위암에서 종양줄기세포 표지자인 CD133과 CD24의 발현여부와 예후인자의 비교

김용진 ( Yong Jin Kim ),장세진 ( Sei Jin Jang ),김병식 ( Byung Sik Kim ),백승삼 ( Seung Sam Paik ) 대한임상종양학회 2010 Korean Journal of Clinical Oncology Vol.6 No.1

배경 : 위암 수술 후 치료 실패의 원인 중 하나로 위암 줄기세포의 역할에 대한 가설이 설정 되고, 동시에 골수에서 기원한 위암 줄기세포의 존재가 증명되면서 이에 대한 관심과 연구가 활발해지고 있는 것이 현실이다. 이에 저자들은 종양줄기세포 표지자인 CD 표지자를 이용해 위암 조직에서 발현여부와 예후인자와의 상관관계를 확인 하고자 본 연구를 고안하였다. 대상 및 방법 : 서울 아산 병원에서 2000년 한 해 동안 위암으로 근치적 위 절제가 시행된 389명을 대상으로 CD133과 CD24에 대한 tissue microarray를 시행하였다. 임상 병리학적 요인과 생존율은 의무기록 및 전산기록을 후향적으로 분석하였다. 결과 : CD133은 66%(N=251)에서, CD24는 32%(N=122)에서 양성소견을 보였다. CD133양성인 경우는 음성인 경우에 비해 조직학적 분화도가 더 좋은 것으로 나타났으나(P=.003), 그 이외의 임상병리학적 요인과 상관관계는 없었다. CD24의 경우 임상병리학적 요인과 아무런 상관관계를 보이지 않았다. 생존율에 있어서도 CD133 발현여부에 따른 무병 생존율 및 전체 생존율 모두 각각 82%와 83%로 차이가 없었으며(P=.9266), CD24발현여부에 따른 무병 생존율 및 전체 생존율은 각각 81%와 88%로 이 역시 차이를 보이지 않았다(P=.1469). 결론 : 종양줄기세포 표지자인 CD133과 CD24의 발현여부는 위암환자에서 임상 병리학적 요인 및 생존율과 상관관계를 보이지 못했다. 비록 위암에서 기존의 종양줄기세포 표지자와 예후인자로서의 관련성은 없었으나, 위암에서 줄기세포의 존재 가능성은 확인할 수 있었다. Background: Cancer stem cells are a small population of tumor cells capable of self-renewal that give rise to all the components of a heterogenous tumor. Recently, this concept has been extended into various solid tumor after the first documentation in acute myeloid leukemia. CD133 and CD 24 were identified as cancer stem cell markers in other solid tumors such as breast cancer, brain cancer, pancreatic cancer and head and neck cancer. The aim of this study was to examine the expression CD133 and CD24 in gastric cancers. Furthermore, their clinical significance was evaluated. Methods: Immunohistochemistry for CD133 and CD24 was performed on the tissue microarray of 388 gastric cancers. We retrospectively analysed the prognostic factors depending on the expression of CD133 and CD24. Results: In gastric cancers, 251 of the 381 cases (66%) tested were positive for CD133 expression and 122 of the 386 cases (32%) tested were positive for CD24 expression. CD133 expression was more present in well differentiated cancer (p=0.003). However other prognostic factors were not related with CD 133 & CD24 expression The survival rate according to CD133 & CD24 expression was not significant. Conclusions: We can figure out the potential presence of cancer stem cells in gastric cancers through confirming the positive expression of CD133 & CD24. However CD expressions didn°Øt show close relationship with prognostic factors and survival rate of gastric cancer.

Clinicopathological Significance of Invasive Ductal Carcinoma with High Prevalence of CD44+/CD24-/low Tumor Cells in Breast Cancer

임성직,성지연,김교영,박용구,이주희,김윤화 대한병리학회 2010 Journal of Pathology and Translational Medicine Vol.44 No.4

Background : Epithelial tumor cells with a CD44+/CD24-/low immunoprofile may have the ability to cause breast cancer. We studied these cells and their clinicopathological significance. Methods : The clinicopathologic findings of 100 invasive ductal carcinoma (IDC) cases and 45 ductal carcinoma in situ (DCIS) cases were reviewed. CD44+/CD24-/low tumor cells were identified by immunohistochemistry, and their clinicopathological implications in IDC and DCIS were analyzed. Results : IDC with a high prevalence of CD44+/CD24-/low tumor cells was significantly associated with larger mass, higher grade, estrogen receptor (ER) negativity, and tumor cells with a higher frequency of metastasis. The proportion of CD44+/CD24-/low tumor cells in IDC, and its DCIS components was not significantly different, whereas the proportion of CD44+/CD24-/low tumor cells was higher in DCIS than in the DCIS component of IDC (p < 0.001). Conclusions : IDC with a high prevalence of CD44+/CD24-/low tumor cells might correlate with aggressive features, such as ER and higher grades. Moreover, the proportion of CD44+/CD24-/low tumor cells in the DCIS components of IDC and DCIS might harbor different biology, which may lead to differences in cancer progression and early carcinogenesis.

담낭종양에서 CD24의 역할

임성철,이용,김동출,강길,변익건,박정희,최석민 朝鮮大學校 附設 醫學硏究所 2004 The Medical Journal of Chosun University Vol.29 No.2

CD24 is a small heavily glycosylated glycosylphosphatidylinosito-linked cell surface protein, which is expressed in hematologic malignancies as well as in a large variety of solid tumors, It appears to function as a ligand of PUselectin, an adhesion molecule that is present in activated platelets and endothelial cells. The authors aimed to evaluate CD24 protein expression in adenoma and adenocarcinoma of gallbladder to correlate to clinicopathologic data. The staining- was evaluated as stainability (negative, weak-, moderate-, strong-positive) and staining' patterns (membranous vs. intracytoplasmic) for statistical analysis. A highly significant association of cytoplasmic CD24 expression with adenocarcinoma compared to the adenoma of gallbladder was demonstrated. The present study demonstrates that CD24 was abundantly expressed on adenocarcinoma rather than on adenoma, but it was not statistically significant, Interrelation between the stainability or intracytoplasmic staining of CD24 and lymph node metastasis was not statistically significant. The authors conclude that CD24 is involved in tumorigenesis of gallbladder mucosa and intracytoplasmic expression of CD24 is an important molecular marker for malignant transformation.

The role of CD24 in epithelial tumor of the gastrointestinal tract

Lim, Sung-Chul,Jeong, Gul-Ae,Lee, Yong,Choi, Jung-Eun,Quan, Duong Hong 朝鮮大學校 附設 醫學硏究所 2006 The Medical Journal of Chosun University Vol.31 No.1

Background and Aim: CD24 is a small heavily glycosylated glycosylphosphatidylinositollinked cell surface protein, which is expressed in hematologic malignancies as well as in a large variety of solid tumors, It appears to function as a ligand of P-selectin, an adhesion molecule that is present in activated platelets and endothelial cells. The authors aimed to evaluate CD24 protein expression in adenoma and adenocarcinoma of stomach, colon and gallbladder to correlate to clinicopathologic data. Methods: The staining was evaluated as stain intensity (negative, weak-, moderate-, strong-positive) and staining patterns (membranous vs. intracytoplasmic) for statistical analysis. Results: CD24 was abundantly expressed on adenocarcinoma rather than on adenoma in colon. Moreover, the intensity of CD24 expression increased with positive nodal status in the advanced gastric carcinoma. A highly significant association of intracytoplasmic CD24 expression with adenocarcinoma of the colon and gallbladder compared to the adenoma group of those organs, respectively and with positive nodal status compared to negative nodal status of the colonic adenocarcinoma were demonstrated, Conclusions: The authors conclude that the intensity and staining pattern of CD24 is an important molecular marker for various epithelial neoplasms that could help to define malignant transformation and to prediet lymphogenous metastasis.

인면역결핍바이러스 감염자에서 ICD - p24항원 탐지가 CD4+T 세포수 및 예후에 미치는 영향

조영걸,이희정 대한바이러스학회 1996 Journal of Bacteriology and Virology Vol.26 No.2

In order to evaluate the effect of viral load on the prognosis of human immunodeficiency virus- 1 (HIV-1)-infected individuals, immune complex dissociated (ICD) serum p24 antigen (p24) by acid treatment was retrospectively measured for 50 HIV-infected patients for 60 months. Among them, 27 patients were p24 positive (p24+) above 25pg/ml for 40.412 months and 23 patients were negative (p24-). Follow-up periods from HIV diagnosis were 63.019 months (range; 40-112) for the p24+ and 68.4+ 19 months (range; 38-106) for the p24-, respectively (P> 0.05). Mean CD4+ T cell counts in the p24+ group decreased from 473+277/ul (median;373) to 157+ 150/ul (median; 111) for 60+ 16 months (5.3/month P280/ul (median; 476) to 432+ 285/ul (median;382) for 63 W 19 months (2.5/month, P<0.01). From CD4+ T cell count >200/ul, the patient who progressed to AIDS of <200/ul were 13 of 23 (56%) in the p24+ and 4 of 22 (18%) in p24-, respectively ((p<0.01). And the number of death in two groups were 6 (22%) and 1 (4%), respectively ((p<0.01). Presumed survival in two groups were about 12 and 24.5 years. These data suggest that viral load itself be very important for the prognosis of HIV-in- fected patients.

HIV 감염자에서 flow cytometry를 이용한 p24 양성 CD4+ T 림프구의 측정

김영봉,조영걸,최병선,장영식,양재명,신영오 대한바이러스학회 1994 Journal of Bacteriology and Virology Vol.24 No.1

The identification of factors that correlate with progression of human immunodificiency virus (HIV) infection is important for prognosis and monitoring of therapy. We tried flow cytometric method for detection of HIV p24 antigen in CD4+ cells. Lymphocytes harvested from HIV infected persons were treated with a methanol:aceton fixative solution for giving permeability and followed by binding of monoclonal antibody specific for HIV p24 antigen. After labeling with a fluorescein isothiocyanate-conjugated F(ab) fragments of goat anti-mouse immunoglobulin antibody, p24 antigen positive CD4+ cells were counted using flow cytometry. We followed 40 HIV infected persons during the period of Sept. 1992 and Sept. 1993. The pro- portion of p24 antigention of CD4+ cells(Y) 3 months before and after the test (Y=-4.59X+ 44.45). On the other hand there was less correlation [r=-0.356(p=0.046)] with absolute CD4 +lymphocyte count which was directly linked to clinical stage. This results suggest that flow cytometry can be used as a rapid, sensitive and quantitative assay system for detection of viral replication status of HIV-seropositive persons and it could be the most accurate prognostic marker for HIV disease.

Histopathological Evidence for the Existence of Primary Liver Progenitor Cell Cancer: Insight from Cancer Stem Cell Pathobiology

( Cheng-maw Ho ),( Shu-li Ho ),( Chia-tung Shun ),( Po-huang Lee ),( Ya-hui Chen ),( Chin-sung Chien ),( Hui-ling Chen ),( Rey-heng Hu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Primary liver progenitor cell cancer is a rare disease entity without definite evidence and characterization. Current nomenclature of primary liver cancer with prominent progenitor features is not comprehensive. This study was aimed to investigate the existence of this kind of primary liver cancer and characterize it immunohistopathologically based on the emerging understanding of cancer stem cell pathobiology. Methods: Surgical specimens from primary liver cancer which posed diagnostic difficulty fitting within current WHO classification of combined hepatocellular-cholangiocellular carcinoma with stem-cell features according to the growth morphology and its suggested immunohistochemical features, were stained with antibodies against well-defined markers of progenitor cells, stemness, and differentiation toward hepatocytes or cholangiocytes. Comparative interpretation of images was processed considering the histological morphology and characteristic markers. Results: The primary liver cancer consisted of CD24+ cancer progenitor cells and CD90+ mesenchymal stromal cells, which were intimately mixed. CD24+ cancer cells demonstrated bi-directional trends of differentiation: bile ductule transformation (cytokeratin 19+, epithelial cell adhesion molecule [EpCAM]+, neural cell adhesion molecule [NCAM]+, CD133+, and delta-like 1 homolog [DLK1]+); and trabecular or nested cell clusters toward hepatic lineage (hepatocyte nuclear factor-4 alpha [HNF-4α]+, Hep Par1+ and negative for CK19, EpCAM, CD133, and DLK1). Moderate lymphocyte (mostly CD4+ and CD8+ T cells) infiltrated in the CD90+ cancer- associated stroma. Conclusions: We provided the corroboration that liver progenitor cells can form primary liver cancer, not just presented as few side population of cancer stem cells. Its existence might pose significance for future stem cell therapeutic intervention targeting liver diseases, albeit the disease is rare.

Stem cell analysis with intraductally treated mammary epithelial cells

Ah Young Yoon,Yun Young Kim,Joon-Hyop Lee,Yoo Seung Chung,Sang Tae Choi,강진모,Heung Kyu Park,Yong Soon Chun 대한종양외과학회 2019 Korean Journal of Clinical Oncology Vol.15 No.1

Purpose: The activity of mammary stem cells (MaSCs) is essential to mammary growth, differentiation and regeneration in cycles of pregnancy, lactation, and involution. The capability to recruit the mammary gland through the cycles is attributed to stem cells. It was shown that the intraductal (i.duc) injection of pegylated liposomal doxorubicin (PLD) to multiparous FVB/N mice was associated with a significantly reduced outgrowth potential of mammary gland cells. We have explored i.duc PLD’s effect on stem cell number and function in mouse mammary gland and aldehyde dehydrogenase (ALDH)’s availability as a mouse MaSC marker. Methods: The total mammary epithelium was purified from 6 to 8-month-old FVB/N control and i.duc PLD-administered mice treated twice and analyzed by flow cytometry and limiting dilution cleared mammary fat pad transplants. Results: There was no significant difference in the proportions of stem cell-enriched population (CD49fhighCD24med) between control and i.duc PLD-treated groups. However, we found a significant reduction in the outgrowth potential of CD49fhighCD24med and CD49fhighCD24medALDH(+) cells from i.duc PLD-treated mammary glands. We discovered that adding ALDH to CD49fhighCD24med had the possibility of better marker selection for MaSC of mice. Conclusion: We present i.duc administration of PLD to reduce MaSC function, but not the number; and ALDH activity may add further selection of MaSCs to CD49f CD24 in mouse mammary glands. Screening of chemotherapeutic drugs or other natural products by this method of stem cell analysis may provide safe i.duc treatment in breast cancer.

생쥐에서 鹿血의 免疫生理活性에 의한 치유效果

홍순복,이형환 한국동방학회 2010 동방논집 Vol.3 No.1

손상된 면역 생리계의 조속한 회복과 치유를 위하여 천연물 자원의 새로운 약제의 개발로서 녹혈의 면역생리활성에 의한 치유효과를 측정하는 것이 본 연구의 목적이었다. Cyclophosphamide ((150 mg/kg)로 면역저하를 유발한생쥐(mouse)에 매일 200 mg/kg의 건조 분말로 된 녹전혈, 녹혈구, 녹혈장, 십전대보탕, 가미육게탕 및 생리식염수 성분을 14일간 투여 후에 CD4, CD24의 빈도를 면역형광법으로 측정하였다. 체중에서는 모든 군에서 유의성이 없었다. 肝/체중비는 terrakraft 투여군과 녹혈구 투여군에서 유의성이 나타났다. 비장/체중비의 영향은 녹전혈 투여군, 녹혈구 투여군, 녹혈장 투여군 모두에서 유의성 있는 증대를 나타내었다. 면역세포 빈도는 14일간 녹혈장을 투여한 군에서 T-세포의 수가 정상대조군보다 높게 나타났다. 녹혈장 투여군에서는 B 세포의 빈도도 정상대조군보다 높았다. NK 세포의빈도는 정상대조군에 비하여서는 낮았으나 saline 투여군에서보다는 높았다.

유방암종에서 CD24의 역할

임진수(Jin Soo Lim),김경종(Kyung Jong Kim),임성철(Sung Chul Lim) 대한외과학회 2005 Annals of Surgical Treatment and Research(ASRT) Vol.68 No.3