Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"METTL3-Mediated m6A Modification of FMRP Drives Hepatocellular Carcinoma Progression and Indicates Poor Prognosis.","authors":"Siyuan Fu,Dapeng Sun,Zongyan Wang,Peng Zhu,Wenbin Ding,Jian Huang,Xinggang Guo,Yun Yang,Fangming Gu","doi":"10.1089/cbr.2023.0186","DOIUrl":"https://doi.org/10.1089/cbr.2023.0186","url":null,"abstract":"Accumulating studies reveal that m6A RNA methylation plays a critical role in cancer pathogenesis and progression. METTL3 as a m6A methyltransferase acts as an oncogene in multiple malignancies including hepatocellular carcinoma (HCC). However, the role and underlying mechanism by which METTL3 contributes to HCC remain unclear. The association of METTL3 expression with clinicopathological characteristics and prognosis in patients with HCC was assessed by reverse transcription polymerase chain reaction, Western blot, and public TCGA dataset. MTT, colony formation, Transwell assays, and xenograft tumor models were executed to reveal the role of METTL3 in HCC. m6A dot blot, RNA immunoprecipitation (RIP), m6A methylated RIP, and Western blot assays were used to uncover the regulatory mechanism of METTL3 in HCC cells. We found that METTL3 was dramatically upregulated in HCC tissue samples and acted as an independent prognostic factor for poor survival and tumor recurrence in patients with HCC. Silencing of METTL3 repressed cell growth and invasion in vitro and in vivo, but restored expression of METTL3 boosted these effects. Mechanistical investigations revealed that METTL3 could directly interact with FMRP and harbor a positive correlation with FMRP expression. Knockdown of METTL3 reduced FMRP m6A levels as well as its mRNA and protein expression. FMRP overexpression drove cell colony formation and cell invasion and abolished METTL3 knockdown-induced antitumor effects and AKT/mTORC1 signaling inactivation. Elevated expression of FMRP could act as an independent prognostic factor for poor survival and tumor recurrence in patients with HCC. Our findings demonstrate that METTL3-mediated m6A modification of FMRP promotes growth and invasion of HCC cells and may provide a promising therapeutic target for HCC.","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"37 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194028","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":"Prognostic Signature in Osteosarcoma Based on Amino Acid Metabolism-Associated Genes.","authors":"Liwen Feng, Yuting Chen, Xiangping Mei, Lei Wang, Wenjing Zhao, Jiannan Yao","doi":"10.1089/cbr.2024.0002","DOIUrl":"10.1089/cbr.2024.0002","url":null,"abstract":"<p><p><b><i>Background:</i></b> Osteosarcoma (OS) is undeniably a formidable bone malignancy characterized by a scarcity of effective treatment options. Reprogramming of amino acid (AA) metabolism has been associated with OS development. The present study was designed to identify metabolism-associated genes (MAGs) that are differentially expressed in OS and to construct a MAG-based prognostic risk signature for this disease. <b><i>Methods:</i></b> Expression profiles and clinicopathological data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena databases. A set of AA MAGs was obtained from the MSigDB database. Differentially expressed genes (DEGs) in GEO dataset were identified using \"limma.\" Prognostic MAGs from UCSC Xena database were determined through univariate Cox regression and used in the prognostic signature development. This signature was validated using another dataset from GEO database. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, single sample gene set enrichment analysis, and GDSC2 analyses were performed to explore the biological functions of the MAGs. A MAG-based nomogram was established to predict 1-, 3-, and 5-year survival. Real-time quantitative polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of MAGs in primary OS and paired adjacent normal tissues. <b><i>Results:</i></b> A total of 790 DEGs and 62 prognostic MAGs were identified. A MAG-based signature was constructed based on four MAGs: <i>PIPOX</i>, <i>PSMC2</i>, <i>SMOX</i>, and <i>PSAT1</i>. The prognostic value of this signature was successfully validated, with areas under the receiver operating characteristic curves for 1-, 3-, and 5-year survival of 0.714, 0.719, and 0.715, respectively. This MAG-based signature was correlated with the infiltration of CD56^dim natural killer cells and resistance to several antiangiogenic agents. The nomogram was accurate in predictions, with a C-index of 0.77. The expression of MAGs verified by experiment was consistent with the trends observed in GEO database. <b><i>Conclusion:</i></b> Four AA MAGs were prognostic of survival in OS patients. This MAG-based signature has the potential to offer valuable insights into the development of treatments for OS.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"517-531"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186385","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":"circ_0080145 Enhances Imatinib Resistance of Chronic Myeloid Leukemia by Regulating miR-326/<i>PPFIA1</i> Axis.","authors":"Hong Che, Hong Ding, Xizhen Jia","doi":"10.1089/cbr.2020.3600","DOIUrl":"10.1089/cbr.2020.3600","url":null,"abstract":"<p><p><b><i>Background:</i></b> Acquired multidrug resistance is often blamed for the failure of chemotherapy in patients with malignant tumors, including chronic myeloid leukemia (CML). In this study, the authors investigated the role of circular RNA 0080145 (circ_0080145) in imatinib (IM) resistance of CML. <b><i>Materials and Methods:</i></b> Quantitative real-time polymerase chain reaction was applied to measure the expression of circ_0080145, microRNA-326 (miR-326), and PTPRF interacting protein alpha 1 (<i>PPFIA1</i>) mRNA. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the half maximal inhibitory concentration (IC50) of IM and cell proliferation. Flow cytometry analysis was utilized to assess cell apoptosis. The levels of glucose uptake and lactate production were examined using specific kits. Protein levels were detected through Western blot assay. The targeting relationship between miR-326 and circ_0080145 or <i>PPFIA1</i> was verified by dual-luciferase reporter assay. The murine xenograft model was constructed to investigate the effect of circ_0080145 <i>in vivo</i>. <b><i>Results:</i></b> circ_0080145 was upregulated in IM-resistant CML patients and cells. circ_0080145 silencing suppressed IM resistance, cell growth, and glycolysis and induced apoptosis in IM-resistant CML cells <i>in vitro</i>. Moreover, circ_0080145 knockdown blocked tumor growth and IM resistance <i>in vivo</i>. miR-326 was a target of circ_0080145, and miR-326 inhibition restored the effects of circ_0080145 silencing on cell progression and IM resistance. In addition, <i>PPFIA1</i> was a target gene of miR-326. The suppressive roles in IM resistance, cell growth and glycolysis, and the promotional role in apoptosis mediated by miR-326 were abolished by PPFIA1 overexpression in IM-resistant CML cells. <b><i>Conclusion:</i></b> circ_0080145 contributes to IM resistance via modulating miR-326/<i>PPFIA1</i> axis, which might provide a novel avenue for CML therapy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"478-491"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38101180","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":"microRNA-106b-5p and Rab10: Potential Markers of Acute Myeloid Leukemia.","authors":"Lingyue Xu, Ailing Wang, Hongzai Guan","doi":"10.1089/cbr.2023.0191","DOIUrl":"10.1089/cbr.2023.0191","url":null,"abstract":"<p><p>This study focuses on acute myeloid leukemia (AML), a condition with a 5-year survival rate below 30% despite various treatment options. Recent strides in targeted therapies have shown promise, leading to better outcomes with minimal toxicity. These advances underscore the importance of discovering new diagnostic and prognostic targets for AML. In this context, the authors investigated the expression of microRNA-106b-5p (miR-106b-5p), Rab10 mRNA, and Rab10 proteins in peripheral blood and bone marrow (BM) samples from both healthy individuals and AML patients at different stages of the disease (initial diagnosis, recurrence, and complete remission). This examination aimed to identify potential biomarkers for AML diagnosis, treatment, and prognosis. From June 2021 to December 2022, they collected 100 BM and peripheral blood samples. The relative expression of miR-106b-5p and Rab10 mRNA in the BM of AML patients was measured using Real-time polymerase chain reaction (qRT-PCR), while the relative expression of Rab10 protein in serum was determined using the ELISA method. The chromosomal karyotype of initially diagnosed patients was analyzed using the R tape. The qRT-PCR results revealed that the expression of miR-106b-5p and Rab10 mRNA were significantly higher in patients at initial diagnosis and recurrence compared with healthy individuals and those in complete remission (<i>p</i> < 0.001). They observed a significant reduction in the expression of miR-106b-5p, Rab10 mRNA, and Rab10 protein in the BM and peripheral blood of patients during complete remission (<i>p</i> < 0.05), as demonstrated by dynamic monitoring of five patients in the initial group. Furthermore, they found a close association between the expression of miR-106b-5p and the number of white blood cells at the initial diagnosis in AML patients (<i>p</i> < 0.05). Spearman correlation analysis revealed a positive correlation among miR-106b-5p, Rab10 mRNA, and Rab10 proteins (<i>p</i> < 0.05). The diagnostic potential of miR-106b-5p and Rab10 proteins was underscored by Receiver Operating Characteristic (ROC) curve analysis, which demonstrated their high accuracy in AML diagnosis (AUC: 0.944 and 0.853, respectively; <i>p</i> < 0.0001). Additionally, Kaplan-Meier survival analysis suggested that lower expression of these markers was associated with better prognoses (<i>p</i> < 0.05). In summary, their findings propose miR-106b-5p and Rab10 proteins as promising biomarkers for AML, offering insights for diagnosis, treatment, and prognosis.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"492-501"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478024","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":"Prediction of Prognosis and Immunotherapy Response with a Novel Natural Killer Cell Marker Genes Signature in Osteosarcoma.","authors":"Qinwen Li, Xiaoyan Huang, Youfang Zhao","doi":"10.1089/cbr.2023.0103","DOIUrl":"10.1089/cbr.2023.0103","url":null,"abstract":"<p><p><b><i>Background:</i></b> Natural killer (NK) cells are characterized by their antitumor efficacy without previous sensitization, which have attracted attention in tumor immunotherapy. The heterogeneity of osteosarcoma (OS) has hindered therapeutic application of NK cell-based immunotherapy. The authors aimed to construct a novel NK cell-based signature to identify certain OS patients more responsive to immunotherapy. <b><i>Materials and Methods:</i></b> A total of eight publicly available datasets derived from patients with OS were enrolled in this study. Single-cell RNA sequencing data obtained from the Gene Expression Omnibus (GEO) database were analyzed to screen NK cell marker genes. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was used to construct an NK cell-based prognostic signature in the TARGET-OS dataset. The differences in immune cell infiltration, immune system-related metagenes, and immunotherapy response were evaluated among risk subgroups. Furthermore, this prognostic signature was experimentally validated by reverse transcription-quantitative real-time PCR (RT-qPCR). <b><i>Results:</i></b> With differentially expressed NK cell marker genes screened out, a five-gene NK cell-based prognostic signature was constructed. The prognostic predictive accuracy of the signature was validated through internal clinical subgroups and external GEO datasets. Low-risk OS patients contained higher abundances of infiltrated immune cells, especially CD8 T cells and naive CD4 T cells, indicating that T cell exhaustion states were present in the high-risk OS patients. As indicated from correlation analysis, immune system-related metagenes displayed a negative correlation with risk scores, suggesting the existence of immunosuppressive microenvironment in OS. In addition, based on responses to immune checkpoint inhibitor therapy in two immunotherapy datasets, the signature helped predict the response of OS patients to anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy. RT-qPCR results demonstrated the roughly consistent relationship of these five gene expressions with predicting outcomes. <b><i>Conclusions:</i></b> The NK cell-based signature is likely to be available for the survival prediction and the evaluation of immunotherapy response of OS patients, which may shed light on subsequent immunotherapy choices for OS patients. In addition, the authors revealed a potential link between immunosuppressive microenvironment and OS.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"502-516"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61566116","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":"Immune Response to Molecular Radiotherapy with ¹⁷⁷Lu-DOTATOC: Predictive Value of Blood Cell Counts for Therapy Outcome.","authors":"Andreas Kluge, Richard P Baum, Norman Bitterlich, Harshad R Kulkarni, Ulrike Schorr-Neufing, Cees J A van Echteld","doi":"10.1089/cbr.2024.0031","DOIUrl":"10.1089/cbr.2024.0031","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> In a prior, retrospective study, 76% of patients with advanced neuroendocrine tumors undergoing ¹⁷⁷Lu-DOTATOC molecular radiotherapy (MRT) showed their best response within 8 months from the first MRT cycle. In 24% of patients, latency was much greater up to >22 months after the first cycle, and long after near-complete decay of ¹⁷⁷Lu from the last cycle. An immune response induced by MRT seems a likely explanation. As a crude measure of immunocompetence, the authors investigated whether blood cell counts (BCCs) may have predictive value for MRT outcome with ¹⁷⁷Lu-DOTATOC. <b><i>Methods:</i></b> 56 Patients with neuroendocrine tumors (NET) were administered ¹⁷⁷Lu-DOTATOC (mean 2.1 cycles; range 1-4) with median radioactivity of 7.0 GBq/cycle at 3-month intervals. Patients' BCCs were evaluated for four responder categories: CR, PR, SD, and PD (RECIST 1.1). Furthermore, baseline BCCs were correlated with progression-free survival (PFS). Finally, BCCs of patients with (PMT⁺) and without prior medical therapy (PMT^-) were compared. <b><i>Results:</i></b> Significant differences between responder categories were found for baseline hemoglobin (Hb), erythrocytes, neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and LEHN-score, integrating lymphocyte, erythrocyte, and neutrophil counts, and Hb level, but not for leukocytes and platelets. LEHN-score yielded an almost complete separation between CR and PD groups. In analogy, PFS times showed significant correlations with baseline Hb, erythrocytes, neutrophils, lymphocytes, NLR, PLR, and LEHN-score, the LEHN-score showing the strongest correlation, but not with leukocytes and platelets. For PMT^- patients, median PFS was 34.5 months, compared with 20.8 months in PMT⁺ patients, with corresponding baseline lymphocyte (32.1 ± 9.6% vs. 24.5 ± 11.6%, <i>p</i> = 0.028) and neutrophil (54.9 ± 11.6% vs. 63.5 ± 13.7%, <i>p</i> = 0.039) counts. <b><i>Conclusion:</i></b> These findings emphasize the significance of an immune response to MRT for obtaining optimal therapy efficacy and support concepts to enhance the immune response of less immunocompetent patients before MRT. It seems advisable to avoid prior or concomitant immunosuppressant medical therapy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"541-550"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437846","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":"LINC00641 Inhibits the Development of Cutaneous Squamous Cell Carcinoma By Downregulating miR-424 in A431 Cells.","authors":"Wenmin Liu, Xinxin Liu","doi":"10.1089/cbr.2020.4325","DOIUrl":"10.1089/cbr.2020.4325","url":null,"abstract":"<p><p><b><i>Background:</i></b> Cutaneous squamous cell carcinoma (CSCC) is the most deadly disease among nonmelanoma skin cancers. LINC00641 plays a role in various cancers, but its role in CSCC has not been reported so far. <b><i>Methods and Materials:</i></b> The expression of LINC00641 and miR-424 in cells was detected by RT-qPCR. CCK-8 and colony formation assay were used to detect the proliferation of cells. Western blot was used to detect the expression levels of proliferation-, invasion-, and migration-related proteins. Wound Healing and Transwell experiments detected the ability of cell invasion and migration. In animal experiments, a tumor-bearing model was established in nude mice, and tumor volume was measured and photographed. The expression levels of proliferation-, invasion-, and migration-related proteins were detected by Western blot. <b><i>Results:</i></b> The expression of LINC00641 was significantly decreased in CSCC cell lines. The overexpression of LINC00641 at the cellular level inhibited the proliferation and migration of CSCC cell line A431 by downregulating the expression of miR-424. The overexpression of LINC00641 in animals inhibited the tumor volume of nude mice by downregulating the expression of miR-424 to inhibit the expression of proliferation- and migration-related proteins. <b><i>Conclusion:</i></b> LINC00641 inhibits the development of CSCC by downregulating miR-424.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"532-540"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38896883","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":"Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for <i>Cancer Biotherapy and Radiopharmaceuticals</i>.","authors":"Alessandra Alessi","doi":"10.1089/cbr.2024.48216.rfs2023","DOIUrl":"https://doi.org/10.1089/cbr.2024.48216.rfs2023","url":null,"abstract":"","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"39 7","pages":"477"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301445","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":"Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating <i>PIK3r1</i>-Mediated Glycose Metabolism.","authors":"Xiaolu Hong, Xiaoping Pan","doi":"10.1089/cbr.2023.0123","DOIUrl":"10.1089/cbr.2023.0123","url":null,"abstract":"<p><p><b><i>Background:</i></b> Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. <b><i>Methods:</i></b> Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (<i>PIK3R1</i>) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. <b><i>Results:</i></b> Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. <i>PIK3R1</i> was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of <i>PIK3R1</i>, <i>p-AKT</i>, <i>c-Myc</i>, <i>HK2</i>, and <i>PKM2</i>, decreased <i>FOXO3</i> expression, and weakened the adriamycin resistance in resistant cells. <b><i>Conclusions:</i></b> miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target <i>PIK3R1</i> and promoted adriamycin resistance in BC cells. [Figure: see text].</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"463-475"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289703","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":"Pyrotinib and Trastuzumab Plus Chemotherapy Serve as an Acceptable Neoadjuvant Regimen Exhibiting Good Efficacy and Tolerance in HER2-Positive Breast Cancer Patients.","authors":"Yibo Chen, Tianyi Zhang, Rui Zhang, Xuchen Cao","doi":"10.1089/cbr.2023.0175","DOIUrl":"10.1089/cbr.2023.0175","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Pyrotinib, a new irreversible dual pan-human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase inhibitor blocking EGFR and HER2, has achieved a promising efficacy for advanced HER2-positive (HER2⁺) breast cancer. This study intended to further investigate the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2⁺ breast cancer treatment. <b><i>Methods:</i></b> Thirty-eight HER2⁺ breast cancer patients who received neoadjuvant pyrotinib and trastuzumab plus chemotherapy (docetaxel and carboplatin) were retrospectively reviewed. Clinical response by Response Evaluation Criteria in Solid Tumors (RECIST), pathological complete response (pCR), and adverse events data was retrieved. <b><i>Results:</i></b> According to the RECIST, the complete response rate was 0.0%, 10.5%, and 15.8% after second-cycle, fourth-cycle, and sixth-cycle therapy, respectively; whereas the objective response rate was 76.3%, 92.1%, and 100.0%, accordingly. The total pCR (tpCR) rate was 52.6%, the pCR rate of the breast was also 52.6%, and the pCR rate of lymph nodes was 86.8%. The tpCR rate was lower in patients with HER2 immunohistochemistry (IHC)++ and amplification by fluorescent <i>in situ</i> hybridization (FISH) than in those with HER2 IHC+++ (14.3% vs. 61.3%, <i>p</i> = 0.024), which was also lower in patients with Ki-67 expression ≥30% than in those with Ki-67 expression <30% (40.0% vs. 76.9%, <i>p</i> = 0.031). The common adverse events included diarrhea (84.2%), anemia (73.7%), nausea and vomiting (63.2%), fatigue (50.0%), hypomagnesemia (44.7%), leukopenia (42.1%), thrombocytopenia (39.5%), elevated transaminase (36.8%), and pruritus (31.6%). <b><i>Conclusions:</i></b> Pyrotinib and trastuzumab plus chemotherapy serve as an acceptable neoadjuvant regimen exhibiting good efficacy and tolerance in HER2⁺ breast cancer patients, while further large-scale validation is warranted.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"435-440"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289704","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}