RESUMO
PURPOSE: This study is to investigate the [68Ga]Ga-DOTA-FAPI PET/CT diagnosis performance in biliary tract carcinoma (BTC) and analyze the association between [68Ga]Ga-DOTA-FAPI PET/CT and clinical indexes. METHODS: A prospective study (NCT05264688) was performed between January 2022 and July 2022. Fifty participants were scanned using [68Ga]Ga-DOTA-FAPI and [18F]FDG PET/CT and acquired pathological tissue. We employed the Wilcoxon signed-rank test to compare the uptake of [68Ga]Ga-DOTA-FAPI and [18F]FDG, and the McNemar test was used to compare the diagnostic efficacy between the two tracers. Spearman or Pearson correlation was used to assess the association between [68 Ga]Ga-DOTA-FAPI PET/CT and clinical indexes. RESULTS: In total, 47 participants (mean age 59.09 ± 10.98 [range 33-80 years]) were evaluated. The [68Ga]Ga-DOTA-FAPI detection rate was greater than [18F]FDG in primary tumors (97.62% vs. 85.71%), nodal metastases (90.05% vs. 87.06%), and distant metastases (100% vs. 83.67%). The uptake of [68Ga]Ga-DOTA-FAPI was higher than [18F]FDG in primary lesions (intrahepatic cholangiocarcinoma, 18.95 ± 7.47 vs. 11.86 ± 0.70, p = 0.001; extrahepatic cholangiocarcinoma, 14.57 ± 6.16 vs. 8.80 ± 4.74, p = 0.004), abdomen and pelvic cavity nodal metastases (6.91 ± 6.56 vs. 3.94 ± 2.83, p < 0.001), and distant metastases (pleural, peritoneum, omentum, and mesentery, 6.37 ± 4.21 vs. 4.50 ± 1.96, p = 0.01; bone, 12.15 ± 6.43 vs. 7.51 ± 4.54, p = 0.008). There was a significant correlation between [68Ga]Ga-DOTA-FAPI uptake and fibroblast-activation protein (FAP) expression (Spearman r = 0.432, p = 0.009), carcinoembryonic antigen (CEA) (Pearson r = 0.364, p = 0.012), and platelet (PLT) (Pearson r = 0.35, p = 0.016). Meanwhile, a significant relationship between [68Ga]Ga-DOTA-FAPI metabolic tumor volume and carbohydrate antigen199 (CA199) (Pearson r = 0.436, p = 0.002) was confirmed. CONCLUSION: [68Ga]Ga-DOTA-FAPI had a higher uptake and sensitivity than [18F]FDG in the diagnosis of BTC primary and metastatic lesions. The correlation between [68Ga]Ga-DOTA-FAPI PET/CT indexes and FAP expression, CEA, PLT, and CA199 were confirmed. TRIAL REGISTRATION: clinicaltrials.gov: NCT 05,264,688.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Gastrointestinais , Quinolinas , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Gálio , Estudos Prospectivos , Fluordesoxiglucose F18 , Ductos Biliares Intra-Hepáticos , FibroblastosRESUMO
Objective This study aims to investigate the effect of geranylgeranyltransferaseâ (GGTase-â ) on the proliferation and growth of tongue squamous cancer cells. Methods Three small interfering RNAs (siRNAs) were designed on the basis of the GGTase-â sequence in GeneBank. These siRNAs were then transfected into tongue squamous cancer cells Cal-27. The mRNA and protein expression of GGTase-â and RhoA were examined by real-time quantitative polymerase chain reaction and Western blotting, respectively. The expression of Cyclin D1 and p21 were examined by Western blotting. The proliferation and growth ability were analyzed by cell counting kit-8 assay and flow cytometry. Results The mRNA and protein expression of GGTase-â in Cal-27 was reduced significantly after the GGTase-â siRNAs were transfected (P<0.05). No significant difference in RhoA mRNA and protein expression was detected (P>0.05). Cyclin D1 expression decreased, whereas p21 expression increased significantly. The cell cycle was altered, and the growth-proliferative activity was inhibited (P<0.05). Conclusion GGTase-â siRNA can inhibit the expression of GGTase-â and the proliferative activity of tongue squamous cancer cells. GGTase-â may be a potential target for gene therapy in tongue squamous cell cancer.
Assuntos
Alquil e Aril Transferases , Linhagem Celular Tumoral , Proliferação de Células , RNA Interferente Pequeno , Carcinoma de Células Escamosas , Ciclo Celular , Ciclina D1/metabolismo , Humanos , RNA Mensageiro , Transfecção , Proteína rhoA de Ligação ao GTPRESUMO
OBJECTIVE: RNA interference was used to silence geranylgeranyltransferase â (GGTase-â ) in vitro and to study the effect of GGTase-â on the migration and invasion of tongue squamous cancer cells. METHODS: Three small interfering RNAs (siRNA) were designed according to the GGTase-â sequence by Genebank and were transfected into tongue squamous cancer cells Cal-27 to knock down GGTase-â expression. The tested cells were divided into three groups, as follows: the RNA-interfered groups (GGTase-â siRNA1, GGTase-â siRNA 2, GGTase-â siRNA 3), a negative control group (disrupted by random sequence NC-siRNA), and a blank control group. GGTase-â and RhoA gene expressions were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The optimum interference group was screened by qRT-PCR and Western blot and was assigned as the experimental group. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were examined by Western blot. GTP-RhoA expression of protein was examined by GST-pull down. The migration and invasion abilities were analyzed by wound healing assay and Transwell motility assay. RESULTS: GGTase-â mRNA and protein expression in Cal-27 decreased significantly after transfection of GGTase-I siRNA (P<0.05). No significant difference of RhoA gene expression was detected. MMP-2, MMP-9, and GTP-RhoA protein expressions decreased significantly (P<0.05). The migration and invasion abilities were inhibited (P<0.05). CONCLUSIONS: To inhibit GGTase-â expression, the migration and invasion abilities of tongue squamous cancer cells should also be inhibited. Further studies on GGTase-â may provide novel effective molecular targets for tongue squamous cancer cells.
Assuntos
Alquil e Aril Transferases , Inativação Gênica , Invasividade Neoplásica , Interferência de RNA , Neoplasias da Língua , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Humanos , RNA Interferente Pequeno , Neoplasias da Língua/genética , TransfecçãoRESUMO
The TES gene was frequently lost in breast cancer, which could inhibit tumor invasion and the formation of distant metastasis. However, the underlying mechanisms remain unknown yet. In the present study, we aimed to investigate how TES was silenced and its roles in EMT--the key step for tumor metastasis. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the mRNA and protein expression of target genes; the status of TES promoter was determined by methylation-specific PCR and subsequently, DNA sequencing. Overexpression or downregulation of TES was achieved by pcDNA3.1-TES or shRNA-TES transfection. Cellular adhesion and migration were investigated by the adhesion and Transwell assays. Morphological changes of breast cancer cells were observed under the optical microscope. The Rho A activity was measured using a commercial kit, and its roles in TES-manipulated EMT were determined by real-time PCR and Western blot. The 42.3% (33/78) breast cancer tissues presented hypermethylation of the TES gene, whereas only 2 (2.6%) non-malignant cases were hypermethylated (P<0.001). Moreover, TES hypermethylation was significantly correlated with larger tumor diameter (P=0.03) and lympho node metastasis (P=0.024). In primary cultured breast cancer cells, the demethylation treatment using 5-aza-dC notably restored the expression of TES. In vitro, overexpression of TES enhanced cellular adhesion inhibited migration and suppressed EMT, while downregulation of TES impaired cellular adhesion, promoted migration, and enhanced EMT. TES overexpression also activated the Rho A signal, which is a critical factor for the effects of TES on the EMT procedure. We firstly proved that frequent loss of TES in breast cancer was caused by promoter hypermethylation, which was correlated with poor prognosis. In vitro, TES enhanced cellular adhesion, suppressed tumor migration, and inhibited EMT. Moreover, the Rho A pathway was critical for the effects of TES on EMT, which can be blocked by the Rho A inhibitor. Therefore, we propose restoration of TES as a potent strategy for breast cancer therapy.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas do Citoesqueleto/metabolismo , Metilação de DNA , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Proteínas com Domínio LIM/metabolismo , Western Blotting , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Adesão Celular , Movimento Celular , Proliferação de Células , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/genética , Feminino , Humanos , Proteínas com Domínio LIM/antagonistas & inibidores , Proteínas com Domínio LIM/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais CultivadasRESUMO
BACKGROUND: The aim of our study was to evaluate the serum concentration of sialic acid (SA) and high-sensitivity C-reactive protein (hs-CRP) in prehypertensive patients and the possible correlations between these 2 factors with blood pressure in such patients. MATERIAL AND METHODS: We studied 61 prehypertensive patients, 70 hypertensive patients, and 50 controls with normal blood pressure. Lipid profile, hs-CRP, SA, and body mass index (BMI) were estimated in all groups. Associations between SA and hs-CRP and blood pressure were analyzed using multiple linear regressions. RESULTS: SA and hs-CRP levels were higher in the prehypertension group than that in the control group and were lower than that in the hypertension group. Multiple linear regression demonstrated that fasting glucose, BMI, SA, and hs-CRP correlated with systolic blood pressure and that low-density lipoprotein, BMI, SA, and hs-CRP correlated independently with diastolic pressure (P<0.05). CONCLUSIONS: Our findings suggest that in prehypertension, there is an association between serum SA and hs-CRP levels and blood pressure.