Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Matrisomics: Beyond the extracellular matrix for unveiling tumor microenvironment","authors":"Jiwon Hong ,&nbsp;Hyo Joon Jin ,&nbsp;Mi Ran Choi ,&nbsp;Darren Wan-Teck Lim ,&nbsp;Jong-Eun Park ,&nbsp;You-Sun Kim ,&nbsp;Su Bin Lim","doi":"10.1016/j.bbcan.2024.189178","DOIUrl":"10.1016/j.bbcan.2024.189178","url":null,"abstract":"<div><p>The matrisome, a group of proteins constituting or interacting with the extracellular matrix (ECM), has garnered attention as a potent regulator of cancer progression. An increasing number of studies have focused on cancer matrisome utilizing diverse -omics approaches. Here, we present diverse patterns of matrisomal populations within cancer tissues, exploring recent -omics studies spanning different ‘-omics’ levels (epigenomics, genomics, transcriptomics, and proteomics), as well as newly developed sequencing techniques such as single-cell RNA sequencing and spatial transcriptomics. Some matrisome genes showed uniform patterns of upregulated or downregulated expression across various cancers, while others displayed different expression patterns according to the cancer types. This matrisomal dysregulation in cancer was further examined according to their originating cell type and spatial location in the tumor tissue. Experimental studies were also collected to demonstrate the identified roles of matrisome genes during cancer progression. Interestingly, many studies on cancer matrisome have suggested matrisome genes as effective biomarkers in cancer research. Although the specific mechanisms and clinical applications of cancer matrisome have not yet been fully elucidated, recent techniques and analyses on cancer matrisomics have emphasized their biological importance in cancer progression and their clinical implications in deciding the efficacy of cancer treatment.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189178"},"PeriodicalIF":9.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304419X24001094/pdfft?md5=4ffcf95b8a13d343bdb639c7efc42b38&pid=1-s2.0-S0304419X24001094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel encapsulation of mesenchymal stem cells-derived extracellular vesicles as a novel therapeutic approach in cancer therapy","authors":"Raheleh Farahzadi ,&nbsp;Ezzatollah Fathi ,&nbsp;Somayeh Vandghanooni ,&nbsp;Behnaz Valipour","doi":"10.1016/j.bbcan.2024.189177","DOIUrl":"10.1016/j.bbcan.2024.189177","url":null,"abstract":"<div><p>Cell therapy has emerged as one of the most promising approaches to treating disease in recent decades. The application of stem cells in anti-tumor therapy is determined by their varying capacity for proliferation, migration, and differentiation. These capacities are derived from different sources. The use of stem cell carriers in cancer treatment is justified by the following three reasons: (I) shield therapeutic agents from swift biological deterioration; (II) reduce systemic side effects; and (III) increase local therapeutic levels since stem cells have an innate ability to target tumors. The quantity of stem cells confined to the tumor microenvironment determines this system's anti-tumor activity. Nevertheless, there are limitations to the use of different types of stem cells. When immune cells are used in cell therapy, it may lead to cytokine storms and improper reactions to self-antigens. Furthermore, the use of stem cells may result in cancer. Additionally, after an intravenous injection, cells could not migrate to the injury location. Exosomes derived from different cells were thus proposed as possible therapeutic options. Exosomes are becoming more and more well-liked because of their small size, biocompatibility, and simplicity in storage and separation. A number of investigations have shown that adding various medications and microRNAs to exosomes may enhance their therapeutic effectiveness. Thus, it is essential to evaluate studies looking into the therapeutic effectiveness of encapsulated exosomes. In this review, we looked at studies on encapsulated exosomes' use in regenerative medicine and the treatment of cancer. The results imply that the therapeutic potential increases when encapsulated exosomes are used rather than intact exosomes. Therefore, in order to optimize the effectiveness of the treatment, it is advised to implement this technique in accordance with the kind of therapy.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189177"},"PeriodicalIF":9.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304419X24001082/pdfft?md5=85144e98d5d5f96e866c7f958896814b&pid=1-s2.0-S0304419X24001082-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive sphingolipids as emerging targets for signal transduction in cancer development","authors":"Wentao Jia ,&nbsp;Jiaying Yuan ,&nbsp;Jinbo Zhang ,&nbsp;Shu Li ,&nbsp;Wanfu Lin ,&nbsp;Binbin Cheng","doi":"10.1016/j.bbcan.2024.189176","DOIUrl":"10.1016/j.bbcan.2024.189176","url":null,"abstract":"<div><p>Sphingolipids, crucial components of cellular membranes, play a vital role in maintaining cellular structure and signaling integrity. Disruptions in sphingolipid metabolism are increasingly implicated in cancer development. Key bioactive sphingolipids, such as ceramides, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), and glycosphingolipids, profoundly impact tumor biology. They influence the behavior of tumor cells, stromal cells, and immune cells, affecting tumor aggressiveness, angiogenesis, immune modulation, and extracellular matrix remodeling. Furthermore, abnormal expression of sphingolipids and their metabolizing enzymes modulates the secretion of tumor-derived extracellular vesicles (TDEs), which are key players in creating an immunosuppressive tumor microenvironment, remodeling the extracellular matrix, and facilitating oncogenic signaling within in situ tumors and distant pre-metastatic niches (PMNs). Understanding the role of sphingolipids in the biogenesis of tumor-derived extracellular vesicles (TDEs) and their bioactive contents can pave the way for new biomarkers in cancer diagnosis and prognosis, ultimately enhancing comprehensive tumor treatment strategies.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189176"},"PeriodicalIF":9.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304419X24001070/pdfft?md5=41eb9b660ce04ee4d3924956c285caf2&pid=1-s2.0-S0304419X24001070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking through therapeutic barriers: Insights into CDK4/6 inhibition resistance in hormone receptor-positive metastatic breast cancer","authors":"Yang Zheng,&nbsp;Zeyuan Zhang,&nbsp;Dan Li,&nbsp;Rong Huang,&nbsp;Shipeng Ning","doi":"10.1016/j.bbcan.2024.189174","DOIUrl":"10.1016/j.bbcan.2024.189174","url":null,"abstract":"<div><p>The therapeutic landscape for hormone receptor-positive (HR+) breast carcinoma has undergone a significant transformation with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors, particularly in combination with endocrine therapy as the primary regimen. However, the evolution of resistance mechanisms in response to CDK4/6 inhibitors in HR+ metastatic breast cancer presents substantial challenges in managing the disease. This review explores the diverse genomic landscape underlying resistance, including disturbances in the cell cycle, deviations in oncogenic signaling pathways, deficiencies in DNA damage response (DDR) mechanisms, and changes in the tumor microenvironment (TME). Additionally, it discusses potential strategies to surmount resistance, including advancements in endocrine therapy, targeted inhibition of cell cycle components, suppression of AKT/mTOR activation, exploration of the FGFR pathway, utilization of antibody-drug conjugates (ADCs), and integration of immune checkpoint inhibitors (ICIs) with endocrine therapy and CDK4/6 inhibitors, providing pathways for enhancing patient outcomes amidst treatment challenges.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189174"},"PeriodicalIF":9.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS: A “booster” for chronic inflammation and tumor metastasis","authors":"Anqi Chen ,&nbsp;Haifeng Huang ,&nbsp;Sumeng Fang ,&nbsp;Qinglei Hang","doi":"10.1016/j.bbcan.2024.189175","DOIUrl":"10.1016/j.bbcan.2024.189175","url":null,"abstract":"<div><p>Reactive oxygen species (ROS) are a group of highly active molecules produced by normal cellular metabolism and play a crucial role in the human body. In recent years, researchers have increasingly discovered that ROS plays a vital role in the progression of chronic inflammation and tumor metastasis. The inflammatory tumor microenvironment established by chronic inflammation can induce ROS production through inflammatory cells. ROS can then directly damage DNA or indirectly activate cellular signaling pathways to promote tumor metastasis and development, including breast cancer, lung cancer, liver cancer, colorectal cancer, and so on. This review aims to elucidate the relationship between ROS, chronic inflammation, and tumor metastasis, explaining how chronic inflammation can induce tumor metastasis and how ROS can contribute to the evolution of chronic inflammation toward tumor metastasis. Interestingly, ROS can have a “double-edged sword” effect, promoting tumor metastasis in some cases and inhibiting it in others. This article also highlights the potential applications of ROS in inhibiting tumor metastasis and enhancing the precision of tumor-targeted therapy. Combining ROS with nanomaterials strategies may be a promising approach to enhance the efficacy of tumor treatment.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189175"},"PeriodicalIF":9.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the role of connexins and specialized intercellular communication pathways in breast cancer: Mechanisms and applications","authors":"Marina Rodríguez-Candela Mateos ,&nbsp;Paula Carpintero-Fernández ,&nbsp;Paz Santiago Freijanes ,&nbsp;Joaquin Mosquera ,&nbsp;Benigno Acea Nebril ,&nbsp;María D. Mayán","doi":"10.1016/j.bbcan.2024.189173","DOIUrl":"10.1016/j.bbcan.2024.189173","url":null,"abstract":"<div><p>Gap junctions, membrane-based channels comprised of connexin proteins (Cxs), facilitate direct communication among neighbouring cells and between cells and the extracellular space through their hemichannels. The normal human breast expresses various Cxs family proteins, such as Cx43, Cx30, Cx32, Cx46, and Cx26, crucial for proper tissue development and function. These proteins play a significant role in breast cancer development, progression, and therapy response. In primary tumours, there is often a reduction and cytoplasmic mislocalization of Cx43 and Cx26, while metastatic lesions show an upregulation of these and other Cxs. Although existing research predominantly supports the tumour-suppressing role of Cxs in primary carcinomas through channel-dependent and independent functions, controversies persist regarding their involvement in the metastatic process. This review aims to provide an updated perspective on Cxs in human breast cancer, with a specific focus on intrinsic subtypes due to the heterogeneous nature of this disease. Additionally, the manuscript will explore the role of Cxs in immune interactions and novel forms of intercellular communication, such as tunneling nanotubes and extracellular vesicles, within the breast tumour context and tumour microenvironment. Recent findings suggest that Cxs hold potential as therapeutic targets for mitigating metastasis and drug resistance. Furthermore, they may serve as novel biomarkers for cancer prognosis, offering promising avenues for future research and clinical applications.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189173"},"PeriodicalIF":9.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304419X24001045/pdfft?md5=0a3ee76109f64fba00341b1262150d41&pid=1-s2.0-S0304419X24001045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating macrophage-mediated programmed cell removal: An attractive strategy for cancer therapy","authors":"Zhenzhen Li ,&nbsp;Bingqian Han ,&nbsp;Menghui Qi ,&nbsp;Yinchao Li ,&nbsp;Yongtao Duan ,&nbsp;Yongfang Yao","doi":"10.1016/j.bbcan.2024.189172","DOIUrl":"10.1016/j.bbcan.2024.189172","url":null,"abstract":"<div><p>Macrophage-mediated programmed cell removal (PrCR) is crucial for the identification and elimination of needless cells that maintain tissue homeostasis. The efficacy of PrCR depends on the balance between pro-phagocytic “eat me” signals and anti-phagocytic “don't eat me” signals. Recently, a growing number of studies have shown that tumourigenesis and progression are closely associated with PrCR. In the tumour microenvironment, PrCR activated by the “eat me” signal is counterbalanced by the “don't eat me” signal of CD47/SIRPα, resulting in tumour immune escape. Therefore, targeting exciting “eat me” signalling while simultaneously suppressing “don't eat me” signalling and eventually inducing macrophages to produce effective PrCR will be a very attractive antitumour strategy. Here, we comprehensively review the functions of PrCR-activating signal molecules (CRT, PS, Annexin1, SLAMF7) and PrCR-inhibiting signal molecules (CD47/SIRPα, MHC-I/LILRB1, CD24/Siglec-10, SLAMF3, SLAMF4, PD-1/PD-L1, CD31, GD2, VCAM1), the interactions between these molecules, and Warburg effect. In addition, we highlight the molecular regulatory mechanisms that affect immune system function by exciting or suppressing PrCR. Finally, we review the research advances in tumour therapy by activating PrCR and discuss the challenges and potential solutions to smooth the way for tumour treatment strategies that target PrCR.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189172"},"PeriodicalIF":9.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling molecular aberrations and pioneering therapeutic strategies in osteosarcoma","authors":"Peng Yan ,&nbsp;Jie Wang ,&nbsp;Bin Yue ,&nbsp;Xinyi Wang","doi":"10.1016/j.bbcan.2024.189171","DOIUrl":"10.1016/j.bbcan.2024.189171","url":null,"abstract":"<div><p>Osteosarcoma, a rare primary bone cancer, presents diverse molecular aberrations that underscore its complexity. Despite the persistent endeavors by researchers, the limited amelioration in the five-year survival rate indicates that current therapeutic strategies prove inadequate in addressing the clinical necessities. Advancements in molecular profiling have facilitated an enhanced comprehension of the biology of osteosarcoma, offering a promising outlook for treatment. There is an urgent need to develop innovative approaches to address the complex challenges of osteosarcoma, ultimately contributing to enhanced patient outcomes. This review explores the nexus between osteosarcoma and cancer predisposition syndromes, intricacies in its somatic genome, and clinically actionable alterations. This review covers treatment strategies, including surgery, chemotherapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs). Innovative treatment modalities targeting diverse pathways, including multi-target tyrosine kinases, cell cycle, PI3K/mTOR pathway, and DNA damage repair (DDR), offer promising interventions. This review also covers promising avenues, including antibody-drug conjugates (ADCs) and immunotherapy strategies, such as cytokines, adoptive cellular therapy (ACT), ICIs, and cancer vaccines. This comprehensive exploration contributes to a holistic understanding, offering guidance for clinical applications to advance the management of osteosarcoma.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189171"},"PeriodicalIF":9.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule in cancer immunotherapy: Revolutionizing cancer treatment with transformative, game-changing breakthroughs","authors":"Soumyadeep Chattopadhyay,&nbsp;Rudradeep Hazra,&nbsp;Arijit Mallick,&nbsp;Sakuntala Gayen,&nbsp;Souvik Roy","doi":"10.1016/j.bbcan.2024.189170","DOIUrl":"10.1016/j.bbcan.2024.189170","url":null,"abstract":"<div><p>Immunotherapy has revolutionized cancer management, with antibody-based treatments leading the charge due to their superior pharmacodynamics, including enhanced effectiveness and specificity. However, these therapies are hampered by limitations such as prolonged half-lives, poor tissue and tumor penetration, and minimal oral bioavailability. Additionally, their immunogenic nature can cause adverse effects. Consequently, the focus is shifting towards small-molecule-based immunotherapies, which potentially overcome these drawbacks. Emerging as a promising alternative, small molecules offer the benefits of therapeutic antibodies and immunomodulators, often yielding synergistic effects when combined. Recent advancements in small-molecule cancer immunotherapy are notable, featuring inhibitors, agonists, and degraders that act as immunomodulators. This article delves into the current landscape of small-molecule immunotherapy in cancer treatment, highlighting novel agents targeting key pathways such as Toll-like receptors (TLR), PD-1/PD-L1, chemokine receptors, and stimulators of interferon genes (STING). The review emphasizes newly discovered molecular entities and their modulatory roles in tumorigenesis, many of which have progressed to clinical trials, that aims to provide a comprehensive snapshot of the evolving frontier in cancer treatment, driven by small-molecule immunomodulators.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189170"},"PeriodicalIF":9.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual perspective on autophagy in glioma: Detangling the dichotomous mechanisms of signaling pathways for therapeutic insights","authors":"Moumita Kundu ,&nbsp;Subhayan Das ,&nbsp;Ankita Dey ,&nbsp;Mahitosh Mandal","doi":"10.1016/j.bbcan.2024.189168","DOIUrl":"10.1016/j.bbcan.2024.189168","url":null,"abstract":"<div><p>Autophagy is a normal physiological process that aids the recycling of cellular nutrients, assisting the cells to cope with stressed conditions. However, autophagy's effect on cancer, including glioma, is uncertain and involves complicated molecular mechanisms. Several contradictory reports indicate that autophagy may promote or suppress glioma growth and progression. Autophagy inhibitors potentiate the efficacy of chemotherapy or radiation therapy in glioma. Numerous compounds stimulate autophagy to cause glioma cell death. Autophagy is also involved in the therapeutic resistance of glioma. This review article aims to detangle the complicated molecular mechanism of autophagy to provide a better perception of the two-sided role of autophagy in glioma and its therapeutic implications. The protein and epigenetic modulators of the cytoprotective and cytotoxic role of autophagy are described in this article. Moreover, several signaling pathways are associated with autophagy and its effects on glioma. We have reviewed the molecular pathways and highlighted the signaling axis involved in cytoprotective and cytotoxic autophagy. Additionally, this article discusses the role of autophagy in therapeutic resistance, including glioma stem cell maintenance and tumor microenvironment regulation. It also summarizes several investigations on the anti-glioma effects of autophagy modulators to understand the associated mechanisms and provide insights regarding its therapeutic implications.</p></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 5","pages":"Article 189168"},"PeriodicalIF":9.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}