Janina Baranowska-Kortylewicz, John G Sharp, Timothy R McGuire, Shantharam Joshi, Don W Coulter
{"title":"Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis.","authors":"Janina Baranowska-Kortylewicz, John G Sharp, Timothy R McGuire, Shantharam Joshi, Don W Coulter","doi":"10.1089/cbr.2019.3112","DOIUrl":"https://doi.org/10.1089/cbr.2019.3112","url":null,"abstract":"<p><p>Osteosarcoma (OST) is the most common bone tumor in children and adolescents with a second peak of incidence in elderly adults usually diagnosed as secondary tumors in Paget's disease or irradiated bone. Subjects with metastatic disease or whose disease relapses after the initial therapy have a poor prognosis. Moreover, multifocal OST contains tumor-initiating cells that are resistant to chemotherapy. The use of aggressive therapies in an attempt to eradicate these cells can have long-term negative consequences in these vulnerable patient populations. <sup>227</sup>Th-labeled molecular probes based on ligands to OST-associated receptors such as IGF-1R (insulin-like growth factor receptor 1), HER2 (human epidermal growth factor receptor 2), and PSMA (prostate-specific membrane antigen) are expected to detect and treat osseous and nonosseous sites of multifocal OST. Published reports indicate that <sup>227</sup>Th has limited myelotoxicity, can be stably chelated to its carriers and, as it decays at targeted sites, <sup>227</sup>Th produces <sup>223</sup>Ra that is subsequently incorporated into the areas of increased osteoblastic activity, that is, osseous metastatic lesions. Linear energy transfer of α particles emitted by <sup>227</sup>Th and its daughter <sup>223</sup>Ra is within the range of the optimum relative biological effectiveness. The radiotoxicity of α particles is virtually independent of the phase in the cell cycle, oxygenation, and the dose rate. For these reasons, even resistant OST cells remain susceptible to killing by high-energy α particles, which can also kill adjacent quiescent OST cells or cells with low expression of targeted receptors. Systemic side effects are minimized by the limited range of these intense radiations. Quantitative single-photon emission computed tomography of <sup>227</sup>Th and <sup>223</sup>Ra is feasible. Additionally, the availability of radionuclide pairs, for example, <sup>89</sup>Zr for positron emission tomography and <sup>227</sup>Th for therapy, establish a strong basis for the theranostic use of <sup>227</sup>Th in the individualized treatment of multifocal OST.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"418-424"},"PeriodicalIF":3.4,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2019.3112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37656825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viviana Frantellizzi, Laura Cosma, Gabriele Brunotti, Arianna Pani, Angela Spanu, Susanna Nuvoli, Flaminia De Cristofaro, Liana Civitelli, Giuseppe De Vincentis
{"title":"Targeted Alpha Therapy with Thorium-227.","authors":"Viviana Frantellizzi, Laura Cosma, Gabriele Brunotti, Arianna Pani, Angela Spanu, Susanna Nuvoli, Flaminia De Cristofaro, Liana Civitelli, Giuseppe De Vincentis","doi":"10.1089/cbr.2019.3105","DOIUrl":"https://doi.org/10.1089/cbr.2019.3105","url":null,"abstract":"<p><p>Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (<sup>223</sup>Ra), the first-in-class α-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (<sup>227</sup>Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter <sup>227</sup>Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies <sup>227</sup>Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike <sup>223</sup>Ra, the parent radionuclide <sup>227</sup>Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of <sup>227</sup>Th TAT in the treatment of several solid as well as hematologic malignancies.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"437-445"},"PeriodicalIF":3.4,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2019.3105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37567851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression and Significance of Periostin in Tissues and Serum in Oral Leukoplakia and Squamous Cell Carcinoma.","authors":"Wei-Qun Guan, Qun Li, Qi-Ming Ouyang","doi":"10.1089/cbr.2018.2764","DOIUrl":"https://doi.org/10.1089/cbr.2018.2764","url":null,"abstract":"<p><p><b><i>Objective:</i></b> This study aims to investigate the expression changes of periostin (PN or OSF-2) in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and analyze its significance in the development of OSCC. <b><i>Study Design:</i></b> The expression of periostin was detected from tissue specimens and serum obtained from normal mucosa, OLK and OSCC by immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. <b><i>Results:</i></b> Periostin was significantly overexpressed in OLK and OSCC, when compared with normal controls (<i>p</i> < 0.05). Furthermore, the overexpression of periostin was positively correlated with TNM stage, depth of invasion, and lymph node metastasis (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> The overexpression of periostin may be involved in the carcinogenesis process of OLK, which may be used as a marker for detecting OLK. In addition, periostin serum levels can be used as a potential indicator of invasion and a prognosis target for OSCC.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"444-450"},"PeriodicalIF":3.4,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2018.2764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40538341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li-Juan Zhang, Xue-Qin Li, Cun-De Wang, Li Zhuang, Quan Gong, Shi-Juan Li, Xin Liu, Hui Dong, Xi-Cai Wang
{"title":"The Correlation of Visfatin and Its Gene Polymorphism with Non-Small Cell Lung Cancer.","authors":"Li-Juan Zhang, Xue-Qin Li, Cun-De Wang, Li Zhuang, Quan Gong, Shi-Juan Li, Xin Liu, Hui Dong, Xi-Cai Wang","doi":"10.1089/cbr.2018.2526","DOIUrl":"https://doi.org/10.1089/cbr.2018.2526","url":null,"abstract":"<p><p><b><i>Objective:</i></b> To investigate the protein expression of visfatin and its gene polymorphism in non-small cell lung cancer (NSCLC) patients. <b><i>Methods:</i></b> The plasma level of visfatin was detected by enzyme-linked immunosorbent assay, and the genotypes rs59744560, rs9770242, and rs61330082 in the visfatin gene were detected by gene sequencing. <b><i>Result:</i></b> This study revealed that plasma levels of visfatin in NSCLC patients were significantly higher than the levels in healthy people (<i>p</i> < 0.01). The high level of plasma visfatin was found to be significantly correlated with TNM stage (<i>p</i> < 0.05). No mutations were detected in rs59744560 and rs9770242 loci. Three genotypes (CC, CT, and TT) were detected in rs61330082 locus, and the differences in the frequency distribution of these genotypes were significant in the two groups (<i>p</i> < 0.05). Central obesity and the CC genotype were independent risk factors in the pathogenesis of NSCLC (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> The plasma visfatin level in NSCLC patients significantly increased, and high plasma visfatin levels were correlated with tumor stage. Gene polymorphism was found in the visfatin gene rs61330082 locus. The CC genotype might increase the risk for patients suffering from NSCLC, while the CT genotype, TT genotype, and T allele may reduce the risk of NSCLC. The rs61330082 locus can be used as genetic markers of high-risk populations.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"460-465"},"PeriodicalIF":3.4,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2018.2526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40444921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renata Madru, Michael Budassi, Helene Benveniste, Hedok Lee, S David Smith, David J Schlyer, Paul Vaska, Linda Knutsson, Sven-Erik Strand
{"title":"Simultaneous Preclinical Positron Emission Tomography-Magnetic Resonance Imaging Study of Lymphatic Drainage of Chelator-Free <sup>64</sup>Cu-Labeled Nanoparticles.","authors":"Renata Madru, Michael Budassi, Helene Benveniste, Hedok Lee, S David Smith, David J Schlyer, Paul Vaska, Linda Knutsson, Sven-Erik Strand","doi":"10.1089/cbr.2017.2412","DOIUrl":"https://doi.org/10.1089/cbr.2017.2412","url":null,"abstract":"<p><strong>Background: </strong>Hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) systems have been taken in use as new clinical diagnostic tools including detection and therapy planning of cancer. To reduce the amount of contrast agents injected in patients while fully benefitting both modalities, dual-modality probes are required.</p><p><strong>Material and methods: </strong>This study was first aimed at developing a hybrid PET-MRI probe by labeling superparamagnetic iron oxide nanoparticles (SPIONs) with <sup>64</sup>Cu using a fast and chelator-free conjugation method, and second, to demonstrate the ability of the agent to target sentinel lymph nodes (SLNs) in vivo using simultaneous PET-MRI imaging.</p><p><strong>Results: </strong>High labeling efficiency of 97% produced within 10-15 min was demonstrated at room temperature. <sup>64</sup>Cu-SPIONs were chemically stable in mouse serum for 24 h and after intradermal injection in the hind paw of C57BL/6J mice, demonstrated specific accumulation in the SLN. Simultaneous PET-MRI clearly demonstrated visualization of <sup>64</sup>Cu-SPIONs, in dynamic and static imaging sequences up to 24 h after administration.</p><p><strong>Conclusion: </strong>The use of a single hybrid probe and simultaneous hybrid imaging provides an efficient, complementary integration of quantitation and is expected to improve preoperative planning and intraoperative guidance of cancer treatments.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"213-220"},"PeriodicalIF":3.4,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2017.2412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40533748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinyin Yan, Bo Song, Wanning Hu, Ying Meng, Fengling Niu, Xiaochen Han, Yuhui Ge, Ning Li
{"title":"Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells.","authors":"Jinyin Yan, Bo Song, Wanning Hu, Ying Meng, Fengling Niu, Xiaochen Han, Yuhui Ge, Ning Li","doi":"10.1089/cbr.2017.2348","DOIUrl":"https://doi.org/10.1089/cbr.2017.2348","url":null,"abstract":"<p><strong>Objective: </strong>Doxorubicin (DOX) can be used to treat malignant tumors, but with multiple adverse effects. Graphene oxide-polyethylene glycol (GO-PEG) is a novel nanoscale carrier material and can elevate solubility and biocompatibility of drugs. This study prepared a GO-PEG-DOX complex, whose toxicity and antitumor effects were evaluated on mouse EMT-6 breast cancer cells.</p><p><strong>Materials and methods: </strong>GO-PEG-DOX complex was prepared for calculating the drug carrier rate of DOX on GO-PEG by MV approach. EMT-6 cells were treated with 40 μg/mL GO-PEG, 1 μg/mL DOX, or 40 μg/mL +1 μg/mL GO-PEG-DOX for 72 h of incubation. Cells without treatment were considered the control group. Cell survival rate and apoptotic rate were tested at different time points.</p><p><strong>Results: </strong>GO-PEG and GO-PEG-DOX complex were successfully prepared with satisfactory solubility. After 72 h of incubation, EMT-6 cells after GO-PEG-DOX treatment had significantly higher survival rate than GO-PEG group (p < 0.05). All three treatment groups had significantly elevated apoptotic rates than control group (p < 0.05). GO-PEG-DOX group had much more apoptosis (p < 0.05 compared with DOX group). Moreover, with elongated treatment time, all groups showed decreased survival rate (p < 0.05).</p><p><strong>Conclusion: </strong>GO-PEG did not reduce the cytotoxicity of DOX on EMT-6 cells. GO-PEG-DOX complex can increase the water solubility and targeting sensitivity of DOX, with facilitating effects on DOX-induced tumor cell apoptosis.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"125-130"},"PeriodicalIF":3.4,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2017.2348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40437843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Influence of POLG on Radiosensitivity of Nasopharyngeal Carcinoma Cells.","authors":"Ruiqing Chen, Zeng Wang, Ruilong Lan, Fei Huang, Jinrong Chen, Yuanteng Xu, Hengshan Zhang, Lurong Zhang","doi":"10.1089/cbr.2017.2346","DOIUrl":"https://doi.org/10.1089/cbr.2017.2346","url":null,"abstract":"<p><strong>Background and objective: </strong>There is a high incidence of nasopharyngeal carcinoma (NPC), malignant head and neck tumors, in southern China. Radioresistance is the main cause affecting the efficacy of NPC treatments. The POLG gene particularly plays an important role in radiation-induced damage repair. In this study, the authors established RNAi CNE-1 and CNE-2 knockdown in two NPC cell lines to observe whether this gene affects the radiosensitivity of NPC cells.</p><p><strong>Materials and methods: </strong>Four short hairpin RNA (shRNA) expression plasmids targeting POLG gene were constructed and transfected into the NPC cell lines CNE-1 and CNE-2. Screening was performed to evaluate the stable expression of cloned cells, which were named CNE-1/POLG-shRNA1, CNE-1/POLG-shRNA2, CNE-2/POLG-shRNA1, and CNE-2/POLG-shRNA2. The negative controls CNE-1/Neg-shRNA and CNE-2/Neg-shRNA were additionally used. The MTT method, flow cytometry, clone formation analysis, cell migration, and other experimental methods were employed to verify changes in the radiosensitivity of the NPC cells.</p><p><strong>Results: </strong>Fluorescent quantitative PCR and Western blot confirmed the downregulation of the PLOG gene through diminished PLOG messenger RNA and protein levels. Consequently, the authors report the stable knockdown of the POLG gene in an NPC model. Dose-dependent radiation exposure of POLG inhibited NPC cell growth and increased apoptosis compared with control cells (p < 0.01), as demonstrated through colony formation assay and flow cytometry. Functional assays indicated that knockdown of the POLG in CNE-1 and CNE-2 cells remarkably reduced cell viability and proliferation. Specifically, POLG knockdown led to G1 phase arrest and apoptosis.</p><p><strong>Conclusions: </strong>Overall, the authors conclude that POLG downregulation alters the radiosensitivity of NPC cells, indicating that the gene is likely involved in conferring the radiation response of the cells. In addition, findings in this study suggest a novel role for POLG as a potential predictive marker for NPC radiotherapy efficiency. POLG gene can be used as a potential clinical target to effectively improve the radiosensitivity of NPC.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"146-154"},"PeriodicalIF":3.4,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2017.2346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40537928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NVP-BEZ235, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, prominently enhances radiosensitivity of prostate cancer cell line PC-3.","authors":"Wenjie Zhu, Weijiang Fu, Likuan Hu","doi":"10.1089/cbr.2012.1443","DOIUrl":"https://doi.org/10.1089/cbr.2012.1443","url":null,"abstract":"<p><strong>Background: </strong>Aberrant activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway may account for development of radioadaptation and is not rare in prostate cancer. Neither PI3K nor mTOR blockade could completely inhibit the pathway owing to paradoxical feedback, so we anticipate dual PI3K/mTOR blockade by NVP-BEZ235 to radiosensitize prostate cancer cells.</p><p><strong>Methods: </strong>We investigated into the radiosensitizing effect of NVP-BEZ235 on PC-3 cells, which are devoid of androgen receptors. Clonogenic survival and MTT assays were performed, and to pursue underlying cellular changes flow cytometric analysis of cell cycle and apoptosis as well as western blot were carried out.</p><p><strong>Results: </strong>Exposure to NVP-BEZ235 and irradiation caused a greater degree of survival inhibition than ionizing radiation (IR) or BEZ235 alone. Dual PI3K/mTOR blockade along with IR induced a G2/M arrest and enhanced proapoptotic effect. NVP-BEZ235 radiosensitized PC-3 cells through counteracting constitutive as well as IR-triggered activation of Akt/mTOR signaling.</p><p><strong>Conclusions: </strong>Our study demonstrated that the dual PI3K/mTOR inhibitor NVP-BEZ235 prominently improved the radiosensitivity of PC-3 cells. It sensitized tumor cells to irradiation via interruption of cell cycle progression and augmentation of cell apoptosis, which was due to its constraint on constitutive and IR-elicited PI3K/Akt/mTOR signaling activation.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"665-73"},"PeriodicalIF":3.4,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2012.1443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31507297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maneesh Jain, Suprit Gupta, Sukhwinder Kaur, Moorthy P Ponnusamy, Surinder K Batra
{"title":"Emerging trends for radioimmunotherapy in solid tumors.","authors":"Maneesh Jain, Suprit Gupta, Sukhwinder Kaur, Moorthy P Ponnusamy, Surinder K Batra","doi":"10.1089/cbr.2013.1523","DOIUrl":"https://doi.org/10.1089/cbr.2013.1523","url":null,"abstract":"<p><p>Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of minimal residual and micrometastatic disease. As a result several modalities for localized therapy and models of minimal disease have been developed for preclinical evaluation. This review provides a brief update on the recent efforts toward improving the efficacy of RIT for solid tumors, and development of RIT strategies for minimal disease associated with solid tumors. Further, some of promising approaches to improve tumor targeting, which showed promise in the past, but have now been ignored are also discussed.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"639-50"},"PeriodicalIF":3.4,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2013.1523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31571693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Armando Pérez-Torres, Jesús Vera-Aguilera, Juan Carlos Hernaiz-Leonardo, Eduardo Moreno-Aguilera, Diego Monteverde-Suarez, Carlos Vera-Aguilera, Daniel Estrada-Bárcenas
{"title":"The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.","authors":"Armando Pérez-Torres, Jesús Vera-Aguilera, Juan Carlos Hernaiz-Leonardo, Eduardo Moreno-Aguilera, Diego Monteverde-Suarez, Carlos Vera-Aguilera, Daniel Estrada-Bárcenas","doi":"10.1089/cbr.2012.1438","DOIUrl":"https://doi.org/10.1089/cbr.2012.1438","url":null,"abstract":"<p><strong>Purpose: </strong>The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal.</p><p><strong>Experimental design: </strong>C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C).</p><p><strong>Results: </strong>The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (p<0.05) in the treated mice. The overall survival rates obtained with surgical treatment at 6 months were 83.33% for group A, 40% for group B, and 0% for group C, with significant differences (p<0.05) among the groups.</p><p><strong>Conclusions: </strong>The GK1 peptide demonstrated therapeutic properties in a mouse melanoma model, as treatment resulted in a significant increase in the mean survival time of the treated animals (42.58%). The potential for GK1 to be used as a primary or adjuvant component of chemotherapeutic cocktails for the treatment of experimental and human cancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"682-90"},"PeriodicalIF":3.4,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2012.1438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31213797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}