Cancer Science最新文献

{"title":"CCL5/CCR5/CYP1A1 pathway prompts liver cancer cells to survive in the combination of targeted and immunological therapies","authors":"Yafei Wang,&nbsp;Biao Gao,&nbsp;Tianyu Jiao,&nbsp;Wenwen Zhang,&nbsp;Huizhong Shi,&nbsp;Hao Jiang,&nbsp;Xuerui Li,&nbsp;Junfeng Li,&nbsp;Xinlan Ge,&nbsp;Ke Pan,&nbsp;Chonghui Li,&nbsp;Guankun Mao,&nbsp;Shichun Lu","doi":"10.1111/cas.16320","DOIUrl":"10.1111/cas.16320","url":null,"abstract":"<p>Combination therapy of anti-programmed cell death protein-1 (PD-1) antibodies and tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis for hepatocellular carcinoma (HCC), but many patients still have unsatisfactory outcomes. CD8 T cells are known to exert a pivotal function in the immune response against tumors. Nevertheless, most CD8 T cells in HCC tissues are in a state of exhaustion, losing the cytotoxic activity against malignant cells. Cytokines, mainly secreted by immune cells, play an important role in the occurrence and development of tumors. Here, we demonstrated the changes in exhausted CD8T cells during combination therapy by single-cell RNA sequencing (scRNA-seq) analysis on tumor samples before and after treatment. Combination therapy exerted a substantial impact on the exhausted CD8T cells, particularly in terms of cytokine expression. CCL5 was the most abundantly expressed cytokine in CD8T cells and exhausted CD8T cells, and its expression increased further after treatment. Subsequently, we discovered the CCL5/CCR5/CYP1A1 pathway through RNA sequencing (RNA-seq) on CCL5-stimulated Huh7 cells and verified through a series of experiments that this pathway can mediate the resistance of liver cancer cells to lenvatinib. Tissue experiments showed that after combination therapy, the CCL5/CCR5/CYP1A1 pathway was activated, which can benefit the residual tumor cells to survive treatment. Tumor-bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3552-3569"},"PeriodicalIF":4.5,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic structural variants analysis in leukemia by a novel cytogenetic technique: Optical genome mapping","authors":"Song Lu,&nbsp;Kefu Liu,&nbsp;Di Wang,&nbsp;Yuan Ye,&nbsp;Zhiping Jiang,&nbsp;Yunhua Gao","doi":"10.1111/cas.16325","DOIUrl":"10.1111/cas.16325","url":null,"abstract":"<p>Genomic structural variants (SVs) play a pivotal role in driving the evolution of hematologic malignancies, particularly in leukemia, in which genetic abnormalities are crucial features. Detecting SVs is essential for achieving precise diagnosis and prognosis in these cases. Karyotyping, often complemented by fluorescence in situ hybridization and/or chromosomal microarray analysis, provides standard diagnostic outcomes for various types of SVs in front-line testing for leukemia. Recently, optical genome mapping (OGM) has emerged as a promising technique due to its ability to detect all SVs identified by other cytogenetic methods within one single assay. Furthermore, OGM has revealed additional clinically significant SVs in various clinical laboratories, underscoring its considerable potential for enhancing front-line testing in cases of leukemia. This review aims to elucidate the principles of conventional cytogenetic techniques and OGM, with a focus on the technical performance of OGM and its applications in diagnosing and prognosticating myelodysplastic syndromes, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphocytic leukemia.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3543-3551"},"PeriodicalIF":4.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel index combining fecal immunochemical test, DNA test, and age improves detection of advanced colorectal adenoma","authors":"Yukari Inoue,&nbsp;Akiyo Ishiguro,&nbsp;Yutaka Suehiro,&nbsp;Yuki Kunimune,&nbsp;Yuko Yamaoka,&nbsp;Shinichi Hashimoto,&nbsp;Katsuhiko Nakamura,&nbsp;Atsushi Goto,&nbsp;Koichi Hamabe,&nbsp;Toshihiko Matsumoto,&nbsp;Shinobu Tomochika,&nbsp;Shingo Higaki,&nbsp;Ikuei Fujii,&nbsp;Chieko Suzuki,&nbsp;Michiko Koga,&nbsp;Takeya Tsutsumi,&nbsp;Lay Ahyoung Lim,&nbsp;Yasuo Matsubara,&nbsp;Hiroshi Yotsuyanagi,&nbsp;Hiroaki Nagano,&nbsp;Naoki Yamamoto,&nbsp;Isao Sakaida,&nbsp;Taro Takami,&nbsp;Mitsuaki Nishioka,&nbsp;Takahiro Yamasaki","doi":"10.1111/cas.16322","DOIUrl":"10.1111/cas.16322","url":null,"abstract":"<p>Although the fecal immunochemical test for hemoglobin (FIT) is a widely used screening test for colorectal cancer, it is not sensitive enough to detect advanced colorectal adenoma. To address this issue, we performed this study to investigate whether combining the FIT and fecal DNA testing of methylated somatostatin (<i>SST</i>) could improve diagnostic performance for advanced colorectal adenoma. We collected feces from 79 healthy subjects with negative results on colonoscopy, 43 patients with non-advanced colorectal adenoma, 117 patients with advanced colorectal adenoma, and 126 patients with colorectal cancer. After fecal DNA was incubated with methylation-sensitive restriction enzymes, <i>SST</i> methylation levels were measured by droplet digital PCR. Using logistic multivariate analysis, we established a prediction formula for detecting colorectal neoplasia and named it the FAMS (FIT, age, methylated <i>SST</i>) index. The diagnostic performance of a single use of FIT for advanced colorectal adenoma showed a sensitivity of 29.1% (34/117) and specificity of 89.3% (109/122). In contrast, the FAMS index showed a sensitivity of 56.4% (66/117) at a similar specificity point of 91.0% (111/122). Furthermore, even at the higher specificity point of 94.3% (115/122), the sensitivity was still higher than that of FIT, reaching 42.7% (50/117). As the FAMS index showed better diagnostic performance for advanced colorectal adenoma than a single use of FIT, the FAMS index could be a promising tool for detecting advanced colorectal adenoma.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3682-3694"},"PeriodicalIF":4.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking Japan's cervical cancer prevention deadlock","authors":"Wiebren A. A. Tjalma","doi":"10.1111/cas.16311","DOIUrl":"10.1111/cas.16311","url":null,"abstract":"<p>Cervical cancer prevention in Japan, which had nearly halted due to misinformation, is now recovering through HPV vaccination and screening efforts. While significant progress has been made, much work remains, yet the recent improvements are highly encouraging.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3486-3487"},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tretinoin synergistically enhances the antitumor effect of combined BRAF, MEK, and EGFR inhibition in BRAFV600E colorectal cancer","authors":"Yuya Yoshida,&nbsp;Masanobu Takahashi,&nbsp;Sakura Taniguchi,&nbsp;Ryunosuke Numakura,&nbsp;Keigo Komine,&nbsp;Chikashi Ishioka","doi":"10.1111/cas.16280","DOIUrl":"10.1111/cas.16280","url":null,"abstract":"<p>Patients with <i>BRAF</i>-mutated colorectal cancer (<i>BRAF</i>^V600E CRC) are currently treated with a combination of BRAF inhibitor and anti-EGFR antibody with or without MEK inhibitor. A fundamental problem in treating patients with <i>BRAF</i>^V600E CRC is intrinsic and/or acquired resistance to this combination therapy. By screening 78 compounds, we identified tretinoin, a retinoid, as a compound that synergistically enhances the antiproliferative effect of a combination of BRAF inhibition and MEK inhibition with or without EGFR inhibition on <i>BRAF</i>^V600E CRC cells. This synergistic effect was also exerted by other retinoids. Tretinoin, added to BRAF inhibitor and MEK inhibitor, upregulated PARP, BAK, and p-H2AX. When either RARα or RXRα was silenced, the increase in cleaved PARP expression by the addition of TRE to ENC/BIN or ENC/BIN/CET was canceled. Our results suggest that the mechanism of the synergistic antiproliferative effect involves modulation of the Bcl-2 family and the DNA damage response that affects apoptotic pathways, and this synergistic effect is induced by RARα- or RXRα-mediated apoptosis. Tretinoin also enhanced the antitumor effect of a combination of the BRAF inhibitor and anti-EGFR antibody with or without MEK inhibitor in a <i>BRAF</i>^V600E CRC xenograft mouse model. Our data provide a rationale for developing retinoids as a new combination agent to overcome resistance to the combination therapy for patients with <i>BRAF</i>^V600E CRC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3740-3754"},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cervical mucus can be used for metabolite screening in cervical cancer","authors":"Rie Kawasaki,&nbsp;Iwao Kukimoto,&nbsp;Tetsuya Tsukamoto,&nbsp;Eiji Nishio,&nbsp;Aya Iwata,&nbsp;Takuma Fujii","doi":"10.1111/cas.16323","DOIUrl":"10.1111/cas.16323","url":null,"abstract":"<p>Approximately 660,000 women are diagnosed with cervical cancer annually. Current screening options such as cytology or human papillomavirus testing have limitations, creating a need to identify more effective ancillary biomarkers for triage. Here, we evaluated whether metabolomic analysis of cervical mucus metabolism could be used to identify biomarkers of cervical intraepithelial neoplasia (CIN) and cervical cancer. The case–control group consisted of 181 CIN, 69 squamous cell carcinoma (SCC) patients, and 48 healthy controls in the primary cohort. We undertook metabolomic analyses using ultra-HPLC–tandem mass spectrometry. Univariate and multivariate analyses were carried out to profile metabolite characteristics, and receiver operating characteristic (ROC) analysis identified biomarker candidates. Five metabolites conferred the highest discriminatory power for SCC: oxidized glutathione (GSSG) (area under the ROC curve, 0.924; 95% confidence interval, 0.877–0.971), malic acid (0.914, 0.859–0.968), kynurenine (0.884, 0.823–0.945), GSSG/glutathione (GSH) (0.936, 0.892–0.979), and kynurenine/tryptophan (0.909, 0.856–0.961). Malic acid was the best marker for detection of CIN2 or worse (0.858, 0.793–0.922) and was a clinically useful metabolite. We confirmed the reproducibility of the results by validation cohort. Additionally, metabolomic analyses revealed eight pathways strongly associated with cervical neoplasia. Of these, only the tricarboxylic acid cycle was strongly associated with all CINs and cancer, indicating active energy production. Aberrant arginine metabolism by decreasing arginine and increasing citrulline might reduce tumor immunity. Changes in cysteine-methionine and GSH pathways might drive the initiation and progression of cervical cancer. These results suggest that metabolic analysis can identify ancillary biomarkers and could improve our understanding of the pathophysiological mechanisms underlying cervical neoplasia.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3672-3681"},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast activation protein constitutes a novel target of chimeric antigen receptor T-cell therapy in solid tumors","authors":"Sikun Meng,&nbsp;Tomoaki Hara,&nbsp;Yutaka Miura,&nbsp;Hideshi Ishii","doi":"10.1111/cas.16285","DOIUrl":"10.1111/cas.16285","url":null,"abstract":"<p>With recent advances in tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has achieved unprecedented success in several hematologic tumors, significantly improving patient prognosis. However, in solid tumors, the efficacy of CAR-T cell therapy is limited because of high antigen uncertainty and the extremely restrictive tumor microenvironment (TME). This challenge has led to the exploration of new targets, among which fibroblast activation protein (FAP) has gained attention for its relatively stable and specific expression in the TME of various solid tumors, making it a potential new target for CAR-T cell therapy. This study comprehensively analyzed the biological characteristics of FAP and discussed its potential application in CAR-T cell therapy, including the theoretical basis, and preclinical and clinical research progress of targeting FAP with CAR-T cell therapy for solid tumor treatment. The challenges and future optimization directions of this treatment strategy were also explored, providing new perspectives and strategies for CAR-T cell therapy in solid tumors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3532-3542"},"PeriodicalIF":4.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACTN4 is associated with the malignant potential of thymic epithelial tumors through the β-catenin/Slug pathway","authors":"Hideki Nagata,&nbsp;Soichiro Funaki,&nbsp;Kenji Kimura,&nbsp;Eriko Fukui,&nbsp;Toru Kimura,&nbsp;Takashi Kanou,&nbsp;Naoko Ose,&nbsp;Eiichi Morii,&nbsp;Yasushi Shintani","doi":"10.1111/cas.16313","DOIUrl":"10.1111/cas.16313","url":null,"abstract":"<p>Thymic epithelial tumors (TETs) are rare tumors arising from the mediastinum. Among TETs, thymoma type B2, B3 and thymic carcinoma are highly malignant and often present invasion and dissemination. However, the biological characteristics of TETs have not been thoroughly studied, and their mechanisms of invasion and dissemination are largely unknown. α-Actinin 4 (ACTN4) is a member of actin-binding proteins and reportedly plays important roles in the progression of several cancers. In this study, we investigated the relationship between ACTN4 and characteristics of the malignant potential of TETs, such as invasion and dissemination. <i>In vitro</i> experiments using Ty-82 thymic carcinoma cells revealed that overexpression of ACTN4 enhanced the proliferative and invasive ability of Ty-82 cells; conversely, knockdown of ACTN4 attenuated the proliferative and invasive potential of Ty-82 cells. In western blotting (WB) experiments, ACTN4 induced the phosphorylation of extracellular signal–regulated kinase and glycogen synthase kinase 3β to regulate the β-catenin/Slug pathway. Furthermore, WB analysis of cancer tissue–origin spheroids from patients with TETs showed results similar to those for Ty-82 cells. In vivo experiments showed that the knockdown of ACTN4 significantly suppressed the dissemination of Ty-82 cells. A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, β-catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the β-catenin/Slug pathway.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3636-3647"},"PeriodicalIF":4.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Exosomal miR-106a-5p Accelerates the Progression of Nasopharyngeal Carcinoma Through FBXW7-Mediated TRIM24 Degradation","authors":"","doi":"10.1111/cas.16312","DOIUrl":"10.1111/cas.16312","url":null,"abstract":"<p><b>RETRACTION</b>: C.-W. Li, J. Zheng, G.-Q. Deng, Y.-G. Zhang, Y. Du and H.-Y. Jiang, “Exosomal miR-106a-5p Accelerates the Progression of Nasopharyngeal Carcinoma Through FBXW7-Mediated TRIM24 Degradation,” <i>Cancer Science</i> 113, no. 5 (2022): 1652–1668, https://doi.org/10.1111/cas.15337.</p><p>The above article, published online on 16 March 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley &amp; Sons Australia, Ltd. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed that images of pathological results were duplicated across other articles in a different scientific context. The authors acknowledge the duplication of the images and apologise for the errors. Despite the authors providing all original data and reconducting the animal pathology experiments, given the extent and nature of duplications found, the editors consider the results and conclusion of this article to be invalid.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 11","pages":"3829"},"PeriodicalIF":4.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood”","authors":"","doi":"10.1111/cas.16318","DOIUrl":"10.1111/cas.16318","url":null,"abstract":"<p>Song S, He X, Wang J, et al. ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood. Cancer Sci. 2021; 112: 4553–4569. 10.1111/cas.15104</p><p>We apologize for this error.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3497"},"PeriodicalIF":4.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}