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Correction to "miR-203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver". 对 "miR-203 抑制促进再生肝脏中残留肝细胞癌的增殖和转移 "的更正。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-30 DOI: 10.1111/cas.16361
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引用次数: 0
RETRACTION: Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs) Exert Their Anti-proliferative Activity by Interfering With Akt-mTOR Signaling and bax:bcl-2 Ratio Modulation in Cells From Chronic Myeloid Leukemic Patients. 返回:吡咯并[1,2-b][1,2,5]苯并噻二氮卓(PBTDs)通过干扰慢性骨髓性白血病患者细胞中 Akt-mTOR 信号传导和 bax:bcl-2 比率调节发挥抗增殖活性。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-30 DOI: 10.1111/cas.16390

Retraction: C. Di Stefano, G. Marfe, M. M. Trawinska, P. Sinibaldi-Salimei, R. Silvestri, S. Amadori and E. Abruzzese, "Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs) Exert Their Anti-proliferative Activity by Interfering With Akt-mTOR Signaling and bax:bcl-2 Ratio Modulation in Cells From Chronic Myeloid Leukemic Patients," Cancer Science 101, no. 4 (2010): 991-1000, https://doi.org/10.1111/j.1349-7006.2010.01490.x. The above article, published online on 07 January 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley & Sons Australia, Ltd. The retraction has been agreed due to several instances of duplications of western blot bands observed in Figures 3, 4, 5 and 8. Furthermore, splicing and deletion of bands was uncovered in Figures 4 and 7 respectively. Finally, western blot bands presented in Figure 4 was also found published earlier in another article. The authors provided partial raw data but the inconsistencies found could not be resolved on this basis. Due to the extent and nature of the duplications, the editors consider the results and conclusions of this study invalid.

撤回:C. Di Stefano、G. Marfe、M. M. Trawinska、P. Sinibaldi-Salimei、R. Silvestri、S. Amadori 和 E. Abruzzese,"吡咯并[1,2-b][1,2,5]苯并噻二氮卓(PBTDs)发挥抗增殖作用"。Abruzzese, "Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs) Exert Their Anti-proliferative Activity by Interfering With Akt-mTOR Signaling and bax:bcl-2 Ratio Modulation in Cells from Chronic Myeloid Leukemic Patients," Cancer Science 101, no.4 (2010):991-1000,https://doi.org/10.1111/j.1349-7006.2010.01490.x。上述文章于 2010 年 1 月 7 日在线发表于 Wiley Online Library (wileyonlinelibrary.com),经杂志主编 Masanori Hatakeyama、日本癌症协会和 John Wiley & Sons Australia, Ltd.协商,该文章已被撤回。同意撤稿的原因是在图 3、图 4、图 5 和图 8 中观察到多处 Western 印迹条带重复。此外,图 4 和图 7 分别发现了条带的拼接和删除。最后,图 4 中显示的 Western 印迹条带也是早先在另一篇文章中发现的。作者提供了部分原始数据,但发现的不一致之处无法据此解决。由于重复的程度和性质,编辑认为这项研究的结果和结论无效。
{"title":"RETRACTION: Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs) Exert Their Anti-proliferative Activity by Interfering With Akt-mTOR Signaling and bax:bcl-2 Ratio Modulation in Cells From Chronic Myeloid Leukemic Patients.","authors":"","doi":"10.1111/cas.16390","DOIUrl":"https://doi.org/10.1111/cas.16390","url":null,"abstract":"<p><strong>Retraction: </strong>C. Di Stefano, G. Marfe, M. M. Trawinska, P. Sinibaldi-Salimei, R. Silvestri, S. Amadori and E. Abruzzese, \"Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs) Exert Their Anti-proliferative Activity by Interfering With Akt-mTOR Signaling and bax:bcl-2 Ratio Modulation in Cells From Chronic Myeloid Leukemic Patients,\" Cancer Science 101, no. 4 (2010): 991-1000, https://doi.org/10.1111/j.1349-7006.2010.01490.x. The above article, published online on 07 January 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley & Sons Australia, Ltd. The retraction has been agreed due to several instances of duplications of western blot bands observed in Figures 3, 4, 5 and 8. Furthermore, splicing and deletion of bands was uncovered in Figures 4 and 7 respectively. Finally, western blot bands presented in Figure 4 was also found published earlier in another article. The authors provided partial raw data but the inconsistencies found could not be resolved on this basis. Due to the extent and nature of the duplications, the editors consider the results and conclusions of this study invalid.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548478","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
Evaluating stiffness of gastric wall using laser resonance frequency analysis for gastric cancer. 利用激光共振频率分析评估胃癌胃壁硬度
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-28 DOI: 10.1111/cas.16383
Tasuku Furube, Daisuke Nakashima, Satoru Matsuda, Katsuhiro Mikami, Takuto Hatakeyama, Masashi Takeuchi, Kazumasa Fukuda, Akihisa Ueno, Hajime Okita, Hirofumi Kawakubo, Masaya Nakamura, Takeo Nagura, Yuko Kitagawa

Tumor stiffness is drawing attention as a novel axis that is orthogonal to existing parameters such as pathological examination. We developed a new diagnostic method that focuses on differences in stiffness between tumor and normal tissue. This study comprised a clinical application of laser resonance frequency analysis (L-RFA) for diagnosing gastric cancer. L-RFA allows for precise and contactless evaluation of tissue stiffness. We used a laser to create vibrations on a sample's surface that were then measured using a vibrometer. The data were averaged and analyzed to enhance accuracy. In the agarose phantom experiments, a clear linear correlation was observed between the Young's modulus of the phantoms (0.34-0.71 MPa) and the summation of normalized vibration peaks (Score) in the 1950-4050 Hz range (R2 = 0.93145). Higher Young's moduli also resulted in lower vibration peaks at the excitation frequency, signal-to-noise (S/N) ratios, and harmonic peaks. We also conducted L-RFA measurements on gastric cancer specimens from two patients who underwent robot-assisted distal gastrectomy. Our results revealed significant waveform differences between tumor and normal regions, similar to the findings in agarose phantoms, with tumor regions exhibiting lower vibration peaks at the excitation frequency, S/N ratios, and harmonic peaks. Statistical analysis confirmed significant differences in the score between normal and tumor regions (p = 0.00354). L-RFA was able to assess tumor stiffness and holds great promise as a noninvasive diagnostic tool for gastric cancer.

肿瘤僵硬度作为一种与病理检查等现有参数正交的新轴心,正在引起人们的关注。我们开发了一种新的诊断方法,重点关注肿瘤和正常组织之间的硬度差异。这项研究包括激光共振频率分析(L-RFA)在胃癌诊断中的临床应用。激光共振频率分析可对组织硬度进行精确的非接触式评估。我们使用激光在样本表面产生振动,然后使用测振仪进行测量。对数据进行平均和分析,以提高准确性。在琼脂糖模型实验中,我们观察到模型的杨氏模量(0.34-0.71 兆帕)与 1950-4050 赫兹范围内归一化振动峰值(Score)的总和之间存在明显的线性相关(R2 = 0.93145)。杨氏模量越大,激励频率的振动峰值、信噪比和谐波峰值也越低。我们还对两名接受机器人辅助远端胃切除术的胃癌标本进行了 L-RFA 测量。我们的结果表明,肿瘤区域和正常区域的波形存在明显差异,这与琼脂糖模型中的结果类似,肿瘤区域在激励频率、信噪比和谐波峰上都表现出较低的振动峰。统计分析证实,正常区域和肿瘤区域的得分存在明显差异(p = 0.00354)。L-RFA 能够评估肿瘤的硬度,有望成为胃癌的无创诊断工具。
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引用次数: 0
Evaluation of cfDNA fragmentation characteristics in plasma for the diagnosis of lung cancer: A prospective cohort study. 评估血浆中用于诊断肺癌的 cfDNA 片段特征:前瞻性队列研究
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-28 DOI: 10.1111/cas.16360
Fudong Xu, Chong Wang, Hongxia Li, Bo Yu, Luyuan Chang, Feng Wang, Chaolian Long, Ling Bai, Hanqing Zhao, Nanying Che

Lung cancer is one of the most prevalent cancers worldwide, yet only approximately 16% of patients are diagnosed in early stage, highlighting the urgent need for novel, highly accurate detection models. In our study, patients with suspected lung cancer or lung disease, as identified through radiographic imaging, along with healthy individuals, were consecutively recruited from Beijing Chest Hospital. Circulating free DNA (cfDNA) was extracted from plasma samples, and low-depth whole-genome sequencing was performed to identify fragmentomic features for model construction. A total of 265 participants were prospectively enrolled, comprising 124 lung cancer patients and 141 noncancer individuals. The model we developed was based on four cfDNA fragmentation characteristics, including 20-bp breakpoint nucleotides motif, fragmentation size coverage, fragmentation size distribution, and copy number variation. In an independent test cohort, the model achieved an area under the curve (AUC) of 0.861 (95% CI: 0.781-0.942) and demonstrated a sensitivity of 70% (95% CI: 53.5%-83.4%) at a specificity of 89.4% (95% CI: 76.9%-96.5%). Notably, the model was also effective in detecting early-stage cancer, with an AUC of 0.808 (95% CI: 0.69-0.925). In summary, our lung cancer detection model shows strong screening capabilities by leveraging four cfDNA fragmentation characteristics, exhibiting robust performance in early cancer diagnosis.

肺癌是全球发病率最高的癌症之一,但仅有约 16% 的患者能在早期确诊,这说明迫切需要新型、高精度的检测模型。在我们的研究中,我们从北京胸科医院连续招募了通过放射成像确定的疑似肺癌或肺部疾病患者以及健康人。我们从血浆样本中提取了循环游离 DNA(cfDNA),并进行了低深度全基因组测序,以确定用于构建模型的片段组特征。共有 265 人参与了前瞻性研究,其中包括 124 名肺癌患者和 141 名非癌症患者。我们建立的模型基于四个cfDNA片段特征,包括20-bp断点核苷酸主题、片段大小覆盖率、片段大小分布和拷贝数变异。在一个独立测试队列中,该模型的曲线下面积(AUC)为 0.861(95% CI:0.781-0.942),灵敏度为 70%(95% CI:53.5%-83.4%),特异度为 89.4%(95% CI:76.9%-96.5%)。值得注意的是,该模型在检测早期癌症方面也很有效,AUC 为 0.808(95% CI:0.69-0.925)。总之,我们的肺癌检测模型利用四种 cfDNA 片段特征显示出强大的筛查能力,在早期癌症诊断中表现出强劲的性能。
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引用次数: 0
Tasurgratinib in patients with cholangiocarcinoma or gastric cancer: Expansion part of the first-in-human phase I study. Tasurgratinib 用于胆管癌或胃癌患者:首次人体I期研究的扩展部分。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-27 DOI: 10.1111/cas.16354
Chigusa Morizane, Makoto Ueno, Tatsuya Ioka, Masahiro Tajika, Masafumi Ikeda, Kensei Yamaguchi, Hiroki Hara, Hiroshi Yabusaki, Atsushi Miyamoto, Satoru Iwasa, Manabu Muto, Tsutomu Takashima, Keiko Minashi, Yoshito Komatsu, Tomohiro Nishina, Takako Eguchi Nakajima, Atsuchi Takeno, Toshikazu Moriwaki, Masayuki Furukawa, Takatoshi Sahara, Hiroki Ikezawa, Maiko Nomoto, Shuya Takashima, Taisuke Uehara, Setsuo Funasaka, Masakazu Yashiro, Junji Furuse

Fibroblast growth factor receptors (FGFRs) are a highly conserved family of transmembrane receptor tyrosine kinases with multiple roles in the regulation of key cellular processes. Specific FGFR mutations have been observed in several types of cancers, including gastric carcinoma and cholangiocarcinoma. Dose escalation data of 24 Japanese patients with solid tumors treated with Tasurgratinib (previously known as E7090), a potent, selective FGFR1-3 inhibitor, was reported in a phase I, first-in-human, single-center study. Based on the safety, pharmacokinetic, and pharmacodynamic profiles observed in this study, the recommended dose of 140 mg once daily was selected for the expansion part (Part 2), a multicenter expansion of the dose-finding study restricted to patients with tumors harboring FGFR gene alterations. Safety and preliminary efficacy were assessed in Part 2. Pharmacodynamic pharmacogenomic markers (serum phosphate, FGF23, and 1,25-(OH)2-vitamin D, circulating tumor DNA) and pharmacokinetic profiles were also evaluated. A total of 16 patients were enrolled in Part 2, six with cholangiocarcinoma and 10 with gastric cancer. The most common treatment-emergent adverse events were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, and paronychia. Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.

成纤维细胞生长因子受体(FGFR)是一个高度保守的跨膜受体酪氨酸激酶家族,在调控关键细胞过程中发挥着多种作用。在胃癌和胆管癌等几种癌症中都观察到了特定的 FGFR 突变。Tasurgratinib 是一种强效、选择性的 FGFR1-3 抑制剂,在一项 I 期、首次进入人体的单中心研究中,报告了 24 名日本实体瘤患者接受 Tasurgratinib(以前称为 E7090)治疗的剂量升级数据。根据该研究中观察到的安全性、药代动力学和药效学特征,该研究选择了每日一次 140 毫克的推荐剂量作为扩展部分(第二部分)的剂量,这是一项多中心扩展剂量探索研究,仅限于携带 FGFR 基因改变的肿瘤患者。第二部分对安全性和初步疗效进行了评估。此外,还评估了药效学药物基因组标记物(血清磷酸盐、FGF23 和 1,25-(OH)2-维生素 D、循环肿瘤 DNA)和药代动力学特征。共有 16 名患者参加了第二部分的研究,其中 6 人患有胆管癌,10 人患有胃癌。治疗过程中最常见的不良反应是高磷血症、掌跖红斑综合征和副癣。在胆管癌患者中观察到5例部分反应(83.3%),在胃癌患者中观察到1例部分反应(11.1%);两组患者的中位无进展生存期分别为8.26个月(95%置信区间[CI] 3.84,不可评估[NE])和3.25个月(95% CI 0.95,4.86),总生存期分别为22.49个月(95% CI 6.37,NE)和4.27个月(95% CI 2.23,7.95)。总之,对于携带FGFR2基因重排的胆管癌患者,塔舒瑞替尼140毫克具有可耐受的安全性和良好的临床疗效。
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引用次数: 0
PPM1G-mediated TBL1X mRNA splicing promotes cell migration in hepatocellular carcinoma. PPM1G 介导的 TBL1X mRNA 剪接可促进肝细胞癌的细胞迁移。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-27 DOI: 10.1111/cas.16372
Liling Hu, Xinyu Shi, Xiaoyi Yuan, Danya Liu, Dandan Zheng, Yuying Li, Fujin Shi, Meifang Zhang, Shu-Guang Su, Chris Zhiyi Zhang

The progression of hepatocellular carcinoma (HCC) is coincident with aberrant splicing of numerous tumor-related genes. Identification of the tumor-specific splice variants that facilitate HCC metastasis may provide a more comprehensive insight into the mechanisms of HCC metastasis. Through RNA sequencing and bioinformatic analyses, PPM1G was identified as a biomarker associated with HCC metastasis. Our data mapped a transcriptome-wide landscape of alternative splicing events modulated by PPM1G in HCC. Notably, we characterized the exon six-skipping transcript of TBL1X as an onco-splice variant regulated by PPM1G. Experimental validation revealed the enrichment of TBL1X-S in response to PPM1G overexpression. Moreover, mRNA stability analyses revealed that PPM1G prolonged the half-life of the TBL1X-S transcript. Both PPM1G and TBL1X-S exhibited metastasis-promoting phenotypes, with PPM1G-driven metastasis in HCC being partially dependent on TBL1X-S. Mechanistically, different TBL1X splice variants showed varying affinities for ZEB1, with TBL1X-S significantly enhancing ZEB1 activation and repressing CDH1 transcription, potentially accelerating the epithelial-mesenchymal transition (EMT) process. In conclusion, our study highlights the biological role of PPM1G and TBL1X-S in tumor metastasis. The PPM1G/TBL1X-S signaling axis presents a new view for investigating liver cancer metastasis mechanisms.

肝细胞癌(HCC)的进展与许多肿瘤相关基因的剪接异常有关。鉴定促进 HCC 转移的肿瘤特异性剪接变异可能有助于更全面地了解 HCC 转移的机制。通过 RNA 测序和生物信息学分析,PPM1G 被鉴定为与 HCC 转移相关的生物标志物。我们的数据绘制了整个转录组范围内受 PPM1G 调节的替代剪接事件图谱。值得注意的是,我们将 TBL1X 的外显子六跳转转录本表征为受 PPM1G 调控的共剪接变体。实验验证表明,TBL1X-S 在 PPM1G 过表达时富集。此外,mRNA稳定性分析表明,PPM1G延长了TBL1X-S转录本的半衰期。PPM1G和TBL1X-S都表现出促进转移的表型,PPM1G驱动的HCC转移部分依赖于TBL1X-S。从机理上讲,不同的TBL1X剪接变体对ZEB1的亲和力不同,TBL1X-S能显著增强ZEB1的活化并抑制CDH1的转录,从而可能加速上皮-间质转化(EMT)过程。总之,我们的研究强调了 PPM1G 和 TBL1X-S 在肿瘤转移中的生物学作用。PPM1G/TBL1X-S信号轴为研究肝癌转移机制提供了新的视角。
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引用次数: 0
Pembrolizumab efficacy in a tumor mutation burden-high glioblastoma patient: A case study and implications for precision oncology. Pembrolizumab对肿瘤突变负荷高的胶质母细胞瘤患者的疗效:病例研究及对精准肿瘤学的影响。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-25 DOI: 10.1111/cas.16370
Akihiro Nishiyama, Shigeki Sato, Hiroyuki Sakaguchi, Hiroshi Kotani, Kaname Yamashita, Koushiro Ohtsubo, Tomoko Sekiya, Atsushi Watanabe, Atsushi Tajima, Chie Shimaguchi, Keishi Mizuguchi, Hiroko Ikeda, Masashi Kinoshita, Mitsutoshi Nakada, Shinji Takeuchi

A glioblastoma (GBM) patient with a high tumor mutation burden (TMB-high) and mismatch repair deficiency (dMMR) exhibited a significant response to pembrolizumab, an immune checkpoint inhibitor (ICI), despite prior treatment with temozolomide (TMZ), known to induce hypermutation and potential resistance to ICIs. The rapid disease progression, indicated by 80% Ki67 positivity, was markedly countered by the positive outcome of pembrolizumab treatment. This case challenges traditional GBM treatment paradigms, demonstrating the potential of precision oncology in patients with significant TMB and dMMR, and underscores the importance of comprehensive genomic profiling in guiding clinical decisions in GBM management.

一位患有高肿瘤突变负荷(TMB-high)和错配修复缺陷(dMMR)的胶质母细胞瘤(GBM)患者对免疫检查点抑制剂(ICI)pembrolizumab的治疗产生了显著反应,尽管患者之前曾接受过替莫唑胺(TMZ)治疗,而已知替莫唑胺会诱发高突变并可能对ICI产生耐药性。Ki67阳性率高达80%,表明疾病进展迅速,而pembrolizumab治疗的积极效果则明显逆转了这一趋势。该病例挑战了传统的 GBM 治疗范式,展示了精准肿瘤学在具有显著 TMB 和 dMMR 的患者中的潜力,并强调了全面基因组分析在指导 GBM 临床治疗决策中的重要性。
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引用次数: 0
Human papillomavirus vaccine to prevent CIN3 or worse (CIN3+): A nationwide case-control study in Japan. 接种人类乳头瘤病毒疫苗预防 CIN3 或更严重(CIN3+):日本全国病例对照研究。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-25 DOI: 10.1111/cas.16375
Sayaka Ikeda, Yutaka Ueda, Asami Yagi, Taichi Mizushima, Akiko Sukegawa, Risa Kudoh, Manako Yamaguchi, Megumi Kurosawa, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto

An increase in cervical cancer incidence has been reported in Japan. The Ministry of Health, Labor, and Welfare of Japan has resumed the active recommendation of regular HPV vaccines in 2022. In Japan, the preventive effect of CIN3+ in the real world has not yet been demonstrated in age-adjusted cohort or case-control studies. This study aimed to estimate the effect of the HPV vaccine against CIN3+ in Japanese women. This nationwide case-control study from April 2013 to March 2020 targeted women aged 20-26 years old at the time of cervical screening. We compared HPV vaccination exposure between those with abnormal and those with normal cytology. Abnormal cytology was classified into cervical intraepithelial neoplasia (CIN)1+, CIN2+, and CIN3+. We calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 -OR) × 100. A total of 2790 cases and 13,990 controls (one-to-five matching) were eligible in 37 municipalities in Japan. In this study, 61 CIN3 (2.2%) and 10 squamous cell carcinomas (SCC) (0.4%) were found. The OR for CIN3+ versus controls was 0.14 (95% CI, 0.03-0.75), equating to a vaccine effectiveness of 86%. Of the 10 patients who had SCC none were vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in CIN3+ among women who did versus those who did not receive HPV vaccination.

据报道,日本的宫颈癌发病率有所上升。日本厚生劳动省已于 2022 年恢复积极推荐定期接种 HPV 疫苗。在日本,年龄调整后的队列研究或病例对照研究尚未证实 CIN3+ 在现实世界中的预防效果。本研究旨在估算 HPV 疫苗对日本女性 CIN3+ 的预防效果。这项全国性的病例对照研究从 2013 年 4 月开始,到 2020 年 3 月结束,研究对象是接受宫颈筛查时年龄在 20-26 岁之间的女性。我们比较了细胞学异常者和细胞学正常者的 HPV 疫苗接种情况。异常细胞学检查分为宫颈上皮内瘤变(CIN)1+、CIN2+ 和 CIN3+。我们使用条件逻辑回归模型计算了上述终点与疫苗接种暴露的几率比(OR)和 95% 的置信区间(CI),并使用公式 (1 -OR) × 100 估算了疫苗的有效性。日本 37 个市共有 2790 例病例和 13990 例对照(一对五匹配)符合条件。在这项研究中,发现了 61 例 CIN3(2.2%)和 10 例鳞状细胞癌 (SCC)(0.4%)。与对照组相比,CIN3+的OR值为0.14(95% CI,0.03-0.75),相当于疫苗有效率为86%。在 10 名患 SCC 的患者中,没有一人接种过疫苗。日本的这项全国性病例对照研究表明,接种 HPV 疫苗的妇女与未接种疫苗的妇女相比,CIN3+ 的风险大大降低。
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引用次数: 0
FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor. FOXP3+/CD8+比率与RUNX3甲基化弥漫性食管胃交界处肿瘤的侵袭行为有关
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-23 DOI: 10.1111/cas.16373
Suguru Maruyama, Yu Imamura, Tasuku Toihata, Ikumi Haraguchi, Manabu Takamatsu, Makiko Yamashita, Yuichiro Nakashima, Eiji Oki, Kenichi Taguchi, Manabu Yamamoto, Shinji Mine, Akihiko Okamura, Jun Kanamori, Souya Nunobe, Takeshi Sano, Shigehisa Kitano, Tetsuo Noda, Masayuki Watanabe

The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

有证据表明,调节性 T 细胞(Tregs)通过干扰细胞毒性 T 细胞(CD8+)而减弱抗肿瘤反应,因此肿瘤免疫微环境正日益成为开发侵袭性癌症治疗方案的关键考虑因素。在这里,我们假设在弥漫性、非爱伯斯坦-巴尔病毒(EBV)/非微卫星不稳定性(MSI)高的胃食管腺癌(GEA)中,调节性 T 细胞(以叉头盒蛋白 3 [FOXP3]为标志)和 CD8+ 细胞的比例与预后有关。在303例化疗无效的非EBV/非MSI-高食管胃交界处(EGJ)腺癌的数字图像上离散计算了瘤内区域和侵袭边缘的FOXP3+/CD8+表达的细胞计数比。在 p 阶段 I-III 肿瘤中,肿瘤组织学对 5 年 EGJ 癌症特异性生存率和浸润边缘的 FOXP3+/CD8+ 比值有明显的预后调节作用(交互作用 p = 0.022;弥漫型高比值[与低比值]的危险比 [HR] = 8.47,95% 置信区间 [CI]为 2.04-35.19;肠型高比值[与低比值]的危险比 [HR] = 1.57,95% CI 为 0.88-2.83)。浸润边缘的高 FOXP3+/CD8+ 比值与 RUNX3 甲基化(p = 0.035)和 RUNX3 甲基化弥漫组织学亚型的不良预后有关(5 年 EGJ 癌特异性生存率,高比值为 52.3%,低比值为 100%,p = 0.015)。癌症基因组图谱》(The Cancer Genome Atlas)的多组学数据将CCL28与非EBV/非MSI-高GEA的RUNX3抑制弥漫组织学亚型联系起来。我们的数据表明,浸润边缘的高FOXP3+/CD8+比值可能表明肿瘤通过CCL28逃避免疫,尤其是在RUNX3甲基化的弥漫组织学亚型中。
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引用次数: 0
P2RY6 deletion promotes UVB-induced skin carcinogenesis by activating the PI3K/AKT signal pathway. P2RY6 基因缺失可通过激活 PI3K/AKT 信号通路促进紫外线诱导的皮肤癌发生。
IF 5.7 2区 医学 Q1 Medicine Pub Date : 2024-10-22 DOI: 10.1111/cas.16378
Peng Xu, Tanglin Liu, Zile Yang, Kai Zang, Xiaoxuan Gao, Yuling Shi, Xiyun Ye, Yongyan Dang

Our previous research has demonstrated that P2RY6 functions as an oncogene in DMBA/TPA-induced two-stage chemical skin carcinogenesis in mice. However, considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB-induced skin carcinogenesis. Surprisingly, we found that P2ry6-deficient mice exhibited marked promotion to UVB-induced skin papilloma formation compared with wild-type mice, suggesting its tumor-suppressive role in UVB-induced skin cancer. Additionally, a P2ry6 gene knockout promoted skin hyperplasia induced by short-term UVB irradiation, while UDP, the ligand of P2RY6, could inhibit the short-term UVB-induced increase of epiderma thickness in mouse skin. Furthermore, UVB irradiation could significantly upregulate P2RY6 expression in human and mouse skin cells. These results indicated that P2RY6 may play a crucial protective role in resisting the UVB-induced formation of skin tumors. At the molecular level, the loss of the P2RY6 gene inhibits the ubiquitination modification and expression of XPC after UVB irradiation in skin keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). We have also demonstrated that P2RY6 deletion activates the PI3K/AKT signaling pathway both in vitro and in vivo. The CPD accumulation and acute inflammatory response enhanced by the loss of the P2RY6 gene can be reversed by an AKT inhibitor. These findings suggest that P2RY6 may act as a tumor suppressor in UVB-induced skin cancer by regulating the PI3K/AKT signaling pathway.

我们之前的研究表明,P2RY6 在 DMBA/TPA 诱导的小鼠两阶段化学皮肤癌变中发挥着癌基因的作用。然而,考虑到人类皮肤癌主要归因于日光中的紫外线辐射,我们需要进行更多的研究来阐明 P2RY6 在紫外线诱导的皮肤癌中的作用。令人惊讶的是,我们发现与野生型小鼠相比,P2ry6 缺陷小鼠对紫外线诱导的皮肤乳头状瘤的形成有明显的促进作用,这表明它在紫外线诱导的皮肤癌中具有抑制肿瘤的作用。此外,P2ry6 基因敲除能促进短期 UVB 照射诱导的皮肤增生,而 P2RY6 的配体 UDP 能抑制短期 UVB 诱导的小鼠皮肤表皮厚度的增加。此外,UVB 照射能显著上调 P2RY6 在人和小鼠皮肤细胞中的表达。这些结果表明,P2RY6可能在抵御紫外线诱导的皮肤肿瘤形成过程中发挥着重要的保护作用。在分子水平上,P2RY6 基因缺失会抑制皮肤角质细胞在紫外线照射后 XPC 的泛素化修饰和表达,导致 CPD(环丁烷嘧啶二聚体)的积累。我们还证实,P2RY6 基因缺失可激活体外和体内的 PI3K/AKT 信号通路。AKT 抑制剂可逆转因 P2RY6 基因缺失而增强的 CPD 积累和急性炎症反应。这些研究结果表明,P2RY6可通过调节PI3K/AKT信号通路,在紫外线诱导的皮肤癌中起到抑制肿瘤的作用。
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Cancer Science
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