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BACKGROUND: In this study, we aimed to establish nomograms to predict the microvascular invasion (MVI) and early recurrence in patients with small hepatocellular carcinoma (SHCC), thereby guiding individualized treatment strategies for prognosis improvement. METHODS: This study retrospectively analyzed 326 SHCC patients who underwent radical resection at Wuhan Union Hospital between April 2017 and January 2022. They were randomly divided into a training set and a validation set at a 7:3 ratio. The preoperative nomogram for MVI was constructed based on univariate and multivariate logistic regression analysis, and the prognostic nomogram for early recurrence was constructed based on univariate and multivariate Cox regression analysis. We used the receiver operating characteristic (ROC) curves, area under the curves (AUCs), and calibration curves to estimate the predictive accuracy and discriminability of nomograms. Decision curve analysis (DCA) and Kaplan-Meier survival curves were employed to further confirm the clinical effectiveness of nomograms. RESULTS: The AUCs of the preoperative nomogram for MVI on the training set and validation set were 0.749 (95%CI: 0.684-0.813) and 0.856 (95%CI: 0.805-0.906), respectively. For the prognostic nomogram, the AUCs of 1-year and 2-year RFS respectively reached 0.839 (95%CI: 0.775-0.903) and 0.856 (95%CI: 0.806-0.905) in the training set, and 0.808 (95%CI: 0.719-0.896) and 0.874 (95%CI: 0.804-0.943) in the validation set. Subsequent calibration curves, DCA analysis and Kaplan-Meier survival curves demonstrated the high accuracy and efficacy of the nomograms for clinical application. CONCLUSIONS: The nomograms we constructed could effectively predict MVI and early recurrence in SHCC patients, providing a basis for clinical decision-making.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Nomogramas , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Microvasos/patología , Pronóstico , Anciano , Curva ROC , Estimación de Kaplan-Meier , Adulto , HepatectomíaRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with retarded lung development and poor lung health in offspring. Mammalian target of rapamycin (mTOR) is a key regulator of vasculogenesis and angiogenesis. The aim of this study was to investigate the role mTOR plays in pulmonary vasculogenesis during fetal lung development under maternal hyperglycemia. METHODS: First, GDM was induced via streptozotocin injection in pregnant C57BL/6 mice before the radial alveolar count (RAC) in the fetal lungs was assessed using hematoxylin and eosin staining. The angiogenic ability of the cultured primary mouse fetal lung endothelial cells (MFLECs) was then assessed using the tube formation assay technique, while western blot and real-time polymerase chain reaction were performed to determine the expression of mTOR, regulatory-associated protein of mTOR (Raptor), rapamycin-insensitive companion of mTOR (Rictor), stress-activated protein kinase interacting protein 1 (Sin1), G protein beta subunit-like protein (GßL), Akt, tumor necrosis receptor associated factor-2 (TRAF2), and OTU deubiquitinase 7B (OTUD7B) in both the fetal lung tissues and the cultured MFLECs. Immunoprecipitation assays were conducted to evaluate the status of GßL-ubiquitination and the association between GßL and mTOR, Raptor, Rictor, and Sin1 in the cultured MFLECs. RESULTS: The GDM fetal lungs exhibited a decreased RAC and reduced expression of von Willebrand factor, CD31, and microvessel density. The high glucose level reduced the tube formation ability in the MFLECs, with the mTOR, p-mTOR, p-Raptor, and TRAF2 expression upregulated and the p-Rictor, p-Sin1, p-Akt, and OTUD7B expression downregulated in both the GDM fetal lungs and the high-glucose-treated MFLECs. Meanwhile, GßL-ubiquitination was upregulated in the high-glucose-treated MFLECs along with an increased GßL/Raptor association and decreased GßL/Rictor and GßL/Sin1 association. Furthermore, TRAF2 knockdown inhibited the high-glucose-induced GßL-ubiquitination and GßL/Raptor association and restored the tube formation ability of the MFLECs. CONCLUSION: Maternal hyperglycemia inhibits pulmonary vasculogenesis during fetal lung development by promoting GßL-ubiquitination-dependent mTORC1 assembly.
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Purpose: CD24 is overexpressed in hepatocellular carcinoma (HCC) tumor tissues and in the highly metastatic HCC cell lines. However, plasma CD24 level in HCC patients and the correlation of plasma CD24 level with clinicopathological factors and prognosis of HCC patients still remain unclear. Materials and Methods: Enzyme-linked immunosorbent assay was used to detect plasma CD24 level in 86 HCC patients, 35 healthy subjects, 26 patients with liver cirrhosis and 23 patients with chronic hepatitis. The relationship between plasma CD24 level with clinicopathological characteristics in HCC patients was assessed using the Mann-Whitney U test. Patient survival between groups was evaluated by the Kaplan-Meier method and the log-rank test, prognostic factors being analyzed by the Cox regression model. Results: Our present study demonstrated that plasma CD24 level in HCC patients was significantly higher than that in the controls. CD24 was significantly associated with tumor differentiation, but was not correlated with other clinicopathologic parameters including gender, age, tumor size, tumor number, capsulation status, HBsAg status, tumor node metastasis stage, ALT, AFP, and GGT level. CD24 might be a prognostic predictor for overall survival and recurrence-free survival. Conclusions: Plasma CD24 level was significantly higher in HCC patients than that in the controls. Plasma CD24 level was associated with tumor differentiation. The HCC patients with high plasma CD24 level had unfavorable prognosis. CD24 might be a prognostic biomarker for HCC in the future.
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Biomarcadores de Tumor/análisis , Antígeno CD24/análisis , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Antígeno CD24/metabolismo , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Hepatectomía , Humanos , Estimación de Kaplan-Meier , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Tasa de Supervivencia , Regulación hacia ArribaRESUMEN
This study investigated the expression of lung surfactant proteins (SP-B and SP-C), and regulatory factors [forkhead box A2 (FOXA2) and nitrolyogenic FOXA2 (N-FOXA2)] in the fetal lung of rats with gestational diabetes mellitus (GDM) in order to study the mechanism of pulmonary dysplasia. The rat GDM model was established by using streptozotocin intraperitoneally in the first stage of pregnancy. There were 10 rats in the GDM group, and 10 healthy rats in normal control group without any treatment. Fetal lungs of two groups were taken at day 21 of pregnancy. Blood glucose levels of maternal rats and fetal rats were measured by Roche blood glucose meter. The histological changes in the fetal lung were observed under the light microscope in both groups. The SP-B, SP-C and FOXA2 were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, total FOXA2, FOXA2 in nucleus (n-FOXA2), N-FOXA2 proteins were detected by Western blotting, and the relative expression levels of SP-B, SP-C, FOXA2 mRNA in the fetal lung of two groups were detected by RTPCR. The results showed that blood glucose levels of maternal rats and fetal rats in GDM group were higher than those in control group. The light microscope revealed fetal lung development retardation in GDM group. The expression of SP-B and SP-C in GDM group was significantly reduced as compared with control group (P<0.05). As compared with control group, the n-FOXA2 expression was significantly decreased in the fetal lung tissue, and N-FOXA2 was significantly increased in control group (P<0.05), but there was no significant changes in the total FOXA2 (P>0.05). It was concluded that GDM can cause fetal lung development and maturation disorders, and FOXA2 in fetal lung tissue decreases while nitrocellulose FOXA2 increases.
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Diabetes Gestacional/genética , Factor Nuclear 3-beta del Hepatocito/genética , Péptidos/genética , Proteína B Asociada a Surfactante Pulmonar/genética , Animales , Glucemia , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Gestacional/sangre , Diabetes Gestacional/patología , Modelos Animales de Enfermedad , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Pulmón/crecimiento & desarrollo , Pulmón/metabolismo , Pulmón/patología , Embarazo , Proteínas Asociadas a Surfactante Pulmonar/sangre , Proteínas Asociadas a Surfactante Pulmonar/genética , RatasRESUMEN
Hyperglycemia during pregnancy is associated with fetal lung development disorders and surfactant protein (SP) deficiency. Here, we examined the role of FOXA2 and Akt signaling in fetal lung development during diabetic pregnancy. Sprague-Dawley rats were injected with streptozocin (STZ) during pregnancy to induce diabetes (DM). DM-exposed fetal lungs exhibited reduced numbers of alveoli, irregularities in the appearance and thickness of the alveolar septum, increased levels of glycogen and lipids in type II alveolar epithelial cells, fewer microvilli and mature lamellar bodies, and swollen mitochondria. SP-B and SP-C in DM amniotic fluid and DM lungs were lower than in the control group (P < 0.05). DM lung nuclear FOXA2 was lower compared with the control group (P < 0.05), but p-FOXA2 was higher (P < 0.05). In murine lung epithelial (MLE) 12 cells, p-AKT levels were increased by high glucose/insulin, but decreased by the Akt inhibitor MK2206 (P < 0.05). Expression of nuclear FOXA2 was increased by MK2206 compared with the high glucose/insulin group (P < 0.05). These results suggest that maternal diabetes induces fetal lung FOXA2 phosphorylation through the Akt pathway, and also affects the maturation of alveolar epithelial cells and reduces levels of SP-B and SP-C in the fetal lungs. An Akt inhibitor reversed the changes in SP expression in vitro.
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The prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because of its high frequency of chemoresistance. Metformin is widely used to treat type II diabetes, and was shown recently to inhibit pancreatic cancer stem cell proliferation. In the present study, we investigated the role of metformin in chemoresistance of pancreatic cancer cells to gemcitabine, and its possible cellular and molecular mechanisms. Metformin increases sensitivity of pancreatic cancer cells to gemcitabine. The mechanism involves, at least in part, the inhibition of CD133(+) cells proliferation and suppression of P70S6K signaling activation via inhibition of ERK phosphorylation. Studies of primary tumor samples revealed a relationship between P70S6K signaling activation and the malignancy of pancreatic cancer. Analysis of clinical data revealed a trend of the benefit of metformin for pancreatic cancer patients with diabetes. The results suggested that metformin has a potential clinical use in overcoming chemoresistance of pancreatic cancer.
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Antígenos CD/metabolismo , Desoxicitidina/análogos & derivados , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glicoproteínas/metabolismo , Metformina/farmacología , Neoplasias Pancreáticas/metabolismo , Péptidos/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Antígeno AC133 , Animales , Línea Celular Tumoral , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Sinergismo Farmacológico , Activación Enzimática , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Fosforilación , Pronóstico , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction (FGR). The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mRNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mRNA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.
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Retardo del Crecimiento Fetal , Pulmón/metabolismo , Péptidos/metabolismo , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Animales , Secuencia de Bases , Cartilla de ADN , Femenino , Pulmón/embriología , Embarazo , Ratas , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
AIM: To assess the application of the Kasai procedure in the surgical management of hilar bile duct strictures. METHODS: Ten consecutive patients between 2005 and 2011 with hilar bile duct strictures who underwent the Kasai procedure were retrospectively analyzed. Kasai portoenterostomy with the placement of biliary stents was performed in all patients. Clinical characteristics, postoperative complications, and long-term outcomes were analyzed. All patients were followed up for 2-60 mo postoperatively. RESULTS: Patients were classified according to the Bismuth classification of biliary strictures. There were two Bismuth III and eight Bismuth IV lesions. Six lesions were benign and four were malignant. Of the benign lesions, three were due to post-cholecystectomy injury, one to trauma, one to inflammation, and one to inflammatory pseudotumor. Of the malignant lesions, four were due to hilar cholangiocarcinoma. All patients underwent Kasai portoenterostomy with the placement of biliary stents. There were no perioperative deaths. One patient experienced anastomotic leak and was managed conservatively. No other complications occurred perioperatively. During the follow-up period, all patients reported a good quality of life. CONCLUSION: The Kasai procedure combined with biliary stents may be appropriate for patients with hilar biliary stricture that cannot be managed by standard surgical methods.
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Anastomosis Quirúrgica/métodos , Conductos Biliares/patología , Conductos Biliares/cirugía , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Constricción Patológica/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.
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Tumor Carcinoide/patología , Quimioembolización Terapéutica , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Tumor Carcinoide/terapia , Femenino , Humanos , Neoplasias Hepáticas/terapia , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Inflammatory pseudotumor of the biliary tract is a benign disease, and is extremely rare. Its diagnosis often depends on pathological examination after operation. The histopathological examination shows inflammatory lesions with a polymorphous infiltration and variable amounts of fibrous tissue. This study was undertaken to elucidate that an inflammatory pseudotumor in the right hepatic duct is especially difficult to distinguish from hilar cholangiocarcinoma. METHOD: The clinical data of one patient with inflammatory pseudotumor of the right hepatic duct were analyzed. RESULTS: An occupying lesion of the right hepatic duct was revealed by abdominal ultrasound and magnetic resonance cholangiopancreatography. The right hepatic duct inflammatory pseudotumor was not identified during the operation but was confirmed by postoperative histopathological analysis. The patient recovered well without any serious complication. CONCLUSIONS: The preoperative evaluation for optimizing surgical management is important to the diagnosis of hepatobiliary occupying lesions. The evaluation involves clinical manifestations, imaging appearance and tumor markers. Malignant tumors and possible benign lesions should be considered to avoid aggressive surgical treatment.