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1.
Tumour Biol ; 37(6): 7413-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26678884

RESUMO

Special AT-rich sequence-binding protein-1 (SATB1) is critical for genome organizer that reprograms chromatin organization and transcription profiles, and associated with tumor growth and metastasis in several cancer types. Many studies suggest that SATB1 overexpression is an indicator of poor prognosis in various cancers, such as breast cancer, malignant cutaneous melanoma, and liver cancer. However, their expression patterns and function values for adult T cell leukemia (ATL) are still largely unknown. The aim of this study is to examine the levels of SATB1 in ATL and to explore its function and mechanisms in Jurkat cell line. Here, we reported that SATB1 expressions were decreased in ATL cells (p < 0.001) compared with normal controls. Knockdown of SATB1 expression significantly enhanced invasion of Jurkat cell in vitro. Furthermore, knockdown of SATB1 gene enhances ß-catenin nuclear accumulation and transcriptional activity and thus may increase the invasiveness of Jurkat cell through the activation of Wnt/ß-catenin signaling pathway in vitro.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação à Região de Interação com a Matriz/fisiologia , Proteínas de Neoplasias/fisiologia , Via de Sinalização Wnt/fisiologia , Adulto , Linhagem Celular Tumoral , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Células Jurkat , Leucemia-Linfoma de Células T do Adulto/sangue , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Proteínas de Ligação à Região de Interação com a Matriz/antagonistas & inibidores , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , Proteínas de Ligação à Região de Interação com a Matriz/genética , Invasividade Neoplásica , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , RNA Interferente Pequeno/genética , Via de Sinalização Wnt/genética
2.
J Cancer Res Ther ; 19(1): 117-123, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37006051

RESUMO

Background: Because patients with diffuse large B-cell lymphoma (DLBCL) aged >80 years old typically experience dismal outcomes, it is essential to improve disease control and reduce side effects in such patients. Methods: This was a multi-center retrospective study. Patients aged ≥80 years with pathologically confirmed DLBCL were treated in four centers in the Guangdong province between January 2010 and November 2020. Clinical data from patients receiving different treatment modalities were extracted from electronic medical records. Results: Finally, 50 patients aged ≥80 years were included; four (8.0%) refused treatment, 19 (38%) patients belonged to the chemotherapy-free group, and 27 (54%) patients were in the chemotherapy group. Patients receiving chemotherapy-free treatment had more often a non-germinal center B phenotype than those treated with chemotherapy (P = 0.006). The median progression-free survival (PFS) in the chemotherapy-free group was longer than that in the chemotherapy group (24.7 vs 6.3 months, P = 0.033). Good performance status (PS <2) was associated with higher PFS and overall survival (OS) (P = 0.03; P = 0.02, respectively). In patients with PS of ≥2, the median PFS and OS did not differ between the chemotherapy-free and chemotherapy groups (P = 0.391; P = 0.911, respectively). After stratifying patients with PS <2, the PFS and OS of the chemotherapy-free group were better than those of the chemotherapy group (58.1 vs 7.7 months, P = 0.006; 58.1 vs 26.5 months, P = 0.050). However, treatment-related toxicity did not differ between groups. Conclusion: PS was an independent prognostic factor of elderly DLBCL patients. Accordingly, patients aged ≥80 years with a PS of <2 could benefit from a chemotherapy-free regimen.


Assuntos
População do Leste Asiático , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Linfoma Difuso de Grandes Células B/terapia , Prognóstico , Estudos Retrospectivos , Idoso de 80 Anos ou mais
3.
Comput Math Methods Med ; 2022: 7451395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36226246

RESUMO

Methods: Data from single-cell RNA sequencing (RNA-seq) of CLL patients were obtained from the Gene Expression Omnibus database. The R package was utilized to analyze the data, and the relation of results was predicted via the GeneMANIA website. The information of 7 samples covered three stages: observation stage, pretreatment by CIT with rituximab, fludarabine, and cyclophosphamide (pre-CIT), and post-CIT. The differentially expressed genes (DEGs) were identified, and functional enrichment analyses were performed. B cell subpopulations and pseudotime trajectories analysis was conducted. Results: A total of 70,659 DEGs were identified. Each patient's DEGs presented their own characteristics, with low similarity. Therefore, it is difficult to identify potential hub genes. Similarly, pathway enrichment analysis showed significant tumor heterogeneity among CLL patients. Analysis of relapsed post-CIT compared to the observation stage suggested that the TP53 pathway should be taken seriously as it is closely related to treatment strategy and patient prognosis. Conclusions: Tumor heterogeneity may be a more common manifestation of CLL. Individualized treatment should be considered for CLL. TP53 abnormality and its regulatory factors should still be the focus of CLL diagnosis and treatment.


Assuntos
Leucemia Linfocítica Crônica de Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Rituximab/uso terapêutico , Vidarabina/análogos & derivados
4.
J Cancer Res Clin Oncol ; 142(2): 389-99, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26319392

RESUMO

PURPOSE: The aim of this study was to investigate how the amplification of HMGA2 contributes to acute myeloid leukemia (AML) cell proliferation. METHODS: The amplification and expression of HMGA2 were examined by FISH, qRT-PCR and Western blot in AML cases. The effect of HMGA2 knockdown on cell proliferation was analyzed with XTT, colony-forming assays and BrdUrd incorporation assays. The effects of HMGA2 knockdown on cell cycle were studied by flow cytometry analysis. The progression of AML cells in vivo was examined by the xenografted tumor model. The interaction between Akt pathway and HMGA2 was examined by Western blot. RESULTS: HMGA2 is amplified in AML, and the levels of HMGA2 messenger RNA (mRNA) and protein expressed in AML cells were significantly higher than those in normal cells, which may be related to NR and prognosis of AML patients. Reduction in HMGA2 expression in AML cells inhibited cell proliferation through a decrease in the protein expression of pAkt and pmTOR, compared with control cells. CONCLUSIONS: HMGA2 is predominantly amplified and expressed in AML cells, and that aberrant expression of HMGA2 induces AML cell proliferation through the PI3K/Akt/mTOR signaling pathway. Inhibition of HMGA2 expression represents an attractive target for AML therapy.


Assuntos
Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adolescente , Adulto , Idoso , Animais , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Amplificação de Genes , Técnicas de Silenciamento de Genes , Células HL-60 , Proteína HMGA2/biossíntese , Xenoenxertos , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Adulto Jovem
5.
Int J Clin Exp Pathol ; 8(8): 9089-96, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464651

RESUMO

OBJECTIVE: The objective of this study was to analyze the expression of TARBP1 and its clinical significance in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 90 patients with primary hepatocellular carcinoma were included in this study. The tumor and paired adjacent non-tumor tissues were collected. TARBP1 expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry. Associations of TARBP1 expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. RESULTS: The result show the expression of TARBP1 mRNA in liver cancer tissues were higher than in the adjacent normal liver tissues in 10 paired samples (P=0.0015). Compared with adjacent normal liver tissues, overexpression of TARBP1 was detected in 61.1% (55/90) HCC patients. TARBP1 expression was associated with the AJCC tumor stage (P=0.004) and clinical stage (P=0.005), and decreased overall survival (P=0.002). In multivariate analysis, TARBP1 expression was an independent prognostic factor for overall survival (Hazard ratio [HR]=2.773, 95% confidence interval [CI] 1.542-4.985; P=0.019). CONCLUSIONS: TARBP1 is up-regulated in HCC, and the expression of TARBP1 was associated with the pathological grading and clinical stage. TARBP1 maybe is an independent prognostic marker of HCC patients.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Prognóstico , Proteínas de Ligação a RNA/genética
6.
Int J Clin Exp Pathol ; 7(12): 8593-601, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25674223

RESUMO

Cyclin kinase subunit 2 (CKS2) protein is a small cyclin-dependent kinase-interacting protein, which is essential for the first metaphase/anaphase transition of mammalian meiosis. CKS2 is up-regulated in various malignancies, suggesting that CKS2 maybe an oncogene. However, data on its expression pattern and clinical relevance in breast cancer are unknown. The aim of this study is to investigate CKS2 expression and its prognostic significance in breast cancer. The CKS2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting analysis in paired breast cancer tissues and the adjacent normal tissues. The expression of CKS2 protein in 126 specimens of breast cancer was determined by immunohistochemistry assay. The relations between CKS2 expression and clinicopathological features were analyzed. The result show the expression of CKS2 mRNA and protein was higher in breast cancer than the adjacent normal tissues. Compared with adjacent normal breast tissues, Overexpression of CKS2 was detected in 56.3% (71/126) patients. Overexpression of CKS2 was significantly associated with large tumor size (P = 0.035), poor cellular differentiation (P = 0.016), lack expression of progesterone receptor (P = 0.006), and decreased overall survival (P = 0.001). In multivariate analysis, CKS2 expression was an independent prognostic factor for overall survival (Hazard ratio [HR] = 3.404, 95% confidence interval [CI] 1.482-7.818; P = 0.004). CKS2 is up-regulated in breast cancer and associated with large tumor size, lack expression of progesterone receptor, poor tumor differentiation and survival. CKS2 may serve as a good prognostic indicator for patients with breast cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Quinases relacionadas a CDC2 e CDC28/biossíntese , Proteínas de Transporte/biossíntese , Proteínas de Ciclo Celular/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
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