OncoTargets and therapy最新文献

{"title":"Cytotoxic Evaluation, Molecular Docking, Molecular Dynamics, and ADMET Prediction of Isolupalbigenin Isolated from <i>Erythrina subumbrans</i> (Hassk). Merr. (Fabaceae) Stem Bark: Unveiling Its Anticancer Efficacy.","authors":"Tati Herlina, Abd Wahid Rizaldi Akili, Vicki Nishinarizki, Ari Hardianto, Allyn Pramudya Sulaeman, Shabarni Gaffar, Euis Julaeha, Tri Mayanti, Unang Supratman, Mohd Azlan Nafiah, Jalifah Binti Latip","doi":"10.2147/OTT.S482469","DOIUrl":"https://doi.org/10.2147/OTT.S482469","url":null,"abstract":"<p><strong>Introduction: </strong><i>Erythrina subumbrans</i>, a medical plant found in sub-Saharan Africa and the Western Ghats of India, shows promise as a potential source of bioactive compounds to treat cancer. In our ongoing research on folk medical plants, we report the isolation of flavonoid compound from the stem bark of <i>E. subumbrans</i> along with its cytotoxic activity against breast cancer (MCF-7 and T47D), and cervical cancer (HeLa) cell lines.</p><p><strong>Purpose: </strong>This study aimed to isolate secondary metabolite from the stem bark of <i>E. subumbrans</i> and evaluate its cytotoxic activity to support the use of folk medicinal plants as alternative therapy against cancer.</p><p><strong>Methods: </strong>Isolupalbigenin was isolated from the stem bark of <i>E. subumbrans</i> by column chromatography. Cytotoxic activity against breast cancer (MCF-7 and T47D) and cervical cancer (HeLa) cell lines was evaluated using the MTT assay, whereas the in silico study was evaluated using molecular docking and molecular dynamics against estrogen receptor alpha (ERα).</p><p><strong>Results: </strong>The cytotoxic assay showed that isolupalbigenin inhibited the growth of MCF-7 cell with an IC₅₀ of 31.62 µg∙mL^-1, while showing no toxicity against normal human cells (Vero cell line). The molecular docking results suggested that isolupalbigenin can bind to ERα with a lower binding affinity than estradiol, whereas the stability of the isolupalbigenin-ERα complex was confirmed by molecular dynamic simulation with a median Root Mean Square Deviation (RMSD) of 2.80 Å. Toxicity prediction suggested that isolupalbigenin was less likely to cause hepatotoxicity or carcinogenicity, whereas pharmacokinetic prediction suggested that isolupalbigenin has high intestinal absorption with medium Caco2 permeability. In addition, isolupalbigenin was predicted to have a medium volume of distribution (Vd).</p><p><strong>Conclusion: </strong>Isolupalbigenin isolated from the stem bark of <i>E. subumbrans</i> with cytotoxic activity supports further development of plants from the genus <i>Erythrina</i> as a medicinal plant for alternative therapy against cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy and Breast Cancer: A Challenge for the Multidisciplinary Team. A Single Center Experience and Narrative Review.","authors":"Fiorella Ruatta, Nerina Denaro, Paola Vanella, Gianluca Tomasello, Ernesto Principe, Grazia Sciancalepore, Carmen Giusy Rea, Ornella Garrone","doi":"10.2147/OTT.S464860","DOIUrl":"https://doi.org/10.2147/OTT.S464860","url":null,"abstract":"<p><strong>Purpose: </strong>The diagnosis of breast cancer during pregnancy is a rare event, but it is more frequent in our daily clinical practice due to the progressing aging of pregnant women. The management of a woman affected by pregnancy-associated breast cancer (PABC) remains a challenge for the clinician as it is related to ethical and psychological decisions.</p><p><strong>Patients and methods: </strong>Here, we retrospectively described 10 cases of PABC in women treated at our Institution. All cases were discussed in the multidisciplinary team. We reviewed available literature data on the topic.</p><p><strong>Results: </strong>Nine out 10 patients were diagnosed with localized breast cancer. The remaining patients were presented with metastatic de novo disease. Median age was 37.5 years (range 26-42). Seven patients presented with grade 3 tumor and 9 patients had Ki-67 value higher than 30%. All but 2 patients received neoadjuvant chemotherapy consisting of sequential anthracyclines and cyclophosphamide followed by weekly paclitaxel during pregnancy. No safety concerns or complications during delivery for both the mothers and the babies were reported.</p><p><strong>Conclusion: </strong>Breast cancer during pregnancy is a challenging clinical situation and all the decisions need to consider both the patients and the fetus safety. Data from our series and from literature confirm the safety of standard chemotherapy approach starting from the second trimester of gestation. More research and effort are needed to offer these patients excellent outcomes and it is mandatory that cases should be closely followed up by a multidisciplinary team.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA PTPRG-AS1 Promotes Breast Cancer Progression by Modulating the miR-4659a-3p/QPCT Axis.","authors":"Mengsi Zhou, Yanting Li, Liu Yang, Shuo Liu, Lixian Yang, Bin Xu, Xiaolong Li, Quanle Wang, Haijun Zhao, Zhenchuan Song","doi":"10.2147/OTT.S474898","DOIUrl":"https://doi.org/10.2147/OTT.S474898","url":null,"abstract":"<p><strong>Background: </strong>Overwhelming evidence has suggested that dysregulated long noncoding RNAs (lncRNAs) play a critical modulating effect in the evolution of breast cancer (BRCA). Nevertheless, the roles of lncRNA PTPRG antisense RNA 1 (PTPRG-AS1) in BRCA and the underlying mechanisms have not been experimentally validated and functionally annotated.</p><p><strong>Methods: </strong>The expression of lncRNA PTPRG-AS1 in BRCA tissues and cell lines was evaluated by reverse transcription-quantitative PCR (RT-qPCR), and by using public databases. The proliferation of BRCA cells was detected using Cell Counting Kit-8 and colony formation assays. Wound healing assay, and Transwell migration and invasion assays were carried out to explore the migratory and invasive abilities of BRCA cells. The interaction between lncRNA PTPRG-AS1, microRNA (miR)-4659a-3p and glutaminyl-peptide cyclotransferase (QPCT) was verified using RT-qPCR, dual-luciferase reporter assay and Western blotting.</p><p><strong>Results: </strong>The results showed that LncRNA PTPRG-AS1 was markedly upregulated in BRCA tissues and cell lines. Knocking down lncRNA PTPRG-AS1 significantly inhibited the proliferation, migration and invasion of BRCA cells, while overexpression of lncRNA PTPRG-AS1 enhanced the aforementioned properties of BRCA cells. Further analyses revealed that PTPRG-AS1 may act as a molecular sponge for miR-4659a-3p, thus regulating QPCT expression, therefore, acting as an oncogene in BRCA.</p><p><strong>Conclusion: </strong>Collectively, the study demonstrates that lncRNA PTPRG-AS1 may act as a competing endogenous RNA by regulating the miR-4659a-3p/QPCT axis in BRCA progression. This lncRNA could potentially be a biomarker and therapeutic target for BRCA.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Synergism from the Combination of Ulinastatin and Curcumin Offers Greater Inhibition against Colorectal Cancer Liver Metastases via Modulating Matrix Metalloproteinase-9 and E-Cadherin Expression [Corrigendum].","authors":"","doi":"10.2147/OTT.S493466","DOIUrl":"https://doi.org/10.2147/OTT.S493466","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/OTT.S57126.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Strategies in Advanced Cervical Cancer Detection, Prevention and Treatment.","authors":"Xolisiwe M Sebutsoe, Nrateng Joyful Nonhlanzeko Tsotetsi, Zodwa Edith Jantjies, Portia Pheladi Raphela-Choma, Mpho S Choene, Lesetja R Motadi","doi":"10.2147/OTT.S475132","DOIUrl":"https://doi.org/10.2147/OTT.S475132","url":null,"abstract":"<p><p>Cervical cancer is ranked the fourth most common cause of cancer related deaths amongst women. The situation is particularly dire in low to lower middle-income countries. It continues to affect these countries due to poor vaccine coverage and screening. Cervical cancer is mostly detected in the advanced stages leading to poor outcomes. This review focuses on the progress made to date to improve early detection and targeted therapy using both circulating RNA. Vaccine has played a major role in cervical cancer control in vaccinated young woman in mainly developed countries yet in low-income countries with challenges of 3 dose vaccination affordability, cervical cancer continues to be the second most deadly amongst women. In this review, we show the progress made in reducing cervical cancer using vaccination that in combination with other treatments that might improve survival in cervical cancer. We further show with both miRNA and siRNA that targeted therapy and specific markers might be ideal for early detection of cervical cancer in low-income countries. These markers are either upregulated or down regulated in cancer providing clue to the stage of the cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Structurally Rare <i>EML4-ALK</i> Identified by Next Generation Sequencing in a Patient with NSCLC with Bilateral Ovarian Metastases.","authors":"Ryusuke Maruta, Daichi Sadato, Makiko Yomota, Ryu Gomikawa, Toru Motoi, Tatsuya Sato, Nao Kino, Masayoshi Kobayashi, Yukio Hosomi","doi":"10.2147/OTT.S474134","DOIUrl":"https://doi.org/10.2147/OTT.S474134","url":null,"abstract":"<p><p>The <i>EML4-ALK</i> oncogene is a fusion of the <i>EML4</i> and <i>ALK</i> genes and is found in approximately 5-6% of the cases of non-small cell lung cancer (NSCLC). Herein, we present a unique case of lung adenocarcinoma with metastases to the bilateral ovaries harboring a rare <i>EML4-ALK</i> fusion gene variant in a 52-year-old patient. The patient had initially received a diagnosis of ovarian cancer, then had undergone neo-adjuvant chemotherapy followed by a surgical resection. Despite two cycles of adjuvant chemotherapy consisting of carboplatin and gemcitabine, CT revealed that the pleural effusion had increased from it before chemotherapy, and the shortness of breath worsened. Molecular profiling revealed an <i>EML4-ALK</i> rearrangement containing <i>ALK -EML4</i> and <i>ALK -NPR2</i> fusion genes. The diagnosis was changed to primary lung adenocarcinoma with metastases to the bilateral ovaries based on a pathological reevaluation. Treatment with alectinib, a second-generation ALK-tyrosine kinase inhibitor, led to a partial response of 18 months' duration, and the shortness of breath improved. No adverse events related to the alectinib therapy occurred. To assess the unique structure of the fusion genes, RNA sequencing was performed. An intronic sequence from both <i>ALK</i> and <i>EML4</i> was found between <i>ALK</i> and <i>EML4</i> exon, possibly because of an unusual insertion of a gene fragment derived from <i>NRP2</i>, indicated by the panel sequencing results. Variations in the drug response among <i>EML4-ALK</i> fusion variants highlight the importance of understanding their molecular structure. Further investigation is warranted to refine fusion gene detection methods and assess the therapeutic implications of rare fusion variants.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Genetic Variants and Platinum Chemotherapy Response in Indonesian Non-Small Cell Lung Cancer Patients: Insights from ERCC2 rs13181","authors":"Nadiya Nurul Afifah, Lanny Indah Permatasari, Ajeng Diantini, Ruri Intania, Indra Wijaya, Hideru Obinata, Melisa Intan Barliana","doi":"10.2147/ott.s475219","DOIUrl":"https://doi.org/10.2147/ott.s475219","url":null,"abstract":"<strong>Purpose:</strong> Individual responses to platinum-based treatment for Non-Small Cell Lung Cancer (NSCLC) are influenced by genetic polymorphisms, including Single Nucleotide Polymorphisms (SNPs). This study aimed to explore the role of ERCC2 in the Nucleotide Excision Repair (NER) pathway for platinum-based chemotherapy in NSCLC. While <em>ERCC2</em> is widely studied, data for Southeast Asian populations are lacking. Addressing this gap could improve personalized treatment strategies for NSCLC in this demographic.<br/><strong>Patients and Methods:</strong> This study recruited 82 NSCLC patients with wildtype mutations of <em>EGFR</em> at Dr. H.A. Rotinsulu Lung Hospital, Bandung, and Dharmais Cancer Hospital, Jakarta. Data were collected prospectively from whole blood samples and medical records, while the effectiveness of chemotherapy was assessed by evaluating the response using RECIST 1.1 criteria on fourth cycle of chemotherapy.<br/><strong>Results:</strong> The results of this study showed the presence of genotype variation among the subjects, with frequency distribution as follows: AA genotype (82.9%), AC genotype (15.9%), and CC genotype (1.2%). The analysis of the association between <em>ERCC2</em> rs13181 CC + AC versus AA with RECIST 1.1 yielded an odds ratio (OR) of 1.042 (95% CI: 0.292– 3.715; p=0.950). A multivariate analysis that included cancer stage and chemotherapy regimen as additional variables produced an adjusted odds ratio (aOR) of 0.970 (95% CI: 0.263– 3.568; p=0.963).<br/><strong>Conclusion:</strong> This study did not find statistically significant associations between <em>ERCC2</em> rs13181 polymorphisms and chemotherapy responses. However, this research highlights the presence of genetic variation within the Indonesian population, with the AA genotype being the most prevalent, which may influence chemotherapy responses. The results provided preliminary data and lay the foundation for future comprehensive cohort observational investigations.<br/><br/><strong>Keywords:</strong> ERCC2, genetic polymorphism, Indonesia, RECIST 1.1, platinum-based<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250267","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":"Knockdown of TRIM37 Promotes Apoptosis and Suppresses Tumor Growth in Gastric Cancer by Inactivation of the ERK1/2 Pathway [Retraction]","authors":"Hongyi Zhu, Yuanwen Chen, Jie Zhang, Changlin Qian, Weiqing Qiu, Huojian Shen, Zhiyong Shen","doi":"10.2147/ott.s495521","DOIUrl":"https://doi.org/10.2147/ott.s495521","url":null,"abstract":"Retraction for the article Knockdown of TRIM37 Promotes Apoptosis and Suppresses Tumor Growth in Gastric Cancer by Inactivation of the ERK1/2 Pathway","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197092","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":"The Study of PIK3CA Hotspot Mutations and Co-Occurring with EGFR, KRAS, and TP53 Mutations in Non-Small Cell Lung Cancer","authors":"YuXuan Zhang, Yuhong Shen, Jiayuan Wu, Jun Zhang, Chenxi Cao, Juanfen Mo, Yi Bao","doi":"10.2147/ott.s468352","DOIUrl":"https://doi.org/10.2147/ott.s468352","url":null,"abstract":"<strong>Objective:</strong> PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center.<br/><strong>Materials and Methods:</strong> We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records. The Log rank test was used to determine the association between PIK3CA mutations and overall survival (OS) in NSCLC patients.<br/><strong>Results:</strong> Common hotspot mutations in PIK3CA were found in exon 9 (c.1633G &gt; A, E545K, and c.1624G &gt; A, E542K) and exon 20 (c.3140A &gt; G, H1047R) in all cohorts. Co-occurring mutations of PIK3CA with EGFR, KRAS, and TP53 have been frequently observed in patients with NSCLC, with different percentages in these datasets generated by different background. PIK3CA mutations were observed to be significantly associated with poor OS in lung adenocarcinomas patients in the MSKCC cohort (hazard ratio [HR] = 0.519, 95% confidence interval [CI] = 0.301– 0.896; <em>P</em> &lt; 0.05).<br/><strong>Conclusion:</strong> PIK3CA co-occurring mutations in other genes may represent distinct subsets of NSCLC. Further elucidation of the roles of PIK3CA hotspot mutations combined with other driver mutations, including EGFR and KRAS, is needed to guide effective treatment in patients with advanced NSCLC.<br/><br/><strong>Keywords:</strong> co-occurring mutation, non-small cell lung cancer, PIK3CA, The Cancer Genome Atlas, Memorial Sloan Kettering Cancer Center<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197090","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":"LncRNA WT1-AS/mir-494-3P Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway In Non-Small Cell Lung Cancer [Retraction]","authors":"Chaohui Wu, Jiansheng Yang, Rongbin Li, Xianbin Lin, Jiayun Wu, Jingyang Wu","doi":"10.2147/ott.s494633","DOIUrl":"https://doi.org/10.2147/ott.s494633","url":null,"abstract":"Retraction for the article LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197091","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}