Neoplasia最新文献

{"title":"ARID1A loss sensitizes colorectal cancer cells to floxuridine","authors":"Cheng Xiang ,&nbsp;Zhen Wang ,&nbsp;Yingnan Yu ,&nbsp;Zelong Han ,&nbsp;Jingyi Lu ,&nbsp;Lei Pan ,&nbsp;Xu Zhang ,&nbsp;Zihuan Wang ,&nbsp;Yilin He ,&nbsp;Kejin Wang ,&nbsp;Wenxuan Peng ,&nbsp;Side Liu ,&nbsp;Yijiang Song ,&nbsp;Changjie Wu","doi":"10.1016/j.neo.2024.101069","DOIUrl":"10.1016/j.neo.2024.101069","url":null,"abstract":"<div><div>The loss-of-function mutation of AT-rich interactive domain 1A (ARID1A) frequently occurs in various types of cancer, making it a promising therapeutic target. In the present study, we performed a screening of an FDA-approved drug library in ARID1A isogenic colorectal cancer (CRC) cells and discovered that ARID1A loss sensitizes CRC cells to floxuridine (FUDR), an antineoplastic agent used for treating hepatic metastases from CRC, both <em>in vivo</em> and <em>in vitro</em>. As a pyrimidine analogue, FUDR induces DNA damage by inhibiting thymidylate synthase (TS) activity. ARID1A, as a regulator of DNA damage repair, when lost, exacerbates FUDR-induced DNA damage, leading to increased cell apoptosis. Specifically, ARID1A deficiency impairs DNA damage repair by downregulating Chk2 phosphorylation, thereby sensitizing cancer cells to FUDR. Notably, we found that FUDR exhibited increased sensitivity in ARID1A-deficient cells compared to 5-fluorouracil (5-FU), a commonly used anticancer drug for CRC. This suggests that FUDR is superior to 5-FU in treating ARID1A-deficient CRC. In conclusion, ARID1A loss significantly heightens sensitivity to FUDR by promoting FUDR-induced DNA damage in CRC. These findings offer a novel therapeutic approach for the treatment of CRC characterized by ARID1A loss-of-function mutations.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441755","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":"Insights into the metastatic bone marrow niche gained from fibronectin and β1 integrin transgenic mice","authors":"Franziska Wirth ,&nbsp;Caren Zoeller ,&nbsp;Alexander Lubosch ,&nbsp;Jutta Schroeder-Braunstein ,&nbsp;Guido Wabnitz ,&nbsp;Inaam A. Nakchbandi","doi":"10.1016/j.neo.2024.101058","DOIUrl":"10.1016/j.neo.2024.101058","url":null,"abstract":"<div><div>Tumor cells can migrate from a primary cancer and form metastases by localizing to niches within other organs including the bone marrow, where tumor cells may exploit the hematopoietic stem cell niche. The precise composition of the premetastatic and the hematopoietic niches and the degree of overlap between them remain elusive. Because the extracellular matrix protein fibronectin is expressed in the pre-metastatic lung microenvironment, we evaluated the implications of its loss, as well as those of loss of its primary receptor subunit, β1 integrin, in various bone marrow cell types both in breast cancer bone metastasis and hematopoiesis.</div><div>Using eight transgenic mouse models, we established that fibronectin production by osterix-expressing marrow cells, or β1 integrin expression (on vav, mx, or leptin receptor expressing cells), affects MDA-MB-231 breast cancer cell numbers in the bone marrow. Additionally, we identified stromal subpopulations that modulate transmigration through blood vessel walls. Not the number of tumor cells, but rather the changes in the microenvironment dictated whether the tumor progresses. Furthermore, hematopoiesis, particularly myelopoiesis, was affected in some of the models showing changes in tumor homing.</div><div>In conclusion, there is partial overlap between the pre-metastatic and the hematopoietic niches in the bone marrow. Moreover, we have delineated a cascade starting with fibronectin secreted by pre-osteoblastic cells, which potentially acts on β1 integrin in specific stromal cell subsets, thereby inhibiting the formation of new breast cancer lesions in the bone marrow. This work therefore sheds light on the role of various stromal cell subpopulations that influence tumor behavior and affect hematopoiesis.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":"Article 101058"},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441754","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":"Doxorubicin resistance involves modulation of interferon signaling, transcriptional bursting, and gene co-expression patterns of U-ISGF3-related genes","authors":"Pawel Trzaskoma ,&nbsp;SeolKyoung Jung ,&nbsp;Yuka Kanno ,&nbsp;John J. O'Shea ,&nbsp;Carson C. Chow","doi":"10.1016/j.neo.2024.101071","DOIUrl":"10.1016/j.neo.2024.101071","url":null,"abstract":"<div><div>Chemotherapy, although effective in treating cancer, can induce various cellular responses, including senescence and drug resistance. Here, we investigate the transcriptomic alterations induced by doxorubicin (DOX), a commonly used chemotherapeutic agent, in human colon cancer cells. Using single-cell RNA sequencing, we identified distinct cell populations and their transcriptional profiles following subtoxic DOX treatment, revealing cell clusters characterized by differential expression of genes involved in cell cycle regulation and interferon (IFN) signaling. DOX-persisting proliferating cells exhibited upregulation of genes reported to be linked to the unphosphorylated form of ISGF3 (U‐ISGF3) transcription factor. Furthermore, we found that <em>HSH2D</em>, a poor prognostic marker, was highly upregulated in doxorubicin-surviving proliferative cells, and its expression was correlated with U-ISGF3-related genes. Analysis of transcription kinetics via mathematical modeling revealed that the number of mRNA molecules produced per transcriptional burst was increased for U-ISGF3-related genes. We also observed altered gene co-expression patterns of U-ISGF3-related genes and others upon DOX treatment, which potentially contributes to chemoresistance of DOX-surviving proliferative cells and may influence cancer cell fate after chemotherapy. Our findings highlight U-ISGF3-related genes and the JAK/STAT pathway as potential therapeutic targets for overcoming chemoresistance in colon cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":"Article 101071"},"PeriodicalIF":4.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434477","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":"Decoding androgen receptor signalling: Genomic vs. non-genomic roles in prostate cancer","authors":"Mohammad Asim","doi":"10.1016/j.neo.2024.101066","DOIUrl":"10.1016/j.neo.2024.101066","url":null,"abstract":"<div><div>The Androgen receptor (AR) is known to manifest the biological actions of male sex hormones. Androgens are now known to exert a multitude of responses, sometimes contrasting, in physiological and pathological conditions. Several groups have attempted to explain the underlying mechanisms of these varying androgen responses, including the non-genomic actions of androgens. These actions lead to increased activity of pro-proliferative signal transduction pathways, resulting in rapid molecular effects that cannot be explained by the conventional model in which AR functions as a transcription factor to modulate target gene expression [<span><span>1</span></span>,<span><span>2</span></span>].</div><div>This spotlight article examines Safi et al.'s research on the androgen receptor (AR) in prostate cancer, revealing that low androgen levels drive proliferation via non-genomic mechanisms involving AR monomers, while high levels suppress growth through genomic actions with AR dimers. These findings challenge current paradigms and suggest novel therapeutic strategies targeting both AR forms, particularly focusing on the role of AR monomers in cancer progression and treatment resistance.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":"Article 101066"},"PeriodicalIF":4.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434478","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":"IGSF9 promotes tumor invasion and metastasis through GSK-3β/β-catenin mediated EMT in lung cancer","authors":"Huiwen Luan ,&nbsp;Ting Wang ,&nbsp;Fangmin Li ,&nbsp;Shuang Sun ,&nbsp;Zhenbo Wang ,&nbsp;Xinyu Zhao ,&nbsp;Feng Kong ,&nbsp;Tao Hu ,&nbsp;Yifan Liu ,&nbsp;Juan Zhang ,&nbsp;Xiaoli Liu ,&nbsp;Hongying Wang ,&nbsp;Xianhui Meng ,&nbsp;Chunling Li ,&nbsp;Jiashen Zhang ,&nbsp;Shuhao Ji ,&nbsp;Lijun Hui ,&nbsp;Siman Nie ,&nbsp;Yaopeng Wang ,&nbsp;Zunling Li","doi":"10.1016/j.neo.2024.101067","DOIUrl":"10.1016/j.neo.2024.101067","url":null,"abstract":"<div><div>We previously reported that immunoglobulin superfamily member 9 (IGSF9) as a tumor specific immune checkpoint promoted the tumor immune escape, however, as an adhesion molecule, whether IGSF9 promotes tumor invasion and metastasis has not been reported. Here, the full length, the intracellular domain (ID) not extracellular domain (ECD) of IGSF9 could alter tumor cell morphology from a flat and polygonal shape to elongated strips, suggesting that IGSF9 signal pathway has the potential to mediate epithelial-to-mesenchymal transition (EMT). Real-time PCR and western blotting also showed that the mesenchymal markers were significantly up-regulated, and the epithelial markers were significantly down-regulated in IGSF9 and IGSF9-ID groups. Meanwhile, immunofluorescence showed that β-catenin was clearly translocated into the nucleus in IGSF9 and IGSF9-ID groups. The <em>in vitro</em> and <em>in vivo</em> data showed that IGSF9, IGSF9-ID and ECD could promote tumor invasion and metastasis. Mechanistically, IGSF9-ID could recruit GSK-3β to result in the accumulation and nuclear translocation of β-catenin to trigger EMT. Anti-IGSF9 could significantly inhibit the invasion and metastasis, and IGSF9 is an effective candidate for lung cancer therapy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":"Article 101067"},"PeriodicalIF":4.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394379","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":"Prenatal p25-activated Cdk5 induces pituitary tumorigenesis through MCM2 phosphorylation-mediated cell proliferation","authors":"Yingwei Huang ,&nbsp;Qiqi Wang ,&nbsp;Weiwei Zhou ,&nbsp;Yawei Jiang ,&nbsp;Kai He ,&nbsp;Wei Huang ,&nbsp;Yating Feng ,&nbsp;Hong Wu ,&nbsp;Lijuan Liu ,&nbsp;Yue Pan ,&nbsp;Yihua Huang ,&nbsp;Zirui Chen ,&nbsp;Wei Li ,&nbsp;Yaowei Huang ,&nbsp;Guanchuan Lin ,&nbsp;Yulong Zhang ,&nbsp;Yongyan Ren ,&nbsp;Kaibiao Xu ,&nbsp;Yanlin Yu ,&nbsp;Yuping Peng ,&nbsp;Yafang Hu","doi":"10.1016/j.neo.2024.101054","DOIUrl":"10.1016/j.neo.2024.101054","url":null,"abstract":"<div><div>Aberrant expression of cyclin-dependent kinase 5 (Cdk5) has been reported in pituitary adenomas. However, the role of Cdk5 in the tumorigenesis remains unclear. We show that prenatal p25-activated Cdk5 phosphorylates minichromosome maintenance protein 2 (Mcm2), enhancing minichromosome maintenance (MCM) family proteins and driving intermediate lobe-located melanotrope-originated pituitary tumorigenesis. In a mouse model with CaMKII promoter-driven transgenic induction of p25, we observed intermediate lobe-originated pituitary adenoma producing non-functional proopiomelanocortin (POMC)-derived peptides under persistent p25 overexpression. Single-cell RNA sequencing revealed Mcm2 may play an important role during tumor progression. Subsequently, Mcm2 was identified as a potential phosphorylated substrate of Cdk5, mediating the tumorous proliferation of melanotrope cells. Silencing Cdk5 or Mcm2 suppressed cell proliferation and colony formation in the 293T cell lines. Therefore, our findings provide a new mouse model of intermediate lobe-originated pituitary adenoma induced by p25/Cdk5 and unveil a previously unappreciated role of Cdk5 and Mcm2 in pituitary adenoma tumorigenesis.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101054"},"PeriodicalIF":4.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376174","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":"Spatial profiling of METex14-altered NSCLC under tepotinib treatment: Shifting the immunosuppressive landscape","authors":"Manon A Simard ,&nbsp;Carlos Cabrera-Galvez ,&nbsp;Santiago Viteri ,&nbsp;Felix Geist ,&nbsp;Nadine Reischmann ,&nbsp;Michael Zühlsdorf ,&nbsp;Niki Karachaliou","doi":"10.1016/j.neo.2024.101063","DOIUrl":"10.1016/j.neo.2024.101063","url":null,"abstract":"<div><div>MET inhibitors have demonstrated efficacy in treating patients with non-small cell lung cancer (NSCLC) harboring <em>MET</em>ex14 skipping alterations. Advancements in spatial profiling technologies have unveiled the complex dynamics of the tumor microenvironment (TME), a crucial factor in cancer progression and therapeutic response.</div><div>This study uses spatial profiling to investigate the effects of the MET inhibitor tepotinib on the TME in a case of locally advanced NSCLC with a <em>MET</em>ex14 skipping alteration. A patient with resectable stage IIIB NSCLC, unresponsive to neoadjuvant platinum-based chemotherapy, received tepotinib following the detection of a <em>MET</em>ex14 skipping alteration. Paired pre- and post-treatment biopsies were subjected to GeoMx Digital Spatial Profiling using the Cancer Transcriptome Atlas and immune-related protein panels to evaluate shifts in the immune TME.</div><div>Tepotinib administration allowed for a successful lobectomy and a pathological downstaging to stage IA1. The TME was transformed from an immunosuppressive to a more permissive state, with upregulation of antigen-presenting and pro-inflammatory immune cells. Moreover, a marked decrease in immune checkpoint molecules, including PD-L1, was noted. Spatial profiling identified discrete immune-enriched clusters, indicating the role of tepotinib in modulating immune cell trafficking and function. Tepotinib appears to remodel the immune TME in a patient with <em>MET</em>ex14 skipping NSCLC, possibly increasing responsiveness to immunotherapy.</div><div>Our study supports the integration of genetic profiling into the management of early and locally advanced NSCLC to guide personalized, targeted interventions. These findings underscore the need to further evaluate combinations of MET inhibitors and immunotherapies.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101063"},"PeriodicalIF":4.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376175","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":"Construction of self-driving anti-αFR CAR-engineered NK cells based on IFN-γ and TNF-α synergistically induced high expression of CXCL10","authors":"Min He ,&nbsp;Xiang Ao ,&nbsp;Yu Yang ,&nbsp;Yanmin Xu ,&nbsp;Tao Liu ,&nbsp;Luoquan Ao ,&nbsp;Wei Guo ,&nbsp;Wei Xing ,&nbsp;Jing Xu ,&nbsp;Cheng Qian ,&nbsp;Jianhua Yu ,&nbsp;Xiang Xu ,&nbsp;Ping Yi","doi":"10.1016/j.neo.2024.101065","DOIUrl":"10.1016/j.neo.2024.101065","url":null,"abstract":"<div><h3>Introduction</h3><div>Ovarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells.</div></div><div><h3>Objectives</h3><div>To elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer.</div></div><div><h3>Methods</h3><div>Study the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo.</div></div><div><h3>Results</h3><div>RNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue.</div></div><div><h3>Conclusion</h3><div>This study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":"Article 101065"},"PeriodicalIF":4.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376176","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":"Distinction of papillary and adamantinomatous craniopharyngioma: Clinical features, surgical nuances and hypothalamic outcomes","authors":"Le Yang ,&nbsp;Yi Liu ,&nbsp;ChaoHu Wang ,&nbsp;ZhanPeng Feng ,&nbsp;Lei Yu ,&nbsp;Jun Pan ,&nbsp;JunXiang Peng ,&nbsp;Jing Nie ,&nbsp;MingFeng Zhou ,&nbsp;YiChao Ou ,&nbsp;Tao Liu ,&nbsp;Songtao Qi ,&nbsp;Jun Fan","doi":"10.1016/j.neo.2024.101060","DOIUrl":"10.1016/j.neo.2024.101060","url":null,"abstract":"<div><h3>Objective</h3><div>Understanding the differences of suprasellar papillary and adamantinomatous craniopharyngiomas (PCPs/ACPs) is pivotal for target therapy, surgical strategy or postoperative management. Here, the clinical features, surgical nuances and postoperative hypothalamic outcomes of PCPs were systematically recapitulated.</div></div><div><h3>Methods</h3><div>24 PCPs and 52 ACPs underwent initial surgery were retrospectively reviewed. Clinical data, quantified third ventricle (3rd V) occupation and optic chiasm distortion were compared, as well as intra-operative findings, operating notes and prognosis. Moreover, analysis of tumor/3rd V relationship and hypothalamic outcomes were also performed.</div></div><div><h3>Results</h3><div>Tumors were more likely to occupies the 3rd V cavity in PCPs. Chiasm distortion of “compressed forward” was the most common pattern (45.8 %) in PCPs, whereas “stretched forward” pattern accounted the highest (42.5 %) in ACPs. Besides, round-shaped with less calcification, duct-like recess, solid consistency, rare subdiaphragmatic invasion, visible lower stalk and improved postoperative visual outcome were more frequently observed in PCPs. The basal membranes of the tumor epithelium and the reactive gliosis were separated by a layer of collagen fibers in most PCPs, which differs from ACPs in the morphological examination of tumor/3rd V floor interface. In daytime sleepiness and memory difficulty, the PCPs showed significantly better outcomes than the ACPs groups, and PCPs suffered less postoperative weight gain (p &lt; 0.05) than ACPs among adult-onset cases.</div></div><div><h3>Conclusion</h3><div>PCPs are different from ACPs regards the clinical features, operative techniques and outcomes. If necessary, PCPs are suggested more amenable to total removal since its less invasiveness to the 3rd V floor and better hypothalamic outcomes.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101060"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367088","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":"Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells","authors":"Xin Hu ,&nbsp;Yifang Shui ,&nbsp;Seiichi Shimizu ,&nbsp;Seisuke Sakamoto ,&nbsp;Mureo Kasahara ,&nbsp;Seiji Okada ,&nbsp;Wen-Zhi Guo ,&nbsp;Masayuki Fujino ,&nbsp;Xiao-Kang Li","doi":"10.1016/j.neo.2024.101061","DOIUrl":"10.1016/j.neo.2024.101061","url":null,"abstract":"<div><div>Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells <em>in vitro</em>, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69⁺ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"58 ","pages":"Article 101061"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367089","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}