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11.
Jamie A. Moore Jayna J. Mistry Charlotte Hellmich Rebecca H. Horton Edyta E. Wojtowicz Aisha Jibril Matthew Jefferson Thomas Wileman Naiara Beraza Kristian M. Bowles Stuart A. Rushworth 《The Journal of clinical investigation》2022,132(5)
The bone marrow (BM) microenvironment regulates acute myeloid leukemia (AML) initiation, proliferation, and chemotherapy resistance. Following cancer cell death, a growing body of evidence suggests an important role for remaining apoptotic debris in regulating the immunologic response to and growth of solid tumors. Here, we investigated the role of macrophage LC3–associated phagocytosis (LAP) within the BM microenvironment of AML. Depletion of BM macrophages (BMMs) increased AML growth in vivo. We show that LAP is the predominate method of BMM phagocytosis of dead and dying cells in the AML microenvironment. Targeted inhibition of LAP led to the accumulation of apoptotic cells (ACs) and apoptotic bodies (ABs), resulting in accelerated leukemia growth. Mechanistically, LAP of AML-derived ABs by BMMs resulted in stimulator of IFN genes (STING) pathway activation. We found that AML-derived mitochondrial damage–associated molecular patterns were processed by BMMs via LAP. Moreover, depletion of mitochondrial DNA (mtDNA) in AML-derived ABs showed that it was this mtDNA that was responsible for the induction of STING signaling in BMMs. Phenotypically, we found that STING activation suppressed AML growth through a mechanism related to increased phagocytosis. In summary, we report that macrophage LAP of apoptotic debris in the AML BM microenvironment suppressed tumor growth. 相似文献
12.
Naiara Rodriguez‐Florez Esther Garcia‐Tunon Quresh Mukadam Eduardo Saiz Karla J Oldknow Colin Farquharson José Luis Millán Alan Boyde Sandra J Shefelbine 《Journal of bone and mineral research》2015,30(5):786-795
Bone is a strong and tough material composed of apatite mineral, organic matter, and water. Changes in composition and organization of these building blocks affect bone's mechanical integrity. Skeletal disorders often affect bone's mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta model, oim‐/‐, mice have a defect in the collagen, which leads to brittle bone; PHOSPHO1 mutants, Phospho1‐/‐, have ductile bone resulting from altered mineralization. Oim‐/‐ and Phospho1‐/‐ were compared with their respective wild‐type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X‐ray diffraction (XRD) and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification to assess the fractions of hydroxyapatite and β‐tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (BSE SEM). Results revealed that although both pathology models had extremely different whole‐bone mechanics, they both had smaller apatite crystals, lower bulk mineral to matrix ratio, and showed more thermal conversion to β‐tricalcium phosphate than their wild types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. In contrast, the degree of mineralization of bone matrix was different for each strain: brittle oim‐/‐ were hypermineralized, whereas ductile Phospho1‐/‐ were hypomineralized. Despite differences in the mineralization, nanoscale alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results indicated that alterations from normal crystal size, composition, and structure are correlated with reduced mechanical integrity of bone. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. 相似文献
13.
Polymorphisms in alcohol and tobacco metabolism genes in head and neck cancer in the Basque Country 下载免费PDF全文
14.
Sara Arévalo Lobera Naiara Sagastibeltza Mariñelarena Ibone Elejoste Echeberría Mireia Melé Olivé Larraitz Egaña Otaño Laura Basterretxea Badiola Adelaida La Casta Muñoa Mikel Azkue Gabilondo 《Clinical & translational oncology》2008,10(11):764-767
Oxaliplatin has been approved for adjuvant treatment of colorectal cancer. Toxicity induced by oxaliplatin is moderate and
manageable, but some isolated cases of severe pulmonary toxicity associated to oxaliplatin have been reported. Two fatal cases
of interstitial pneumonitis rapidly evolving to pulmonary fibrosis are reported here. 相似文献
15.
Carvalho LS Cintra RM Moura FA Martins NV Quinaglia E Silva JC Coelho OR Sposito AC;Brasilia Heart Study Group 《Atherosclerosis》2012,220(1):231-236
ObjectiveDuring myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia, which is followed by a substantial increase in mortality. Recent findings in cellular models indicate that HDL may act on glucose homeostasis by improving insulin sensitivity and secretion. In this study, we explored this potential effect in patients during the acute phase of MI.MethodsPlasma glucose, insulin and C-peptide were measured at admission in the first 24 h and on the fifth day after MI with ST-segment elevation in 183 consecutive non-diabetic patients. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31–38, Q3: 38–47 and Q4: >47 mg/dL). The Homeostasis Model Assessment version 2 was used to assess insulin sensitivity (HOMA2S) and beta-cell function (HOMA2B).ResultsOn admission, no difference was found between the quartiles in glucose (p = 0.6), insulin (p = 0.6) or C-peptide (p = 0.5) levels, HOMA2S (p = 0.9) or HOMA2B (p = 1.0). On the fifth day there was a reduction in glucose levels whose intensity was directly proportional to the HDL-C quartile (p < 0.001). At the same time, there was a reduction in plasma insulin (p < 0.001) and C-peptides (p < 0.001) whose magnitude was inversely proportional to the HDL-C quartile. Consistently, the increase of HOMA2S (p < 0.001) and HOMA2B (p = 0.01) were also positively associated with HDL-C levels. Furthermore, plasma HDL-C levels were inversely and independently associated with blood glucose change during the acute phase.ConclusionThis study demonstrates the association between low plasma HDL-C levels and increased duration of stress hyperglycemia during MI and suggests in humans the interaction between HDL and insulin secretion and sensitivity. 相似文献
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Naiara Schaffazick Tatiane F. Fonseca Glauco A. Gaban Sabrina Calil-Elias Paulo A. Melo Valéria M.N. Cunha 《Toxicon》2010,55(1):52-60
Ca2+ ions are essential to myonecrosis, a serious complication of snake envenomation, and heparin seems to counteract this effect. We investigated the effect of local injection of Bothrops jararacussu venom in mouse fast-twitch extensor digitorum longus (EDL) muscle, without or with heparin, on functional/molecular alterations of two central proteins involved in intracellular Ca2+ homeostasis, sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and Na+/K+-ATPase. EDL-specific SERCA1 isoform expression dropped significantly just after venom administration (up to 60% compared to control EDL values at days 1 and 3; p < 0.05) while SERCA2 and Na+/K+-ATPase α1 isoform expression increased at the same time (3-6- and 2-3-fold, respectively; p < 0.05). Although not significant, Na+/K+-ATPase α2 isoform followed the same trend. Except for SERCA2, all proteins reached basal levels at the 7th day. Intravenous heparin treatment did not affect these profiles. Ca2+-ATPase activity was also decreased during the first days after venom injection, but here heparin was effective to reinstate activity to control levels within 3 days. We also showed that B. jararacussu venom directly inhibited Ca2+-ATPase activity in a concentration-dependent manner. Our results indicate that EDL SERCA and Na+/K+-ATPase are importantly affected by B. jararacussu venom and heparin has protective effect on activity but not on protein expression. 相似文献
19.
Danieli B. Martins Cinthia M. Mazzanti Roselia Spanevello Roberta Schmatz Juliana F. Cargnelutti Candice Schmidt Carolina K. Traesel Naiara Stefanello Vera M. Morsh Maria R. C. Schetinger Sonia T. A. Lopes 《Comparative clinical pathology》2012,21(3):265-268
Health sciences have recently discovered the medical uses of nandrolone decanoate (ND), an androgenic anabolic steroid (AAS), and reported its use in human and animal patients. Clinical evidences suggest that the AAS excess may affect the cholinergic system, which is responsible for several vital functions like learning, memory, and the organization of the movements. Thus, our aim is to research the subchronic effect of ND when administered in varying doses on the acetylcholinesterase (AChE) activity in these brain structures: cerebellum (CE), hippocampus, striatum (ST), and cortex of adult rats. We used 36 male Wistar rats, which were divided into six groups (n?=?6). The groups were divided into: G1—control (physiologic solution), G2—diluents control (only an oleaginous vehicle of vegetal origin—olive oil), G3—0.42?mg?kg?1 of ND, G4—1.8?mg?kg?1 of ND, G5—4.6?mg?kg?1 of ND, and G6—10.0?mg?kg?1 of ND. We applied the doses once every week during a 3-week period. The values obtained demonstrated a significant increase in the AChE activity (referring to ST and CE for the 4.6 and 10.0?mg?kg?1 doses of ND). The ND causes increase in AChE activity, which could impair neurotransmission and cholinergic modulation. 相似文献