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Sample records for factor receptor-targeted gelatin-based

  1. Growth factor receptors as molecular targets for cancer diagnosis and therapy

    International Nuclear Information System (INIS)

    Zalutsky, M. R.

    1997-01-01

    Growth factor receptors are of great interest as molecular targets for the diagnosis and treatment of cancer. Growth factor receptors are frequently over expressed on malignant cell populations since many cellular oncogenes encode either growth factors of their receptors. The wild-type epidermal growth factor receptor has a molecular weight of 170 kD and is over expressed on gliomas, bladder tumors, squamous cells carcinomas and breast carcinomas. Another growth factor oncogene, c-erb B-2, encodes a 185-kD glycoprotein found on the surface of gliomas, breast and ovarian cancers as well as other carcinomas of epithelial origin. In addition to causing over expression, oncogenic transformation also can result in genomic re-arrangements. An important example from the perspective of targeting is EGFRvIII, a deletion mutant which lacks amino acids 6-273 in the extracellular domain of the epiderma growth factor receptor. The EGFRvIII molecule (145 kD) may be of great value for targeting because it appears to be tumor-specific. Antibodies have been developed with specific reactivity with these growth factor receptors. Since these antibodies are internalized into the cell after receptor binding, it is necessary to use radiolabeling methods which residualize the radioactivity in the tumor cell after intracellular catabolism. To investigate this problem they have evaluated the effect of radioiodination method on the in vitro an in vivo properties of an anti-EGFRvIII antibody. Methods studied were Iodogen, tyramine-cellobiose, and N-succinimidyl 5-iodo-3-pyridine-carboxylate with the last offering optimal localization in a human xenograft model

  2. Electrospun Gelatin/β-TCP Composite Nanofibers Enhance Osteogenic Differentiation of BMSCs and In Vivo Bone Formation by Activating Ca2+-Sensing Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Xuehui Zhang

    2015-01-01

    Full Text Available Calcium phosphate- (CaP- based composite scaffolds have been used extensively for the bone regeneration in bone tissue engineering. Previously, we developed a biomimetic composite nanofibrous membrane of gelatin/β-tricalcium phosphate (TCP and confirmed their biological activity in vitro and bone regeneration in vivo. However, how these composite nanofibers promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs is unknown. Here, gelatin/β-TCP composite nanofibers were fabricated by incorporating 20 wt% β-TCP nanoparticles into electrospun gelatin nanofibers. Electron microscopy showed that the composite β-TCP nanofibers had a nonwoven structure with a porous network and a rough surface. Spectral analyses confirmed the presence and chemical stability of the β-TCP and gelatin components. Compared with pure gelatin nanofibers, gelatin/β-TCP composite nanofibers caused increased cell attachment, proliferation, alkaline phosphatase activity, and osteogenic gene expression in rat BMSCs. Interestingly, the expression level of the calcium-sensing receptor (CaSR was significantly higher on the composite nanofibrous scaffolds than on pure gelatin. For rat calvarial critical sized defects, more extensive osteogenesis and neovascularization occurred in the composite scaffolds group compared with the gelatin group. Thus, gelatin/β-TCP composite scaffolds promote osteogenic differentiation of BMSCs in vitro and bone regeneration in vivo by activating Ca2+-sensing receptor signaling.

  3. Fibroblast growth factor receptors in breast cancer.

    Science.gov (United States)

    Wang, Shuwei; Ding, Zhongyang

    2017-05-01

    Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

  4. Development of epidermal growth factor receptor targeted therapy in pancreatic cancer.

    Science.gov (United States)

    Qing, Liu; Qing, Wang

    2018-02-01

    The epidermal growth factor receptor (EGFR) family are a series of important cancer therapeutic targets involved in cancer biology. These genes play an important role in tumor biological characteristics including angiogenesis, cell survival, invasion and glucose metabolism. In recent years, progresses have been achieved upon the cellular and molecular biological characteristics of EGFR and its role in cancer development based on the study of tumor specimens and experimental animal model. EGFR(HER1/ErbB) is overexpressed in over sixty percent of triple-negative breast cancers and occurs in pancreatic, bladder, lung and head-and-neck cancers. Up to now, EGFR inhibitors have been applied in various of cancer, such as lung, breast, bladder and head and neck cancers etc., in which the combination of EGFR inhibitors plus chemotherapeutic agents is now seen as the standard of care for advanced/metastatic pancreatic cancer. For these reasons, EGFR inhibitors and their therapeutic effect for pancreatic cancer is becoming the focus in Laboratory and clinical research. In this paper, research progress of the development of epidermal growth factor receptor targeted therapy in pancreatic cancer is introduced.

  5. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  6. Gelatin-Based Hydrogels for Organ 3D Bioprinting

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    Xiaohong Wang

    2017-08-01

    Full Text Available Three-dimensional (3D bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment.

  7. Molecular beacon-based real-time PCR method for detection of porcine DNA in gelatin and gelatin capsules.

    Science.gov (United States)

    Mohamad, Nurhidayatul Asma; Mustafa, Shuhaimi; Khairil Mokhtar, Nur Fadhilah; El Sheikha, Aly Farag

    2018-03-05

    The pharmaceutical industry has boosted gelatin consumption worldwide. This is supported by the availability of cost-effective gelatin production from porcine by-products. However, cross-contamination of gelatin materials, where porcine gelatin was unintentionally included in the other animal sources of gelatin, has caused significant concerns about halal authenticity. The real-time polymerase chain reaction (PCR) has enabled a highly specific and sensitive animal species detection method in various food products. Hence, such a technique was employed in the present study to detect and quantify porcine DNA in gelatin using a molecular beacon probe, with differences in performance between mitochondrial (cytochrome b gene) and chromosomal DNA-(MPRE42 repetitive element) based porcine-specific PCR assays being compared. A higher sensitivity was observed in chromosomal DNA (MPRE-PCR assay), where this assay allows the detection of gelatin DNA at amounts as as low as 1 pg, whereas mitochondrial DNA (CBH-PCR assay) can only detect at levels down to 10 pg of gelatin DNA. When an analysis with commercial gelatin and gelatin capsule samples was conducted, the same result was observed, with a significantly more sensitive detection being provided by the repetitive element of chromosomal DNA. The present study has established highly sensitive DNA-based porcine detection systems derived from chromosomal DNA that are feasible for highly processed products such as gelatin and gelatin capsules containing a minute amount of DNA. This sensitive detection method can also be implemented to assist the halal authentication process of various food products available on the market. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  8. A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors.

    Science.gov (United States)

    Sarris, Panagiotis F; Duxbury, Zane; Huh, Sung Un; Ma, Yan; Segonzac, Cécile; Sklenar, Jan; Derbyshire, Paul; Cevik, Volkan; Rallapalli, Ghanasyam; Saucet, Simon B; Wirthmueller, Lennart; Menke, Frank L H; Sohn, Kee Hoon; Jones, Jonathan D G

    2015-05-21

    Defense against pathogens in multicellular eukaryotes depends on intracellular immune receptors, yet surveillance by these receptors is poorly understood. Several plant nucleotide-binding, leucine-rich repeat (NB-LRR) immune receptors carry fusions with other protein domains. The Arabidopsis RRS1-R NB-LRR protein carries a C-terminal WRKY DNA binding domain and forms a receptor complex with RPS4, another NB-LRR protein. This complex detects the bacterial effectors AvrRps4 or PopP2 and then activates defense. Both bacterial proteins interact with the RRS1 WRKY domain, and PopP2 acetylates lysines to block DNA binding. PopP2 and AvrRps4 interact with other WRKY domain-containing proteins, suggesting these effectors interfere with WRKY transcription factor-dependent defense, and RPS4/RRS1 has integrated a "decoy" domain that enables detection of effectors that target WRKY proteins. We propose that NB-LRR receptor pairs, one member of which carries an additional protein domain, enable perception of pathogen effectors whose function is to target that domain. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Deng, Tianzheng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an, 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Zhang Yongjie [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Feng Feng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Jin Yan [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)], E-mail: yanjin@fmmu.edu.cn

    2008-07-28

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 {mu}m) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering.

  10. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    International Nuclear Information System (INIS)

    Huang Sha; Wang Yijuan; Deng, Tianzheng; Jin Fang; Liu Shouxin; Zhang Yongjie; Feng Feng; Jin Yan

    2008-01-01

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 μm) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering

  11. Detection of porcine DNA in gelatine and gelatine-containing processed food products-Halal/Kosher authentication.

    Science.gov (United States)

    Demirhan, Yasemin; Ulca, Pelin; Senyuva, Hamide Z

    2012-03-01

    A commercially available real-time PCR, based on a multi-copy target cytochrome b (cyt b) using porcine specific primers, has been validated for the Halal/Kosher authentication of gelatine. Extraction and purification of DNA from gelatine were successfully achieved using the SureFood® PREP Animal system, and real-time PCR was carried out using SureFood® Animal ID Pork Sens kit. The minimum level of adulteration that could be detected was 1.0% w/w for marshmallows and gum drops. A small survey was undertaken of processed food products such as gum drops, marshmallows and Turkish delight, believed to contain gelatine. Of fourteen food products from Germany, two samples were found to contain porcine gelatine, whereas of twenty-nine samples from Turkey twenty-eight were negative. However, one product from Turkey contained porcine DNA and thus was not Halal, and neither was the use of porcine gelatine indicated on the product label. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    International Nuclear Information System (INIS)

    Xu, Ling; Hausmann, Martin; Dietmaier, Wolfgang; Kellermeier, Silvia; Pesch, Theresa; Stieber-Gunckel, Manuela; Lippert, Elisabeth; Klebl, Frank; Rogler, Gerhard

    2010-01-01

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  13. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Kellermeier Silvia

    2010-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Methods Expression of EGFR (epithelial growth factor receptor, HGFR (hepatocyte growth factor receptor IGF1R (insulin-like growth factor 1 receptor, IGF2R (insulin-like growth factor 2 receptor and VEGFR1-3 (vascular endothelial growth factor receptor 1-3 were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1. The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. Results EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml, with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D. HuH28, OZ and TFK-1 lacked KRAS mutation. Conclusion CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab.

  14. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

    2017-04-01

    Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

  15. Influence of lyophilization factors and gelatin concentration on pore structures of atelocollagen/gelatin sponge biomaterial.

    Science.gov (United States)

    Yang, Longqiang; Tanabe, Koji; Miura, Tadashi; Yoshinari, Masao; Takemoto, Shinji; Shintani, Seikou; Kasahara, Masataka

    2017-07-26

    This study aimed to investigate influences of lyophilization factors and gelatin concentration on pore structures of ACG sponge. ACG sponges of different freezing temperatures (-30, -80 and -196 o C), freezing times (1, 2 and 24 h), gelatin concentrations (0.6%AC+0.15%G, 0.6%AC+0.6%G and 0.6%AC+2.4%G), and with 500 μM fluvastatin were fabricated. Pore structures including porosity and pore size were analyzed by scanning electron microscopy and ImageJ. The cytotoxic effects of ACG sponges were evaluated in vitro. Freezing temperature did not affect porosity while high freezing temperature (-30 o C) increased pore size. The high gelatin concentration group (0.6%AC+2.4%G) had decreased porosity and pore size. Freezing time and 500 μM fluvastatin did not affect pore structures. The cytotoxicity and cell proliferation assays revealed that ACG sponges had no cytotoxic effects on human mesenchymal stromal cell growth and proliferation. These results indicate that ACG sponge may be a good biomaterial scaffold for bone regeneration.

  16. Dextran and gelatin based photocrosslinkable tissue adhesive.

    Science.gov (United States)

    Wang, Tao; Nie, Jun; Yang, Dongzhi

    2012-11-06

    A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.

    Science.gov (United States)

    Philip, Philip A; Lutz, Manfred P

    2015-10-01

    Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.

  18. Detection of growth factor binding to gelatin and heparin using a photonic crystal optical biosensor

    International Nuclear Information System (INIS)

    Morgan, Abby W.; Chan, Leo L.; Sendemir-Urkmez, Aylin; Cunningham, Brian T.; Jamison, Russell D.

    2010-01-01

    Drug-carrier interactions are important to protein controlled release systems to protect the protein from denaturation and ensure properly timed release. A novel photonic crystal biosensor was used to investigate a gelatin-protein controlled release system to determine the amount of protein bound to the carrier at physiological conditions. The Biomolecular Interaction Detection (BIND) system reflects a narrow band of wavelengths when white light is shone incident to the grating. As mass is deposited onto the surface, the peak wavelength value is shifted due to changes in the optical density of the biosensor. The BIND system was used to detect the binding of growth factors onto acidic gelatin, basic gelatin, and heparin on the sensor surface. Through a series of experiments, including functionalizing the sensor, adjusting the ionic strength of the solution, adjusting the substrate concentration, and minimizing non-specific signal, the adsorption of the gelatins and heparin on the sensor was enhanced. The binding interaction of recombinant human transforming growth factor (rhTGF)-β1 and bone morphogenetic protein (rhBMP)-2 with the two types of gelatin and heparin were investigated. The strength of the interaction between rhTGF-β1 and the substrates is in the following order: heparin > acidic gelatin > basic gelatin. RhBMP-2 bound to the substrates but with less intensity than TGF-β1: heparin > basic gelatin > acidic gelatin. This work provides support for the controlled release mechanism through degradation of the gelatin carrier.

  19. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

    2018-01-01

    Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

  20. Epidermal Growth Factor Receptor targeting in non-small cell lung cancer: revisiting different strategies against the same target.

    Science.gov (United States)

    Castañón, Eduardo; Martín, Patricia; Rolfo, Christian; Fusco, Juan P; Ceniceros, Lucía; Legaspi, Jairo; Santisteban, Marta; Gil-Bazo, Ignacio

    2014-01-01

    Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also reviewed and discussed.

  1. The Feasibility of Gelatin-Based Retronasal Stimuli to Assess Olfactory Perception

    Directory of Open Access Journals (Sweden)

    Daniel Shepherd

    2015-10-01

    Full Text Available Links between some psychological disorders and olfactory deficits are well documented, and screening tests have been developed to exploit these associations. Odors can take one of two routes to the olfactory receptors in the nasal epithelium, the orthonasal or retronasal route. This article discusses the potential use of the retronasal route to assess olfaction using gelatin-based stimuli delivered orally. Using a relatively new psychophysical method, the Single-Interval Adjustment Matrix task, we estimated vanillin thresholds for five healthy participants sampling small vanillin flavored gels. Our data demonstrate the feasibility of using solid-state gustatory stimuli to assess retronasal perception.

  2. Gelatin-based laser direct-write technique for the precise spatial patterning of cells.

    Science.gov (United States)

    Schiele, Nathan R; Chrisey, Douglas B; Corr, David T

    2011-03-01

    Laser direct-writing provides a method to pattern living cells in vitro, to study various cell-cell interactions, and to build cellular constructs. However, the materials typically used may limit its long-term application. By utilizing gelatin coatings on the print ribbon and growth surface, we developed a new approach for laser cell printing that overcomes the limitations of Matrigel™. Gelatin is free of growth factors and extraneous matrix components that may interfere with cellular processes under investigation. Gelatin-based laser direct-write was able to successfully pattern human dermal fibroblasts with high post-transfer viability (91% ± 3%) and no observed double-strand DNA damage. As seen with atomic force microscopy, gelatin offers a unique benefit in that it is present temporarily to allow cell transfer, but melts and is removed with incubation to reveal the desired application-specific growth surface. This provides unobstructed cellular growth after printing. Monitoring cell location after transfer, we show that melting and removal of gelatin does not affect cellular placement; cells maintained registry within 5.6 ± 2.5 μm to the initial pattern. This study demonstrates the effectiveness of gelatin in laser direct-writing to create spatially precise cell patterns with the potential for applications in tissue engineering, stem cell, and cancer research.

  3. Controlled Fabrication of Gelatin Nanoparticles as Drug Carriers

    Science.gov (United States)

    Jahanshahi, M.; Sanati, M. H.; Minuchehr, Z.; Hajizadeh, S.; Babaei, Z.

    2007-08-01

    In recent years, significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes by either localized or targeted delivery to the tissue of interest. Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as nanoparticles, nanocapsules, micellar systems, and conjugates. Protein nanoparticles (BSA, HAS and gelatin) generally vary in size from 50-300 nm and they hold certain advantages such as greater stability during storage, stability in vivo, non-toxicity, non-antigen and ease to scale up during manufacture over the other drug delivery systems. The primary structure of gelatin offers many possibilities for chemical modification and covalent drug attachment. Here nanoparticles of gelatin type A were prepared by a two-step desolvation method as a colloidal drug delivery system and the essential parameters in fabrication were considered. Gelatin was dissolved in 25 mL distilled water under room temperature range. Then acetone was added to the gelatin solution as a desolvating agent to precipitate the high molecular weight (HMW) gelatin. The supernatant was discarded and the HMW gelatin re-dissolved by adding 25 mL distilled water and stirring at 600 rpm. Acetone were added drop-wise to form nanoparticles. At the end of the process, glutaraldehyde solution was used for preparing nanoparticles as a cross-linking agent, and stirred for 12h at 600 rpm. For purification stage we use centrifuge with 600rpm for 3 times. The objective of the present study is consideration of some factors such as temperature, gelatin concentration, agitation speed and the amount of acetone and their effects on size and distribution of nanoparticles. Among the all conditions, 60° C, 50 mg/ml gelatin concentration, 75 ml acetone had the best result and the nanoparticle size was under 170 nm. The effect

  4. Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Szlachcic A

    2016-08-01

    Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

  5. Development of a gelatin-based polyurethane vascular graft by spray, phase-inversion technology

    International Nuclear Information System (INIS)

    Losi, Paola; Al Kayal, Tamer; Briganti, Enrica; Volpi, Silvia; Soldani, Giorgio; Mancuso, Luisa; Cao, Giacomo; Celi, Simona; Gualerzi, Alice

    2015-01-01

    The capacity of a composite vascular graft constituting polyurethane (PU) and gelatin to support cell growth was investigated using human mesenchymal stem cells (hMSCs). Gelatin-based polyurethane grafts were fabricated by co-spraying polyurethane and gelatin using a spray, phase-inversion technique. Graft microstructure was investigated by light and scanning electron microscopy. Uniaxial tensile tests were performed to assess the grafts’ mechanical properties in longitudinal and circumferential directions. hMSCs obtained from bone marrow aspirate were seeded onto flat graft samples. After 24, 48, and 72 h of incubation, cell morphology was evaluated by Giemsa staining and cell viability was calculated by XTT assay. SEM analysis evidenced that PU samples display a microporous structure, whereas the gelatin-based PU samples show a fibrillar appearance. The presence of cross-linked gelatin produced a significant increase of ultimate tensile strength and ultimate elongation in circumferential directions compared to PU material. Qualitative analysis of hMSC adhesion onto the grafts revealed remarkable differences between gelatin-based PU and control graft. hMSCs grown onto gelatin-based PU graft form a monolayer that reached confluence at 72 h, whereas cells seeded onto the control graft were not able to undergo appropriate spreading. hMSCs grown onto gelatin-based PU graft showed significantly higher viability than cells seeded onto bare PU at all time points. In conclusion, a composite vascular graft was successfully manufactured by simultaneous co-spraying of a synthetic polymer and a protein to obtain a scaffold that combines the mechanical characteristics of polyurethanes with the favorable cell interaction features of gelatin. (paper)

  6. Fish gelatin.

    Science.gov (United States)

    Boran, Gokhan; Regenstein, Joe M

    2010-01-01

    Gelatin is a multifunctional ingredient used in foods, pharmaceuticals, cosmetics, and photographic films as a gelling agent, stabilizer, thickener, emulsifier, and film former. As a thermoreversible hydrocolloid with a narrower gap between its melting and gelling temperatures, both of which are below human body temperature, gelatin provides unique advantages over carbohydrate-based gelling agents. Gelatin is mostly produced from pig skin, and cattle hides and bones. Some alternative raw materials have recently gained attention from both researchers and the industry not just because they overcome religious concerns shared by Jews and Muslims but also because they provide, in some cases, technological advantages over mammalian gelatins. Fish skins from a number of fish species are among the other sources that have been comprehensively studied as sources for gelatin production. Fish skins have a significant potential for the production of high-quality gelatin with different melting and gelling temperatures over a much wider range than mammalian gelatins, yet still have a sufficiently high gel strength and viscosity. Gelatin quality is industrially determined by gel strength, viscosity, melting or gelling temperatures, the water content, and microbiological safety. For gelatin manufacturers, yield from a particular raw material is also important. Recent experimental studies have shown that these quality parameters vary greatly depending on the biochemical characteristics of the raw materials, the manufacturing processes applied, and the experimental settings used for quality control tests. In this review, the gelatin quality achieved from different fish species is reviewed along with the experimental procedures used to determine gelatin quality. In addition, the chemical structure of collagen and gelatin, the collagen-gelatin conversion, the gelation process, and the gelatin market are discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Tyrosine dephosphorylation enhances the therapeutic target activity of epidermal growth factor receptor (EGFR) by disrupting its interaction with estrogen receptor (ER).

    Science.gov (United States)

    Ma, Shao; Yin, Ning; Qi, Xiaomei; Pfister, Sandra L; Zhang, Mei-Jie; Ma, Rong; Chen, Guan

    2015-05-30

    Protein-protein interactions can increase or decrease its therapeutic target activity and the determining factors involved, however, are largely unknown. Here, we report that tyrosine-dephosphorylation of epidermal growth factor receptor (EGFR) increases its therapeutic target activity by disrupting its interaction with estrogen receptor (ER). Protein tyrosine phosphatase H1 (PTPH1) dephosphorylates the tyrosine kinase EGFR, disrupts its interaction with the nuclear receptor ER, and increases breast cancer sensitivity to small molecule tyrosine kinase inhibitors (TKIs). These effects require PTPH1 catalytic activity and its interaction with EGFR, suggesting that the phosphatase may increase the sensitivity by dephosphorylating EGFR leading to its dissociation with ER. Consistent with this notion, a nuclear-localization defective ER has a higher EGFR-binding activity and confers the resistance to TKI-induced growth inhibition. Additional analysis show that PTPH1 stabilizes EGFR, stimulates the membranous EGFR accumulation, and enhances the growth-inhibitory activity of a combination therapy of TKIs with an anti-estrogen. Since EGFR and ER both are substrates for PTPH1 in vitro and in intact cells, these results indicate that an inhibitory EGFR-ER protein complex can be switched off through a competitive enzyme-substrate binding. Our results would have important implications for the treatment of breast cancer with targeted therapeutics.

  8. Gelatin- and starch-based hydrogels. Part A: Hydrogel development, characterization and coating.

    Science.gov (United States)

    Van Nieuwenhove, Ine; Salamon, Achim; Peters, Kirsten; Graulus, Geert-Jan; Martins, José C; Frankel, Daniel; Kersemans, Ken; De Vos, Filip; Van Vlierberghe, Sandra; Dubruel, Peter

    2016-11-05

    The present work aims at constructing the ideal scaffold matrix of which the physico-chemical properties can be altered according to the targeted tissue regeneration application. Ideally, this scaffold should resemble the natural extracellular matrix (ECM) as close as possible both in terms of chemical composition and mechanical properties. Therefore, hydrogel films were developed consisting of methacrylamide-modified gelatin and starch-pentenoate building blocks because the ECM can be considered as a crosslinked hydrogel network consisting of both polysaccharides and structural, signaling and cell-adhesive proteins. For the gelatin hydrogels, three different substitution degrees were evaluated including 31%, 72% and 95%. A substitution degree of 32% was applied for the starch-pentenoate building block. Pure gelatin hydrogels films as well as interpenetrating networks with gelatin and starch were developed. Subsequently, these films were characterized using gel fraction and swelling experiments, high resolution-magic angle spinning (1)H NMR spectroscopy, rheology, infrared mapping and atomic force microscopy. The results indicate that both the mechanical properties and the swelling extent of the developed hydrogel films can be controlled by varying the chemical composition and the degree of substitution of the methacrylamide-modified gelatin applied. The storage moduli of the developed materials ranged between 14 and 63kPa. Phase separation was observed for the IPNs for which separated starch domains could be distinguished located in the surrounding gelatin matrix. Furthermore, we evaluated the affinity of aggrecan for gelatin by atomic force microscopy and radiolabeling experiments. We found that aggrecan can be applied as a bioactive coating for gelatin hydrogels by a straightforward physisorption procedure. Thus, we achieved distinct fine-tuning of the physico-chemical properties of these hydrogels which render them promising candidates for tissue engineering

  9. Physicochemical and antifungal properties of bio-nanocomposite film based on gelatin-chitin nanoparticles.

    Science.gov (United States)

    Sahraee, Samar; Milani, Jafar M; Ghanbarzadeh, Babak; Hamishehkar, Hamed

    2017-04-01

    The gelatin-based nanocomposite films containing chitin nanoparticles (N-chitin) with concentrations of 0, 3, 5 and 10% were prepared and their physical, thermal and anti-microbial properties were investigated. Scanning electron microscopy (SEM) micrographs showed that N-chitin size distribution was around 60-70nm which dispersed appropriately at low concentration in gelatin matrix. The results showed that incorporation of N-chitin significantly influenced apparent color and transparency of the gelatin films. The reduced water vapor permeability (WVP) and solubility and higher surface hydrophobicity of the nanocomposite films were obtained by enhancing N-chitin concentration in film formulation. The use of N-chitin up to 5% concentration in the gelatin based nanocomposite film led to improved mechanical properties. Also, the results of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed improved stability of nanocomposite films against melting and degradation at high temperatures in comparison to neat gelatin film. The well compatibility of chitin nanoparticles with gelatin polymer was concluded from Fourier transform infrared (FTIR) spectra and X-ray diffraction (XRD) plots. Finally, the gelatin based nanocomposite films had anti-fungal properties against Aspergillus niger in the contact surface zone. Increasing the concentration of N-chitin up to 5% enlarged inhibition zone diameter, but the nanocomposite film containing 10% N-chitin showed smaller inhibition zone. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Development of antibody-based c-Met inhibitors for targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Lee D

    2015-02-01

    Full Text Available Dongheon Lee, Eun-Sil Sung, Jin-Hyung Ahn, Sungwon An, Jiwon Huh, Weon-Kyoo You Hanwha Chemical R&D Center, Biologics Business Unit, Daejeon, Republic of Korea Abstract: Signaling pathways mediated by receptor tyrosine kinases (RTKs and their ligands play important roles in the development and progression of human cancers, which makes RTK-mediated signaling pathways promising therapeutic targets in the treatment of cancer. Compared with small-molecule compounds, antibody-based therapeutics can more specifically recognize and bind to ligands and RTKs. Several antibody inhibitors of RTK-mediated signaling pathways, such as human epidermal growth factor receptor 2, vascular endothelial growth factor, epidermal growth factor receptor or vascular endothelial growth factor receptor 2, have been developed and are widely used to treat cancer patients. However, since the therapeutic options are still limited in terms of therapeutic efficacy and types of cancers that can be treated, efforts are being made to identify and evaluate novel RTK-mediated signaling pathways as targets for more efficacious cancer treatment. The hepatocyte growth factor/c-Met signaling pathway has come into the spotlight as a promising target for development of potent cancer therapeutic agents. Multiple antibody-based therapeutics targeting hepatocyte growth factor or c-Met are currently in preclinical or clinical development. This review focuses on the development of inhibitors of the hepatocyte growth factor/c-Met signaling pathway for cancer treatment, including critical issues in clinical development and future perspectives for antibody-based therapeutics. Keywords: hepatocyte growth factor, ligands, receptor tyrosine kinase, signaling pathway, therapeutic agent

  11. Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR)

    DEFF Research Database (Denmark)

    Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

    2017-01-01

    Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhib...... with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer....

  12. Ultra thin hydro-films based on lactose-crosslinked fish gelatin for wound healing applications.

    Science.gov (United States)

    Etxabide, Alaitz; Vairo, Claudia; Santos-Vizcaino, Edorta; Guerrero, Pedro; Pedraz, Jose Luis; Igartua, Manoli; de la Caba, Koro; Hernandez, Rosa Maria

    2017-09-15

    This study focuses on the development and characterization of an ultra thin hydro-film based on lactose-mediated crosslinking of fish gelatin by Maillard reaction. Lactose results in the only efficient crosslinker able to produce resistant to handling hydro-films when compared to conventional crosslinkers such as glutaraldehyde or genipin (tested at 25 and 37°C in phosphate buffer saline solution (PBS)).The disappearance of the peak related to the N-containing groups (XPS) and the images obtained by SEM and AFM demonstrate the highly ordered nano-scaled structure of lactose-crosslinked gelatin, confirming the crosslinking efficiency. This dressing presents high hydrophilicity and mild occlusivity, as shown by the swelling curve (max swelling at 5min) and by the occlusion factor of 25.17±0.99%, respectively. It demonstrates high stability to hydrolysis or cell-mediated degradation. Moreover, ISO 10993-5:2009 biocompatibility assay results in undetectable cytotoxicity effects. Spreading, adhesion and proliferation assays confirm the excellent adaptability of the cells onto the hydro-film surface without invading the dressing. Finally, the hydro-film enables the controlled delivery of therapeutic factors, such as the epidermal growth factor (EGF). This study demonstrates that lactose-mediated crosslinking is able to produce ultra thin gelatin hydro-films with suitable properties for biomedical applications, such as wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Formulation and Evaluation of Microspheres Based on Gelatin ...

    African Journals Online (AJOL)

    Formulation and Evaluation of Microspheres Based on Gelatin-Mucin Admixtures for the Rectal Delivery of Cefuroxime Sodium. K C Ofokansi, M U Adikwu. Abstract. Purpose: Swellable microspheres based on polymers or their admixtures are frequently employed as drug delivery systems to achieve a controlled release ...

  14. Evaporation-based method for preparing gelatin foams with aligned tubular pore structures

    Energy Technology Data Exchange (ETDEWEB)

    Frazier, Shane D.; Srubar, Wil V., E-mail: wsrubar@colorado.edu

    2016-05-01

    Gelatin-based foams with aligned tubular pore structures were prepared via liquid-to-gas vaporization of tightly bound water in dehydrated gelatin hydrogels. This study elucidates the mechanism of the foaming process by investigating the secondary (i.e., helical) structure, molecular interactions, and water content of gelatin films before and after foaming using X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry and thermogravimetric analysis (TGA), respectively. Experimental data from gelatin samples prepared at various gelatin-to-water concentrations (5–30 wt.%) substantiate that resulting foam structures are similar in pore diameter (approximately 350 μm), shape, and density (0.05–0.22 g/cm{sup 3}) to those fabricated using conventional methods (e.g., freeze-drying). Helical structures were identified in the films but were not evident in the foamed samples after vaporization (~ 150 °C), suggesting that the primary foaming mechanism is governed by the vaporization of water that is tightly bound in secondary structures (i.e., helices, β-turns, β-sheets) that are present in dehydrated gelatin films. FTIR and TGA data show that the foaming process leads to more disorder and reduced hydrogen bonding to hydroxyl groups in gelatin and that no thermal degradation of gelatin occurs before or after foaming. - Highlights: • A new method is presented for fabricating gelatin foams with aligned, tubular pores. • Gelatin hydrogels were dehydrated then heated to 150 °C to induce foaming. • Vaporization of tightly (vs. loosely) bound water is the primary foaming mechanism • Foaming induced no thermal degradation but caused disorder in secondary structures • Foam microstructures are similar to those prepared using conventional methods.

  15. Evaporation-based method for preparing gelatin foams with aligned tubular pore structures

    International Nuclear Information System (INIS)

    Frazier, Shane D.; Srubar, Wil V.

    2016-01-01

    Gelatin-based foams with aligned tubular pore structures were prepared via liquid-to-gas vaporization of tightly bound water in dehydrated gelatin hydrogels. This study elucidates the mechanism of the foaming process by investigating the secondary (i.e., helical) structure, molecular interactions, and water content of gelatin films before and after foaming using X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry and thermogravimetric analysis (TGA), respectively. Experimental data from gelatin samples prepared at various gelatin-to-water concentrations (5–30 wt.%) substantiate that resulting foam structures are similar in pore diameter (approximately 350 μm), shape, and density (0.05–0.22 g/cm"3) to those fabricated using conventional methods (e.g., freeze-drying). Helical structures were identified in the films but were not evident in the foamed samples after vaporization (~ 150 °C), suggesting that the primary foaming mechanism is governed by the vaporization of water that is tightly bound in secondary structures (i.e., helices, β-turns, β-sheets) that are present in dehydrated gelatin films. FTIR and TGA data show that the foaming process leads to more disorder and reduced hydrogen bonding to hydroxyl groups in gelatin and that no thermal degradation of gelatin occurs before or after foaming. - Highlights: • A new method is presented for fabricating gelatin foams with aligned, tubular pores. • Gelatin hydrogels were dehydrated then heated to 150 °C to induce foaming. • Vaporization of tightly (vs. loosely) bound water is the primary foaming mechanism • Foaming induced no thermal degradation but caused disorder in secondary structures • Foam microstructures are similar to those prepared using conventional methods.

  16. Properties of gelatin-based films incorporated with chitosan-coated microparticles charged with rutin.

    Science.gov (United States)

    Dammak, Ilyes; Bittante, Ana Mônica Quinta Barbosa; Lourenço, Rodrigo Vinicius; do Amaral Sobral, Paulo José

    2017-08-01

    The aim of this study was development an active film based on gelatin incorporated with antioxidant, rutin carried into microparticles. The complexation between oppositely charged lecithin and chitosan was applied to prepare the chitosan-coated microparticles. The generated microparticles had an average size of 520±4nm and a span of 0.3 were formulated by a rotor-stator homogenize at the homogenization speed 10,000rpm. Composite films were prepared by incorporating chitosan-coated microparticles, at various concentrations (0.05, 0.1, 0.5, or 1% (based on the weight of the gelatin powder)) in the gelatin-based films. For the prepared films, the results showed that obtained physicochemical, water vapor barrier, and mechanical were compared with native gelatin film with a slight decrease for chitosan concentration higher than 0.5%. The microstructure studies done by scanning electron microscopes, revealed different micropores embedded with oil resulting from the incorporation of the microparticles into the gelatin matrix. Moreover, the calorimetric results were comparable to those of gelatin control film with T g value 45°C and increased crystallinity percentage with increasing incorporation of microparticles. This original concept of composite biodegradable films may thus be a good alternative to incorporate liposoluble active compounds to design an active packaging with good properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Gelatin-Based Films and Coatings for Food Packaging Applications

    Directory of Open Access Journals (Sweden)

    Marina Ramos

    2016-09-01

    Full Text Available This review discusses the latest advances in the composition of gelatin-based edible films and coatings, including nanoparticle addition, and their properties are reviewed along their potential for application in the food packaging industry. Gelatin is an important biopolymer derived from collagen and is extensively used by various industries because of its technological and functional properties. Nowadays, a very wide range of components are available to be included as additives to improve its properties, as well as its applications and future potential. Antimicrobials, antioxidants and other agents are detailed due to the fact that an increasing awareness among consumers regarding healthy lifestyle has promoted research into novel techniques and additives to prolong the shelf life of food products. Thanks to its ability to improve global food quality, gelatin has been particularly considered in food preservation of meat and fish products, among others.

  18. Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

    Science.gov (United States)

    Narayanan, Ramesh; Dalton, James T.

    2016-01-01

    Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER) and human epidermal growth factor receptor (HER2) are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR) is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease. Ironically, both nonsteroidal agonists and antagonists for the AR are undergoing clinical trials, making AR a complicated target to understand in breast cancer. This review provides a detailed account of AR’s therapeutic role in breast cancer. PMID:27918430

  19. Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ramesh Narayanan

    2016-12-01

    Full Text Available Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER and human epidermal growth factor receptor (HER2 are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease. Ironically, both nonsteroidal agonists and antagonists for the AR are undergoing clinical trials, making AR a complicated target to understand in breast cancer. This review provides a detailed account of AR’s therapeutic role in breast cancer.

  20. Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs.

    Science.gov (United States)

    Lim, Hyun-Tae; Balakrishnan, Prabagar; Oh, Dong Hoon; Joe, Kwan Hyung; Kim, Young Ran; Hwang, Doo Hyung; Lee, Yong-Bok; Yong, Chul Soon; Choi, Han-Gon

    2010-09-15

    To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The solid dispersions prepared with gelatin gave higher drug solubility than those prepared without gelatin, irrespective of the amount of polymer. The sibutramine base-loaded solid dispersions containing hydrophilic polymer and citric acid showed higher drug solubility compared to sibutramine base and sibutramine hydrochloride monohydrate. Among the formulations tested, the solid dispersion composed of sibutramine base/gelatin/HPMC/citric acid at the weight ratio of 1/0.8/0.2/0.5 gave the highest solubility of 5.03+/-0.24 mg/ml. Our DSC and powder X-ray diffraction results showed that the drug was present in an altered amorphous form in this solid dispersion. The difference factor (f(1)) values between solid dispersion and commercial product were 2.82, 6.65 and 6.31 at pH 1.2, 4.0 and 6.8, respectively. Furthermore, they had the similarity factor (f(2)) value of 65.68, 53.43 and 58.97 at pH 1.2, 4.0 and 6.8, respectively. Our results suggested that the solid dispersion and commercial product produced a similar correlation of dissolution profiles at all pH ranges. The AUC, C(max) and T(max) of the parent drug and metabolite I and II from the solid dispersion were not significantly different from those of the commercial product, suggesting that the solid dispersion might be bioequivalent to the commercial product in beagle dogs. Thus, the sibutramine base-loaded solid dispersion prepared with gelatin, HPMC and citric acid is a promising candidate for improving the

  1. Cosilencing Intestinal Transglutaminase-2 and Interleukin-15 Using Gelatin-Based Nanoparticles in an in Vitro Model of Celiac Disease.

    Science.gov (United States)

    Attarwala, Husain; Clausen, Valerie; Chaturvedi, Prasoon; Amiji, Mansoor M

    2017-09-05

    In this study, we have developed a type B gelatin nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge, and morphology of gelatin nanoparticles were evaluated using a Zetasizer instrument and transmission electron microscopy. siRNA encapsulation efficiency was determined using an siRNA specific stem-loop quantitative polymerase chain reaction (qPCR) assay. Cellular uptake of siRNA-containing gelatin nanoparticles was determined using fluorescent microscopy and stem-loop qPCR assay. siRNA loading in the RISC (RNA-induced silencing complex) was determined by immunoprecipitation of argonaute 2 (AGO2) protein followed by stem-loop qPCR for siRNA quantification. Gene expression analysis of TG2, IL-15, and the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), was performed using qPCR assays. Efficacy of silencing TG2 and IL-15 knockdown was evaluated in an in vitro model of celiac disease by utilizing immunogenic α-gliadin peptide p31-43 in cultured J774A.1 cells. siRNA-containing gelatin nanoparticles were spherical in shape with mean particle size and charge of 217 ± 8.39 nm and -6.2 ± 0.95 mV, respectively. siRNA loading efficiency within gelatin nanoparticles was found to be 89.3 ± 3.05%. Evaluations of cellular uptake using fluorescent microscopy showed rapid internalization of gelatin nanoparticles within 2 h of dosing, with cytosolic localization of delivered siRNA in Caco-2 cells. Gelatin nanoparticles showed greater intracellular siRNA exposure with a longer half-life, when compared to Lipofectamine-mediated siRNA delivery. Approximately 0.1% of total intracellular si

  2. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

    Directory of Open Access Journals (Sweden)

    Ping Zhao

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

  3. Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics

    LENUS (Irish Health Repository)

    Gerard, Valerie A

    2011-11-10

    Abstract Background Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target-specific which can be achieved by conjugating them with Folic Acid (FA). Results The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco-2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. Conclusions The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics.

  4. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    International Nuclear Information System (INIS)

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance

  5. Comparison of ballistic impact effects between biological tissue and gelatin.

    Science.gov (United States)

    Jin, Yongxi; Mai, Ruimin; Wu, Cheng; Han, Ruiguo; Li, Bingcang

    2018-02-01

    Gelatin is commonly used in ballistic testing as substitute for biological tissue. Comparison of ballistic impact effects produced in the gelatin and living tissue is lacking. The work in this paper was aimed to compare the typical ballistic impact effects (penetration trajectory, energy transfer, temporary cavity) caused by 4.8mm steel ball penetrating the 60kg porcine hind limbs and 10wt% gelatin. The impact event in the biological tissue was recorded by high speed flash X-ray machine at different delay time, while the event in the gelatin continuously recorded by high speed video was compared to that in the biological tissue. The collected results clearly displayed that the ballistic impact effects in the muscle and gelatin were similar for the steel ball test; as for instance, the projectile trajectory in the two targets was basically similar, the process of energy transfer was highly coincident, and the expansion of temporary cavity followed the same pattern. This study fully demonstrated that choosing gelatin as muscle simulant was reasonable. However, the maximum temporary cavity diameter in the gelatin was a little larger than that in the muscle, and the expansion period of temporary cavity was longer in the gelatin. Additionally, the temporary cavity collapse process in the two targets followed different patterns, and the collapse period in the gelatin was two times as long as that in the muscle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy.

    Science.gov (United States)

    Dharmawardana, Pathirage G; Peruzzi, Benedetta; Giubellino, Alessio; Burke, Terrence R; Bottaro, Donald P

    2006-01-01

    Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has revealed other fundamental roles for Grb2 in cell motility and angiogenesis--processes that also contribute to tumor growth, invasiveness and metastasis. This functional profile makes Grb2 a high priority target for anti-cancer drug development. Knowledge of Grb2 protein structure, its component Src homology domains and their respective structure-function relationships has facilitated the rapid development of sophisticated drug candidates that can penetrate cells, bind Grb2 with high affinity and potently antagonize Grb2 signaling. These novel compounds offer considerable promise in our growing arsenal of rationally designed anti-cancer therapeutics.

  7. Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer.

    Science.gov (United States)

    Brown, Wells S; Tan, Li; Smith, Andrew; Gray, Nathanael S; Wendt, Michael K

    2016-09-01

    Therapeutic targeting of late-stage breast cancer is limited by an inadequate understanding of how tumor cell signaling evolves during metastatic progression and by the currently available small molecule inhibitors capable of targeting these processes. Herein, we demonstrate that both β3 integrin and fibroblast growth factor receptor-1 (FGFR1) are part of an epithelial-mesenchymal transition (EMT) program that is required to facilitate metastatic outgrowth in response to fibroblast growth factor-2 (FGF2). Mechanistically, β3 integrin physically disrupts an interaction between FGFR1 and E-cadherin, leading to a dramatic redistribution of FGFR1 subcellular localization, enhanced FGF2 signaling and increased three-dimensional (3D) outgrowth of metastatic breast cancer cells. This ability of β3 integrin to drive FGFR signaling requires the enzymatic activity of focal adhesion kinase (FAK). Consistent with these mechanistic data, we demonstrate that FGFR, β3 integrin, and FAK constitute a molecular signature capable of predicting decreased survival of patients with the basal-like subtype of breast cancer. Importantly, covalent targeting of a conserved cysteine in the P-loop of FGFR1-4 with our newly developed small molecule, FIIN-4, more effectively blocks 3D metastatic outgrowth as compared with currently available FGFR inhibitors. In vivo application of FIIN-4 potently inhibited the growth of metastatic, patient-derived breast cancer xenografts and murine-derived metastases growing within the pulmonary microenvironment. Overall, the current studies demonstrate that FGFR1 works in concert with other EMT effector molecules to drive aberrant downstream signaling, and that these events can be effectively targeted using our novel therapeutics for the treatment of the most aggressive forms of breast cancer. Mol Cancer Ther; 15(9); 2096-106. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Structure-based drug design approach to target toll-like receptor ...

    African Journals Online (AJOL)

    TLRs are now viewed as potential therapeutic targets in the treatment of autoimmune diseases. This ... Vascular endothelial growth factor. NMR .... induces the release of tumor necrosis factor ... Alternative anticancer drugs called CpG-based.

  9. Soft, chewable gelatin-based pharmaceutical oral formulations: a technical approach.

    Science.gov (United States)

    Dille, Morten J; Hattrem, Magnus N; Draget, Kurt I

    2018-06-01

    Hard tablets and capsules for oral drug delivery cause problems for people experiencing dysphagia. This work describes the formulation and properties of a gelatin based, self-preserved, and soft chewable tablet as an alternative and novel drug delivery format. Gelatin (8.8-10% in 24.7-29% water) constituted the matrix of the soft, semi-solid tablets. Three different pharmaceuticals (Ibuprofen 10%, Acetaminophen 15%, and Meloxicam 1.5%) were tested in this formulation. Microbial stability was controlled by lowering the water activity with a mixture of sorbitol and xylitol (45.6-55%). Rheological properties were tested applying small strain oscillation measurements. Taste masking of ibuprofen soft-chew tablets was achieved by keeping the ibuprofen insoluble at pH 4.5 and keeping the processing temperature below the crystalline-to-amorphous transition temperature. Soft-chew formulations showed good stability for all three pharmaceuticals (up to 24 months), and the ibuprofen containing formulation exhibited comparable dissolution to a standard oral tablet as well as good microbial stability. The rheological properties of the ibuprofen/gelatin formulation had the fingerprint of a true gelatin gel, albeit higher moduli, and melting temperature. The results suggest that easy-to-swallow and well taste-masked soft chewable tablet formulations with extended shelf life are within reach for several active pharmaceutical ingredients (APIs).

  10. Platelet-Derived Growth Factor (PDGF/PDGF Receptors (PDGFR Axis as Target for Antitumor and Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Anca Maria Cimpean

    2010-03-01

    Full Text Available Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF, fibroblast growth factor (FGF-2 or platelet-derived growth factors (PDGF. From these, VEGF and FGF-2 were extensively investigated and it was shown that they significantly contribute to the induction and progression of angiogenesis. A lot of evidence has been accumulated in last 10 years that supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-β in angiogenesis has been demonstrated by gene targeting experiments, and their expression correlates with increased vascularity and maturation of the vascular wall. PDGF and their receptors were identified in a large variety of human tumor cells. In experimental models it was shown that inhibition of PDGF reduces interstitial fluid pressure in tumors and enhances the effect of chemotherapy. PDGFR have been involved in the cardiovascular development and their loss leads to a disruption in yolk sac blood vessels development. PDGFRβ expression by pericytes is necessary for their recruitment and integration in the wall of tumor vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR. Based on these data, it was suggested the potential benefit of targeting PDGFR in the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated angiogenesis are not fully understood, but it was shown that tyrosine kinase inhibitors reduce tumor growth and angiogenesis in experimental xenograft models, and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo effects of PDGFR inhibitors are more complex, based on the cross-talk with other angiogenic factors. In this review, we summarize data regarding the mechanisms and

  11. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    Directory of Open Access Journals (Sweden)

    Maryam Rakhshandehroo

    2010-01-01

    Full Text Available The peroxisome proliferator-activated receptor alpha (PPARα is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well.

  12. Preparation and physicochemistry properties of smart edible films based on gelatin-starch nanoparticles.

    Science.gov (United States)

    Tao, Furong; Shi, Chengmei; Cui, Yuezhi

    2018-04-24

    Among the natural polymers able to form edible films, starch and gelatin (Gel) are potential sources. Corn starch is a polysaccharide widely produced around the world, and gelatin differs from other hydrocolloids as a fully digestible protein, containing nearly all the essential amino acids, except tryptophan. Based on this, with advantages such as abundance, relatively low cost, biodegradability, and edibility, studies considering alternative systems for food protection that utilize biopolymers have increased significantly in the recent years. A novel macromolecular crosslinker Starch-BTCAD-NHS (starch - butanetetracarboxylic acid dianhydride - N-hydroxysuccinimide, SBN) was successfully prepared to modify gelatin film. Compared with the blank gelatin films, the resulting SBN-Gel films exhibited the improved surface hydrophobicity, the higher tense strength and elongation-at-break, the lower Young's modulus values, the greater opacity, the poorer water vapor uptake properties and better anti-degradation capacity. The modified gelatin film material with advanced properties obtained in this work was safe, stable eco-friendly and biorefractory, and was an ideal choice to form a packaging in food industry. Also, the crosslinking SBN-gelatin coating was effective in reducing the corruption and extending the shelf life for the peeled apple substantially. This article is protected by copyright. All rights reserved.

  13. Transplantation of artificial gelatin-co-bletillastriata gelatin/ Salvia ...

    African Journals Online (AJOL)

    Purpose: To evaluate the growth of the composite corium (constructed with fibroblast cells and gelatinco- Bletillastriata gelatin/Salvia miltiorrhiza materials) on rats. Methods: The composite artificial corium was constructed by culturing fibroblast cells in gelatin-co- Bletillastriata gelatin/Salvia miltiorrhiza materials.

  14. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    Green, Mark A.

    2000-01-01

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

  15. A receptor model for urban aerosols based on oblique factor analysis

    DEFF Research Database (Denmark)

    Keiding, Kristian; Sørensen, Morten S.; Pind, Niels

    1987-01-01

    A procedure is outlined for the construction of receptor models of urban aerosols, based on factor analysis. The advantage of the procedure is that the covariation of source impacts is included in the construction of the models. The results are compared with results obtained by other receptor......-modelling procedures. It was found that procedures based on correlating sources were physically sound as well as in mutual agreement. Procedures based on non-correlating sources were found to generate physically obscure models....

  16. Effect of Graphite Concentration on Shear-Wave Speed in Gelatin-Based Tissue-Mimicking Phantoms

    Science.gov (United States)

    Anderson, Pamela G.; Rouze, Ned C.; Palmeri, Mark L.

    2011-01-01

    Elasticity-based imaging modalities are becoming popular diagnostic tools in clinical practice. Gelatin-based, tissue mimicking phantoms that contain graphite as the acoustic scattering material are commonly used in testing and validating elasticity-imaging methods to quantify tissue stiffness. The gelatin bloom strength and concentration are used to control phantom stiffness. While it is known that graphite concentration can be modulated to control acoustic attenuation, the impact of graphite concentrationon phantom elasticity has not been characterized in these gelatin phantoms. This work investigates the impact of graphite concentration on phantom shear stiffness as characterized by shear-wave speed measurements using impulsive acoustic-radiation-force excitations. Phantom shear-wave speed increased by 0.83 (m/s)/(dB/(cm MHz)) when increasing the attenuation coefficient slope of the phantom material through increasing graphite concentration. Therefore, gelatin-phantom stiffness can be affected by the conventional ways that attenuation is modulated through graphite concentration in these phantoms. PMID:21710828

  17. Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy

    NARCIS (Netherlands)

    Bremer, Edwin

    2013-01-01

    The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective

  18. Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF

    International Nuclear Information System (INIS)

    Rosenberg, M.B.

    1986-01-01

    Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125 I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 4 0 C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125 I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

  19. Targeting the epidermal growth factor receptor in solid tumor malignancies

    DEFF Research Database (Denmark)

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...... to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal...... agents to the EGFR/EGFRvIII-positive cells; among these are radio-labelled mAbs and immunotoxins. This article reviews the current status and efficacy of EGFR/EGFRvIII-targeted therapies....

  20. Water Vapor Sensors Based on the Swelling of Relief Gelatin Gratings

    Directory of Open Access Journals (Sweden)

    Sergio Calixto

    2015-01-01

    Full Text Available We report on a novel device to measure relative humidity. The sensor is based on surface diffraction gratings made of gelatin. This material swells and shrinks according to the content of water vapor in air. By sending a light beam to the grating, diffracted orders appear. Due to the gelatin swelling or shrinking, first order intensity changes according to the relative humidity. Calibration curves relating intensity versus relative humidity have been found. The fabrication process of diffraction gratings and the testing of the prototype sensing devices are described.

  1. New polymeric formulation for control of biomphalaria Alexandria based on pharmaceutical waste gelatin

    International Nuclear Information System (INIS)

    Kenawy, E.; El-Maghraby, A.

    2005-01-01

    In the recent years, important new areas of application for plastics have emerged in medicine such as devices for the controlled release of drugs. The increases in the use of plastic materials in all sectors of industry have led to a continuous increase in the generation of plastic wastes. Recycling allow the waste to be reintroduced into the consumption cycle. Pharmaceutical companies which manufacture soft gels with different shapes, sizes and colors based mainly on gelatin formulations produce huge amount of gelatin waste. Schistosomiasis is one of the most important public health problems in our country. We now report the utilization of gelatin scrap by incorporating them in biodegradable films containing the molluscicide niclosamide for control of Biomphalaria Alexandrina snails. The preparation of the gelatin films will be described. The release of niclosamide from the prepared blends was investigated. The prepared formulations proved to be useful compared with free niclosamide

  2. Gelatin-hydroxypropyl methylcellulose water-in-water emulsions as a new bio-based packaging material.

    Science.gov (United States)

    Esteghlal, Sara; Niakosari, Mehrdad; Hosseini, Seyed Mohammad Hashem; Mesbahi, Gholam Reza; Yousefi, Gholam Hossein

    2016-05-01

    Gelatin and hydroxypropyl methylcellulose (HPMC) are two incompatible and immiscible biopolymers which cannot form homogeneous composite films using usual methods. In this study, to prevent phase separation, gelatin-HPMC water-in-water (W/W) emulsion was utilized to from transparent composite films by entrapment the HPMC dispersed droplets in gelatin continuous network. The physicochemical and mechanical properties of emulsion-based films containing different amounts (5-30%) of dispersed phase were determined and compared with those of individual polymer-based films. Incorporating HPMC into W/W emulsion-based films had no significant effect on the tensile strength. The flexibility of composite films decreased at HPMC concentrations below 20%. The depletion layer at the droplets interface reduced the diffusion of water vapor molecules because of its hydrophobic nature, so the water vapor permeability remained constant. Increasing the HPMC content in the emulsion films increased the swelling and decreased the transparency. The entrapment of HPMC in continuous gelatin phase decreased its solubility. Therefore, W/W emulsions are capable of holding two incompatible polymers alongside each other within a homogeneous film network without weakening the physical properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Hierarchical axon targeting of Drosophila olfactory receptor neurons specified by the proneural transcription factors Atonal and Amos.

    Science.gov (United States)

    Okumura, Misako; Kato, Tomoko; Miura, Masayuki; Chihara, Takahiro

    2016-01-01

    Sensory information is spatially represented in the brain to form a neural map. It has been suggested that axon-axon interactions are important for neural map formation; however, the underlying mechanisms are not fully understood. We used the Drosophila antennal lobe, the first olfactory center in the brain, as a model for studying neural map formation. Olfactory receptor neurons (ORNs) expressing the same odorant receptor target their axons to a single glomerulus out of approximately 50 glomeruli in the antennal lobe. Previous studies have showed that the axons of Atonal ORNs, specified by Atonal, a basic helix-loop-helix (bHLH) transcription factor, pioneer antennal lobe formation; however, the details remain to be elucidated. Here, we show that genetic ablation of Atonal ORNs affects antennal lobe structure and axon targeting of Amos ORNs, another type of ORN specified by the bHLH transcription factor Amos. During development, Atonal ORNs reach the antennal lobe and form the axon commissure before Amos ORNs. We also found that N-cadherin knockdown specifically in Atonal ORNs disrupts the glomerular boundary in the whole antennal lobe. Our results suggest that Atonal ORNs function as pioneer axons. Thus, correct axon targeting of Atonal ORNs is essential for formation of the whole antennal lobe. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  4. The epidermal growth factor receptor as a target for gastrointestinal cancer therapy.

    Science.gov (United States)

    Tedesco, Karen L; Lockhart, A Craig; Berlin, Jordan D

    2004-10-01

    The epidermal growth factor receptor (EGFR) is a member of the family of transmembrane protein kinase receptors known as the erbB or HER receptor family. When activated, EGFR phosphorylates and activates other intracellular proteins that affect cell signaling pathways, cellular proliferation, control of apoptosis and angiogenesis. EGFR signaling is best thought of as a network of activating and inactivating proteins with EGFR as the entry point into the network. EGFR overexpression occurs in most GI malignancies and while data are not entirely consistent, EGFR overexpression often confers a poor prognosis in those GI malignancies that have been studied. It often correlates with poorly differentiated histology, more advanced stage and other known poor prognostic markers. The EGFR is a tempting target because of its presence and overexpression on so many tumor types. However, downstream of the EGFR are several proteins that may be activated without EGFR thus allowing blockade to be overcome. Therefore, while blocking the activity of the EGFR protein appears to be a promising anticancer strategy, a simplistic strategy of blocking only EGFR is likely to only impact a minority of patients. It is time for the laboratory and clinical researchers to work closely together to develop this treatment strategy, moving back and forth from clinical to laboratory to best understand how to block this network effectively enough to produce a broader antitumor effect. While multiple methods of targeting the EGFR pathway are under development, including the inhibition of downstream proteins, only two modalities have entered clinical trials in GI malignancies: small molecule inhibitors of the intracellular kinase domain of EGFR and antibodies designed to block the extracellular ligand-binding domain of EGFR. EGFR inhibitors are still experimental in every GI malignancy with the notable exception of cetuximab that is approved for second or third-line therapy of metastatic colorectal

  5. Radiation as a processing aid for upgrading gelatin and gelatin capsules

    International Nuclear Information System (INIS)

    Patel, K.M.; Tantry, M.; Sharma, G.; Gopal, N.G.S.

    1979-01-01

    Gelatin for pharmaceutical use should not contain more than 1000 microorganisms per gram and must not contain pathogenic microorganisms like Salmonella species and E.Coli. For some biological studies spore free gelatin is essential. Locally available gelatin and gelatin capsules have been found to contain a good number of microorganisms. Gelatin and its capsules containing different colours were exposed to graded doses of radiation and stored at different temperatures. They were then examined for microbial content, disintegration characteristics, pH, viscosity and colour change. The study shows that radiation treatment is useful to upgrade microbiologically both gelatin and its capsules. This technique provides apparently a useful and economic method for producing spore free gelatin which in commerce is relatively expensive. (auth.)

  6. Radiation as a processing aid for upgrading gelatin and gelatin capsules

    Energy Technology Data Exchange (ETDEWEB)

    Patel, K M; Tantry, M; Sharma, G; Gopal, N G.S. [Bhabha Atomic Research Centre, Bombay (India). ISOMED

    1979-01-01

    Gelatin for pharmaceutical use should not contain more than 1000 microorganisms per gram and must not contain pathogenic microorganisms like Salmonella species and E.Coli. For some biological studies spore free gelatin is essential. Locally available gelatin and gelatin capsules have been found to contain a good number of microorganisms. Gelatin and its capsules containing different colours were exposed to graded doses of radiation and stored at different temperatures. They were then examined for microbial content, disintegration characteristics, pH, viscosity and colour change. The study shows that radiation treatment is useful to upgrade microbiologically both gelatin and its capsules. This technique provides apparently a useful and economic method for producing spore free gelatin which in commerce is relatively expensive.

  7. Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A.; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I.

    2015-01-01

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R–OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–CRF1R–OX1R complex promotes a long-term disruption of the orexin-A–CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. PMID:25926444

  8. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

    2015-04-29

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

  9. Yersinia pestis targets neutrophils via complement receptor 3

    Science.gov (United States)

    Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

    2015-01-01

    Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

  10. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography.

    Science.gov (United States)

    Toth, Marta; Sohail, Anjum; Fridman, Rafael

    2012-01-01

    Gelatin zymography is a simple yet powerful method to detect proteolytic enzymes capable of degrading gelatin from various biological sources. It is particularly useful for the assessment of two key members of the matrix metalloproteinase family, MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their potent gelatin-degrading activity. This polyacrylamide gel electrophoresis-based method can provide a reliable assessment of the type of gelatinase, relative amount, and activation status (latent, compared with active enzyme forms) in cultured cells, tissues, and biological fluids. The method can be used to investigate factors that regulate gelatinase expression and modulate zymogen activation in experimental systems. The system provides information on the pattern of gelatinase expression and activation in human cancer tissues and how this relates to cancer progression. Interpretation of the data obtained in gelatin zymography requires a thorough understanding of the principles and pitfalls of the technique; this is particularly important when evaluating enzyme levels and the presence of active gelatinase species. If properly used, gelatin zymography is an excellent tool for the study of gelatinases in biological systems.

  11. Novel approaches for targeting the adenosine A2A receptor.

    Science.gov (United States)

    Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

    2015-01-01

    The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

  12. Preparation and Characterization of Gelatin-Based Mucoadhesive Nanocomposites as Intravesical Gene Delivery Scaffolds

    Directory of Open Access Journals (Sweden)

    Ching-Wen Liu

    2014-01-01

    Full Text Available This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM was carried out. The optimal hydrogels (H, composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.. Lentivirus from lentivector constructed green fluorescent protein (GFP was then entrapped in hydrogels (H-LV-GFP. H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds.

  13. Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

    Science.gov (United States)

    Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

    2012-07-15

    Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

  14. The physico-chemical properties of pangas catfish (Pangasius pangasius) skin gelatin

    Science.gov (United States)

    Pradarameswari, K. A.; Zaelani, K.; Waluyo, E.; Nurdiani, R.

    2018-04-01

    Gelatin can be used as emulsifier and stabilizer in food products. Until now, the most widely used raw materials for the production of gelatin industry are cow bone, cow skin and pig skin. Fish gelatin has been highlighted as a better alternative to replace mammals gelatin based on ethical and religious perspective. Fish gelatin was extracted from Pangas catfish skin to determine its physico-chemical properties. Different temperatures (45 °C, 50 °C, 55 °C) were employed during gelatin extraction. Higher temperature increased the yield and fat contents of Pangas catfish skin gelatin. In contrary, higher water, protein, ash contents were observed during lower temperature. Temperature significantly (p fish skin gelatin. Based on the FTIR spectrum catfish skin gelatin functional groups can be identified as N-H, O-H, C = H, C-O and C-H.

  15. Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

    Directory of Open Access Journals (Sweden)

    Inês Gomes Ferreira

    2018-02-01

    Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

  16. The development of epidermal growth factor receptor molecular imaging in cancer

    International Nuclear Information System (INIS)

    Zhou Xiaoliang; Wang Hao; Shi Peiji; Liu Jianfeng; Meng Aimin

    2013-01-01

    In vivo epidermal growth factor receptor (EGFR) targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects. Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which could enable monitoring of receptor drug binding and receptor occupancy in vivo, and identification of the mutation in EGFR. PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders, predicting therapeutic outcome and monitoring EGFR-targeted treatment. This review analyzed the present situation and research progress of molecular imaging agents. (authors)

  17. Transcriptome Analysis of Gelatin Seed Treatment as a Biostimulant of Cucumber Plant Growth

    Directory of Open Access Journals (Sweden)

    H. T. Wilson

    2015-01-01

    Full Text Available The beneficial effects of gelatin capsule seed treatment on enhanced plant growth and tolerance to abiotic stress have been reported in a number of crops, but the molecular mechanisms underlying such effects are poorly understood. Using mRNA sequencing based approach, transcriptomes of one- and two-week-old cucumber plants from gelatin capsule treated and nontreated seeds were characterized. The gelatin treated plants had greater total leaf area, fresh weight, frozen weight, and nitrogen content. Pairwise comparisons of the RNA-seq data identified 620 differentially expressed genes between treated and control two-week-old plants, consistent with the timing when the growth related measurements also showed the largest differences. Using weighted gene coexpression network analysis, significant coexpression gene network module of 208 of the 620 differentially expressed genes was identified, which included 16 hub genes in the blue module, a NAC transcription factor, a MYB transcription factor, an amino acid transporter, an ammonium transporter, a xenobiotic detoxifier-glutathione S-transferase, and others. Based on the putative functions of these genes, the identification of the significant WGCNA module and the hub genes provided important insights into the molecular mechanisms of gelatin seed treatment as a biostimulant to enhance plant growth.

  18. Preparation of Astaxanthin Nanodispersions Using Gelatin-Based Stabilizer Systems

    Directory of Open Access Journals (Sweden)

    Navideh Anarjan

    2014-09-01

    Full Text Available The incorporation of lipophilic nutrients, such as astaxanthin (a fat soluble carotenoid in nanodispersion systems can either increase the water solubility, stability and bioavailability or widen their applications in aqueous food and pharmaceutical formulations. In this research, gelatin and its combinations with sucrose oleate as a small molecular emulsifier, sodium caseinate (SC as a protein and gum Arabic as a polysaccharide were used as stabilizer systems in the formation of astaxanthin nanodispersions via an emulsification-evaporation process. The results indicated that the addition of SC to gelatin in the stabilizer system could increase the chemical stability of astaxanthin nanodispersions significantly, while using a mixture of gelatin and sucrose oleate as a stabilizer led to production of nanodispersions with the smallest particle size (121.4 ± 8.6 nm. It was also shown that a combination of gelatin and gum Arabic could produce optimal astaxanthin nanodispersions in terms of physical stability (minimum polydispersity index (PDI and maximum zeta-potential. This study demonstrated that the mixture of surface active compounds showed higher emulsifying and stabilizing functionality compared to using them individually in the preparation of astaxanthin nanodispersions.

  19. Performance of high amylose starch-composited gelatin films influenced by gelatinization and concentration.

    Science.gov (United States)

    Wang, Wenhang; Wang, Kun; Xiao, Jingdong; Liu, Yaowei; Zhao, Yana; Liu, Anjun

    2017-01-01

    In order to study the impact of starch in film performance, high amylose corn starch was composited in gelatin films under different gelatinization conditions and, in high and low concentrations (10 and 50wt.%). It was found that hot water gelatinized starch (Gel-Shw) increased film mechanical strength and was dependent upon the starch concentration. The addition of an alkali component to the starch significantly enhanced the swelling of the starch granules and expedited the gelatinization process. Incorporation of starch, especially the alkalized starch (Sha), into the gelatin films decreased film solubility which improved its water resistance and water vapor permeability (WVP). Multiple techniques (DSC, TGA, FT-IR, and XRD) were used to characterize the process and results, including the crosslinking of the dissolved starch molecules and the particles formed from gelatinized starch during retrogradation process, which played an important role in improving the thermal stability of the composited gelatin films. Overall, the starch-gelatin composition provides a potential approach to improve gelatin film performance and benefit its applications in the food industry. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Targeting the TAM Receptors in Leukemia.

    Science.gov (United States)

    Huey, Madeline G; Minson, Katherine A; Earp, H Shelton; DeRyckere, Deborah; Graham, Douglas K

    2016-11-08

    Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

  1. Targeting the TAM Receptors in Leukemia

    Directory of Open Access Journals (Sweden)

    Madeline G. Huey

    2016-11-01

    Full Text Available Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

  2. Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters.

    Science.gov (United States)

    Oliveira, Camila Areias de; Peres, Daniela D'Almeida; Graziola, Fabiana; Chacra, Nádia Araci Bou; Araújo, Gabriel Lima Barros de; Flórido, Ana Catarina; Mota, Joana; Rosado, Catarina; Velasco, Maria Valéria Robles; Rodrigues, Luís Monteiro; Fernandes, Ana Sofia; Baby, André Rolim

    2016-01-01

    The encapsulation of natural ingredients, such as rutin, can offer improvements in sun protection effectiveness. This strategy can provide enhanced flavonoid content and produces an improved bioactive compound with new physical and functional characteristics. As an alternative to common synthetic-based sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate (EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose of this study was to develop rutin-loaded gelatin nanoparticles and characterize their physicochemical, thermal, functional and safety properties. Rutin-loaded gelatin nanoparticles increased antioxidant activity by 74% relative to free-rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor (SPF) by 48%, indicating its potential as a raw material for bioactive sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA) decreased HaCaT cell viability in a concentration/time-dependent manner. However, both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good performance on skin compatibility tests. These results functionally characterized rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in association with UV filters. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The study of consistent properties of gelatinous shampoo with minoxidil

    Directory of Open Access Journals (Sweden)

    I. V. Gnitko

    2016-04-01

    Full Text Available The aim of the work is the study of consistent properties of gelatinous shampoo with minoxidil 1% for the complex therapy and prevention of alopecia. This shampoo with minoxidil was selected according to the complex physical-chemical, biopharmaceutical and microbiological investigations. Methods and results. It has been established that consistent properties of the gelatinous minoxidil 1% shampoo and the «mechanical stability» (1.70 describe the formulation as exceptionally thixotropic composition with possibility of restoration after mechanical loads. Also this fact allows to predict stability of the consistent properties during long storage. Conclusion. Factors of dynamic flowing for the foam detergent gel with minoxidil (Кd1=38.9%; Kd2=78.06% quantitatively confirm sufficient degree of distribution at the time of spreading composition on the skin surface of the hairy part of head or during technological operations of manufacturing. Insignificant difference of «mechanical stability» for the gelatinous minoxidil 1% shampoo and its base indicates the absence of interactions between active substance and the base.

  4. Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

    Science.gov (United States)

    Salamon, Achim; van Vlierberghe, Sandra; van Nieuwenhove, Ine; Baudisch, Frank; Graulus, Geert-Jan; Benecke, Verena; Alberti, Kristin; Neumann, Hans-Georg; Rychly, Joachim; Martins, José C.; Dubruel, Peter; Peters, Kirsten

    2014-01-01

    Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies. PMID:28788517

  5. Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

    Directory of Open Access Journals (Sweden)

    Chui-Mian Zeng

    2018-05-01

    Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

  6. Enhanced intestinal anastomotic healing with gelatin hydrogel incorporating basic fibroblast growth factor.

    Science.gov (United States)

    Hirai, Kenjiro; Tabata, Yasuhiko; Hasegawa, Suguru; Sakai, Yoshiharu

    2016-10-01

    Anastomotic leakage is a common complication of intestinal surgery. In an attempt to resolve this issue, a promising approach is enhancement of anastomotic wound healing. A method for controlled release of basic fibroblast growth factor (bFGF) using a gelatin hydrogel was developed with the objective of investigating the effects of this technology on intestinal anastomotic healing. The small intestine of Wistar rats was cut, end-to-end anastomosis was performed and rats were divided into three groups: bFGF group (anastomosis wrapped with a hydrogel sheet incorporating bFGF), PBS group (wrapped with a sheet incorporating phosphate-buffered saline solution) and NT group (no additional treatment). Degradation profiles of gelatin hydrogels in vivo and histological examinations were performed using gelatin hydrogels with various water contents and bFGF concentrations to define the optimal bFGF dose and hydrogel biodegradability. The anastomotic wound healing process was evaluated by histological examinations, adhesion-related score and bursting pressure. The optimal water content of the hydrogel and bFGF dose was determined as 96% and 30 µg per sheet, respectively. Application of bFGF significantly enhanced neovascularization, fibroblast infiltration and collagen production around the anastomotic site when compared with the other groups. Bursting pressure was significantly increased in the bFGF group. No significant difference was observed in the adhesion-related score among the groups and no anastomotic obstruction and leakage were observed. Therefore controlled release of bFGF enhanced healing of an intestinal anastomosis during the early postoperative period and is a promising method to suppress anastomotic leakage. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  7. THE EFFECT OF PLASTICIZER CONTENT AND DISACCHARIDE TYPE ON THE MECHANICAL, BARRIER AND PHYSICAL PROPERTIES OF BOVINE GELATIN-BASED FILMS

    Directory of Open Access Journals (Sweden)

    PEDRO GUERRERO1

    2014-06-01

    Full Text Available Gelatins are regarded as alternative raw materials to prepare films for food packaging. However, the improvement of their mechanical and water barrier properties is necessary in order to obtain useful materials in service conditions. To improve these functional properties, two strategies have been carried out in this work. First, glycerol was added as plasticizer to increase the flexibility of the films. Second, lactose or sucrose was added to react with gelatin and increase water resistance of gelatin-based films. Commercial gelatin, glycerol and lactose or sucrose were employed in this work and processing of the films was carried out by solution casting. All gelatin films obtained were transparent and flexible. Moreover, the hydrophobic character of the films was increased and the film solubility was decreased by the addition of glycerol and disaccharides. As was observed via FTIR, the changes were due to the interactions between gelatin and glycerol and Maillard reaction between gelatin and disaccharides.

  8. Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Achim Salamon

    2014-02-01

    Full Text Available Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies.

  9. Thermal characterisation of gelatin extracted from yellowfin tuna skin and commercial mammalian gelatin.

    Science.gov (United States)

    Rahman, Mohammad Shafiur; Al-Saidi, Ghalib Said; Guizani, Nejib

    2008-05-15

    Glass transition and other thermal characteristics of gelatin from different sources were studied by differential scanning calorimetry (DSC) and modulated DSC (MDSC). The initial glass transition temperatures of equilibrated gelatin samples at 11.3% relative humidity, determined from reversible heat flow thermogram of MDSC, were 23, 75 and 59°C, respectively, for tuna skin, bovine and porcine gelatin. When gelatin samples were equilibrated at higher relative humidity of 52.9%, glass transition temperature of fish skin and bovine gelatin decreased to -3 and 57°C, respectively. Further increase of equilibration relative humidity to 75.3% showed increased value in the case of tuna skin, whereas bovine and porcine did not show any significant change. DSC and MDSC results indicated that tuna gelatin showed lower glass transition compared to mammalian source gelatin equilibrated at the same constant relative humidity. In general glass transition measured by DSC was found lower than the values measured by MDSC. The results in this study showed that the degree of plasticization varied with the source of gelatin as well as their extraction methods. Copyright © 2007 Elsevier Ltd. All rights reserved.

  10. Designer interface peptide grafts target estrogen receptor alpha dimerization

    International Nuclear Information System (INIS)

    Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

    2016-01-01

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  11. Designer interface peptide grafts target estrogen receptor alpha dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

    2016-09-09

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  12. Therapies based on inhibitors of the epidermal growth factor receptor: enclosing the future

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Lage, Agustin

    2007-01-01

    The Epidermal Growth Factor Receptor (EGFR) is considered an important target for rational drug design due to its key role in numerous tumors. Potential contribution of EGFR-related signaling pathways to promote tumorigenic processes, including cell proliferation, angiogenesis, and resistance to apoptosis has been well established. Two classes of anti-EGFR agents in late-stage clinical testing include monoclonal antibodies against extracellular EGFR domain (Cetuximab, Nimotuzumab) and small molecules tyrosine kinase inhibitors, which inhibit the receptor enzyme activity (Gefitinib, Erlotinib). A considerable body of evidence has emerged since its introduction in the treatment of cancer patients. However, important questions such as reliable surrogate markers to predict response to the treatment, or optimal sequence and combination of these agents with conventional therapies remain to be addressed. Identify and validate predictive factors to select patients likely to respond to EGFR inhibitors, such as mutations that confer resistance versus those associated with sensitivity is required. A better understanding of molecular mechanisms associated with antitumor activity will useful to predict the interaction of these agents with other therapies in order to avoid antagonisms or overlapping effects resulting in no adding effects. Finally, the benefits derived from EGFR inhibitors as first-line therapy in selected populations, and the optimal doses and ways to delivery to the tumor site resulting in optimal target modulation should be established by the ongoing investigation. (Author)

  13. Effect of tuna skin gelatin-based coating enriched with seaweed extracts on the quality of tuna fillets during storage at 4 °C

    Directory of Open Access Journals (Sweden)

    Milene Vala

    2017-10-01

    Full Text Available Nowadays, consumers demand high quality food products with an extended shelf-life without chemical additives. Edible coatings (EC containing natural compounds are a promising preservation technology for raw seafood without compromising fresh-like appeal and nutritional content.The aim of this work was to evaluate the effect of Thunnus obesus skin gelatin-based EC containing Codium spp. or Fucus vesiculosus extracts on raw tuna preservation. Three gelatin-based EC (gelatin (5 % + glycerol (25 %; gelatin (5 % + Codium spp. (1 % + glycerol (25 %; gelatin (5 % + Fucus vesiculosus (1 % + glycerol (25 % were applied directly on the surface of tuna fillets. Functional properties of gelatin and gelatin-based EC containing seaweed extracts were also studied. The gelatin was extracted by an acid-swelling process in the presence/absence of pepsin, followed by subsequent heating/refrigeration, after a pre-treatment with NaOH. The type of acid, temperature and concentration of NaOH greatly influence the process yield. The higher extraction yield was achieved using acetic acid in the presence of pepsin by subsequent refrigeration, especially when skins were previously treated with NaOH (0.2 M. Tuna quality was assessed over 12 days of storage at 4 ± 1 °C in terms of chemical and microbial indices. Results showed that tuna skin gelatin-based EC avoids tuna deterioration. Microbial growth, assessed by total viable counts, and total volatile basic nitrogen were maintained below the maximum limits recommended, contrarily to the control. Additionally, the use of EC increased the stability of red colour during storage. 

  14. Extraction and physicochemical characterization of broiler (Gallus gallus domesticus) skin gelatin compared to commercial bovine gelatin.

    Science.gov (United States)

    Aykin-Dinçer, E; Koç, A; Erbas, M

    2017-09-01

    Gelatin was extracted from broiler (Gallus gallus domesticus) skins and analyzed to compare its physicochemical properties with those of commercial bovine gelatin. The average yield of broiler skin gelatin was 6.5% on a wet weight basis. Broiler skin gelatin had more α1-and α2-chains than β-chain and contained high molecular weight (γ-chain) polymers. Glycine was the dominant amino acid in broiler skin gelatin (20.26%), followed by proline (Pro) (15.12%) then hydroxyproline (Hyp) (11.36%). Compared to commercial bovine gelatin, broiler skin gelatin had less total imino acids (Pro and Hyp) but a higher (33.65 vs. 31.38°C) melting temperature (P commercial bovine gelatins appeared to be associated with differences in their amino acid composition and molecular weight distribution. The sensory evaluation results revealed that broiler skin gelatin could be a potential alternative to commercial bovine gelatin, useful in various food products. © 2017 Poultry Science Association Inc.

  15. Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease.

    Science.gov (United States)

    Chakraborty, Ashok; Hatzis, Christos; DiGiovanna, Michael P

    2017-05-01

    Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor). Proliferation and apoptosis assays were performed in a large panel of cell lines representing varying receptor expression levels. Mechanistic effects were studied using phospho-protein immunoblotting. Analyses of drug interaction effects were performed using linear mixed-effects regression models. Enhanced anti-proliferative effects of HER/IGF-insulin co-targeting were seen in most, though not all, cell lines, including HER2-normal lines. For ER+ lines, triple targeting with inclusion of anti-estrogen generally resulted in the greatest anti-tumor effects. Double or triple targeting generally resulted in marked increases in apoptosis in the sensitive lines. Mechanistic studies demonstrated that the synergy between drugs was correlated with maximal inhibition of Akt and ERK pathway signaling. Dual HER/IGF-insulin targeting, and triple targeting with inclusion of anti-estrogen drugs, shows striking anti-tumor activity across breast cancer types, and drugs with broader receptor specificity may be more effective than single receptor selective drugs, particularly for ER- cells.

  16. Formulating gelatin free products

    NARCIS (Netherlands)

    Buwalda, P.L.

    2014-01-01

    Gels are applied in many systems in particular in foods. Gelatin is the most common of all gelling agents. In the food industry there is a long quest for replacing gelatin. This chapter focuses on a more application by application approach where a dominant property of gelatin is matched with a

  17. Effect of Pre-gelatinized Wheat Starch on Physical and Rheological Properties of Shortened Cake Batter and Cake Texture

    Directory of Open Access Journals (Sweden)

    F. Ebrahimi

    2016-10-01

    Full Text Available The focus of this study was the effect of 1.5%, 3% and 4.5% pre-gelatinized wheat starch (based on the total weight of cake batter on improving the qualitative properties of shortened cake batter. Specific volume and viscosity of the shortened cake batter were measured for controls, 1.5%, 3% and 4.5% gelatinized starch; some important properties such as texture and sensory evaluation were examined. By increasing pre-gelatinized wheat starch used in the batter, a significant difference was observed in the rheological properties of the batter. Cake batter properties were found improved compared to the control samples. The sample with 3% pre-gelatinized starch had a lower viscosity than other treatments. The treatment with 4.5% pre-gelatinized starch had the lowest specific volume compared to other treatments. The overall results showed that the shortened cake with 3% pre-gelatinized starch was the best treatment in terms of texture and sensory evaluation factors.

  18. Dielectric properties of single wall carbon nanotubes-based gelatin phantoms

    Science.gov (United States)

    Altarawneh, M. M.; Alharazneh, G. A.; Al-Madanat, O. Y.

    In this work, we report the dielectric properties of Single wall Carbon Nanotubes (SWCNTs)-based phantom that is mainly composed of gelatin and water. The fabricated gelatin-based phantom with desired dielectric properties was fabricated and doped with different concentrations of SWCNTs (e.g., 0%, 0.05%, 0.10%, 0.15%, 0.2%, 0.4% and 0.6%). The dielectric constants (real ɛ‧ and imaginary ɛ‧‧) were measured at different positions for each sample as a function of frequency (0.5-20GHz) and concentrations of SWCNTs and their averages were found. The Cole-Cole plot (ɛ‧ versus ɛ‧‧) was obtained for each concentration of SWCNTs and was used to obtain the static dielectric constant ɛs, the dielectric constant at the high limit of frequency ɛ∞ and the average relaxation time τ. The measurements showed that the fabricated samples are in good homogeneity and the SWCNTs are dispersed well in the samples as an acceptable standard deviation is achieved. The study showed a linear increase in the static dielectric constant ɛs and invariance of the average relaxation time τ and the value of ɛ∞ at room temperature for the investigated concentrations of SWCNTs.

  19. Gelatin/chitosan biofilm: preparation and characterization

    International Nuclear Information System (INIS)

    Trindade, Luciane da C.; Nunes, Raquel A.; Diniz, Nadie K.S.; Braga, Carla R.C.; Silva, Suedina M. de Lima

    2011-01-01

    In this study, gelatin, chitosan and gelatin/chitosan bio films using the ratio of gelatin/chitosan (50/50) were prepared by casting method. The bio films prepared were characterized by X-ray diffraction, scanning electron microscopy and dissolution ratio. According to the results, the incorporation of chitosan into gelatin indicate the decrease of crystallinity of chitosan, a compact structure without large pores and that the dissolution of gelatin/chitosan film is little influenced by hot water than gelatin films. (author)

  20. Controlled release of sphingosine-1-phosphate agonist with gelatin hydrogels for macrophage recruitment.

    Science.gov (United States)

    Murakami, Masahiro; Saito, Takashi; Tabata, Yasuhiko

    2014-11-01

    The objective of this study is to design a drug delivery system (DDS) for the in vivo promotion of macrophage recruitment. As the drug, a water-insoluble agonist of sphingosine-1-phosphate type 1 receptor (SEW2871) was selected. SEW2871 (SEW) was water-solubilized by micelle formation with gelatin grafted by L-lactic acid oligomer. SEW micelles were mixed with gelatin, followed by dehydrothermal crosslinking of gelatin to obtain gelatin hydrogels incorporating SEW micelles. SEW was released from the hydrogels incorporating SEW micelles in vitro and in vivo. The water-solubilized SEW showed in vitro macrophage migration activity. When implanted into the back subcutis or the skin wound defect of mice, the hydrogel incorporating SEW micelles promoted macrophage migration toward the tissue around the implanted site to a significantly great extent compared with SEW-free hydrogel and that mixed with SEW micelles. The hydrogel is a promising DDS to enhance macrophage recruitment in vivo. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges

    International Nuclear Information System (INIS)

    Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

    2015-01-01

    Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group. (paper)

  2. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

    Science.gov (United States)

    Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

    2015-10-20

    Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group.

  3. Novel targeted agents for gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Lian

    2012-06-01

    Full Text Available Abstract Contemporary advancements have had little impact on the treatment of gastric cancer (GC, the world’s second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs and receptor tyrosine kinase inhibitors (TKIs. Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2 gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF, mammalian target of rapamycin (mTOR, and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers.

  4. Isolation of fish skin and bone gelatin from tilapia (Oreochromis niloticus): Response surface approach

    Science.gov (United States)

    Arpi, N.; Fahrizal; Novita, M.

    2018-03-01

    In this study, gelatin from fish collagen, as one of halal sources, was extracted from tilapia (Oreochromis niloticus) skin and bone, by using Response Surface Methodology to optimize gelatin extraction conditions. Concentrations of alkaline NaOH and acid HCl, in the pretreatment process, and temperatures in extraction process were chosen as independent variables, while dependent variables were yield, gel strength, and emulsion activity index (EAI). The result of investigation showed that lower NaOH pretreatment concentrations provided proper pH extraction conditions which combine with higher extraction temperatures resulted in high gelatin yield. However, gelatin emulsion activity index increased proportionally to the decreased in NaOH concentrations and extraction temperatures. No significant effect of the three independent variables on the gelatin gel strength. RSM optimization process resulted in optimum gelatin extraction process conditions using alkaline NaOH concentration of 0.77 N, acid HCl of 0.59 N, and extraction temperature of 66.80 °C. The optimal solution formula had optimization targets of 94.38%.

  5. Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Rogier P.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Urology, Rotterdam (Netherlands); Weerden, W.M. van; Bangma, C.H.; Reneman, S. [Erasmus MC, Department of Urology, Rotterdam (Netherlands); Krenning, E.P.; Berndsen, S.; Grievink-de Ligt, C.H.; Groen, H.C.; Blois, E. de; Breeman, W.A.P.; Jong, M. de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands)

    2011-07-15

    Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the {sup 68}Ga-labelled bombesin analogue AMBA with metabolism-based targeting using {sup 18}F-methylcholine ({sup 18}F-FCH) in nude mice bearing human prostate VCaP xenografts. PET and biodistribution studies were performed with both {sup 68}Ga-AMBA and {sup 18}F-FCH in all VCaP tumour-bearing mice, with PC-3 tumour-bearing mice as reference. Scanning started immediately after injection. Dynamic PET scans were reconstructed and analysed quantitatively. Biodistribution of tracers and tissue uptake was expressed as percent of injected dose per gram tissue (%ID/g). All tumours were clearly visualized using {sup 68}Ga-AMBA. {sup 18}F-FCH showed significantly less contrast due to poor tumour-to-background ratios. Quantitative PET analyses showed fast tumour uptake and high retention for both tracers. VCaP tumour uptake values determined from PET at steady-state were 6.7 {+-} 1.4%ID/g (20-30 min after injection, N = 8) for {sup 68}Ga-AMBA and 1.6 {+-} 0.5%ID/g (10-20 min after injection, N = 8) for {sup 18}F-FCH, which were significantly different (p <0.001). The results in PC-3 tumour-bearing mice were comparable. Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 {+-} 4.8%ID/g (N = 8) for {sup 68}Ga-AMBA and 2.1 {+-} 0.4%ID/g (N = 8) for {sup 18}F-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for {sup 68}Ga-AMBA than for {sup 18}F-FCH. Tumour uptake of {sup 68}Ga-AMBA was higher while overall background activity was lower than observed for {sup 18}F-FCH in the same PC-bearing mice. These results

  6. Rheometric Non-Isothermal Gelatinization Kinetics of Chickpea Flour-Based Gluten-Free Muffin Batters with Added Biopolymers

    Directory of Open Access Journals (Sweden)

    María Dolores Alvarez

    2017-01-01

    Full Text Available An attempt was made to analyze the elastic modulus (G0 of chickpea flour (CF-based muffin batters made with CF alone and with added biopolymers (whey protein (WP, xanthan gum (XG, inulin (INL, and their blends in order to evaluate their suitability to be a wheat flour (WF substitute in muffins, and to model the heat-induced gelatinization of batters under non-isothermal heating condition from 25 ◦C to 90 ◦C. A rheological approach is proposed to determine the kinetic parameters (reaction order (n, frequency factor (k0, and activation energy (Ea using linearly-increasing temperature. Zero-order reaction kinetics adequately described batter gelatinization process, therefore assuming a constant rate independent of the initial G0 value. The change of the derivative of G0 with respect to time (dG0/dt versus temperature is described by one exponential function with activation energies ranging from 118 to 180 kJ·mol−1. Control wheat gluten batter, with higher and lower starch and protein contents, respectively, than CF-based batters, exhibited the highest Ea value. Formulation of CF-based gluten-free batters with starch and protein contents closer to the levels of WF-based batter could be a strategy to decrease differences in kinetic parameters of muffin batters and, therefore, in technological characteristics of baked muffins.

  7. ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers

    International Nuclear Information System (INIS)

    Wellstein, Anton

    2012-01-01

    The intracellular anaplastic lymphoma kinase (ALK) fragment shows striking homology with members of the insulin receptor family and was initially identified as an oncogenic fusion protein resulting from a translocation in lymphoma and more recently in a range of cancers. The full-length ALK transmembrane receptor of ~220 kDa was identified based on this initial work. This tyrosine kinase receptor and its ligands, the growth factors pleiotrophin (PTN) and midkine (MK) are highly expressed during development of the nervous system and other organs. Each of these genes has been implicated in malignant progression of different tumor types and shown to alter phenotypes as well as signal transduction in cultured normal and tumor cells. Beyond its role in cancer, the ALK receptor pathway is thought to contribute to nervous system development, function, and repair, as well as metabolic homeostasis and the maintenance of tissue regeneration. ALK receptor activity in cancer can be up-regulated by amplification, overexpression, ligand binding, mutations in the intracellular domain of the receptor and by activity of the receptor tyrosine phosphatase PTPRz. Here we discuss the evidence for ligand control of ALK activity as well as the potential prognostic and therapeutic implications from gene expression and functional studies. An analysis of 18 published gene expression data sets from different cancers shows that overexpression of ALK, its smaller homolog LTK (leukocyte tyrosine kinase) and the ligands PTN and MK in cancer tissues from patients correlate significantly with worse course and outcome of the disease. This observation together with preclinical functional studies suggests that this pathway could be a valid therapeutic target for which complementary targeting strategies with small molecule kinase inhibitors as well as antibodies to ligands or the receptors may be used.

  8. Emerging growth factor receptor antagonists for the treatment of renal cell carcinoma.

    Science.gov (United States)

    Zahoor, Haris; Rini, Brian I

    2016-12-01

    The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.

  9. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials

    DEFF Research Database (Denmark)

    Voldborg, B R; Damstrup, L; Spang-Thomsen, M

    1997-01-01

    The epidermal growth factor receptor (EGFR) is a growth factor receptor that induces cell differentiation and proliferation upon activation through the binding of one of its ligands. The receptor is located at the cell surface, where the binding of a ligand activates a tyrosine kinase in the intr...... aspects of therapeutic targeting of EGFR....

  10. Determine Age-structure of Gelatinous Zooplankton Using Optical Coherence Tomography

    Science.gov (United States)

    Bi, H.; Shahrestani, S.; He, Y.

    2016-02-01

    Gelatinous are delicate and transparent by nature, but are conspicuous in many ecosystems when in bloom. Their proliferations are a bothersome and costly nuisance and influencing important food webs and species interactions. More importantly, gelatinous zooplankton respond to climate change rapidly and understanding their upsurge needs information on their recruitment and population dynamics which in turn require their age-structure. However, ageing gelatinous zooplankton is often restricted by the fact that they shrink under unfavorable conditions. In the present study, we examine the potential of using optical coherence tomography (OCT) to age gelatinous zooplankton. OCT is a non-invasive imaging technique that uses light waves to examine 2D or 3D structure of target objects at a resolution of 3-5 µm. We were able to successfully capture both 3D and 2D images of sea nettle muscle fibers. Preliminary results on ctenophores will be discussed. Overall, this non-destructive sampling allows us to scan and capture images of mesoglea from jellyfish cultured in the lab, using the same individual repeatedly through time, documenting its growth which will provide precise measurements to construct an age key that will be applied to gelatinous zooplankton captured in the field. Coupled with information on abundance, we can start to quantify their recruitment timing and success rate.

  11. Virus-encoded chemokine receptors--putative novel antiviral drug targets

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M

    2005-01-01

    Large DNA viruses, in particular herpes- and poxviruses, have evolved proteins that serve as mimics or decoys for endogenous proteins in the host. The chemokines and their receptors serve key functions in both innate and adaptive immunity through control of leukocyte trafficking, and have...... receptors belong to the superfamily of G-protein coupled 7TM receptors that per se are excellent drug targets. At present, non-peptide antagonists have been developed against many chemokine receptors. The potentials of the virus-encoded chemokine receptors as drug targets--ie. as novel antiviral strategies...

  12. Characteristic study of chitosan addition in Tilapia (Oreochromis niloticus) bone based gelatin film

    Science.gov (United States)

    Atmaka, W.; Yudhistira, B.; Putro, M. I. S.

    2018-03-01

    Tilapia (Oreochromis niloticus) is one of popular fish species in Indonesia. The high number in tilapia’s production and export of tilapia resulting in the increase of bone fish waste. an attempt to decrease the amount of the aforementioned waste, the fish bones were turned into gelatine. The gelatine produced from this waste can be put to good use by turning it into edible film due to its high water resistance and low tensile strength value. However, in order to make a proper film, both the water resistance and the tensile strength value needs another appropriate additional biopolymer. In this case, the appropriate biopolymer needed both to form the film and to repair its characteristics is chitosan. The purpose of this research is to find out the effect of the chitosan addition on the tilapia bone based gelatine film. The research used several mixtures of gelatine (G) and chitosan (C) with the following ratio: G100:C0 (GC1), G75:C25 (GC2), G50:C50 (GC3), G25:C75 (GC4), G0:C100 (GC5). ANOVA results (Psolubility, tensile strength, elongation at break, Fourier Transform Infrared (FTIR), color a, and color b but no significant effects on the vapor permeability and color L. The best result is shown on GC2 with thickness 0.119 mm; solubility 74.95%; tensile strength 2.635 Mpa; elongation at break 68.26%; water vapor permeability 5.897 g/h m2 and FTIR. The parameters in GC2 shows good compatibility between the two biopolymers.

  13. Targeting Discoidin Domain Receptors in Prostate Cancer

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...AND SUBTITLE 5a. CONTRACT NUMBER Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0226 5c. PROGRAM ELEMENT...response to collagen in prostate cancer. The project’s goal is to define the expression and therapeutic potential of DDRs in prostate cancer. During

  14. Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

    International Nuclear Information System (INIS)

    Luce, A.; Courtin, A.; Levalois, C.; Altmeyer-Morel, S.; Chevillard, S.; Lebeau, J.; Romeo, P.H.

    2009-01-01

    Delayed cell death by mitotic catastrophe is a frequent mode of solid tumor cell death after γ-irradiation, a widely used treatment of cancer. Whereas the mechanisms that underlie the early γ-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-α death receptor pathways mediate the delayed cell death observed after γ-irradiation of breast cancer cells. Early after irradiation, we observe the increased expression of Fas, TRAIL-R and TNF-R that first sensitizes cells to apoptosis. Later, the increased expression of FasL, TRAIL and TNF-α permit the apoptosis engagement linked to mitotic catastrophe. Treatments with TNF-α, TRAIL or anti-Fas antibody, early after radiation exposure, induce apoptosis, whereas the neutralization of the three death receptors pathways impairs the delayed cell death. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands that can induce the death of sensitive bystander cells. Overall, these results define the molecular basis of the delayed cell death of irradiated cancer cells and identify the death receptors pathways as crucial actors in apoptosis induced by targeted as well as non-targeted effects of ionizing radiation. (authors)

  15. Insulin-like growth factor receptor inhibitors: baby or the bathwater?

    Science.gov (United States)

    Yee, Douglas

    2012-07-03

    The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.

  16. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  17. Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

    Directory of Open Access Journals (Sweden)

    David Olmos

    2011-01-01

    Full Text Available Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response.

  18. Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

    Science.gov (United States)

    Olmos, David; Martins, Ana Sofia; Jones, Robin L.; Alam, Salma; Scurr, Michelle; Judson, Ian R.

    2011-01-01

    Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response. PMID:21647361

  19. Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose.

    Science.gov (United States)

    Mullins, Raymond James; James, Hayley; Platts-Mills, Thomas A E; Commins, Scott

    2012-05-01

    We have observed patients clinically allergic to red meat and meat-derived gelatin. We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test result, and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and galactose-α-1,3-galactose (α-Gal). Adult patients evaluated in the 1997-2011 period for suspected allergy/anaphylaxis to medication, insect venom, or food were skin tested with gelatin colloid. In vitro (ImmunoCAP) testing was undertaken where possible. Positive gelatin test results were observed in 40 of 1335 subjects: 30 of 40 patients with red meat allergy (12 also clinically allergic to gelatin), 2 of 2 patients with gelatin colloid-induced anaphylaxis, 4 of 172 patients with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02-0.4 g), and 4 of 368 patients with drug allergy. Test results were negative in all patients with venom allergy (n = 241), nonmeat food allergy (n = 222), and miscellaneous disorders (n = 290). ImmunoCAP results were positive to α-Gal in 20 of 24 patients with meat allergy and in 20 of 22 patients with positive gelatin skin test results. The results of gelatin skin testing and anti-α-Gal IgE measurements were strongly correlated (r = 0.46, P meat were sensitized to gelatin, and a subset was clinically allergic to both. The detection of α-Gal in gelatin and correlation between the results of α-Gal and gelatin testing raise the possibility that α-Gal IgE might be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, α-Gal, and gelatin (with or without clinical reactivity) remains uncertain. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. Safety and efficacy evaluation of gelatin-based nanoparticles associated with UV filters.

    Science.gov (United States)

    Oliveira, Camila Areias de; Dario, Michelli Ferrera; Sarruf, Fernanda Daud; Mariz, Inês Fátima Afonso; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

    2016-04-01

    The safety and efficacy assessment of nanomaterials is a major concern of industry and academia. These materials, due to their nanoscale size, can have chemical, physical, and biological properties that differ from those of their larger counterparts. The encapsulation of natural ingredients can provide marked improvements in sun protection efficacy. This strategy promotes solubility enhancement of flavonoids and yields an improved active ingredient with innovative physical, physicochemical and functional characteristics. Rutin, a flavonoid, has chemical and functional stability in topical vehicles exerting a synergistic effect in association with ultraviolet (UV) filters. However, the solubility of rutin is a limiting factor. Additionally, this bioactive compound does not have tendency to permeate across the stratum corneum. As an alternative to common synthetic based sunscreens, rutin-entrapped gelatin nanoparticles were designed. The present study investigated the pre-clinical safety of gelatin nanoparticles (GNPs) using an in vitro method and also assessed the clinical safety and efficacy of the association of GNPs with three commonly used chemical UV filters (ethylhexyl dimethyl PABA, ethylhexyl methoxycinnamate and methoxydibenzoylmethane). The non-irritant and adequate safety profile under sun-exposed skin conditions of the nanomaterials and the emulsions qualified the products for clinical efficacy assays. The in vivo results indicated that the GNPs increased the antioxidant protection of the emulsions developed. However, the presence of rutin in the nanosized material did not enhance performance on the SPF test. In conclusion, these findings characterized the nanomaterials as an innovative platform for multifunctional bioactive sunscreens. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Novel formulations of ballistic gelatin. 1. Rheological properties.

    Science.gov (United States)

    Zecheru, Teodora; Său, Ciprian; Lăzăroaie, Claudiu; Zaharia, Cătălin; Rotariu, Traian; Stănescu, Paul-Octavian

    2016-06-01

    Ballistic gelatin is the simulant of the human body during field tests in forensics and other related fields, due to its physical and mechanical similarities to human trunk and organs. Since the ballistic gelatin used in present has important issues to overcome, an alternative approach is the use of gelatin-polymer composites, where a key factor is the insertion of biocompatible materials, which replicate accurately the human tissues. In order to be able to obtain an improved material in terms of mechanical performances by an easy industrial-scale technology, before the verification of the ballistic parameters by shooting in agreement with military standards, one of the best and cheapest solutions is to perform a thorough check of their rheological properties, in standard conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Gelatin-based microspheres crosslinked with glutaraldehyde and rutin oriented to cosmetics

    Directory of Open Access Journals (Sweden)

    Fabiana Graziola

    Full Text Available ABSTRACT Glutaraldehyde (GTA has been extensively used as a gelatin crosslinking agent, however, new natural ones have been suggested as more biocompatible. Polyphenols are possible candidates and the flavonols, such as rutin (RUT, also exhibit potential synergism with sunscreens and antioxidant agents used in cosmetics. In this work, gelatin microspheres (M0 were obtained and crosslinked with GTA 10 mM (MG or RUT 10 mM (MR, dissolved in acetone:NaOH 0,01M (70:30 v/v. MG exhibited crosslinking extent of 54.4%. Gelatin, M0, MG and MR did not elicit any signs of skin damage, regarding the formation of erythema, the barrier function disruption and negative interference in the stratum corneum hydration. Oily dispersions containing M0, MG or MR, isolated or combined with benzophenone-3 or octyl methoxycinnamate, suggested that the microspheres, at a 5.0% w/w, had no additional chemical or physical photoprotective effect in vitro. Crosslinking with RUT had occurred, but in a lower degree than GTA. Microspheres had not improved sun protection parameters, although, non-treated gelatin interfered positively with the SPF for both UV filters. The in vivo studies demonstrated that these materials had very good skin compatibility.

  3. The correlation between gelatin macroscale differences and nanoparticle properties: providing insight into biopolymer variability.

    Science.gov (United States)

    Stevenson, André T; Jankus, Danny J; Tarshis, Max A; Whittington, Abby R

    2018-05-21

    From therapeutic delivery to sustainable packaging, manipulation of biopolymers into nanostructures imparts biocompatibility to numerous materials with minimal environmental pollution during processing. While biopolymers are appealing natural based materials, the lack of nanoparticle (NP) physicochemical consistency has decreased their nanoscale translation into actual products. Insights regarding the macroscale and nanoscale property variation of gelatin, one of the most common biopolymers already utilized in its bulk form, are presented. Novel correlations between macroscale and nanoscale properties were made by characterizing similar gelatin rigidities obtained from different manufacturers. Samples with significant differences in clarity, indicating sample purity, obtained the largest deviations in NP diameter. Furthermore, a statistically significant positive correlation between macroscale molecular weight dispersity and NP diameter was determined. New theoretical calculations proposing the limited number of gelatin chains that can aggregate and subsequently get crosslinked for NP formation were presented as one possible reason to substantiate the correlation analysis. NP charge and crosslinking extent were also related to diameter. Lower gelatin sample molecular weight dispersities produced statistically smaller average diameters (<75 nm), and higher average electrostatic charges (∼30 mV) and crosslinking extents (∼95%), which were independent of gelatin rigidity, conclusions not shown in the literature. This study demonstrates that the molecular weight composition of the starting material is one significant factor affecting gelatin nanoscale properties and must be characterized prior to NP preparation. Identifying gelatin macroscale and nanoscale correlations offers a route toward greater physicochemical property control and reproducibility of new NP formulations for translation to industry.

  4. Biofabrication of implants for articular joint repair : Cartilage regeneration in reinforced gelatin-based hydrogels

    NARCIS (Netherlands)

    Visser, J.

    2015-01-01

    Implants were biofabricated for the repair of chondral and osteochondral articular joint defects. The implants were based on gelatin methacrylamide (GelMA) hydrogels combined with printed fibers from polycaprolactone (PCL) for mechanical reinforcement. In Part I of the thesis, biological

  5. Gelatin Nano-coating for Inhibiting Surface Crystallization of Amorphous Drugs.

    Science.gov (United States)

    Teerakapibal, Rattavut; Gui, Yue; Yu, Lian

    2018-01-05

    Inhibit the fast surface crystallization of amorphous drugs with gelatin nano-coatings. The free surface of amorphous films of indomethacin or nifedipine was coated by a gelatin solution (type A or B) and dried. The coating's effect on surface crystallization was evaluated. Coating thickness was estimated from mass change after coating. For indomethacin (weak acid, pK a  = 4.5), a gelatin coating of either type deposited at pH 5 and 10 inhibited its fast surface crystal growth. The coating thickness was 20 ± 10 nm. A gelatin coating deposited at pH 3, however, provided no protective effect. These results suggest that an effective gelatin coating does not require that the drug and the polymer have opposite charges. The ineffective pH 3 coating might reflect the poor wetting of indomethacin's neutral, hydrophobic surface by the coating solution. For nifedipine (weak base, pK a  = 2.6), a gelatin coating of either type deposited at pH 5 inhibited its fast surface crystal growth. Gelatin nano-coatings can be conveniently applied to amorphous drugs from solution to inhibit fast surface crystallization. Unlike strong polyelectrolyte coatings, a protective gelatin coating does not require strict pairing of opposite charges. This could make gelatin coating a versatile, pharmaceutically acceptable coating for stabilizing amorphous drugs.

  6. The relationship between red meat allergy and sensitization to gelatin and galactose-alpha-1,3-galactose

    Science.gov (United States)

    Mullins, Raymond James; James, Hayley; Platts-Mills, Thomas A.E.; Commins, Scott

    2012-01-01

    Background We have observed patients clinically allergic to red meat and meat-derived gelatin. Objective We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and alpha-Gal. Methods Adult patients evaluated 1997-2011 for suspected allergy/anaphylaxis to medication, insect venom or food were skin tested with gelatin colloid. In vitro (ImmunoCap) testing was undertaken where possible. Results Positive gelatin tests were observed in 40/1335 individuals; 30/40 patients with red meat allergy (12 also clinically allergic to gelatin); 2/2 with gelatin colloid anaphylaxis; 4/172 with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02 to 0.4g); 4/368 with drug allergy. Testing was negative in all patients with venom allergy (n=241), non-meat food allergy (n=222), and miscellaneous disorders (n=290). ImmunoCap was positive to alpha-Gal in 20/24 meat allergics and in 20/22 with positive gelatin skin tests. The results of gelatin skin testing and anti-alpha-Gal IgE were strongly correlated (r=0.46; Pmeat were sensitized to gelatin and a subset was clinically allergic to both. The detection of alpha-Gal in gelatin and correlation between the results of alpha-Gal and gelatin testing raises the possibility that alpha-Gal IgE may be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, alpha-Gal and gelatin (with or without clinical reactivity) remains uncertain. PMID:22480538

  7. Factors affecting use of ballistics gelatin in laboratory studies of bacterial contamination in projectile wounds.

    Science.gov (United States)

    Evans, Jessica J; Bost, Aaron; Muci-Küchler, Karim H; DeVeaux, Linda C

    2018-05-25

    Ballistics gelatin is a common tissue surrogate used in bacterial contamination models for projectile wounds. Although these studies have demonstrated that bacteria are transferred from the surface of the gelatin to the wound track by a projectile, quantifiable results have been inconsistent and not repeatable in successive tests. In this study, five areas of a typical contamination model in which bacterial recovery or survival are affected were identified for optimization. The first was a contaminated "skin" surrogate, where the novel use of vacuum filtration of a bacterial culture and buffer onto filter paper was employed. The other possibly problematic areas of the bacterial distribution model included the determination of bacterial survival when the contamination model is dried, survival in solid and molten gelatin, and the effect of high-intensity lights used for recording high-speed video. Vacuum filtration of bacteria and buffer resulted in a consistent bacterial distribution and recovery. The use of phosphate buffer M9 (pH 7) aided in neutralizing the ballistics gelatin and improving bacterial survival in solid gelatin. Additionally, the use of high-intensity lights to record high-speed video and the use of a 42 ° C water bath to melt the gelatin were found to be bactericidal for gram-positive and gram-negative bacteria. Multiple areas of a typical contamination model in which bacterial survival may be impeded were identified, and methods were proposed to improve survival in each area. These methods may be used to optimize the results of bacterial contamination models for medical applications, such as understanding the progression of infection in penetrating wounds and to identify possible sources of contamination for forensic purposes.

  8. Graphene oxide decorated electrospun gelatin nanofibers: Fabrication, properties and applications

    Energy Technology Data Exchange (ETDEWEB)

    Jalaja, K. [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram, Kerala 695 547 (India); Sreehari, V.S. [Indian Institute of Science Education and Research Bhopal, Bhauri, Madhya Pradesh 462066 (India); Kumar, P.R. Anil [Tissue culture laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India); Nirmala, R. James, E-mail: nirmala@iist.ac.in [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram, Kerala 695 547 (India)

    2016-07-01

    Gelatin nanofiber fabricated by electrospinning process is found to mimic the complex structural and functional properties of natural extracellular matrix for tissue regeneration. In order to improve the physico-chemical and biological properties of the nanofibers, graphene oxide is incorporated in the gelatin to form graphene oxide decorated gelatin nanofibers. The current research effort is focussed on the fabrication and evaluation of physico-chemical and biological properties of graphene oxide-gelatin composite nanofibers. The presence of graphene oxide in the nanofibers was established by transmission electron microscopy (TEM). We report the effect of incorporation of graphene oxide on the mechanical, thermal and biological performance of the gelatin nanofibers. The tensile strength of gelatin nanofibers was increased from 8.29 ± 0.53 MPa to 21 ± 2.03 MPa after the incorporation of GO. In order to improve the water resistance of nanofibers, natural based cross-linking agent, namely, dextran aldehyde was employed. The cross-linked composite nanofibers showed further increase in the tensile strength up to 56.4 ± 2.03 MPa. Graphene oxide incorporated gelatin nanofibers are evaluated for bacterial activity against gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria and cyto compatibility using mouse fibroblast cells (L-929 cells). The results indicate that the graphene oxide incorporated gelatin nanofibers do not prevent bacterial growth, nevertheless support the L-929 cell adhesion and proliferation. - Highlights: • Graphene oxide nano reinforced gelatin nanofibers are fabricated by electrospinning. • Graphene oxide (0.5%) loading resulted in increased tensile strength. • GO/gelatin nanofibers are cross-linked with dextran aldehyde. • Composite nanofibers favoured adhesion of L-929 cells. • GO/gelatin mats do not prevent bacterial growth.

  9. Toll-like receptors as therapeutic targets in cystic fibrosis.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2008-12-01

    Background: Toll-like receptors (TLRs) are pattern recognition receptors that act as a first-line of defence in the innate immune response by recognising and responding to conserved molecular patterns in microbial factors and endogenous danger signals. Cystic fibrosis (CF)-affected airways represent a milieu potentially rich in TLR agonists and the chronic inflammatory phenotype evident in CF airway epithelial cells is probably due in large part to activation of TLRs. Objective\\/methods: To examine the prospects of developing novel therapies for CF by targeting TLRs. We outline the expression and function of TLRs and explore the therapeutic potential of naturally-occurring and synthetic TLR inhibitors for CF. Results\\/conclusion: Modulation of TLRs has therapeutic potential for the inflammatory lung manifestations of CF.

  10. Comparative biodistribution of 12 {sup 111}In-labelled gastrin/CCK2 receptor-targeting peptides

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Joosten, Lieke; Eek, Annemarie; Roosenburg, Susan; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Peitl, Petra Kolenc [University Medical Centre Ljubljana, Department of Nuclear Medicine, Ljubljana (Slovenia); Maina, Theodosia [National Center for Scientific Research Demokritos, Molecular Radiopharmacy, Institute of Radioisotopes-Radiodiagnostic Products, Athens (Greece); Maecke, Helmut [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Aloj, Luigi [Fondazione ' ' G. Pascale' ' , Department of Nuclear Medicine, Istituto Nazionale Tumouri, Naples (Italy); Guggenberg, Elisabeth von [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Sosabowski, Jane K. [Queen Mary, University of London, Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, London (United Kingdom); Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Reubi, Jean-Claude [University of Berne, Institute of Pathology, Berne (Switzerland)

    2011-08-15

    Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 {sup 111}In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with {sup 111}In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrin analogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides, a cyclized peptide and a divalent peptide were tested. Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may

  11. Pectin- and gelatin-based film: effect of gamma irradiation on the mechanical properties and biodegradation

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Cheorun; Kang, Hojin; Lee, Na Young; Kwon, Joong Ho; Byun, Myung Woo E-mail: mwbyun@kaeri.re.kr

    2005-04-01

    Agricultural by-products, pectin and gelatin, were used to prepare a biodegradable film. The film casting solution including the pectin and gelatin was irradiated at 0, 10, 20, and 30 kGy to investigate the irradiation effect on the mechanical properties of the film. The tensile strength of the 10 kGy-irradiated film was the highest among the treatments but the elongation at break, water vapour permeability, and swelling ratio were the lowest. Hunter color L*- and a*-values decreased but the b*-value increased as the irradiation dose increased. The total organic carbon content produced from the Paenibacillus polymyxa and Pseudomonas aeruginosa also showed that the film of 10 kGy-irradiated was lower than those of 0, 20, and 30 kGy-irradiated films. In conclusion, irradiation of the film casting solution at 10 kGy increased the mechanical properties of the pectin and gelatin based film. To manufacture the film by agricultural by-products, however, the irradiation dose of the film casting solution should be determined to achieve better mechanical properties.

  12. The under-appreciated promiscuity of the epidermal growth factor receptor family.

    Directory of Open Access Journals (Sweden)

    Sean P Kennedy

    2016-08-01

    Full Text Available Each member of the epidermal growth factor receptor (EGFR family plays a key role in normal development, homeostasis and a variety of pathophysiological conditions, most notably in cancer. According to the prevailing dogma, these four receptor tyrosine kinases (RTKs; EGFR, ERBB2, ERBB3 and ERBB4 function exclusively through the formation of homodimers and heterodimers within the EGFR family. These combinatorial receptor interactions are known to generate increased interactome diversity and therefore influence signalling output, subcellular localization and function of the heterodimer. This molecular plasticity is also thought to play a role in the development of resistance towards targeted cancer therapies aimed at these known oncogenes. Interestingly, many studies now challenge this dogma and suggest that the potential for EGFR family receptors to interact with more distantly related RTKs is much greater than currently appreciated. Here we discuss how the promiscuity of these oncogenic receptors may lead to the formation of many unexpected receptor pairings and the significant implications for the efficiency of many targeted cancer therapies.

  13. Effects of chicken by-product gelatin on the physicochemical properties and texture of chocolate spread.

    Science.gov (United States)

    Almeida, Poliana Fernandes; Lannes, Suzana Caetano da Silva

    2017-10-01

    Chocolate spread has a fat-based formulation and the application of gelatin as a fat replacement is related to the demand for healthier foods. The aim of this study was to evaluate the influence of gelatin as a by-product from the poultry industry in the fat replacement of chocolate spread. Vegetable fat was replaced (15, 25, 50, 75, and 100%) with gelatin (0.3, 0.5, 0.8, 1.0, and 1.2%) using a central composite rotatable design and the effects were evaluated by a response surface methodology. Formulations with a greater proportion of fat were lighter, of higher volume and lower density. As expected, water activity was intensified in low-fat formulations. The consistency was controlled mainly by the properties of the gelatin phase. The formulations with 50 and 75% fat replacement and 0.5-1.0% gelatin had satisfactory spreadability at 10C. All formulations were spreadable at 20C. Low-fat samples with low gelatin concentrations, at 30C, had very low consistency. Statistically, the properties were significantly influenced by the factors analyzed according to the mathematical models. Although several studies have been conducted on obtaining alternative gelatin sources for mammals, the extracted gelatin from poultry by-product is still little explored and the knowledge on the application in food products, particularly in complex systems such as emulsions, has not been well established. The development of a low-fat food should take into account the complexity of the system involved, such as the emulsion spreads. The incorporation of gelatin in aqueous solution is a challenging task because the physical properties and the rheological behavior can be strongly influenced. Given the nutritional and functional properties of the gelatin and chocolate and its wide acceptability among the consumers, the incorporation of these two ingredients in the development of a new product sets up a promising study. © 2016 Wiley Periodicals, Inc.

  14. Modified gum arabic cross-linked gelatin scaffold for biomedical applications

    International Nuclear Information System (INIS)

    Sarika, P.R.; Cinthya, Kuriakose; Jayakrishnan, A.; Anilkumar, P.R.; James, Nirmala Rachel

    2014-01-01

    The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture. - Highlights: • Gum arabic cross-linked gelatin scaffold was developed for tissue engineering. • Cross-linking was achieved by Schiff's base reaction. • The scaffold is non-cytotoxic and non adherent to fibroblast and hepatocytes. • The scaffolds are potential candidates for spheroid cell culture

  15. Modified gum arabic cross-linked gelatin scaffold for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Sarika, P.R. [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram, Kerala 695 547 (India); Cinthya, Kuriakose [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India); Jayakrishnan, A. [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600 036 (India); Anilkumar, P.R., E-mail: anilkumarpr@sctimst.ac.in [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India); James, Nirmala Rachel, E-mail: nirmala@iist.ac.in [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram, Kerala 695 547 (India)

    2014-10-01

    The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture. - Highlights: • Gum arabic cross-linked gelatin scaffold was developed for tissue engineering. • Cross-linking was achieved by Schiff's base reaction. • The scaffold is non-cytotoxic and non adherent to fibroblast and hepatocytes. • The scaffolds are potential candidates for spheroid cell culture.

  16. Halal authenticity of gelatin using species-specific PCR.

    Science.gov (United States)

    Shabani, Hessam; Mehdizadeh, Mehrangiz; Mousavi, Seyed Mohammad; Dezfouli, Ehsan Ansari; Solgi, Tara; Khodaverdi, Mahdi; Rabiei, Maryam; Rastegar, Hossein; Alebouyeh, Mahmoud

    2015-10-01

    Consumption of food products derived from porcine sources is strictly prohibited in Islam. Gelatin, mostly derived from bovine and porcine sources, has many applications in the food and pharmaceutical industries. To ensure that food products comply with halal regulations, development of valid and reliable analytical methods is very much required. In this study, a species-specific polymerase chain reaction (PCR) assay using conserved regions of mitochondrial DNA (cytochrome b gene) was performed to evaluate the halal authenticity of gelatin. After isolation of DNA from gelatin powders with known origin, conventional PCR using species-specific primers was carried out on the extracted DNA. The amplified expected PCR products of 212 and 271 bp were observed for porcine and bovine gelatin, respectively. The sensitivity of the method was tested on binary gelatin mixtures containing 0.1%, 1%, 10%, and 100% (w/w) of porcine gelatin within bovine gelatin and vice versa. Although most of the DNA is degraded due to the severe processing steps of gelatin production, the minimum level of 0.1% w/w of both porcine and bovine gelatin was detected. Moreover, eight food products labeled as containing bovine gelatin and eight capsule shells were subjected to PCR examination. The results showed that all samples contained bovine gelatin, and the absence of porcine gelatin was verified. This method of species authenticity is very useful to verify whether gelatin and gelatin-containing food products are derived from halal ingredients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Biodegradable microspheres for the sustained release of PDGF-receptor directed PPB-HSA targeted to the fibrotic kidney

    NARCIS (Netherlands)

    Teekamp, Naomi; van Dijk, Fransien; Beljaars, Eleonora; Hinrichs, Wouter; Poelstra, Klaas; Frijlink, H.W.; Olinga, Peter

    2016-01-01

    Platelet Derived Growth Factor (PDGF) plays a key role in the development of fibrotic processes in several tissues. Accordingly, the PDGFβ receptor is abundantly present in these fibrotic tissues. Specific targeting to this receptor is established for a series of compounds in different animal

  18. OPTIMIZATION OF MARSHMALLOW GELATIN FUNCTIONAL PURPOSE

    Directory of Open Access Journals (Sweden)

    G. O. Magomedov

    2015-01-01

    Full Text Available Marshmallow on gelatin or marshmallow items finely porous foam structure. This product is a popular and widely demanded confectionery products to the public, especially children and students. Urgent by the NE-a method for producing a mini-marshmallow functionality in terms of domestic production with natural-functional ingredient – gum-arabic «Instantgum», which is the source of natural-fiber, improving gastrointestinal function, lowering blood glucose levels that especially important in the use of products of diabetics. The inclusion of gum-arabic in the diet leads to a prebiotic effect, stimulating human immune system and improves the functioning intestines. Technology mini marshmallow gelatin with gum-arabic comprises the following manufacturing steps of: preparing a gelatin solution, an aqueous solution of gum-arabic, sugar syrup, invert syrup, whipped gelatinous mass density of 400-600 kg / m3, molding or pressing off mass fractionation followed by cooling and cutting, exposure and dusting starch and sugar mixture housings mini marshmallows. The optimization formulation mini marshmallows on gelatin with functional ingredients «Instantgum» based on gum-arabic method of multicriteria optimization of op-using desirability function Harrington. The greatest value generalized desirability function had a sample with 10% in-functional ingredient, since it belongs to the best set of parameters optimization. The developed product has high organoleptic, physical and chemical parameters, satisfactory form-retaining ability elastic chewing consistency and a functional purpose by NIJ-containing dietary fiber. Proposed can be recommended for the production on-time with continuous mechanized lines to develop Pastila products.

  19. Insulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater?

    OpenAIRE

    Yee, Douglas

    2012-01-01

    The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response...

  20. Pattern of hormone receptors and human epidermal growth factor ...

    African Journals Online (AJOL)

    Introduction: Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or ...

  1. Preparation of Rhodamine B Fluorescent Poly(methacrylic acid Coated Gelatin Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhenhai Gan

    2011-01-01

    Full Text Available Poly(methacrylic acid (PMAA-coated gelatin nanoparticles encapsulated with fluorescent dye rhodamine B were prepared by the coacervation method with the aim to retard the release of rhodamine B from the gelatin matrix. With sodium sulfate as coacervation reagent for gelatin, a kind of biopolymer with excellent biocompatibility, the formed gelatin nanoparticles were cross-linked by formaldehyde followed by the polymerization of methacrylic acid coating. The fluorescent poly(methacrylic acid coated gelatin (FPMAAG nanoparticles had a uniform spherical shape and a size distribution of 60±5 nm. Infrared spectral analysis confirmed the formation of PMAA coating on the gelatin nanoparticles. Based on UV-Vis spectra, the loading efficiency of rhodamine B for the FPMAAG nanoparticles was 0.26 μg per mg nanoparticles. The encapsulated rhodamine B could sustain for two weeks. Favorable fluorescence property and fluorescence imaging of cells confirmed that the FPMAAG nanoparticles have promising biochemical, bioanalytical, and biomedical applications.

  2. Personalized Radiation Oncology: Epidermal Growth Factor Receptor and Other Receptor Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Higgins, Geoff S; Krause, Mechthild; McKenna, W Gillies; Baumann, Michael

    Molecular biomarkers are currently evaluated in preclinical and clinical studies in order to establish predictors for treatment decisions in radiation oncology. The receptor tyrosine kinases (RTK) are described in the following text. Among them, the most data are available for the epidermal growth factor receptor (EGFR) that plays a major role for prognosis of patients after radiotherapy, but seems also to be involved in mechanisms of radioresistance, specifically in repopulation of tumour cells between radiotherapy fractions. Monoclonal antibodies against the EGFR improve locoregional tumour control and survival when applied during radiotherapy, however, the effects are heterogeneous and biomarkers for patient selection are warranted. Also other RTK´s such as c-Met and IGF-1R seem to play important roles in tumour radioresistance. Beside the potential to select patients for molecular targeting approaches combined with radiotherapy, studies are also needed to evluate radiotherapy adaptation approaches for selected patients, i.e. adaptation of radiation dose, or, more sophisticated, of target volumes.

  3. Drug delivery with microsecond laser pulses into gelatin

    Science.gov (United States)

    Shangguan, Hanqun; Casperson, Lee W.; Shearin, Alan; Gregory, Kenton W.; Prahl, Scott A.

    1996-07-01

    Photoacoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 mu m when the gelatin structure was not fractured. localized drug delivery, cavitation bubble, laser thrombolysis.

  4. The Nicotinic Acetylcholine Receptor as a Target for Antidepressant Drug Development

    Directory of Open Access Journals (Sweden)

    Noah S. Philip

    2012-01-01

    Full Text Available An important new area of antidepressant drug development involves targeting the nicotinic acetylcholine receptor (nAChR. This receptor, which is distributed widely in regions of the brain associated with depression, is also implicated in other important processes that are relevant to depression, such as stress and inflammation. The two classes of drugs that target nAChRs can be broadly divided into mecamylamine- and cytisine-based compounds. These drugs probably exert their effects via antagonism at α4β2 nAChRs, and strong preclinical data support the antidepressant efficacy of both classes when used in conjunction with other primary antidepressants (e.g., monoamine reuptake inhibitors. Although clinical data remain limited, preliminary results in this area constitute a compelling argument for further evaluation of the nAChR as a target for future antidepressant drug development.

  5. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

    2009-09-25

    The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

  6. Microencapsulation of Ginger Volatile Oil Based on Gelatin/Sodium Alginate Polyelectrolyte Complex.

    Science.gov (United States)

    Wang, Lixia; Yang, Shiwei; Cao, Jinli; Zhao, Shaohua; Wang, Wuwei

    2016-01-01

    The coacervation between gelatin and sodium alginate for ginger volatile oil (GVO) microencapsulation as functions of mass ratio, pH and concentration of wall material and core material load was evaluated. The microencapsulation was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), and thermal gravimetric analysis (TGA). SEM and FT-IR studies indicated the formation of polyelectrolyte complexation between gelatin and sodium alginate and successful encapsulation of GVO into the microcapsules. Thermal property study showed that the crosslinked microparticles exhibited higher thermal stability than the neat GVO, gelatin, and sodium alginate. The stability of microencapsulation of GVO in a simulated gastric and an intestinal situation in vitro was also studied. The stability results indicated that the release of GVO from microcapsules was much higher in simulated intestinal fluid, compared with that in simulated-gastric fluid.

  7. Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating β-tricalcium phosphate: a preclinical study in dogs.

    Science.gov (United States)

    Hoshi, S; Akizuki, T; Matsuura, T; Ikawa, T; Kinoshita, A; Oda, S; Tabata, Y; Matsui, M; Izumi, Y

    2016-02-01

    Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating β-tricalcium phosphate (β-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/β-TCP sponge on ridge augmentation in dogs. Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/β-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/β-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). The combined use of rhFGF-2 and gelatin/β-TCP sponge promotes ridge augmentation in canine saddle-type bone defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Dan PU

    2013-11-01

    Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

  9. Colloidal probe dynamics in gelatin solution during the sol-gel transition.

    Science.gov (United States)

    Hong, Wei; Xu, Guozhi; Ou, Xiaogang; Sun, Weixiang; Wang, Tao; Tong, Zhen

    2018-05-16

    The dynamics of the colloidal probes in a gelatin solution during the time-dependent sol-gel transition was investigated by multi-particle tracking. The relationship between the relaxation of the medium at the critical gel point and the mean square displacement of the probes was elucidated. Based on this understanding, the critical gel point of gelatin and the corresponding critical exponent n were unambiguously determined by the loss angle criterion and the time-cure superposition. The shift factors of the latter are further used to estimate the time/length-scale evolution of the gelatin during the sol-gel transition. The growth of the medium length scale crossed with the two measuring length scales successively at the pre-gel regime. Coinciding with the length-scale crossovers, the probability density function (PDF) of the probe displacements displayed two transient peaks of non-Gaussianity. In the post-gel regime, the third peak of Gaussianity suggested inhomogeneity in the gel network. The non-Gaussianity results from the bifurcation of diffusivity. The present work showed that the non-Gaussian dynamics of the probes are not the direct equivalence of that of the medium, but an effect of length-scale coupling.

  10. Incidence of thromboembolic events after use of gelatin-thrombin-based hemostatic matrix during intracranial tumor surgery.

    Science.gov (United States)

    Gazzeri, Roberto; Galarza, Marcelo; Conti, Carlo; De Bonis, Costanzo

    2018-01-01

    Association between the use of hemostatic agents made from collagen/gelatin mixed with thrombin and thromboembolic events in patients undergoing tumor resection has been suggested. This study evaluates the relationship between flowable hemostatic matrix and deep vein thrombosis in a large cohort of patients treated for brain tumor removal. The authors conducted a retrospective, multicenter, clinical review of all craniotomies for tumor removal performed between 2013 and 2014. Patients were classified in three groups: group I (flowable gelatin hemostatic matrix with thrombin), group II (gelatin hemostatic without thrombin), and group III (classical hemostatic). A total of 932 patients were selected: tumor pathology included 441 gliomas, 296 meningiomas, and 195 metastases. Thromboembolic events were identified in 4.7% of patients in which gelatin matrix with thrombin was applied, in 8.4% of patients with gelatin matrix without thrombin, and in 3.6% of cases with classical methods of hemostasis. Patients with venous thromboembolism had an increased proportion of high-grade gliomas (7.2%). Patients receiving a greater dose than 10 ml gelatin hemostatic had a higher rate of thromboembolic events. Intracranial hematoma requiring reintervention occurred in 19 cases: 4.5% of cases of group III, while reoperation was performed in 1.3 and 1.6% of patients in which gelatin matrix with or without thrombin was applied. Gelatin matrix hemostat is an efficacious tool for neurosurgeons in cases of difficult intraoperative bleeding during cranial tumor surgery. This study may help to identify those patients at high risk for developing thromboembolism and to treat them accordingly.

  11. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild

    2004-01-01

    Background and purpose: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. Materials and methods: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. Results: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux[reg]; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. Conclusions and outlook: Further investigations at all levels of the translational research chain exploring the mechanisms of

  12. Targeting Insulin-Like Growth Factor 1 Receptor Inhibits Pancreatic Cancer Growth and Metastasis

    Science.gov (United States)

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Arumugam, Arunkumar; Nandy, Sushmita; Boopalan, Thiyagarajan; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer. PMID:24809702

  13. Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

    International Nuclear Information System (INIS)

    McNeeley, Kathleen M; Annapragada, Ananth; Bellamkonda, Ravi V

    2007-01-01

    Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas

  14. Epidermal Growth Factor Receptor in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Oliveira-Cunha, Melissa; Newman, William G.; Siriwardena, Ajith K.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

  15. Genomewide Analysis of Aryl Hydrocarbon Receptor Binding Targets Reveals an Extensive Array of Gene Clusters that Control Morphogenetic and Developmental Programs

    Science.gov (United States)

    Sartor, Maureen A.; Schnekenburger, Michael; Marlowe, Jennifer L.; Reichard, John F.; Wang, Ying; Fan, Yunxia; Ma, Ci; Karyala, Saikumar; Halbleib, Danielle; Liu, Xiangdong; Medvedovic, Mario; Puga, Alvaro

    2009-01-01

    Background The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. The naive receptor is believed to reside in an inactive cytosolic complex that translocates to the nucleus and induces transcription of xenobiotic detoxification genes after activation by ligand. Objectives We conducted an integrative genomewide analysis of AHR gene targets in mouse hepatoma cells and determined whether AHR regulatory functions may take place in the absence of an exogenous ligand. Methods The network of AHR-binding targets in the mouse genome was mapped through a multipronged approach involving chromatin immunoprecipitation/chip and global gene expression signatures. The findings were integrated into a prior functional knowledge base from Gene Ontology, interaction networks, Kyoto Encyclopedia of Genes and Genomes pathways, sequence motif analysis, and literature molecular concepts. Results We found the naive receptor in unstimulated cells bound to an extensive array of gene clusters with functions in regulation of gene expression, differentiation, and pattern specification, connecting multiple morphogenetic and developmental programs. Activation by the ligand displaced the receptor from some of these targets toward sites in the promoters of xenobiotic metabolism genes. Conclusions The vertebrate AHR appears to possess unsuspected regulatory functions that may be potential targets of environmental injury. PMID:19654925

  16. Modification of gelatin functionality for culinary applications by using transglutaminase

    DEFF Research Database (Denmark)

    Calvarro, Julia; Pérez-Palacios, Trinidad; Ruiz Carrascal, Jorge

    2016-01-01

    TGase turned rapidly into liquid in less than 10 min at 80 °C. Hardness and chewiness of the gels were strongly enhanced by gelatin content, but very especially by TGase concentration. Gels tended to be less springy with increasing amounts of TGase. Modification of gelatin-based foams and gels...

  17. IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

    Science.gov (United States)

    Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

    2017-11-01

    The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. The androgen receptor as an emerging target in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kanda T

    2015-06-01

    Full Text Available Tatsuo Kanda, Osamu Yokosuka Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan Abstract: Hepatocellular carcinoma (HCC is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase–, v-akt murine thymoma viral oncogene homolog 1–, or signal-transducer and activator of transcription–signaling pathway, which has been implicated in the development of HCC. It has been reported that more than 200 RNA expression levels are altered by androgen treatment. In the liver, androgen-responsive genes are cytochrome P450s, transforming growth factor , vascular endothelial growth factor, and glucose-regulated protein 78 kDa, which are also associated with human hepatocarcinogenesis. Recent studies also revealed that AR plays a role in cell migration and metastasis. It is possible that cross-talk among AR-signaling, endoplasmic reticulum stress, and innate immune response is important for human hepatocarcinogenesis and HCC development. This review shows that AR could play a potential role in human HCC and represent one of the important target molecules for the treatment of HCC. Keywords: vascular endothelial growth factor, angiogenesis, glucose-regulated protein 78 kDa, hepatocarcinogenesis, molecular targets 

  19. Prostanoid receptor EP2 as a therapeutic target.

    Science.gov (United States)

    Ganesh, Thota

    2014-06-12

    Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and peripheral) injury models where COX-2 levels correlate with disease progression. Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2 inhibitors, which proved to be effective in reducing the pain and inflammation in patients with arthritis and menstrual cramps, but they have not provided any benefit to patients with chronic inflammatory neurodegenerative disease. Recently, two COX-2 drugs, rofecoxib and valdecoxib, were withdrawn from the United States market due to cardiovascular side effects. Thus, future anti-inflammatory therapy could be targeted through a specific prostanoid receptor downstream of COX-2. The PGE2 receptor EP2 is emerging as a pro-inflammatory target in a variety of CNS and peripheral diseases. Here we highlight the latest developments on the role of EP2 in diseases, mechanism of activation, and small molecule discovery targeted either to enhance or to block the function of this receptor.

  20. Biodegradable microspheres for the sustained release of PDGF-receptor directed pPB-HSA targeted to the fibrotic kidney

    NARCIS (Netherlands)

    Teekamp, Naomi; van Dijk, Fransien; Beljaars, Eleonora; Hinrichs, Wouter; Steendam, Rob; Zuidema, Johan; Poelstra, Klaas; Frijlink, H.W.; Olinga, Peter

    2016-01-01

    Platelet Derived Growth Factor (PDGF) plays a key role in the development of fibrotic processes in several tissues. Accordingly, the PDGF receptor is abundantly present in these fibrotic tissues. Specific targeting to this receptor is established for a series of compounds in different animal models,

  1. Assembly and activation of neurotrophic factor receptor complexes.

    Science.gov (United States)

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  2. Enzyme-Gelatin Electrochemical Biosensors: Scaling Down

    Directory of Open Access Journals (Sweden)

    Hendrik A. Heering

    2012-03-01

    Full Text Available In this article we investigate the possibility of scaling down enzyme-gelatin modified electrodes by spin coating the enzyme-gelatin layer. Special attention is given to the electrochemical behavior of the selected enzymes inside the gelatin matrix. A glassy carbon electrode was used as a substrate to immobilize, in the first instance, horse heart cytochrome c (HHC in a gelatin matrix. Both a drop dried and a spin coated layer was prepared. On scaling down, a transition from diffusion controlled reactions towards adsorption controlled reactions is observed. Compared to a drop dried electrode, a spin coated electrode showed a more stable electrochemical behavior. Next to HHC, we also incorporated catalase in a spin coated gelatin matrix immobilized on a glassy carbon electrode. By spincoating, highly uniform sub micrometer layers of biocompatible matrices can be constructed. A full electrochemical study and characterization of the modified surfaces has been carried out. It was clear that in the case of catalase, gluteraldehyde addition was needed to prevent leaking of the catalase from the gelatin matrix.

  3. Mechanical, physico-chemical, and antimicrobial properties of gelatin-based film incorporated with catechin-lysozyme

    Directory of Open Access Journals (Sweden)

    Rawdkuen Saroat

    2012-11-01

    Full Text Available Abstract Background Microbial activity is a primary cause of deterioration in many foods and is often responsible for reduced quality and safety. Food-borne illnesses associated with E. coli O157:H7, S. aureus, S. enteritidis and L. monocytogenes are a major public health concern throughout the world. A number of methods have been employed to control or prevent the growth of these microorganisms in food. Antimicrobial packaging is one of the most promising active packaging systems for effectively retarding the growth of food spoilage and pathogenic microorganisms. The aim of this study was to determine the mechanical, physico-chemical properties and inhibitory effects of the fish gelatin films against selected food spoilage microorganisms when incorporated with catechin-lysozyme. Results The effect of the catechin-lysozyme combination addition (CLC: 0, 0.125, 0.25, and 0.5%, w/v on fish gelatin film properties was monitored. At the level of 0.5% addition, the CLC showed the greatest elongation at break (EAB at 143.17% with 0.039 mm thickness, and the lowest water vapor permeability (WVP at 6.5 x 10−8 g·mm·h-1·cm-2·Pa-1, whereas the control showed high tensile strength (TS and the highest WVP. Regarding color attributes, the gelatin film without CLC addition gave the highest lightness (L* 91.95 but lowest in redness (a*-1.29 and yellowness (b* 2.25 values. The light transmission of the film did not significantly decrease and nor did film transparency (p>0.05 with increased CLC. Incorporating CLC could not affect the film microstructure. The solubility of the gelatin based film incorporated with CLC was not affected, especially at a high level of addition (p>0.05. Inhibitory activity of the fish gelatin film against E.coli, S.aureus, L. innocua and S. cerevisiae was concentration dependent. Conclusions These findings suggested that CLC incorporation can improve mechanical, physico-chemical, and antimicrobial properties of the resulting films

  4. Biosynthesis and Characterization of Nanocellulose-Gelatin Films

    Directory of Open Access Journals (Sweden)

    Muenduen Phisalaphong

    2013-02-01

    Full Text Available A nanocellulose-gelatin (bacterial cellulose gelatin (BCG film was developed by a supplement of gelatin, at a concentration of 1%–10% w/v, in a coconut-water medium under the static cultivation of Acetobacter xylinum. The two polymers exhibited a certain degree of miscibility. The BCG film displayed dense and uniform homogeneous structures. The Fourier transform infrared spectroscopy (FTIR results demonstrated interactions between the cellulose and gelatin. Incorporation of gelatin into a cellulose nanofiber network resulted in significantly improved optical transparency and water absorption capacity of the films. A significant drop in the mechanical strengths and a decrease in the porosity of the film were observed when the supplement of gelatin was more than 3% (w/v. The BCG films showed no cytotoxicity against Vero cells.

  5. Instrumental texture profile analysis of gelatin gel extracted from grouper skin and commercial (bovine and porcine) gelatin gels.

    Science.gov (United States)

    Rahman, Mohammad Shafiur; Al-Mahrouqi, Abdullah Issa

    2009-01-01

    Mechanical compression was used to study the gelling characteristics of gelatin gels. Texture profile analysis (TPA) showed that the hardness of fish and mammalian gelatin increased significantly as the concentrations of gels increased. TPA attributes of 10% fish skin gel showed significant differences from those obtained from 20% and 30% gels. In bovine and porcine cases, such generic trends were not observed. Mechanical characteristics of 10% gels of gelatin from fish skin, determined from one cycle compression, were significantly lower than other sources of gelatin gels, while bovine and porcine gels did not show any significant differences. In the case of TPA, hardness of bovine gelatin gel was highest at 41 N for 10% gel, followed by porcine (30 N) then fish skin (5 N) gelatin gels. The gels prepared from different sources did not show any generic trends when all other mechanical attributes were considered.

  6. Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

    LENUS (Irish Health Repository)

    2012-02-01

    In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

  7. Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-07-26

    In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

  8. Enzymatic degradation of polycaprolactone–gelatin blend

    International Nuclear Information System (INIS)

    Banerjee, Aditi; Chatterjee, Kaushik; Madras, Giridhar

    2015-01-01

    Blends of polycaprolactone (PCL), a synthetic polymer and gelatin, natural polymer offer a optimal combination of strength, water wettability and cytocompatibility for use as a resorbable biomaterial. The enzymatic degradation of PCL, gelatin and PCL–gelatin blended films was studied in the presence of lipase (Novozym 435, immobilized) and lysozyme. Novozym 435 degraded the PCL films whereas lysozyme degraded the gelatin. Though Novozym 435 and lysozyme individually could degrade PCL–gelatin blended films, the combination of these enzymes showed the highest degradation of these blended films. Moreover, the enzymatic degradation was much faster when fresh enzymes were added at regular intervals. The changes in physico-chemical properties of polymer films due to degradation were studied by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. These results have important implications for designing resorbable biomedical implants. (paper)

  9. A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

    Directory of Open Access Journals (Sweden)

    Han CY

    2013-04-01

    Full Text Available Cui-yan Han,1,2 Li-ling Yue,2 Ling-yu Tai,1 Li Zhou,2 Xue-yan Li,2 Gui-hua Xing,2 Xing-gang Yang,1 Ming-shuang Sun,1 Wei-san Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Qiqihar Medical University, Qiqihar, People’s Republic of China Abstract: The epidermal growth factor receptor (EGFR serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy. Keywords: EGFR, small peptide, tumor targeting, lung cancer, NLC

  10. Bilayer porous scaffold based on poly-({epsilon}-caprolactone) nanofibrous membrane and gelatin sponge for favoring cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Zhihua; Zhou Yang [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Chen Yiwang, E-mail: ywchen@ncu.edu.cn [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Institute of Polymers, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Nie Huarong, E-mail: niehr@iccas.ac.cn [Institute of Polymers, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wang Yang [First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Road, Nanchang 330006 (China); Li Fan; Zheng Yan [Institute of Polymers, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China)

    2011-12-15

    Electrospun poly-({epsilon}-caprolactone) (PCL) nanofibers has been widely used in the medical prosthesis. However, poor hydrophilicity and the lack of natural recognition sites for covalent cell-recognition signal molecules to promote cell attachment have limited its utility as tissue scaffolds. In this study, Bilayer porous scaffolds based on PCL electrospun membranes and gelatin (GE) sponges were fabricated through soft hydrolysis of PCL electrospun followed by grafting gelatin onto the fiber surface, through crosslinking and freeze drying treatment of additional gelatin coat and grafted gelatin surface. GE sponges were stably anchored on PCL membrane surface with the aid of grafted GE molecules. The morphologies of bilayer porous scaffolds were observed through SEM. The contact angle of the scaffolds was 0 Degree-Sign , the mechanical properties of scaffolds were measured by tensile test, Young's moduli of PCL scaffolds before and after hydrolysis are 66-77.3 MPa and 62.3-75.4 MPa, respectively. Thus, the bilayer porous scaffolds showed excellent hydrophilic surface and desirable mechanical strength due to the soft hydrolysis and GE coat. The cell culture results showed that the adipose derived mesenchymal stem cells did more favor to adhere and grow on the bilayer porous scaffolds than on PCL electrospun membranes. The better cell affinity of the final bilayer scaffolds not only attributed to the surface chemistry but also the introduction of bilayer porous structure.

  11. Bilayer porous scaffold based on poly-(ε-caprolactone) nanofibrous membrane and gelatin sponge for favoring cell proliferation

    International Nuclear Information System (INIS)

    Zhou Zhihua; Zhou Yang; Chen Yiwang; Nie Huarong; Wang Yang; Li Fan; Zheng Yan

    2011-01-01

    Electrospun poly-(ε-caprolactone) (PCL) nanofibers has been widely used in the medical prosthesis. However, poor hydrophilicity and the lack of natural recognition sites for covalent cell-recognition signal molecules to promote cell attachment have limited its utility as tissue scaffolds. In this study, Bilayer porous scaffolds based on PCL electrospun membranes and gelatin (GE) sponges were fabricated through soft hydrolysis of PCL electrospun followed by grafting gelatin onto the fiber surface, through crosslinking and freeze drying treatment of additional gelatin coat and grafted gelatin surface. GE sponges were stably anchored on PCL membrane surface with the aid of grafted GE molecules. The morphologies of bilayer porous scaffolds were observed through SEM. The contact angle of the scaffolds was 0°, the mechanical properties of scaffolds were measured by tensile test, Young's moduli of PCL scaffolds before and after hydrolysis are 66-77.3 MPa and 62.3-75.4 MPa, respectively. Thus, the bilayer porous scaffolds showed excellent hydrophilic surface and desirable mechanical strength due to the soft hydrolysis and GE coat. The cell culture results showed that the adipose derived mesenchymal stem cells did more favor to adhere and grow on the bilayer porous scaffolds than on PCL electrospun membranes. The better cell affinity of the final bilayer scaffolds not only attributed to the surface chemistry but also the introduction of bilayer porous structure.

  12. Antimicrobial and Barrier Properties of Bovine Gelatin Films Reinforced by Nano TiO2

    Directory of Open Access Journals (Sweden)

    R. Nassiri

    2013-11-01

    Full Text Available The effects of nano titanium dioxide incorporation were investigated on the water vaporpermeability, oxygen permeability, and antimicrobial properties of bovine gelatin films. The nano TiO2 (TiO2-N was homogenized by sonication and incorporated into bovine gelatin solutions at different concentrations(e.g. 1, 2, 3, and 5% w/w of dried gelatin. The permeability of the films to water vapor and oxygen wassignificantly decreased by incorporating of low concentration TiO2-N to gelatin solutions. TiO2-N gelatin filmsshowed an excellent antimicrobial activity against Staphylococcus aureus and Escherichia coli. Theseproperties suggest that TiO2-N has the potential as filler in gelatin-based films for using as an active packagingmaterials in pharmaceutical and food packaging industries.

  13. Anaphylaxis to gelatin-containing rectal suppositories.

    Science.gov (United States)

    Sakaguchi, M; Inouye, S

    2001-12-01

    Some children--though the number is few-have been sensitized with gelatin. To investigate the relationship between the presence of antigelatin IgE and anaphylaxis to gelatin-containing rectal suppository, we measured antigelatin IgE in the sera of the children with anaphylaxis. Ten children showed systemic allergic reactions, including anaphylaxis, to a chloral hydrate rectal suppository containing gelatin (231 mg/dose) that had been used as a sedative. These children's clinical histories and serum samples were submitted from physicians to the National Institute of Infectious Diseases during a 2-year period from 1996 to 1997. Of the 10 children, 5 showed apparent anaphylaxis, including hypotension and/or cyanosis, along with urticaria or wheezing; 2 showed both urticaria and wheezing without hypotension or cyanosis; the other 3 showed only urticaria. All of the children had antigelatin IgE (mean value +/- SD, 7.9 +/- 8.4 Ua/mL). As a control, samples from 250 randomly selected children had no antigelatin IgE. These findings suggest that the 10 children's systemic allergic reactions to this suppository were caused by the gelatin component. Gelatin-containing suppositories must be used with the same caution as gelatin-containing vaccines and other medications.

  14. Electrospun gelatin fiber mats containing a herbal—Centella asiatica—extract and release characteristic of asiaticoside

    Science.gov (United States)

    Sikareepaisan, Panprung; Suksamrarn, Apichart; Supaphol, Pitt

    2008-01-01

    Ultra-fine gelatin (type A, porcine skin, ~180 Bloom) fiber mats containing a methanolic crude extract of Centella asiatica (L.) Urban, a medicinal plant widely known for its traditional medical applications including its wound healing ability, were fabricated, for the first time, from the neat gelatin solution (22% w/v in 70 vol% acetic acid) containing the crude extract (mCA) in various amounts (i.e. 5-30 wt% based on the weight of gelatin powder) by electrospinning. Incorporation of mCA in the neat gelatin solution did not affect both the morphology and the size of the mCA-loaded gelatin fibers, as both of the neat and the mCA-loaded gelatin fibers were smooth and the average diameters of these fibers ranged between 226 and 232 nm. The cross-linked mCA-loaded e-spun gelatin fiber mat from the neat gelatin solution containing 30 wt% of mCA was further investigated for the release characteristic of asiaticoside, identified as the most active compound associated with the healing of wounds, in two different types of releasing medium, i.e. acetate buffer and the buffer containing 10 vol% of methanol, based on the thin-layer chromatography (TLC)-densitometry technique. Based on the unit weight of the actual amount of asiaticoside present in the specimens, the total amount of asiaticoside released from the fiber mat specimens was lower than that from the film counterparts while, based on the unit weight of the specimens, an opposite trend was observed.

  15. Electrospun gelatin fiber mats containing a herbal-Centella asiatica-extract and release characteristic of asiaticoside

    International Nuclear Information System (INIS)

    Sikareepaisan, Panprung; Suksamrarn, Apichart; Supaphol, Pitt

    2008-01-01

    Ultra-fine gelatin (type A, porcine skin, ∼180 Bloom) fiber mats containing a methanolic crude extract of Centella asiatica (L.) Urban, a medicinal plant widely known for its traditional medical applications including its wound healing ability, were fabricated, for the first time, from the neat gelatin solution (22% w/v in 70 vol% acetic acid) containing the crude extract (mCA) in various amounts (i.e. 5-30 wt% based on the weight of gelatin powder) by electrospinning. Incorporation of mCA in the neat gelatin solution did not affect both the morphology and the size of the mCA-loaded gelatin fibers, as both of the neat and the mCA-loaded gelatin fibers were smooth and the average diameters of these fibers ranged between 226 and 232 nm. The cross-linked mCA-loaded e-spun gelatin fiber mat from the neat gelatin solution containing 30 wt% of mCA was further investigated for the release characteristic of asiaticoside, identified as the most active compound associated with the healing of wounds, in two different types of releasing medium, i.e. acetate buffer and the buffer containing 10 vol% of methanol, based on the thin-layer chromatography (TLC)-densitometry technique. Based on the unit weight of the actual amount of asiaticoside present in the specimens, the total amount of asiaticoside released from the fiber mat specimens was lower than that from the film counterparts while, based on the unit weight of the specimens, an opposite trend was observed

  16. Characterization and cytological effects of a novel glycated gelatine substrate

    International Nuclear Information System (INIS)

    Boonkaew, Benjawan; Supaphol, Pitt; Tompkins, Kevin; Manokawinchoke, Jeeranan; Pavasant, Prasit

    2014-01-01

    Hyperglycemia in diabetes results in the glycation of long-lived proteins. Protein glycation leads to the formation of advanced glycation end products (AGEs), which are implicated in delayed wound healing and other diabetes-associated pathologies, one of which is periodontal disease. Research into the mechanisms by which glycated long-lived proteins such as collagen exert their effects can allow for the understanding of diabetic pathologies and the development of appropriate treatments. However, the high cost of purified protein can be a limitation for many laboratories around the world. The objective of this study was to develop a low-cost in vitro model of glycated gelatine as an alternative to the glycated collagen model. We investigated the glycation of gelatine type A, a denatured form of collagen, which is low-cost and abundantly available. In this study, gelatine was incubated for 7 days with ribose or methylglyoxal (MG). Cross-linking, autofluorescence and UV–Vis spectrophotometry assays were performed and indicated a dose-dependent linear increase in cross-linking and autofluorescence of gelatine by ribose and MG. MG produced more cross-linking compared to ribose at the same concentrations. The UV–Vis spectra of the glycated gelatines confirmed the presence of AGE fluorophores. Because diabetes is a risk factor for periodontal disease, the effect of the glycated substrates on the basic behaviour of human periodontal ligament (HPDL) cells was evaluated. Glycation dose dependently reduced HPDL attachment and cell spreading, indicating that the novel glycated gelatine substrate affects cell behaviour. These results show that gelatine glycated with ribose or MG can be used as low-cost in vitro models to study the effects of protein glycation on cell behaviour in diabetes and ageing. (paper)

  17. Activity ranking of synthetic analogs targeting vascular endothelial growth factor receptor 2 by an integrated cell membrane chromatography system.

    Science.gov (United States)

    Wang, Dongyao; Lv, Diya; Chen, Xiaofei; Liu, Yue; Ding, Xuan; Jia, Dan; Chen, Langdong; Zhu, Zhenyu; Cao, Yan; Chai, Yifeng

    2015-12-01

    Evaluating the biological activities of small molecules represents an important part of the drug discovery process. Cell membrane chromatography (CMC) is a well-developed biological chromatographic technique. In this study, we have developed combined SMMC-7721/CMC and HepG2/CMC with high-performance liquid chromatography and time-of-flight mass spectrometry to establish an integrated screening platform. These systems was subsequently validated and used for evaluating the activity of quinazoline compounds, which were designed and synthesized to target vascular endothelial growth factor receptor 2. The inhibitory activities of these compounds towards this receptor were also tested using a classical caliper mobility shift assay. The results revealed a significant correlation between these two methods (R(2) = 0.9565 or 0.9420) for evaluating the activities of these compounds. Compared with traditional methods of evaluating the activities analogous compounds, this integrated cell membrane chromatography screening system took less time and was more cost effective, indicating that it could be used as a practical method in drug discovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas

    NARCIS (Netherlands)

    Fleuren, Emmy D. G.; Versleijen-Jonkers, Yvonne M. H.; Heskamp, Sandra; Roeffen, Melissa H. S.; Bouwman, Wilbert H.; Molkenboer-Kuenen, Janneke D. M.; van Laarhoven, Hanneke W. M.; Oyen, Wim J. G.; Boerman, Otto C.; van der Graaf, Winette T. A.

    2013-01-01

    To investigate whether F(ab')2-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')2-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8)

  19. Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

    Science.gov (United States)

    Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

    2016-11-01

    Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

  20. Recombinant Gelatin Microspheres : Novel Formulations for Tissue Repair?

    NARCIS (Netherlands)

    Tuin, Annemarie; Kluijtmans, Sebastiaan G.; Bouwstra, Jan B.; Harmsen, Martin C.; Van Luyn, Marja J. A.

    Microspheres (MSs) can function as multifunctional scaffolds in different approaches of tissue repair (TR), as a filler, a slow-release depot for growth factors, or a delivery vehicle for cells. Natural cell adhesion-supporting extracellular matrix components like gelatin are good materials for

  1. Chimeric Monoclonal Antibody Cetuximab Targeting Epidermal Growth Factor-Receptor in Advanced Non-Melanoma Skin Cancer.

    Science.gov (United States)

    Wollina, Uwe; Tchernev, Georgi; Lotti, Torello

    2018-01-25

    Non-melanoma skin cancer (NMSC) is the most common malignancy in humans. Targeted therapy with monoclonal antibody cetuximab is an option in case of advanced tumor or metastasis. We present and update of the use of cetuximab in NMSC searching PUBMED 2011-2017. The monoclonal antibody cetuximab against epidermal growth factor receptor (EGFR) has been investigated for its use in NMSC during the years 2011 to 2017 by a PUBMED research using the following items: "Non-melanoma skin cancer AND cetuximab," "cutaneous squamous cell carcinoma AND cetuximab," and "basal cell carcinoma AND cetuximab", and "cetuximab AND skin toxicity". Available data were analyzed including case reports. Current evidence of cetuximab efficacy in NMSC was mainly obtained in cutaneous SCC and to a lesser extend in BCC. Response rates vary for neoadjuvant, adjuvant, mono- and combined therapy with cetuximab. Management of cutaneous toxicities is necessary. Guidelines are available. Cetuximab is an option for recurrent or advanced NMSC of the skin. It seems to be justified particularly in very high-risk tumors. There is a need for phase III trials.

  2. Molecular interactions in gelatin/chitosan composite films.

    Science.gov (United States)

    Qiao, Congde; Ma, Xianguang; Zhang, Jianlong; Yao, Jinshui

    2017-11-15

    Gelatin and chitosan were mixed at different mass ratios in solution forms, and the rheological properties of these film-forming solutions, upon cooling, were studied. The results indicate that the significant interactions between gelatin and chitosan promote the formation of multiple complexes, reflected by an increase in the storage modulus of gelatin solution. Furthermore, these molecular interactions hinder the formation of gelatin networks, consequently decreasing the storage modulus of polymer gels. Both hydrogen bonds and electrostatic interactions are formed between gelatin and chitosan, as evidenced by the shift of the amide-II bands of polymers. X-ray patterns of composite films indicate that the contents of triple helices decrease with increasing chitosan content. Only one glass transition temperature (T g ) was observed in composite films with different composition ratios, and it decreases gradually with an increase in chitosan proportion, indicating that gelatin and chitosan have good miscibility and form a wide range of blends. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. In vivo anticancer evaluation of the hyperthermic efficacy of anti-human epidermal growth factor receptor-targeted PEG-based nanocarrier containing magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Baldi G

    2014-06-01

    Full Text Available Giovanni Baldi,1 Costanza Ravagli,1 Filippo Mazzantini,1 George Loudos,2 Jaume Adan,3 Marc Masa,3 Dimitrios Psimadas,2 Eirini A Fragogeorgi,2 Erica Locatelli,4 Claudia Innocenti,5,6 Claudio Sangregorio,5,7 Mauro Comes Franchini4 1CERICOL, Sovigliana-Vinci, Italy; 2Technological Educational Institute of Athens, Athens, Greece; 3Leitat Technological Center, Barcelona, Spain; 4Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, 5Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, 6Dipartimento di Chimica U Schiff, Università di Firenze, Firenze, 7Centro Nazionale delle Ricerche (ICCOM – CNR, Firenze, Italy Abstract: Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer. Here we report the chemical synthesis and characterization of a poly(D,L-lactide-co-glycolide-b-poly(ethylene glycol-based nanocarrier containing iron oxide nanoparticles and human epithelial growth factor receptor on the outer shell. The nanocarrier was also radiolabeled with 99mTc and tested as a theranostic nanomedicine, ie, it was investigated for both its diagnostic ability in vivo and its therapeutic hyperthermic effects in a standard A431 human tumor cell line. Following radiolabeling with 99mTc, the biodistribution and therapeutic hyperthermic effects of the nanosystem were studied noninvasively in vivo in tumor-bearing mice. A substantial decrease in tumor size correlated with an increase in both nanoparticle concentration and local temperature was achieved, confirming the possibility of using this multifunctional nanosystem as a therapeutic tool for epidermoid carcinoma. Keywords: magnetic nanoparticles, polymeric nanocarriers, skin cancer, hyperthermia, single-photon emission computed tomography, imaging

  4. Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

    Science.gov (United States)

    Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

    2006-08-01

    Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

  5. Peptide drugs to target G protein-coupled receptors.

    Science.gov (United States)

    Bellmann-Sickert, Kathrin; Beck-Sickinger, Annette G

    2010-09-01

    Major indications for use of peptide-based therapeutics include endocrine functions (especially diabetes mellitus and obesity), infectious diseases, and cancer. Whereas some peptide pharmaceuticals are drugs, acting as agonists or antagonists to directly treat cancer, others (including peptide diagnostics and tumour-targeting pharmaceuticals) use peptides to 'shuttle' a chemotherapeutic agent or a tracer to the tumour and allow sensitive imaging or targeted therapy. Significant progress has been made in the last few years to overcome disadvantages in peptide design such as short half-life, fast proteolytic cleavage, and low oral bioavailability. These advances include peptide PEGylation, lipidisation or multimerisation; the introduction of peptidomimetic elements into the sequences; and innovative uptake strategies such as liposomal, capsule or subcutaneous formulations. This review focuses on peptides targeting G protein-coupled receptors that are promising drug candidates or that have recently entered the pharmaceutical market. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury.

    Science.gov (United States)

    Terabayashi, Takeshi; Ito, Yasuhiko; Mizuno, Masashi; Suzuki, Yasuhiro; Kinashi, Hiroshi; Sakata, Fumiko; Tomita, Takako; Iguchi, Daiki; Tawada, Mitsuhiro; Nishio, Ryosuke; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshifumi

    2015-09-01

    Appropriate fluid balance is important for good clinical outcomes and survival in patients on peritoneal dialysis. We recently reported that lymphangiogenesis associated with fibrosis developed in the peritoneal cavity via the transforming growth factor-β1-vascular endothelial growth factor-C (VEGF-C) pathway. We investigated whether VEGF receptor-3 (VEGFR-3), the receptor for VEGF-C and -D, might be a new target to improve net ultrafiltration by using adenovirus-expressing soluble VEGFR-3 (Adeno-sVEGFR-3) in rodent models of peritoneal injury induced by methylglyoxal (MGO). We demonstrated that lymphangiogenesis developed in these MGO models, especially in the diaphragm, indicating that lymphangiogenesis is a common feature in the peritoneal cavity with inflammation and fibrosis. In MGO models, VEGF-D was significantly increased in the diaphragm; however, VEGF-C was not significantly upregulated. Adeno-sVEGFR-3, which was detected on day 50 after administration via tail vein injections, successfully suppressed lymphangiogenesis in the diaphragm and parietal peritoneum in mouse MGO models without significant effects on fibrosis, inflammation, or neoangiogenesis. Drained volume in the peritoneal equilibration test using a 7.5% icodextrin peritoneal dialysis solution (the 7.5% icodextrin peritoneal equilibration test) was improved by Adeno-sVEGFR-3 on day 22 (Ptarget to improve net ultrafiltration by suppressing lymphatic absorption and that the 7.5% icodextrin peritoneal equilibration test is useful for estimation of lymphatic absorption.

  7. Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Paul S. Rennie

    2013-06-01

    Full Text Available Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the androgen/ligand binding site. Unfortunately, with the inevitable progression of the cancer to castration resistance, many of these drugs become ineffective. However, there are numerous other regulatory sites on this protein that have not been exploited therapeutically. The regulation of AR activity involves a cascade of complex interactions with numerous chaperones, co-factors and co-regulatory proteins, leading ultimately to direct binding of AR dimers to specific DNA androgen response elements within the promoter and enhancers of androgen-regulated genes. As part of the family of nuclear receptors, the AR is organized into modular structural and functional domains with specialized roles in facilitating their inter-molecular interactions. These regions of the AR present attractive, yet largely unexploited, drug target sites for reducing or eliminating androgen signaling in prostate cancers. The design of small molecule inhibitors targeting these specific AR domains is only now being realized and is the culmination of decades of work, including crystallographic and biochemistry approaches to map the shape and accessibility of the AR surfaces and cavities. Here, we review the structure of the AR protein and describe recent advancements in inhibiting its activity with small molecules specifically designed to target areas distinct from the receptor’s androgen binding site. It is anticipated that these new classes of anti-AR drugs will provide an additional

  8. Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

    Science.gov (United States)

    Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

    2013-12-23

    Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

  9. Radio-peptides targeting g-protein coupled receptors in cancer: from bench to bed

    International Nuclear Information System (INIS)

    Maecke, H.R.

    2015-01-01

    Full text of publication follows. In the development of targeted imaging and therapy agents the most important challenge and prerequisite is to identify and validate the molecular targets of any disease. The targets should be specific, relevant, easily accessible and highly expressed. In addition they should have no or at least very low expression in normal tissue. Among the many drug targets is the large family of G-protein coupled receptors (GPCRs). It is the most important family of marketed drugs and the basic accomplishments in the field were recognised by the award of the recent Nobel price in chemistry. GPCRs also play a role in cancer. Several of these receptors are massively over-expressed in different human tumors such as neuroendocrine tumors (over-expression of the somatostatin receptor family), prostate and breast tumors (bombesin receptor family), brain tumors (NK1 receptor) etc.. This allows to develop (nuclear, MRI, optical) probes for imaging and potentially targeted therapy (theragnostics). Natural ligands targeting GPCRs are often peptides. They need to be modified for metabolic stability, modified for labeling with radio-metals (conjugation of bifunctional chelators) or radio-halogens (prosthetic groups). Preserved biological integrity after modification and labeling needs to be assured, long retention times in the tumor is important, conferred by internalisation. Radio-metal labeling in particular needs to be reasonably fast and the radio metal complexes have to show high stability with regard to radio-metal release. These prerequisites will be discussed for somatostatin receptor based radio-peptides in particular. For a successful clinical application preclinical imaging and biodistribution in adequate animal models are mandatory. New tracers for positron emission tomography (PET) and single photon emission computed tomography (SPECT) will be presented for neuroendocrine tumors and prostate cancer. In particular radiolabeled antagonists will

  10. Wnt signalling via the epidermal growth factor receptor: a role in breast cancer?

    International Nuclear Information System (INIS)

    Musgrove, Elizabeth A

    2004-01-01

    Recent data have suggested the epidermal-growth-factor receptor (EGFR) as a point of convergence for several different classes of receptor. Civenni and colleagues have now demonstrated crosstalk between Wnt signalling and the EGFR, showing that in breast epithelial cells Wnts activate downstream targets of the EGFR, including cyclin D1. Given the role of members of these pathways in the aetiology of breast cancer and as markers of outcome and potential therapeutic targets in breast cancer, this observation has a number of potential implications important for both the basic biology of breast cancer and the clinical management of the disease

  11. Preservation and storage of prepared ballistic gelatine.

    Science.gov (United States)

    Mattijssen, E J A T; Alberink, I; Jacobs, B; van den Boogaard, Y

    2016-02-01

    The use of ballistic gelatine, generally accepted as a human muscle tissue simulant in wound ballistic studies, might be improved by adding a preservative (Methyl 4-hydroxybenzoate) which inhibits microbial growth. This study shows that replacing a part of the gelatine powder by the preservative does not significantly alter the penetration depth of projectiles. Storing prepared blocks of ballistic gelatine over time decreased the penetration depth of projectiles. Storage of prepared gelatine for 4 week already showed a significant effect on the penetration depth of projectiles. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Physico-functional and mechanical properties of chitosan and calcium salts incorporated fish gelatin scaffolds.

    Science.gov (United States)

    Jeevithan, E; Jeya Shakila, R; Varatharajakumar, A; Jeyasekaran, G; Sukumar, D

    2013-09-01

    Four types of fish gelatin scaffolds viz. gelatin (G), gelatin-chitosan (GC), gelatin-calcium acetate (GCA) and gelatin-chitosan-calcium acetate (GCCA) prepared were investigated for their functional properties, biomechanical strength, microstructural changes in relation to biodegradation. GC scaffold was superior with pH 3.15 and viscosity 9.40 cP. Chitosan and calcium acetate improved tensile strength (TS) and Young's modulus (YM), but lowered elongation at break (EAB). GCCA scaffold possessed moderate TS of 19.6 MPa, EAB of 4.76% and YM of 185 MPa. Foaming ability ratio of GC scaffold was high (3.41). GCA and GCCA scaffolds remained for 4 days before complete in vitro biodegradation. GC scaffold had larger cavities (180-300 μm) that were responsible for low swelling ratios and shrinkage factor. GCCA scaffold with moderate swelling rates, mechanical, functional properties and lowered biodegradation rate were found more suitable for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Use and application of gelatin as potential biodegradable packaging materials for food products.

    Science.gov (United States)

    Nur Hanani, Z A; Roos, Y H; Kerry, J P

    2014-11-01

    The manufacture and potential application of biodegradable films for food application has gained increased interest as alternatives to conventional food packaging polymers due to the sustainable nature associated with their availability, broad and abundant source range, compostability, environmentally-friendly image, compatibility with foodstuffs and food application, etc. Gelatin is one such material and is a unique and popularly used hydrocolloid by the food industry today due to its inherent characteristics, thereby potentially offering a wide range of further and unique industrial applications. Gelatin from different sources have different physical and chemical properties as they contain different amino acid contents which are responsible for the varying characteristics observed upon utilization in food systems and when being utilized more specifically, in the manufacture of films. Packaging films can be successfully produced from all gelatin sources and the behaviour and characteristics of gelatin-based films can be altered through the incorporation of other food ingredients to produce composite films possessing enhanced physical and mechanical properties. This review will present the current situation with respect to gelatin usage as a packaging source material and the challenges that remain in order to move the manufacture of gelatin-based films nearer to commercial reality. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Comparison of starch and gelatin hydrogels for non-toxic supercapacitor electrolytes

    Science.gov (United States)

    Railanmaa, Anna; Lehtimäki, Suvi; Lupo, Donald

    2017-06-01

    Starch and gelatin are two of the most abundantly available natural polymers. Their non-toxicity, low cost, and compatibility with aqueous solvents make them ideal for use in ubiquitous, environmentally friendly electronics systems. This work presents the results of conductivity measurements through impedance spectroscopy for gelatin- and starch-based aqueous gel electrolytes. The NaCl-based gels were physically cross-linked. The conductivity values were 84.6 mS/cm at 1.5 mol L-1 and 71.5 mS/cm at 2 mol L-1 for gelatin and starch, respectively. The mechanical properties of gelatin were found preferable to those of starch, although they deteriorated significantly when the salt concentration exceeded 2 mol L-1. The ability of the gels to successfully act as a supercapacitor electrolyte was demonstrated with printed electrodes on plastic substrate. The devices were characterized through cyclic voltammetry measurements. The results imply that these polymer gel electrolytes are very promising for replacing the traditional aqueous liquid electrolytes in supercapacitors in applications where, for example, user and environmental safety is essential.

  15. Immunocompatibility of gelatin-based hydrogels supporting ex vivo gene therapy

    Czech Academy of Sciences Publication Activity Database

    Šírová, Milada; Pakanová, Veronika; Rossmann, Pavel; Kovář, Lubomír; van Vlierberghe, S.; Dubruel, P.; Schacht, E. H.; Říhová, Blanka

    2009-01-01

    Roč. 39, - (2009), s. 545-545 ISSN 0014-2980. [European Congress of Immunology /2./. 13.09.2009-16.09.2009, Berlin] Institutional research plan: CEZ:AV0Z50200510 Keywords : gelatin B hydrogel * gene therapy Subject RIV: EC - Immunology

  16. Characterization of Fish Skin Gelatin Yellowfin Tuna

    Directory of Open Access Journals (Sweden)

    Mala Nurilmala

    2017-08-01

    Full Text Available Gelatin is one of the products which become a necessity for various industries, i.e. food and non-food industries. The application of gelatin has been increasing year by year in Indonesia. However, there is nogelatin industry in Indonesia so far. Thus, it is necessary to find an alternative source of gelatin, especially from fishery by products.Thus, the purpose of this research was to extract fish skin gelatin of yellowfin tuna with temperature treatments (55, 65 and 75oC. In addition, the properties of resulted gelatin were determined including yield, pH, gel strength, viscosity, functional groups, molecular weight profiles, and amino acid composition. The extraction at 75oC was chosen as the best result. The yield was 17%; pH 5.3; gel strength 1789.55 gf, viscosity 104.2 Cp, respectively. There was functional group amide A, I, II, dan III. SDS-PAGE showed β, α1 dan α2 bands for tuna skin gelatin. In addition, the main amino acids were glycine and proline.

  17. Fabrication and Physical Evaluation of Gelatin-Coated Carbonate Apatite Foam

    Directory of Open Access Journals (Sweden)

    Kanae Hara

    2016-08-01

    Full Text Available Carbonate apatite (CO3Ap foam has gained much attention in recent years because of its ability to rapidly replace bone. However, its mechanical strength is extremely low for clinical use. In this study, to understand the potential of gelatin-reinforced CO3Ap foam for bone replacement, CO3Ap foam was reinforced with gelatin and the resulting physical characteristics were evaluated. The mechanical strength increased significantly with the gelatin reinforcement. The compressive strength of gelatin-free CO3Ap foam was 74 kPa whereas that of the gelatin-reinforced CO3Ap foam, fabricated using 30 mass % gelatin solution, was approximately 3 MPa. Heat treatment for crosslinking gelatin had little effect on the mechanical strength of the foam. The gelatin-reinforced foam did not maintain its shape when immersed in a saline solution as this promoted swelling of the gelatin; however, in the same conditions, the heat-treated gelatin-reinforced foam proved to be stable. It is concluded, therefore, that heat treatment is the key to the fabrication of stable gelatin-reinforced CO3Ap foam.

  18. Influence of palm oil and glycerol on properties of fish skin gelatin-based films.

    Science.gov (United States)

    Nilsuwan, Krisana; Benjakul, Soottawat; Prodpran, Thummanoon

    2016-06-01

    Properties of fish skin gelatin film incorporated with palm oil at 50 and 75 % (w/w) as affected by glycerol at 0-30 % (w/w) were investigated. Increases in water vapour permeability and elongation at break along with decrease in tensile strength were noticed when levels of glycerol were increased (p fish skin gelatin films without drastic alteration of mechanical properties.

  19. Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.

    Science.gov (United States)

    Ming, Li; Zhipeng, Yuan; Fei, Yu; Feng, Rao; Jian, Weng; Baoguo, Jiang; Yongqiang, Wen; Peixun, Zhang

    2018-03-26

    Cartilage defect is common in clinical but notoriously difficult to treat for low regenerative and migratory capacity of chondrocytes. Biodegradable tissue engineering nano-scaffold with a lot of advantages has been the direction of material to repair cartilage defect in recent years. The objective of our study is to establish a biodegradable drug-loading synthetic polymer (PLA) and biopolymer (Gelatine) composite 3D nano-scaffold to support the treatment of cartilage defect. We designed a microfluidic chip-based drug-screening device to select the optimum concentration of resveratrol, which has strong protective capability for chondrocyte. Then biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds were fabricated and used to repair the cartilage defects. As a result, we successfully cultured primary chondrocytes and screened the appropriate concentrations of resveratrol by the microfluidic device. We also smoothly obtained superior biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds and compared the properties and therapeutic effects of cartilage defect in rats. In summary, our microfluidic device is a simple but efficient platform for drug screening and resveratrol-loading PLA/Gelatine 3D nano-scaffolds could greatly promote the cartilage formation. It would be possible for materials and medical researchers to explore individualized pharmacotherapy and drug-loading synthetic polymer and biopolymer composite tissue engineering scaffolds for the repair of cartilage defect in future.

  20. Targeting pro-apoptotic trail receptors sensitizes HeLa cervical cancer cells to irradiation-induced apoptosis

    NARCIS (Netherlands)

    Maduro, John H.; de Vries, Elisabeth G. E.; Meersma, Gert-Jan; Hougardy, Brigitte M. T.; van der Zee, Ate G. J.; De Jong, Steven

    2008-01-01

    Purpose: To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and their mechanism of action in a cervical cancer cell line. Methods and Materials: Recombinant human TRAIL

  1. Stavudine loaded gelatin liposomes for HIV therapy: Preparation, characterization and in vitro cytotoxic evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Debasis; Boxi, Ankita; Ashe, Sarbani; Thathapudi, Neethi Chandra; Nayak, Bismita, E-mail: nayakb@nitrkl.ac.in

    2017-04-01

    Despite continuous research and availability of 25 different active compounds for treating chronic HIV-1 infection, there is no absolute cure for this deadly disease. Primarily, the residual viremia remains hidden in latently infected reservoir sites and persistently release the viral RNA into the blood stream. The study proposes the dual utilization of the prepared stavudine-containing nanoformulations to control the residual viremia as well as target the reservoir sites. Gelatin nanoformulations containing very low dosage of stavudine were prepared through classical desolvation process and were later loaded in soya lecithin-liposomes. The nanoformulations were characterized through dynamic light scattering (DLS), Transmission electron microscopy (TEM), X-ray diffraction (XRD) and ATR-FTIR. All the formulations were in nano regime with high hemocompatibility and exhibited dose-dependent cytotoxicity towards Raw 264.7 macrophages. Among the various formulations, SG-3 (Stavudine-Gelatin Nanoformulation sample 3) and SG-LP-3 (Stavudine-Gelatin Nano-Liposome formulation sample 3) showed the best results in terms of yield, size, charge, encapsulation efficiency, hemocompatibility and % cell viability. For the first time, liposomal delivery of antiretroviral drugs using nanocarriers has been demonstrated using very low dosage (lower than the recommended WHO dosage) showing the prominent linear release of stavudine for up to 12 h which would reduce the circulatory viremia as well as reach the sanctuary reservoir sites due to their nanosize. This method of liposomal delivery of antiretroviral drugs in very low concentrations using nanocarriers could provide a novel therapeutic alternative to target HIV reservoir sites. - Highlights: • Stavudine entrapped gelatin nanocarriers prepared with two step desolvation process • Linear and release of stavudine from liposomal formulations up to 12 h • All the SG nanoparticles and SG-LP formulations showed negligible

  2. Stavudine loaded gelatin liposomes for HIV therapy: Preparation, characterization and in vitro cytotoxic evaluation

    International Nuclear Information System (INIS)

    Nayak, Debasis; Boxi, Ankita; Ashe, Sarbani; Thathapudi, Neethi Chandra; Nayak, Bismita

    2017-01-01

    Despite continuous research and availability of 25 different active compounds for treating chronic HIV-1 infection, there is no absolute cure for this deadly disease. Primarily, the residual viremia remains hidden in latently infected reservoir sites and persistently release the viral RNA into the blood stream. The study proposes the dual utilization of the prepared stavudine-containing nanoformulations to control the residual viremia as well as target the reservoir sites. Gelatin nanoformulations containing very low dosage of stavudine were prepared through classical desolvation process and were later loaded in soya lecithin-liposomes. The nanoformulations were characterized through dynamic light scattering (DLS), Transmission electron microscopy (TEM), X-ray diffraction (XRD) and ATR-FTIR. All the formulations were in nano regime with high hemocompatibility and exhibited dose-dependent cytotoxicity towards Raw 264.7 macrophages. Among the various formulations, SG-3 (Stavudine-Gelatin Nanoformulation sample 3) and SG-LP-3 (Stavudine-Gelatin Nano-Liposome formulation sample 3) showed the best results in terms of yield, size, charge, encapsulation efficiency, hemocompatibility and % cell viability. For the first time, liposomal delivery of antiretroviral drugs using nanocarriers has been demonstrated using very low dosage (lower than the recommended WHO dosage) showing the prominent linear release of stavudine for up to 12 h which would reduce the circulatory viremia as well as reach the sanctuary reservoir sites due to their nanosize. This method of liposomal delivery of antiretroviral drugs in very low concentrations using nanocarriers could provide a novel therapeutic alternative to target HIV reservoir sites. - Highlights: • Stavudine entrapped gelatin nanocarriers prepared with two step desolvation process • Linear and release of stavudine from liposomal formulations up to 12 h • All the SG nanoparticles and SG-LP formulations showed negligible

  3. Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer

    International Nuclear Information System (INIS)

    Berasain, Carmen; Latasa, María Ujue; Urtasun, Raquel; Goñi, Saioa; Elizalde, María; Garcia-Irigoyen, Oihane; Azcona, María; Prieto, Jesús; Ávila, Matías A.

    2011-01-01

    Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment

  4. The folate receptor as a molecular target for tumor-selective radionuclide delivery

    International Nuclear Information System (INIS)

    Ke, C.-Y.; Mathias, Carla J.; Green, Mark A.

    2003-01-01

    The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We review here some background on the folate receptor as tumor-associated molecular target for drug delivery, and briefly survey the literature on tumor-targeting with radiolabeled folate-chelate conjugates

  5. Traceability System Model for Quality Gelatin Raw Material of Cattle Hides

    Directory of Open Access Journals (Sweden)

    S Nur

    2010-09-01

    Full Text Available Several criteria must be accomplished within the provision of quality products in terms of the types of materials, the processing methods and effort to get it. Traceability system involves various parties that have different needs and goals in the process of supplying raw materials. Hence, there is a need for institutional systems engineering that can organize and manage the tracking process, the procurement of raw materials that guarantee the origin of gelatin raw materials, and facilitate the industry and customer to create a standardized quality of product. The purpose of the study formulates the institutional tracking models of gelatin raw material from cattle hide based on various criteria and assessment of the expert opinion. The methods used in this study were Interpretative structural modeling to formulate a representation of institutional tracking efficiently and analytical hierarchy process to determine the tracking strategy of industrial gelatin raw materials from cowhide. The results obtained from the study were some key elements of institutional tracking model for industrial gelatin raw materials from cowhide and the traceability strategies for industrial raw materials from cattle hide gelatin Indonesia. (Animal Production 12(3: 190-198 (2010 Key Words: traceability, institutional model, cattle hide, gelatin

  6. Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ming-Ju Chou

    2018-02-01

    Full Text Available Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.

  7. The insect ecdysone receptor is a good potential target for RNAi-based pest control.

    Science.gov (United States)

    Yu, Rong; Xu, Xinping; Liang, Yongkang; Tian, Honggang; Pan, Zhanqing; Jin, Shouheng; Wang, Na; Zhang, Wenqing

    2014-01-01

    RNA interference (RNAi) has great potential for use in insect pest control. However, some significant challenges must be overcome before RNAi-based pest control can become a reality. One challenge is the proper selection of a good target gene for RNAi. Here, we report that the insect ecdysone receptor (EcR) is a good potential target for RNAi-based pest control in the brown planthopper Nilaparvata lugens, a serious insect pest of rice plants. We demonstrated that the use of a 360 bp fragment (NlEcR-c) that is common between NlEcR-A and NlEcR-B for feeding RNAi experiments significantly decreased the relative mRNA expression levels of NlEcR compared with those in the dsGFP control. Feeding RNAi also resulted in a significant reduction in the number of offspring per pair of N. lugens. Consequently, a transgenic rice line expressing NlEcR dsRNA was constructed by Agrobacterium- mediated transformation. The results of qRT-PCR showed that the total copy number of the target gene in all transgenic rice lines was 2. Northern blot analysis showed that the small RNA of the hairpin dsNlEcR-c was successfully expressed in the transgenic rice lines. After newly hatched nymphs of N. lugens fed on the transgenic rice lines, effective RNAi was observed. The NlEcR expression levels in all lines examined were decreased significantly compared with the control. In all lines, the survival rate of the nymphs was nearly 90%, and the average number of offspring per pair in the treated groups was significantly less than that observed in the control, with a decrease of 44.18-66.27%. These findings support an RNAi-based pest control strategy and are also important for the management of rice insect pests.

  8. Dichromated gelatin and its importance for optical hologram recording

    Czech Academy of Sciences Publication Activity Database

    Šmíd, Petr; Hiklová, H.; Keprt, Jiří

    2004-01-01

    Roč. 54, č. 12 (2004), s. 1461-1472 ISSN 0011-4626 R&D Projects: GA MŠk(CZ) LN00A015 Keywords : dichromated gelatin * holography * volume program Subject RIV: BH - Optics, Masers, Lasers Impact factor: 0.292, year: 2004

  9. Sex, Receptors and Attachment: A Review of Individual Factors Influencing Response to Oxytocin

    Directory of Open Access Journals (Sweden)

    Kai S Macdonald

    2013-01-01

    Full Text Available As discussed in the larger review in this special issue (MacDonald and Feifel, intranasal oxytocin (IN OT is demonstrating a growing potential as a therapeutic agent in psychiatry. Importantly, research suggests that a variety of individual factors may influence a person’s response to OT. In this mini-review, I provides a review of three: (1 sex and hormonal status; (2 genetic variation in aspects of the OT system (i.e. OT receptors; and (3 attachment history. Each of these factors will be important to monitor as we strive to develop a richer understanding of OT's role in human development, brain-based disease, and the potential for individualized, OT-targeted treatments.

  10. Comparative evaluation of zinc oxide eugenol versus gelatin sponge soaked in plasma rich in growth factor in the treatment of dry socket: An initial study

    Science.gov (United States)

    Pal, U. S.; Singh, Balendra Pratap; Verma, Vikas

    2013-01-01

    Purpose: The aim of this study was to report a comparison between the zinc oxide eugenol dressing and plasma rich in growth factor (PRGF) with gelatin sponge in the treatment of dry socket. Materials and Methods: This study comprised of 45 patients of dry socket in the span of one year. The patients were randomly divided into three groups on the basis of treatments: Group A (PRGF with gelatin sponge), group B (zinc oxide eugenol group), and group C (irrigation with sterile saline only). The clinical progress was noted at 1st, 2nd, 3rd, 7th, and 15th day after the treatment. Results: Patient's healing was better in group A than in group B but symptomatic pain relief was faster in group B. Group C fared worst in both aspects. Conclusion: We conclude that PRGF with gelatin sponge might be a treatment of choice in the management of dry socket. PMID:23853450

  11. Comparative evaluation of zinc oxide eugenol versus gelatin sponge soaked in plasma rich in growth factor in the treatment of dry socket: An initial study

    Directory of Open Access Journals (Sweden)

    U S Pal

    2013-01-01

    Full Text Available Purpose: The aim of this study was to report a comparison between the zinc oxide eugenol dressing and plasma rich in growth factor (PRGF with gelatin sponge in the treatment of dry socket. Materials and Methods: This study comprised of 45 patients of dry socket in the span of one year. The patients were randomly divided into three groups on the basis of treatments: Group A (PRGF with gelatin sponge, group B (zinc oxide eugenol group, and group C (irrigation with sterile saline only. The clinical progress was noted at 1 st , 2 nd , 3 rd , 7 th , and 15 th day after the treatment. Results: Patient′s healing was better in group A than in group B but symptomatic pain relief was faster in group B. Group C fared worst in both aspects. Conclusion: We conclude that PRGF with gelatin sponge might be a treatment of choice in the management of dry socket.

  12. Orexin Receptor Targets for Anti-Relapse Medication Development in Drug Addiction

    Directory of Open Access Journals (Sweden)

    Ronald E. See

    2011-06-01

    Full Text Available Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches.

  13. Targeting the interleukin-11 receptor α in metastatic prostate cancer: A first-in-man study.

    Science.gov (United States)

    Pasqualini, Renata; Millikan, Randall E; Christianson, Dawn R; Cardó-Vila, Marina; Driessen, Wouter H P; Giordano, Ricardo J; Hajitou, Amin; Hoang, Anh G; Wen, Sijin; Barnhart, Kirstin F; Baze, Wallace B; Marcott, Valerie D; Hawke, David H; Do, Kim-Anh; Navone, Nora M; Efstathiou, Eleni; Troncoso, Patricia; Lobb, Roy R; Logothetis, Christopher J; Arap, Wadih

    2015-07-15

    Receptors in tumor blood vessels are attractive targets for ligand-directed drug discovery and development. The authors have worked systematically to map human endothelial receptors ("vascular zip codes") within tumors through direct peptide library selection in cancer patients. Previously, they selected a ligand-binding motif to the interleukin-11 receptor alpha (IL-11Rα) in the human vasculature. The authors generated a ligand-directed, peptidomimetic drug (bone metastasis-targeting peptidomimetic-11 [BMTP-11]) for IL-11Rα-based human tumor vascular targeting. Preclinical studies (efficacy/toxicity) included evaluating BMTP-11 in prostate cancer xenograft models, drug localization, targeted apoptotic effects, pharmacokinetic/pharmacodynamic analyses, and dose-range determination, including formal (good laboratory practice) toxicity across rodent and nonhuman primate species. The initial BMTP-11 clinical development also is reported based on a single-institution, open-label, first-in-class, first-in-man trial (National Clinical Trials number NCT00872157) in patients with metastatic, castrate-resistant prostate cancer. BMTP-11 was preclinically promising and, thus, was chosen for clinical development in patients. Limited numbers of patients who had castrate-resistant prostate cancer with osteoblastic bone metastases were enrolled into a phase 0 trial with biology-driven endpoints. The authors demonstrated biopsy-verified localization of BMTP-11 to tumors in the bone marrow and drug-induced apoptosis in all patients. Moreover, the maximum tolerated dose was identified on a weekly schedule (20-30 mg/m(2) ). Finally, a renal dose-limiting toxicity was determined, namely, dose-dependent, reversible nephrotoxicity with proteinuria and casts involving increased serum creatinine. These biologic endpoints establish BMTP-11 as a targeted drug candidate in metastatic, castrate-resistant prostate cancer. Within a larger discovery context, the current findings indicate that

  14. Gel-Based Gelatin Zymography to Examine Matrix Metalloproteinase Activity in Cell Culture.

    Science.gov (United States)

    Chhabra, Aastha; Rani, Vibha

    2018-01-01

    Gelatin zymography, first described by Heussen and Dowdle in the 1980s, is a widely used valuable tool in research and diagnostics. The technique identifies gelatinases by the degradation of their preferential substrate as well as by their molecular weight (kDa). We here describe detailed methodology for the detection of pro- and active- forms of both MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in cells using norepinephrine-stimulated H9c2 cardiomyoblasts as model. An easy to follow step-by-step protocol has been carefully written for reliable results. We also suggest an acceptable method for quantification of gelatin zymograms.

  15. Extraction and electrospinning of gelatin from fish skin.

    Science.gov (United States)

    Songchotikunpan, Panida; Tattiyakul, Jirarat; Supaphol, Pitt

    2008-04-01

    Ultra-fine gelatin fibers were successfully fabricated by electrospinning from the solutions of Nile tilapia (Oreochromis niloticus) skin-extracted gelatin in either acetic acid or formic acid aqueous solutions. The extracted gelatin contained 7.3% moisture, 89.4% protein, 0.3% lipid, and 0.4% ash contents (on the basis of wet weight), while the bloom gel strength, the shear viscosity, and the pH values were 328 g, 17.8 mPa s, and 5.0, respectively. Both the acid concentration and the concentration of the gelatin solutions strongly influenced the properties of the as-prepared solutions and the obtained gelatin fibers. At low acid concentrations (i.e., 15% (w/v) extracted gelatin solutions in 10 and 20% (v/v) acetic acid solvents or 10-60% (v/v) formic acid solvents), a combination between smooth and beaded fibers was observed. At low concentrations of the gelatin solutions in either 40% (v/v) acetic acid solvent or 80% (v/v) formic acid solvent (i.e., 5-11%, w/v), either discrete beads or beaded fibers were obtained, while, at higher concentrations (i.e., 14-29%, w/v), only smooth or a combination of smooth and beaded fibers were obtained. The average diameters of the obtained fibers, regardless of the types of the acid solvents used, ranged between 109 and 761 nm. Lastly, cross-linking of the obtained gelatin fiber mats with glutaraldehyde vapor caused slight shrinkage from their original dimension, and the cross-linked gelatin fiber mats became stiffer.

  16. Cavitation nucleation in gelatin: Experiment and mechanism.

    Science.gov (United States)

    Kang, Wonmo; Adnan, Ashfaq; O'Shaughnessy, Thomas; Bagchi, Amit

    2018-02-01

    results of the present work are (1) quantitative characterization of cavitation nucleation in gelatin samples as a function of gel concentration utilizing well-controlled mechanical impacts and (2) mechanistic understanding of complex coupling between cavitation and liquid-/solid-like material properties of gel. The new capabilities of testing soft gels, which can be tuned to mimic material properties of target organs, at high loading rate conditions and accurately predicting their cavitation behavior are an important step towards developing reliable cavitation criteria in the scope of their biomedical applications. Copyright © 2017 Acta Materialia Inc. All rights reserved.

  17. Getting a Handle on Neuropharmacology by Targeting Receptor-Associated Proteins.

    Science.gov (United States)

    Maher, Michael P; Matta, Jose A; Gu, Shenyan; Seierstad, Mark; Bredt, David S

    2017-12-06

    Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable. This emerging pharmacology of receptor-associated proteins provides a new approach for improving drug efficacy while mitigating side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Improved cellular infiltration into nanofibrous electrospun cross-linked gelatin scaffolds templated with micrometer-sized polyethylene glycol fibers

    International Nuclear Information System (INIS)

    Skotak, Maciej; Ragusa, Jorge; Gonzalez, Daniela; Subramanian, Anuradha

    2011-01-01

    Gelatin-based nanofibrous scaffolds with a mean fiber diameter of 300 nm were prepared with and without micrometer-sized polyethylene glycol (PEG) fibers that served as sacrificial templates. Upon fabrication of the scaffolds via electrospinning, the gelatin fibers were crosslinked with glutaraldehyde, and the PEG templates were removed using tert-butanol to yield nanofibrous scaffolds with pore diameters ranging from 10 to 100 μm, as estimated with mercury intrusion porosimetry. Non-templated gelatin-based nanofibrous matrices had an average pore size of 1 μm. Fibroblasts were seeded onto both types of the gelatin-based nanofibrous surfaces and cultured for 14 days. For comparative purposes, chitosan-based and polyurethane-based macroporous scaffolds with pore sizes of 100 and 170 μm, respectively, were also included. The number of cells as a function of the depth into the scaffold was judged and quantitatively assessed using nuclei staining. Cell penetration up to a depth of 250 and 90 μm was noted in gelatin scaffolds prepared with sacrificial templates and gelatin-only nanofibrous scaffolds. Noticeably, scaffold preparation protocol presented here allowed the structural integrity to be maintained even with high template content (95%) and can easily be extended toward other classes of electrospun polymer matrices for tissue engineering.

  19. An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters

    International Nuclear Information System (INIS)

    Babic, Steven; Schreiner, L John

    2006-01-01

    In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters

  20. Evaluation of acute tryptophan depletion and sham depletion with a gelatin-based collagen peptide protein mixture

    DEFF Research Database (Denmark)

    Stenbæk, Dea Siggaard; Einarsdottir, H S; Goregliad-Fjaellingsdal, T

    2016-01-01

    Acute Tryptophan Depletion (ATD) is a dietary method used to modulate central 5-HT to study the effects of temporarily reduced 5-HT synthesis. The aim of this study is to evaluate a novel method of ATD using a gelatin-based collagen peptide (CP) mixture. We administered CP-Trp or CP+Trp mixtures...

  1. Mineralization and Characterization of Composite Lyophilized Gelatin Sponges Intended for Early Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Isaac Rodriguez

    2014-01-01

    Full Text Available The application of freeze-dried gelatin sponges as alternative bone grafting substitutes has many advantages, including the ability to swell, high porosity, tailorable degradation, and versatility to incorporate multiple components such as growth factors and nanofillers. The purpose of this study was to mineralize (M and further characterize 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers (PHCE. Sponges were characterized for their swelling and in vitro mineralization potential, surface characteristics, protein release, mechanical properties, and MG-63 cell attachment and infiltration. All sponges swelled up to 50% of their original volume upon hydration. Scanning electron microscopy showed sparse mineral deposition for gelatin-M scaffolds while PHCE-M scaffolds exhibited more uniform mineral nucleation. Over 21 days, PHCE-M scaffolds cumulatively released significantly more (30% of its initial protein content than all other scaffolds. PHCE-M scaffolds reported lower modulus values (1.3–1.6 MPa when compared to gelatin control scaffolds (1.6–3.2 MPa. Increased cell attachment and infiltration was noticed on PHCE and PHCE-M scaffolds. The results of the study demonstrate the enhanced performance of PHCE and PHCE-M scaffolds to serve as bone healing scaffolds. Their potential to release incorporated factors, comparable composition/mechanical properties to tissues developed in the early stages of bone healing, and enhanced initial cellular response make them suitable for further studies evaluating more complex cellular interactions.

  2. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    International Nuclear Information System (INIS)

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

  3. Solubilization of bovine gelatin using power ultrasound: gelation without heating.

    Science.gov (United States)

    Farahnaky, Asgar; Zendeboodi, Fatemeh; Azizi, Rezvan; Mesbahi, Gholamreza; Majzoobi, Mahsa

    2017-04-01

    The aim of this study was to investigate the efficacy of power ultrasound without using any heating stage in solubilizeing gelatin dispersions, and to characterize the mechanical and microstructural properties of the resulting gels using texture analysis and scanning electron microscopy, respectively. Usually to prepare a gel from gelatin, a primary heating stage of at about 40C or above is required to solubilize gelatin macromolecules. In this study solubilizing gelatin dispersions using power ultrasound without any heating was successfully performed. For solubilising gelatin, an ultrasound equipment with a frequency of 20 kHz, amplitude of 100% and power range of 50-150 W was used. Aqueous gelatin dispersions (4% w/v) were subjected to ultrasound for different times (40-240 s) at a constant temperature of 13C. Applying ultrasound to gelatin dispersions caused increases in water absorption and water solubility of the hydrocolloid. The textural parameters of the resulting gelatin gels, increased with increasing time and power of ultrasound. Moreover, a generalized Maxwell model with three elements was used for calculating relaxation times of the gels. The microstructural observations by SEM showed that the structural cohesiveness of the gels increased by increasing ultrasonication time. Ultrasound-assisted solubilization of gelatin can have emerging implications for industrial uses in pharmaceuticals, food and non-food systems. Usually to prepare a gel from gelatin, a primary heating stage of at about 40C or above is required to solubilize gelatin macromolecules. Therefore, the use of gelatin as a hydrocolloid in food processings or pharmaceutical formulations which lack a heating step has been a technological and practical challenge. In this study solubilizing gelatin dispersions using power ultrasound without any heating was successfully performed. Ultrasound-assisted solubilisation of gelatin can have emerging implications for industrial uses in pharmaceuticals

  4. Preparation and characterization of hydroxyapatite/gelatin composite membranes for immunoisolation

    Science.gov (United States)

    Chen, Jyh-Ping; Chang, Feng-Nian

    2012-12-01

    Composite membranes are fabricated from hydroxyapatite (HAP) and gelatin for immunoisolation of cells. The films were fabricated by crosslinking 5 wt%, 10 wt%, and 20 wt% gelatin with 1 wt% glutaraldehyde (GA) in the presence of HAP. Fourier transform infrared spectroscopy analysis confirms imide bond formation between GA and gelatin, while the crystal structure of HAP powder remains unchanged from X-ray diffraction analysis. The degree of crosslinking depends on crosslinking time and gelatin concentration. For 5% and 10% gelatin, the degree of crosslinking levels off at 90% within 48 h. From scanning electron microscopy micrographs, the microstructure of the composite membrane depends on the amount of gelatin used in the crosslinking reaction. The mechanical strength of the composite membrane could be enhanced by increasing the gelatin concentration. BET analysis indicates that pore size of the micropores on the surface HAP/gelatin agglomerates decreases with increasing gelatin concentration. However, the macropore, through which diffusion of molecules occurs, is larger at higher gelatin concentrations. The permeability coefficients of different molecules through a HAP/gelatin composite membrane increase with increasing gelatin concentration and is inversely correlated with the molecular weight of the molecule. For immunoisolation of cells, the diffusion of large molecules stimulated by the immune system can be rejected by a chamber constructed from the HAP/gelatin membrane. Insulinoma cells were encapsulated in alginate-poly-L-lysine-alginate microcapsules and enclosed in a HAP/gelatin chamber. The chamber did not impair the viability and function of insulinoma cells and cells can secrete insulin in response to glucose concentration change. The chamber is therefore useful for the physiologically controlled secretion of insulin in response to the blood glucose level. Intraperitoneal transplantation of the chamber into streptozotocin-induced diabetic SD rats could

  5. Gelatin controversies in food, pharmaceuticals, and personal care products: Authentication methods, current status, and future challenges.

    Science.gov (United States)

    Ali, Eaqub; Sultana, Sharmin; Hamid, Sharifah Bee Abd; Hossain, Motalib; Yehya, Wageeh A; Kader, Abdul; Bhargava, Suresh K

    2018-06-13

    Gelatin is a highly purified animal protein of pig, cow, and fish origins and is extensively used in food, pharmaceuticals, and personal care products. However, the acceptability of gelatin products greatly depends on the animal sources of the gelatin. Porcine and bovine gelatins have attractive features but limited acceptance because of religious prohibitions and potential zoonotic threats, whereas fish gelatin is welcomed in all religions and cultures. Thus, source authentication is a must for gelatin products but it is greatly challenging due to the breakdown of both protein and DNA biomarkers in processed gelatins. Therefore, several methods have been proposed for gelatin identification, but a comprehensive and systematic document that includes all of the techniques does not exist. This up-to-date review addresses this research gap and presents, in an accessible format, the major gelatin source authentication techniques, which are primarily nucleic acid and protein based. Instead of presenting these methods in paragraph form which needs much attention in reading, the major methods are schematically depicted, and their comparative features are tabulated. Future technologies are forecasted, and challenges are outlined. Overall, this review paper has the merit to serve as a reference guide for the production and application of gelatin in academia and industry and will act as a platform for the development of improved methods for gelatin authentication.

  6. Blockade of epidermal growth factor receptors chemosensitizes breast cancer cells through up-regulation of Bnip3L

    NARCIS (Netherlands)

    Real, PJ; Benito, A; Cuevas, J; Berciano, MT; de Juan, A; Coffer, P; Gomez-Roman, J; Lafarga, M; Lopez-Vega, JM; Fernandez-Luna, JL

    2005-01-01

    Epidermal growth factor receptor-1 (EGFR) and EGFR-2 (HER2) have become major targets for cancer treatment. Blocking antibodies and small-molecule inhibitors are being used to silence the activity of these receptors in different tumors with varying efficacy. Thus, a better knowledge on the signaling

  7. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    May, Felicity EB, E-mail: F.E.B.May@ncl.ac.uk [Northern Institute for Cancer Research and Department of Pathology, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne (United Kingdom)

    2014-05-23

    The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel

  8. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

    International Nuclear Information System (INIS)

    May, Felicity EB

    2014-01-01

    The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel

  9. Multifunctional nano-hydroxyapatite and alginate/gelatin based sticky gel composites for potential bone regeneration

    International Nuclear Information System (INIS)

    Cai, Yurong; Yu, Juhong; Kundu, Subhas C.; Yao, Juming

    2016-01-01

    To improve the fixations of the implant and implant-bone integration after joint arthroplasty from locally preventing inflammation and promoting the bone regeneration, we design a multifunctional biomaterial consisting of recombinant human bone morphogenetic protein 2 (rhBMP-2) and antibiotic loaded nano-hydroxyapatite with an alginate/gelatin sticky gel. We investigate its role for the prevention of the inflammation and possibility of inducing a new bone growth along with its adhesive ability. The stickiness exists in the composite, which may help to fix itself on the bone fracture surface. The composite sustains the antibacterial effect and promotes the proliferation and differentiation of MG63 cells in vitro. In vivo experimentation also shows that the composite gel has a role for the reduction of inflammation. It enhances the formation of new bone and blood vessels compared to both the sole rhBMP-2 and non-rhBMP-2/antibiotic loaded composite gels. The multifunctional composite provides a promising material for the prosthetic and bone tissue regeneration. - Highlights: • Multifunctional nanohydroxyapatite composite is fabricated. • The composite consists of nHAP, growth factor, antibiotic and alginate/gelatin gel. • The composite shows antibacterial effect and good cytocompatibility. • No adverse effect to the cells tested in vitro and in vivo.

  10. Multifunctional nano-hydroxyapatite and alginate/gelatin based sticky gel composites for potential bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yurong; Yu, Juhong [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Kundu, Subhas C. [Department of Biotechnology, Indian Institute of Technology (IIT) Kharagpur, West Bengal 721302 (India); Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714 (Korea, Republic of); Yao, Juming, E-mail: yaoj@zstu.edu.cn [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China)

    2016-09-15

    To improve the fixations of the implant and implant-bone integration after joint arthroplasty from locally preventing inflammation and promoting the bone regeneration, we design a multifunctional biomaterial consisting of recombinant human bone morphogenetic protein 2 (rhBMP-2) and antibiotic loaded nano-hydroxyapatite with an alginate/gelatin sticky gel. We investigate its role for the prevention of the inflammation and possibility of inducing a new bone growth along with its adhesive ability. The stickiness exists in the composite, which may help to fix itself on the bone fracture surface. The composite sustains the antibacterial effect and promotes the proliferation and differentiation of MG63 cells in vitro. In vivo experimentation also shows that the composite gel has a role for the reduction of inflammation. It enhances the formation of new bone and blood vessels compared to both the sole rhBMP-2 and non-rhBMP-2/antibiotic loaded composite gels. The multifunctional composite provides a promising material for the prosthetic and bone tissue regeneration. - Highlights: • Multifunctional nanohydroxyapatite composite is fabricated. • The composite consists of nHAP, growth factor, antibiotic and alginate/gelatin gel. • The composite shows antibacterial effect and good cytocompatibility. • No adverse effect to the cells tested in vitro and in vivo.

  11. Impact of particle size, thermal processing, fat inclusion, and moisture addition on starch gelatinization of broiler feeds

    Directory of Open Access Journals (Sweden)

    K Muramatsu

    2014-12-01

    Full Text Available The present study evaluated the effect of feed particle size, thermal processing different levels of fat inclusion and of moisture addition on the amount of gelatinized starch in a corn-soybean broiler diet. The different processing factors were combined in a 2 x 4 x 4 x 2 factorial arrangement in a three randomized block design consisting of three production series: two particle sizes (coarse: 1041 microns and medium: 743 microns, four fat inclusion levels at the mixer (15, 25, 35, and 45 g/kg of feed, four moisture addition levels in the conditioner (0, 7, 14, and 21g/kg of feed, and two thermal processing treatments (conditioning-pelleting or conditioning-expanding-pelleting which resulted in 64 different processed feeds. For the determination of the amount of gelatinized starch one feed sample was collected per treatment in each of three production series, totaling three replicates/treatment. Data were transformed using a variation of Box-Cox transformation in order to fit normal distribution (p>0.05. Adding moisture up to 21g/kg of feed in the conditioner linearly increased the amount of gelatinized starch (p<0.05. The conditioner-expander-pelleting treatment of the diets (at 110°C increased (p<0.05 the degree of starch gelatinization from 32.0 to 35.3 % compared with the conditioner-pelleting treatment (at 80-82°C. The gelatinized starch content increased from 30.2 to 37.2% in the feed (p<0.05 as the particle size increased from medium to coarse. Fat inclusion had a quadratic effect (p<0.05 on starch gelatinization. The degree of starch gelatinization was significantly reduced with fat inclusion levels higher than 35 g/kg of diet. The factors evaluated in this study resulted in interactions and significant effects on degree of starch gelatinization.

  12. Effects of Gelatin-Based Edible Films Enriched with Laurel Essential Oil on the Quality of Rainbow Trout (Oncorhynchus mykiss Fillets During Refrigerated Storage

    Directory of Open Access Journals (Sweden)

    Tuba Baygar

    2014-01-01

    Full Text Available The effects of gelatin films enriched with laurel leaf essential oil on the quality of rainbow trout (Oncorhynchus mykiss during refrigerated storage at (4±1 °C were examined over a period of 26 days. Fish fillets were wrapped with 8 % gelatin films containing 0, 0.1 and 1 % (by volume per mass of laurel essential oil and vacuum packaged. Sensory (raw and cooked fish, microbiological (total viable counts, psychrotrophic bacteria counts, Enterobacteriaceae and lactic acid bacteria and chemical (proximate composition, pH, total volatile base nitrogen (TVB-N, thiobarbituric acid (TBA, free fatty acid (FFA and peroxide value (PV analysis, and colour measurement were carried out during the storage period and shelf-life was determined periodically. The obtained results showed that the gelatin film enriched with laurel essential oil was suitable for the preservation of rainbow trout fillet and the ability of laurel essential oil to preserve the film depended on its ratio. Combined effects of gelatin film and laurel essential oil (1 % by volume per mass was efficient in maintaining the quality characteristics at an acceptable level up to 22 days of storage, while the control and gelatin film without the essential oil reached an unacceptable level at 15 and 20 days, respectively.

  13. Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

    Directory of Open Access Journals (Sweden)

    Ma P

    2015-03-01

    Full Text Available Pengkai Ma,1 Xuemei Zhang,1 Ling Ni,2 Jinming Li,2 Fengpu Zhang,1 Zheng Wang,1 Shengnan Lian,1 Kaoxiang Sun1 1School of Pharmacy, Yantai University, Yantai, Shandong Province, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, People’s Republic of China Background: Antibody-dendrimer conjugates have the potential to improve the targeting and release of chemotherapeutic drugs at the tumor site while reducing adverse side effects caused by drug accumulation in healthy tissues. In this study, trastuzumab (TMAB, which binds to human epidermal growth factor receptor 2 (HER2, was used as a targeting agent in a TMAB-polyamidoamine (PAMAM conjugate carrying paclitaxel (PTX specifically to cells overexpressing HER2. Methods: TMAB was covalently linked to a PAMAM dendrimer via bifunctional polyethylene glycol (PEG. PTX was conjugated to PAMAM using succinic anhydride as a cross-linker, yielding TMAB-PEG-PAMAM-PTX. Dynamic light scattering and transmission electron microscopy were used to characterize the conjugates. The cellular uptake and in vivo biodistribution were studied by fluorescence microscopy, flow cytometry, and Carestream In Vivo FX, respectively. Results: Nuclear magnetic resonance spectroscopy demonstrated that PEG, PTX, fluorescein isothiocyanate, and cyanine7 were conjugated to PAMAM. Ultraviolet-visible spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that TMAB was conjugated to PEG-PAMAM. Dynamic light scattering and transmission electron microscopy measurements revealed that the different conjugates ranged in size between 10 and 35 nm and had a spherical shape. In vitro cellular uptake demonstrated that the TMAB-conjugated PAMAM was taken up by HER2-overexpressing BT474 cells more efficiently than MCF-7 cells that expressed lower levels of HER2. Co-localization experiments indicated that TMAB-conjugated PAMAM was

  14. A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.

    Science.gov (United States)

    Tiefenbach, Jens; Moll, Pamela R; Nelson, Meryl R; Hu, Chun; Baev, Lilia; Kislinger, Thomas; Krause, Henry M

    2010-03-22

    Nuclear receptors (NRs) belong to a superfamily of transcription factors that regulate numerous homeostatic, metabolic and reproductive processes. Taken together with their modulation by small lipophilic molecules, they also represent an important and successful class of drug targets. Although many NRs have been targeted successfully, the majority have not, and one third are still orphans. Here we report the development of an in vivo GFP-based reporter system suitable for monitoring NR activities in all cells and tissues using live zebrafish (Danio rerio). The human NR fusion proteins used also contain a new affinity tag cassette allowing the purification of receptors with bound molecules from responsive tissues. We show that these constructs 1) respond as expected to endogenous zebrafish hormones and cofactors, 2) facilitate efficient receptor and cofactor purification, 3) respond robustly to NR hormones and drugs and 4) yield readily quantifiable signals. Transgenic lines representing the majority of human NRs have been established and are available for the investigation of tissue- and isoform-specific ligands and cofactors.

  15. A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.

    Directory of Open Access Journals (Sweden)

    Jens Tiefenbach

    2010-03-01

    Full Text Available Nuclear receptors (NRs belong to a superfamily of transcription factors that regulate numerous homeostatic, metabolic and reproductive processes. Taken together with their modulation by small lipophilic molecules, they also represent an important and successful class of drug targets. Although many NRs have been targeted successfully, the majority have not, and one third are still orphans. Here we report the development of an in vivo GFP-based reporter system suitable for monitoring NR activities in all cells and tissues using live zebrafish (Danio rerio. The human NR fusion proteins used also contain a new affinity tag cassette allowing the purification of receptors with bound molecules from responsive tissues. We show that these constructs 1 respond as expected to endogenous zebrafish hormones and cofactors, 2 facilitate efficient receptor and cofactor purification, 3 respond robustly to NR hormones and drugs and 4 yield readily quantifiable signals. Transgenic lines representing the majority of human NRs have been established and are available for the investigation of tissue- and isoform-specific ligands and cofactors.

  16. Preparation and characterization of hydroxyapatite/gelatin composite membranes for immunoisolation

    International Nuclear Information System (INIS)

    Chen, Jyh-Ping; Chang, Feng-Nian

    2012-01-01

    Highlights: ► Cross-linking gelatin in the presence of hydroxyapatite forms composite membranes. ► The membrane was used for immunoisolation and encapsulation of cells. ► Encapsulated islet cells secrete insulin in response to glucose concentrations. ► The membrane is a good candidate for bioartificial pancreas development. - Abstract: Composite membranes are fabricated from hydroxyapatite (HAP) and gelatin for immunoisolation of cells. The films were fabricated by crosslinking 5 wt%, 10 wt%, and 20 wt% gelatin with 1 wt% glutaraldehyde (GA) in the presence of HAP. Fourier transform infrared spectroscopy analysis confirms imide bond formation between GA and gelatin, while the crystal structure of HAP powder remains unchanged from X-ray diffraction analysis. The degree of crosslinking depends on crosslinking time and gelatin concentration. For 5% and 10% gelatin, the degree of crosslinking levels off at 90% within 48 h. From scanning electron microscopy micrographs, the microstructure of the composite membrane depends on the amount of gelatin used in the crosslinking reaction. The mechanical strength of the composite membrane could be enhanced by increasing the gelatin concentration. BET analysis indicates that pore size of the micropores on the surface HAP/gelatin agglomerates decreases with increasing gelatin concentration. However, the macropore, through which diffusion of molecules occurs, is larger at higher gelatin concentrations. The permeability coefficients of different molecules through a HAP/gelatin composite membrane increase with increasing gelatin concentration and is inversely correlated with the molecular weight of the molecule. For immunoisolation of cells, the diffusion of large molecules stimulated by the immune system can be rejected by a chamber constructed from the HAP/gelatin membrane. Insulinoma cells were encapsulated in alginate-poly-L-lysine-alginate microcapsules and enclosed in a HAP/gelatin chamber. The chamber did not impair

  17. Preparation and characterization of hydroxyapatite/gelatin composite membranes for immunoisolation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, 259 Wen Hwa 1st Rd., Kwei-San, Taoyuan 333, Taiwan (China); Chang, Feng-Nian [Department of Chemical and Materials Engineering, Chang Gung University, 259 Wen Hwa 1st Rd., Kwei-San, Taoyuan 333, Taiwan (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Cross-linking gelatin in the presence of hydroxyapatite forms composite membranes. Black-Right-Pointing-Pointer The membrane was used for immunoisolation and encapsulation of cells. Black-Right-Pointing-Pointer Encapsulated islet cells secrete insulin in response to glucose concentrations. Black-Right-Pointing-Pointer The membrane is a good candidate for bioartificial pancreas development. - Abstract: Composite membranes are fabricated from hydroxyapatite (HAP) and gelatin for immunoisolation of cells. The films were fabricated by crosslinking 5 wt%, 10 wt%, and 20 wt% gelatin with 1 wt% glutaraldehyde (GA) in the presence of HAP. Fourier transform infrared spectroscopy analysis confirms imide bond formation between GA and gelatin, while the crystal structure of HAP powder remains unchanged from X-ray diffraction analysis. The degree of crosslinking depends on crosslinking time and gelatin concentration. For 5% and 10% gelatin, the degree of crosslinking levels off at 90% within 48 h. From scanning electron microscopy micrographs, the microstructure of the composite membrane depends on the amount of gelatin used in the crosslinking reaction. The mechanical strength of the composite membrane could be enhanced by increasing the gelatin concentration. BET analysis indicates that pore size of the micropores on the surface HAP/gelatin agglomerates decreases with increasing gelatin concentration. However, the macropore, through which diffusion of molecules occurs, is larger at higher gelatin concentrations. The permeability coefficients of different molecules through a HAP/gelatin composite membrane increase with increasing gelatin concentration and is inversely correlated with the molecular weight of the molecule. For immunoisolation of cells, the diffusion of large molecules stimulated by the immune system can be rejected by a chamber constructed from the HAP/gelatin membrane. Insulinoma cells were encapsulated in alginate

  18. Effect of dose rate on radical and property of gelatin

    International Nuclear Information System (INIS)

    Geng Shengrong; Chen Yuxia; Zu Xiaoyan; Li Xin; Jiang Hongyou

    2015-01-01

    The gelatin was irradiated respectively in the range of 0-32 kGy by dose rates of 60 Gy/min 60 Co, 480 Gy/min 60 Co and 12000 Gy/min accelerator, and the relationships of the radical character and gelatin property with dose rate were investigated through electron spin resonance (ESR) and gelatin permeation chromatogram. The results show that there is weak ESR signal from unirradiated gelatin, but irradiated one presents typical double peak. The order of ESR signal intensity of gelatin with the same absorbed dosage from high to low is 60 Gy/min 60 Co, 480 Gy/min 60 Co and 12000 Gy/min accelerator. The linear relationship between ESR signal intensity from 60 Co irradiated gelatin and absorbed dose is y= 26.983x 2 +1 641.8x-205.69. The intrinsic viscosity, average relative molecular weight, gelatin strength and breaking elongation of irradiated gelatin from high to low are 480 Gy/min 60 Co, 12000 Gy/min accelerator and 60 Gy/min 60 Co. The protection mechanism of high dose rate radiation on gelatin degradation is that the production of effective long life free radicals reduces. (authors)

  19. Novel Dual Mitochondrial and CD44 Receptor Targeting Nanoparticles for Redox Stimuli-Triggered Release

    Science.gov (United States)

    Wang, Kaili; Qi, Mengjiao; Guo, Chunjing; Yu, Yueming; Wang, Bingjie; Fang, Lei; Liu, Mengna; Wang, Zhen; Fan, Xinxin; Chen, Daquan

    2018-02-01

    In this work, novel mitochondrial and CD44 receptor dual-targeting redox-sensitive multifunctional nanoparticles (micelles) based on oligomeric hyaluronic acid (oHA) were proposed. The amphiphilic nanocarrier was prepared by (5-carboxypentyl)triphenylphosphonium bromide (TPP), oligomeric hyaluronic acid (oHA), disulfide bond, and curcumin (Cur), named as TPP-oHA-S-S-Cur. The TPP targeted the mitochondria, the antitumor drug Cur served as a hydrophobic core, the CD44 receptor targeting oHA worked as a hydrophilic shell, and the disulfide bond acted as a connecting arm. The chemical structure of TPP-oHA-S-S-Cur was characterized by 1HNMR technology. Cur was loaded into the TPP-oHA-S-S-Cur micelles by self-assembly. Some properties, including the preparation of micelles, morphology, redox sensitivity, and mitochondrial targeting, were studied. The results showed that TPP-oHA-S-S-Cur micelles had a mean diameter of 122.4 ± 23.4 nm, zeta potential - 26.55 ± 4.99 mV. In vitro release study and cellular uptake test showed that TPP-oHA-S-S-Cur micelles had redox sensibility, dual targeting to mitochondrial and CD44 receptor. This work provided a promising smart multifunctional nanocarrier platform to enhance the solubility, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs.

  20. Structure and surface properties of chitosan/PEO/gelatin nanofibrous membrane

    Czech Academy of Sciences Publication Activity Database

    Barchuk, M.; Čapková, P.; Kolská, Z.; Matoušek, J.; Poustka, J.; Šplíchalová, L.; Benada, Oldřich; Munzarová, M.

    2016-01-01

    Roč. 23, č. 2 (2016), s. 20 ISSN 1022-9760 R&D Projects: GA MŠk(CZ) LO1509 Institutional support: RVO:61388971 Keywords : Chitosan * Gelatin * Nanofiber textile Subject RIV: EE - Microbiology, Virology Impact factor: 1.615, year: 2016

  1. Transplantation of artificial gelatin-co-bletillastriata gelatin/Salvia ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2016; 15 (4): 735-741 ... Methods: The composite artificial corium was constructed by culturing fibroblast cells in gelatin-co- ... Conclusion: The composite artificial corium has some clinical prospects for use in the treatment of ... burns, and treatment of large areas of skin.

  2. Recombinant gelatin and collagen from methylotrophic yeasts

    NARCIS (Netherlands)

    Bruin, de E.C.

    2002-01-01

    Based on its structural role and compatibility within the human body, collagen is a commonly used biomaterial in medical applications, such as cosmetic surgery, wound treatment and tissue engineering. Gelatin is in essence denatured and partly degraded collagen and is,

  3. Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment.

    Directory of Open Access Journals (Sweden)

    Ruben R Bender

    2016-06-01

    Full Text Available Receptor-targeted lentiviral vectors (LVs can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance. Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4 was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.

  4. Physico-mechanical and structural properties of eggshell membrane gelatin- chitosan blend edible films

    DEFF Research Database (Denmark)

    Mohammadi, Reza; Mohammadifar, Mohammad Amin; Rouhi, Milad

    2018-01-01

    This study investigated the physico-mechanical and structural properties of composite edible films based on eggshell membrane gelatin (G) and chitosan (Ch) (75G:25Ch, 50G:50Ch, 25G:75Ch). The results demonstrated that the addition of Ch increased elongation at break significantly (p< 0.05), but r......This study investigated the physico-mechanical and structural properties of composite edible films based on eggshell membrane gelatin (G) and chitosan (Ch) (75G:25Ch, 50G:50Ch, 25G:75Ch). The results demonstrated that the addition of Ch increased elongation at break significantly (p... interactions introduced by the addition of chitosan to eggshell membrane gelatin as new resources could improve the films’ functional properties....

  5. Microarray-Based Identification of Transcription Factor Target Genes

    NARCIS (Netherlands)

    Gorte, M.; Horstman, A.; Page, R.B.; Heidstra, R.; Stromberg, A.; Boutilier, K.A.

    2011-01-01

    Microarray analysis is widely used to identify transcriptional changes associated with genetic perturbation or signaling events. Here we describe its application in the identification of plant transcription factor target genes with emphasis on the design of suitable DNA constructs for controlling TF

  6. Irradiation of gelatin. Important applications for the development of new materials

    Energy Technology Data Exchange (ETDEWEB)

    Del Mastro, N. L., E-mail: nlmastro@ipen.br [Instituto de Pesquisas Energeticas e Nucleares IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242, 05008-900 Sao Paulo (Brazil)

    2011-11-15

    Gelatin is obtained from a naturally occurring protein, collagen, by chemical and thermal hydrolysis. As a protein, gelatin is biodegradable. Among biomaterials, gelatin is an interesting material because the dehydrated gelatin is a partially crystalline polymer and has a relatively low melting point. Gelatin melts to a liquid when heated and solidifies when cooled again. Together with water, it forms a semi-solid colloid gel. If gelatin is placed in contact with cold water, some of the material dissolves, their solubility being determined by their manufacturing method. Ionizing radiation acting on aqueous biological systems produces labile intermediates. Macromolecular free radicals may be diffusion ally mobile in homogenous solutions but relatively immobile in gelled systems. In this paper, different works, some of them performed in our laboratory, are firstly described showing gelatin irradiation in diverse systems. We have already studied the mechanical properties of gelatin composites prepared with a natural fiber, plasticizer and treated by electron beam irradiation. Departing from that, the range of novel applications for gelatin composites like gelatin nanoparticles as biodegradable s and low cell toxic alternative carrier delivery systems are outlined. The potential and the possibilities of using gelatin irradiation for important applications for the development of new materials for medical and food industry are presented. (Author)

  7. The decontamination effects of gamma irradiation on the edible gelatin

    International Nuclear Information System (INIS)

    Fu, Junjie; Shen, Weiqiao; Bao, Jinsong; Chen, Qinglong

    2000-01-01

    The decontamination effects of gamma irradiation on the edible gelatin were studied. The results indicated that the bacterium and mold in the gelatin decreased significantly with the dose of 5 kGy treatment. However, the content of crude protein, microelement, amino acid in the gelatin remained unchanged under the irradiation of 4 and 8 kGy. The viscosity of the gelatin decreased with the increase of the irradiation dose, but the gelatin with a dose of 5 kGy treatment still accorded with the standard of the second-order class. These results suggested that the optimum irradiation dose for edible gelatin for the purpose of decontamination was in the range 3-5 kGy. (author)

  8. PANC-1 pancreatic cancer cell growth inhibited by cucurmosin alone and in combination with an epidermal growth factor receptor-targeted drug.

    Science.gov (United States)

    Wang, Congfei; Yang, Aiqin; Zhang, Baoming; Yin, Qiang; Huang, Heguang; Chen, Minghuang; Xie, Jieming

    2014-03-01

    To investigate the inhibition of PANC-1 pancreatic cancer cell growth by cucurmosin (CUS) and its possible mechanism. We observed the inhibition of PANC-1 cell growth by sulforhodamine B and colony-forming experiments in vitro and established nonobese diabetic/severe combined immunodeficiency mouse subcutaneous tumor models in vivo. We used Western blot to analyze protein levels related to apoptosis and epidermal growth factor receptor (EGFR) signaling pathways after drug intervention, whereas the messenger RNA expression of EGFR was analyzed by quantitative real-time polymerase chain reaction. Sulforhodamine B and colony-forming experiments indicated that CUS inhibited PANC-1 cell proliferation in a dose- and time-dependent manner. A stronger inhibitory effect was observed when CUS was combined with gefitinib. The subcutaneous tumor growth was also inhibited. Western blot showed that all the examined proteins decreased, except for 4E-BP1 and the active fragments of caspase 3 and caspase 9 increased. Epidermal growth factor receptor expression did not change significantly in quantitative real-time polymerase chain reaction. Cucurmosin can strongly inhibit the growth of PANC-1 cells in vitro and in vivo. Cucurmosin can down-regulate EGFR protein expression, but not at the messenger RNA level. Cucurmosin can also inhibit the ras/raf and phosphatidylinositol 3-kinase/Akt downstream signaling pathways and enhance the sensitivity of the EGFR-targeted drug gefitinib.

  9. Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic

    Science.gov (United States)

    2016-09-01

    AR) is more widely expressed than estrogen receptor alpha (ER) or the progesterone receptor (PR) (1), which are used as therapeutic targets and...19 6. Products …………………………………….……….….…………….20 7. Participants & Other Collaborating Organizations……………22 8. Special Reporting...estrogen receptor alpha (ER) or the progesterone receptor (PR), which are used as therapeutic targets and biomarkers, suggesting a potential role

  10. Enhancing the effect of radionuclide tumor targeting, using lysosomotropic weak bases

    International Nuclear Information System (INIS)

    Sundberg, Asa Liljegren; Steffen, Ann-Charlott

    2007-01-01

    Purpose: The aim of the present study was to investigate if treatment with lysosomotropic weak bases could increase the intracellular retention of radiohalogens and thereby increase the therapeutic effect of radionuclide tumor targeting. Methods and Materials: Four different lysosomotropic bases, chloroquine, ammonium chloride, amantadine, and thioridazine, were investigated for their ability to increase radiohalogen retention in vitro. The two most promising substances, chloroquine and ammonium chloride, were studied in several cell lines (A431, U343MGaCl2:6, SKOV-3, and SKBR-3) in combination with radiolabeled epidermal growth factor (EGF) or the HER2 binding affibody (Z HER2:4 ) 2 . Results: The uptake and retention of radionuclides was found to be substantially increased by simultaneous treatment with the lysosomotropic bases. The effect was, however, more pronounced in the epidermal growth factor:epidermal growth factor receptor (EGF:EGFR) system than in the (Z HER2:4 ) 2 :HER2 system. The therapeutic effect of ammonium chloride treatment combined with 211 At-EGF was also studied. The effect obtained after combined treatment was found to be much better than after 211 At-EGF treatment alone. Conclusions: The encouraging results from the present study indicate that the use of lysosomotropic weak bases is a promising approach for increasing the therapeutic effect of radionuclide targeting with radiohalogens

  11. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Joseph A., E-mail: jaludwig@mdanderson.org; Lamhamedi-Cherradi, Salah-Eddine [Departments of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Lee, Ho-Young [Departments of Thoracic Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Naing, Aung [Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Benjamin, Robert [Departments of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2011-07-26

    The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas.

  12. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

    International Nuclear Information System (INIS)

    Ludwig, Joseph A.; Lamhamedi-Cherradi, Salah-Eddine; Lee, Ho-Young; Naing, Aung; Benjamin, Robert

    2011-01-01

    The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas

  13. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

    Directory of Open Access Journals (Sweden)

    Aung Naing

    2011-07-01

    Full Text Available The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R, in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas.

  14. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

    Science.gov (United States)

    Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

    2015-09-01

    Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Study and characterization of powder mackerel (Scomberomorus commerson) bone gelatin through hydrolysis of hydrochloric acid

    Science.gov (United States)

    Mardawati, E.; Sugandi, H.; Kayaputri, I. L.; Cahyana, Y.; Wira, D. W.; Pujianto, T.; Kastaman, R.

    2018-02-01

    Gelatin is one of the most common food additives in the food and beverage industry. Gelatin is generally made of leather or pig bones, causing concerns about the halal and safety of its product. Mackerel fish bone (Scomberomorus commerson) is a waste fish that has not been utilized well and it contains 18.6% of collagen so that it can be made into gelatin. The purpose of this research is to know the relation between HCl concentration with physical and chemical characteristics of gelatin and to know the best HCl concentration for gelatin production. Based on the physical and chemical analysis of gelatin, it is known that the concentration of hydrochloric acid influences the yield, viscosity, gel strength and pH produced. The higher HCl concentration there will be decrease in the pH value, gel strength, viscosity and protein. The yield will rise to the optimum point then decrease with respect to the high HCl concentration. Gelatin with 2% HCl concentration was the best treatment, with pH value 3.83, viscosity 3.65cP, gel strength 190.50 blooms which fulfilled British Standard, yield 10.16%, protein content 43.34%. It has functional group such as amino acids glycine, proline and hydroxyproline and 15 other amino acids, the gelatin group uptake in the region of amide wave numbers A, amides I, II and III, with a gelatin molecular weight of 290.35 g/mol.

  16. Emerging Paradigm of Intracellular Targeting of G Protein-Coupled Receptors.

    Science.gov (United States)

    Chaturvedi, Madhu; Schilling, Justin; Beautrait, Alexandre; Bouvier, Michel; Benovic, Jeffrey L; Shukla, Arun K

    2018-05-04

    G protein-coupled receptors (GPCRs) recognize a diverse array of extracellular stimuli, and they mediate a broad repertoire of signaling events involved in human physiology. Although the major effort on targeting GPCRs has typically been focused on their extracellular surface, a series of recent developments now unfold the possibility of targeting them from the intracellular side as well. Allosteric modulators binding to the cytoplasmic surface of GPCRs have now been described, and their structural mechanisms are elucidated by high-resolution crystal structures. Furthermore, pepducins, aptamers, and intrabodies targeting the intracellular face of GPCRs have also been successfully utilized to modulate receptor signaling. Moreover, small molecule compounds, aptamers, and synthetic intrabodies targeting β-arrestins have also been discovered to modulate GPCR endocytosis and signaling. Here, we discuss the emerging paradigm of intracellular targeting of GPCRs, and outline the current challenges, potential opportunities, and future outlook in this particular area of GPCR biology. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Markers of angiogenesis and epidermal growth factor receptor signalling in patients with pancreatic and gastroesophageal junction cancer

    DEFF Research Database (Denmark)

    Rohrberg, Kristoffer Staal; Skov, Birgit Guldhammer; Lassen, Ulrik

    2010-01-01

    The epidermal growth factor receptor (EGFR) and angiogenesis are well established targets in anti-cancer therapy. Several targeted anti-cancer therapies are in clinical trials in pancreatic and gastroesophageal (GEJ) cancer. However, many patients do not respond to these targeted therapies...... in pancreatic and GEJ cancer patients, and could be investigated further as predictive biomarkers in such patients treated with EGFR or angiogenesis targeted therapies....

  18. Lipid-Polymer Nanoparticles for Folate-Receptor Targeting Delivery of Doxorubicin.

    Science.gov (United States)

    Zheng, Mingbin; Gong, Ping; Zheng, Cuifang; Zhao, Pengfei; Luo, Zhenyu; Ma, Yifan; Cai, Lintao

    2015-07-01

    A biocompatible PLGA-lipid hybrid nanoparticles (NPs) was developed for targeted delivery of anticancer drugs with doxorubicin (DOX). The hydrodynamic diameter and zeta potential of DOX-loaded PLGA-lipid NPs (DNPs) were affected by the mass ratio of Lipid/PLGA or DSPE-PEG-COOH/Lecithin. At the 1:20 drug/polymer mass ratio, the mean hydrodynamic diameter of DNPs was the lowest (99.2 1.83 nm) and the NPs presented the encapsulation efficiency of DOX with 42.69 1.30%. Due to the folate-receptor mediated endocytosis, the PLGA-lipid NPs with folic acid (FA) targeting ligand showed significant higher uptake by folate-receptor-positive MCF-7 cells as compared to PLGA-lipid NPs without folate. Confocal microscopic observation and flow cytometry analysis also supported the enhanced cellular uptake of the FA-targeted NPs. The results indicated that the FA-targeted DNPs exhibited higher cytotoxicity in MCF-7 cells compared with non-targeted NPs. The lipid-polymer nanoparticles provide a solution of biocompatible nanocarrier for cancer targeting therapy.

  19. A Non-destructive and Continuous Measurement of Gelatinization of Rice in Rice Cooking Process

    OpenAIRE

    Hagura, Yoshio; Suzuki, Kanichi

    2002-01-01

    A non-destructive and continuous method to measure gelatinization of rice samples in a rice-water system during rice cooking process was examined. An aluminum pot and a lid of a rice cooker were used as two electrode plates, and changes in dielectric properties (capacitance : C, and dielectric dissipation factor : tan δ) of the samples in the rice cooking process were measured by a capacitance meter. Differential scanning calorimetry (DSC) was used to measure gelatinization enthalpy and to de...

  20. Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

    Science.gov (United States)

    Hahn, Ulrich

    2017-12-06

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  1. Electron beam effects on gelatin polymer

    Energy Technology Data Exchange (ETDEWEB)

    Inamura, Patricia Y.; Shimazaki, Kleber; Souza, Clecia de M.; Moura, Esperidiana A.B.; Mastro, Nelida L. del, E-mail: patyoko@yahoo.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Colombo, Maria A., E-mail: mascolombo@yahoo.com.b [Faculdade de Tecnologia da Zona Leste, Sao Paulo, SP (Brazil)

    2009-07-01

    The main field of electron-beam radiation processing applications is the modification of polymeric material. Polymer development includes new pathways to produce natural polymers with better mechanical and barrier properties and thermal stability. The aim of this paper was to investigate the behavior of a gelatin/acrylamide polymer treated by electron-beam radiation. Gelatin is a heterogeneous mixture of water-soluble proteins of high average molecular mass derived by hydrolytic action from animal collagen, a fibrous insoluble protein, which is widely found in nature as the major constituent of skin, bones and connective tissue. Hydrolyzed collagen is composed of a unique sequence of amino acids, characterized particularly by the high content of glycine, proline and hydroxyproline. Among biomaterials, gelatin is an interesting material because is a partially crystalline polymer and has a relatively low melting point. Samples of gelatin together with glycerin as plasticizer and acrylamide as copolymer were irradiated with doses of 10 kGy and 40 kGy, using an electron beam accelerator, dose rate 22.41kGy/s, at room temperature in presence of air. After irradiation, some preliminary analyses were done like viscometry, texture analyses and colorimetry. The results of the diverse tests showed changes that can be ascribed to radiation-induced crosslinking. The electron-beam processed acrylamide-gelatin polymer using glycerin as plasticizer must be first extensively characterized before to be used for general applications. (author)

  2. Electron beam effects on gelatin polymer

    International Nuclear Information System (INIS)

    Inamura, Patricia Y.; Shimazaki, Kleber; Souza, Clecia de M.; Moura, Esperidiana A.B.; Mastro, Nelida L. del; Colombo, Maria A.

    2009-01-01

    The main field of electron-beam radiation processing applications is the modification of polymeric material. Polymer development includes new pathways to produce natural polymers with better mechanical and barrier properties and thermal stability. The aim of this paper was to investigate the behavior of a gelatin/acrylamide polymer treated by electron-beam radiation. Gelatin is a heterogeneous mixture of water-soluble proteins of high average molecular mass derived by hydrolytic action from animal collagen, a fibrous insoluble protein, which is widely found in nature as the major constituent of skin, bones and connective tissue. Hydrolyzed collagen is composed of a unique sequence of amino acids, characterized particularly by the high content of glycine, proline and hydroxyproline. Among biomaterials, gelatin is an interesting material because is a partially crystalline polymer and has a relatively low melting point. Samples of gelatin together with glycerin as plasticizer and acrylamide as copolymer were irradiated with doses of 10 kGy and 40 kGy, using an electron beam accelerator, dose rate 22.41kGy/s, at room temperature in presence of air. After irradiation, some preliminary analyses were done like viscometry, texture analyses and colorimetry. The results of the diverse tests showed changes that can be ascribed to radiation-induced crosslinking. The electron-beam processed acrylamide-gelatin polymer using glycerin as plasticizer must be first extensively characterized before to be used for general applications. (author)

  3. Differences in cytocompatibility between collagen, gelatin and keratin

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yanfang; Zhang, Weiwei; Yuan, Jiang, E-mail: jyuan@njnu.edu.cn; Shen, Jian, E-mail: jshen@njnu.edu.cn

    2016-02-01

    Keratins are cysteine-rich intermediate filament proteins found in the cytoskeleton of the epithelial cells and in the matrix of hair, feathers, wool, nails and horns. The natural abundance of cell adhesion sequences, RGD (Arg-Gly-Asp) and LDV (Leu-Asp-Val), makes them suitable for tissue engineering applications. The purpose of our study is to evaluate their cytocompatibility as compared to well-known collagen and gelatin proteins. Herein, collagen, gelatin and keratin were blended with poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and electrospun to afford nanofibrous mats, respectively. These PHBV/protein composite mats were characterized by field emission scanning electron microscopy (FE-SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and dynamic mechanical analysis (DMA). The cytocompatibility was evaluated with cell adhesion, cell viability and cell proliferation. The data from MTT and BrDU revealed that collagen had significantly superior cytocompatibility as compared to gelatin and keratin. Gelatin showed a better cytocompatibility than keratin without statistical significance difference. Finally, we gave the reasons to account for the above conclusions. - Highlights: • Collagen, gelatin and keratin were coelectrospun with PHBV to afford nanofibrous mats. • Cytocompatibility was evaluated with cell adhesion, cell viability and cell proliferation. • Collagen had significantly superior cytocompatibility as compared to gelatin and keratin.

  4. High-expression β(1) adrenergic receptor/cell membrane chromatography method based on a target receptor to screen active ingredients from traditional Chinese medicines.

    Science.gov (United States)

    Yue, Yuan; Xue, Hui; Wang, Xin; Yang, Qian; Song, Yanhong; Li, Xiaoni

    2014-02-01

    β-Adrenergic receptors are important targets for drug discovery. We have developed a new β1 -adrenergic receptor cell membrane chromatography (β1 AR-CMC) with offline ultra-performance LC (UPLC) and MS method for screening active ingredients from traditional Chinese medicines. In this study, Chinese hamster ovary-S cells with high β1 AR expression levels were established and used to prepare a cell membrane stationary phase in a β1 AR-CMC model. The retention fractions were separated and identified by the UPLC-MS system. The screening results found that isoimperatorin from Rhizoma et Radix Notopterygii was the targeted component that could act on β1 AR in similar manner of metoprolol as a control drug. In addition, the biological effects of active component were also investigated in order to search for a new type of β1 AR antagonist. It will be a useful method for drug discovery as a leading compound resource. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Preparation and Characterization of an Antibody Antagonist That Targets the Porcine Growth Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Huanzhong Cui

    2016-10-01

    Full Text Available A series of antagonists specifically targeting growth hormone receptors (GHR in different species, such as humans, rats, bovines, and mice, have been designed; however, there are currently no antagonists that target the porcine growth hormone (GH. Therefore, in this study, we developed and characterized a porcine GHR (pGHR antibody antagonist (denoted by AN98 via the hybridoma technique. The results from enzyme-linked immunosorbent assay, fluorescence activated cell sorter, indirect immunoinfluscent assay, and competitive receptor binding analysis showed that AN98 could specifically recognize pGHR, and further experiments indicated that AN98 could effectively inhibit pGH-induced signalling in CHO-pGHR cells and porcine hepatocytes. In addition, AN98 also inhibited GH-induced insulin-like growth factor-1 (IGF-1 secretion in porcine hepatocytes. In summary, these findings indicated that AN98, as a pGHR-specific antagonist, has potential applications in pGH-pGHR-related research on domestic pigs.

  6. Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

    Energy Technology Data Exchange (ETDEWEB)

    Strauch, Eva-Maria; Bernard, Steffen M.; La, David; Bohn, Alan J.; Lee, Peter S.; Anderson, Caitlin E.; Nieusma, Travis; Holstein, Carly A.; Garcia, Natalie K.; Hooper, Kathryn A.; Ravichandran, Rashmi; Nelson, Jorgen W.; Sheffler, William; Bloom, Jesse D.; Lee, Kelly K.; Ward, Andrew B.; Yager, Paul; Fuller, Deborah H.; Wilson, Ian A.; Baker , David (UWASH); (Scripps); (FHCRC)

    2017-06-12

    Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

  7. Evaluation of hemocompatibility and endothelialization of hybrid poly(vinyl alcohol) (PVA)/gelatin polymer films.

    Science.gov (United States)

    Ino, Julia M; Sju, Ervi; Ollivier, Véronique; Yim, Evelyn K F; Letourneur, Didier; Le Visage, Catherine

    2013-11-01

    Engineered grafts are still needed for small diameter blood vessels reconstruction. Ideal materials would prevent thrombosis and intimal hyperplasia by displaying hemocompatibility and mechanical properties close to those of native vessels. In this study, poly(vinyl alcohol) (PVA)/gelatin blends were investigated as a potential vascular support scaffold. We modified a chemically crosslinked PVA hydrogel by incorporation of gelatin to improve endothelial cell attachment with a single-step method. A series of crosslinked PVA/gelatin films with specific ratios set at 100:0, 99:1, 95:5, and 90:10 (w/w) were prepared and their mechanical properties were examined by uniaxial tensile testing. Tubes, obtained from sutured films, were found highly compliant (3.1-4.6%) and exhibited sufficient mechanical strength to sustain hemodynamic strains. PVA-based hydrogels maintained low level of platelet adhesion and low thrombogenic potential. Endothelial cell adhesion and proliferation were drastically improved on PVA/gelatin films with a feed gelatin content as low as 1% (w/w), leading to the formation of a confluent endothelium. Hydrogels with higher gelatin content did not sustain complete endothelialization because of modifications of the film surface, including phase segregation and formation of microdomains. Thus, PVA/gelatin (99:1, w/w) hydrogels appear as promising materials for the design of endothelialized vascular materials with long-term patency. Copyright © 2013 Wiley Periodicals, Inc.

  8. Projectile penetration into ballistic gelatin.

    Science.gov (United States)

    Swain, M V; Kieser, D C; Shah, S; Kieser, J A

    2014-01-01

    Ballistic gelatin is frequently used as a model for soft biological tissues that experience projectile impact. In this paper we investigate the response of a number of gelatin materials to the penetration of spherical steel projectiles (7 to 11mm diameter) with a range of lower impacting velocities (projectile velocity are found to be linear for all systems above a certain threshold velocity required for initiating penetration. The data for a specific material impacted with different diameter spheres were able to be condensed to a single curve when the penetration depth was normalised by the projectile diameter. When the results are compared with a number of predictive relationships available in the literature, it is found that over the range of projectiles and compositions used, the results fit a simple relationship that takes into account the projectile diameter, the threshold velocity for penetration into the gelatin and a value of the shear modulus of the gelatin estimated from the threshold velocity for penetration. The normalised depth is found to fit the elastic Froude number when this is modified to allow for a threshold impact velocity. The normalised penetration data are found to best fit this modified elastic Froude number with a slope of 1/2 instead of 1/3 as suggested by Akers and Belmonte (2006). Possible explanations for this difference are discussed. © 2013 Published by Elsevier Ltd.

  9. Irradiated gelatin-potato starch blends: evaluation of physicochemical properties

    International Nuclear Information System (INIS)

    Inamura, Patricia Y.; Regis, Wellington; Mastro, Nelida L.

    2015-01-01

    Macromolecular polysaccharides of large chains as starch can interlace with gelatin modifying their mechanical resistance. In this work, biodegradable bovine gelatin-potato starch blends films were developed using glycerol as plasticizer. Three formulations of gelatin/starch proportions (w/w) were used (1:0; 3:1; 1:1) and casting was the chosen method. The dried samples were then submitted to ionizing radiation coming from an electron beam (EB) accelerator with doses of 20 and 40 kGy, at room temperature, in the presence of air. Mechanical properties such as puncture strength and elongation at break were measured. Color measurements, water absorption, moisture, and film solubility were assessed. The results showed that starch addition to films based on gelatin as well as irradiation affected physical and structural properties of the films. Although the increase of starch content in the mixture led to decrease of the puncture force even in samples irradiated with the higher dose, there was a decrease of water absorption of films with the increase of the dose, and also by the higher starch content. Samples irradiated at 20 kGy presented higher moisture and film solubility. The methodology developed in this paper can be applied to other composite systems to establish the best protein:starch ratio, and the contribution of the radiation crosslinking in each specific case. (author)

  10. Irradiated gelatin-potato starch blends: evaluation of physicochemical properties

    Energy Technology Data Exchange (ETDEWEB)

    Inamura, Patricia Y.; Regis, Wellington; Mastro, Nelida L., E-mail: nlmastro@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Macromolecular polysaccharides of large chains as starch can interlace with gelatin modifying their mechanical resistance. In this work, biodegradable bovine gelatin-potato starch blends films were developed using glycerol as plasticizer. Three formulations of gelatin/starch proportions (w/w) were used (1:0; 3:1; 1:1) and casting was the chosen method. The dried samples were then submitted to ionizing radiation coming from an electron beam (EB) accelerator with doses of 20 and 40 kGy, at room temperature, in the presence of air. Mechanical properties such as puncture strength and elongation at break were measured. Color measurements, water absorption, moisture, and film solubility were assessed. The results showed that starch addition to films based on gelatin as well as irradiation affected physical and structural properties of the films. Although the increase of starch content in the mixture led to decrease of the puncture force even in samples irradiated with the higher dose, there was a decrease of water absorption of films with the increase of the dose, and also by the higher starch content. Samples irradiated at 20 kGy presented higher moisture and film solubility. The methodology developed in this paper can be applied to other composite systems to establish the best protein:starch ratio, and the contribution of the radiation crosslinking in each specific case. (author)

  11. Microencapsulation of sulforaphane from broccoli seed extracts by gelatin/gum arabic and gelatin/pectin complexes.

    Science.gov (United States)

    García-Saldaña, Jesús S; Campas-Baypoli, Olga N; López-Cervantes, Jaime; Sánchez-Machado, Dalia I; Cantú-Soto, Ernesto U; Rodríguez-Ramírez, Roberto

    2016-06-15

    Sulforaphane is a phytochemical that has received attention in recent years due to its chemopreventive properties. However, the uses and applications of this compound are very limited, because is an unstable molecule that is degraded mainly by changes in temperature and pH. In this research, the use of food grade polymers for microencapsulation of sulforaphane was studied by a complex coacervation method using the interaction of oppositely charged polymers as gelatin/gum arabic and gelatin/pectin. The polymers used were previously characterized in moisture content, ash and nitrogen. The encapsulation yield was over 80%. The gelatin/pectin complex had highest encapsulation efficiency with 17.91%. The presence of sulforaphane in the complexes was confirmed by FTIR and UV/visible spectroscopy. The materials used in this work could be a new and attractive option for the protection of sulforaphane. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Development of mechanically expanded gelatin-AAc-PLLA/PLCL nanofibers for vascular tissue engineering by radiation-based techniques

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Oh; Jeong, Sung In; Seo, Da Eun; Park, Jong Seok; Gwon, Hui Jeong; Ahn, Sung Jun; Lim, Youn Mook [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Shin, Young Min [Dept. of Bioengineering, Division of Applied Chemical and Bio Engineering, Hanyang University, Seoul (Korea, Republic of)

    2015-12-15

    Vascular tissue engineering has been accessed to mimic the natural composition of the blood vessel containing inmate, media, and adventitia layers. We fabricated mechanically expanded PLLA/PLCL nanofibers using electrospinning and UTM. The pore size of the meshes was increased the gelatin immobilized AAc-PLLA/PLCL nanofibers (203.30±49.62 microns) than PLLA/PLCL nanofibers (59.99±8.66 microns) after mechanical expansion. To increase the cell adhesion and proliferation, we introduced carboxyl group, and gelatin was conjugated on them. The properties of the PLLA/PLCL nanofibers were analyzed with SEM, ATR-FTIR, TBO staining, and water contact angle measurement, general cell responses on the PLLA/PLCL nanofibers such as adhesion, proliferation, and infiltration were also investigated using smooth muscle cell (SMC). During the SMC culture, the initial viability of the cells was significantly increased on the gelatin immobilized AAc-PLLA/PLCL nanofibers, and infiltration of the cells was also enhanced on them. Therefore, gelatin immobilized AAc-PLLA/PLCL nanofibers and mechanically expanded meshes may be a good tool for vascular tissue engineering application.

  13. DMPD: Toll-like receptors: novel pharmacological targets for the treatment ofneurological diseases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17974478 Toll-like receptors: novel pharmacological targets for the treatment ofneu...png) (.svg) (.html) (.csml) Show Toll-like receptors: novel pharmacological targets for the treatment ofneur...ological diseases. PubmedID 17974478 Title Toll-like receptors: novel pharmacological target

  14. Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor.

    Directory of Open Access Journals (Sweden)

    Emma E Vincent

    Full Text Available Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R antibody figitumumab in non-small cell lung cancer (NSCLC patients have been discontinued owing to lack of survival benefit. We investigated whether inhibition of the highly homologous insulin receptor (IR in addition to the IGF1R would be more effective than inhibition of the IGF1R alone at preventing the proliferation of NSCLC cells. Signalling through IGF1R and IR in the NSCLC cell lines A549 and Hcc193 was stimulated by a combination of IGF1, IGF2 and insulin. It was inhibited by antibodies that block ligand binding, αIR3 (IGF1R and IR47-9 (IR, and by the ATP-competitive small molecule tyrosine kinase inhibitors AZ12253801 and NVPAWD742 which inhibit both IGF1R and IR tyrosine kinases. The effect of inhibitors was determined by an anchorage-independent proliferation assay and by analysis of Akt phosphorylation. In Hcc193 cells the reduction in cell proliferation and Akt phosphorylation due to anti-IGF1R antibody was enhanced by antibody-mediated inhibition of the IR whereas in A549 cells, with a relatively low IR:IGF1R expression ratio, it was not. In each cell line proliferation and Akt phosphorylation were more effectively inhibited by AZ12253801 and NVPAWD742 than by combined αIR3 and IR47-9. When the IGF1R alone is inhibited, unencumbered signalling through the IR can contribute to continued NSCLC cell proliferation. We conclude that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease.

  15. Preparation of gelatin-assisted polypyrrole-poly(3,4-ethylenedioxythiophene) composites

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Eun Jin; Male, Umashankar; Huh, Do Sung [Dept.of Chemistry and Nanosystem Engineering, Center for Nano Manufacturing, Inje University, Kimhae (Korea, Republic of)

    2016-11-15

    Conductive polymer composite was synthesized by the polymerization of pyrrole with 3,4-ethylenedioxythiophene using ammonium persulfate as an oxidant with different concentrations of gelatin dispersed in aqueous medium along with the polymerization. Differently from pure polypyrrole–poly(3,4-ethylenedioxythiophene) (PPy–PEDOT) copolymer, the gelatin-assisted composites showed good solubility in aqueous media. The prepared PPy–PEDOT/gelatin composites were identified with Fourier-transform infrared, UV–visible spectroscopy, and X-ray diffraction. Morphological analysis and temperature-dependent direct current conductivity of PPy–PEDOT/gelatin composites were carried out. Obtained results revealed that added gelatin greatly increased conductivity due to the improved mobility of charge carriers.

  16. Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation

    International Nuclear Information System (INIS)

    Diermeier, Simone; Horvath, Gabor; Knuechel-Clarke, Ruth; Hofstaedter, Ferdinand; Szoellosi, Janos; Brockhoff, Gero

    2005-01-01

    heterointeractions, as well as the presence or absence of growth factors. C-erbB2 overexpression alone is insufficient to predict the impact of growth factors and antibodies on cell proliferation. The optimization and specification of therapeutic approaches based on erbB-receptor targeting requires to account for EGFR coexpression as well as the potential presence of erbB-receptor relevant growth factors

  17. Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...

  18. Targeting death receptors to fight cancer: from biological rational to clinical implementation.

    Science.gov (United States)

    Mocellin, S

    2010-01-01

    Considering that most currently available chemotherapeutic drugs work by inducing cell apoptosis, it is not surprising that many expectations in cancer research come from the therapeutic exploitation of the naturally occurring death pathways. Receptor mediated apoptosis depends upon the engagement of specific ligands with their respective membrane receptors and - within the frame of complex regulatory networks - modulates some key physiological and pathological processes such as lymphocyte survival, inflammation and infectious diseases. A pivotal observation was that some of these pathways may be over activated in cancer under particular circumstances, which opened the avenue for tumor-specific therapeutic interventions. Although one death-related ligand (e.g., tumor necrosis factor, TNF) is currently the basis of effective anticancer regimens in the clinical setting, the systemic toxicity is hampering its wide therapeutic exploitation. However, strategies to split the therapeutic from the toxic TNF activity are being devised. Furthermore, other death receptor pathways (e.g., Fas/FasL, TRAIL/TRAIL receptor) are being intensively investigated in order to therapeutically exploit their activity against cancer. This article summarizes the current knowledge on the molecular features of death receptor pathways that make them an attractive target for anticancer therapeutics. In addition, the results so far obtained in the clinical oncology setting as well as the issues to be faced while interfering with these pathways for therapeutic purposes will be overviewed.

  19. Effectiveness of a new gelatin sealant system for dural closure.

    Science.gov (United States)

    Kawai, Hisashi; Nakagawa, Ichiro; Nishimura, Fumihiko; Motoyama, Yasushi; Park, Young-Su; Nakamura, Mitsutoshi; Nakase, Hiroyuki; Suzuki, Shuko; Ikada, Yoshito

    2014-10-01

    Watertight dural closure is imperative after neurosurgical procedures because inadequately treated leakage of cerebrospinal fluid (CSF) can have serious consequences. In this study, the authors test the use of a new gelatin glue as a dural sealant in in vitro and in vivo canine models of transdural CSF leakage. The in vitro model was sutured semicircles of canine dura mater and artificial dural substitute. The sutures were sealed with gelatin glue (n  =  20), fibrin glue (n  =  20), or a polyethylene glycol (PEG)-based hydrogel sealant (n  =  20). Each sample was set in a device to measure water pressure, and pressure was increased until leakage occurred. Bonding strength was subjectively evaluated. The in vivo model was dogs who underwent dural excision and received either no sealant (control group; n  =  5) or gelatin glue sealant (n  =  5) before dural closure. Twenty-eight days post-surgery, the maximum intracranial pressure was measured at the cisterna magna using Valsalva maneuver and tissue adhesion was evaluated. The water pressure at which leakage occurred in the in vitro model was higher with gelatin glue (76·5 ± 39·8 mmHg) than with fibrin glue (38·3 ± 27·4 mmHg, P control group (13·8 ± 4·0 mmHg, P control group (P  =  0·005). The new gelatin glue provides an effective watertight closure when used as an adjunct to sutured dural repair.

  20. Gelatin as a carrier system for delivery of polyphenols compounds

    Directory of Open Access Journals (Sweden)

    Jovanović Aleksandra

    2017-01-01

    Full Text Available In the present study, the influence of different encapsulation techniques (lyophilization and spray drying on gelatin, as a carrier system for delivery of polyphenols compounds, on wild thyme extracts and on encapsulated extracts was investigated. FTIR analyses has shown the presence of carbohydrates, polysaccharides, polyphenols, flavonoids, monoterpenes and carboxylates in the dried extracts, while FTIR spectrum of the encapsulated extracts has shown almost exclusively gelatin-based stripes, indicating the efficient encapsulation of the active ingredients of the extracts and therefore their protection. Scanning electron microscopy has shown that the lyophilization process produced irregularly shaped particles, while spray drying formed spherical and pseudo-spherical particles with rough surface. Using the method of diffraction of laser light, it has been found that spray dried encapsulate possessed significantly lower particle size and significantly better uniformity in comparison to the lyophilized sample. According to the results obtained in differential scanning calorimetry, endothermic peak of lyophilized gelatin encapsulate appeared at higher temperature, thus it can be concluded that lyophilized sample was more thermostable than spray dried parallel. Additionally, the values of enthalpy of gelatin encapsulates were significantly higher compared to pure extracts, which confirmed the presence of stabilizing interactions between the encapsulated components and a carrier.

  1. Synthesis and Property of Ag(NP)/catechin/Gelatin Nanofiber

    Science.gov (United States)

    Nasir, Muhamad; Apriani, Dita

    2017-12-01

    Nanomaterial play important role future industry such as for the medical, food, pharmaceutical and cosmetic industry. Ag (NP) and catechin exhibit antibacterial property. Ag(NP) with diameter around 15 nm was synthesis by microwaved method. We have successfully produce Ag(NP)/catechin/gelatin nanofiber composite by electrospinning process. Ag(NP)/catechin/gelatin nanofiber was synthesized by using gelatin from tuna fish, polyethylene oxide (PEO), acetic acid as solvent and silver nanoparticle(NP)/catechin as bioactive component, respectively. Morphology and structure of bioactive catechin-gelatin nanofiber were characterized by scanning electron microscopy (SEM) and fourier transform infrared spectroscopy (FTIR), respectively. SEM analysis showed that morphology of nanofiber composite was smooth and had average diameter 398.97 nm. FTIR analysis results were used to confirm structure of catechin-gelatin nanofiber. It was confirmed by FTIR that specific vibration band peak amide A (N-H) at 3286,209 cm-1, amide B (N-H) 3069,396 cm-1, amide I (C=O) at 1643,813 cm-1, amide II (N-H and CN) at 1538,949 cm-1, amide III (C-N) at 1276,789 cm-1, C-O-C from polyethylene oxide at 1146,418 cm-1, respectively. When examined to S. Aureus bacteria, Ag/catechin/gelatin nanofiber show inhabitation performance around 40.44%. Ag(NP)/catechin/gelatin nanofiber has potential application antibacterial medical application.

  2. Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Yuan, Lilai; Li, Jiasu; Zha, Jinmiao; Wang, Zijian

    2016-01-01

    Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. - Highlights: • Significant inhibition of AChE and BChE activities by CPF was observed. • None of the OPFRs had similar effects on the cholinesterase like the CPF. • TDCPP showed significant effects on the neurotrophic factor genes in rare minnow. - Although none of the tested OPFRs showed any significant effects on cholinesterase activities and neurotransmitter levels, TDCPP did elicit widespread effects on neurotrophic factor genes.

  3. Macrophage galactose-type C-type lectin receptor for DC targeting of antitumor glycopeptide vaccines

    DEFF Research Database (Denmark)

    Nuti, M; Zizzari, I; Napoletano, C

    2011-01-01

    e13528 Background: Dendritic cells (DCs) are the most potent antigen presenting cells and are employed in cancer vaccination. Several receptors are being studied in order to identif strategies to increase DCs activating capacity. The C-type lectin macrophage galactose type C-type lectin (MGL...... of IFNg and IL-2 secretion by both CD8 and CD4 T cells. CONCLUSIONS: These results demonstrate that MGL engagement profoundly affects DC plasticity inducing and directing a Th1 immune response. Moreover, MGL receptor expressed on human DC can be targeted by glycopeptide based vaccines with adjuvant...

  4. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

    Directory of Open Access Journals (Sweden)

    Campbell Craig I

    2011-11-01

    Full Text Available Abstract Background Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor. Results MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice, it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis. Conclusion During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.

  5. RENDEMEN DAN KOMPOSISI PROKSIMAT GELATIN KULIT IKAN BELUT DAN LELE PADA KEADAAN SEGAR DAN KERING (YIELD AND PROXIMATE OF GELATIN EXTRACTED FROM FRESH AND DRY SWAMP ELL AND CATFISH SKIN

    Directory of Open Access Journals (Sweden)

    Hafni Rahmawati

    2017-02-01

    Full Text Available Kulit ikan belut dan lele berpotensi untuk diekstrak gelatinnya. Kulit ikan belut dan lele tidak bersisik, berlendir dan berlemak untuk ikan lele, berbeda dengan kulit ikan pada umumnya yang dijadikan gelatin. Penelitian ini mempelajari tentang gelatin kulit ikan belut dan lele dari segi rendemen dan komposisi proksimat. Untuk mengetahui pengaruh pengeringan, kondisi kulit segar dan kering juga dipelajari. Tahapan ekstraksi yang dilakukan untuk keseluruhan jenis ikan sama, kecuali penanganan kulit ikan kering yang sebelumnya direndam dalam air selama 4 jam. Kulit ikan direndam kembali dalam 0,05M asam asetat selama 10 jam, kemudian dicuci dan diekstraksi dengan aquadest pada suhu 80OC selama 2 jam, cairan yang didapat difiltrasi. Filtratnya dikeringkan dalam cabinet dryer suhu 55OC selama        48 jam hingga diperoleh lembaran gelatin, kemudian diblender menjadi granula gelatin. Hasil penelitian menunjukkan bahwa gelatin kulit ikan kering mempunyai rendemen sedikit lebih rendah dibandingkan gelatin dari kulit ikan segarnya. Kadar protein gelatin kulit ikan kering telihat tinggi dibandingkan kulit segarnya. Pengeringan kulit ikan berpengaruh pada penurunan kadar abu dan lemak, namun tidak mempengaruhi kadar air gelatin hasil ekstraksi. Gelatin kulit segar ikan lele memiliki nilai rendemen tertinggi yaitu 22,01%. Komposisi proksimat yang terbaik diantara keseluruhan kondisi dan jenis kulit dapat dilihat pada gelatin kulit segar ikan belut dimana memiliki kadar air 9,91%; kadar abu 3,07%; kadar protein 91,61%; dan kadar lemak 0,82%. Skin of swam ell and catfish were potential to gelatin extracted. Swamp ell skin doesn’t have scales, with much mucus and a few fat for catfish, it’s different from another fish skin that gelatin extracted usually. This research was studied yield and proximate gelatin extracted from skin of swam ell and catfish. Influence of drying was observed too. The first stage of the research was raw

  6. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Science.gov (United States)

    2017-01-01

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld. PMID:29211023

  7. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ulrich Hahn

    2017-12-01

    Full Text Available Interleukin-6 (IL-6 is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT. Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  8. Novel drugs targeting Toll-like receptors for antiviral therapy.

    Science.gov (United States)

    Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

    2014-09-01

    Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

  9. Glycation and transglutaminase mediated glycosylation of fish gelatin peptides with glucosamine enhance bioactivity.

    Science.gov (United States)

    Hong, Pui Khoon; Gottardi, Davide; Ndagijimana, Maurice; Betti, Mirko

    2014-01-01

    A mixture of novel glycopeptides from glycosylation between cold water fish skin gelatin hydrolysates and glucosamine (GlcN) via transglutaminase (TGase), as well as glycation between fish gelatin hydrolysate and GlcN were identified by their pattern of molecular distribution using MALDI-TOF-MS. Glycated/glycosylated hydrolysates showed superior bioactivity to their original hydrolysates. Alcalase-derived fish skin gelatin hydrolysate glycosylated with GlcN in the presence of TGase at 25°C (FAT25) possessed antioxidant activity when tested in a linoleic acid oxidation system, when measured according to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and when tested at the cellular level with human hepatocarcinoma (HepG2) cells as target cells. In addition, Alcalase-derived glycosylated hydrolysates showed specificity toward the inhibition of Escherichia coli (E. coli). The Flavourzyme-derived glycopeptides prepared at 37°C (FFC37 and FFT37) showed better DPPH scavenging activity than their native hydrolysates. The glycated Flavourzyme-derived hydrolysates were found to act as potential antimicrobial agents when incubated with E. coli and Bacillus subtilis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Targeting study of gelatin adsorbed clodronate in reticuloendothelial system and its potential application in immune thrombocytopenic purpura of rat model

    International Nuclear Information System (INIS)

    Li, P.; Tan, Z.; Zhu, Y.

    2007-01-01

    Full text: Depletion of splenic and hepatic macrophages has potentials to alleviate hemorrhage in patients who suffered from immune thrombocytopenic purpura (ITP). This investigation was aimed to assess whether nanotechnology can play a role in this clinical setting by absorbing bisphosphonate clodronate (CLOD) to type A gelatin nanospheres (GNS) to form CLOD-GNS. First, the stability of CLOD-GNS was assessed in- vitro and up to 6 mg CLOD can be adsorbed in 1 mg GNS. The ability of CLOD-GNS to target the spleen and the liver was then evaluated by biodistribution assay and 99mTc-CLOD-GNS scintigraphy in rats. It showed that up to 70.6% of CLOD-GNS could be accumulated in the liver and spleen. The survival of the macrophages in vitro and the phagocytic ability of hepatic and splenic macrophage in vivo were reduced and later demonstrated by99mTc-phytic colloid scintigraphy. In rats with induced ITP, administration of CLOD-GNS successfully prevented peripheral platelet levels from decreasing. Our preliminary data demonstrate that CLOD-GNS can effectively target the reticuloendothelial system and has potentials in the treatment of ITP warrants further study. (author)

  11. Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

    Science.gov (United States)

    Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

    1999-01-01

    The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

  12. Targeting cellular adhesion molecules, chemokines and chemokine receptors in rheumatoid arthritis

    NARCIS (Netherlands)

    Haringman, Jasper J.; Oostendorp, Roos L.; Tak, Paul P.

    2005-01-01

    The development of specific targeted therapies, such as anti-TNF-alpha treatment, for chronic inflammatory disorders such as rheumatoid arthritis, has significantly improved treatment, although not all patients respond. Targeting cellular adhesion molecules and chemokines/chemokine receptors as

  13. Pharmacological receptors of nematoda as target points for action of antiparasitic drugs

    Directory of Open Access Journals (Sweden)

    Trailović Saša M.

    2010-01-01

    Full Text Available Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD, act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

  14. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: A New Therapeutic Approach

    International Nuclear Information System (INIS)

    Muñoz, Miguel; Coveñas, Rafael

    2015-01-01

    Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert an antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC

  15. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: A New Therapeutic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Miguel, E-mail: mmunoz@cica.es [Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, 41013 Sevilla (Spain); Coveñas, Rafael [Laboratory of Neuroanatomy of the Peptidergic System (Lab. 14), Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, 37008 Salamanca (Spain)

    2015-07-06

    Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert an antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC.

  16. Structure evolution of gelatin particles induced by pH and ionic strength.

    Science.gov (United States)

    Xu, Jing; Li, Tianduo; Tao, Furong; Cui, Yuezhi; Xia, Yongmei

    2013-03-01

    Microstructure of gelatin particles played a key role in determining the physicochemical properties of gelatin. Ionic strength and pH as systematic manners were considered to affect gelatin particles structure on the micrometer scale. Scanning electron microscopy was used for depicting the morphologies of gelatin particles. Increasing pH to 10.0 or decreasing pH to 4.0, spherical, spindle, and irregular aggregates of gelatin particles at 2, 6, 10, and 14% solution (w/w) were all transformed to spindle aggregates. When NaCl was added to the system, the molecular chains of gelatin possibly rearranged themselves in a stretched state, and the ribbon aggregates was observed. The structural transitions of gelatin aggregates were strongly depended on the electrostatic repulsion. In the gelatin-sodium dodecyl sulfate (SDS) case, the micrometer scale of aggregates was larger and the different degrees of cross-links were induced through hydrophobic interaction and electrostatic repulsion. Copyright © 2012 Wiley Periodicals, Inc.

  17. Starvation marrow – gelatinous transformation of bone marrow

    Directory of Open Access Journals (Sweden)

    Eric Osgood

    2014-09-01

    Full Text Available Gelatinous bone marrow transformation (GMT, also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management.

  18. Toll-like receptors as targets for immune disorders.

    LENUS (Irish Health Repository)

    Keogh, Brian

    2012-02-01

    Since the identification of the first Toll-like receptor (TLR) in humans in 1997, understanding of the molecular basis for innate immunity has increased significantly. The TLR family and downstream signalling pathways have been extensively characterised, There is now significant evidence suggesting a role for TLRs in human inflammatory and immune diseases such as rheumatoid arthritis, diabetes, allergy\\/asthma and atherosclerosis. Various approaches have been taken to identify novel therapeutic agents targeting TLRs including biologics, small molecules and nucleic acid-based drugs. Several are now being evaluated in the clinic and showing promise against various diseases. This review paper outlines the recent advances in the understanding of TLR biology and highlights novel TLR agonists and antagonists in development for the treatment of immune diseases.

  19. Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

    NARCIS (Netherlands)

    Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Boezen, Hendrika; de Bock, Geertruida H; van der Graaf, Wilhelmina; Wesseling, Jelle

    2011-01-01

    The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast

  20. EGF receptor targeted tumor imaging with biotin-PEG-EGF linked to 99mTc-HYNIC labeled avidin and streptavidin

    International Nuclear Information System (INIS)

    Jung, Kyung-Ho; Park, Jin Won; Paik, Jin-Young; Quach, Cung Hoa Thien; Choe, Yearn Seong; Lee, Kyung-Han

    2012-01-01

    Introduction: As direct radiolabeled peptides suffer limitations for in vivo imaging, we investigated the usefulness of radioloabeled avidin and streptavidin as cores to link peptide ligands for targeted tumor imaging. Methods: Human epidermal growth factor (EGF) was site specifically conjugated with a single PEG-biotin molecule and linked to 99m Tc-HYNIC labeled avidin-FITC (Av) or streptavidin-Cy5.5 (Sav). Receptor targeting was verified in vitro, and in vivo pharmacokinetic and biodistribution profiles were studied in normal mice. Scintigraphic imaging was performed in MDA-MB-468 breast tumor xenografted nude mice. Results: Whereas both 99m Tc-Av-EGF and 99m Tc-Sav-EGF retained receptor-specific binding in vitro, the two probes substantially diverged in pharmacokinetic and biodistribution behavior in vivo. 99m Tc-Av-EGF was rapidly eliminated from the circulation with a T1/2 of 4.3 min, and showed intense hepatic accumulation but poor tumor uptake (0.6%ID/gm at 4 h). 99m Tc-Sav-EGF displayed favorable in vivo profiles of longer circulation (T1/2β, 51.5 min) and lower nonspecific uptake that resulted in higher tumor uptake (3.8 %ID/gm) and clear tumor visualization at 15 h. Conclusion: 99m Tc-HYNIC labeled streptavidin linked with growth factor peptides may be useful as a protein-ligand complex for targeted imaging of tumor receptors.

  1. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Xingguo, E-mail: chengx@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Vispute, Saurabh G. [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Cheng, Christine; Kharitonenkov, Alexei [Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, IN 46285 (United States); Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression.

  2. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    International Nuclear Information System (INIS)

    Cheng, Xingguo; Vispute, Saurabh G.; Liu, Jie; Cheng, Christine; Kharitonenkov, Alexei; Klaassen, Curtis D.

    2014-01-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression

  3. In-vivo fluorescence detection of breast cancer growth factor receptors by fiber-optic probe

    Science.gov (United States)

    Bustamante, Gilbert; Wang, Bingzhi; DeLuna, Frank; Sun, LuZhe; Ye, Jing Yong

    2018-02-01

    Breast cancer treatment options often include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2/neu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression. Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug. This requires diagnostic tools to provide tumor molecular signatures, as well as locational information. In this study, we utilized a fiber-optic probe to characterize in vivo HER2 and EGFR overexpressed tumors through the fluorescence of targeted dyes. HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors. The fiber was inserted into the samples via a 30-gauge needle. Different wavelengths of a supercontinuum laser were selected to couple into the fiber and excite the corresponding fluorophores in the samples. The fluorescence from the dyes was collected through the same fiber and quantified by a time-correlated single photon counter. Fluorescence at different antibody-dye concentrations was measured for calibration. Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates and were later probed at the tumor sites. The measured fluorescence was used to distinguish between tumor types and to calculate the concentration of the antibody-dye conjugates, which were detectable at levels as low as 40 nM. The fiber-optic probe presents a minimally invasive instrument to characterize the molecular signatures of breast cancer in vivo.

  4. A library of 7TM receptor C-terminal tails - Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, A.; Sondergaard, B.P.; Ersbøll, Bjarne Kjær

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK1 receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  5. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, Arne; Søndergaard, Birgitte P; Ersbøll, Bjarne

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1) receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  6. Variation of Hydroxyapatite Content in Soft Gelatin Affects Mesenchymal Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Fahsai Kantawong

    2016-01-01

    Full Text Available Gelatin is a common material used in tissue engineering and hydroxyapatite (HA has a composition and structure similar to natural bone mineral. HA is also used to increase the adhesion ability of scaffolds. The physical and mechanical properties of gelatin, together with the chemical properties of HA, can affect cell differentiation. The main purpose of this study is to investigate the gene expression of human mesenchymal stem cells (HMSCs upon culturing on gelatin composite with HA. Low amounts of HA were introduced into the gelatin in order to modulate properties of gelatin. Three types of hydrogel were fabricated by glutaraldehyde crosslinking before lyophilization to produce the porous 3D structure: (1 pure gelatin, (2 0.5 mg/ml HA in gelatin, and (3 1 mg/ml HA in gelatin. The fabricated hydrogels were used as scaffolds to cultivate HMSCs for two periods - 24 hours and 3 weeks. The results showed that all types of fabricated hydrogels could be used to cultivate HMSCs. Changes of gene expressions indicated that the HMSCs cultured on the 1 mg/ml HA in gelatin showed neuronal lineage-specific differentiation.

  7. The PACAP receptor: a novel target for migraine treatment

    DEFF Research Database (Denmark)

    Schytz, Henrik W; Olesen, Jes; Ashina, Messoud

    2010-01-01

    The origin of migraine pain has not yet been clarified, but accumulating data point to neuropeptides present in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in s......) receptor, which suggests a possible signaling pathway implicated in migraine pain. This review summarizes the current evidence supporting the involvement of PACAP in migraine pathophysiology and the PAC(1) receptor as a possible novel target for migraine treatment....

  8. Preparation of Rhodamine B Fluorescent Poly(methacrylic acid) Coated Gelatin Nanoparticles

    OpenAIRE

    Gan, Zhenhai; Ju, Jianhui; Zhang, Ting; Wu, Daocheng

    2011-01-01

    Poly(methacrylic acid) (PMAA)-coated gelatin nanoparticles encapsulated with fluorescent dye rhodamine B were prepared by the coacervation method with the aim to retard the release of rhodamine B from the gelatin matrix. With sodium sulfate as coacervation reagent for gelatin, a kind of biopolymer with excellent biocompatibility, the formed gelatin nanoparticles were cross-linked by formaldehyde followed by the polymerization of methacrylic acid coating. The fluorescent poly(methacrylic acid)...

  9. Gelatin Nanoparticles with Enhanced Affinity for Calcium Phosphate

    NARCIS (Netherlands)

    Farbod, K.; Diba, M.; Zinkevich, T.; Schmidt, S.; Harrington, M.J.; Kentgens, A.P.; Leeuwenburgh, S.C.

    2016-01-01

    Gelatin nanoparticles can be tuned with respect to their drug loading efficiency, degradation rate, and release kinetics, which renders these drug carriers highly suitable for a wide variety of biomedical applications. The ease of functionalization has rendered gelatin an interesting candidate

  10. Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle†

    OpenAIRE

    Xiao, Bo; Yang, Yang; Viennois, Emilie; Zhang, Yuchen; Ayyadurai, Saravanan; Baker, Mark; Laroui, Hamed; Merlin, Didier

    2014-01-01

    Treatment strategies for inflammatory bowel disease have been constrained by limited therapeutic efficacy and serious adverse effects owing to a lack of receptor for targeted drug delivery to the inflamed colon. Upon inflammation, CD98 expression is highly elevated in colonic epithelial cells and infiltrating immune cells. To investigate whether CD98 can be used as a colitis-targeted delivery receptor, we constructed CD98 Fab′-bearing quantum dots (QDs)-loaded nanoparticles (Fab′-NPs). The re...

  11. A mechanistic overview of herbal medicine and botanical compounds to target transcriptional factors in Breast cancer.

    Science.gov (United States)

    Zhao, Yingke; Liu, Yue

    2018-04-01

    The abnormalities of transcription factors, such as NF-κB, STAT, estrogen receptor, play a critical role in the initiation and progression of breast cancer. Due to the limitation of current treatment, transcription factors could be promising therapeutic targets, which have received close attention. In this review, we introduced herbal medicines, as well as botanical compounds that had been verified with anti-tumor properties via regulating transcription factors. Herbs, compounds, as well as formulae reported with various transcriptional targets, were summarized thoroughly, to provide implication for the future research on basic experiment and clinical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Preparation and Characterization of Gelatin Nanofibers Containing Silver Nanoparticles

    Science.gov (United States)

    Jeong, Lim; Park, Won Ho

    2014-01-01

    Ag nanoparticles (NPs) were synthesized in formic acid aqueous solutions through chemical reduction. Formic acid was used for a reducing agent of Ag precursor and solvent of gelatin. Silver acetate, silver tetrafluoroborate, silver nitrate, and silver phosphate were used as Ag precursors. Ag+ ions were reduced into Ag NPs by formic acid. The formation of Ag NPs was characterized by a UV-Vis spectrophotometer. Ag NPs were quickly generated within a few minutes in silver nitrate (AgNO3)/formic acid solution. As the water content of formic acid aqueous solution increased, more Ag NPs were generated, at a higher rate and with greater size. When gelatin was added to the AgNO3/formic acid solution, the Ag NPs were stabilized, resulting in smaller particles. Moreover, gelatin limits further aggregation of Ag NPs, which were effectively dispersed in solution. The amount of Ag NPs formed increased with increasing concentration of AgNO3 and aging time. Gelatin nanofibers containing Ag NPs were fabricated by electrospinning. The average diameters of gelatin nanofibers were 166.52 ± 32.72 nm, but these decreased with the addition of AgNO3. The average diameters of the Ag NPs in gelatin nanofibers ranged between 13 and 25 nm, which was confirmed by transmission electron microscopy (TEM). PMID:24758929

  13. Novel receptor targets for production and action of allopregnanolone in the central nervous system: a focus on pregnane xenobiotic receptor

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2014-04-01

    Full Text Available Neurosteroids are cholesterol-based hormones that can be produced in the brain, independent of secretion from peripheral endocrine glands, such as the gonads and adrenals. A focus in our laboratory for over 25 years has been how production of the pregnane neurosteroid, allopregnanolone, is regulated and the novel (i.e. non steroid receptor targets for steroid action for behavior. One endpoint of interest has been lordosis, the mating posture of female rodents. Allopregnanolone is necessary and sufficient for lordosis, and the brain circuitry underlying it, such as actions in the midbrain ventral tegmental area (VTA, has been well-characterized. Published and recent findings supporting a dynamic role of allopregnanolone are included in this review. First, contributions of ovarian and adrenal sources of precursors of allopregnanolone, and the requisite enzymatic actions for de novo production in the central nervous system will be discussed. Second, how allopregnanolone produced in the brain has actions on behavioral processes that are independent of binding to steroid receptors, but instead involve rapid modulatory actions via neurotransmitter targets (e.g. -amino butyric acid-GABA, n-methyl-D-aspartate- NMDA will be reviewed. Third, a recent focus on characterizing the role of a promiscuous nuclear receptor, pregnane xenobiotic receptor (PXR, involved in cholesterol metabolism and expressed in the VTA, as a target for allopregnanolone and how this relates to both actions and production of allopregnanolone will be addressed. For example, allopregnanolone can bind PXR and knocking down expression of PXR in the midbrain VTA attenuates actions of allopregnanolone via NMDA and/or GABAA for lordosis. Our understanding of allopregnanolone’s actions in the VTA for lordosis has been extended to reveal the role of allopregnanolone for broader, clinically-relevant questions, such as neuropsychiatric disorders, epilepsy, and aging.

  14. Enhanced Sternal Healing via Platelet-Rich Plasma and Biodegradable Gelatin Hydrogel.

    Science.gov (United States)

    Shibata, Masafumi; Takagi, Gen; Kudo, Mitsuhiro; Kurita, Jiro; Kawamoto, Yoko; Miyagi, Yasuo; Kanazashi, Mikimoto; Sakatani, Takashi; Naito, Zenya; Tabata, Yasuhiko; Miyamoto, Masaaki; Nitta, Takashi

    2018-05-16

    Platelet-rich plasma (PRP) contains numerous growth factors and promotes bone fracture healing. The aim of this study was to evaluate the effectiveness of the controlled release of PRP from biodegradable gelatin hydrogel for promoting healing in a rabbit ischemic sternal model. PRP was prepared from the whole blood of a Japanese white rabbit. Sixteen rabbits were randomized into four groups (each n = 4) and all underwent median sternotomy and bilateral internal thoracic artery removal. Before the sternum was closed, the following solutions were applied between the sternum incisions in three of the groups: 30 mg of gelatin hydrogel incorporating 300 μL of phosphate-buffered saline, 300 μL of a solution form of PRP, or 30 mg of gelatin hydrogel incorporating 300 μL of PRP (PRP+Gel). The fourth group acted as a control. Sternal healing was evaluated by histology and micro-computed tomography 7 days after the intervention. The PRP+Gel group showed a significantly higher proportion of fibrosis within the fracture area (an indicator of sternal healing) than the other groups and a significantly higher mean intensity of osteocalcin. These results indicate that the controlled release of PRP from locally applied gelatin hydrogel was markedly effective in enhancing sternal healing in the early postoperative period. This novel therapy could potentially help prevent complications such as deep sternal wound infection and could result in early postoperative ambulation after median sternotomy.

  15. Distribution of C-myc Antisense Oligonucleotides in Rabbits after Local Delivery by Implanted Gelatin Coated Piatinium -iridium Stent

    Institute of Scientific and Technical Information of China (English)

    张新霞; 庞志功; 崔长琮; 许香广; 胡雪松; 方卫华

    2003-01-01

    Objectives To assess the feasibility, efficiency and tissue distribution of localdelivered c - myc antisense oligonucleotides (ASODN)by implanted gelatin coated Platinium- Iridium (Pt-Ir) stent. Methods Gelatin coated Pt- Ir stentwhich absorbed carboxyfluorescein - 5 - succimidylester (FAM) labeled c -myc ASODN were implantedin the right carotid arteries of 6 rabbits under vision.Blood samples were collected at the indicated times.The target artery、 left carotid artery、 heart、 liver andkidney obtained at 45 minutes、 2 hours and 6hours. The concentration of c - myc ASODN in plasmaand tissues were determined by Thin Layer Fluorome-try. Tissue distribution of c- myc ASODN were as-sessed by fluorescence microscopy. Results At 45min, 2 h, 6 h, the concentration of FAM labeled c -myc ASODN in target artery was 244.39, 194.44,126.94(μg/g tissues) respectively, and the deliveryefficiency were 44.4% 、 35.4% and 23.1% respec-tively. At the same indicated time point, the plasmaconcentration was 8.41, 5. 83, 14.75 (μg/ml) respec-tively. Therefore c -myc ASODN concentrations in thetarget vessel were 29、 33 and 9 -fold higher than thatin the plasma. There was circumferential distribution oflabeled c -myc in the area of highest fluorescein co-inciding with the site of medial dissecting from stent-ing, and the label was most intense in target vesselmedia harvested at 45 min time point and then dis-persed to adventitia. Conclusions Gelatin coated Pt- Ir stent mediated local delivery of c - myc ASODN isfeasible and efficient. The localization of ASODN ismainly in target vessel wall.

  16. Novel Drosophila receptor that binds multiple growth factors

    International Nuclear Information System (INIS)

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-01-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10 -6 to 10 -8 M. The 100 kDa protein can be affinity-labeled with these 125 I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by 125 I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors

  17. Mechanical and barrier properties of maize starch-gelatin composite films: effects of amylose content.

    Science.gov (United States)

    Wang, Kun; Wang, Wenhang; Ye, Ran; Xiao, Jingdong; Liu, Yaowei; Ding, Junsheng; Zhang, Shaojing; Liu, Anjun

    2017-08-01

    In order to obtain new reinforcing bio-fillers to improve the physicochemical properties of gelatin-based films, three types of maize starch, waxy maize starch (Ap), normal starch (Ns) and high-amylose starch (Al), were incorporated into gelatin film and the resulting film properties were investigated, focusing on the impact of amylose content. The thickness, opacity and roughness of gelatin film increased depending on the amylose content along with the starch concentration. The effects of the three starches on the mechanical properties of gelatin film were governed by amylose content, starch concentration as well as environmental relative humidity (RH). At 75% RH, the presence of Al and Ns in the gelatin matrix increased the film strength but decreased its elongation, while Ap exhibited an inverse effect. Starch addition decreased the oxygen permeability of the film, with the lowest value at 20% Al and Ns. All starches, notably at 30% content, led to a decrease in the water vapor permeability of the film at 90% RH, especially Ns starch. Furthermore, the starches improved the thermal stability of the film to some extent. Fourier transform infrared spectra indicated that some weak intermolecular interactions such as hydrogen bonding occurred between gelatin and starch. Moreover, a high degree of B-type crystallinity of starch was characterized in Gel-Al film by X-ray diffraction. Tailoring the properties of gelatin film by the incorporation of different types of maize starch provides the potential to extend its applications in edible food packaging. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Effects of Long-term exposure of Gelatinated and Non-gelatinated Cadmium Telluride Quantum Dots on Differentiated PC12 cells

    LENUS (Irish Health Repository)

    Prasad, Babu R

    2012-01-20

    Abstract Background The inherent toxicity of unmodified Quantum Dots (QDs) is a major hindrance to their use in biological applications. To make them more potent as neuroprosthetic and neurotherapeutic agents, thioglycolic acid (TGA) capped CdTe QDs, were coated with a gelatine layer and investigated in this study with differentiated pheochromocytoma 12 (PC12) cells. The QD - cell interactions were investigated after incubation periods of up to 17 days by MTT and APOTOX-Glo Triplex assays along with using confocal microscopy. Results Long term exposure (up to 17 days) to gelatinated TGA-capped CdTe QDs of PC12 cells in the course of differentiation and after neurites were grown resulted in dramatically reduced cytotoxicity compared to non-gelatinated TGA-capped CdTe QDs. Conclusion The toxicity mechanism of QDs was identified as caspase-mediated apoptosis as a result of cadmium leaking from the core of QDs. It was therefore concluded that the gelatine capping on the surface of QDs acts as a barrier towards the leaking of toxic ions from the core QDs in the long term (up to 17 days).

  19. Gelatin promotes rapid restoration of the blood brain barrier after acute brain injury.

    Science.gov (United States)

    Kumosa, Lucas S; Zetterberg, Valdemar; Schouenborg, Jens

    2018-01-01

    Gelatin coating of brain implants is known to provide considerable benefits in terms of reduced inflammatory sequalae and long-term neuroprotective effects. However, the mechanisms for gelatin's protective role in brain injury are still unknown. To address this question, cellular and molecular markers were studied with quantitative immunohistochemical microscopy at acute (implantable devices for stimulation based therapy. Currently, this field is struggling to find solutions for reducing tissue reactions to implanted micro and nanotechnology. Prior studies have recently shown that gelatin coatings lower activation of digestive microglia and mitigate the ubiquitous loss of neurons adjacent to implanted probes, both of which impede implant function. The underlying mechanisms remain to be elucidated, however. Our findings demonstrate for the first time that gelatin has a significant effect on the BBB by promoting rapid restoration of integrity after injury. Moreover, gelatin alters microglia phenotypes and modulates gelatinase activity for up to 2weeks favoring anti-inflammation and restoration of the tissue. Given the key importance of the BBB for normal brain functions, we believe our findings have substantial significance and will be highly interesting to researchers in the biomaterial field. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Overview of receptor-based source apportionment studies for speciated atmospheric mercury

    OpenAIRE

    Cheng, I.; Xu, X.; Zhang, L.

    2015-01-01

    Receptor-based source apportionment studies of speciated atmospheric mercury are not only concerned with source contributions but also with the influence of transport, transformation, and deposition processes on speciated atmospheric mercury concentrations at receptor locations. Previous studies applied multivariate receptor models including principal components analysis and positive matrix factorization, and back trajectory receptor models including potential source contri...

  1. Barrier, structural and mechanical properties of bovine gelatin-chitosan blend films related to biopolymer interactions.

    Science.gov (United States)

    Benbettaïeb, Nasreddine; Kurek, Mia; Bornaz, Salwa; Debeaufort, Frédéric

    2014-09-01

    The increased use of synthetic packaging films has led to a high ecological problem due to their total non-biodegradability. Thus, there is a vital need to develop renewable and environmentally friendly bio-based polymeric materials. Films and coatings made from polysaccharide polymers, particularly chitosans and gelatins have good gas barrier properties and are envisaged more and more for applications in the biomedical and food fields, as well as for packaging. In this study a casting method was used to develop an edible plasticised film from chitosan and gelatin. Aiming to develop a blend film with enhanced properties, the effects of mixing chitosan (CS) and gelatin (G) in different proportions (CS:G, 75:25, 50:50, 25:75, w/w) on functional and physico-chemical properties have been studied. Mean film thickness increased linearly (R2 =0.999) with surface density of the film forming solution. An enhancement of mechanical properties by increasing the tensile strength (38.7±11 MPa for pure chitosan and 76.8±9 MPa for pure gelatin film) was also observed in blends, due to gelatin content.When the gelatin content in blend filmswas increased an improvement of both water vapour barrier properties [(4±0.3)×10(-10) g m(-1) s(-1) Pa(-1) for pure chitosan and (2.5±0.14)×10(-10) g m(-1) s(-1) Pa(-1) for pure gelatin, at 70% RH gradient] and oxygen barrier properties ((822.62±90.24)×10(-12) g m(-1) s(-1) Pa(-1) for blend film chitosan:gelatin (25:75 w/w) and (296.67±18.76)×10(-12) g m(-1) s(-1) Pa(-1) for pure gelatin was observed. Fourier transform infrared spectra of blend films showed a shift in the peak positions related to the amide groups (amide-I and amide-III) indicating interactions between biopolymers. Addition of gelatin in chitosan induced greater functional properties (mechanical, barrier) due to chemical interactions, suggesting an inter-penetrated network. © 2014 Society of Chemical Industry.

  2. Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties

    International Nuclear Information System (INIS)

    Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Nasri-Nasrabadi, Bijan; Ghaedi, Kamran; Salehi, Hossein; Dolatshahi-Pirouz, Alireza; Arpanaei, Ayyoob

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974 ± 68 nm for the pure PLGA scaffolds vs 832 ± 70, 764 ± 80, and 486 ± 64 for the PLGA/gelatin, PLGA/10 wt% MSNPs, and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes. - Highlights: • PLGA-based random nanofibers embedded with mesoporous silica nanoparticles were fabricated using electrospinning method • Incorporation of gelatin and MSNPs into PLGA-based scaffolds increased the hydrophilicity of scaffold • Addition of nanoparticles also improved the tensile mechanical properties of scaffolds • Introduction of MSNPs led to improved cell attachment and proliferation

  3. Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties

    Energy Technology Data Exchange (ETDEWEB)

    Mehrasa, Mohammad [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of); Asadollahi, Mohammad Ali, E-mail: ma.asadollahi@ast.ui.ac.ir [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Nasri-Nasrabadi, Bijan [Department of Chemical Engineering, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Ghaedi, Kamran [Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Salehi, Hossein [Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Dolatshahi-Pirouz, Alireza [DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark (DTU), DK-2800 Kgs. Lyngby (Denmark); Arpanaei, Ayyoob, E-mail: arpanaei@yahoo.com [Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of)

    2016-09-01

    Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974 ± 68 nm for the pure PLGA scaffolds vs 832 ± 70, 764 ± 80, and 486 ± 64 for the PLGA/gelatin, PLGA/10 wt% MSNPs, and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes. - Highlights: • PLGA-based random nanofibers embedded with mesoporous silica nanoparticles were fabricated using electrospinning method • Incorporation of gelatin and MSNPs into PLGA-based scaffolds increased the hydrophilicity of scaffold • Addition of nanoparticles also improved the tensile mechanical properties of scaffolds • Introduction of MSNPs led to improved cell attachment and proliferation.

  4. Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

    2018-06-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

  5. Carboxymethylated ɩ-carrageenan conjugated amphotericin B loaded gelatin nanoparticles for treating intracellular Candida glabrata infections.

    Science.gov (United States)

    Aparna, V; Melge, Anu Rohit; Rajan, V K; Biswas, Raja; Jayakumar, R; Gopi Mohan, C

    2018-04-15

    Intercellular Candida glabrata infections are difficult to treat due to poor penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B) into the macrophages where the pathogen inhabits is an effective solution. We are studying the macrophage targeting proficiency of ɩ-carrageenan for the delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A was the outcome of in silico inspections where the amino functionalized polymer having the best docking score with Amp B was selected. We prepared a sustained release formulation of amp B loaded carboxymethyl ɩ-carrageenan conjugated gelatin nanoparticles (CMC-Amp B-GNPs) with size 343±12nm and -25±5.3mV zeta potential. The formulations were found to be stable, biocompatible and non-haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced antifungal activity than bare Amp B and Amp B-GNPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Barium-cross-linked alginate-gelatine microcapsule as a potential platform for stem cell production and modular tissue formation.

    Science.gov (United States)

    Alizadeh Sardroud, Hamed; Nemati, Sorour; Baradar Khoshfetrat, Ali; Nabavinia, Mahbobeh; Beygi Khosrowshahi, Younes

    2017-08-01

    Influence of gelatine concentration and cross-linker ions of Ca 2+ and Ba 2+ was evaluated on characteristics of alginate hydrogels and proliferation behaviours of model adherent and suspendable stem cells of fibroblast and U937 embedded in alginate microcapsules. Increasing gelatine concentration to 2.5% increased extent of swelling to 15% and 25% for barium- and calcium-cross-linked hydrogels, respectively. Mechanical properties also decreased with increasing swelling of hydrogels. Both by increasing gelatine concentration and using barium ions increased considerably the proliferation of encapsulated model stem cells. Barium-cross-linked alginate-gelatine microcapsule tested for bone building block showed a 13.5 ± 1.5-fold expansion for osteoblast cells after 21 days with deposition of bone matrix. The haematopoietic stem cells cultured in the microcapsule after 7 days also showed up to 2-fold increase without adding any growth factor. The study demonstrates that barium-cross-linked alginate-gelatine microcapsule has potential for use as a simple and efficient 3D platform for stem cell production and modular tissue formation.

  7. Shooting with sound: optimizing an affordable ballistic gelatin recipe in a graded ultrasound phantom education program.

    Science.gov (United States)

    Tanious, Shariff F; Cline, Jamie; Cavin, Jennifer; Davidson, Nathan; Coleman, J Keegan; Goodmurphy, Craig W

    2015-06-01

    The goal of this study was to investigate the durability and longevity of gelatin formulas for the production of staged ultrasound phantoms for education. Gelatin phantoms were prepared from Knox gelatin (Kraft Foods, Northfield, IL) and a standard 10%-by-mass ordinance gelatin solution. Phantoms were durability tested by compressing to a 2-cm depth until cracking was visible. Additionally, 16 containers with varying combinations of phenol, container type, and storage location were tested for longevity against desiccation and molding. Once formulation was determined, 4 stages of phantoms from novice to clinically relevant were poured, and clinicians with ultrasound training ranked them on a 7-point Likert scale based on task difficulty, phantom suitability, and fidelity. On durability testing, the ballistic gelatin outperformed the Knox gelatin by more than 200 compressions. On longevity testing, gelatin with a 0.5% phenol concentration stored with a lid and refrigeration lasted longest, whereas containers without a lid had desiccation within 1 month, and those without phenol became moldy within 6 weeks. Ballistic gelatin was more expensive when buying in small quantities but was 7.4% less expensive when buying in bulk. The staged phantoms were deemed suitable for training, but clinicians did not consistently rank the phantoms in the intended order of 1 to 4 (44%). Refrigerated and sealed ballistic gelatin with phenol was a cost-effective method for creating in-house staged ultrasound phantoms suitable for large-scale ultrasound educational training needs. Clinician ranking of phantoms may be influenced by current training methods that favor biological tissue scanning as easier. © 2015 by the American Institute of Ultrasound in Medicine.

  8. Evaluation of tilapia skin gelatin as a mammalian gelatin replacer in acid milk gels and low-fat stirred yogurt.

    Science.gov (United States)

    Pang, Zhihua; Deeth, Hilton; Yang, Hongshun; Prakash, Sangeeta; Bansal, Nidhi

    2017-05-01

    Tilapia skin gelatin (TSG) was studied in a 3-stage process (cooling, annealing, and heating) for pure gelatin gels and in a 4-stage process (acidification, cooling, annealing, and heating) for acid milk gels and cultured yogurt. The aim was to evaluate the use of TSG as a replacement for mammalian gelatin in yogurt. In pure TSG gels, stronger gels with higher melting temperatures were formed with increasing TSG concentrations. Compared with bovine gelatin (BG), which gelled at a concentration of 2.5%, TSG gels had lower gelling (14.1°C) and melting (24°C) temperatures but comparable storage moduli during annealing. In acid milk gels, addition of TSG increased the firmness of the gels with increasing concentration. Gelling and melting points of TSG in milk gels were observed at sufficient concentrations during cooling and heating. Strands and sheets were observed in the electron micrographs of milk gels with 1% TSG and a very dense structure was observed with 2.5% TSG. Yogurt with 0.4% TSG had similar viscosity, consistency, pseudoplasticity, and thixotropy as yogurt containing 0.4% BG; no difference was perceived by sensory panelists according to a triangle test. Addition of 0.4% TSG completely prevented whey separation from the acid milk gel and yogurt. The results suggest that TSG could be a suitable replacement for mammalian gelatin in low-fat stirred yogurt. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Physicochemical properties, antimicrobial activity and oil release of fish gelatin films incorporated with cinnamon essential oil

    Directory of Open Access Journals (Sweden)

    Jiulin Wu

    2017-07-01

    Full Text Available Fish skin gelatin films incorporated with various concentrations of cinnamon essential oil (CEO were prepared and characterized. The results showed that tensile strength (TS, elongation at break (EAB, and water content (WC of the gelatin based film decreased with the increasing concentrations of CEO, but water vapor permeability (WVP increased. Addition of CEO improved light barrier property of the film. The Scanning electron microscope (SEM showed that the heterogeneous surface and porous formation appeared in gelatin-CEO films. Fourier transform infrared spectroscopy analyses (FTIR-ATR spectra indicated the interactions existed between gelatin and CEO. The gelatin-CEO films exhibited good inhibitory effects against the tested microorganisms (Escherichia coli, Staphylococcus aureus, Aspergillus niger, Rhizopus oryzae, and Paecilomyces varioti and their antifungal activity seemed to be more effective than the resistance to bacterial growth. In vitro release studies showed an initial burst effect of CEO release and that subsequently slowed down at 40 °C, but the initial burst release was not obvious at 4 °C. The obtained results suggested that incorporation of CEO as a natural antimicrobial agent into gelatin film has potential for developing as active food packaging.

  10. Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

    Science.gov (United States)

    Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  11. Comparison of water gel desserts from fish skin and pork gelatins using instrumental measurements.

    Science.gov (United States)

    Zhou, Peng; Regenstein, Joe M

    2007-05-01

    The objective of this study was to compare water gel desserts from various gelatins using instrumental measurements. The puncture test and texture profile analysis (TPA) with compression were determined at 25% and 75% deformation; the melting properties were determined rheologically by monitoring the change of storage modulus (G') with increasing temperature. The measurements with 25% deformation were always nondestructive, while measurements with 75% deformation were mostly destructive. Desserts made from Alaska pollock gelatin (AG) or gelatin mixtures containing AG were more resistant to the destruction caused by the large deformation than tilapia gelatin and pork gelatins. In addition, the gel dessert made from AG melted at a lower temperature than those from tilapia skin gelatin and pork gelatins, while desserts made from gelatin mixtures reflected the melting properties of the separate gelatins.

  12. Evaluation of cross-linked gelatin membranes as delivery carriers for retinal sheets

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Jui-Yang, E-mail: jylai@mail.cgu.edu.tw [Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302 Taiwan (China); Biomedical Engineering Research Center, Chang Gung University, Taoyuan, 33302 Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302 Taiwan (China); Li, Ya-Ting [Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302 Taiwan (China)

    2010-06-15

    The delivery of intact sheet transplants to the subretinal space can prevent cell loss that is generally associated with the injection of cell suspensions or cell aggregates. The aim of this study was to develop chemically modified gelatin matrices that enhance the delivery efficiency and analyze whether the gelatin membranes cross-linked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) can be considered as potential carriers for retinal sheets. The characteristics of EDC cross-linked gelatin membranes were determined by mechanical and in vitro degradation tests, melting point measurements, cell proliferation assays, cytokine expression analyses, and tissue delivery studies. Gelatin membranes without cross-linking and glutaraldehyde cross-linked gelatin samples were used for comparison. Results of this study indicated that introduction of cross-links is capable of rendering the gelatin network more stable against mechanical stresses and deformations as well as rapid hydrolysis during intraocular delivery of delicate tissue sheets. In comparison with the glutaraldehyde treated samples, the EDC cross-linked gelatin membranes showed a better degradation profile and a relatively higher cytocompatibility. In addition, after EDC cross-linking, the gelatin matrices having an acceptable melting point could be used for the fabrication of a sandwich-like carrier with a high transfer and encapsulation efficiency. These findings suggest that the cross-linking agent type gives an influence on delivery functionality of gelatin membranes. In summary, the EDC cross-linked gelatin is an ideal candidate for use as a carrier material in retinal sheet delivery applications.

  13. Insight into pattern of codon biasness and nucleotide base usage in serotonin receptor gene family from different mammalian species.

    Science.gov (United States)

    Dass, J Febin Prabhu; Sudandiradoss, C

    2012-07-15

    5-HT (5-Hydroxy-tryptamine) or serotonin receptors are found both in central and peripheral nervous system as well as in non-neuronal tissues. In the animal and human nervous system, serotonin produces various functional effects through a variety of membrane bound receptors. In this study, we focus on 5-HT receptor family from different mammals and examined the factors that account for codon and nucleotide usage variation. A total of 110 homologous coding sequences from 11 different mammalian species were analyzed using relative synonymous codon usage (RSCU), correspondence analysis (COA) and hierarchical cluster analysis together with nucleotide base usage frequency of chemically similar amino acid codons. The mean effective number of codon (ENc) value of 37.06 for 5-HT(6) shows very high codon bias within the family and may be due to high selective translational efficiency. The COA and Spearman's rank correlation reveals that the nucleotide compositional mutation bias as the major factors influencing the codon usage in serotonin receptor genes. The hierarchical cluster analysis suggests that gene function is another dominant factor that affects the codon usage bias, while species is a minor factor. Nucleotide base usage was reported using Goldman, Engelman, Stietz (GES) scale reveals the presence of high uracil (>45%) content at functionally important hydrophobic regions. Our in silico approach will certainly help for further investigations on critical inference on evolution, structure, function and gene expression aspects of 5-HT receptors family which are potential antipsychotic drug targets. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Wet method for measuring starch gelatinization temperature using electrical conductivity.

    Science.gov (United States)

    Morales-Sanchez, E; Figueroa, J D C; Gaytan-Martínez, M

    2009-09-01

    The objective of the present study was to develop a method for obtaining the gelatinization temperature of starches by using electrical conductivity. Native starches from corn, rice, potato, and wheat were prepared with different proportions of water and heated from room temperature to 90 degrees C, in a device especially designed for monitoring the electrical conductivity as a function of temperature. The results showed a linear trend of the electrical conductivity with the temperature until it reaches the onset gelatinization temperature. After that point, the electrical conductivity presented an increment or decrement depending on the water content in the sample and it was related to starch swelling and gelatinization phenomena. At the end gelatinization temperature, the conductivity becomes stable and linear, indicating that there are no more changes of phase. The starch gelatinization parameter, which was evaluated in the 4 types of starches using the electrical conductivity, was compared with those obtained by using differential scanning calorimeter (DSC). The onset temperature at which the electrical conductivity increased or decreased was found to be similar to that obtained by DSC. Also, the final temperature at which the electrical conductivity returned to linearity matched the end gelatinization temperature of the DSC. Further, a wet method for measuring the onset, peak, and end gelatinization temperatures as a function of temperature using the electrical conductivity curves is presented for a starch-water suspension.

  15. Chitosan-based DNA delivery vector targeted to gonadotropin-releasing hormone (GnRH) receptor.

    Science.gov (United States)

    Boonthum, Chatwalee; Namdee, Katawut; Boonrungsiman, Suwimon; Chatdarong, Kaywalee; Saengkrit, Nattika; Sajomsang, Warayuth; Ponglowhapan, Suppawiwat; Yata, Teerapong

    2017-02-10

    The main purpose of this study was to investigate the application of modified chitosan as a potential vector for gene delivery to gonadotropin-releasing hormone receptor (GnRHR)-expressing cells. Such design of gene carrier could be useful in particular for gene therapy for cancers related to the reproductive system, gene disorders of sexual development, and contraception and fertility control. In this study, a decapeptide GnRH was successfully conjugated to chitosan (CS) as confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The synthesized GnRH-conjugated chitosan (GnRH-CS) was able to condense DNA to form positively charged nanoparticles and specifically deliver plasmid DNA to targeted cells in both two-dimensional (2D) and three-dimensional (3D) cell cultures systems. Importantly, GnRH-CS exhibited higher transfection activity compared to unmodified CS. In conclusion, GnRH-conjugated chitosan can be a promising carrier for targeted DNA delivery to GnRHR-expressing cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

    Science.gov (United States)

    Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

    2018-01-01

    The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

  17. Acid-base and electrolyte status during normovolemic hemodilution with succinylated gelatin or HES-containing volume replacement solutions in rats.

    Directory of Open Access Journals (Sweden)

    Johanna K Teloh

    Full Text Available BACKGROUND: In the past, several studies have compared different colloidal replacement solutions, whereby the focus was usually on the respective colloid. We therefore systematically studied the influence of the carrier solution's composition of five approved colloidal volume replacement solutions (Gelafundin, Gelafusal, Geloplasma, Voluven and Volulyte on acid-base as well as electrolyte status during and following acute severe normovolemic hemodilution. The solutions differed in the colloid used (succinylated gelatin vs. HES and in the presence and concentration of metabolizable anions as well as in their electrolyte composition. METHODS: Anesthetized Wistar rats were subjected to a stepwise normovolemic hemodilution with one of the solutions until a final hematocrit of 10%. Subsequent to dilution (162 min, animals were observed for an additional period (150 min. During dilution and observation time blood gas analyses were performed eight times in total. Additionally, in the Voluven and Volulyte groups as well as in 6 Gelafundin animals, electrolyte concentrations, glucose, pH and succinylated gelatin were measured in urine and histopathological evaluation of the kidney was performed. RESULTS: All animals survived without any indications of injury. Although the employed solutions differed in their respective composition, comparable results in all plasma acid-base and electrolyte parameters studied were obtained. Plasma pH increased from approximately 7.28 to 7.39, the plasma K(+ concentration decreased from circa 5.20 mM to 4.80-3.90 mM and the plasma Cl(- concentration rose from approximately 105 mM to 111-120 mM. Urinary analysis revealed increased excretion of K(+, H(+ and Cl(-. CONCLUSIONS: The present data suggest that the carrier solution's composition with regard to metabolizable anions as well as K(+, Ca(2+ only has a minor impact on acid-base and electrolyte status after application of succinylated gelatin or HES-containing colloidal

  18. Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation on Tumor-Associated Endothelial Cells Leads to Treatment of Orthotopic Human Colon Cancer in Nude Mice

    Directory of Open Access Journals (Sweden)

    Takamitsu Sasaki

    2007-12-01

    Full Text Available The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-α and vascular endothelial growth factor (VEGF but were negative for EGFR, human epidermal growth factor receptor 2 (HER2, VEGFR. Double immunofluorescence staining revealed that tumorassociated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR, phosphorylated VEGFR (pVEGFR. Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase or CPT-11 as single agents significantly inhibited the growth of cecal tumors (P < .01; this decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001. AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and pVEGFR on tumor-associated endothelial cells, significantly decreased vascularization and tumor cell proliferation, increased the level of apoptosis in both tumorassociated endothelial cells and tumor cells. These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer.

  19. Translational PK-PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576.

    Science.gov (United States)

    Bursi, Roberta; Erdemli, Gul; Campbell, Robert; Hutmacher, Matthew M; Kerbusch, Thomas; Spanswick, David; Jeggo, Ross; Nations, Kari R; Dogterom, Peter; Schipper, Jacques; Shahid, Mohammed

    2011-12-01

    The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor potentiator Org 26576 represents an interesting pharmacological tool to evaluate the utility of glutamatergic enhancement towards the treatment of psychiatric disorders. In this study, a rat-human translational pharmacokinetic-pharmacodynamic (PK-PD) model of AMPA receptor modulation was used to predict human target engagement and inform dose selection in efficacy clinical trials. Modelling and simulation was applied to rat plasma and cerebrospinal fluid (CSF) pharmacokinetic and pharmacodynamic measurements to identify a target concentration (EC(80)) for AMPA receptor modulation. Human plasma pharmacokinetics was determined from 33 healthy volunteers and eight major depressive disorder patients. From four out of these eight patients, CSF PK was also determined. Simulations of human CSF levels were performed for several doses of Org 26576. Org 26576 (0.1-10 mg/kg, i.v.) potentiated rat hippocampal AMPA receptor responses in an exposure-dependant manner. The rat plasma and CSF PK data were fitted by one-compartment model each. The rat CSF PK-PD model yielded an EC(80) value of 593 ng/ml (90% confidence interval 406.8, 1,264.1). The human plasma and CSF PK data were simultaneously well described by a two-compartment model. Simulations showed that in humans at 100 mg QD, CSF levels of Org 26576 would exceed the EC(80) target concentration for about 2 h and that 400 mg BID would engage AMPA receptors for 24 h. The modelling approach provided useful insight on the likely human dose-molecular target engagement relationship for Org 26576. Based on the current analysis, 100 and 400 mg BID would be suitable to provide 'phasic' and 'continuous' AMPA receptor engagement, respectively.

  20. Investigating Linear and Nonlinear Viscoelastic behaviour and microstructures of Gelatine-Multiwalled carbon nanotubes composites

    KAUST Repository

    Yang, Zhi

    2015-12-01

    We have investigated the linear and nonlinear rheology of various gelatine-multiwalled carbon nanotube (gel-MWNT) composites, namely physically-crosslinked-gelatine gel-MWNT composites, chemically-crosslinked-gelatine gel-MWNT composites, and chemically-physically-crosslinked-gelatine gel-MWNT composites. Further, the internal structures of these gel-MWNT composites were characterized by ultra-small angle neutron scattering and scanning electron microscopy. The adsorption of gelatine onto the surface of MWNT is also investigated to understand gelatine-assisted dispersion of MWNT during ultrasonication. For all gelatine gels, addition of MWNT increases their complex modulus. The dependence of storage modulus with frequency for gelatine-MWNT composites is similar to that of the corresponding neat gelatine matrix. However, by incorporating MWNT, the dependence of the loss modulus on frequency is reduced. The linear viscoelastic region is decreased approximately linearly with the increase of MWNT concentration. The pre-stress results demonstrate that the addition of MWNT does not change the strain-hardening behaviour of physically-crosslinked gelatine gel. However, the addition of MWNT can increase the strain-hardening behaviour of chemically-crosslinked gelatine gel, and chemically-physically crosslinked gelatine gel. Results from light microscopy, cryo-SEM, and USANS demonstrate the hierarchical structures of MWNT, including that tens-of-micron scale MWNT agglomerates are present. Furthermore, the adsorption curve of gelatine onto the surface of MWNT follows two-stage pseudo-saturation behaviour.

  1. Gelatin Tight-Coated Poly(lactide-co-glycolide Scaffold Incorporating rhBMP-2 for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2015-03-01

    Full Text Available Surface coating is the simplest surface modification. However, bioactive molecules can not spread well on the commonly used polylactone-type skeletons; thus, the surface coatings of biomolecules are typically unstable due to the weak interaction between the polymer and the bioactive molecules. In this study, a special type of poly(lactide-co-glycolide (PLGA-based scaffold with a loosened skeleton was fabricated by phase separation, which allowed gelatin molecules to more readily diffuse throughout the structure. In this application, gelatin modified both the internal substrate and external surface. After cross-linking with glutaraldehyde, the surface layer gelatin was tightly bound to the diffused gelatin, thereby preventing the surface layer gelatin coating from falling off within 14 days. After gelatin modification, PLGA scaffold demonstrated enhanced hydrophilicity and improved mechanical properties (i.e., increased compression strength and elastic modulus in dry and wet states. Furthermore, a sustained release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2 was achieved in the coated scaffold. The coated scaffold also supported the in vitro attachment, proliferation, and osteogenesis of rabbit bone mesenchymal stem cells (BMSCs, indicating the bioactivity of rhBMP-2. These results collectively demonstrate that the cross-linked-gelatin-coated porous PLGA scaffold incorporating bioactive molecules is a promising candidate for bone tissue regeneration.

  2. Structure-based drug design for G protein-coupled receptors.

    Science.gov (United States)

    Congreve, Miles; Dias, João M; Marshall, Fiona H

    2014-01-01

    Our understanding of the structural biology of G protein-coupled receptors has undergone a transformation over the past 5 years. New protein-ligand complexes are described almost monthly in high profile journals. Appreciation of how small molecules and natural ligands bind to their receptors has the potential to impact enormously how medicinal chemists approach this major class of receptor targets. An outline of the key topics in this field and some recent examples of structure- and fragment-based drug design are described. A table is presented with example views of each G protein-coupled receptor for which there is a published X-ray structure, including interactions with small molecule antagonists, partial and full agonists. The possible implications of these new data for drug design are discussed. © 2014 Elsevier B.V. All rights reserved.

  3. Identification of potential pathway mediation targets in Toll-like receptor signaling.

    Directory of Open Access Journals (Sweden)

    Fan Li

    2009-02-01

    Full Text Available Recent advances in reconstruction and analytical methods for signaling networks have spurred the development of large-scale models that incorporate fully functional and biologically relevant features. An extended reconstruction of the human Toll-like receptor signaling network is presented herein. This reconstruction contains an extensive complement of kinases, phosphatases, and other associated proteins that mediate the signaling cascade along with a delineation of their associated chemical reactions. A computational framework based on the methods of large-scale convex analysis was developed and applied to this network to characterize input-output relationships. The input-output relationships enabled significant modularization of the network into ten pathways. The analysis identified potential candidates for inhibitory mediation of TLR signaling with respect to their specificity and potency. Subsequently, we were able to identify eight novel inhibition targets through constraint-based modeling methods. The results of this study are expected to yield meaningful avenues for further research in the task of mediating the Toll-like receptor signaling network and its effects.

  4. Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

    International Nuclear Information System (INIS)

    Hu, Zhiwei; Rao, Benqiang; Chen, Shimin; Duanmu, Jinzhong

    2010-01-01

    The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia. Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers

  5. Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis.

    Science.gov (United States)

    Yu-Wai-Man, Cynthia; Tagalakis, Aristides D; Manunta, Maria D; Hart, Stephen L; Khaw, Peng T

    2016-02-24

    There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

  6. A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging.

    Science.gov (United States)

    Sano, Kohei; Masuda, Ryo; Hisada, Hayato; Oishi, Shinya; Shimokawa, Kenta; Ono, Masahiro; Fujii, Nobutaka; Saji, Hideo; Mukai, Takahiro

    2014-03-01

    We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. (67)Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with (67)Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Sigma-1 receptor: The novel intracellular target of neuropsychotherapeutic drugs

    Directory of Open Access Journals (Sweden)

    Teruo Hayashi

    2015-01-01

    Full Text Available Sigma-1 receptor ligands have been long expected to serve as drugs for treatment of human diseases such as neurodegenerative disorders, depression, idiopathic pain, drug abuse, and cancer. Recent research exploring the molecular function of the sigma-1 receptor started unveiling underlying mechanisms of the therapeutic activity of those ligands. Via the molecular chaperone activity, the sigma-1 receptor regulates protein folding/degradation, ER/oxidative stress, and cell survival. The chaperone activity is activated or inhibited by synthetic sigma-1 receptor ligands in an agonist-antagonist manner. Sigma-1 receptors are localized at the endoplasmic reticulum (ER membranes that are physically associated with the mitochondria (MAM: mitochondria-associated ER membrane. In specific types of neurons (e.g., those at the spinal cord, sigma-1 receptors are also clustered at ER membranes that juxtapose postsynaptic plasma membranes. Recent studies indicate that sigma-1 receptors, partly in sake of its unique subcellular localization, regulate the mitochondria function that involves bioenergetics and free radical generation. The sigma-1 receptor may thus provide an intracellular drug target that enables controlling ER stress and free radical generation under pathological conditions.

  8. EKSTRAKSI GELATIN DARI KAKI AYAM BROILER MELALUI BERBAGAI LARUTAN ASAM DAN BASA DENGAN VARIASI LAMA PERENDAMAN

    Directory of Open Access Journals (Sweden)

    Muhammad Rasyid Indrawan

    2016-12-01

    Full Text Available Gelatin is a biopolymer that can be obtained from partially hydrolysis of collagen present in skin, bone, and connective tissues of animals This study used chicken Broiler feet as a source of collagen. This study was conducted to determine the effect of soaking treatment with solution of acid and base, and with variety of soaking time. The solution used is HCl, CH3COOH, and NaOH with different concentration. The process of soaking followed by extraction, filtration, and drying to obtain a sheet of gelatin. Gelatin was analyzed qualitatively with chemical reaction. The best results of yield can be obtained from various methods of soaking given by HCl 2% for 2 days, CH3COOH 2% for 3 days, and NaOH 2% for 1 day. Keywords : Gelatin, Chicken feet Broiler’s, Acid-treated, Alkali-treated ABSTRAK Gelatin merupakan biopolimer yang biasanya diperoleh dari hidrolisis parsial kolagen jaringan kulit, tulang, dan jaringan ikat hewan. Penelitian ini menggunakan kaki ayam broiler sebagai sumber kolagen. Penelitian dilakukan untuk melihat pengaruh perlakuan perendaman kaki ayam broiler melalui berbagai larutan asam dan basa dengan variasi lama perendaman. Larutan yang digunakan yaitu HCl, CH3COOH, dan NaOH dengan berbagai konsentrasi. Proses perendaman dilanjutkan dengan ekstraksi, filtrasi, dan pengeringan untuk mendapatkan lembaran gelatin. Gelatin yang diperoleh dianalisis secara kualitatif melalui reaksi kimia. Hasil rendemen terbaik dapat diperoleh dari berbagai metode perendaman yaitu HCl 2% selama 2 hari, CH3COOH 2% selama 3 hari, dan NaOH 2% selama 1 hari. Kata Kunci : Gelatin, Kaki ayam Broiler, Metode asam, Metode basa

  9. Dehydration of pollock skin prior to gelatin production

    Science.gov (United States)

    Alaska pollock (Theragra chalcogramma) is the U.S.A.'s largest commercial fishery, with an annual catch of over 1 million tons. During pollock processing, the skins are discarded or made into fish meal, despite their value for gelatin production. The absence of gelatin-processing facilities in Alask...

  10. Characterization of cell-surface receptors for monoclonal-nonspecific suppressor factor (MNSF)

    International Nuclear Information System (INIS)

    Nakamura, M.; Ogawa, H.; Tsunematsu, T.

    1990-01-01

    Monoclonal-nonspecific suppressor factor (MNSF) is a lymphokine derived from murine T cell hybridoma. The target tissues are both LPS-stimulated B cells and Con A-stimulated T cells. Since the action of MNSF may be mediated by its binding to specific cell surface receptors, we characterized the mode of this binding. The purified MNSF was labeled with 125 I, using the Bolton-Hunter reagent. The labeled MNSF bound specifically to a single class of receptor (300 receptors per cell) on mitogen-stimulated murine B cells or T cells with an affinity of 16 pM at 24 degrees C, in the presence of sodium azide. Competitive experiments showed that MNSF bound to the specific receptor and that the binding was not shared with IL2, IFN-gamma, and TNF. Various cell types were surveyed for the capacity to specifically bind 125 I-MNSF. 125 I-MNSF bound to MOPC-31C (a murine plasmacytoma line) and to EL4 (a murine T lymphoma line). The presence of specific binding correlates with the capacity of the cells to respond to MNSF. These data support the view that like other polypeptide hormones, the action of MNSF is mediated by specific cell surface membrane receptor protein. Identification of these receptors will provide insight into the apparently diverse activities of MNSF

  11. Extraction and characterisation of gelatin from the skin of striped ...

    African Journals Online (AJOL)

    Functional properties of gelatin from skin of striped catfish with and without bleaching for 48 h by 5% H2O2 (w/v)) were studied. Gelatin from skin bleached with 5% H2O2 for 48 h showed the highest yield (16.18 g). Bleaching not only improved the colour of gelatin gel by increasing the L* (lightness)-value and decreasing ...

  12. Biomimetic Synthesis of Gelatin Polypeptide-Assisted Noble-Metal Nanoparticles and Their Interaction Study

    Science.gov (United States)

    Liu, Ying; Liu, Xiaoheng; Wang, Xin

    2011-12-01

    Herein, the generation of gold, silver, and silver-gold (Ag-Au) bimetallic nanoparticles was carried out in collagen (gelatin) solution. It first showed that the major ingredient in gelatin polypeptide, glutamic acid, acted as reducing agent to biomimetically synthesize noble metal nanoparticles at 80°C. The size of nanoparticles can be controlled not only by the mass ratio of gelatin to gold ion but also by pH of gelatin solution. Interaction between noble-metal nanoparticles and polypeptide has been investigated by TEM, UV-visible, fluorescence spectroscopy, and HNMR. This study testified that the degradation of gelatin protein could not alter the morphology of nanoparticles, but it made nanoparticles aggregated clusters array (opposing three-dimensional α-helix folding structure) into isolated nanoparticles stabilized by gelatin residues. This is a promising merit of gelatin to apply in the synthesis of nanoparticles. Therefore, gelatin protein is an excellent template for biomimetic synthesis of noble metal/bimetallic nanoparticle growth to form nanometer-sized device.

  13. The characterisation of a genipin-gelatin gel dosimeter

    International Nuclear Information System (INIS)

    Davies, J B; Bosi, S; Baldock, C

    2010-01-01

    Genipin cross links gelatin to slowly form a blue colour that bleaches upon irradiation. Spectrophotometric measurements of the absorbance change following irradiation to doses up to 100 Gy gives a linear dose response for certain concentrations of the gel ingredients; genipin, gelatin and sulphuric acid. Dose sensitivity increases with increasing concentrations of sulphuric acid and genipin and is also strongly dependent on the time allowed for the genipin-gelatin cross linking reaction (referred to here as blending) to take place. The optimum formulation of this gel was found for genipin concentration between 0.3 - 0.5 mM and blending time of at least 4 h.

  14. Gelatin/piassava composites treated by Electron Beam Radiation

    International Nuclear Information System (INIS)

    Takinami, Patricia Yoko Inamura; Shimazaki, Kleber; Moura, Esperidiana Augusta Barretos de; Mastro, Nelida Lucia del; Colombo, Maria Aparecida

    2010-01-01

    Piassava (Attalea funifera Mart) fiber has been investigated as reinforcement for polymer composites with potential for practical applications. The purpose of the present work was to assess the behavior of specimens of piassava fiber and gelatin irradiated with electron beam at different doses and percentage. The piassava/gelatin specimens were made with 5 and 10% (w/w) piassava fiber, gelatin 25% (w/w), glycerin as plasticizer and acrylamide as copolymer. The samples were irradiated up to 40 kGy using an electron beam accelerator, at room temperature in presence of air. Preliminary results showed mechanical properties enhancement with the increase in radiation dose. (author)

  15. A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network

    Directory of Open Access Journals (Sweden)

    De Graaf David

    2007-07-01

    Full Text Available Abstract Background The nuclear receptors are a large family of eukaryotic transcription factors that constitute major pharmacological targets. They exert their combinatorial control through homotypic heterodimerisation. Elucidation of this dimerisation network is vital in order to understand the complex dynamics and potential cross-talk involved. Results Phylogeny, protein-protein interactions, protein-DNA interactions and gene expression data have been integrated to provide a comprehensive and up-to-date description of the topology and properties of the nuclear receptor interaction network in humans. We discriminate between DNA-binding and non-DNA-binding dimers, and provide a comprehensive interaction map, that identifies potential cross-talk between the various pathways of nuclear receptors. Conclusion We infer that the topology of this network is hub-based, and much more connected than previously thought. The hub-based topology of the network and the wide tissue expression pattern of NRs create a highly competitive environment for the common heterodimerising partners. Furthermore, a significant number of negative feedback loops is present, with the hub protein SHP [NR0B2] playing a major role. We also compare the evolution, topology and properties of the nuclear receptor network with the hub-based dimerisation network of the bHLH transcription factors in order to identify both unique themes and ubiquitous properties in gene regulation. In terms of methodology, we conclude that such a comprehensive picture can only be assembled by semi-automated text-mining, manual curation and integration of data from various sources.

  16. Buffer capacity of 4% succinylated gelatin does not provide any advantages over acidic 6% hydroxyethyl starch 130/0.4 for acid-base balance during experimental mixed acidaemia in a porcine model.

    Science.gov (United States)

    Esche, V; Russ, M; Melzer, S; Grossmann, B; Boemke, W; Unger, J K

    2008-11-01

    Four percent gelatine is an alkaline compound due to NH2 groups, whereas 6% hydroxyethyl starch 130/0.4 (HES130) has acidic features. We investigated whether these solutions lead to differences in acid-base balance in pigs during acidaemia and correction of pH. Anaesthetized pigs were randomized to HES130 or gelatine infusion (n = 5 per group). Animals received acid infusion (0.4 M solution of lactic acid and HCl diluted in normal saline) and low tidal volume ventilation (6-7 mL kg(-1), PaCO2 of 80-85 mmHg, pH 7.19-7.24). Measurements were made before and after induction of acidaemia, before and after correction of pH with haemofiltration (continuous venovenous haemofiltration) and tris-hydroxymethylaminomethane infusion. We measured parameters describing acid-base balance according to Stewart's approach, ketone body formation, oxygen delivery, haemodynamics, diuresis and urinary pH. Acid-base balance did not differ significantly between the groups. In HES130-treated pigs, the haemodilution-based drop of haemoglobin (1.4 +/- 1.0 g dL(-1), median +/- SD) was paralleled by an increase in the cardiac output (0.5 +/- 0.4 L min(-1). Lacking increases in cardiac output, gelatine-treated pigs demonstrated a reduction in oxygen delivery (149.4 +/- 106.0 mL min(-1)). Tris-hydroxymethylaminomethane volumes required for pH titration to desired values were significantly higher in the gelatine group (0.7 +/- 0.1 mL kg(-1) h(-1) vs. HES130: 0.5 +/- 0.2 mL kg(-1) h(-1)). The buffer capacity of gelatine did not lead to favourable differences in acid-base balance in comparison to HES130.

  17. MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis

    International Nuclear Information System (INIS)

    Guo, Li-Juan; Liao, Lan; Yang, Li; Li, Yu; Jiang, Tie-Jian

    2014-01-01

    MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and block of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease. - Highlights: • MiR-125a was significantly down-regulated in osteoclastogenesis of CD14+ PBMCs. • MiR-125a inhibited osteoclast differentiation by targeting TRAF6. • NFATc1 inhibited miR-125a transciption by binding to the promoter of miR-125a. • TRAF6/NFATc1 and miR-125a form a regulatory feedback loop in osteoclastogenesis

  18. Electron beam irradiation and addition of poly(vinyl alcohol) affect gelatin based-films properties

    International Nuclear Information System (INIS)

    Inamura, Patricia Y.; Mastro, Nelida L. del

    2015-01-01

    Gelatin is a mixture of high molecular weight polypeptides, product of denaturation, and partial structural degradation of collagen, and one of the first materials employed as biomaterials. Aqueous solutions of gelatin (10%), glycerin as plasticizer and poly(vinyl alcohol) (PVA) up to 10% were prepared in a water bath at 70 deg C under constant stirring. Films were irradiated with 10 and 20 kGy using an electron beam accelerator, dose rate of 22.4 kGy s -1 , energy 1.407 MeV, at room temperature, in the presence of air. After irradiation, mechanical properties, color measurements, water absorption, moisture and film solubility were analyzed. The films showed an improvement in maximum force to rupture the film with increase of the irradiation dose. The higher the puncture force to rupture the lower the elongation at break. Colorimetric tests showed significant differences between samples, and also differences depending of the applied radiation dose, and analyzed color parameter. In water absorption tests a decrease of absorption percentage was found with the increase of the dose for PVA free and 5% PVA samples. The addition of PVA increased the water absorption for all applied doses. The modifications in gelatin colloids can be appointed to radiation-induced crosslinking. Also, the PVA concentration in the samples influenced the resultant material properties. (author)

  19. Electron beam irradiation and addition of poly(vinyl alcohol) affect gelatin based-films properties

    Energy Technology Data Exchange (ETDEWEB)

    Inamura, Patricia Y.; Mastro, Nelida L. del, E-mail: pinamura@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Gelatin is a mixture of high molecular weight polypeptides, product of denaturation, and partial structural degradation of collagen, and one of the first materials employed as biomaterials. Aqueous solutions of gelatin (10%), glycerin as plasticizer and poly(vinyl alcohol) (PVA) up to 10% were prepared in a water bath at 70 deg C under constant stirring. Films were irradiated with 10 and 20 kGy using an electron beam accelerator, dose rate of 22.4 kGy s{sup -1}, energy 1.407 MeV, at room temperature, in the presence of air. After irradiation, mechanical properties, color measurements, water absorption, moisture and film solubility were analyzed. The films showed an improvement in maximum force to rupture the film with increase of the irradiation dose. The higher the puncture force to rupture the lower the elongation at break. Colorimetric tests showed significant differences between samples, and also differences depending of the applied radiation dose, and analyzed color parameter. In water absorption tests a decrease of absorption percentage was found with the increase of the dose for PVA free and 5% PVA samples. The addition of PVA increased the water absorption for all applied doses. The modifications in gelatin colloids can be appointed to radiation-induced crosslinking. Also, the PVA concentration in the samples influenced the resultant material properties. (author)

  20. Gold Nanorods Targeted to Delta Opioid Receptor: Plasmon-Resonant Contrast and Photothermal Agents

    Directory of Open Access Journals (Sweden)

    Kvar C. Black

    2008-01-01

    Full Text Available Molecularly targeted gold nanorods were investigated for applications in both diagnostic imaging and disease treatment with cellular resolution. The nanorods were tested in two genetically engineered cell lines derived from the human colon carcinoma HCT-116, a model for studying ligand-receptor interactions. One of these lines was modified to express delta opioid receptor (δOR and green fluorescent protein, whereas the other was receptor free and expressed a red fluorescent protein, to serve as the control. Deltorphin, a high-affinity ligand for δOR, was stably attached to the gold nanorods through a thiol-terminated linker. In a mixed population of cells, we demonstrated selective imaging and destruction of receptor-expressing cells while sparing those cells that did not express the receptor. The molecularly targeted nanorods can be used as an in vitro ligand-binding and cytotoxic treatment assay platform and could potentially be applied in vivo for diagnostic and therapeutic purposes with endoscopic technology.

  1. Characterization of pre-gelatinized rice and bean flour

    Directory of Open Access Journals (Sweden)

    Ana Vânia Carvalho

    2013-06-01

    Full Text Available The objective of this study was to develop a pre-gelatinized flour using a mixture of broken rice and split beans by thermoplastic extrusion, and to evaluate the physicochemical, nutritional, and technological quality of the final product. The extrusion parameters were maintained using three heating zones with temperatures of 30 ºC, 40 ºC, and 70 ºC; screw speed of 177 rpm; feed rate of 257 g/m, and circular matrix of 3.85 mm. The following characterization analyses were performed: physicochemical, nutritional, water absorption index (WAI, water solubility index (WSI, and paste viscosity. The pre-gelatinized rice and bean flour had an intermediate value of WAI, 7.51 g/g, and high WSI value, 24.61%. Regarding proteins, it was verified an average content of 12.9% in the final product. The amino acid contents found in the pre-gelatinized flour indicate that the mixture has the essential amino acids. It was also found that the pre-gelatinized flour supplies more than 60% of the essential amino acids recommended for children aged one to three years old. The gelatinized flour composed of broken rice and split beans is an alternative to the use of these by-products of the manufacture process of rice and beans to obtain a product with viable technological characteristics and high nutritional value.

  2. Emulsion stability and properties of fish gelatin-based films as affected by palm oil and surfactants.

    Science.gov (United States)

    Nilsuwan, Krisana; Benjakul, Soottawat; Prodpran, Thummanoon

    2016-05-01

    Gelatin films exhibit the poor water vapour barrier properties. The use of palm oil, which is abundant and available in Thailand, can be a means to lower water vapour migration. To disperse oil in film-forming dispersion (FFD), a surfactant along with appropriate homogenization is required. The study aimed to investigate the influence of palm oil level and surfactants in the absence or presence of glycerol on characteristics of FFD and resulting gelatin films. Similar oil droplet sizes, both d32 and d43 values, of FFD containing soy lecithin were observed, regardless of palm oil level used (P > 0.05). FFD with Tween-20 had larger droplet size as the levels of oil increased (P palm oil level increased (P 0.05). FFD containing 500 or 750 g kg(-1) palm oil using soy lecithin as a surfactant in the presence of 300 g kg(-1) glycerol had the enhanced homogeneity and stability of oil droplets. The resulting gelatin film had the improved water vapour barrier properties. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  3. Gelatin Functionalization of Biomaterial Surfaces: Strategies for Immobilization and Visualization

    Directory of Open Access Journals (Sweden)

    Peter Dubruel

    2011-01-01

    Full Text Available In the present work, the immobilization of gelatin as biopolymer on two types of implantable biomaterials, polyimide and titanium, was compared. Both materials are known for their biocompatibility while lacking cell-interactive behavior. For both materials, a pre-functionalization step was required to enable gelatin immobilization. For the polyimide foils, a reactive succinimidyl ester was introduced first on the surface, followed by covalent grafting of gelatin. For the titanium material, methacrylate groups were first introduced on the Ti surface through a silanization reaction. The applied functionalities enabled the subsequent immobilization of methacrylamide modified gelatin. Both surface modified materials were characterized in depth using atomic force microscopy, static contact angle measurements, confocal fluorescence microscopy, attenuated total reflection infrared spectroscopy and X-ray photo-electron spectroscopy. The results indicated that the strategies elaborated for both material classes are suitable to apply stable gelatin coatings. Interestingly, depending on the material class studied, not all surface analysis techniques are applicable.

  4. Integration of bio-inspired, control-based visual and olfactory data for the detection of an elusive target

    Science.gov (United States)

    Duong, Tuan A.; Duong, Nghi; Le, Duong

    2017-01-01

    In this paper, we present an integration technique using a bio-inspired, control-based visual and olfactory receptor system to search for elusive targets in practical environments where the targets cannot be seen obviously by either sensory data. Bio-inspired Visual System is based on a modeling of extended visual pathway which consists of saccadic eye movements and visual pathway (vertebrate retina, lateral geniculate nucleus and visual cortex) to enable powerful target detections of noisy, partial, incomplete visual data. Olfactory receptor algorithm, namely spatial invariant independent component analysis, that was developed based on data of old factory receptor-electronic nose (enose) of Caltech, is adopted to enable the odorant target detection in an unknown environment. The integration of two systems is a vital approach and sets up a cornerstone for effective and low-cost of miniaturized UAVs or fly robots for future DOD and NASA missions, as well as for security systems in Internet of Things environments.

  5. Targeting the dopamine D3 receptor: an overview of drug design strategies.

    Science.gov (United States)

    Cortés, Antoni; Moreno, Estefanía; Rodríguez-Ruiz, Mar; Canela, Enric I; Casadó, Vicent

    2016-07-01

    Dopamine is a neurotransmitter widely distributed in both the periphery and the central nervous system (CNS). Its physiological effects are mediated by five closely related G protein-coupled receptors (GPCRs) that are divided into two major subclasses: the D1-like (D1, D5) and the D2-like (D2, D3, D4) receptors. D3 receptors (D3Rs) have the highest density in the limbic areas of the brain, which are associated with cognitive and emotional functions. These receptors are therefore attractive targets for therapeutic management. This review summarizes the functional and pharmacological characteristics of D3Rs, including the design and clinical relevance of full agonists, partial agonists and antagonists, as well as the capacity of these receptors to form active homodimers, heterodimers or higher order receptor complexes as pharmacological targets in several neurological and neurodegenerative disorders. The high sequence homology between D3R and the D2-type challenges the development of D3R-selective compounds. The design of new D3R-preferential ligands with improved physicochemical properties should provide a better pharmacokinetic/bioavailability profile and lesser toxicity than is found with existing D3R ligands. It is also essential to optimize D3R affinity and, especially, D3R vs. D2-type binding and functional selectivity ratios. Developing allosteric and bitopic ligands should help to improve the D3R selectivity of these drugs. As most evidence points to the ability of GPCRs to form homomers and heteromers, the most promising therapeutic strategy in the future is likely to involve the application of heteromer-selective drugs. These selective ligands would display different affinities for a given receptor depending on the receptor partners within the heteromer. Therefore, designing novel compounds that specifically target and modulate D1R-D3R heteromers would be an interesting approach for the treatment of levodopa (L-DOPA)-induced dyskinesias.

  6. Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo.

    Science.gov (United States)

    Traboulsi, Wael; Sergent, Frédéric; Boufettal, Houssine; Brouillet, Sophie; Slim, Rima; Hoffmann, Pascale; Benlahfid, Mohammed; Zhou, Qun Y; Balboni, Gianfranco; Onnis, Valentina; Bolze, Pierre A; Salomon, Aude; Sauthier, Philippe; Mallet, François; Aboussaouira, Touria; Feige, Jean J; Benharouga, Mohamed; Alfaidy, Nadia

    2017-11-15

    Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors, PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy. Experimental Design: Three approaches were used: (i) a clinical investigation comparing circulating EG-VEGF in control ( n = 20) and in distinctive CHM ( n = 38) and CC ( n = 9) cohorts, (ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and (iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice. Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (×5) patients. EG-VEGF increased JEG3 proliferation, migration, and invasion in two-dimensional (2D) and three-dimensional (3D) culture systems. JEG3 injection in the placenta caused CC development with large metastases compared with their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions. Conclusions: Our work describes a novel preclinical animal model of CC and presents evidence that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared with the currently used multi-agent chemotherapies. Clin Cancer Res; 23(22); 7130-40. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. PENGARUH JENIS LARUTAN PERENDAM SERTA METODE PENGERINGAN TERHADAP SIFAT FISIK, KIMIA, DAN FUNGSIONAL GELATIN DARI KULIT CUCUT [The Influence of Solvent Variety and Drying Method on Physical, Chemical and Functional Characteristic of Shark Skin Gelatin

    Directory of Open Access Journals (Sweden)

    Made Astawan 1

    2003-04-01

    Full Text Available Gelatin is a denaturation product of collagen and has been widely utilized for foods, photography uses, medical materials, and culture materials for microorganisms. Recently, gelatin’s uses has expanded to new applications such as health foods. Gelatin of land animal origin such as bovine and porcine has been mainly used. However, gelatin with new properties is desired to develop expanded applications. In this research gelatin was made from shark skin. The shark skin collagen was distended by acetic acid solution (acid process and sodium hydroxide solution (alkali process, and gelatin was then extracted at 80oC of water. The extracted gelatin was dried by vacuum drying and freeze drying to obtain powder product. Shark gelatin produced by the combination of alkali and vacuum drying process (OVB gelatin had better qualities on yield, water content, gel strength, melting point, and emulsion stability as compared to the others. Sensory evaluation indicated that shark gelatin had lower values in color, odor, and performance as compared to the commercial gelatin of fish, pig and bovine (SKW Biosystem. However, as compared to the commercial gelatins, OVB gelatin had a similar values on gel strength (202 bloom and emulsion stability (100%, but higher values on viscosity (8 cP and pH (9.3. Those values indicated that ray skin gelatin can be used to substitute the commercial gelatin in some food industries

  8. Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis.

    Science.gov (United States)

    Chiu, Christopher W; Nozawa, Hiroaki; Hanahan, Douglas

    2010-10-10

    Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics. Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy. Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.

  9. Viscoelastic shock wave in ballistic gelatin behind soft body armor.

    Science.gov (United States)

    Liu, Li; Fan, Yurun; Li, Wei

    2014-06-01

    Ballistic gelatins are widely used as a surrogate of biological tissue in blunt trauma tests. Non-penetration impact tests of handgun bullets on the 10wt% ballistic gelatin block behind soft armor were carried out in which a high-speed camera recorded the crater׳s movement and pressure sensors imbedded in the gelatin block recorded the pressure waves at different locations. The observed shock wave attenuation indicates the necessity of considering the gelatin׳s viscoelasticity. A three-element viscoelastic constitutive model was adopted, in which the relevant parameters were obtained via fitting the damping free oscillations at the beginning of the creep-mode of rheological measurement, and by examining the data of published split Hopkinson pressure bar (SHPB) experiments. The viscoelastic model is determined by a retardation time of 5.5×10(-5)s for high oscillation frequencies and a stress relaxation time of 2.0-4.5×10(-7)s for shock wave attenuation. Using the characteristic-line method and the spherical wave assumption, the propagation of impact pressure wave front and the subsequent unloading profile can be simulated using the experimental velocity boundary condition. The established viscoelastic model considerably improves the prediction of shock wave attenuation in the ballistic gelatin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Radiation synthesis and characterization of nanosilver/gelatin/carboxymethyl chitosan hydrogel

    International Nuclear Information System (INIS)

    Zhou Ying; Zhao Yinghui; Wang Lu; Xu Ling; Zhai Maolin; Wei Shicheng

    2012-01-01

    A series of antibacterial hydrogels were fabricated from an aqueous solution of AgNO 3 , gelatin and carboxymethyl chitosan (CM-chitosan) by radiation-induced reduction and crosslinking at ambient temperature. The nanosilver particles were in situ synthesized accompanying with the formation of gelatin/CM-chitosan hydrogel. Transmission Electron Microscope and UV–vis analysis have verified the formation and homogeneous distribution of nanosilver particles in the hydrogel matrix. The nanosilver/gelatin/CM-chitosan hydrogels possessed interconnected porous structure, had a compressive modulus of 44 to 56 kPa, and could absorb 62 to 108 times of deionized water to its dry weight. Furthermore, the hydrogels were found to have sound antibacterial effect on Escherichia coli (E. coli), and their antibacterial ability could be significantly enhanced by the increasing of AgNO 3 content. The comprehensive results of this study suggest that nanosilver/gelatin/CM-chitosan hydrogels have potential as an antibacterial wound dressing. - Highlights: ► Nanosilver/gelatin/CM-chitosan hydrogel was synthesized by radiation crosslinking. ► Nanosilver particles distributed homogeneously in the hydrogel. ► The size of nanosilver increased with the increase of AgNO 3 concentration. ► The nanosilver/gelatin/CM-chitosan hydrogel has antibacterial ability.

  11. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity

    DEFF Research Database (Denmark)

    Brandt, Julia P; Aziz-Zaman, Sonya; Juozaityte, Vaida

    2012-01-01

    . We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2). The ETS-5 transcription factor is necessary for the specification of CO(2)-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient...

  12. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

    Knapp DW. Targeting folate receptors to treat invasive urinary bladder cancer . Cancer Res 2013;73(2):875–884. 71. Holm J, Hansen SI, Hoier-Madsen M...purpose of this review, active targeting in cancer research encompasses strategies wherein a ligand for a cell surface receptor expressed on tumor...trafficking, thus impacting the efficacy of receptor -mediated drug delivery for cancer therapy. These factors include the following: (i) the rate of ligand

  13. Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    The effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)-directed changes in vascular permeability are poorly characterized. This study investigated whether adenosine modulates activated PMN vascular endothelial growth factor (vascular permeability factor; VEGF) release and transendothelial migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng\\/mL) were incubated with adenosine and its receptor-specific analogues. Culture supernatants were assayed for VEGF. PMN transendothelial migration across human umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro. Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine and some of its receptor-specific analogues dose-dependently inhibited activated PMN VEGF release. The rank order of potency was consistent with the affinity profile of human A2B receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100 microM) or the A2B receptor agonist 5\\'-N-ethylcarboxamidoadenosine (NECA, 100 microM) significantly reduced PMN transendothelial migration. However, expression of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A2B receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.

  14. From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation

    Directory of Open Access Journals (Sweden)

    Ken Howick

    2017-01-01

    Full Text Available Ghrelin is the only known peripherally-derived orexigenic hormone, increasing appetite and subsequent food intake. The ghrelinergic system has therefore received considerable attention as a therapeutic target to reduce appetite in obesity as well as to stimulate food intake in conditions of anorexia, malnutrition and cachexia. As the therapeutic potential of targeting this hormone becomes clearer, it is apparent that its pleiotropic actions span both the central nervous system and peripheral organs. Despite a wealth of research, a therapeutic compound specifically targeting the ghrelin system for appetite modulation remains elusive although some promising effects on metabolic function are emerging. This is due to many factors, ranging from the complexity of the ghrelin receptor (Growth Hormone Secretagogue Receptor, GHSR-1a internalisation and heterodimerization, to biased ligand interactions and compensatory neuroendocrine outputs. Not least is the ubiquitous expression of the GHSR-1a, which makes it impossible to modulate centrallymediated appetite regulation without encroaching on the various peripheral functions attributable to ghrelin. It is becoming clear that ghrelin’s central signalling is critical for its effects on appetite, body weight regulation and incentive salience of food. Improving the ability of ghrelin ligands to penetrate the blood brain barrier would enhance central delivery to GHSR-1a expressing brain regions, particularly within the mesolimbic reward circuitry.

  15. Intraoperative fluorescence delineation of head and neck cancer with a fluorescent Anti-epidermal growth factor receptor nanobody

    NARCIS (Netherlands)

    Van Driel, P.B.A.A.; Van Der Vorst, J.R.; Verbeek, F.P.R.; Oliveira, S.|info:eu-repo/dai/nl/304841455; Snoeks, T.J.A.; Keereweer, S.; Chan, B.; Boonstra, M.C.; Frangioni, J.V.; Van Bergen En Henegouwen, P.M.P.|info:eu-repo/dai/nl/071919481; Vahrmeijer, A.L.; Lowik, C.W.G.M.

    2014-01-01

    Intraoperative near-infrared (NIR) fluorescence imaging is a technology with high potential to provide the surgeon with real-time visualization of tumors during surgery. Our study explores the feasibility for clinical translation of an epidermal growth factor receptor (EGFR)-targeting nanobody for

  16. Gelatin behaviour in dilute aqueous solution : designing a nanoparticulate formulation

    OpenAIRE

    Farrugia, Claude; Groves, Michael J.

    1999-01-01

    Although it has been claimed that nanoparticles can be produced from gelatin, a naturally occurring polypeptide, the commercial conversion of animal collagen to gelatin results in a heterogeneous product with a wide molecular-weight range. This is probably responsible for the widely observed variation in the experimental conditions required for nanoparticle formation. In this study, 0.2% w/v aqueous B225 gelatin solutions were incubated under various conditions of time, temperature, pH an...

  17. Targeting Multiple Tumors Using T-Cells Engineered to Express a Natural Cytotoxicity Receptor 2-Based Chimeric Receptor

    Directory of Open Access Journals (Sweden)

    Vasyl Eisenberg

    2017-09-01

    Full Text Available Recent developments in cancer treatment are demonstrating the increasing and powerful potential of immunotherapeutic strategies. In this regard, the adoptive transfer of tumor-specific T-lymphocytes approaches can lead to tumor regression in cancer patients. More recently, the use of T-cells genetically engineered to express cancer-specific receptors such as the anti-CD19 chimeric antigen receptor (CAR continues to show promise for the treatment of hematological malignancies. Still, there is a crucial need to develop efficient CAR-T cell approaches for the treatment of solid tumors. It has been shown that other lymphocytes such as natural killer (NK cells can demonstrate potent antitumor function—nonetheless, their use in immunotherapy is rather limited due to difficulties in expanding these cells to therapeutically relevant numbers and to suppression by endogenous inhibitory mechanisms. Cancer recognition by NK cells is partly mediated by molecules termed natural cytotoxicity receptors (NCRs. In the present study, we hypothesize that it is possible to endow T-cells with an NK recognition pattern, providing them with a mean to recognize tumor cells, in a non-MHC restricted way. To test this, we genetically modified human T-cells with different chimeric receptors based on the human NCR2 molecule and then assessed their antitumor activity in vitro and in vivo. Our results show that expression in primary lymphocytes of an NCR2-derived CAR, termed s4428z, confers T-cells with the ability to specifically recognize heterogeneous tumors and to mediate tumor cytotoxicity in a mouse model. This study demonstrates the benefit of combining tumor recognition capability of NK cells with T cell effectiveness to improve cancer immunotherapy.

  18. Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

    NARCIS (Netherlands)

    van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

    1990-01-01

    Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

  19. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    Science.gov (United States)

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  20. The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

    International Nuclear Information System (INIS)

    Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.; Anderson, Redmond-Craig; Zeng, Chenbo; Xu, Kuiying; Hou, Catherine; McDonald, Elizabeth S.; Pryma, Daniel A.; Mach, Robert H.

    2015-01-01

    Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with

  1. The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.; Anderson, Redmond-Craig; Zeng, Chenbo; Xu, Kuiying; Hou, Catherine; McDonald, Elizabeth S.; Pryma, Daniel A.; Mach, Robert H., E-mail: rmach@mail.med.upenn.edu

    2015-11-27

    Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with

  2. Single-mode biological distributed feedback lasers based on vitamin B2 doped gelatin

    DEFF Research Database (Denmark)

    Vannahme, Christoph; Maier-Flaig, F.; Lemmer, U.

    Biological second-order distributed feedback (DFB) lasers are presented. Riboflavin (vitamin B2) doped gelatin as active material is spin-coated onto nanoimprinted polymer with low refractive index. DFB grating periods of 368 nm and 384 nm yield laser emission at 543 nm and 562 nm, respectively....

  3. Hydrophilic PCU scaffolds prepared by grafting PEGMA and immobilizing gelatin to enhance cell adhesion and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Changcan; Yuan, Wenjie; Khan, Musammir; Li, Qian [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Feng, Yakai, E-mail: yakaifeng@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072 (China); Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine, Tianjin 300072 (China); Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin) Tianjin 300072 (China); Yao, Fanglian [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072 (China); Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine, Tianjin 300072 (China); Zhang, Wencheng, E-mail: wenchengzhang@yahoo.com [Department of Physiology and Pathophysiology, Logistics University of Chinese People' s Armed Police Force, Tianjin 300162 (China)

    2015-05-01

    Gelatin contains many functional motifs which can modulate cell specific adhesion, so we modified polycarbonate urethane (PCU) scaffold surface by immobilization of gelatin. PCU-g-gelatin scaffolds were prepared by direct immobilizing gelatins onto the surface of aminated PCU scaffolds. To increase the immobilization amount of gelatin, poly(ethylene glycol) methacrylate (PEGMA) was grafted onto PCU scaffolds by surface initiated atom transfer radical polymerization. Then, following amination and immobilization, PCU-g-PEGMA-g-gelatin scaffolds were obtained. Both modified scaffolds were characterized by chemical and biological methods. After immobilization of gelatin, the microfiber surface became rough, but the original morphology of scaffolds was maintained successfully. PCU-g-PEGMA-g-gelatin scaffolds were more hydrophilic than PCU-g-gelatin scaffolds. Because hydrophilic PEGMA and gelatin were grafted and immobilized onto the surface, the PCU-g-PEGMA-g-gelatin scaffolds showed low platelet adhesion, perfect anti-hemolytic activity and excellent cell growth and proliferation capacity. It could be envisioned that PCU-g-PEGMA-g-gelatin scaffolds might have potential applications in tissue engineering artificial scaffolds. - Graphical abstract: PCU-g-gelatin scaffolds were prepared by direct immobilizing gelatin onto the surface of aminated PCU scaffolds (method a). To increase the immobilization amount of gelatin, PEGMAs were grafted onto the scaffold surface by SI-ATRP. PCU-g-PEGMA-g-gelatin scaffolds were prepared by method b. The gelatin modified scaffolds exhibited high hydrophilicity, low platelet adhesion, perfect anti-hemolytic activity, and excellent cell adhesion and proliferation capacity. They might have potential applications as tissue engineering scaffolds for artificial blood vessels. - Highlights: • Hydrophilic scaffolds were prepared by grafting PEGMA and immobilization of gelatins. • Grafting PEGMA enhanced the immobilization amount of gelatin

  4. Healing improvement after rotator cuff repair using gelatin-grafted poly(L-lactide) electrospun fibrous membranes.

    Science.gov (United States)

    Zhao, Song; Xie, Xiaoxing; Pan, Guoqing; Shen, Peng; Zhao, Jinzhong; Cui, Wenguo

    2015-01-01

    Rotator cuff tears (RCTs) are a common cause of shoulder pain and disability in middle and older age. Despite improvements in the understanding of this disease process and advances in surgical treatment, rotator cuff (RC) repair failure rates remain high. Insufficient healing capacity is likely the main factor for failure of reconstruction. We fabricated implantable biodegradable gelatin-grafted poly(L-lactide) (PLLA) fibrous membranes using electrospinning technology and evaluated them using in vitro cell proliferation assays. Then, we established chronic rat RCT models and randomly assigned rats into one of three groups. In group 1 (n = 48), the detached supraspinatus tendon was repaired to its anatomic footprint (transosseous repair). In groups 2 and 3, the rats underwent transosseous repair and were implanted with either pure PLLA membranes (n = 48) or gelatin-PLLA membranes (n = 48) to augment the repairs. The animals were killed at 2, 4, and 8 wk postoperatively, which was followed by histomorphometric and biomechanical evaluation. Histologic observations revealed that gelatin-PLLA membranes have excellent biocompatibility and biodegradability. At 2, 4, and 8 wk postoperatively, the gelatin-PLLA membranes significantly increased the area of glycosaminoglycan staining at the tendon-bone interface compared with the control group (P < 0.05) and significantly improved collagen organization, as measured by birefringence under polarized light at the healing enthesis compared with the control and PLLA groups (P < 0.05). Biomechanical testing revealed that the gelatin-PLLA group had a greater ultimate load to failure and stiffness than the control group at 4 and 8 wk (P < 0.05). The gelatin-PLLA membranes had the highest stress of the healing enthesis. Local application of gelatin-PLLA fibrous membranes to the healing tendon-bone interface after RC repair in a rat chronic RCT model was found to strengthen the healing enthesis, increase the area of

  5. Enhancement of recovery of Neisseria meningitidis by gelatin in blood culture media.

    OpenAIRE

    Pai, C H; Sorger, S

    1981-01-01

    The efficacy of gelatin for the recovery of Neisseria meningitidis from blood cultures was evaluated in a clinical setting. The organism was isolated from seven patients with meningococcal infections in blood culture media containing 1% gelatin. In contrast, only two blood cultures from these patients were positive in media without gelatin (P less than 0.05). Gelatin did not influence the recovery of other organisms isolated during this study. Conventional blood culture media may be supplemen...

  6. Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

    Science.gov (United States)

    Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

    2011-07-01

    We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

  7. Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders

    International Nuclear Information System (INIS)

    Agarwal, Swati; Yadav, Anuradha; Chaturvedi, Rajnish Kumar

    2017-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found that the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models. - Highlights: • Peroxisome -activated receptors (PPARs) serve to be a promising therapeutic target for several neurodegenerative disorders. • PPAR agonist as well as provides neuroprotection in vitro as well as in vivo animal models of neurodegenerative disorders. • PPAR activating anti-inflammatory drugs use is effective in decreasing progression of neurodegenerative diseases.

  8. Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

    Science.gov (United States)

    Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

    2013-03-01

    Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

  9. Plasma and tissue insulin-like growth factor-I receptor (IGF-IR) as a prognostic marker for prostate cancer and anti-IGF-IR agents as novel therapeutic strategy for refractory cases: a review.

    Science.gov (United States)

    Ozkan, Emine Elif

    2011-09-15

    Cancer database analysis indicates that prostate cancer is one of the most seen cancers in men meanwhile composing the leading cause of morbidity and mortality among developed countries. Current available therapies are surgery, radiotherapy and androgene ablation for prostate carcinoma. The response rate is as high nearly 90% however, most of these recur or become refractory and androgene independent (AI). Therefore recent studies intensified on molecular factors playing role on development of prostate carcinoma and novel treatment strategies targetting these factors and their receptors. Insulin-like growth factor-I (IGF-I) and its primary receptor insulin-like growth factor receptor-I (IGF-IR) are among these factors. Biologic functions and role in malign progression are primarily achieved via IGF-IR which is a type 2 tyrosine kinase receptor. IGF-IR plays an important role in mitogenesis, angiogenesis, transformation, apoptosis and cell motility. It also generates intensive proliferative signals leading to carcinogenesis in prostate tissue. So IGF-IR and its associated signalling system have provoked considerable interest over recent years as a novel therapeutic target in cancer. In this paper it is aimed to sum up the lately published literature searching the relation of IGF-IR and prostate cancer in terms of incidence, pathologic features, and prognosis. This is followed by a discussion of the different possible targets within the IGF-1R system, and drugs developed to interact at each target. A systems-based approach is then used to review the in vitro and in vivo data in the published literature of the following compounds targeting IGF-1R components using specific examples: growth hormone releasing hormone antagonists (e.g. JV-1-38), growth hormone receptor antagonists (e.g. pegvisomant), IGF-1R antibodies (e.g. CP-751,871, AVE1642/EM164, IMC-A12, SCH-717454, BIIB022, AMG 479, MK-0646/h7C10), and IGF-1R tyrosine kinase inhibitors (e.g. BMS-536942, BMS-554417

  10. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  11. A new crystal structure fragment-based pharmacophore method for G protein-coupled receptors

    DEFF Research Database (Denmark)

    Fidom, Kimberley; Isberg, Vignir; Hauser, Alexander Sebastian

    2015-01-01

    and receptor residue pairs, from crystal structure complexes. We describe the procedure to collect a library with more than 250 fragments covering 29 residue positions within the generic transmembrane binding pocket. We describe how the library fragments are recombined and inferred to build pharmacophores...... for new targets. A validating retrospective virtual screening of histamine H1 and H3 receptor pharmacophores yielded area-under-the-curves of 0.88 and 0.82, respectively. The fragment-based method has the unique advantage that it can be applied to targets for which no (homologous) crystal structures...... or ligands are known. 47% of the class A G protein-coupled receptors can be targeted with at least four-element pharmacophores. The fragment libraries can also be used to grow known ligands or for rotamer refinement of homology models. Researchers can download the complete fragment library or a subset...

  12. Comparative biodistribution of 12 111In-labelled gastrin/CCK2 receptor-targeting peptides

    NARCIS (Netherlands)

    P. Laverman (Peter); L. Joosten; A. Eek (Annemarie); S. Roosenburg (Susan); P.K. Peitl; T. Maina (Theodosia); H.R. Mäcke (Helmut); L. Aloj (Luigi); E. von Guggenber (Elisabeth); J.K. Sosabowski (Jane); M. de Jong (Marion); J.-C. Reubi (Jean-Claude); W.J.G. Oyen (Wim); O.C. Boerman (Otto)

    2011-01-01

    textabstractPurpose Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide

  13. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

    Science.gov (United States)

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

    2017-09-01

    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  14. Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

    Science.gov (United States)

    Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

    2015-01-01

    The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

  15. Investigations on the Chemical Degradation of Silver Gelatine Prints

    Directory of Open Access Journals (Sweden)

    Maha Ahmed ALI

    2012-06-01

    Full Text Available Photographs are considered composite objects with complex chemical and physical structures. Therefore they are more prone to damage as compared to other objects. Chemical degradation is by far the most common decay form found among photographic collections. This study investigates the chemical degradation of silver gelatin prints (DOP and the reaction of the image, silver, gelatin, and paper to accelerated aging, to the action of light, and oxidizing gases, in terms of their physical and chemical nature. The test materials used are properly washed and poorly washed grayscale, black-and-white processed images on photographic paper (Black & White Photographic Paper BH 0 Bromofort 6P0661 Tropical from Forte Photochemical Company Vác, Hungary. After exposure, the results were studied by means of visual inspection, amino acid analyzer, Fourier transform infrared and transmission electron microscope. The results were compared with those of the control samples. Our study revealed that the image, silver, gelatin and photographic paper are greatly affected by oxidizing agents and that the effect increased if the photographic prints were inadequately washed at the time of their processing. Furthermore, our results indicated that an increased amount of ammonia and amino acid in the silver gelatin print is a reliable indicator of the degradation of its gelatine emulsion.

  16. Gelatin as a new humidity sensing material: Characterization and limitations

    Energy Technology Data Exchange (ETDEWEB)

    Shapardanis, Steven [School of Engineering and Technology, Central Michigan University, Mt. Pleasant, Michigan, 48859 (United States); Hudpeth, Mathew [Department of Physics, Central Michigan University, Mt. Pleasant, Michigan, 48859 (United States); Kaya, Tolga, E-mail: kaya2t@cmich.edu [School of Engineering and Technology, Central Michigan University, Mt. Pleasant, Michigan, 48859 (United States); Science of Advanced Materials Program, Central Michigan University, Mt. Pleasant, Michigan, 48859 (United States)

    2014-12-15

    The goal of this work is to assert the utility of collagen and its denatured counterpart gelatin as cost-effective alternatives to existing sensing layers comprised of polymers. Rather than producing a material that will need to be discarded or recycled, collagen, as a by-product of the meat and leather industry, could be repurposed. This work examines the feasibility of using collagen as a sensing layer. Planar electrodes were patterned with lift-off process to work with the natural characteristics of gelatin by utilizing metal vapor deposition, spin coating, and photolithography. Characterization methods have also been optimized through the creation of specialized humidity chambers that isolate specific characteristics such as response time, accuracy, and hysteresis. Collagen-based sensors are found to have a sensitivity to moisture in the range of 0.065 pF/%RH. Diffusion characteristics were also analyzed with the diffusion coefficient found to be 2.5 × 10{sup −5} cm{sup 2}/s. Absorption and desorption times were found to be 20 seconds and 8 seconds, respectively. Hysteresis present in the data is attributed to temperature cross-sensitivity. Ultimately, the utility of collagen as a dielectric sensing material is, in part, due to its fibrous macrostructures as well its hydrophilic sites along the peptide chains. Gelatin was patterned between and below interdigitated copper electrodes and tested as a relative humidity sensor. This work shows that gelatin, which is inexpensive, widely available, and easy to process, can be an effective dielectric sensing polymer for capacitive-type relative humidity sensors.

  17. Gelatin as a new humidity sensing material: Characterization and limitations

    Directory of Open Access Journals (Sweden)

    Steven Shapardanis

    2014-12-01

    Full Text Available The goal of this work is to assert the utility of collagen and its denatured counterpart gelatin as cost-effective alternatives to existing sensing layers comprised of polymers. Rather than producing a material that will need to be discarded or recycled, collagen, as a by-product of the meat and leather industry, could be repurposed. This work examines the feasibility of using collagen as a sensing layer. Planar electrodes were patterned with lift-off process to work with the natural characteristics of gelatin by utilizing metal vapor deposition, spin coating, and photolithography. Characterization methods have also been optimized through the creation of specialized humidity chambers that isolate specific characteristics such as response time, accuracy, and hysteresis. Collagen-based sensors are found to have a sensitivity to moisture in the range of 0.065 pF/%RH. Diffusion characteristics were also analyzed with the diffusion coefficient found to be 2.5 × 10−5 cm2/s. Absorption and desorption times were found to be 20 seconds and 8 seconds, respectively. Hysteresis present in the data is attributed to temperature cross-sensitivity. Ultimately, the utility of collagen as a dielectric sensing material is, in part, due to its fibrous macrostructures as well its hydrophilic sites along the peptide chains. Gelatin was patterned between and below interdigitated copper electrodes and tested as a relative humidity sensor. This work shows that gelatin, which is inexpensive, widely available, and easy to process, can be an effective dielectric sensing polymer for capacitive-type relative humidity sensors.

  18. Pemisahan krom pada limbah cair industri penyamakan kulit menggunakan gelatin dan flokulan anorganik

    Directory of Open Access Journals (Sweden)

    Sugihartono

    2016-06-01

    Full Text Available ABSTRACT The aim of the study was to determine the ability of gelatin, ferrous sulfate, aluminium sulfate, and combination of gelatin with ferrous sulfate or aluminium sulfate for total chromium content (trivalent chromium and hexavalent chromium separation from tannery wastewater. Reduction of total chromium content in the wastewater was conducted using combination of gelatin and ferrous sulfate or gelatin and aluminium sulfate with a ratio of 4:0; 3:1; 2:2; 1:3; and 0:4 (w/w. The results showed that gelatin, ferrous sulfate, and aluminium sulfate, were able to reduce total chromium content in the wastewater. Combination of gelatin/ferrous sulfate or gelatin/aluminium sulfate as flocculants provide synergistic work in reducing the total chromium content. A 94.75% removal of total chromium content was achieved by combining gelatine and aluminium sulfate with a ratio of 3:1, clearer wastewater, and followed by reduction of degree of turbidity up to 74.47%. The total chromium content after treatment was 0.61 ppm, which met the requirements of wastewater for business and or daily activities especially for tanning industry.

  19. Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

    Science.gov (United States)

    Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

    2016-03-01

    Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

  20. Novel GABA receptor pesticide targets.

    Science.gov (United States)

    Casida, John E; Durkin, Kathleen A

    2015-06-01

    The γ-aminobutyric acid (GABA) receptor has four distinct but overlapping and coupled targets of pesticide action importantly associated with little or no cross-resistance. The target sites are differentiated by binding assays with specific radioligands, resistant strains, site-directed mutagenesis and molecular modeling. Three of the targets are for non-competitive antagonists (NCAs) or channel blockers of widely varied chemotypes. The target of the first generation (20th century) NCAs differs between the larger or elongated compounds (NCA-IA) including many important insecticides of the past (cyclodienes and polychlorocycloalkanes) or present (fiproles) and the smaller or compact compounds (NCA-IB) highly toxic to mammals and known as cage convulsants, rodenticides or chemical threat agents. The target of greatest current interest is designated NCA-II for the second generation (21st century) of NCAs consisting for now of isoxazolines and meta-diamides. This new and uniquely different NCA-II site apparently differs enough between insects and mammals to confer selective toxicity. The fourth target is the avermectin site (AVE) for allosteric modulators of the chloride channel. NCA pesticides vary in molecular surface area and solvent accessible volume relative to avermectin with NCA-IBs at 20-22%, NCA-IAs at 40-45% and NCA-IIs at 57-60%. The same type of relationship relative to ligand-docked length is 27-43% for NCA-IBs, 63-71% for NCA-IAs and 85-105% for NCA-IIs. The four targets are compared by molecular modeling for the Drosophila melanogaster GABA-R. The principal sites of interaction are proposed to be: pore V1' and A2' for NCA-IB compounds; pore A2', L6' and T9' for NCA-IA compounds; pore T9' to S15' in proximity to M1/M3 subunit interface (or alternatively an interstitial site) for NCA-II compounds; and M1/M3, M2 interfaces for AVE. Understanding the relationships of these four binding sites is important in resistance management and in the discovery and use

  1. Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

    Science.gov (United States)

    Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

    2016-01-01

    Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  2. Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

    Science.gov (United States)

    Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

    2017-01-01

    The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma

  3. Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer.

    Science.gov (United States)

    Huang, Yan-Shan; Wen, Xiao-Fang; Wu, Yi-Liang; Wang, Ye-Fei; Fan, Min; Yang, Zhi-Yu; Liu, Wei; Zhou, Lin-Fu

    2010-03-01

    The plasma half-life of therapeutic proteins is a critical factor in many clinical applications. Therefore, new strategies to prolong plasma half-life of long-acting peptides and protein drugs are in high demand. Here, we designed an artificial gelatin-like protein (GLK) and fused this hydrophilic GLK polymer to granulocyte-colony-stimulating factor (G-CSF) to generate a chimeric GLK/G-CSF fusion protein. The genetically engineered recombinant GLK/G-CSF (rGLK/G-CSF) fusion protein was purified from Pichia pastoris. In vitro studies demonstrated that rGLK/G-CSF possessed an enlarged hydrodynamic radius, improved thermal stability and retained full bioactivity compared to unfused G-CSF. Following a single subcutaneous administration to rats, the rGLK/G-CSF fusion protein displayed a slower plasma clearance rate and stimulated greater and longer lasting increases in circulating white blood cells than G-CSF. Our findings indicate that fusion with this artificial, hydrophilic, GLK polymer provides many advantages in the construction of a potent hematopoietic factor with extended plasma half-life. This approach could be easily applied to other therapeutic proteins and have important clinical applications. (c) 2009 Elsevier B.V. All rights reserved.

  4. Extraction and characterization of gelatin biopolymer from black tilapia (Oreochromis mossambicus) scales

    Energy Technology Data Exchange (ETDEWEB)

    Sockalingam, K., E-mail: gd130106@siswa.uthm.edu.my; Abdullah, H. Z., E-mail: hasan@uthm.edu.my [Faculty of Mechanical and Manufacturing Engineering, Universiti Tun Hussein Onn Malaysia, 86400 Parit Raja, Batu Pahat, Johor (Malaysia)

    2015-07-22

    Black tilapia (Oreochromis mossambicus) fish wastes (scales) were evaluated for its suitability as sources of gelatin. Scales were subjected to acid treatment for demineralization before it undergoes thermal extraction process. The raw scales were characterized via Scanning Electron Microscopy (SEM), which demarcated the cycloid pattern of the scales. SEM images also reveal the presence of collagen fiber in the fish scale. The black tilapia fish scales yields 11.88 % of gelatin, indicating the possibility of this fish species as sources of gelatin. Further characterizations were done on both raw scale and extracted gelatin through Fourier Transform Infrared Spectroscopy (FTIR) and proximate analysis. The scale gelatin shows high protein content (86.9 %) with low moisture (8.2 %) and ash (1.4 %). This further proves the effectiveness of the demineralization and extraction method used. The black tilapia fish scale is found to be a prospective source of gelatin with good chemical and functional properties.

  5. Extraction and characterization of gelatin biopolymer from black tilapia (Oreochromis mossambicus) scales

    International Nuclear Information System (INIS)

    Sockalingam, K.; Abdullah, H. Z.

    2015-01-01

    Black tilapia (Oreochromis mossambicus) fish wastes (scales) were evaluated for its suitability as sources of gelatin. Scales were subjected to acid treatment for demineralization before it undergoes thermal extraction process. The raw scales were characterized via Scanning Electron Microscopy (SEM), which demarcated the cycloid pattern of the scales. SEM images also reveal the presence of collagen fiber in the fish scale. The black tilapia fish scales yields 11.88 % of gelatin, indicating the possibility of this fish species as sources of gelatin. Further characterizations were done on both raw scale and extracted gelatin through Fourier Transform Infrared Spectroscopy (FTIR) and proximate analysis. The scale gelatin shows high protein content (86.9 %) with low moisture (8.2 %) and ash (1.4 %). This further proves the effectiveness of the demineralization and extraction method used. The black tilapia fish scale is found to be a prospective source of gelatin with good chemical and functional properties

  6. Extraction and characterization of gelatin biopolymer from black tilapia (Oreochromis mossambicus) scales

    Science.gov (United States)

    Sockalingam, K.; Abdullah, H. Z.

    2015-07-01

    Black tilapia (Oreochromis mossambicus) fish wastes (scales) were evaluated for its suitability as sources of gelatin. Scales were subjected to acid treatment for demineralization before it undergoes thermal extraction process. The raw scales were characterized via Scanning Electron Microscopy (SEM), which demarcated the cycloid pattern of the scales. SEM images also reveal the presence of collagen fiber in the fish scale. The black tilapia fish scales yields 11.88 % of gelatin, indicating the possibility of this fish species as sources of gelatin. Further characterizations were done on both raw scale and extracted gelatin through Fourier Transform Infrared Spectroscopy (FTIR) and proximate analysis. The scale gelatin shows high protein content (86.9 %) with low moisture (8.2 %) and ash (1.4 %). This further proves the effectiveness of the demineralization and extraction method used. The black tilapia fish scale is found to be a prospective source of gelatin with good chemical and functional properties.

  7. Evaluation of proanthocyanidin-crosslinked electrospun gelatin nanofibers for drug delivering system

    International Nuclear Information System (INIS)

    Huang, Chiung-Hua; Chi, Chin-Ying; Chen, Yueh-Sheng; Chen, Kuo-Yu; Chen, Pei-Lain; Yao, Chun-Hsu

    2012-01-01

    Electrospun nanofibers are excellent candidates for various biomedical applications. We successfully fabricated proanthocyanidin‐crosslinked gelatin electrospun nanofibers. Proanthocyanidin, a low cytotoxic collagen crosslinking reagent, increased the gelatin crosslinking percentage in the nanofibers from 53% to 64%. The addition of proanthocyanidin kept the nanofibers from swelling, and, thus, made the fibers more stable in the aqueous state. The compatibility and the release behavior of the drug in the nanofibers were examined using magnesium ascorbyl phosphate as the model drug. Proanthocyanidin also promoted drug loading and kept the drug release rate constant. These properties make the proanthocyanidin‐crosslinked gelatin nanofibers an excellent material for drug delivery. In the cell culture study, L929 fibroblast cells had a significantly higher proliferation rate when cultured with the gelatin/proanthocyanidin blended nanofibers. This characteristic showed that proanthocyanidin‐crosslinked gelatin electrospun nanofibers could potentially be employed as a wound healing material by increasing cell spreading and proliferation. - Highlights: ► Proanthocyanidin‐crosslinked gelatin nanofibers (GEL/PA) is synthesized. ► Proanthocyanidin promoted drug loading and kept the drug release rate constant. ► The GEL/PA nanofibers accelerate fibroblast cell proliferation. ► The GEL/PA nanofibers increase the drug loading efficiency.

  8. Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment.

    Directory of Open Access Journals (Sweden)

    Juan-Juan Yin

    Full Text Available Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+] cancer. Water-soluble folic acid (FA-conjugated CD carriers (FACDs were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR, matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS, high performance liquid chromatography (HPLC, Fourier transform infrared spectroscopy (FTIR, and circular dichroism. Drug complexes of adamatane (Ada and cytotoxic doxorubicin (Dox with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant K a was 1,639 M(-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+ cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release

  9. Creating 3D gelatin phantoms for experimental evaluation in biomedicine

    Directory of Open Access Journals (Sweden)

    Stein Nils

    2015-09-01

    Full Text Available We describe and evaluate a setup to create gelatin phantoms by robotic 3D printing. Key aspects are the large workspace, reproducibility and resolution of the created phantoms. Given its soft tissue nature, the gelatin is kept fluid during inside the system and we present parameters for additive printing of homogeneous, solid objects. The results indicate that 3D printing of gelatin can be an alternative for quickly creating larger soft tissue phantoms without the need for casting a mold.

  10. Rheological evaluation of the irradiated pectin/gelatin mixed systems

    International Nuclear Information System (INIS)

    Inamura, Patricia Y.; Mastro, Nelida L. del

    2011-01-01

    The main biopolymers used in the edible films production are polysaccharides and proteins. Pectin is a heterosaccharidic polymer derived from the vegetal cell wall. Gelatin is a heterogeneous mixture of water-soluble proteins of high average molecular mass derived by hydrolytic action from animal collagen. The aim of this research was to evaluate the effect of ionizing radiation on either the biopolymers alone or on the mixed systems prepared with high-and low-methoxyl pectin and gelatin in solution and mixed gel. The results showed that gelatin viscosity remained almost unaffected by the irradiation with doses from 1 to 15 kGy, with a slight increase at 3 kGy. On the other hand, there was a sharp decrease of viscosity values of all pectin solutions upon irradiation, being this behavior predominant when both polysaccharides and proteins were present in a mixed system. The gel hardness and gel brittleness of the gelatin were affected by the increase of radiation dose. (author)

  11. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network

    Directory of Open Access Journals (Sweden)

    Avijit Podder

    2017-06-01

    Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  12. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    International Nuclear Information System (INIS)

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-01-01

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of 10 B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10 5 -10 6 EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10 8 boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight (∼ 6 kD), this has allowed us to construct relatively small bioconjugates containing ∼ 900 boron atoms per EGF molecule 3 , which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using 131 I- or 99m T c -labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma

  13. A novel method for creating custom shaped ballistic gelatin trainers using plaster molds.

    Science.gov (United States)

    Doctor, Michael; Katz, Anne; McNamara, Shannon O; Leifer, Jessica H; Bambrick-Santoyo, Gabriela; Saul, Turandot; Rose, Keith M

    2018-03-01

    Simulation based procedural training is an effective and frequently used method for teaching vascular access techniques which often require commercial trainers. These can be prohibitively expensive, which allows for homemade trainers made of gelatin to be a more cost-effective and attractive option. Previously described trainers are often rectangular with a flat surface that is dissimilar to human anatomy. We describe a novel method to create a more anatomically realistic trainer using ballistic gelatin, household items, and supplies commonly found in an emergency department such as the plaster wrap typically used to make splints.

  14. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

    Science.gov (United States)

    Ralevic, Vera

    2015-01-01

    This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

  15. Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)

    Science.gov (United States)

    Lai, Kuo-Pao; Huang, Chiung-Kuei; Fang, Lei-Ya; Izumi, Kouji; Lo, Chi-Wen; Wood, Ronald; Kindblom, Jon; Yeh, Shuyuan

    2013-01-01

    Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size, which could be used in future therapy. PMID:23893956

  16. IL-13 and the IL-13 receptor as therapeutic targets for asthma and allergic disease.

    Science.gov (United States)

    Mitchell, Jesse; Dimov, Vesselin; Townley, Robert G

    2010-05-01

    It is widely accepted that T-helper 2 cell (Th2) cytokines play an important role in the maintenance of asthma and allergy. Emerging evidence has highlighted the role of IL-13 in the pathogenesis of these diseases. In particular, IL-13 is involved in the regulation of IgE synthesis, mucus hypersecretion, subepithelial fibrosis and eosinophil infiltration, and has been associated with the regulation of certain chemokine receptors, notably CCR5. Thus, targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. Pharmaceutical and biotechnology companies are researching various strategies, based on this approach, aimed at binding IL-13, increasing the level of the IL-13 decoy receptor, IL-13Ralpha2, or blocking the effect of the chemokine receptor CCR5. This review focuses on the therapeutic potential of anti-IL-13 agents and their role in the treatment of asthma and allergy.

  17. Atomic Force Microscopy Probing of Receptor–Nanoparticle Interactions for Riboflavin Receptor Targeted Gold–Dendrimer Nanocomposites

    Science.gov (United States)

    2015-01-01

    Riboflavin receptors are overexpressed in malignant cells from certain human breast and prostate cancers, and they constitute a group of potential surface markers important for cancer targeted delivery of therapeutic agents and imaging molecules. Here we report on the fabrication and atomic force microscopy (AFM) characterization of a core–shell nanocomposite consisting of a gold nanoparticle (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We designed this nanocomposite for potential applications such as a cancer targeted imaging material based on its surface plasmon resonance properties conferred by AuNP. We employed AFM as a technique for probing the binding interaction between the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled precise measurement of the AuNP height distribution before (13.5 nm) and after chemisorption of riboflavin-conjugated dendrimer (AuNP–dendrimer; 20.5 nm). Binding of RfBP to the AuNP–dendrimer caused a height increase to 26.7 nm, which decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand, supporting interaction of AuNP–dendrimer and its target protein. In summary, physical determination of size distribution by AFM imaging can serve as a quantitative approach to monitor and characterize the nanoscale interaction between a dendrimer-covered AuNP and target protein molecules in vitro. PMID:24571134

  18. Anisotropic silk fibroin/gelatin scaffolds from unidirectional freezing

    Energy Technology Data Exchange (ETDEWEB)

    Asuncion, Maria Christine Tankeh, E-mail: christine.asuncion@u.nus.edu [National University of Singapore, Department of Biomedical Engineering (Singapore); Goh, James Cho-Hong [National University of Singapore, Department of Biomedical Engineering (Singapore); National University of Singapore, Department of Orthopedic Surgery (Singapore); Toh, Siew-Lok [National University of Singapore, Department of Biomedical Engineering (Singapore); National University of Singapore, Department of Mechanical Engineering (Singapore)

    2016-10-01

    Recent studies have underlined the importance of matching scaffold properties to the biological milieu. Tissue, and thus scaffold, anisotropy is one such property that is important yet sometimes overlooked. Methods that have been used to achieve anisotropic scaffolds present challenges such as complicated fabrication steps, harsh processing conditions and toxic chemicals involved. In this study, unidirectional freezing was employed to fabricate anisotropic silk fibroin/gelatin scaffolds in a simple and mild manner. Morphological, mechanical, chemical and cellular compatibility properties were investigated, as well as the effect of the addition of gelatin to certain properties of the scaffold. It was shown that scaffold properties were suitable for cell proliferation and that mesenchymal stem cells were able to align themselves along the directed fibers. The fabricated scaffolds present a platform that can be used for anisotropic tissue engineering applications such as cardiac patches. - Highlights: • Silk/gelatin scaffolds with unidirectional alignment were fabricated using a simple and scalable process • Presence of gelatin in silk resulted to lesser shrinkage, better water retention and improved cell proliferation. • Mesenchymal stem cells were shown to align themselves according to the fiber alignment.

  19. The use of gelatine in wound ballistics research.

    Science.gov (United States)

    Carr, D J; Stevenson, T; Mahoney, P F

    2018-04-25

    Blocks of gelatine are used in both lethality and survivability studies for broadly the same reason, i.e. comparison of ammunition effects using a material that it is assumed represents (some part of) the human body. The gelatine is used to visualise the temporary and permanent wound profiles; elements of which are recognised as providing a reasonable approximation to wounding in humans. One set of researchers aim to improve the lethality of the projectile, and the other to understand the effects of the projectile on the body to improve survivability. Research areas that use gelatine blocks are diverse and include ammunition designers, the medical and forensics communities and designers of ballistic protective equipment (including body armour). This paper aims to provide an overarching review of the use of gelatine for wound ballistics studies; it is not intended to provide an extensive review of wound ballistics as that already exists, e.g. Legal Med 23:21-29, 2016. Key messages are that test variables, projectile type (bullet, fragmentation), impact site on the body and intermediate layers (e.g. clothing, personal protective equipment (PPE)) can affect the resulting wound profiles.

  20. Synthesis of fish scales gelatin-chitosan crosslinked films by gamma irradiation techniques

    International Nuclear Information System (INIS)

    Erizal; Perkasa, D.P.; Abbas, B.; Sulistioso, G.S.

    2013-01-01

    Gelatin is an important component of fish scales. Nowadays, attention has increased concerning the application of gelatin.The aim of this research was to improve the mechanical properties of gelatin produced from fish scales, which concurrently could increase the usefulness of fish scales. Gelatin (G) is prone to degrade or dissolve in water at room temperature, therefore to enhance its lifetime, it has to be modified with other compound such as chitosan. Chitosan (Cs) is a biodegradable polymer, which has biocompatibility and antibacterial properties. In this study, gelatin solution was mixed with chitosan solution in various ratios (G/Cs: 100/0, 75/25, 50/50, 25/75, 0/100), casted at room temperature to make composite films, then tested for the effectiveness of various gamma irradiation doses (10-40 kGy) for crosslinking of the two polymers. Chemical changes of the films were measured by FT-IR, gel fractions were determined by gravimetry, and mechanical properties were determined by tensile strength and elongation at break using universal testing machine. At optimum conditions ( 30 kGy and 75% Cs), the gel fraction, tensile strength, and elongation at break were higher leading to a stronger composite films as compared to the gelatin film. FTIR spectral analysis showed that gelatin and chitosan formed a crosslinked network. It was concluded that G-Cs films prepared by gamma irradiation have improved their mechanical properties than the gelatin itself. (author)

  1. Differential expression of growth factor receptors and membrane-bound tumor markers for imaging in male and female breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available INTRODUCTION: Male breast cancer accounts for 0.5-1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with female breast cancer. METHODS: Tissue microarrays containing 133 male breast cancer and 32 gynecomastia cases were stained by immunohistochemistry for a panel of membrane-bound targets and compared with data on 266 female breast cancers. RESULTS: Growth factor receptors were variably expressed in 4.5% (MET up to 38.5% (IGF1-R of male breast cancers. Compared to female breast cancer, IGF1-R and carbonic anhydrase 12 (CAXII were more frequently and CD44v6, MET and FGFR2 less frequently expressed in male breast cancer. Expression of EGFR, HER2, CAIX, and GLUT1 was not significantly different between male and female breast cancer. Further, 48.1% of male breast cancers expressed at least one and 18.0% expressed multiple growth factor receptors. Since individual membrane receptors are expressed in only half of male breast cancers, a panel of membrane markers will be required for molecular imaging strategies to reach sensitivity. A potential panel of markers for molecular imaging, consisting of EGFR, IGF1-R, FGFR2, CD44v6, CAXII, GLUT1, and CD44v6 was positive in 77% of male breast cancers, comparable to female breast cancers. CONCLUSIONS: Expression patterns of growth factor receptors and hypoxia membrane proteins in male breast cancer are different from female breast cancer. For molecular imaging strategies, a putative panel consisting of markers for EGFR, IGF1-R, FGFR2, GLUT1, CAXII, CD44v6 was positive in 77% of cases and might be considered for development of

  2. Synthesis and characterization of hydroxyapatite-gelatine composite materials for orthopaedic application

    International Nuclear Information System (INIS)

    Yanovska, A.; Kuznetsov, V.; Stanislavov, A.; Husak, E.; Pogorielov, M.; Starikov, V.; Bolshanina, S.; Danilchenko, S.

    2016-01-01

    The composite materials based on hydroxyapatite (HA) and gelatine (Gel) with addition of silver and zirconium oxide were obtained. The study investigates a combination of low powered ultrasonic irradiation and low concentration of gelatine in the co-precipitation synthesis. These composites have different weight ratios of organic/inorganic components and may be synthesized in two ways: simple mixing and co-precipitation. Both of which were compared. The estimation of porosity, in vivo testing, surface morphology and phase composition as well as the IR-analysis were provided. Hydroxyapatite was the main crystalline phase in obtained composites. While around powdered HA-Gel composite the connective tissue capsule is formed without bone tissue formation, HA-Gel-Ag porous composite implantation leads to formation of new bone tissue and activation of cell proliferation. Addition of silver ions into composite material allows decreasing inflammation on the first stage of implantation and has positive effect on bone tissue formation. Some of the obtained composite materials containing silver or ZrO_2 are biocompatible. bio-resorbable and osteoconductive with high level of porosity (75–85%). - Highlights: • Hydroxyapatite-gelatine composites with addition of Ag"+ and ZrO_2 were obtained. • Composites were synthesized in two ways: simple mixing and co-precipitation. • Co-precipitation synthesis combined ultrasonic treatment and low concentration of gelatine. • Obtained composites have different weight ratios of organic/inorganic components. • Some composites are osteoconductive and all of them have high level of porosity (75–85%).

  3. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  4. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

    2015-01-01

    c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

  5. Identification of novel peptide ligands for the cancer-specific receptor mutation EFGRvIII using a mixture-based synthetic combinatorial library

    DEFF Research Database (Denmark)

    Denholt, Charlotte Lund; Hansen, Paul Robert; Pedersen, Nina

    2009-01-01

    We report here, the design and synthesis of a positional scanning synthetic combinatorial library for the identification of novel peptide ligands targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in se...

  6. Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

    Science.gov (United States)

    Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

    2018-04-01

    The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

  7. Characteristics and Gel Properties of Gelatin from Goat Skin as Influenced by Alkaline-pretreatment Conditions

    Directory of Open Access Journals (Sweden)

    Sulaiman Mad-Ali

    2016-06-01

    Full Text Available Characteristics and properties of gelatin from goat skin pretreated with NaOH solutions (0.50 and 0.75 M for various times (1 to 4 days were investigated. All gelatins contained α-chains as the predominant component, followed by β-chain. Gelling and melting temperatures of those gelatins were 23.02°C to 24.16°C and 33.07°C to 34.51°C, respectively. Gel strength of gelatins increased as NaOH concentration and pretreatment time increased (p<0.05. Pretreatment for a longer time yielded gelatin with a decrease in L*-value but an increase in b*-value. Pretreatment of goat skin using 0.75 M NaOH for 2 days rendered the highest yield (15.95%, wet weight basis as well as high gel strength (222.42 g, which was higher than bovine gelatin (199.15 g. Gelatin obtained had the imino acid content of 226 residues/1,000 residues and the gelatin gel had a fine and ordered structure. Therefore, goat skin gelatin could be used as a potential replacer of commercial gelatin.

  8. Hyaluronic Acid Immobilized Polyacrylamide Nanoparticle Sensors for CD44 Receptor Targeting and pH Measurement in Cells

    DEFF Research Database (Denmark)

    Sun, Honghao; Benjaminsen, Rikke Vicki; Almdal, Kristoffer

    2012-01-01

    Our ability to design receptor-targeted nanocarriers aimed at drug release after endocytosis is limited by the current knowledge of intracellular nanoparticle (NP) trafficking. It is not clear if NP size, surface chemistry, and/or targeting of cell surface receptors changes the intracellular fate...... of NPs; i.e., will all NPs enter acidic compartments and eventually end up in lysosomes or are there escape mechanisms or receptor-specific signaling that can be induced to change the cellular processing of an internalized NP? To give new insight into the intracellular trafficking of NPs that target...... nanosensors indicates that the intracellular trafficking is aimed at lysosomes regardless of whether CD44 receptor-specific or unspecific uptake is induced....

  9. SIFAT FISIKO-KIMIA GELATIN KULIT IKAN BELUT DAN LELE PADA KEADAAN SEGAR DAN KERING

    Directory of Open Access Journals (Sweden)

    Hafni Rahmawati

    2016-06-01

    The first stage of the research was raw material preparation (fresh and dry fish skin soaked in aquadest for 4 hours. Fish skin extracted using 0,05 M acetic acid for 10 hours, washed in water and then extracted using aquadest at 80OC for 2 hours to get gelatin liquid, the liquid was filtrated. Filtrat was dried in cabinet dryer at 55OC for  48 hours to get gelatin layers, and then blended to get gelatin granule. The results were showing viscosity of gelatin from dry fish skin as same as from fresh fish skin, gel strength and melting point of gelatin from dry fish skin was higher than from fresh fish skin. Influence of fish skin drying was increase turbidity and color of gelatin. The best gelatin was ekstracted from dry skin swamp ell with viscosity 6,65 cps, gel strength 206,30 Bloom, melting point 22,33OC. Gelatin from fresh skin swamp ell was the best turbidity 1,65 ntu and color (L = 41,87, a = 8,90, b = 27,27.

  10. Structural Modification of Fish Gelatin by the Addition of Gellan, κ-Carrageenan, and Salts Mimics the Critical Physicochemical Properties of Pork Gelatin.

    Science.gov (United States)

    Sow, Li Cheng; Kong, Karmaine; Yang, Hongshun

    2018-05-01

    Pork gelatin is not suitable for halal and kosher application; however, fish gelatin (FG) can be modified for use as a pork gelatin (PG) mimetic. Herein, low-acyl gellan (GE), κ-carrageenan (KC), and salts (CaCl 2 or KCl) were combined with a 180 Bloom tilapia FG. A formulation comprising 5.925% (w/v) FG + 0.025% (w/v) GE + 3mM CaCl 2 best matched the physicochemical properties of PG. The modification increased the FG gel strength from 115 ± 2 to 149 ± 2 g (matching the 148 ± 2 of PG), while the T m increased from 27.9 ± 1.0 to 32.4 ± 0.8 °C (matching the 33.1 ± 0.3 °C of PG). Nanoaggregates (diameter between 150 and 300 nm) could be an important structural factor affecting the physicochemical properties, as both PG and GE-modified FG showed a similar frequency distribution in this size group (57.4 ± 1.6% (PG) compared with 56.3 ± 2.2% (modified FG)). To further explore the differences between KC and GE in modifying of FG's structure, the FG-KC and FG-GE gels were compared. The zeta potential and Fourier transform infrared (FTIR) spectroscopy results for the FG-KC gel supported an associative interaction with complex formation, as indicated from the large aggregates and amorphous phase under atomic force microscopy (AFM). Contrastingly, a segregative FG-GE interaction took place in presence of CaCl 2 . These structures and interaction differences between FG-GE and FG-KC influenced the macro-properties of FG, possibly explaining the differences in the modification of the melting temperature of FG. A diagram representing the interaction-structure-physicochemical properties was proposed to explain the differences between the FG-GE and FG-KC gels. Certain people cannot consume any pork product or derivatives for religious reasons, thus it is essential to find a pork gelatin (PG) substitute for food product development. The commonly used polysaccharides, gellan and carrageenan, together with salt, can be added to fish gelatin (FG) to match the

  11. Effects of Pressure-shift Freezing on the Structural and Physical Properties of Gelatin Hydrogel Matrices

    Science.gov (United States)

    Kim, Byeongsoo; Gil, Hyung Bae; Min, Sang-Gi; Lee, Si-Kyung; Choi, Mi-Jung

    2014-01-01

    This study investigates the effects of the gelatin concentration (10-40%, w/v), freezing temperatures (from -20℃ to -50℃) and freezing methods on the structural and physical properties of gelatin matrices. To freeze gelatin, the pressure-shift freezing (PSF) is being applied at 0.1 (under atmospheric control), 50 and 100 MPa, respectively. The freezing point of gelatin solutions decrease with increasing gelatin concentrations, from -0.2℃ (10% gelatin) to -6.7℃ (40% gelatin), while the extent of supercooling did not show any specific trends. The rheological properties of the gelatin indicate that both the storage (G') and loss (G") moduli were steady in the strain amplitude range of 0.1-10%. To characterize gelatin matrices formed by the various freezing methods, the ice crystal sizes which were being determined by the scanning electron microscopy (SEM) are affected by the gelatin concentrations. The ice crystal sizes are affected by gelatin concentrations and freezing temperature, while the size distributions of ice crystals depend on the freezing methods. Smaller ice crystals are being formed with PSF rather than under the atmospheric control where the freezing temperature is above -40℃. Thus, the results of this study indicate that the PSF processing at a very low freezing temperature (-50℃) offers a potential advantage over commercial atmospheric freezing points for the formation of small ice crystals. PMID:26760743

  12. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease.

    Science.gov (United States)

    Beck, Michael W; Derrick, Jeffrey S; Kerr, Richard A; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D; Kim, Kwang S; Lee, Joo-Yong; Ruotolo, Brandon T; Lim, Mi Hee

    2016-10-13

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

  13. Effect of egg albumen protein addition on physicochemical properties and nanostructure of gelatin from fish skin.

    Science.gov (United States)

    Cai, Luyun; Feng, Jianhui; Peng, Xichun; Regenstein, Joe M; Li, Xiuxia; Li, Jianrong; Zhao, Wei

    2016-12-01

    The physicochemical properties and nanostructure of mixtures of egg albumen protein (EAP) and gelatin from under-utilised grass carp ( Ctenopharyngodon idella ) skins were studied. The gelatin with 1% EAP had an acceptable gel strength. The addition of 5% EAP significantly increased the melting and gelling temperatures of gelatin gels. Additionally, the colour turned white and the crystallinity was higher in gelatin gels with gradient concentrations of EAP (1, 3, and 5%). Gelatin with 5% EAP had the highest G' values while gelatin with 1% EAP had the lowest G' values. Atomic force microscopy showed the heterogeneous nanostructure of fish gelatin, and a simple coacervate with a homogeneous distribution was only observed with the addition of 1% EAP, indicating interaction between gelatin and EAP. These results showed that EAP effect fish gelatin's physicochemical and nanostructure properties and has potential applications in foods and pharmaceuticals.

  14. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Yuxin Feng

    Full Text Available Estrogen receptor alpha (ERα, a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER's ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy.

  15. Extraction optimization and characterization of gelatine from fish dry skin of Spanish mackerel (Scomberromorus commersoni)

    Science.gov (United States)

    Kusumaningrum, I.; Pranoto, Y.; Hadiwiyoto, S.

    2018-04-01

    This work was to optimized gelatin extraction from dry skin of Spanish mackerel (Scomberromorus commersoni) using Response Surface Methodology (RSM). The aim of this study was to determine the optimal condition of temperature and time for extraction process and properties of the gelatin extracted from dry mackerel skin. The optimal condition for extraction was 59.71°C for 4.25 hours. Results showed that predicted yield by RSM was 13.69% and predicted gel strength was 291.93 Bloom, whereas the actual experiment for yield and gel strength were 13.03% and 291.33 Bloom, respectively. The gelatin extracted from dried skin were analyzed for their proximate composition, yield, gel strength, viscosity, color, and amino acid composition. The results of dried skin gelatin properties compared to the commercial gelatin. Gelatin extracted from the dried skin gave content lower moisture, ash and protein content but higher fat compared to commercial gelatin. This study also shows that the gelatin extracted from the dried skin gave higher gel strength and pH but the lower amino acid composition compared to commercial gelatin.

  16. Neutralization of IL-8 prevents the induction of dermatologic adverse events associated with the inhibition of epidermal growth factor receptor

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Houtkamp, Mischa; Schuurhuis, Danita H

    2012-01-01

    Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance to treatm......Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance......, characterized by acute follicular neutrophil-rich hair follicle inflammation, and thus mimicked adverse events induced by systemic administration of EGFR inhibitors. In this model, we tested the hypothesis that neutrophils, attracted by IL-8, play a central role in the observed rash. Indeed, concomitant local...

  17. A compound chimeric antigen receptor strategy for targeting multiple myeloma.

    Science.gov (United States)

    Chen, K H; Wada, M; Pinz, K G; Liu, H; Shuai, X; Chen, X; Yan, L E; Petrov, J C; Salman, H; Senzel, L; Leung, E L H; Jiang, X; Ma, Y

    2018-02-01

    Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

  18. Electrospun Zein/Gelatin Scaffold-Enhanced Cell Attachment and Growth of Human Periodontal Ligament Stem Cells

    Directory of Open Access Journals (Sweden)

    Fanqiao Yang

    2017-10-01

    Full Text Available Periodontitis is a widespread dental disease affecting 10 to 15% of worldwide adult population, yet the current treatments are far from satisfactory. The human periodontal ligament stem cell is a promising potential seed cell population type in cell-based therapy and tissue regeneration, which require appropriate scaffold to provide a mimic extracellular matrix. Zein, a native protein derived from corn, has an excellent biodegradability, and therefore becomes a hotspot on research and application in the field of biomaterials. However, the high hydrophobicity of zein is unfavorable for cell adhesion and thus greatly limits its use. In this study, we fabricate co-electrospun zein/gelatin fiber scaffolds in order to take full advantages of the two natural materials and electrospun fiber structure. Zein and gelatin in four groups of different mass ratios (100:00, 100:20, 100:34, 100:50, and dissolved the mixtures in 1,1,1,3,3,3-hexafluoro-2-propanol, then produced membranes by electrospinning. The results showed that the scaffolds were smooth and homogeneous, as shown in scanning electron micrographs. The diameter of hybrid fibers was increased from 69 ± 22 nm to 950 ± 356 nm, with the proportion of gelatin increase. The cell affinity of zein/gelatin nanofibers was evaluated by using human periodontal ligament stem cells. The data showed that hydrophilicity and cytocompatibility of zein nanofibers were improved by blended gelatin. Taken together, our results indicated that the zein/gelatin co-electrospun fibers had sufficient mechanical properties, satisfied cytocompatibility, and can be utilized as biological scaffolds in the field of tissue regeneration.

  19. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

    Science.gov (United States)

    Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, Daegab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

    2016-03-01

    Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

  20. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    Directory of Open Access Journals (Sweden)

    Pranshu eBansal

    2016-05-01

    Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

  1. Utilization of the Tango beta-arrestin recruitment technology for cell-based EDG receptor assay development and interrogation.

    Science.gov (United States)

    Wetter, Justin A; Revankar, Chetana; Hanson, Bonnie J

    2009-10-01

    Cellular assay development for the endothelial differentiation gene (EDG) family of G-protein-coupled receptors (GPCRs) and related lysophospholipid (LP) receptors is complicated by endogenous receptor expression and divergent receptor signaling. Endogenously expressed LP receptors exist in most tissue culture cell lines. These LP receptors, along with other endogenously expressed GPCRs, contribute to off-target signaling that can complicate interpretation of second-messenger-based cellular assay results. These receptors also activate a diverse and divergent set of cellular signaling pathways, necessitating the use of a variety of assay formats with mismatched procedures and functional readouts. This complicates examination and comparison of these receptors across the entire family. The Tango technology uses the conserved beta-arrestin-dependent receptor deactivation process to allow interrogation of the EDG and related receptors with a single functional assay. This method also isolates the target receptor signal, allowing the use of tissue culture cell lines regardless of their endogenous receptor expression. The authors describe the use of this technique to build cell-based receptor-specific assays for all 8 members of the EDG receptor family as well as the related LPA receptors GPR23, GPR92, and GPR87. In addition, they demonstrate the value of this technology for identification and investigation of functionally selective receptor compounds as demonstrated by the immunosuppressive compound FtY720-P and its action at the EDG(1) and EDG(3) receptors.

  2. Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1.

    Science.gov (United States)

    Kim, Ah-Yeon; Shim, Hyun-Jin; Shin, Hyeon-Myeong; Lee, Yoo Jung; Nam, Hyeonjeong; Kim, Su Yeon; Youn, Hyung-Sun

    2018-04-01

    Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of andrographolide in TLR signaling pathways. Andrographolide suppressed NF-κB activation as well as COX-2 expression induced by TLR3 or TLR4 agonists. Andrographolide also suppressed the activation of IRF3 and the expression of interferon inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. Andrographolide attenuated ligand-independent activation of IRF3 following overexpression of TRIF, TBK1, or IRF3. Furthermore, andrographolide inhibited TBK1 kinase activity in vitro. These results indicate that andrographolide modulates the TRIF-dependent pathway of TLRs by targeting TBK1 and represents a potential new anti-inflammatory candidate. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Report: Optimization study of the preparation factors for argan oil microcapsule based on hybrid-level orthogonal array design via SPSS modeling.

    Science.gov (United States)

    Zhao, Xi; Wu, Xiaoli; Zhou, Hui; Jiang, Tao; Chen, Chun; Liu, Mingshi; Jin, Yuanbao; Yang, Dongsheng

    2014-11-01

    To optimize the preparation factors for argan oil microcapsule using complex coacervation of chitosan cross-linked with gelatin based on hybrid-level orthogonal array design via SPSS modeling. Eight relatively significant factors were firstly investigated and selected as calculative factors for the orthogonal array design from the total of ten factors effecting the preparation of argan oil microcapsule by utilizing the single factor variable method. The modeling of hybrid-level orthogonal array design was built in these eight factors with the relevant levels (9, 9, 9, 9, 7, 6, 2 and 2 respectively). The preparation factors for argan oil microcapsule were investigated and optimized according to the results of hybrid-level orthogonal array design. The priorities order and relevant optimum levels of preparation factors standard to base on the percentage of microcapsule with the diameter of 30~40 μm via SPSS. Experimental data showed that the optimum factors were controlling the chitosan/gelatin ratio, the systemic concentration and the core/shell ratio at 1:2, 1.5% and 1:7 respectively, presetting complex coacervation pH at 6.4, setting cross-linking time and complex coacervation at 75 min and 30 min, using the glucose-delta lactone as the type of cross-linking agent, and selecting chitosan with the molecular weight of 2000~3000.

  4. Targeting the urokinase plasminogen activator receptor inhibits ovarian cancer metastasis.

    Science.gov (United States)

    Kenny, Hilary A; Leonhardt, Payton; Ladanyi, Andras; Yamada, S Diane; Montag, Anthony; Im, Hae Kyung; Jagadeeswaran, Sujatha; Shaw, David E; Mazar, Andrew P; Lengyel, Ernst

    2011-02-01

    To understand the functional and preclinical efficacy of targeting the urokinase plasminogen activator receptor (u-PAR) in ovarian cancer. Expression of u-PAR was studied in 162 epithelial ovarian cancers, including 77 pairs of corresponding primary and metastatic tumors. The effect of an antibody against u-PAR (ATN-658) on proliferation, adhesion, invasion, apoptosis, and migration was assessed in 3 (SKOV3ip1, HeyA8, and CaOV3) ovarian cancer cell lines. The impact of the u-PAR antibody on tumor weight, number, and survival was examined in corresponding ovarian cancer xenograft models and the mechanism by which ATN-658 blocks metastasis was explored. Only 8% of all ovarian tumors were negative for u-PAR expression. Treatment of SKOV3ip1, HeyA8, and CaOV3 ovarian cancer cell lines with the u-PAR antibody inhibited cell invasion, migration, and adhesion. In vivo, anti-u-PAR treatment reduced the number of tumors and tumor weight in CaOV3 and SKOV3ip1 xenografts and reduced tumor weight and increased survival in HeyA8 xenografts. Immunostaining of CaOV3 xenograft tumors and ovarian cancer cell lines showed an increase in active-caspase 3 and TUNEL staining. Treatment with u-PAR antibody inhibited α(5)-integrin and u-PAR colocalization on primary human omental extracellular matrix. Anti-u-PAR treatment also decreased the expression of urokinase, u-PAR, β(3)-integrin, and fibroblast growth factor receptor-1 both in vitro and in vivo. This study shows that an antibody against u-PAR reduces metastasis, induces apoptosis, and reduces the interaction between u-PAR and α(5)-integrin. This provides a rationale for targeting the u-PAR pathway in patients with ovarian cancer and for further testing of ATN-658 in this indication. ©2010 AACR.

  5. Development and Characterization of a Camelid Single Domain Antibody-Urease Conjugate That Targets Vascular Endothelial Growth Factor Receptor 2.

    Science.gov (United States)

    Tian, Baomin; Wong, Wah Yau; Uger, Marni D; Wisniewski, Pawel; Chao, Heman

    2017-01-01

    Angiogenesis is the process of new blood vessel formation and is essential for a tumor to grow beyond a certain size. Tumors secrete the pro-angiogenic factor vascular endothelial growth factor, which acts upon local endothelial cells by binding to vascular endothelial growth factor receptors (VEGFRs). In this study, we describe the development and characterization of V21-DOS47, an immunoconjugate that targets VEGFR2. V21-DOS47 is composed of a camelid single domain anti-VEGFR2 antibody (V21) and the enzyme urease. The conjugate specifically binds to VEGFR2 and urease converts endogenous urea into ammonia, which is toxic to tumor cells. Previously, we developed a similar antibody-urease conjugate, L-DOS47, which is currently in clinical trials for non-small cell lung cancer. Although V21-DOS47 was designed from parameters learned from the generation of L-DOS47, additional optimization was required to produce V21-DOS47. In this study, we describe the expression and purification of two versions of the V21 antibody: V21H1 and V21H4. Each was conjugated to urease using a different chemical cross-linker. The conjugates were characterized by a panel of analytical techniques, including SDS-PAGE, size exclusion chromatography, Western blotting, and LC-MS E peptide mapping. Binding characteristics were determined by ELISA and flow cytometry assays. To improve the stability of the conjugates at physiologic pH, the pIs of the V21 antibodies were adjusted by adding several amino acid residues to the C-terminus. For V21H4, a terminal cysteine was also added for use in the conjugation chemistry. The modified V21 antibodies were expressed in the E. coli BL21 (DE3) pT7 system. V21H1 was conjugated to urease using the heterobifunctional cross-linker succinimidyl-[( N -maleimidopropionamido)-diethyleneglycol] ester (SM(PEG) 2 ), which targets lysine resides in the antibody. V21H4 was conjugated to urease using the homobifunctional cross-linker, 1,8-bis(maleimido)diethylene glycol

  6. Development and Characterization of a Camelid Single Domain Antibody–Urease Conjugate That Targets Vascular Endothelial Growth Factor Receptor 2

    Directory of Open Access Journals (Sweden)

    Baomin Tian

    2017-08-01

    Full Text Available Angiogenesis is the process of new blood vessel formation and is essential for a tumor to grow beyond a certain size. Tumors secrete the pro-angiogenic factor vascular endothelial growth factor, which acts upon local endothelial cells by binding to vascular endothelial growth factor receptors (VEGFRs. In this study, we describe the development and characterization of V21-DOS47, an immunoconjugate that targets VEGFR2. V21-DOS47 is composed of a camelid single domain anti-VEGFR2 antibody (V21 and the enzyme urease. The conjugate specifically binds to VEGFR2 and urease converts endogenous urea into ammonia, which is toxic to tumor cells. Previously, we developed a similar antibody–urease conjugate, L-DOS47, which is currently in clinical trials for non-small cell lung cancer. Although V21-DOS47 was designed from parameters learned from the generation of L-DOS47, additional optimization was required to produce V21-DOS47. In this study, we describe the expression and purification of two versions of the V21 antibody: V21H1 and V21H4. Each was conjugated to urease using a different chemical cross-linker. The conjugates were characterized by a panel of analytical techniques, including SDS-PAGE, size exclusion chromatography, Western blotting, and LC-MSE peptide mapping. Binding characteristics were determined by ELISA and flow cytometry assays. To improve the stability of the conjugates at physiologic pH, the pIs of the V21 antibodies were adjusted by adding several amino acid residues to the C-terminus. For V21H4, a terminal cysteine was also added for use in the conjugation chemistry. The modified V21 antibodies were expressed in the E. coli BL21 (DE3 pT7 system. V21H1 was conjugated to urease using the heterobifunctional cross-linker succinimidyl-[(N-maleimidopropionamido-diethyleneglycol] ester (SM(PEG2, which targets lysine resides in the antibody. V21H4 was conjugated to urease using the homobifunctional cross-linker, 1,8-bis

  7. Insulin/insulin like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms and new blocking strategies

    Directory of Open Access Journals (Sweden)

    Travis B Salisbury

    2015-02-01

    Full Text Available The insulin-like growth factor 1 receptor (IGF1R and the insulin receptor (IR are receptor tyrosine kinases (RTKs that are expressed in cancer cells. The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include: anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin β3 receptors in some cancer cells. Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. Novel aspects of IGF1R/IR in cancer, such as biased agonism, integrin β3 signaling, AHR and new therapeutic targeting strategies will be discussed.

  8. Chitosan scaffold modified with D-(+) raffinose and enriched with thiol-modified gelatin for improved osteoblast adhesion

    International Nuclear Information System (INIS)

    Galli, C; Parisi, L; Smerieri, A; Lumetti, S; Manfredi, E; Macaluso, G M; Elviri, L; Bianchera, A; Bettini, R; Lagonegro, P

    2016-01-01

    The aim of the present study was to investigate whether chitosan-based scaffolds modified with D-(+) raffinose and enriched with thiol-modified gelatin could selectively improve osteoblast adhesion and proliferation. 2, 3 and 4.5% chitosan films were prepared. Chitosan suitability for tissue engineering was confirmed by protein adsorption assay. Scaffolds were incubated with a 2.5 mg ml −1 BSA solution and the decrease of protein content in the supernatants was measured by spectrophotometry. Chitosan films were then enriched with thiol-modified gelatin and their ability to bind BSA was also measured. Then, 2% chitosan discs with or without thiol-modified gelatin were used as culture substrates for MC3T3-E1 cells. After 72 h cells were stained with trypan blue or with calcein AM and propidium iodide for morphology, viability and proliferation assays. Moreover, cell viability was measured at 48, 72, 96 and 168 h to obtain a growth curve. Chitosan films efficiently bound and retained BSA proportionally to the concentration of chitosan discs. The amount of protein retained was higher on chitosan enriched with thiol-modified gelatin. Moreover, chitosan discs allowed the adhesion and the viability of cells, but inhibited their proliferation. The functionalization of chitosan with thiol-modified gelatin enhanced cell spreading and proliferation. Our data confirm that chitosan is a suitable material for tissue engineering. Moreover, our data show that the enrichment of chitosan with thiol-modified gelatin enhances its biological properties. (paper)

  9. Extraction and characterization of gelatin from two edible Sudanese insects and its applications in ice cream making.

    Science.gov (United States)

    Mariod, Abdalbasit Adam; Fadul, Hadia

    2015-07-01

    Three methods were used for extraction of gelatin from two insects, melon bug (Coridius viduatus) and sorghum bug (Agonoscelis versicoloratus versicoloratus). Extraction of insect gelatin using hot water gave higher yield reached up to 3.0%, followed by mild acid extraction which gave 1.5% and distilled water extraction which gave only 1.0%, respectively. The obtained gelatins were characterized by FTIR and the spectra of insect's gelatin seem to be similar when compared with commercial gelatin. Amide II bands of gelatins from melon and sorghum bug appeared around at 1542-1537 cm(-1). Slight differences in the amino acid composition of gelatin extracted from the two insects were observed. Ice cream was made by using 0.5% insect's gelatin and compared with that made using 0.5% commercial gelatin as stabilizing agent. The properties of the obtained ice cream produced using insects gelatin were significantly different when compared with that made using commercial gelatin. © The Author(s) 2014.

  10. New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

    Science.gov (United States)

    Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

    2016-01-01

    Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

  11. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    Science.gov (United States)

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  12. Eco-friendly biorefractory films of gelatin and TEMPO-oxidized cellulose ester for food packaging application.

    Science.gov (United States)

    Zhuang, Chen; Tao, Furong; Cui, Yuezhi

    2017-08-01

    In recent years, many types of food-packaging films and composites have been prepared using gelatin because of its good film-forming ability, non-toxic nature and cost-effectiveness. However, the relatively weak thermal stability, poor mechanical properties and easily-degradable quality limit the potential application of gelatin as a practical material. Microcrystalline cellulose (MCC), which comprises one of the most abundant biomass resources, has been regarded as a safe and reliable food additive because it has the same ingredients as the cellulose in people's daily intake. Food-packaging films with the excellent properties provided by gelatin and oxidized-cellulose represent a topic of great interest. MCC was modified by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation and chosen as the base of the macromolecule cross-linker (TMN). After modification of gelatin film by TMN, the minimum amount of free -NH 2 in solution was 4.8 × 10 -4  mol g -1 ). The thermal property obviously increased (from 322.31  o C to 352.63  o C) and was crucial for usage in the food industry. The highest water contact value 123.09° (η = 25%) indicated a better surface hydrophobicity. The higher E ab (58.88%) and lower E m (77.16%) demonstrated that a more flexible and shatter-proof material was obtained. Water vapor uptake studies suggested increased moisture absorption and greater swelling ability. The film material obtained in the present study was safe, stable, eco-friendly and biorefractory and could also be decomposed completely by the environment after disposal as a result of the properties of the ingredients gelatin and cellulose. The incorporation of a cellulosic cross-linker to gelatin-based films was an ideal choice with respect to developing a packaging for the food industry. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  13. Inhibition of ice crystal growth in ice cream mix by gelatin hydrolysate.

    Science.gov (United States)

    Damodaran, Srinivasan

    2007-12-26

    The inhibition of ice crystal growth in ice cream mix by gelatin hydrolysate produced by papain action was studied. The ice crystal growth was monitored by thermal cycling between -14 and -12 degrees C at a rate of one cycle per 3 min. It is shown that the hydrolysate fraction containing peptides in the molecular weight range of about 2000-5000 Da exhibited the highest inhibitory activity on ice crystal growth in ice cream mix, whereas fractions containing peptides greater than 7000 Da did not inhibit ice crystal growth. The size distribution of gelatin peptides formed in the hydrolysate was influenced by the pH of hydrolysis. The optimum hydrolysis conditions for producing peptides with maximum ice crystal growth inhibitory activity was pH 7 at 37 degrees C for 10 min at a papain to gelatin ratio of 1:100. However, this may depend on the type and source of gelatin. The possible mechanism of ice crystal growth inhibition by peptides from gelatin is discussed. Molecular modeling of model gelatin peptides revealed that they form an oxygen triad plane at the C-terminus with oxygen-oxygen distances similar to those found in ice nuclei. Binding of this oxygen triad plane to the prism face of ice nuclei via hydrogen bonding appears to be the mechanism by which gelatin hydrolysate might be inhibiting ice crystal growth in ice cream mix.

  14. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    International Nuclear Information System (INIS)

    Ayyagari, R.R.; Khan-Dawood, F.S.

    1987-01-01

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol 125 I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function

  15. FGFR a promising druggable target in cancer: Molecular biology and new drugs.

    Science.gov (United States)

    Porta, Rut; Borea, Roberto; Coelho, Andreia; Khan, Shahanavaj; Araújo, António; Reclusa, Pablo; Franchina, Tindara; Van Der Steen, Nele; Van Dam, Peter; Ferri, Jose; Sirera, Rafael; Naing, Aung; Hong, David; Rolfo, Christian

    2017-05-01

    The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Most of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously. It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this, it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. A gelatin composite scaffold strengthened by drug-loaded halloysite nanotubes.

    Science.gov (United States)

    Ji, Lijun; Qiao, Wei; Zhang, Yuheng; Wu, Huayu; Miao, Shiyong; Cheng, Zhilin; Gong, Qianming; Liang, Ji; Zhu, Aiping

    2017-09-01

    Mechanical properties and anti-infection are two of the most concerned issues for artificial bone grafting materials. Bone regeneration porous scaffolds with sustained drug release were developed by freeze-drying the mixture of nanosized drug-loaded halloysite nanotubes (HNTs) and gelatin. The scaffolds showed porous structure and excellent biocompatibility. The mechanical properties of the obtained composite scaffolds were enhanced significantly by HNTs to >300%, comparing to those of gelatin scaffold, and match to those of natural cancellous bones. The ibuprofen-loaded HNTs incorporated in the scaffolds allowed extended drug release over 100h, comparing to 8h when directly mixed the drug into the gelatin scaffold. The biological properties of the composite scaffolds were investigated by culturing MG63 cells on them. The HNTs/gelatin scaffolds with excellent mechanical properties and sustained drug release could be a promising artificial bone grating material. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Involvement of ways of death receptors in the target and non target effects of ionizing radiations

    International Nuclear Information System (INIS)

    Luce, A.

    2008-10-01

    Delayed cell death by mitotic catastrophe is a frequent mode of breast cancer cell death after γ-irradiation. Whereas the mechanisms that underlie the early γ-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, TRAIL and TNF-α death receptor pathways mediate the delayed cell death observed after γ-irradiation of breast cancer cells. Receptors of the three pathways are over expressed early after irradiation and sensitize cells to apoptosis, whereas their ligands are over expressed three to four days after γ-irradiation, leading to apoptosis of the irradiated cells through a mitotic catastrophe. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands which can induce the death of sensitive bystander cells. Altogether, these results define the molecular basis of the delayed cell death induced by targeted and non-targeted effects of γ-irradiation. (author)

  18. 99m Tc-anti-epidermal growth factor receptor nanobody for tumor imaging.

    Science.gov (United States)

    Piramoon, Majid; Hosseinimehr, Seyed Jalal; Omidfar, Kobra; Noaparast, Zohreh; Abedi, Seyed Mohammad

    2017-04-01

    Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti-epidermal growth factor receptor (EGFR) nanobody OA-cb6 with 99m Tc(CO) 3 + and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor-to-muscle ratio at 4-hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA-cb6- 99m Tc-tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression. © 2016 John Wiley & Sons A/S.

  19. Preparation of Gelatin coated hydroxyapatite nanorods and the stability of its aqueous colloidal

    International Nuclear Information System (INIS)

    Chen Minfang; Tan Junjun; Lian Yuying; Liu Debao

    2008-01-01

    This paper describes a novel process for preparing Gelatin coated hydroxyapatite (HAp) nanorods to improve the stability of its aqueous colloid. As Gelatin is a typical protein with abundant hydroxyls, carboxys and imines, it is a very effective functional group to attach onto the surfaces of the HAp particles. Our data show that the Gelatin layer firmly coated on the hydroxyapatite nanorods, and their structure and interfacial chemical bonding have been studied using various techniques, such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), high-resolution transmission electron microscopy (HRTEM), differential thermal analysis (DTA) and thermal gravimetric analysis (TGA). The reaction temperature, pH, amount of Gelatin, and Ca/P molar ratio in the material determine the quality of Gelatin coating and the stability of the HAp in aqueous solution. Moreover, an interesting phenomenon was found that the Gelatin coated HAp sediment separated by centrifugal was easily dispersed in water and forms HAp aqueous suspension. The suspension was stable for more than 24 h

  20. Steroid hormone and epidermal growth factor receptors in meningiomas.

    Science.gov (United States)

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  1. Surface engineering of Ti-O films by photochemical immobilization of gelatin

    International Nuclear Information System (INIS)

    Weng, Y.J.; Ren, J.R.; Huang, N.; Wang, J.; Chen, J.Y.; Leng, Y.X.; Liu, H.Q.

    2008-01-01

    Crystalline Ti-O films were prepared by unbalanced magnetron sputtering and the structure was confirmed by XRD. An organic layer of 3-aminopropylphosphonic acid (APP) was first introduced on the Ti-O films by self-assembling. The stability of the APP on Ti-O films was confirmed by XPS and FTIR analysis. Simultaneously, azido group was introduced in gelatin molecule to act as photoreactive point. The derivated gelatin was spin-coated onto the self-assembled layer and immobilized by UV irradiating. Chemical patterned surface was obtained by using a photomask when irradiating and confirmed by sirius red staining and surface profile analysis. Measured by surface profilometer, the thickness of the immobilized gelatin was about 5-20 nm. The adhering of human endothelial EVC304 cells on APP modified surface was enhanced in the cell culture test. Moreover, the adherence and growth of cells were prior on gelatin-immobilized region visually seen on the patterned surface. This result indicated gelatin-immobilized Ti-O surface can serve as a biocompatible biomaterial for endothelialization

  2. Preparation and characterization of alginate and gelatin microcapsules containing Lactobacillus rhamnosus.

    Science.gov (United States)

    Lopes, Susiany; Bueno, Luciano; Aguiar, Francisco DE; Finkler, Christine

    2017-01-01

    This paper describes the preparation and characterization of alginate beads coated with gelatin and containing Lactobacillus rhamnosus. Capsules were obtained by extrusion method using CaCl2 as cross linker. An experimental design was performed using alginate and gelatin concentrations as the variables investigated, while the response variable was the concentration of viable cells. Beads were characterized in terms of size, morphology, scanning electron microscopy (SEM), moisture content, Fourier Transform Infrared Spectrometry (FTIR), thermal behavior and cell viability during storage. The results showed that the highest concentration of viable cells (4.2 x 109 CFU/g) was obtained for 1 % w/v of alginate and 0.1 % w/v of gelatin. Capsules were predominantly spherical with a rough surface, a narrow size distribution ranging from 1.53 to 1.90 mm and a moisture content of 97.70 ± 0.03 %. Furthermore, FTIR and thermogravimetric analysis indicated an interaction between alginate-gelatin. Cell concentration of alginate/gelatin microcapsules was 105 CFU/g after 4 months of storage at 8 oC.

  3. Preparation and characterization of alginate and gelatin microcapsules containing Lactobacillus rhamnosus

    Directory of Open Access Journals (Sweden)

    SUSIANY LOPES

    2017-08-01

    Full Text Available ABSTRACT This paper describes the preparation and characterization of alginate beads coated with gelatin and containing Lactobacillus rhamnosus. Capsules were obtained by extrusion method using CaCl2 as cross linker. An experimental design was performed using alginate and gelatin concentrations as the variables investigated, while the response variable was the concentration of viable cells. Beads were characterized in terms of size, morphology, scanning electron microscopy (SEM, moisture content, Fourier Transform Infrared Spectrometry (FTIR, thermal behavior and cell viability during storage. The results showed that the highest concentration of viable cells (4.2 x 109 CFU/g was obtained for 1 % w/v of alginate and 0.1 % w/v of gelatin. Capsules were predominantly spherical with a rough surface, a narrow size distribution ranging from 1.53 to 1.90 mm and a moisture content of 97.70 ± 0.03 %. Furthermore, FTIR and thermogravimetric analysis indicated an interaction between alginate-gelatin. Cell concentration of alginate/gelatin microcapsules was 105 CFU/g after 4 months of storage at 8 oC.

  4. Synthesis and characterization of hydroxyapatite-gelatine composite materials for orthopaedic application

    Energy Technology Data Exchange (ETDEWEB)

    Yanovska, A., E-mail: biophy@yandex.ru [Institute of Applied Physics, National Academy of Sciences of Ukraine, 58 Petropavlovskaya Str., 40000, Sumy (Ukraine); Sumy State University, Ministry of Education and Science of Ukraine, 2 R. Korsakova Str., 40007, Sumy (Ukraine); Kuznetsov, V. [Institute of Applied Physics, National Academy of Sciences of Ukraine, 58 Petropavlovskaya Str., 40000, Sumy (Ukraine); Sumy State University, Ministry of Education and Science of Ukraine, 2 R. Korsakova Str., 40007, Sumy (Ukraine); Stanislavov, A. [Institute of Applied Physics, National Academy of Sciences of Ukraine, 58 Petropavlovskaya Str., 40000, Sumy (Ukraine); Husak, E. [Institute of Applied Physics, National Academy of Sciences of Ukraine, 58 Petropavlovskaya Str., 40000, Sumy (Ukraine); Sumy State University, Ministry of Education and Science of Ukraine, 2 R. Korsakova Str., 40007, Sumy (Ukraine); Pogorielov, M. [Sumy State University, Ministry of Education and Science of Ukraine, 2 R. Korsakova Str., 40007, Sumy (Ukraine); Starikov, V. [National Technical University ”Kharkov Polytechnic Institute”, 21 Frunze Str., 61002, Kharkov (Ukraine); Bolshanina, S. [Sumy State University, Ministry of Education and Science of Ukraine, 2 R. Korsakova Str., 40007, Sumy (Ukraine); Danilchenko, S. [Institute of Applied Physics, National Academy of Sciences of Ukraine, 58 Petropavlovskaya Str., 40000, Sumy (Ukraine)

    2016-11-01

    The composite materials based on hydroxyapatite (HA) and gelatine (Gel) with addition of silver and zirconium oxide were obtained. The study investigates a combination of low powered ultrasonic irradiation and low concentration of gelatine in the co-precipitation synthesis. These composites have different weight ratios of organic/inorganic components and may be synthesized in two ways: simple mixing and co-precipitation. Both of which were compared. The estimation of porosity, in vivo testing, surface morphology and phase composition as well as the IR-analysis were provided. Hydroxyapatite was the main crystalline phase in obtained composites. While around powdered HA-Gel composite the connective tissue capsule is formed without bone tissue formation, HA-Gel-Ag porous composite implantation leads to formation of new bone tissue and activation of cell proliferation. Addition of silver ions into composite material allows decreasing inflammation on the first stage of implantation and has positive effect on bone tissue formation. Some of the obtained composite materials containing silver or ZrO{sub 2} are biocompatible. bio-resorbable and osteoconductive with high level of porosity (75–85%). - Highlights: • Hydroxyapatite-gelatine composites with addition of Ag{sup +} and ZrO{sub 2} were obtained. • Composites were synthesized in two ways: simple mixing and co-precipitation. • Co-precipitation synthesis combined ultrasonic treatment and low concentration of gelatine. • Obtained composites have different weight ratios of organic/inorganic components. • Some composites are osteoconductive and all of them have high level of porosity (75–85%).

  5. Massive consumption of gelatinous plankton by Mediterranean apex predators.

    Directory of Open Access Journals (Sweden)

    Luis Cardona

    Full Text Available Stable isotopes of carbon and nitrogen were used to test the hypothesis that stomach content analysis has systematically overlooked the consumption of gelatinous zooplankton by pelagic mesopredators and apex predators. The results strongly supported a major role of gelatinous plankton in the diet of bluefin tuna (Thunnus thynnus, little tunny (Euthynnus alletteratus, spearfish (Tetrapturus belone and swordfish (Xiphias gladius. Loggerhead sea turtles (Caretta caretta in the oceanic stage and ocean sunfish (Mola mola also primarily relied on gelatinous zooplankton. In contrast, stable isotope ratios ruled out any relevant consumption of gelatinous plankton by bluefish (Pomatomus saltatrix, blue shark (Prionace glauca, leerfish (Lichia amia, bonito (Sarda sarda, striped dolphin (Stenella caerueloalba and loggerhead sea turtles (Caretta caretta in the neritic stage, all of which primarily relied on fish and squid. Fin whales (Balaenoptera physalus were confirmed as crustacean consumers. The ratios of stable isotopes in albacore (Thunnus alalunga, amberjack (Seriola dumerili, blue butterfish (Stromaeus fiatola, bullet tuna (Auxis rochei, dolphinfish (Coryphaena hyppurus, horse mackerel (Trachurus trachurus, mackerel (Scomber scombrus and pompano (Trachinotus ovatus were consistent with mixed diets revealed by stomach content analysis, including nekton and crustaceans, but the consumption of gelatinous plankton could not be ruled out completely. In conclusion, the jellyvorous guild in the Mediterranean integrates two specialists (ocean sunfish and loggerhead sea turtles in the oceanic stage and several opportunists (bluefin tuna, little tunny, spearfish, swordfish and, perhaps, blue butterfish, most of them with shrinking populations due to overfishing.

  6. A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Andrew J. Spence

    2013-04-01

    Full Text Available The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma, hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone.

  7. A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

    Science.gov (United States)

    Rodriguez, Isaac A.; Sell, Scott A.; McCool, Jennifer M.; Saxena, Gunjan; Spence, Andrew J.; Bowlin, Gary L.

    2013-01-01

    The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma), hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone. PMID:24709699

  8. Anti-PDGF receptor β antibody-conjugated squarticles loaded with minoxidil for alopecia treatment by targeting hair follicles and dermal papilla cells.

    Science.gov (United States)

    Aljuffali, Ibrahim A; Pan, Tai-Long; Sung, Calvin T; Chang, Shu-Hao; Fang, Jia-You

    2015-08-01

    This study developed lipid nanocarriers, called squarticles, conjugated with anti-platelet-derived growth factor (PDGF)-receptor β antibody to determine whether targeted Minoxidil (MXD) delivery to the follicles and dermal papilla cells (DPCs) could be achieved. Squalene and hexadecyl palmitate (HP) were used as the matrix of the squarticles. The PDGF-squarticles showed a mean diameter and zeta potential of 195 nm and -46 mV, respectively. Nanoparticle encapsulation enhanced MXD porcine skin deposition from 0.11 to 0.23 μg/mg. The antibody-conjugated nanoparticles ameliorated follicular uptake of MXD by 3-fold compared to that of the control solution in the in vivo mouse model. Both vertical and horizontal skin sections exhibited a wide distribution of nanoparticles in the follicles, epidermis, and deeper skin strata. The encapsulated MXD moderately elicited proliferation of DPCs and vascular endothelial growth factor (VEGF) expression. The active targeting of PDGF-squarticles may be advantageous to improving the limited success of alopecia therapy. Topical use of minoxidil is only one of the very few treatment options for alopecia. Nonetheless, the current delivery method is far from ideal. In this article, the authors developed lipid nanocarriers with anti-platelet-derived growth factor receptor ? antibody to target dermal papilla cells, and showed enhanced uptake of minoxidil. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Stepwise Progress in Epidermal Growth Factor Receptor/Radiation Studies for Head and Neck Cancer

    International Nuclear Information System (INIS)

    Harari, Paul M.

    2007-01-01

    The U.S. Food and Drug Administration approval of four new epidermal growth factor receptor (EGFR) inhibitors for cancer therapy (cetuximab, panitumumab, gefitinib, and erlotinib) over the last 3 years is a remarkable milestone in oncology. Indeed, molecular inhibition of EGFR signaling represents one of the most promising current arenas for the development of molecular-targeted cancer therapies. Epidermal growth factor receptor inhibitors from both the monoclonal antibody and tyrosine kinase inhibitor class have demonstrated clinical activity in the treatment of a broad spectrum of common human malignancies. For the discipline of radiation oncology, the 2006 report of a phase III trial demonstrating a survival advantage for advanced head and neck cancer patients with the addition of weekly cetuximab during a 7-week course of radiation is particularly gratifying. Indeed, this is the first phase III trial to confirm a survival advantage with the addition of a molecular-targeted agent to radiation. Furthermore, this result seems to have been achieved with only a modest increment in overall treatment toxicity and with very high compliance to the prescribed treatment regimen. Nevertheless, much remains to be learned regarding the rational integration of EGFR inhibitors into cancer treatment regimens, as well as methods to optimize the selection of patients most likely to benefit from EGFR inhibitor strategies

  10. A peptide antagonist of the ErbB1 receptor inhibits receptor activation, tumor cell growth and migration in vitro and xenograft tumor growth in vivo

    DEFF Research Database (Denmark)

    Xu, Ruodan; Povlsen, Gro Klitgaard; Soroka, Vladislav

    2010-01-01

    The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization...... constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF)-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced Erb....... Structural studies have revealed that ErbB receptor dimers are stabilized by receptor-receptor interactions, primarily mediated by a region in the second extracellular domain, termed the "dimerization arm". The present study is the first biological characterization of a peptide, termed Inherbin3, which...

  11. Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Cui DT

    2017-09-01

    Full Text Available Danting Cui,1 Xiaodan Lu,1 Chenggong Yan,1 Xiang Liu,1 Meirong Hou,1 Qi Xia,2 Yikai Xu,1 Ruiyuan Liu2,3 1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China Abstract: Bombesin (BBN, an analog of gastrin-releasing peptide (GRP, specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC. Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3 nanoprobe containing fluorescein (Gd2O3-5(6-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN for targeted magnetic resonance (MR/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r1 of Gd2O3-FI-PEG-BBN (r1 =4.23 mM–1s–1 is comparable to that of clinically used Magnevist (Gd-DTPA. Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the Gd2O3-FI-PEG-BBN in PC-3 tumor cells. Moreover, Gd2O3-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted Gd2O3-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated Gd2O3 may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications. Keywords: magnetic resonance imaging, gadolinium oxide, bombesin, gastrin-releasing peptide receptor, molecular imaging

  12. Evaluation of fibrin-gelatin hydrogel as biopaper for application in skin bioprinting: An in-vitro study.

    Science.gov (United States)

    Hakam, Mohammad Sadjad; Imani, Rana; Abolfathi, Nabiollah; Fakhrzadeh, Hossein; Sharifi, Ali Mohammad

    2016-01-01

    Recent advances in tissue engineering have led to the development of the concept of bioprinting as an interesting alternative to traditional tissue engineering approaches. Biopaper, a biomimetic hydrogel, is an essential component of the bioprinting process. The aim of this work was to synthesize a biopaper made of fibrin-gelatin hybrid hydrogel for application in skin bioprinting. Different composition percentages of the two biopolymer hydrogels, fibrin-gelatin, have been studied for the construction of the biopaper and were examined in terms of water absorption, biodegradability, glucose absorption, mechanical properties and water vapor transmission. Subsequently, tissue fusion study was performed on prepared 3T3 fibroblast cell line pellets embedded into the hydrogel. Based on the obtained results, fibrin-gelatin blend hydrogel with the same proportion of two components provides a natural scaffold for fibroblast-based bioink embedding and culture. The suggested optimized hydrogel was a suitable candidate as a biopaper for skin bioprinting technology.

  13. A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons.

    Science.gov (United States)

    Li, Shu-Jing; Vaughan, Alexander; Sturgill, James Fitzhugh; Kepecs, Adam

    2018-06-06

    Retrogradely transported neurotropic viruses enable genetic access to neurons based on their long-range projections and have become indispensable tools for linking neural connectivity with function. A major limitation of viral techniques is that they rely on cell-type-specific molecules for uptake and transport. Consequently, viruses fail to infect variable subsets of neurons depending on the complement of surface receptors expressed (viral tropism). We report a receptor complementation strategy to overcome this by potentiating neurons for the infection of the virus of interest-in this case, canine adenovirus type-2 (CAV-2). We designed AAV vectors for expressing the coxsackievirus and adenovirus receptor (CAR) throughout candidate projection neurons. CAR expression greatly increased retrograde-labeling rates, which we demonstrate for several long-range projections, including some resistant to other retrograde-labeling techniques. Our results demonstrate a receptor complementation strategy to abrogate endogenous viral tropism and thereby facilitate efficient retrograde targeting for functional analysis of neural circuits. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Dynamic Load Measurement of Ballistic Gelatin Impact Using an Instrumented Tube

    Science.gov (United States)

    Seidt, J. D.; Periira, J. M.; Hammer, J. T.; Gilat, A.; Ruggeri, C. R.

    2012-01-01

    Bird strikes are a common problem for the aerospace industry and can cause serious damage to an aircraft. Ballistic gelatin is frequently used as a surrogate for actual bird carcasses in bird strike tests. Numerical simulations of these tests are used to supplement experimental data, therefore it is necessary to use numerical modeling techniques that can accurately capture the dynamic response of ballistic gelatin. An experimental technique is introduced to validate these modeling techniques. A ballistic gelatin projectile is fired into a strike plate attached to a 36 in. long sensor tube. Dynamic load is measured at two locations relative to the strike plate using strain gages configured in a full Wheatstone bridge. Data from these experiments are used to validate a gelatin constitutive model. Simulations of the apparatus are analyzed to investigate its performance.

  15. Determination of the gelatinization temperature of starch presented in maize flours

    Energy Technology Data Exchange (ETDEWEB)

    Coral, D F; Pineda-Gomez, P; Rosales-Rivera, A [Laboratorio de Magnetismo y Materiales Avanzados, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Colombia, Manizales, Caldas (Colombia); Rodriguez-Garcia, M E, E-mail: dfcoralc@unal.edu.c [Departamento de Nanotecnologia, Centro de Fisica Aplicada y Tecnologia Avanzada, UNAM, Queretaro, Qro. (Mexico)

    2009-05-01

    A study of the influence of the moisture and the grain size on the gelatinization temperature (Tp1) of starch from four industrial maize flours as well as an unprocessed maize sample is presented. The gelatinization is a phase transition that can be observed using Differential Scanning Calorimetry (DSC), and it is manifest as an endothermic peak in the DSC thermogram. Results show that for 60, 65, 70 and 75% of moisture, the endothermic peak temperature increases from 70 to 75 deg. C when the moisture increases, and decrease when the grain size increases from 250 to 420mum. A study of the gelatinization enthalpy (DELTAHp) is also presented, this is related with the gelatinized starch present in the sample. The enthalpy decrease when the moisture increases and it decrease when grain size is increased.

  16. Application of Bio-digestion for Capsule Gelatin-- From the Pharmaceutical Wastes to the Manure

    Science.gov (United States)

    Pan, C.; Huang, S.; Chang, Y.; Wen, J.

    2013-12-01

    The purpose of this study was to bio-digest the capsule gelatin from the waste of pharmaceutical processes such as cutting and stamping for capsule shells producing. We screened soil bacterial flora for capsule gelatin biolysis, and found the most competent one named Yuntech-7. A 15% (w/w) of capsule gelatin could fully digested by Yuntech-7 for 3 days growth with an N-limited medium in a 37°C incubator. In order to recycle and reuse the gelatin waste, the different percentages of capsule gelatin were co-composted with the vegetable residues to produce manure in an anaerobic fermentation by an extra Yuntech-7 inoculation. After 14 days incubation, we collected the filtrate to examine the contents of N, P, and K. The data shows that the P and K keep the same value by roughly between the blank and the control sets, but the total N values were approximately a 5-fold increase in 20% and a 10-fold increase in 40% of capsule gelatin integrated. We suggested that the capsule gelatin was majorly decomposed by Yuntech-7, because the total N value was no observable change in the capsule gelatin and vegetable residues co-compost with a Yuntech-7-free condition. We also performed some field tests using the capsule gelatin generated liquid manure, and the preliminary test shows the plants got great benefits on culture size and in environmental resistance. In conclusion, the process in bio-digestion of waste capsule gelatin by soil bacteria, Yuntech-7, was produced a valuable manure not only aliment the plants but also complement the soil bacterial populations.

  17. Physicochemical Properties of Gelatin Extracted from Buffalo Hide Pretreated with Different Acids.

    Science.gov (United States)

    Mulyani, Sri; Setyabudi, Francis M C Sigit; Pranoto, Yudi; Santoso, Umar

    2017-01-01

    The acid pretreatment of collagen molecules disrupts their crosslinks and assists in the release of acid-soluble proteins, fats, and other components. Generally, to achieve optimum extraction efficiency, strong acids may be used at a lower acid concentration compared to weak acids. This study aimed to determine the yield and physicochemical properties of gelatins extracted from buffalo hides pretreated with different acids. Hides were extracted with hydrochloric, citric, and acetic acids at concentrations of 0.3, 0.6, 0.9, 1.2, and 1.5 M. A completely randomized design and the least significant difference test were used in the experimental design, and all measurements were performed in triplicate. The highest yield (29.17%) was obtained from pretreatment with 0.9 M HCl. The gel strength did not differ significantly ( p >0.05) according to acid type (280.26-259.62 g Bloom), and the highest viscosity was obtained from the 0.6 M citric acid pretreatment. All the gelatins contained α- and β-chain components and several degraded peptides (24-66 kDa). The color and Fourier-transform infrared spectrum of the gelatin extracted using 0.9 M HCl were similar to those of commercial bovine skin gelatin. In general, the physicochemical properties of the gelatin complied with the industry standard set by the Gelatin Manufacturers Institute of America, revealing that buffalo hide could serve as a potential alternative source of gelatin.

  18. Evaluation of the potential anti-adhesion effect of the PVA/Gelatin membrane.

    Science.gov (United States)

    Bae, Sang-Ho; Son, So-Ra; Kumar Sakar, Swapan; Nguyen, Thi-Hiep; Kim, Shin-Woo; Min, Young-Ki; Lee, Byong-Taek

    2014-05-01

    A common and prevailing complication for patients with abdominal surgery is the peritoneal adhesion that follows during the post-operative recovery period. Biodegradable polymers have been suggested as a barrier to prevent the peritoneal adhesion. In this work, as a preventive method, PVA/Gelatin hydrogel-based membrane was investigated with various combinations of PVA and gelatin (50/50, 30/70/, and 10/90). Membranes were made by casting method using hot PVA-gelatin solution and the gelatin was cross-linked by exposing UV irradiation for 5 days to render stability of the produced sheathed form in the physiological environment. Physical crosslinking was chosen to avoid the problems of potential cytotoxic effect of chemical crosslinking. Their materials characterization and mechanical properties were evaluated by SEM surface characterization, hydrophilicity, biodegradation rate, and so forth. Cytocompatibility was observed by in vitro experiments with cell proliferation using confocal laser scanning microscopy and the MTT assay by L-929 mouse fibroblast cells. The fabricated PVA/Gel membranes were implanted between artificially defected cecum and peritoneal wall in rats and were sacrificed after 1 and 2 weeks post-operative to compare their tissue adhesion extents with that of control group where the defected surface was not separated by PVA/Gel membrane. The PVA/Gel membrane (10/90) significantly reduced the adhesion extent and showed to be a potential candidate for the anti-adhesion application. Copyright © 2013 Wiley Periodicals, Inc.

  19. Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties.

    Science.gov (United States)

    Ullm, Sandra; Krüger, Anne; Tondera, Christoph; Gebauer, Tim P; Neffe, Axel T; Lendlein, Andreas; Jung, Friedrich; Pietzsch, Jens

    2014-12-01

    Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Hybrid chitosan-ß-glycerol phosphate-gelatin nano-/micro fibrous scaffolds with suitable mechanical and biological properties for tissue engineering.

    Science.gov (United States)

    Lotfi, Marzieh; Bagherzadeh, Roohollah; Naderi-Meshkin, Hojjat; Mahdipour, Elahe; Mafinezhad, Asghar; Sadeghnia, Hamid Reza; Esmaily, Habibollah; Maleki, Masoud; Hasssanzadeh, Halimeh; Ghayaour-Mobarhan, Majid; Bidkhori, Hamid Reza; Bahrami, Ahmad Reza

    2016-03-01

    Scaffold-based tissue engineering is considered as a promising approach in the regenerative medicine. Graft instability of collagen, by causing poor mechanical properties and rapid degradation, and their hard handling remains major challenges to be addressed. In this research, a composite structured nano-/microfibrous scaffold, made from a mixture of chitosan-ß-glycerol phosphate-gelatin (chitosan-GP-gelatin) using a standard electrospinning set-up was developed. Gelatin-acid acetic and chitosan ß-glycerol phosphate-HCL solutions were prepared at ratios of 30/70, 50/50, 70/30 (w/w) and their mechanical and biological properties were engineered. Furthermore, the pore structure of the fabricated nanofibrous scaffolds was investigated and predicted using a theoretical model. Higher gelatin concentrations in the polymer blend resulted in significant increase in mean pore size and its distribution. Interaction between the scaffold and the contained cells was also monitored and compared in the test and control groups. Scaffolds with higher chitosan concentrations showed higher rate of cell attachment with better proliferation property, compared with gelatin-only scaffolds. The fabricated scaffolds, unlike many other natural polymers, also exhibit non-toxic and biodegradable properties in the grafted tissues. In conclusion, the data clearly showed that the fabricated biomaterial is a biologically compatible scaffold with potential to serve as a proper platform for retaining the cultured cells for further application in cell-based tissue engineering, especially in wound healing practices. These results suggested the potential of using mesoporous composite chitosan-GP-gelatin fibrous scaffolds for engineering three-dimensional tissues with different inherent cell characteristics. © 2015 Wiley Periodicals, Inc.

  1. alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.

    Science.gov (United States)

    Taherzadeh, S; Sharma, S; Chhajlani, V; Gantz, I; Rajora, N; Demitri, M T; Kelly, L; Zhao, H; Ichiyama, T; Catania, A; Lipton, J M

    1999-05-01

    The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.

  2. Effect of silver nanoparticles on the spectral luminescent properties of a gelatin film

    Science.gov (United States)

    Efendiev, T. Sh.; Kruchenok, J. V.; Rubinov, A. N.

    2013-03-01

    We studied the absorption and fluorescence spectra of a rhodamine 6G-activated gelatin film of thickness 10 μm, with and without silver nanoparticles. We observed that doping the film with nanoparticles of diameter 5 nm leads to an increase in the intensity of the absorption spectrum by a factor of 1.17 and its short-wavelength shift (~1.5 nm), while the intensity of the fluorescence spectrum increases by a factor of ~2.

  3. Fabrication of chemically cross-linked porous gelatin matrices.

    Science.gov (United States)

    Bozzini, Sabrina; Petrini, Paola; Altomare, Lina; Tanzi, Maria Cristina

    2009-01-01

    The aim of this study was to chemically cross-link gelatin, by reacting its free amino groups with an aliphatic diisocyanate. To produce hydrogels with controllable properties, the number of reacting amino groups was carefully determined. Porosity was introduced into the gelatin-based hydrogels through the lyophilization process. Porous and non-porous matrices were characterized with respect to their chemical structure, morphology, water uptake and mechanical properties. The physical, chemical and mechanical properties of the porous matrices are related to the extent of their cross-linking, showing that they can be controlled by varying the reaction parameters. Water uptake values (24 hours) vary between 160% and 200% as the degree of cross-linking increases. The flexibility of the samples also decreases by changing the extent of cross-linking. Young's modulus shows values between 0.188 KPa, for the highest degree, and 0.142 KPa for the lowest degree. The matrices are potential candidates for use as tissue-engineering scaffolds by modulating their physical chemical properties according to the specific application.

  4. Drug addiction: targeting dynamic neuroimmune receptor interactions as a potential therapeutic strategy.

    Science.gov (United States)

    Jacobsen, Jonathan Henry W; Hutchinson, Mark R; Mustafa, Sanam

    2016-02-01

    Drug addiction and dependence have proven to be difficult psychiatric disorders to treat. The limited efficacy of neuronally acting medications, such as acamprosate and naltrexone, highlights the need to identify novel targets. Recent research has underscored the importance of the neuroimmune system in many behavioural manifestations of drug addiction. In this review, we propose that our appreciation for complex phenotypes such as drug addiction and dependence will come with a greater understanding that these disorders are the result of intricate, interconnected signalling pathways that are, if only partially, determined at the receptor level. The idea of receptor heteromerisation and receptor mosaics will be introduced to explain cross talk between the receptors and signalling molecules implicated in neuroimmune signalling pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Extraction and characterisation of gelatin from the skin of striped ...

    African Journals Online (AJOL)

    Prabjeet Singh

    2017-01-04

    Jan 4, 2017 ... squid skin in 1% H2O2 in 0.01 M NaOH for 48 h could improve the ... of fish skin gelatin. Gelatin was extracted from washed giant catfish skin as described ..... bleached, because the flesh could be stained by ink, viscera and ...

  6. Molecular analysis of the nerve growth factor receptor

    International Nuclear Information System (INIS)

    Hempstead, B.; Patil, N.; Olson, K.; Chao, M.

    1988-01-01

    An essential molecule in the translocation of information by nerve growth factor (NGF) to responsive cells is the cell-surface receptor for NGF. This paper presents information on the genomic structure of the NGF receptor gene, NGF receptor models, and transfection of NGF receptors. Equilibrium binding of [ 125 I]NGF to cells reveals two distinct affinity states for the NGF receptor. The human NGF receptor gene is a single-copy gene, consisting of six exons that span 23 kb. The receptor gene is capable of being transferred to fibroblast cells from human genomic DNA and expressed at high levels. The constitutive nature of the receptor promoter sequence is a partial explanation of why this tissue-specific gene is expressed efficiently in a variety of nonneuronal cells after genomic gene transfer. The two kinetic forms of the NGF receptor appear to be encoded by the same protein, which is the product of a single gene

  7. Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.

    Science.gov (United States)

    Navaei, Ali; Saini, Harpinder; Christenson, Wayne; Sullivan, Ryan Tanner; Ros, Robert; Nikkhah, Mehdi

    2016-09-01

    The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly

  8. Targeted therapies in the treatment of urothelial cancers.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2017-07-01

    Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Polymer-Based Novel Lung Targeted Delivery Systems.

    Science.gov (United States)

    Elmowafy, Enas; Osman, Rihab; Ishak, Rania A H

    2017-01-01

    Due to its unique features, the respiratory tract had received great attention as a promising non-invasive route for drug administration to achieve both local and systemic effects. Efforts spent to tailor systems able to overcome the lung defence mechanisms and biological barriers are followed in this review. Aerodynamic diameter, morphology, lung deposition and drug release profiles are the main criteria describing the selected new smart lung targeted delivery systems. Novel systems such as nanoparticles, nano-embedded-in microparticles (NEM), small microparticles (MP), large porous particles (LPP), PulmospheresTM and polymeric micelles are used to passively target different areas in the respiratory tract. The most common preparation methods are outlined in the article. Special emphasis was given to the characteristics of the polymers used to fabricate the developed systems. Efforts made to prepare systems using chitosan (CS), alginate (alg), hyaluronic acid (HA), gelatin and albumin as examples of natural polymers and poly lactic-co-glycolic acid (PLGA) and poly(Ɛ-caprolactone) (PCL) as synthetic polymers were compiled. The continuous development and work in the area of lung targeting resulted in the development of engineered smart platforms with the capability to carry small drug molecules, proteins and genes to treat a variety of local and systemic diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Gelatine-assisted synthesis of magnetite nanoparticles for magnetic hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Alves, André F.; Mendo, Sofia G. [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal); Ferreira, Liliana P. [Universidade de Lisboa, Biosystems and Integrative Sciences Institute, Faculdade de Ciências (Portugal); Mendonça, Maria Helena [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal); Ferreira, Paula [University of Aveiro, Department of Materials and Ceramic Engineering, CICECO - Aveiro Institute of Materials (Portugal); Godinho, Margarida; Cruz, Maria Margarida [Universidade de Lisboa, Biosystems and Integrative Sciences Institute, Faculdade de Ciências (Portugal); Carvalho, Maria Deus, E-mail: mdcarvalho@ciencias.ulisboa.pt [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal)

    2016-01-15

    Magnetite nanoparticles were synthesized by the co-precipitation method exploring the use of gelatine and agar as additives. For comparison, magnetite nanoparticles were also prepared by standard co-precipitation, by co-precipitation with the addition of a surfactant (sodium dodecyl sulphate) and by the thermal decomposition method. The structure and morphology of the synthesized nanoparticles were investigated by powder X-ray diffraction and transmission electron microscopy. Their magnetic properties were studied by SQUID magnetometry and {sup 57}Fe Mössbauer spectroscopy. The nanoparticles potential for applications in magnetic hyperthermia was evaluated through heating efficiency under alternating magnetic field. The results show that all synthesis methods produce Fe{sub 3−x}O{sub 4} nanoparticles with similar sizes. The nanoparticles synthesized in the gelatine medium display the narrowest particle size distribution, the lowest oxidation degree, one of the highest saturation magnetization values and the best hyperthermia efficiency, proving that this gelatine-assisted synthesis is an efficient, environmental friendly, and low-cost method to produce magnetite nanoparticles. Graphical Abstract: A new gelatine-assisted method is an efficient and low-cost way to synthesize magnetite nanoparticles with enhanced magnetic hyperthermia.

  11. Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target

    Science.gov (United States)

    Beningo, Karen A.; Wang, Yu-li

    2002-01-01

    Phagocytosis is an actin-based process used by macrophages to clear particles greater than 0.5 microm in diameter. In addition to its role in immunological responses, phagocytosis is also necessary for tissue remodeling and repair. To prevent catastrophic autoimmune reactions, phagocytosis must be tightly regulated. It is commonly assumed that the recognition/selection of phagocytic targets is based solely upon receptor-ligand binding. Here we report an important new criterion, that mechanical parameters of the target can dramatically affect the efficiency of phagocytosis. When presented with particles of identical chemical properties but different rigidity, macrophages showed a strong preference to engulf rigid objects. Furthermore, phagocytosis of soft particles can be stimulated with the microinjection of constitutively active Rac1 but not RhoA, and with lysophosphatidic acid, an agent known to activate the small GTP-binding proteins of the Rho family. These data suggest a Rac1-dependent mechanosensory mechanism for phagocytosis, which probably plays an important role in a number of physiological and pathological processes from embryonic development to autoimmune diseases.

  12. Triple-negative breast cancer: new perspectives for targeted therapies

    Directory of Open Access Journals (Sweden)

    Tomao F

    2015-01-01

    Full Text Available Federica Tomao,1 Anselmo Papa,2 Eleonora Zaccarelli,2 Luigi Rossi,2 Davide Caruso,2 Marina Minozzi,2 Patrizia Vici,3 Luigi Frati,4 Silverio Tomao21Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, 3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy; 4Department of Molecular Medicine, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, ItalyAbstract: Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.Keywords: basal-like breast cancer, estrogen–progesterone receptors, gene-expression microarray, human epidermal growth factor receptor 2, chemotherapy, target therapy

  13. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

  14. Curcumin-Loaded Chitosan/Gelatin Composite Sponge for Wound Healing Application

    Directory of Open Access Journals (Sweden)

    Van Cuong Nguyen

    2013-01-01

    Full Text Available Three composite sponges were made with 10% of curcumin and by using polymers, namely, chitosan and gelatin with various ratios. The chemical structure and morphology were evaluated by FTIR and SEM. These sponges were evaluated for water absorption capacity, antibacterial activity, in vitro drug release, and in vivo wound healing studies by excision wound model using rabbits. The in vivo study presented a greater wound closure in wounds treated with curcumin-composite sponge than those with composite sponge without curcumin and untreated group. These obtained results showed that combination of curcumin, chitosan and gelatin could improve the wound healing activity in comparison to chitosan, and gelatin without curcumin.

  15. Preparation of biodegradable gelatin/PVA porous scaffolds for skin regeneration.

    Science.gov (United States)

    Mahnama, Hossein; Dadbin, Susan; Frounchi, Masoud; Rajabi, Sareh

    2017-08-01

    Porous scaffolds composed of gelatin/poly (vinyl alcohol), (Gel/PVA), were prepared using combination of freeze gelation and freeze drying methods. The effect of polymer concentration, gelatin/PVA ratio, and glutaraldehyde/gelatin ratio (GA/Gel) was investigated on morphology of pores, swelling ratio, biodegradation, and skin cell culture. At optimum preparation conditions the scaffolds had uniform pore size distributions showing high swelling ratio of 23.6. The scaffolds were of biodegradable nature and almost degraded in 28 days. Human dermal fibroblast cells (HDF) were cultured on the scaffolds and MTS assay was conducted to evaluate the influence of PVA on growth and proliferation of the cells.

  16. In vitro evaluation of crosslinked electrospun fish gelatin scaffolds

    International Nuclear Information System (INIS)

    Gomes, S.R.; Rodrigues, G.; Martins, G.G.; Henriques, C.M.R.; Silva, J.C.

    2013-01-01

    Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. - Highlights: ► Electrospinning of fish gelatin dissolved in both water or concentrated acetic acid ► Glutaraldehyde, genipin and dehydrothermal treatment effectively crosslink the fish gelatin fibers ► Fibroblasts effectively adhere to and propagate on all scaffolds ► Cell population is highest for glutaraldehyde crosslinked scaffolds ► Cells exhibit more filopodia and stress fibers on glutaraldehyde crosslinked scaffolds

  17. In vitro evaluation of crosslinked electrospun fish gelatin scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, S.R. [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Rodrigues, G.; Martins, G.G. [Centro de Biologia Ambiental / Departamento de Biologia Animal, Faculdade de Ciências da Universidade de Lisboa, FCUL, 1749-016 Campo Grande, Lisboa (Portugal); Henriques, C.M.R. [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Silva, J.C., E-mail: jcs@fct.unl.pt [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2013-04-01

    Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. - Highlights: ► Electrospinning of fish gelatin dissolved in both water or concentrated acetic acid ► Glutaraldehyde, genipin and dehydrothermal treatment effectively crosslink the fish gelatin fibers ► Fibroblasts effectively adhere to and propagate on all scaffolds ► Cell population is highest for glutaraldehyde crosslinked scaffolds ► Cells exhibit more filopodia and stress fibers on glutaraldehyde crosslinked scaffolds.

  18. Fibroblast growth factor receptor (FGFR) alterations in squamous differentiated bladder cancer: a putative therapeutic target for a small subgroup.

    Science.gov (United States)

    Baldia, Philipp H; Maurer, Angela; Heide, Timon; Rose, Michael; Stoehr, Robert; Hartmann, Arndt; Williams, Sarah V; Knowles, Margaret A; Knuechel, Ruth; Gaisa, Nadine T

    2016-11-01

    Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis). Only single cases displayed enhanced protein expression, most frequently FGFR3 overexpression (9.4% (6/64)). FISH showed no amplifications of FGFR1, 2 or 3. Break apart events were only slightly above the cut off in 12.1% (8/66) of cases and no FGFR3-TACC3 rearrangements could be proven by qPCR. FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 protein overexpression (p bladder cancer (n = 85), which revealed reduced overall expression of FGFR1 and FGFR2 in tumors compared to normal tissue, while expression of FGFR3 remained high. In the TCGA "squamous-like" subtype FGFR3 mutations were found in 4.9% and correlated with high FGFR3 RNA expression. Mutations of FGFR1 and FGFR2 were less frequent (2.4% and 1.2%). Hence, our comprehensive study provides novel insights into a subgroup of squamous differentiated bladder tumors that hold clues for novel therapeutic regimens and may benefit from FGFR3-targeted therapies.

  19. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting

    International Nuclear Information System (INIS)

    Reubi, Jean Claude; Waser, Beatrice

    2003-01-01

    Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy. Recent in vitro studies have shown that many cancers can overexpress not only one but several peptide receptors concomitantly. One of the challenges for nuclear medicine in this field in the coming decade will be to take advantage of the co-expression of peptide receptors for multireceptor tumour targeting. In vitro receptor studies can reveal which peptide receptor is overexpressed in which tumour and which receptors are co-expressed in an individual tumour; such knowledge is a prerequisite for successful in vivo development. One group of tumours of particular interest in this respect is the neuroendocrine tumours, which have previously been shown often to express peptide receptors. This review summarises our investigations of the concomitant expression of 13 different peptide receptors, in more than 100 neuroendocrine tumours of the human intestine, pancreas and lung, using in vitro receptor autoradiography with subtype-selective ligands. The incidence and density of the somatostatin receptors sst 1 -sst 5 , the VIP receptors VPAC 1 and VPAC 2 , the CCK 1 and CCK 2 receptors, the three bombesin receptor subtypes BB 1 (NMB receptor), BB 2 (GRP receptor) and BB 3 , and GLP-1 receptors were evaluated. While the presence of VPAC 1 and sst 2 was detected in the majority of these neuroendocrine tumours, the other receptors, more differentially expressed, revealed a characteristic receptor pattern in several tumour types. Ileal carcinoids expressed sst 2 and VPAC 1 receptors in virtually all cases and had CCK 1 , CCK 2 , sst 1 or sst 5 in approximately half of the cases; they were the only tumours of this series to express NMB receptors. Insulinomas were characterised by a very high incidence of GLP-1, CCK 2 and VPAC 1 receptors, with the GLP-1 receptors expressed in a particularly high density; they expressed sst 2 in two-thirds and sst 1 in approximately half of

  20. Synthesis of biocompatible hydrophobic silica-gelatin nano-hybrid by sol-gel process.

    Science.gov (United States)

    Smitha, S; Shajesh, P; Mukundan, P; Nair, T D R; Warrier, K G K

    2007-03-15

    Silica-biopolymer hybrid has been synthesised using colloidal silica as the precursor for silica and gelatin as the biopolymer counterpart. The surface modification of the hybrid material has been done with methyltrimethoxysilane leading to the formation of biocompatible hydrophobic silica-gelatin hybrid. Here we are reporting hydrophobic silica-gelatin hybrid and coating precursor for the first time. The hybrid gel has been evaluated for chemical modification, thermal degradation, hydrophobicity, particle size, transparency under the UV-visible region and morphology. FTIR spectroscopy has been used to verify the presence of CH(3) groups which introduce hydrophobicity to the SiO2-MTMS-gelatin hybrids. The hydrophobic property has also been tailored by varying the concentration of methyltrimethoxysilane. Contact angle by Wilhelmy plate method of transparent hydrophobic silica-gelatin coatings has been found to be as high as approximately 95 degrees . Oxidation of the organic group which induces the hydrophobic character occurs at 530 degrees C which indicates that the surface hydrophobicity is retained up to that temperature. Optical transmittance of SiO2-MTMS-gelatin hybrid coatings on glass substrates has been found to be close to 100% which will enable the hybrid for possible optical applications and also for preparation of transparent biocompatible hydrophobic coatings on biological substrates such as leather.