• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7703-7705
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• 2014

Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6625-6629
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• 2013

Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy.

• 생명과학회지
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• 제21권6호
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• pp.912-922
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• 2011

Cancer-testis (CT) antigen은 다양한 종양과 정상 고환에서 제한적으로 발현되고, 암환자에서 체액성 면역과 세포성 면역반응을 일으키는 종양항원이다. 지금까지 MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2, NY-SAR-35를 포함하여 100개 이상의 CT antigen들이 동정되었고, 이러한 CT antigen들은 백신을 이용한 면역치료에 있어서 중요한 요소로 작용할 것으로 사료된다. CT antigen은 여러 가지 방법들을 통해 확인할 수 있고, X 염색체에 암호화 되어있는 CT-X gene과 X 염색체에 암호화 되어있지 않은 non-X CT gene으로 나눌 수 있다. 또한 몇몇의 종양에서 비정상적으로 활성화되지 않거나 발현되지 않는 CT antigen도 존재한다. 생식세포 조직과 종양에서 CT-X gene의 생물학적 역할이 아직 명확하게 규명되지 않았지만, 현재 여러 종류의 CT antigen을 이용한 암백신 치료법이 시도되고 있다. 본 논문은 암의 면역치료를 위한 CT antigen의 최근 연구동향과 앞으로의 연구방향에 대해 서술하고자 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4623-4628
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• 2015

Breast cancer still remains as the most frequent cancer with second mortality rate in women worldwide. There are no validated biomarkers for detection of the disease in early stages with effective power in diagnosis and therapeutic approaches. Cancer/testis antigens are recently promising tumor antigens and suitable candidates for targeted therapies and generating cancer vaccines. We conducted the present study to analyze transcript changes of two cancer/testis antigens, OIP5 and TAF7L, in breast tumors and cell lines in comparison with normal breast tissues by quantitative real time RT-PCR for the first time. Significant over-expression of OIP5 was observed in breast tumors and three out of six cell lines including MDA-MB-468, T47D and SKBR3. Not significant expression of TAF7L was evident in breast tumors but significant increase was noted in three out of six cell lines including MDA-MB-231, BT474 and T47D. OIP5 has ssignificant role in chromatin organization and cell cycle control during cell cycle exit and normal chromosome segregation during mitosis and TAF7L is a component of the transcription factor IID, which is involved in transcription initiation of most protein coding genes. TAF7Lis located at X chromosome and belongs to the CT-X gene family of cancer/testis antigens which contains about 50% of CT antigens, including those which have been used in cancer immunotherapy.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.326.1-326.1
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• 2002

We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. (omitted)

• Journal of Korean Neurosurgical Society
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• 제43권4호
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• pp.190-193
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• 2008

Objective : Cancer-testis (CT) genes are considered promising candidates for immunotherapeutic approaches. The aim of this study was to investigate which CT genes should be targeted in immunotherapy for brain tumors. Methods : We investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4, and HOMTES-85) using reverse-transcription polymerase chain reaction in 26 meningiomas and 32 other various brain tumor specimens, obtained from the patients during tumor surgery from 2000 to 2005. Results : The most frequently expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%) meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2 (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6. Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1 (2/6 or 33%). Conclusion : The data presented here suggest that MAGE-E1 and SOX-6 genes are expressed in a high percentage of human central nervous system tumors, which implies the CT genes could be the potential targets of immunotherapy for human central nervous system tumors.

• 생명과학회지
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• 제19권7호
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• pp.886-891
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• 2009

Cancer/testis(CT) antigens은 여러 종료의 암에서는 발현이 되지만, 정상조직에서는 고환에서만 발현이 되는 특이성을 가지고 있다. 이러한 특이성은 immunotherapy을 하기 위한 항암백신 개발에 매력적인 유전자로 알려져 있다. 본 연구에서는 29개의 한국유방암조직에서 13개의 CT antigens (NY-SAR35, SCP-1, SSX-1, SSX-2, SSX-4, MAGE-1, MAGE-3, MAGE-4, MAGE-10, CT-7, NY-TLU57, NY-ESO-1, and LAGE-1)의 발현빈도를 RT-PCR을 통하여 조사하고 환자의 임상학적 분류와 CT antigens의 발현빈도에 대하여 조사하였다. 29개의 유방암조직에 RT-PCR결과, 13개의 CT antigen중에 MAGE-3 (66%)와 MAGE-1(57%)에서 발현빈도가 가장 높았고 LAGE-1 (55%),NY-SAR-35 (49%),MAGE-4(41%), NY-ESO-1(38%), CT-7(24%), SSX-4(24%)순으로 발현빈도를 보였다. 그러나 SSX-1, SSX-2. MAGE-10와 NY-TLU-57의 발현은 3-7%로 매우 낮았고 특히 SCP-1는 발현되지 않았다. 29 유방암 조직에서 적어도 하나 이상의 CT antigen이 발현되는 샘플은 28(98%)이였다. 그러나 환자의 임상학적 분류와 CT antigens의 발현빈도와는 특징적인 관꼐가 없음을 알수있었다. 29개의 유방암조직에서 MAGE-3와 NY-ESO-1의 Protein level에서의 발현을 알아보기 위하여monoclonal antibody를 이용하여 면역조직염색을 하였다. MAGE-3은 29개 조직중에서 12개의 조직에서 발현되었으며 NY-ESO-1은 11개의 조직에서 발현되었다. 그러므로 CT antigens은 한국 유방암 조직에서 빈번하게 발현된 것을 알 수 있었으며 CT antigens을 기반으로 한 암 백신개발의 잠재적인 표적이 될 수 있을 것이라 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5865-5869
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• 2012

RHOXF1 has been shown to be expressed in embryonic stem cells, adult germline stem cells and some cancer lines. It has been proposed as a candidate gene to encode transcription factors regulating downstream genes in the human testis with antiapoptotic effects. Its expression in cancer cell lines has implied a similar role in the process of tumorigenesis. The human breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in DMEM medium and transfected with a pGFP-V-RS plasmid bearing an RHOXF1 specific shRNA. Quantitative real-time RT-PCR was performed for RHOXF1, CASP8, BCL2 and HPRT genes. Decreased RHOXF1 expression was confirmed in cells after transfection. shRNA knock down of RHOXF1 resulted in significantly decreased BCL2 expression in both cell lines but no change in CASP8 expression. shRNA targeting RHOXF1 was shown to specifically mediate RHOXF1 gene silencing, so RHOXF1 can mediate transcriptional activation of the BCL2 in cancers and may render tumor cells resistant to apoptotic cell death induced by anticancer therapy. shRNA mediated knock down of RHOXF1 can be effective in induction of apoptotic pathway in cancer cells via BCL2 downregulation, so it can have potential therapeutic utility for human breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4255-4259
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• 2014

Lactobacilli are probiotics shown to have antitumor activities. In addition, they can regulate gene expression through epigenetic mechanisms. In this study, we aimed to assess anti tumor activities of Lactobacillus acidophilus and Lactobacillus crispatus on the MDA-MB-231 breast cancer cell line. The effects of culture supernatants were determined by MTT [3-(4,5-dimethylthiazol-2-y-2,5-diphenyltetrazolium bromide] assay. Changes in expression of 5 cancer-testis antigens (CTAs), namely AKAP4, ODF4, PIWIL2, RHOXF2 and TSGA10, were analyzed by quantitative real time RT-PCR. The culture supernatants of the 2 lactobacilli inhibited MDA-MB-231 cell proliferation. In addition, transcriptional activity of all mentioned CTAs except AKAP4 was significantly decreased after 24 hour treatment with culture supernatants. This study shows that Lactobacillus acidophilus and Lactobacillus crispatus have antiproliferative activity against MDA-MB-231 cells. In addition, these lactobacilli could decrease transcriptional activity of 4 CTAs. Previous studies have shown that expression of CTAs is epigenetically regulated, so it is possible that lactobacilli cause this expression downregulation through epigenetic mechanisms. As expression of CTAs in cancers is usually associated with higher grades and poor prognosis, downregulation of their expression by lactobacilli may have clinical implications.

• Journal of Gastric Cancer
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• 제5권3호
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• pp.180-185
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• 2005

목적: 정상세포와는 달리 종양세포에서만 비교적 특이적으로 발현되는 것을 tumor specific antigens이라고 하며 대표적인 것은 악성흑색종에서 처음 발견된 MAGE (melanoma antigen)가 있다. 위암조직에서의 MAGE subtype의 발현율은 약 $20{\sim}40%$ 정도로 알려져 있는데 진행성 위암은 전체적으로 예후가 불량하기 때문에 면역치료법과 같은 새로운 치료법을 고려해 볼 수 있다. 본 연구에서는 술 후에 얻은 정상 및 암 조직에서의 MAGE의 발현정도를 각 subtypes에 공통으로 존재하는 유전자를 Primers로 이용하여 조사하였다. 대상 및 방법: 내시경에서 진행성 암으로 진단된 후 수술받은 환자 53명을 대상으로 하였으며, 수술 중 절제된 위에서 정상조직과 암 조직을 얻어 $-70^{\circ}C$에서 보관하였다. 환자는 남자가 35명, 여자가 18명이었고 이들의 평균 연령은 57세였다. 보관된 조직에서 m-RNA를 분리한 후 RT-PCR과 nested PCR로 MAGE의 발현여부를 알아보았다. 기존에 알려진 MAGE gene의 subtypes에 공통으로 존재하는 oligonucleotides를 일차 primers로 이용하여 증폭시켰다. 그 후 또 다른 primers를 이용한 nested RT-PCR을 시행하여 각 조직에서의 발현율을 조사하였다. 결과: 위암환자에서 53예의 암조직 중 13개(24.5%)에서 MAGE gene이 양성으로 나왔고 정상조직에서는 MAGE gene이 모두 음성이었다. 위암의 조직형, ABO type, CEA, CA19-9와 cancer의 위치와는 상관관계가 없었다. 결론: 위암환자의 $20{\sim}30%$에서 MAGE gene이 발현되었으며, 이에 MAGE gene을 이용한 면역치료법의 시도가 필요 할 것으로 생각한다.