Cancer Science
1349-7006
1347-9032
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Cơ quản chủ quản: Wiley-Blackwell , WILEY
Lĩnh vực:
Cancer ResearchMedicine (miscellaneous)Oncology
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Thông tin về tạp chí
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
Các bài báo tiêu biểu
Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications Aldehyde dehydrogenase 1 (ALDH1) is expressed in stem/progenitor cells, including cancer‐initiating cells (CIC) of various organs. In the present study, ALDH1 expression was immunohistochemically examined in uterine endometrioid adenocarcinoma. The ALDH1 was expressed in a small portion of tumor cells, and these ALDH1‐expressing cells were less mature than ALDH1‐non‐expressing cells. The ALDH1‐expressing (ALDH1‐hi) cells were more tumorigenic, resistant to anti‐cancer agents and more invasive than ALDH1‐lo cells. Culture of the sorted ALDH1‐hi cells yielded both ALDH1‐hi and ALDH1‐lo cells, whereas ALDH1‐lo cells yielded ALDH‐lo cells alone. Clinically, a high‐level of ALDH1 expression in tumor cells was correlated with T category, lymphatic invasion, recurrence and prognosis of patients. Patients with high ALDH1 expression showed poorer prognoses than those with low expression (P = 0.015 for disease‐free survival [DFS] and P = 0.010 for overall survival [OS]), and high ALDH1 expression was an independent factor for poor prognosis. Aldehyde dehydrogenase 1 is a candidate for CIC marker for uterine endometrioid adenocarcinoma. (Cancer Sci 2011; 102: 903–908)
Tập 102 Số 4 - Trang 903-908 - 2011
Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients Malignant pleural mesothelioma (MPM) is an asbestos‐related malignancy that is highly resistant to current therapeutic modalities. We established four MPM cell lines (ACC‐MESO‐1, ACC‐MESO‐4, Y‐MESO‐8A and Y‐MESO‐8D) from Japanese patients, with the latter two from the same patient with biphasic‐like characteristics of MPM, showing epithelial and sarcomatous phenotypes, respectively, in cell culture. These cells grew well in RPMI‐1640 medium supplemented with 10% fetal bovine serum under 5% CO2 . Mutation and expression analyses demonstrated that the tumor suppressor gene NF2 , which is known to be one of the most frequently mutated in MPM, is mutated in ACC‐MESO‐1. We detected homozygous deletion of p16 INK4A p14 ARF TP53 , and protooncogenes, including KRAS , NRAS , BRAF , EGFR and HER2 , were not found in these cell lines. Polymerase chain reaction amplification of the simian virus 40 sequence did not detect any products. We also analyzed genetic alterations of six other MPM cell lines and confirmed frequent mutations of NF2 and p16 INK4A /p14 ARF Cancer Sci 2006; 97)
Tập 97 Số 5 - Trang 387-394 - 2006
Genomic profiling of malignant pleural mesothelioma with array‐based comparative genomic hybridization shows frequent non‐random chromosomal alteration regions including <i>JUN</i> amplification on 1p32 Genome‐wide array‐based comparative genomic hybridization analysis of malignant pleural mesotheliomas (MPM) was carried out to identify regions that display DNA copy number alterations. Seventeen primary tumors and nine cell lines derived from 22 individuals were studied, some of them originating from the same patients. Regions of genomic aberrations observed in >20% of individuals were 1q, 5p, 7p, 8q24 and 20p with gains, and 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 4q34‐qter, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q with losses. Two regions at 1p32.1 and 11q22 showed a high copy gain. The 1p32.1 region contained a protooncogene, JUN , and we further demonstrated overexpression of JUN with real‐time polymerase chain reaction analysis. As MPM cell lines did not overexpress JUN , our findings suggested that induction of JUN expression was involved in the development of MPM cells in vivo , which also might result in gene amplification in a subset of MPM. Meanwhile, the most frequent alteration was the 9p21.3 deletion, which includes the p16 INK4a p14 ARF p16 INK4a p14 ARF Cancer Sci 2007; 98: 438–446)
Tập 98 Số 3 - Trang 438-446 - 2007
Silencing of <i>microRNA‐122</i> is an early event during hepatocarcinogenesis from non‐alcoholic steatohepatitis Non‐alcoholic steatohepatitis (NASH ) has emerged as a common cause of chronic liver disease and virus‐independent hepatocellular carcinoma (HCC ) in patients with obesity, diabetes, and metabolic syndrome. To reveal the molecular mechanism underlying hepatocarcinogenesis from NASH , microRNA (miRNA ) expression profiles were analyzed in STAM mice, a NASH ‐HCC animal model. MicroRNA expression was also examined in 42 clinical samples of HCC tissue. Histopathological images of the liver of STAM mice at the ages of 6, 8, 12, and 18 weeks showed findings compatible with fatty liver, NASH , liver cirrhosis (LC ), and HCC , respectively. Expression of miR‐122 in non‐tumor LC at the age of 18 weeks was significantly lower than that in LC at the age of 12 weeks. Expression of miR‐122 was further decreased in HCC s relative to non‐tumor LC at the age of 18 weeks. Expression of miR‐122 was also decreased in clinical samples of liver tissue showing macrovesicular steatosis and HCC , being consistent with the findings in the NASH model mice. DNA methylation analysis revealed that silencing of miR‐122 was not mediated by DNA hypermethylation of the promoter region. These results suggest that silencing of miR‐122 is an early event during hepatocarcinogenesis from NASH , and that miR‐122 could be a novel molecular marker for evaluating the risk of HCC in patients with NASH .
Tập 105 Số 10 - Trang 1254-1260 - 2014
Oncogenic role of miR‐17‐92 cluster in anaplastic thyroid cancer cells Micro RNAs (miRNAs) are non‐coding small RNAs and constitute a novel class of negative gene regulators that are found in both plants and animals. Several miRNAs play crucial roles in cancer cell growth. To identify miRNAs specifically deregulated in anaplastic thyroid cancer (ATC) cells, we performed a comprehensive analysis of miRNA expressions in ARO cells and primary thyrocytes using miRNA microarrays. MiRNAs in a miR‐17‐92 cluster were overexpressed in ARO cells. We confirmed the overexpression of those miRNAs by Northern blot analysis in ARO and FRO cells. In 3 of 6 clinical ATC samples, miR‐17‐3p and miR‐17‐5p were robustly overexpressed in cancer lesions compared to adjacent normal tissue. To investigate the functional role of these miRNAs in ATC cells, ARO and FRO cells were transfected with miRNA inhibitors, antisense oligonucleotides containing locked nucleic acids. Suppression of miR‐17‐3p caused complete growth arrest, presumably due to caspase activation resulting in apoptosis. MiR‐17‐5p or miR‐19a inhibitor also induced strong growth reduction, but only miR‐17‐5p inhibitor led to cellular senescence. On the other hand, miR‐18a inhibitor only moderately attenuated the cell growth. Thus, we have clarified functional differences among the members of the cluster in ATC cells. In conclusion, these findings suggest that the miR‐17‐92 cluster plays an important role in certain types of ATCs and could be a novel target for ATC treatment. (Cancer Sci 2008; 99: 1147–1154)
Tập 99 Số 6 - Trang 1147-1154 - 2008
Clinical significance of macrophage heterogeneity in human malignant tumors The fact that various immune cells, including macrophages, can be found in tumor tissue has long been known. With the recent introduction of the novel concept of macrophage differentiation into a classically activated phenotype (M 1) and an alternatively activated phenotype (M 2), the role of tumor‐associated macrophages (TAM s) is gradually beginning to be elucidated. Specifically, in human malignant tumors, TAM s that have differentiated into M 2 macrophages act as “protumoral macrophages” and contribute to the progression of disease. Based on recent basic and preclinical research, TAM s that have differentiated into protumoral or M 2 macrophages are believed to be intimately involved in the angiogenesis, immunosuppression, and activation of tumor cells. In this paper, we specifically discuss both the role of TAM s in human malignant tumors and the cell–cell interactions between TAM s and tumor cells.
Tập 105 Số 1 - Trang 1-8 - 2014
Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma Recently, an association between tumor infiltrating Forkhead box P3 regulatory T cells (Treg ) and an unfavorable prognosis has been clinically shown in some cancers, but the mechanism of Treg induction in the tumor microenvironment remains uncertain. The aims of the present study were to examine the relationship between Treg and patient outcome and to investigate whether Treg induction is influenced by the characteristics of cancer‐associated fibroblasts (CAF) in lung adenocarcinoma. The numbers of Treg in both the tumor stroma and the tumor nest were counted in 200 consecutive pathological stage I lung invasive adenocarcinoma specimens. To examine whether the characteristics of CAF influence Treg induction, we selected and cultured CAF from low Treg and high Treg adenocarcinoma. The number of Treg was much higher in the stroma than in the nest (P < 0.01). Patients with high Treg had a significantly poorer prognosis than those with low Treg (overall survival: P = 0.03; recurrence‐free survival: P = 0.02; 5‐year overall survival: 85.4% vs 93.0%). Compared with the CAF from low Treg adenocarcinoma, culture supernatant of the CAF from high Treg adenocarcinoma induced more Treg (P = 0.01). Also, CAF from high Treg adenocarcinoma expressed significantly higher mRNA levels of transforming growth factor‐β (P = 0.01) and vascular endothelial growth factor (P = 0.01), both of which are involved in Treg induction. Our studies suggest the possibility that CAF expressing immunoregulatory cytokines may induce Treg in the stroma, creating a tumor‐promoting microenvironment in lung adenocarcinoma that leads to a poor outcome.
Tập 104 Số 4 - Trang 409-415 - 2013
Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas We previously performed gene expression profile analyses of 20 intestinal‐type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non‐cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11) . Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal‐type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer‐testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11‐specific CTL. As a result, we successfully established oligo‐clonal CTL by stimulation with IGSF11‐9‐207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11‐9V (ALSSGLYQV), anchor‐modified peptides of IGSF11‐9‐207. These peptides showed IGSF11‐specific cytotoxic activity in an HLA‐A*0201‐restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers. (Cancer Sci 2005; 96: 498 –506)
Tập 96 Số 8 - Trang 498-506 - 2005
Ubiquitin‐mediated control of oncogene and tumor suppressor gene products Cellular levels of products from both oncogenes and tumor suppressor genes in normal cells need to be critically regulated to avoid malignant transformation. These products are often controlled by the ubiquitin proteasome pathway, the specific degradation mechanism in the cell. E3 ubiquitin ligases polyubiquitylate their specific substrates by collaborating with E1 and E2, and then the modified substrates are degraded in the proteasome. Mdm2 targets p53 and retinoblastoma protein, two major tumor suppressor gene products, for ubiquitin‐dependent degradation. SCFSkp2 targets other tumor suppressor gene products and CDK inhibitors such as p130, Tob1, p27Kip1 Kip2 Cip1 Fbw7 . Fbw7 is often deleted or mutated in human cancers and acts like a tumor suppressor. As well as growth factor receptors and signal transduction regulators, DNA repair‐related proteins are also regulated via the ubiquitin–proteasome pathway mediated by their specific E3 ligases. The stabilization of oncogene products and enhanced degradation of tumor suppressor gene products or DNA repair proteins might be associated with carcinogenesis and malignant progression, due to defects or the abnormal expression of their E3 ligases. (Cancer Sci 2009)
Tập 100 Số 8 - Trang 1374-1381 - 2009
B7‐H5/<scp>CD</scp>28H is a co‐stimulatory pathway and correlates with improved prognosis in pancreatic ductal adenocarcinoma B7‐H5 and its cognate receptor CD 28H are T lymphocyte second signaling transduction molecules. Here we aimed to explore the function of this pathway in pancreatic cancer in vitro and in vivo, and evaluated the clinical significance in 136 patients with pancreatic ductal adenocarcinoma enrolled from January 2012 to February 2017 in our hospital. Surgical tumor specimens were collected for immunohistochemical staining to evaluate B7‐H5 expression. Patients’ baseline characteristics, including gender, age, tumor size, tumor location, tumor grading, clinical TNM staging, tumor infiltrating lymphocytes, CA 19‐9 and chemotherapy treatment, along with the subsequent follow‐up data, were documented and analyzed. When co‐cultured with T cells, pancreatic cancer PC cells with high B7‐H5 expression induced a more potent immune reaction, indicated by elevated cytokine release and increased proliferation of T lymphocytes compared with cells exhibiting low B7‐H5 expression. Xenograft pancreatic tumors derived from high B7‐H5 expression PC cells exhibited attenuated growth compared to tumors from low B7‐H5 expression cells after transfusion with T lymphocytes in immune‐deficient mice. Of the 136 PDAC tumor tissues, 93 (68.38%) were strong and 43 (31.62%) were weak B7‐H5 expression. Patients with strong B7‐H5 expression had significantly longer overall survival than those with weak expression (median: 16.5 vs 11.5 months, P = .017). TNM staging, tumor location and subsequent chemotherapy were also prognostic factors in these patients. Collectively, B7‐H5/CD 28H is a co‐stimulatory signal pathway, and expression of B7‐H5 is associated with improved disease prognosis in patients with pancreatic cancer.
Tập 110 Số 2 - Trang 530-539 - 2019