Anticancer research最新文献

{"title":"Anti-tumor Effects of Idarubicin Hydrochloride in Desmoid Tumors.","authors":"Yehyeong Lee, Yonghyo Kim, Hyeran Shin, Yeong Chan Ryu, Dong-Woo Kang, Tae Il Kim, Yong-Hee Cho","doi":"10.21873/anticanres.17359","DOIUrl":"https://doi.org/10.21873/anticanres.17359","url":null,"abstract":"<p><strong>Background/aim: </strong>Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs.</p><p><strong>Materials and methods: </strong>Mouse models with Apc mutations, specifically Apc^1638N/+ and Apc^1638N/+/Trp53^-/-, were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc^1638N/+ mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells.</p><p><strong>Results: </strong>The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc^1638N/+ and Apc^1638N/+/Trp53^-/- cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc^1638N/+ mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model.</p><p><strong>Conclusion: </strong>IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5313-5322"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudogene KRT17P3 Promotes NSCLC Progression Through Mir-338-3p/USP7/C-Myc.","authors":"Liping Wei, Zhaoyan Jiang, Shujuan Chen, Ning Xia, Jiejun Kong, Yan Chang, Zhibo Hou","doi":"10.21873/anticanres.17367","DOIUrl":"https://doi.org/10.21873/anticanres.17367","url":null,"abstract":"<p><strong>Background/aim: </strong>Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, yet its underlying molecular mechanisms remain poorly understood. Previous research has identified the pseudogene KRT17P3 as a key player in NSCLC chemoresistance, but its functional role in tumor development has not been thoroughly investigated.</p><p><strong>Materials and methods: </strong>In this study, we utilized in vitro assays to evaluate the impact of KRT17P3 on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Additionally, we conducted in vivo experiments to assess tumor metastasis. The mechanisms underlying the action of KRT17P3 were explored through bioinformatics analyses, as well as RNA immunoprecipitation (RIP), luciferase, and chromatin immunoprecipitation (ChIP) assays.</p><p><strong>Results: </strong>Our findings revealed that KRT17P3 significantly enhances NSCLC cell proliferation, migration, invasion, and EMT, while also promoting tumor metastasis. We discovered that KRT17P3 stabilizes the oncogenic protein c-Myc by competitively binding to miR-338-3p, which leads to upregulation of deubiquitinase USP7. This stabilization of c-Myc serves as a critical driver of NSCLC tumorigenesis, with KRT17P3 expression being upregulated through FOXA1-mediated activation of its promoter.</p><p><strong>Conclusion: </strong>KRT17P3 plays a pivotal role in NSCLC progression by regulating the USP7/c-Myc axis via miR-338-3p, suggesting its potential as both a prognostic biomarker and a therapeutic target for NSCLC treatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5405-5423"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryoablation for Malignant Bone and Soft Tissue Tumors and Histological Assessment of Ablated Tumors.","authors":"Kunihiro Asanuma, Atsuhiro Nakatsuka, Tomoki Nakamura, Masashi Fujimori, Takashi Yamanaka, Tomohito Hagi, Yumi Matsuyama, Takahiro Iino, Masahiro Hasegawa","doi":"10.21873/anticanres.17372","DOIUrl":"https://doi.org/10.21873/anticanres.17372","url":null,"abstract":"<p><strong>Background/aim: </strong>Cryoablation is a new, minimally invasive option for local tumor therapy that is attracting attention due to its potential interactions with the immune system. The purpose of this study was to evaluate the efficacy of cryoablation for local control of bone and soft tissue lesions, to elucidate risk factors for recurrence, and to clarify histological changes.</p><p><strong>Patients and methods: </strong>Participants comprised 25 patients who underwent cryoablation for 53 discrete lesions of bone or soft tissue recurrence after resection or as metastases of cancer or sarcoma. Local progression-free survival was evaluated after completion of cryoablation. The histology of tumor tissues resected after cryoablation was assessed for seven cases.</p><p><strong>Results: </strong>Local progression-free survival rates were 88.1% at 1 year and 79.7% at 2 and 3 years. Risk of local progression was significantly higher for recurrent lesions after resection, and for lesions ≥4.0 cm in diameter than for metastatic lesions, or lesions <4.0 cm, respectively (p<0.05 each). In a subgroup analysis of bone lesions, lesions with an extraskeletal component tended to be associated with worse local recurrence-free survival than those without an extraskeletal component. On histological examination, tissue in the ablated area was completely necrotic. In the border area between ablated and non-ablated areas, CD68-positive cells including CD16-M1-like and CD204-positive M2-like cells were more frequently observed than T cells.</p><p><strong>Conclusion: </strong>Cryoablation has shown good anti-tumor efficacy across various tumor types, including those affecting the bone. However, local control was inadequate for recurrent lesions and tumors larger than 4.0 cm in diameter. Further analysis of the relationship between macrophages and cryoablation is needed and may provide critical insights into achieving a more effective anti-tumor response.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5463-5476"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOOK3 Amplification in Bladder Urothelial Carcinoma: Insights from Gene Expression and Survival Analysis.","authors":"Jaber H Jaradat, Yassine Alami Idrissi, Anwaar Saeed","doi":"10.21873/anticanres.17343","DOIUrl":"https://doi.org/10.21873/anticanres.17343","url":null,"abstract":"<p><strong>Background/aim: </strong>Bladder urothelial carcinoma (BUC) poses a significant health challenge, ranking as the fourth most common cancer among men in the United States, with a mortality rate of approximately 20%. Genetic abnormalities such as mutations in the telomerase reverse transcriptase (TERT) gene and loss of heterozygosity (LOH) on chromosome 9 are commonly observed in BUC; however, many genes involved remain unidentified. This study aimed to explore the role of HOOK3 in BUC and its impact on survival.</p><p><strong>Materials and methods: </strong>Using data from The Cancer Genome Atlas (TCGA) and cBioPortal, we performed differential gene expression and survival analyses to compare the patients with and without HOOK3 amplification.</p><p><strong>Results: </strong>Our findings revealed that 2.2% of genes were up-regulated and 5.3% down-regulated in the HOOK3-amplified group. These changes suggest that HOOK3 amplification is linked to distinct gene expression patterns, with a higher proportion of down-regulated genes. Pathway enrichment related to chromatin remodeling, ion transport, and mitochondrial function suggests that HOOK3 may promote genomic stability and transcriptional regulation, contributing to tumor suppression. The involvement of mitochondrial and ribosomal pathways in protein synthesis and chromosome segregation may also protect against chromosomal abnormalities and uncontrolled cell growth. HOOK3 amplification appears to correlate with improved patient survival.</p><p><strong>Conclusion: </strong>These results suggest a potential protective role of HOOK3 amplification in BUC. Further research is needed to explore the underlying mechanisms and their therapeutic potential for reducing BUC-related mortality.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5175-5185"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of <i>GJB1</i> in Breast Cancer: Its Implications in Survival and Molecular Mechanisms.","authors":"Engin Ozcivici, Gulistan Mese","doi":"10.21873/anticanres.17365","DOIUrl":"https://doi.org/10.21873/anticanres.17365","url":null,"abstract":"<p><strong>Background/aim: </strong>Breast cancer is the leading cause of cancer-related mortality among women worldwide. The connexin (Cx) family, including GJB1 (Cx32), plays complex roles in tumor progression depending on cellular context and cancer subtype. While Cx32 overexpression has been linked to lymph node metastasis, its effects on survival and molecular processes remain unclear. Herein, we aimed to investigate the role of GJB1 in breast cancer by examining its impact on survival and cellular processes in addition to its expression pattern in tumor subtypes, using public datasets.</p><p><strong>Materials and methods: </strong>We conducted a comprehensive analysis of GJB1 in breast cancer using METABRIC patient dataset, Cancer Cell Line Encylopedia, and other publicly available databases. We examined the association between GJB1 expression and patient survival, performed differential gene expression analysis, and explored gene set enrichment to identify biological processes associated with high GJB1 expression.</p><p><strong>Results: </strong>GJB1 was significantly down-regulated in breast cancer tissues compared to normal tissues. However, patients with high GJB1 expression had significantly poorer survival compared to those with low expression, with the median survival reduced by over 25 months. Gene ontology (GO) analysis revealed that down-regulated genes in the GJB1-high group were enriched in extracellular matrix components and membrane junctions, while up-regulated genes were associated with mitochondrial function and cellular respiration.</p><p><strong>Conclusion: </strong>Our findings suggest a dual role for GJB1 in breast cancer. Although it is generally down-regulated, high GJB1 expression is associated with poorer survival, implying a potential oncogenic role. Further studies are needed to clarify the role of GJB1 in breast cancer and explore its therapeutic implications.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5379-5391"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorhexidine Dihydrochloride Shows Anti-tumor Effects in Desmoid Tumors and Colorectal Cancer.","authors":"Hyeran Shin, Yonghyo Kim, Yehyeong Lee, Jisoo Kim, Yeong Chan Ryu, Dong-Woo Kang, Tae Il Kim, Yong-Hee Cho","doi":"10.21873/anticanres.17369","DOIUrl":"https://doi.org/10.21873/anticanres.17369","url":null,"abstract":"<p><strong>Background/aim: </strong>Desmoid tumors (DTs), or aggressive fibromatosis, are rare neoplasms arising from connective tissue, frequently exhibiting local invasiveness. The limited treatment options and high recurrence rates of DTs highlight the need for novel therapeutic strategies. This study investigated the efficacy of chlorhexidine dihydrochloride (CD) in inhibiting the growth of DTs and colorectal cancer (CRC).</p><p><strong>Materials and methods: </strong>A mouse model with Apc mutations, specifically Apc^1638N/+, was generated to study DTs. DT cells (Apc^1638N+) (DTA) were collected from the mice for in vitro experiments. DTA were treated with CD, along with a CRC cell line (HCT-116), and tumor organoids derived from Apc^1638N/+ mice. The effects of CD were assessed through cell viability assay (WST assay), colony formation assay, and cell migration assay. We tested the induction of cell apoptosis through caspase 3/7 activity assays and immunoblot analysis of cleaved-caspase 3 and cleaved-PARP1. Additionally, CD was tested for its anti-tumor efficacy using an in vivo CRC xenograft model with the HCT-116 cell line.</p><p><strong>Results: </strong>CD significantly inhibited the viability, migration, and colony formation of DTA and CRC cells. It remarkably decreased the tumor growth in organoids derived from intestinal tumor cells in the Apc^1638N/+ mouse model. Furthermore, CD showed anti-tumor effects in an in vivo CRC xenograft model using the HCT-116 cell line.</p><p><strong>Conclusion: </strong>CD represents a promising therapeutic strategy for treating both DTs and CRC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5435-5443"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrence Risk and Its Impact on Current Treatment Strategies in Early and Locally Advanced NSCLC.","authors":"Charlotte Tegenbosch, Karolien Vekens","doi":"10.21873/anticanres.17375","DOIUrl":"10.21873/anticanres.17375","url":null,"abstract":"<p><strong>Background/aim: </strong>Recurrence rates in early and locally advanced non-small-cell lung cancer (NSCLC) remain high despite curative treatment. Recently, the survival benefit of immune checkpoint inhibitors (ICI) in the (neo)adjuvant setting in patients with stage II-III NSCLC has been demonstrated. This study aimed to identify predisposing factors for disease recurrence to select patients who would benefit from multimodality treatment.</p><p><strong>Patients and methods: </strong>This retrospective observational study included patients with stage I-IIIA NSCLC discussed at the Thoracic Multidisciplinary Tumour Board of the University Hospital, Brussels, between 2017 and 2021.</p><p><strong>Results: </strong>Of the 167 patients, 34% had a recurrence, with a median time to recurrence of 9.1 months [272 (interquartile range=175-621.5) days]. The highest recurrence rate (56.5%) was observed in cTNM stage IIIA. Of surgical patients who were not eligible for (neo)adjuvant ICI according to current European reimbursement criteria, 21.7% developed disease recurrence. Twelve out of 20 patients eligible for ICI had no recurrence at a median follow-up of 34.1 months and would have been overtreated if they had received ICI therapy. Treatment modality and TNM stage were significantly associated with recurrence and worse progression-free survival (p<0.05). Stereotactic body radiotherapy, higher TNM stage and the presence of serine/threonine kinase 11 (STK11) mutation were significantly associated with worse overall survival.</p><p><strong>Conclusion: </strong>European reimbursement criteria for (neo)adjuvant ICI in surgical patients are based on TNM stage (T≥4 cm or N1/N2 disease). However, TNM stage alone does not give the full picture. In patients undergoing surgery, the presence of the STK11 mutation was significantly associated with worse overall survival. We suggest the integration of analysis of circulating tumour DNA into perioperative strategies to reduce over- and undertreatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5495-5500"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting EGFR Activation to Overcome Gemcitabine Resistance in Cholangiocarcinoma.","authors":"Sonexai Kidoikhammouan, Worachart Lert-Itthiporn, Raksawan Deenonpoe, Charupong Saengboonmee, Sumalee Obchoei, Sopit Wongkham, Wunchana Seubwai","doi":"10.21873/anticanres.17366","DOIUrl":"https://doi.org/10.21873/anticanres.17366","url":null,"abstract":"<p><strong>Background/aim: </strong>Chemotherapy resistance is an important problem in the treatment of patients with cholangiocarcinoma (CCA) who are not eligible for surgery. This study aimed to overcome gemcitabine (Gem) resistance in CCA by investigating and targeting Gem resistance-associated molecules.</p><p><strong>Materials and methods: </strong>Three stable Gem-resistant CCA cell lines (CCA-GemR) were established by gradually exposing CCA cell lines to Gem. The cells were characterized in terms of growth, cross-resistance to chemotherapeutic drugs, cell cycle distribution, and colony formation. The molecular mechanisms related to Gem resistance were assessed using a phosphorylation array assay and protein expression was confirmed using western blotting analysis. The targeted molecules were subsequently analyzed using PanDrugs to identify potential targeted therapies. The drug was used to enhance Gem sensitivity.</p><p><strong>Results: </strong>The results demonstrated that CCA-GemR cells grow more slowly compared to their parental cell lines. Cell cycle analysis revealed an increase in KKU-213A-GemR and KKU-213B-GemR cell accumulation in the G1 phase. Moreover, cross-resistance to 5-FU and cisplatin was observed in all CCA-GemR cells. The Proteome Profiler Human Phospho-Kinase Array showed increased phosphorylation of EGFR in CCA-GemR cells. Erlotinib, a specific inhibitor of EGFR, significantly enhanced the anti-tumor activity of Gem with a synergistic effect (Combination index <1). Western blot analysis confirmed that phosphorylation of EGFR increased in cells treated with Gem, whereas the expression was significantly decreased in cells treated with either erlotinib alone or in combination with Gem.</p><p><strong>Conclusion: </strong>EGFR is a potential target molecule for reducing Gem resistance and enhancing its anti-tumor effects in patients with CCA.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5393-5404"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurine Protects Irinotecan-induced Muscle Dysfunction by Modulating Oxidative Stress and Endoplasmic Reticulum Stress in Human Skeletal Muscle Cells.","authors":"Chih-I Chen, Yu-Chi Chen, Yi-Kai Kao, Chia-Hung Chen, Po-Wen Yang, Pin-Chun Chen, Ling-Chiao Song, Kai Lung Tsai","doi":"10.21873/anticanres.17364","DOIUrl":"https://doi.org/10.21873/anticanres.17364","url":null,"abstract":"<p><strong>Background/aim: </strong>Irinotecan is a key component of standard first-line treatment for metastatic colorectal cancer. However, irinotecan-induced muscle dysfunction is a contributing factor to cancer cachexia. Here, we present the protective effect of taurine, a conditionally essential amino acid with great antioxidant properties, in attenuating muscle dysfunction induced by irinotecan.</p><p><strong>Materials and methods: </strong>Irinotecan (20 μg/ml) was added to human skeletal muscle cells (HSkMCs) with or without pre-treatment of taurine (5 mM). The effects of taurine and irinotecan on the viability, cytotoxicity, and differentiation ability of HSkMC myoblasts were examined. The intracellular reactive oxygen species (ROS) and endoplasmic reticulum stress (ERS) were also monitored.</p><p><strong>Results: </strong>Irinotecan caused cytotoxicity of HSkMCs, while taurine pretreatment increased cell viability and inhibited adenylate kinase release significantly in both myoblasts and myotubes. During differentiation, taurine increased ROS clearance and preserved the myotube differentiation ability impaired by irinotecan. Irinotecan exposure resulted in the up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78). Taurine pretreatment could combat such irinotecan-induced ERS.</p><p><strong>Conclusion: </strong>The current in vitro study provides molecular evidence that taurine plays a beneficial role in protecting against irinotecan-induced muscle dysfunction by modulating oxidative stress and endoplasmic reticulum stress.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5371-5378"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue Expression and Plasma Soluble PD-L1 Levels in Patients With Endometrial Cancer.","authors":"Emmanuel Kontomanolis, Antonios Koutras, Achilleas G Mitrakas, Grigorios Trypsianis, Konstantinos Nikolettos, Panagiotis Tsikouras, Nikolaos Nikolettos, Alexandra Giatromanolaki, Michael Koukourakis","doi":"10.21873/anticanres.17378","DOIUrl":"https://doi.org/10.21873/anticanres.17378","url":null,"abstract":"<p><strong>Background/aim: </strong>The prognostic role of tissue PD-L1 expression in endometrial cancer (EC) remains controversial. Moreover, its value in guiding anti-PD1/PD-L1 immunotherapy is questionable. The eventual role of soluble PD-L1 (sPD-L1), released by cancer tissue and circulating immune cells, is largely unexplored.</p><p><strong>Patients and methods: </strong>In this pilot study, we investigated the expression of PD-L1 in cancer cells and tumor stroma infiltrating inflammatory cells (TIICs), in parallel with sPD-L1 levels in the plasma of 19 patients with early-stage endometrioid EC, before and after hysterectomy.</p><p><strong>Results: </strong>Cancer cell membrane staining was noted in 5/19 (26.3%) cases (range=1-5%; median 1% of the cancer cell population). IICs showed positive reactivity in 14/19 (73.7%) cases. sPD-L1 plasma levels ranged from 53-408 pg/ml and 113-557 pg/ml, respectively, in the plasma of patients before and after hysterectomy (p=0.01). High PD-L1 expression by IIC was marginally associated with a high histology grade (p=0.08). High sPD-L1 levels before surgery were significantly associated with ICC PD-L1 expression (p=0.0007), high histology grade (p=0.04), and marginally with T2-stage (p=0.08).</p><p><strong>Conclusion: </strong>sPD-L1 is easily detectable in the plasma of EC patients and may be associated with aggressive clinical features and PD-L1-expressing immune cells infiltrating the tumor stroma. sPD-L1 plasma levels in EC patients undergoing immunotherapy can be further tested as a biomarker for therapeutic stratification.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5525-5530"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}