AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC bef...AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP) in these patients was also determined.RESULTS:The positive rate of MAGE-1,SSX-1 and CTp11 transcripts was 37.7%,34.4%,31.1% in PBMC samples,and 74.4%,73.3%,62.2% in their resected tumor samples,respectively.The positive rate for at least one of the transcripts of three CTA genes was 66.7% in PBMC samples and 91.1% in their resected tumor samples.MAGE-1,SSX-1 and/or CTp11 mRNA were not detected in the PBMC of those patients from whom the resected tumor samples were MAGE-1,SSX-1 and/or CTp11 mRNA negative,nor in the PBMC samples from 20 healthy donors and 10 cirrhotic patients.Among the 90 patients,the serum AFP in 44 patients met the general diagnostic standard(AFP > 400 μg/L) for HCC,and was negative(AFP ≤ 20 μg/L) or positive with a low concentration(20 μg/L < AFP ≤ 400 μg/L) in the other patients.The positive rate for at least one of the transcripts of three CTA genes in PBMC samples from the AFP negative or positive patients with a low concentration was 69.2% and 45.0%,respectively.Of the 90 patients,71(78.9%) were diagnosed as HCC by nested RT-PCR and serum AFP.Although the positive rate for at least one of the transcripts of three CTA genes in PBMC samples from 53 patients at TNM stage or was obviously higher than that in PBMC samples from 37 patients at stage or(77.9% vs 51.4%,P = 0.010),the CTA mRNA was detected in 41.7% and 56.0% of PBMC samples from HCC patients at stages andrespectively.CONCLUSION:Detecting MAGE-1,SSX-1 and CTp11 mRNA in PBMC improves the total diagnostic rate of HCC.展开更多
AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this stu...AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.展开更多
BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk...BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.展开更多
GAGE基因是Van den Eynde等应用细胞毒性T淋巴细胞（CTL）筛选法，从一黑色素瘤细胞株cDNA文库中筛选出的肿瘤抗原基因，它能在多种来源不同的肿瘤组织表达，而在正常组织的表达仅限于睾丸组织，因此属于癌-睾丸抗原（CT抗原）。本研究...GAGE基因是Van den Eynde等应用细胞毒性T淋巴细胞（CTL）筛选法，从一黑色素瘤细胞株cDNA文库中筛选出的肿瘤抗原基因，它能在多种来源不同的肿瘤组织表达，而在正常组织的表达仅限于睾丸组织，因此属于癌-睾丸抗原（CT抗原）。本研究中采用逆转录聚合酶链反应（RT-PCR）技术检测肝细胞癌（HCC）组织及相应癌旁组织中GAGE基因mRNA4的表达情况，展开更多
印记位点调节子的弟兄(brother of regulator of imprinted sites,BORIS)或者类CCCTC结合因子(CCCTC binding factor-like,CTCFL)是一个相对发现不久的癌症睾丸抗原。与之相关的药物研发已经在小分子、小RNA、多肽药、疫苗以及细胞等多...印记位点调节子的弟兄(brother of regulator of imprinted sites,BORIS)或者类CCCTC结合因子(CCCTC binding factor-like,CTCFL)是一个相对发现不久的癌症睾丸抗原。与之相关的药物研发已经在小分子、小RNA、多肽药、疫苗以及细胞等多个方向展开。因独特的干扰基因组空间高级结构的能力,BORIS可能代表着一类全新药物靶点。本综述系统梳理BORIS相关分子生物学研究结果,包括BORIS基因产物的多样性,由其介导的分子间互作,受到影响的信号传导通路,以及现有相关药物研发策略,以期明了BORIS的上下游调控分子机制及可能进一步突破的研究方向。展开更多
Background Cancer-testis antigen （CTA） is a family of the most noticeable tumor antigens which could be potential tumor markers for cancer diagnosis. In this research we aimed to investigate the expression of SSX-1 ...Background Cancer-testis antigen （CTA） is a family of the most noticeable tumor antigens which could be potential tumor markers for cancer diagnosis. In this research we aimed to investigate the expression of SSX-1 and NY-ESO-1 mRNA, two members of the CTA family, in tissue and peripheral blood of patients with hepatocellular carcinoma （HCC） to assess their feasibility for the immunotherapy and diagnosis of HCC and the association of their expression levels with diverse clinical indicators. Methods Thirty-six north Chinese patients with HCC and 30 normal controls were enrolled in this study. Reverse transcription-polymerase chain reaction （RT-PCR） was used to detect the expression of SSX-1 and NY-ESO-1 mRNA in tumor tissues and corresponding levels in peripheral blood of patients. Results The positive rates of SSX-1 and NY-ESO-1 mRNA expression were 61.1% （22/36） and 11.1% （4/36）, respectively, in cancer tissues; 38.9% （14/36） and 5.6% （2/36）, respectively, in the corresponding peripheral blood samples. No positive expression of either SSX-1 or NY-ESO-1 mRNA was detected in the samples of cancer-adjacent tissues, cirrhotic tissues, normal liver tissue or the peripheral blood of control patients. No significant relationship was found between the expression of these two genes and clinical indicators such as age, gender, tumor size, extent of differentiation, serum a-fetoprotein （AFP） level or infection with hepatitis B virus （P〉0.05）. The short term recurrence rate was 46.2% （6/13） in patients whose peripheral blood expressed SSX-1 mRNA, while the recurrence rate in patients with negative SSX-1 mRNA was 28.6% （4/14）. Conclusions SSX-1 and NY-ESO-1 antigens might be new potentially promising targets for antigen-specific immunotherapy for HCC. High specific expression of SSX-1 and NY-ESO-1 mRNA suggested that we could apply them as tumor markers. The short term recurrence rate was significantly higher in patients whose peripheral blood expressed SSX-1 mRNA, suggesting tha展开更多
Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is a...Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.展开更多
基金Supported by National Natural Science Foundation of China,No 30200271
文摘AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP) in these patients was also determined.RESULTS:The positive rate of MAGE-1,SSX-1 and CTp11 transcripts was 37.7%,34.4%,31.1% in PBMC samples,and 74.4%,73.3%,62.2% in their resected tumor samples,respectively.The positive rate for at least one of the transcripts of three CTA genes was 66.7% in PBMC samples and 91.1% in their resected tumor samples.MAGE-1,SSX-1 and/or CTp11 mRNA were not detected in the PBMC of those patients from whom the resected tumor samples were MAGE-1,SSX-1 and/or CTp11 mRNA negative,nor in the PBMC samples from 20 healthy donors and 10 cirrhotic patients.Among the 90 patients,the serum AFP in 44 patients met the general diagnostic standard(AFP > 400 μg/L) for HCC,and was negative(AFP ≤ 20 μg/L) or positive with a low concentration(20 μg/L < AFP ≤ 400 μg/L) in the other patients.The positive rate for at least one of the transcripts of three CTA genes in PBMC samples from the AFP negative or positive patients with a low concentration was 69.2% and 45.0%,respectively.Of the 90 patients,71(78.9%) were diagnosed as HCC by nested RT-PCR and serum AFP.Although the positive rate for at least one of the transcripts of three CTA genes in PBMC samples from 53 patients at TNM stage or was obviously higher than that in PBMC samples from 37 patients at stage or(77.9% vs 51.4%,P = 0.010),the CTA mRNA was detected in 41.7% and 56.0% of PBMC samples from HCC patients at stages andrespectively.CONCLUSION:Detecting MAGE-1,SSX-1 and CTp11 mRNA in PBMC improves the total diagnostic rate of HCC.
基金Supported by Grant-in-Aid for research by Kitasato University Medical Center,No.H25-0006 and the JSPS,KAKENHI,No.26670609 to Futawatari Nthe JSPS,KAKENHI,No.21700510 and No.17K16578,Takeda Science Foundation and Kitasato University Research Grant for Young Researchers to Fukuyama T
文摘AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.
基金Supported by Grant-in-Aid for research by the Kitasato University Medical Center,No.H26-008the JSPS KAKENHI,No.17K16578+3 种基金the JSPS KAKENHI,No.26670609Takeda Science FoundationKitasato University Research Grant for Young ResearchersGrant-in-Aid for research from the Kitasato University Medical Center,No.H25-0006
文摘BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.
文摘GAGE基因是Van den Eynde等应用细胞毒性T淋巴细胞（CTL）筛选法，从一黑色素瘤细胞株cDNA文库中筛选出的肿瘤抗原基因，它能在多种来源不同的肿瘤组织表达，而在正常组织的表达仅限于睾丸组织，因此属于癌-睾丸抗原（CT抗原）。本研究中采用逆转录聚合酶链反应（RT-PCR）技术检测肝细胞癌（HCC）组织及相应癌旁组织中GAGE基因mRNA4的表达情况，
文摘印记位点调节子的弟兄(brother of regulator of imprinted sites,BORIS)或者类CCCTC结合因子(CCCTC binding factor-like,CTCFL)是一个相对发现不久的癌症睾丸抗原。与之相关的药物研发已经在小分子、小RNA、多肽药、疫苗以及细胞等多个方向展开。因独特的干扰基因组空间高级结构的能力,BORIS可能代表着一类全新药物靶点。本综述系统梳理BORIS相关分子生物学研究结果,包括BORIS基因产物的多样性,由其介导的分子间互作,受到影响的信号传导通路,以及现有相关药物研发策略,以期明了BORIS的上下游调控分子机制及可能进一步突破的研究方向。
文摘Background Cancer-testis antigen （CTA） is a family of the most noticeable tumor antigens which could be potential tumor markers for cancer diagnosis. In this research we aimed to investigate the expression of SSX-1 and NY-ESO-1 mRNA, two members of the CTA family, in tissue and peripheral blood of patients with hepatocellular carcinoma （HCC） to assess their feasibility for the immunotherapy and diagnosis of HCC and the association of their expression levels with diverse clinical indicators. Methods Thirty-six north Chinese patients with HCC and 30 normal controls were enrolled in this study. Reverse transcription-polymerase chain reaction （RT-PCR） was used to detect the expression of SSX-1 and NY-ESO-1 mRNA in tumor tissues and corresponding levels in peripheral blood of patients. Results The positive rates of SSX-1 and NY-ESO-1 mRNA expression were 61.1% （22/36） and 11.1% （4/36）, respectively, in cancer tissues; 38.9% （14/36） and 5.6% （2/36）, respectively, in the corresponding peripheral blood samples. No positive expression of either SSX-1 or NY-ESO-1 mRNA was detected in the samples of cancer-adjacent tissues, cirrhotic tissues, normal liver tissue or the peripheral blood of control patients. No significant relationship was found between the expression of these two genes and clinical indicators such as age, gender, tumor size, extent of differentiation, serum a-fetoprotein （AFP） level or infection with hepatitis B virus （P〉0.05）. The short term recurrence rate was 46.2% （6/13） in patients whose peripheral blood expressed SSX-1 mRNA, while the recurrence rate in patients with negative SSX-1 mRNA was 28.6% （4/14）. Conclusions SSX-1 and NY-ESO-1 antigens might be new potentially promising targets for antigen-specific immunotherapy for HCC. High specific expression of SSX-1 and NY-ESO-1 mRNA suggested that we could apply them as tumor markers. The short term recurrence rate was significantly higher in patients whose peripheral blood expressed SSX-1 mRNA, suggesting tha
文摘Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.
