Anticancer research最新文献

{"title":"Dosimetric Comparison of Brain Sparing Between HyperArc and GammaKnife for Single to Triple Brain Metastases.","authors":"Yoshihiro Ueda, Kanji Mori, Shingo Ohira, Kazuo Tarutani, Naoyuki Kanayama, Ayako Okamura, Koji Konishi","doi":"10.21873/anticanres.17544","DOIUrl":"https://doi.org/10.21873/anticanres.17544","url":null,"abstract":"<p><strong>Background/aim: </strong>A novel linac-bases radiosurgery (SRS) system, HyperArc, applied to the non-coplanar volume-modulated arc therapy (VMAT) technique, was developed and released in clinical practice. The aim of the study was to evaluate the dosimetric performance of brain sparing in single-target to three-target cases, for two types of SRS systems: GammaKnife and HyperArc.</p><p><strong>Patients and methods: </strong>A total of 83 patients treated with GammaKnife SRS (35 with single, 24 with double, and 24 with triple metastases) were retrospectively analyzed. Treatment plans were recalculated using HyperArc. Dosimetric parameters, including conformity index (CI), gradient index (GI), and brain volume receiving 2-20 Gy (V₂-V₂₀), were compared between the two systems.</p><p><strong>Results: </strong>No significant difference in D₉₉ of the planning target volume (PTV) was observed between GammaKnife and HyperArc. HyperArc exhibited superior CI₁₀₀, with values approaching 1.0. V₄-V₂₀ for the whole brain minus PTV were significantly lower for HyperArc than GammaKnife. In single-target cases, GI was significantly lower for HyperArc, while in triple-target cases, it was higher. V₁₂ volumes for HyperArc were comparable to those for GammaKnife, even in cases with volumes <1.0 cm³.</p><p><strong>Conclusion: </strong>HyperArc demonstrated dosimetric performance comparable to or better than GammaKnife in brain sparing for single-to-triple metastases. These findings support HyperArc as an effective alternative for SRS planning.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1631-1641"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741855","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":"Akt Regulates Extracellular Vesicle Secretion in Hypoxia-adapted Multiple Myeloma RPMI8226 Cells.","authors":"Yuki Toda, Sayaka Nakayama, Yuna Yamamoto, Asuka Fujimoto, Shigekuni Hosogi, Eishi Ashihara","doi":"10.21873/anticanres.17521","DOIUrl":"https://doi.org/10.21873/anticanres.17521","url":null,"abstract":"<p><strong>Background/aim: </strong>Hypoxia, a characteristic of the tumor microenvironment, affects tumor cell behavior by altering the secretion pattern of extracellular vesicles (EVs). We investigated the regulatory mechanism and biological significance of EV secretion in multiple myeloma (MM) cells grown under hypoxic culture conditions.</p><p><strong>Materials and methods: </strong>Human MM cell lines (RPMI8226 and AMO1) were exposed to long-term hypoxia to generate hypoxia-adapted (HA) cells. EVs released into the culture supernatant were quantified by enzyme-linked immunosorbent assay. The expression of proteins involved in hypoxia-induced signaling was analyzed by western blotting. EV secretion was inhibited using GW4869.</p><p><strong>Results: </strong>Exposure to hypoxia altered the amount of EVs secreted and the phosphorylation levels of Akt and its target molecule AS160. Pharmacological inhibition of Akt phosphorylation suppressed the increase in EV secretion and phosphorylated AS160 expression in HA RPMI8226 cells. GW4869 induced apoptosis in HA RPMI8226 cells, but not in the parental cell line, in the presence or absence of the secretome including EVs. GW4869 altered the expression of proteins related to glycolysis (HK2) and autophagy (LC3).</p><p><strong>Conclusion: </strong>Akt signaling modulates EV secretion to maintain homeostasis in RPMI8226 cells exposed to hypoxic conditions.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1355-1366"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742030","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":"Clinical Utilization and Infrastructure of Radiation Therapy in Korea in 2020 and 2021.","authors":"Jin-Kyu Kang, Won Il Jang, Mi-Sook Kim, Eunji Kim, Hee Jin Kim, Jaesun Yoon, Young-Joo Shin, Jongwoo Kim, Kum-Bae Kim, Jung Young Kim","doi":"10.21873/anticanres.17556","DOIUrl":"https://doi.org/10.21873/anticanres.17556","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to evaluate the clinical status of radiation therapy (RT), including the RT utilization (RTU) rate and infrastructure of RT in Korea in 2020 and 2021.</p><p><strong>Patients and methods: </strong>Patient data for individuals undergoing RT in 2020 and 2021 were sourced from the Health Insurance Review and Assessment Service. Through these data, we assessed the following aspects: total number of patients who received RT in 2020 and 2021, RTU rate for patients with cancer, RTU rate by cancer diagnosis, number of patients treated with RT by age, RT rate by region, rate of hypofractionated RT for breast cancer, and RT by specific modality.</p><p><strong>Results: </strong>In 2020 and 2021, 90,351 and 97,840 patients, respectively, underwent RT in Korea, indicating an annual increase in treatment frequency. The RTU rates for patients with cancer were 32.8% in 2020 and 31.7% in 2021. Breast, lung, prostate, colorectal, and liver cancer were the most commonly treated types, with prostate cancer showing the most rapid growth in RTU rate. The adoption of intensity-modulated RT is swiftly replacing conventional RT, and there continues to be a concentration of RT services in Seoul. Hypofractionated RT for breast cancer saw a steady increase, with rates rising from 23.5% in 2017 to 38.6% in 2020. As the total number of patients receiving RT increased, the number of RT centers, machines, and human resources in radiation oncology departments nationwide also steadily increased.</p><p><strong>Conclusion: </strong>The number of patients in Korea treated with RT has been consistently increasing, with corresponding expansion in RT infrastructure and application of high-precision techniques. The utilization of hypofractionated RT has demonstrated an increasing trend in breast cancer cases and is anticipated to continue expanding in the future.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1761-1775"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742047","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":"Significance of Systemic Inflammatory Markers as Prognostic Predictors in Stage II/III Gastric Cancer Among Older Patients.","authors":"Kenji Kuroda, Takahiro Toyokawa, Gen Tsujio, Yuichiro Miki, Mami Yoshii, Hiroaki Kasashima, Tatsunari Fukuoka, Tatsuro Tamura, Masatsune Shibutani, Shigeru Lee, Masakazu Yashiro, Kiyoshi Maeda","doi":"10.21873/anticanres.17549","DOIUrl":"https://doi.org/10.21873/anticanres.17549","url":null,"abstract":"<p><strong>Background/aim: </strong>Determining treatment for older patients is difficult because of their life expectancy and reduced physiological function. Recently, systemic inflammatory markers have been recognized as prognostic predictors in various cancers. However, few studies have focused on older patients with advanced gastric cancer. This study compared the prognostic significance of various markers in stage II and III gastric cancer in patients ≥75 years old.</p><p><strong>Patients and methods: </strong>In total, 133 cases of R0 excision for stage II/III gastric cancer in patents ≥75 years old were analyzed. The ratio of neutrophils to lymphocytes (NLR), the ratio of platelets to lymphocytes (PLR), C-reactive protein to albumin (CAR), the prognostic nutritional index (PNI), and the Glasgow Prognostic Score (GPS) were used as preoperative markers. Cutoff value was determined based on the time-dependent ROC curve with the 5-year survival rate as the endpoint. Patients were divided into two groups based on these cutoff values, and their prognoses were compared.</p><p><strong>Results: </strong>The cutoff values for NLR, PLR, CAR, and PNI were 2.83, 272, 0.06, and 44.8, respectively. In multivariate analysis for overall survival (OS), NLR (HR=1.972, 95%CI=1.231-3.158, <i>p</i>=0.005), CAR (HR=1.855, 95%CI=1.166-2.952, <i>p</i>=0.009), and PNI (HR=0.585, 95%CI=0.356-0.960, <i>p</i>=0.034) were independent prognostic factors. The NLR-CAR score, calculated based on the NLR and CAR cutoff values, was also an independent prognostic factor for OS (HR=1.883, 95%CI=1.162-3.051, <i>p</i>=0.010). In patients treated with adjuvant chemotherapy, the group with a high NLR-CAR score had significantly worse OS than the group with a low NLR-CAR score (<i>p</i>=0.001).</p><p><strong>Conclusion: </strong>The combination of NLR and CAR may be useful for predicting the prognosis of older patients with advanced gastric cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1681-1694"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742061","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":"Nivolumab Plus 5-Fluorouracil/Leucovorin+Oxaliplatin for Gastric Cancer With Severe Peritoneal Metastasis.","authors":"Kyoko Furusawa, Mitsuhiro Furuta, Misa Onishi, Takanori Hama, Shuntaro Ishikawa, Kei Hayashi, Hiroshi Nakanoma, Kazuo Shiotsuki, Kohei Takizawa, Nozomu Machida, Junji Furuse, Shin Maeda","doi":"10.21873/anticanres.17539","DOIUrl":"https://doi.org/10.21873/anticanres.17539","url":null,"abstract":"<p><strong>Background/aim: </strong>Based on the CheckMate 649 study, nivolumab plus chemotherapy is the first-line treatment for human epidermal growth factor receptor 2-negative advanced gastric cancer (AGC). 5-fluorouracil/leucovorin+oxaliplatin (FOLFOX) is often used for patients with AGC with severe peritoneal metastasis (PM) who cannot tolerate oral intake. Nivolumab monotherapy has shown efficacy against PM. However, the efficacy and safety of nivolumab plus FOLFOX (NIVO+FOLFOX) remain unclear.</p><p><strong>Patients and methods: </strong>We retrospectively examined 15 patients with AGC with severe peritoneal metastasis who received NIVO+FOLFOX between January 2022 and December 2023 at our institution. Severe PM was defined as massive ascites and/or inadequate oral intake.</p><p><strong>Results: </strong>Patients had a median age of 68 years, with 73.3% being male. Eastern Cooperative Oncology Group Performance Status 2 was observed in 20% of patients. Massive ascites was present in 86.7%, and 26.7% had inadequate oral intake. Combined positive score ≥5 was observed in 60%, and no patient had microsatellite instability-high. Median progression-free survival was 4.2 months [95% confidence interval (CI)=0.62-10.6], and median overall survival was 4.5 months (95%CI=1.48-22.5). Despite poor overall prognosis, 20.0% achieved disease control beyond 1 year. Of 13 patients with massive ascites, 38.5% responded, and 30.7% achieved complete ascites resolution. Grade ≥3 immune-related adverse events included sialadenitis, myocarditis, and hepatitis (n=1 each). No treatment-related deaths occurred.</p><p><strong>Conclusion: </strong>NIVO+FOLFOX was feasible for patients with AGC with severe PM, providing potential for long-term survival and ascites reduction.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1583-1592"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742050","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":"PCD-CT <i>Versus</i> EID-CT in Imaging of Pancreatic Ductal Adenocarcinoma: A Prospective Comparative Pilot Study.","authors":"Hakon Blomstrand, Erik Tesselaar, Bergthor Björnsson, Wolf Bartholomä, Tomas Bjerner, Michael Sandborg, Nils O Elander, Mischa Woisetschläger","doi":"10.21873/anticanres.17536","DOIUrl":"https://doi.org/10.21873/anticanres.17536","url":null,"abstract":"<p><strong>Background/aim: </strong>Photon-counting detector computerised tomography (PCD-CT) is a novel imaging technique that may be beneficial in diagnostics and follow-up of pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Patients and methods: </strong>A prospective pilot including eight patients with confirmed PDAC was designed. Patients underwent conventional energy integrating detector CT (EID-CT) and PCD-CT, and corresponding arterial and venous phase images were compared in quantitative and qualitative manners. Five independent and method blinded reviewers scored each intra-individual pair of images.</p><p><strong>Results: </strong>Quantitative assessment showed an advantage favouring PCD-CT in terms of signal to noise ratio (SNR) in aortic, pancreatic, and PDAC tissue (<i>p</i>=0.003, 0.001, and 0.040, respectively). There was a non-significant tendency towards better edge sharpness in the PCD-CT images. Qualitative assessments of image quality revealed minor differences in some aspects of arterial phase, favouring the conventional EID-CT, however no statistically significant differences in terms of overall or venous phase parameters between the methods were evident.</p><p><strong>Conclusion: </strong>PCD-CT offers a novel method with potential benefits in imaging of pancreatic tumours. Further development of the protocol, including optimisation and validation in larger cohorts of patients, are necessary to define a potential role of PCD-CT in the management of PDAC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1547-1558"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742053","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":"Exploration of Lipid Mediators for Therapeutic Monitoring of Pancreatic Cancer Patients.","authors":"Nobuhiko Nakagawa, Masamichi Hayashi, Daigo Kobayashi, Tomohisa Otsu, Fuminori Sonohara, Keisuke Kurimoto, Haruyoshi Tanaka, Yoshikuni Inokawa, Hideki Takami, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Yasuhiro Kodera","doi":"10.21873/anticanres.17520","DOIUrl":"https://doi.org/10.21873/anticanres.17520","url":null,"abstract":"<p><strong>Background/aim: </strong>Multimodal treatment is now the primary strategy for managing pancreatic cancer. Blood-based protein markers are sometimes useless for evaluating the real-time disease condition to determine treatment strategies. This study focused on detecting novel exosomal lipid biomarkers, as exosomes contain several biological mediators.</p><p><strong>Materials and methods: </strong>Lipidomic analysis was conducted by liquid chromatography-mass spectrometry (LC-MS) using serum exosome-derived lipid samples from four pancreatic ductal adenocarcinoma (PDAC) patients and four healthy controls. Some candidates were ascertained using multiple time-point blood samples from four additional PDAC patients. Furthermore, we validated them using an additional twelve multimodal-treated PDAC patient cohort.</p><p><strong>Results: </strong>Nontarget LC-MS analysis revealed that lysophosphatidylcholine (LPC) expression levels were significantly decreased in PDAC patients compared to healthy controls. Multiple time-point blood samples demonstrated that LPC (16:0) and LPC (18:1) consistently showed lower levels in relapsed cases than in non-relapsed cases over time. In the validation cohort, a low LPC level before initial treatment was associated with histological lymphatic invasion (<i>p</i>=0.04) and was linked to progressive-free survival (PFS) (<i>p</i>=0.04).</p><p><strong>Conclusion: </strong>PDAC patients with initially low LPC levels in the blood exosomes demonstrated an unfavorable PFS. Exosomal lipid markers may serve as potential indicators for disease monitoring in pancreatic cancer patients undergoing multimodal treatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1343-1353"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741821","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":"Efficacy of Methionine Restriction and the PARP-inhibitor Olaparib and Their Combination on <i>BRCA1</i> Mutant and Wild-type Triple-negative Breast Cancer Cell Lines.","authors":"Mayuko Miki, Sachiko Inubushi, Qinghong Han, Shotaro Inoue, Tomonari Kunihisa, Hirokazu Tanino, Robert M Hoffman","doi":"10.21873/anticanres.17522","DOIUrl":"https://doi.org/10.21873/anticanres.17522","url":null,"abstract":"<p><strong>Background/aim: </strong>Triple-negative breast cancer (TNBC) is a recalcitrant disease. The present study examined the efficacy of methionine restriction and the poly ADP-ribose polymerase (PARP)-inhibitor olaparib on <i>BRCA1/2</i> wild-type and <i>BRCA1</i> mutated TNBC cell lines.</p><p><strong>Materials and methods: </strong>The human <i>BRCA1/2</i> wild-type cell line MDA-MB-231, and <i>BRCA1</i>-mutant cell lines MDA-MB-436 and HCC1937 were used to examine sensitivity to recombinant methioninase (rMETase) or a methionine-free medium or to olaparib or the combination of a methionine-free medium and olaparib. Cell viability was examined using the WST-8 reagent as well as by direct cell counting after Hoechst 33342 staining.</p><p><strong>Results: </strong>MDA-MB-231 was sensitive to a methionine-free medium and rMETase and resistant to olaparib. The combination of olaparib and a methionine-free medium was not synergistic on MDA-MB-231 cells. MDA-MB-436 cells were not sensitive to a methionine-free medium but were sensitive to olaparib and rMETase. The combination of olaparib and a methionine medium was not synergistic in MDA-MB-436 cells. HCC1937 cells were sensitive to a methionine-free medium, partially sensitive to rMETase, partially resistant to olaparib, and sensitive to the combination of a methionine-free medium and olaparib. All three cell lines were sensitive to rMETase, with MDA-MB-436 being the most sensitive.</p><p><strong>Conclusion: </strong>Methionine restriction and olaparib showed synergistic efficacy on the <i>BRCA1</i>-mutant TNBC cell line HCC1937. The BRCA1-mutant cell line MDA-MB-436 was most sensitive to rMETase. The <i>BRCA1/2</i> wild-type TNBC cell line MDA-MB-231 was sensitive to a methionine-free medium but resistant to olaparib. Therefore, methionine restriction has clinical potential for <i>BRCA1/2</i> wild-type and <i>BRCA1</i>-mutant olaparib-resistant and -sensitive TNBC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1367-1372"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741869","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":"Hepatic Stellate Cells Activated by Cancer Cell-derived AMIGO2-containing Small Extracellular Vesicles Promote Cancer Cell Migration by Producing IL-8.","authors":"Runa Izutsu, Mitsuhiko Osaki, Heekyung Seong, Reo Sato, Futoshi Okada","doi":"10.21873/anticanres.17528","DOIUrl":"https://doi.org/10.21873/anticanres.17528","url":null,"abstract":"<p><strong>Background/aim: </strong>Our previous studies have demonstrated that amphoterin-induced gene and open reading frame 2 (AMIGO2) functions as a driver gene for liver metastasis, regulating adhesion between cancer cells and liver endothelial cells. AMIGO2-containing small extracellular vesicles (sEVs) derived from gastric cancer (GC) cells were shown to enhance adhesion to hepatic endothelial cells, contributing to pre-metastatic niche formation. However, their role in promoting cancer cell migration into the liver parenchyma remained unclear. This study investigated whether AMIGO2-containing sEVs activate hepatic stellate cells (HSCs) and promote cancer cell migration.</p><p><strong>Materials and methods: </strong>AMIGO2-over-expressing and control cell lines (MKN28) were established. sEVs isolated from each cell line were added to human HSCs (TWINT-1). The supernatant collected was added to MKN28 to quantitatively evaluate migration ability and nuclear translocation of NF-kB. A chemokine array identified secreted factors affected by sEV treatment.</p><p><strong>Results: </strong>HSCs were activated by AMIGO2-containing EVs, resulting in increased IL-8 secretion through NF-kB nuclear translocation. This IL-8-rich supernatant significantly enhanced GC cell migration. Neutralizing IL-8 with antibodies suppressed this migration, confirming its pivotal role.</p><p><strong>Conclusion: </strong>AMIGO2-containing sEVs derived from GC cells actively modify the hepatic microenvironment by activating HSCs and inducing IL-8 secretion, which promotes GC cell migration into the liver parenchyma. This process contributes to the formation of a pre-metastatic niche, highlighting AMIGO2-containing sEVs as potential therapeutic targets for preventing liver metastasis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1435-1446"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741829","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":"Activation of the γ-Aminobutyric Acid Receptor Type B Suppresses the Proliferation of Lung Adenocarcinoma Cells.","authors":"Yubin Zhou, Kullanat Khawkhiaw, Kanyarat Thithuan, Charupong Saengboonmee","doi":"10.21873/anticanres.17533","DOIUrl":"https://doi.org/10.21873/anticanres.17533","url":null,"abstract":"<p><strong>Background/aim: </strong>The roles of γ-aminobutyric acid (GABA) and its receptors in lung cancer development and progression remain controversial. This study aimed to investigate the effects of activating GABA receptor type B (GABA-B receptor) using baclofen, a GABA-B receptor agonist, on the proliferation of lung adenocarcinoma cells and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Differential expression of GABA-B receptors was analyzed using the online Gene Expression Profiling Interactive Analysis tool. Lung adenocarcinoma cell lines, A549 and PC-9, were cultured in RPMI-1640 medium and used for <i>in vitro</i> experiments. Effects of baclofen on cancer cell proliferation were determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Mechanisms of how baclofen inhibits cell proliferation were determined using flow cytometry and western blots.</p><p><strong>Results: </strong>The expression of GABA-B1 receptor was down-regulated in lung adenocarcinoma compared with normal lung tissues, while GABA-B2 receptor expression was not different between cancer and normal samples. Baclofen significantly inhibited the proliferation of lung adenocarcinoma cells in a dose-dependent manner in both cell lines. Flow cytometry suggested that cancer cells were arrested at the G₁ phase of the cell cycle after being treated with baclofen. Thus, the expression of proteins of the G₁ cell cycle machinery, namely cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 4, and CDK6, were significantly suppressed. The phosphorylation of CDK2 was also suppressed after baclofen treatment. Moreover, baclofen treatment increased phosphorylated glycogen synthase kinase 3 (GSK3) levels, suggesting inhibition of carcinogenic GSK3 signaling pathway in lung adenocarcinoma.</p><p><strong>Conclusion: </strong>GABA-B1 receptors were down-regulated in lung adenocarcinoma cells. Non-specific activation of the GABA-B receptor by baclofen significantly inhibited lung adenocarcinoma cell proliferation by cell cycle arrest and suppressed the GSK3 signaling pathway.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1513-1523"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742014","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}