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1.
J Clin Oncol ; 42(20): 2436-2445, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38710003

RESUMEN

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Quimioradioterapia , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Fluorouracilo , Oxaliplatino , Humanos , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Capecitabina/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Fluorouracilo/análogos & derivados , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Quimioradioterapia/efectos adversos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Oxaliplatino/efectos adversos , Adulto , Oxaloacetatos
2.
J Med Case Rep ; 18(1): 189, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38555435

RESUMEN

BACKGROUND: Piriformis muscle mass is rare, which is particular for intrapiriformis lipoma. Thus far, only 11 cases of piriformis muscle mass have been reported in the English literature. Herein, we encountered one patient with intrapiriformis lipoma who was initially misdiagnosed. CASE PRESENTATION: The patient is a 50-year-old Chinese man. He complained of osphyalgia, right buttock pain, and radiating pain from the right buttock to the back of the right leg. Both ultrasound and magnetic resonance imaging demonstrated a cyst-like mass in the right piriformis muscle. Ultrasonography-guided aspiration was performed on this patient first, but failed. He was then recommended to undergo mass resection and neurolysis of sciatic nerve. Surprisingly, final histology revealed the diagnosis of intrapiriformis lipoma. The patient exhibited significant relief of symptoms 3 days post-surgery. CONCLUSION: Diagnosis and differential diagnosis of radicular pain are potentially challenging but necessary. Atypical lipoma is prone to be misdiagnosed, especially in rare sites. It is notable for clinicians to be aware of the presence of intrapiriformis lipoma to avoid misdiagnosis and inappropriate treatment.


Asunto(s)
Lipoma , Nervio Ciático , Masculino , Humanos , Persona de Mediana Edad , Nervio Ciático/patología , Músculo Esquelético , Dolor , Nalgas , Lipoma/diagnóstico por imagen , Lipoma/cirugía
3.
Front Public Health ; 12: 1275447, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38532972

RESUMEN

Objective: To explore the effect of a video teach-back method on continuous family nursing care of stroke patients. Methods: Stroke patients hospitalized in our hospital between March 2020 and March 2023 who met the inclusion criteria were randomly divided into an intervention group (n = 45), who received routine health education plus video teach-back training of caregivers, and a control group (n = 45), who received routine health education only. The effects on nursing-related variables were compared between the two groups. Results: Total scores representing the caring ability of caregivers in the intervention group increased significantly over time relative to baseline and were higher than those of the control group. Scores representing the care burden of caregivers in the intervention group decreased significantly over time and were lower than those of the control group. Conclusion: The teach-back method combined with video education improves the nursing ability of family caregivers and can improve the self-care ability of stroke patients.


Asunto(s)
Accidente Cerebrovascular , Humanos , Educación en Salud/métodos , Pacientes
5.
Materials (Basel) ; 17(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38276417

RESUMEN

In this paper, a novel precast concrete composite wall connected by tooth groove and grouted sleeve was introduced, which is produced in factories by means of structure-insulation integrated prefabrication, and the prefabrication and assembly process were presented minutely. To verify the feasibility and reliability of this novel tooth groove and grouted sleeve connection method and explore the joint connection performance and the seismic performance of the precast concrete composite wall connected by tooth groove and grouted sleeve, low-cyclic reversed loading tests with an axial compressive ratio of 0.1 were performed on two full-scale precast concrete composite walls. Moreover, the failure mode, hysteretic curve, skeleton curve, stiffness degradation, displacement ductility, energy dissipation capacity, and reinforcement strain were comprehensively discussed. The research results showed that under the vertical axial load and low-cyclic reversed load, the distributed reinforcements in the wall panel only played a structural role, while the connecting reinforcements at horizontal joints can always effectively transfer stress without bond failure, and the tooth groove and grouted sleeve connection performance was reliable. In addition, the hysteretic curves of the precast concrete composite wall connected by tooth groove and grouted sleeve were full, showing good ductile deformation capacity and energy dissipation capacity. In general, the precast concrete composite wall connected by tooth groove and grouted sleeve not only possessed favorable seismic performance but also showed obvious advantages such as green energy saving, high assembly rate, and less on-site wet operation, which can be applied to practical engineering under reasonable design.

6.
J Mater Chem B ; 12(3): 667-677, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38063821

RESUMEN

Ferroptosis is a non-apoptotic form of cell death that is dependent on the accumulation of intracellular iron that causes elevation of toxic lipid peroxides. Therefore, it is crucial to improve the levels of intracellular iron and reactive oxygen species (ROS) in a short time. Here, we first propose ultrasound (US)-propelled Janus nanomotors (Au-FeOx/PEI/ICG, AFPI NMs) to accelerate cellular internalization and induce cancer cell ferroptosis. This nanomotor consists of a gold-iron oxide rod-like Janus nanomotor (Au-FeOx, AF NMs) and a photoactive indocyanine green (ICG) dye on the surface. It not only exhibits accelerating cellular internalization (∼4-fold) caused by its attractive US-driven propulsion but also shows good intracellular motion behavior. In addition, this Janus nanomotor shows excellent intracellular ROS generation performance due to the synergistic effect of the "Fenton or Fenton-like reaction" and the "photochemical reaction". As a result, the killing efficiency of actively moving nanomotors on cancer cells is 88% higher than that of stationary nanomotors. Unlike previous passive strategies, this work is a significant step toward accelerating cellular internalization and inducing cancer-cell ferroptosis in an active way. These novel US-propelled Janus nanomotors with strong propulsion, efficient cellular internalization and excellent ROS generation are suitable as a novel cell biology research tool.


Asunto(s)
Ferroptosis , Neoplasias , Especies Reactivas de Oxígeno , Hierro , Neoplasias/diagnóstico por imagen
7.
Materials (Basel) ; 16(23)2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38068115

RESUMEN

In order to explore the horizontal joint connection performance of the innovative tooth groove connection and vertical reinforcement lapping in the reserved hole, five horizontal joint specimens were designed and constructed in this paper. Through the combination of monotonic horizontal load tests and finite element simulation analysis, the effects of axial compression ratio, vertical reinforcement connection degree, reserved hole type, mortar strength, and tooth groove depth on the horizontal joint connection performance of innovative tooth groove connections and vertical reinforcement lapping in reserved holes were comprehensively analyzed and discussed. The results indicated that the specimens were subjected to penetration failure at the tooth groove joint, but the vertical reinforcements and UHPC in reserved holes can effectively transfer the stress, ensuring satisfactory connection performance. With the increase in axial compression ratio and vertical reinforcement connection degree, the joint connection performance enhanced gradually, while the reserved hole type had little effect on the joint connection performance. In addition, it was found that increasing the mortar strength and the tooth groove depth can significantly improve the peak bearing capacity through finite element analysis. Finally, the optimization design suggestions for this innovative tooth groove connection and vertical reinforcement lapping in the reserved hole were given considering factors such as joint connection performance and construction assembly.

8.
Int J Gynecol Cancer ; 33(12): 1861-1868, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37875323

RESUMEN

OBJECTIVE: There is an unmet need to improve clinical outcomes for patients with recurrent/metastatic cervical cancer. Checkpoint inhibitors represent a promising treatment strategy. We evaluated the safety and anti-tumor activity of zimberelimab, an anti-programmed cell death protein-1 antibody, in patients with previously treated, recurrent, metastatic cervical cancer. METHODS: This phase II, single-arm, open-label study used a Simon two-stage minimax design. Eligible patients were women aged 18-75 years with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line chemotherapy (Eastern Cooperative Oncology Group (ECOG) performance status 0-1). Patients received intravenous zimberelimab (240 mg every 2 weeks) for 2 years until disease progression, intolerable adverse effects, or withdrawal from the study. The primary endpoint was objective response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, by an independent review committee. RESULTS: A total of 105 patients were enrolled. Median age was 51 (range, 31-75) years; 63.8% had an ECOG performance status of 1. The median number of previous treatment lines was 1 (range, 1-4). Median follow-up was 16.9 (range, 16.3-18.4) months. The objective response rate was 27.6%, and the disease control rate was 55.2%. Median duration of response was not reached. Median overall survival was 16.8 months, and median progression-free survival was 3.7 months. The incidence of treatment-related adverse events of any grade was 78.1%, of which the most common were hypothyroidism (26.7%) and anemia (19.0%). CONCLUSION: Zimberelimab monotherapy demonstrated durable anti-tumor activity and an acceptable safety profile in patients with cervical cancer. CLINICAL TRIAL REGISTRATION: NCT03972722.


Asunto(s)
Neoplasias del Cuello Uterino , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico
9.
Materials (Basel) ; 16(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37049211

RESUMEN

Rebar corrosion is the primary cause of the durability degradation of reinforced concrete (RC) structures, where non-uniform corrosion is the typical pattern in engineering. This study experimentally and numerically investigated the tensile degradation properties of non-uniform corroded rebars. Corrosion morphology was accurately determined by three-dimensional (3D) laser scanning techniques, studying the characteristics of longitudinal non-uniform corrosion. The results showed that the non-uniformity of corrosion increased with an increase in corrosion levels. From tensile tests, the differences in nominal stress-strain curves among rebars with similar average corrosion levels indicated that corrosion non-uniformity has appreciable effects on the tensile behavior of rebars. The residual load-bearing capacity of corroded rebars was dominated by the reduced critical cross-section, while residual ductility was associated with the cross-section loss throughout the entire length of rebars. The degradation relations of nominal yield and ultimate strength, ultimate strain, and elongation after fracture were better correlated to the maximum cross-section loss than to the average volume loss. Additionally, numerical calculation based on the cross-sectional areas of corroded rebars was conducted to evaluate the tensile behavior of non-uniform corroded rebars. Equivalent distribution models simulating the longitudinal non-uniform corrosion were proposed, on the basis of probability characteristics of cross-sectional areas, for practical application of the numerical method.

10.
Materials (Basel) ; 15(21)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36363141

RESUMEN

Using high strength wire (HSW) as a longitudinal reinforcement in UHPC can make full use of the outstanding properties of UHPC. In this paper, the flexural test was carried out on normal rebar-reinforced UHPC (NRRU) and HSW reinforced UHPC (HSWRU) slabs. The cracking resistance, failure modes, bearing capacity and deformation characteristics of specimens were investigated. The test results indicated that both HSWRU and NRRU specimens exhibited excellent flexural performance under concentrated loads. Fewer inclined cracks and a slower cracking development process were observed for HSWRU specimens, and brittle failure did not occur during the whole loading process. As compared to HSWRU specimens, the cracking and ultimate load of NRRU specimens increased by 24.64% and 85.47%, respectively, due to a higher reinforcement ratio. Then the theoretical method available for flexural capacity and ductility calculation was proposed, and the feasibility was substantiated through test results. In addition, the traditional deformation ductility coefficient was found to be 30% conservative against the applied energy ductility coefficient. Finally, the extensive parametric analysis revealed that the increase of the reinforcement ratio and the strength of the steel rebar significantly enhanced the ultimate capacity, while the ductility coefficient was obviously weakened. Inversely, those two factors had little impact on the cracking capacity. Moreover, section height was found to be beneficial for both the flexural capacity and ductility of specimens.

11.
Front Pediatr ; 10: 964413, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36275048

RESUMEN

Objective: The purpose of this study was to evaluate the use of sound touch elastography (STE) in conjunction with conventional ultrasound in the differential diagnosis of diffuse thyroid disease (DTD) and normal thyroid in children. Methods: Studies performed on 62 children with DTD and 30 normal volunteers were reviewed. Standard gray scale ultrasound, Doppler ultrasound and STE of the examinees, and the serum test results of children with DTD were collected, analyzed and compared. Results: The STE-Mean values in the Graves' disease (GD) group, Hashimoto's thyroiditis (HT) group, and normal control group, respectively, were 19.35 ± 5.00 kPa, 19.43 ± 6.06 kPa, and 11.24 ± 1.99 kPa. With an area under the ROC curve (AUC) of 0.945, STE-Mean values differentiated DTD from normal children. The peak systolic velocity (PSV) of the superior thyroid artery separated DTD from normal children and AUC from children with GD and HT, respectively, and was 0.992 and 0.864. The PSV of superior thyroid artery revealed a somewhat favorable connection with FT3 and FT4. Conclusion: The STE results revealed that thyroid stiffness was higher in children with DTD than in normal children, but further differentiation into GD and HT subgroups lacked specificity, and the superior thyroid artery flow velocity might be a good supplement to distinguish both.

12.
Lung Cancer ; 166: 98-106, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35248866

RESUMEN

BACKGROUND: There are no approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC) without EGFR T790M mutation after progression on first- or second-generation EGFR-TKIs. METHODS: We conducted this phase I, open-label, multicenter, dose-escalation/dose-expansion study to evaluate the safety, tolerability, antitumor activity, and pharmacokinetics of FCN-411, a TKI targeting EGFR, HER2, and HER4, in patients with EGFR-mutated advanced NSCLC whose disease had progressed during treatment of EGFR-TKIs. Adult patients with stage IIIB-IV NSCLC harboring EGFR mutations (exon 18/19/20/21) who had progressed on prior EGFR-TKIs were enrolled. In the dose-escalation phase, patients received 4 mg, 8 mg, 12 mg, and 16 mg FCN-411 once daily until the maximum tolerated dose (MTD). In the dose-expansion phase, patients received FCN-411 at the recommended phase II dose (RP2D) continuously in 21-day cycles. The primary endpoints were safety, tolerability, MTD, and RP2D. RESULTS: From July 23, 2018 to September 29, 2020, 77 patients were enrolled, including 30 with EGFR T790M mutation in tumor tissues. The cut-off date was February 1, 2021. No dose-limiting toxicities were observed. The most common grade ≥ 3 treatment-emergent adverse events among all patients were diarrhea (8; 10.4%) and dermatitis acneiform (7; 9.1%). Ten of 67 evaluable patients achieved confirmed partial response, with an objective response rate (ORR) of 14.9% (95% confidence interval [CI], 8.3-24.0); the ORR was 33.3%, 14.0%, 0, and 25.0% at 4 mg, 8 mg, 12 mg, and 16 mg, respectively. Besides, the ORR in patients without and with EGFR T790M mutation was 20.5% and 7.4%, respectively. Moreover, 39 patients achieved stable disease across all doses, and the disease control rate was 73.1% (95% CI, 60.9-83.2). Median progression-free survival was 4.1 (95% CI, 2.9-5.3) months. Median duration of response and overall survival have not been reached. CONCLUSIONS: FCN-411 was well tolerated and demonstrated preliminary antitumor activity in patients with EGFR-mutated NSCLC after progression on EGFR-TKIs, especially in those without EGFR T790M mutation. The RP2D was defined as 8 mg once daily. Future studies are warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420079.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos
13.
Materials (Basel) ; 15(6)2022 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-35329753

RESUMEN

There are many horizontal joints on precast concrete (PC) wall panel structures, which certainly has a significant impact on the seismic behavior of structures. This paper proposes a novel alveolar-type horizontal joint, which has advantages of convenient and rapid assembly. Six precast concrete wall specimens with alveolar-type joints were designed and constructed, and they were weakly connected by spliced rebars anchored into grouted sleeves to meet the requirements of structural performance. The pseudo-static loading tests on these specimens were conducted to investigate the effects of influencing factors, such as the axial compression ratio, the thickness of wall (interface contact area), and the addition of a vertical grouted sleeve connection at the horizontal joint, on the seismic performance of PC walls. Analyses and comparisons were conducted in terms of the cracking propagation pattern, failure modes, force-displacement hysteretic curves, skeleton curves, bearing capacity, ductility factors, and energy dissipation of PC walls. It was concluded that the axial compression ratio and adding grouted sleeve connection had a significant influence on the cracking mode of PC walls, whereas the impact of the wall thickness was slight. The shear capacity and energy dissipation capacity of specimen dramatically enhanced by increasing the axial compression ratio or adding grouted sleeve connection. The PC wall exhibits good ductility after adding the vertical grouted sleeve connection at a horizontal joint. However, the ductility factor increases firstly and then decreases in the enhancement of the axial compression ratio. The reduction in wall thickness has remarkable impacts on the shear strength and energy dissipation capacity of specimens, but the influences on ductility were not significant. The prediction method for calculating the shear capacity of PC walls with alveolar-type horizontal joints was proposed based on the experimental data, and these calculated results are in good agreement with the experimental results.

14.
Front Immunol ; 12: 715508, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899684

RESUMEN

Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.


Asunto(s)
Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Canales Iónicos/genética , Proteínas de la Membrana/genética , Neoplasias , Humanos , Inmunoterapia , Canales Iónicos/análisis , Proteínas de la Membrana/análisis , Pronóstico , Resultado del Tratamiento
15.
Pest Manag Sci ; 76(8): 2619-2626, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32083373

RESUMEN

BACKGROUND: Non-target-site resistance (NTSR) to herbicides is a serious threat to global agriculture. Although metabolic resistance is the dominant mechanism of NTSR, the molecular mechanisms are not yet well-characterized. This study aimed to uncover the likely metabolism-related genes in Beckmannia syzigachne (American sloughgrass) resistant to fenoxaprop-p-ethyl. RESULTS: Ultra-performance liquid chromatography - tandem mass spectrometry experiments showed that the resistant American sloughgrass biotype (R, SD-04-SS) showed enhanced degradation of this herbicide compared to the susceptible biotype (S, SD-12). R and S biotype were harvested at 24 h after fenoxaprop-p-ethyl treatment to conduct RNA sequencing (RNA-Seq) analysis to investigate the likely fenoxaprop-p-ethyl metabolic genes. The RNA-Seq libraries yield 417 969 980 clean reads. The de novo assembly generated 115 112 unigenes, of which 57 906 unigenes were annotated. Finally, we identified 273 cytochrome P450s, 178 oxidases, 47 glutathione S-transferases (GSTs), 166 glucosyltransferases (GTs) and 180 ABC transporter genes to determine the likely fenoxaprop-p-ethyl metabolism-related genes in R biotype. Twelve overlapping up-regulated genes in the R biotype (fenoxaprop-p-ethyl-treated R/non-treated R, fenoxaprop-p-ethyl-treated R/fenoxaprop-p-ethyl-treated S) were identified by RNA-Seq and the results were validated using qRT-PCR. Ten were identified as fenoxaprop-p-ethyl metabolism-related genes, including three P450s (homologous to CYP71D7, CYP99A2 and CYP71D10), one GST (homologous to GSTF1), two GTs (homologous to UGT90A1 and UGT83A1) and four oxidase genes. CONCLUSION: This work demonstrates that the NTSR mechanism by means of enhanced detoxification of fenoxaprop-p-ethyl in American sloughgrass is very likely driven by herbicide metabolism related genes. The RNA-Seq data presented here provide a valuable resource for understanding the molecular mechanism of NTSR in American sloughgrass. © 2020 Society of Chemical Industry.


Asunto(s)
Poaceae , Sistema Enzimático del Citocromo P-450 , Herbicidas , Mutación
16.
Ann Transl Med ; 8(24): 1661, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33490173

RESUMEN

BACKGROUND: In recent years, nanotechnology has attracted a plethora of attention due of its ability to effectively diagnose and treat various tumors. Virus-like particles (VLPs) have good biocompatibility, are safe and non-toxic, and have an internal hollow space, and as such they are often used as nano drug carriers. In recent years, it has become one of the hot spots in the field of biopharmaceutical engineering. METHODS: In this study, the tumor-targeting peptide RGD (Arg-Gly-Asp) was genetically inserted into the major immunodominant region (MIR) of the hepatitis B virus core protein (HBc). A series of characterization, including stability and optical properties, were evaluated. A visual diagnosis and analysis of the efficacy against tumor cells were conducted at the cell level and using a live animal model. RESULTS: This study demonstrated that the recombinant HBc-based VLPs could participate in self-assembly of monodispersed nanoparticles with well-defined morphology, and the near-infrared dye indocyanine green (ICG) could be packaged into the VLPs without any chemical modification. Moreover, the HBc-based VLPs could specifically target cancer cells via the interaction with overexpressed integrin αvß3. The treatment with ICG-loaded HBc-based VLPs showed significant inhibition of 4T1 breast cancer cell growth (84.87% tumor growth inhibition). The in vivo imaging experiments demonstrated that the ICG-loaded HBc-based VLPs generated excellent fluorescence in tumor sites in 4T1 breast cancer bearing mice. This provided crucial information on tumor mass location, boundaries, and shape. Moreover, compared to free ICG, the nanosystem showed significantly longer blood circulation time and superior accuracy in targeting the tumor. CONCLUSIONS: The ICG-loaded HBc-based VLPs prepared in this study were of good stability and biocompatibility. It showed strong tumor targeting specificity and tumor visualization. Thus, it is expected to provide a new experimental basis and theoretical support for the integration of VLPs in the clinical diagnosis and treatment of breast cancer.

17.
PeerJ ; 7: e7659, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31576238

RESUMEN

The clinicopathological features of inflammatory breast carcinoma (IBC), the effect of therapeutic options on survival outcome and the identification of prognostic factors were investigated in this study. Information on IBC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Cox proportional hazard regression was used to determine potential significant prognostic factors of IBC. A nomogram was then constructed to evaluate patient survival based on certain variables. Univariate and multivariate analyses revealed that race (p < 0.001), M stage (p < 0.001), surgery (p = 0.010), chemotherapy (CT) (p < 0.001), tumor size (p = 0.010), estrogen receptor (p < 0.001), progesterone receptor (p = 0.04), and human epidermal growth factor receptor 2 (p < 0.001) were all independent risk factors. The concordance index (C-index) of the nomogram was 0.735, which showed good predictive efficiency. Survival analysis indicated that IBC patients without CT had poorer survival than those with CT (p < 0.001). Stratified analyses showed that modified radical mastectomy (MRM) had significant survival advantages over non-MRM in patients with stage IV IBC (p = 0.031). Patients treated with or without CT stratified by stage III and stage IV showed better survival than those without stage III and IV (p < 0.001). Trimodality therapy resulted in better survival than surgery combined with CT or CT alone (p < 0.001). Competing risk analysis also showed the same results. The nomogram was effectively applied to predict the 1, 3 and 5-year survival of IBC. Our nomogram showed relatively good accuracy with a C-index of 0.735 and is a visualized individually predictive tool for prognosis. Treatment strategy greatly affected the survival of patients. Trimodality therapy was the preferable therapeutic strategy for IBC. Further prospective studies are needed to validate these findings.

18.
Oncol Rep ; 42(5): 1667-1676, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31485620

RESUMEN

It has been demonstrated that microRNA­192 (miR­192) serves important roles in different cancer types, including breast cancer, prostate cancer and colorectal cancer. However, its biological role and function in breast cancer remains largely unknown. The present study aimed to determine the role of miR­192 in breast cancer. In the present study, one normal breast and two breast tumor cells lines were used, which included the normal mammary fibroblast cell line Hs578Bst, a more aggressive breast tumor cell line MDA­MB­231 and a less aggressive breast tumor cell line MCF­7. The effect of miR­192 on proliferation of breast cancer cells was detected with an MTT assay. Western blot analysis was performed to determine protein expression of caveolin 1 (CAV1). A lentiviral vector that overexpresses pre­miR­192 and control lentiviral packaging plasmids were used in the present study. The Student's t­test was performed to analyze the significance of differences between samples. In the present study, it was determined that the expression of miR­192 is downregulated in breast cancer, compared with the adjacent normal tissues. Overexpression of miR­192 significantly inhibited cell proliferation, and induced cell apoptosis and cell cycle arrest in MCF7 and MDA­MB­231 cells. Using a bioinformatics method, CAV1 was considered a potential target of miR­192. Furthermore, it was demonstrated that CAV1 is a direct target of miR­192 and its protein expression is negatively regulated by miR­192. Therefore, the present study demonstrated that miR­192 serves an important role as a regulator in breast cancer and the miR­192/CAV1 axis has a potential as a therapeutic target for treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Caveolina 1/genética , Caveolina 1/metabolismo , MicroARNs/genética , Regiones no Traducidas 3' , Anciano , Animales , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Ratones , Persona de Mediana Edad , Trasplante de Neoplasias
19.
Am J Transl Res ; 11(7): 4460-4469, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31396349

RESUMEN

Breast cancer is a leading cause of cancer-related death in the women worldwide. Apatinib is a novel tyrosine kinase inhibitor that selectively binds and inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). The clinical trials have demonstrated the objective efficacy of Apatinib against metastatic breast cancer. However, the underlying mechanism is not well established. In the present study, the breast cell lines, BT-474 and MCF-7, were investigated. The effect of Apatinib on the cell viability was determined using CCK-8 assay. The migration, invasion, cell cycle distribution and the downstream signaling of VEGFR-2 in the cells were determined after 48 h treatment with this drug. Subsequently, Vector of angiomotin (AMOT) cDNA was transfected into MCF-7 cells. The cells were either exposed to Apatinib or vehicle and then examined for cell viabilities, migration, invasion, cell cycle distribution and the downstream signaling of VEGFR-2. Apatinib demonstrated a dose-dependent, significant inhibition of cell viabilities, migration and invasion of BT-474 and MCF-7 cells, with an increase in the percentage of cells in G1 phase and a decrease in S phase. In addition, in MCF-7 cells, Apatinib decreased AMOT expression, accompanied with the decreased expression of LATS1/2, YAP, ERK1/2 phosphorylation and cyclin D1. The inhibitory effect of Apatinib on the cell activities and protein expressions were significantly suppressed by AMOT overexpression. The results of this study indicated that Apatinib inhibited MCF-7 cell proliferation and invasion through AMOT/VEGFR-2 pathway.

20.
Pestic Biochem Physiol ; 159: 80-84, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31400787

RESUMEN

The plastid acetyl coenzyme carboxylase (ACCase) Trp1999Leu mutation was identified in a Beckmannia syzigachne population resistant to fenoxaprop-p-ethyl. The pattern of cross-resistance for the Trp1999Leu mutation is still ambiguous. In this paper, mutant homozygote (1999Leu/Leu, RR) and wild type (1999Trp/Trp, SS) B. syzigachne plants with the same genetic background were purified from the JS-26 population using the dCAPS method. The activity of ACCase in RR and SS was determined. Then, the cross-resistance pattern to ACCase inhibiting herbicides of the Trp1999Leu mutation was determined using the whole-plant method. ACCase activity showed that the Trp1999Leu mutation decreased ACCase sensitivity to fenoxaprop-p-ethyl by 2.73-fold. A dose-response experiment indicated that the Trp1999Leu mutation conferred high resistance to quizalofop-p-ethyl (20.29-fold), metamifop (12.22-fold) and pinoxaden (18.60-fold), moderate resistance to fenoxaprop-p-ethyl (8.20-fold) and sethoxydim (6.38-fold), low resistance to cyhalofop-butyl (2.73-fold) and no resistance to clodinafop-propargyl (1.42 fold) and clethodim (1.59-fold). This is the first report of the role of Trp1999Leu in fenoxaprop-p-ethyl resistance and of the patterns of cross-resistance to ACCase-inhibiting herbicides in B. syzigachne.


Asunto(s)
Acetil-CoA Carboxilasa/genética , Herbicidas/farmacología , Poaceae/efectos de los fármacos , Poaceae/genética , Anilidas/farmacología , Benzoxazoles/farmacología , Ciclohexanonas/farmacología , Resistencia a los Herbicidas/genética , Compuestos Heterocíclicos con 2 Anillos/farmacología , Mutación/genética , Propionatos/farmacología , Piridinas/farmacología , Quinoxalinas/farmacología
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