Journal of cancer biology最新文献

{"title":"Changing the landscape of non-small cell lung cancer disparities.","authors":"Joab O Odera,&nbsp;Muthana Al Abo,&nbsp;Steven R Patierno,&nbsp;Jeffrey M Clarke,&nbsp;Jennifer A Freedman","doi":"10.46439/cancerbiology.2.020","DOIUrl":"https://doi.org/10.46439/cancerbiology.2.020","url":null,"abstract":"<p><p>In the United States, lung and bronchus cancers are the second most common types of cancer and are responsible for the largest number of deaths from cancer, with African Americans suffering disproportionately from lung and bronchus cancers. This disparity likely results from a complex interplay among social, psycho-social, lifestyle, environmental, health system, and biological determinants of health. Toward improving outcomes for lung cancer patients of all races and ethnicities and mitigating lung cancer disparities, in this commentary, we bring forward biological factors that contribute to lung cancer disparities, efforts to identify, functionally characterize, and modulate novel ancestry-related RNA splicing-related targets in lung cancer for precision intervention, and translational and clinical research needs to improve outcomes for lung cancer patients of all races and ethnicities and mitigate lung cancer disparities.</p>","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/54/nihms-1769960.PMC9347607.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695814","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":"Chromatin dynamics: Nucleosome occupancy and sensitivity as determinants of gene expression and cell fate.","authors":"Jane Benoit,&nbsp;Mahdi Khadem Sheikhbahaei,&nbsp;Jonathan Dennis","doi":"10.46439/cancerbiology.2.024","DOIUrl":"https://doi.org/10.46439/cancerbiology.2.024","url":null,"abstract":"<p><p>The nucleosome, consisting of ~150bp of DNA wrapped around a core histone octamer, is a regulator of nuclear events that contributes to gene expression and cell fate. Nucleosome organization at promoters and their associated remodeling events are important regulators of access to the genome. Occupancy alone, however, is not the only nucleosomal characteristic that plays a role in genome regulation. Nucleosomes at the transcription start sites (TSSs) of genes show differential sensitivity to micrococcal nuclease (MNase) and this differential sensitivity is linked to transcription and regulatory factor binding events. Recently, lymphoblastoid cells treated with heat-killed <i>Salmonella typhimurium</i> were shown to exhibit increased MNase sensitivity specifically at genes implicated in immune responses. Increased sensitivity at the -1-nucleosome permitted transcription factor and RNA Pol II binding events. This system illustrates how cytoplasmic signals induce altered chromatin states to produce a specific cellular response to a stimulus. Innate immune activation is a longstanding model for inducible promoters, transcriptional activation, and differential nucleosomal sensitivity in response to immune activation and offers a model that may be largely applicable to other specific cellular responses including viral infection and cancer. Previous work has shown that early transformation events are associated with prolonged nucleosome occupancy changes that are not observed later in cancer progression. Herein, we propose a model in which we suggest that detailed studies of nucleosomal occupancy and sensitivity in response to specific stimuli will provide insight into the regulation of nuclear events in cancer and other biological processes.</p>","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9435377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40353860","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":"Breaking malignant nuclei as a non-mitotic mechanism of taxol/paclitaxel.","authors":"Elizabeth R Smith,&nbsp;Xiang-Xi Xu","doi":"10.46439/cancerbiology.2.031","DOIUrl":"10.46439/cancerbiology.2.031","url":null,"abstract":"<p><p>Discovered in a large-scale screening of natural plant chemicals, Taxol/paclitaxel and the taxane family of compounds are surprisingly successful anti-cancer drugs, used in treatment of the majority of solid tumors, and especially suitable for metastatic and recurrent cancer. Paclitaxel is often used in combination with platinum agents and is administrated in a dose dense regimen to treat recurrent cancer. The enthusiasm and clinical development were prompted by the discovery that Taxol binds beta-tubulins specifically found within microtubules and stabilizes the filaments, and consequently inhibits mitosis. However, questions on how paclitaxel suppresses cancer persist, as other specific mitotic inhibitors are impressive in pre-clinical studies but fail to achieve significant clinical activity. Thus, additional mechanisms, such as promoting mitotic catastrophe and impacting non-mitotic targets, have been proposed and studied. A good understanding of how paclitaxel, and additional new microtubule stabilizing agents, kill cancer cells will advance the clinical application of these common chemotherapeutic agents. A recent study provides a potential non-mitotic mechanism of paclitaxel action, that paclitaxel-induced rigid microtubules act to break malleable cancer nuclei into multiple micronuclei. Previous studies have established that cancer cells have a less sturdy, more pliable nuclear envelope due to the loss or reduction of lamin A/C proteins. Such changes in nuclear structure provide a selectivity for paclitaxel to break the nuclear membrane and kill cancer cells over non-neoplastic cells that have a sturdier nuclear envelope. The formation of multiple micronuclei appears to be an important aspect of paclitaxel in the killing of cancer cells, either by a mitotic or non-mitotic mechanism. Additionally, by binding to microtubule, paclitaxel is readily sequestered and concentrated within cells. This unique pharmacokinetic property allows the impact of paclitaxel on cells to persist for several days, even though the circulating drug level is much reduced following drug administration/infusion. The retention of paclitaxel within cells likely is another factor contributing to the efficacy of the drugs. Overall, the new understanding of Taxol/paclitaxel killing mechanism-rigid microtubule-induced multiple micronucleation-will likely provide new strategies to overcome drug resistance and for rational drug combination.</p>","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835016","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":"Implications of the USP10-HDAC6 axis in lung cancer - A path to precision medicine.","authors":"Xiaohong Mary Zhang, Navnath Gavande, Prahlad Parajuli, Gerold Bepler","doi":"10.46439/cancerbiology.2.015","DOIUrl":"10.46439/cancerbiology.2.015","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer death among both men and women in the United States. Because lung cancer is genetically heterogeneous, tailored therapy alone or in combination with chemotherapy would increase patient overall survival as compared with the one-size-fits-all chemotherapy. <i>TP53</i>-mutant lung cancer accounts for more than half of all lung cancer cases and is oftentimes more aggressive and resistant to chemotherapy. Directly targeting mutant p53 has not yet been successful, so identification of novel therapy targets and biomarkers in the <i>TP53</i>-mutant lung cancer is urgently needed to increase the overall survival in this subgroup. Deubiquitinating enzymes (DUBs) regulate a vast majority of proteins (DUBs' substrates) via removal of ubiquitin moieties or ubiquitin chains from these proteins, thereby altering the stability and/or functions of these substrates. In this review, we will focus on a DUB, referred to as ubiquitin-specific peptidase 10 (USP10) whose substrates include both oncogenic proteins and tumor suppressors. Therefore, targeting USP10 in cancer is highly context-dependent. Here, we will discuss USP10's functions in cancer by examining its various known substrates. In particular, we will elaborate our recent findings in the oncogenic role of USP10 in the <i>TP53</i>-mutant subgroup of lung cancer, focusing on USP10's function in the DNA damage response (DDR) via histone deacetylase 6 (HDAC6). Overall, these findings support the notion that targeting USP10 in the <i>TP53</i>-mutant subgroup of NSCLC would sensitize patients to cisplatin-based chemotherapy. Generating potent and specific clinically relevant USP10 inhibitors would benefit the <i>TP53</i>-mutant subgroup of NSCLC patients.</p>","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39688285","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":"Can electronic-cigarette vaping cause cancer?","authors":"Moon-Shong Tang,&nbsp;Yen-Len Tang","doi":"10.46439/cancerbiology.2.027","DOIUrl":"https://doi.org/10.46439/cancerbiology.2.027","url":null,"abstract":"The relative safety of E-cigarette (E-cig) has been an emerging topic in the public domain as well as the medical and scientific communities as vaping associated health problems arose. While there were significant amounts of intelligent discussions and opinions on the benefits and deleterious effects of E-cig vaping, there is a lack of solid evidence of the fundamental biochemical and biological effects of E-cig aerosol and nicotine.","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40404954","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":"COVID-19 in patients with and without cancer: Examining differences in patient characteristics and outcomes.","authors":"Nihal E Mohamed, Emma Kt Benn, Varuna Astha, Qainat N Shah, Yasmine Gharib, Holden E Kata, Heather Honore-Goltz, Zachary Dovey, Natasha Kyprianou, Ashutosh K Tewari","doi":"10.46439/cancerbiology.2.019","DOIUrl":"10.46439/cancerbiology.2.019","url":null,"abstract":"<p><p>This study examines differences between patients with and without cancer in patient demographic and clinical characteristics and COVID-19 mortality and discusses the implications of these differences in relation to existing cancer disparities and COVID-19 vulnerabilities. Data was collected as a part of a retrospective study on a cohort of COVID-19 positive patients across Mount Sinai Health System from March 28, 2020 to April 26, 2020. Descriptive, comparative, and regression analyses were applied to examine differences between patients with and without cancer in demographic and clinical characteristics and COVID-19 mortality and whether cancer status predicts COVID-19 mortality controlling for these covariates using SAS 9.4. Results showed that, of 4641 patients who tested positive for COVID-19, 5.1% (N=236) had cancer. The median age of the total sample was 58 years (Q1-Q3: 41-71); 55.3% were male, 19.2% were current/former smokers, 6.1% were obese. The most commonly reported comorbidities were hypertension (22.6%) and diabetes (16.0%). Overall, the COVID-19 mortality rate was 8.3%. Examining differences between COVID-19 patients with and without cancer revealed significant differences (p<0.05) in COVID-19 mortality, hospitalization rates, age, gender, race, smoking status, obesity, and comorbidity indicators (e.g., diabetes) with cancer patients more likely to be older, male, black, obese, smokers, and with existing comorbidities. Controlling for these clinical, demographic, and behavioral characteristics, results of logistic regression analyses showed significant effects of older age and male gender on COVID-19 mortality (p<0.05). While cancer patients with COVID-19 were more likely to experience worse COVID-19 outcomes, these associations might be related to common cancer and COVID-19 vulnerability factors such as older age and gender. The coexistence of these vulnerability age and gender factors in both cancer and COVID-19 populations emphasizes the need for better understanding of their implications for cancer and COVID-19 disparities, both diseases prevention efforts, policies, and clinical management.</p>","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/4d/nihms-1709776.PMC8386503.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39371814","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":"Role of H3K9 demethylases in DNA double-strand break repair.","authors":"Hee-Young Jeon,&nbsp;Arif Hussain,&nbsp;Jianfei Qi","doi":"10.46439/cancerbiology.1.003","DOIUrl":"https://doi.org/10.46439/cancerbiology.1.003","url":null,"abstract":"<p><p>H3K9 demethylases can remove the repressive H3K9 methylation marks on histones to alter chromatin structure, gene transcription and epigenetic state of cells. By counteracting the function of H3K9 methyltransferases, H3K9 demethylases have been shown to play an important role in numerous biological processes, including diseases such as cancer. Recent evidence points to a key role for some H3K9 demethylases in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) and/or non-homologous end joining (NHEJ) pathways. Mechanistically, H3K9 demethylases can upregulate the expression of DNA repair factors. They can also be recruited to the DNA damage sites and regulate the recruitment or function of DNA repair factors. Here, we will discuss the role and mechanisms of H3K9 demethylases in the regulation of DSB repair.</p>","PeriodicalId":73632,"journal":{"name":"Journal of cancer biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373221/pdf/nihms-1604168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38186720","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}