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1.
Environ Res ; 203: 111834, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34358501

RESUMO

Age-specific discrepancy of mortality burden attributed to temperature, measured as years of life lost (YLL), has been rarely investigated. We investigated age-specific temperature-YLL rates (per 100,000) relationships and quantified YLL per death caused by non-optimal temperature in China. We collected daily meteorological data, population data and daily death counts from 364 locations in China during 2006-2017. YLL was divided into three age groups (0-64 years, 65-74 years, and ≥75 years). A distributed lag non-linear model was first employed to estimate the associations of temperature with age-specific YLL rates in each location. Then we pooled the associations using a multivariate meta-analysis. Finally, we calculated age-specific average YLL per death caused by temperature by cause of death and region. We observed greater effects of cold and hot temperature on YLL rates for the elderly compared with the young population by region or cause of death. However, YLL per death due to non-optimal temperature for different regions or causes of death decreased with age, with 2.0 (95 % CI:1.5, 2.5), 1.2 (1.1, 1.4) and 1.0 years (0.9, 1.2) life loss per death for populations aged 0-64 years, 65-74 years and over 75 years, respectively. Most life loss per death results from moderate temperature, especially moderate cold for all age groups. The effect of non-optimal temperature on YLL rates is smaller for younger populations than older ones, while the temperature-related life loss per death was more prominent for younger populations.

2.
Nat Prod Res ; : 1-7, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726089

RESUMO

The endophytic fungus Periconia sp. TJ403-rc01 (Dematiaceae) isolated from the leaves of Rosa chinensis Jacq. (Rosaceae) was cultivated on rice medium and chemically investigated, affording two new lanostane-type triterpenoids, namely pericinones A and B (1 and 2). Their structures were determined mainly by 1 D and 2 D NMR and HRESIMS data. Notably, it is the first report of lanostane-type triterpenoids from species of Periconia. Compounds 1 and 2 showed moderate anti-inflammatory activity against the NO production with IC50 values of 24.12 ± 0.73 and 11.38 ± 1.56 µM, respectively.

3.
Acta Radiol ; : 2841851211054191, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34719964

RESUMO

BACKGROUND: The clinicopathological predictors of sentinel lymph node (SLN) metastasis in clinical T1-T2 N0 (cT1-T2 N0) patients with a normal axillary ultrasound (AUS) are unclear. PURPOSE: To assess the association between clinicopathological characteristics of a primary tumor and SLN metastasis in cT1-T2 N0 patients with a normal AUS. MATERIAL AND METHODS: Patients who were diagnosed with cT1-T2 N0 invasive breast cancer and who obtained normal AUS results between October 2016 and September 2018 in a single hospital were included. Clinicopathological data were collected to explore the predictors of SLN metastasis using a multivariate logistic regression model. RESULTS: SLN metastasis occurred in 26 patients (18.4%) among 141 AUS-normal patients, of which 24 cases (17.0%) had one or two nodal involvements. In the univariate analysis, tumor location, estrogen receptor (ER) status, progesterone receptor (PR) status, and lymphovascular invasion (LVI) were significantly associated with SLN metastasis (P < 0.05). The multivariate analysis showed that tumor location in the upper outer quadrant (odds ratio [OR] = 4.49, 95% confidence interval [CI] = 1.63-12.37; P = 0.004), positive PR status (OR = 13.35, 95% CI = 1.60-111.39; P = 0.017), and positive LVI (OR = 8.66, 95% CI = 2.20-34.18; P = 0.002) were independent high-risk factors for SLN metastasis. The area under the receiver operating characteristic curve of the regression model was 0.787 (95% CI = 0.694-0.881; P < 0.001). CONCLUSION: Tumor location in the upper outer quadrant, positive PR, and LVI status were found to be significantly high-risk factors for SLN metastasis among cT1-T2 N0 breast cancer patients with a normal AUS result.

4.
Bioorg Chem ; 117: 105452, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742026

RESUMO

Three pairs of undescribed enantiomeric α-pyrone derivatives (1a/1b-3a/3b) and six undescribed congeners (4-9), were obtained from the fungus Alternaria brassicicola that was isolated from the fresh leaves of Siegesbeckia pubescens Makino (Compositae). The structures of these new compounds were characterized by extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were further elucidated by a modified Mosher's method, chemical conversion, single-crystal X-ray diffraction analysis, and ECD calculations. This is the first report of three pairs of enantiomeric α-pyrone derivatives from the fungus A. brassicicola, and these enantiomers were successfully acquired from scalemic mixtures via chiral HPLC. Compounds 1a/1b-3a/3b and 4-9 were evaluated for the herbicidal activity against Echinochloa crusgalli, Setaria viridis, Portulaca oleracea, and Taraxacum mongolicum. At a concentration of 100 µg/mL, compounds 1a and 1b could significantly inhibit the germination of monocotyledon weed seeds (E. crusgalli and S. viridis) with inhibitory ratios ranging from 68.6 ± 6.4% to 84.2 ± 5.1%, which was equivalent to that of the positive control (glyphosate). The potential structure-herbicidal activity relationship of these compounds was also discussed. To a certain extent, the results of this study will attract great interest for the potential practical application of promising fungal metabolites, α-pyrone derivatives, as ecofriendly herbicides.

5.
Asian J Psychiatr ; 67: 102896, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34773803

RESUMO

BACKGROUND: Berberine could improve antipsychotic-induced weight gain in obese cell lines and animal models. This study aimed to exam the effect of berberine on weight gain in patients with schizophrenia. METHODS: Each subject who met DSM-IV-TR criteria for schizophrenia had been on stable dose of a single antipsychotic for at least one month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either berberine (900 mg per day) or placebo. Anthropometric parameters, leptin and adiponectin were measured at baseline, week 4, and week 8. RESULTS: A total of 65 patients were enrolled, 49 of which completed the treatment. At the 8th week, the mean weight of patients in the berberine group (N = 27) lost 1.10 kg, while in the placebo group (N = 22) gained 1.45 kg. There were significant differences in body weight (Ftime*group=10.493, P = 0.001), BMI (Ftime*group=9.344, P = 0.002) and leptin (Ftime*group=6.265, P = 0.003). Further, the change of leptin had significant positive correlations with the changes of body weight(r = 0.395, P = 0.041) and BMI(r = 0.389, P = 0.045). There was no significant difference in adverse events between the two groups (P > 0.05). CONCLUSION: This study suggests that berberine is a potential weight loss and weight maintenance drug for patients with schizophrenia. The effect of berberine on weight gain may be related to the regulation of leptin, but not adiponectin.

6.
Sci Rep ; 11(1): 21383, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725393

RESUMO

Electromagnetic spectrum detection is the basis of the next generation wireless communication technology. Wireless signal identification is an important part of electromagnetic spectrum detection and management activities. This paper proposes to extract the distribution features of different modulated signals from the signal I/Q data. A two-dimensional gradient matrix is used to describe the characteristics of the signal classification. The minimum gradient cumulative distance (GCD) estimate between the sample and the model is used as the decision criterion for the signal classification. According to the result of the confusion matrix, the weight of the model is adjusted. Experiments show that the recognition rate of the modulated signal mentioned in this paper can reach 82.75%. The I/Q data sample was extracted under actual engineering conditions involving random noise, and the recognition rate dropped to approximately 79%. Based on the initial model gradient matrix, a reasonable algorithm is set to adjust the weight of the model, which can effectively improve the recognition rate of the modulated signal.

7.
Transl Lung Cancer Res ; 10(9): 3759-3770, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733626

RESUMO

Background: Patients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected. Methods: From June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated. Results: ENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment. Conclusions: For medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.

8.
Org Lett ; 23(22): 8947-8951, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34743520

RESUMO

The flavoprotein monooxygenase (FPMO) TerC is encoded by all known cyclopentene biosynthetic gene clusters. It can catalyze oxidative dearomatization toward a series of 6-HM analogues and further induces different skeletal distortions to form either benzoquinone or pyrone by bimodal reaction cascades, which is only governed by the C7 substitutions. Beyond our study demonstrated bimodal reaction cascades and advanced the biosynthetic knowledge of fungal cyclopentenes, this work also sets the stage for the bioengineering of 6-HM polyketides.

9.
Mar Drugs ; 19(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34822459

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a devastating digestive system carcinoma with high incidence and death rates. PDAC cells are dependent on the Gln metabolism, which can preferentially utilize glutamic oxaloacetate transaminase 1 (GOT1) to maintain the redox homeostasis of cancer cells. Therefore, small molecule inhibitors targeting GOT1 can be used as a new strategy for developing cancer therapies. In this study, 18 butyrolactone derivatives (1-18) were isolated from a marine-derived Aspergillus terreus, and asperteretone B (5), aspulvinone H (AH, 6), and (+)-3',3'-di-(dimethylallyl)-butyrolactone II (12) were discovered to possess significant GOT1-inhibitory activities in vitro, with IC50 values of (19.16 ± 0.15), (5.91 ± 0.04), and (26.38 ± 0.1) µM, respectively. Significantly, the molecular mechanism of the crystal structure of GOT1-AH was elucidated, wherein AH and the cofactor pyrido-aldehyde 5-phosphate competitively bound to the active sites of GOT1. More importantly, although the crystal structure of GOT1 has been discovered, the complex structure of GOT1 and its inhibitors has never been obtained, and the crystal structure of GOT1-AH is the first reported complex structure of GOT1/inhibitor. Further in vitro biological study indicated that AH could suppress glutamine metabolism, making PDAC cells sensitive to oxidative stress and inhibiting cell proliferation. More significantly, AH exhibited potent in vivo antitumor activity in an SW1990-cell-induced xenograft model. These findings suggest that AH could be considered as a promising lead molecule for the development of anti-PDAC agents.

10.
Mar Drugs ; 19(11)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34822488

RESUMO

Optimizing the alkali treatment process alone without tracking the changes of algae and agar quality with each pretreatment process will not achieve the optimal agar yield and final quality. In this study, we monitored the changes of the morphology and weight of algae with each treatment process, and comprehensively analyzed the effects of each pretreatment process on the quality of agar by combining the changes of the physicochemical properties of agar. In conventional alkali-extraction technology, alkali treatment (7%, w/v) alone significantly reduced the weight of algae (52%), but hindered the dissolution of algae, resulting in a lower yield (4%). Acidification could solve the problem of algal hardening after alkali treatment to improve the yield (12%). In enzymatic extraction technology, agar with high purity cannot be obtained by enzyme treatment alone, but low gel strength (405 g/cm2) and high sulfate content (3.4%) can be obtained by subsequent acidification and bleaching. In enzyme-assisted extraction technology, enzyme damage to the surface fiber of algae promoted the penetration of low-concentration alkali (3%, w/v), which ensured a high desulfurization efficiency and a low gel degradation rate, thus improving yield (24.7%) and gel strength (706 g/cm2), which has the potential to replace the traditional alkali-extraction technology.

11.
Phytochemistry ; 193: 113012, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34773753

RESUMO

Under OSMAC strategy, seven unreported multioxidized aromatic polyketides, penicanesins A‒G, were discovered from a soil-derived fungus Penicillium canescens along with seven known compounds. Their structures were assigned by extensive 1D and 2D NMR spectra in combination with HRESIMS and single crystal X-ray diffraction. Absolute stereochemistry of penicanesins A and D were elucidated by theoretical ECD calculation. (±)-Penicanesins A and B are two pairs of racemic aromatic polyketides with an unusual 6/6/6/6 heterotetracyclic ring core. In bioassay, (-)-penicanesin A shows potential cytotoxicity against human cancer cell lines HL-60 and SW480 with IC50 values at 13.8 ± 0.6 and 12.5 ± 0.9 µM, respectively, whereas the enantiomer (+)-penicanesin A is less active.

12.
J Asian Nat Prod Res ; : 1-7, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647840

RESUMO

A new megastimane sesquiterpenoid, cassianol A (1), and five known analogues (2-6) were isolated from the leaves extract of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. All the isolates were isolated from C. cassia for the first time. The anti-inflammatory activities of compounds 1-6 were evaluated against nitric oxide (NO) production in LPS-induced RAW 264.7 mouse macrophages.

13.
Opt Express ; 29(19): 29651-29660, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34614706

RESUMO

In this report, we investigate the impact of a thin p-GaN layer on the efficiency for AlGaN-based deep-ultraviolet light-emitting diodes (DUV LEDs). According to our results, the light extraction efficiency (LEE) becomes higher with the decrease of the p-GaN layer thickness, which can be ascribed to the decreased absorption of DUV emission by the thin p-GaN layer. Moreover, we also find that the variation trend of external quantum efficiency (EQE) is consistent with that of LEE. Therefore, we can speculate that high-efficiency DUV LEDs can be achieved by using thin p-GaN layer to increase the LEE. However, a thin p-GaN layer can also cause severe current crowding effect and the internal quantum efficiency (IQE) will be correspondingly reduced, which will restrict the improvement of EQE. In this work, we find that the adoption of a current spreading layer for such DUV LED with very thin p-GaN layer can facilitate the current spreading effect. For the purpose of demonstration, we then utilize a well-known p-AlGaN/n-AlGaN/p-AlGaN (PNP-AlGaN) structured current spreading layer. Our experimental and numerical results show that, as long as the current crowding effect can be suppressed, the DUV LED with thin p-GaN layer can significantly increase the EQE and the optical power thanks to the enhanced LEE.

14.
Opt Express ; 29(19): 30532-30542, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34614776

RESUMO

It is known that light extraction efficiency (LEE) for AlGaN-based deep ultraviolet light-emitting didoes (DUV LEDs) can be enhanced by using truncated cone arrays with inclined sidewalls. In this work, the air-cavity-shaped inclined sidewall is applied and the p-GaN layer at the top of the truncated cone is laterally over-etched so that more light escape paths are generated for AlGaN-based DUV LEDs. The experimental results manifest that when compared with DUV LEDs only having the air-cavity-shaped inclined sidewall, the optical power for the DUV LEDs with laterally over-etched p-GaN at the top of the truncated cone is enhanced by 30% without sacrificing the forward bias. It is because the over-etched p-GaN makes little effect on the carrier injection and does not affect the ohmic contact resistance. Moreover, the simulation results show that the truncated cone with laterally over-etched p-GaN layer can enhance the LEE because the reduced p-GaN area can suppress the optical absorption and supplies additional light paths for DUV photos. Then, more light will be reflected into escape cones at the sapphire side.

15.
Opt Express ; 29(20): 31201-31211, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615218

RESUMO

Due to the increased surface-to-volume ratio, the surface recombination caused by sidewall defects is a key obstacle that limits the external quantum efficiency (EQE) for GaN-based micro-light-emitting diodes (µLEDs). In this work, we propose selectively removing the periphery p+-GaN layer so that the an artificially formed resistive ITO/p-GaN junction can be formed at the mesa edge. Three types of LEDs with different device dimensions of 30 × 30 µm2, 60 × 60 µm2 and 100 × 100 µm2 are investigated, respectively. We find that such resistive ITO/p-GaN junction can effectively prevent the holes from reaching the sidewalls for µLEDs with smaller size. Furthermore, such confinement of injection current also facilitates the hole injection into the active region for µLEDs. Therefore, the surface-defect-caused nonradiative recombination in the edge of mesa can be suppressed. Meantime, a reduction of current leakage caused by the sidewall defects can also be obtained. As a result, the measured and calculated external quantum efficiency (EQE) and optical output power for the proposed LED with small sizes are increased.

16.
Toxicology ; 463: 152991, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34673133

RESUMO

4-Nitrophenol (PNP) has been extensively used in manufacturing for several decades. Its toxic effects on the male reproductive system have been reported, but the underlying mechanisms remain unclear. In this study, we utilized two testicular somatic cell lines (TM3 and TM4 cells) to explore the possible toxic effects of PNP on the male reproductive system. The activity of the cells after exposure to different doses of PNP (0.01, 0.1, 1, 10 and 100 µM) was evaluated. PNP treatment at 10 µM significantly inhibited cell viability, and 10 µM PNP was thus selected for subsequent experiments. Although PNP (10 µM) inhibited cell proliferation, promoted cell apoptosis, and changed the cell cycle distribution and ultrastructure in both types of cells, these effects were more significant in the TM4 cells. In addition, an Agilent mouse mRNA array was used to identify the gene expression differences between the control and PNP (10 µM) exposed TM3 and TM4 cells. The microarray analysis identified 67 and 1372 differentially expressed genes mainly concentrated in endothelial cell morphogenesis and anatomical structure development in TM3 cells and associated with cardiovascular system development and circulatory system development in TM4 cells. Moreover, a pathway analysis revealed that PNP not only predominately affected meiotic recombination and meiosis in TM3 cells, but also influenced axon guidance and developmental biology in TM4 cells. These results suggest that TM3 and TM4 cells exhibit different responses to PNP, which might mediate different toxic mechanisms.

17.
Phytochemistry ; 193: 112982, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34700067

RESUMO

Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11α,14α-epoxy-13α,14ß,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC50 value of 4.60 ± 0.85 µM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds.

18.
J Hepatocell Carcinoma ; 8: 1023-1034, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513745

RESUMO

Background and Aims: To explore the long-term trend of liver cancer survival, based on the real-world data (RWD) in the past 45 years from a population-based cancer registry, in Qidong, China. Methods: A number of 32,556 patients with liver cancer were registered during the period of 1972 to 2016. Mixed methods by active and passive follow-up were performed. Life table method was employed for survival analysis by SPSS22 software. Wilcoxon (Gehan) statistics was considered as a significant test. Relative survival was calculated by using SURV software, and its annual percent change (APC) was estimated by the Joinpoint Regression Program. Results: The overall observed survival (OS) rates of 1-, 5-, 10-, and 20-year rates from the data series were 18.51%, 6.28%, 4.03%, and 2.84%, and their relative survival (RS) rates were 18.88%, 6.95%, 4.96%, and 4.49%, respectively. For 24,338 male cases, the 5-year OS and RS rates were 5.93% and 6.54%, and for 8218 female cases, 7.34% and 8.15%, respectively, with P values less than 0.01. Survival rates of liver cancer from three 15-year periods of 1972-1986, 1987-2001, and 2002-2016 have increased significantly, with 5-year OS rates of 2.02%, 4.40%, and 10.76%, 5-year RS rates of 2.18%, 4.83%, and 12.18%; 10-year OS and RS rates of 0.95%, 3.00%, and 7.02%, vs 1.13%, 3.65%, and 8.96%, respectively, showing a very significant upward trend (P<0.01). There are significant differences among age groups (P<0.01): those aged 55-64 demonstrated the best OS and RS rates of 5-year, being 8.44% and 9.09%, respectively. Conclusion: There are significant gender and age differences in the survival rate of liver cancer in Qidong. RWD indicates the relative lower survival rate of liver cancer in this area, but great improvement has been achieved over the past decades.

19.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3076-3086, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467698

RESUMO

Due to their fascinating chemical structures and extensive pharmacological activities, polycyclic polyprenylated acylphloroglucinols(PPAPs) have become one of the current research hotspots of natural products. In particular, some of the PPAPs not only have novel non-traditional skeleton types, but also contain more unknown possible activities, which are of great significance for the development of lead compounds. The structure, source, biosynthetic pathway and pharmacological activities of PPAPs with non-traditio-nal skeleton types isolated and identified in recent years are reviewed, in order to provide references for further research on such compounds.


Assuntos
Produtos Biológicos , Hypericum , Estrutura Molecular , Floroglucinol
20.
Cell Oncol (Dordr) ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491549

RESUMO

PURPOSE: Treatment-associated upregulation of suppressive checkpoints and a lack of costimulatory signals compromise the antitumor efficacy of oncolytic virus immunotherapy. Therefore, we aimed to identify highly effective therapeutic targets to provide a proof-of-principle for immune checkpoint together with oncolytic virus-mediated viro-immunotherapy for cancer. METHODS: A fusion protein containing both the extracellular domain of programmed death-1 (PD-1) and the poliovirus receptor (PVR) was designed. Next, the corresponding expression fragment was inserted into the genome of a replication-competent adenovirus to generate Ad5sPD1PVR. The infection, expression, replication and oncolysis of Ad5sPD1PVR were investigated in hepatocellular carcinoma (HCC) cell lines. Immune activation and the antitumor efficacy of Ad5sPD1PVR were examined in HCC tumor models including a humanized immunocompetent mouse model. RESULTS: Ad5sPD1PVR effectively infected and replicated in HCC cells and secreted sPD1PVR. In a H22 ascitic HCC mouse model, intraperitoneal injection of Ad5sPD1PVR markedly recruited lymphocytes and activated antitumor immune responses. Ad5sPD1PVR exerted a profound antitumor effect on ascitic HCC. Furthermore, we found that Ad5sPD1PVR-H expressing sPD1PVR of human origin exhibited potent antitumor effects in a HCC humanized mouse model. We also found that CD8+ T cells mediated the antitumor effects and long-term tumor-specific immune surveillance induced by Ad5sPD1PVR. Finally, when combined with fludarabine, the antitumor efficacy of Ad5sPD1PVR was found to be further improved in the ascitic HCC model. CONCLUSIONS: From our data we conclude that the newly designed recombinant Ad5sPD1PVR virus significantly enhances CD8+ T cell-mediated antitumor efficacy with long-term tumor-specific immune surveillance in hepatocellular carcinoma, and that fludarabine is a promising therapeutic partner for Ad5sPD1PVR.

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