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Добірка наукової літератури з теми "Leptomeningeal Stem Cell"

Автор: Grafiati

Опубліковано: 11 березня 2023

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Статті в журналах з теми "Leptomeningeal Stem Cell"

Jiang, Wulin, Alain Valdivia, Alison Mercer-Smith, Carey Anders, and Shawn Hingtgen. "56. TUMOR-HOMING STEM CELL THERAPY INHIBITS THE PROGRESSION OF BREAST CANCER LEPTOMENINGEAL CARCINOMATOSIS." Neuro-Oncology Advances 2, Supplement_2 (August 2020): ii11—ii12. http://dx.doi.org/10.1093/noajnl/vdaa073.044.

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Abstract INTRODUCTION Leptomeningeal carcinomatosis remains one of the most lethal forms of central nervous system metastasis, with a median survival of only 4 months. Effective new therapies are urgently needed to treat this highly aggressive cancer. In this study, we used models of both prophylactic and established leptomeningeal disease to investigate the efficacy of engineered tumor-homing neural stem cells (NSCs) therapy for breast cancer leptomeningeal carcinomatosis. METHODS Personalized NSC carriers were created using Sox2 overexpression to transdifferentiate human fibroblasts into induced NSCs (iNSCs) that home to cancer cells and carry therapeutic agents to induce tumor kill. Leptomeningeal models were created by engineering MDA-MB231-Br human breast cancer cells with fluorescent and bioluminescent reporters, then using intracisternal injection to inoculate Nude mice with the tumor cells. iNSC therapy was evaluated by infusing iNSCs releasing the pro-apoptotic agent TRAIL into the lateral ventricle of mice either 1 week prior to or 3 days after tumor inoculation for prophylactic or established tumor treatment respectively. Tumor progression in the brain and spinal cord was monitored by serial bioluminescence imaging (BLI). RESULTS Serial BLI showed that intracerebroventricular (ICV) iNSC-TRAIL therapy reduced the volume of metastatic tumor burden 99.49% in the brain and 99.80% in the spine within 2 weeks post-infusion and extended survival from 24 to 42 days. Additionally, prophylactic iNSC-TRAIL therapy delivered ICV markedly delayed tumor development, with tumors in the brain remaining >1000-fold smaller than control through 1-month post-treatment, below the limit of detection in the spinal cord through 1 month, and eliminating mortality through 50 days post-therapy. CONCLUSION These data suggest that iNSC therapy could be a promising treatment option for breast cancer patients with leptomeningeal carcinomatosis.

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Mercer-Smith, Alison, Wulin Jiang, Alain Valdivia, Noah Bell, Alex Woodell, Scott Floyd, and Shawn Hingtgen. "MMAP-04 CYTOTOXIC, TUMOR-HOMING INDUCED NEURAL STEM CELLS AS AN ADJUVANT TO RADIATION IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER LEPTOMENINGEAL METASTASES." Neuro-Oncology Advances 4, Supplement_1 (August 1, 2022): i15. http://dx.doi.org/10.1093/noajnl/vdac078.060.

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Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common cancer to spread to the brain, and spread to the leptomeninges is particularly devastating, with a median survival of only months. While radiation may offer symptomatic relief, new adjuvant therapies are needed for more durable tumor kill. Spheroidal, human induced neural stem cells (hiNeuroS) transdifferentiated from fibroblasts are inherently tumoritropic. When engineered to secrete the cytotoxic protein TRAIL, they provide the potential for a personalized, targeted approach to NSCLC leptomeningeal metastases. METHODS hiNeuroS-TRAIL in vivo efficacy was determined by tracking the progression and survival of mice with NSCLC leptomeningeal tumors treated with intracerebroventricular hiNeuroS, radiation, or both. To determine the impact of radiation on the tumor tropism of hiNeuroS, we performed 2-dimensional motion assays on hiNeuroS with and without the presence of NSCLC pre- and post-radiation. Migrational capacity in vivo was determined by infusing hiNeuroS into the lateral ventricles of mice with established NSCLC tumors and monitoring hiNeuroS accumulation using post-mortem fluorescent analysis. RESULTS/CONCLUSION Mice treated with the combination of hiNeuroS-TRAIL and 2 Gy showed a significantly reduced mean tumor signal (2.7%) compared to controls (100%) or 2 Gy-only (54.9%). Mice treated with 2 Gy alone showed no significant survival difference compared to controls. Both combination and hiNeuroS-TRAIL-only-treated mice showed a significant improvement in median survival compared to controls (36.6% and 46.3% improvement, respectively). hiNeuroS showed enhanced directionality and displacement in the presence of NSCLC in 2-dimensional motion assays, indicating directional migration, and they maintained this ability following exposure to radiation. Co-localization of hiNeuroS with NSCLC was also observed in vivo. These results suggest the potential of hiNeuroS-TRAIL as a powerful adjuvant to radiation in the treatment of leptomeningeal NSCLC.

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Savage, David G., J. Gregory Mears, Casilda Balmaceda, John Rescigno, Igor Shendrik, Mahesh Mansukhani, and Attilio Orazi. "Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation." Leukemia Research 26, no. 7 (July 2002): 689–92. http://dx.doi.org/10.1016/s0145-2126(01)00190-4.

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Fults, Daniel W., Michael D. Taylor, and Livia Garzia. "Leptomeningeal dissemination: a sinister pattern of medulloblastoma growth." Journal of Neurosurgery: Pediatrics 23, no. 5 (May 2019): 613–21. http://dx.doi.org/10.3171/2018.11.peds18506.

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Leptomeningeal dissemination (LMD) is the defining pattern of metastasis for medulloblastoma. Although LMD is responsible for virtually 100% of medulloblastoma deaths, it remains the least well-understood part of medulloblastoma pathogenesis. The fact that medulloblastomas rarely metastasize outside the CNS but rather spread almost exclusively to the spinal and intracranial leptomeninges has fostered the long-held belief that medulloblastoma cells spread directly through the CSF, not the bloodstream. In this paper the authors discuss selected molecules for which experimental evidence explains how the effects of each molecule on cell physiology contribute mechanistically to LMD. A model of medulloblastoma LMD is described, analogous to the invasion–metastasis cascade of hematogenous metastasis of carcinomas. The LMD cascade is based on the molecular themes that 1) transcription factors launch cell programs that mediate cell motility and invasiveness and maintain tumor cells in a stem-like state; 2) disseminating medulloblastoma cells escape multiple death threats by subverting apoptosis; and 3) inflammatory chemokine signaling promotes LMD by creating an oncogenic microenvironment. The authors also review recent experimental evidence that challenges the belief that CSF spread is the sole mechanism of LMD and reveal an alternative scheme in which medulloblastoma cells can enter the bloodstream and subsequently home to the leptomeninges.

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Bifari, Francesco, Ilaria Decimo, Christian Chiamulera, Emanuela Bersan, Giorgio Malpeli, Jan Johansson, Veronica Lisi, et al. "Novel stem/progenitor cells with neuronal differentiation potential reside in the leptomeningeal niche." Journal of Cellular and Molecular Medicine 13, no. 9b (February 18, 2009): 3195–208. http://dx.doi.org/10.1111/j.1582-4934.2009.00706.x.

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Di Trapani, Mariano, Giulio Bassi, Mario Ricciardi, Emanuela Fontana, Francesco Bifari, Luciano Pacelli, Luca Giacomello, et al. "Immune Regulatory Properties Are a Common Feature Of Stem Cells." Blood 122, no. 21 (November 15, 2013): 5419. http://dx.doi.org/10.1182/blood.v122.21.5419.5419.

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Abstract Allogeneic stem cell-based therapy is a promising tool for the treatment of a range of human degenerative and inflammatory diseases. Many reports highlighted the immune modulatory properties of some stem cell (SC) types, such as mesenchymal stromal cells (MSCs), but a comparative study with SCs of different origin, to assess whether immune regulation is a general SC property, is still lacking. To this aim, we applied highly standardized methods employed for MSC characterization to compare the immunological properties of bone marrow-MSCs, olfactory ecto-mesenchymal stem cells, leptomeningeal stem cells, and three different c-Kit-positive SC types, i.e. amniotic fluid SCs, cardiac SCs, and lung SCs. We found that all the analyzed human SCs share a common pattern of immunological features, in terms of expression of activation markers, modulatory activity towards immune effector cells, immunogenicity and molecular inhibitory pathways, with some SC type-related peculiarities. In addition, we found that the inhibitory behaviour is not a constitutive property of SCs, but is acquired as a consequence of immune effector cell activation, as previously described for MSCs. Thus, immune regulation is a general property of stem cells and the characterization of this phenomenon may be useful for a proper therapeutical use of SCs. Disclosures: No relevant conflicts of interest to declare.

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Mercer-Smith, Alison, Morrent Thang, Andrew Buckley, Alain Valdivia, Wulin Jiang, Noah Bell, Rashmi Kumar, et al. "EXTH-01. SECOND GENERATION OF INDUCED NEURAL STEM CELLS TO MIGRATE AND KILL AS AN ADJUVANT TO RADIOTHERAPY IN NON-SMALL CELL LUNG CANCER METASTASIS." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi163. http://dx.doi.org/10.1093/neuonc/noab196.640.

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Abstract Non-small cell lung cancer (NSCLC) spread to the leptomeninges is devastating with a median survival of only a few months. Radiation is frequently offered for symptomatic relief but alone does not eliminate leptomeningeal metastases (LMM). With no standard-of-care for patients with LMM, new adjuvant therapies are desperately needed in order to combat this disease. Neural stem cells (NSCs) have shown remarkable promise as drug delivery vehicles in the treatment of brain tumors due to their inherent tumoritropic properties. Using a cell sphere culture-based system, we have transdifferentiated fibroblasts into a second-generation induced neural stem cell (hiNeuroS) secreting the cytotoxic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to allow for the possibility of readily available, autologous cell carriers. Herein, we provide evidence that hiNeuroS-TRAIL cells can migrate to and suppress growth of NSCLC metastases in combination with radiation. In vitro time-lapse motional analysis and in vivo post-mortem tissue analysis showed that hiNeuroS-TRAIL cells migrate to NSCLC tumors. In vitro co-cultures with isobologram analysis suggests that TRAIL and radiation together have a synergistic cytotoxic effect on NSCLC tumors. In an intratumoral injection model of hiNeuroS-TRAIL, mice treated with the combination therapy of hiNeuroS-TRAIL and 2 Gy together had a small fraction of the mean tumor volume (6.4%) of controls (100%) compared to monotherapies (107.3% radiation-only, 46.6% hiNeuroS-TRAIL only). Only combination-treated mice demonstrated a significant extension in survival, which amounted to a 42% extension compared to controls. In the LMM model with ICV-infused therapy, the combination-treated mice showed significantly smaller tumor volumes (2.0%) compared to control (100%) or 2 Gy (54.9%) treated mice. Mice treated with hiNeuroS-TRAIL-only also showed only 4.6% of the tumor volume of control mice. Combination-treated mice and hiNeuroS-TRAIL-treated mice both showed significant improvements in survival (36.6% and 46.3% median extension in survival, respectively compared to controls).

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Reynoso, Eduardo E., and Carlos Quintero. "How to Treat Isolated Leptomeningeal Relapse of Multiple Myeloma 11 Years after Autologous Stem Cell Transplantation (ASCT)." Blood 140, Supplement 1 (November 15, 2022): 12503. http://dx.doi.org/10.1182/blood-2022-163447.

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Jiang, Wulin, Alain Valdivia, Alison Mercer-Smith, Carey Anders, and Shawn Hingtgen. "EXTH-02. TUMOR-HOMING INDUCED NEURAL STEM CELL THERAPY INHIBITS THE PROGRESSION OF BREAST CANCER BRAIN METASTASIS AND LEPTOMENINGEAL CARCINOMATOSIS." Neuro-Oncology 22, Supplement_2 (November 2020): ii86—ii87. http://dx.doi.org/10.1093/neuonc/noaa215.356.

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Abstract INTRODUCTION Breast cancer brain metastasis, including leptomeningeal carcinomatosis (LC), remains one of the most lethal CNS diseases. New therapies are urgently needed to treat this highly aggressive disease. Here we used models of both breast cancer brain parenchymal metastasis and leptomeningeal metastasis to investigate the efficacy of engineered tumor-homing neural stem cells (NSCs) therapy. METHODS Personalized NSCs were created using Sox2 overexpression to transdifferentiate human fibroblasts into induced NSCs (iNSCs), followed by genetic engineering to enable iNSCs to secrete cytotoxic TRAIL (iNSC-TRAIL). For the parenchymal metastasis study, iNSC-TRAIL therapy was infused intracerebroventricularly (ICV) into Nude mice bearing established intracranial MDA-MB-231-Br human breast cancer cells expressing fluorescent and bioluminescent reporters. For LC studies, we established the disease model by inoculating Nude mice with MDA-MB-231-Br tumor cells via intracisternal infusion. iNSC-TRAIL therapy was evaluated by infusing therapy ICV either 1 week prior to or 3 days after tumor inoculation to mirror prophylactic or established tumor treatment, respectively. Tumor progression in the brain and spine was monitored by serial bioluminescence imaging (BLI), and survival was analyzed. RESULTS Serial BLI showed ICV-infused iNSC-TRAIL reduced parenchymal tumor volumes by 72% 3 weeks post-ICV infusion, and extended median survival from 37 to 52 days. Testing iNSC-TRAIL therapy against established LC tumors, serial BLI showed ICV iNSC-TRAIL therapy reduced established tumors 196-fold in the brain and 500-fold in the spine within 2 weeks post-infusion, while extending median survival from 25 to 47 days. In the prophylactic LC model, iNSC-TRAIL therapy markedly delayed tumor development with tumors in the brain remaining > 1000-fold smaller than control, and tumors in the spine below the limit of detection through 1 month post-treatment. The therapy also eliminated mortality through 50 days post-therapy. CONCLUSION These data suggest iNSC therapy could be a promising treatment option for breast cancer brain metastasis patients.

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Quach, H., G. Ryan, V. Ganju, and H. M. Prince. "Effective treatment of leptomeningeal multiple myeloma with total craniospinal irradiation supported by second allogeneic donor stem cell infusion." Bone Marrow Transplantation 35, no. 4 (December 20, 2004): 423–24. http://dx.doi.org/10.1038/sj.bmt.1704777.

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Більше джерел

Частини книг з теми "Leptomeningeal Stem Cell"

Faure, Gilbert, Emilie Le Rhun, Qien Tu, Chantal Kohler, Luc Taillandier, Huili Cai, Xianglei Wu, and Marcelo De Carvalho. "Identification and Quantification of Malignant Cells in Cerebrospinal Fluid." In Stem Cells and Regenerative Medicine. IOS Press, 2021. http://dx.doi.org/10.3233/bhr210031.

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Usual diagnostic methods of leptomeningeal metastases (LM) in CerebroSpinal fluid (CSF), lack both specificity and sensitivity. The Veridex CellSearch® technique quantifying circulating tumour cells (CTCs) in blood was adapted to detect Tumour Cells (CSFTCs) in CSF from cancer patients with LM. CSF samples from 60 patients with established or suspected breast cancer or lung cancer LM and/or melanoma were evaluated. 5 mL CSF samples were collected on CellSave® preservative and analyzed within 3 days after CSF sampling. Gold Standard cytological analysis on 1 to 10 mL CSF samples from patients with established LM allowed sometimes the detection but usually not the quantification of TCs. In established LM, EpCAM+/cytokeratin+ or CD146+/HMW-MAA+ nucleated (DAPI+) cells were observed and enumerated with precision from one to up to 10 000 cells/mL. Their morphology on digital images galleries could be discriminant between breast and lung cancer. This methodology, established on a limited volume of CSF compared to the Gold Standard and allowing delayed processing, is of great interest in the diagnosis and follow-up of cancer patients with LM. The reliability of the method also opens new fields of investigation for other biological fluids and to precise the stem cell potential of metastatic cells in CSF.

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