Pig‐to‐baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments

2021 ◽  
Author(s):  
Lars Burdorf ◽  
Christopher T. Laird ◽  
Donald G. Harris ◽  
Margaret R. Connolly ◽  
Zahra Habibabady ◽  
...  
Keyword(s):  
Genetic Modifications ◽  
Pharmacologic Treatments ◽  
Extended Survival

Introduction of the Detection Methods of Genetic Modifications Content in Food, Feed and Cosmetic Products

2008 ◽  
Vol 4 (2) ◽  
pp. 40-48 ◽  
Author(s):  
Ya.B. Blume ◽  
◽  
M.O. Bannikova ◽  
P.A. Karpov ◽  
I.K. Komarnitsky ◽  
...  
Keyword(s):  
Detection Methods ◽  
Cosmetic Products ◽  
Genetic Modifications

Extended survival of MHC-compatible islet grafts from diabetes-resistant donors in spontaneously diabetic BB/W rat

Diabetes ◽  
1987 ◽  
Vol 36 (9) ◽  
pp. 1061-1067 ◽  
Author(s):  
H. Selawry ◽  
R. Fojaco ◽  
K. Whittington
Keyword(s):  
Extended Survival

Lone Atrial Fibrillation: Electrophysiology, Risk Factors, Catheter Ablation and Other Non-pharmacologic Treatments

2014 ◽  
Vol 21 (5) ◽  
pp. 580-590 ◽  
Author(s):  
Arun Kanmanthareddy ◽  
Martin Emert ◽  
Rhea Pimentel ◽  
Yeruva Reddy ◽  
Sudharani Bommana ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Lone Atrial Fibrillation ◽  
Pharmacologic Treatments

Cancer and Cancer Treatment-Related Cognitive Impairment

2019 ◽  
pp. 60-83
Author(s):  
James C.  Root ◽  
Elizabeth Ryan ◽  
Tim A. Ahles
Keyword(s):  
Cancer Survivors ◽  
Cancer Treatment ◽  
Clinical Presentation ◽  
Functional Neuroimaging ◽  
Theoretical Models ◽  
Future Research ◽  
Cognitive Changes ◽  
Central Nervous System Cancer ◽  
Pharmacologic Treatments

As the population of cancer survivors has grown into the millions, there is increasing emphasis on understanding how late effects of treatment impact survivors’ ability return to work/school, ability to function and live independently, and overall quality of life. Cognitive changes are one of the most feared problems among cancer survivors. This chapter describes the growing literature examining cognitive changes associated with non-central nervous system cancer and cancer treatment. Typical elements of cancer treatment are discussed, followed by a description of clinical presentation, self-reported and objectively assessed cognitive findings, and results of structural and functional neuroimaging research. Genetic and other risk factors for cognitive decline following treatment are identified and discussed, together with biomarkers and animal models of treatment-related effects. This is followed by a discussion of behavioral and pharmacologic treatments. Finally, challenges and recommendations for future research are provided to help guide subsequent research and theoretical models.

scholarly journals Ten-year all-cause death after percutaneous or surgical revascularization for men and women with multivessel or left main coronary artery disease: insights from the SYNTAX extended survival study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Hara ◽  
K Takahashi ◽  
D Klaveren ◽  
M Ono ◽  
H Kawashima ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Left Main Coronary Artery ◽  
Mortality Rates ◽  
Public Institution ◽  
Funding Source ◽  
Left Main ◽  
Main Coronary Artery Disease ◽  
Artery Disease ◽  
Extended Survival

Abstract Background In patients with complex coronary artery disease (CAD), women favored coronary artery bypass grafting surgery (CABG) compared to percutaneous coronary intervention (PCI) at 5 years in the SYNTAX trial, whereas mortality rates after PCI and CABG were not different in men. On the other hand, poor outcomes of women undergoing PCI were not observed in the PRECOMBAT and BEST trials. The long-term optimal revascularization strategy according to gender has not been fully evaluated. Purpose In the SYNTAX Extended Survival (SYNTAXES) study, no significant difference existed in all-cause death between PCI and CABG at 10 years. This study aimed to assess treatment effect of PCI and CABG for 10-year all-cause death according to gender. Methods The SYNTAXES study evaluated vital status up to 10 years in 1,800 patients with de novo three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to treatment with CABG or PCI in the SYNTAX trial, and the pre-specified primary endpoint was all-cause death at 10 years. In this prespecified analysis, all-cause death at 10 years according to gender in patients undergoing PCI or CABG was evaluated. Results Of 1800 patients, 402 (22.3%) were women and 1398 (77.7%) were men. In women, the rate of mortality was significantly higher in the PCI arm at 5 years than in the CABG arm (19.3% vs. 10.3%; Log-rank p=0.010, Figure A), but the rates of mortality were not different at 10 years between the PCI and CABG arms (33.0% vs. 32.5%; Log-rank p=0.600, Figure A). In men, the mortality rate tended to be higher in the PCI arm at 10 years than in the CABG arm (27.0% vs. 22.5%; Log-rank p=0.082, Figure B), although the mortality rates were not different at 5 years between the PCI and CABG arms (12.4% vs. 12.3%; Log-rank p=0.957, Figure B). Conclusion The efficacy of CABG observed at 5 years disappeared at 10 years in women, whereas the efficacy of CABG became apparent after 5 years in men. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Erasmus University Medical Centre, Rotterdam, Netherlands, reference: MEC-2016-716

scholarly journals EXTH-46. ARTIFICIAL INTELLIGENCE-BASED IDENTIFICATION OF COMBINED VANDETANIB AND EVEROLIMUS IN THE TREATMENT OF ACVR1-MUTANT DIFFUSE INTRINSIC PONTINE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii97-ii97
Author(s):  
Diana Carvalho ◽  
Peter Richardson ◽  
Nagore Gene Olaciregui ◽  
Reda Stankunaite ◽  
Cinzia Emilia Lavarino ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Cell Viability ◽  
Xenograft Model ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
Serine Threonine Kinase ◽  
Orthotopic Xenografts ◽  
Extended Survival

Abstract Somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2 receptor, are found in a quarter of children with the currently incurable brain tumour diffuse intrinsic pontine glioma (DIPG). Treatment of ACVR1-mutant DIPG patient-derived models with multiple inhibitor chemotypes leads to a reduction in cell viability in vitro and extended survival in orthotopic xenografts in vivo, though there are currently no specific ACVR1 inhibitors licensed for DIPG. Using an Artificial Intelligence-based platform to search for approved compounds which could be used to treat ACVR1-mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an approved inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 (Kd=150nM) and reduce DIPG cell viability in vitro, but has been trialed in DIPG patients with limited success, in part due to an inability to cross the blood-brain-barrier. In addition to mTOR, everolimus inhibits both ABCG2 (BCRP) and ABCB1 (P-gp) transporter, and was synergistic in DIPG cells when combined with vandetanib in vitro. This combination is well-tolerated in vivo, and significantly extended survival and reduced tumour burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Based on these preclinical data, three patients with ACVR1-mutant DIPG were treated with vandetanib and everolimus. These cases may inform on the dosing and the toxicity profile of this combination for future clinical studies. This bench-to-bedside approach represents a rapidly translatable therapeutic strategy in children with ACVR1 mutant DIPG.

scholarly journals New insights in phenotype and treatment of lung disease immuno-deficiency and chromosome breakage syndrome (LICS)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Brigitte W. M. Willemse ◽  
Saskia N. van der Crabben ◽  
Wilhelmina S. Kerstjens-Frederikse ◽  
Wim Timens ◽  
Joris M. van Montfrans ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lung Disease ◽  
Chromosome Breakage ◽  
Recurrent Infections ◽  
Hematopoietic Stem ◽  
Chromosome Breakage Syndrome ◽  
Severe Immunodeficiency ◽  
Extended Survival ◽  
Immunological Abnormalities

AbstractWe report five patients with lung disease immuno-deficiency and chromosome breakage syndrome (LICS) but without recurrent infections and severe immunodeficiency. One patient had extended survival to 6.5 years. Hematopoietic stem-cell transplantation failed to cure another patient. Our findings suggest that the immunological abnormalities can be limited and do not fully explain the LICS phenotype.

scholarly journals Effect of Spaceflight on Tomato Seed Quality and Biochemical Characteristics of Mature Plants

Horticulturae ◽  
2021 ◽  
Vol 7 (5) ◽  
pp. 89
Author(s):  
Elena Dzhos ◽  
Nadezhda Golubkina ◽  
Marina Antoshkina ◽  
Irina Kondratyeva ◽  
Andrew Koshevarov ◽  
...  
Keyword(s):  
Seed Quality ◽  
Space Station ◽  
Field Conditions ◽  
Tomato Seed ◽  
Tomato Plants ◽  
Biochemical Characteristics ◽  
Tomato Seeds ◽  
Genetic Modifications ◽  
Total Antioxidant

Intensive space exploration includes profound investigations on the effect of weightlessness and cosmic radiation on plant growth and development. Tomato seeds are often used in such experiments though up to date the results have given rather vague information about biochemical changes in mature plants grown from seeds subjected to spaceflight. The effect of half a year of storage in the International Space Station (ISS) on tomato seeds (cultivar Podmoskovny ranny) was studied by analyzing the biochemical characteristics and mineral content of mature plants grown from these seeds both in greenhouse and field conditions. A significant increase was recorded in ascorbic acid, polyphenol and carotenoid contents, and total antioxidant activity (AOA), with higher changes in the field conditions compared to greenhouse. Contrary to control plants, the ones derived from space-stored seeds demonstrated a significant decrease in root AOA. The latter plants also showed a higher yield, but lower content of fruit dry matter, sugars, total dissolved solids and organic acids. The fruits of plants derived from space-stored seeds demonstrated decreased levels of Fe, Cu and taste index. The described results reflect the existence of oxidative stress in mature tomato plants as a long-term consequence of the effect of spaceflight on seed quality, whereas the higher yield may be attributed to genetic modifications.

scholarly journals TMOD-15. EFFICACY OF THE MDM2 INHIBITOR KRT-232 IN GLIOBLASTOMA PATIENT-DERIVED XENOGRAFT MODELS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii231-ii231
Author(s):  
Rachael Vaubel ◽  
Ann Mladek ◽  
Yu Zhao ◽  
Shiv K Gupta ◽  
Minjee Kim ◽  
...  
Keyword(s):  
Target Genes ◽  
Xenograft Model ◽  
Culture Conditions ◽  
Patient Derived Xenograft ◽  
Fold Induction ◽  
Extended Survival ◽  
Mdm2 Amplification ◽  
Mdm2 Inhibitor

Abstract Non-genotoxic reactivation of p53 by MDM2 inhibitors represents a promising therapeutic strategy for tumors with wild-type TP53, particularly tumors harboring MDM2 amplification. MDM2 controls p53 levels by targeting it for degradation, while disruption of the MDM2-p53 interaction causes rapid accumulation of p53 and activation of the p53 pathway. We examined the efficacy of the small molecule MDM2 inhibitor KRT-232, alone and in combination with radiation therapy (RT), in MDM2-amplified and/or p53 wildtype patient-derived xenograft (PDX) models of glioblastoma in vitro and in vivo. In vitro, glioblastoma PDX explant cultures showed sensitivity to KRT-232, both tumors with MDM2 amplification (GBM108 and G148) and non-amplified but TP53-wildtype lines (GBM10, GBM14, and GBM39), with IC50s ranging from 300-800 nM in FBS culture conditions. A TP53 p.F270C mutant PDX (GBM43) was inherently resistant, with IC50 >3000 nM. In the MDM2-amplified GBM108 line, KRT-232 led to a robust (5-6 fold) induction of p53-target genes p21, PUMA, and NOXA, with initiation of both apoptosis and senescence. Expression of p21 and PUMA was greater with KRT-232 in combination with RT (25-35 fold induction), while stable knock-down of p53 in GBM108 led to complete resistance to KRT-232. In contrast, GBM10 showed lower induction of p21 and PUMA (2-3 fold) and was more resistant to KRT-232. In an orthotopic GBM108 xenograft model, treatment with KRT-232 +/- RT for one week extended survival from 22 days (placebo) to 46 days (KRT-232 alone); combination KRT-232 + RT further extended survival (77 days) over RT alone (31 days). KRT-232 is an effective treatment in a subset of glioblastoma pre-clinical models alone and in combination with RT. Further studies are underway to understand the mechanisms conferring innate sensitivity or resistance to KRT-232.

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