Cancer Translational Medicine最新文献

{"title":"Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines","authors":"Javier de la Rosa, Alejandro Urdiciain, Juan Aznar-Morales, B. Meléndez, J. Rey, M. Idoate, J. Castresana","doi":"10.4103/ctm.ctm_12_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_12_18","url":null,"abstract":"Aim: Glioblastoma is the most malignant primary brain tumor. The treatment consists of surgery, with or without radiotherapy, and temozolomide, with a life expectancy of 12–15 months after diagnosis. Glioblastoma is resistant to conventional antitumor therapies. In this work, we present a preliminary in vitro study of two epigenetic drugs against GOS-3 glioblastoma cells. Methods: We used (1) panobinostat, a histone deacetylase inhibitor, and (2) 3-deazaneplanocin-A (DZ-Nep), an inhibitor of enhancer of zeste homolog 2 (EZH2) (enzyme of the polycomb repressor complex 2, polycomb group of proteins that trimethylate lysine 27 of histone 3-H3K27 me3-), as treatments that might modulate the PI3K pathway, affected in GOS-3 cells due to PTEN haploinsufficiency. The glioblastoma cell line GOS-3 was exposed to DZ-Nep and panobinostat treatments, separately and in combination, over a period of 2 days, after which cell migration, clonogenicity, and molecular expression characterization assays were performed. Results: Panobinostat alone or the combination of panobinostat plus DZ-Nep inhibited clonogenicity, metastasis, angiogenesis, epithelial–mesenchymal transition, and entry in the S phase of the cell cycle and induced apoptosis in GOS-3 glioblastoma cells. On the contrary, DZ-Nep inhibited cell migration (single treatment) and O(6)-methylguanine-DNA methyltransferase expression (DZ-Nep or double treatment). Conclusion: Panobinostat alone or the combination of panobinostat and DZ-Nep induce apoptosis and inhibit in vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"65 1","pages":"39 - 47"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91477904","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":"The mechanism of BMI1 in regulating cancer stemness maintenance, metastasis, chemo- and radiation resistance","authors":"Xiaoshan Xu, Zhen Wang, Nan Liu, Pengxing Zhang, Hui Liu, Jing Qi, Y. Tu","doi":"10.4103/ctm.ctm_7_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_7_18","url":null,"abstract":"BMI1 is involved in the occurrence and development of many types of cancer through a variety of signaling pathways. BMI1, which is overexpressed in cancer, is often associated with chemo- and radiation resistance and poor prognosis in cancer patients. This article reviews the current understanding of the mechanism of BMI1 in maintaining tumor stemness, promoting metastasis, and inducing chemo- and radiation resistance, aiming at providing updated information supportive of targeting BMI1 in cancer treatment.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"381 ","pages":"59 - 63"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91519564","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":"Suppressive effect of mesenchymal stromal cells on interferon-γ-producing capability of spleen cells was specifically enhanced through humoral mediator(s) from mouse oral squamous cell carcinoma Sq-1979 Cells In Vitro","authors":"T. Inagaki, M. Mizuno-Kamiya, E. Takayama, Harumi Kawaki, E. Chihara, Y. Muramatsu, S. Sumitomo, N. Kondoh","doi":"10.4103/ctm.ctm_34_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_34_17","url":null,"abstract":"Aim: The aim of this study was to compare the immunomodulatory effects in the tumor milieu of mouse oral squamous cell carcinoma (OSCC) cells harboring primary and advanced phenotypes. We established an in vitro co-culture system using mouse OSCC cells, spleen cells, and mesenchymal stromal cells. Methods: Sq-1979 is an OSCC cell line derived from C3H mice; 233-11 cells were established from a primary Sq-1979 tumor; L3–5, L5–11, and L6–8 cells were established from lymph node-metastasized Sq-1979 cells. 10T1/2 is a fibroblast line derived from C3H mice. The OSCC cells were co-cultured with anti-CD3 antibody-stimulated mouse spleen cells in the presence or absence of 10T1/2 cells, and the producing capability of interferon (IFN)-γ and interleukin (IL)-10 was evaluated using enzyme-linked immunosorbent assay. Results: The production of IFN-γ by the stimulated spleen cells was specifically enhanced in the presence of co-cultured L-cells. The production of IL-10 was conversely reduced in the co-culture with all the OSCC cell lines used. The production of IFN-γ was significantly reduced in the co-culture with directly contacted 10T1/2 cells, and further reduction was observed in the presence of Sq-1979 and 233-11 cells but remained unchanged in the presence of L-cells. The reduction of IFN-γ production was also observed by the addition of conditioned medium from the Sq-1979-1 cells. Conclusion: Sq-1979 cells specifically enhanced the immune-suppressive activity of mesenchymal stromal cells through humoral factor (s).","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"19 1","pages":"9 - 16"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75432329","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":"MicroRNAs differentially expressed in prostate cancer of African-American and European-American men","authors":"E. Amankwah","doi":"10.4103/ctm.ctm_1_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_1_18","url":null,"abstract":"African-American (AA) men have higher rates of prostate cancer incidence and mortality compared with European-American (EA) men. Although several socioeconomic and environmental factors may contribute to the disparity, recent studies suggest a biological component, including differential microRNA (miRNA) expression, to the disparity. miRNAs comprise a large family of about 22-nucleotide-long nonprotein coding RNAs that regulate gene expression posttranscriptionally and participate in the regulation of almost every known cellular process investigated to date. miRNAs have been associated with prostate cancer progression, and recent studies indicate that they are differentially expressed between AA and EA. They could therefore contribute, at least in part, to the disparity in prostate cancer between the two groups. In this review, existing evidence on differential miRNA expression between AA and EA prostate cancer patients or cell lines is summarized.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"46 1","pages":"28 - 34"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84968516","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":"Retreatment with cabazitaxel in a long-surviving patient with castration-resistant prostate cancer and visceral metastasis","authors":"R. Luque Caro, Carmen Sánchez Toro, Lucia Ochoa Vallejo","doi":"10.4103/ctm.ctm_14_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_14_18","url":null,"abstract":"Prostate tumors are the most frequent malignant cancer among men. In recent years, we have seen a significant progress in the knowledge of the carcinogenesis of prostate cancer, leading to the development of effective drugs in this scenario. Prostate cancer patients had no effective therapeutic alternatives after docetaxel failure, limiting their survival rates. However, new drugs have markedly improved this. Cabazitaxel, a new generation taxane, has shown improved patient survival, despite the disease progression seen after docetaxel treatment. Herein, we present the case of a prostate cancer patient with poor prognosis and lung metastases in < 6 months postdocetaxel treatment. The patient was treated with cabazitaxel, achieving a long and maintained response. Later, on developing a new progressive disease, the patient was retreated with cabazitaxel, achieving a partial response and obtaining a widespread survival and clinical benefit. We currently have no predictive response factors to establish the most appropriate therapeutic sequence. Close monitoring of these patients is of paramount importance to detect early disease progression and try a new line of treatment, while the patient still has the chance to respond.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"32 1","pages":"83 - 88"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74625138","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":"I-Kappa-B kinase-epsilon activates nuclear factor-kappa B and STAT5B and supports glioblastoma growth but amlexanox shows little therapeutic potential in these tumors","authors":"Nadège Dubois, S. Berendsen, Aurélie Henry, M. Nguyen, V. Bours, P. Robe","doi":"10.4103/ctm.ctm_3_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_3_18","url":null,"abstract":"Aim: This study aims to analyze the role of I-kappa-B kinase (IKK)-epsilon in glioblastoma (GBM). Methods: A series of in vitro, in vivo, microarray, and immunohistochemical assessments were performed to evaluate the biological effects of IKK-epsilon on cell signaling, radiation sensitivity, and patient survival in GBM condition. Results: IKK-epsilon was strongly expressed in 75% of 195 primary GBM samples but did not correlate with patient survival. No correlation was established between the copy number, messenger RNA (mRNA) expression, and protein expression in 38 fresh tumor samples, nor between IKK-epsilon mRNA expression and survival in 543 GBM of the TCGA repository. In vitro, IKK-epsilon contributed to the growth and migration of glioma cells, independent of their EGFRVIII status. IKK-epsilon activated nuclear factor (NF)-κB and STAT5B in vitro, confirming the observed correlation surgical GBM samples. IKK-epsilon silencing did not alter the sensitivity of GBM cells to ionizing radiation. Amlexanox, inhibitor of IKK-epsilon and TBK1, poorly (IC50 > 100 μM) decreased cell growth and increased NF-κB activity in GBM cells, in vitro, notably due to TBK1 inhibition. In vivo, oral amlexanox failed to inhibit the growth of intracerebral U87 GBM xenografts in nude mice. Conclusion: The results confirm a moderate pro-oncogenic role of IKK-epsilon in GBM, but question the potential of amlexanox as a therapeutic drug.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"10 1","pages":"1 - 8"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80854632","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":"An interplay between MicroRNA and SOX4 in the regulation of epithelial–mesenchymal transition and cancer progression","authors":"Anjali Geethadevi, Ansul Sharma, M. Sharma, D. Parashar","doi":"10.4103/ctm.ctm_4_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_4_18","url":null,"abstract":"MicroRNAs (miRNAs) are abundant class of small, noncoding RNAs which are emerging as a potential therapeutic target for various cancers. Sex-determining region Y-related high-mobility group box 4 (SOX4) is an important member of SOX family and a crucial master regulator of epithelial–mesenchymal transition (EMT) that has been implicated in tumor growth and progression. In cancers of epithelial origin and in some others, growing evidence has revealed a close association between miRNAs and SOX4. Most miRNAs are reported to modulate SOX4 by directly binding to SOX4 3'-untranslated region, thereby regulating cancer cell proliferation, invasion, and EMT. In this review, we highlight the interaction of miRNAs with SOX4 in various cancers and discuss the possibility of combined miRNA-SOX4-based therapeutic approach that may serve as a targeted therapy for several cancers.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"36 1","pages":"17 - 27"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81261011","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":"The “Wild”-type gastrointestinal stromal tumors: Heterogeneity on molecule characteristics and clinical features","authors":"Yan-hua Mou, Quan Wang, Bin Li","doi":"10.4103/ctm.ctm_17_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_17_18","url":null,"abstract":"KIT and platelet-derived growth factor receptor alpha (PDGFRA) are known as the most driven genes in gastrointestinal stromal tumors (GISTs). However, about 10%–15% of GISTs without KIT and PDGFRA mutation are named “Wild-type” (WT) GISTs. Gene abnormalities and clinical features of WT GISTs are significantly different from KIT/PDGFRA-mutated GISTs. Recently, based on the findings of next-generation sequencing, WT GISTs have been shown to be not a single disease entity, but instead a set of various pathologic and clinical diseases. Nevertheless, although several genetic alterations have been identified in WT GISTs, the exact roles of these molecules have not yet been well defined. We herein summarize the recent progression on KIT/PDGFRA WT GISTs.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"11 1","pages":"75 - 82"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88669512","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":"The role of reactive oxygen species in screening anticancer agents","authors":"Xiaohui Xu, Zi-long Dang, Taoli Sun, Shengping Zhang, Hongyan Zhang","doi":"10.4103/ctm.ctm_6_18","DOIUrl":"https://doi.org/10.4103/ctm.ctm_6_18","url":null,"abstract":"Development of anticancer agents with high efficacy and low toxicity has always been a challenge in cancer therapeutics. Reactive oxygen species (ROS) are one of the most important physiological stimuli and have been correlated with several cancer conditions. Cancer cells adapt to new higher ROS environment. Meanwhile, elevated ROS render cancer cells vulnerable to oxidative stress-induced cell death. Anticancer drugs are involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. Thus, it is useful to study the level of ROS generated by anticancer agents in cancer cells, while sparing the normal cells, which is one of the target methods to study the pharmacological properties of anticancer agents. In this review, we discuss the relation between ROS and anticancer agents, as well as the application of ROS in anticancer agents' activity screening.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"43 1","pages":"35 - 38"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90617314","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":"Markerless Four-Dimensional-Cone Beam Computed Tomography Projection-Phase Sorting Using Prior Knowledge and Patient Motion Modeling: A Feasibility Study","authors":"Lei Zhang, Yawei Zhang, You Zhang, W. Harris, F. Yin, Jing Cai, L. Ren","doi":"10.4103/ctm.ctm_38_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_38_17","url":null,"abstract":"Aim: During cancer radiotherapy treatment, on-board four-dimensional-cone beam computed tomography (4D-CBCT) provides important patient 4D volumetric information for tumor target verification. Reconstruction of 4D-CBCT images requires sorting of acquired projections into different respiratory phases. Traditional phase sorting methods are either based on external surrogates, which might miscorrelate with internal structures; or on 2D internal structures, which require specific organ presence or slow gantry rotations. The aim of this study is to investigate the feasibility of a 3D motion modeling-based method for markerless 4D-CBCT projection-phase sorting. Methods: Patient 4D-CT images acquired during simulation are used as prior images. Principal component analysis (PCA) is used to extract three major respiratory deformation patterns. On-board patient image volume is considered as a deformation of the prior CT at the end-expiration phase. Coefficients of the principal deformation patterns are solved for each on-board projection by matching it with the digitally reconstructed radiograph (DRR) of the deformed prior CT. The primary PCA coefficients are used for the projection-phase sorting. Results: PCA coefficients solved in nine digital phantoms (XCATs) showed the same pattern as the breathing motions in both the anteroposterior and superoinferior directions. The mean phase sorting differences were below 2% and percentages of phase difference < 10% were 100% for all the nine XCAT phantoms. Five lung cancer patient results showed mean phase difference ranging from 1.62% to 2.23%. The percentage of projections within 10% phase difference ranged from 98.4% to 100% and those within 5% phase difference ranged from 88.9% to 99.8%. Conclusion: The study demonstrated the feasibility of using PCA coefficients for 4D-CBCT projection-phase sorting. High sorting accuracy in both digital phantoms and patient cases was achieved. This method provides an accurate and robust tool for automatic 4D-CBCT projection sorting using 3D motion modeling without the need of external surrogate or internal markers.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"3 1","pages":"185 - 193"},"PeriodicalIF":0.0,"publicationDate":"2017-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85277785","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}