Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Cancer Lett ; 592: 216927, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38697460

RESUMO

Glioblastoma (GBM), one of the most malignant brain tumors in the world, has limited treatment options and a dismal survival rate. Effective and safe disease-modifying drugs for glioblastoma are urgently needed. Here, we identified a small molecule, Molephantin (EM-5), effectively penetrated the blood-brain barrier (BBB) and demonstrated notable antitumor effects against GBM with good safety profiles both in vitro and in vivo. Mechanistically, EM-5 not only inhibits the proliferation and invasion of GBM cells but also induces cell apoptosis through the reactive oxygen species (ROS)-mediated PI3K/Akt/mTOR pathway. Furthermore, EM-5 causes mitochondrial dysfunction and blocks mitophagy flux by impeding the fusion of mitophagosomes with lysosomes. It is noteworthy that EM-5 does not interfere with the initiation of autophagosome formation or lysosomal function. Additionally, the mitophagy flux blockage caused by EM-5 was driven by the accumulation of intracellular ROS. In vivo, EM-5 exhibited significant efficacy in suppressing tumor growth in a xenograft model. Collectively, our findings not only identified EM-5 as a promising, effective, and safe lead compound for treating GBM but also uncovered its underlying mechanisms from the perspective of apoptosis and mitophagy.


Assuntos
Apoptose , Neoplasias Encefálicas , Proliferação de Células , Glioblastoma , Mitofagia , Espécies Reativas de Oxigênio , Ensaios Antitumorais Modelo de Xenoenxerto , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Mitofagia/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Camundongos , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos Nus , Serina-Treonina Quinases TOR/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo
2.
Korean J Radiol ; 25(1): 86-102, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38184772

RESUMO

Early diagnosis, accurate assessment, and localization of peritoneal metastasis (PM) are essential for the selection of appropriate treatments and surgical guidance. However, available imaging modalities (computed tomography [CT], conventional magnetic resonance imaging [MRI], and 18fluorodeoxyglucose positron emission tomography [PET]/CT) have limitations. The advent of new imaging techniques and novel molecular imaging agents have revealed molecular processes in the tumor microenvironment as an application for the early diagnosis and assessment of PM as well as real-time guided surgical resection, which has changed clinical management. In contrast to clinical imaging, which is purely qualitative and subjective for interpreting macroscopic structures, radiomics and artificial intelligence (AI) capitalize on high-dimensional numerical data from images that may reflect tumor pathophysiology. A predictive model can be used to predict the occurrence, recurrence, and prognosis of PM, thereby avoiding unnecessary exploratory surgeries. This review summarizes the role and status of different imaging techniques, especially new imaging strategies such as spectral photon-counting CT, fibroblast activation protein inhibitor (FAPI) PET/CT, near-infrared fluorescence imaging, and PET/MRI, for early diagnosis, assessment of surgical indications, and recurrence monitoring in patients with PM. The clinical applications, limitations, and solutions for fluorescence imaging, radiomics, and AI are also discussed.


Assuntos
Inteligência Artificial , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Imagem Óptica , Microambiente Tumoral
3.
PLoS One ; 18(12): e0295356, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38060546

RESUMO

The high pressure in some gas wells, such as those in the Xushen gas field in Daqing, China, makes them susceptible to freezing and hydrate blockages. Downhole throttling technology is widely used to reduce costs during well construction, however, due to the limitations of temperature, pressure and depth structure, this technology is sometime applied independently in some gas wells in which freezing and blockages are a frequent problem that can seriously affect production capacity. Moreover, artificial alcohol injection of 'passive plugging' to prevent hydrate formation not only consumes significant amounts of methanol but its efficiency is also dependent on factors such as weather, personnel and equipment, so it is not a continuous solution. In order to solve the above problems, the mechanism of hydrate formation was analyzed in this study, from which a combined mechanical and chemical hydrate control process was developed. OLGA software was used to design the process parameters of the novel mechanical and chemical inhibition technology for hydrate prevention and control, and also to simulate and analyze the wellhead temperature, pressure and hydrate generation once the process was implemented. Based on the results of the parameters calculation, the downhole throttle and hydrate inhibitor automatic filling device are used to realize the functions of downhole throttle depressurization and hydrate inhibitor continuous filling, reduce the wellhead pressure and hydrate generation temperature, and ensure the continuous production of gas well. This novel combination process was subsequently tested in three wells in the Daqing gas oilfield. Measurements showed that the average daily gas increase from a single well was 0.5×104m3, methanol consumption was reduced from the original maximum daily amount of 1750 kg to just 60 kg, the manual maintenance workload was reduced by 80%, and the rate of the well openings was increased from 45% to 100%. These results proved that this technology is feasible and efficient for applications in gas wells with high downhole pressure and low wellhead temperature, and, thus, provides important technical support for the prevention of gas hydrate and improvement of gas well production.


Assuntos
Metanol , Campos de Petróleo e Gás , China , Temperatura Baixa , Tecnologia
4.
Neuroreport ; 34(18): 853-859, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37942736

RESUMO

The interaction between the µ opioid receptor (MOR) and ß-arrestin2 serves as a model for addressing morphine tolerance. A peptide was designed to alleviate morphine tolerance through interfering with the interaction of MOR and ß-arrestin2. We developed a peptide derived from MOR. The MOR-TAT-pep peptide was expressed in E. coli Bl21(DE3) and purified. The effects of MOR-TAT-pep in alleviating morphine tolerance was examined through behavior tests. The potential mechanism was detected by Western blotting, Mammalian Two-Hybrid and other techniques. The pretreatment with MOR-TAT-pep prior to morphine usage led to an enhanced analgesic effectiveness of morphine and a significant reduction in the development of morphine tolerance. The peptide directly interacted with ß-arrestin2 during morphine treatment and deceased the membrane recruitment of ß-arrestin2. MOR-TAT-pep effectively suppressed the increase of ß-arrestin2 induced by morphine. The MOR-TAT-pep could alleviate morphine tolerance through inhibition of ß-arrestin2.


Assuntos
Analgésicos Opioides , Morfina , Animais , Morfina/farmacologia , Analgésicos Opioides/farmacologia , beta-Arrestina 1 , Receptores Opioides mu/metabolismo , Escherichia coli/metabolismo , Peptídeos , Mamíferos/metabolismo
5.
Food Chem X ; 19: 100847, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37780298

RESUMO

Dietary vegetables rich in bioactive compounds are major responsible for promoting human health. Herein, the effect of hydrogen peroxide (H2O2), an important signaling compound, on growth and quality of two hydroponic lettuce genotypes was investigated. The maximum enhancement of growth traits was shown in lettuce elicited with 10 mmol/L H2O2, while 40 mmol/L H2O2 significantly reduced above growth traits. H2O2 elicitation increased pigment contents and photosynthetic process, which consequently caused enhancements of phenolic compounds, ascorbic acid, glutathione, carotenoids, soluble sugars, free amino acids, soluble protein, minerals, and antioxidant capacity, while above alterations appeared in a genotype-dependent manner. The phenolic accumulation was correlated with improved activity of phenylalanine ammonia lyase (PAL) and expression levels of genes related to phenolic biosynthesis, including PAL, chalcone synthase, flavanone 3-hydroxylase, dihydroflavonol-4 reductase, and UDP-glucose: flavonoid 3-O-glucosyltransferase. Therefore, elicitation with H2O2 is a promising strategy to develop lettuce with high bioactive compounds and biomass.

6.
ACS Omega ; 8(39): 35964-35974, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37810666

RESUMO

The permeability and diffusion coefficient of coal show multiscale characteristics due to the influence of multiscale pore sizes. The gas pressure will continuously decrease during the coalbed methane (CBM) extraction. However, there are contradictory perceptions in the effect of gas pressure on the diffusion coefficient and permeability. Therefore, it is essential to clarify the influence mechanism of gas pressure on multiscale diffusion-seepage. Diffusion-seepage experiments are carried out using particle coal and cylindrical coal without stress loading. Meanwhile, seepage experiments measured by the steady-state method are conducted under stress loading. The results show that the apparent diffusion coefficient is dynamically attenuated with time in the experiments of particle and cylindrical coal. A new model of multiscale dynamic apparent diffusion is proposed. The mechanism of gas flow in multiscale pores is elucidated. The multiscale pores determine the attenuation of the diffusivity and permeability of coal. The initial apparent permeability decreases and then increases with the increase of gas pressure, which is caused by the effect of gas pressure stretching and multiscale flow regime. Three patterns of permeability with gas pressure, monotonically increasing, monotonically decreasing, and U-shaped changes, will occur.

7.
Open Life Sci ; 18(1): 20220656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589009

RESUMO

The aim of this study is to explore a novel classification and investigate the clinical significance of hepatocellular carcinoma (HCC) cells. We analyzed integrated single-cell RNA sequencing and bulk RNA-seq data obtained from HCC samples. Cell trajectory analysis divided HCC cells into three subgroups with different differentiation states: state 1 was closely related to phosphoric ester hydrolase activity, state 2 was involved in eukaryotic initiation factor 4E binding, translation regulator activity and ribosome, and state 3 was associated with oxidoreductase activity and metabolism. Three molecular classes based on HCC differentiation-related genes (HDRGs) from HCC samples were identified, which revealed immune checkpoint gene expression and overall survival (OS) of HCC patients. Moreover, a prognostic risk scoring (RS) model was generated based on eight HDRGs, and the results showed that the OS of the high-risk group was worse than that of the low-risk group. Further, potential therapeutic drugs were screened out based on eight prognostic RS-HDRGs. This study highlights the importance of HCC cell differentiation in immunotherapy, clinical prognosis, and potential molecular-targeted drugs for HCC patients, and proposes a direction for the development of individualized treatments for HCC.

8.
J Cancer Res Clin Oncol ; 149(10): 7259-7273, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36912943

RESUMO

BACKGROUND: There are limited studies on the association between angiogenesis-related genes (ARGs) and the predictive risk of melanoma, even though angiogenic factors, which are essential for tumor growth and metastasis, might be secreted by angiogenesis-related protein in skin cutaneous melanoma (SKCM). To forecast patient outcomes, this study attempts to develop a predictive risk signature linked to angiogenesis in cutaneous melanoma. METHODS: In 650 patients with SKCM, the expression and mutation of ARGs were examined, and this information was related to the clinical prognosis. SKCM patients were split into two groups based on how well they performed on the ARG. The link between ARGs, risk genes, and immunological microenvironment was examined using a range of algorithmic analysis techniques. Based on these five risk genes, an angiogenesis risk signature was created. We developed a nomogram and examined the sensitivity of antineoplastic medications to help the proposed risk model's clinical applicability. RESULTS: The risk model developed by ARGs revealed that the prognosis for the two groups was significantly different. The predictive risk score was negatively connected with memory B cells, activated memory CD4 + T cells, M1 macrophages, and CD8 + T cells, and favorably correlated with dendritic cells, mast cells, and neutrophils. CONCLUSIONS: Our findings offer fresh perspectives on prognostic evaluation and imply that ARG modulation is implicated in SKCM. Potential medications for the treatment of individuals with various SKCM subtypes were predicted by drug sensitivity analysis.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Microambiente Tumoral/genética , Transporte Biológico , Prognóstico , Melanoma Maligno Cutâneo
9.
J Ethnopharmacol ; 305: 116086, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36587879

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Peritoneal metastasis is a manifestation of advanced cancer often associated with a poor prognosis and poor response to treatment. Astragalus membranaceus (Fisch.) Bunge is a commonly used medicinal material in traditional Chinese medicine with various biological activities. In patients with cancer, Astragalus membranaceus has demonstrated anti-tumor effects, immune regulation, postoperative recurrence and metastasis prevention, and survival prolongation. AIM OF THE STUDY: Peritoneal metastasis results from tumor cell and peritoneal microenvironment co-evolution. We aimed to introduce and discuss the specific mechanism of action of Astragalus membranaceus in peritoneal metastasis treatment to provide a new perspective for treatment and further research. MATERIALS AND METHODS: We consulted reports on the anti-peritoneal metastases effects of Astragalus membranaceus from PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases, as well as Google Scholar. Meanwhile, we also obtained data from published medical works and doctoral and master's theses. Then, we focused on the research progress of Astragalus membranaceus in peritoneal metastatic cancer treatment. Plant names are provided in accordance with "The Plant List" (www.theplantlist.org). RESULTS: To date, more than 200 compounds have been isolated from Astragalus membranaceus. Among them, Astragalus polysaccharides, saponins, and flavonoids are the main bioactive components, and their effects on cancer have been extensively studied. In this review, we systematically summarize the effects of Astragalus membranaceus on the peritoneal metastasis microenvironment and related mechanisms, including maintaining the integrity of peritoneal mesothelial cells, restoring the peritoneal immune microenvironment, and inhibiting the formation of tumor blood vessels, matrix metalloproteinase, and dense tumor spheroids. CONCLUSIONS: Our analysis demonstrates that Astragalus membranaceus could be a potential therapeutic for preventing the occurrence of peritoneal metastasis. However, it might be too early to recommend its use owing to the paucity of reliable in vivo experiment, clinical data, and evidence of clinical efficacy. In addition, previous studies of Astragalus membranaceus report inconsistent and contradictory findings. Therefore, detailed in vitro, in vivo, and clinical studies on the mechanism of Astragalus membranaceus in peritoneal metastatic cancer treatment are warranted.


Assuntos
Astrágalo , Neoplasias Peritoneais , Humanos , Astragalus propinquus/química , Neoplasias Peritoneais/tratamento farmacológico , Astrágalo/química , Flavonoides/análise , Polissacarídeos/química , Microambiente Tumoral
10.
Eur J Pharmacol ; 938: 175449, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36473596

RESUMO

One of the most important and effective components of Astragalus membranaceus is astragaloside IV (AS-IV), which can exert anti-tumor effects through various pathways. For instance, AS-IV exerts an anti-tumor effect by acting at the cellular level, regulating the phenotype switch of tumor-associated macrophages, or inhibiting the development of tumor cells. Furthermore, AS-IV inhibits tumor cell progression by enhancing its sensitivity to antitumor drugs or reversing the drug resistance of tumor cells. This article reviews the different mechanisms of AS-IV inhibition of epithelial-mesenchymal transition (EMT), migration, proliferation, and invasion of tumor cells, inducing apoptosis and improving the sensitivity of anti-tumor drugs. This review summarizes recent progress in the current research into AS-IV anti-tumor effect and provides insight on the next anti-tumor research of AS-IV.


Assuntos
Antineoplásicos , Saponinas , Triterpenos , Saponinas/farmacologia , Saponinas/uso terapêutico , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Astragalus propinquus , Transição Epitelial-Mesenquimal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
11.
J Laparoendosc Adv Surg Tech A ; 33(1): 74-80, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35723625

RESUMO

Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) has advantages over traditional radical gastrectomy. We investigated whether enhanced recovery after surgery (ERAS) protocols are appropriate in the ESD perioperative period. Materials and Methods: We screened 129 consecutive patients, and 12 were excluded. All study patients underwent ESD for EGC. Of the 117 included patients, 57 received traditional perioperative care between January 2017 and December 2018, and 60 patients received perioperative care according to ERAS protocols between January 2019 and September 2020. The primary study endpoint was ESD-related complications. Secondary endpoints included the following postoperative parameters: anal exhaust time, incidence of nausea or vomiting, length of hospitalization, fever rate, abdominal pain on the visual analog scale (VAS), and reported perioperative satisfaction. Results: Complications were comparable between the 2 groups. In the ERAS group, no patients experienced delayed bleeding or perforation. One traditional group patient bled, and one perforated. Postoperative anal exhaust time, nausea or vomiting incidence, hospitalization, fever rate, and VAS pain scores were significantly lower, and perioperative satisfaction rate was significantly higher in the ERAS group. Conclusions: ERAS protocols are both feasible and safe for patients undergoing ESD. ERAS protocols enhance the advantages of ESD for EGC without increasing complications.


Assuntos
Ressecção Endoscópica de Mucosa , Recuperação Pós-Cirúrgica Melhorada , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Gástricas/cirurgia , Estudos de Viabilidade , Mucosa Gástrica/cirurgia , Resultado do Tratamento
12.
Cancer Biother Radiopharm ; 38(6): 364-370, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34529925

RESUMO

Objective: This study explored the application value of the maximum standard uptake value (SUVmax) of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) in gastric cancer. Materials and Methods: Data of 164 patients with gastric cancer who had undergone18F-FDG PET/CT before a biopsy were collected, and the correlation of SUVmax with clinical stage, pathological differentiation degree, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index of gastric cancer was analyzed. Results: The SUVmax of poorly differentiated adenocarcinoma was significantly higher than that of moderately differentiated adenocarcinoma and signet-ring cell carcinoma (p < 0.01), and SUVmax in the well-differentiated adenocarcinoma group was higher than that in the signet-ring cell carcinoma group (p < 0.01). The SUVmax in the HER-2 negative group was higher than that in the HER-2 positive group (p < 0.01). The SUVmax was higher in the Ki-67 high expression group than in the low expression group (p < 0.01), and there was a significant positive correlation between the two (p < 0.01). Conclusion: 18F-FDG PET/CT SUVmax can, to some extent, predict the degree of differentiation, HER-2 status, and Ki-67 index of gastric cancer patients.


Assuntos
Adenocarcinoma , Carcinoma de Células em Anel de Sinete , Neoplasias Gástricas , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Gástricas/patologia , Antígeno Ki-67 , Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Estudos Retrospectivos
14.
Food Chem X ; 16: 100481, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36299865

RESUMO

Reduced nitrogen availability is an efficient strategy for increasing the accumulation of phenolic compounds in vegetables, but related mechanisms remain unknown. Here, the production of hydrogen peroxide (H2O2) and its potential roles in regulating phenolic biosynthesis and enhancing the antioxidant quality of lettuce under low nitrogen (LN) conditions were investigated. The LN treatment caused a rapid production of H2O2, which effectively increased lettuce quality by enhancing the levels of phenolic compounds and other nutrients such as ascorbic acid, glutathione, soluble sugar, and soluble protein. The increased phenolic content was related to the higher expression levels of phenolic biosynthesis genes, including PAL, CHS, DFR, F35H, and UFGT, and higher photosynthetic capacity after H2O2 addition under LN conditions. However, these positive effects were suppressed by dimethylthiourea (DMTU), a scavenger of H2O2. These results suggest that H2O2 as an important signal molecular mediates the LN-caused phenolic accumulation and antioxidant quality enhancement in lettuce.

15.
Pathol Res Pract ; 239: 154179, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36274380

RESUMO

OBJECTIVE: High stromal ratio of gastric cancer is associated with a poor prognosis. Fibronectin 1(FN1) is the main component of gastric cancer stroma. The focus of this research was to investigate the FN1 express pattern, the connection between FN1 expression, clinicopathological parameters, survival, and mismatch repair genes (MMR) or immune checkpoints in gastric cancer patients. METHODS: Eighty-six paired stomach cancer tissues, neighboring normal tissues, and eight independent gastric cancer tissues were used to create 180 points tissue microarrays. The association between epithelial fibronectin (E-FN1), stromal fibronectin (S-FN1) expression, and clinical characteristics was analyzed using the chi-square test or Fisher's exact test, and the survival analysis curve was analyzed using the log-rank test, followed by univariate and multivariate Cox regression. The correlation between FN1 and MMR or immune checkpoints was analyzed by Spearman correlation. RESULTS: FN1 is mainly expressed in gastric cancer tissues, with low or no expression in adjacent normal tissues. In tumor tissues, FN1 is mostly distributed in the stroma. High E-FN1 expression was associated with a decreased overall survival (OS), while S-FN1 expression did not. High S-FN1 expression correlated with older age (P<0.001), higher pathological grade (P<0.001), pathological type (P<0.001), vessel/lymphatic invasion (P<0.001), advanced T stage (P=0.001), N stage (P=0.01), and worse TNM stage(P = 0.033). FN1 expression was not associated with MMR or immune checkpoints (MLH1, MSH2, MSH6, PDL1, PD1, PMS2, and CD8). CONCLUSIONS: High E-FN1 expression predicted poor OS, while S-FN1 is associated with gastric cancer progression.


Assuntos
Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA , Fibronectinas/genética , Prognóstico , Neoplasias Gástricas/patologia
16.
Lancet Oncol ; 23(10): 1249-1260, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075260

RESUMO

BACKGROUND: Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer. METHODS: CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478. FINDINGS: Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group. INTERPRETATION: In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile. FUNDING: Jiangsu Hengrui Pharmaceuticals.


Assuntos
Antagonistas de Androgênios , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Próstata , Antagonistas de Androgênios/efeitos adversos , Androgênios , Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Humanos , Masculino , Nitrilas , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Compostos de Tosil
17.
J Am Chem Soc ; 144(34): 15562-15568, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35980604

RESUMO

Graphene has been widely used as a solar absorber for its broad-band absorption. However, targeting a higher photothermal efficiency, the intrinsic infrared radiation loss of graphene requires to be further reduced. Herein, band structure engineering is performed to modulate graphene infrared radiation. Nitrogen-doped vertical graphene is grown on quartz foam (NVGQF) by the plasma-enhanced chemical vapor deposition method. Under the premise of keeping high solar absorption (250-2500 nm), graphitic nitrogen doping effectively modulates the infrared emissivity (2.5-25 µm) of NVGQF from 0.96 to 0.68, reducing the radiation loss by ∼31%. Based on the excellent photothermal properties of NVGQF, a temperature-gradient-driven crude oil collecting raft is designed, where the crude oil flows along the collecting path driven by the viscosity gradient without any external electric energy input. Compared with a nondoped vertical graphene quartz foam raft, the NVGQF raft with a superior photothermal efficiency shows a significantly enhanced crude oil collecting efficiency by three times. The advances in this work suggest broad radiation-managed application platforms for graphene materials, such as seawater desalination and personal or building thermal management.

18.
Nano Lett ; 22(15): 6391-6401, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35876503

RESUMO

Exosomes derived from mesenchymal stem cells (MSCs) have been proven to exhibit great potentials in spinal cord injury (SCI) therapy. However, conventional two-dimensional (2D) culture will inevitably lead to the loss of stemness of MSCs, which substantially limits the therapeutic potency of MSCs exosomes (2D-Exo). Exosomes derived from three-dimensional culture (3D-Exo) possess higher therapeutic efficiency which have wide applications in spinal cord therapy. Typically, conventional exosome therapy that relies on local repeated injection results in secondary injury and low efficiency. It is urgent to develop a more reliable, convenient, and effective exosome delivery method to achieve constant in situ exosomes release. Herein, we proposed a controlled 3D-exohydrogel hybrid microneedle array patch to achieve SCI repair in situ. Our studies suggested that MSCs with 3D-culturing could maintain their stemness, and consequently, 3D-Exo effectively reduced SCI-induced inflammation and glial scarring. Thus, it is a promising therapeutic strategy for the treatment of SCI.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Humanos , Hidrogéis , Traumatismos da Medula Espinal/terapia
19.
Cancers (Basel) ; 14(12)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35740521

RESUMO

Peritoneal metastatic cancer comprises a heterogeneous group of primary tumors that originate in the peritoneal cavity or metastasize into the peritoneal cavity from a different origin. Metastasis is a characteristic of end-stage disease, often indicative of a poor prognosis with limited treatment options. Peritoneal mesothelial cells (PMCs) are a thin layer of cells present on the surface of the peritoneum. They display differentiated characteristics in embryonic development and adults, representing the first cell layer encountering peritoneal tumors to affect their progression. PMCs have been traditionally considered a barrier to the intraperitoneal implantation and metastasis of tumors; however, recent studies indicate that PMCs can either inhibit or actively promote tumor progression through distinct mechanisms. This article presents a review of the role of PMCs in the progression of peritoneum implanted tumors, offering new ideas for therapeutic targets and related research.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA