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1.
Acta Biochim Pol ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629578

RESUMO

Gastric adenocarcinoma is a major challenge to human health worldwide. Abnormal expression of miR-621 was found in many types of cancer. This research aimed to investigate the effects and detailed molecular mechanisms of miR-621 on gastric adenocarcinoma progression. The present study first showed that miR-621 was downregulated in gastric cancer patients, and its expression level was correlated with tumor size. MiR-621 overexpression inhibited viability, colony formation and proliferation of gastric cancer cells. AURKA was identified as a direct target of miR-621. AURKA knockdown induced decrease of p-GSK-3ß/GSK-3ß ratio and increase of p-ß-catenin/ß-catenin ratio which confirmed that AURKA positively regulated GSK-3ß phosphorylation. AURKA knockdown also inhibited proliferation of gastric adenocarcinoma cells. AURKA expression was negatively correlated with miR-621 level. In addition, AURKA overexpression reversed the effect of miR-621 on the growth of cancer cells. Taken together, our results suggest that miR-621 is an important tumor suppressor in gastric cancer and could be a promising target for the cancer treatment.

2.
Int Immunopharmacol ; 93: 107422, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548579

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline in vascular dementia (VaD). We have previously shown that diabetes mellitus (DM) synergistically promotes CCH-induced cognitive dysfunction via exacerbating neuroinflammation. Furthermore, curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. However, the effects of curcumin on CCH-induced cognitive impairments in DM have remained unknown. METHODS: Rats were fed with a high-fat diet (HFD) and injected with low-dose streptozotocin (STZ), followed by bilateral common carotid artery occlusion (BCCAO), to model DM and CCH in vivo. After BCCAO, curcumin (50 mg/kg) was administered intraperitoneally every two days for eight weeks to evaluate its therapeutic effects. Additionally, mouse BV2 microglial cells were exposed to hypoxia and high glucose to model CCH and DM pathologies in vitro. RESULTS: Curcumin treatment significantly improved DM/CCH-induced cognitive deficits and attenuated neuronal cell death. Molecular analysis revealed that curcumin exerted protective effects via suppressing neuroinflammation induced by microglial activation, regulating the triggering receptor expressed on myeloid cells 2 (TREM2)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, alleviating apoptosis, and reducing nod-like receptor protein 3 (NLRP3)-dependent pyroptosis. CONCLUSIONS: Taken together, our findings suggest that curcumin represents a promising therapy for DM/CCH-induced cognitive impairments.

3.
Med Phys ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33474727

RESUMO

PURPOSE: To enable generation of high-quality deep learning segmentation models from severely limited contoured cases (e.g., ~10 cases). METHODS: Thirty head and neck computed tomography (CT) scans with well-defined contours were deformably registered to 200 CT scans of the same anatomic site without contours. Acquired deformation vector fields were used to train a principal component analysis (PCA) model for each of the 30 contoured CT scans by capturing the mean deformation and most prominent variations. Each PCA model can produce an infinite number of synthetic CT scans and corresponding contours by applying random deformations. We used 300, 600, 1000, and 2000 synthetic CT scans and contours generated from one PCA model to train V-Net, a 3D convolutional neural network architecture, to segment parotid and submandibular glands. We repeated the training using same numbers of training cases generated from 7, 10, 20, and 30 PCA models, with the data distributed evenly between each PCA model. Performance of the segmentation models was evaluated with Dice similarity coefficients between auto-generated contours and physician-drawn contours on 162 test CT scans for parotid glands and another 21 test CT scans for submandibular glands. RESULTS: Dice values varied with the number of synthetic CT scans and the number of PCA models used to train the network. By using 2000 synthetic CT scans generated from 10 PCA models, we achieved Dice values of 82.8% ± 6.8% for right parotid, 82.0% ± 6.9% for left parotid, and 74.2% ± 6.8% for submandibular glands. These results are comparable with those obtained from state-of-the-art auto-contouring approaches, including a deep learning network trained from more than 1000 contoured patients and a multi-atlas algorithm from 12 well-contoured atlases. Improvement was marginal when >10 PCA models or >2000 synthetic CT scans were used. CONCLUSIONS: We demonstrated an effective data augmentation approach to train high-quality deep learning segmentation models from a limited number of well-contoured patient cases.

4.
Bioinformatics ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492356

RESUMO

MOTIVATION: Multiple events extraction from biomedical literature is a challenging task for biomedical community. Usually, biomedical event extraction is modeled as two sub-tasks, trigger identification and argument detection. Most existing methods perform these two sub-tasks sequentially, and fail to make full use of the interaction between them, leading to suboptimal results for multiple biomedical events extraction. METHOD: We propose a novel framework of reinforcement learning (RL) for the task of multiple biomedical events extraction. More specifically, trigger identification and argument detection are treated as main-task and subsidiary-task, respectively. Assigning the event type of triggers (in the main-task) is viewed as the action taken in RL, and the result of corresponding argument detection (i.e. the subsidiary-task) for the identified trigger is used for computing the reward of the taken action. Moreover, the result of the subsidiary-task is modeled as part of environment information in RL to help the procedure of trigger identification. In addition, external biomedical knowledge bases are employed for representation learning of biomedical text, which can improve the performance of biomedical event extraction. RESULTS: Results on two widely used biomedical corpora demonstrate that the proposed framework performs better than the selected baselines on the task of multiple events extraction. The ablation test indicates the contributions of RL and external KBs to the performance improvement in the proposed method. In addition, by modeling multiple events extraction under the RL framework, the supervised information is exploited more effectively than the classical supervised learning paradigm.

5.
Analyst ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481970

RESUMO

At present, conventional microdialysis (MD) techniques cannot efficiently sample lipids in vivo, possibly due to the high mass transfer resistance and/or the serious adsorption of lipids onto the semi-permeable membrane of a MD probe. The in vivo monitoring of lipids could be of great significance for the study of disease development and mechanisms. In this work, an open-flow microperfusion (OFM) probe was fabricated, and the conditions for sampling lipids via OFM were optimized. Using OFM, the recovery of lipid standards was improved to more than 34.7%. OFM is used for the in vivo sampling of lipids in mouse liver tissue with fibrosis, and it is then combined with mass spectrometry (MS) to perform lipidomic analysis. 156 kinds of lipids were identified in the dialysate collected via OFM, and it was found that the phospholipid levels, including PC, PE, and SM, were significantly higher in a liver suffering from fibrosis. For the first time, OFM combined with MS to sample and analyze lipids has provided a promising platform for in vivo lipidomic studies.

6.
Int Urol Nephrol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386583

RESUMO

PURPOSE: To investigate the effect of detrusor underactivity on the efficacy of TURP in patients with benign prostate obstruction. METHODS: A retrospective study of 350 patients with benign prostate obstruction who underwent TURP was carried out. Different degrees of bladder outlet obstruction were grouped by the bladder outlet obstruction index. ROC curves were used to calculate the optimal cut-off point for the bladder contractility index used to divide the DU patients into mild DU and severe DU patients. The effect of DU on the efficacy of TURP in benign prostate obstruction patients was studied by comparing the subjective and objective parameters preoperatively and 3 months postoperatively between severe DU, mild DU and non-DU benign prostate obstruction patients in two obstruction groups (20 ≤ BOOI < 40 and BOOI ≥ 40). RESULTS: According to the ROC curve, the optimal cut-off point for the bladder contractility index was 82; thus, 69 patients were considered mild DU patients (82 ≤ BCI < 100), 67 patients were considered severe DU patients (BCI < 82), and 214 patients were considered non-DU patients (BCI ≥ 100). Both the postoperative subjective and objective parameters of the non-DU, mild DU and severe DU patients significantly improved in two obstruction groups. However, in the 20 ≤ BOOI < 40 group, the successful improvement rates for the IPSS, IPSS-S, IPSS-V, QoL and fQmax in the severe DU patients were only 38.2%, 38.2%, 44.1%, 41.2% and 38.2%, respectively. CONCLUSION: Patients with varying degrees of benign prostate obstruction can benefit from TURP, but for patients with severe DU in the 20 ≤ BOOI < 40 group, TURP should be considered only after deliberation.

7.
Phys Chem Chem Phys ; 23(1): 94-106, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33325463

RESUMO

The fundamental factor affecting the stability of perovskite solar cells, ion migration, has been reviewed, which is found to be closely related to the degradation of perovskite solar cells. Characterization methods like impedance spectroscopy and galvanostatic measurement to identify ion migration in perovskite films have been reviewed. The influence of light on ion migration was further discussed, which could largely explain the photo-stability decay in most perovskite solar cells. Finally, several solutions to inhibit ion migration for better operational stability of perovskite solar cells were summarized, including bulk passivation, interface passivation and grain boundary passivation. Several strategies have also been proposed to further improve the stablity of perovskite solar cells.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33278595

RESUMO

Saikosaponin a (SSa), a triterpene saponin extracted from Bupleurumfalcatum L., has been reported to have anti-inflammatory activity. In the present study, we investigated the effects of SSa on lead-induced kidney injury in common carp. Kidney histological changes were detected by H&E staining. The levels of TNF-α, IL-1ß, MPO, MDA, GSH, and SOD activity were also measured. Furthermore, the NF-κB and Nrf2 signaling pathways were tested by western blot analysis. The results showed that lead-induced kidney histological change was attenuated by SSa. Lead-induced TNF-α, IL-1ß, MPO, and MDA production were also suppressed by SSa. Meanwhile, lead could decrease GSH level and SOD activity and the decreases were inhibited by SSa. Furthermore, we found SSa significantly inhibited lead-induced NF-κB translocation. In addition, the expression of Nrf2 and HO-1 were increased by the treatment of SSa and Keap1 expression was decreased by SSa. In conclusion, this study indicated that SSa inhibited lead-induced kidney injury in carp through suppressing inflammatory and oxidative responses, and the mechanism may be involved in the inhibition of NF-κB and activation of Nrf2 signaling pathway.

9.
ACS Nano ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33283501

RESUMO

Excessive oxidative stress in cancer cells can induce cancer cell death. Anticancer activity and drug resistance of chemotherapy are closely related to the redox state of tumor cells. Herein, five lipophilic Pt(IV) prodrugs were synthesized on the basis of the most widely used anticancer drug cisplatin, whose anticancer efficacy and drug resistance are closely related to the intracellular redox state. Subsequently, a series of cisplatin-sensitive and drug-resistant cell lines as well as three patient-derived primary ovarian cancer cells have been selected to screen those prodrugs. To verify if the disruption of redox balance can be combined with these Pt(IV) prodrugs, we then synthesized a polymer with a diselenium bond in the main chain for encapsulating the most effective prodrug to form nanoparticles (NP(Se)s). NP(Se)s can efficiently break the redox balance via simultaneously depleting GSH and augmenting ROS, thereby achieving a synergistic effect with cisplatin. In addition, genome-wide analysis via RNA-seq was employed to provide a comprehensive understanding of the changes in transcriptome and the alterations in redox-related pathways in cells treated with NP(Se)s and cisplatin. Thereafter, patient-derived xenograft models of hepatic carcinoma (PDXHCC) and multidrug-resistant lung cancer (PDXMDR) were established to evaluate the therapeutic effect of NP(Se)s, and a significant antitumor effect was achieved on both models with NP(Se)s. Overall, this study provides a promising strategy to break the redox balance for maximizing the efficacy of platinum-based cancer therapy.

10.
FEBS Open Bio ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33289299

RESUMO

Leukemic stem cells (LSCs) are a very rare cell population that result in the development of acute myeloid leukemia (AML). The selective targeting of drivers in LSCs with small molecule inhibitors holds promise for treatment of AML. Recently, we reported the identification of inhibitors of the histone lysine demethylase JMJD1C that preferentially kill MLL rearranged acute leukemia cells. Here, we report the identification of JMJD1C Jumomji domain Modulator 7 (JDM-7). Surface plasmon resonance (SPR) analysis showed that JDM-7 binds to JMJD1C and its family homolog JMJD1B. JDM-7 did not significantly suppress cell proliferation in liquid cell culture at higher doses, but led to a significant decrease in semi-solid colony formation experiments at lower concentrations. Moreover, low doses of JDM-7 did not suppress the proliferation of erythroid progenitor cells. We identified that JDM-7 downregulates the LSC self-renewal gene HOXA9 in leukemia cells. We further found that the structure of JDM-7 is similar to that of Tadalafil, an FDA approved drug. Molecular docking and surface plasmon resonance (SPR) analysis showed that Tadalafil binds to JMJD1C. Moreover, like JDM-7, Tadalafil suppressed colony formation of leukemia cells in semi-solid cell culture at a concentration that did not affect primary umbilical cord blood cells. In summary, we have identified JDM-7 and Tadalafil as potential JMJD1C modulators that selectively inhibit the growth of LSCs.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33306467

RESUMO

Despite the remarkable advances in visual saliency analysis for natural scene images (NSIs), salient object detection (SOD) for optical remote sensing images (RSIs) still remains an open and challenging problem. In this paper, we propose an end-to-end Dense Attention Fluid Network (DAFNet) for SOD in optical RSIs. A Global Context-aware Attention (GCA) module is proposed to adaptively capture long-range semantic context relationships, and is further embedded in a Dense Attention Fluid (DAF) structure that enables shallow attention cues flow into deep layers to guide the generation of high-level feature attention maps. Specifically, the GCA module is composed of two key components, where the global feature aggregation module achieves mutual reinforcement of salient feature embeddings from any two spatial locations, and the cascaded pyramid attention module tackles the scale variation issue by building up a cascaded pyramid framework to progressively refine the attention map in a coarse-to-fine manner. In addition, we construct a new and challenging optical RSI dataset for SOD that contains 2,000 images with pixel-wise saliency annotations, which is currently the largest publicly available benchmark. Extensive experiments demonstrate that our proposed DAFNet significantly outperforms the existing state-of-the-art SOD competitors. https://github.com/rmcong/DAFNet TIP20.

12.
Front Public Health ; 8: 609974, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33344408

RESUMO

Background: COVID-19 developed into a global pandemic in 2020 and poses challenges regarding the prevention and control capabilities of countries. A large number of inbound travelers from other regions could lead to a renewed outbreak of COVID-19 in the local regions. Globally, as a result of the imbalance in the control of the epidemic, all countries are facing the risk of a renewed COVID-19 outbreak brought about by travelers from epidemic areas. Therefore, studies on a proper management of the inbound travelers are urgent. Methods: We collected a total of 4,733,414 inbound travelers and 174 COVID-19 diagnosed patients in Yunnan province from 21 January 2020 to 20 February 2020. Data on place of origin, travel history, age, and gender, as well as whether they had suspected clinical manifestations for inbound travelers in Yunnan were collected. The impact of inbound travelers on the local epidemic was analyzed with a collinear statistical analysis and the effect of the control measures on the epidemic was evaluated with a sophisticated modeling approach. Results: Of the 174 COVID-19 patients, 60.9% were not from Yunnan, and 76.4% had a history of travel in Hubei. The amount of new daily cases in Yunnan was significant correlated with the number of inbound travelers from Hubei and suspected cases among them. Using Susceptible-Exposed-Infectious-Recovered (SEIR) model analysis, we found that the prevention and control measures dropped the local R0 down to 1.07 in Yunnan province. Conclusions: Our preliminary analysis showed that the proper management of inbound travelers from outbreak areas has a significantly positive effect on the prevention and control of the virus. In the process of resettlement, some effective measures taken by Yunnan province may provide an important reference for preventing the renewed COVID-19 outbreak in other regions.


Assuntos
/transmissão , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Transmissão de Doença Infecciosa/prevenção & controle , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Viagem/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Transmissão de Doença Infecciosa/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-33337851

RESUMO

In recent years, shape-memory polymers (SMPs) have received extensive attention to be used as actuators in a broad range of applications such as medical and robotic devices. Their ability to recover large deformations and their capability to be stimulated remotely have made SMPs a superior choice among different smart materials in various applications. In this study, a ductile SMP composite with enhanced shape recovery ability is synthesized and characterized. This SMP composite is made by a mixture of acrylate-based crosslinkers and monomers, as well as polystyrene (PS) with UV curing. The composite can achieve almost 100% shape recovery in 2 s by hot water or hot air. This shape recovery speed is much faster than typical acrylate-based SMPs. In addition, the composite shows excellent ductility and viscoelasticity with reduced hardness. Molecular dynamics (MD) simulations are performed for understanding the curing mechanism of this composite. With the combination of the experimental and computational works, this study paves the way in front of designing and optimizing the future SMP devices.

14.
Expert Rev Anti Infect Ther ; : 1-12, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33164585

RESUMO

Objectives: Chronicity could be a serious threat to hepatitis B virus (HBV)-infected children. The necessity of antiviral treatment to HBV-infected children has caused much controversy. The authors aimed to conduct a systematic review and meta-analysis of synthesized evidence regarding the spontaneous loss of chronic HBV infection markers in treatment-naïve children for exploring their long-term management. Methods: Observational cohort studies and non-treatment arms of randomized controlled trials were searched that reported the spontaneous loss of chronic HBV infection markers in untreated children (characterized by the presence of HBsAg ≥6-month), via the rates of hepatitis B surface antigen (HBsAg) loss, hepatitis B e antigen (HBeAg) seroconversion, and HBV DNA suppression with random-effects model. Results: Of 7,427 studies screened, 20 were included in meta-analysis. With cumulative 23,153 person-years of follow-up, the pooled annual incidences of HBsAg and HBeAg loss, HBV DNA suppression were 1, 6, 7%, respectively. Rates within HBeAg loss and HBV DNA suppression did differ by the transmission modes and ALT levels, not in HBsAg. Conclusion: Spontaneous HBsAg loss (function cure) occurs infrequently in treatment-naïve children with chronic HBV infection. Design of practically applicable programs aiming at therapeutics of children may be necessary to support the goal of eliminating HBV infection worldwide.

15.
Mol Med ; 26(1): 106, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176682

RESUMO

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (LncRNAs) can influence bone cell differentiation and formation. However, it is unclear whether lncRNA HCG18 is involved in osteoporosis (OP). This study was conducted to investigate the regulation of HCG18 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated and cultured from mouse pathological models and osteoporosis patients. RT-qPCR was performed to detect the expression of HCG18 and miR-30a-5p in BMSCs. The interaction between HCG18 and miR-30a-5p was analyzed by dual luciferase assay and RNA pulldown assay. The interaction between miR-30a-5p and NOTCH1 3'-UTR was analyzed by dual luciferase assay. RT-qPCR and Western blotting were used to detect the expression of osteogenic genes Runx2, OCN and OPN. Hindlimb-unloaded (HU) mice model was established, and HCG18 was knocked down on bone-formation surfaces by using lentivirus mediated shRNA transfection. RESULTS: The expression of HCG18 was increased in BMSCs of OP patients, while the expression of miR-30a-5p was decreased. The expression of HCG18 and miR-30a-5p was negatively correlated in BMSCs. During the differentiation from BMSCs to osteoblasts, the expression of HCG18 was significantly downregulated, and the expression of miR-30a-5p was significantly upregulated. Overexpression of HCG18 was able to reverse the osteogenic-induced upregulation of miR-30a-5p expression, and knockdown of HCG18 further promoted the expression of miR-30a-5p. In addition, miR-30a-5p partially abolished the effect of HCG18 on osteogenic differentiation of BMSCs. NOTCH1 was a target protein of miR-30a-5p, and upregulation of NOTCH1 reversed the effect of miR-30a-5p on osteogenic differentiation of BMSCs. Furthermore, this study found that lentivirus mediated HCG18 knockdown on the bone-formation surfaces of hindlimb-unloaded (HU) mice partially alleviated unloading-induced bone loss CONCLUSIONS: HCG18 inhibited osteogenic differentiation of BMSCs induced by OP via the miR-30a-5p/NOTCH1 axis. HCG18 can be identified as a regulator of osteogenic differentiation of BMSCs.

17.
Anal Chem ; 92(23): 15517-15525, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33203209

RESUMO

In situ visualization of proteins of interest in single cells is attractive in cell biology, molecular biology, and biomedicine fields. Time-of-flight-secondary ion mass spectrometry (ToF-SIMS) is a powerful tool for imaging small organic molecules in single cells, yet difficult to image biomacromolecules such as proteins and DNA. Herein, a universal strategy is reported to image specific proteins in single cells by ToF-SIMS following genetic incorporation of fluorine-containing unnatural amino acids as a chemical tag into the proteins via a genetic code expansion technique. The method was developed and validated by imaging a green fluorescence protein (GFP) in Escherichia coli (E. coli) and human HeLa cancer cells and then utilized to visualize the characteristic polar distribution of chemotaxis protein CheA in E. coli cells and the interaction between high-mobility group box 1 protein and cisplatin-damaged DNA in HeLa cells. The present work highlights the power of ToF-SIMS imaging combined with genetically encoded chemical tags for in situ visualization of specific proteins as well as the interactions between proteins and drugs or drug-damaged DNA in single cells.

18.
Dalton Trans ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33244530

RESUMO

Photoactivatable diazidodihydroxido Pt(iv) complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1; py = pyridine) is a promising anticancer agent which can be activated by visible light to induce cancer cell death. DNA has been thought to be involved in the mechanism of action of this kind of Pt(iv) prodrug. However, the detailed photodecomposition pathways of complex 1 and its interaction modes with DNA are complex. Herein we report that upon light irradiation complex 1 can bind to all four nucleosides covalently with the reduced Pt(ii) species. Moreover, apart from the covalent coordination, various oxidation adducts of these four nucleosides induced by the reactive oxidative species (ROS) generated during the photoactivation of the complex 1 have also been identified, especially the induced oxidation of adenosine and cytidine which was firstly reported for this kind of photoactivatable Pt(iv) prodrug. Such dual-action may contribute to the highly potent photo-antiproliferativity of complex 1 towards cancer cells, which may account for the unique mechanism of action of the photoactivatable diazido Pt(iv) anticancer complexes.

19.
Anticancer Drugs ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33105152

RESUMO

This study was performed to investigate pneumothorax characteristics and association with clinical outcomes in patients with osteosarcoma treated with apatinib. We retrospectively reviewed the medical records of osteosarcoma patients treated with apatinib between January 2016 and April 2020 at three institutions. We evaluated the prevalence, healing time, recurrence, severity, clinical management, and prognosis of pneumothorax in these patients. A total of 54 osteosarcoma patients who received apatinib treatment were enrolled in this study. Among them, 14 patients had pneumothorax. There were significant differences between the patients with and without pneumothorax with regard to the cavitating rate of lung metastases (92.86 vs. 32.50%, respectively, P < 0.001), objective response rate (42.86 vs. 10.00%, P = 0.013), disease control rate (85.71 vs. 42.50%, P = 0.006), 4-month progression-free survival (PFS) rate (57.10 vs. 20.00%, P < 0.001), and median PFS (5.65 vs. 2.90 months, P = 0.011). Compared with pneumothorax patients treated with chest tube drainage only [non-staphylococcal enterotoxin C (SEC) group], those treated with chest tube drainage and SEC thoracic perfusion in parallel (SEC group) had a shorter pneumothorax healing time (12.00 ± 4.50 days vs. 24.00 ± 14.63 days for SEC group and non-SEC group, respectively, P = 0.103), a lower recurrence rate of pneumothorax (25.00% vs. 66.67%, P = 0.277), and a longer median PFS (5.9 months vs. 4.75 months, P = 0.964). however, these numerical differences for the SEC/non-SEC data did not reach statistical significance. Pneumothorax and cavitation in lung metastases may be effective prognostic markers for patients with osteosarcoma treated with apatinib. SEC may be effective for treatment of such pneumothorax patients, warranting further study.

20.
ACS Nano ; 14(11): 14831-14845, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33084319

RESUMO

DNA alkylating agents generally kill tumor cells by covalently binding with DNA to form interstrand or intrastrand cross-links. However, in the case of cisplatin, only a few DNA adducts (<1%) are highly toxic irreparable interstrand cross-links. Furthermore, cisplatin is rapidly detoxified by high levels of intracellular thiols such as glutathione (GSH). Since the discovery of its mechanism of action, people have been looking for ways to directly and efficiently remove intracellular GSH and increase interstrand cross-links to improve drug efficacy and overcome resistance, but there has been little breakthrough. Herein, we hypothesized that the anticancer efficiency of cisplatin can be enhanced through iodo-thiol click chemistry mediated GSH depletion and increased formation of DNA interstrand cross-links via mild hyperthermia triggered by near-infrared (NIR) light. This was achieved by preparing an amphiphilic polymer with platinum(IV) (Pt(IV)) prodrugs and pendant iodine atoms (iodides). The polymer was further used to encapsulate IR780 and assembled into Pt-I-IR780 nanoparticles. Induction of mild hyperthermia (43 °C) at the tumor site by NIR light irradiation had three effects: (1) it accelerated the GSH-mediated reduction of Pt(IV) in the polymer main chain to platinum(II) (Pt(II)); (2) it boosted the iodo-thiol substitution click reaction between GSH and iodide, thereby attenuating the GSH-mediated detoxification of cisplatin; (3) it increased the proportion of highly toxic and irreparable Pt-DNA interstrand cross-links. Therefore, we find that mild hyperthermia induced via NIR irradiation can enhance the killing of cancer cells and reduce the tumor burden, thus delivering efficient chemotherapy.

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