Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
1.
Langmuir ; 40(19): 10346-10354, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38695309

RESUMO

To fully exploit pore engineering in the design of more efficient zeolite adsorbents for volatile organic compound (VOC) treatment, the roles of meso- and micropores need to be clarified to provide the theoretical basis and feasible measures. In this work, the three VOC sorption properties of conventional and hierarchical porous beta zeolites were comparatively investigated to study the roles of meso- and micropores. There is a division of functions between micro- and mesopores, with micropores being the main VOC adsorption sites and mesopores greatly enhancing VOC diffusion and adsorbent reusability. On the one hand, micropores should be preserved as much as possible because obtaining mesopores by sacrificing micropores (i.e., alkali treatment) results in 28-60% decreases in adsorption capacities. On the other hand, mesopore introduction is highly desirable, which results in an enhancement of VOC intraparticle diffusion rates by 1.3-2.3 times (at the VOC concentration of 600 ppm) and chlorobenzene adsorption capacity on the 20th cycle increasing from 78% of the initial value to 89 and 93%. The findings may provide valuable information about zeolite-based adsorbents for adsorption removal or recovery of VOCs.

2.
Dalton Trans ; 53(10): 4781-4789, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38363199

RESUMO

Highly crystalline nano-MFI-type zeolites containing different elements were synthesized, and the sorption effects of the elements on volatile organic compounds (VOCs) were investigated. The results showed that the optimal toluene and acetone breakthrough time of the synthesized zeolites was 2.1 and 1.9 times as long as that of the commercial zeolite, respectively. For a weakly polar toluene molecule, MFI zeolites (aluminum-free) showed better adsorption properties than aluminum-containing zeolites. For the highly polar acetone molecule, zeolites with a Si/Al ratio of 87 showed the highest adsorption capacity, which was 7% higher than that of the all-silica zeolite and 1.4 times that of the commercial zeolite. Furthermore, MFI zeolites with Ti replacing part of Al proved to have better performance for highly polar molecules. In the adsorption process of VOCs, in addition to internal diffusion, diffusion on the external surface of the zeolite also played a remarkable role, and the adsorption data of all samples fitted better with the pseudo-first-order model. This study may provide a reliable structure-performance relationship for the synthesis of nanosized zeolite-based adsorbents and their use in the industrial recovery/treatment of VOCs.

4.
Materials (Basel) ; 16(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37834710

RESUMO

In order to analyze the axial compressive properties of ultra-high-toughness cementitious composite (UHTCC)-confined recycled aggregate concrete (RAC), a batch of UHTCC-confined RAC components was designed and manufactured according to the requirements of GB/T50081-2002 specifications. After analyzing the surface failure phenomenon, load-displacement curves, scanning electron microscope (SEM), and parameter analysis of the specimen, the result shows that UHTCC-confined RAC is an effective confinement method, which can effectively improve the mechanical properties and control the degree of surface failure of RAC structures. Compared with the unconfined specimen, the maximum peak load of the UHTCC confinement layer with a thickness of 10 mm and 20 mm increased by 44.61% and 79.27%, respectively, meeting the requirements of engineering practice. Different fiber mixing amounts have different effects on improving the mechanical performance of RAC structural. The specific rule was steel fiber (SF) > polyvinyl alcohol fiber (PVAF) > polyvinyl alcohol fiber (PEF) > no fiber mixture, and the SF improves the axial compression properties of UHTCC most significantly. When there are strict requirements for improving the mechanical properties of the structure, SF should be added to UHTCC. On the contrary, PVAF should be added to UHTCC.

5.
Breast Cancer Res Treat ; 200(1): 23-36, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37160814

RESUMO

OBJECTIVE: Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. METHODS: We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. RESULTS: A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. CONCLUSIONS: MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma de Células Escamosas , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/patologia , Carcinoma Ductal de Mama/patologia , Prognóstico
6.
RSC Adv ; 13(13): 9109-9118, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36950075

RESUMO

Si-containing transition-metal nitrides Ti0.5Si0.5N, Zr0.5Si0.5N and Hf0.5Si0.5N with conventional rock salt B1 structure exhibit superior hardness, strength and oxidation resistance. However, the potential phases of the ternary systems at various pressures remain unexplored. In this work, we firstly studied the potential structures of Ti0.5Si0.5N, Zr0.5Si0.5N and Hf0.5Si0.5N in pressures of 0-100 GPa. A hexagonal phase with P63/mmc symmetry was uncovered and verified to be quenchable in the ambient conditions. The structural, mechanical and electronic properties were systematically studied and compared with the well-known ordered B1 structure. We surprisingly found that Ti0.5Si0.5N within this hexagonal phase displayed much improved ideal indentation shear strength from about 10 GPa for a B1 structure to 30 GPa. The estimated hardness based on the empirical formula is up to 38 GPa, greatly exceeding that of the B1 structure. By the detailed electronic analysis, the underlying atomic mechanism for the outstanding mechanical properties was also studied.

7.
Molecules ; 27(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36296502

RESUMO

The rapid heat loss and corrosion of nano-aluminum limits the energy performance of metastable intermolecular composites (MICs) in aquatic conditions. In this work, superhydrophobic n-Al/PVDF films were fabricated by the cryogel-templated method. The underwater ignition performance of the energetic films was investigated. The preparation process of energetic materials is relatively simple, and avoids excessively high temperatures, ensuring the safety of the entire experimental process. The surface of the n-Al/PVDF energetic film exhibits super-hydrophobicity. Because the aluminum nanoparticles are uniformly encased in the hydrophobic energetic binder, the film is more waterproof and anti-aging. Laser-induced underwater ignition experiments show that the superhydrophobic modification can effectively induce the ignition of energetic films underwater. The results suggest that the cryogel-templated method provides a feasible route for underwater applications of energetic materials, especially nanoenergetics-on-a-chip in underwater micro-scale energy-demanding systems.

8.
Technol Cancer Res Treat ; 21: 15330338221124658, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172744

RESUMO

Introduction: Although there have been significant advances in research and treatments over the past decades, cancer remains a leading cause of morbidity and mortality, mostly due to resistance to standard therapies. Pulsed electromagnetic field (PEMF), a newly emerged therapeutic strategy, has been highly regarded as less invasive and almost safe to patients, is now a clinically accepted form to treat diseases including cancer. Breast and lung cancer are the most prevalent forms of human cancers, yet reported investigations on exploring regimes including PEMF are limited. Methods: Intended to examine the anti-tumor effects of a clinically accepted osteogenic PEMF and the possibility of including PEMF in breast and lung cancer treatments, we studied the effects of 2 PEMF signals (PMF1 and PMF2) on breast and lung cancer cell growth and proliferation, as well as the possible underline mechanisms in vitro and in vivo. Results: We found that both signals caused modest but significant growth inhibition (∼5%) in MCF-7 and A549 cancer cells. Interestingly, mice xenograft tumors with A549 cells treated by PEMF were smaller in sizes than controls. However, for mice with MCF-7 tumor implants, treatment with PMF1 resulted in a slight increase (2.8%) in mean tumor size, while PMF2 treated tumors showed a 9% reduction in average size. Furthermore, PEMF increased caspase 3/7 expression levels and percentage of annexin stained cells, indicating the induction of apoptosis. It also increased G0 by 8.5%, caused changes in the expression of genes associated with cell growth suppression, DNA damage, cell cycle arrest, and apoptosis. When cancer cells or xenograft tumors treated with combined PEMF and chemotherapy drugs, PEMF showed growth inhibition effect independent of cisplatin in A549 cells, but with added effect by pemetrexed for the inhibition of MCF-7 growth. Conclusion: Together, our data suggested that clinically used osteogenic PEMF signals moderately suppressed cancer cell growth and proliferation both in vitro and in vivo.


Assuntos
Neoplasias da Mama , Campos Eletromagnéticos , Neoplasias Pulmonares , Células A549 , Animais , Anexinas , Neoplasias da Mama/terapia , Caspase 3 , Cisplatino , Humanos , Neoplasias Pulmonares/terapia , Células MCF-7 , Camundongos , Pemetrexede
9.
Clin Transl Med ; 12(8): e1014, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35998020

RESUMO

BACKGROUND: Cancer cell-specific variation and circulating tumour DNA (ctDNA) methylation are promising biomarkers for non-invasive cancer detection and molecular classification. Nevertheless, the applications of ctDNA to the early detection and screening of cancer remain highly challenging due to the scarcity of cancer cell-specific ctDNA, the low signal-to-noise ratio of DNA variation, and the lack of non-locus-specific DNA methylation technologies. METHODS: We enrolled three cohorts of breast cancer (BC) patients from two hospitals in China (BC: n = 123; healthy controls: n = 40). We developed a ctDNA whole-genome bisulfite sequencing technology employing robust trace ctDNA capture from up to 200 µL plasma, mini-input (1 ng) library preparation, unbiased genome-wide coverage and comprehensive computational methods. RESULTS: A diagnostic signature comprising 15 ctDNA methylation markers exhibited high accuracy in the early (area under the curve [AUC] of 0.967) and advanced (AUC of 0.971) BC stages in multicentre patient cohorts. Furthermore, we revealed a ctDNA methylation signature that discriminates estrogen receptor status (Training set: AUC of 0.984 and Test set: AUC of 0.780). Different cancer types, including hepatocellular carcinoma and lung cancer, could also be well distinguished. CONCLUSIONS: Our study provides a toolset to generate unbiased whole-genome ctDNA methylomes with a minimal amount of plasma to develop highly specific and sensitive biomarkers for the early diagnosis and molecular subtyping of cancer.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , DNA Tumoral Circulante/análise , DNA Tumoral Circulante/genética , Feminino , Humanos , Sulfitos
10.
Sci Rep ; 12(1): 13628, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948561

RESUMO

The prefabricated artificial filled jointed rock specimens are impacted by a self-made drop hammer impact device for many times, and the specimens with different degrees of cumulative damage characteristics are obtained. Then, the static and dynamic compression mechanical properties are studied by using universal testing machine and SHPB device. Through the static compression test, the strength and deformation characteristics of jointed rock specimens after multiple impacts are obtained, and the influence of the damage degree of jointed rock specimens characterized by wave velocity on the compressive strength of filled joints is analysed. Based on the results of SHPB impact test, the dynamic strength and deformation evolution, wave propagation law and energy dissipation law of filled joints after multiple impacts are analysed. During the SHPB test, the impact failure process of rock specimens is recorded by a high-speed camera. The experimental results show that the damage degree of jointed rock samples increases nonlinearly after multiple impacts. The attenuation laws of static strength and dynamic strength of rock samples under the same damage evolution conditions are different. With the increase of impact times, the failure mode of jointed rock samples after damage is simpler and tends to compression failure.

11.
Front Surg ; 9: 843913, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242809

RESUMO

OBJECTIVE: The clinical features of solitary pulmonary nodules (SPN) in breast cancer patients were retrospectively analyzed, and the clinical features of primary lung cancer (PLC) and metastatic pulmonary breast cancer (MBC) in breast cancer patients were compared, and the treatment plan, curative effect and influencing factors were analyzed. METHODS: The clinical data of 106 patients of SPN combined with breast cancer surgery in our hospital from January 2015 to June 2020 were analyzed. There were 65 patients of PLC and 41 patients of MBC. Record the characteristics of the primary breast cancer lesion in our patient, the interval between the initial diagnosis of breast cancer and the appearance of SPN, the previous treatment history of our patient, and the characteristics and surgical method of SPN. The survival status of all patients during the follow-up period was recorded. RESULTS: The onset age, interval, maximum nodule diameter, ER expression positive rate and radiotherapy history ratio of PLC patients were higher than those of MBC patients, and the lymph node positive rate and triple negative rate were lower than those of MBC patients (P < 0.05). Median survival was 51 months in patients with PLC and 37 months in patients with MBC. The 1, 3, and 5 year overall survival rates in patients with PLC were higher than those in patients with MBC (P < 0.05). Vascular tumor thrombus, SPN type and chemotherapy were all independent factors affecting the prognosis of patients with breast cancer combined with SPN (P < 0.05). CONCLUSION: PLC patients and MBC patients have significant differences in pathological characteristics, like the onset age, interval, maximum nodule diameter, ER expression positive rate, radiotherapy history ratio, the lymph node positive rate, and triple negative rate. Septum, vascular tumor thrombus, SPN type, and chemotherapy are all independent factors that affect the curative effect of breast cancer patients with SPN. Based on the nature of SPN, it can provide reference for clinicians to decide the treatment plan, improve patients' quality of life and prolong their survival time.

12.
Polymers (Basel) ; 15(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36616390

RESUMO

In this study, polyurea was experimentally tested under various spraying temperatures and pressures. The number of holes and the pore size produced after the tensile fracture of the polyurea were counted to illustrate the effect of the various spraying temperatures and pressures on the performance of the polyurea. The tensile characteristics of polyurea were greatly influenced by the spraying temperatures and pressures, according to the experimental findings and statistical analysis. The polyurea tensile performance was best when the spraying pressure was 17.25 MPa with a spraying temperature of 70 °C. The fracture mechanism was illustrated by the silver streaking phenomenon generated during the tensile stretching process. The fracture energy was absorbed by the fracture holes and pores during silver streaking, thus creating the huge gap in tensile properties.

13.
Technol Cancer Res Treat ; 20: 15330338211064434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34931914

RESUMO

Objective: This study aimed to investigate the tolerance and pharmacokinetic characteristics of recombinant human endostatin (rh-endostatin) administered as single-dose or multiple-dose infusions in patients with advanced solid tumors. Methods: This phase I trial was designed as a single-center, single-arm, nonrandomized, open-label, dose-escalation study. The trial consisted of 2 parts: a single-dose part and a multiple-dose part, each with 3 dose comparison groups. Rh-endostatin was administered as an intravenous injection only once at a dose of 5 mg/m2, 7.5 mg/m2, or 10 mg/m2 in the single-dose part and as a daily intravenous injection for 14 days at the same doses in the multiple-dose part. The serum pharmacokinetics, toxicity and immunogenicity of rh-endostatin were evaluated. Results: Dose-limiting toxicity (DLT) was not observed in any group. A few patients developed cardiotoxicity, such as QT prolongation or narrow arrhythmia. Other adverse events were slight coagulation abnormalities and haematological abnormalities. For rh-endostatin doses of 5 mg/m2, 7.5 mg/m2, and 10 mg/m2, the mean Cmax values in the single-dose part were 344 ± 38.7 ng/mL, 524 ± 157 ng/mL, and 800 ± 201 ng/mL, respectively, and the average AUC0-t values were 3290 ± 3790 ng•h/mL, 4940 ± 4380 ng•h/mL, and 5050 ± 3980 ng•h/mL, respectively. The Cmax ss values of the 3 doses in the multiple-dose part were 575 ± 270 ng/mL, 531 ± 106 ng/mL, and 864 ± 166 ng/mL, respectively, and the AUC0-τ values were 3610 ± 1040 ng•h/mL, 3290 ± 1090 ng•h/mL, and 5180 ± 1210 ng•h/mL, respectively. The Cmax of a single-dose regimen showed linear kinetic characteristics. The patients in the single-dose group were negative for serum antibodies against rh-endostatin, while one patient in the multiple-dose group was positive. Conclusions: Rh-endostatin as a daily intravenous injection for 14 days in patients with advanced solid tumors is safe and well tolerated, without DLT, at doses of 5 mg/m2, 7.5 mg/m2, and 10 mg/m2. Serum antibodies against rh-endostatin were very low after multiple infusions. For phase II trials, the recommended rh-endostatin dose is 10 mg/m2 as a daily intravenous injection for 14 days.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Endostatinas/administração & dosagem , Endostatinas/farmacocinética , Neoplasias/tratamento farmacológico , Proteínas Recombinantes , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacocinética , Antineoplásicos/efeitos adversos , Gerenciamento Clínico , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Endostatinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Prognóstico , Resultado do Tratamento
14.
ACS Omega ; 6(42): 27702-27710, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34722970

RESUMO

This work established a high-speed camera-assisted visualization system that investigated the effect of volatile matter and fixed carbon content in biomass particles on single-particle combustion phases and their luminous properties. Three types of biomass particles, namely, sawdust (a mixture of pine and willow), corncob, and rice husk, were examined on a Hencken flat-flame burner. The luminous region and intensity of single biomass particles were closely related to the flammability and calorific value of biomass fuel and derived by analyzing a sequence of images captured using a high-speed camera. The combustion temperature was determined through analysis of its radiant energy. The results showed that the ignition mechanisms of volatile matter and fixed carbon corresponded to homogeneous and heterogeneous reactions, respectively. The maximum luminous region values of 1.75 × 106, 2.1 × 106, and 1.0 × 106 µm2 for sawdust (SD), corncob (CC), and rice husk (RH) correlated to the volatile matter content of each biomass sample, which was 69.38, 74.15, and 64.56%, respectively. Because of the high fixed carbon content, the peak temperature of the SD particles could reach 1549 °C. The luminous region and intensity of the combusting particles were significantly affected by the volatile matter and fixed carbon, respectively.

15.
J Cancer ; 12(21): 6445-6453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659535

RESUMO

Background: This study aimed to investigate the metastasis patterns and prognosis of breast cancer (BC) in patients aged ≥ 80 years with distant metastases, as the current literature lacks studies in this population. Methods: A retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results (SEER) database was conducted to evaluate 36,203 patients with BC from 2010 to 2016. Patients were classified into three groups, the older group (aged ≥ 80 years), middle-aged group (aged 60-79 years), and younger group (aged < 60 years). The role of age at the time of BC diagnosis in metastasis patterns was investigated, and the survival of different age groups of patients with BC was assessed. Results: Overall, 4,359 (12%) patients were diagnosed with BC at age ≥ 80 years, 19,688 (54%) at 60-79 years, and 12,156 (34%) at < 60 years. Compared with the other two groups, those in the older group had a lower rate of treatment acceptance. Statistical analysis revealed that older patients were more likely to have lung invasion only (odds ratio [OR]: 1.274, 95% confidence interval [CI]: 1.163-2.674) and less likely to have bone invasion only (OR: 0.704, 95% CI: 0.583-0.851), brain invasion only (OR: 0.329, 95% CI: 0.153-0.706), or multiple metastatic sites (OR: 0.361, 95% CI: 0.284-0.458) compared to the other two groups. Age at diagnosis was an independent prognostic factor for survival. The older group had the worst overall survival (OS, P<0.001) and BC-specific survival (CSS, P<0.001). Furthermore, patients aged ≥ 80 years with only liver metastasis had the worst CSS and OS. Conclusion: Patients aged ≥ 80 years were less likely to be receptive to cancer-related therapy and had the highest cancer mortality rate among all patients. Our findings will hopefully help clinicians develop more appropriate modalities of cancer treatment in elderly BC patients.

16.
J Int Med Res ; 49(4): 3000605211004024, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33840248

RESUMO

OBJECTIVES: The efficiencies of osteogenesis and angiogenesis present challenges that need to be overcome before bone tissue engineering can be widely applied to clinical uses. We aimed to optimize an in vitro culture system to enhance osteogenesis and angiogenesis. We investigated if hematopoietic stem cells (HSCs) promoted osteogenesis in vitro when co-cultured with mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs). METHODS: MSC/HSC, MSC/EPC/HSC, and MSC/EPC co-cultures were incubated for 21 days. Alkaline phosphatase (ALP) activity and calcium content were analyzed to assess mineralization. Expression levels of genes encoding osteogenesis-related proteins (ALP (ALPL), collagen type IA (COL1A1), osteocalcin (BGLAP), and osteopontin (OSTP)) were also evaluated by measuring mRNA levels at day 28. Angiogenesis was evaluated by tube-formation assay. RESULTS: COL1A1, OSTP, ALPL, and BGLAP genes were upregulated in MSC/HSC and MSC/EPC/HSC co-cultures compared with the MSC/EPC group. Upregulation was strongest in the MSC/EPC/HSC co-cultures. There were no significant changes in ALP levels and calcium content, but ALP activity was slightly higher and calcium content was relatively lower in the MSC/EPC and MSC/EPC/HSC groups. CONCLUSIONS: Co-culture of MSCs with HSCs or EPCs/HSCs upregulated the expression of osteogenesis-related genes but did not affect the efficiency of osteogenesis.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Expressão Gênica , Osteogênese/genética , Células-Tronco
17.
Mol Ther ; 29(4): 1541-1556, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33412308

RESUMO

HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resistant cells. HER2 overexpression is partially maintained because E3 ubiquitin ligase Cullin5 (CUL5), which degrades HER2, is frequently mutated or underexpressed, while the client-protective co-chaperones cell division cycle 37 (Cdc37) and heat shock protein 90 (Hsp90) are increased translating to diminished survival. The Th1 cytokine interferon (IFN)-γ caused increased CUL5 expression and marked dissociation of both Cdc37 and Hsp90 from HER2, causing significant surface loss of HER2, diminished growth, and induction of tumor senescence. In HER2-resistant mammary carcinoma, either IFN-γ or Th1-polarizing anti-HER2 vaccination, when administered with anti-HER2 antibodies, demonstrated increased intratumor CUL5 expression, decreased surface HER2, and tumor senescence with significant therapeutic activity. IFN-γ synergized with multiple HER2-targeted agents to decrease surface HER2 expression, resulting in decreased tumor growth. These data suggest a novel function of IFN-γ that regulates HER2 through the PDP pathway and provides an opportunity to impact HER2 responses through anti-tumor immunity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proteínas Culina/genética , Interferon gama/genética , Receptor ErbB-2/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Senescência Celular/genética , Senescência Celular/imunologia , Chaperoninas/genética , Proteínas Culina/imunologia , Citocinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Interferon gama/imunologia , Proteólise , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Células Th1/efeitos dos fármacos , Células Th1/metabolismo , Vacinação
18.
Mol Ther Oncolytics ; 19: 188-196, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33251331

RESUMO

Metastasis is associated with poor prognosis in cancer and is a multistep process that includes invasion and migration. Several epigenetic factors are involved in this process, including chromobox protein homolog 8 (CBX8). Here, we show that CBX8 is overexpressed in many cancers compared with normal tissues. Functional analyses indicated that CBX8 promoted invasion and migration in glioblastoma, breast cancer, and lung cancer in vitro and in vivo. WNK2 was identified as a target gene of CBX8, which interacted with the WNK2 promoter to suppress WNK2 expression and activity. WNK2 acted as an antioncogene, and decreased WNK2 levels resulted in high activity of matrix metalloprotease (MMP)-2 and RAC1, which play a central role in invasion and migration, respectively. There was a positive relationship between MMP2 and RAC1 activity in CBX8-modulated cell lines. In addition, WNK2 negatively regulated MMP2 and RAC1 activity. Collectively, the results indicated that CBX8 promoted invasion and migration by targeting WNK2, which resulted in increased RAC1 and MMP2 expression and activity. Therefore, CBX8 may be a novel therapeutic target to treat metastatic cancers.

19.
J Cancer Res Ther ; 16(5): 1069-1076, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004749

RESUMO

BACKGROUND: Previous studies have shown that vinorelbine/capecitabine (NX) and docetaxel/capecitabine (TX) chemotherapy has a certain effect in advanced breast cancer. However, there are few clinical studies directly comparing TX and NX regimen chemotherapy, especially in patients with advanced breast cancer previously treated with anthracycline and taxane. The purpose of this Phase II study was to compare survival and side effects between patients with anthracycline- and taxane-resistant advanced breast cancer treated with NX and those treated with TX chemotherapy. PATIENTS AND METHODS: From February 2012 to March 2014, a total number of 97 patients were randomly assigned to NX (n = 55) or TX (n = 42). Baseline characteristics were relatively well-balanced in the two treatment arms. The clinical trial registration number (clincaltrials.gov) is NCT01635465. RESULTS: After a median follow-up of 46.0 months, there was no significant difference between the NX and TX arms in objective response rate (17.9% vs. 21.1%; P = 0.686) and progression-free survival (6 months vs. 7 months; P = 0.560). The overall survival period of the TX arm was longer than that of the NX arm (32 months vs. 27 months) but without statistical significance. Both regimens were well-tolerated. The main toxicities were neutropenia, leukopenia, and anemia. In the TX arm, hand-foot syndrome occurred more frequently than in the NX arm (P < 0.01), but frequencies of other minor adverse effects were similar between the two arms. CONCLUSION: NX and TX regimens are both alternative treatments for patients with anthracycline- and taxane-resistant advanced breast cancer, but the safety profile was more favorable and manageable with the NX regimen. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01635465. Registered 09 July 2012.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Antraciclinas/administração & dosagem , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Taxa de Sobrevida , Resultado do Tratamento , Vinorelbina/administração & dosagem
20.
Biomed Res Int ; 2020: 8124570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33015182

RESUMO

Large quantities of long noncoding RNAs (lncRNAs) have been verified to exert vital functions in the process of breast cancer (BC). lncRNA heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) was reported to suppress the development of several cancers. However, its detailed function in BC remained unclear. In the current study, HAND2-AS1 was discovered to be low expressed in BC cell lines, and overexpression of HAND2-AS1 could repress proliferation, migration, and invasion but facilitate apoptosis in BC cells. Moreover, HAND2-AS1 was found to act as a sponge of miR-3118 which was detected to be upregulated in BC cell lines. miR-3118 depletion could constrict the progression of BC. HAND-AS1 hindered the course of BC by reducing the expression of miR-3118. Besides, PHLPP2 was treated as a downstream target of miR-3118 under the selection of RNA pull-down assays. HAND2-AS1 inhibited the process of BC by enhancing expression of PHLPP2. In summary, our study testified that HAND2-AS1 suppressed BC growth by targeting the miR-3118/PHLPP2 axis, indicating that HAND2-AS1 could be regarded as a potential target for BC treatment.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Fosfoproteínas Fosfatases/genética , RNA Longo não Codificante/metabolismo , Regulação para Cima/genética , Animais , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Masculino , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...