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We review the basic ideas of the tensor renormalization group method and show how they can be applied for lattice field theory models involving relativistic fermions and Grassmann variables in arbitrary dimensions. We discuss recent progress for entanglement filtering, loop optimization, bond-weighting techniques and matrix product decompositions for Grassmann tensor networks. The new methods are tested with two-dimensional Wilson-Majorana fermions and multi-flavor Gross-Neveu models. We show that the methods can also be applied to the fermionic Hubbard model in 1+1 and 2+1 dimensions.
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TFAP2E is a member of the activator protein-2 transcription factor family and acts as a tumor suppressor in several types of cancer. Downregulation of TFAP2E expression is significantly associated with a shorter overall survival period in patients with oral squamous cell carcinoma (OSCC). To evaluate the molecular mechanisms by which TFAP2E suppresses the development or progression of OSCC, the present study investigated the effects of TFAP2E downregulation on OSCC-derived Ca9-22 and HSC-4 cells. The present study demonstrated that small interfering RNA mediated-knockdown of TFAP2E accelerated the proliferation of these OSCC cell lines compared with that in the control group, as determined by the standard water-soluble tetrazolium salt-8 assay. To analyze the cell cycle progression rate, the cell cycle distribution patterns of TFAP2E-knockdown and control cells cultured in the presence of nocodazole, which prevents the completion of mitosis, were analyzed by fluorescence-activated cell sorting at different time points. When analyzing cellular DNA contents, no major differences in cell cycle profiles were observed; however, the rate of increase in cells positive for histone H3 Serine 28 phosphorylation, a standard molecular marker of early M phase, was significantly higher in TFAP2E-knockdown cells than in the control cells. Collectively, these results suggested that TFAP2E may attenuate the proliferation of OSCC cells by regulating G2/M transition.
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Motor nerve organoids could be generated by culturing a spheroid of motor neurons differentiated from human induced pluripotent stem (iPS) cells within a polydimethylsiloxane (PDMS) chip which guides direction and fasciculation of axons extended from the spheroid. To isolate axon bundles from motor nerve organoids, we developed a rapid laser dissection method based on localized photothermal combustion. By illuminating a blue laser on a black mark on the culture device using a dry-erase marker, we induced highly localized heating near the axon bundles. Moving the laser enabled spatial control over the local heating and severing of axon bundles. This laser dissection requires a black mark, as other colors did not produce the same localized heating effect. A CO2 laser destroyed the tissue and the device and could not be used. With this simple, economical laser dissection technique, we could rapidly collect abundant pure axon samples from motor nerve organoids for biochemical analysis. Extracted axonal proteins and RNA were indistinguishable from manual dissection. This method facilitates efficient axon isolation for further analyses.
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PURPOSE: Guided bone regeneration (GBR) is an accepted method in dental practice that can successfully increase the bone volume of the host at sites chosen for implant placement; however, existing GBR membranes exhibit rapid absorption and lack of adequate space maintenance capabilities. We aimed to compare the effectiveness of a newly developed resorbable bilayer membrane composed of poly (L-lactic acid) and poly (-caprolactone) (PLACL) with that of a collagen membrane in a rat GBR model. METHODS: The rat calvaria was used as an experimental model, in which a plastic cylinder was placed. We operated on 40 male Fisher rats and subsequently performed micro-computed tomography and histomorphometric analyses to assess bone regeneration. RESULTS: Significant bone regeneration was observed, which was and similar across all the experimental groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, and sporadic partial degradation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. CONCLUSIONS: The PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane could address the limitations of the current membranes. Nevertheless, further studies and clinical trials are warranted to validate the efficacy and safety of The PLACL membrane in humans.
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Caproatos , Dioxanos , Lactonas , Mustelidae , Proyectos de Investigación , Humanos , Masculino , Animales , Ratas , Microtomografía por Rayos X , Regeneración ÓseaRESUMEN
For millimeter and submillimeter-wave astronomy, it is highly desirable to have vacuum windows within the receiver cryostat that exhibit low reflection, low loss, and a wide bandpass. The use of antireflective (AR) sub-wavelength structures (SWSs) on substrates has expanded the possibilities for creating new vacuum windows. Recently, a novel method of fabricating AR SWS on a silicon-on-insulator wafer has been proposed, and a vacuum window with a two-layer AR SWS has been developed for use with the Atacama Submillimeter Telescope Experiment Band 10 receiver. To thoroughly assess the characteristics of the silicon window sample, we conducted transmittance measurements using terahertz time-domain spectroscopy, and noise and beam measurements using an Atacama Large Millimeter/submillimeter Array (ALMA) Band 10 receiver. We found that the silicon window sample exhibits characteristics comparable to the quartz window of the ALMA Band 10 receiver. The result strongly encourages applications of AR silicon windows in receivers with wider bandwidths.
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The patient was a 6-year-old girl with clinically isolated syndrome-like anti-myelin oligodendrocyte glycoprotein-associated disease (MOG-AD). Methylprednisolone pulse therapy resolved her cerebral lesion, and her visual acuity and field fully recovered after plasma exchange. This is the first case report presenting the therapeutic course in a child with clinically isolated syndrome-like MOG-AD. [J Pediatr Ophthalmol Strabismus. 2023;60(2):e11-e15.].
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Autoanticuerpos , Intercambio Plasmático , Femenino , Humanos , Corticoesteroides , Glicoproteína Mielina-Oligodendrócito , Oligodendroglía , NiñoRESUMEN
Age-related decline in lower limb motor control may cause errors in pedal operation when driving a car. This study aimed to clarify the kinematics and electrophysiological characteristics of the pedal-switching operation associated with emergency braking in the case of elderly drivers. The participants in this study consisted of 11 young drivers and 10 elderly drivers. An experimental pedal was used, and the muscle activity and kinematic data during braking action were analyzed using the light from a light-emitting diode installed in the front as a trigger. The results showed that elderly drivers took the same time from viewing the visual stimulus to releasing the accelerator pedal as younger drivers, but took longer to switch to the brake pedal. The elderly drivers had higher soleus muscle activity throughout the process, from accelerator release to brake contact; furthermore, the rectus femoris activity was delayed, and the simultaneous activity between the rectus femoris and biceps femoris was low. Furthermore, elderly drivers tended to have low hip adduction velocity and tended to switch pedals by hip internal rotation. Thus, the alteration in joint movements and muscle activity of elderly drivers can reduce their pedal operability and may be related to the occurrence of pedal errors.
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The objective of this study was to verify whether loss of posterior occlusal support induced displacement of the mandibular condyles from a physiological point of view. Stabilization-type splints were fabricated for 12 healthy dentulous individuals. Each splint was designed to cover the bilateral maxillary teeth up to the second molars. To reproduce loss of posterior occlusal support, the extent of the splint was reduced one tooth at a time, bilaterally, starting from the back and moving forward sequentially. Tapping movement and lateral excursions were performed with each splint and a jaw movement tracking device with 6-degrees of freedom used to observe condylar displacement. Evaluation of 3-dimensional (3-D) displacement of the kinematic axis of the condyle during experimental jaw movement was performed under each occlusal condition with occlusal contact on all teeth, including the maxillary second molars. The habitual closing position was used as the reference. An increase was observed in 3-D displacement of the kinematic axis at the terminal point of the tapping movement with loss of occlusal support, and significant differences were observed in both condyles. An increase was also observed in 3-D displacement of the kinematic axis on the working side during lateral excursion with loss of occlusal support, and a statistically significant difference was observed in the left condyle. A small increase was observed in 3-D displacement of the kinematic axis on the non-working side during lateral excursion with loss of occlusal support. The results of this study suggest that loss of posterior occlusal support induces displacement of the mandibular condyles, suggesting that occlusal support in the molar region is an important factor in stabilization of the condylar position.
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Cóndilo Mandibular , Diente , Humanos , Diente Molar , Movimiento , Férulas (Fijadores)RESUMEN
Two novel 18-electron titanium germylene complexes, Cp2 Ti(L)=Ge[Si3 (SiMet Bu2 )4 ] 3 b (L=Me3 P) and 3 c (L=XylNC), were synthesized, isolated, and structurally characterized. The length of the titanium-germanium bonds of 2.5387(3)â Å and 2.5276(3)â Å (in 3 b and 3 c, respectively) well match those expected for the double bond, which was further supported by the DFT study. Based on their structural characteristics, as well as their atomic charges calculations which revealed Ti(δ+)=Ge(δ-) bond polarization, both 3 b and 3 c are classified as the Schrock-type titanium germylidenes, as the germanium analogues of the widely known titanium alkylidenes. By contrast, germylene complexes of the group 6 metals 8 a (M=Mo) and 8 b (M=W) are better described as Fischer-type germylene complexes.
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BACKGROUND AND PURPOSE: Stiff-knee gait, which is a gait abnormality observed after stroke, is characterized by decreased knee flexion angles during the swing phase, and it contributes to a decline in gait ability. This study aimed to identify the immediate effects of pedaling exercises on stiff-knee gait from a kinesiophysiological perspective. METHODS: Twenty-one patients with chronic post-stroke hemiparesis and stiff-knee gait were randomly assigned to a pedaling group and a walking group. An ergometer was set at a load of 5 Nm and rotation speed of 40 rpm, and gait was performed at a comfortable speed; both the groups performed the intervention for 10 min. Kinematic and electromyographical data while walking on flat surfaces were immediately measured before and after the intervention. RESULTS: In the pedaling group, activity of the rectus femoris significantly decreased from the pre-swing phase to the early swing phase during gait after the intervention. Flexion angles and flexion angular velocities of the knee and hip joints significantly increased during the same period. The pedaling group showed increased step length on the paralyzed side and gait velocity. CONCLUSIONS: Pedaling increases knee flexion during the swing phase in hemiparetic patients with stiff-knee gait and improves gait ability.
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Accidentes por Caídas/prevención & control , Ciclismo , Terapia por Ejercicio , Trastornos Neurológicos de la Marcha/rehabilitación , Marcha , Articulación de la Rodilla/fisiopatología , Paresia/rehabilitación , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/terapia , Adulto , Anciano , Fenómenos Biomecánicos , Femenino , Análisis de la Marcha , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Japón , Masculino , Persona de Mediana Edad , Paresia/diagnóstico , Paresia/etiología , Paresia/fisiopatología , Proyectos Piloto , Rango del Movimiento Articular , Recuperación de la Función , Método Simple Ciego , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cancer stem cells (H1299-sdCSCs) were obtained from tumour spheres of H1299 human lung cancer cells. We studied low stiffness, a unique biophysical property of cancer cells, in H1299-sdCSCs and parental H1299. Atomic force microscopy revealed an average Young's modulus value of 1.52 kPa for H1299-sdCSCs, which showed low stiffness compared with that of H1299 cells, with a Young's modulus value of 2.24 kPa. (-)-Epigallocatechin gallate (EGCG) reversed the average Young's modulus value of H1299-sdCSCs to that of H1299 cells. EGCG treatment inhibited tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. AXL receptor tyrosine kinase is highly expressed in H1299-sdCSCs and AXL knockdown with siAXLs significantly reduced tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. An AXL-high population of H1299-sdCSCs was similarly reduced by treatment with EGCG and siAXLs. Transplantation of an AXL-high clone isolated from H1299 cells into SCID/Beige mice induced faster development of bigger tumour than bulk H1299 cells, whereas transplantation of the AXL-low clone yielded no tumours. Oral administration of EGCG and green tea extract (GTE) inhibited tumour growth in mice and reduced p-AXL, ALDH1A1, and SLUG in tumours. Thus, EGCG inhibits the stemness and tumourigenicity of human lung cancer cells by inhibiting AXL.
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Anticarcinógenos/farmacología , Carcinogénesis/efectos de los fármacos , Catequina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Animales , Anticarcinógenos/uso terapéutico , Carcinogénesis/metabolismo , Carcinogénesis/patología , Catequina/farmacología , Catequina/uso terapéutico , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones SCID , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Tirosina Quinasa del Receptor AxlRESUMEN
We developed the effective Mn-doping procedure for AgInS2(AIS)/ZnS core/shell nanocrystals (NCs) to exhibit dual photoluminescence (PL) peaks. Although the AIS/ZnS core/shell NCs showed solely a single PL peak at ~530 nm, incorporation of a small amount of Mn as a dopant within the AIS/ZnS NCs resulted in the simultaneous emergence of dual PL peaks at ~500 nm (green PL) arising from AIS/ZnS NCs and ~600 nm (orange PL) from the Mn dopants. Furthermore, we succeeded in significantly increasing the absolute PL quantum yield value of dual emissive AIS/ZnS NCs incorporated with Mn dopants from 10% to 34% after surface passivation with another ZnS shell for the formation of core/shell/shell structures.
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(1) Background: Crude drugs used in traditional Japanese Kampo medicine or folk medicine are major sources of new chemical entities for drug discovery. We screened the inhibitory potential of these crude drugs against urate transporter 1 (URAT1) to discover new drugs for hyperuricemia. (2) Methods: We prepared the MeOH extracts of 107 different crude drugs, and screened their inhibitory effects on URAT1 by measuring the uptake of uric acid by HEK293/PDZK1 cells transiently transfected with URAT1. (3) Results: We found that the extract of the dried mature fruit of Cnidium monnieri inhibited urate uptake via URAT1. We isolated and identified osthol as the active ingredient from this extract. Osthol noncompetitively inhibited URAT1 with an IC50 of 78.8 µM. We evaluated the effects of other coumarins and found that the prenyl group, which binds at the 8-position of coumarins, plays an important role in the inhibition of URAT1. (4) Conclusions: Cnidium monnieri fruit may be useful for the treatment of hyperuricemia or gout in traditional medicine, and its active ingredient, osthol, is expected to be a leading compound for the development of new drugs for hyperuricemia.
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Cnidium/química , Cumarinas/farmacología , Frutas/química , Transportadores de Anión Orgánico/antagonistas & inhibidores , Extractos Vegetales/farmacología , Línea Celular , Fraccionamiento Químico , Cumarinas/química , Cumarinas/aislamiento & purificación , Humanos , Cinética , Transportadores de Anión Orgánico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1.
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Adenocarcinoma/genética , Inestabilidad Cromosómica , Metilación de ADN , ADN Polimerasa II/genética , Neoplasias Gastrointestinales/genética , Homólogo 1 de la Proteína MutL/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Adenocarcinoma/clasificación , Aneuploidia , Proteínas de Unión al ADN , Epigénesis Genética , Femenino , Neoplasias Gastrointestinales/clasificación , Redes Reguladoras de Genes , Ribonucleoproteínas Nucleares Heterogéneas/genética , Humanos , Masculino , Inestabilidad de Microsatélites , Mutación , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas de Unión al ARN , Factor de Transcripción SOX9/genéticaRESUMEN
To study the role of cell softening in malignant progression, Transwell assay and atomic force microscope were used to classify six human non-small cell lung cancer cell lines into two groups: a high motility-low stiffness (HMLS) group and a low motility-high stiffness (LMHS) group. We found a significant role of activity of the AXL receptor tyrosine kinase, which belongs to the TAM (Tyro3, AXL, Mer) family, in the stimulation of motility and cell softening. HMLS cells expressed higher AXL levels than LMHS cells and contained phosphorylated AXL. H1703 LMHS cells transfected with exogenous AXL exhibited increased motility and decreased stiffness, with low levels of actin stress fibre formation. Conversely, the AXL-specific inhibitor R428 and AXL-targeting siRNA reduced motility and increased stiffness in H1299 HMLS cells. Knockdown of AXL stimulated actin stress fibre formation, which inhibited tumour formation in a mouse xenograft model. The Ras/Rac inhibitor SCH 51344, which blocks disruption of actin stress fibres, exerted similar effects to AXL inactivation. We therefore propose that the Ras/Rac pathway operates downstream of AXL. Thus, AXL activation-induced cell softening promotes malignant progression in non-small cell lung cancer and represents a key biophysical property of cancer cells.
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Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Células A549 , Animales , Apoptosis/fisiología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Progresión de la Enfermedad , Femenino , Humanos , Ratones , Ratones SCID , Fosforilación/fisiología , ARN Interferente Pequeño/metabolismo , Tirosina Quinasa c-Mer/metabolismo , Tirosina Quinasa del Receptor AxlRESUMEN
BACKGROUND: Ample evidence on etiological and pathological differences between femoral neck and trochanteric fracture cases suggests the possibility of individualized treatment. There are many issues related to areal bone mineral density and other quantitative computed tomography parameters of the proximal femur. Although osteoporosis is a systemic problem, little has been reported regarding differences in bone structural parameters, including bone mineral density, between them in regions other than the proximal femur. METHODS: Participants were consecutive female patients >50 years of age admitted to the Saiseikai Suita Hospital (Osaka prefecture, Japan) for their first hip fracture between January 2012 and September 2014. Cortical thickness (CoTh, mm), volumetric trabecular bone mineral density (TBD, mg/cm3), and elastic modulus of trabecular bone (EMTb, GPa) were obtained as the new QUS parameters using the LD-100 system (Oyo Electric, Kyoto, Japan). The mean values of these parameters were compared between femoral neck and trochanteric fracture cases. In addition, correlations between age and each QUS parameter were investigated for each fracture type. A receiver operating characteristic (ROC) curve analysis was performed to examine the degree of effect each parameter on the fracture types. The area under the curve (AUC) for each parameter was compared to the AUC for age. RESULTS: There were 63 cases of femoral neck fracture (mean age, 78.2 years) and 37 cases of trochanteric fracture (mean age, 85.9 years). Mean TBD and EMTb were significantly higher for femoral neck fractures. There were significant negative correlations between QUS parameters and age for femoral neck fractures (P < 0.005). The regression lines for femoral neck fractures were above those for trochanteric fractures for TBD and EMTb. AUCs were 0.72 for age, and 0.61, 0.65, and 0.65 for CoTh, TBD, and EMTb, respectively. CONCLUSIONS: The new QUS parameters indicated that TR fracture cases were more osteoporotic than were FN fracture cases, even at the distal radius. There might be systemic differences between them, in addition to localized factors at the proximal femur.
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Acid-catalyzed degradation of lignin in toluene containing methanol selectively yields C6-C2 lignin monomers and releases lignin oligomers, a potential raw feedstock for epoxy resins. We herein characterize the structures of the lignin oligomers by focusing on the changes in the interunit linkage types during solvolysis. The oligomeric lignin products were analyzed via thioacidolysis and 2D-HSQC-NMR. The results show that lignin oligomers ranging from monomers to tetramers are released through considerable cleavage of the ß-O-4 linkages. The lignin oligomers from Cryptomeria japonica (softwood) mainly comprise ß-5, ß-1, and tetrahydrofuran ß-ß linkages, whereas Eucalyptus globulus (hardwood) yields oligomers rich in ß-1 and syringaresinol ß-ß linkages. Both wood samples exhibit selective release of ß-ß dimers and a relative decrease in 5-5 and 4-O-5 bonds during solvolysis. The method presented for the separation of lignin oligomers without ß-O-4 linkages and with linkages unique to each wood species will be useful for the production of lignin-based materials.
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Cryptomeria/química , Eucalyptus/química , Lignina/química , Madera/química , Furanos/química , Cromatografía de Gases y Espectrometría de Masas , Lignanos/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer.
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Adenocarcinoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Pulmonares/genética , Mutación , Adenocarcinoma del Pulmón , Animales , Línea Celular Tumoral , Perfilación de la Expresión Génica , Xenoinjertos , Humanos , Ratones , Oncogenes , FenotipoRESUMEN
Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC) cell lines resistant to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.