Biochemistry & physiology最新文献

{"title":"Impact of Temperature on Heparin and Protein Interactions.","authors":"Jing Zhao,&nbsp;Yan Kong,&nbsp;Fuming Zhang,&nbsp;Robert J Linhardt","doi":"10.4172/2168-9652.1000241","DOIUrl":"10.4172/2168-9652.1000241","url":null,"abstract":"<p><p>Heparin has many important biological activities, associated with a diverse set of interactions with biologically functional proteins. The binding mechanisms and biological significance of heparin-protein interactions have attracted wide attention. However, the temperature sensitivity of heparin-protein interaction is relatively unstudied. The impact of temperature on the binding of heparin to three representative heparin-binding proteins, antithrombin III (AT III), fibroblast growth factor-1 (FGF1) and fibroblast growth factor-2 (FGF2) are evaluated. The affinity and kinetics of these interactions were measured at 10°C, 25°C and 30°C. The association rate, dissociation rate, binding affinity and binding mass were compared at different temperatures. In the two state binding process between AT III and heparin, temperature played a negligible role on ATIII binding to heparin (1st state reaction), but demonstrated a role in the conformational change process (2nd state reaction). In the case of FGF1 and FGF2, the kinetics and affinity, while distinctly different at the temperatures studies, were still within the same order of magnitude. Based these results, we conclude that it many cases it is possible to perform surface plasmon resonance measurements of heparin-protein interaction at different temperatures, especially at reduced (ambient or lower) temperatures, and obtain comparable binding data.</p>","PeriodicalId":91216,"journal":{"name":"Biochemistry & physiology","volume":"7 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2168-9652.1000241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36539688","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":"Cancer Therapeutics Following Newton’s Third Law","authors":"A. Arbab, Meenu Jain, B. R. Achyut","doi":"10.4172/2168-9652.1000e145","DOIUrl":"https://doi.org/10.4172/2168-9652.1000e145","url":null,"abstract":"Cancer is a wound that never heals. This is suggested by the data produced after several years of cancer research and therapeutic interventions done worldwide. There is a strong similarity between Newton’s third law and therapeutic behavior of tumor. According to Newton’s third law “for every action, there is an equal and opposite reaction”. In cancer therapeutics, tumor exerts strong pro-tumor response against applied treatment and imposes therapeutic resistance, one of the major problems seen in preclinical and clinical studies. There is an urgent need to understand the tumor biology of therapy resistant tumors following the therapy. Here, we have discussed the problem and provided possible path for future studies to treat cancer.","PeriodicalId":91216,"journal":{"name":"Biochemistry & physiology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72627473","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":"Vascular Mimicry: The Next Big Glioblastoma Target","authors":"A. Arbab, Meenu Jain, B. Achyut","doi":"10.4172/2168-9652.1000e140","DOIUrl":"https://doi.org/10.4172/2168-9652.1000e140","url":null,"abstract":"Glioblastoma (GBM), a grade IV glioma classified by World Health Organization (WHO), is considered highly malignant, vascular and invasive subtype [1]. GBM is most lethal during first year after initial diagnosis despite surgical resection, radiotherapy and/or chemotherapy [1,2]. Median survival of patients diagnosed with GBM is only 12 to 15 months [1,2]. Anti-angiogenic therapies (AAT) were used as an adjuvant mainly against vascular endothelial growth factor and its receptors (VEGF-VEGFRs) to normalize tumor vasculatures in GBM patients. However, all of them provided minimal to none effect with no change in overall survival [3]. Hypoxia and neovascularization are histopathologic features of GBM [4]. Hypoxia activated proangiogenic, invasion and metastasis associated gene signatures, enabling tumor to become more angiogenic, invasive and malignant in a compromised microenvironment [5,6]. GBM tumor vessels are tortuous, disorganized, highly permeable, and have abnormal endothelial cells (ECs), pericyte coverage, and basement membrane structure [7,8]. Conventionally, tumor vessel formation occurs through angiogenesis, which is mediated by proliferation and migration of resident ECs [9]. Instead, vasculogenesis originates from circulating bone marrow derived cells (BMDCs) or endothelial progenitor cells (EPCs), which express VEGFR2, are recruited by VEGF followed by differentiation and incorporation into new tumor blood vessels [10].","PeriodicalId":91216,"journal":{"name":"Biochemistry & physiology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88715915","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":"When Seed and Soil Theory Meets Chicken or Egg Theory in Cancer Metastasis","authors":"Meenu Jain, A. Arbab, B. Achyut","doi":"10.4172/2168-9652.1000e131","DOIUrl":"https://doi.org/10.4172/2168-9652.1000e131","url":null,"abstract":"Cancer metastasis has been a serious problem since decades. Seed and soil hypothesis of metastasis remains true and all the metastatic tumors follow this nature’s law [1,2]. Advance metastasis or multi-organ metastasis is difficult to treat due to multi-organ dysfunction. One of the major issues in metastasis is that diagnosis occurs at the advanced stages. Secondly, we have not understood the complete mechanisms so well so far due to intricate nature of metastasis. In metastasis, seed (tumor cell) migrates to the soil (distant organs, e.g. lung, liver, brain, and bone). Several experimental studies have been done that suggested the role of bone marrow derived progenitor cells [3] (e.g. CD11b+ [4] and VEGFR1+ [5] cells) in the initiation of metastasis. Several chemokines, such as SDF-1, TNF-α, TGF-β and VEGF-A influence the recruitment of different cell types to pre-metastatic sites resulting into increased expression of specific molecules in the niche like S100A8, S100A9, lysyl oxidase (LOX), fibronectin, MMP9 and MMP2 in the initiation of premetastatic niche [6,7], which are bonafide candidates of therapeutic targeting [8]. In addition, tumor induced hypoxia has been shown to promote the premetastatic niche formation by recruiting CD11b+/Ly6Cmed/Ly6G+ cells [9] and producing LOX [10]. \u0000 \u0000Recently, much attention has been given to the tumor-derived exosomes or micro vesicles that carry almost every essential cellular macromolecule and has signals to polarize cells in the tumor microenvironment and create premetastatic niche in the distant organs, before the seed (tumor cell) arrives [11,12]. Exosomes derived from melanomas were shown to educate pro-metastatic progenitor cells in the bone marrow [13]. Renal-carcinoma-derived exosomes were found to promote angiogenesis in lung tumor metastases [14]. In addition, using murine mammary carcinoma demonstrated that, tumor-derived microvesicles use osteopontin to mobilize pro-angiogenic cells from the bone marrow [15]. Surprisingly, exosomes perform cell independent miRNA biogenesis to promote tumorigenesis and metastasis [16]. Firstly, tumor derived exosomes has pro-angiogenic functions that helps tumor in building required vasculature for tumor growth. For example, Yoon et al. [17] investigated pro-angiogenic role of tumor-secreted exosomes by showing Egr-1 activation in endothelial cells through ERK1/2 and JNK signaling pathways and endothelial cell migration, which was facilitated by the tumor cell derived extracellular vesicles. On the other hand, tumor derived exosomes involved in the destruction of vasculature integrity for metastasis. For example, miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is reported as a potent regulator of tumor cell migration through targeting the tight junction protein ZO-1 via exosomes. Tumor cell secreted exosomes deliver miR-105 to the site of endothelial monolayers that efficiently destroys tight junctions and hence th","PeriodicalId":91216,"journal":{"name":"Biochemistry & physiology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91322326","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":"Myeloid Derived Suppressor Cells: Fuel the Fire","authors":"B. R. Achyut, A. Arbab","doi":"10.4172/2168-9652.1000e123","DOIUrl":"https://doi.org/10.4172/2168-9652.1000e123","url":null,"abstract":"Low oxygen tension, hypoxia, is a characteristic of many tumors and associated with the poor prognosis. Hypoxia invites bone marrow derived cells (BMDCs) from bone marrow to the site of tumor. These recruited CXCR4+ BMDCs provide favorable environment for the tumor growth by acquiring pro-angiogenic phenotype such as CD45+VEGFR2+ Endothelial Progenitor Cells (EPC), or CD45+Tie2+ myeloid cells. CD11b+CD13+ myeloid population of the BMDCs modulate tumor progression. These myeloid populations retain immunosuppressive characteristics, for example, myeloid derived suppressor cells (MDSCs), and regulates immune- suppression by inhibiting cytotoxic T cell function. In addition, MDSCs were observed at the premetastatic niche of the distant organs in other tumors. Protumorigenic and prometastatic role of the myeloid cells provides a basis for therapeutic targeting of immunosuppression and thus inhibiting tumor development and metastasis.","PeriodicalId":91216,"journal":{"name":"Biochemistry & physiology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86943659","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}