Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells.","authors":"Lei Wang,&nbsp;Andre Alcon,&nbsp;Hongwei Yuan,&nbsp;Jeffrey Ho,&nbsp;Qi-Jing Li,&nbsp;M Martins-Green","doi":"10.1039/c0ib00122h","DOIUrl":"https://doi.org/10.1039/c0ib00122h","url":null,"abstract":"<p><p>Prostate cancer is the second leading cause of cancer-related deaths among US males. Pomegranate juice (PJ), a natural product, was shown in a clinical trial to inhibit progression of this disease. However, the underlying mechanisms involved in the anti-progression effects of PJ on prostate cancer remain unclear. Here we show that, in addition to causing cell death of hormone-refractory prostate cancer cells, PJ also increases cell adhesion and decreases cell migration of the cells that do not die. We hypothesized that PJ does so by stimulating the expression and/or activation of molecules that alter the cytoskeleton and the adhesion machinery of prostate cancer cells, resulting in enhanced cell adhesion and reduced cell migration. We took an integrative approach to these studies by using Affimetrix gene arrays to study gene expression, microRNA arrays to study the non-coding RNAs, molecules known to be disregulated in cancer cells, and Luminex Multiplex array assays to study the level of secreted pro-inflammatory cytokines/chemokines. PJ up-regulates genes involved in cell adhesion such as E-cadherin, intercellular adhesion molecule 1 (ICAM-1) and down-regulates genes involved in cell migration such as hyaluranan-mediated motility receptor (HMMR) and type I collagen. In addition, anti-invasive microRNAs such as miR-335, miR-205, miR-200, and miR-126, were up-regulated, whereas pro-invasive microRNA such as miR-21 and miR-373, were down-regulated. Moreover, PJ significantly reduced the level of secreted pro-inflammatory cytokines/chemokines such as IL-6, IL-12p40, IL-1β and RANTES, thereby having the potential to decrease inflammation and its impact on cancer progression. PJ also inhibits the ability of the chemokine SDF1α to chemoattract these cancer cells. SDF1α and its receptor CXCR4 are important in metastasis of cancer cells to the bone. Discovery of the mechanisms by which this enhanced adhesion and reduced migration are accomplished can lead to sophisticated and effective prevention of metastasis in prostate and potentially other cancers.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"742-54"},"PeriodicalIF":2.5,"publicationDate":"2011-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00122h","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40093648","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}

{"title":"Topographic enhancement mapping of the cancer-associated breast stroma using breast MRI.","authors":"Nima Nabavizadeh,&nbsp;Catherine Klifa,&nbsp;David Newitt,&nbsp;Ying Lu,&nbsp;Yunn-Yi Chen,&nbsp;Howard Hsu,&nbsp;Clark Fisher,&nbsp;Taku Tokayasu,&nbsp;Adam B Olshen,&nbsp;Paul Spellman,&nbsp;Joe W Gray,&nbsp;Nola Hylton,&nbsp;Catherine C Park","doi":"10.1039/c0ib00089b","DOIUrl":"https://doi.org/10.1039/c0ib00089b","url":null,"abstract":"<p><p>In animal and laboratory models, cancer-associated stroma, or elements of the supporting tissue surrounding a primary tumor, has been shown to be necessary for tumor evolution and progression. However, little is understood or studied regarding the properties of intact stroma in human cancer in vivo. In addition, for breast cancer patients, the optimal volume of local tissue to treat surrounding a primary tumor is not clear. Here, we performed an interdisciplinary study of normal-appearing breast tissue using breast magnetic resonance imaging (MRI), correlative histology and array comparative genomic hybridization to identify a cancer-associated stroma in humans. Using a novel technique for segmenting breast fibroglandular tissue, quantifiable topographic percent enhancement mapping of the stroma surrounding invasive breast cancer was found to be significantly elevated within 2 cm of the tumor edge. This region was also found to harbor increased microvessel density, and genomic changes that were closely associated with host normal breast tissue. These findings indicate that a cancer-associated stroma may be identified and characterized in human breast cancer using non-invasive imaging techniques. Identification of a cancer-associated stroma may be further developed to help guide local therapy to reduce recurrence and morbidity in breast cancer patients.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"490-6"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00089b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29751540","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":"Gene transcriptional networks integrate microenvironmental signals in human breast cancer.","authors":"Ren Xu, Jian-Hua Mao","doi":"10.1039/c0ib00087f","DOIUrl":"10.1039/c0ib00087f","url":null,"abstract":"<p><p>A significant amount of evidence shows that microenvironmental signals generated from extracellular matrix (ECM) molecules, soluble factors, and cell-cell adhesion complexes cooperate at the extra- and intracellular level. This synergetic action of microenvironmental cues is crucial for normal mammary gland development and breast malignancy. To explore how the microenvironmental genes coordinate in human breast cancer at the genome level, we have performed gene co-expression network analysis in three independent microarray datasets and identified two microenvironment networks in human breast cancer tissues. Network I represents crosstalk and cooperation of ECM microenvironment and soluble factors during breast malignancy. The correlated expression of cytokines, chemokines, and cell adhesion proteins in Network II implicates the coordinated action of these molecules in modulating the immune response in breast cancer tissues. These results suggest that microenvironmental cues are integrated with gene transcriptional networks to promote breast cancer development.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"368-74"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121540/pdf/nihms-302479.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29542090","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":"L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways.","authors":"Feng Gao, Sergio X Vasquez, Feng Su, Svetlana Roberts, Neha Shah, Victor Grijalva, Satoshi Imaizumi, Arnab Chattopadhyay, Ekambaram Ganapathy, David Meriwether, Brad Johnston, G M Anantharamaiah, Mohamad Navab, Alan M Fogelman, Srinivasa T Reddy, Robin Farias-Eisner","doi":"10.1039/c0ib00147c","DOIUrl":"10.1039/c0ib00147c","url":null,"abstract":"<p><p>We recently reported that apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor growth and improve survival in a mouse model of ovarian cancer. The current study was designed to examine whether inhibition of angiogenesis is one of the mechanisms for the observed anti-tumorigenic effects. The apoA-I mimetic peptide L-5F had no affect on proliferation and cell viability of human umbilical vascular endothelial cells (HUVECs) in the basal state; however, treatment with L-5F at 1, 3, and 10 μg ml(-1), dose-dependently inhibited both vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced proliferation, cell viability, migration, invasion and tube formation in HUVECs. L-5F inhibited VEGF- and bFGF-induced activation of their corresponding receptors, VEGFR2 and FGFR1, as well as downstream signaling pathways, including Akt and ERK1/2. MicroCT scanning and immunohistochemistry staining demonstrated that daily injection of L-5F (10 mg kg(-1)) decreased both the quantity and size of tumor vessels in mice. L-5F treated mice showed significantly reduced levels of VEGF in both tumor tissue and the circulation, which is consistent with in vitro data showing that L-5F inhibited production and secretion of VEGF from mouse and human ovarian cell lines in the absence and presence of exogenously added lysophosphatidic acid, a potent tumor promoter. In conclusion, our data that L-5F inhibits angiogenesis suggests that apoA-I mimetic peptides may serve as novel anti-angiogenesis agents for the treatment of angiogenesis-associated diseases, including cancer.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"479-89"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248743/pdf/nihms345566.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29640737","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":"Biophysical regulation of tumor cell invasion: moving beyond matrix stiffness.","authors":"Amit Pathak,&nbsp;Sanjay Kumar","doi":"10.1039/c0ib00095g","DOIUrl":"https://doi.org/10.1039/c0ib00095g","url":null,"abstract":"<p><p>Invasion of cancer cells into the extracellular matrix (ECM) is a key step in tumor infiltration and metastasis. While the strong influence of ECM stiffness in governing tumor cell migration has been well established in two-dimensional culture paradigms, investigation of this parameter in three-dimensional (3D) ECMs has proven considerably more challenging, in part because perturbations that change 3D ECM stiffness often concurrently change microscale matrix parameters that critically regulate cell migration, such as pore size, fiber architecture, and local material deformability. Here we review the potential importance of these parameters in the context of tumor cell migration in 3D ECMs. We begin by discussing biophysical mechanisms of cell motility in 3D ECMs, with an emphasis on the cell-matrix mechanical interactions that underlie this process and key signatures of mesenchymal and amoeboid modes of motility. We then consider microscale matrix physical properties that are particularly relevant to 3D culture and would be expected to regulate motility, including matrix microstructure and nonlinear elasticity. We also discuss how changes in 3D matrix properties might be expected to trigger transitions in subcellular mechanisms, which in turn contribute to mesenchymal-amoeboid transition (MAT) by imposing restrictions on 3D motility. We expect that the field will gain valuable insight into invasion and metastasis by deepening its understanding of microscale, biophysical interactions between tumor cells and matrix elements and by creating new 3D scaffolds that permit orthogonal manipulation of specific matrix parameters.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"267-78"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00095g","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29578638","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}

{"title":"Cancer evolution and individual susceptibility.","authors":"Jesús Pérez-Losada, Andrés Castellanos-Martín, Jian-Hua Mao","doi":"10.1039/c0ib00094a","DOIUrl":"10.1039/c0ib00094a","url":null,"abstract":"<p><p>Cancer susceptibility is due to interactions between inherited genetic factors and exposure to environmental carcinogens. The genetic component is constituted mainly by weakly acting low-penetrance genetic variants that interact among themselves, as well as with the environment. These low susceptibility genes can be categorized into two main groups: one includes those that control intrinsic tumor cell activities (i.e. apoptosis, proliferation or DNA repair), and the other contains those that modulate the function of extrinsic tumor cell compartments (i.e. stroma, angiogenesis, or endocrine and immune systems). Genome-Wide Association Studies (GWAS) of human populations have identified numerous genetic loci linked with cancer risk and behavior, but nevertheless the major component of cancer heritability remains to be explained. One reason may be that GWAS cannot readily capture gene-gene or gene-environment interactions. Mouse model approaches offer an alternative or complementary strategy, because of our ability to control both the genetic and environmental components of risk. Recently developed genetic tools, including high-throughput technologies such as SNP, CGH and gene expression microarrays, have led to more powerful strategies for refining quantitative trait loci (QTL) and identifying the critical genes. In particular, the cross-species approaches will help to refine locations of QTLs, and reveal their genetic and environmental interactions. The identification of human tumor susceptibility genes and discovery of their roles in carcinogenesis will ultimately be important for the development of methods for prediction of risk, diagnosis, prevention and therapy for human cancers.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"316-28"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125395/pdf/nihms-302478.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29624464","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":"Special issue in honor of Mina J. Bissel.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"253-496"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30110702","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}

{"title":"Antibody-based targeting of interferon-alpha to the tumor neovasculature: a critical evaluation.","authors":"Katharina Frey,&nbsp;Andjelija Zivanovic,&nbsp;Kathrin Schwager,&nbsp;Dario Neri","doi":"10.1039/c0ib00099j","DOIUrl":"https://doi.org/10.1039/c0ib00099j","url":null,"abstract":"<p><p>The antibody-mediated targeted delivery of cytokines, growth factors and immunomodulators offers great potential for the therapy of cancer and other serious conditions. Interferon-alpha has long been used in the clinic for the treatment of patients with certain malignancies or with viral disease. Promising anticancer activity has recently been reported for two fusion proteins consisting of immunoglobulins bearing the interferon-alpha polypeptide at the C-terminal end of the molecule. Here we describe the design, production and characterization of a novel immunocytokine, in which murine interferon-alpha2 was sequentially fused with the tumor-targeting antibody fragment scFv(F8), specific to the alternatively-spliced EDA domain of fibronectin. The resulting fusion protein (F8-IFNa) could be produced to homogeneity and was shown to retain both antigen binding activity and interferon-alpha activity. Biodistribution studies in tumor-bearing mice with radioiodinated protein preparations confirmed the ability of F8-IFNa to selectively localize at the tumor site. However, using two different murine models of cancer (F9 teratocarcinomas and Cloudman S91 melanomas in immunocompetent mice), we could not detect a striking superiority for the therapeutic performance of F8-IFNa as compared to KSF-IFNa, a fusion protein of irrelevant specificity in the mouse which was used as negative control. In the paper, we present hypotheses why the antibody-based pharmacodelivery of interferon-alpha fails to eradicate tumors, in contrast to the situation observed by our group for other immunocytokines, which benefit from a selective localization at the tumor site.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"468-78"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00099j","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29590305","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}

{"title":"Breast on-a-chip: mimicry of the channeling system of the breast for development of theranostics.","authors":"Meggie M G Grafton,&nbsp;Lei Wang,&nbsp;Pierre-Alexandre Vidi,&nbsp;James Leary,&nbsp;Sophie A Lelièvre","doi":"10.1039/c0ib00132e","DOIUrl":"https://doi.org/10.1039/c0ib00132e","url":null,"abstract":"<p><p>Improved detection and therapy of breast neoplasia might benefit from nanodevices traveling inside mammary ducts. However, the decreasing size of branched mammary ducts prevents access to remote areas of the ductal system using a pressure-driven fluid-based approach. Magnetic field guidance of superparamagnetic submicron particles (SMPs) in a stationary fluid might provide a possible alternative but it is critical to first reproduce the breast ductal system to assess the use of such devices for future therapeutic & diagnostic (\"theranostic\") purposes. Here we describe the engineering of a portion of a breast ductal system using polydimethylsiloxane (PDMS) microfluidic channels with a total volume of 0.09 μl. A magnet was used to move superparamagnetic/fluorescent SMPs through a static fluid inside the microchannels. Non-neoplastic mammary epithelial S1 cells developed basoapical polarity as a flat monolayer on the PDMS surface when cultured in the presence of laminin 111, and incubation with SMPs did not result in detectable toxicity. Cells could not withstand the fluid pressure if microinjected directly in completed channels. Whereas, they readily covered laminin 111-coated PDMS surfaces when cultured in U-shaped \"hemichannels\" before completing the channels. This breast-on-chip model represents a critical step towards the mimicry of the tree-like ductal system of the breast for further testing and targeting of SMPs.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"451-9"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00132e","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29598289","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}

{"title":"In honor of Mina J. Bissell.","authors":"Mary Helen Barcellos-Hoff","doi":"10.1039/c1ib90008k","DOIUrl":"https://doi.org/10.1039/c1ib90008k","url":null,"abstract":"","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"253-4"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c1ib90008k","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29777900","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}