• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6721-6726
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• 2013

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

• Radiation Oncology Journal
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• 제12권3호
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• pp.377-386
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• 1994

1989년에서 1993년까지 중앙 길 병원에서, 자궁경부암으로 수술후 국소재발하여 방사선치료를 시행한 28명의 환자를 대상으로, 치료성적, 예후인자 및 치료후 실패양상 등을 분석하였다. 8명은 질부에 국한된 재발을 보였으며, 나머지 19명은 골반부위를 침윤하는 양상을 보였다. 수쑬후 24개월 이내에 $82\%$가 재발을 보였으며, 완전관해율은 $64\%$였고, 그 중 $28\%$가 후속적 재발을 보였다. 모든 환자가 전 골반부위에 방사선 치료를 받았으며, 그 중 15명이 강내치료를 겸하였다. 치료에 대한 관해율은 재발된 암의 크기와 재발부위 그리고, 방사선 조사양과 관계있었다. 2년 생존율은 $43\%$였고, 무병생존율은 $31\%$였다. 원발병소의 크기, 초기치료등은 생존율에 영향을 끼치지 못하였으나, 임파선 전이 여부와 세포형 등은 유의한 영향을 미쳤다. 6개월 이내에 재발한 경우, 모두 2년 이내에 사망하였으며, 그 후 재발을 보인 경우는, 2년 생존율 $66\%$였다. 재발된 암의 크기가 5cm미만이었던 16명의 환자가가 $71\%$의 2년 생존율을 보인 반면, 5cm이상이었던 12명의 경우는 모두 2년이내 사망하였다. 질부에만 재발한 환자의 2년 생존율은 $100\%$였고, 골반부까지 침윤한 경우는 $20\%$였다. 질점막으로부터 1.0cm 깊이에 75Gy이상의 방사선 치료를 시행받은 경우가, 그 이하를 시행받은 경우보다 좋은 성적을 보였다. 강내치료를 시행받은 15명의 경우, 2년 생존율이 $67\%$였고, 그렇지 않은 경우는 $29\%$였다. 한편, 60.0Gy이하를 시행받은 9명 중 5명이 7개월 이내에 사망하였다. 완전관해를 보인 환자의 2년 생존율을 $83\%$였고, 고렇지 않은 경우는 1년 생존율이 $15\%$였다. 주 사망 원인은 폐전이었다. 좋은 관해율과 높은 생존율은 직접 관계가 있으며, 이를 위하여, 강내치료를 겸한 외부방사선치료가 충분한 조사양으로 시행되어야 하며, 근치적수술후 국소 재발된 자궁경부암의 경우, 생존율을 높이며 삶의 질을 높인다는 점에서 조기발견파 적극적인 방사선 치료가 절대적으로 필요함을 시사하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4669-4675
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• 2012

Objective: Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used to investigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing and thawing for ovarian tissue transplantation. Methods: Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP-2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. The tissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry, negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer tissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyze overt and occult carcinogenesis rates after transplantation. Results: When all indicators or the main indicators, CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition the occult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin (P<0.01). After subcutaneous and orthotopic transplantation of ovarian tissues, rates did not change (P>0.05). There was no statistical significance among rates after transplantation of ovarian tissues which were obtained under different severity conditions (P>0.05). Conclusion: Negative expression of CK-7, CA125 and survivin can be treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methods can be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. The initial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovarian tissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3937-3940
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• 2013

Objective: To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Materials and Methods: Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. Results: The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Conclusions: Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer.

• Nuclear Medicine and Molecular Imaging
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• 제41권3호
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• pp.185-193
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• 2007

이 종설은 이차성 원발암에서의 $^{18}F-FDG$ PET/CT의 이용을 다루었다. 암환자에서 이차성 원발암의 발병 유무는 주요한 예후인자 중의 하나이다. 이차성 원발암을 조기에 진단하고 치료하는 것은 이와 관련된 암 사망률을 낮추는 데 중요하다. $^{18}F-FDG$ PET/CT는 해부학적 및 대사적 정보를 동시에 제공함으로써 종양 영역에서 CT나 기존의 PET보다 진단성능이 더 우수하다. 이러한 우수한 진단성능과 전신영상이 가능하다는 장점 때문에 PET/CT는 이차성 원발암을 발견하는 데에 CT나 기존의 PET보다 더 적합하다. $^{18}F-FDG$ PET/CT는 이차성 원발암에 대한 선별검사로서 높은 예민도와 비교적 좋은 양성예측도를 보이므로 유용하다. PET/CT 영상에서 이차성 원발암이 의심되는 병변이 보일 경우 추가적인 진단적 검사는 필수적이다. PET/CT는 이차성 원발암을 발견하는데 PET보다 우수하다.

• 대한방사성의약품학회지
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• 제5권2호
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• pp.89-100
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• 2019

In our previous studies, we developed a ¹⁸F-labeled TSPO-binding ligand, named [¹⁸F]CB251, which has been proved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expression in pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Based on these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as a targeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues. In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescence dye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. Three CB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additive on their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-c was lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO (Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates are characterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consist of five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length for developing new TSPO-targeting drug carriers.

• Journal of Yeungnam Medical Science
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• 제20권2호
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• pp.105-116
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• 2003

위암은 한국에서뿐만 아니라 세계적으로도 가장 중요한 암 사망 원인의 한가지로 보고되고 있다. 현재까지 외과적 수술이 위암에 대한 유일한 근치적 치료수단으로 인정되고 있으며, 가능한 한 조기에 발견하여 근치적 절제술을 시행하는 것이 가장 중요하다. 근치적 수술을 위한 술기의 표준화 및 각 수술 술기의 우열에 대한 논란이 현재까지 그치지 않고 있으나, 여기에서는 한국 및 일본에서 가장 보편적으로 인정되고 있는 위암에 대한 수술 치료의 원칙을 기술하고자 한다. 위장 절제술은 위아전절제술과 위전절제술로 대별되며 절제연은 종양의 침윤이 없는 충분한 정상조직을 확보하여야 하고 주변 림프절의 동반절제가 포함되어야 한다. 병변의 상태에 따라 주변장기의 동반절제와 광범위한 림프절 곽청술이 요구되기도 한다. 소화관의 복구는 구조적 혹은 기능적인 면에서 환자의 삶의 질과 밀접한 관련을 가지므로 상황에 따라 적절한 방법의 선택을 요한다. 술 후 환자의 삶의 질을 향상시키기 위해서 저침습성 혹은 최소한의 절제를 목적으로 하는 새로운 술기들이 소개되기도 하였다. 유문보존 위절제술, 복강경을 이용한 위설상절제 및 위아전절제술, 내시경점막절제술등을 그 예로 들수 있으며, 이러한 시술의 적응증과 안전성은 향후 임상성적의 분석을 통해 정립되어야 한다. 근치적 절제술이 불가능한 위암환자에서는 환자의 고통감소와 경구적 영양 섭취를 위해서 고식적 수술을 시행할 수 있으며, 특히, 진행성 위암에 의한 합병증으로 인해 생명이 위태로운 경우에는 응급수술이 요구되기도 한다. 진행성 위암은 수술적 치료를 하더라도 예후가 불량하므로 조기에 발견하는 것이 가장 중요하다. 최근, 한국에서는 상부 위장관에 대한 내시경 시술의 보편화로 전체 위암에서 조기위암이 차지하는 비율이 향상되고 있으며, 적절한 근치적 수술을 통해 위암의 생존율이 향상되고 있다.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.780-803
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• 2003

Exposure of skin cells, particularly keratinocytes to various nuclear factor-kappaB ($\textrm{NF}_{-{\kappa}}\textrm{B}$) activators [e.g. tumor necrosis factor-$\alpha$, interleukin-1, lipopolysaccharides, and ultraviolet light] leads to phosphorylation and degradation of the inhibitory protein, $\textrm{I}_{{\kappa}}\textrm{B}$. Liberated $\textrm{NF}_{-{\kappa}}\textrm{B}$ is translocated into the nucleus where it can change or alter expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting melanocyte. In order to demonstrate the possible role of $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of $\textrm{NF}_{-{\kappa}}\textrm{B}$ induced by melanogenic inhibitors (MIs) were determined in human HaCaT keratinocytes transfected with $\textrm{pNF}_{-{\kappa}}\textrm{B}$-SEAP-NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the $\textrm{NF}_{-{\kappa}}\textrm{B}$ activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selection marker for geneticin resistance. MIs such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin, and glycolic acid were preincubated with transfectant HaCaT cells for 3 h and then ultraviolet B (UVB) was irradiated. $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation was measured with the SEAP reporter gene assay using a fluorescence detection method. Of the Mis tested, kojic acid ($IC_{50}$/ = 60 $\mu$M) was found to be the most potent inhibitor of UVB-upregulating $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation in transfectant HaCaT cells, which is followed by niacinamide ($IC_{50}$/= 540 $\mu$M). Pretreatment of the transfectant HaCaT cells with the Mis, especially kojic acid and niacinamide, effectively lowered $\textrm{NF}_{-{\kappa}}\textrm{B}$ binding measured by electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL-6, one of melanotrophic factors, triggered by UV-radiation of the HaCaT cells. These observations suggest that Mis working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocyte.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권5호
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• pp.315-322
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• 2003

Background : Important factors to determine treatment method and prognosis of oral cancer are anatomical site, tumor size, metastatic lesion, histologic cell differenciation and microvascular invasion. Anatomical site has great effect to oral cancer patient's survival rate because each site's accessibility and lymph node metastasis is different but this factor was't studied much than other factors. Patients and Methods : 228 patients with squamous cell carcinoma of common primary sites(Mandible, Maxilla, Floor of Mouth and Tongue) in oral cavity who were diagnosed in the Korea Cancer Center Hospital from January 1989 to December 1999, were clinically studied and analyzed on survival rate. Results : 1. Survival rates of each anatomical sites were Tongue(36.8%), Mandible(33.3%), Maxilla(28.7%) and Floor of Mouth(24.5%). Survival rates difference between Tongue and Floor of Mouth has significance(p<0.05). 2. Survival rates for early cancer of each site were Maxilla(100%), Mandible(57.1%), Tongue(54.2%) and Floor of Mouth(46.7%). Survival rates difference between Maxilla and Floor of Mouth has significance(p<0.05). 3. Survival rates by surgery method of each site were Maxilla(60.6%), Tongue(56.9%), Mandible(44.8%) and Floor of Mouth(26.3%). Survival rates difference between Maxilla and Floor of Mouth has significance(p<0.05). 4. Survival rates by radiation or chemo method of each site were Floor of Mouth(23.5%), Mandible(20.0%), Maxilla(9.5%), and Tongue(9.1%). Survival rates difference between each site doesn't have significance(p>0.05). 5. In advance stage, Survival rates by single therapy of each site were Tongue(33.6%), Mandible(23.5%), Floor of Mouth(16.7%), Maxilla(0%), and Survival rates difference between Maxilla and Tongue has significance (p<0.05). Survival rates by combination therapy of each site were Mandible(38.1%), Maxilla(30.0%), Floor of mouth(18.2%), Tongue(12.5%), and Survival rates difference between Mandible and Tongue has significance(p<0.05). Conclusion : Survival rate of tongue is higher than the other sites, early detection of oral cancer can increase survival rate at any site and combination therapy is the most effetive method, especially at maxilla.

• 생명과학회지
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• 제20권8호
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• pp.1281-1286
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• 2010

고셔병은 세포내의 글루코세레브로시데이즈의 결핍으로 인하여 리소좀 내의 글루코세레브로사이드가 분해되지 못하고 축적되는 질환으로 알려져 있으며, 유형의 종류에 따라 신경퇴행성 질환으로 나타나는 것으로 보고되어 있으나 아직까지 정확한 기전이 밝혀져 있지 않다. 본 논문에서는 항산화 효과 및 신경보호 효과가 있는 것으로 알려진 레스베라트롤을 고셔병 환자의 fibroblast 세포에 투여하여 세포 생존율 변화 여부 및 세포주기 조절에 관하여 분자 생물학적 기전을 알아보고자 하였다. 고셔병 세포의 p21의 mRNA 발현 수준과 단백질 발현 양상을 확인한 결과 mRNA 상의 정량적 차이는 관찰되지 않았으나 단백질 발현수준은 레스베라트롤의 농도가 높아짐에 따라 증가 되는 것을 확인하였다. 또한 세포사멸의 표지 인자 단백질로 알려진 PARP의 변화양상을 확인한 결과 레스베라트롤의 농도가 높아짐에 따라 감소하는 것을 확인 할 수 있었다. 이를 통해 폴리페놀계 천연물인 레스베라트롤이 고셔병에서 세포 손상을 치유하며, 궁극적으로 세포사멸을 억제하는 효과를 가져올 것으로 생각할 수 있으며, 본 질환에서 병증을 완화 시킬 수 있을 것으로 사료된다.