Anticancer research最新文献

{"title":"The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment.","authors":"Ryuki Esashi, Toru Aoyama, Yukio Maezawa, Itaru Hashimoto, Sosuke Yamamoto, Mamoru Uchiyama, Koji Numata, Shinnosuke Kawahara, Keisuke Kazama, Ayako Tamagawa, Aya Saito, Norio Yukawa","doi":"10.21873/anticanres.17327","DOIUrl":"https://doi.org/10.21873/anticanres.17327","url":null,"abstract":"<p><strong>Background/aim: </strong>The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection.</p><p><strong>Patients and methods: </strong>Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm³) × platelet count (cell/mm³ ×10³)/lymphocyte count (cell/mm³). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed.</p><p><strong>Results: </strong>A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006).</p><p><strong>Conclusion: </strong>The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5035-5041"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543288","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":"A Prospective Observational Study Analyzing the Diversity and Specific Composition of the Oral and Gut Microbiota in Lung Cancer Patients.","authors":"Fumihiro Shoji, Ayaka Minemura, Yuka Kozuma, Takashi Nouno, Hiroaki Takeoka, Asami Matsumoto, Masaki Okamoto, Masafumi Yamaguchi, Koji Yamazaki, Yoshihiko Maehara","doi":"10.21873/anticanres.17331","DOIUrl":"10.21873/anticanres.17331","url":null,"abstract":"<p><strong>Background/aim: </strong>Host microbiota dysbiosis has been recognized as a key factor in lung cancer. However, the specific diversity and composition of microbiota in lung cancer patients remain unknown. This single-center prospective observational study analyzed both saliva and fecal samples from 74 participants [lung cancer (LC) patients: n=53; lung inflammation (LI) patients: n=11; healthy control (HC): n=10].</p><p><strong>Patients and methods: </strong>We performed 16S ribosomal RNA gene sequencing and analyzed the associations between oral and gut microbiota diversity and composition across the three groups.</p><p><strong>Results: </strong>Alpha diversity of the oral microbiota was significantly lower in the LC group than in the HC group (Chao 1, p=0.004; Simpson, p=0.018; Shannon, p=0.009). Beta diversity of both oral and gut microbiota showed significant differences among the three groups (PERMANOVA, oral: p=0.005; gut: p=0.002). Compositional differences in the oral microbiota were observed between the HC and LC or LI groups; in particular, Bacilli class, Streptococcaceae family, Streptococcus genus, Firmicutes phylum, and Lactobacillales order were more abundant in the LC group. Additionally, six oral-related microbiota showed significant abundance in the gut of the LC group (p=0.00182).</p><p><strong>Conclusion: </strong>The oral microbiota in lung cancer patients is significantly different from that in healthy individuals. Specific changes in oral microbiota and oral-related gut microbiota compositions were evident in lung cancer patients. These findings might be useful for identifying novel biomarkers to predict the risk of lung cancer and prevent the disease.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5067-5080"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543260","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":"Association of Plasma Nestin With Response to Immune Checkpoint Inhibitors Combined With Chemotherapy in Extensive-stage Small-cell Lung Cancer: A Pilot Study.","authors":"Yuto Suzuki, Ken Maeno, Yusuke Kagawa, Kazuki Sone, Satoshi Fukuda, Takehiro Uemura, Ayako Masaki, Sanae Toda, Yuta Mori, Kensuke Fukumitsu, Yoshihiro Kanemitsu, Tomoko Tajiri, Yutaka Ito, Tetsuya Oguri, Akio Niimi","doi":"10.21873/anticanres.17334","DOIUrl":"10.21873/anticanres.17334","url":null,"abstract":"<p><strong>Background/aim: </strong>Nestin, an intermediate filament protein expressed in stem/progenitor cells of the developing central nervous system, is involved in the progression and poor prognosis of various malignancies. Difficulties in small-cell lung cancer (SCLC) tissue biopsy reduce the accuracy of immunohistochemistry analyses; therefore, evaluating nestin in blood samples is preferred in clinical practice. This study examined the clinical significance of plasma nestin levels in SCLC.</p><p><strong>Patients and methods: </strong>A single-center observational study of patients with untreated SCLC was conducted from 2019 to 2021. We determined plasma nestin levels before and after two treatment cycles, and the results were analyzed in relation to clinical outcome.</p><p><strong>Results: </strong>Twenty-five SCLC patients were enrolled. When patients were divided into high-plasma nestin (h-pNES) and low-plasma nestin (l-pNES) groups based on pre-treatment plasma nestin levels, among nine extensive-stage SCLC (ES-SCLC) patients treated with immune checkpoint inhibitor (ICI) combination chemotherapy, h-pNES patients had shorter progression-free survival and overall survival than l-pNES patients (p=0.0150 and p=0.0353, respectively). CD8/FoxP3- and CD8/CD3-positive T-cell ratios in biopsy specimens from h-pNES patients were lower than those of l-pNES patients (p=0.0458 and p=0.0218, respectively).</p><p><strong>Conclusion: </strong>This pilot study indicated that h-pNES patients exhibited a poorer response to ICI combination chemotherapy than l-pNES patients. Plasma nestin levels are easy to measure in ES-SCLC, in which sufficient tissue is difficult to obtain, and may potentially serve as a predictor of response to ICI combination chemotherapy. A large cohort is needed to investigate the clinical role of plasma nestin.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5095-5104"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543263","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":"Identification of New Potential Targets for Pancreatic Ductal Adenocarcinoma by Integrated Bioinformatic Analysis.","authors":"Rujia Li, Ting Yang, K E Ren, Jun Li, Yuichi Nagakawa, Yuhao Zeng, Yutaro Natsuyama, Shuang-Qin Yi","doi":"10.21873/anticanres.17254","DOIUrl":"https://doi.org/10.21873/anticanres.17254","url":null,"abstract":"<p><strong>Background/aim: </strong>Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women worldwide. The 5-year relative survival rate for pancreatic ductal adenocarcinoma (PDAC) is 10%, which is the lowest among all cancers. This study aimed to find more effective targets to improve the diagnosis, prognostic prediction, and treatment of PDAC.</p><p><strong>Materials and methods: </strong>Three datasets were selected from the GEO database. Correlation analysis was used to screen the datasets and samples. Differentially expressed genes were identified using GEO2R. Metascape was used to perform pathway and process enrichment analysis. Survival analysis using the GEPIA2 and Kaplan-Meier plotter databases was conducted to filter hub genes. Principal component analysis and LASSO regression analyses were used to further filter the key genes. Gene expression in PDAC and normal tissues and in different pathological stages was analyzed using the GEPIA2 database. Thereafter, gene expression was detected in three PDAC and HPDE cell lines using real-time polymerase chain reaction.</p><p><strong>Results: </strong>LPAR5, CYP2C18, SERPINH1, ACSL5, and HCAR3 exhibited higher transcription levels in PDAC tissues compared to matched normal tissues, whereas the PNLIP expression was lower. LPAR5, CYP2C18, SERPINH1 and ACSL5 were markedly upregulated in stage IV PDAC. LPAR5, CYP2C18, SERPINH1 and ACSL5 were upregulated in PDAC cell lines. Further verification suggested that the expression levels of these four genes were closely related to histological type, pathologic stage, therapeutic effects and prognosis of pancreatic cancer.</p><p><strong>Conclusion: </strong>LPAR5, CYP2C18, SERPINH1 and ACSL5 may serve as potential diagnostic, prognostic, and therapeutic targets for PDAC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4233-4250"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339881","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":"Contribution of Immunoscore to Survival Prediction in Pancreatic Ductal Adenocarcinoma.","authors":"Haruki Mori, Toru Miyake, Hiromitsu Maehira, Masanori Shiohara, Hiroya Iida, Nobuhito Nitta, Masaji Tani","doi":"10.21873/anticanres.17277","DOIUrl":"https://doi.org/10.21873/anticanres.17277","url":null,"abstract":"<p><strong>Background/aim: </strong>The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated as a prognostic factor in colorectal cancer after surgical resection of malignancy, but knowledge on their role in pancreatic cancer is lacking. The Immunoscore (IS) assesses TILs at the core of the tumor (CT) and invasive margin (IM) and is being evaluated as a new concept in tumor immunity. The aim of this study was to evaluate the relationship between IS and prognosis in PDAC.</p><p><strong>Patients and methods: </strong>The IS was analyzed by immunohistochemistry using surgical tissue blocks from 131 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgery to investigate the relationship between immune cell infiltration into the tumor and prognosis in PDAC.</p><p><strong>Results: </strong>A high IS in both CT and IM of the tumor was significantly associated with prolonged overall survival (OS) (p<0.01) and relapse-free survival (RFS) (p<0.01). In multivariate logistic regression models adjusted for clinical pathology data, IS predicted survival and recurrence (p<0.01 and p<0.01, respectively). Moreover, in patients who received preoperative chemotherapy, a high IS was statistically significantly associated with longer OS and RFS (p<0.01 and p<0.01, respectively).</p><p><strong>Conclusion: </strong>The immunohistochemically assessed IS might be a useful prognostic marker for patients with PDAC who underwent primary tumor resection.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4483-4492"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339875","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":"Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma.","authors":"Hyeon Ji Kim, DO-Yeon Kim","doi":"10.21873/anticanres.17260","DOIUrl":"10.21873/anticanres.17260","url":null,"abstract":"<p><strong>Background/aim: </strong>Given the high frequency and mortality rate of lung cancer, diverse molecular studies have been undertaken to understand cancer pathophysiology and develop novel treatment strategies. The PDIA4 gene, which is involved in protein assembly and endoplasmic reticulum homeostasis, is overexpressed in various lung cancer subtypes. However, its exact function in lung adenocarcinoma (LUAD) remains elusive. The study aimed to investigate the role of PDIA4 in LUAD and explore its role as double-agent gene.</p><p><strong>Materials and methods: </strong>PDIA4 expression was knocked out in A549 and LA-4 lung adenoma cells using the Crispr/Cas9 technology. Cell growth, migration, and apoptosis were analyzed in control and PDIA4-deficient cells.</p><p><strong>Results: </strong>PDIA4 deficiency resulted in increased cell growth, enhanced migration capacity, and greater resistance to apoptosis in both A549 and LA-4 lung cancer cells. Mechanistically, up-regulation of oxidative stress followed by NF-[Formula: see text]B activation may contribute to tumor-promoting effects observed upon PDIA4 silencing.</p><p><strong>Conclusion: </strong>PDIA4 appears to function as a tumor suppressor in lung adenocarcinoma, suggesting that PDIA4 may act as a double-agent gene, with roles both on tumor suppression and promotion depending on the context.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4309-4315"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339894","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":"Promising Approach for Optimizing <i>In Vivo</i> Fluorescence Imaging in a Tumor Mouse Model: Precision in Cancer Research.","authors":"Yu-Jeong Choi, Sonny C Ramos, Hyun Bo Sim, Ji Yeon Han, Dae-Han Park, Seul-Ki Mun, Ju-Bin Lee, Chi-Ho Lee, Yong-An Lee, Jong-Jin Kim","doi":"10.21873/anticanres.17264","DOIUrl":"https://doi.org/10.21873/anticanres.17264","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer remains a major global health concern due to its high mortality rates. Advanced diagnostic imaging, such as in vivo near-infrared (NIR) fluorescence imaging, enhances early detection by reducing autofluorescence and enabling deeper tissue penetration, addressing some limitations of conventional methods. Understanding the underlying causes of autofluorescence, even in mouse model fluorescence imaging, is crucial for accurate interpretation. This study investigated the origins of autofluorescence observed in experimental animals under NIR wavelengths, achieving successful fluorescence imaging in a clinically relevant tumor mouse model.</p><p><strong>Materials and methods: </strong>Both fasting and non-fasting groups were evaluated to assess the dietary impact on autofluorescence, with various feeds tested. Subcutaneous and lung tumor models were established in C57BL/6 and BALB/c nude mice using LL/2-iRFP cells. Cryo-sectioning and lung tissue imaging were conducted to confirm tumor presence and assess fluorescence signals.</p><p><strong>Results: </strong>It was found that autofluorescence, notably common in the abdomen, is attributed to dietary factors. By selecting feed that lacks autofluorescence, the impact of dietary fluorescence on imaging was evaluated, leading to the establishment of optimized imaging conditions suited to the presence or absence of autofluorescence. Subsequently, utilizing lung cancer cells expressing near-infrared proteins (LL/2-iRFP), intratracheal, and subcutaneous tumor mouse models were developed, and successful in vivo imaging was achieved using the optimized imaging protocols, effectively bypassing autofluorescence.</p><p><strong>Conclusion: </strong>This study emphasizes the importance of understanding and addressing autofluorescence in fluorescence imaging, presenting valuable insights for enhancing the reliability and accuracy of diagnostic imaging techniques in cancer research and clinical practice.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4347-4358"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339896","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":"Sparing Effect on Cell Survival Under Normoxia Using Ultra-high Dose Rate Proton Beams from a Compact Superconducting AVF Cyclotron.","authors":"Masashi Yagi, Kazumasa Minami, Kazuki Fujita, Shinji Nomura, Nagaaki Kamiguchi, Kana Nagata, Ryo Hidani, Daizo Amano, Kenzo Sasai, Shinichi Shimizu, Kazuhiko Ogawa","doi":"10.21873/anticanres.17255","DOIUrl":"https://doi.org/10.21873/anticanres.17255","url":null,"abstract":"<p><strong>Background/aim: </strong>The purpose of this study was to evaluate whether the sparing effect on cell survival is observed under normoxia.</p><p><strong>Materials and methods: </strong>A superconducting spiral sector-type azimuthally varying field (AVF) cyclotron produced 230 MeV proton beams at 250 Gy/s as ultra-high dose rate (uHDR) and 1 Gy/s as normal dose rate (NDR) to irradiate tumor and normal cell lines (HSGc-c5 and HDF up to 24 Gy at the center of spread-out Bragg peak (SOBP). The Advanced Markus chamber and Gafchromic film were used to measure the examined absolute dose and field sizes. Colony formation assay and immunofluorescence staining were conducted to evaluate the sparing effect.</p><p><strong>Results: </strong>A homogeneous field was achieved at the center of the SOBP for both uHDR and NDR scanned proton beams, and dose reproducibility and linearity were adequate for experiments. There were significant differences in cell surviving fractions of HSGc-C5 and HDF cells irradiated at uHDRs compared to NDRs at 20 Gy and 24 Gy. Increasing γ-H2AX foci were observed for both cell lines at NDR.</p><p><strong>Conclusion: </strong>The sparing effect on cell survival was first observed under normoxic conditions for tumor and normal cells with doses exceeding 20 Gy, using proton irradiation at 250 Gy/s extracted from a superconducting AVF cyclotron. This study marks a significant milestone in advancing our understanding of the underlying mechanism behind the sparing effect.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4251-4260"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339903","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":"Anticancer Effects of BAF312 (Siponimod) in Epithelial Ovarian Cancer.","authors":"Heeeun Ha, Ji-Yoon Ryu, Suin Yoon, Young-Jae Cho, Jung-Joo Choi, Jae Ryoung Hwang, Ju-Yeon Choi, Hee Dong Han, Jeong-Won Lee","doi":"10.21873/anticanres.17257","DOIUrl":"https://doi.org/10.21873/anticanres.17257","url":null,"abstract":"<p><strong>Background/aim: </strong>Epithelial ovarian cancer (EOC) is a lethal disease that is the fifth leading cause of cancer-related death in women. BAF312 (siponimod) is a potent and selective sphingosine-1-phosphate (S1P) receptor modulator that has been approved as a treatment for multiple sclerosis. In addition to its immunomodulatory action, BAF312 shows preclinical antitumor effects in several cancer types. This study sought to determine whether BAF312 had anticancer properties against EOC using in vitro and in vivo models.</p><p><strong>Materials and methods: </strong>EOC cell lines A2780, SKOV3ip1, A2780-CP20, and SKOV3-TR were treated with BAF312 and tested for cell proliferation, apoptosis, and migration using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting, and migration assays. We investigated the expression of sphingosine-1-phosphate receptor 1 (S1PR1) in most EOC cell lines through western blot analysis. To investigate potential mechanisms, western blot analysis was used to assess the expression of AKT serine/threonine kinase 1 (AKT) and extracellular-regulated kinase (ERK) after BAF312 treatment. We also created poly(D,L-lactide-co-glycolide) nanoparticles encapsulating BAF312 (PLGA-NP-BAF312) for in vivo therapy. The average size and zeta potential of PLGA-NP-BAF312 were determined using dynamic light scattering. The therapeutic efficacy of PLGA-NP-BAF312 was tested in an A2780 tumor-bearing orthotopic mouse model of EOC.</p><p><strong>Results: </strong>S1PR1 was overexpressed in most EOC cell lines. BAF312 significantly reduced cell proliferation and migration while inducing significant apoptosis in all EOC cell lines. PLGA-NP-BAF312 treatment significantly reduced tumor weights in A2780 tumor-bearing mice. Furthermore, the anticancer effects of BAF312 were associated with reduced phosphorylation of ERK and AKT.</p><p><strong>Conclusion: </strong>Our findings show that BAF312 has significant anticancer effects in EOC cells by inhibiting the ERK and AKT pathways, and might potentially be used to treat EOCs.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4273-4282"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339837","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":"Antitumor Potential of Guttiferone E Combined With Carboplatin Against Osimertinib-resistant H1975 Lung Cancer Through Apoptosis.","authors":"Aakash Nathani, Islauddin Khan, Matheus Hikaru Tanimoto, Jennyfer Andrea Aldana Mejía, Aline Mayrink DE Miranda, Arun Rishi, Satyanarayan Dev, Jairo Kenupp Bastos, Mandip Singh","doi":"10.21873/anticanres.17248","DOIUrl":"https://doi.org/10.21873/anticanres.17248","url":null,"abstract":"<p><strong>Background/aim: </strong>Low selectivity and high frequency of side-effects are the major problems of currently used chemotherapeutics. Among natural compounds, the polyprenylated acylphloroglucinol, guttiferone E, isolated from Brazilian red propolis, has attracted attention due to its marked anticancer properties and was evaluated here for its role against osimertinib-resistant H1975 cells (with double mutations of epidermal growth factor receptor: EGFR L858R/T790M).</p><p><strong>Materials and methods: </strong>Guttiferone E was obtained from red propolis using established extraction procedures. Guttiferone E was tested using the H1975 cell line in in vitro (2D and 3D) cell cultures and in vivo in BALB/c athymic nude mice. Live/dead assay was also performed to support the results. Tumor tissues obtained from in vivo studies were used for western blotting. Guttiferone E reduced H1975 cell viability in a concentration-dependent manner. The IC₅₀ values in 2D and 3D cell lines were 2.56±0.12 μM and 11.25±0.34 μM. Furthermore, at 10 mg/kg intraperitoneally, guttiferone E significantly reduced the tumor volume in tumor xenografts when used alone and in combination with carboplatin. Guttiferone E and carboplatin displayed synergistic inhibition of H1975 cells and animal tumors. Co-treatment of guttiferone E with carboplatin induced more prominent apoptosis than treatment with either drug alone. Guttiferone E treatment induced cleavage of poly-ADP ribose polymerase and induced apoptosis by significantly reducing levels of mammalian target of rapamycin, sirtuin 1, sirtuin 7, superoxide dismutase, programmed death-ligand 1, and programmed cell death 1 in tumor tissues.</p><p><strong>Conclusion: </strong>Our results show guttiferone E to be a promising, novel and potent antitumor drug candidate for osimertinib-resistant lung cancer with EGFR L858R/T790M mutations.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 10","pages":"4175-4188"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339838","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}