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1.
Front Oncol ; 14: 1387735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720807

RESUMO

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Methods: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. Results: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. Conclusions: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

2.
Nat Struct Mol Biol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658622

RESUMO

The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, the piRNA pathway and its targeted transposons have coevolved rapidly in a species-specific manner, but how the piRNA pathway adapts specifically to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRNA-induced silencing complexes (piRISCs) bind and cleave targets more efficiently than their invertebrate counterparts from the sponge Ephydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared with EfPiwi piRISC, consistent with their ability to capture targets more efficiently than EfPiwi piRISC. In the presence of target, the seed gate-which enforces seed-target fidelity in microRNA RISC-adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mice and humans, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.

3.
Sci Rep ; 14(1): 8630, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622211

RESUMO

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Doença de Depósito de Glicogênio Tipo I , Doenças Inflamatórias Intestinais , Criança , Humanos , Masculino , Feminino , Adolescente , Constrição Patológica/complicações , Úlcera , Hiperplasia , Estudos Prospectivos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo I/genética , Proteínas de Transporte de Monossacarídeos/genética , Antiporters/genética
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 158-163, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38436313

RESUMO

OBJECTIVES: To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children. METHODS: A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group (n=10), 46,XY group (n=87), and sex chromosome abnormality group (n=35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed. RESULTS: There was no significant difference in the multiple increase of testosterone after stimulation among the three groups (P>0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue (P<0.05). CONCLUSIONS: The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , Transtorno 46,XY do Desenvolvimento Sexual , Hipospadia , Desenvolvimento Sexual , Erros Inatos do Metabolismo de Esteroides , Testosterona , Criança , Humanos , Estudos Retrospectivos , Gonadotropina Coriônica
5.
Artigo em Inglês | MEDLINE | ID: mdl-38032026

RESUMO

Surface engineering is an effective strategy to improve the photoelectrochemical (PEC) catalytic activity of hematite, and the defect states with abundant coordinative unsaturation atoms can serve as anchoring sites for constructing intimate connections between semiconductors. On this basis, we anchored an ultrathin FeSe2 layer on Nb5+-doped Fe2O3 (FeSe2/Nb:Fe2O3) via interfacial Se-O chemical bonds to tune the surface potential. Density functional theory (DFT) calculations indicate that amorphous FeSe2 decoration could generate electron delocalization over the composite photoanodes so that the electron mobility was improved to a large extent. Furthermore, electrons could be transferred via the newly formed Se-O bonds at the interface and holes were collected at the surface of electrode for PEC water oxidation. The desired charge redistribution is in favor of suppressing charge recombination and extracting effective holes. Later, work function calculations and Mott-Schottky (M-S) plots demonstrate that a type-II heterojunction was formed in FeSe2/Nb:Fe2O3, which further expedited carrier separation. Except for spatial carrier modulation, the amorphous FeSe2 layer also provided abundant active sites for intermediates adsorption according to the d band center results. In consequence, the target photoanodes attained an improved photocurrent density of 2.42 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (RHE), 2.5 times as that of the bare Fe2O3. This study proposed a defect-anchoring method to grow a close-connected layer via interfacial chemical bonds and revealed the spatial charge distribution effects of FeSe2 on Nb:Fe2O3, giving insights into rational designation in composite photoanodes.

7.
Small ; 19(39): e2302665, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37264749

RESUMO

Interfacial charge recombination is a permanent issue that impedes the photon energy utilization in photoelectrochemical (PEC) water splitting. Herein, a conjugated polymer, urea linked perylene diimide polymer (PDI), is introduced to the designation of hematite-based composite photoanodes. On account of its unique molecule structure with abundant electronegative atoms, the O and N atoms with lone electron pairs can bond with Fe atoms at the surface of Zr4+ doped α-Fe2 O3 (Zr:Fe2 O3 ) and thus establish charge transfer channels for expediting hole separation and migration. Meanwhile, PDI molecules can passivate the surface states in Zr:Fe2 O3 , which is in favor of suppressing carrier recombination. Particularly, Co2+ is used to coordinate with PDI (Co-PDI) to accelerate hole extraction as well as utilization, and the as-obtained Co-PDI form type-II heterojunction with Zr:Fe2 O3 . Such a photoanode configuration takes advantage of the unique molecule structure of PDI, and the target Co-PDI/Zr:Fe2 O3 photoanodes eventually attain a photocurrent density of 2.17 mA cm-2 , which is inspirational for unearthing the potential use of conjugative molecules in PEC fields.

8.
J Colloid Interface Sci ; 644: 124-133, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37105036

RESUMO

It is necessary for photoelectrochemical (PEC) water splitting to reduce the electron-hole recombination rate and enhance the water oxidation reaction kinetics. Here, we prepared Ni2P2O7-Nd-BiVO4 composite photoanodes by coupling Ni2P2O7 co-catalysts to neodymium (Nd)-doped BiVO4 surfaces through photo-assisted electrodeposition. The Ni2P2O7-Nd-BiVO4 photoanode exhibits a high photocurrent density of 3.6 mA cm-2 at 1.23 V vs reversible hydrogen electrode (RHE), which is three times higher than that of the bare BiVO4 (1.2 mA cm-2). Detailed characterizations demonstrate that Nd doping reduces the band gap, significantly increases the carrier density and effectively reduces the charge transfer resistance. More importantly, the Ni2P2O7 co-catalyst has multiple roles. Specifically, it can act as a hole extraction layer to accelerate hole migration and inhibit hole-electron recombination. At the same time, it significantly improves the water oxidation reaction kinetics. In addition, it also provides more water oxidation active sites. This work provides ideas for the design and study of efficient BiVO4-based photoanodes.

10.
Front Pediatr ; 10: 919238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928676

RESUMO

Background and Aims: Congenital hyperinsulinism of infancy (CHI) is a rare condition that may cause irreversible severe neurological damage in infants. For children in whom medical management fails, partial or near-total pancreatectomy is then required according to the type of lesion. Currently, open surgery of near-total pancreatic head resection is a mature technique for the treatment of focal-form CHI located in the head of the pancreas, but a minimally invasive laparoscopic procedure has not been reported yet. The aim of this study was to verify the feasibility, safety, and efficacy of laparoscopic pancreatic head resection and Roux-en-Y pancreaticojejunostomy for focal-form CHI. Methods: Two infants with persistent hypoglycemia and increased insulin levels were diagnosed with CHI and underwent laparoscopic near-total pancreatic head resection due to a suboptimal response to medical therapy and the likelihood of focal disease amenable to surgery. Clinical records, operative findings, and postoperative follow-up were collected and analyzed. Results: The operative duration was 300-330 min, and the intraoperative blood loss was minimal. The duration of postoperative abdominal drainage was 4-5 days. Neither intra- nor postoperative abdominal complications occurred. Oral feeding was resumed 3-4 days after the operation, and the blood glucose level was gradually stabilized to within the normal range. Normal blood glucose was observed in both patients over a follow-up period of 3-6 months. Conclusions: Laparoscopic pancreatic head resection and Roux-en-Y pancreaticojejunostomy can be considered a safe and effective procedure with minimal morbidity and excellent outcomes for the treatment of focal CHI in the head of the pancreas.

11.
J Colloid Interface Sci ; 610: 944-952, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34863544

RESUMO

Development of good support materials is widely adopted as a valid strategy to fabricate high performance electrocatalysts for the ethanol oxidation reaction (EOR). In this study, the small diameter Ti3C2Tx MXene thin nanosheets inserted into three-dimensional nitrogen-doped grapheme (NG) was constructed via a facile hydrothermal method and employed as support materials for anchoring Pd nanocrystals (Pd/Ti3C2Tx@NG). The obtained-Pd/Ti3C2Tx@NG as EOR electrocatalyst in alkaline media outperforms the commercial Pd/C with better electrocatalytic activity, enhanced long-term stability and high CO tolerance. The Ti3C2Tx inserted into NG probably plays a key role for enhancing the properties of the synthesized-catalyst. Inserting Ti3C2Tx into NG allows the electrocatalysts to have high porosity, surface hydrophilicity, sufficient number of anchor sites for Pd nanocrystals and modifies its electronic properties, which can promote the electrocatalytic activity and durability. The enhanced EOR performance endows Pd/Ti3C2Tx@NG with great application potential in fuel cells as an anode catalyst. Furthermore, the prepared Ti3C2Tx@NG is also suitable in various desired applications, especially other oxidation reactions.

12.
BMC Pediatr ; 20(1): 200, 2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386507

RESUMO

BACKGROUND: To report the outcomes of hepatoblastoma resected in our institution. METHODS: We diagnosed 135 children with hepatoblastoma at our institution between January 2010 and December 2017. Patients who underwent liver resection were included for analysis. However, patients who abandoned treatment after diagnosis were excluded from analysis, but their clinical characteristics were provided in the supplementary material. RESULTS: Forty-two patients abandoned treatment, whereas 93 patients underwent liver resection and were included for statistical analysis. Thirty-six, 23, 3, and 31 patients had PRETEXT stages II, III, IV, and unspecified tumours, respectively. Seven patients had ruptured tumour; 9 had lung metastasis (one patient had portal vein thrombosis concurrently). Sixteen patients underwent primary liver resection; 22, 25, and 30 patients received cisplatin-based neoadjuvant chemotherapy and delayed surgery, preoperative transarterial chemoembolization (TACE) and delayed surgery, and a combination of cisplatin-based neoadjuvant chemotherapy, TACE, and delayed surgery, respectively. Forty patients had both PRETEXT and POST-TEXT information available for analysis. Twelve patients were down-staged after preoperative treatment, including 2, 8, and 2 patients from stages IV to III, III to II, and II to I, respectively. Ten patients with unspecified PRETEXT stage were confirmed to have POST-TEXT stages II (n = 8) and I (n = 2) tumours. Seven tumours were associated with positive surgical margins, and 12 patients had microvascular involvement. During a median follow-up period of 30.5 months, 84 patients survived without relapse, 9 experienced tumour recurrence, and 4 died. The 2-year event-free survival (EFS) and overall survival (OS) rates were 89.4 ± 3.4%, and 95.2 ± 2.4%, respectively; they were significantly better among patients without metastasis (no metastasis vs metastasis: EFS, 93.5 ± 3.7% vs 46.7 ± 19.0%, adjusted p = 0.002. OS, 97.6 ± 2.4% vs 61.0 ± 18.1%, adjusted p = 0.005), and similar among patients treated with different preoperative strategies (chemotherapy only vs TACE only vs Both: EFS, 94.7 ± 5.1% vs 91.7 ± 5.6% vs 85.6 ± 6.7%, p = 0.542. OS, 94.1 ± 5.7% vs 95.7 ± 4.3% vs 96.7 ± 3.3%, p = 0.845). CONCLUSION: The OS for patients with hepatoblastoma who underwent liver resection was satisfactory. Neoadjuvant chemotherapy and TACE seemed to have a similar effect on OS. However, the abandonment of treatment by patients with hepatoblastoma was common, and may have biased our results.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatoblastoma , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Criança , China , Hepatoblastoma/cirurgia , Humanos , Lactente , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento
13.
Nat Commun ; 10(1): 112, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30631060

RESUMO

Wilms tumor gene on the X chromosome (WTX) is a putative tumor suppressor gene in Wilms tumor, but its expression and functions in other tumors are unclear. Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in women and the second leading cause in men in the United States. We demonstrated that WTX frequently lost in CRC which was highly correlated with cell proliferation, tumor invasion and metastasis. Mechanistically, WTX loss disrupts the interaction between RhoGDIα and CDC42 by losing of the binding with RhoGDIα and triggers the activation of CDC42 and its downstream cascades, which promotes CRC development and liver metastasis. The aberrant upregulation of miR-20a/miR-106a were identified as the reason of WTX loss in CRC both in vivo and in vitro. These study defined the mechanism how miR-20a/miR-106a-mediated WTX loss regulates CRC progression and metastasis, and provided a potential therapeutic target for preventing CRC progression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias do Colo/genética , MicroRNAs/genética , Proteínas Supressoras de Tumor/genética , Proteína cdc42 de Ligação ao GTP/genética , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais/genética , Transplante Heterólogo , Proteínas Supressoras de Tumor/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo
15.
BMC Bioinformatics ; 18(1): 388, 2017 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-28865443

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide with poor prognosis. Studies have showed that abnormal microRNA (miRNA) expression can affect CRC pathogenesis and development through targeting critical genes in cellular system. However, it is unclear about which miRNAs play central roles in CRC's pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes. RESULTS: To address this issue, we systematically explored the major regulation motifs, namely feed-forward loops (FFLs), that consist of miRNAs, TFs and CRC-related genes through the construction of a miRNA-TF regulatory network in CRC. First, we compiled CRC-related miRNAs, CRC-related genes, and human TFs from multiple data sources. Second, we identified 13,123 3-node FFLs including 25 miRNA-FFLs, 13,005 TF-FFLs and 93 composite-FFLs, and merged the 3-node FFLs to construct a CRC-related regulatory network. The network consists of three types of regulatory subnetworks (SNWs): miRNA-SNW, TF-SNW, and composite-SNW. To enhance the accuracy of the network, the results were filtered by using The Cancer Genome Atlas (TCGA) expression data in CRC, whereby we generated a core regulatory network consisting of 58 significant FFLs. We then applied a hub identification strategy to the significant FFLs and found 5 significant components, including two miRNAs (hsa-miR-25 and hsa-miR-31), two genes (ADAMTSL3 and AXIN1) and one TF (BRCA1). The follow up prognosis analysis indicated all of the 5 significant components having good prediction of overall survival of CRC patients. CONCLUSIONS: In summary, we generated a CRC-specific miRNA-TF regulatory network, which is helpful to understand the complex CRC regulatory mechanisms and guide clinical treatment. The discovered 5 regulators might have critical roles in CRC pathogenesis and warrant future investigation.


Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Humanos , Transcrição Gênica
16.
J Exp Clin Cancer Res ; 36(1): 19, 2017 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-28126034

RESUMO

BACKGROUND: Gastric cancer is one of the major causes of cancer-related mortality worldwide. Most of patients presenting with inoperable gastric cancers rely on systemic chemotherapy for prolongation of survival. Doxorubicin (DOX) is one of the important agents against gastric cancer. Acquired DOX-resistance severely impedes the chemotherapeutic effect, invariably leading to poor prognosis. Resveratrol (RES) as a kind of phytoalexin has demonstrated anti-tumor functions in breast cancer and myeloid leukemia, but its function and mechanism are still unknown in gastric cancer treatment. METHODS: CCK8 assay was used to detect the cytotoxicity of DOX and RES to gastric cancer cells. DOX-resistant subclone cell line (SGC7901/DOX) was derived from SGC7901 cells exposed to stepwise increasing concentrations of DOX treatment. We measured the migratory capabilities of SGC7901/DOX cells by Cell scratch test and Transwell assay. SGC7901/DOX cells were treated with DOX, RES, neither or both. Then we analyzed cell survival by CCK8 assay, colony formation by Colony-forming assay, cell apoptosis by Annexin-V-FITC and PI dual staining assay and cell migration by Cell scratch test and Transwell assay. Western blotting was conducted to detect the protein expressions of PTEN/Akt signaling pathway and EMT-related markers. Immunofluorescence was performed to confirm the EMT-related markers expressions. The xenograft model was used to assess the effect of DOX and RES in vivo. The key molecules associated with proliferation, apoptosis and EMT were evaluated by immunohistochemistry in tumor specimens. RESULTS: SGC7901/DOX cells acquired drug resistance and enhancive migratory capability. RES enabled SGC7901/DOX cells to regain DOX sensitivity, mitigated the aggressive biological features, promoted cell apoptosis in vitro and inhibited tumor growth in vivo. Mechanistic studies revealed that SGC7901/DOX cells underwent epithelial-mesenchymal transition (EMT) which was induced by Akt activation, and through activating PTEN, RES inhibited the Akt pathway, and then achieved the reversion of EMT. CONCLUSION: RES serves as a novel solution to reverse the DOX-resistance of gastric cancer via preventing EMT by modulating PTEN/Akt signaling pathway. DOX-RES combined treatment provides a promising future for gastric cancer patients to postpone drug resistance and prolong survival.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Estilbenos/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Pathol Oncol Res ; 23(2): 439-446, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28032309

RESUMO

WTX (Wilms' tumor suppressor X chromosome) is a novel putative tumor suppressor gene in Wilms' tumor of kidney, its expression and function in other human cancers had not been explored. This study detected the expression of WTX in 459 cases of 15 organs of cancers and adjacent normal tissues by using immunohistochemical staining (IHC), and validated them by in situ hybridization (ISH) and quantitative real-time reverse transcription PCR (qRT-PCR). IHC and ISH data showed that WTX protein was generally expressed in normal tissues, but reduced expression in corresponding cancers. This study demonstrated that WTX downregulation is a common phenomenon in human cancers, WTX might be a general tumor-suppressor gene and biological marker of multiple cancer tissues. Apart from kidney, stomach is another target tissue of WTX gene. The germline and somatic mutations of WTX were screened in 12 gastric cancer patients and identified in one cases (8.3%). Mutation in the WTX gene might be one of the reasons of WTX loss in gastric cancer patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Expressão Gênica/genética , Neoplasias/genética , Proteínas Supressoras de Tumor/genética , Biomarcadores Tumorais/genética , Regulação para Baixo/genética , Humanos , Mutação/genética
18.
Zhonghua Bing Li Xue Za Zhi ; 44(9): 648-52, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26705281

RESUMO

OBJECTIVE: To investigate clinical and pathological features of lung lesions in children. METHODS: Clinical manifestations, radiologic imaging, histopathological features and immunohistochemical results were analyzed in 215 cases of lung lesions in children. RESULTS: A total of 215 cases of lung lesions in children aged 0 day to 13 years (average age of 27.2 months and the median age of 18.0 months) were selected, including 137 male and 78 female patients with a male to female ratio of 1.76:1.00. The incidence of congenital lung disease was higher in patients of less than 1 year old than those of over 1 year old age, and the difference of the two groups was statistically significant (P = 0.004). 142 cases had acquired lung diseases, and 73 cases had congenital bronchopulmonary dysplasia. Lung abscess was the most common lesion seen in 86 cases (40.0%), including 1 case of fungal abscess. Congenital pulmonary airway malformation (CPAM) was the second most common, seen in 44 patients (20.5%), including 20 cases of type 1, 18 cases of type 2 and 6 cases of type 4 CPAM. Pulmonary sequestration was found in 25 cases (11.6%) including 14 cases of intralobar type and 11 cases of extralobar type. Two cases of extralobar pulmonary sequestration showed simultaneous CPAM2 type 2 lesion. Other lesions included tuberculosis (13 cases, 6.0%), emphysema (12 cases, 5.6%), interstitial pneumonia (7 cases, 3.2%), pulmonary hemorrhage (6 cases, 2.8%), bronchogenic cyst (4 cases, 1.9%), bronchiolitis obliterans (2 cases, 0.9%), idiopathic pulmonary hemosiderin deposition disease (2 cases, 0.9%) and 1 cases of lung non-specific changes. 13 cases of neoplastic lesions (6.0%) were found, of which 11 cases were primary tumors (5.1%), including inflammatory myofibroblastic tumor in 5 patients (2.3%), pleuropulmonary blastoma in 5 cases (1 case of type I, 2 type II and 2 type III) and 1 case of mucoepidermoid carcinoma (0.5%) and 2 cases of metastatic tumors (hepatoblastoma and Wilm's tumor, 0.9%). CONCLUSIONS: Infectious diseases are the most common lung diseases in children. Congenital bronchopulmonary dysplasia is the most common in children of less than 1 year old. Malignant lesions are rare.


Assuntos
Pneumopatias/patologia , Pulmão/patologia , Abscesso/patologia , Adolescente , Sequestro Broncopulmonar/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Blastoma Pulmonar/patologia
19.
Gene ; 572(2): 222-6, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26162674

RESUMO

Congenital hyperinsulinism (CHI) is a severe heterogeneous disorder due to dysregulation of insulin secretion from the pancreatic ß-cells leading to severe hypoglycemia in infancy. 18-fluoro-l-3,4-dihydroxyphenylalanine positron emission tomography ((18)F­DOPA­PET)/CT is a useful tool in distinguishing between focal and diffuse disease preoperatively. But recent studies have suggested that the scanning may not be accurate as initially estimated. In this study we characterize a case of CHI with a compound heterozygous mutation of ABCC8 gene. The results of clinical investigation, gene mutation analysis, (18)F­DOPA­PET/CT scan, and pathological examination showed some new characteristics that have never been reported. The patient was unresponsive to medical therapy with diazoxide and received pancreatectomy twice. Genetic analysis identified a compound heterozygous mutation in ABCC8 genes. Imaging with (18)F­DOPA­PET/CT indicated a focal lesion in the head of the pancreas. The pathological diagnosis was an atypical form of CHI. The patient presented with a phenotype of atypical CHI unresponsive to diazoxide. It is considered that a relationship existed between the compound heterozygous mutation and the atypical form. (18)F­DOPA­PET/CT is a useful tool in distinguishing between focal and diffuse forms preoperatively but the accuracy is not 100%. The scan result is best combined with genetic analysis and intra-operative biopsy to confirm the histological subtypes. The combination will provide the optimal strategy for the surgical treatment of patients with CHI.


Assuntos
Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/patologia , Pâncreas/patologia , Receptores de Sulfonilureias/genética , Diagnóstico Diferencial , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/metabolismo , Heterozigoto , Humanos , Masculino , Mutação , Tomografia por Emissão de Pósitrons/métodos
20.
Zhonghua Bing Li Xue Za Zhi ; 44(2): 111-7, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25916642

RESUMO

OBJECTIVE: To summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT. METHODS: The clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed. RESULTS: The study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05). CONCLUSIONS: NT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.


Assuntos
Amplificação de Genes , Neuroblastoma/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Adolescente , Diferenciação Celular , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Proteína Proto-Oncogênica N-Myc , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Prognóstico , Análise de Sobrevida , Taxa de Sobrevida
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