Onco Pub Date : 2022-08-25 DOI: 10.3390/onco2030014

S. Qazi, F. Uckun

引用次数: 1

Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets 基因组和基因表达研究有助于确定小细胞肺癌癌症和其他肺部神经内分泌肿瘤的异质性，并确定新的治疗靶点

Onco Pub Date : 2022-08-15 DOI: 10.3390/onco2030013

U. Testa, E. Pelosi, G. Castelli

{"title":"Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets","authors":"U. Testa, E. Pelosi, G. Castelli","doi":"10.3390/onco2030013","DOIUrl":"https://doi.org/10.3390/onco2030013","url":null,"abstract":"Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, corresponding to about 15% of lung cancers, occurring predominantly in smokers and associated with a very poor prognosis. Key genetic alterations very frequently observed in SCLC are represented by the loss of TP53 and RB1, due to mutational events or deletions; frequent amplification or overexpression of MYC family genes (MYC, MYCL and MYCN); frequent genetic alterations by mutation/deletion of KMT2D, RB family members p107 (RBL1) and p130 (RBL2), PTEN, NOTCH receptors and CREBBP. The profile of expression of specific transcription factors allowed to differentiate four subtypes of SCLC defined according to levels of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POUF23 (SCLC-P) or YAP1 (SCLC-Y). A recent study identified the subgroup SCLC-I, characterized by the expression of inflammatory/immune-related genes. Recent studies have characterized at molecular level other lung neuroendocrine tumors, including large cell neuroendocrine cancers (LCNECs) and lung carcinoids. These molecular studies have identified some therapeutic vulnerabilities that can be targeted using specific drugs and some promising biomarkers that can predict the response to this treatment. Furthermore, the introduction of immunotherapy (immune checkpoint blockade) into standard first-line treatment has led to a significant clinical benefit in a limited subset of patients.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49535508","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}

引用次数: 0

The Role of Liquid Biopsy in the Diagnostic Testing Algorithm for Advanced Lung Cancer 液体活检在晚期肺癌诊断检测算法中的作用

Onco Pub Date : 2022-07-14 DOI: 10.3390/onco2030012

A. Tan

引用次数: 2

The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia 免疫检查点阻断在急性髓系白血病中的作用

Onco Pub Date : 2022-07-11 DOI: 10.3390/onco2030011

Margarida F B Silva, D. Martins, F. Mendes

{"title":"The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia","authors":"Margarida F B Silva, D. Martins, F. Mendes","doi":"10.3390/onco2030011","DOIUrl":"https://doi.org/10.3390/onco2030011","url":null,"abstract":"Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and/or combined therapy (with chemotherapy (QT), for AML patients. The PRISMA statement was used. The literature used comprised clinical trials, randomized controlled trials, and systematic reviews published within the last 7 years. The blockade of CTLA-4 presented a 42% of complete remission within AML. Nivolumab in high-risk AML showed a median recurrence-free survival (RFS) of 8.48 months. The same drug on relapsed hematologic malignancies after allogenic transplantation shows a 1-year OS of 56%. The use of prophylaxis post allogenic transplantation cyclophosphamide (PTCy), following checkpoint inhibition, demonstrated different baseline disease and transplantation characteristics when compared to no-PCTy patients, being 32% and 10%, respectively. CTLA-4 blockage was a worthy therapeutic approach in relapsed hematologic malignancies, presenting long-lasting responses. The approach to AML and myelodysplastic syndrome patients with ICI before allogenic hematopoietic stem cell transplantation and the use of a graft-versus-host disease prophylaxis have shown improvement in the transplantation outcomes, and therefore AML treatment.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41393704","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}

引用次数: 2

Fucoxanthinol Promotes Apoptosis in MCF-7 and MDA-MB-231 Cells by Attenuating Laminins–Integrins Axis 岩藻黄嘌呤通过减弱层粘连蛋白-整合素轴促进MCF-7和MDA-MB-231细胞凋亡

Onco Pub Date : 2022-07-08 DOI: 10.3390/onco2030010

Ayaka Yasuda, Momoka Wagatsuma, Wataru Murase, Atsuhito Kubota, Hiroyuki Kojima, Tohru Ohta, Junichi Hamada, Hayato Maeda, Masaru Terasaki

{"title":"Fucoxanthinol Promotes Apoptosis in MCF-7 and MDA-MB-231 Cells by Attenuating Laminins–Integrins Axis","authors":"Ayaka Yasuda, Momoka Wagatsuma, Wataru Murase, Atsuhito Kubota, Hiroyuki Kojima, Tohru Ohta, Junichi Hamada, Hayato Maeda, Masaru Terasaki","doi":"10.3390/onco2030010","DOIUrl":"https://doi.org/10.3390/onco2030010","url":null,"abstract":"Fucoxanthinol (FxOH), the main metabolite of the marine carotenoid fucoxanthin, exerts anti-cancer effects. However, fragmentary information is available on the growth-inhibiting effects of FxOH on breast cancer (BC). We investigated the growth-inhibiting effects of FxOH on human BC cells (MCF-7 and MDA-MB-231 cells), and the underlying mechanisms, differently from previous studies, by using comprehensive transcriptome analysis. The molecular mechanisms of FxOH were evaluated using flow cytometry, microarray, Western blotting, and gene knockdown analyses. FxOH (20 μM) significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. Transcriptome analysis revealed that FxOH modulated the following 12 signaling pathways: extracellular matrix (ECM), adhesion, cell cycle, chemokine and cytokine, PI3K/AKT, STAT, TGF-β, MAPK, NF-κB, RAS/Rho, DNA repair, and apoptosis signals. FxOH downregulated the levels of laminin β1, integrin α5, integrin β1, integrin β4, cyclin D1, Rho A, phosphorylated (p)paxillin (Tyr31), pSTAT3(Ser727), and pSmad2(Ser465/467), which play critical roles in the 12 signaling pathways mentioned above. Additionally, FxOH upregulated the levels of pERK1/2(Thr202/Tyr204) and active form of caspase-3. Integrin β1 or β4 knockdown significantly inhibited the growth of MCF7 and MDA-MB-231 cells. These results suggest that FxOH induces apoptosis in human BC cells through some core signals, especially the ECM–integrins axis, and the downstream of cell cycle, STAT, TGF-β, RAS/Rho, MAPK, and/or DNA repair signals.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41973617","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}

引用次数: 3

Whole Genome Variant Dataset for Enriching Studies across 18 Different Cancers. 全基因组变异数据集，用于18种不同癌症的丰富研究。

Onco Pub Date : 2022-06-01 Epub Date: 2022-06-17 DOI: 10.3390/onco2020009

John Torcivia, Kawther Abdilleh, Fabian Seidl, Owais Shahzada, Rebecca Rodriguez, David Pot, Raja Mazumder

引用次数: 0

Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics 利用数据库和综合生物信息学分析神经母细胞瘤细胞外基质相关基因的预后作用

Onco Pub Date : 2022-05-19 DOI: 10.3390/onco2020007

L. Jahangiri

{"title":"Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics","authors":"L. Jahangiri","doi":"10.3390/onco2020007","DOIUrl":"https://doi.org/10.3390/onco2020007","url":null,"abstract":"A complex interaction occurs between cancer cells and the extracellular matrix (ECM) in the tumour microenvironment (TME). In this study, the expressions and mutational profiles of 964 ECM-related genes and their correlations with patient overall survival (OS) in neuroblastoma, an aggressive paediatric malignancy, were investigated using cBioPortal and PCAT databases. Furthermore, extended networks comprising protein-protein, protein-long non-coding RNA (lncRNA), and protein-miRNA of 12 selected ECM-related genes were established. The higher expressions of 12 ECM-related genes, AMBN, COLQ, ELFN1, HAS3, HSPE1, LMAN1, LRP5, MUC6, RAMP2, RUVBL2, SSBP1 and UMOD in neuroblastoma patients displayed a significant correlation with patient OS, while similar associations with neuroblastoma patient risk groups, histology and MYCN amplification were obtained. Furthermore, extended gene networks formed by these 12 ECM-related genes were established using Cytoscape, STRING, MSigDB/BioGRID, GeneMANIA and Omicsnet. Finally, the implications of the 12 ECM-related genes in other cancers were revealed using GEPIA2 and the Human Pathology Atlas databases. This meta-analysis showed the significance of these 12 ECM-related genes as putative prognostic predictors in neuroblastoma and other cancers.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42641203","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}

引用次数: 1

Angiodrastic Chemokines Production by Colonic Cancer Cell Lines 结肠癌细胞系血管趋化因子的产生

Onco Pub Date : 2022-04-29 DOI: 10.3390/onco2020006

Emmanouil George, Moursellas Andrew, Tzardi Maria, Voumvouraki Argyro, Kouroumalis Elias

{"title":"Angiodrastic Chemokines Production by Colonic Cancer Cell Lines","authors":"Emmanouil George, Moursellas Andrew, Tzardi Maria, Voumvouraki Argyro, Kouroumalis Elias","doi":"10.3390/onco2020006","DOIUrl":"https://doi.org/10.3390/onco2020006","url":null,"abstract":"Purpose: To study the production of angiodrastic chemokines by colonic cancer cell lines. Methods: A pro-angiogenic factor (VEGF), two angiogenic chemokines (CXCL8, CXCL6), and one angiostatic (CXCL4) chemokine were measured by ELISA in the supernatants of the colon cancer cell lines HT-29 and Caco-2. Cells were cultured for 24 h in the presence of serum from cancer patients or healthy individuals. Results were analyzed by one-way ANOVA and the General Linear Model for repeated measures. Results: Colonic epithelial cells are potent producers of angiodrastic chemokines. HT-29 and Caco-2 cells produce all four chemokines under basal conditions and 24 h after incubation with human serum. The secretion response, however, was completely different. HT-29 cells produce more CXCL8 and VEGF irrespective of culture conditions, while Caco-2 cells seem unresponsive with respect to CXCL6 and CXCL4. Moreover, HT-29 cells produce more CXCL8 and VEGF when incubated with cancer serum, contrary to Caco-2 cells which produce more CXCL4 under the same conditions. Conclusions: The two colon cancer cell lines were producers of all chemokines studied, but their responses were not uniform under similar culture conditions. CXCL8 and VEGF are differently regulated compared to CXCL4 and CXCL6 in these two cell lines","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45871671","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}

引用次数: 1

Sparse-Input Neural Networks to Differentiate 32 Primary Cancer Types on the Basis of Somatic Point Mutations 基于体细胞点突变的稀疏输入神经网络鉴别32种原发性癌症类型

Onco Pub Date : 2022-03-31 DOI: 10.3390/onco2020005

Nikolaos Dikaios

{"title":"Sparse-Input Neural Networks to Differentiate 32 Primary Cancer Types on the Basis of Somatic Point Mutations","authors":"Nikolaos Dikaios","doi":"10.3390/onco2020005","DOIUrl":"https://doi.org/10.3390/onco2020005","url":null,"abstract":"Background and Objective: This paper aimed to differentiate primary cancer types from primary tumor samples on the basis of somatic point mutations (SPMs). Primary cancer site identification is necessary to perform site-specific and potentially targeted treatment. Current methods such as histopathology and lab tests cannot accurately determine cancer origin, which results in empirical patient treatment and poor survival rates. The availability of large deoxyribonucleic acid sequencing datasets has allowed scientists to examine the ability of somatic mutations to classify primary cancer sites. These datasets are highly sparse since most genes will not be mutated, have a low signal-to-noise ratio, and are often imbalanced since rare cancers have fewer samples. Methods: To overcome these limitations a sparse-input neural network (SPINN) is suggested that projects the input data in a lower-dimensional space, where the more informative genes are used for learning. To train and evaluate SPINN, an extensive dataset for SPM was collected from the cancer genome atlas containing 7624 samples spanning 32 cancer types. Different sampling strategies were performed to balance the dataset. SPINN was further validated on an independent ICGC dataset that contained 226 samples spanning four cancer types. Results and Conclusions: SPINN consistently outperformed classification algorithms such as extreme gradient boosting, deep neural networks, and support vector machines, achieving an accuracy up to 73% on independent testing data. Certain primary cancer types/subtypes (e.g., lung, brain, colon, esophagus, skin, and thyroid) were classified with an F-score > 0.80.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48029223","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}

引用次数: 0

Akt/mTOR Activation in Lung Cancer Tumorigenic Regulators and Their Potential Value as Biomarkers 肺癌症致瘤调节因子Akt/mTOR的激活及其作为生物标志物的潜在价值

Onco Pub Date : 2022-02-25 DOI: 10.3390/onco2010004

C. Sousa, B. Silva‐Lima, M. Videira

{"title":"Akt/mTOR Activation in Lung Cancer Tumorigenic Regulators and Their Potential Value as Biomarkers","authors":"C. Sousa, B. Silva‐Lima, M. Videira","doi":"10.3390/onco2010004","DOIUrl":"https://doi.org/10.3390/onco2010004","url":null,"abstract":"The high incidence and modest therapeutic outcomes of lung cancer have prompted the identification of cell molecular targets/biomarkers within the complex networks of interactions involved in cell malignancy. Most of the EMT-related regulatory mediators underline patients’ biologic variations, therapeutic refractory events, and tumor cell heterogeneity. Patient stratification based on the understanding of the relevant pathways, such as the PI3K/Akt axis crucial in EMT initiation, could favorably alter disease management. Significant clinical advantage could be expected when overexpressed Akt tyrosine kinase (Akt2) is addressed as a malignant biomarker to guide clinical management decisions, improving prognosis in lung cancer patients. Moreover, one should not miss the opportunity of using it as a druggable target aiming at the inhibition of the downstream complexity that underlies cell proliferation and survival, expression of stemness markers and drug resistance. The value of mTOR, as a downstream target of Akt, and the further activation of EMT transcription factors Twist, Snail and Zeb1 are revisited in this review. An in-depth state-of-the-art assessment provides evidence of its role in the mechanistic inhibition of epithelial markers, such as E-cadherin and miR-200, while inducing the expression of the mesenchymal ones, such as vimentin, N-cadherin, and miR-21. Lastly, evidence suggesting another transcription factor, FOXM1, as the link between the PI3K/Akt and Wnt/β-catenin pathways, prompting cell metabolism through the regulation of p70S6K, is analyzed. A more realistic approach is advised to address unmet clinical needs and support decision making at a clinical level. Taking into consideration several complex intracellular interactions might further improve patient stratification and result in better outcomes.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45967147","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}

引用次数: 2

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