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The development of nanotechnology has provided numerous possibilities for the diagnosis and treatment of cancer. Paradoxically, some in vivo experimental studies have also shown that nanoparticles (NPs) could promote tumor progression, but the specific mechanism is not yet clear. Primary tumors can release extracellular vesicles (EVs) which can promote the inoculation and growth of tumor cells that have metastasized to distant organs. So, whether nanomaterials can promote tumor progression through tumor-derived EVs deserves further research. Here, we showed that TiO2 NPs, widely used in nanomedicine, could trigger tumor-derived EVs with enhanced pro-metastatic capacity in vitro and in vivo. Mechanically, miR-301a-3p derived from NPs-elicited EVs could be delivered into vascular endothelial cells, which inhibited the expression of VEGFR2 and VE-cadherin by targeting S1PR1, leading to disrupt the tight junctions of vascular endothelial cells, thus to promote vascular permeability and angiogenesis, and induce the formation of pre-metastasis niches in vivo. This study emphasizes that it is urgent to consider the effect of NPs on EVs under long-term use conditions when designing nanodrugs for cancer treatment.
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Vesículas Extracelulares , MicroRNAs , Nanopartículas , Neoplasias , Humanos , Células Endoteliais , Neoplasias/metabolismo , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismoRESUMO
BACKGROUND: Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition. CASE PRESENTATION: A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up. CONCLUSIONS: Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.
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Hemangioma , Ureter , Neoplasias Ureterais , Adulto , Erros de Diagnóstico/efeitos adversos , Feminino , Tecido de Granulação/patologia , Hemangioma/complicações , Hemangioma/diagnóstico , Hemangioma/cirurgia , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Masculino , Ureter/patologia , Ureter/cirurgia , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgiaRESUMO
Mucin 1 (MUC1), as an oncogene, is overexpressed in hepatocellular carcinoma (HCC) cells and promotes the progression and tumorigenesis of HCC through JNK/TGF-ß signaling pathway. In the present study, RNA interference (RNAi) and JNK inhibitor SP600125, which target MUC1 and/or JNK, were used to treat HCC cells in vitro, and the results showed that both silencing the expression of MUC1 and blocking the activity of JNK inhibited the proliferation of HCC cells. In addition, MUC1-stable-knockdown and SP600125 significantly inhibited the growth of tumors in the subcutaneous transplant tumor models that established in BALB/c nude mice rather than MUC1 or JNK siRNAs transiently transfection. Furthermore, the results from immunohistochemical staining assays showed that the inhibitory effects of MUC1 gene silencing and SP600125 on the proliferation of HCC cells in vivo were through the JNK/TGF-ß signaling pathway. These results indicate that MUC1 and JNK are attractive targets for HCC therapy and may provide new therapeutic strategies for the treatment of HCC.
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Carcinoma Hepatocelular/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Neoplasias Hepáticas/patologia , Mucina-1/genética , Interferência de RNA , Animais , Antracenos/farmacologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: A significant barrier to organ transplantation is the cellular rejection that occurs and mediated by antibodies, T cells, and innate immune cells. This study was aimed to determine the number of CD4(+)CD25(+)Foxp3(+) Treg, CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells in renal transplant recipients (RTR). METHODS: Renal transplantation was performed for a total of 35 patients with end-stage renal failure. The number of CD4(+)CD25(+)Foxp3(+) Treg, CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells, and the serum level of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17 were measured in pre- and post-transplant patients and 10 healthy controls (HC) using flow cytometry and Cytometric Bead Array (CBA). The association between the number of different subsets of CD4(+) T-cells and clinical parameters were analyzed among the pre- and post-transplant patients, and the healthy controls. RESULTS: The number of CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells were significantly increased in patients with End-Stage Renal Failure (ESRF) compared to the HC. Stratification analysis indicated that AMR (Acute antibody mediated acute rejection), AR (acute rejection) and CR (chronic rejection) groups displayed greater number of CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells as well as high level of serum IL-2, IFN-γ, TNF-α and IL-17. But, the AMR, AR and CR groups have shown lower level of CD4(+)CD25(+)Foxp3(+) T cells and serum IL-10 compared to transplant stable (TS) patients. Moreover, the number of Tregs were negatively correlated with the number of Th17 cells in RTR patients. The number of Tregs and Th17 cells were positively correlated with the eGFR and serum creatinine values, respectively. CONCLUSION: The imbalance between different types of CD4(+) T cells and dysregulated inflammatory cytokines may contribute towards renal transplantation rejection.
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Citocinas/sangue , Mediadores da Inflamação/sangue , Transplante de Rim , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Transplantados , Adulto , Biomarcadores , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunofenotipagem , Testes de Função Renal , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
AIMS: To determine the number of CD4(+)CD25(-)Foxp3(+), CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells in renal transplant recipients that are transplanted stable (TS), or experiencing accelerated rejection (ALR), or acute rejection (AR). METHODS: Renal transplantation was conducted in 28 patients with end-stage renal failure (ESRF). The number of peripheral CD4(+)CD25(-)Foxp3(+), CD4(+)CD25(+)Foxp3(+), or CD4(+)CXCR5(+)Foxp3(+) T cells and the serum levels of interleukin-10 (IL-10) were measured in pre- and post-transplant patients and these results were compared to 10 healthy controls (HC). Correlation between CD4(+)CD25(+)Foxp3(+) and estimated glomerular filtration rate (eGFR), CD4(+)CD25(-)Foxp3(+) and serum creatinine (Cr) levels, or Cr and IL-10 levels in TS patients was also determined. RESULTS: The number of CD4(+)CD25(-)Foxp3(+) T cells was significantly increased in patients with ESRF, as compared to HC. Stratification analysis demonstrated that TS patients contained greater numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells, higher levels of serum IL-10, and fewer numbers of CD4(+)CD25(-)Foxp3(+) T cells than ESRF patients. In contrast, ALR and AR patients contained fewer numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells, greater numbers of CD4(+)CD25(-)Foxp3(+) T cells, and lower levels of serum IL-10 than ESRF patients. In TS patients, the numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were positively correlated with eGFR and serum Cr levels, respectively. CONCLUSION: An imbalance of different types of CD4(+)Foxp3(+) T cells might be involved in renal transplant rejection.
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Rejeição de Enxerto/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Doença Aguda , Adulto , Antígenos CD4/metabolismo , Creatinina/sangue , Feminino , Fatores de Transcrição Forkhead/metabolismo , Taxa de Filtração Glomerular , Humanos , Interleucina-10/sangue , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores CXCR5/metabolismoRESUMO
Introduction: Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body's own immunity, thus effectively killing tumor cells. Therefore, a drug delivery system loaded with DOX and JQ1 was devised in this study. Methods: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo. Results: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo. Conclusion: We have successfully prepared a multifunctional platform for synergistic prostate cancer therapy.
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Apoptose , Azepinas , Doxorrubicina , Indóis , Nanopartículas , Polímeros , Neoplasias da Próstata , Masculino , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/farmacocinética , Doxorrubicina/administração & dosagem , Indóis/química , Indóis/farmacologia , Indóis/farmacocinética , Polímeros/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Nanopartículas/química , Humanos , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Azepinas/química , Azepinas/farmacologia , Azepinas/farmacocinética , Sinergismo Farmacológico , Sobrevivência Celular/efeitos dos fármacos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Antígeno B7-H1/metabolismo , TriazóisRESUMO
Multiparametric magnetic resonance imaging (mpMRI) has emerged as a first-line screening and diagnostic tool for prostate cancer, aiding in treatment selection and noninvasive radiotherapy guidance. However, the manual interpretation of MRI data is challenging and time-consuming, which may impact sensitivity and specificity. With recent technological advances, artificial intelligence (AI) in the form of computer-aided diagnosis (CAD) based on MRI data has been applied to prostate cancer diagnosis and treatment. Among AI techniques, deep learning involving convolutional neural networks contributes to detection, segmentation, scoring, grading, and prognostic evaluation of prostate cancer. CAD systems have automatic operation, rapid processing, and accuracy, incorporating multiple sequences of multiparametric MRI data of the prostate gland into the deep learning model. Thus, they have become a research direction of great interest, especially in smart healthcare. This review highlights the current progress of deep learning technology in MRI-based diagnosis and treatment of prostate cancer. The key elements of deep learning-based MRI image processing in CAD systems and radiotherapy of prostate cancer are briefly described, making it understandable not only for radiologists but also for general physicians without specialized imaging interpretation training. Deep learning technology enables lesion identification, detection, and segmentation, grading and scoring of prostate cancer, and prediction of postoperative recurrence and prognostic outcomes. The diagnostic accuracy of deep learning can be improved by optimizing models and algorithms, expanding medical database resources, and combining multi-omics data and comprehensive analysis of various morphological data. Deep learning has the potential to become the key diagnostic method in prostate cancer diagnosis and treatment in the future.
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Recent immunotherapy research has focused on chimeric antigen receptor-modified T cells (CAR-Ts). CAR-T therapies have been clinically applied to manage hematologic malignancies with satisfactory effectiveness. However, the application of CAR-T immunotherapy in solid tumors remains challenging. Even so, current CAR-T immunotherapies for prostate cancer (PCa) have shown some promise, giving hope to patients with advanced metastatic PCa. This review aimed to elucidate different types of prostate tumor-associated antigen targets, such as prostate-specific membrane antigen and prostate stem cell antigen, and their effects. The current status of the corresponding targets in clinical research through their applications was also discussed. To improve the efficacy of CAR-T immunotherapy, we addressed the possible applications of multimodal immunotherapy, chemotherapy, and CAR-T combined therapies. The obstacles of solid tumors were concisely elaborated. Further studies should aim to discover novel potential targets and establish new models by overcoming the inherent barriers of solid tumors, such as tumor heterogeneity and the immunosuppressive nature of the tumor microenvironment.
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Prostate cancer (PCa) is a prevalent malignancy with increasing incidence in middle-aged and older men. Despite various treatment options, advanced metastatic PCa remains challenging with poor prognosis and limited effective therapies. Nanomedicine, with its targeted drug delivery capabilities, has emerged as a promising approach to enhance treatment efficacy and reduce adverse effects. Prostate-specific membrane antigen (PSMA) stands as one of the most distinctive and highly selective biomarkers for PCa, exhibiting robust expression in PCa cells. In this review, we explore the applications of PSMA-targeted nanomedicines in advanced PCa management. Our primary objective is to bridge the gap between cutting-edge nanomedicine research and clinical practice, making it accessible to the medical community. We discuss mainstream treatment strategies for advanced PCa, including chemotherapy, radiotherapy, and immunotherapy, in the context of PSMA-targeted nanomedicines. Additionally, we elucidate novel treatment concepts such as photodynamic and photothermal therapies, along with nano-theragnostics. We present the content in a clear and accessible manner, appealing to general physicians, including those with limited backgrounds in biochemistry and bioengineering. The review emphasizes the potential benefits of PSMA-targeted nanomedicines in enhancing treatment efficiency and improving patient outcomes. While the use of PSMA-targeted nano-drug delivery has demonstrated promising results, further investigation is required to comprehend the precise mechanisms of action, pharmacotoxicity, and long-term outcomes. By meticulous optimization of the combination of nanomedicines and PSMA ligands, a novel horizon of PSMA-targeted nanomedicine-based combination therapy could bring renewed hope for patients with advanced PCa.
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Nanomedicina , Neoplasias da Próstata , Masculino , Pessoa de Meia-Idade , Humanos , Idoso , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Terapia Combinada , Resultado do TratamentoRESUMO
Purpose: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated. Results: Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57-0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59-0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39-0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30-0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68-12.63; OR: 1.07, 95% CrI: 0.03-36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15-2.11). Conclusion: Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.
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Prostate cancer (PCa) is the most common new cancer case and the second most fatal malignancy in men. Surgery, endocrine therapy, radiotherapy and chemotherapy are the main clinical treatment options for PCa. However, most prostate cancers can develop into castration-resistant prostate cancer (CRPC), and due to the invasiveness of prostate cancer cells, they become resistant to different treatments and activate tumor-promoting signaling pathways, thereby inducing chemoresistance, radioresistance, ADT resistance, and immune resistance. Nanotechnology, which can combine treatment with diagnostic imaging tools, is emerging as a promising treatment modality in prostate cancer therapy. Nanoparticles can not only promote their accumulation at the pathological site through passive targeting techniques for enhanced permeability and retention (EPR), but also provide additional advantages for active targeting using different ligands. This property results in a reduced drug dose to achieve the desired effect, a longer duration of action within the tumor and fewer side effects on healthy tissues. In addition, nanotechnology can create good synergy with radiotherapy, chemotherapy, thermotherapy, photodynamic therapy and gene therapy to enhance their therapeutic effects with greater scope, and reduce the resistance of prostate cancer. In this article, we intend to review and discuss the latest technologies regarding the use of nanomaterials as therapeutic and diagnostic tools for prostate cancer.
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Nanopartículas , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Nanomedicina , Neoplasias de Próstata Resistentes à Castração/patologia , Nanotecnologia , Nanopartículas/uso terapêuticoRESUMO
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA-DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA-DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA-DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
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Antígeno B7-H1 , Nanopartículas , Linhagem Celular Tumoral , Membrana Celular , Doxorrubicina/farmacologia , Imunoterapia , Indóis , Polímeros , RNA Interferente PequenoRESUMO
Prostate cancer (PCa) is a common malignant tumor in elderly men worldwide. Most primary PCas inevitably progress into castration-resistant prostate cancer (CRPC) after androgen deprivation therapy. The mechanisms contributing to this progression are still controversial. In this study, functional module genes, DNA methylations, core regulators, and potential drugs in primary PCa and CRPC were explored by integrating a series of bioinformatics analyses. First, 588 differentially expressed genes (DEGs) were identified. Combined with related genes, protein-protein interaction networks were constructed, and 22 and 14 significant modules were identified in primary PCa and CRPC, respectively. More DEGs were identified in differentially methylated genes in CRPC modules. The hub genes in CRPC included CDC20 and CDK1. Moreover, core noncoding RNAs and transcription factors that significantly regulate CRPC modules were identified, including TUG1, MALAT1, E2F3, and MED1. Finally, the prediction of potential drugs for primary PCa and CRPC was also performed. Exisulind and phosphodiesterase-4 inhibitors were predicted as potential drugs for CRPC. The results of this study provide a new way for biologists and pharmacists to understand the potential molecular mechanisms of CRPC and also provide valuable references for drug redirection and new drug development for PCa.
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Biologia Computacional , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Fatores de Transcrição/genéticaRESUMO
Prostate carcinoma is a global health problem and is estimated to be diagnosed in 1.1 million men/year, making this malignancy the second most frequently diagnosed cancer in males worldwide. micro RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. miRNAs contribute to cancer development and progression, and are expressed differently in normal tissues and cancers. In the present study, the biological function of miR-106a in the human prostate carcinoma and the associated regulatory mechanisms were investigated. miR-106a was significantly upregulated in human prostate cancer tissues when compared with normal tissues (P<0.05), and the overexpression of miR-106a was identified to promote PC-3 cell growth. Additionally, miRNA-106a inhibition significantly suppressed PC-3 cell growth. Furthermore, it was observed that the phosphatase and tensin homolog (PTEN) expression level was negatively associated with miR-106a expression level, and miRNA-106a directly targeted PTEN in the PC-3 cells. PTEN overexpression has a similar effect on PC-3 cell growth as loss of miR-106a. Taken together, the results of the present study indicate that upregulated miR-106a regulates PC-3 cell proliferation through PTEN. These results suggest that appropriate manipulation of miR-106a may provide a novel strategy in the future treatment of human prostate cancer.
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Prostate cancer is the second most common cancer in men worldwide. This study focused to clarify the roles of Metadherin (MTDH) and miR-342-3p in prostate cancer. We identified that MTDH was up-regulated and miR-342-3p was down-regulated in the prostate tissues, and there is an inverse correlation between MTDH and miR-342-3p. Functional studies revealed that miR-342-3p directly targets MTDH via binding to the 3' untranslated regions (UTRs) in the prostate cancer cells. Moreover, we also found MTDH overexpression in DU145 and PC3 cells inhibited apoptosis. Subsequently, miR-342-3p has been revealed to reverse the MTDH effect on the cellular apoptosis in the further studies. Our results indicate that MTDH repress apoptosis of prostate cancer in vitro and provides a new strategy for human prostate cancer therapy in the future.
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Thrombosis or embolism is the leading cause of death and long-term adult disability worldwide. To reduce the risk of thrombosis and hemorrhaging in patients, a facile and versatile method was developed to fabricate microcapsules for targeted antithrombotic drug delivery. The microcapsules were prepared via oxidative polymerization of dopamine on polystyrene microspheres, followed by immobilization of fibrinogen onto the surface of poly(dopamine) layers. Subsequently, microcapsules were obtained by removing the cores with THF. Nattokinase was loaded into the microcapsules via diffusion. The loading amount was approximately 0.05 mg g-1 at 37 °C, and the loading efficiency was nearly 75%, based on the initial concentration of nattokinase in PBS. The release of nattokinase was a gradual process at 37 °C, and the activity of the targeted activated platelets was highly efficient. The antithrombotic activity of the nattokinase microcapsules was evidenced by the sharp dissolution of fibrin clots and the blood clotting time indexes. A gradual release mechanism of platelet-inspired microcapsules used for targeted antithrombotic therapy was proposed. This strategy for targeted antithrombotic drug delivery, which lowers the demand dose and minimizes side effects while maximizing drug efficacy, provides a potential new way to treat life-threatening diseases caused by vascular disruption.
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Ovarian cancer is the most common gynecological malignancy. At present, cisplatin is used to treat ovarian cancer; however, the development of cisplatin resistance during therapy is a common obstacle to achieving favorable outcomes. Recently, the Bcell lymphoma 2 (Bcl2) BH4 domain has been reported to mediate the prosurvival activity of Bcl2 in cancer; however, the involvement of the BH4 domain of Bcl2 in the cisplatin resistance of ovarian carcinoma cells is not entirely clear. In this study, we observed the cytoplasmic and mitochondrial levels of Ca2+ by confocal laser microscopy. We also detected cell apoptosis using western blot analysis and flow cytometry. The present study demonstrated that TATfused inositol 1,4,5trisphosphate receptorderived peptide (TATIDPS), which targets the BH4 domain of Bcl2, increased cisplatininduced Ca2+ flux from the endoplasmic reticulum (ER) into the cytosol and mitochondria. In addition, TATIDPS increased cisplatininduced expression of mitochondrial apoptosisassociated proteins and ER stressassociated proteins. These results indicated that TATIDPS may enhance the cytotoxicity of cisplatin toward ovarian carcinoma cells by increasing ER Ca2+ release.
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Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Peptídeos/administração & dosagem , Peptídeos/genética , Domínios Proteicos/genéticaRESUMO
The highly conserved extracellular domain of M2 protein (M2e) of influenza A viruses has limited immunogenicity on its own. Hence, aiming to enhance immunogenicity of M2e protein, optimal approaches remain to be established. In this study, we created recombinant fusion protein vaccines by linking M2e consensus sequence of influenza A viruses with C-terminal domain of human serum albumin (HSA). Then HSA/M2e recombinant fusion protein was studied. Our results showed that HSA/M2e could induce strong anti-M2e specific humoral immune responses in the established mice model. Administration of HSA/M2e with Freund's adjuvant resulted in a higher number of IFN-γ-producing cells compared to HSA/M2e or M2e peptide emulsified in Freund's adjuvant. Furthermore, HSA/M2e was able to reduce viral load in the mice lungs and provide significant protection against lethal challenge with an H1N1 or an H3N2 virus compared to controls. In conclusion, this study has demonstrated a potential vaccine that could provide protection in preventing the threat of influenza outbreak because of rapid variation of the influenza virus.
Assuntos
Anticorpos Antivirais/sangue , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Albumina Sérica , Proteínas da Matriz Viral/imunologia , Animais , Proteção Cruzada , Surtos de Doenças/prevenção & controle , Feminino , Adjuvante de Freund/imunologia , Humanos , Imunidade Humoral , Vírus da Influenza A Subtipo H1N1/química , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/química , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Vacinação , Vacinas Sintéticas , Carga Viral , Proteínas da Matriz Viral/genéticaRESUMO
Atrazine, a widely used pesticide, is frequently detected in soil and surface water, which alarms epidemiologists and medical professionals because of its potential deleterious effects on health. Indeed, atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. Both animal and human studies have suggested that atrazine is possibly carcinogenic, although discrepant results have been reported. In this study, RM1 cells were used to explore the atrazine effects on prostate cancer. Proliferation, migration and invasion of RM1 cells were assessed by colony formation, wound-healing and invasion assays, respectively, after in vitro exposure to atrazine. In addition, an RM1 cell xenograft model was generated to evaluate the effects of atrazine in vivo. To explore the molecular mechanisms, qRTPCR, immunohistochemistry, and western blot analyses were employed to detect mRNA and protein levels of STAT3 signaling and cell cycle related proteins, including p53, p21, cyclin B1 and cyclin D1. Interestingly, RM1 cell proliferation was increased after treatment with atrazine, concomitantly with STAT3 signaling activation. These results suggest that atrazine promotes RM1 cell growth in vitro and in vivo by activating STAT3 signaling.
Assuntos
Atrazina/efeitos adversos , Praguicidas/efeitos adversos , Neoplasias da Próstata/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To clarify the composition of wound fluid (WF) and investigate the impact of WF on breast cancer cell lines. METHODS: The proliferation and migration of WF-treated breast cancer cells MDA-MB-231 and MCF-7 were assessed with colony formation test, MTT cell proliferation test and scratch wound test. The quantitative profiles of WF were analyzed using Bio-Plex Pro kits. RESULTS: The proliferation and migration of WF-treated breast cancer cells were significantly higher than that of untreated cells. Fifteen cytokines, 29 chemokines and 9 matrix metalloproteinases (MMPs) were assessed in WF. The concentrations of these factors were influenced by post-surgery days, neoadjuvant chemotherapy (NAC), TNM stage, pathological type and molecular subtype. The WF harvested from patients underwent NAC showed significant higher profiles of interleukin-1ß (IL-1ß), IL-4, IL-6, IL-17F, IL-21, IL-23, IL-25, IL-31, Interferon γ (IFNγ), CD40 ligand (CD40L), tumor necrosis factor α (TNFα), CXCL1, CXCL2, CXCL5, CCL3, CCL7 and CCL20. CONCLUSIONS: Surgery-induced WF promotes the proliferation and migration of breast cancer cells. The composition of WF is influenced by various clinical features and provides potential therapeutic targets to control local recurrence and tumor progression.