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MSC-TRAIL

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https://www.readbyqxmd.com/read/30060445/mesenchymal-stem-cell-expressing-trail-as-targeted-therapy-against-sensitised-tumour
#1
REVIEW
Kamal Shaik Fakiruddin, Nadiah Ghazalli, Moon Nian Lim, Zubaidah Zakaria, Syahril Abdullah
Tapping into the ability of engineered mesenchymal stem cells (MSCs) to mobilise into the tumour has expanded the scope of cancer treatment. Engineered MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) could serve as a platform for an efficient and targeted form of therapy. However, the presence of cancer stem cells (CSCs) that are resistant to TRAIL and apoptosis may represent a challenge for effective treatment. Nonetheless, with the discovery of small molecular inhibitors that could target CSCs and tumour signalling pathways, a higher efficacy of MSC-TRAIL mediated tumour inhibition can be achieved...
July 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28553285/antitumor-activity-of-a-mesenchymal-stem-cell-line-stably-secreting-a-tumor-targeted-tnf-related-apoptosis-inducing-ligand-fusion-protein
#2
Irene Marini, Martin Siegemund, Meike Hutt, Roland E Kontermann, Klaus Pfizenmaier
Mesenchymal stem cells (MSCs) are currently exploited as gene delivery systems for transient in situ expression of cancer therapeutics. As an alternative to the prevailing viral expression, we here describe a murine MSC line stably expressing a therapeutic protein for up to 42 passages, yet fully maintaining MSC features. Because of superior antitumoral activity of hexavalent TNF-related apoptosis-inducing ligand (TRAIL) formats and the advantage of a tumor-targeted action, we choose expression of a dimeric EGFR-specific diabody single-chain TRAIL (Db-scTRAIL) as a model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/25525034/antitumor-effects-of-trail-expressing-mesenchymal-stromal-cells-in-a-mouse-xenograft-model-of-human-mesothelioma
#3
M J Lathrop, E K Sage, S L Macura, E M Brooks, F Cruz, N R Bonenfant, D Sokocevic, M B MacPherson, S L Beuschel, C W Dunaway, A Shukla, S M Janes, C Steele, B T Mossman, D J Weiss
Malignant mesothelioma (MM) remains a highly deadly malignancy with poor treatment option. The MM cells further promote a highly inflammatory microenvironment, which contributes to tumor initiation, development, severity and propagation. We reasoned that the anti-inflammatory actions of mesenchymal stromal cells (MSCs) and further antitumor effects of MSCs engineered to overexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein (MSC-TRAIL) would effectively inhibit mesothelioma growth...
January 2015: Cancer Gene Therapy
https://www.readbyqxmd.com/read/25420617/mesenchymal-progenitors-expressing-trail-induce-apoptosis-in-sarcomas
#4
Giulia Grisendi, Carlotta Spano, Naomi D'souza, Valeria Rasini, Elena Veronesi, Malvina Prapa, Tiziana Petrachi, Serena Piccinno, Filippo Rossignoli, Jorge S Burns, Stefania Fiorcari, Donatella Granchi, Nicola Baldini, Edwin M Horwitz, Valentina Guarneri, Pierfranco Conte, Paolo Paolucci, Massimo Dominici
Sarcomas are frequent tumors in children and young adults that, despite a relative chemo-sensitivity, show high relapse rates with up to 80% of metastatic patients dying in 5 years from diagnosis. The real ontogeny of sarcomas is still debated and evidences suggest they may derive from precursors identified within mesenchymal stromal/stem cells (MSC) fractions. Recent studies on sarcoma microenvironment additionally indicated that MSC could take active part in generation of a supportive stroma. Based on this knowledge, we conceived to use modified MSC to deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) targeting different sarcoma histotypes...
March 2015: Stem Cells
https://www.readbyqxmd.com/read/24436439/potential-application-of-temozolomide-in-mesenchymal-stem-cell-based-trail-gene-therapy-against-malignant-glioma
#5
Seong Muk Kim, Ji Sun Woo, Chang Hyun Jeong, Chung Heon Ryu, Jae-Deog Jang, Sin-Soo Jeun
Because the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, it is one of the most promising candidates for cancer treatment. TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) provide targeted and prolonged delivery of TRAIL in glioma therapy. However, acquired resistance to TRAIL of glioma cells is a major problem to be overcome. We showed a potential therapy that used MSC-TRAIL combined with the chemotherapeutic agent temozolomide (TMZ). The antitumor effects of the combination with MSC-TRAIL and TMZ on human glioma cells were determined by using an in vitro coculture system and an in vivo experimental xenografted mouse model...
February 2014: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/23428290/carbenoxolone-enhances-trail-induced-apoptosis-through-the-upregulation-of-death-receptor-5-and-inhibition-of-gap-junction-intercellular-communication-in-human-glioma
#6
Yulyana Yulyana, Berwini B Endaya, Wai H Ng, Chang M Guo, Kam M Hui, Paula Y P Lam, Ivy A W Ho
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been used extensively in cancer therapy. However, more than half of glioblastoma multiforme are insensitive to the apoptotic effect of TRAIL. Improvement in therapeutic modalities that enhances the efficacy of TRAIL in glioma is much sought after. In this study, we combined the tumor selectivity of TRAIL and tumor-homing properties of mesenchymal stem cells (MSC) with gap junction (GJ) inhibitory effect of carbenoxolone (CBX) to target orthotopic glioma...
July 1, 2013: Stem Cells and Development
https://www.readbyqxmd.com/read/23108118/a-therapeutic-strategy-for-metastatic-malignant-fibrous-histiocytoma-through-mesenchymal-stromal-cell-mediated-trail-production
#7
Hyun Joo Lee, Heung-Mo Yang, Young-Sil Choi, Sang-Hoon Park, Sung-Hwan Moon, Yong-Soo Lee, Young Chul Sung, Sung Joo Kim
OBJECTIVE: To overcome the therapeutic limitations of malignant fibrous histiocytoma (MFH), we evaluated human adipose tissue-derived mesenchymal stromal cells (MSCs) that secrete tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on metastatic MFH. BACKGROUND: MFH is a highly malignant and metastatic type of sarcoma but surgical removal is the only effective method for treating MFH. MSCs are easily transduced to express a high level of transgene and can migrate toward cancer...
May 2013: Annals of Surgery
https://www.readbyqxmd.com/read/22962275/effective-combination-therapy-for-malignant-glioma-with-trail-secreting-mesenchymal-stem-cells-and-lipoxygenase-inhibitor-mk886
#8
Seong Muk Kim, Ji Sun Woo, Chang Hyun Jeong, Chung Heon Ryu, Jung Yeon Lim, Sin-Soo Jeun
The apoptotic ligand TRAIL is believed to have promise as a cancer gene therapy, yet many types of cancer, including gliomas, have exhibited resistance to TRAIL-induced apoptosis. Here, we show that therapeutic combination of the lipoxygenase inhibitor MK886 and TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) provide targeted and prolonged delivery of TRAIL both in vitro and in orthotopic mouse models of glioma. Treatment of either TRAIL-sensitive or TRAIL-resistant human glioma cells with MK886 and MSC-TRAIL resulted in significantly enhanced apoptosis compared with each agent alone...
September 15, 2012: Cancer Research
https://www.readbyqxmd.com/read/22110190/msc-trail-mediated-hepg2-cell-death-in-direct-and-indirect-co-cultures
#9
Xu-Yong Sun, Jiang Nong, Ke Qin, Hong Lu, Mani R Moniri, Long-Jun Dai, Garth L Warnock
BACKGROUND: Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy since the discovery of their tumor tropism. This study was performed to investigate the effects of TNF-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on hepatocellular carcinoma (HCC) cells (HepG2) under different culture conditions. MATERIALS AND METHODS: MSCs engineered with non-secreting TRAIL (MSC(TRAIL-GFP)) (GFP, green fluorescence protein) and secreting TRAIL (MSC(stTRAIL)) were used for the direct co-cultures, and conditioned media (CM) from corresponding cultures were applied to HepG2 as indirect co-cultures...
November 2011: Anticancer Research
https://www.readbyqxmd.com/read/21062796/therapeutic-efficacy-and-safety-of-trail-producing-human-adipose-tissue-derived-mesenchymal-stem-cells-against-experimental-brainstem-glioma
#10
Seung Ah Choi, Sung-Kyun Hwang, Kyu-Chang Wang, Byung-Kyu Cho, Ji Hoon Phi, Ji Yeoun Lee, Hee Won Jung, Do-Hun Lee, Seung-Ki Kim
Mesenchymal stem cells (MSCs) have an extensive migratory capacity for gliomas, which is comparable to that of neural stem cells. Among the various types of MSCs, human adipose tissue-derived MSCs (hAT-MSC) emerge as one of the most attractive vehicles for gene therapy because of their high throughput, lack of ethical concerns, and availability and ease of isolation. We evaluated the therapeutic potential and safety of genetically engineered hAT-MSCs encoding the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against brainstem gliomas...
January 2011: Neuro-oncology
https://www.readbyqxmd.com/read/20945331/irradiation-enhances-the-tumor-tropism-and-therapeutic-potential-of-tumor-necrosis-factor-related-apoptosis-inducing-ligand-secreting-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-in-glioma-therapy
#11
Seong Muk Kim, Ji Hyeon Oh, Soon A Park, Chung Heon Ryu, Jung Yeon Lim, Dal-Soo Kim, Jong Wook Chang, Wonil Oh, Sin-Soo Jeun
Irradiation is a standard therapy for gliomas and many other cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer gene therapy. Here, we show that tumor irradiation enhances the tumor tropism of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and the therapeutic effect of TRAIL delivered by UCB-MSCs. The sequential treatment with irradiation followed by TRAIL-secreting UCB-MSCs (MSC-TRAIL) synergistically enhanced apoptosis in either TRAIL-sensitive or TRAIL-resistant glioma cells by upregulating the death receptor 5 and by inducing caspase activation...
December 2010: Stem Cells
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