Cancer Science最新文献

H. Jiang, Z. Zhou, S. Jin, K. Xu, H. Zhang, J. Xu, Q. Sun, J. Wang, and J. Xu, “PRMT9 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating PI3K/Akt/GSK-3β/Snail Signaling,” Cancer Science 109, no. 5 (2018): 1414–1427, https://doi.org/10.1111/cas.13598.

Concerns were raised by a third party regarding overlapping image panels within the article (Figures 2D and 5D). The authors admitted to the image compilation error and were able to provide the raw data of the article. The research integrity office of the authors' institute has investigated the concerns and recommended the publication of a correction. The authors confirm that all the experimental results and corresponding conclusions mentioned in the paper remain unaffected and sincerely apologize for this mistake.

FIGURE 5 (D) Invasion assays showing that LY294002 inhibits PRMT9-induced cell invasion.

Liang W, Zhou Z, Gao Q, et al. Tumor-derived Prevotella intermedia aggravates gastriccancer by enhancing Perilipin 3 expression. Cancer Sci. 2024;115:1141–1153. doi:10.1111/cas.16080.

In the Abstract section, the text “The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.042)”. It should instead be “The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.040)”.

We apologize for this error.

RETRACTION: K. Shigeta, M. Hasegawa, E. Kikuchi, Y. Yasumizu, T. Kosaka, R. Mizuno, S. Mikami, A. Miyajima, D. Kufe and M. Oya, “Role of the MUC1-C Oncoprotein in the Acquisition of Cisplatin Resistance by Urothelial Carcinoma,” Cancer Science 111, no. 10 (2020): 3639–3652, https://doi.org/10.1111/cas.14574.

The above article, published online on 16 July 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley & Sons Australia Ltd.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 upon due to several instances of duplications of western blot bands observed between Figures 2E and 3B; 4A and 4D; S1b and S3a; and within S1d. The authors commented that this was due to inadvertent errors and provided some data including replacement images. However, the data supplied did not meet acceptable standards for raw data and the editors were not satisfied with the explanation provided. Due to the extent of the errors, the editors have lost confidence in the results and conclusions of this study. The authors disagree with the retraction.

Accurate diagnosis is essential for effective cancer treatment, particularly in peritoneal surface malignancies, where failure to detect metastatic lesions can mislead the treatment plan. This study assessed the diagnostic accuracy of staging laparoscopy using the integration of artificial intelligence (AI)-guided photodynamic diagnosis (PDD) with the photosensitizer Phonozen, activated at 405 nm in a rabbit model. To create peritoneal carcinomatosis, VX2 cells were inoculated laparoscopically into the peritoneum of female white New Zealand rabbits. Conventional and PDD-guided laparoscopy utilized a customized light source that emitted broad-spectrum white light or 405-nm blue light, respectively. The surgical procedure comprised a tripartite approach: exploration and labeling of suspected nodules under white-light visualization, identification of additional metastatic tumors under blue-excitation fluorescent light, and confirmatory open laparotomy to locate overlooked nodules by palpation. Our results showed that the initial experimental data from 371 nodules in 14 rabbits, comparing conventional diagnostic laparoscopy and PDD, showed increased detection sensitivity from 67% ± 1.9% (conventional) to 98% ± 0.7% (PDD) in the small-size nodule. In the second experimental data set from 265 nodules in 10 rabbits, the addition of a real-time AI algorithm further increased the sensitivity to 100% ± 0.0%. Combining PDD with AI enhances the detection of peritoneal cancer metastasis in staging laparoscopy.

Despite the importance of genetic testing for risk assessment and treatment in breast cancer, the prognostic impact of germline pathogenic variants (PVs), especially in Asian populations, is unclear. We assessed the impact of germline PVs in patients with early-stage breast cancer. This study included 7278 Japanese multihospital registry patients. PVs of ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, and TP53 were evaluated. PV and non-PV carriers were matched by age, histology, and stage. Associations between PVs and survival were assessed. The primary outcome was invasive disease-free survival (IDFS). Secondary outcomes included relapse-free survival (RFS), overall survival, and breast cancer-specific survival. We identified 320 (4.4%) patients with BRCA1/2 PVs and 79 (1.1%) with PVs other than BRCA1/2 (non-BRCA1/2). A total of 360 patients (BRCA1/2, n = 289; non-BRCA1/2, n = 71) were matched to 720 noncarriers. Patients with BRCA1/2 PVs had significantly shorter 10-year IDFS (adjusted hazard ratio (aHR) = 2.15; 95% confidence interval (CI), 1.61–2.86; p < 0.001); and RFS (aHR = 1.74; 95% CI, 1.25–2.44; p = 0.001) than noncarriers. Among patients with hormone receptor-positive HER2-negative breast cancer, BRCA1/2 PV carriers exhibited significantly shorter 10-year IDFS than noncarriers, even those with stage I/II disease (total, aHR = 2.23; 95% CI, 1.55–3.23; p < 0.001, Stage I/II, aHR = 2.22; 95% CI, 1.43–3.44; p < 0.001). There was no significant difference in 10-year IDFS between the non-BRCA1/2 PV carrier and noncarrier groups (aHR = 1.40; 95% CI, 0.67–2.93; p = 0.37). Asian patients with breast cancer carrying germline BRCA1/2 PV, even those with a low recurrence risk, have significantly shorter 10-year IDFS than noncarriers.

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal proliferative malignant disease characterized by abnormal T-cell development. The classification of T-ALL primarily hinges on immunophenotype, encompassing early T-cell precursor (ETP)-ALL, near-ETP-ALL, and non-ETP-ALL. We summarized clinical information from 117 patients, with genetic data available for 77 patients and transcriptomic data available for 24 patients. An ETP-like score model was established based on transcriptome, aiming to address the subjectivity in the current T-ALL immunophenotype classification. The retrospective analysis indicated that ETP immunophenotype was not a prognostic factor for T-ALL patients. Compared to non-ETP-ALL patients, ETP-like patients including ETP-ALL and near-ETP-ALL were more likely to carry MED12 gene mutations, which may predict a dismal outcome. Transcriptomic analysis suggested that T-ALL patients with different immunophenotypes were in accordance with the T-cell development trajectory, while ETP-like patients exhibited characteristics of early T-cell development. Finally, we established an ETP-like score model and confirmed its efficiency across four independent cohorts, with sensitivity exceeding 80%. And T-ALL patients with high ETP-like score were associated with poor prognosis. In conclusion, our study elucidated the clinical and molecular features of distinct subtypes of T-ALL patients, providing new valuable insights for T-ALL classification.

Glioblastoma (GBM) involves disruptions in the blood–brain barrier (BBB) and alterations in the immune microenvironment, including the activation of glioma-associated macrophages (GAMs). Vascular endothelial growth factor inhibitors, commonly used in recurrent GBM treatment, can influence these processes. This study investigates the relationship between BBB disruption and GAM activation, focusing on plasmalemma vesicle-associated protein (PLVAP), a marker of BBB disruption, and α1-acid glycoprotein (AGP), an inflammatory protein implicated in tumor progression. PLVAP expression was analyzed by immunohistochemistry (IHC) in human GBM samples to determine correlations with tumor grade, proliferation, and GAM activation. Pre- and post-bevacizumab treatment GBM samples were compared to assess changes in BBB integrity and macrophage activity. AGP's role in GAM activation was studied through in vitro assays and glioma implantation in AGP knockout mice, with assessments of tumor growth and angiogenesis. Results showed elevated PLVAP expression in higher-grade gliomas, correlating with increased tumor proliferation and GAM activation, particularly around PLVAP-positive vessels. Bevacizumab treatment reduced PLVAP expression and macrophage activity. AGP localized to regions of BBB disruption, promoting macrophage-mediated tumor growth in vitro. AGP knockout mice demonstrated reduced angiogenesis and prolonged survival. Spatial analysis revealed increased expression of macrophage-inducing molecules near PLVAP-positive vessels. These findings suggest PLVAP as a marker of BBB disruption and glioma malignancy. AGP, associated with BBB leakage, contributes to GAM activation and tumor progression, highlighting its potential as a therapeutic target for GBM.

While various glycosphingolipids were identified as cancer-associated carbohydrate antigens to be used as tumor markers, disialylated gangliosides such as GD3 and GD2 have particularly attracted attention from many researchers as promising cancer-associated antigens. Simultaneously, their functions in cancer and normal tissues have also been reported. Although GD3 is expressed at the early neural developmental stage and in various cancers, it is also found in the activated status of some normal cells such as astrocytes and lymphocytes. On the other hand, GD2 is expressed in more restricted cells than GD3, enabling anti-GD2 immune therapy to be more applicable for immunotherapy. Recently, the expression of GD2 has been reported in various epithelial cancers and neuroectoderm-derived tumors. The involvement of GD2 in cancer stem cell propertiesand the roles of GD2 in the signal modulation to bring about cancer stemness are now some of the most fascinating research topics. Cancer immunotherapy targeting GD2 by anti-GD2 antibody or anti-GD2 CAR-T is now widely being challenged with various modifications such as combination with cytokines, chemotherapy, or immune checkpoint blocking.

While antibody-dependent cellular cytotoxicity (ADCC) by anti-disialoganglioside GD2 monoclonal antibody (mAb) has succeeded in increasing the survival rate of high-risk patients with neuroblastoma, approximately 40%–50% of patients die from the disease. Recently, we developed induced pluripotent stem cell-derived natural killer T (iPS-NKT) cells, which exhibit NK-like cytotoxicity. However, whether iPS-NKT cells can induce ADCC function is unclear. Here, we investigated the ADCC of iPS-NKT cells and the efficacy of the combination treatment of anti-GD2 mAb and iPS-NKT cells against neuroblastoma. Anti-GD2 mAb enhanced the cytotoxicity and secretion of cytokines and cytotoxic granules of iPS-NKT cells, which expressed CD16 to GD2-expressing neuroblastoma cell lines. We also examined which Fcγ receptors contribute to ADCC of iPS-NKT cells. CD16 stimulation against iPS-NKT cells caused cytotoxicity and secretion of interferon-gamma, tumor necrosis factor, and granzyme B. In contrast, CD32 and CD64 stimulation did not. In vivo, the intratumor administration of anti-GD2 mAb and iPS-NKT cells significantly inhibited tumor growth compared with the other treatment groups: no treatment, anti-GD2 mAb alone, and iPS-NKT cells alone. In conclusion, iPS-NKT cells exhibit CD16-mediated ADCC, and the addition of iPS-NKT cells to anti-GD2 mAb therapy may be a potential approach for immunotherapy against neuroblastoma.

Anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) shows marked tumor shrinkage by ALK-tyrosine kinase inhibitors (TKIs). However, tumors almost inevitably relapse owing to the development of acquired resistance. Resistance mechanisms include secondary ALK mutations and the activation of bypass pathways, such as cMET, cKIT, or EGFR, though some remain unknown. In this study, we analyzed alectinib-resistant patient samples and identified a significant increase in AXL expression in the tumor, and a high level of GAS6, the ligand for AXL, in the pleural effusion. AXL-overexpressing H3122 ALK-rearranged NSCLC cells exhibited partial resistance to alectinib, which was enhanced by GAS6 supplementation but could be overcome by the ALK/AXL inhibitor gilteritinib. Moreover, GAS6-overexpressing NIH3T3 cells and AXL-expressing H3122 cells were subcutaneously injected into the left and right sides of nude mice simultaneously, followed by alectinib treatment. The supply of GAS6 from NIH3T3 may have accelerated tumor relapse under alectinib treatment. However, even without GAS6-overexpressing NIH3T3, AXL-overexpressing H3122 tumor relapsed within 1 month possibly due to increased host mouse Gas6 expression. Single-cell RNA sequencing revealed that specific cancer-associated fibroblasts (CAFs) and a subset of tumor-associated macrophages (TAMs) are the primary sources of Gas6 in the tumor microenvironment (TME). During alectinib treatment, TAMs increased their infiltration into the TME, whereas CAFs altered their expression patterns, substantially upregulating Mmp11. These findings suggest that AXL expression in resistant cancer cells, combined with increased Gas6 production in the TME, contributes to enhanced ALK-TKI resistance.