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1.
Environ Monit Assess ; 196(4): 361, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472544

RESUMO

In this study, we collected 56 species of fishery organisms (including fish, crustaceans, cephalopods, gastropods, and bivalves) from four seasonal survey cruises at the Dachen fishery grounds. We measured the concentrations of seven heavy metals (Cd, Zn, Cu, Pb, Cr, As, and Hg) in these fisheries organisms. We determined their trophic levels using carbon and nitrogen stable isotope techniques. We analyzed the characteristics of heavy metal transfer in the food chain. The results showed significant differences in heavy metal concentrations among different species. Among all biological groups, bivalves and gastropods exhibited higher levels of heavy metal enrichment than other biological groups, while fish had the lowest levels of heavy metal enrichment. Heavy metals exhibited different patterns of nutritional transfer in the food chain. While Hg showed a biomagnification phenomenon in the food chain, it was not significant. Cd, Zn, Cu, Pb, Cr, and As exhibited a trend of biodilution with increasing nutritional levels, except for As, which showed no significant correlation with δ15N.


Assuntos
Gastrópodes , Mercúrio , Metais Pesados , Poluentes Químicos da Água , Animais , Cádmio , Caça , Chumbo , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Metais Pesados/análise , Cadeia Alimentar , Isótopos de Nitrogênio , China , Músculos/química
2.
J Nanobiotechnology ; 21(1): 312, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660121

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) possesses special biological behavior and clinicopathological characteristics, which is highly invasive and propensity to metastasize to lymph nodes, leading to a worse prognosis than other types of breast cancer. Thus, the development of an effective therapeutic method is significant to improve the survival rate of TNBC patients. RESULTS: In this work, a liposome-based theranostic nanosystem (ILA@Lip) was successfully prepared by simultaneously encapsulating IR 780 as the photosensitizer and lenvatinib as an anti-angiogenic agent, together with banoxantrone (AQ4N) molecule as the hypoxia-activated prodrug. The ILA@Lip can be applied for the near-infrared (NIR) fluorescence diagnostic imaging of TNBC and its lymph node metastasis for multimodal therapy. Lenvatinib in ILA@Lip can inhibit angiogenesis by cutting oxygen supply, thereby leading to enhanced hypoxia levels. Meanwhile, large amounts of reactive oxygen species (ROS) were produced while IR 780 was irradiated by an 808 nm laser, which also rapidly exhausted oxygen in tumor cells to worsen tumor hypoxia. Through creating an extremely hypoxic in TNBC, the conversion of non-toxic AQ4N to toxic AQ4 was much more efficiency for hypoxia-activated chemotherapy. Cytotoxicity assay of ILA@Lip indicated excellent biocompatibility with normal cells and tissues, but showed high toxicity in hypoxic breast cancer cells. Also, the in vivo tumors treated by the ILA@Lip with laser irradiation were admirably suppressed in both subcutaneous tumor model and orthotopic tumor models. CONCLUSION: Utilizing ILA@Lip is a profound strategy to create an extremely hypoxic tumor microenvironment for higher therapeutic efficacy of hypoxia-activated chemotherapy, which realized collective suppression of tumor growth and has promising potential for clinical translation.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Metástase Linfática , Hipóxia , Oxigênio , Imagem Óptica , Microambiente Tumoral
3.
Int J Mol Sci ; 24(10)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37240270

RESUMO

The search for and characterization of new lipases with excellent properties has always been urgent and is of great importance to meet industrial needs. In this study, a new lipase, lipB, from Pseudomonas fluorescens SBW25, belonging to the lipase subfamily I.3, was cloned and expressed in Bacillus subtilis WB800N. Enzymatic properties studies of recombinant LipB found that it exhibited the highest activity towards p-nitrophenyl caprylate at 40 °C and pH 8.0, retaining 73% of its original activity after incubation at 70 °C for 6 h. In addition, Ca2+, Mg2+, and Ba2+ strongly enhanced the activity of LipB, while Cu2+, Zn2+, Mn2+, and CTAB showed an inhibiting effect. The LipB also displayed noticeable tolerance to organic solvents, especially acetonitrile, isopropanol, acetone, and DMSO. Moreover, LipB was applied to the enrichment of polyunsaturated fatty acids from fish oil. After hydrolyzing for 24 h, it could increase the contents of polyunsaturated fatty acids from 43.16% to 72.18%, consisting of 5.75% eicosapentaenoic acid, 19.57% docosapentaenoic acid, and 46.86% docosahexaenoic acid, respectively. The properties of LipB render it great potential in industrial applications, especially in health food production.


Assuntos
Lipase , Pseudomonas fluorescens , Lipase/metabolismo , Pseudomonas fluorescens/genética , Pseudomonas fluorescens/metabolismo , Ácidos Graxos Insaturados , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Estabilidade Enzimática
4.
Sensors (Basel) ; 22(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35890858

RESUMO

Internet of Things (IoT) and Big Data technologies are becoming increasingly significant parts of national defense and the military, as well as in the civilian usage. The proper deployment of large-scale wireless sensor network (WSN) provides the foundation for these advanced technologies. Based on the Fruchterman-Reingold graph layout, we propose the Fruchterman-Reingold Hexagon (FR-HEX) algorithm for the deployment of WSNs. By allocating edges of hexagonal topology to sensor nodes, the network forms hexagonal network topology. A comprehensive evaluation of 50 simulations is conducted, which utilizes three evaluation metrics: average moving distance, pair correlation diversion (PCD), and system coverage rate. The FR-HEX algorithm performs consistently, the WSN topologies are properly regulated, the PCD values are below 0.05, and the WSN system coverage rate reaches 94%. Simulations involving obstacles and failed nodes are carried out to explore the practical applicability of the FR-HEX algorithm. In general, the FR-HEX algorithm can take full advantage of sensors' hardware capabilities in the deployment. It may be a viable option for some IoT and Big Data applications in the near future.

5.
Nano Lett ; 21(6): 2461-2469, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33686851

RESUMO

Circulating cell-free DNA (cfDNA) released by damaged cells causes inflammation and has been associated with the progression of sepsis. One proposed strategy to treat sepsis is to scavenge this inflammatory circulating cfDNA. Here, we develop a cfDNA-scavenging nanoparticle (NP) that consists of cationic polyethylenimine (PEI) of different molecular weight grafted to zeolitic imidazolate framework-8 (PEI-g-ZIF) in a simple one-pot process. PEI-g-ZIF NPs fabricated using PEI 1800 and PEI 25k but not PEI 600 suppressed cfDNA-induced TLR activation and subsequent nuclear factor kappa B pathway activity. PEI 1800-g-ZIF NPs showed greater inhibition of cfDNA-associated inflammation and multiple organ injury than naked PEI 1800 (lacking ZIF), and had greater therapeutic efficacy in treating sepsis. These results indicate that PEI-g-ZIF NPs acts as a "nanotrap" that improves upon naked PEI in scavenging circulating cfDNA, reducing inflammation, and reversing the progression of sepsis, thus providing a novel strategy for sepsis treatment.


Assuntos
Ácidos Nucleicos Livres , Estruturas Metalorgânicas , Nanopartículas , Sepse , Humanos , Polietilenoimina , Sepse/tratamento farmacológico
6.
Int J Mol Sci ; 23(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35409302

RESUMO

The acidic tumor microenvironment stands as a major obstacle to the efficient elimination of tumor cells. Norcantharidin (NCTD) is a powerful antitumor agent with multiple bioactivities. However, the effect of NCTD under acidic conditions is still unclear. Here, we report that NCTD can efficiently kill bladder cancer (BC) cells in acidic culture, and more intriguingly, NCTD can induce immunogenic cell death (ICD), thereby promoting antitumor immunity. In NCTD-treated BC cells, the surface-exposed calreticulin (ecto-CALR) was significantly increased. Consistently, co-culture with these cells promoted dendritic cell (DC) maturation. The NCTD-induced ICD is autophagy dependent, as autophagy inhibition completely blocked the NCTD-induced ecto-CALR and DC maturation. In addition, the DC showed a distinct maturation phenotype (CD80high CD86low) in acidic culture, as compared to that in physiological pH (CD80 high CD86high). Finally, the NCTD-induced ICD was validated in a mouse model. NCTD treatment significantly increased the tumor-infiltrating T lymphocytes in MB49 bladder cancer mice. Immunizing mice with NCTD-treated MB49 cells significantly increased tumor-free survival as compared to control. These findings demonstrate that NCTD could induce ICD in an acidic environment and suggest the feasibility to combine NCTD with anticancer immunotherapy to treat BC.


Assuntos
Antineoplásicos , Neoplasias da Bexiga Urinária , Animais , Antineoplásicos/farmacologia , Apoptose , Autofagia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Morte Celular Imunogênica , Camundongos , Microambiente Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico
7.
Eur J Immunol ; 50(2): 192-204, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710099

RESUMO

Mucosal-associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19-Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iVα19TCR and their regulation in MAIT cells are unknown. Diacylglycerol (DAG) is a critical second messenger that relays the TCR signal to multiple downstream signaling cascades. DAG is terminated by DAG kinase (DGK)-mediated phosphorylation and conversion to phosphatidic acid. We have demonstrated here that downregulation of DAG caused by enhanced DGK activity impairs late-stage MAIT cell maturation in both thymus and spleen. Moreover, deficiency of DGKζ but not DGKα by itself causes modest decreases in MAIT cells, and deficiency of both DGKα and ζ results in severe reductions of MAIT cells in an autonomous manner. Our studies have revealed that DAG signaling is not only critical but also must be tightly regulated by DGKs for MAIT cell development and that both DGKα and, more prominently, DGKζ contribute to the overall DGK activity for MAIT cell development.


Assuntos
Diacilglicerol Quinase/imunologia , Diacilglicerol Quinase/metabolismo , Diglicerídeos/imunologia , Diglicerídeos/metabolismo , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Animais , Camundongos , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia
8.
Scand J Gastroenterol ; 56(11): 1349-1354, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34396876

RESUMO

BACKGROUND AND OBJECTIVE: The N-ethylmaleimide-sensitive fusion protein attachment protein receptor YKT6 is a key protein that controls the release of exosomes, was reported to play important roles in multiple cancers. However, the role of YKT6 in hepatocellular carcinoma (HCC) is still unknown. METHODS: Here we first used bioinformatics tools to analyze the YKT6 mRNA expression in HCC. In addition, we retrospectively collected 330 cancer tissue specimens from HCC patients and 180 para-cancerous tissue specimens, and detected YKT6 expression using immunohistochemical staining. Then the relationship between YKT6 expression and the clinical characteristics of HCC was analyzed, Kaplan-Meier analysis and Cox regression model were also performed to evaluate the impact of YKT6 expression on prognosis of HCC. Protein-protein interaction network of YKT6, and the gene enrichment analysis (GSEA) database were used to predict possible signal pathways regulated by YKT6 in HCC. RESULTS: The high expression rate of YKT6 in HCC (72.40%, 239/330) was higher than that in adjacent tissues (17.80%, 32/180, p < .001), and high expression of YKT6 was correlated with tumor size (p = 0.002), Edmondson Grade (p < .001), metastasis (p < .001), microvascular invasion (p = .005), AFP level (p = .002). Kaplan-Meier survival analysis showed that HCC patients with high YKT6 expression level had poorer prognosis. Meanwhile, multivariate Cox regression analysis showed that Edmondson grade (p = .009), metastasis (p = .049), YKT6 expression (p = .037) are independent risk factors for poor prognosis of HCC. Conclusions: Our results suggested that the upregulated expression of YKT6 is closely related to the progression HCC, which may be used as a potential biomarker for poor prognosis in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Prognóstico , Proteínas R-SNARE , Estudos Retrospectivos
9.
Sensors (Basel) ; 21(22)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34833652

RESUMO

With the rapid progress of hardware and software, a wireless sensor network has been widely used in many applications in various fields. However, most discussions for the WSN node deployment mainly concentrated on the two-dimensional plane. In such a case, some large scale applications, such as information detection in deep space or deep sea, will require a good three dimensional (3D) sensor deployment scenario and also attract most scientists' interests. Excellent deployment algorithms enable sensors to be quickly deployed in designated areas with the help of unmanned aerial vehicles (UAVs). In this paper, for the first time, we present a three dimensional network deployment algorithm inspired by physical dusty plasma crystallization theory in large-scale WSN applications. Four kinds of performance evaluation methods in 3D space, such as the moving distance, the spatial distribution diversion, system coverage rate, and the system utilization are introduced and have been carefully tested.Furthermore, in order to improve the performance of the final deployment, we integrated the system coverage rate and the system utilization to analyze the parameter effects of the Debye length and the node sensing radius. This criterion attempts to find the optimal sensing radius with a fixed Debye length to maximize the sensing range of the sensor network while reducing the system redundancy. The results suggest that our 3D algorithm can quickly complete an overall 3D network deployment and then dynamically adjust parameters to achieve a better distribution. In practical applications, engineers may choose appropriate parameters based on the sensor's hardware capabilities to achieve a better 3D sensor network deployment. It may be significantly used in some large-scale 3D WSN applications in the near future.

10.
Int J Mol Sci ; 22(19)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34639080

RESUMO

The unconventional yeast Yarrowia lipolytica is extensively applied in bioproduction fields owing to its excellent metabolite and protein production ability. Nonetheless, utilization of this promising host is still restricted by the limited availability of precise and effective gene integration tools. In this study, a novel and efficient genetic tool was developed for targeted, repeated, and markerless gene integration based on Cre/lox site-specific recombination system. The developed tool required only a single selection marker and could completely excise the unnecessary sequences. A total of three plasmids were created and seven rounds of marker-free gene integration were examined in Y. lipolytica. All the integration efficiencies remained above 90%, and analysis of the protein production and growth characteristics of the engineered strains confirmed that genome modification via the novel genetic tool was feasible. Further work also confirmed that the genetic tool was effective for the integration of other genes, loci, and strains. Thus, this study significantly promotes the application of the Cre/lox system and presents a powerful tool for genome engineering in Y. lipolytica.


Assuntos
Proteínas Fúngicas/genética , Edição de Genes , Vetores Genéticos , Integrases/metabolismo , Plasmídeos/genética , Yarrowia/genética , Engenharia Genética , Integrases/genética , Recombinação Genética , Yarrowia/crescimento & desenvolvimento
11.
Macromol Rapid Commun ; 41(17): e2000313, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32767476

RESUMO

Multiple-stimuli responsive soft actuators with tunable initial shapes would have substantial potential in broad technological applications, ranging from advanced sensors, smart robots to biomedical devices. However, existing soft actuators are often limited to single initial shape and are unable to reversibly reconfigure into desirable shapes, which severely restricts the multifunctions that can be integrated into one actuator. Here, a novel reconfigurable supramolecular polymer/polyethylene terephthalate (PET) bilayer actuator exhibiting multiple-stimuli responses is presented. In this bilayer actuator, the supramolecular polymer layer constructed of poly(5-Norbornene-2-carboxylic acid-1,3-cyclooctadiene) (PNCCO) and azopyridine derivative (PyAzoPy) via H-bonds provides multiple-stimuli responses: PyAzoPy offers light response and carboxylic groups in PNCCO endow the actuator with humidity response. Meanwhile thermoplastic PET layer enables the bilayer actuators to be reconfigured into various shapes by thermal stimuli. The rationally designed actuators exhibit versatile capabilities to reversibly reconfigure into a set of initial shapes and carry out multiple functions, such as photo-driven "foldback-clip" and Ω-shaped crawling robots. In addition, bio-inspired plants constructed by reconfiguration of such actuators demonstrate reversible multiple-stimuli responses. It is anticipated that these novel actuators with highly tunable geometries and actuation modes would be useful to develop multifunctional devices capable of performing diverse tasks.

12.
Surg Endosc ; 34(10): 4382-4387, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31664578

RESUMO

BACKGROUND: Radical resection is the only curative option for patients with hilar cholangiocarcinoma (HCCA) to achieve long-term survival. However, due to the fact that radical resection of HCCA has high technical requirements, the safety and efficacy of laparoscopic resection for HCCA remains controversial. METHOD: From January 2015 to December 2018, 23 cases of HCCA underwent radical resection in our center. Clinical data of those patients were collected and analyzed retrospectively. RESULTS: 14 patients underwent laparoscopic resection and 9 cases received open resection. 2 patients in laparoscopic group were converted to laparotomy. Operation time in laparoscopic group was significantly longer than that in open group (519.4 ± 155.4 min vs 366.7 ± 93.1 min). Estimated blood loss (620.0 ± 681.2 ml vs 821.4 ± 713.8 ml) and incidence of intraoperative blood transfusion (5/9 vs 8/14) did not differ significantly between two groups. Pathological outcomes were comparable between two groups. Length of postoperative hospital stay (23.4 ± 13.4 days vs 17.8 ± 7.1 days), severe postoperative morbidity (3/9 vs 5/14), bile leakage of Grade A or B (5/9 vs 5/14), intra-abdominal bleeding (0/9 vs 1/14), intra-abdominal abscess (1/9 vs 0/14), wound infection (0/9 vs 1/14), pulmonary infection (2/9 vs 0/14), and liver failure (0/9 vs 0/14) did not differ significantly between two groups. One patient in laparoscopic group died (1/14) at 21 postoperative days due to intra-abdominal bleeding, while no 30-day mortality was observed in open group. CONCLUSION: Our results demonstrate that laparoscopic radical resection of HCCA is safe and feasible in experienced hands. Although laparoscopic resection for HCCA, which is still in initial and exploratory stage, fails to show any advantage over open resection in this study, we are optimistic with its wide application in future with the improvement of surgical techniques and experience.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/cirurgia , Laparoscopia , Idoso , Ductos Biliares/patologia , Feminino , Hepatectomia , Humanos , Fígado/cirurgia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Int J Med Sci ; 17(11): 1652-1664, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669967

RESUMO

Cancer cells can enter quiescent or dormant state to resist anticancer agents while maintaining the potential of reactivation. However, the molecular mechanism underlying quiescence entry and reactivation remains largely unknown. In this paper, cancer cells eventually entered a reversible quiescent state to resist long-term paclitaxel (PTX) stress. The quiescent cells were characterized with Na+/H+ exchanger 1 (NHE1) downregulation and showed acidic intracellular pH (pHi). Accordingly, decreasing pHi by NHE1 inhibitor could induce cell enter quiescence. Further, acidic pHi could activate the ubiquitin-proteasome system and inhibiting proteasome activity by MG132 prevented cells entering quiescence. In addition, we show that after partial release, the key G1-S transcription factor E2F1 protein level was not recovered, while MCM7 protein returned to normal level in the reactivated cells. More importantly, MCM7 knockdown inhibited G1/S genes transcription and inhibited the reactivated proliferation. Taken together, this study demonstrates a regulatory function of intracellular acidification and subsequent protein ubiquitination on quiescence entry, and reveals a supportive effect of MCM7 on the quiescence-reactivated proliferation.


Assuntos
Trocador 1 de Sódio-Hidrogênio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Leupeptinas/farmacologia , Paclitaxel/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Trocador 1 de Sódio-Hidrogênio/genética
14.
Int J Mol Sci ; 21(11)2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32516879

RESUMO

Candida tropicalis is a pathogenic fungus that can cause opportunistic infections in humans. The ability of Candida species to transition between yeast and filamentous growth forms is essential to their ability to undergo environmental adaptation and to maintain virulence. In other fungal species, such as Candida albicans, N-acetylglucosamine (GlcNAc) can induce filamentous growth, whereas it suppresses such growth in C. tropicalis. In the present study, we found that knocking out the GlcNA-specific transporter gene NGT1 was sufficient to enhance C. tropicalis filamentous growth on Lee's plus GlcNAc medium. This suggests that GlcNAc uptake into C. tropicalis cells is essential to the disruption of mycelial growth. As such, we further studied how GlcNAc catabolism-related genes were able to influence C. tropicalis filamentation. We found that HXK1 overexpression drove filamentous growth on Lee's media containing glucose and GlcNAc, whereas the deletion of the same gene disrupted this filamentous growth. Interestingly, the deletion of the DAC1 or NAG1 genes impaired C. tropicalis growth on Lee's plus GlcNAc plates. Overall, these results indicate that HXK1 can serve as a positive regulator of filamentous growth, with excess GlcNAc-6-PO4 accumulation being toxic to C. tropicalis. These findings may highlight novel therapeutic targets worthy of future investigation.


Assuntos
Acetilglucosamina/metabolismo , Candida tropicalis/fisiologia , Candidíase/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Deleção de Genes , Glucose/metabolismo , Humanos , Modelos Biológicos , Virulência
15.
Cancer Sci ; 110(1): 31-39, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30343514

RESUMO

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin-interleukin-2 (SA-IL-2) surface-modified tumor cell vaccine developed through our protein-anchor technology could induce specific antitumor T-cell responses, but this immunotherapy cannot completely eradicate the tumor. These effector T cells highly expressed programmed death receptor-1 (PD-1), and the expression of programmed death ligand-1 (PD-L1) in the tumor environment also was upregulated after SA-IL-2-modified vaccine therapy. PD-1/PD-L1 interaction promotes tumor immune evasion. Adding PD-1 blockade to SA-IL-2-modified vaccine therapy increased the number of CD4+ , CD8+ and CD8+ interferon-γ+ but not CD4+ Foxp3+ T cells. PD-1 blockade could rescue the activity of tumor-specific T lymphocytes induced by the SA-IL-2-modified vaccine. Combination therapy delayed tumor growth and protected mice against a second Renca cells but not melanoma cells challenge. Taken together, PD-1 blockade could reverse immune evasion in the treatment with SA-IL-2-modified vaccine, and eventually induce a stronger specific antitumor immune response against renal cell carcinoma.


Assuntos
Vacinas Anticâncer/administração & dosagem , Carcinoma de Células Renais/terapia , Imunoterapia/métodos , Interleucina-2/imunologia , Neoplasias Renais/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Terapia Combinada , Interferon gama/imunologia , Interferon gama/metabolismo , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Camundongos Endogâmicos BALB C , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-31279678

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

18.
Int J Cancer ; 142(10): 2106-2117, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29243219

RESUMO

Eliminating cancer stem cells (CSCs) is a key issue in eradicating tumor. The streptavidin-granulocyte-macrophage-colony stimulating factor (SA-GM-CSF) surface-modified bladder CSCs vaccine previously developed using our protein-anchor technology could effectively induce specific immune response for eliminating CSCs. However, program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling in tumor microenvironment results in tumor-adaptive immune resistance. Although the CSCs vaccine could increase the number of CD8+ T cells, a part of these CD8+ T cells expressed PD-1. Moreover, the CSCs vaccine upregulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1 blockade to the CSCs vaccine therapy increased the population of CD4+ , CD8+ and CD8+ IFN-γ+ but not CD4+ Foxp3+ T cells and induced the highest production of IFN-γ. PD-1 blockade could effectively enhance the functions of tumor-specific T lymphocytes generated by the CSCs vaccine. This combination therapy improved the cure rate among mice and effectively protected the mice against a second CSCs cell challenge, but not a RM-1 cell challenge. These results indicate that PD-1 blockade combined with the GM-CSF-modified CSCs vaccine effectively induced a strong and specific antitumor immune response against bladder cancer.


Assuntos
Vacinas Anticâncer/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Células-Tronco Neoplásicas/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Animais , Antígeno B7-H1/biossíntese , Antígeno B7-H1/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/terapia , Linhagem Celular Tumoral , Citocinas/sangue , Citocinas/imunologia , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Receptor de Morte Celular Programada 1/biossíntese , Receptor de Morte Celular Programada 1/imunologia , Distribuição Aleatória , Subpopulações de Linfócitos T/imunologia
19.
Cancer Sci ; 109(7): 2109-2118, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29770533

RESUMO

Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cell vaccine. The results of the in vitro study showed that NCTD induced apoptosis and inhibited proliferation of regulatory T cells (Tregs). Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in a pro-apoptotic effect. The results of the in vivo study showed that more tumor-infiltrating Tregs existed within peripheral blood and tumor tissue after treatment with the vaccine. Adding NCTD to vaccine treatment could decrease the number of tumor-infiltrating Tregs and increase the number of CD4+ and CD8+ T cells. Combination therapy with NCTD and vaccine was more effective in inhibiting tumor growth than the vaccine alone. In general, this is the first report that NCTD could induce apoptosis of Tregs and enhance the vaccine-induced immunity.


Assuntos
Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Vacinas Anticâncer/farmacologia , Neoplasias da Próstata/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Camundongos
20.
Surg Endosc ; 32(3): 1581-1582, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28779241

RESUMO

BACKGROUND: Pure laparoscopic radical resection of hilar cholangiocarcinoma is still a challenging procedure, in which laparoscopic lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy were included [1-4]. Relative report is rare in the world up to now. Hilar cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis or vessel invasion [5, 6]. We recently had a patient who underwent a pure laparoscopic extended right hepatectomy and lymph node dissection and hepaticojejunostomy for a type IIIa hilar cholangiocarcinoma. METHODS: The tumor was 20 × 15 × 12 mm in diameter and located in the right bile duct and common hepatic duct. Radiological examination showed that hepatic artery and portal vein was not invaded. After the division and mutilation of the right hepatic artery and the right portal vein, short hepatic veins were divided and cut off with clip and ultrasound knife from the anterior face of the vena cava. Mobilization was performed after the devascularization of the right liver, followed by the transection of liver parenchymal with CUSA and ultrasound knife. Finally, left hepatic bile duct jejunum Roux-en-Y reconstruction was performed. RESULTS: This patient underwent successfully with a totally laparoscopic procedure. An extended right hepatectomy (right hemihepatectomy combined with caudate lobectomy) and complete lymph node dissection and hepaticojejunostomy were performed in this operation. The operation time was nearly 590 min, and the intraoperative blood loss was about 300 ml. No obvious complication was observed and the postoperative hospital stay was 11 days. The final diagnosis of the hilar cholangiocarcinoma with no lymph node metastasis was pT2bN0M0 stage II (American Joint Committee on Cancer, AJCC). CONCLUSIONS: Pure laparoscopic resection for hilar cholangiocarcinoma was proved safe and feasible, which enabled the patient to recover early and have an opportunity to receive chemotherapy as soon as possible. We present a video of the described procedure.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia/métodos , Tumor de Klatskin/cirurgia , Laparoscopia/métodos , Anastomose Cirúrgica , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Artéria Hepática/cirurgia , Ducto Hepático Comum/cirurgia , Veias Hepáticas/cirurgia , Humanos , Jejunostomia , Tumor de Klatskin/patologia , Fígado/cirurgia , Excisão de Linfonodo , Metástase Linfática , Estadiamento de Neoplasias , Veia Porta/cirurgia
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