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

{"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}

{"title":"An outsider's perspective--ecotaxis revisited: an integrative review of cancer environment, iron and immune system cells.","authors":"Maria de Sousa","doi":"10.1039/c0ib00116c","DOIUrl":"https://doi.org/10.1039/c0ib00116c","url":null,"abstract":"<p><p>Lymphoid cell and tumor cell migration share similarities: 1. migration to specific microenvironments; 2. increased microvasculature with increased growth; 3. cell division. At the same time, contrasting aspects between the two merit attention: 1. failure of tumors to return to microvasculature quiescence; 2. failure of malignant cells to stop dividing; 3. failure of tumor cells to re-enter the circulation after returning to a non-activated phenotype. Analysis of these contrasting aspects leads to the reviewing of unexpected roles of immune cells in the tumor environment, recent work on ferroportin expression with lack of iron export by tumor cells, iron export by M2 macrophages, and deficient dendritic cells (DCs) in the tumor environment. DCs in lymph nodes have recently been found to bring lymph node vasculature to quiescence after antigen stimulation. Contrary to current dogma, the evidence is that some immune system cells in the tumor environment may be favoring regulators instead of diminishing tumor growth. In addition, recent data herein reviewed will make it difficult not to consider iron and iron gene expression as relevant components of the tumor environment. Finally, I conclude with wondering how much longer what I call the 'Hunter Paradigm' will dominate cancer research and immunology and how timely it is to acknowledge in the first decade of a new century, Mina Bissell as a pioneer in the change of that paradigm in Cancer Research. \"Suppose he'd listened to the erudite committee; He would have only found where not to look\" WH Auden.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"343-9"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00116c","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555139","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":"Social selection and the evolution of cooperative groups: the example of the cellular slime moulds.","authors":"Vidyanand Nanjundiah,&nbsp;Santosh Sathe","doi":"10.1039/c0ib00115e","DOIUrl":"https://doi.org/10.1039/c0ib00115e","url":null,"abstract":"<p><p>In social selection the phenotype of an individual depends on its own genotype as well as on the phenotypes, and so genotypes, of other individuals. This makes it impossible to associate an invariant phenotype with a genotype: the social context is crucial. Descriptions of metazoan development, which often is viewed as the acme of cooperative social behaviour, ignore or downplay this fact. The implicit justification for doing so is based on a group-selectionist point of view. Namely, embryos are clones, therefore all cells have the same evolutionary interest, and the visible differences between cells result from a common strategy. The reasoning is flawed, because phenotypic heterogeneity within groups can result from contingent choices made by cells from a flexible repertoire as in multicellular development. What makes that possible is phenotypic plasticity, namely the ability of a genotype to exhibit different phenotypes. However, co-operative social behaviour with division of labour requires that different phenotypes interact appropriately, not that they belong to the same genotype, or have overlapping genetic interests. We sketch a possible route to the evolution of social groups that involves many steps: (a) individuals that happen to be in spatial proximity benefit simply by virtue of their number; (b) traits that are already present act as preadaptations and improve the efficiency of the group; and (c) new adaptations evolve under selection in the social context--that is, via interactions between individuals--and further strengthen group behaviour. The Dictyostelid or cellular slime mould amoebae (CSMs) become multicellular in an unusual way, by the aggregation of free-living cells. In nature the resulting group can be genetically homogeneous (clonal) or heterogeneous (polyclonal); in either case its development, which displays strong cooperation between cells (to the extent of so-called altruism) is not affected. This makes the CSMs exemplars for the study of social behaviour.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"329-42"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00115e","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29624136","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":"Apoptotic cell signaling in cancer progression and therapy.","authors":"Jessica Plati, Octavian Bucur, Roya Khosravi-Far","doi":"10.1039/c0ib00144a","DOIUrl":"10.1039/c0ib00144a","url":null,"abstract":"<p><p>Apoptosis is a tightly regulated cell suicide program that plays an essential role in the development and maintenance of tissue homeostasis by eliminating unnecessary or harmful cells. Impairment of this native defense mechanism promotes aberrant cellular proliferation and the accumulation of genetic defects, ultimately resulting in tumorigenesis, and frequently confers drug resistance to cancer cells. The regulation of apoptosis at several levels is essential to maintain the delicate balance between cellular survival and death signaling that is required to prevent disease. Complex networks of signaling pathways act to promote or inhibit apoptosis in response to various cues. Apoptosis can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors. Various upstream signaling pathways can modulate apoptosis by converging on, and thereby altering the activity of, common central control points within the apoptotic signaling pathways, which involve the BCL-2 family proteins, inhibitor of apoptosis (IAP) proteins, and FLICE-inhibitory protein (c-FLIP). This review highlights the role of these fundamental regulators of apoptosis in the context of both normal apoptotic signaling mechanisms and dysregulated apoptotic pathways that can render cancer cells resistant to cell death. In addition, therapeutic strategies aimed at modulating the activity of BCL-2 family proteins, IAPs, and c-FLIP for the targeted induction of apoptosis are briefly discussed.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"279-96"},"PeriodicalIF":0.0,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130501/pdf/nihms300528.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29688746","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":"Hyaluronan metabolism in remodeling extracellular matrix: probes for imaging and therapy of breast cancer.","authors":"M Veiseh,&nbsp;E A Turley","doi":"10.1039/c0ib00096e","DOIUrl":"https://doi.org/10.1039/c0ib00096e","url":null,"abstract":"<p><p>Clinical and experimental evidence increasingly support the concept of cancer as a disease that emulates a component of wound healing, in particular abnormal stromal extracellular matrix remodeling. Here we review the biology and function of one remodeling process, hyaluronan (HA) metabolism, which is essential for wound resolution but closely linked to breast cancer (BCA) progression. Components of the HA metabolic cycle (HAS2, SPAM1 and HA receptors CD44, RHAMM/HMMR and TLR2) are discussed in terms of their known functions in wound healing and in breast cancer progression. Finally, we discuss recent advances in the use of HA-based platforms for developing nanoprobes to image areas of active HA metabolism and for therapeutics in breast cancer.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"304-15"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00096e","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29624013","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":"Communication theory and multicellular biology.","authors":"I S Mian,&nbsp;C Rose","doi":"10.1039/c0ib00117a","DOIUrl":"https://doi.org/10.1039/c0ib00117a","url":null,"abstract":"<p><p>In this Perspective, we propose that communication theory--a field of mathematics concerned with the problems of signal transmission, reception and processing--provides a new quantitative lens for investigating multicellular biology, ancient and modern. What underpins the cohesive organisation and collective behaviour of multicellular ecosystems such as microbial colonies and communities (microbiomes) and multicellular organisms such as plants and animals, whether built of simple tissue layers (sponges) or of complex differentiated cells arranged in tissues and organs (members of the 35 or so phyla of the subkingdom Metazoa)? How do mammalian tissues and organs develop, maintain their architecture, become subverted in disease, and decline with age? How did single-celled organisms coalesce to produce many-celled forms that evolved and diversified into the varied multicellular organisms in existence today? Some answers can be found in the blueprints or recipes encoded in (epi)genomes, yet others lie in the generic physical properties of biological matter such as the ability of cell aggregates to attain a certain complexity in size, shape, and pattern. We suggest that Lasswell's maxim \"Who says what to whom in what channel with what effect\" provides a foundation for understanding not only the emergence and evolution of multicellularity, but also the assembly and sculpting of multicellular ecosystems and many-celled structures, whether of natural or human-engineered origin. We explore how the abstraction of communication theory as an organising principle for multicellular biology could be realised. We highlight the inherent ability of communication theory to be blind to molecular and/or genetic mechanisms. We describe selected applications that analyse the physics of communication and use energy efficiency as a central tenet. Whilst communication theory has and could contribute to understanding a myriad of problems in biology, investigations of multicellular biology could, in turn, lead to advances in communication theory, especially in the still immature field of network information theory.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"350-67"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00117a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29757786","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":"Connexins and the gap in context.","authors":"R M Mroue,&nbsp;M E El-Sabban,&nbsp;R S Talhouk","doi":"10.1039/c0ib00158a","DOIUrl":"https://doi.org/10.1039/c0ib00158a","url":null,"abstract":"<p><p>Gap junctions (GJ) can no longer be thought of as simple channel forming structures that mediate intercellular communication. Hemi-channel and channel-independent functions of connexins (Cxs) have been described and numerous Cx interacting partners have been uncovered ranging from enzymes to structural and scaffolding molecules to transcription factors. With the growing number of Cx partners and functions, including well-documented roles for Cxs as conditional tumor suppressors, it has become essential to understand how Cxs are regulated in a context-dependent manner to mediate distinct functions. In this review we will shed light on the tissue and context-dependent regulation and function of Cxs and on the importance of Cx-interactions in modulating tissue-specific function. We will emphasize how the context-dependent functions of Cxs can help in understanding the impact of Cx mis-expression on cancer development and, ultimately, explore whether Cxs can be used as potential therapeutic targets in cancer treatment. In the end, we will address the need for developing relevant assays for studying Cx and GJ functions and will highlight how advances in bioengineering tools and the design of 3D biological platforms can help studying gap junction function in real time in a non-intrusive manner.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"255-66"},"PeriodicalIF":2.5,"publicationDate":"2011-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00158a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29768791","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":"Intracellular degradation of low-density lipoprotein probed with two-color fluorescence microscopy.","authors":"William H Humphries,&nbsp;Nicole C Fay,&nbsp;Christine K Payne","doi":"10.1039/c0ib00035c","DOIUrl":"https://doi.org/10.1039/c0ib00035c","url":null,"abstract":"<p><p>The intracellular vesicle-mediated degradation of extracellular cargo is an essential cellular function. Using two-color single particle tracking fluorescence microscopy, we have probed the intracellular degradation of low-density lipoprotein (LDL) in living cells. To detect degradation, individual LDL particles were heavily labeled with multiple fluorophores resulting in a quenched fluorescent signal. The degradation of the LDL particle then resulted in an increase in fluorescence. Endocytic vesicles were fluorescently labeled with variants of GFP. We imaged the transient colocalization of LDL with endocytic vesicles while simultaneously measuring the intensity of the LDL particle as an indicator of degradation. These studies demonstrate that late endosomes are active sites of degradation for LDL. Measurement of the time from colocalization with lysosome-associated membrane protein 1 (LAMP1) vesicles to degradation suggests that LAMP1-vesicles initiate the degradative event. Observing degradation as it occurs in living cells makes it possible to describe the complete endocytic pathway of LDL from internalization to degradation. More generally, this research provides a model for the intracellular degradation of extracellular cargo and a method for its study in living cells.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"536-44"},"PeriodicalIF":2.5,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00035c","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40080091","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}