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1.
Cancer Med ; 13(13): e7419, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38970348

RESUMEN

BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first-order branch of the bile ducts (B1-type bile duct invasion; B1-BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB-TACE with cTACE in this patient population. MATERIALS AND METHODS: Using data from five tertiary medical centers (January 2017-December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1-BDI who underwent DEB-TACE or cTACE after successful biliary drainage. X-tile software calculated the pre-TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. RESULTS: The study included 108 patients with unresectable HCC (B1-BDI) who underwent DEB-TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB-TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB-TACE group exhibited fewer post-procedural increments in the mean albumin-bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p < 0.05). The pre-TACE TBil cutoff value was 99 µmol/L; patients with higher values (>99 µmol/L) had poorer OS in both groups (p < 0.05). CONCLUSION: DEB-TACE is safe and effective after successful biliary drainage in unresectable HCC with B1-BDI, potentially better than cTACE in terms of liver toxicity, TTP, and ORR. Lowering TBil below 99 µmol/L through successful drainage may create ideal conditions for sequential TACE.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Drenaje , Neoplasias Hepáticas , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Masculino , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Femenino , Drenaje/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Invasividad Neoplásica , Resultado del Tratamiento
2.
J Biol Chem ; 299(8): 104982, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37390992

RESUMEN

Endoplasmic reticulum (ER) stress and unfolded protein response are cells' survival strategies to thwart disruption of proteostasis. Tumor cells are continuously being challenged by ER stress. The prion protein, PrP, normally a glycosylphosphatidylinositol (GPI)-anchored protein exists as a pro-PrP retaining its GPI-peptide signal sequence in human pancreatic ductal cell adenocarcinoma (PDAC). Higher abundance of pro-PrP indicates poorer prognosis in PDAC patients. The reason why PDAC cells express pro-PrP is unknown. Here, we report that persistent ER stress causes conversion of GPI-anchored PrP to pro-PrP via a conserved ATF6-miRNA449c-5p-PIGV axis. Mouse neurons and AsPC-1, a PDAC cell line, express GPI-anchored PrP. However, continuous culture of these cells with the ER stress inducers thapsigargin or brefeldin A results in the conversion of a GPI-anchored PrP to pro-PrP. Such a conversion is reversible; removal of the inducers allows the cells to re-express a GPI-anchored PrP. Mechanistically, persistent ER stress increases the abundance of an active ATF6, which increases the level of miRNA449c-5p (miR449c-5p). By binding the mRNA of PIGV at its 3'-UTRs, miR449c-5p suppresses the level of PIGV, a mannosyltransferase pivotal in the synthesis of the GPI anchor. Reduction of PIGV leads to disruption of the GPI anchor assembly, causing pro-PrP accumulation and enhancing cancer cell migration and invasion. The importance of ATF6-miR449c-5p-PIGV axis is recapitulated in PDAC biopsies as the higher levels of ATF6 and miR449c-5p and lower levels of PIGV are markers of poorer outcome for patients with PDAC. Drugs targeting this axis may prevent PDAC progression.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Estrés del Retículo Endoplásmico , Glicosilfosfatidilinositoles , Neoplasias Pancreáticas , Proteínas Priónicas , Animales , Humanos , Ratones , Factor de Transcripción Activador 6/genética , Adenocarcinoma/patología , Glicosilfosfatidilinositoles/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Priónicas/genética , Proteínas Priónicas/metabolismo , Neoplasias Pancreáticas
3.
PLoS One ; 18(4): e0283806, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37014882

RESUMEN

Muscle wasting is one of the main characteristics of cachexia associated with cancer and other chronic diseases and is often exacerbated by antineoplastic agents. Increased oxidative stress is associated with muscle wasting, along with depletion of glutathione, the most abundant endogenous antioxidant. Therefore, boosting endogenous glutathione has been proposed as a therapeutic strategy to prevent muscle wasting. Here, we tested this hypothesis by inactivating CHAC1, an intracellular glutathione degradation enzyme. We found CHAC1 expression is increased under multiple muscle wasting conditions in animal models, including fasting, cancer cachexia, and chemotherapy. The elevation of muscle Chac1 expression is associated with reduced glutathione level. CHAC1 inhibition via CRSPR/Cas9 mediated knock-in of an enzyme inactivating mutation demonstrates a novel strategy to preserve muscle glutathione levels under wasting conditions but fails to prevent muscle wasting in mice. These results suggest that preserving intracellular glutathione level alone may not be sufficient to prevent cancer or chemotherapy induced muscle wasting.


Asunto(s)
Caquexia , Neoplasias , gamma-Glutamilciclotransferasa , Animales , Ratones , Caquexia/prevención & control , Caquexia/metabolismo , Glutatión/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/patología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , gamma-Glutamilciclotransferasa/metabolismo
4.
J Cancer Res Clin Oncol ; 149(5): 1873-1882, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35788728

RESUMEN

PURPOSE: To investigate the effectiveness and safety of the combination of sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of early intrahepatic stage-progressed advanced hepatocellular carcinoma (ISPA-HCC). METHODS: This study was approved by the ethics committees of six tertiary medical centers in China. Between October 2017 and October 2020, 213 patients with advanced HCC received either sorafenib combined with on-demand DEB-TACE (DTS group, n = 103) or sorafenib monotherapy (S group, n = 110). Overall survival (OS), time to progression (TTP), local tumor response, and adverse events (AEs) were compared between the two groups. RESULTS: The incidences of nause/vomiting, abdonimal pain, hyperbilirubinemia, fever and ALT/AST increasing were higher in the DTS group. The post-treatment partial response, objective response, and disease control rates were significantly higher in the DTS group than in the S group (51.5% vs. 23.6%; 56.3% vs. 25.5%; 77.7% vs. 56.4%, respectively). The median OS was significantly longer in the DTS group than in the S group [16.3 vs. 10.0 months; hazard ratio (HR) = 0.43; P < 0.001], as was the TTP (6.7 vs. 4.3 months; HR = 0.60; P = 0.001). In the DTS group, patients who received ≥ 2 sessions of DEB-TACE benefited more than those who received two sessions of DEB-TACE. Multivariate analysis revealed that the α-fetoprotein level and treatment allocation were independent predictors of OS and TTP. CONCLUSION: The combination of sorafenib and DEB-TACE is safe and effective for the treatment of early ISPA-HCC.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Sorafenib , Neoplasias Hepáticas/tratamiento farmacológico , Quimioembolización Terapéutica/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos
7.
Front Med (Lausanne) ; 9: 972879, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36619647

RESUMEN

Background: The aim of this study was to establish and validate a nomogram model for accurate prediction of patients' survival with T1aN0M0 none small cell lung cancer (NSCLC). Methods: The patients, diagnosed with the stage IA NSCLC from 2004-2015, were identified from the Surveillance, Epidemiology and End Results (SEER) database. The variables with a P-value < 0.05 in a multivariate Cox regression were selected to establish the nomogram. The discriminative ability of the model was evaluated by the concordance index (C-index). The proximity of the nomogram prediction to the actual risk was depicted by a calibration plot. The clinical usefulness was estimated by the decision curve analysis (DCA). Survival curves were made with Kaplan-Meier method and compared by Log-Rank test. Results: Eight variables, including treatment, age, sex, race, marriage, tumor size, histology, and grade were selected to develop the nomogram model by univariate and multivariate cox regression. The C-index was 0.704 (95% CI, 0.694-0.714) in the training set and 0.713 (95% CI, 0.697-0.728) in the test set, which performed significantly better than 8th edition AJCC TNM stage system (0.550, 95% CI, 0.408-0.683, P < 0.001). The calibration curve showed that the prediction ability of 3-years and 5-years survival rate demonstrated a high degree of agreement between the nomogram model and the actual observation. The DCA curves also proved that the nomogram-assisted decisions could improve patient outcomes. Conclusion: We established and validated a prognostic nomogram to predict 3-years and 5-years overall survival in stage IA NSCLC.

8.
J Clin Invest ; 131(22)2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34499619

RESUMEN

The endocannabinoid system regulates appetite and energy expenditure and inhibitors of cannabinoid receptor 1 (CB-1) induce weight loss with improvement in components of the metabolic syndrome. While CB-1 blockage in brain is responsible for weight loss, many of the metabolic benefits associated with CB-1 blockade have been attributed to inhibition of CB-1 signaling in the periphery. As a result, there has been interest in developing a peripherally restricted CB-1 inhibitor for the treatment of nonalcoholic fatty liver disease (NAFLD) that would lack the unwanted centrally mediated side effects. Here, we produced mice that lacked CB-1 in hepatocytes or stellate cells to determine if CB-1 signaling contributes to the development of NAFLD or liver fibrosis. Deletion of CB-1 in hepatocytes did not alter the development of NAFLD in mice fed a high-sucrose diet (HSD) or a high-fat diet (HFD). Similarly, deletion of CB-1 specifically in stellate cells also did not prevent the development of NAFLD in mice fed the HFD, nor did it protect mice from carbon tetrachloride-induced fibrosis. Combined, these studies do not support a direct role for hepatocyte or stellate cell CB-1 signaling in the development of NAFLD or liver fibrosis.


Asunto(s)
Células Estrelladas Hepáticas/metabolismo , Hepatocitos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Receptor Cannabinoide CB1/fisiología , Animales , Dieta Alta en Grasa , Cirrosis Hepática/etiología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptor Cannabinoide CB1/antagonistas & inhibidores , Transducción de Señal/fisiología
9.
Front Oncol ; 11: 582511, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33968713

RESUMEN

Purpose: 125I seeds were effective in the treatment of non-small cell lung cancer in previous research. However, the exact signaling pathway-mediated apoptosis mechanism is still unclear. The present study analyzed the effects and potential mechanisms of 125I seed on the growth and migration of A549 cells. Methods: Lung cancer A549 cells were irradiated with 125I seed for various times. MTT, invasion assay, and flow cytometry were used to detect the proliferation, invasion, and apoptosis of treated cells, respectively. A Nimblegen genome-wide expression profile chip was used to evaluate gene expression changes in 125I seed-treated A549 cells. Validation studies were performed using phosphorylated protein chip technology, Western blot, nude mouse tumor xenograft assay, and immunohistochemical experiments. All statistical analyses were performed using unpaired Student's t tests and Kruskal-Wallis test. Results: Irradiation with 125I seed inhibited A549 cell proliferation and invasion and induced apoptosis (primarily early apoptosis). Irradiation with 125I seed also caused the downregulation of p38MAPK, degradation of mouse double-minute 2 homolog (MDM2), and higher expression of p53, which eventually resulted in non-small cell lung cancer cell apoptosis. Conclusion: 125I seed irradiation activated the p38MAPK/MDM2/p53 signaling pathway and promoted non-small cell lung cancer cell apoptosis. Future clinical studies targeting this signal may provide a new potential therapeutic approach for non-small cell lung cancer.

10.
J Contemp Brachytherapy ; 12(4): 343-350, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33293973

RESUMEN

PURPOSE: To evaluate the safety and efficacy of computed tomography (CT)-guided 125I radioactive seed implantation in patients with malignant airway compression induced by advanced lung cancer. MATERIAL AND METHODS: Between June 2015 and June 2018, 40 patients from three medical institutions with malignant airway compression induced by advanced lung cancer were treated with 125I seed implantation. The outcomes were measured in technical success and safety, objective response rate, complications, Karnofsky performance status (KPS) score, and survival time. RESULTS: All 40 patients successfully underwent implantation procedure. No procedure-associated death occurred. The most common complications were irritable cough, temporary hemoptysis, chest pain, fever, and pneumothorax, which occurred in 26 (65.0%), 31 (77.5%), 12 (30.0%), 15 (37.5%), and 11 (27.5%) patients, respectively. The objective response rates were 100%, 100%, 100%, 87.5%, and 83.3% at the 3rd, 6th, 12th, 24th, and 36th months post-procedure, respectively. The KPS score significantly improved at post-procedure. Median survival time was 25.1 months. Actuarial survival rates were 100%, 60%, and 15% at the 12th, 24th, and 36th months after the procedure, respectively. CONCLUSIONS: For patients with malignant airway compression induced by advanced lung cancer, implantation with 125I seed is a safe and effective alternative treatment option.

11.
Lab Chip ; 20(19): 3653, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-32756648

RESUMEN

Correction for 'A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions' by Kelly Tan et al., Lab Chip, 2019, 19, 1556-1566, DOI: .

12.
Front Oncol ; 10: 574668, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33425729

RESUMEN

This study aims to compare the effectiveness and complications of transarterial chemoembolization (TACE) combined with sorafenib (S-TACE) and TACE monotherapy in HCC patients with diffuse recurrence (DR). This retrospective study was approved by our hospital ethics committee, and all patients provided informed consent. We retrospectively enrolled 356 DR patients from January 2005 to December 2014, who underwent either S-TACE or TACE monotherapy. Treatment complications, overall survival (OS) and progression-free survival (PFS) were evaluated. Survival curves were constructed using the Kaplan-Meier method and compared using a log-rank test. Our results found a significant difference between S-TACE and TACE monotherapy in the PFS and OS of HCC patients with early diffuse recurrence (EDR) (p=0.011 and 0.049, respectively). Patients with late diffuse recurrence (LDR) who underwent S-TACE had longer OS (median 24.0 vs. 16.0 months; p=0.044) compared with those in the TACE monotherapy group. Subgroup analysis revealed that S-TACE therapy resulted in higher OS of EDR patients with tumors > 5 cm and HBV-DNA >100 (p=0.036 and 0.035, respectively), compared with patients given TACE monotherapy. S-TACE therapy also resulted in better OS in LDR patients with AFP≥400 ng/ml, AFP<400 ng/ml, TB<28 g/L, TB>28 g/L, and a maximum tumor diameter < 5 cm (p=<0.001, 0.042, <0.001, <0.001, and <0.001, respectively). The rate of major complications in patients who underwent S-TACE was not significantly different to those who underwent TACE monotherapy (33.5% vs. 28.2%, p= 0.69). Overall, patients given S-TACE had better OS in both EDR and LDR patients, but only EDR patients had better PFS.

13.
J Food Sci Technol ; 56(11): 4785-4794, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31741502

RESUMEN

TiO2/Ti(NO2) hybrid films were prepared using N2 atmospheric pressure plasma jet treatment on TiO2 coating. The film structure and morphology have been investigated using optical emission spectra, Fourier-transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The formed TiO2/Ti(NO2) photocatalystic thin films were applied for C2H4 photodegradation under UV irradiation. The results showed that the composite films exhibited superior photocatalytic activity over the untreated TiO2 film. The C2H4 concentration after 120 min varied from 12 to 6.2 mg/L, 6.7 mg/L, 7 mg/L for TiO2 with 1 min, 2 min and 3 min plasma treatment, respectively. In the banana storage experiment, the concentration of C2H4 was reduced from 15 to 9 ppm after 36 h with TiO2/Ti(NO2) nanocomposite film illuminated by UV light. The photocatalytic mechanism has been discussed. The composite film is able to more effectively separate the photo-excited electrons and holes, thus leading to the much high activity in C2H4 degradation. The current work has paved a way towards postharvest fruit preservation.

14.
Biotechnol Bioeng ; 116(12): 3409-3420, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-30963546

RESUMEN

Hepatic in vitro platforms ranging from multi-well cultures to bioreactors and microscale systems have been developed as tools to recapitulate cellular function and responses to aid in drug screening and disease model development. Recent developments in microfabrication techniques and cellular materials enabled fabrication of next-generation, advanced microphysiological systems (MPSs) that aim to capture the cellular complexity and dynamic nature of the organ presenting highly controlled extracellular cues to cells in a physiologically relevant context. Historically, MPSs have heavily relied on elastomeric materials in their manufacture, with unfavorable material characteristics (such as lack of structural rigidity) limiting their use in high-throughput systems. Herein, we aim to create a microfluidic bilayer model (microfluidic MPS) using thermoplastic materials to allow hepatic cell stabilization and culture, retaining hepatic functional phenotype and capturing cellular interactions. The microfluidic MPS consists of two overlapping microfluidic channels separated by a porous tissue-culture membrane that acts as a surface for cellular attachment and nutrient exchange; and an oxygen permeable material to stabilize and sustain primary human hepatocyte (PHH) culture. Within the microfluidic MPS, PHHs are cultured in the top channel in a collagen sandwich gel format with media exchange accomplished through the bottom channel. We demonstrate PHH culture for 7 days, exhibiting measures of hepatocyte stabilization, secretory and metabolic functions. In addition, the microfluidic MPS dimensions provide a reduced media-to-cell ratio in comparison with multi-well tissue culture systems, minimizing dilution and enabling capture of cellular interactions and responses in a hepatocyte-Kupffer coculture model under an inflammatory stimulus. Utilization of thermoplastic materials in the model and ability to incorporate multiple hepatic cells within the system is our initial step towards the development of a thermoplastic-based high-throughput microfluidic MPS platform for hepatic culture. We envision the platform to find utility in development and interrogation of disease models of the liver, multi-cellular interactions and therapeutic responses.


Asunto(s)
Comunicación Celular , Técnicas de Cultivo de Célula , Hepatocitos , Dispositivos Laboratorio en un Chip , Hígado , Técnicas Analíticas Microfluídicas , Evaluación Preclínica de Medicamentos , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Hígado/citología , Hígado/metabolismo
15.
Lab Chip ; 19(9): 1556-1566, 2019 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-30855604

RESUMEN

Microphysiological systems (MPSs) are dynamic cell culture systems that provide micro-environmental and external cues to support physiologically relevant, organ-specific functions. Recent progresses in MPS fabrication technologies have enabled the development of advanced models to capture microenvironments with physiological relevance, while increasing throughput and reducing material-based artefacts. In addition to conventional cell culture systems, advanced MPSs are emerging as ideal contenders for disease modeling and incorporation into drug screening. Since liver is a central organ for drug metabolism, liver-on-chip models have been developed to recapitulate hepatic microenvironment with varying complexities, while allowing long-term culture. Recently, we have developed a novel thermoplastic, oxygen-permeable MPS for primary human hepatocyte (PHH) culture. Herein, we have adapted and extended the MPS to a) a 96 microfluidic array (PREDICT-96 array) and b) integrated a novel, ultra-low volume, re-circulating pumping system (PREDICT-96 pump) - collectively known as the PREDICT-96 platform. The PREDICT-96 platform conforms to the industrial standard 96-well footprint and enables media re-circulation. First, we demonstrate the introduction of PHHs into the PREDICT-96 array using standard handling procedures for multi-well plates and allow cells to stabilize in static conditions. Next, we introduce recirculating flow into the bottom channel (using PREDICT-96 pump) to mimic mass transport in vivo. Our results indicate an increase in metabolic and secretory functions of PHHs in the PREDICT-96 platform, and their maintenance over 10 days of flow. Furthermore, long-term culture with fluid flow allows for the periodic introduction of media components (e.g., fatty acids, cytokines) and capture cellular responses to chronic stimuli. The low-volume footprint of the pump and small media volume in the MPS allow for the interrogation of hepatic responses incorporating secretion feedback to a stimulus, which is essential for disease model development and drug interrogation. We envision future development of this liver model to incorporate key primary hepatic cells, multi-cellular co-cultures and adaptation, integration with high-throughput analytical tools.

16.
Clin Res Hepatol Gastroenterol ; 43(4): 451-459, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30348520

RESUMEN

OBJECTIVES: To compare the efficacy and safety of combination iodine [131I] metuximab infusion and transcathether arterial chemoembolization (TACE) with those of TACE-alone for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, Cochrane Library, Embase, Web of Science, China Biology Medicine, China Science and Technology Journal Database, Wan Fang Data, and Chinese knowledge resource integrated databases were used for the literature search regarding controlled clinical trials comparing combination TACE and iodine [131I] metuximab infusion with TACE-alone for HCC treatment before February 1, 2016. The Jadad system evaluation method for research quality and RevMan 5.0 software were used for the meta-analysis. RESULTS: In total, 1302 patients from 10 studies were included. The meta-analysis showed that the combination TACE and iodine [131I] metuximab infusion treatment for HCC was more effective than TACE alone, including 6-month survival (odds ratio [OR] = 2.05, 95% confidence interval [CI]: 1.41-2.98, P = 0.0002), 1-year survival (OR = 1.90, 95% CI: 1.41-2.55, P < 0.00001), and the total response rate (OR = 2.91, 95% CI: 2.08-4.07, P < 0.00001). Nine studies reported adverse reactions, mainly comprising poor appetite, nausea, vomiting, and abdominal discomfort. Fever, chills, and bone marrow suppression were more common in the combined treatment group, but abnormal liver function was not different between the two treatment groups. There was no report on serious complications or death directly related to either treatment. CONCLUSIONS: Compared with TACE alone, the combination of TACE with iodine [131I] metuximab infusion for treating unresectable HCC may improve local efficacy and overall survival in these types of patients.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Radioisótopos de Yodo/administración & dosificación , Neoplasias Hepáticas/terapia , Anticuerpos Monoclonales/efectos adversos , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Intervalos de Confianza , Humanos , Radioisótopos de Yodo/efectos adversos , Marcaje Isotópico , Neoplasias Hepáticas/mortalidad , Oportunidad Relativa , Sesgo de Publicación
17.
Diabetes Metab Syndr Obes ; 11: 565-577, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30319281

RESUMEN

BACKGROUND: Methionine aminopeptidase 2 (MetAP2) cleaves the initiator methionine from nascent peptides during translation. In both preclinical and clinical studies, the pharmacological inhibition of MetAP2 in obese subjects results in the suppression of food intake and body weight loss. However, the mechanism of action of body weight loss caused by MetAP2 inhibition remains to be elucidated, and the sites of action by pharmacological MetAP2 inhibition remain unknown. METHODS: In the present study, a comprehensive analysis of the MetAP2 expression pattern in mice was performed. RESULTS: Except for the relatively low expression in adipose tissues, MetAP2 protein was well-expressed in tissues important for metabolism, including liver, whole brain, skeletal muscle and intestine tissues. In comparison to lean mice, MetAP2 mRNA level was elevated in the intestines of diet-induced obese (DIO) mice. At the cellular level, MetAP2 exhibited a distinct high expression in central and peripheral neurons, as well as in epithelial cells lining both the small intestine and colon. In the liver of lean mice, MetAP2 protein exhibited punctate staining, which was enriched in zone three hepatocytes surrounding the central veins. In contrast, MetAP2 expression was diffuse in the liver of DIO mice. Furthermore, MetAP2 was highly expressed in immune cells that infiltrated DIO livers. CONCLUSION: Overall, these results delineate the MetAP2 expression at both tissue and cellular levels and highlight the altered MetAP2 expression under pathological conditions.

18.
Int J Hyperthermia ; 35(1): 239-245, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30200796

RESUMEN

PURPOSE: To evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with cryoablation (TACE-cryoablation) in large (main tumor ≥5 cm in diameter) hepatocellular carcinomas (HCCs). METHODS: From January 2010 to December 2015, 56 lesions in 56 patients were treated with combination therapy via a single TACE session followed by one to three percutaneous cryoablation sessions twice a week (TACE-cryoablation group). A total of 54 lesions in 54 patients were treated with TACE alone for two to six sessions once a month (TACE group). The decision between TACE and TACE cryoablation was based on patient choice. Outcomes of patients in two groups were compared according to the largest tumor diameter (subgroup): Group A (5 cm ≤ tumor <10 cm), Group B (10 cm ≤ tumor <15 cm), and Group C (tumor ≥15 cm). RESULTS: The mean number of cryoablation sessions per patient was 2.3 (range: 1-6). Within Group B, TACE-cryoablation significantly improved survival compared with TACE alone (11.0 vs 6.0 months; p = .008). This was also seen in Group C (8.0 vs 5.0 months; p = .001). However, no significant difference was noted in Group A (17.0 vs 13.0 months; p = .674). The complications related to TACE were comparable between the two groups. Two adverse events of grade 3 - 4 related to cryoablation occurred in two patients (3.6%). The independent prognostic factors for survival included: TACE cryoablation, AFP level, main tumor size and extrahepatic metastasis. CONCLUSIONS: TACE-cryoablation may improve overall survival in patients with HCC who presented with a tumor diameter ≥10 cm, with minimal complications, when compared with TACE alone.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Criocirugía/métodos , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Anciano , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
19.
Cancer Commun (Lond) ; 38(1): 14, 2018 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-29764483

RESUMEN

BACKGROUND: The association between type 2 diabetes mellitus (T2DM) and the risk of esophageal cancer remains unclear. The present study aimed to evaluate the impact of T2DM on short-term outcomes and long-term survival in patients with esophageal squamous cell cancer (ESCC). METHODS: The present retrospective study included 862 patients diagnosed with ESCC between January 2001 and December 2010. Among them, 280 patients had T2DM. A 1:1 propensity score-matched cohort consisting of 280 patients with and 280 without T2DM was selected from the 862 patients. The associations between T2DM and clinicopathologic characteristics were assessed using the χ2 or Fisher's exact test. Survival of ESCC patients with and without T2DM was calculated by using the Kaplan-Meier method and compared by using the Cox regression model between the two groups. RESULTS: The occurrence rate of anastomotic leakage was significantly higher in patients with T2DM than in those without T2DM (P < 0.001). In the subgroup with weight loss rate ≤ 5.05%, ESCC patients with T2DM had a significant longer overall survival than did those without T2DM (P = 0.003), whereas in the subgroup with weight loss rate > 5.05%, the patients without T2DM showed a longer survival (P = 0.001). Univariate and multivariate analysis results showed that T2DM was not an independent prognostic factor for patient survival. CONCLUSIONS: Type 2 diabetes mellitus is not an independent prognostic factor in patients with ESCC. However, the combination of T2DM with severe weight loss would be a predictor of poor prognosis.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Diabetes Mellitus Tipo 2/complicaciones , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Anciano , Índice de Masa Corporal , Carcinoma de Células Escamosas/complicaciones , Neoplasias Esofágicas/complicaciones , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos
20.
Oncol Res Treat ; 41(1-2): 22-28, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29393244

RESUMEN

BACKGROUND: To assess the feasibility and safety of percutaneous intraductal radiofrequency ablation (RFA) for malignant biliary obstruction caused by recurrence and metastasis after primary tumor resection. PATIENTS AND METHODS: Percutaneous intraductal biliary RFA and stent placement were performed in 19 consecutive patients with 24 RFA procedures. Procedure-related complications, stent patency, and survival after treatment were investigated. RESULTS: During 30 days after each RFA procedure there was no 30-day mortality, hemorrhage, bile duct perforation, or pancreatitis. Of the 19 patients, 2 are still alive and 17 are dead with a median survival time of 6.0 (range 1.2-16) months and a median stent patency of 3.2 (range 1.2-14) months. 10 patients had their stent patent at the time of last follow-up or death. 3 patients with stent blockage at 50, 182, and 200 days post procedure underwent repeat ablation. 1 patient with stent blockage underwent 2 repeat RFA procedures at 192 days after the first ablation and at 86 days after the repeat ablation. CONCLUSION: Percutaneous intraductal RFA is a technically safe and feasible therapeutic option for palliative treatment of these selected patients.


Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Colestasis/cirugía , Recurrencia Local de Neoplasia/complicaciones , Ablación por Radiofrecuencia/métodos , Adulto , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Colestasis/etiología , Drenaje , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Ablación por Radiofrecuencia/efectos adversos , Stents/efectos adversos
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