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1.
Ann Vasc Surg ; 98: 194-200, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37385339

RESUMEN

BACKGROUND: The purpose of the study is to evaluate the efficacy of thromboendarterectomy (TEA) for common femoral occlusive disease using bovine pericardium patch angioplasty. METHODS: The subjects were patients who underwent TEA for common femoral occlusive disease with bovine pericardium patch angioplasty from October 2020 to August 2021. The study had a prospective, multicenter, and observational design. The primary end point was primary patency (freedom from restenosis). The secondary end points were secondary patency, amputation-free survival (AFS), postoperative wound complication, hospital death within 30 days, and major adverse cardiovascular events (MACE) within 30 days. RESULTS: Forty-seven TEA procedures with a bovine patch were performed in 42 patients (34 males; median age, 78 years; diabetes mellitus, 57%; end-stage renal disease with hemodialysis, 19%). Clinical presentations were intermittent claudication (68%) and critical limb-threatening ischemia (32%). Sixteen (34%) limbs underwent TEA alone and 31 (66%) underwent a combined procedure. Surgical site infection (SSI) occurred in 4 limbs (9%) and lymphatic fistulas in 3 limbs (6%). One limb with SSI required surgical debridement 19 days after the procedure, and 1 limb (2%) without postoperative wound complications required additional treatment due to acute bleeding. Hospital death within 30 days occurred in 1 case due to panperitonitis. There was no MACE within 30 days. Claudication was improved in all cases. Postoperative ABI of 0.92 [0.72-1.00] was significantly higher than the preoperative value (P < 0.001). The median follow-up period was 10 months [9-13 months]. One limb (2%) required additional endovascular therapy due to stenosis at the endarterectomy site at 5 months postoperatively. Primary and secondary patencies were 98% and 100% at 12 months, respectively, and the AFS rate was 90% at 12 months. CONCLUSIONS: Common femoral TEA with bovine pericardium patch angioplasty has satisfactory clinical outcomes.


Asunto(s)
Endarterectomía , Isquemia , Masculino , Humanos , Bovinos , Animales , Anciano , Estudios Prospectivos , Resultado del Tratamiento , Endarterectomía/efectos adversos , Claudicación Intermitente , Angioplastia/efectos adversos , Pericardio , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/cirugía , Estudios Retrospectivos , Grado de Desobstrucción Vascular
2.
Angew Chem Int Ed Engl ; 58(8): 2230-2235, 2019 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-30517769

RESUMEN

Ru is an important catalyst in many types of reactions. Specifically, Ru is well known as the best monometallic catalyst for oxidation of carbon monoxide (CO) and has been practically used in residential fuel cell systems. However, Ru is a minor metal, and the supply risk often causes violent fluctuations in the price of Ru. Performance-improved and cost-reduced solid-solution alloy nanoparticles of the Cu-Ru system for CO oxidation are now presented. Over the whole composition range, all of the Cux Ru1-x nanoparticles exhibit significantly enhanced CO oxidation activities, even at 70 at % of inexpensive Cu, compared to Ru nanoparticles. Only 5 at % replacement of Ru with Cu provided much better CO oxidation activity, and the maximum activity was achieved by 20 at % replacement of Ru by Cu. The origin of the high catalytic performance was found as CO site change by Cu substitution, which was investigated using in situ Fourier transform infrared spectra and theoretical calculations.

3.
J Am Chem Soc ; 140(1): 176-184, 2018 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-29224338

RESUMEN

The dynamic behavior of Rh species in 1 wt% Rh/Al2O3 catalyst during the three-way catalytic reaction was examined using a micro gas chromatograph, a NOx meter, a quadrupole mass spectrometer, and time-resolved quick X-ray absorption spectroscopy (XAS) measurements at a public beamline for XAS, BL01B1 at SPring-8, operando. The combined data suggest different surface rearrangement behavior, random reduction processes, and autocatalytic oxidation processes of Rh species when the gas is switched from a reductive to an oxidative atmosphere and vice versa. This study demonstrates an implementation of a powerful operando XAS system for heterogeneous catalytic reactions and its importance for understanding the dynamic behavior of active metal species of catalysts.

4.
Cancer Sci ; 109(4): 1158-1165, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29465769

RESUMEN

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation-enhanced cell migration and invasion. A sublethal dose of X-ray radiation promoted human breast cancer MDA-MB-231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose-dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X-ray-enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X-ray-enhanced migration and invasion. In addition, the results suggested that X-ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon-enhanced cell migration and invasion.


Asunto(s)
Movimiento Celular/fisiología , Movimiento Celular/efectos de la radiación , Citoesqueleto/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Matriz Nuclear/metabolismo , Línea Celular Tumoral , Citoesqueleto/efectos de la radiación , Humanos , Mecanotransducción Celular/fisiología , Mecanotransducción Celular/efectos de la radiación , Proteínas de la Membrana/metabolismo , Invasividad Neoplásica/patología , Membrana Nuclear/metabolismo , Matriz Nuclear/efectos de la radiación , Proteínas Nucleares/metabolismo , Unión Proteica/efectos de la radiación , Empalme del ARN/efectos de la radiación , Rayos X
5.
Chemistry ; 24(35): 8742-8746, 2018 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-29717523

RESUMEN

Solid oxide fuel cells (SOFCs) with liquefied petroleum gas (LPG) reduce CO2 emissions due to their high-energy-conversion efficiency. Although SOFCs can convert LPG directly, coking occurs easily by decomposition of hydrocarbons, including C-C bonds on the electrode of fuel cell stacks. It is therefore necessary to develop an active steam pre-reforming catalyst that eliminates the hydrocarbons at low temperature, in which waste heat of SOFCs is used. Herein, we show that the crystal structure of the TiO2 that anchors Rh particles is crucial for catalytic activity of Rh/TiO2 catalysts for propane pre-reforming. Our experimental results revealed that strong metal support interaction (SMSI) induced during H2 pre-reduction were optimized over Rh/TiO2 with a rutile structure; this catalyst catalyzed the reaction much more effectively than conventional Rh/γ-Al2 O3 . In contrast, the SMSI was too strong for Rh/TiO2 with an anatase structure, and the surface of the Rh particles was therefore covered mostly with partially reduced TiO2 . The result was very low activity.

6.
J Am Chem Soc ; 139(13): 4643-4646, 2017 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-28338315

RESUMEN

We report on novel solid-solution alloy nanoparticles (NPs) of Ru and Cu that are completely immiscible even above melting point in bulk phase. Powder X-ray diffraction, scanning transmission electron microscopy, and energy-dispersive X-ray measurements demonstrated that Ru and Cu atoms were homogeneously distributed in the alloy NPs. Ru0.5Cu0.5 NPs demonstrated higher CO oxidation activity than fcc-Ru NPs, which are known as one of the best monometallic CO oxidation catalysts.

7.
Cancer Sci ; 108(10): 2004-2010, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28718972

RESUMEN

Our aim was to evaluate whether repetition of C-ion (carbon ion beam) irradiation induces radioresistance as well as repeated X-ray irradiation in cancer cell lines, and to find the key molecular pathway for radioresistance by comparing radioresistant cancer cells with their parental cells. A mouse squamous cell carcinoma cell line, NR-S1, and radioresistant cancer cells, NR-S1-C30 (C30) and NR-S1-X60 (X60), established by repetition of C-ion and X-ray irradiation, respectively, were used. X-ray and C-ion sensitivity, changes in lysosome, mitochondria, intracellular ATP and reactive oxygen species (ROS) level, and mechanistic target of rapamycin (mTOR) signaling were evaluated. Moreover, the effect of rapamycin on radioresistance was also assessed. X-ray and C-ion resistance of C30 cells was moderate, and the resistance of X60 cells was the highest in this study. In X60 cells, the amount of lysosome, mitochondria, intracellular ATP and ROS level were significantly increased, and mTOR and p70S6K (ribosomal protein S6 kinase p70) phosphorylation were enhanced compared with C30 and NR-S1 cells. The inhibition of mTOR signaling was effective for X-ray and C-ion radiosensitization in both cell lines, especially in X60 cells in which X-ray and C-ion resistance was decreased to the same level as that in NR-S1 cells. Our results indicated that the contribution to generate X-ray and C-ion resistance was less for repeated C-ion irradiations compared with repeated X-ray irradiation. Moreover, we found that activated mTOR signaling contributes to X-ray and C-ion resistance in the X60 cancer cells.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Tolerancia a Radiación , Especies Reactivas de Oxígeno/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Línea Celular Tumoral , Radioterapia de Iones Pesados , Ratones , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Fosforilación/efectos de la radiación , Transducción de Señal , Terapia por Rayos X , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Cancer Sci ; 108(11): 2287-2294, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28796317

RESUMEN

In addition to BRCA1 and BRCA2, RAD51C, PALB2 and BRIP1 are known as breast cancer susceptibility genes. However, the mutation status of these genes in Japanese familial breast cancer cases has not yet been evaluated. To this end, we analyzed the exon sequence and genomic rearrangement of RAD51C, PALB2 and BRIP1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA1 and BRCA2 mutations. We detected a large deletion from exons 6 to 9 in RAD51C, 4 novel BRIP1 missense variants containing 3 novel non-synonymous variants, c.89A>C, c.736A>G and c.2131A>G, and a splice donor site variant c.918+2T>C. No deleterious variant of PALB2 was detected. The results of pedigree analysis showed that the proband with a large deletion on RAD51C had a family history of both breast and ovarian cancer, and the families of probands with novel BRIP1 missense variants included a male patient with breast cancer or many patients with breast cancer within the second-degree relatives. We showed that the mutation frequency of RAD51C in Japanese familial breast cancer cases was similar to that in Western countries and that the prevalence of deleterious mutation of PALB2 was possibly lower. Furthermore, our results suggested that BRIP1 mutation frequency in Japan might differ from that in Western countries.


Asunto(s)
Neoplasias de la Mama/genética , Proteínas de Unión al ADN/genética , Proteína del Grupo de Complementación N de la Anemia de Fanconi/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , ARN Helicasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/patología , Exones/genética , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , Japón , Persona de Mediana Edad , Mutación Missense , Linaje
9.
Chemistry ; 23(1): 57-60, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27787925

RESUMEN

The first synthesis of pure Rh1-x Cux solid-solution nanoparticles is reported. In contrast to the bulk state, the solid-solution phase was stable up to 750 °C. Based on facile density-functional calculations, we made a prediction that the catalytic activity of Rh1-x Cux can be maintained even with 50 at % replacement of Rh with Cu. The prediction was confirmed for the catalytic activities on CO and NOx conversions.

10.
J Am Chem Soc ; 136(5): 1864-71, 2014 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-24455969

RESUMEN

Pd(x)Ru(1-x) solid solution alloy nanoparticles were successfully synthesized over the whole composition range through a chemical reduction method, although Ru and Pd are immiscible at the atomic level in the bulk state. From the XRD measurement, it was found that the dominant structure of Pd(x)Ru(1-x) changes from fcc to hcp with increasing Ru content. The structures of Pd(x)Ru(1-x) nanoparticles in the Pd composition range of 30-70% consisted of both solid solution fcc and hcp structures, and both phases coexist in a single particle. In addition, the reaction of hydrogen with the Pd(x)Ru(1-x) nanoparticles changed from exothermic to endothermic as the Ru content increased. Furthermore, the prepared Pd(x)Ru(1-x) nanoparticles demonstrated enhanced CO-oxidizing catalytic activity; Pd0.5Ru0.5 nanoparticles exhibit the highest catalytic activity. This activity is much higher than that of the practically used CO-oxidizing catalyst Ru and that of the neighboring Rh, between Ru and Pd.


Asunto(s)
Aleaciones/química , Monóxido de Carbono/química , Hidrógeno/química , Nanopartículas/química , Paladio/química , Rodio/química , Rutenio/química , Catálisis , Microscopía Electrónica de Transmisión , Oxidación-Reducción , Propiedades de Superficie , Termodinámica
11.
iScience ; 27(8): 110452, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39108704

RESUMEN

Hydrogen is a promising combustion improver for use with ammonia fuels, but a cost-effective method for easily producing hydrogen from ammonia at a high rate has yet to be developed. Here, we show that microwave irradiation instantly triggers oxidative decomposition of ammonia over a Co/Ce0.5Zr0.5O2 catalyst to produce hydrogen at a high rate. The microwave irradiation rapidly heats the inside of the catalyst from room temperature to the catalytic auto-ignition temperature of ammonia, thus initiating exothermic oxidative decomposition of ammonia to produce hydrogen. This method provides a highly efficient means of producing hydrogen for potential use in a carbon-free, ammonia-fueled power generation process.

12.
Cancer Res Commun ; 4(3): 946-957, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38457262

RESUMEN

Epithelial-mesenchymal transition (EMT) in cancer promotes metastasis and chemotherapy resistance. A subset of triple-negative breast cancer (TNBC) exhibits a mesenchymal gene signature that is associated with poor patient outcomes. We previously identified PTK6 tyrosine kinase as an oncogenic driver of EMT in a subset of TNBC. PTK6 induces EMT by stabilizing SNAIL, a key EMT-initiating transcriptional factor. Inhibition of PTK6 activity reverses mesenchymal features of TNBC cells and suppresses their metastases by promoting SNAIL degradation via a novel mechanism. In the current study, we identify membrane-associated RING-CH2 (MARCH2) as a novel PTK6-regulated E3 ligase that promotes the ubiquitination and degradation of SNAIL protein. The MARCH2 RING domain is critical for SNAIL ubiquitination and subsequent degradation. PTK6 inhibition promotes the interaction of MARCH2 with SNAIL. Overexpression of MARCH2 exhibits tumor suppressive properties and phenocopies the effects of SNAIL downregulation and PTK6 inhibition in TNBC cells, such as inhibition of migration, anoikis resistance, and metastasis. Consistent with this, higher levels of MARCH2 expression in breast and other cancers are associated with better prognosis. We have identified MARCH2 as a novel SNAIL E3 ligase that regulates EMT and metastases of mesenchymal TNBC. SIGNIFICANCE: EMT is a process directly linked to drug resistance and metastasis of cancer cells. We identified MARCH2 as a novel regulator of SNAIL, a key EMT driver, that promotes SNAIL ubiquitination and degradation in TNBC cells. MARCH2 is oncogene regulated and inhibits growth and metastasis of TNBC. These insights could contribute to novel strategies to therapeutically target TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Ubiquitina-Proteína Ligasas , Humanos , Regulación de la Expresión Génica , Oncogenes , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo
13.
J Am Chem Soc ; 135(15): 5493-6, 2013 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-23557199

RESUMEN

We report the first discovery of pure face-centered-cubic (fcc) Ru nanoparticles. Although the fcc structure does not exist in the bulk Ru phase diagram, fcc Ru was obtained at room temperature because of the nanosize effect. We succeeded in separately synthesizing uniformly sized nanoparticles of both fcc and hcp Ru having diameters of 2-5.5 nm by simple chemical reduction methods with different metal precursors. The prepared fcc and hcp nanoparticles were both supported on γ-Al2O3, and their catalytic activities in CO oxidation were investigated and found to depend on their structure and size.

14.
ChemSusChem ; 16(22): e202300942, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37877342

RESUMEN

An important part of realizing a carbon-neutral society using ammonia will be the development of an inexpensive yet efficient catalyst for ammonia synthesis under mild reaction conditions (<400 °C, <10 MPa). Here, we report Fe/K(3)/MgO, fabricated via an impregnation method, as a highly active catalyst for ammonia synthesis under mild reaction conditions (350 °C, 1.0 MPa). At the mentioned conditions, the activity of Fe/K(3)/MgO (17.5 mmol h-1 gcat -1 ) was greater than that of a commercial fused iron catalyst (8.6 mmol h-1 gcat -1 ) currently used in the Haber-Bosch process. K doping was found to increase the ratio of Fe0 on the surface and turnover frequency of Fe in our Fe/K(3)/MgO catalyst. In addition, increasing the pressure to 3.0 MPa at the same temperature led to a significant improvement of the ammonia synthesis rate to 29.6 mmol h-1 gcat -1 , which was higher than that of two more expensive, benchmark Ru-based catalysts, which are also potential alternative catalysts. A kinetics analysis revealed that the addition of K enhanced the ammonia synthesis activity at ≥300 °C by changing the main adsorbed species from NH to N which can accelerate dissociative adsorption of nitrogen as the rate limiting step in ammonia synthesis.

15.
JACS Au ; 2(7): 1627-1637, 2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35911446

RESUMEN

Hydrogen is a promising clean energy source. In domestic polymer electrolyte fuel cell systems, hydrogen is produced by reforming of natural gas; however, the reformate contains carbon monoxide (CO) as a major impurity. This CO is removed from the reformate by a combination of the water-gas shift reaction and preferential oxidation of CO (PROX). Currently, Ru-based catalysts are the most common type of PROX catalyst; however, their durability against ammonia (NH3) as an impurity produced in situ from trace amounts of nitrogen also contained in the reformate is an important issue. Previously, we found that addition of Pt to an Ru catalyst inhibited deactivation by NH3. Here, we conducted operando XAFS and FT-IR spectroscopic analyses with simultaneous gas analysis to investigate the cause of the deactivation of an Ru-based PROX catalyst (Ru/α-Al2O3) by NH3 and the mechanism of suppression of the deactivation by adding Pt (Pt/Ru/α-Al2O3). We found that nitric oxide (NO) produced by oxidation of NH3 induces oxidation of the Ru nanoparticle surface, which deactivates the catalyst via a three-step process: First, NO directly adsorbs on Ru0 to form NO-Ruδ+, which then induces the formation of O-Ru n+ by oxidation of the surrounding Ru0. Then, O-Ru m+ is formed by oxidation of Ru0 starting from the O-Ru n+ nuclei and spreading across the surface of the nanoparticle. Pt inhibits this process by alloying with Ru and inducing the decomposition of adsorbed NO, which keeps the Ru in a metallic state.

16.
ACS Omega ; 7(28): 24452-24460, 2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35874216

RESUMEN

Ruthenium catalysts may allow for realization of renewable energy-based ammonia synthesis processes using mild reaction conditions (<400 °C, <10 MPa). However, ruthenium is relatively rare and therefore expensive. Here, we report a Co nanoparticle catalyst loaded on a basic Ba/La2O3 support and prereduced at 700 °C (Co/Ba/La2O3_700red) that showed higher ammonia synthesis activity at 350 °C and 1.0-3.0 MPa than two benchmark Ru catalysts, Cs+/Ru/MgO and Ru/CeO2. The synthesis rate of the catalyst at 350 °C and 1.0 MPa (19.3 mmol h-1 g-1) was 8.0 times that of Co/Ba/La2O3_500red and 6.9 times that of Co/La2O3_700red. The catalyst showed ammonia synthesis activity at temperatures down to 200 °C. Reduction at the high temperature induced the formation of BaO-La2O3 nanofractions around the Co nanoparticles by decomposition of BaCO3, which increased turnover frequency, inhibited the sintering of Co nanoparticles, and suppressed ammonia poisoning. These strategies may also be applicable to other non-noble metal catalysts, such as nickel.

17.
Hiroshima J Med Sci ; 60(4): 83-6, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22389952

RESUMEN

We report three cases of iliac artery rupture during percutaneous transluminal angioplasty (PTA). In all three cases, bleeding was temporarily controlled by inflating an angioplasty balloon at the site of bleeding. Two patients underwent subsequent surgical revascularization, and one underwent endovascular stent grafting but ultimately required a surgical bypass. Arterial rupture is a rare but potentially fatal complication of PTA. Although stent grafts for peripheral arteries are not yet covered by Japanese medical insurance, it is a useful treatment for arterial injury during PTA.


Asunto(s)
Angioplastia/efectos adversos , Arteria Ilíaca/patología , Rotura/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino
18.
Clin Case Rep ; 9(1): 274-277, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33489172

RESUMEN

Acute aortic dissection combined with cardiac tamponade is fatal. The radical treatment is an aortic replacement; however, the risk is high. We suggest conservative treatment with pericardial drainage as a treatment option in elderly patients with comorbidities.

19.
Elife ; 102021 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-34579806

RESUMEN

KNOX and BELL transcription factors regulate distinct steps of diploid development in plants. In the green alga Chlamydomonas reinhardtii, KNOX and BELL proteins are inherited by gametes of the opposite mating types and heterodimerize in zygotes to activate diploid development. By contrast, in land plants such as Physcomitrium patens and Arabidopsis thaliana, KNOX and BELL proteins function in meristem maintenance and organogenesis during the later stages of diploid development. However, whether the contrasting functions of KNOX and BELL were acquired independently in algae and land plants is currently unknown. Here, we show that in the basal land plant species Marchantia polymorpha, gamete-expressed KNOX and BELL are required to initiate zygotic development by promoting nuclear fusion in a manner strikingly similar to that in C. reinhardtii. Our results indicate that zygote activation is the ancestral role of KNOX/BELL transcription factors, which shifted toward meristem maintenance as land plants evolved.


Asunto(s)
Evolución Biológica , Células Germinativas/fisiología , Plantas/metabolismo , Factores de Transcripción/metabolismo , Diploidia
20.
Nat Commun ; 12(1): 4671, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34344863

RESUMEN

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest and apoptosis of TNBC cells. In vivo, 108600 treatment of mice bearing triple negative tumors results in the induction of apoptosis and overcomes chemotherapy resistance. Finally, treatment with 108600 and chemotherapy suppresses growth of pre-established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Nitrobencenos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Tiazinas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Quinasa de la Caseína II/antagonistas & inhibidores , Quinasa de la Caseína II/química , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Ratones , Células Madre Neoplásicas/patología , Nitrobencenos/química , Nitrobencenos/farmacología , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/química , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/química , Tiazinas/química , Tiazinas/farmacología , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Quinasas DyrK
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