Oncoscience最新文献

{"title":"Repeated stereotactic radiosurgery for the treatment of relapsed brain metastases: is it time to give up whole-brain radiotherapy?","authors":"Luca Nicosia, Vanessa Figlia, Niccolò Giaj-Levra, Giuseppe Minniti, Filippo Alongi","doi":"10.18632/oncoscience.500","DOIUrl":"https://doi.org/10.18632/oncoscience.500","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37952839","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":"Metabolic Reprogramming by c-MET Inhibition as a Targetable Vulnerability in Glioblastoma.","authors":"Trang Thi Thu Nguyen,&nbsp;Enyuan Shang,&nbsp;Georg Karpel-Massler,&nbsp;Markus D Siegelin","doi":"10.18632/oncoscience.498","DOIUrl":"https://doi.org/10.18632/oncoscience.498","url":null,"abstract":"<p><p>The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days. At the forefront of these developments are the extracellular flux and carbon tracing analyses. Through utilization of these techniques our group made the recent observation that acute and chronic c-MET inhibition drives fatty acid oxidation that in turn can be therapeutically targeted for drug combination therapies. Herein, we summarize and comment on some of our key findings related to this study.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37811310","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":"Cracking the riddle of dedifferentiated liposarcoma: is EV-MDM2 a key?","authors":"Lucia Casadei,&nbsp;Raphael E Pollock","doi":"10.18632/oncoscience.497","DOIUrl":"https://doi.org/10.18632/oncoscience.497","url":null,"abstract":"<p><p>Dedifferentiated liposarcoma (DDLPS) is molecularly characterized by wt p53 and MDM2 gene amplification causing MDM2 protein over-production, the key oncogenic process in DDLPS. Commonly located in fat-bearing retroperitoneal areas, almost 60% of DDLPS patients undergo multifocal recurrence, typically amenable to palliative treatment only, and occasionally develop distant metastasis. These factors lead to an abysmal 10% 10 year overall survival rate. Tumor cell-derived extracellular vesicles (EVs) can facilitate loco-regional malignancy dissemination by depositing molecular factors that participate in the development of pre-metastatic niches for tumor cell implantation and growth. High number of MDM2 DNA molecules was identified within EVs from DDLPS patient serum (ROC vs normal; 0.95) as well as from DDLPS cell lines. This MDM2 DNA could be transferred to preadipocytes (P-a), a major and ubiquitous cellular component of the DDLPS tumor microenvironment (TME), with subsequent P-a production of matrix metalloproteinase 2 (MMP2), a critical component in the metastatic cascade. From here the hypothesis that the DDLPS microenvironment (specifically P-a cells) may participate in DDLPS recurrence events. Since multifocal loco-regional DDLPS spreading is the main cause of the remarkably high lethality of this disease, a better understanding of the underlying oncogenic processes and their regulatory mechanisms is essential to improve the outcome of this devastating disease.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37811309","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":"Overexpression of microRNA-145 inhibits tumorigenesis through autophagy in chemotherapy and radiation resistant neuroblastoma cells.","authors":"Kwang Woon Kim,&nbsp;Jingbo Qiao,&nbsp;Julia Y Kim,&nbsp;Kyungho Park,&nbsp;Dai H Chung","doi":"10.18632/oncoscience.496","DOIUrl":"https://doi.org/10.18632/oncoscience.496","url":null,"abstract":"<p><p>MicroRNA-145 (miR-145) plays a suppressive role in the process of tumorigenesis and an important role in induction of autophagy. However, the exact role of miR-145 in therapeutically resistant neuroblastoma cells remain elusive. Herein, we sought to evaluate the effects of miR-145 overexpression in chemo‑ and radiation-resistant neuroblastoma cells. We hypothesized that miR-145 affects the aggressiveness of resistant cells by enhancing autophagy. We established Cisplatin-resistant (CDDP-R), Vincristine-resistant (Vin-R), and radiation-resistant (Rad-R) neuroblastoma cells and found that miR-145 expression was significantly decreased in the resistant cells compared to the parental cells. Exogenously expression of miR-145 inhibited oncogenic properties such as proliferation, clonogenicity, anchorage-independent growth, cell migration, and tubule formation in the resistant cells. In addition, we also found that an autophagy protein marker, LC3, was only minimally expressed in the resistant cells. In particular, when miR-145 was overexpressed in the resistant cells, LC3 I and II were expressed and an increased punctate fluorescence of LC3 protein was found indicating the induction of autophagy. Taken together, our data suggests that miR-145 inhibits tumorigenesis and aggressiveness via modulation of autophagy in neuroblastoma.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37811308","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":"Precision health for breast cancer metastasis: biomaterial scaffolds as an engineered metastatic niche to define, study, and monitor metastatic progression.","authors":"Grace G Bushnell,&nbsp;Max S Wicha,&nbsp;Jacqueline S Jeruss,&nbsp;Lonnie D Shea","doi":"10.18632/oncoscience.493","DOIUrl":"https://doi.org/10.18632/oncoscience.493","url":null,"abstract":"<p><p>Metastasis represents the greatest challenge to treatment of cancer patients. Biomaterial scaffolds that recruit tumor cells to a defined site in vivo are an emerging platform for the diagnosis, treatment, and study of metastasis. Recruitment of immune cells and metastatic tumor cells to a defined location provides a precision health platform to assess current clinical cancer biomarkers in a metastatic setting, and to define the next generation of biomarkers. These platforms represent an opportunity to create a molecular staging of metastasis that could aid in both the early diagnosis and treatment of metastasis.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37581613","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":"SOCS1: phosphorylation, dimerization and tumor suppression.","authors":"Frédéric Lessard,&nbsp;Emmanuelle Saint-Germain,&nbsp;Lian Mignacca,&nbsp;Gerardo Ferbeyre","doi":"10.18632/oncoscience.495","DOIUrl":"https://doi.org/10.18632/oncoscience.495","url":null,"abstract":"<p><p>Suppressor of cytokine signaling (SOCS) family members are upregulated following JAK-STAT pathway activation by cytokines. SOCS proteins are recognized inhibitors of cytokine signaling playing roles in cell growth and differentiation. Moreover, SOCS1 and SOCS3 have been shown to be involved in tumor suppression through their ability to interact with p53 leading to the activation of its transcriptional program and showing the implication of SOCS family members in the regulation of apoptosis, ferroptosis and senescence. More recently, we demonstrated that the SRC family of non-receptor tyrosine kinases (SFK) can phosphorylate SOCS1 leading to its homodimerization and inhibiting its interaction with p53. Then, we reactivated the SOCS1-p53 tumor suppressor axis with the SFK inhibitor dasatinib in combination with the p53 activating compound PRIMA. This work suggests new avenues for cancer treatment and leaves open several new questions that deserve to be addressed.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37581615","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":"Improving patient classification and biomarker assessment using Gaussian Mixture Models and Bayes' rule.","authors":"Marina A Guvakova","doi":"10.18632/oncoscience.494","DOIUrl":"https://doi.org/10.18632/oncoscience.494","url":null,"abstract":"<p><p>In clinical research, determining cutoff values for continuous variables in test results remains challenging, particularly when considering candidate biomarkers or therapeutic targets for disease. Distribution of a continuous variable into two populations is known as dichotomization and has been commonly used in clinical studies. We recently reported a new method for determining multiple cutoffs for continuous variables. The development of this original approach was based on fitting Gaussian Mixture Models (GMM) onto real-world clinical data. We also explored how to leverage Bayesian probability to minimize uncertainty while classifying individual patients into respective subpopulations. In addition, we investigated the performance of the proposed method for the distribution of classical prognostic markers in breast cancer. Finally, we applied the proposed method to analyze a candidate marker and a target for cancer therapy. Here, we present an overview of this method and our prospects for its implementation in biomedical and clinical research.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37581614","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":"ZC3H12A Expression in Different Stages of Colorectal Cancer.","authors":"Tao Chen,&nbsp;Di Du,&nbsp;Jian Chen,&nbsp;Pinghong Zhou,&nbsp;John N Weinstein,&nbsp;Liqing Yao,&nbsp;Yuexin Liu","doi":"10.18632/oncoscience.480","DOIUrl":"https://doi.org/10.18632/oncoscience.480","url":null,"abstract":"<p><p>Identification of CRC patients with early-stage disease provides the opportunity for curative local resection. However, robust markers for stage I tumor prediction are yet to be developed. We analyzed RNA-sequencing data of 221 CRC samples using the TCGA dataset to identify novel biomarkers for stage I CRC. We next validated the TCGA finding in an independent GEO cohort of 290 CRC patients and in a third cohort of 110 CRC tumors and matched normal samples. We further performed correlative analysis of ZC3H12A gene expression with clinicopathologic features and disease-free survival. Expression correlation of ZC3H12A with the chemokine ligands was evaluated via Student's t-test. In the TCGA cohort, stage I CRC patients had significantly higher ZC3H12A mRNA expression as compared with the other three stages combined and with the other individual stages in a pairwise manner (P<0.001 for all comparisons). The significant association of ZC3H12A gene expression with stages was further validated in the GEO cohort and in the additional third cohort. In support of these findings, we further found that patients with lower ZC3H12A expression had more aggressive tumor features and shorter disease-free survival. Biologically, ZC3H12A expression was significantly correlated with expression of three chemokine ligands (CXCL1, CXCL2 and CXCL3), suggesting that immune response dysregulation likely contributes to CRC development. Our results demonstrate ZC3H12A's potential role in identification of CRC patients with early-stage disease.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37257715","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":"Localized RAS signaling drives cancer.","authors":"Sandip K Basu, Srikanta Basu, Peter F Johnson","doi":"10.18632/oncoscience.479","DOIUrl":"10.18632/oncoscience.479","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37257714","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":"Liquid Biopsies Using Plasma Exosomal Nucleic Acids.","authors":"Lino Möhrmann,&nbsp;Filip Janku","doi":"10.18632/oncoscience.478","DOIUrl":"https://doi.org/10.18632/oncoscience.478","url":null,"abstract":"Liquid biopsies, which represent isolation of tumor nucleic acids from body fluids to assess molecular profile of cancer, are increasingly accepted as a useful approach in cancer diagnostics and treatment. [1] Liquid biopsies include analysis of tumor circulating cellfree DNA (cfDNA), exosomal nucleic acids or DNA isolated from circulating tumor cells. Liquid biopsies offer a minimally-invasive alternative to the molecular testing of tumor tissue, which is usually obtained from surgical therapeutic or diagnostic procedures. PCR-based methods such as digital PCR or BEAMing digital PCR offer high sensitivity; however, the number of molecular alterations that can be tested is often limited.[1-3] In contrast, next-generation sequencing can detect a broad range of molecular alterations; however, it is often at the cost of lower sensitivity. In addition, the next-generation sequencing workflow is more complex and bioinformatics expertise is needed. [1, 4] Applications of liquid biopsies include detection of molecular targets for cancer therapy, assessment of prognosis, assessment of treatment outcomes, dynamic assessment of clonal evolution, assessment of pharmacodynamics endpoints and early detection. Results of molecular testing of plasma cfDNAbased liquid biopsies were found to be largely concordant with results of molecular testing of tumor tissue especially if blood and tumor tissue were collected around the same time. [2, 3, 5-7] In addition, high amount of mutated cfDNA was found to be associated with shorter survival and/or time to treatment failure. [3, 5-7] Tumor cfDNA is released to the circulation from dying cancer cells, which arguably might not fully represent the prevailing cancer biology. Unlike cfDNA, exosomes contain DNA and RNA originating from living cells. [1, 8] Furthermore, in contrast to short fragments of cfDNA exosomes contain full length DNA, which can reduce complexity of molecular testing. In addition, exosomes also have abundance of RNA, which can be a more suitable material than cfDNA for molecular testing of complex alteration such as fusions. Recently, we demonstrated that combined next-generation sequencing-based molecular testing of plasma-derived exosomal RNA and cfDNA for common oncogenic alterations in BRAF, KRAS, and EGFR genes in patients with advanced cancers has high sensitivity (95%) and specificity (100%) compared to standard clinical testing of tumor tissue. [8] These results were comparable to sensitivity of plasma cfDNA testing with droplet digital PCR (92%) and BEAMing digital PCR (97%). In addition, we also demonstrated that the amount of mutated exosomal RNA and cfDNA is predictive of survival, time to treatment failure and response to treatment. Specifically, patients with a low amount of exosomal mutated RNA and cfDNA in samples collected before therapy had longer median survival (11.8 vs. 5.9 months; P = 0.006) and time to treatment failure (7.4 vs. 2.3 months; P = 0.009) than patients with higher am","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.18632/oncoscience.478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37257713","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}