Cancer Science最新文献_第6页

Single-Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-13 DOI: 10.1111/cas.70022

Kosuke Yoshida, Akira Yokoi, Hironori Suzuki, Satoshi Tamauchi, Masami Kitagawa, Eri Inami, Jun Nakayama, Yutaro Mori, Koji Okamoto, Yutaka Suzuki, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto

{"title":"Single-Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma.","authors":"Kosuke Yoshida, Akira Yokoi, Hironori Suzuki, Satoshi Tamauchi, Masami Kitagawa, Eri Inami, Jun Nakayama, Yutaro Mori, Koji Okamoto, Yutaka Suzuki, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto","doi":"10.1111/cas.70022","DOIUrl":"https://doi.org/10.1111/cas.70022","url":null,"abstract":"Squamous cell carcinoma arising from mature teratoma (SCC-MT) is a rare ovarian malignancy. The detailed molecular pathology of SCC-MT is not well understood. Moreover, the prognosis of the patients remains poor because no standard treatment has been established. In this study, we performed single-nucleus RNA sequencing and spatial transcriptomics using clinical SCC-MT samples to identify novel therapeutic candidates. snRNA-seq revealed three epithelial cell clusters, of which one was significantly associated with epidermis and keratinocyte development. Moreover, spatial transcriptomics revealed that the epithelial-mesenchymal transition was significantly inhibited, and the MYC and E2F targets were significantly activated in cancer spots on specimen sections. We focused on KLF5, which was one of the upregulated genes in cancer cells, and performed a functional analysis using NOSCC-1, a cell line derived from an SCC-MT. KLF5 downregulation significantly decreased cell proliferation and increased apoptosis. Furthermore, we previously identified miR-145-5p as a downregulated miRNA in SCC-MT. We demonstrated that miR-145-5p overexpression attenuated cell proliferation and decreased KLF5 expression. In conclusion, through multi-omics analyses, we identified unique gene expression profiles of SCC-MT and determined a role for KLF5 in SCC-MT development. Therefore, KLF5-related factors may be novel therapeutic targets, and further studies are needed to improve the diagnosis and treatment of SCC-MT.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mefloquine Suppresses Metastasis in Renal Cell Carcinoma Through Targeting SPC25.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-13 DOI: 10.1111/cas.70001

Yongbo Wang, He Wang, Yipeng Xu, Jiawei Ling, Chuhong Zong, Yan Zhang, Xiaoxuan Guo, Guanan Zhao, Yuan Zhou, Jiahui Zhao, Pengrong Lou, Xigao Liu, Tengfei Xu, Qi Ma

{"title":"Mefloquine Suppresses Metastasis in Renal Cell Carcinoma Through Targeting SPC25.","authors":"Yongbo Wang, He Wang, Yipeng Xu, Jiawei Ling, Chuhong Zong, Yan Zhang, Xiaoxuan Guo, Guanan Zhao, Yuan Zhou, Jiahui Zhao, Pengrong Lou, Xigao Liu, Tengfei Xu, Qi Ma","doi":"10.1111/cas.70001","DOIUrl":"https://doi.org/10.1111/cas.70001","url":null,"abstract":"Renal cell carcinoma (RCC) is the third most common malignant tumor in the urinary system, often presenting with distant metastases at diagnosis. Approximately one-quarter of patients undergoing nephrectomy experience distant recurrence. Despite the recent advancements in combination-targeted and immune checkpoint inhibitor therapies, the development of new therapeutic strategies and the identification of biomarkers for metastatic risk remain crucial. The study found that high SPC25 expression is closely associated with poor clinical outcomes, and knocking down SPC25 significantly inhibits tumor cell proliferation and migration. Non-targeted metabolomics analysis also revealed that SPC25 knockdown reduces tumor cell activity, resulting in a low-invasive state. Additionally, this study utilized high-throughput molecular docking to screen small molecule drugs targeting SPC25, aiming to find drugs that inhibit RCC metastasis. The research discovered that mefloquine, at concentrations that do not significantly kill tumor cells, can markedly inhibit RCC metastasis. It was the first to report that mefloquine achieves its anti-metastatic effects by binding to SPC25 and inhibiting epithelial-mesenchymal transition. These results suggest that SPC25 has the potential to serve as an early biomarker for metastatic risk in RCC and highlight a novel strategy where mefloquine inhibits RCC metastasis through SPC25 binding, offering new avenues to improve the prognosis of RCC patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-13 DOI: 10.1111/cas.70021

Hideki Yamaguchi, Makoto Miyazaki

{"title":"Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment.","authors":"Hideki Yamaguchi, Makoto Miyazaki","doi":"10.1111/cas.70021","DOIUrl":"https://doi.org/10.1111/cas.70021","url":null,"abstract":"Peritoneal metastasis, also known as peritoneal dissemination or carcinomatosis, refers to the spread of cancer to the peritoneum that lines the abdominal and pelvic cavities and covers the abdominal organs. Peritoneal metastasis typically occurs in advanced cancers of abdominal origin, most commonly gastrointestinal and gynecological cancers. Conventional chemotherapy has limited efficacy, and no effective molecular-targeted therapy is currently available for peritoneal metastasis. As a result, peritoneal metastasis is associated with poor outcomes and significantly reduced quality of life in patients with advanced cancers. This is largely due to a limited understanding of the molecular and cellular mechanisms underlying peritoneal metastasis. However, recent studies employing innovative approaches have provided novel insights into the mechanisms of peritoneal metastasis, contributing to the development of novel therapeutic strategies. In this review, we summarize recent findings on the cell biological aspects of peritoneal metastasis and potential therapeutic target molecules. In particular, we emphasize the importance of cancer cell clustering within the abdominal cavity, which drives multiclonal peritoneal seeding. We also focus on the interactions of cancer cells with mesothelial cells and cancer-associated fibroblasts within the peritoneal tumor microenvironment.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma tsRNA Signatures Serve as a Novel Biomarker for Bladder Cancer.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-13 DOI: 10.1111/cas.70003

Xinyan Xu, Jinbang Chen, Ming Bai, TianYao Liu, Shoubin Zhan, Jiazheng Li, YuanChun Ma, Yulin Zhang, Liming Wu, Zihan Zhao, Siyang Liu, Xi Chen, Feng Fang, Hongqian Guo, Ying Sun, Rong Yang

{"title":"Plasma tsRNA Signatures Serve as a Novel Biomarker for Bladder Cancer.","authors":"Xinyan Xu, Jinbang Chen, Ming Bai, TianYao Liu, Shoubin Zhan, Jiazheng Li, YuanChun Ma, Yulin Zhang, Liming Wu, Zihan Zhao, Siyang Liu, Xi Chen, Feng Fang, Hongqian Guo, Ying Sun, Rong Yang","doi":"10.1111/cas.70003","DOIUrl":"https://doi.org/10.1111/cas.70003","url":null,"abstract":"Bladder cancer (BLCA) is one of the most common tumors of the urinary tract. The diagnosis of BLCA is mostly by invasive tests, which are damaging and unsuitable for early screening. Current non-invasive diagnostic modalities are insufficient in sensitivity and specificity. Therefore, novel diagnostic markers are urgently needed to facilitate early detection of bladder cancer. tRNA-derived small RNAs (tsRNAs) are considered to be novel and potentially biologically functional non-coding RNAs (ncRNAs). tsRNAs have been used to help early diagnosis of a variety of tumors. However, whether tsRNAs in BLCA are altered or involved in BLCA progression or regulation remains unclear. Here, we identified a group of up-regulated tsRNAs in BLCA by sequencing tsRNAs in the plasma of BLCA patients and normal controls and further screened two highly correlated tsRNAs with BLCA in the training set and validation set, which were named as tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2. ROC analyses of the expression profiles of these two tsRNAs by the validation set identified a high diagnostic value. We also found that circulating tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2 were specifically expressed and released by BLCA cells and were positively correlated with the degree of disease malignancy. In vitro and in vivo experiments revealed that the two tsRNAs exacerbated BLCA progression and played a role in promoting tumor lipid metabolism. Our study screened two plasma tsRNAs that could serve as valuable early screening and diagnostic biomarkers for BLCA and is also expected to provide potential novel molecular targets for the treatment of BLCA.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRAS^G12C Inhibitors in Nonsmall Cell Lung Cancer.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-12 DOI: 10.1111/cas.70017

Zehao Pan, Yuxian Qian, Yajing Wang, Te Zhang, Xuming Song, Hanling Ding, Rutao Li, Yijian Zhang, Zi Wang, Hui Wang, Wenjie Xia, Lei Wei, Lin Xu, Gaochao Dong, Feng Jiang

{"title":"STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASG12C Inhibitors in Nonsmall Cell Lung Cancer.","authors":"Zehao Pan, Yuxian Qian, Yajing Wang, Te Zhang, Xuming Song, Hanling Ding, Rutao Li, Yijian Zhang, Zi Wang, Hui Wang, Wenjie Xia, Lei Wei, Lin Xu, Gaochao Dong, Feng Jiang","doi":"10.1111/cas.70017","DOIUrl":"https://doi.org/10.1111/cas.70017","url":null,"abstract":"KRASG12C inhibitors exhibit conspicuous clinical response in KRASG12C-mutant lung cancer, yet adaptive resistance, the rapid onset of intrinsic resistance, dampens their therapeutic success. Rational combination strategies could tackle this challenging problem. A high-throughput screening of a pharmacological library with 423 compounds revealed that napabucasin, a signal transducer and activator of transcription 3 (STAT3) inhibitor, synergistically potentiated the growth inhibition effect of the KRASG12C inhibitor sotorasib in sensitive and resistant KRASG12C NSCLC cell lines. Functional assays further revealed that the coordinated targeting of KRAS with STAT3 improved the inhibitory effect on tumor growth and augmented the infiltration and activation of natural killer (NK) cells within the tumor microenvironment. Mechanistically, KRASG12C inhibition induced compensatory activation of STAT3, contingent on concomitant suppression of downstream ERK signaling, abrogated by napabucasin. Moreover, we unveiled and verified the binding site of phosphorylated STAT3 at the HLA-B promoter, an inhibitor ligand for NK cells. Our study dissected an unknown mechanism of adaptive resistance to KRASG12C inhibitors, with the STAT3 activation sustaining the regrowth of tumor cells under KRAS inhibition and up-regulating HLA-B transcription to dampen the cytotoxicity of infiltrated NK cells.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FGFR2/3 Gene Alterations and Clinical Outcomes in Advanced/Metastatic Urothelial Cancer in Japan: MONSTAR-SCREEN Database Study.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-11 DOI: 10.1111/cas.70000

Nobuaki Matsubara, Takahiro Osawa, Takashige Abe, Mototsugu Oya, Koshiro Nishimoto, Toshiyuki Iwahori, Hiroaki Tsuchiya, Maiko Murota, Masaki Yoshida, Yohei Tatematsu, Yosuke Nakano, Masatoshi Eto, Norio Nonomura

{"title":"FGFR2/3 Gene Alterations and Clinical Outcomes in Advanced/Metastatic Urothelial Cancer in Japan: MONSTAR-SCREEN Database Study.","authors":"Nobuaki Matsubara, Takahiro Osawa, Takashige Abe, Mototsugu Oya, Koshiro Nishimoto, Toshiyuki Iwahori, Hiroaki Tsuchiya, Maiko Murota, Masaki Yoshida, Yohei Tatematsu, Yosuke Nakano, Masatoshi Eto, Norio Nonomura","doi":"10.1111/cas.70000","DOIUrl":"https://doi.org/10.1111/cas.70000","url":null,"abstract":"Advanced/metastatic urothelial cancer (a/m UC) still has a poor prognosis despite the recent medical advances. Recent studies demonstrated that fibroblast growth factor receptor (FGFR) gene alterations (GAs) may be driver genes for UC; however, the proportion of UC genetic panel testing in Japan remains low. We clarified the proportion of patients with FGFR2/3 GAs, treatment patterns, and clinical outcomes in a/m UC patients in Japan. This study was a descriptive epidemiological study using the MONSTAR-SCREEN database, and 138 patients with a/m UC were evaluated. The primary endpoint was the proportion of patients with FGFR2/3 GAs. The secondary endpoints included treatment patterns, clinical outcomes, genomic status before and after treatment, etc. The proportion of FGFR GA-positive patients in a/m UC was 11.9%. The most common FGFR mutation variant and fusion gene were S249C (4.4%) and FGFR3-TACC3 fusion (3.7%), respectively. Fifty-one patients were tested two or more times; a few changes were observed in the FGFR GA status, regardless of the treatment regimen. Co-occurrence association was observed in FGFR1 with TET2, and in FGFR3 with CHEK2 or MLL2. During the first-, second-, and third-line treatment, median progression-free survival (PFS) of GA-positive patients was 7.3, 2.9, and 6.2 months, while for GA-negative patients, 6.9, 3.1, and 6.9 months, respectively. This study revealed that one in eight a/m UC patients had FGFR2/3 GAs, and a few changes were observed in FGFR GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Second Opinion Referrals of Cancer Patients in Japan-A Nationwide Study.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-11 DOI: 10.1111/cas.70012

Mieko Takasawa, Norihiro Teramoto, Natsumi Yamashita, Takahiro Higashi

{"title":"Second Opinion Referrals of Cancer Patients in Japan-A Nationwide Study.","authors":"Mieko Takasawa, Norihiro Teramoto, Natsumi Yamashita, Takahiro Higashi","doi":"10.1111/cas.70012","DOIUrl":"https://doi.org/10.1111/cas.70012","url":null,"abstract":"Seeking a second opinion (SO) is a patient's right that is essential to appropriate decision-making for their care and treatment. In Japan, however, no previous studies have provided objective data on the nationwide practice of SO among cancer patients. In this study, we investigated SO referrals, including delays in initiating care, using data from nationwide hospital-based cancer registries and 2018-2020 the Diagnosis Procedure Combination (DPC) survey. Among the more than 2.6 million patients diagnosed with cancer, 1.6% received SO referral letters as reimbursement. The referral rates varied based on sex, age, and geographic regions. A total of 52.1% of SO were sought before active treatment of the tumor. Approximately 60% of the patients who sought SO prior to the initial treatment returned to their original provider for treatment. The average period from diagnosis to the start of treatment among those who sought SO was 18 days and 22 days longer for non-small lung cancer and breast cancer, respectively, than among those who did not seek SO. In the future, the risk-benefit of SO referral should be examined, considering both the prognostic impact of treatment delay due to SO and the psychological benefits for the patient gained from SO.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of BTK knockdown on lung adenocarcinoma growth and immune response. BTK基因敲低对肺腺癌生长和免疫应答的影响。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-04 DOI: 10.1111/cas.16394

Jilan Huang, Yufan Yuan, Linghong Guo, Guojin Xia, Yan Chen, Qi Chen, Min Wang

引用次数: 0