327 research outputs found
Anti-GD2 chimeric antigen receptor & trail modified mesenchymal progenitors as novel strategy against ewing’s sarcoma
No full textDeveloping cell therapies as drug products
No full textIn the last 20 years, the global regulatory frameworks for drug assessment have been managing the challenges posed by using cellular products as new therapeutic tools. Currently, they are defined as “Advanced Therapy Medicinal Products”, comprising a large group of cellular types that either alone or in combination with gene and tissue engineering technology. They have the potential to change the natural course of still lethal or highly debilitating diseases, including cancers, opportunistic infections and chronic inflammatory conditions. Globally, more than 50 cell-based products have obtained market authorization. This overview describes the advantages and unsolved challenges on developing cells as innovative therapeutic vehicles. The main cell therapy players and the legal framework are discussed, starting from chimeric antigen receptor T-cells for leukaemia and solid tumours, dealing then with lymphocytes as potent anti-microbiological tools and then focusing on mesenchymal stem/stromal cells whose role covers regenerative medicine, immunology and anti-tumour therapy
5P Anti-GD2 chimeric antigen receptor & TRAIL modified mesenchymal progenitors as novel strategy against Ewing’s sarcoma
No full textSTUDI PERANCANGAN JEMBATAN GANTUNG DI DESA AIK PRAPA DENGAN GELAGAR WEB OPENING BEAM
No full textPerancangan jembatan gantung yang terletak di Desa Aik Prapa, Kabupaten Lombok Timur, Provinsi Nusa Tenggara Barat. Dengan bentang 96 meter dan lebar 1,8 meter termasuk jembatan kelas I. Salah satu permasalahan yang sering menghambat perkembangan suatu daerah yaitu kurangnya prasarana transportasi penyebrangan seperti jembatan. Penggunaan baja web opening beam bertujuan untuk mengetahui dan meningkatkan kekuatan serta kekakuan pada struktur atas jembatan. Jembatan gantung adalah sistem struktur jembatan yang menggunakan wirerop sebagai pemikul utama beban lalu lintas dan berat sendiri. Pada sistem ini wirerop utama memikul beberapa hanger (penggangtung) yang menghubungkan antara wirerop utama dengan gelagar atau struktur jembatan. Wirerop utama dihubungkan pada kedua pylon (menara) dan memanjang disepanjang jembatan yang berakhir pada pengangkeran di kedua ujung jembatan untuk menahan pergerakan vertikal dan horizontal akibat beban beban yang berkerja. Pada pylon tersebut dipasang saddle (dudukan) beserta roller yang berfungsi sebagai pengarah wirerop utama.
Pada tugas akhir ini struktur atas jembatan yang akan dirancang menggunakan metodologi meliputi pengumpulan data dan studi lietratur, pemodelan jembatan menggunakan SAP 2000 V.14, pembebanan rencana, analisis truktur atas dan bawah jembatan yang meliputi. Tiang sandaran, plat lantai, tegnagan kabel dan mennara, perencanaan gelagar melintang dan memanjang dengan menggunakan web opening beam, baut angkur dan base plate, elastamor, pondasi sumuran, dan perencanaan blok angkur.
Berdasarkan hasil perencanaan yang diperoleh hasil sebagai berikut: perencanaan tiang sandaran menggunakan profil L 40. 40. 4. gelagar menggunakan web opening beam WF.225. 150. 7. 10. Menara menggunakan WF. 400. 400. 18. 28 dengan tinggi 12, 5 m. Kabel utama menggunakan tali kawat baja 6 x WS (36) IWRC diameter 50 mm dengan lendutan 0,154 m dan hanger 20 mm. Elastamor dengan ukuran 450 x 450 x 104 mm. Pondasi sumuran menggunakan tulanagan D22 – 400 mm dan tulangan geser D16 – 400 mm dengan kedalaman 6 m dan diameter 2 m. Blok angkur dengan dimensi 4,5 x 3 x 5 m mutu beton 20 MPa dan mutu tulanagan 240 MPa.
Kata Kunci : Studi perancangan, Jembatan Gantung, Web Opening Beam
Targeting GD2-positive glioblastoma by chimeric antigen receptor empowered mesenchymal progenitors
No full textTumor targeting by genetically modified mesenchymal stromal/stem cells (MSCs) carrying anti-cancer molecules represents a promising cell-based strategy. We previously showed that the pro-apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be successfully delivered by MSCs to cancer sites. While the interaction between TRAIL and its receptors is clear, more obscure is the way in which MSCs can selectively target tumors and their antigens. Several neuroectoderm-derived neoplasms, including glioblastoma (GBM), sarcomas, and neuroblastoma, express high levels of the tumor-associated antigen GD2. We have already challenged this cell surface disialoganglioside by a chimeric antigen receptor (CAR)-T cell approach against neuroblastoma. With the intent to maximize the therapeutic profile of MSCs delivering TRAIL, we here originally developed a bi-functional strategy where TRAIL is delivered by MSCs that are also gene modified with the truncated form of the anti-GD2 CAR (GD2 tCAR) to mediate an immunoselective recognition of GD2-positive tumors. These bi-functional MSCs expressed high levels of TRAIL and GD2 tCAR associated with a robust anti-tumor activity against GD2-positive GBM cells. Most importantly, the anti-cancer action was reinforced by the enhanced targeting potential of such bi-functional cells. Collectively, our results suggest that a truncated anti-GD2 CAR might be a powerful new tool to redirect MSCs carrying TRAIL against GD2-expressing tumors. This affinity-based dual targeting holds the promise to combine site-specific and prolonged retention of MSCs in GD2-expressing tumors, thereby providing a more effective delivery of TRAIL for still incurable cancers. © 2018, Springer Nature America, Inc
Inovasi Ember Kompos untuk Menghasilkan Pupuk Organik Dalam Menunjang Pertanian Maju dan Berkelanjutan di Desa Aik Prapa, Lombok Timur
No full textThe composter bucket used to be an alternative that could be applied in Aik Prapa Village, Aikmel District, East Lombok to produce organic fertilizer as well as an alternative solution to the problem of environmental pollution and limited fertilizers. The process of making organic fertilizer using a composter bucket was an innovation based on the fermentation process of organic matter. The fermentation process in the composter bucket has produced solid and liquid organic fertilizer or Pupuk Organik Cair (POC). Solid and liquid organic fertilizers contain nutrients needed by plants. Provision of solid and liquid organic fertilizers on agricultural land can increase soil fertility. This community service activity aims to improve the community's ability to prevent environmental pollution and produce organic fertilizer independently. The method used to realize this program was socialization and the practice of making composter buckets. Socialization was carried out in the form of counseling and distribution of leaflets (brochures). While the practice of making composter buckets was carried out independently by participants accompanied by supervisors. The targets of this activity were members of the Family Welfare Development or Pembinaan Kesejahteraan Keluarga (PKK), youth organizations and representatives of several farmer groups in Aik Prapa Village. The success of this activity was indicated by the high level of enthusiasm of the participants during counseling, discussion and practice activities, the increased skill of the participants to make composter buckets, and the high desire of the participants to implement composter buckets in their own home.
 
Detection of microparticles from human red blood cells by multiparametric flow cytometry
No full textBACKGROUND: During storage, red blood cells (RBC) undergo chemical and biochemical changes referred to as "storage lesions". These events determine the loss of RBC integrity, resulting in lysis and release of microparticles. There is growing evidence of the clinical importance of microparticles and their role in blood transfusion-related side effects and pathogen transmission. Flow cytometry is currently one of the most common techniques used to quantify and characterise microparticles. Here we propose multiparametric staining to monitor and quantify the dynamic release of microparticles by stored human RBC.
MATERIAL AND METHODS: RBC units (n=10) were stored under blood bank conditions for up to 42 days. Samples were tested at different time points to detect microparticles and determine the haemolysis rate (HR%). Microparticles were identified by flow cytometry combining carboxyfluorescein diacetate succinimidyl ester (CFSE) dye, annexin V and anti-glycophorin A antibody.
RESULTS: We demonstrated that CFSE can be successfully used to label closed vesicles with an intact membrane. The combination of CFSE and glycophorin A antibody was effective for monitoring and quantifying the dynamic release of microparticles from RBC during storage. Double staining with CFSE/glycophorin A was a more precise approach, increasing vesicle detection up to 4.7-fold vs the use of glycophorin A/annexin V alone. Moreover, at all the time points tested, we found a robust correlation (R=0.625; p=0.0001) between HR% and number of microparticles detected.
DISCUSSION: Multiparametric staining, based on a combination of CFSE, glycophorin A antibody and annexin V, was able to detect, characterise and monitor the release of microparticles from RBC units during storage, providing a sensitive approach to labelling and identifying microparticles for transfusion medicine and, more broadly, for cell-based therapies
Anti-GD2 CAR MSCs against metastatic Ewing's sarcoma
No full textBackground: Ewing's sarcoma (ES) is an aggressive cancer affecting children and young adults. We pre-clinically demonstrated that mesenchymal stromal/stem cells (MSCs) can deliver tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) against primary ES after local injection. However, ES is often metastatic calling for approaches able to support MSC targeting to the ES multiple remote sites. Considering that the disialoganglioside GD2 is expressed by ES and to optimise MSC tumour affinity, bi-functional (BF) MSCs expressing both TRAIL and a truncated anti-GD2 chimeric antigen receptor (GD2 tCAR) were generated and challenged against ES. Methods: The anti-GD2 BF MSCs delivering a soluble variant of TRAIL (sTRAIL) were tested in several in vitro ES models. Tumour targeting and killing by BF MSCs was further investigated by a novel immunodeficient ES metastatic model characterized by different metastatic sites, including lungs, liver and bone, mimicking the deadly clinical scenario. Findings: In vitro data revealed both tumour affinity and killing of BF MSCs. In vivo, GD2 tCAR molecule ameliorated the tumour targeting and persistence of BF MSCs counteracting ES in lungs but not in liver. Interpretation: We here generated data on the potential effects of BF MSCs within a complex ES metastatic in vivo model, exploring also the biodistribution of MSCs. Our BF MSC-based strategy promises to pave the way for potential improvements in the therapeutic delivery of TRAIL for the treatment of metastatic ES and other deadly GD2-positive malignancies
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