Anticancer research最新文献

{"title":"Genome-wide microRNA Analysis Identified <i>miR-210-3p</i> Over-expression in Pancreatic Cancer Tissues as a Predictor of their Local Invasiveness.","authors":"Tomohisa Otsu, Masamichi Hayashi, Keizo Fujita, Daigo Kobayashi, Nobuhiko Nakagawa, Keisuke Kurimoto, Hideki Takami, Koki Nakanishi, Shinichi Umeda, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Yasuhiro Kodera","doi":"10.21873/anticanres.17297","DOIUrl":"10.21873/anticanres.17297","url":null,"abstract":"<p><strong>Background/aim: </strong>The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor's gene profile is crucial to avoid positive MSM.</p><p><strong>Materials and methods: </strong>Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets.</p><p><strong>Results: </strong>Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests.</p><p><strong>Conclusion: </strong>Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4709-4721"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543296","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":"Contributions of Tissue Inhibitor of Metalloproteinase-1 Genotypes to the Risk of Metastasis in Gastric Cancer.","authors":"Chun-Kai Fu, Hsu-Tung Lee, Jaw-Chyun Chen, Mei-Due Yang, Hsu-Chen Cheng, Mei-Chin Mong, Chia-Wen Tsai, Wen-Shin Chang, Yi-Chih Hung, DA-Tian Bau","doi":"10.21873/anticanres.17309","DOIUrl":"10.21873/anticanres.17309","url":null,"abstract":"<p><strong>Background/aim: </strong>In gastric cancer (GCa) tissues, the mRNA and protein levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly elevated compared to adjacent non-cancerous tissues. Moreover, the abnormal up-regulation of TIMP-1 has been associated with a poor prognosis. However, the role of TIMP-1 genotypes in susceptibility to GCa has seldom been investigated. This study aimed to evaluate the influence of TIMP-1 genotypes on GCa susceptibility and their potential interactions with clinico-pathological factors, including age, sex, body mass index, smoking, alcohol consumption, Helicobacter pylori (H. pylori) infection, and metastasis status.</p><p><strong>Materials and methods: </strong>TIMP-1 rs4898, rs6609533, and rs2070584 genotypes were analyzed in 161 patients with GCa and 483 non-cancer control subjects from a Taiwanese population using PCR-RFLP methodology and direct sequencing.</p><p><strong>Results: </strong>The genotypic (p for trend=0.1987) and allelic (p=0.0733) frequencies of TIMP-1 rs4898 did not differ significantly between GCa cases and controls. Under the dominant model, combined CT+CC genotypes were not associated with GCa risk [odds ratio (OR)=0.74, 95% confidence interval (95%CI)=0.51-1.07, p=0.1272]. Similarly, no significant association was found for TIMP-1 rs6609533 or rs2070584 polymorphisms. Importantly, patients with GCa carrying the TIMP-1 rs4898 TT genotype exhibited a significantly enhanced risk of GCa when they had smoking (p=0.0140) and alcohol drinking habits (p=0.0011). Furthermore, the CC genotype of TIMP-1 rs4898 was linked to a lower risk of distant metastasis.</p><p><strong>Conclusion: </strong>The TIMP-1 rs4898 CC genotype may serve as a prognostic biomarker and could inform lifestyle modifications aimed at GCa prevention. Validation of TIMP-1 genotypic profile in diverse populations is warranted.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4833-4841"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543281","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":"Development of a Tumor Growth-responsive Robust Planning Method for Head and Neck Cancer in Carbon-ion Radiotherapy.","authors":"Yuya Miyasaka, Yohsuke Kusano, Nobutaka Mizoguchi, Yoshiki Takayama, Tadashi Kamada, Takeo Iwai, Hiroyuki Katoh","doi":"10.21873/anticanres.17336","DOIUrl":"https://doi.org/10.21873/anticanres.17336","url":null,"abstract":"<p><strong>Background/aim: </strong>The current study aimed to evaluate a treatment planning method that is robust against tumor growth and to assess its effectiveness in particle therapy for head and neck cancer.</p><p><strong>Patients and methods: </strong>The proposed method optimizes dose distribution by replacing the relative stopping power ratio (rSPR) of the clinical target volume (CTV) cavity region with a tumor-equivalent rSPR (Condition 1). The optimized initial treatment plan template was then recalculated using in-room CT images acquired in the same treatment position, and the doses to the tumor and organs at risk were compared with those in the initial treatment plan. We evaluated this method in 10 patients with head and neck cancer treated with carbon ion radiotherapy. To evaluate the effectiveness of the proposed method, we compared it to the initial treatment plan without the replacement (Condition 2).</p><p><strong>Results: </strong>CTV V95% reduction relative to that of the initial treatment plan at the end of treatment was 1.3%±2.9% and 2.6%±3.7% for Condition 1 and Condition 2, respectively, with Condition 1 (Replacement condition) providing better CTV coverage. Subgroup analysis showed a higher change in target coverage in the mucosal melanoma than in the adenoid cystic carcinoma, suggesting that this was influenced by the rate of tumor growth.</p><p><strong>Conclusion: </strong>The proposed treatment planning method, which adjusts for tumor growth by modifying the rSPR in the cavity region, improved robustness in carbon ion radiotherapy for head and neck cancer. Condition 1 (with replacement) achieved better CTV coverage than Condition 2 (without replacement), particularly in fast-growing tumors like mucosal melanoma. This method ensures consistent dose delivery to tumors while maintaining safe doses to organs at risk, offering potential for improved treatment outcomes.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5113-5122"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543291","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":"Fenbendazole and Diisopropylamine Dichloroacetate Exert Synergistic Anti-cancer Effects by Inducing Apoptosis and Arresting the Cell Cycle in A549 Lung Cancer Cells.","authors":"Thai Q Nguyen, Dang H Nguyen, Uyen T T Phan, Phuong T T Tran, Huong T LE, Son H Nguyen, Jolie Nguyen, B O Han, Ba X Hoang","doi":"10.21873/anticanres.17302","DOIUrl":"https://doi.org/10.21873/anticanres.17302","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for approximately 2 million new cases and 1.8 million deaths annually. Standard treatment options include surgery, radiation therapy, chemotherapy, and targeted therapies. Despite advancements over the past 25 years, the prognosis of patients with lung cancer remains poor. This study evaluated the synergistic anticancer effects of fenbendazole (FZ) and diisopropylamine dichloroacetate (DADA) on A549 lung cancer cells.</p><p><strong>Materials and methods: </strong>Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a broad-spectrum benzimidazole anthelmintic commonly used in veterinary medicine. Diisopropylamine Dichloroacetate (DADA), an over-the-counter treatment for chronic liver disease, has demonstrated anti-tumor properties as an inhibitor of pyruvate dehydrogenase kinase.</p><p><strong>Results: </strong>The combination of FZ and DADA exhibited a synergistic effect on inhibiting the proliferation of A549 lung cancer cells. After 48 h of treatment, the FZ-DADA combination produced reactive oxygen species (ROS) and promoted apoptosis by down-regulating Bcl2 and up-regulating BAX protein expression. The combination activated caspase-3, caspase-7, and PARP, further driving apoptosis in A549 cells. The FZ-DADA treatment also induced cell cycle arrest, as evidenced by the inhibition of Cyclin A and Cyclin E proteins.</p><p><strong>Conclusion: </strong>The synergistic anticancer effects of the FZ-DADA combination were confirmed at both cellular and protein levels in A549 lung cancer cells. The combination modulates key apoptotic proteins, induces cell cycle arrest, and increases mitochondrial ROS production, suggesting a promising approach for lung cancer treatment that warrants further investigation and development.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4761-4772"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543294","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":"Nomogram Predicting Axillary Lymph Node Dissection Omission After Neoadjuvant Chemotherapy for Node-positive Breast Cancer.","authors":"Hirohito Seki, Yuki Ishiguro, Akitsugu Makino, Kei Yamaguchi, Shigeru Imoto","doi":"10.21873/anticanres.17338","DOIUrl":"https://doi.org/10.21873/anticanres.17338","url":null,"abstract":"<p><strong>Background/aim: </strong>To develop an accurate method to predict nodal pathological complete response (ypN0) in patients after neoadjuvant chemotherapy (NAC) for clinically node-positive breast cancer.</p><p><strong>Patients and methods: </strong>We included 128 patients with clinically node-positive primary breast cancer who underwent axillary lymph node dissection after NAC.</p><p><strong>Results: </strong>Breast primary tumor clinical complete response (ycT0) was observed in 29.7% and nodal clinical complete response (ycN0) in 44.5% of cases. When ycN0 was predicted as ypN0, the negative predictive value was 77.2%, and the false-negative rate was 19.7%. Estrogen receptor status, ycT0, and ycN0 were independent predictive factors for ypN0 after NAC in patients with clinically node-positive breast cancer. These factors were used to develop a nomogram for ypN0 prediction. The following points were added: 82 in case of estrogen receptor-negative, 56 in case of ycT0, and 100 in case of ycN0. Score summation was used to prognosticate the manifestation of ypN0. Our nomogram predicted ypN0 with a negative predictive value of 92.9% and false-negative rate of 4.5%, demonstrating an approximate 15% improvement over ypN0 prediction using ycN0 alone.</p><p><strong>Conclusion: </strong>Estrogen receptor-negativity, ycT0, and ycN0 are independent predictive factors for ypN0 after NAC in clinically node-positive breast cancer. The nomogram may improve individualized axillary treatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5131-5138"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543269","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":"Long-term Responders to Nanoparticle Albumin-bound Paclitaxel Following Immune Checkpoint Inhibitor in Non-small Cell Lung Cancer.","authors":"Koki Nakashima, Yukihiro Umeda, Yoshiki Demura, Koji Yamaoka, Tomoaki Sonoda, Toshihiko Tada, Yuko Waseda, Tamotsu Ishizuka","doi":"10.21873/anticanres.17335","DOIUrl":"10.21873/anticanres.17335","url":null,"abstract":"<p><strong>Background/aim: </strong>The efficacy of cytotoxic chemo-therapy has been reported to improve after immune checkpoint inhibitor (ICI) administration. We previously conducted a multicenter prospective clinical study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) after ICI treatment. In that study, some patients showed a long-term response to nab-PTX, which is not usually observed with single-agent chemotherapy. The present study aimed to evaluate the clinical characteristics of these patients.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed updated data from 29 patients enrolled in our clinical study who received nab-PTX monotherapy after ICI treatment. We defined a \"long-term responder\" as a patient who achieved a 1-year progression-free survival (PFS).</p><p><strong>Results: </strong>Among the 29 patients, 10 (34.5%) were long-term responders, two of whom achieved a 5-year PFS. A key difference between long-term and non-long-term responders was that the long-term responders had a significantly higher number of patients with Eastern Cooperative Oncology Group-performance status of 0 (70.0% versus 10.5%; p=0.002). Furthermore, median cycles of previous ICIs and median treatment cycles were significantly higher in long-term responders than in non-long-term responders (8 cycles versus 3 cycles; p=0.03) (5.9 months versus 2.0 months; p=0.02). In the 10 long-term responders, six patients required at least a one-stage dose reduction owing to adverse events, and four patients required a two-stage dose reduction.</p><p><strong>Conclusion: </strong>Nab-PTX administration after ICI treatment may elicit a long-term response. A long-term response can be achieved even with a dose reduction due to adverse events.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5105-5111"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543314","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":"Predictive Value of Immune Activity Changes in Breast Cancer Patients Treated With Dose-dense Neoadjuvant Chemotherapy: A Retrospective Study.","authors":"Wataru Goto, Saeko Henmi, Hanae Matsuda, Kei Nakata, Yuko Kikukawa, Mariko Nishikawa, Asuka Kouchi, Rika Sugahara, Koji Takada, Yukie Tauchi, Kana Ogisawa, Tamami Morisaki, Shinichiro Kashiwagi","doi":"10.21873/anticanres.17337","DOIUrl":"https://doi.org/10.21873/anticanres.17337","url":null,"abstract":"<p><strong>Background/aim: </strong>Dose-dense chemotherapy is recommended for patients with breast cancer who have a high recurrence risk. However, whether dose-dense neoadjuvant chemotherapy (ddNAC) improves patient prognoses compared to the normal-dose regimen remains controversial. In this study, we evaluated the predictive value of immune activities on short-term outcomes for patients treated with ddNAC.</p><p><strong>Patients and methods: </strong>We classified 82 patients with human epidermal growth factor receptor 2-negative breast cancer treated with NAC into a normal dose group (62 patients) and ddNAC group (20 patients) and examined the differences in clinicopathological features. The ddNAC group was further divided according to patient responses to NAC and the predictive factors for pathological complete response (pCR) were evaluated.</p><p><strong>Results: </strong>There were no differences in the clinicopathological features before NAC between the normal dose and ddNAC groups. Although the pCR rates tended to be higher in the ddNAC group compared than those in the normal dose group (35.0% vs. 25.8%), there was not significant difference (p=0.264). Among all patients treated with ddNAC, the absolute lymphocyte count decreased and the neutrophil-to-lymphocyte ratio increased during dose-dense doxorubicin plus cyclophosphamide treatment. There was no significant correlation between the pCR and any of the clinicopathological parameters tested including systemic peripheral markers and tumor-infiltrating lymphocyte levels.</p><p><strong>Conclusion: </strong>ddNAC affected the levels of systemic peripheral immune markers. However, monitoring these markers may not be useful for predicting responses to ddNAC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5123-5129"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543274","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":"Combined Treatment of Caffeic Acid Phenethyl Ester With Docetaxel Inhibits Survival of Non-small-cell Lung Cancer Cells <i>via</i> Suppression of c-MYC.","authors":"Li-Kuo Kuo, Yu-Ke Fu, Chien-Chih Yeh, Ching-Yi Lee, Chi-Jung Chung, Li-Jane Shih, Hsin-Ying Lu, Chih-Pin Chuu","doi":"10.21873/anticanres.17317","DOIUrl":"10.21873/anticanres.17317","url":null,"abstract":"<p><strong>Background/aim: </strong>Non-small-cell lung cancer (NSCLC) comprises approximately 85% of lung cancer. Treatment with docetaxel prolongs the survival of patients with NSCLC. However, the development of resistance to docetaxel has compromised its efficacy. Caffeic acid phenethyl ester (CAPE) has been reported to suppress survival and radiotherapy resistance in lung cancer cells. We determined in this study if combination treatment of docetaxel with CAPE suppresses the proliferation and the survival of NSCLC cells more effectively.</p><p><strong>Materials and methods: </strong>Proliferation, viability, flow cytometric and comet assays were used to examine the difference in anticancer effects of combined treatment as compared to docetaxel treatment alone. Western blot and gene overexpression were used to unravel the underlying molecular mechanism.</p><p><strong>Results: </strong>Treatment with docetaxel or CAPE alone dose-dependently suppressed the proliferation and survival of H1299 and A549 cells. Combined treatment of docetaxel with CAPE caused greater inhibition of survival of H1299 and A549 cells. Docetaxel alone and the combined treatment both dose-dependently increased apoptosis of H1299 cells; however, combined treatment induced much more apoptosis than docetaxel alone. Combined treatment suppressed the protein expression of phospho-protein kinase B (AKT, Ser 473), S-phase protein 2 (SKP2), MYC proto-oncogene bHLH transcription factor (c-MYC), epidermal growth factor receptor (EGFR), phospho-EGFR (Tyr 1045, and Tyr 992) but increased levels of cleaved caspase 3 and cytochrome c proteins in H1299 and A549 cells. The inhibition of expression of SKP2, c-MYC, phospho-EGFR (Tyr 992) proteins by combined treatment was significantly greater than that with treatment using either CAPE or docetaxel alone. Overexpression of c-MYC in rescued proliferation of H1299 cells under combination treatment.</p><p><strong>Conclusion: </strong>Our study revealed that the combination of CAPE with docetaxel is more effective at reducing the proliferation and survival of NSCLC cells, and this is via inhibition of c-MYC. Combined therapy of docetaxel and CAPE may benefit patients with NSCLC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4915-4928"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543277","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":"Compound #41 Targets Acute Myelogenous Leukemia by Inhibiting the Wnt/β-catenin Signaling Pathway.","authors":"Yuki Hadate, Yasunao Hattori, Yuki Toda, Shigekuni Hosogi, Seiji Okada, Yoshihiro Hayashi, Eishi Ashihara","doi":"10.21873/anticanres.17305","DOIUrl":"10.21873/anticanres.17305","url":null,"abstract":"<p><strong>Background/aim: </strong>Aberrant activation of the Wnt/β-catenin signaling pathway contributes to the pathogenesis of acute myelogenous leukemia (AML). Thus, targeting this pathway offers a promising therapeutic strategy against AML. Here, we synthesized a novel dipeptide-type inhibitor of the Wnt/β-catenin signaling pathway, compound #41, and explored its anti-tumor effects on AML cells.</p><p><strong>Materials and methods: </strong>We evaluated the inhibitory effect of compound #41 on T cell factor (TCF)/β-catenin transcriptional activity using a luciferase (Luc) reporter assay. The anti-tumor effects were assessed on KG1a and MV4;11 human AML cells using RT-qPCR, western blotting, and WST-8, cell cycle, and apoptosis assays. Differentially expressed genes were analyzed by RNA-sequencing (RNA-seq). Additionally, we investigated the in vivo effects of compound #41 using KG1a-Luc/GFP cells in an orthotopic mouse model.</p><p><strong>Results: </strong>The Luc reporter assay showed that compound #41 decreased the TCF/β-catenin transcriptional activity. Compound #41 blocked the cell cycle progression, inhibited cell proliferation, and induced apoptosis in AML cells. Treatment with compound #41 down-regulated the expression of β-catenin, Survivin, and β-catenin-specific target genes, as demonstrated by RNA-seq. In vivo analysis showed that compound #41 blocked the expansion of KG1a-Luc/GFP cells in the bone marrow and prolonged the overall survival of KG1a-Luc/GFP-transplanted mice.</p><p><strong>Conclusion: </strong>Compound #41 suppressed the Wnt/β-catenin signaling pathway by reducing CTNNB1 levels and induced apoptosis in AML cells. Furthermore, compound #41 inhibited the proliferation of KG1a-Luc/GFP cells in the bone marrow and extended the overall survival of mice. Thus, compound #41 is an attractive Wnt/β-catenin signaling pathway inhibitor of AML.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4789-4799"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543279","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":"Role of Glutamine Synthetase on Vascular Permeability in Gliomas.","authors":"Dandan Wang, Tianwei Song, Zongtao Hu, Hongzhi Wang, Junchao Qian","doi":"10.21873/anticanres.17312","DOIUrl":"10.21873/anticanres.17312","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to investigate the effect and underlying mechanism of inhibiting glutamine synthetase (GS) on the vascular permeability of gliomas.</p><p><strong>Materials and methods: </strong>C6 glioma rat models were randomly divided into control and L-methionine sulfoximine (MSO) treatment groups. MSO was intraperitoneally injected once every other day for a total of three injections in the MSO group. We assessed the effect of MSO on tumor vascular permeability by tail vein injection of Evans blue dye. GS activity, glutamate (Glu) concentration, glutamine (Gln) concentration, and arginine concentration in tumor tissues were measured using the corresponding kits. qPCR experiments were then conducted to examine the effect of glutamate concentration on N-methyl-D-aspartate (NMDA) receptor expression. Finally, the nitric oxide synthase (NOS) assay kit and the nitric oxide (NO) assay kit were employed to detect NOS activity and NO concentration changes, respectively.</p><p><strong>Results: </strong>Increased glioma tumor vascular permeability was observed after intraperitoneal injection of MSO; MSO acted as an inhibitor of GS, leading to a decrease in GS activity; increased glutamate levels caused activation of NMDA receptors and further activation of NOS; additionally, elevated NO levels were detected in association with an increase in arginine and NOS.</p><p><strong>Conclusion: </strong>Inhibiting GS results in increased vascular permeability in gliomas, which is associated with elevated NO levels and the vasodilatory effects of NO.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4869-4875"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543285","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}