{"title":"<i>TIGD1</i> Is an Independent Prognostic Factor that Promotes the Progression of Colon Cancer.","authors":"Junwei Zou, Hesong Zhang, Zhaoying Wu, Weichao Hu, Tingting Zhang, Hao Xie, Yong Huang, Hailang Zhou","doi":"10.1089/cbr.2022.0052","DOIUrl":"10.1089/cbr.2022.0052","url":null,"abstract":"<p><p><b><i>Background:</i></b> Trigger transposable element-derived 1 (<i>TIGD1</i>) is a human-specific gene, but no studies have been conducted to determine its mechanism of action. Our aim is to ascertain the function and mode of action of <i>TIGD1</i> in the development of colon cancer. <b><i>Materials and Methods:</i></b> The authors used bioinformatics to analyze the relationship between <i>TIGD1</i> and the clinical characteristics of colon cancer, as well as its prognosis. A series of cell assays were conducted to assess the function of <i>TIGD1</i> in the proliferation and migration of colon cancer, and flow cytometry was used to explore its effects on apoptosis and the cell cycle. <b><i>Results:</i></b> The authors discovered that the expression of <i>TIGD1</i> was remarkably elevated in colon cancer. Clinical correlation analysis demonstrated that <i>TIGD1</i> expression was elevated in the tissues of advanced-stage patients, and it was remarkably elevated in individuals with both lymph node and distant metastasis. Further, the authors found that individuals showing elevated <i>TIGD1</i> expression levels had a shortened survival time. Univariate and multivariate Cox regression analyses revealed that <i>TIGD1</i> was an independent prognostic factor. Overexpression of the <i>TIGD1</i> gene remarkedly enhances the proliferation and metastasis of colon cancer cells and suppresses apoptosis. In addition, the overexpression of <i>TIGD1</i> can enhance the transition of tumor cells from the G1 toward the S phase. Western blot results suggested that <i>TIGD1</i> may promote the malignant activity of colon cancer cells via the Wnt/β-catenin signaling pathway, Bcl-2, N-cadherin, BAX, E-cadherin, CDK6, and CyclinD1. <b><i>Conclusions:</i></b> <i>TIGD1</i> may be an independent prognostic factor in the advancement of colon cancer, and therefore function as a therapeutic target.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"223-235"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10315020","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}
Marcel C Langenbach, Thomas J Vogl, Gulia Said, Jan-Erik Scholtz, Renate Hammerstingl, Tatjana Gruber-Rouh
{"title":"Lipiodol as a Predictive Indicator for Therapy Response to Transarterial Chemoembolization of Hepatocellular Carcinoma.","authors":"Marcel C Langenbach, Thomas J Vogl, Gulia Said, Jan-Erik Scholtz, Renate Hammerstingl, Tatjana Gruber-Rouh","doi":"10.1089/cbr.2020.4137","DOIUrl":"10.1089/cbr.2020.4137","url":null,"abstract":"<p><p><b><i>Background:</i></b> The predictive value of Lipiodol was evaluated for response evaluation of hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE) by analysis of the enhancement pattern during angiography and in postinterventional computed tomography (CT). <b><i>Materials and Methods:</i></b> This retrospective study included 30 patients (mean age 63 years, range: 36 to 82 years, 22 males) with HCC. Patients received three Lipiodol-based cTACE sessions, each followed by an unenhanced CT within 24-h. Contrast-enhanced magnetic resonance imaging (MRI) was acquired before and after the treatment to determine tumor response. Lipiodol enhancement pattern, tumor vascularization, and density were evaluated by angiography and CT. Initial tumor size and response to cTACE were analyzed by MRI according to modified response evaluation criteria in solid tumors (mRECIST) in a 4-week follow-up. <b><i>Results:</i></b> Analysis of HCC lesions (68 lesions in 30 patients) during cTACE revealed clear visibility and hypervascularization in angiography as a potential independent parameter able to predict tumor response. A significant correlation was found for response measurements by volume (<i>p</i> = 0.012), diameter (<i>p</i> = 0.006), and according to mRECIST (<i>p</i> = 0.039). The amount of Lipiodol and enhancement pattern in postinterventional CT did not correlate with therapy response. Measurements of Hounsfield unit values after cTACE do not allow sufficient prediction of the tumor response. <b><i>Conclusion:</i></b> Hypervascularized HCC lesions with clear visibility after Lipiodol administration in the angiography respond significantly better to cTACE compared to hypo- or nonvascularized lesions.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"196-202"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38848165","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":"Unraveling Interaction of Rhenium-188 Microspheres with Primary Hepatic Cancer Cell: A Breakthrough Study.","authors":"Aarti Aggarwal, Gurjeet Kaur, Ravjit Singh Jassal, Bikash Medhi, Bhagwant Rai Mittal, Jaya Shukla","doi":"10.1089/cbr.2023.0146","DOIUrl":"10.1089/cbr.2023.0146","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Hepatocellular carcinoma is a prevalent contributor to global mortality rates. The main palliative treatments are trans-arterial chemoembolization and selective intra-arterial radionuclide therapy. <b><i>Methods:</i></b> A novel freeze-dried nonradioactive microsphere kit formulation has been developed, and the behavior and therapeutic potential of <sup>188</sup>Re microspheres have been assessed. The microspheres were labeled with fluorescein isothiocyanate (FITC) and <sup>188</sup>ReO<sub>4</sub><sup>-</sup>. The uptake of FITC microspheres by HepG2 cells was examined at various time intervals. The impact of <sup>188</sup>Re microspheres on cell viability and the mode of cell death were investigated with HepG2 cells using MTT and Annexin FITC-V/propidium iodide (PI) apoptosis assay. <b><i>Results:</i></b> The labeling efficiency of microspheres was more than 99% with FITC and <sup>188</sup>ReO<sub>4</sub><sup>-</sup>. The maximum uptake of FITC microspheres by HepG2 cells was achieved at 6 h. The exposure to <sup>188</sup>Re microspheres has shown a decrease in cellular viability from 77.81% ± 0.015% to 42.03% ± 0.148% at 192 h of incubation (∼11 half-lives). The cellular uptake of <sup>188</sup>Re microspheres was 0.255-0.901 MBq. These values were concordant with Annexin FITC-V/PI apoptosis assay. At 192 h, 53.28% ± 0.01% of cells entered the apoptotic phase after treatment with <sup>188</sup>Re microspheres, and only 39.34% ± 0.02% of cells remained viable. However, in the cells treated with <sup>188</sup>ReO<sub>4</sub><sup>-</sup> alone, 74.86% ± 0.005% of cells were viable, and only 24.75% ± 0.577% of cells were in the early apoptotic phase at 192 h. <b><i>Conclusion:</i></b> The data revealed that <sup>188</sup>Re microspheres treatment led to significant growth inhibition in HepG2 cells compared with <sup>188</sup>ReO<sub>4</sub><sup>-</sup>.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"188-195"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139503098","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}
Ruoyang Li, Xuewei Zhao, Yunfei Huang, Chunxiao Li, Lei Liu, Meiqi Wang, Jiaxing Wang, Zhenchuan Song
{"title":"The Survival Benefit of Pegylated Liposomal Doxorubicin-Based Neoadjuvant Chemotherapy in the Management of Breast Cancer.","authors":"Ruoyang Li, Xuewei Zhao, Yunfei Huang, Chunxiao Li, Lei Liu, Meiqi Wang, Jiaxing Wang, Zhenchuan Song","doi":"10.1089/cbr.2024.0011","DOIUrl":"https://doi.org/10.1089/cbr.2024.0011","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> This study aims to evaluate the short-term outcomes and prognosis and the cardiac safety of pegylated liposomal doxorubicin (PLD)-based neoadjuvant chemotherapy (NAC) compared with epirubicin-based therapy in breast cancer treatment. <b><i>Methods:</i></b> In total, 304 patients diagnosed with stages II and III breast cancer were enrolled that included 97 cases treated with PLD and 207 controls treated with epirubicin in NAC. The effectiveness of the antibreast cancer treatment was evaluated using overall survival (OS) and disease-free survival (DFS) metrics, whereas cardiac toxicity was measured through the left ventricular ejection fraction (LVEF) and electrocardiogram (ECG) assessments. <b><i>Results:</i></b> The 5-year DFS and OS rates in the PLD group were 84.5% and 88.7% (with 15 recurrences and 11 deaths), respectively, whereas in the control group, these rates were 72.9% and 79.2% (with 56 recurrences and 43 deaths). Regarding cardiac toxicity, there was no significant difference in ECG abnormalities or LVEF decline between the two groups. <b><i>Conclusions:</i></b> The study suggests that PLD-based NAC may provide substantial benefits in terms of DFS and OS, along with a safe cardiac toxicity profile, in patients with stage II-III breast cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186386","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}
Jian Wen, Yan Ding, Shaohua Zheng, Xin Li, Ying Xiao
{"title":"Sevoflurane Suppresses Glioma Cell Proliferation, Migration, and Invasion Both <i>In Vitro</i> and <i>In Vivo</i> Partially Via Regulating KCNQ1OT1/miR-146b-5p/STC1 Axis.","authors":"Jian Wen, Yan Ding, Shaohua Zheng, Xin Li, Ying Xiao","doi":"10.1089/cbr.2020.3762","DOIUrl":"10.1089/cbr.2020.3762","url":null,"abstract":"<p><p><b><i>Background:</i></b> Sevoflurane (Sev), a volatile anesthetic agent, is widely used in neurosurgery for anesthesia maintenance, accompanied with antitumor activity postanesthesia in multiple human cancers, including glioma. However, the molecular mechanism of Sev in glioma is largely unclear, including associated informative noncoding RNAs, such as long noncoding RNAs (lncRNA) and microRNAs (miRNAs). <b><i>Methods:</i></b> Expression of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), miRNA <i>(miR)-146b-5p</i>, and stanniocalcin-1 (STC1) was measured by real-time quantitative polymerase chain reaction and Western blotting. Cell proliferation, apoptosis, migration, and invasion <i>in vitro</i> were examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, fluorescence-activated cell sorting method, and transwell assays, respectively. Tumor growth <i>in vivo</i> was determined by xenograft models. The direct interaction between genes was confirmed by dual-luciferase reporter assay. <b><i>Results:</i></b> Sev enhanced apoptotic rate, but inhibited cell viability, migration, and invasion abilities of human glioma A172 and U251 cells <i>in vitro</i>, as well as tumor growth inhibition <i>in vivo</i>. The tumor-suppressive role of Sev in glioma was accompanied with downregulated KCNQ1OT1 and STC1, and upregulated miR-146b-5p. Overexpression of KCNQ1OT1 through transfection reversed, while KCNQ1OT1 silencing aggravated the antitumor role of Sev in A172 and U251 cells. Moreover, KCNQ1OT1-mediated tumor-promoting activity in A172 and U251 cells under Sev treatment was abrogated by miR-146b-5p restoration or STC1 deletion. Essentially, KCNQ1OT1 could positively regulate STC1 by acting as miR-146b-5p decoy. <b><i>Conclusion:</i></b> KCNQ1OT1 knockdown mediated the role of Sev in glioma cell proliferation, apoptosis, migration, and invasion both <i>in vitro</i> and <i>in vivo</i> through miR-146b-5p/STC1 pathway.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"105-116"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38438472","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}
Dong Wang, Zhijun Wang, Xuedong Dai, Liang Zhang, Min Li
{"title":"Apigenin and Temozolomide Synergistically Inhibit Glioma Growth Through the <i>PI3K</i>/<i>AKT</i> Pathway.","authors":"Dong Wang, Zhijun Wang, Xuedong Dai, Liang Zhang, Min Li","doi":"10.1089/cbr.2020.4283","DOIUrl":"10.1089/cbr.2020.4283","url":null,"abstract":"<p><p><b><i>Background:</i></b> Glioma is a devastating disease with the worst prognosis among human malignant tumors. Although temozolomide (TMZ) improves the overall survival of glioma patients, there are still many glioma patients who are resistant to TMZ. In this study, we focused on the effect of apigenin (API) and TMZ on glioma cells <i>in vitro</i> and <i>in vivo</i>, and we studied the underlying molecular mechanisms. <b><i>Materials and Methods:</i></b> To investigate the effect of API on glioblastoma cell proliferation, cell viability was assessed after glioma cells were incubated with various concentrations of API with or without TMZ using MTT assays. Then, we explored the synergistic effect of API and TMZ on glioma cell cycle, apoptosis, and migration. To investigate the molecular mechanism behind the synergism of API and TMZ, we examined the related genes of the major signaling pathways involved in glioma pathogenesis by Western blotting. <b><i>Results:</i></b> In this study, we found that API significantly suppressed the proliferation of glioma cells in a dose- and time-dependent manner. Combining API and TMZ significantly induced glioma cells arrest at the G2 phase and inhibited glioma cells proliferation compared with API or TMZ alone. In addition, API promoted the ability of TMZ to induce glioma cells apoptosis and inhibit glioma cells invasion. Furthermore, compared with treatment with individual agents, the combination of API and TMZ significantly inhibited the growth of subcutaneous tumors in mice. These results implied that API could synergistically suppress the growth of glioma cells when combined with TMZ. Combining API and TMZ significantly inhibited the protein expression of <i>p-AKT</i>, <i>cyclin D1</i>, Bcl-2, Matrix Metallopeptidase 2, and Matrix Metallopeptidase 9. <b><i>Conclusion:</i></b> API and TMZ synergistically inhibited glioma growth through the <i>PI3K</i>/<i>AKT</i> pathway.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"125-132"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38839741","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":"Upregulation of miR-519d-3p Inhibits Viability, Proliferation, and G1/S Cell Cycle Transition of Oral Squamous Cell Carcinoma Cells Through Targeting CCND1.","authors":"Wenjie Zhang, Wei Hong","doi":"10.1089/cbr.2020.3984","DOIUrl":"10.1089/cbr.2020.3984","url":null,"abstract":"<p><p><b><i>Background:</i></b> MicroRNA (miR)-519d-3p suppresses tumor development, however, its role in oral squamous cell carcinoma (OSCC) has yet to be determined. <b><i>Materials and Methods:</i></b> OSCC and adjacent tissues were collected (<i>n</i> = 45 for adjacent; <i>n</i> = 21 for Stage I-II OSCC; <i>n</i> = 24 for Stage III-IV OSCC). The cell viability, proliferation, and cell cycle of OSCC were, respectively, assessed by the Cell Counting Kit-8 (CCK-8), colony formation assay, and flow cytometry. Relative expressions of cell cycle-regulated proteins (Cyclin D1 [CCND1], CDK4, and CDK6) and miR-519d-3p were measured with Western blot and quantitative real-time polymerase chain reaction as needed. Dual-luciferase reporter assay was performed to verify the prediction of TargetScan that miR-519d-3p and CCND1 shared potential binding sites. Correlation analysis between miR-519d-3p and CCND1 was performed with Pearson's correlation test. <b><i>Results:</i></b> In OSCC tissues, downregulating miR-519d-3p expression correlated with a higher tumor grade. Upregulating miR-519d-3p expression inhibited OSCC cell viability and proliferation, increased cells in G0/G1 phase and reduced those in S/G2 phase, and downregulated the expressions of cell cycle-related protein (CDK4, CDK6). CCND1 was the target gene of miR-519d-3p, and overexpressed CCND1 reversed the effects of upregulation of miR-519d-3p on suppressing the viability, proliferation, and cell cycle of OSCC cells. <b><i>Conclusions:</i></b> miR-519d-3p upregulation suppressed the cell viability, proliferation, and G1/S cell cycle transition of OSCC through targeting CCND1. The current findings provide a possible clinical option for OSCC treatment.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"153-163"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38486408","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":"Sevoflurane Represses Proliferation and Migration of Glioma Cells by Regulating the ANRIL/let-7b-5p Axis.","authors":"Yufeng Gao, Hui Ma, Dongnan Hou","doi":"10.1089/cbr.2020.3596","DOIUrl":"10.1089/cbr.2020.3596","url":null,"abstract":"<p><p><b><i>Background:</i></b> Glioma is a malignant brain tumor with poor prognosis. Sevoflurane has been shown to have antitumor effects in various cancers. However, the underlying role and mechanism of sevoflurane in glioma is still unclear. <b><i>Materials and Methods:</i></b> Glioma cell lines were exposed different concentrations of sevoflurane (sev). The cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. All protein levels were measured by Western blot. The levels of noncoding RNA in the INK4 locus (ANRIL) and let-7b-5p were detected by quantitative real-time polymerase chain reaction. The binding sites between ANRIL and let-7b-5p were predicted by StarBase v.3.0 and confirmed using dual-luciferase reporter assay. <b><i>Results:</i></b> Sevoflurane treatment suppressed proliferation and migration of glioma cells. The expression of ANRIL was downregulated in glioma cells after treatment with sevoflurane in a dose-dependent manner, and overexpression of ANRIL reversed sevoflurane-induced inhibition of proliferation and migration of glioma cells. Furthermore, let-7b-5p was targeted by ANRIL, and ANRIL knockdown recovered the promoting effects of silencing let-7b-5p on proliferation, migration, and JAK2/STAT3 pathway in sevoflurane-treated glioma cells. <b><i>Conclusions:</i></b> Sevoflurane hindered proliferation and migration through JAK2/STAT3 pathway mediated by ANRIL and let-7b-5p in glioma cells, indicating a new reference for the application of anesthetics like sevoflurane in glioma.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"117-124"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38285117","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":"<i>Call for Special Issue Papers:</i> Advances in Molecular Medicine.","authors":"Maulin P Shah","doi":"10.1089/cbr.2024.29017.cfp","DOIUrl":"https://doi.org/10.1089/cbr.2024.29017.cfp","url":null,"abstract":"","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708540","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}
K V Vimalnath, Ardhi Rajeswari, Anupam Dixit, Rubel Chakravarty, Haldhar D Sarma, Suyash Kulkarni, Ashish Jha, Ameya Puranik, Venkatesh Rangarajan, Madhumita Goswami, Sudipta Chakraborty
{"title":"[<sup>90</sup>Y]Yttria Alumino Silicate Glass Microspheres: A Biosimilar Formulation to \"TheraSphere\" for Cost-Effective Treatment of Liver Cancer.","authors":"K V Vimalnath, Ardhi Rajeswari, Anupam Dixit, Rubel Chakravarty, Haldhar D Sarma, Suyash Kulkarni, Ashish Jha, Ameya Puranik, Venkatesh Rangarajan, Madhumita Goswami, Sudipta Chakraborty","doi":"10.1089/cbr.2023.0118","DOIUrl":"10.1089/cbr.2023.0118","url":null,"abstract":"<p><p><b><i>Background:</i></b> Selective internal radiation therapy (SIRT) using a suitable β<sup>-</sup>-emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (<sup>90</sup>Y) [<i>T</i><sub>1/2</sub> = 64.2 h, <i>E</i><sub>β</sub>(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. <b><i>Objective:</i></b> The present study describes indigenous development and evaluation of intrinsically radiolabeled [<sup>90</sup>Y]yttria alumino silicate ([<sup>90</sup>Y]YAS) glass microsphere, a formulation biosimilar to \"TheraSphere\" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. <b><i>Methods:</i></b> YAS glass microspheres of composition 40Y<sub>2</sub>O<sub>3</sub>-20Al<sub>2</sub>O<sub>3</sub>-40SiO<sub>2</sub> (w/w) and diameter ranging between 20 and 36 μm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [<sup>90</sup>Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to <i>in vitro</i> evaluations and <i>in vivo</i> studies in healthy Wistar rats, customized doses of [<sup>90</sup>Y]YAS glass microspheres were administered in human patients. <b><i>Results:</i></b> [<sup>90</sup>Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (∼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent <i>in vitro</i> stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [<sup>90</sup>Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. <b><i>Conclusions:</i></b> The study confirmed the suitability of indigenously prepared [<sup>90</sup>Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"82-91"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543979","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}