Tumor Biology最新文献

{"title":"Poster Presentations' Abstracts.","authors":"","doi":"10.3233/TUB-239004","DOIUrl":"https://doi.org/10.3233/TUB-239004","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"45 s1","pages":"S47-S69"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851794","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":"A statement regarding the mass retraction of Iranian papers in November 2016.","authors":"Aram Mokarizadeh","doi":"10.3233/TUB-220031","DOIUrl":"https://doi.org/10.3233/TUB-220031","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"45 1","pages":"23-24"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9428731","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":"Book of Abstracts.","authors":"","doi":"10.3233/TUB-239001","DOIUrl":"https://doi.org/10.3233/TUB-239001","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"45 s1","pages":"S1-S3"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10861008","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":"Bithiophene derivative induced apoptosis and suppression of Akt pathway in mouse leukemic model.","authors":"Ali Samy Algharib, G. Shanab, Abdel-Rahman B Abdel-Ghaffar, Mohamed A Ismail, R. H. Mohamed","doi":"10.3233/tub-211538","DOIUrl":"https://doi.org/10.3233/tub-211538","url":null,"abstract":"BACKGROUND\u0000Bithiophene derivatives show a promising anti-cancer potential. We previously showed that Bithienyl Fluorobenzamidine (BFB) has an anti-proliferative effect against several leukemia cell lines. Acute myeloid leukemia (AML) accounts for 18% of the total leukemia cases worldwide with heavier burden during the past 30 years. Therefore, the main aim remains the discovery of safe and effective medications.\u0000\u0000\u0000OBJECTIVE\u0000The current research aims to investigate the anti-cancer efficacy of BFB and its effect on the apoptosis in the 7,12-Dimethylbenz[a]anthracene (DMBA) induced AML in mice.\u0000\u0000\u0000METHODS\u0000AML was induced in mice by DMBA and then treated by 2 different doses of BFB. After BFB treatment, the hematological and histological pattern changes was examined. Furthermore, the molecular effect of BFB on apoptosis, cell cycle markers and Protein kinase B (Akt) pathway was examined using qPCR, Western blotting and ELISA.\u0000\u0000\u0000RESULTS\u0000BFB treatment ameliorates leukemia histological and hematological markers significantly, despite non-significant changes in normal mice. This improvement exhibits cell cycle arrest and apoptosis induction, represented by elevation of tp53/p53, p21/p21, Caspase3 and downregulation of ckk1/Cdk1 in the bone marrow, as well as Akt pathway suppression.\u0000\u0000\u0000CONCLUSIONS\u0000Our results establishes BFB as a promising therapeutic candidate against AML through cell cycle arrest, apoptosis induction and Akt pathway modulation.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"13 1","pages":"53-67"},"PeriodicalIF":0.0,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90837375","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":"Tumor-associated CD3- and CD8-positive immune cells in colorectal cancer: The additional prognostic value of CD8+-to-CD3+ ratio remains debatable.","authors":"Jussi Kasurinen, J. Hagström, T. Kaprio, Ines Beilmann-Lehtonen, C. Haglund, C. Böckelman","doi":"10.3233/tub-211571","DOIUrl":"https://doi.org/10.3233/tub-211571","url":null,"abstract":"BACKGROUND\u0000A large number of infiltrating CD3- and CD8-positive inflammatory cells indicates an improved survival in colorectal cancer (CRC), similar to many other cancers.\u0000\u0000\u0000OBJECTIVE\u0000We investigated the prognostic value of different combinations of CD3- and CD8-positive immune cells in CRC patients.\u0000\u0000\u0000METHODS\u0000The densities of CD3- and CD8-positive cells in intratumoral and stromal tissues were evaluated from 539 patients, for which we calculated a CD3 tumor-stroma index, a CD8 tumor-stroma index, and a CD3-CD8 tumor-stroma index.\u0000\u0000\u0000RESULTS\u0000High CD3 and CD8 tumor-stroma indices associated with stage I to II disease (p <  0.001 for both). The CD3 tumor-stroma index associated with a colonic tumor location (p = 0.006), while the CD8 tumor-stroma index associated with right-sided tumors (p <  0.001) and histological grade 3 tumors (p = 0.032). High intratumoral and stromal densities for CD3- and CD8-positive immune cells, the CD3 tumor-stroma index, the CD8 tumor-stroma index, and the CD3-CD8 tumor-stroma index all indicated a better DSS.\u0000\u0000\u0000CONCLUSIONS\u0000The CD3 tumor-stroma index carries a strong prognostic value in CRC, and none of the CD3 and CD8 combinations we analyzed proved superior.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"343 1","pages":"37-52"},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79585202","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":"Vitamin B12 enhances the antitumor activity of 1,25-dihydroxyvitamin D3 via activation of caspases and targeting actin cytoskeleton.","authors":"Manar F Atoum,&nbsp;Foad E Alzoughool,&nbsp;Zainab A Al-Mazaydeh,&nbsp;Majdoleen S Rammaha,&nbsp;Lubna H Tahtamouni","doi":"10.3233/TUB-211536","DOIUrl":"https://doi.org/10.3233/TUB-211536","url":null,"abstract":"<p><strong>Background: </strong>1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an effective anticancer agent, and when combined with other agents it shows superior activities. Vitamin B12 has been shown to contribute to increasing the effectiveness of anticancer drugs when used in combination. Thus, the current study aimed at investigating the anticancer potential of the combination of 1,25(OH)2D3 and vitamin B12.</p><p><strong>Methods: </strong>MTT assay was used to determine the cytotoxic activity of combining 1,25(OH)2D3 and vitamin B12 against six different cancer cell lines and one normal cell line. The surviving fraction after clonogenic assay was measured, and the effects of 1,25(OH)2D3/B12 combination on the activity of different caspases, cell adhesion, actin cytoskeleton, cell morphology, and percentage of polarized cells were evaluated.</p><p><strong>Results: </strong>Vitamin B12 did not cause cytotoxicity, however, it enhanced the cytotoxicity of 1,25(OH)2D3 against cancer cells. The cytotoxic effects of 1,25(OH)2D3 and its combination with vitamin B12 was not evident in the normal mammary MCF10A cell line indicating cancer cell-specificity. The cytotoxic effects of 1,25(OH)2D3/B12 combination occurred in a dose-dependent manner and was attributed to apoptosis induction which was mediated by caspase 4 and 8. Moreover, 1,25(OH)2D3/B12-treated cells showed enhanced inhibition of clonogenic tumor growth, reduced cell adhesion, reduced cell area, reduced percentage of cell polarization, and disorganized actin cytoskeleton resulting in reduced migratory phenotype when compared to cells treated with 1,25(OH)2D3 alone.</p><p><strong>Conclusion: </strong>1,25(OH)2D3 and vitamin B12 exhibited synergistic anticancer effects against different cancer cell lines. The combination therapy of 1,25(OH)2D3 and vitamin B12 may provide a potential adjunctive treatment option for some cancer types.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"17-35"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39935488","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":"Role of colony-stimulating factor 1 in the neoplastic process of tenosynovial giant cell tumor.","authors":"William D Tap, John H Healey","doi":"10.3233/TUB-220005","DOIUrl":"10.3233/TUB-220005","url":null,"abstract":"<p><p>Tenosynovial giant cell tumors (TGCTs) are rare, locally aggressive, mesenchymal neoplasms, most often arising from the synovium of joints, bursae, or tendon sheaths. Surgical resection is the first-line treatment, but recurrence is common, with resulting impairments in patients' mobility and quality of life. Developing and optimizing the role of systemic pharmacologic therapies in TGCT management requires an understanding of the underlying disease mechanisms. The colony-stimulating factor 1 receptor (CSF1R) has emerged as having an important role in the neoplastic processes underlying TGCT. Lesions appear to contain CSF1-expressing neoplastic cells derived from the synovial lining surrounded by non-neoplastic macrophages that express the CSF1R, with lesion growth stimulated by both autocrine effects causing proliferation of the neoplastic cells themselves and by paracrine effects resulting in recruitment of CSF1 R-bearing macrophages. Other signaling pathways with evidence for involvement in TGCT pathogenesis include programmed death ligand-1, matrix metalloproteinases, and the Casitas B-cell lymphoma family of ubiquitin ligases. While growing understanding of the pathways leading to TGCT has resulted in the development of both regulatory approved and investigational therapies, more detail on underlying disease mechanisms still needs to be elucidated in order to improve the choice of individualized therapies and to enhance treatment outcomes.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"44 1","pages":"239-248"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10355512","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}

{"title":"Induction of alternative NF-κB within TAg-induced basal mammary tumors in activation-resistant inhibitor of κ-B kinase (IKKα) mutant mice.","authors":"Fares Ould-Brahim,&nbsp;Andrea Sau,&nbsp;David A Carr,&nbsp;Tianqi Jiang,&nbsp;M A Christine Pratt","doi":"10.3233/TUB-220006","DOIUrl":"https://doi.org/10.3233/TUB-220006","url":null,"abstract":"<p><strong>Background: </strong>The alternative NF-κB pathway is activated by the NF-κB-inducing kinase (NIK) mediated phosphorylation of the inhibitor of κ-B kinase α (IKKα). IKKα then phosphorylates p100/NFKB2 to result in its processing to the active p52 subunit. Evidence suggests that basal breast cancers originate within a subpopulation of luminal progenitor cells which is expanded by signaling to IKKα.</p><p><strong>Objective: </strong>To determine the role of IKKα in the development of basal tumors.</p><p><strong>Methods: </strong>Kinase dead IkkαAA/AA mice were crossed with the C3(1)-TAg mouse model of basal mammary cancer. Tumor growth and tumor numbers in WT and IkkαAA/AA mice were assessed and immunopathology, p52 expression and stem/progenitor 3D colony forming assays were performed. Nik-/- mammary glands were isolated and mammary colonies were characterized.</p><p><strong>Results: </strong>While tumor growth was slower than in WT mice, IkkαAA/AA tumor numbers and pathology were indistinguishable from WT tumors. Both WT and IkkαAA/AA tumors expressed p52 except those IkkαAA/AA tumors where NIK, IKKαAA/AA and ErbB2 were undetectable. Colonies formed by WT and IkkαAA/AA mammary cells were nearly all luminal/acinar however, colony numbers and sizes derived from IkkαAA/AA cells were reduced. In contrast to IkkαAA/AA mice, virgin Nik-/- mammary glands were poorly developed and colonies were primarily derived from undifferentiated bipotent progenitor cells.</p><p><strong>Conclusions: </strong>C3(1)-TAg induced mammary tumors express p100/p52 even without functional IKKα. Therefore the development of basal-like mammary cancer does not strictly rely on IKKα activation. Signal-induced stabilization of NIK may be sufficient to mediate processing of p100NFKB2 which can then support basal-like mammary tumor formation. Lastly, in contrast to the pregnancy specific role of IKKα in lobuloalveogenesis, NIK is obligatory for normal mammary gland development.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"187-203"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33462098","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":"MicroRNA-99b-5p targets mTOR/AR axis, induces autophagy and inhibits prostate cancer cell proliferation.","authors":"Suryakant Niture,&nbsp;Lucas Tricoli,&nbsp;Qi Qi,&nbsp;Sashi Gadi,&nbsp;Kala Hayes,&nbsp;Deepak Kumar","doi":"10.3233/TUB-211568","DOIUrl":"https://doi.org/10.3233/TUB-211568","url":null,"abstract":"<p><strong>Objectives: </strong>MicroRNAs (miRNAs) are the small non-coding regulatory RNA molecules involved in gene regulation via base-pairing with complementary sequences in mRNAs. The dysregulation of specific miRNAs, such as miR-99b-5p (miR-99b), is associated with prostate cancer (PCa) progression. However, the mechanistic role of miR-99b in PCa remains to be determined. In this study, we aimed to investigate the functional and clinical significance of miR-99b in PCa.</p><p><strong>Study design: </strong>The expression of miR-99b and its downstream targets mTOR/AR in the PCa samples were analyzed by RT/qPCR. The effects of miR-99b overexpression/inhibition on PCa cell survival/proliferation, spheroid formation, and cell migration were examined by specific assays. Luciferase reporter assays were performed to determine the binding of miR-99b to 3' untranslated region (UTR) of the mTOR gene. The effects of miR-99b on the expression of mTOR, AR, and PSA proteins, as well as on AKT/mTOR signaling, autophagy, and neuroendocrine differentiation markers were analyzed by western blotting. The expression of miR-99b, mTOR, AR, PSA in AR-negative PC3 and AR-positive LNCaP cells was analyzed by RT/qPCR. The effect of miR-99b on global gene expression in PC3 cells was analyzed by RNA-seq.</p><p><strong>Results: </strong>The expression of miR-99b was downregulated in tumor samples from PCa patients, whereas the expression of mTOR and AR was upregulated. In PCa cell lines, overexpression of miR-99b inhibited cell proliferation and cell colony/spheroid formation; induced apoptosis, and increased sensitivity towards docetaxel (DTX). In contrast, inhibition of miR-99b by miR-99b inhibitor resulted in increased cell growth in PCa cells. Mechanistically, miR-99b inhibited the expression of the mammalian target of the rapamycin (mTOR) gene by binding to its 3' UTR and induced autophagy. Furthermore, miR-99b inhibited androgen receptor (AR) activity in LNCaP cells and induced apoptosis. Activation of AR signaling by dihydrotestosterone (DHT) downregulated miR-99b expression and promoted cell PCa cell growth/survival, whereas inactivation of mTOR by rapamycin or AR by enzalutamide decreased miR-99b mediated PCa cell growth.</p><p><strong>Conclusion: </strong>Our data suggest that miR-99b functions as a tumor suppressor by targeting the mTOR/AR axis in PCa cells, implicating miR-99b as a novel biomarker and therapeutic target for PCa management.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"107-127"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40488476","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":"β-Catenin is reduced in membranes of human prolactinoma cells and it is inhibited by temozolomide in prolactin secreting tumor models.","authors":"Gianina Demarchi,&nbsp;Sofía Valla,&nbsp;Sofía Perrone,&nbsp;Agustina Chimento,&nbsp;Nadia Bonadeo,&nbsp;Daiana Luján Vitale,&nbsp;Fiorella Mercedes Spinelli,&nbsp;Andrés Cervio,&nbsp;Gustavo Sevlever,&nbsp;Laura Alaniz,&nbsp;Silvia Berner,&nbsp;Carolina Cristina","doi":"10.3233/TUB-211500","DOIUrl":"https://doi.org/10.3233/TUB-211500","url":null,"abstract":"<p><strong>Introduction: </strong>Prolactinomas are the most frequent pituitary tumor subtype. Despite most of them respond to medical treatment, a proportion are resistant and become a challenge in clinical management. Wnt/β-Catenin pathway has been implicated in several cancers including pituitary tumors and other sellar region malignancies. Interestingly, Wnt/β-Catenin inhibition augments the cytotoxicity of the chemotherapeutic agent Temozolomide (TMZ) in different cancers. TMZ is now being implemented as rescue therapy for aggressive pituitary adenoma treatment. However, the molecular mechanisms associated with TMZ action in pituitary tumors remain unclear.</p><p><strong>Objectives: </strong>Our aims in the present study were to evaluate differential β-Catenin expression in human resistant prolactinomas and Wnt/β-Catenin signaling activation and involvement in Prolactin (PRL) secreting experimental models treated with TMZ.</p><p><strong>Results: </strong>We first evaluated by immunohistochemistry β-Catenin localization in human resistant prolactinomas in which we demonstrated reduced membrane β-Catenin in prolactinoma cells compared to normal pituitaries, independently of the Ki-67 proliferation indexes. In turn, in vivo 15 mg/kg of orally administered TMZ markedly reduced PRL production and increased prolactinoma cell apoptosis in mice bearing xenografted prolactinomas. Intratumoral β-Catenin strongly correlated with Prl and Cyclin D1, and importantly, TMZ downregulated both β-Catenin and Cyclin D1, supporting their significance in prolactinoma growth and as candidates of therapeutic targets. When tested in vitro, TMZ directly reduced MMQ cell viability, increased apoptosis and produced G2/M cell cycle arrest. Remarkably, β-Catenin activation and VEGF secretion were inhibited by TMZ in vitro.</p><p><strong>Conclusions: </strong>We concluded that dopamine resistant prolactinomas undergo a β-Catenin relocalization in relation to normal pituitaries and that TMZ restrains experimental prolactinoma tumorigenicity by reducing PRL production and β-Catenin activation. Together, our findings contribute to the understanding of Wnt/β-Catenin implication in prolactinoma maintenance and TMZ therapy, opening the opportunity of new treatment strategies for aggressive and resistant pituitary tumors.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"85-105"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40488475","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}