Journal of Cancer Metastasis and Treatment最新文献

{"title":"Introduction to this special issue \"Breast Cancer Metastasis\".","authors":"William P Schiemann","doi":"10.20517/2394-4722.2020.01","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.01","url":null,"abstract":"Breast cancer remains the most common malignancy and most frequent cause of cancerrelated death in women, a devasting reality that annually claims more than 600,000 lives across the globe[1]. The vast majority of deaths due to breast cancer are attributed to metastasis and its associated relapse[2,3], which typically transpires in patients ~5-20 years after their initial diagnosis[4]. Although metastasis is the most lethal characteristic of breast cancer, our understanding of the molecular mechanisms that govern this event remains incomplete, a stark reality reinforced by the finding that diagnosis of distant-stage disease has remained unchanged over the course of the last two decades[5].","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39198145","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":"Deubiquitination in prostate cancer progression: role of USP22.","authors":"Nivedita Nag,&nbsp;Samikshan Dutta","doi":"10.20517/2394-4722.2020.23","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.23","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the leading cause of cancer death in men. With more therapeutic modalities available, the overall survival in PCa has increased significantly in recent years. Patients with relapses after advanced secondgeneration anti-androgen therapy however, often show poor disease prognosis. This group of patients often die from cancer-related complicacies. Multiple approaches have been taken to understand disease recurrence and to correlate the gene expression profile. In one such study, an 11-gene signature was identified to be associated with PCa recurrence and poor survival. Amongst them, a specific deubiquitinase called ubiquitin-specific peptidase 22 (USP22) was selectively and progressively overexpressed with PCa progression. Subsequently, it was shown to regulate androgen receptors and Myc, the two most important regulators of PCa progression. Furthermore, USP22 has been shown to be associated with the development of therapy resistant PCa. Inhibiting USP22 was also found to be therapeutically advantageous, especially in clinically challenging and advanced PCa. This review provides an update of USP22 related functions and challenges associated with PCa research and explains why targeting this axis is beneficial for PCa relapse cases.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39527181","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":"Evaluating different routes of extracellular vesicle administration for cranial therapies.","authors":"Pericles Ioannides,&nbsp;Erich Giedzinski,&nbsp;Charles L Limoli","doi":"10.20517/2394-4722.2020.22","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.22","url":null,"abstract":"<p><strong>Aim: </strong>Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple administration routes for the potential treatment of various forms of brain injury.</p><p><strong>Methods: </strong>Human neural stem cell-derived EV were isolated from conditioned media and administered via three distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered after which brains were evaluated to determine the capability of EV to translocate into normal tissue.</p><p><strong>Results: </strong>Data showed no significant differences in the amount of EV able to translocate across the brain, indicating the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma.</p><p><strong>Conclusion: </strong>Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery) afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point to a translationally tractable option for treating certain neurological disorders including those resulting from cranial irradiation procedures.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 15","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39198143","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":"Extracellular RNAs as potential biomarkers for cancer.","authors":"Christine Happel, Aniruddha Ganguly, Danilo A Tagle","doi":"10.20517/2394-4722.2020.71","DOIUrl":"10.20517/2394-4722.2020.71","url":null,"abstract":"<p><p>The discovery that all cells secrete extracellular vesicles (EVs) to shuttle proteins and nucleic acids to recipient cells suggested they play an important role in intercellular communication. EVs are widely distributed in many body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes are nano-sized EVs of endosomal origin that regulate many pathophysiological processes including immune responses, inflammation, tumour growth, and infection. Healthy individuals release exosomes with a cargo of different RNA, DNA, and protein contents into the circulation, which can be measured non-invasively as biomarkers of healthy and diseased states. Cancer-derived exosomes carry a unique set of DNA, RNA, protein and lipid reflecting the stage of tumour progression, and may serve as diagnostic and prognostic biomarkers for various cancers. However, many gaps in knowledge and technical challenges in EVs and extracellular RNA (exRNA) biology, such as mechanisms of EV biogenesis and uptake, exRNA cargo selection, and exRNA detection remain. The NIH Common Fund-supported exRNA Communication Consortium was launched in 2013 to address major scientific challenges in this field. This review focuses on scientific highlights in biomarker discovery of exosome-based exRNA in cancer and its possible clinical application as cancer biomarkers.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38855731","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":"Letting go of the physical exam: embracing telehealth solutions to oncology.","authors":"Michael J Overman","doi":"10.20517/2394-4722.2020.06","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.06","url":null,"abstract":"Despite the diminishing value of the physical exam in the management of many chronic diseases, it still represents a core component of clinical office visits[1]. In part, this reflects the reimbursement landscape that continues to support its use at every clinical encounter. However, as healthcare pivots towards a new focus on value-based care, it is imperative that we move beyond the confines of the in-person clinical encounter and embrace the tremendous potential for telehealth solutions to healthcare delivery.","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927120","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":"Burden of chronic diseases among sarcoma survivors treated with anthracycline chemotherapy: results from an observational study.","authors":"Laurence H Baker,&nbsp;Philip S Boonstra,&nbsp;Denise K Reinke,&nbsp;Erin J Peregrine Antalis,&nbsp;Bradley J Zebrack,&nbsp;Richard L Weinberg","doi":"10.20517/2394-4722.2020.36","DOIUrl":"https://doi.org/10.20517/2394-4722.2020.36","url":null,"abstract":"<p><strong>Aim: </strong>Cardiovascular disease is a leading cause of mortality among long-term cancer survivors treated with large total doses of doxorubicin. An increase in coronary artery disease (CAD) among childhood cancer survivors by age 45 has been observed and is driven by primarily anthracycline chemotherapy and to a lesser extent chest radiation that includes the heart in the radiation field. The risk factors and associated chronic diseases (hypertension, <i>etc</i>.) are well known for CAD and can be often prevented or treated, thus reducing the risk of CAD in these patients. We piloted a risk-based survivorship clinic in an academic medical center to characterize the distribution of risk factors for CAD and improve the quality of life in a population of sarcoma survivors treated with doxorubicin.</p><p><strong>Methods: </strong>We followed a prospective cohort of sixty-one survivors of bone and soft tissue sarcoma treated with doxorubicin chemotherapy (> 400 mg/m²) and at least 2 years post-therapy attending the sarcoma survivorship clinic. We collected clinical, demographic data, and patient reported outcomes via PROMIS questionnaires annually.</p><p><strong>Results: </strong>We demonstrated a high burden of chronic diseases in this population. Among six chronic conditions that are known risk factors for CAD (hypertension, diabetes, obesity, chronic inflammation, kidney disease and dyslipidemia), more than one-fourth (26%, 16/61) of patients had three or more of these risk factors at baseline visit, and 49% (30/61) had two or more.</p><p><strong>Conclusion: </strong>The results of this pilot study support the presence of modifiable CAD risk factors in this population of sarcoma survivors. Evidence-based guidelines for high-risk survivors of rare cancers are needed.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39519295","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":"Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance.","authors":"Ahmad R Safa","doi":"10.20517/2394-4722.2020.55","DOIUrl":"10.20517/2394-4722.2020.55","url":null,"abstract":"<p><p>Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-to-mesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-to-cell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs are summarised. This information may provide potential therapeutic strategies to prevent EMT and trigger CSC growth inhibition and cell death.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927121","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":"Introduction to this Special Issue: \"Biomarker Discovery and Precision Medicine\".","authors":"Bingliang Fang","doi":"10.20517/2394-4722.2019.42","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.42","url":null,"abstract":"With advances in genomics, transcriptomics, proteomics, and metabolomics, blooming data have been available for exploring molecular alternations in cancers. Many of these molecular alternations have been investigated as biomarkers for cancer diagnosis, prognosis, and precision therapies. It is my privilege to introduce this Special Issue of the Journal of Cancer Metastasis and Treatment, which contains four review articles and four original articles that focus on the topic of biomarker discoveries for cancer diagnosis and precision therapy.","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39624642","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":"Mouse tumor susceptibility genes identify drug combinations for multiple myeloma.","authors":"Shuling Zhang, Wendy DuBois, Ke Zhang, John K Simmons, V Keith Hughitt, Sayeh Gorjifard, Snehal Gaikwad, Tyler J Peat, Beverly A Mock","doi":"10.20517/2394-4722.2020.40","DOIUrl":"10.20517/2394-4722.2020.40","url":null,"abstract":"<p><p>Long-term genetic studies utilizing backcross and congenic strain analyses coupled with positional cloning strategies and functional studies identified <i>Cdkn2a</i>, <i>Mtor</i>, and <i>Mndal</i> as mouse plasmacytoma susceptibility/resistance genes. Tumor incidence data in congenic strains carrying the resistance alleles of <i>Cdkn2a</i> and <i>Mtor</i> led us to hypothesize that drug combinations affecting these pathways are likely to have an additive, if not synergistic effect in inhibiting tumor cell growth. Traditional and novel systems-level genomic approaches were used to assess combination activity, disease specificity, and clinical potential of a drug combination involving rapamycin/everolimus, an <i>Mtor</i> inhibitor, with entinostat, an histone deacetylase inhibitor. The combination synergistically repressed oncogenic <i>MYC</i> and activated the <i>Cdkn2a</i> tumor suppressor. The identification of <i>MYC</i> as a primary upstream regulator led to the identification of small molecule binders of the G-quadruplex structure that forms in the NHEIII region of the <i>MYC</i> promoter. These studies highlight the importance of identifying drug combinations which simultaneously upregulate tumor suppressors and downregulate oncogenes.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"6 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38377188","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":"A new view of the mammary epithelial hierarchy and its implications for breast cancer initiation and metastasis.","authors":"Lindsey J Anstine,&nbsp;Ruth Keri","doi":"10.20517/2394-4722.2019.24","DOIUrl":"https://doi.org/10.20517/2394-4722.2019.24","url":null,"abstract":"<p><p>The existence of mammary epithelial stem cell (MaSC) populations capable of mediating mammary gland development and homeostasis has been established for over a decade. A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner; however, these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal relationships. The advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high resolution. In the last two years, the remarkable advances in single cell RNA sequencing (scRNA-seq) technologies have been leveraged to address the heterogeneity of the mammary epithelium. These studies have afforded fresh insights into the transcriptional differentiation hierarchy and its chronology. Importantly, these data have led to a major conceptual shift in which the rigid boundaries separating stem, progenitor, and differentiated epithelial populations have been deconstructed, resulting in a new more fluid and flexible model of epithelial differentiation. The emerging view of the mammary epithelial hierarchy has important implications for mammary development, carcinogenesis, and metastasis, providing novel insights into the underlying cellular states that may promote malignant phenotypes.</p>","PeriodicalId":15167,"journal":{"name":"Journal of Cancer Metastasis and Treatment","volume":"5 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213536/pdf/nihms-1578731.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37925289","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}