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1.
Front Immunol ; 12: 697854, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220860

RESUMO

Graft versus host disease (GVHD) is a common complication and the leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Pharmacological immunosuppression used in GVHD prophylaxis and treatment lacks specificity and can increase the likelihood of infection and relapse. Regulatory T lymphocytes (Tregs) play a vital role in restraining excessive immune responses and inducing peripheral immune tolerance. In particular, clinical trials have demonstrated that Tregs can prevent and treat GVHD, without increasing the risk of relapse and infection. Hence, adoptive transfer of Tregs to control GVHD using their immunosuppressive properties represents a promising therapeutic approach. To optimally apply Tregs for control of GVHD, a thorough understanding of their biology is necessary. In this review, we describe the biological characteristics of Tregs, including how the stability of FOXP3 expression can be maintained. We will also discuss the mechanisms underlying Tregs-mediated modulation of GVHD and approaches to effectively increase Tregs' numbers. Finally, we will examine the developing trends in the use of Tregs for clinical therapy.

2.
Nat Commun ; 12(1): 4230, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244494

RESUMO

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXß2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXß2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXß2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXß2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Assuntos
Processamento Alternativo , Carcinoma Epitelial do Ovário/genética , Proteínas da Matriz Extracelular/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas da Matriz Extracelular/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Integrina alfaXbeta2/genética , Integrina alfaXbeta2/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Fosforilação/genética , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Ovarian Res ; 14(1): 68, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33993885

RESUMO

BACKGROUND: Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China. METHODS: Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. RESULTS: Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060-0.759) and disease control rate (DCR) of 50% (95%CI = 0.140-0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. CONCLUSION: It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.

4.
Anticancer Agents Med Chem ; 21(1): 91-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32798378

RESUMO

BACKGROUND: Photodynamic Therapy (PDT) is a photoactivation or photosensitization process, wherein vitamin K3 (Vit K3) serves as a photosensitizer to produce Reactive Oxygen Species (ROS) against bacteria at appropriate wavelengths. In this study, we used Vit K3 treatment combined with Ultraviolet radiation A (UVA) to produce photodynamic effects on cervical cancer. METHODS: The dose-concentration relationship between Vit K3 treatment and UVA on tumor cells was analyzed through the Cell Counting Kit-8 method. Then, the morphological characteristics of apoptosis cells were observed through fluorescent staining and fluorescence microscopy. Apoptosis after treatment with Vit K3 treatment, UVA, and Vit K3 treatment plus UVA was further observed through Western blot analysis, flow cytometry, and TUNEL assay. The xenograft models from HeLa cells were established for the exploration of the photodynamic effect of Vit K3 treatment on cervical cancer in vivo. RESULTS: Vit K3 treatment plus UVA reduced tumor cell viability in a dose-dependent manner. Further studies indicated that Vit K3 treatment plus UVA can inhibit tumor growth and enhance the apoptosis of cervical cancer cells. In the combination group, the expression levels of cleaved caspase-3, cleaved caspase-9, B-cell lymphoma- extra large (Bcl-xl), and cytochrome c (cyt-c) increased obviously, whereas the expression level of Bcell lymphoma 2 (Bcl-2) decreased relative to the expression levels of UVA- or Vit K3-treated cells. In the in vivo experiments, tumor growth was inhibited significantly in the VitK3 treatment plus UVA group. Additionally, we demonstrated that the combination therapy mediated an increase in cleaved caspase-3 and cleaved caspase-9 expression and decrease in Bcl-2 expression in vivo. CONCLUSION: Our results showed that Vit K3 treatment combined with UVA exerted photodynamic effects on cervical cancer cells by activating mitochondrial apoptosis pathways.


Assuntos
Antineoplásicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Vitamina K 3/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Terapia Combinada , Citocromos c/genética , Citocromos c/metabolismo , Descoberta de Drogas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Células HeLa , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Raios Ultravioleta , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
5.
J Clin Pathol ; 74(4): 223-227, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32220941

RESUMO

AIMS: The aim of this study is to investigate the expression profiles of cell cycle related proteins in nasal extranodal NK/T cell lymphoma, nasal type (ENKTCL). METHODS: The expression profiles of cell cycle related proteins were assessed with a cell cycle antibody array and validated by immunohistochemistry. Correlations between the expression levels of proteins and clinical outcomes of patients with nasal ENKTCL were evaluated. RESULTS: The expression of full length ataxia telangiectasia mutated (ATM) in nasal ENKTCL significantly decreased compared with that in nasal benign lymphoid proliferative disease (NBLPD), but the expression levels of p-ATM, CHK2 and RAD51 significantly increased in nasal ENKTCL compared with that in NBLPD. Kaplan-Meier analysis showed that the expression levels of p-ATM and CHK2 in nasal ENKTCL were inversely related to overall survival (p=0.011 and p=0.025, respectively). CONCLUSION: Abnormalities in the ATM pathway may play a crucial role in the oncogenesis and chemoradiotherapy resistance of nasal ENKTCL.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/análise , Biomarcadores Tumorais/análise , Quinase do Ponto de Checagem 2/análise , Linfoma Extranodal de Células T-NK/enzimologia , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Humanos , Imuno-Histoquímica , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/terapia , Gradação de Tumores , Fosforilação , Rad51 Recombinase/análise , Tolerância a Radiação , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
6.
Environ Res ; 196: 110415, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33159927

RESUMO

Rapid urbanization and industrialization in China have incurred serious air pollution and consequent health concerns. In this study, we examined the modifying effects of urbanization and socioeconomic factors on the association between PM2.5 and incidence of esophageal cancer (EC) in 2000-2015 using spatiotemporal techniques and a quasi-Poisson generalized linear model. The results showed a downward trend of EC and high-risk areas aggregated in North China and Huai River Basin. In addition, a stronger association between PM2.5 and incidence was observed in low urbanization group, and the association was stronger for females than males. When exposure time-windows were adjusted as 0, 5, 10, 15 years, the incidence risk increased by 2.48% (95% CI: 2.23%, 2.73%), 2.20% (95% CI: 1.91%, 2.49%), 2.18% (95% CI%: 1.92%, 2.43%), 1.87% (95% CI%:1.64, 2.10%) for males, respectively and 4.03% (95% CI: 3.63%, 4.43%), 2.20% (95% CI: 1.91%, 2.49%), 3.97% (95% CI: 3.54%, 4.41%), 3.06% (95% CI: 2.71%, 3.41%) for females, respectively. The findings indicated people in low urbanization group faced with a stronger EC risk caused by PM2.5, which contributes to a more comprehensive understanding of combating EC challenges related to PM2.5 pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Esofágicas , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Masculino , Material Particulado/análise , Material Particulado/toxicidade , Fatores Socioeconômicos , Análise Espaço-Temporal
7.
J Hazard Mater ; 404(Pt A): 124106, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33053472

RESUMO

Recently, black phosphorous (BP) nanosheets as an emerging nanomaterial have presented significant fire safety improvement in polymer nanocomposites. However, as elemental phosphorus, fire safety improvement effect of BP nanosheets on polymer composites builds on the conversion of gaseous pyrolysis products into smoke particles, which inevitably promotes the formation and release of smoke particles. From the perspective of overall fire safety improvement, it is vital to simultaneously suppress the heat release and smoke production of polymer/BP composites. Herein, melamine-mediated graphene/black phosphorous nanohybrids (GNS/MA/BP) were fabricated through electrostatic-driving self-assembly process and introduced into polyether thermoplastic polyurethane (TPU). During combustion, the barrier function provided by thermally stable layered structure of graphene (GNS) enables more pyrolysis products of BP nanosheets to be kept within condensed phase and react with polymer matrix. Compared to pure TPU, the incorporated hierarchical nanostructure (GNS/MA/BP-2) decreases PHRR, THR, and total CO2 release of TPU composite by 54.7%, 23.5%, and 32.5%, respectively. Beside, in contrast to TPU-BP composite, the release rate of toxic smoke and CO gas of TPU-GNS/MA/BP-2 composite are reduced by 46.7% and 49.4%. With barrier function of graphene, the heat and smoke release behavior of polymer/BP nanocomposites is effectively suppressed.

8.
Theriogenology ; 161: 140-150, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310232

RESUMO

Luman has been reported to be involved in the formation of COP II-mediated transport vesicles that affect protein transportation and secretion. Western blotting, immunohistochemistry, immunofluorescence, and RT-qPCR indicated that Luman is widely expressed in the male mouse reproductive system. In sperm, Luman was mainly located in the sperm tail, and the expression level increased with sperm maturity. In the testis, Luman was located in Leydig cells. In MLTC-1, a high-concentration hCG treatment significantly increased GRP78, ATF6, p-IRE1, and p-EIF2S1 expression but had no effect on Luman expression. To investigate the role of Luman in hCG-induced ER stress (ERS), experiments were conducted to examine the consequences of short hairpin RNA (shRNA)-mediated Luman knockdown in MLTC-1 cells. Luman knockdown decreased the percentage of S phase cells and up-regulated Cyclin A1, Cyclin B1, and Cyclin D2 expression. ELISA and WB results showed that with Luman knockdown, Cyp11a1, p-IRE1, and p-EIF2S1 expression and testosterone secretion were significantly increased, while GRP78 and CHOP expression were decreased. Flow cytometry results showed that Luman knockdown reduced MLTC-1 cell apoptosis. RT-qPCR and WB results showed that Luman knockdown significantly up-regulated BCL-2 expression and decreased Caspase-3 and BAX expression. These data suggest that Luman is widely expressed in the male mouse reproductive system. In MLTC-1 cells, Luman knockdown up-regulated p-IRE1, p-EIF2S1, and BCL-2 expression and decreased GRP78, CHOP, BAX, and Caspase-3 expression. We propose that Luman knockdown reduces cell apoptosis through the ERS pathway, thereby promoting cell survival and testosterone secretion. These findings provide new insights into the role of Luman in hCG-induced ERS.


Assuntos
Apoptose , Células Intersticiais do Testículo , Animais , Sobrevivência Celular , Masculino , Camundongos , RNA Interferente Pequeno , Testículo
9.
Cancer Manag Res ; 12: 11085-11093, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173341

RESUMO

Purpose: Platinum resistance is a primary barrier to improving the survival rate of ovarian cancer. The relationship between mtDNA somatic mutations and response to platinum-based chemotherapy in ovarian cancer has not been well clarified. Patients and Methods: Here, we employed the next-generation sequencing (NGS) platform to identify mtDNA mutations of the unrelated high-grade serous ovarian cancer (HGSOC) patients. Results: We identified 569 germline variants and 28 mtDNA somatic mutations, and found the platinum-sensitive relapsed HGSOC patients had more synonymous mutations while the platinum-resistant relapsed HGSOC patients had more missense mutations in the mtDNA somatic mutations. Meanwhile, we found that the HGSOC patients who harbored heteroplasmic pathogenic mtDNA somatic mutations had significantly higher prevalence of both platinum-resistance and relapse than those without (80.0% versus 16.7%, p=0.035). Additionally, we observed that the tumor tissues had significantly higher lactate-to-pyruvate (L/P) ratio than the paired nontumor tissues (p<0.001), and L/P ratio of tumors with any heteroplasmic pathogenic mtDNA mutations was significantly higher than that of the tumors free of pathogenic mtDNA mutations (p=0.025). Conclusion: Our findings indicate that these heteroplasmic pathogenic mtDNA somatic mutations may cause decreased respiratory chain activity and lead to the metabolism remodeling that seem to be beneficial for progression of both platinum-based chemotherapy resistance and relapse.

10.
Onco Targets Ther ; 13: 9857-9863, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116571

RESUMO

Purpose: Survival of platinum-resistant ovarian cancer (PROC) patients is significantly shortened to around 12 months. Anlotinib is a new multi-target tyrosine kinase inhibitor. The goal of this study is to evaluate the efficacy and safety of anlotinib in PROC patients. Patients and Methods: PROC patients treated with anlotinib in Jiangsu Cancer Hospital between June 2018 to September 2019 were recruited. Most patients received an initial bolus of 12mg orally once daily on days 1-14 of a 21-day cycle (except one received a dose of 10mg and another one received a dose of 8mg orally once a day). The adverse events (AEs) and efficacy were analyzed by CTCAE 4.0 and RECIST 1.1. Results: Of all 15 enrolled patients, 12 patients received anlotinib as multi-line therapy and 3 patients received it as maintenance therapy. In the multi-line therapy group, eight patients received anlotinib monotherapy and four patients received anlotinib combined with chemotherapy. Ultimately, evaluation showed that one patient achieved partial response (PR), five patients achieved stable disease (SD) and one patient had progressive disease (PD) with monotherapy, yielding objective response rate (ORR) of 14.3% (95% CI=0.01-0.58) and disease control rate (DCR) of 85.7% (95% CI=0.42-0.99). One patient achieved PR, two patients achieved SD with combination therapy, yielding ORR of 33.3% (95% CI=0.02-0.87) and DCR of 100% (95% CI=0.31-1.00). Three patients with maintenance therapy were followed up for 5, 8, and 11 months, respectively. The most grade 1-2 AEs were hand-foot syndrome, nausea, and hypertension. Serious AEs (SAEs) (Grade 3-4) were observed in one patient with oral ulcer and another patient with hand-foot syndrome that were managed by dose reduction. Conclusion: Anlotinib was of promising efficacy and well tolerated in PROC patients. This is the first retrospective study about exploratory therapy for ovarian cancer patients with anlotinib.

11.
J Hazard Mater ; 399: 123015, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937706

RESUMO

The black phosphorus (BP) can be compounded with other two-dimensional materials with flame retardant effect to achieve better synergistic effect. Herein, the multifunctional BP-RGO nanohybrids was fabricated by solvothermal strategy to improve the dispersion state of BP in epoxy resin (EP) and enhance its fire safety performance, where the reduced graphene oxide (RGO) was attached on the surface of BP via PC and POC bonds. With the incorporation of 2.0 wt% BP-RGO into EP matrix, 54.4 % reduction in total heat release (THR) was achieved along with 55.2 % decrease in peak heat release rate (PHRR) compared with neat EP. As a similar trend, the toxic CO and aromatic compounds were significantly inhibited, and the maximum decrease (28.5 %) in total smoke production (TSP) was achieved, indicating the enhanced fire safety performance of EP nanocomposites. These positive results is attributed to the synergistic effect of physical nano-barrier, free radicals trapping and char formation between BP and RGO components. Meanwhile, the EP/BP-RGO2.0 nanocomposites exhibited satisfying air stability even after being immersed in water for a month. This work enriches the strategies for enhancing the air stability of BP, and confirms its potential for smoke toxicity and fire hazard suppression in polymer nanocomposites.

12.
Curr Med Sci ; 40(4): 719-728, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32862383

RESUMO

Cancer testis (CT) antigens have received particular attention in cancer immunotherapy. OY-TES-1 is a member of CT antigens. This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma (HCC). OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR (RT-PCR). Of the 56 cases of HCC tissues tested, 37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR. OY-TES-1 protein was subsequently observed on a panel of tissue microarrays. Sera from patients were tested for OY-TES-1 antibody by ELISA. To identify OY-TES-1 capable of inducing cellular immune response, OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro. The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56 (73.21%) HCC tissues, whereas none in 5 normal liver tissues. OY-TES-1 mRNA was frequently expressed not only in HCC tissues (72.97%, 27/37), but also in paired adjacent non-cancer tissues (64.86%, 24/37). But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues (0.76854 vs. 0.09834, P=0.021). Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues, and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues. Seropositivity was detected in 10 of the 45 HCC patients, but not detected in 17 cirrhosis patients and 76 healthy donors. The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2+ HCC cell line which expressed OY-TES-1. The target lysis was mainly HLA class I -dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule. In summary, OY-TES-1 expression is up-regulated in HCC tissues and can be recognized by humoral and cellular responses, which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Neoplasias Hepáticas/patologia , Regulação para Cima , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Estadiamento de Neoplasias , Linfócitos T Citotóxicos/imunologia
13.
Mol Oncol ; 14(6): 1348-1364, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32306523

RESUMO

High-mobility group protein B1 (HMGB1) has important functions in cancer cell proliferation and metastasis. However, the mechanisms of HMGB1 function in non-small-cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the underlying mechanism of HMGB1-dependent tumor cell proliferation and NSCLC metastasis. Firstly, we found high HMGB1 expression in NSCLC and showed that HMBG1 promoted proliferation, migration, and invasion of NSCLC cells. HMGB1 could bind to SNAI1 promoter and activate the expression of SNAI1. In addition, HMGB1 could transcriptionally regulate the lncRNA RSF1-IT2. RSF1-IT2 was found to function as ceRNA, sponging miR-129-5p, which targets SNAI1. Notably, HMGB1 was also identified as a target of miR-129-5p, which indicates the establishment of a positive feedback loop. Consequently, high expression of RSF1-IT2 and SNAI1 was found to closely correlate with tumor progression in both HMGB1-overexpressing xenograft nude mice and patients with NSCLC. Taken together, our findings provide new insights into molecular mechanisms of HMGB1-dependent tumor metastasis. Components of the HMGB1-RSF1-IT2-miR-129-5p-SNAI1 pathway may have a potential as prognostic and therapeutic targets in NSCLC.

14.
Biosci Rep ; 40(5)2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32242897

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is a malignant disease arising from the abnormal proliferation of T lymphocyte in marrow. Long non-coding RNAs (lncRNAs) are one kind of non-coding RNAs (ncRNAs), which were reported to modulate the initiation or progression of diverse cancers. However, the role of LINC00511 in T-ALL was unknown. To figure out the function and mechanism of LINC00511 in T-ALL, a series of experiments were carried out. Based on the experimental results, we discovered that LINC00511 boosted cell proliferation and invasion, but hindered cell apoptosis in T-ALL cells. Besides, based on bio-informatics tool, miR-195-5p was selected for further exploration. Then, miR-195-5p was validated to bind with LINC00511. Hereafter, LRRK1 was testified to serve as a target gene of miR-195-5p. At last, rescue assays suggested that LRRK1 overexpression restored sh-LINC00511#1-mediated effects on cell proliferation and apoptosis. All in all, LINC00511 exacerbated T-ALL progression via miR-195-5p/LRRK1 axis, implying a potential therapeutic clue for the patients with T-ALL.


Assuntos
MicroRNAs/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Leucêmica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proteínas Serina-Treonina Quinases/genética , RNA Longo não Codificante/genética , Transdução de Sinais
15.
J Ovarian Res ; 13(1): 29, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183851

RESUMO

BACKGROUND: Olaparib, a poly ADP-ribose polymerase (PARP) inhibitor, has proven to be effective and safe as maintenance therapy and multiline therapy in ovarian cancer, especially in patients with BRCA mutations. This study intended to observe the influence of tumor load on the efficacy and safety of olaparib in recurrent ovarian cancer. CASES PRESENTATION: Three patients harbored gBRCAwt with low tumor load (LTL), while two women harbored BRCAmt with high tumor load (HTL) were recruited. Two of the three LTL patients achieved partial response, and the other showed stable disease. Both HTL patients were assessed to have progressive disease in a short time. Olaparib appears to be effective and safe for LTL recurrent ovarian cancer patients even if it is gBRCAwt, while the response is poor in HTL patients. CONCLUSIONS: Tumor load may be another potential marker to predict the effect of PARP inhibitors. The present head-to-head observational series provides new evidence on this issue for further research from bench to bedside in the future.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biomarcadores Tumorais , Biópsia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/mortalidade , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Ultrassonografia
16.
J Matern Fetal Neonatal Med ; 33(24): 4133-4138, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30890003

RESUMO

Objective: The results of the study on the relationship between obesity and cord blood irisin were far apart. The aim of this study was to explore the relationship between cord blood irisin levels and neonatal growth in China.Methods: A cross-sectional study of 400 neonates and their mothers was conducted in the obstetrics department of Shandong provincial hospital in China. Neonates were divided into a fetal macrosomia group and a normal birth weight group based on customized birth-weight standards and divided into non-high-ponderal index group and high ponderal index group based on ponderal index. Levels of irisin in umbilical cord blood were measured by enzyme-linked immunosorbent assay.Results: Irisin concentrations in the fetal macrosomia group were significantly higher than in the normal birth weight group (p = .032). Irisin levels in the high ponderal index group were significantly higher compared with the non-high-ponderal index group (p = .032). After adjustment for confounding variables, logistic regression analysis identified macrosomia affected factors include weight gained during pregnancy (OR = 1.15, p = .028), infant's sex (OR = 9.73, p = .001) and found that affected factors of high ponderal index include weight gained during pregnancy (OR = 1.08, p = .025), maternal age (OR = 1.10, p = .018). Compared with the reference category (<108.62 ng/ml), infants with a cord blood irisin level above 241.44 ng/ml had significantly elevated risk of macrosomia (OR = 8.57, p = .010) and had significantly elevated risk of high birth ponderal index (PI) (OR = 3.15, p = .002). A nonlinear relationship was observed between irisin levels and fetal macrosomia. The higher the concentration of irisin, the greater the risk of fetal macrosomia.Conclusions: We found that as the cord blood irisin increased, the risk of having fetal macrosomia was greater. Weight gained during pregnancy and high cord blood irisin levels were independent predictors of fetal adiposity.


Assuntos
Sangue Fetal , Macrossomia Fetal , Fibronectinas , Peso ao Nascer , China/epidemiologia , Estudos Transversais , Feminino , Sangue Fetal/química , Macrossomia Fetal/epidemiologia , Humanos , Recém-Nascido , Gravidez
17.
Minerva Endocrinol ; 45(1): 61-69, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29160049

RESUMO

INTRODUCTION: Irisin is a newly discovered myokine, which is involved in energy metabolism and associated with "browning" of the white adipose tissue, obesity, diabetes mellitus and metabolic syndrome. It is still uncertain that whether irisin level is associated with coronary artery disease. The purpose of this study was to explore the relationship between irisin levels and coronary artery disease. EVIDENCE ACQUISITION: A search of PubMed, MEDLINE, Elsevier Science Direct, Springer, Web of Science and China National Knowledge Infrastructure (CNKI) for studies published from 2000 to 2017 was undertaken to identify relevant studies. Case-control studies that reported the association between irisin levels and coronary artery disease were included. Methodological quality of the studies was assessed according to the Newcastle-Ottawa Scale. Random-efforts models were used to analyze the weighted mean difference (WMD) and its 95% confidence interval (CI). Subgroup analysis was performed to explore potential sources of heterogeneity. EVIDENCE SYNTHESIS: From 741 studies, 7 case-control studies involving 867 patients and 700 controls were selected for meta-analysis based on our inclusion and exclusion criteria. In these case-control studies, irisin concentrations were lower in coronary artery disease patients compared with healthy controls. In the meta-analysis, the pooled data indicated that irisin levels were -18.10 ng/mL ([95% CI: -35.53 to -0.68 ng/mL]; P<0.05) lower in patients with cardiovascular disease or atherosclerosis than healthy controls. CONCLUSIONS: This study confirmed that irisin levels were significantly lower in patients with coronary artery disease.


Assuntos
Doença da Artéria Coronariana/sangue , Fibronectinas/sangue , Animais , Humanos , Estudos Observacionais como Assunto
18.
Am J Surg Pathol ; 44(4): 456-466, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31651526

RESUMO

A malignant gastrointestinal neuroectodermal tumor (GNET) is rare, and it is therefore yet to be completely understood. This study aimed to present the clinicopathologic features of GNET, including treatment information. We included 19 patients with GNET with a mean tumor size of 4.2 cm. The most common site of tumor origin was the small intestine (57.9%), followed by the stomach (15.8%), colon (10.5%), ileocecal junction (5.3%), lower esophagus (5.3%), and anal canal (5.3%). Microscopically, the tumors were composed of epithelioid cells with eosinophilic or clear cytoplasm arranged in nest, sheet-like, papillary, or pseudoalveolar patterns and/or spindle tumor cells with eosinophilic cytoplasm arranged in a fascicular pattern. Immunohistochemically, the tumor cells stained positively for S100 (19/19,100%), SOX10 (14/15, 93.3%), vimentin (17/17, 100%), synaptophysin (Syn) (7/17, 41.2%), CD56 (4/13, 30.8%), CD99 (1/5, 20%), and CD117 (1/15, 6.7%), and negatively for HMB45, Melan A, DOG1, CD34, AE1/AE3, CAM5.2, chromogranin A, smooth muscle actin, and desmin. In total, 14/15 (93.3%) cases showed split Ewing sarcoma breakpoint region 1 gene (EWSR1) signals consistent with a chromosomal translocation involving EWSR1. Within a mean follow-up of 29.7 months (range: 3 to 63 mo), 2/15 (13.3%) patients died of disease, 5 (33.3%) were alive with disease, and 8 (53.3%) had no evidence of disease. Two and 1 patients showed partial response to apatinib and anlotinib, respectively. In conclusion, GNET has distinctive morphologic, immunohistochemical, and molecular genetic features and should be distinguished from other gastrointestinal tract malignancies. Apatinib and anlotinib might be effective for the treatment of advanced GNET and could prolong patient survival.


Assuntos
Biomarcadores Tumorais , Neoplasias Gastrointestinais , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Tumores Neuroectodérmicos , Proteína EWS de Ligação a RNA/genética , Translocação Genética , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Feminino , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Predisposição Genética para Doença , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tumores Neuroectodérmicos/química , Tumores Neuroectodérmicos/tratamento farmacológico , Tumores Neuroectodérmicos/genética , Tumores Neuroectodérmicos/patologia , Valor Preditivo dos Testes , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Resultado do Tratamento , Carga Tumoral
19.
J Ovarian Res ; 12(1): 117, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31775908

RESUMO

PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitor, is a milestone in treatment of ovarian cancer. However, there is no real world study from China regarding the clinical outcome of the taking PARP inhibitor (PARPi), Olaparib(Lynparza™). The goal of this research is to evaluate the side effects and short-term efficacy in advanced ovarian cancer patients who administered Olaparib. METHODS: Patients with ovarian cancer, fallopian tube cancer and peritoneal cancer that treated with Olaparib in The Affiliated Cancer Hospital of Nanjing Medical University between September 2018 and June 2019 were recruited. The drug associated Adverse Events (AEs) were collected and short-term efficacy were analyzed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) . RESULTS: Of all 28 enrolled patients, 92.9% were ovarian cancer, 7.1% were fallopian tube cancer, and 39.3% cases harbored germline BRCA-mutation. There were 6(21.4%) patients received Olaparib after multi-line chemotherapy, and 10 patients (35.7%) as second-line maintenance therapy and 2 patients (7.1%) as first-line maintenance therapy. There were still other 10 cases (35.7%) received Olaparib as exploratory therapy. Abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling were newly reported AEs. Serious Adverse Events(SAEs) were usually managed by dose interruption or dose reduction, rather than discontinuation. 3 patients discontinued treatment, 8 patients received reduced dose of Olaparib, and 4 patients stopped therapy after the alleviation of AEs. Of all 28 enrolled cases, in monotherapy group, 1 of 6 patients achieved stable disease(SD) and also 2 patients achieved stable disease(SD) combined with anti-angiogenic drugs when disease progressed. 2 patients achieved complete remission(CR) and 3 patients were stable with exploratory therapy. CONCLUSIONS: The AEs of Olaparib were all manageable. For the first time, we also identified several AEs such as abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling during the follow-up which have not been reported. The short-term efficacy was observed in some exploratory cases that provided new potential indication to PARPi-related clinical trials.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Proteína BRCA1/genética , Proteína BRCA2/genética , Antígeno Ca-125/sangue , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Resultado do Tratamento
20.
Environ Monit Assess ; 191(7): 462, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31240492

RESUMO

Coastal soils are particularly sensitive to nonnative species invasion. In this context, spatially explicit soil information is essential for improving the knowledge of the role of soil in changing environments, supporting coastal sustainable management. Synthetic-aperture radar (SAR) data provides an attractive opportunity to monitor soil because the acquisition of images is independent of weather and daylight. However, SAR has not been commonly used for soil prediction. In this study, we firstly investigated the temporal variation of vegetation canopy and the soil-vegetation relationship using Sentinel-1 data in an invaded coastal wetland. And then we built 3D models to predict soil properties at multiple depths. A total of 16 Sentinel-1 images were acquired in a growing season. A series of soil physicochemical properties were examined including soil bulk density, texture, organic/inorganic carbon, pH, salinity, total nitrogen, and C/N ratio, relating to three depth layers in the top 1-m depth. Our results showed that time-series Sentinel-1 data can capture temporal characteristics of vegetation, and VH/VV was more sensitive to the vegetation growth than VH and VV. The soil-vegetation relationship captured by time-series SAR data was beneficial to predict soil properties, especially for soil chemical properties. The models provided permissible prediction accuracy, with an average RPD of 0.99. We concluded that the prior understanding of the temporal variation of SAR data is essential for developing practical soil prediction strategy. Our results highlight that SAR has the potential to predict a diverse set of soil properties in coastal wetlands with dense vegetation cover.


Assuntos
Monitoramento Ambiental/métodos , Imagens de Satélites/métodos , Solo/química , Áreas Alagadas , Carbono/análise , China , Espécies Introduzidas/estatística & dados numéricos , Nitrogênio/análise , Salinidade , Estações do Ano
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