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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 781-787, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533124

RESUMO

Objective To investigate the effect of RS102895, a specific C-C motif chemokine receptor 2 (CCR2) antagonist, on the biological behavior of prostate cancer (PCa) cells with different degrees of malignancy. Methods Non-androgen-dependent prostate cancer cells PC-3 and androgen-dependent prostate cancer cells 22RV1 were cultured in vitro. A control group, a recombinant C-C motif chemokine ligand 2 (rCCL2) treatment group, and a rCCL2 combined with RS102895 treatment group were established. Cell proliferation ability was detected by CCK-8 assay, cell invasion and migration abilities were detected by TranswellTM assay, mRNA expressions of cell antigen KI-67 (ki67) and matrix metalloproteinase 2 (MMP2) were detected by real-time quantitative PCR, and protein expression levels of ki67 and MMP2 were detected by Western blotting. Results The proliferation, invasion, and migration abilities of PC-3 cells were significantly enhanced by rCCL2, and the proliferation ability of 22RV1 cells was significantly increased as well. Meanwhile, the mRNA and protein expression levels of ki67 and MMP2 in PC-3 cells were significantly up-regulated by rCCL2. After RS102895 treatment, the above effects of rCCL2 were reversed. Conclusion RS102895 can inhibit the proliferation, invasion, and migration of PC-3 prostate cancer cells by specifically blocking the CCL2/CCR2 pathway and down-regulating the expressions of ki67 and MMP2.


Assuntos
Quimiocina CCL2 , Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CCL2/genética , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Invasividade Neoplásica , Células PC-3 , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Receptores CCR2/genética , Receptores de Quimiocinas
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 808-814, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533128

RESUMO

Objective To investigate the effect of lysine-specific demethylase 3A (KDM3A) on the invasion and migration of MDA-MB-231 breast cancer cells. Methods The mRNA and the protein expressions of KDM3A in MDA-MB-231 breast cancer cells and MCF-10A normal breast cells were detected by real-time quantitative PCR and Western blotting, respectively; the KDM3A level of MDA-MB-231 cells was knocked down by lentivirus infection of KDM3A short hairpin RNA (shKDM3A). The change of invasion and migration ability of MDA-MB-231 cells was detected by TranswellTM assay, and the change in the cell cycle was detected by flow cytometry. Results The expression of KDM3A in MDA-MB-231 breast cancer cells was significantly increased compared with that in MCF-10A epithelial cells; after KDM3A knockdown, the invasion and migration abilities of MDA-MB-231 cells were significantly decreased, and the cell cycle was arrested in the G0/G1 phase. Conclusion Knockdown of KDM3A inhibits the invasion and migration of MDA-MB-231 breast cancer cells and arrests the cell cycle in G0/G1 phase.


Assuntos
Neoplasias da Mama , Lisina , Neoplasias da Mama/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Fase G1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Invasividade Neoplásica/genética
3.
Harefuah ; 160(9): 559-564, 2021 Sep.
Artigo em Hebraico | MEDLINE | ID: mdl-34482666

RESUMO

INTRODUCTION: Neoadjuvant cisplatin-based chemotherapy prior radical cystectomy is the standard of care in patients with a muscle invasive bladder cancer. It is intended to treat micro-metastases. However, most patients do not develop metastases even without chemotherapy and are receiving this treatment in vain. In this study, we looked for pre-operative risk factors for developing metastases that can triage the patients that really need neoadjuvant therapy. METHODS: From 1998 to 2018, 285 patients underwent radical cystectomy without neoadjuvant chemotherapy. During a median follow-up of 42.5 months, 99 patients (34%) developed recurrent disease after a median duration of 12 months. The study compared 10 different preoperative parameters of patients who developed or did not develop recurrence. RESULTS: An increased risk of metastases was found in older patients (39.8% in older than 69 years vs. 33.3% in younger patients, p=0.045), in patients with a high Charlson Comorbidity index (46.2% in 5 and above vs. 28.2% when lower than 4, p=0.003), and in patients with large tumor diameter (p=0.01). No difference was found in the other variables examined including: gender, primary versus secondary tumor, tumor stage, presence of histological variant, hydronephrosis, carcinoma in situ (CIS) or sarcomatoid differentiation. CONCLUSIONS: Older age, comorbidity, and large tumor diameter predict the risk of recurrence after radical cystectomy. However, overlap between the groups precludes the use of these parameters for clinical decisions. Therefore, neoadjuvant chemotherapy treatment should currently be offered to all candidates for radical cystectomy. Hopefully, future molecular markers will be able to predict the risk of metastases.


Assuntos
Terapia Neoadjuvante , Neoplasias da Bexiga Urinária , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Cistectomia , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia
4.
Zhonghua Zhong Liu Za Zhi ; 43(9): 968-972, 2021 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-34530581

RESUMO

Objective: To investigate the relationship of microcystic elongated fragmented (MELF) and clinicopathological features of patients with low grade endometrial endometrioid carcinoma, and to analyze its impact on prognosis. Methods: The clinical pathological data of 512 cases with low grade endometrial endometrioid adenocarcinoma were collected. The MELF invasive pattern in all of the sections were reappraised. The correlations between MELF pattern and clinicopathological features were analyzed by chi-square test, and the independent risk factor of lymph node metastasis were evaluated by Logistic multivariate regression analysis. Survival curves was drawn by Kaplan-Meier method, and Log-rank test was used to compare progression free survival (PFS) between patients with or without MELF pattern. Disease progression-related multivariate analysis was carried out by Cox proportional hazards model. Results: MELF pattern was observed in 12.9% (66/512) low grade endometrioid adenocarcinoma. It was significantly associated with cervical stroma invasion, more than half of the depth of myometrial invasion, lymph node metastasis and vessel invasion (P<0.05). In addition, MELF pattern was an independent risk factor for lymph node metastasis (P<0.05). The 5-year PFS of patients with and without MELF pattern were 95.0% and 96.0% respectively (P>0.05). Conclusions: The patients with MELF pattern are more likely accompany with cervical stroma and deeper myometrium invasion, vessel invasion, and lymph node metastasis, and it is an independent risk factor of lymph node metastasis. However, MELF pattern has no significant impact on prognosis of patients with endometrioid carcinoma.


Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
6.
Arch Esp Urol ; 74(7): 681-691, 2021 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34472437

RESUMO

OBJECTIVES: Most patients at first diagnosis of bladder cancer (BC) present with non muscle invasive disease (NMIBC). BCG intravesical therapy after transurethral resection of the bladder tumor is the gold standard in intermediate and high risk NMIBC patients. However, it is estimated that approximately 50% of these patients will present with BCG failure which increases their risk for progression to muscle invasive disease. Currently, the best option for these patients is radical cystectomy. Thus, it is of great interest to pursue new, therapeutic options for BCG failure patients to avoid the necessity of radical cystectomy. We hereby review novel treatment modalities for BCG failure patients. METHODS: This is a narrative review. Keywords for the search were BCG failure, BCG unresponsive, BCG refractory, BCG relapsing and BCG intolerance. Evidence was identified through a search for publications with a ''BCG unresponsive'' tag through 2020. Studies were selected if they contained clinical data on BCG unresponsive therapeutics with near-term availability. Clinical trial landscape evaluation for emerging therapies was performed by searching ClinicalTrials.gov for recruiting/ open interventional trials in 2020. RESULTS: Novel treatment modalities for BCG failure include intravesical chemotherapy, BCG re-challenge or combination of BCG with IFN-α2ß, valrubicin, radiotherapy, electromotive drug administration, vicinium, chemohyperthermia, photodynamic therapy, gene therapy, vaccine therapy and immunotherapy. For patients in whom BCG has once failed a repeat course of BCG or BCG plus interferon appears to be a reasonable practice. Likewise, single agent gemcitabine may be considered a treatment modality. However, after 2 or more BCG failures, especially in patients with earlier relapses or cancer persistence, single agent intravesical chemotherapy with valrubicin, gemcitabine or docetaxel appears to be less active than doublet/triplet intravesical chemotherapy or mitomycin chemothermotherapy. Gene therapy or conjugated antibodies may play a role upon further relapse. Single agent pembrolizumab is unlikely to be used as first line, but may be useful, along with multiple new immunotherapeutics, as part of a multimodal approach towards BCG unresponsive disease. CONCLUSIONS: Results from ongoing trials will provide us useful information about many of the existing regimens and probably new drugs will soon be available for this group of patients.


Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Cistectomia , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/tratamento farmacológico
7.
Anticancer Res ; 41(9): 4365-4375, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475056

RESUMO

BACKGROUND/AIM: Ouabain has been shown to induce human cancer cell death via apoptosis. Still, its anti-metastatic effect on cell migration and invasion of human gastric cancer cells has not been addressed. MATERIALS AND METHODS: Cell proliferation and viability were measured by the MTT assay and flow cytometry, respectively. Cell motitlity was analysed by wound healing assay. Cell migration and invasion were analysed by the transwell system. Protein expression was assayed by western blotting. RESULTS: Ouabain decreased AGS cell proliferation, cell viability, and motility. In addition, ouabain inhibited AGS cell migration and invasion. Furthermore, ouabain decreased matrix metalloproteinase-2 (MMP-2) activity at 48 h. Ouabain reduced the levels of proteins associated with PI3K/AKT and p38/MAPK pathways. In addition, ouabain decreased the expressions of N-cadherin, tissue inhibitor of metalloproteinases-1 (TIMP-1), urokinase-type plasminogen activator (c-uPA), and MMP-2 at 48 h. CONCLUSION: Ouabain suppresses cell metastasis through multiple signaling pathways in AGS cells.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Ouabaína/farmacologia , Neoplasias Gástricas/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Inibidor Tecidual de Metaloproteinase-1/metabolismo
8.
Nat Commun ; 12(1): 5232, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475402

RESUMO

Disseminated tumor cells often fall into a long term of dormant stage, characterized by decreased proliferation but sustained survival, in distant organs before awakening for metastatic growth. However, the regulatory mechanism of metastatic dormancy and awakening is largely unknown. Here, we show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels of dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) NR2F1-AS1 (NAS1) is up-regulated in the dormant mesenchymal-like BCSCs, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanistically, NAS1 binds to NR2F1 mRNA and recruits the RNA-binding protein PTBP1 to promote internal ribosome entry site (IRES)-mediated NR2F1 translation, thus leading to suppression of ΔNp63 transcription by NR2F1. Furthermore, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall, the study links BCSC plasticity with metastatic dormancy, and reveals the lncRNA as an important regulator of both processes.


Assuntos
Neoplasias da Mama/patologia , Fator I de Transcrição COUP/genética , Neoplasias Pulmonares/secundário , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Regiões 5' não Traduzidas , Animais , Neoplasias da Mama/genética , Fator I de Transcrição COUP/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Sítios Internos de Entrada Ribossomal , Pulmão/patologia , Neoplasias Pulmonares/genética , Camundongos , Invasividade Neoplásica , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
9.
Zhonghua Yi Xue Za Zhi ; 101(34): 2692-2697, 2021 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-34510875

RESUMO

Objective: To elucidate the biological role and potential mechanism of integrin α5 (ITGA5) in gastric cancer (GC). Methods: From January 2019 to December 2020, 35 pairs of GC tissue [21 males and 14 females, aged (53.8±5.4) years] and matched adjacent tissue samples were collected from GC patients who underwent surgical resection in Zhejiang Provincial People's Hospital. GC and normal gastric mucosa cells were purchased from Beijing Biobw Biotech Company. Quantitative real-time PCR (qRT-PCR), immunohistochemistry, Western blotting were performed to detect the mRNA and protein expression levels of ITGA5, cell adhesion-related genes (pFAK, pSrc, aRac1) in GC cells. Cell Counting Kit-8 (CCK-8), Transwell invasion, wound healing and cell adhesion assays were conducted for GC cell phenotype detection. Results: ITGA5 was highly expressed in GC compared with normal gastric mucosa cells (relative expression increased from 1.00±0.26 to 1.23±0.27,P<0.05). In addition, ITGA5 overexpression promoted the cell proliferation [from (1.14±0.14) OD to (1.61±0.14) OD], migration ability [from (20.3±2.3)% to (56.4±6.1)%], invasion ability (from 144.0±4.6 to 216.7±6.6), and adhesion ability of matrix protein (from 99.0±8.5 to 152.0±12.3) through FAK/Src/Rac1 signaling pathway in GC.(all P<0.05) Conclusions: ITGA5 acts as a cancer-promoting factor in GC. The current study provides theoretical evidence for probing the novel molecular targets for the treatment of GC.


Assuntos
Integrina alfa5 , Integrinas/metabolismo , Neoplasias Gástricas , Movimento Celular , Proliferação de Células , Feminino , Humanos , Integrina alfa5/metabolismo , Masculino , Invasividade Neoplásica , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo
10.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445170

RESUMO

Triple-negative breast cancer (TNBC) is a highly aggressive disease with invasive and metastasizing properties associated with a poor prognosis. The STAT3 signaling pathway has shown a pivotal role in cancer cell migration, invasion, metastasis and drug resistance of TNBC cells. IL-6 is a main upstream activator of the JAK2/STAT3 pathway. In the present study we examined the impact of the NO-donor glyceryl trinitrate (GTN) on the activation of the JAK2/STAT3 signaling pathway and subsequent migration, invasion and metastasis ability of TNBC cells through in vitro and in vivo experiments. We used a subtoxic dose of carboplatin and/or recombinant IL-6 to activate the JAK2/STAT3 signaling pathway and its functional outcomes. We found an inhibitory effect of GTN on the activation of the JAK2/STAT3 signaling, migration and invasion of TNBC cells. We discovered that GTN inhibits the activation of JAK2, the upstream activator of STAT3, and mediates the S-nitrosylation of JAK2. Finally, the effect of GTN (Nitronal) on lung metastasis was investigated to assess its antitumor activity in vivo.


Assuntos
Janus Quinase 2/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroglicerina/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica/prevenção & controle , Doadores de Óxido Nítrico/uso terapêutico , Nitroglicerina/uso terapêutico , Neoplasias de Mama Triplo Negativas/metabolismo
11.
Medicina (Kaunas) ; 57(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34356991

RESUMO

Background and Objectives: Matrix metalloproteinases (MMP) have been implicated as major determinants of tumour growth and metastasis, which are considered two of the main hallmarks of cancer. The interaction of MMP8 and other signalling molecules within and adjacent tumoral tissues, including immune cells, are rather elusive, particularly of adenocarcinoma cell type. In this study, we aimed to investigate the role of MMP8 in non-small cell lung cancer proliferation and invasiveness potential. Materials and Methods: We individually lipofected with two different single guide RNA (sgRNAs) that specifically targeted on MMP8, with CRISPR-Cas 9 protein into the cells. Results: Our results clearly indicated that the lipofection of these complexes could lead to reduced ability of A549 cells to survive and proliferate to form colonies. In addition, when compared to non-transfected cells, the experimental cell groups receiving sgRNAs demonstrated relatively decreased migration rate, hence, wider wound gaps in scratch assay. The quantitative real time-polymerase chain reaction (qRT-PCR) demonstrated significant reduction in the MAP-K, survivin and PI3-K gene expression. MMP8 might have protective roles over tumour growth and spread in our body. Conclusions: The delivery of sgRNAs targeting on the MMP8 gene could induce tumour cell death and arrest cell migratory activity.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Neoplasias Pulmonares/genética , Metaloproteinase 8 da Matriz , Invasividade Neoplásica , RNA Guia
12.
Hinyokika Kiyo ; 67(7): 303-308, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34353010

RESUMO

Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is expected to be useful in preventing oversight of non-muscle-invasive bladder cancer (NMIBC) and in reducing the intravesical recurrence rate after transurethral resection of bladder tumor (TURBT). We report our initial experience with28 cases of PDD-assisted TURBT (122 samples) performed at our hospital from February 2018 to April 2019. The median age of the patients was 74.5 years, and 18 of the 28 were primary cases. Each patient underwent TURBT with oral administration of 5-ALA 20 mg/kg 3 hours before endoscopic examination. The sensitivity was 89.8% when both white light and blue light were used, which was superior to the sensitivity of 67.8% when using only white light (p<0.01, McNemar's test). Among the first several cases, we experienced high false positivity, which suggested that some experience may be required to discriminate tumors from inflammatory lesions. In fact, the specificity and the positive likelihood ratio improved with experience. No grade 2 or higher adverse events were observed among our cases. The median follow-up period was 738 days, and 9 of 28 patients (32. 1%) had recurrence within the follow-up period. In conclusion, our initial experience with PDD-assisted TURBT demonstrated its excellent diagnostic sensitivity and safety, as previously reported.


Assuntos
Neoplasias da Bexiga Urinária , Idoso , Ácido Aminolevulínico , Cistectomia , Cistoscopia , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia
13.
Nat Commun ; 12(1): 5066, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417456

RESUMO

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.


Assuntos
Colesterol/biossíntese , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Esqualeno Mono-Oxigenase/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular , Estudos de Coortes , Simulação por Computador , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Esqualeno Mono-Oxigenase/genética , Esqualeno Mono-Oxigenase/metabolismo , Terbinafina/farmacologia , Ativação Transcricional/genética
14.
Nat Commun ; 12(1): 5056, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417458

RESUMO

Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::NrasQ61K; Cdkn2a-/- melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism.


Assuntos
Epigênese Genética , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fator de Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Acetilação , Animais , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Adesão Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 2/metabolismo , Histonas/metabolismo , Humanos , Melanócitos/metabolismo , Melanócitos/patologia , Camundongos Nus , Camundongos Transgênicos , Invasividade Neoplásica , Micrometástase de Neoplasia , Ligação Proteica , Carga Tumoral
15.
Medicina (Kaunas) ; 57(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34440955

RESUMO

Bladder cancer (BCa) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. While the clinical approach to BCa has remained largely unchanged for many years, recent discoveries have paved the way to a new era of diagnosis and management of the disease. BCa-specific mortality started to decrease in the regions with a wide range of activities leading to greater social awareness of the risk factors and the decline in carcinogenic exposure. The urologic community refines the role of transurethral surgery towards more rigorous and high-quality techniques. New agents have been approved for patients with BCG failure who faced radical cystectomy so far. Although radical removal of the bladder is the gold standard for muscle invasive cancer management, the extent and clinical value of lymphadenectomy is currently heavily challenged in randomized trials. Furthermore, alternatives to perioperative chemotherapy have arisen to increase the likelihood of complete treatment delivery and successful oncological outcomes. Finally, improvements in molecular biology and our understanding of tumorigenesis open the era of personalized medicine in bladder cancer. In the present review, the status and future directions in bladder cancer epidemiology, diagnosis and management are thoroughly discussed.


Assuntos
Neoplasias da Bexiga Urinária , Cistectomia , Humanos , Excisão de Linfonodo , Invasividade Neoplásica , Fatores de Risco , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/terapia
16.
Biomed Res Int ; 2021: 4959381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337014

RESUMO

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays in vitro and in vivo. Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration in vitro. Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed in vivo. Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC in vitro and in vivo. Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/metabolismo , Fatores de Transcrição TCF/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Modelos Biológicos , Invasividade Neoplásica , Metástase Neoplásica , Estabilidade Proteica , RNA Longo não Codificante/genética , Fatores de Transcrição TCF/química , Ubiquitinação , Regulação para Cima/genética
17.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(4): 413-418, 2021 Aug 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34409796

RESUMO

OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. METHODS: B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. CONCLUSIONS: PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.


Assuntos
Melanoma , Estilbenos , Animais , Linhagem Celular Tumoral , Movimento Celular , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Melanoma/tratamento farmacológico , Camundongos , Invasividade Neoplásica , Estilbenos/farmacologia , Quinase Syk , Fator A de Crescimento do Endotélio Vascular
18.
Ann Clin Lab Sci ; 51(4): 470-486, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452885

RESUMO

OBJECTIVE: Epithelium-specific ETS protein 3 (Ese-3) is a member of the ETS family that is associated with tumor progression. However, there is little knowledge about Ese-3 in skin cancer. This study was conducted to explore the effects of Ese-3 on clinical prognosis in skin cancer and the functions of HaCaT cells. MATERIALS AND METHODS: Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and three GSE datasets (GSE15605, GSE46517, and GSE114445). Comparison of data between groups was performed by Student's t-test and chi square test. Survival analysis was performed using log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models. Enrichment analysis was used to predict Ese-3 related functions. Cell proliferation assays, colony formation assays, and flow cytometry were used to assess cell proliferation, while Transwell assays analyzed cell migration and invasion. RESULTS: Compared with normal tissues, the Ese-3 mRNA in cutaneous malignant melanoma (CMM) patients was downregulated (P<0.0001). Ese-3 mRNA was associated with the T stage (χ 2=10.015, P=0.018), clinical stage (χ 2=4.122, P=0.042), and prognosis in CMM patients (P=0.0219) and was an independent prognostic predictor in CMM (HR=1.878, P=0.048). Enrichment analysis showed that differentially expressed proteins were associated with "protein kinase B (AKT) binding." CONCLUSION: Ese-3 inhibited the proliferation, migration, and invasion of HaCaT cells by downregulating PSIP1 and NUCKS1 expression levels to inactivate the phosphorylation of AKT.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/antagonistas & inibidores , Fosfoproteínas/antagonistas & inibidores , Neoplasias Cutâneas/patologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Células HaCaT , Humanos , Masculino , Invasividade Neoplásica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Taxa de Sobrevida , Fatores de Transcrição/genética
19.
Ann Clin Lab Sci ; 51(4): 494-502, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452887

RESUMO

OBJECTIVE: Gastric cancer is one of the most common gastrointestinal malignancies. miRNAs (microRNAs) have been reported to play a pivotal role in the tumorigenesis of gastric cancer. However, the role of miR-643 in gastric cancer is not fully understood. METHODS: The expression of miR-643 in gastric cancer cell lines was detected by qRT-PCR (quantitative reverse transcription PCR). Cell viability, apoptosis, migration, and invasion were assessed using the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound scratch and Transwell assays, respectively. The target gene of miR-643 was predicted by bioinformatics analysis and validated using luciferase reporter assay. RESULTS: The expression level of miR-643 in gastric cancer cell lines was lower than in the normal gastric epithelium cell line (GES-1). Overexpression of miR-643 inhibited cell viability and colony formation but promoted cell apoptosis in gastric cancer. Transwell invasion assay and in vitro scratch assay evidenced that miR-643 overexpression inhibited gastric cancer cell migration and invasion. Bioinformatics analysis revealed that miR-643 could directly target TXNDC9 (Thioredoxin domain containing 9), and luciferase reporter assay validated this result. Further analysis showed that miR-643 mimics caused a significant reduction of TXNDC9 in gastric cancer cells. Moreover, TXNDC9 overexpression reversed the effects of miR-643 mimics on gastric cancer cell viability, invasion, and migration. CONCLUSION: miR-643 functions as a potential tumor suppressor in gastric cancer by inhibiting cell viability, colony formation, migration, and invasion via targeting TXNDC9, which provides a novel target for the diagnostic treatment of gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Gástricas/patologia , Tiorredoxinas/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Transição Epitelial-Mesenquimal , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tiorredoxinas/genética , Células Tumorais Cultivadas
20.
Ann Clin Lab Sci ; 51(4): 521-528, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452890

RESUMO

OBJECTIVE: Radioresistance-induced locoregional recurrence remains a major cause of low survival rates. However, the mechanism of treatment failure in these lung cancer patients has not been determined. In the current study, we tried to explore the potential molecular mechanism. METHODS: The fractionated irradiations were continued until the total concentration reached 80 Gy, and we established radioresistant subclones derived from A549 lines (designated as A549/R). The MTT assay, wound healing assay, transwell assay, and soft agar colony formation assay were employed to detect the proliferation, migration, invasion, and clonogenicity of the cells, respectively. Western blot and Fluorescence Activating Cell Sorter (FACS) indicated the expression of the markers. RESULTS: A549/R cells proliferated more slowly than the parental A549 cells. A significant acceleration in cell migration and invasion was revealed in A549/R cells compared with A549 cells. The expression levels of mesenchymal markers (N-cadherin, vimentin, claudin-1, and Snail) increased, while epithelial markers (E-cadherin and ß-catenin) decreased in A549/R cells. Meanwhile, the expression levels of stemness markers (Oct4, Notch1, and CD133) increased in A549/R cells, and A549/R cells showed more sphere-forming activity compared with A549 cells. CONCLUSION: Fractionated irradiation could promote epithelial-mesenchymal transition and enhance the migration, invasion, and stemness-like properties in A549 cells, elucidating the possible radioresistance mechanisms of the cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Raios gama , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/patologia , Células A549 , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Movimento Celular , Proliferação de Células , Fracionamento da Dose de Radiação , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação
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