react specially, with human gastrointestinal cancers, were administered to 10 patients with colorectal (7), stomach(2) and pancreas(1) cancer for scintigraphic detection. All patients were known or postoperatively recurrent cases, and serum tumor markers, CA 19-9 and CEA, were measured with immunoradiometric assay, just before immunoscintigraphy (ISG). The tumor marker's level in serum is not correlated with positive tumor uptake in ISG. The sensitivity and specificity of ISG in detection of 21 tumor sites, based on surgery, CT, ultrasonography and pathology, were 90.5% and 100% One case of colon cancer showed gall bladder metastasis, which was neglected on CT study. Tumor/non tumor uptake ratio of radiolabelled antibody were progressively increased from day 3 to day 7 during study. We summerized as follows 1) The use of cocktails of CEA and CA 19-9 MCAB $F(at')_2$ increased sensitivity and specificity in ISG. 2) Delayed imaging (later than 5 days) increases sensitivitv and specificity due to exclusion of nonspecific iodine accumulation in stomach and lung. 3) Second tracer technique is essential for anatomical landmark by use of a double isotope scan, but subtraction technique, a possible source of artifacts, is no longer necessory when delayed imaging is performed. 4) It may be possible to use two MCAB cocktails of CA 19-9 and CEA in Radioimmunodetection of stomach and pancreas cancer. In conclusion, ISG using MCAB cocktails, $F(ab')_2$ fragment of anti CA 19-9 and Anti CEA, provide additional opportunity for tumor localization and detection of colorectal and other G-I cancer, such as stomach and pancreas.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2447-2451
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• 2015

Background: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. Materials and Methods: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. Results: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. Conclusions: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.

• Radiation Oncology Journal
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• 제30권4호
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• pp.205-212
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• 2012

Purpose: To evaluate the effect of pelvic radiotherapy (RT) in patients with stage IV rectal cancer treated with resection of primary tumor with or without metastasectomy. Materials and Methods: Medical records of 112 patients with stage IV rectal cancer treated with resection of primary tumor between 1990 and 2011 were retrospectively reviewed. Fifty-nine patients received synchronous or staged metastasectomy whereas fifty-three patients did not. Twenty-six patients received pelvic radiotherapy. Results: Median overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS) of all patients was 27, 70, and 11 months, respectively. Pathologic T (pT), N (pN) classification and complete metastasectomy were statistically significant factors in OS (p = 0.040, 0.020, and 0.002, respectively). RT did not improve OS or LRFS. There were no significant factors in LRFS. pT and pN classification were also significant prognostic factors in PFS (p = 0.010 and p = 0.033, respectively). In the subgroup analysis, RT improved LRFS in patients with pT4 disease (p = 0.026). The locoregional failure rate of the RT group and the non-RT group were 23.1% and 33.7%, showing no difference in the failure pattern of both groups (p = 0.260). Conclusion: Postoperative pelvic RT did not improve LRFS of all metastatic rectal cancer patients; however, it can be recommended to patients with pT4 disease. A complete resection of metastatic masses should be performed if possible.

• BMB Reports
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• 제53권10호
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6311-6318
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• 2012

Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

• Tuberculosis and Respiratory Diseases
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• 제56권2호
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• pp.169-177
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• 2004

연구배경 : Cyclooxygenase는 비스테로이드성 항염증제의 주요 작용부위로 실험적 모델이나 역학적 연구에서 암 발생을 억제하는 것으로 알려져 있다. COX-2는 prostaglandin E2와 같은 prostaglandin 합성을 통해 종양의 성장, 침윤 그리고 신생혈관에 중요한 역할을 하는 것으로 알려져 있다. 본 연구에서는 절제된 비소세포폐암조직에서 COX-2의 발현과 COX-2의 예후인자로서의 의의를 조사해 보았다. 대상 및 방법 : 1997년부터 2002년까지 본원에 내원하여 원발성 비소세포폐암으로 진단 받은 후 근치 목적의 절제술을 받았던 환자 84명을 대상으로 파라핀 포매된 조직을 택하여 면역 화학염색 방법을 통하여 COX-2 의 발현을 관찰하였다. COX-2가 발현된 암세포의 비율이 10% 이상인 경우를 양성으로 하였다. 결 과 : 평균 연령은 63세, 남녀 비는 67:17이었으며, 조직병리학적 분류는 편평상피암 53례, 선암 24례, 대세포암 7례였다. 병기는 I 병기 37례, II 병기 29례, IIIA 병기 18례였다. 총 84례 중 COX-2는 양성군이 73%(61/84례), 음성군이 27%(23/84례)이었다. COX-2 발현과 TNM 병기, 조직학적 분류와는 유의한 상관관계가 없었으나, 중간 생존기간은 COX-2 양성군이 음성군보다 통계적으로 유의하게 짧았다. 결 론 : 비소세포폐암에서 COX-2 항원 발현 음성군이 중간 생존기간이 길었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6397-6403
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• 2014

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3451-3455
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• 2014

Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.