RESUMO
Although angiogenesis is a critical event in hepatocellular carcinoma (HCC), and this process provides the tumor with sufficient oxygen and nutrients, the precise molecular mechanism by which it occurs is not fully understood. NEDD4 binding protein 3 (N4BP3) was identified in this study as a novel pro-angiogenic factor in HCC cell lines and tissues. We discovered that N4BP3 was significantly expressed in HCC and that its level of expression was positively correlated with the density of tumor microvessels in HCC tissues. Cell biology experiments have shown that N4BP3 knockdown in HCC cells significantly inhibits the formation of complete tubular structures by HUVECs in vitro and HCC angiogenesis in vivo. In HCC cells, overexpression of N4BP3 has the opposite effects. Further cell and molecular biology experiments have revealed that N4BP3 interacts with KAT2B (lysine acetyltransferase 2B), increasing signal transducer and activator of transcription 3 (STAT3) expression by regulating the distribution of acetyl-histone H3 (Lys27) (H3K27ac) in its promoter region. This, in addition, regulates the activity of the STAT3 signaling pathway, which promotes the proliferation of microvessels in HCC and accelerates the malignant process of the tumor. In vivo experiments in nude mice have confirmed our findings, and also suggested that N4BP3 could be a potential target for the treatment of HCC in combination with sorafenib.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Lisina Acetiltransferases , Indutores da Angiogênese , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Histonas , Humanos , Neoplasias Hepáticas/patologia , Lisina Acetiltransferases/metabolismo , Camundongos , Camundongos Nus , Neovascularização Patológica/patologia , Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , SorafenibeRESUMO
BACKGROUND: High concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were found in the serum of patients with colon cancer. We performed the present work to investigate the association between elevated levels of serum biomarkers (CEA and CA19-9) and shortened survival in patients with colon cancer. METHODS: We examined patients who underwent colonoscopies between 2001 and 2014 and measured and analyzed the serum CEA and CA19-9 levels of 362 participants. RESULTS: Elevated CEA concentrations were found to be associated with advanced invasion, lymph node metastasis, and short survival. Elevated CA19-9 concentrations also were associated with lymph node metastasis and short survival. CONCLUSIONS: Elevated serum CEA or CA19-9 levels were found to be associated with shortened survival.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUNDS: Special AT-rich sequence-binding protein 1 (SATB1) belongs to the chromatin-remodeling protein which regulates different genes expression. High expression of SATB1 was found to be associated with the development of certain carcinomas. However, the functions of SATB1 in colon adenocarcinoma (CAC) remains unclear yet. Our study aims to investigate the potential role of SATB1 in CAC and whether it is associated with the unfavorable symptoms of CAC patients. METHODS: The expression pattern of SATB1 was measured in CAC samples and adjacent noncancerous samples through quantitative real-time polymerase chain reaction and immunohistochemistry staining. We performed univariate and multivariate analyses to evaluate the clinical role of SATB1 in enrolled patients. The Kaplan-Meier analyses and log-rank tests were carried out to assess the clinicopathologic characteristics. The effect of SATB1 in human colon cancer cells was examined through cellular experiments. RESULTS: The expression level of SATB1 in CAC tissues was significantly elevated compared with adjacent control tissues. High expression of SATB1 in tumor tissue was found to be associated with lymph node metastasis and advanced TNM stage. Higher SATB1 level in CAC patients indicated a worse 5-year survival time. Moreover, high SATB1 was defined as an independent poor prognostic factor. Cellular experiments showed that inhibition of the SATB1 protein level in human colon cells could suppress the migration and invasion capabilities. CONCLUSIONS: Our findings revealed that high expression of SATB1 was significantly correlated with the poor clinical features and prognosis of CAC patients. It indicated that SATB1 might serve as a potential prognostic predictor and novel drug target for CAC treatment.
Assuntos
Adenocarcinoma , Neoplasias do Colo , Proteínas de Ligação à Região de Interação com a Matriz , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Fatores de TranscriçãoRESUMO
This study was conducted in order to compare the performance of the rapid urease test (RUT) with that of the polymerase chain reaction (PCR) for H. pylori diagnosis. Of 536 patients, 81% were concordant between RUT and PCR, 16% were concordant between two PCR assays but not between RUT and PCR, and the remaining 3% showed discrepant results between two PCR assays evaluated. Low bacterial load was shown to be a significant factor associated with false-negative diagnosis by RUT, and non-H. pylori urease activity or bacterial alkaline-generating activity was the cause of false-positive diagnosis. Disagreement between the PCR assays was due to single nucleotide polymorphisms in primers or probes causing decreased amplification efficiency and false-negative diagnosis when the bacterial load in the samples was low.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Primers do DNA , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/genética , Humanos , Reação em Cadeia da Polimerase , Urease/químicaRESUMO
Abstract We aimed to evaluate the effects of somatostatin combined with early hemoperfusion on inflammatory and stress responses during acute pancreatitis (AP) treatment. A total of 159 AP patients treated from September 2016 to January 2020 were randomly divided into three groups A-C (n=53). In addition to routine treatment, groups A-C were additionally given somatostatin, early hemoperfusion, and somatostatin combined with early hemoperfusion, respectively. Their inflammatory factors, stress response, intestinal mucosal barrier, hemorheological indices, recovery time, length of stay, clinical efficacy, and adverse reactions were compared. The levels of serum interleukin-10 (IL - 10), catalase and glutathione peroxidase rose in the three groups after ten days of treatment, compared with values before treatment, being the highest rise in group C. The levels of IL -18, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, procalcitonin, high mobility group protein B1, lipid hydrogen peroxide, advanced oxidation protein products, epinephrine, cortisol, D-lactic acid, diamine oxidase, and endotoxin decreased after ten days of treatment compared with those before treatment, which were lowest in group C (P<0.05). After ten days of treatment, the levels of hemorheological indices were significantly lower than those before treatment (P<0.05). Compared with groups A and B, group C had a shorter recovery time of urine amylase, bowel sound and passing gas, remission time of abdominal pain, length of stay, and a higher total response rate (P<0.05). During AP treatment, somatostatin combined with early hemoperfusion effectively relieved inflammatory and stress responses, protected the intestinal mucosal barrier function and improved the hemorheology, thereby promoting the recovery and benefiting the prognosis of patients.
Resumen Nuestro objetivo fue evaluar los efectos de la somatostatina combinada con hemoperfusión temprana sobre las respuestas inflamatorias y de estrés durante el tratamiento de la pancreatitis aguda (PA). Un total de 159 pacientes con PA tratados entre septiembre de 2016 y enero de 2020 se dividieron aleatoriamente en tres grupos A-C (n=53). Con base en el tratamiento de rutina, los grupos A-C recibieron además somatostatina, hemoperfusión temprana y somatostatina combinada con hemoperfusión temprana, respectivamente. Se compararon sus factores inflamatorios, respuesta al estrés, barrera de la mucosa intestinal, índices hemorreológicos, tiempo de recuperación, tiempo de estancia, eficacia clínica y reacciones adversas. Los niveles séricos de interleucina-10 (IL -10), catalasa y glutatión peroxidasa aumentaron en los tres grupos después de 10 días de tratamiento, comparados con los valores antes del tratamiento, siendo más elevados en el grupo C. Los niveles de IL - 18, factor de necrosis tumoral α, molécula de adhesión intercelular 1 soluble, procalcitonina, proteína B1 del grupo de alta movilidad, peróxido de hidrógeno lipídico, los productos proteicos de oxidación avanzada, epinefrina, cortisol, ácido D-láctico, diaminooxidasa y endotoxina disminuyeron después de 10 días de tratamiento en comparación con los previos al tratamiento, que fueron más bajos en el grupo C (P<0,05). Después de 10 días de tratamiento, los índices hemorreológicos fueron significativamente menores que los previos al tratamiento (P<0,05). En comparación con los grupos A y B, el grupo C tuvo un tiempo de recuperación más corto de amilasa en orina, sonido y escape intestinal, tiempo de remisión del dolor abdominal y tiempo de estancia, y una tasa de respuesta total más alta (P<0,05). Durante el tratamiento de la AP, la somatostatina combinada con hemoperfusión precoz alivia eficazmente las respuestas inflamatorias y de estrés, protege la función de la barrera de la mucosa intestinal y mejora la hemorología, favoreciendo la recuperación y beneficiando el pronóstico de los pacientes.