Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
Int J Cancer ; 150(11): 1745-1759, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34952967

RESUMO

Poly(ADP-ribose) polymerase (PARP) enzymes, especially PARP1, play important roles in the DNA damage response and in the maintenance of genome stability, which makes PARPis a classic synthetic lethal therapy for BRCA-deficient tumors. Conventional mechanisms suggest that PARPis exert their effects via catalytic inhibition and PARP-DNA trapping. Recently, PARP1 has been found to play a role in the immune modulation of tumors. The blockade of PARP1 is able to induce innate immunity through a series of molecular mechanisms, thus allowing the prediction of the feasibility of PARPis combined with immune agents in the treatment of tumors. PARPis combined with immunomodulators may have a stronger tumor suppressive effect on inhibiting tumor growth and blocking immune escape.


Assuntos
Dano ao DNA , Inibidores de Poli(ADP-Ribose) Polimerases , Poli(ADP-Ribose) Polimerases , Animais , Instabilidade Genômica , Humanos , Imunidade Inata , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo
2.
Ophthalmology ; 129(7): 771-780, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35245602

RESUMO

PURPOSE: To assess the predictive value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, and histologic features for outcomes and metastasis patterns in conjunctival melanoma (CM). DESIGN: Retrospective, single-center cohort study. PARTICIPANTS: Eighty-three patients with CM were treated at Shanghai Ninth People's Hospital between 2000 and 2021. METHODS: We reviewed the clinical and histologic parameters and used Kaplan-Meier survival curves and Cox proportional hazards regression models for risk factor analyses. MAIN OUTCOME MEASURES: Time to nodal/distant metastasis, disease-specific survival, metastatic pattern, and metastatic site. RESULTS: At presentation, 5 patients (6%) had clinical tumor (cT)1 disease, 34 patients (41%) had cT2 disease, and 44 patients (53%) had cT3 disease. Four patients (5%) had nodal metastasis (N1), and none had distant metastasis (M1). During follow-up, 12 patients (14%) developed nodal metastasis, 29 patients (35%) developed distant metastasis, and 26 patients (31%) died of disease. The brain, liver, and lung were common distant metastasis sites. Higher cT category was associated with increased risks of distant metastasis (P < 0.001) and disease-specific death (P = 0.002). The separate analysis of primary and recurrent tumors at presentation showed that the patients with cT3 tumors had a higher risk of distant metastasis than those with cT2 tumors. Greater tumor thickness, ulceration, and the presence of regression were correlated with distant metastasis. Previously unreported mutations were detected in the tumor suppressor genes FAT atypical cadherin 4 (FAT4) and spleen associated tyrosine kinase (SYK). Among the 29 patients who developed distant metastasis, we analyzed 2 patterns of metastasis: Eleven patients (38%) developed nodal metastasis before distant metastasis, and 18 patients (62%) developed distant metastasis without previously known nodal metastasis. The patients with cT3 tumors were more likely to follow the latter metastasis pattern (P = 0.02). CONCLUSIONS: Conjunctival melanoma presented with mostly advanced stages and high rates of distant metastasis in the current Chinese cohort. This study confirmed the prognostic value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, for Chinese patients. Histologic features, such as tumor thickness and ulceration, should be emphasized when assessing prognosis and guiding the treatment of CM.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Neoplasias da Túnica Conjuntiva , Melanoma , Neoplasias da Mama/patologia , China/epidemiologia , Estudos de Coortes , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Humanos , Metástase Linfática , Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Úlcera , Estados Unidos
3.
Prep Biochem Biotechnol ; 49(6): 584-589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30929563

RESUMO

PGHX is a polymer of ß (1-3)-galactose which posses the gel-forming property. As previously reported in the flask culture experiment, the crude PGHX (24.9 g/L, 48.2% in yield) with the maximum gel strength of 957 g/cm2 can be generated. However, PGHX produced in the stirred bioreactor had no gel-forming property when using the same medium. Hence, the effects of different glycerol concentrations on both the yield and the gel-forming property of PGHX were investigated and the reason for gel-forming property losing was explored. We proposed a new strategy for the production of PGHX with enhanced gel formation in the stirred bioreactor by mediating both the concentration of carbon source and the duration of fermentation. As a result, we managed to obtain the crude PGHX (22 g/L, 42.4% in yield) with the maximum gel strength of 438 g/cm2 at 56 h in the bioreactor. This strategy would help the enhancement of PGHX yield in the industrial production.


Assuntos
Agrobacterium/metabolismo , Galactanos/biossíntese , Glicerol/metabolismo , Aminoácidos/análise , Biomassa , Reatores Biológicos , Fermentação/efeitos dos fármacos , Galactanos/química , Géis
4.
Eur J Ophthalmol ; : 11206721241249503, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689460

RESUMO

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

5.
Cell Discov ; 10(1): 63, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862482

RESUMO

Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8+ T cells and an increase in the proportion of naive CD8+ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.

6.
Acta Ophthalmol ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420891

RESUMO

PURPOSE: To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). METHODS: Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. RESULTS: Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). CONCLUSIONS: Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

7.
Br J Ophthalmol ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383070

RESUMO

AIMS: Conjunctival melanoma (CoM) is a rare but highly lethal ocular melanoma and there is limited understanding of its genetic background. To update the genetic landscape of CoM, whole-exome sequencing (WES) and targeted next-generation sequencing (NGS) were performed. METHODS: Among 30 patients who were diagnosed and treated at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2018 to January 2023, WES was performed on 16 patients, while targeted NGS was conducted on 14 patients. Samples were analysed to identify the mutated genes, and the potential predictive factors for progression-free survival were evaluated. Furthermore, the expression of the mutated gene was detected and validated in a 30-patient cohort by immunofluorescence. RESULTS: Mutations were verified in classic genes, such as BRAF (n=9), NRAS (n=5) and NF1 (n=6). Mutated FAT4 and BRAF were associated with an increased risk for the progression of CoM. Moreover, decreased expression of FAT4 was detected in CoM patients with a worse prognosis. CONCLUSIONS: The molecular landscape of CoM in Chinese patients was updated with new findings. A relatively high frequency of mutated FAT4 was determined in Chinese CoM patients, and decreased expression of FAT4 was found in patients with worse prognoses. In addition, both BRAF mutations and FAT4 mutations could serve as predictive factors for CoM patients.

8.
Mutat Res ; 751(2): 127-9, 2013 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-23295244

RESUMO

Adult male ICR mice were pre-exposed to non-ionizing radiofrequency fields (RF), 900MHz at 120µW/cm(2) power density for 4h/day for 7 days (adaptation dose, AD) and then subjected to an acute whole body dose of 3Gy γ-radiation (challenge dose, CD). The classical micronucleus (MN) assay was used to determine the extent of genotoxicity in immature erythrocytes in peripheral blood and bone marrow. The data obtained in mice exposed to AD+CD were compared with those exposed to CD alone. The results indicated that in both tissues, the MN indices were similar in un-exposed controls and those exposed to AD alone while a significantly increased MN frequency was observed in mice exposed to CD alone. Exposure of mice to AD+CD resulted in a significant decrease in MN indices compared to those exposed to CD alone. Thus, the data suggested that pre-exposure of mice to non-ionizing RF is capable of 'protecting' the erythrocytes in the blood and bone marrow from genotoxic effects of subsequent γ-radiation. Such protective phenomenon is generally described as 'adaptive response' (AR) and is well documented in human and animal cells which were pre-exposed to very low doses of ionizing radiation. It is interesting to observe AR being induced by non-ionizing RF.


Assuntos
Adaptação Fisiológica , Dano ao DNA , Ondas de Rádio/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Camundongos , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Tolerância a Radiação
9.
Eye (Lond) ; 37(11): 2272-2280, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36522530

RESUMO

OBJECTIVES: To identify the risk factors of orbital exenteration and to evaluate the prognosis of exenterated patients with conjunctival melanoma (CM). METHODS: 79 consecutive CM patients treated at our centre from January 2000 to September 2021 were included. The demographic, clinical and pathological characteristics were compared between eye-sparing patients and orbital exenteration patients. Main outcomes including progression-free survival (PFS), distant metastasis-free survival (DFS) and disease specific survival (DSS) were assessed in exenterated patients. RESULTS: The mean follow-up period was 46 ± 39 months. Risk factors for orbital exenteration were identified as worse cT category (OR, 50.75; 95% CI, 5.40-477.07; P = 0.001) and greater tumour thickness (OR, 1.27; CI, 1.04-1.55; P = 0.02). Of the 32 patients who underwent orbital exenteration, three (9.4%) had local recurrence; six (18.8%) experienced regional metastasis; sixteen (50.0%) suffered distant metastasis and fifteen (46.9%) died of metastatic disease. In patients who received orbital exenteration, palpebral conjunctiva involvement (PFS: P < 0.01; DFS: P < 0.05; DSS: P = 0.04), histological ulceration (PFS: P = 0.03; DFS: P = 0.01; DSS: P = 0.03) and regression (PFS: P = 0.01; DFS: P < 0.01; DSS: P = 0.04) were identified as risk factors for poor prognosis. Caruncle involvement (P = 0.01) was also associated with increased risk of melanoma related mortality in exenterated patients. CONCLUSIONS: Histopathological factors should be taken into account when formulating surgical plans for orbital exenteration and when evaluating patients' prognosis following exenteration. For CM patients with caruncle or palpebral conjunctiva involvement, orbital exenteration should be considered for unresectable disease.


Assuntos
Neoplasias da Mama , Neoplasias da Túnica Conjuntiva , Melanoma , Humanos , Feminino , Neoplasias da Túnica Conjuntiva/patologia , Prognóstico , Exenteração Orbitária , Melanoma/patologia , Fatores de Risco , Estudos Retrospectivos
10.
Cell Death Dis ; 14(6): 348, 2023 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-37270643

RESUMO

The cytidine deaminase, Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B, herein termed A3B), is a critical mutation driver that induces genomic instability in cancer by catalyzing cytosine-to-thymine (C-to-T) conversion and promoting replication stress (RS). However, the detailed function of A3B in RS is not fully determined and it is not known whether the mechanism of A3B action can be exploited for cancer therapy. Here, we conducted an immunoprecipitation-mass spectrometry (IP-MS) study and identified A3B to be a novel binding component of R-loops, which are RNA:DNA hybrid structures. Mechanistically, overexpression of A3B exacerbated RS by promoting R-loop formation and altering the distribution of R-loops in the genome. This was rescued by the R-loop gatekeeper, Ribonuclease H1 (RNASEH1, herein termed RNH1). In addition, a high level of A3B conferred sensitivity to ATR/Chk1 inhibitors (ATRi/Chk1i) in melanoma cells, which was dependent on R-loop status. Together, our results provide novel insights into the mechanistic link between A3B and R-loops in the promotion of RS in cancer. This will inform the development of markers to predict the response of patients to ATRi/Chk1i.


Assuntos
Neoplasias , Estruturas R-Loop , Humanos , Mutação , Neoplasias/genética , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
11.
Invest Ophthalmol Vis Sci ; 62(15): 11, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34901994

RESUMO

Purpose: Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, making the development of targeted therapy an urgent need. Therefore, we intended to find a potential drug for human retinoblastoma by screening an in-house compound library that included 89 purified and well-characterized natural products. Methods: We screened a panel of 89 natural products in retinoblastoma cell lines to find the inhibitor. The inhibition of the identified inhibitor xanthatin on cell growth was detected through half-maximal inhibitory concentration (IC50), flow cytometry assay, and zebrafish model system. RNA-seq further selected the target gene PLK1. Results: We reported the discovery of xanthatin as an effective inhibitor of retinoblastoma. Mechanistically, xanthatin selectively inhibited the proliferation of retinoblastoma cells by inducing cell cycle arrest and promoting apoptosis. Interestingly, xanthatin targeted PLK1-mediated cell cycle progression. The efficacy of xanthatin was further confirmed in zebrafish models. Conclusions: Collectively, our data suggested that xanthatin significantly inhibited tumor growth in vitro and in vivo, and xanthatin could be a potential drug treatment for retinoblastoma.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Proteínas de Ciclo Celular/antagonistas & inibidores , Ciclo Celular/efeitos dos fármacos , Furanos/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Western Blotting , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Retina/enzimologia , Neoplasias da Retina/patologia , Retinoblastoma/enzimologia , Retinoblastoma/patologia , Transdução de Sinais/efeitos dos fármacos , Sincalida/metabolismo , Quinase 1 Polo-Like
12.
Cell Death Dis ; 12(12): 1100, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815392

RESUMO

Retinoblastoma is a childhood retinal tumour that is the most common primary malignant intraocular tumour. However, it has been challenging to identify the cell types associated with genetic complexity. Here, we performed single-cell RNA sequencing on 14,739 cells from two retinoblastoma samples to delineate the heterogeneity and the underlying mechanism of retinoblastoma progression. Using a multiresolution network-based analysis, we identified two major cell types in human retinoblastoma. Cell trajectory analysis yielded a total of 5 cell states organized into two main branches, and the cell cycle-associated cone precursors were the cells of origin of retinoblastoma that were required for initiating the differentiation and malignancy process of retinoblastoma. Tumour cells differentiation reprogramming trajectory analysis revealed that cell-type components of multiple tumour-related pathways and predominantly expressed UBE2C were associated with an activation state in the malignant progression of the tumour, providing a potential novel "switch gene" marker during early critical stages in human retinoblastoma development. Thus, our findings improve our current understanding of the mechanism of retinoblastoma progression and are potentially valuable in providing novel prognostic markers for retinoblastoma.


Assuntos
Retinoblastoma/genética , Animais , Diferenciação Celular , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Retinoblastoma/patologia , Análise de Célula Única
13.
Pathol Res Pract ; 212(5): 365-71, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26997491

RESUMO

Glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which exists mainly in the liver, is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the formation of primary hyperoxaluria type 2 (PH2). Here, we investigated GRHPR expression and its potential role in both human Crohn's disease (CD) and experimental colitis. Murine experimental colitis models were established by administration of trinitrobenzenesulphonic acid (TNBS). As shown by Western blot, significant up-regulation of GRHPR was found in TNBS-treated mice as compared with normal controls. Immunohistochemistry (IHC) also showed increased GRHPR expression, and the molecule was located in intestinal epithelial cells (IECs). This phenomenon also occurred in patients with Crohn's disease. Besides, in an in vitro study, human IEC line HT-29 cells cultured with tumor necrosis factor α (TNF-α) were used to evaluate the changes in expression of GRHPR. Moreover, overexpression of GRHPR was accompanied by active caspase-3 and cleaved poly ADP-ribose polymerase (PARP) accumulation. Furthermore, knock-down GRHPR could inhibit the accumulation of active caspase-3 and cleaved PARP as shown by Western blot in TNF-α treated HT-29 cells. Flow cytometry assay indicated that interference of GRHPR led to increasing apoptosis of IECs. These data suggested that GRHPR might exert its pro-apoptosis function in IECs. Thus, GRHPR might play an important role in regulating IECs apoptosis, and might be a potential therapeutic target for CD.


Assuntos
Oxirredutases do Álcool/metabolismo , Apoptose/fisiologia , Colite/metabolismo , Mucosa Intestinal/metabolismo , Regulação para Cima , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/patologia , Intestinos/patologia , Camundongos , Ácido Trinitrobenzenossulfônico
14.
Int J Radiat Biol ; 91(3): 270-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25347145

RESUMO

PURPOSE: To determine whether mice exposed to radiofrequency fields (RF) and then injected with a radiomimetic drug, bleomycin (BLM), exhibit adaptive response and provide some mechanistic evidence for such response. MATERIALS AND METHODS: Adult mice were exposed to 900 MHz RF at 120 µW/cm(2) power density for 4 hours/day for 7 days. Immediately after the last exposure, some mice were sacrificed while the others were injected with BLM 4 h later. In each animal: (i) The primary DNA damage and BLM-induced damage as well as its repair kinetics were determined in blood leukocytes; and (ii) the oxidative damage was determined from malondialdehyde (MDA) levels and the antioxidant status was assessed from superoxide dismutase (SOD) levels in plasma, liver and lung tissues. RESULTS: There were no indications for increased DNA and oxidative damages in mice exposed to RF alone in contrast to those treated with BLM alone. Mice exposed to RF+ BLM showed significantly: (a) reduced BLM-induced DNA damage and that remained after each 30, 60, 90, 120 and 150 min repair time, and (b) decreased levels of MDA in plasma and liver, and increased SOD level in the lung. CONCLUSIONS: The overall data suggested that RF exposure was capable of inducing adaptive response and mitigated BLM- induced DNA and oxidative damages by activating certain cellular processes.


Assuntos
Bleomicina/efeitos adversos , Dano ao DNA , Reparo do DNA , Ondas de Rádio/efeitos adversos , Adaptação Fisiológica/efeitos da radiação , Animais , Antineoplásicos/efeitos adversos , Cinética , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Tolerância a Radiação , Radiobiologia , Superóxido Dismutase/metabolismo
15.
Pathol Res Pract ; 211(3): 240-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25547899

RESUMO

Vacuolar protein sorting 4B (VPS4B) is a member of ATPase family proteins that have been shown to play important roles in the formation of MVBs, virus budding and abscission of cytokinesis. In this study, we investigated the prognostic role of VPS4B in human hepatocellular carcinoma (HCC) and its effect on the growth of HCC cells. Western blot and immunohistochemistrical analyses revealed that VPS4B was significantly upregulated in 98 HCC tissues, compared with adjacent nontumorous samples. Meanwhile, clinicopathological variables and univariate and multivariate survival analyses showed that high VPS4B expression was correlated with multiple clinicopathological factors, including AJCC stage, microvascular invasion, Ki-67 and a poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that VPS4B served as an independent prognostic factor for survival in HCC patients. Furthermore, we found that VPS4B was lowly expressed in serum-starved Huh7 and HepG2 HCC cells, and was progressively increased after serum-refeeding. To study whether VPS4B could regulate the proliferation of HCC cells, VPS4B was knocked down in both Huh7 and HepG2 cells through the transfection of VPS4B-siRNA oligos. Flow cytometry and CCK-8 assay results indicated that interference of VPS4B led to cell cycle arrest and reduced cell proliferation of HCC cells. Taken together, our results implied that VPS4B could be a candidate prognostic biomarker as well as a potential therapeutical target of HCC.


Assuntos
Adenosina Trifosfatases/metabolismo , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/fisiologia , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Neoplasias Hepáticas/metabolismo , Regulação para Cima , ATPases Associadas a Diversas Atividades Celulares , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Adulto Jovem
16.
PLoS One ; 7(9): e46102, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23029402

RESUMO

Human promyelocytic leukemia HL-60 cells were pre-exposed to non-ionizing 900 MHz radiofrequency fields (RF) at 12 µW/cm(2) power density for 1 hour/day for 3 days and then treated with a chemotherapeutic drug, doxorubicin (DOX, 0.125 mg/L). Several end-points related to toxicity, viz., viability, apoptosis, mitochondrial membrane potential (MMP), intracellular free calcium (Ca(2+)) and Ca(2+)-Mg(2+) -ATPase activity were measured. The results obtained in un-exposed and sham-exposed control cells were compared with those exposed to RF alone, DOX alone and RF+DOX. The results indicated no significant differences between un-exposed, sham-exposed control cells and those exposed to RF alone while treatment with DOX alone showed a significant decrease in viability, increased apoptosis, decreased MMP, increased Ca(2+) and decreased Ca(2+)-Mg(2+-)ATPase activity. When the latter results were compared with cells exposed RF+DOX, the data showed increased cell proliferation, decreased apoptosis, increased MMP, decreased Ca(2+) and increased Ca(2+)-Mg(2+)-ATPase activity. Thus, RF pre-exposure appear to protect the HL-60 cells from the toxic effects of subsequent treatment with DOX. These observations were similar to our earlier data which suggested that pre-exposure of mice to 900 MHz RF at 120 µW/cm(2) power density for 1 hours/day for 14 days had a protective effect in hematopoietic tissue damage induced by subsequent gamma-irradiation.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Leucemia Promielocítica Aguda/terapia , Terapia por Radiofrequência , Adenosina Trifosfatases/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Magnésio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos da radiação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA