{"title":"Salmonella typhi induced oncogenesis in gallbladder cancer: Co-relation and progression","authors":"Aditya Upadhayay, Dharm Pal, Awanish Kumar","doi":"10.1016/j.adcanc.2022.100032","DOIUrl":"10.1016/j.adcanc.2022.100032","url":null,"abstract":"<div><p>Generally, bacteria cause infectious diseases. The role of bacteria as a causative agent of oncogenesis or mediators has been less known and elucidated. To date, <em>Helicobacter pylori</em> and <em>Chlamydia pneumonia</em> were identified and reported as cancer-causing bacterial pathogens. Research reports also indicated <em>Salmonella typhi</em> as oncogenic bacteria that alter the human immune system and establishes gall bladder cancer (GBC). <em>S. typhi</em> releases the carcinogenic toxic molecules at the chronic phase with the asymptomatic sign and facilitates the process of transformation of normal cells into the carcinogenic cell. <em>S. typhi</em> infection may work as a key indicator for future GBC and lethality in planktonic conditions. The clinician identified the typhoid infection and break down the association at the primary stage in GBC. This article contains the relationship between gallbladder cancer and <em>S. typhi</em> and gets attention in the field of oncology because pathogen may work as a carcinogen. Because the pathogenic drive cancer field is not fully described.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000065/pdfft?md5=ccfe5bbb4dff91e86636008488831d3e&pid=1-s2.0-S2667394022000065-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43475065","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":"Understanding the association of stem cells in fetal development and carcinogenesis during pregnancy","authors":"Kasturi Banerjee , Agnibha Chattopadhyay , Satarupa Banerjee","doi":"10.1016/j.adcanc.2022.100042","DOIUrl":"10.1016/j.adcanc.2022.100042","url":null,"abstract":"<div><p>Cancer during pregnancy is a rare event in the realm of obstetric statistics. Stem cells are known for their capability to renew their demographic to a variety of cell lineages. Embryonic stem cells (ESCs) originating from the blastocyst include haematopoietic stem cells (HSC) and mesenchymal stem cells (MSC). These cells play vital roles in the complex course of fetal growth and development. MSCs are found to suppress tumour growth by inhibiting PI3K/AKT pathway. Although a notable amount of literature is available about the occurrence of cancer during pregnancy, there is a lacuna about the interaction between the fetal stem cell (FSCs) and the cancer cells. A literature review revealed that the risk of ovarian cancer is reduced with an increase in fetal stem cells. After delivery, fetal microchimerism is observed to promote or suppress tumour growth under specific conditions. This review highlights the mechanism and extent of the association of FSC with the occurrence of various cancers during pregnancy. A new perspective on mother to fetus cancer transmission, which is commonly leukemia and melanoma, and the reasons for FSCs to respond differently to these cancers under various conditions have been identified by analyzing recent pieces of literature. This review also gives an idea about the existing and probable therapeutic benefits obtained from the FSCs in curbing the extent of maternal tumour metastasis. Stem cells are presently being manipulated to consistently express different chimeric antigen receptors or T cell receptors, countering tumour-associated antigens. Thus, this study highlights the therapeutic potential of the interesting crosstalk against haematological malignancies and solid tumours.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000168/pdfft?md5=798f707e75397a1e515bd6a25c7f74e9&pid=1-s2.0-S2667394022000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47948820","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}
Lindsay R. Dresang , Christian A. Van Scoyk , Kirby J. Kuehn , Taylor A. Tauber , Arthur R. Tondin , Morgan A. Broske , Cody J. Schreiner
{"title":"Comparing transcriptomic profiles from seven cell lines to elucidate liver metastatic potential","authors":"Lindsay R. Dresang , Christian A. Van Scoyk , Kirby J. Kuehn , Taylor A. Tauber , Arthur R. Tondin , Morgan A. Broske , Cody J. Schreiner","doi":"10.1016/j.adcanc.2021.100018","DOIUrl":"10.1016/j.adcanc.2021.100018","url":null,"abstract":"<div><h3>Overview</h3><p>The liver is a vital organ, performing over 500 functions. Metastasis to the liver can disrupt these functions, resulting in poor prognoses. It is not always clear why liver metastasis arises in one case but not another involving the same cancer type. We sought to understand which transcripts and cellular pathways are dysregulated in cell lines shown to metastasize substantially to the liver in a NOD-Scid-Gamma (NSG) mouse-xenograft model. Cancer cell lines of the same type not observed to metastasize to the liver were used for comparison, reducing cell type-specific changes or general pathways associated with cancer not linked to liver metastasis. Three metastatic versus non-metastatic pairs of diverse origin–Merkel cell, colorectal, and pancreatic carcinomas–as well as a normal fibroblast control were used for deep sequencing and transcriptome analysis with subsequent pathway identification.</p></div><div><h3>Results</h3><p>Dysregulated pathways involve cell adhesion, proliferation, and motility (among others), which are consistent with increased malignant potential in the cell lines that support liver metastasis. In addition, dysregulated peroxisome proliferating activated receptor (PPAR) signaling and lipid metabolic / trafficking pathways are candidates for fostering homing to the liver. A surprise was a significant drop in <em>AGR2</em> expression in cells favoring liver metastasis, while still remaining elevated relative to normal fibroblast controls. Newer clinical data revealed declining levels of <em>AGR2</em> correlate with higher grade lesions and poorer prognoses in patients with various cancer types. Decreased expression of <em>FOXA2</em> similarly correlates with clinical data as a prognostic factor. A drop in <em>FOXA2</em> expression was observed in cell lines favoring liver metastasis, as well as a cell line generated from an NSG-xenograft liver metastasis, which may also explain the liver site preference of select cancer cell lines. Both genes correlate with PPAR signaling dysregulation and either directly or indirectly link to such pathways. Meanwhile, <em>LOXL2</em> is lower in the cancer cell lines supporting liver metastasis compared to normal fibroblasts, but is substantially elevated relative to paired cancer cell lines which did not metastasize to the liver. <em>LOXL2</em> is a gene involved in epithelial-mesenchymal transition (EMT), which is expressed at high levels in both normal and cancer-associated fibroblasts.</p></div><div><h3>Conclusions</h3><p>Using only a normal fibroblast control for comparison, or only comparing cancer cells as separate pairs, would have masked several potential candidate genes and pathways linked to liver metastasis. Our findings correlate well with newer clinical data and reinforce biomarkers of disease progression. The dysregulated genes and pathways highlight potential targets to slow disease progression.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394021000186/pdfft?md5=82d3eef63d51cdc137904bd41b5ecfd3&pid=1-s2.0-S2667394021000186-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49035238","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}
Anjali Singh , Shivani Malvankar , Y.S. Ravi Kumar , Mahendra Seervi , Rupesh K. Srivastava , Bhupendra Verma
{"title":"Role of various non-coding RNAs in EMT, cancer, and metastasis: Recent trends and future perspective","authors":"Anjali Singh , Shivani Malvankar , Y.S. Ravi Kumar , Mahendra Seervi , Rupesh K. Srivastava , Bhupendra Verma","doi":"10.1016/j.adcanc.2022.100039","DOIUrl":"10.1016/j.adcanc.2022.100039","url":null,"abstract":"<div><p>Epithelial-to-mesenchymal transition (EMT) is a key cellular process involved in the various biological processes ranging from embryonic development, wound healing, and cancer metastasis. EMT is the key player in cancer progression to a metastatic state. The transformed tumor cells acquire the migratory property and invade surrounding tissues, which ultimately leads to cancer metastasis <em>via</em> EMT. Epithelial cells undergo certain phenotypic changes to acquire mesenchymal status. At a molecular level, this transition process is elicited by several signaling cascades that include cytokines and a group of transcription factors like Twist, snail, and Zeb1/2. Emerging evidence suggests that various non-coding RNAs (ncRNAs) play a significant role in modulating EMT-associated transcription factors (EMT-TFs) and molecular signaling at the transcriptional and post-transcriptional level and thus, regulating the EMT process. Various noncoding-RNAs like miRNAs, piRNAs, tsRNAs, lncRNAs, T-UCRs, CircRNAs, eRNAs, snoRNAs can either promote or can inhibit the process of EMT and thus modulates cancer progression. Here we review the recent research advances in delineating the role of various non-coding RNAs in the EMT, cancer, and metastasis process as well as their potential roles as biomarkers and therapeutic targets.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000132/pdfft?md5=255c95f88b043ea5fa80942ef490e3fb&pid=1-s2.0-S2667394022000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53939169","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":"Expression of CD91 in extracellular vesicles: A potential biomarker for the diagnosis of non-small cell lung cancer","authors":"Shayista Akbar , Shahnaz Qadri , Sarmadia Ashraf , Aijaz Parray , Afsheen Raza , Wafa Abualainin , Said Dermime , Yousef Haik","doi":"10.1016/j.adcanc.2022.100046","DOIUrl":"10.1016/j.adcanc.2022.100046","url":null,"abstract":"<div><p>Lung cancer is the leading cause of death; by the time it is diagnosed, the patient is usually in late-stage grade IV. Late-stage lung cancer is mainly associated with metastasis in the liver, brain, and lymphoid tissues; as a result, a localized lung cancer treatment remains meaningless. Early diagnosis of non-small cell lung cancer (NSCLC) may be curable or will improve the survival rate. Although with advanced developments to screen high-risk patients by LDCT scan, false-positive rates and limited resolution necessitated the development of advanced diagnostic techniques for NSCLC. Extracellular vesicles (EVs) released from cells freely circulate in the blood and contain various transmembrane proteins, and they may be a non-invasive biomarker for cancer diagnosis and prognosis. Current studies predict that the CD91 marker in EVs may be a potential biomarker of NSCLC; however, the expression of CD91 in lung cancer tissues is not fully known. Here, this study determines the differential expression of CD91 in lung cancer cells and in circulating EVs in blood as a potential biomarker of NSCLC patients. Our results confirmed the expression of CD91 in NCI–H1975 cultured cells and NSCLC lung biopsy tissues. Furthermore, biophysical characterization of EVs from lung cancer cells determines the substantial expression of CD91, which the Transmission Electron Microscope confirms. Thus, this study suggests EVs containing CD91 could be an asset to studying the development of diagnostic and prognostic biomarkers in NSCLC disease.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266739402200020X/pdfft?md5=5799b7c09d395e8b7860463585a65723&pid=1-s2.0-S266739402200020X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42374109","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":"Synergistic anti-cancer effects of NIR-light responsive nanotherapeutics for chemo-photothermal therapy and photothermal immunotherapy: A combined therapeutic approach","authors":"Laxmanan Karthikeyan, Raju Vivek","doi":"10.1016/j.adcanc.2022.100044","DOIUrl":"10.1016/j.adcanc.2022.100044","url":null,"abstract":"<div><p>Cancer nanomedicine is an important medical application in nanotechnology research tools that have special properties such as flexibility, easy modulation, and high targeting efficiency on tumor tissues. The designing of controlled drug delivery at a nanoscale level to target tumor cells is known as the nano-drug delivery system (NDDS). Nanoparticles (NPs) - based NDDS has distinct advantages over traditional pharmaceuticals, including greater stability and biocompatibility, enhanced permeability and retention effect (EPR), and precisely targeted tumor tissue. Near-infrared (NIR) light-responsive NPs utilized for photothermal effects are called photothermal therapy (PTT). PTT is the most significant aspect of nanotechnology to cure tumors because, thermal heat energy directly induces tumor ablation, without any normal cell damage and side effects. Chemotherapy is one of the most efficient strategies for cancer therapy but it has side effects. Cancer immunotherapy aims to reactivate autoimmune responses for fighting cancer cells. Hence, the combination of chemotherapy, PTT, and Immunotherapy can be efficiently achieved to enhance antitumor efficacy. This comprehensive review is mainly focused on the combined therapeutic effects of chemo-PTT (CPTT) and photothermal immunotherapy (PIT) on cancer treatment and metastatic inhibition. Nowadays, a specific combination of CPTT and PIT is one of the most effective methods to treat cancers. Therefore, the combined therapeutic approach has a great potential effect to fight against cancer for tumor regression and metastatic inhibition.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000181/pdfft?md5=48a69450fc017d0e8a7e2cb7f02f095a&pid=1-s2.0-S2667394022000181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48383266","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}
Mona N. Oliveira , Micheli M. Pillat , Juliana Baranova , Roberta Andrejew , Balbino Lino dos Santos , Silvia Lima Costa , Tamara T. Lah , Henning Ulrich
{"title":"Glioblastoma cell invasiveness and epithelial-to-mesenchymal transitioning are modulated by kinin receptors","authors":"Mona N. Oliveira , Micheli M. Pillat , Juliana Baranova , Roberta Andrejew , Balbino Lino dos Santos , Silvia Lima Costa , Tamara T. Lah , Henning Ulrich","doi":"10.1016/j.adcanc.2022.100045","DOIUrl":"10.1016/j.adcanc.2022.100045","url":null,"abstract":"<div><p>Glioblastoma (GB) is the most aggressive primary tumor of central nervous system, where no efficient therapy has been found so far. This is due to high intra- and inter- tumor heterogeneity, fast invasion and the therapy-resistant subpopulation of GB stem cells and their plasticity. Tumor heterogeneity involves interactions among cancer cells and stromal cells, such as mesenchymal stem cells (MSCs), that are recruited into the tumor microenvironment and migrate to the tumor site. Here, we characterized the impact of kinin receptors on the interaction of MSCs with GB cells which is further enhanced by kinin receptor agonists. Interactions between GB cells and MSCs were studied in two- and three-dimensional co-cultures. Kinin receptor activity was modulated by selective agonists and antagonists to evaluate their influence on cell viability, cell-cell interactions, GB U87 cell invasiveness, and phenotype alterations. Tumor cell invasion was enhanced by the kinin-B2 receptor agonist bradykinin, while it was blocked by B2 receptor antagonists applied in U87 cells monoculture and in co-culture with MSCs. Kinin receptor inhibition correlated with enhanced direct U87/MSC interactions, such as heterotypic fusion, vesicle transfer and entosis. Furthermore, kinin receptor modulation influenced expression of F-actin expression and genes associated with epithelial-to-mesenchymal transition in U87 cells upon U87/MSCs co-cultures. Our data support ongoing investigations of kinin receptor inhibition as an adjuvant approach in GB therapy. MSC impacts on cancer progression need further investigation, as they may have a synergistic effect with kininergic receptor activation.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000193/pdfft?md5=78b7b741fbd80336fd1572d7560b8069&pid=1-s2.0-S2667394022000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45016001","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}
Yulieth Ximena Torres-Llanos , Alba Lucia Combita-Rojas
{"title":"Relation between tumor micro-environment and epigenetic alterations in hematological malignancies","authors":"Yulieth Ximena Torres-Llanos , Alba Lucia Combita-Rojas","doi":"10.1016/j.adcanc.2021.100024","DOIUrl":"10.1016/j.adcanc.2021.100024","url":null,"abstract":"<div><p>The bone marrow microenvironment is an anatomical site from which we can learn more. It is important to consider the different molecular mechanisms developed there, to obtain possible therapeutic targets that help prevent relapse and chemoresistance. This review addresses epigenetic mechanisms (DNA methylation, histone modification, miRNAs and lnRNAs) involved in the modulation of the microenvironment, which, in turn, contribute to the acquisition of chemoresistance and relapse. Addressing these aspects can contribute to a better understanding of interactions in the bone marrow, which helps turn chemotherapy into a more personalized treatment that not only evaluates alterations in malignant cells, but also considers epigenetic changes present in non-tumor cells, the release of cytokines and exosomes, as well as cell-cell communication. These interactions are described in different neoplastic diseases of hematological origin.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394021000241/pdfft?md5=72fbb05914d3da812f0ae7848fb6e57e&pid=1-s2.0-S2667394021000241-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45237064","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":"The role of exosome heterogeneity in epithelial ovarian cancer","authors":"Amy H. Lee , Ivy L. Koh , Michelle R. Dawson","doi":"10.1016/j.adcanc.2022.100040","DOIUrl":"10.1016/j.adcanc.2022.100040","url":null,"abstract":"<div><p>Ovarian cancer results in more deaths than any other gynecological malignancy, with a 5-year survival of only 30%. It is typically diagnosed after it has spread from the primary site to the secondary site. Exosomes are membrane-bound nanovesicles that play a critical role in tumor biology and metastasis by promoting intercellular communication. Tumor-associated exosome populations are widely acknowledged to be heterogenous, as various cell types and hallmark tumor microenvironment stressors impact exosome synthesis. Ovarian cancer cells metastasize using intraperitoneal fluids that are rich in exosomes, suggesting that these circulating exosomes assist detached cancer cells to maintain invasive phenotypes prior to secondary site invasion. Studies show that tumor-secreted exosomes direct organ-specific colonization by fusing exosome integrins with target cells in a tissue-specific fashion. Exosome signaling molecules (mRNA, miRNA, proteins) are encapsulated by cholesterol-rich membranes, and thus protects biomaterials from enzymatic degradation. Therefore, they represent an ideal system for studying the expression of sensitive proteins and RNA and for future drug delivery vehicles. Proteins and RNA exchanged through exosomes also influence the molecular and mechanical properties of ovarian cancer cells promoting adaptations that contribute to invasive and metastatic cell behavior. Tumor-derived exosomes also interact with stromal cells to alter their molecular profiles, thus promoting the development of a more malignant tumor microenvironment (TME), invasive cell behavior, and cancer progression. This review provides an overview on exosome structure and biogenesis and summarizes recent studies on ovarian cancer exosomes, exosome mediated interactions in the tumor microenvironment, and exosome heterogeneity.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000144/pdfft?md5=fdeea657ba9b65c941372859563f41ae&pid=1-s2.0-S2667394022000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47418216","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}