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1.
Aging (Albany NY) ; 15(13): 6264-6291, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37405952

RESUMO

BACKGROUND: Individuals with low-grade glioma (LGG) have a dismal prognosis, and most patients will eventually progress to high-grade disease. Therefore, it is crucial to accurately determine their prognoses. METHODS: Seventy-nine NK cell genes were downloaded from the LM22 database and univariate Cox regression analysis was utilized to detect NK cell-related genes affecting prognosis. Molecular types were established for LGG using the "ConsensusClusterPlus" R package. The results from a functional enrichment analysis and the immune microenvironment were intensively explored to determine molecular heterogeneity and immune characteristics across distinct subtypes. Furthermore, a RiskScore model was developed and verified using expression profiles of NK cells, and a nomogram consisting of the RiskScore model and clinical traits was constructed. Moreover, pan-cancer traits of NK cells were also investigated. RESULTS: The C1 subtype included the greatest amount of immune infiltration and the poorest prognosis among well-established subtypes. The majority of enriched pathways were those involved in tumor progression, including epithelial-mesenchymal transition and cell cycle pathways. Differentially expressed genes among distinct subtypes were determined and used to develop a novel RiskScore model. This model was able to distinguish low-risk patients with LGG from those with high-risk disease. An accurate nomogram including the RiskScore, disease grade and patient's age was constructed to predict clinical outcomes of LGG patients. Finally, a pan-cancer analysis further highlighted the crucial roles of NK cell-related genes in the tumor microenvironment. CONCLUSIONS: An NK cell-related RiskScore model can accurately predict the prognoses of patients with LGG and provide valuable insights into personalized medicine.


Assuntos
Glioma , Humanos , Prognóstico , Glioma/genética , Nomogramas , Células Matadoras Naturais , Ciclo Celular , Microambiente Tumoral/genética
2.
Front Genet ; 13: 921823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061189

RESUMO

Background: Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma of central nervous system, which is often found in immunocompromised patients. The common clinical treatment of PCNSL is methotrexate (MTX) and whole brain radiation therapy. With the development of tumour immunology research, the tumour microenvironment of PCNSL is characterised by abnormal expression of different immune signature molecules and patients with PCNSL may benefit from tumour immunotherapy. Methods: In our research, RNA-seq data from 82 PCNSL patients were collated by mining the microarray data from the GEO database. All samples were classified into three types related to tumour immune response by the Cibersort algorithm and consistent clustering. Differential analysis of genes was used to uncover 2 sets of differential genes associated with tumour immunity. The ICI scores of each sample were obtained by PCA algorithm, and the relationship between ICI scores and immune checkpoint expression, immunotherapy and drug sensitivity was investigated. Genes associated with ICI scores and their functional characteristics were investigated by WGCNA analysis and PPI analysis, based on the ICI scores of each sample. Results: The tumour microenvironment in PCNSL has a greater relationship with the tumour immune response. ICI scores obtained from 375 differential genes were associated with multiple immune responses in PCNSL. PCNSL patients with higher ICI scores had a better tumour microenvironment and were sensitive to immunotherapy and some small molecule drug. This study also identified 64 genes associated with ICI scores, which may serve as important therapeutic and prognostic targets for PCNSL. Conclusion: The presence of multiple immunosuppressive responses in the tumour microenvironment of PCNSL which suggested that improving the immune function of PCNSL patients through immunotherapy and targeted therapies can be an effective treatment for PCNSL. And the ICI score and associated genes may also provide a better predictor of the clinical use of immunotherapy.

3.
World J Clin Cases ; 10(13): 4288-4293, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35665132

RESUMO

BACKGROUND: Determining a subdural hematoma (SDH) to be chronic by definition takes 3 wk, whereas organized chronic SDH (OCSDH) is an unusual condition that is believed to form over a much longer period of time, which generally demands large craniotomy. Therefore, it is a lengthy process from the initial head trauma, if any, to the formation of an OCSDH. Acute SDH (ASDH) with organization-like, membranaceous appearances has never been reported. CASE SUMMARY: A 56-year-old woman presented to our hospital with a seizure, and computed tomography (CT) on admission was negative for signs of intracranial hemorrhage. She had clear consciousness and unimpaired motor functions on arrival and remained stable for the following week, during which she underwent necessary examinations. On the morning of day 10 of hospitalization, she accidentally hit her head hard against the wall in the bathroom and promptly lapsed into complete coma within 2 h. Therefore, we performed emergency CT and identified a left supratentorial SDH that was an absolute indication for surgery. However, the intraoperative findings were surprising, with no liquefaction observed. Instead, a solid hematoma covered with a thick membrane was noted that strongly resembled an organized hematoma. Evacuation was successful, but the family stopped treatment the next day due to financial problems, and the patient soon died. CONCLUSION: Neurosurgeons should address SDHs, especially ASDHs, with discretion and individualization due to their highly diversified features.

4.
Sci Total Environ ; 819: 153090, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35038504

RESUMO

Stabilizing the hazardous calcium arsenic residues (CAR) and monitoring the subsequent fate of arsenic (As) are critical to reduce its risk to the environment. In this work, a novel in situ method has been proposed to stabilize CAR by adding FeIII solution and subsequent formation of the secondary mineral (yukonite). The experiments were conducted at pH 6-9 with different Fe/As molar ratios (0.28-0.66) and the solid phases were characterized by using X-ray diffraction and scanning/transmission electron microscopy. Results showed that the stability of the CAR was significantly increased after the addition of FeIII solution, indicating good fixation effectiveness. The dissolved As concentration in the treated CAR samples continuously decreased to <5 mg/L after 490 days of treatment at Fe/As molar ratio ≥ 0.54 and pH ≥ 8, with the leached As concentration lower than 5 mg/L (US EPA standard) for most of the treated CAR in the TCLP and HVM tests. The formation of yukonite under different experimental conditions is closely related to the enhanced stability of the treated CAR. This work provides a novel in situ method to treat CAR which might have potential for future industrial applications.


Assuntos
Arsênio , Arsênio/química , Cálcio , Concentração de Íons de Hidrogênio , Ferro/química , Difração de Raios X
6.
Sci Total Environ ; 807(Pt 1): 150749, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34619194

RESUMO

Adsorption of molybdate (Mo(VI)) on the surfaces of ferrihydrite is one of the most critical processes that control its mobility and fate in the environment. However, the sorption mechanism and the effect of pH on the speciation of Mo(VI) on ferrihydrite surfaces are not well understood. In this study, X-ray diffraction (XRD), Raman, Fourier transform infrared (FTIR), and Mo K-edge and L3-edge X-ray absorption spectroscopy (XAS) have been utilized to characterize the Mo(VI) species sorbed on ferrihydrite under various pH conditions. XRD, Raman, and FTIR results show that at acidic pH, surface precipitation of poorly crystalline ferric molybdate (PCFM) occurs under apparently undersaturated conditions (theoretical log IAP < log Ksp) and is enhanced by the aging process, whereas Mo(VI) is mainly present as surface adsorbed species at circum-neutral pH. The Mo K-edge and L3-edge X-ray absorption near edge structure (XANES) analyses show that a mixture of tetrahedrally and octahedrally coordinated Mo(VI) simultaneously exists at pH 3-7 and the octahedral Mo(VI) species decreases with increasing pH. The Mo-Fe interatomic distances (3.52-3.56 Å) derived from EXAFS fittings suggest the corner-sharing complexation of both MoO4 and MoO6 with FeO6 octahedra. As the pH decreases from 7 to 3, the coordination number of the Mo-Fe shell (CNMo-Fe) increases from 0.6(3) to 1.9(3), possibly due to the gradual transformation of surface adsorbed Mo(VI) to PCFM. These findings on the observation of Mo(VI) complexation, surface precipitation, and their marked pH dependence during the Mo(VI) adsorption on ferrihydrite have important implications for both understanding the mobility and fate of Mo(VI) in natural and hydrometallurgical industry impacted environments and developing optimal applications for the remediation of Mo contamination in aqueous environments.


Assuntos
Compostos Férricos , Ferro , Adsorção , Molibdênio
7.
Artigo em Inglês | MEDLINE | ID: mdl-34870539

RESUMO

Natural organic matter (NOM) has been considered a critical substance in the transport and transformation of arsenic. NOM is a complex mixture of multifunctional organic components with a wide molecular weight (MW) distribution, and it is necessary to understand the complexation of arsenic with MW-dependent NOM fractions. In this study, humic acid (HA) was chosen as the representative fraction of NOM to investigate the complexation mechanism with arsenic. The bulk HA sample was fractionated to five fractions by ultrafiltration technology, and the complexing property of HA fractions with arsenic was analyzed by the dialysis method. We observed that the acidic and neutral conditions favor the complexation of HA fractions with arsenate (As(V)). The HA fractions with molecular weight > 100 kDa, 1-10 kDa, and <1 kDa have the stronger complexing capacity of As(V) than the other HA fractions. The bound As(V) percentage was positively associated with carboxyl content, phenolic content, and especially total acidity. A two-site ligand-binding model can describe the complexing capacity of arsenic onto HA fractions. The results can provide some fundamental information about the complexation of arsenic with MW-dependent HA fractions quantitatively.


Assuntos
Arsênio , Substâncias Húmicas , Arseniatos , Arsênio/química , Substâncias Húmicas/análise , Peso Molecular , Água
8.
J Cancer Res Ther ; 17(5): 1253-1260, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34850775

RESUMO

OBJECTIVE: The effect of CO2 pneumoperitoneum (CDP) on the oncology outcomes of patients undergoing laparoscopic radical hysterectomy for cervical cancer remains unclear. In this study, we investigated the effects of CDP on the proliferation of cervical cancer cells and examined the molecular mechanism. MATERIALS AND METHODS: We established an in vitro CDP model to study the effects of CDP on the proliferation of cervical cancer cells by Cell Counting Kit-8 (CCK-8) assay, xenografted tumor assay. Tandem mass tag-based quantitative proteomics were used to study the proteomic changes in HeLa cells after CDP treatment. Western blot assay was used to detect the expressions of PI3K/Akt signaling pathway proteins. RESULTS: CDP increased cell proliferation after a short period of inhibition in vitro and promoted tumorigenesis in vivo. Proteomic analysis showed that the expression levels of 177 and 309 proteins were changed significantly 24 and 48 h after CDP treatment, respectively. The acidification caused by CO2 inhibited the proliferation of cervical cancer cells by inhibiting the phosphorylation of PI3K and Akt. CONCLUSIONS: CDP promoted the proliferation of human cervical cancer cells after a short time of inhibition. The mechanism of which is related to the inhibition of phosphorylation of the PI3K/Akt signaling pathway.


Assuntos
Biomarcadores Tumorais/metabolismo , Dióxido de Carbono/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Pneumoperitônio/metabolismo , Proteoma/análise , Proteoma/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Laparoscopia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pneumoperitônio/tratamento farmacológico , Pneumoperitônio/patologia , Proteômica/métodos , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Sci Total Environ ; 799: 149474, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426338

RESUMO

The coprecipitation and subsequent aging of Fe(III)-As(III)-As(V)-SO42- play an important role in controlling As behavior in acidic systems, such as acid mine drainage and hydrometallurgical acid waste. In this study, we investigated the redistribution and transformation of As in the Fe(III)-As(III)-As(V)-SO42- system (As(III)/As(V) ≈ 1) at different Fe/As molar ratios (i.e., 0.25, 0.5, and 1) and pH (1.2 and 1.8) at 60 °C. The results showed that As(III) and SO42- can be incorporated into the amorphous ferric arsenate and scorodite host phases by forming a Fe(AsO4)x(AsO3)y(SO4)z solid solution. As(III) contents in the freshly coprecipitated solids increased with pH and initial As(III) concentrations. During aging process, As(III) contents in the solid products with Fe/As molar ratios of 0.5 and 1 increased with aging time at pH 1.8. In contrast, As(III) was gradually expelled from aging products with aging time at pH 1.2, regardless of Fe/As molar ratio. X-ray diffraction (XRD), scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and Raman spectroscopy characterization results showed that an As(III)-SO42--doped scorodite was formed at Fe/As molar ratio ≤0.5 during the aging process. It was also found that As(III) had an inhibitory effect on the transformation of poorly crystalline ferric arsenate to scorodite. The present study may have important implications for understanding the geochemical cycle of As, Fe, and SO42- in acidic solutions and give further understanding on the mechanisms involved in As removal and fixation in hydrometallurgical unit operations.


Assuntos
Arsênio , Arsênio/análise , Compostos Férricos , Concentração de Íons de Hidrogênio , Ferro , Mineração
10.
Int Urogynecol J ; 32(4): 1047, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33595674
11.
Int Urogynecol J ; 32(4): 1043-1045, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33001217

RESUMO

INTRODUCTION AND HYPOTHESIS: We present a surgical video that describes the technical considerations for performing a modified LeFort partial colpocleisis. METHODS: Hydro-dissection with diluted pituitrin was performed before the creation of anterior and posterior mid-line incisions through which lateral flaps were created bilaterally to expose the bladder and rectum fascia. Several purse-string sutures were placed to push the bladder and rectum back to their normal positions and reinforce the fascia under the vaginal wall. After removing the excess part of the vaginal wall, the lateral margins were re-approximated to create lateral channels that were wide enough to fit one finger. Perineoplasty was then performed to reduce the length of the genital hiatus. RESULTS: The procedure was performed in a 76-year-old woman with stage III vaginal vault prolapse (POP-Q C + 2), stage IV anterior prolapse (POP-Q Ba+5), stage II posterior prolapse (POP-Q Bp-1), and mild occult stress urinary incontinence. The patient recovered well postoperatively, without recurrent prolapse and/or stress incontinence during 6 months of follow-up. CONCLUSIONS: Our modified technique used traditional suture methods to strengthen the bladder and rectum fascia, keeping most of the vaginal wall to create a solid longitudinal septum in the center of the vagina that supported the vaginal vault.


Assuntos
Prolapso de Órgão Pélvico , Incontinência Urinária por Estresse , Idoso , Colpotomia , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , Gravidez , Resultado do Tratamento , Bexiga Urinária , Vagina/cirurgia
12.
Cancer Manag Res ; 12: 12011-12020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262651

RESUMO

PURPOSE: To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. MATERIALS AND METHODS: The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. RESULTS: SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. CONCLUSION: SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.

13.
Medicine (Baltimore) ; 98(47): e18171, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764859

RESUMO

RATIONALE: Sclerosing stromal tumor (SST) of the ovary is rare. We describe the first case of ovarian SST with estrogen excess with both clinical and serological evidence in a postmenopausal woman. PATIENT CONCERNS: A 70-year-old female who referred menopause 14 years ago was admitted with postmenopausal bleeding for 3 months. Ultrasonography revealed thickened endometrium of 6 mm and no adnexal masses. An elevated serum estradiol level of 49.78 ng/L was revealed in laboratory examination with normal ranges less than 27.25 ng/L in postmenopausal women. DIAGNOSES: The final histology diagnosis is SST of left ovary and endometrial hyperplasia with polyps. INTERVENTIONS: Laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed and a solid tumor with a diameter of 3 cm × 2 cm from the left ovary was found intraoperatively. OUTCOMES: Three days after removal of the tumor, the serum estrogen level was decreased to normal which indicated the estrogen activity of the tumor. LESSONS: To the best of our knowledge, it is the first reported case of ovarian SST with estrogen excess with both clinical and serological evidence. The present case illustrates the necessity to consider the rare possibility of ovarian SST as a cause for estrogen excess leading to postmenopausal bleeding. Hormonal evaluation (estrogens, androgens) should be considered in women with postmenopausal bleeding regardless of imaging examination.


Assuntos
Estrogênios/sangue , Neoplasias Ovarianas/sangue , Tumores do Estroma Gonadal e dos Cordões Sexuais/sangue , Idoso , Feminino , Humanos , Pós-Menopausa
14.
Medicine (Baltimore) ; 97(49): e13520, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544453

RESUMO

RATIONALE: Reports of malignant ovarian tumor with hyperamylasemia are very rare. We present a patient with hyperamylasemia who was diagnosed with a malignant ovarian tumor. PATIENT CONCERNS: A 46-year-old woman was hospitalized complaining of a 2-day history of abdominal discomfort and fever. On physical examination, she showed abdominal distention and tenderness, with rebound pain. Laboratory evaluation showed significantly elevated serum amylase levels. Computed tomography (CT) revealed a solid mass with uneven density in the pelvis. DIAGNOSES: Based on her clinical symptoms and hyperamylasemia, she was suspected to have acute pancreatitis at first. However, the final pathology showed advanced serous papillary ovarian carcinoma. INTERVENTIONS: She underwent initial therapy for acute pancreatitis, followed by laparotomy once her symptoms had disappeared. A tumor mass with maximum diameter 12 cm was detected originating from the right ovary, and the patient underwent hysterectomy, bilateral salpingo-oophorectomy with omentectomy, and appendectomy. On the 14th day after the surgery, she received 5 courses of chemotherapy with paclitaxel and carboplatin. However, distant metastasis before the 6th course of chemotherapy were detected by CT, she was therefore changed to a chemotherapy regimen containing gemcitabine and capecitabine. OUTCOMES: The final pathology showed advanced serous papillary ovarian carcinoma. On the 14th day after the surgery, she received 5 courses of chemotherapy with paclitaxel and carboplatin. However, her serum CA125 levels rose again before the 6th course of chemotherapy, and CT of the abdomen and pelvis revealed multiple abnormal-density lesions in the peritoneum and pelvic cavity. We considered these to be metastases, and the patient was deemed unresponsive to her previous chemotherapy. She was therefore changed to a chemotherapy regimen containing gemcitabine and capecitabine, and remained on this regimen at the time of writing. LESSONS: Ovarian carcinoma should be considered as a possibility in patients with hyperamylasemia after ruling out other potential common causes. The final diagnosis depends mainly on the clinical manifestation, laboratory results, and CT examination, though pathology is mandatory to confirm the diagnosis. The main treatment is surgical excision.


Assuntos
Carcinoma Papilar/complicações , Carcinoma Papilar/diagnóstico , Hiperamilassemia/diagnóstico , Hiperamilassemia/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Diagnóstico Diferencial , Feminino , Humanos , Hiperamilassemia/terapia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia
15.
Med Sci Monit ; 23: 2445-2452, 2017 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-28531169

RESUMO

BACKGROUND In view of the important function of nuclear receptor liver receptor homolog 1 (LRH 1) in various biological processes and the physiological changes accompanying unexplained recurrent spontaneous abortion (USRA), our study was carried out to investigate the potential roles of LRH-1 in USRA. MATERIAL AND METHODS Thirty patients with URSA at early the early state of pregnancy were selected, and 30 patients with normal early pregnancy were also selected from Aug 2015 to Sep 2016 as a control group. The expression of LRH-1 protein in decidua and villi were detected by immunohistochemistry and Western blot analysis, and the expression of LRH-1 mRNA was detected by RT-PCR. The expression levels of CYP19 and P450scc were detected by RT-PCR and Western blot analysis at mRNA and protein levels, respectively. RESULTS The levels of LRH-1, CYP19, and P450scc mRNA and protein in villi of the patients in the URSA group were significantly lower than in the control group. There were no significant differences between the URSA group and control group in the levels of LRH-1, CYP19, and P450scc mRNA and protein in villi in decidua. CONCLUSIONS URSA was related to the reduced expression level of LRH-1 in villous tissues but not in decidua, and expression of LRH-1 may be related to the expression of CYP19 and P450scc. We believe that the expression level of LRH-1 can be used as a marker in the early diagnosis of URSA, and the regulation of LRH-1 expression many lead to new URSA treatments.


Assuntos
Aborto Habitual/genética , Aborto Espontâneo/genética , Vilosidades Coriônicas/metabolismo , Decídua/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Adulto , Aromatase/genética , Aromatase/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Vilosidades Coriônicas/patologia , Decídua/patologia , Feminino , Humanos , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo
16.
Sci Rep ; 6: 27626, 2016 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-27282089

RESUMO

Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people's adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics.


Assuntos
Adaptação Fisiológica , Consenso , Aprendizagem , Modelos Teóricos , Comportamento Social , Humanos
17.
Tumour Biol ; 37(4): 5375-83, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26563365

RESUMO

Peptidylarginine deiminase 4 (PADI4) is an enzyme that converts both histone arginine and mono-methyl arginine residues to citrulline, and it has been detected in various subtypes of ovarian cancer. However, the mechanism of action of PADI4 in ovarian carcinogenesis remains unknown. To examine the function of PADI4, we transfected two ovarian cancer cell lines, wild-type p53 A2780 and p53-null SKOV3, with PADI4-siRNA and negative control siRNA. The proliferation of both A2780 and SKOV3 cells decreased significantly following PADI4-siRNA treatment (P A2780 < 0.01; P SKOV3 < 0.001). The invasion and migration ability of A2780 cells also significantly decreased in response to PADI4-siRNA treatment (P < 0.001), but SKOV3 cells showed no such decrease. The apoptotic rate of A2780 cells increased in the presence of PADI4-siRNA, but there was no such increase in SKOV3 cells (P > 0.05). PCR arrays of A2780 cells treated with PADI4-siRNA revealed the up-regulated expression of six genes, including cell death-inducing DFFA-like effector a (CIDEA) and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and the down-regulation of seven genes, including integrin beta 3 (ITGB3) and BCL2-antagonist/killer 1 (BAK1). These results suggest an important role for PADI4 in the p53 pathway and the regulation of the proliferation, apoptosis, invasion and migration of ovarian cancer cells. Our study also demonstrated that PADI4 contributes to tumor metastasis by regulating the gene expression of insulin-like growth factor 1 (IGF1) and WAS/WASL-interacting protein family member 1 (WIPF1).


Assuntos
Carcinogênese/genética , Proliferação de Células/genética , Hidrolases/genética , Neoplasias Ovarianas/genética , Apoptose/genética , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hidrolases/biossíntese , Fator de Crescimento Insulin-Like I/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Metástase Neoplásica , Proteínas de Neoplasias/biossíntese , Neoplasias Ovarianas/patologia , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas
18.
Tumour Biol ; 35(12): 11845-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25204671

RESUMO

Golgi phosphoprotein 3 (GOLPH3) has important roles in the pathogenesis of cancer, and overexpression of GOLPH3 has been found in several kinds of cancers. However, the relationship between GOLPH3 overexpression and prognosis in patients with epithelial ovarian cancer remains unknown. This study aimed to investigate the relationship between GOLPH3 overexpression and overall survival in patients with epithelial ovarian cancer. The expression of GOLPH3 protein in tumor tissue was evaluated using immunohistochemistry. Seventy-five patients with epithelial ovarian cancer with the data of GOLPH3 expression and follow-up were included. GOLPH3 overexpression was significantly associated with advanced stage, histology, high grade, and lymph node metastases (P < 0.05). Kaplan-Meier analysis showed that patients with GOLPH3 overexpression had significantly poorer overall survival than those with low expression of GOLPH3 (log-rank P < 0.001). In the multivariate Cox proportional hazards analysis, GOLPH3 overexpression was independently associated with poorer overall survival (hazard ratio [HR] = 3.60; 95 % confidence interval (CI0 1.14-11.33, P = 0.03). Therefore, overexpression of GOLPH3 protein is closely related to poorer prognosis in patients with epithelial ovarian cancer.


Assuntos
Proteínas de Membrana/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Prognóstico
19.
J Mater Chem B ; 2(19): 2920-2928, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-25045521

RESUMO

To obtain efficient non-viral vectors, a series of Gemini cationic lipids with carbamate linkers between headgroups and hydrophobic tails were synthesized. They have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails, designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. The DNA-bonding ability of these Gemini cationic liposomes was much better than their mono-head counterparts (designated as M12, M14, M16 and M18, respectively). In the same series of liposomes, bonding ability declined with an increase in tail length. They were tested for their gene-transferring capabilities in Hep-2 and A549 cells. They showed higher transfection efficiency than their mono-head counterparts and were comparable or superior in transfection efficiency and cytotoxicity to the commercial liposomes, DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene-transferring capabilities of these cationic lipids depended on hydrocarbon chain length. Gene transfection efficiency was maximal at a chain length of 14, as G14 can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate that Gemini lipid delivery systems could be internalised by cells very efficiently. Thus, the Gemini cationic lipids could be used as synthetic non-viral gene delivery carriers for further study.

20.
J Neurooncol ; 102(2): 237-45, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20700755

RESUMO

The relationship between estrogen and pituitary prolactinoma is well documented. The biological effects of estrogen are mainly mediated by estrogen receptor α (ERα). Several lines of evidence demonstrate that growth factors such as pituitary tumor transforming gene (PTTG), basic fibroblast growth factor (bFGF), transforming growth factor ß1 (TGFß1), transforming growth factor ß3 (TGFß3), and transforming growth factor ß receptor type II (TGFßRII) play an important role in prolactinoma pathogenesis induced by estrogen, but the relationship between ERα and such growth factors is still unclear. The aims of this study are to investigate the functional role of ERα in proliferation, prolactin (PRL) secretion, and expression of the above-mentioned growth factors in MMQ cells in the absence of estrogen and to discuss the feasibility of using an estrogen receptor antagonist to treat prolactinoma. Fulvestrant, a "pure" antiestrogen without any estrogen-like activity, was used to block expression of ERα in the MMQ cell line. Proliferation and PRL secretion of MMQ cells were measured using CellTiter 96(®) AQueous One Solution Cell Proliferation Assay (MTS) and the enzyme-linked immunosorbent assay (ELISA) method. Levels of ERα, PTTG, bFGF, TGFß1, TGFß3, and TGFßRII were analyzed by real-time polymerase chain reaction (PCR) and Western blot. Fulvestrant significantly inhibited cell proliferation (up to 60.80%) and PRL secretion (up to 77.95%), and changed expression of TGFß3 and TGFßRII in the absence of estrogen. In conclusion, ERα plays an important functional role in proliferation and PRL secretion of pituitary prolactinomas and also can change expression of some growth factors even under the condition of no estrogen. Fulvestrant could potentially be an effective therapy for treating such tumors.


Assuntos
Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Hipofisárias/metabolismo , Prolactinoma/metabolismo , Western Blotting , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Estrogênios/metabolismo , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Prolactina/metabolismo , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
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