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1.
Gan To Kagaku Ryoho ; 48(3): 410-412, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790171

RESUMEN

A 67-year-old man was admitted to our hospital because of nausea, anorexia and tarry stool. In the blood examination, serum α-fetoprotein(AFP)level was 1,650 ng/mL, and the upper gastrointestinal endoscopy showed a large hemorrhage tumor at the gastric body. Abdominal enhanced computed tomography(CT)showed a solitary mass in segment 4 of the liver. We performed distal gastrectomy, and administered S-1 plus cisplatin therapy. After 13 months, abdominal CT showed complete response for the metastatic tumor according to the Response Evaluation Criteria in Solid Tumors. Because of adverse events, S-1 monotherapy was administered from postoperative month 23. The patients survived for 66 months with no recurrence.


Asunto(s)
Neoplasias Hepáticas , Neoplasias Gástricas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Gastrectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Recurrencia Local de Neoplasia , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , alfa-Fetoproteínas
2.
Gan To Kagaku Ryoho ; 48(3): 416-418, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790173

RESUMEN

Conversion surgery for patients with initially unresectable colorectal liver metastases is increasingly being performed because of effective systemic chemotherapy. Additionally, many studies have reported the benefit of the liver-first approach for advanced liver metastasis. We report a case of an initially unresectable advanced colon cancer with multiple liver and lung metastases that was successfully treated with the liver-first approach following chemotherapy. The patient was a 36-year- old woman who was diagnosed with advanced rectal cancer, cT4aN2aM1b, cStage Ⅳb. After a temporary transverse colostomy, she was administered systemic chemotherapy for 9 months. The primary tumor and liver metastases showed partial response while the lung metastases showed complete response. Since it was considered that liver metastases were the main prognostic factors, we performed a right hemihepatectomy plus S3 partial hepatectomy, followed by laparoscopic high anterior resection. A partial pneumonectomy was also performed because of the regrowth of the lung metastases, and we succeeded in complete resection. The liver-first approach was a beneficial treatment option for this patient with unresectable colorectal liver metastases.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Pulmonares , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía
3.
Gan To Kagaku Ryoho ; 48(3): 443-445, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790182

RESUMEN

This is the case of a 72-year-old man in whom multiple colorectal cancers including rectal and appendiceal cancers and synchronous S3 liver metastases were observed in 2014, and resection was performed in 2 stages. In 2017, a single recurrence was found in the liver S8, and he underwent a liver S8 sub-segmental resection. Implantation of a CV port for postoperative chemotherapy was planned. At the time of insertion, the catheter was punctured from the exterior portion of the left subclavian vein to avoid the pinch-off syndrome wherein the catheter is crushed between the clavicle and the first rib. Subsequently, FOLFOX therapy was started, but it was discontinued because of allergic symptoms, which appeared during the third course. Two years after the CV port was implanted, a catheter fracture was found on a chest X-ray performed during a regular visit. Since the detached catheter did not fall into the vein, it was possible to remove the port under fluoroscopy. When a catheter is implanted, even under ultrasound guidance, it is considered important to always keep in mind the possibility of a catheter fracture and to detect and respond to it early.


Asunto(s)
Cateterismo Venoso Central , Catéteres Venosos Centrales , Neoplasias Hepáticas , Anciano , Catéteres de Permanencia , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Recurrencia Local de Neoplasia
7.
Anticancer Res ; 41(4): 2187-2192, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813432

RESUMEN

BACKGROUND/AIM: The present study aimed to examine the therapeutic efficacy of ramucirumab compared with that of sorafenib as subsequent systemic therapy for patients with hepatocellular carcinoma (HCC) and serum α-fetoprotein (AFP) levels ≥400 ng/ml. PATIENTS AND METHODS: In our prospectively registered, real-world cohort, 13 and 11 patients treated with ramucirumab or sorafenib, respectively, were analyzed. Progression-free survival (PFS) was primarily compared between the ramucirumab and sorafenib groups. RESULTS: The PFS was significantly longer in the ramucirumab group than in the sorafenib group (median, 2.7 vs. 0.9 months, respectively; p=0.005). There were no significant differences in the objective response rates or the disease control rates between the ramucirumab and sorafenib groups (9.1% and 54.5% vs. 0.0% and 22.2%, respectively). CONCLUSION: Subsequent systemic therapy with ramucirumab showed a better ability to control tumor progression than sorafenib in HCC patients with serum AFP levels ≥400 ng/ml.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioterapia Adyuvante/métodos , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Japón/epidemiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Tasa de Supervivencia , Resultado del Tratamiento , alfa-Fetoproteínas/metabolismo
8.
Anticancer Res ; 41(4): 1883-1893, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813393

RESUMEN

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a highly prevalent disease and treatment is limited. Therefore, development of new therapeutic agents is urgent. The aim of this study was to investigate the in vitro and in vivo anti-cancer effects of Nardostachys jatamansi root extract (NJRE) against HCC and underlying mechanisms involved in such effects. MATERIALS AND METHODS: Effects of NJRE on viability of HCC cell lines were determined by MTT analysis and annexin/PI apoptosis assays. Expression levels of proteins in MAPK and STAT3 pathways and caspase-3 and PARP after treatment with NJRE in HCC cell lines were determined by western blotting. In a syngeneic model using mouse HCC cells Hepa1-6, inhibition of tumor formation after oral administration of NJRE was determined and expression levels of phospho-ERK and phospho-STAT3 in liver tissues were analyzed by immunohistochemical staining. RESULTS: NJRE reduced the activation of STAT3 by inhibiting the expression of ERK and finally attenuated the proliferation of HCC. CONCLUSION: NJRE has anti-cancer effects against HCC. It has potential to be used in the treatment of human HCC.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Nardostachys , Raíces de Plantas , Factor de Transcripción STAT3/metabolismo , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/patología , Masculino , Ratones Endogámicos C57BL , Nardostachys/química , Fosforilación , Raíces de Plantas/química , Transducción de Señal , Carga Tumoral/efectos de los fármacos
9.
Anticancer Res ; 41(4): 2007-2016, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813407

RESUMEN

BACKGROUND/AIM: The benefit of direct-acting antiviral therapy (DAA) in chronic hepatitis C (CHC) infected patients who received curative treatment for early-stage hepatocellular carcinoma (HCC) is well known, but is unclear for intermediate stage HCC. PATIENTS AND METHODS: CHC patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC receiving chemoembolization were identified. Univariate, multivariate analyses, and Kaplan-Meier curve were used to identify factors associated with survival outcomes. RESULTS: Among 113 included patients, the median survival of DAA treated group (n=14) and non-treated group (n=99) were 40.1 months and 22.9 months, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score, DAA, and serum albumin were key independent factors associated with overall survival. Moreover, the time-to-complete remission (TTCR) was improved in the DAA treated group. CONCLUSION: ECOG, DAA, and serum albumin were prognostic factors for CHC/intermediate-stage HCC patients. DAA was also a beneficial factor for TTCR.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Estudios de Cohortes , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
10.
Anticancer Res ; 41(4): 2025-2032, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813409

RESUMEN

BACKGROUND: The age of patients with advanced hepatocellular carcinoma (HCC) eligible for molecular-targeted drug treatment is increasing. We assessed liver function after lenvatinib administration according to age in patients with advanced HCC. PATIENTS AND METHODS: In this retrospective, multicenter, observational study, we reviewed the records of patients with HCC who received lenvatinib treatment (March 2018-March 2020). Liver function was measured using the Albumin-Bilirubin Index (ALBI). RESULTS: Of 119 patients, with a median age of 72.0 years, median overall survival was 15.3 months. Overall survival was significantly better in the group which maintained liver function (p=0.02). Older age (≥72 years) was associated with liver-function deterioration within 8 weeks (odds ratio=2.47, 95% confidence interval=1.06-5.75, p=0.035). The ALBI score was significantly higher in the older group at 4 and 8 weeks after lenvatinib administration. CONCLUSION: Lenvatinib administration was more likely to adversely affect liver function in older patients; dose adjustment should be considered in such patients.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/fisiopatología , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/fisiopatología , Femenino , Humanos , Hígado/patología , Pruebas de Función Hepática , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/fisiopatología , Masculino , Compuestos de Fenilurea/farmacología , Quinolinas/farmacología , Estudios Retrospectivos
11.
BMC Surg ; 21(1): 188, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836701

RESUMEN

BACKGROUND: Expansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis. METHODS: The subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (-) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed. RESULTS: Before PS matching, the L-OHP (+) and (-) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1-3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (-) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.40, 95% CI 0.17-0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.42, 95% CI 0.17-1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (-) groups. CONCLUSIONS: PS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Oxaliplatino , Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Oxaliplatino/uso terapéutico , Cuidados Posoperatorios , Puntaje de Propensión , Estudios Retrospectivos , Resultado del Tratamiento
12.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-33802299

RESUMEN

Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have shown selectively higher affinity and toxicity towards cancer cells, highlighting their potential to serve as chemotherapeutic agents or adjuvants. At varying doses, selenite extensively regulates cellular signaling and modulates many cellular processes. In this study, we report the identification of Delta-Notch signaling as a previously uncharacterized selenite inhibited target. Our transcriptomic results in selenite treated primary mouse hepatocytes revealed that the transcription of Notch1, Notch2, Hes1, Maml1, Furin and c-Myc were all decreased following selenite treatment. We further showed that selenite can inhibit Notch1 expression in cultured MCF7 breast adenocarcinoma cells and HEPG2 liver carcinoma cells. In mice acutely treated with 2.5 mg/kg selenite via intraperitoneal injection, we found that Notch1 expression was drastically lowered in liver and kidney tissues by 90% and 70%, respectively. Combined, these results support selenite as a novel inhibitor of Notch signaling, and a plausible mechanism of inhibition has been proposed. This discovery highlights the potential value of selenite applied in a pathological context where Notch is a key drug target in diseases such as cancer, fibrosis, and neurodegenerative disorders.


Asunto(s)
Receptores Notch/metabolismo , Ácido Selenioso/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Células MCF-7 , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Selenio/metabolismo , Transcriptoma/efectos de los fármacos
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(3): 313-318, 2021 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-33849820

RESUMEN

OBJECTIVE: To elucidate the risk and synergistic factors of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B-associated cirrhosis (CHB-Cir) complicated by type 2 diabetes (T2DM). OBJECTIVE: The patients with CHB-Cir who were followed up in Hepatology Center of Nanfang Hospital from June 2010 to June 2019 were divided based on their T2DM status into two cohorts matched for gender, age, HBeAg status and HBV DNA load: CHB-Cir with T2DM group (observation group) and CHB-Cir without T2DM group (control group). All the patients were followed up at a 6-month interval, and the cases with complete clinical data and follow-up data for more than 2 years were included in the analysis. Kaplan- Meier method was used to compare the cumulative incidence of HCC between the two groups. A Cox proportional hazard regression model was used to analyze the relationship between T2DM and the risk of HCC in these patients. OBJECTIVE: A total of 467 patients with a mean follow-up time of 4.4±1.62 years were included in the analysis, including 203 in the observation group and 264 in the control group. Sixty-nine and forty-eight new HCC cases occurred in the observation group and control group, respectively, showing a significantly higher incidence rate of HCC in the observation group (P < 0.001). The cumulative incidence of HCC in the observation group was significantly higher than that in the control group (P < 0.001), with a relative risk of 2.096 (P < 0.01). After adjustment for age (≥40 years), family history of liver cancer, previous antiviral therapy, elevated cholesterol and elevated LDL cholesterol, T2DM remained an independent risk factor for HCC in CHB-Cir patients (P=0.000). OBJECTIVE: T2DM is an independent risk factor for HCC, and the risk of HCC increases by more than two folds in CHB-Cir patients complicated by T2DM, suggesting the clinical significance of early interventions of diabetes to reduce the risk of HCC in CHB-Cir patients.


Asunto(s)
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hepatitis B Crónica , Neoplasias Hepáticas , Adulto , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo
15.
Anticancer Res ; 41(3): 1563-1570, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788750

RESUMEN

BACKGROUND/AIM: This study aimed to evaluate how NAD(P)H: quinone oxidoreductase-1 (NQO1) affects survival after hepatectomy in patients with colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A retrospective analysis was conducted of 88 consecutive patients who underwent hepatectomy for CRLM. Of the 88 patients, preoperative chemotherapy was administered to 30 patients. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody. RESULTS: NQO1-positive expression in tumor cells of CRLM was associated with worse overall survival (p=0.026) and was an independent adverse prognostic factor in multivariate analysis (hazard ratio=5.296, p=0.007). Among 30 patients who received preoperative chemotherapy, patients with loss of NQO1 expression in non-neoplastic epithelial cells of the bile ducts (NQO1 polymorphism: n=19) showed significantly better response to preoperative chemotherapy for CRLM (p=0.004). CONCLUSION: NQO1-positive expression in tumor cells of CRLM may be an adverse prognostic factor after hepatectomy for CRLM.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , NAD(P)H Deshidrogenasa (Quinona)/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , NAD(P)H Deshidrogenasa (Quinona)/genética , Polimorfismo Genético , Pronóstico
16.
Anticancer Res ; 41(3): 1571-1577, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788751

RESUMEN

BACKGROUND/AIM: Tumor-infiltrating Foxp3+ regulatory T-cells (Ti-Tregs) promote tumor progression and contribute to poor prognosis in gastric cancer, but the relationship between Ti-Tregs and response to chemotherapy for liver metastases from gastric cancer (LMGC) is unclear. We estimated the correlation between pathological response to chemotherapy and Ti-Tregs in LMGC. PATIENTS AND METHODS: Ti-Tregs were analyzed with immunohistochemistry as CD3+ Foxp3+ cells in patients with synchronous LMGC. RESULTS: Of 53 patients with LMGC, 49 received chemotherapy as initial treatment and 10 underwent R0 resection. LMGC disappeared pathologically in 5 resected cases despite radiologically residual disease. Ti-Tregs were found frequently in residual LMGC and primary lesions but rarely in tumor scar tissue. There was no relationship between frequency of CD8+ cells and pathological response. CONCLUSION: Marked reduction in Ti-Tregs correlates with pathological complete remission of LMGC. Ti-Tregs may be a biomarker to predict the effects of chemotherapy when used in combination with radiological findings.


Asunto(s)
Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Linfocitos Infiltrantes de Tumor/fisiología , Neoplasias Gástricas/patología , Linfocitos T Reguladores/fisiología , Anciano , Biomarcadores de Tumor , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad
17.
Int J Mol Sci ; 22(4)2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33670268

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide, and its incidence is rising. HCC develops almost exclusively on the background of chronic liver inflammation, which can be caused by chronic alcohol consumption, viral hepatitis, or an unhealthy diet. The key role of chronic inflammation in the process of hepatocarcinogenesis, including in the deregulation of innate and adaptive immune responses, has been demonstrated. The inhibition of Akt (also known as Protein Kinase B) directly affects cancer cells, but this therapeutic strategy also exhibits indirect anti-tumor activity mediated by the modulation of the tumor microenvironment, as demonstrated by using Akt inhibitors AZD5363, MK-2206, or ARQ 092. Moreover, the isoforms of Akt converge and diverge in their designated roles, but the currently available Akt inhibitors fail to display an isoform specificity. Thus, selective Akt inhibition needs to be better explored in the context of HCC and its possible combination with immunotherapy. This review presents a compact overview of the current knowledge concerning the role of Akt in HCC and the effect of Akt inhibition on the HCC and liver tumor microenvironment.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Microambiente Tumoral , Aminopiridinas/uso terapéutico , Carcinoma Hepatocelular/enzimología , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Imidazoles/uso terapéutico , Neoplasias Hepáticas/enzimología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico
18.
AAPS PharmSciTech ; 22(3): 96, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33694067

RESUMEN

Increasing the drug tumor-specific accumulation and controlling their release is considered one of the most effective ways to increase the efficacy of drugs. Here, we developed a vesicle system that can target hepatoma and release drugs rapidly within tumor cells. This non-ionic surfactant vesicle is biodegradable. Galactosylated stearate has been used to glycosylate the vesicles to achieve liver targeting; replacement of a portion (Chol:CHEMS = 1:1) of cholesterol by cholesteryl hemisuccinate (CHEMS) allows for a rapid release of drugs in an acidic environment. In vitro release experiments confirmed that galactose-modified pH-sensitive niosomes loaded with tanshinone IIA had excellent drug release performance in acid medium. In vitro experiments using ovarian cancer cells (A2780), colon cancer cells (HCT8), and hepatoma cell (Huh7, HepG2) confirmed that the preparation had specific targeting ability to hepatoma cells compared with free drugs, and this ability was dependent on the galactose content. Furthermore, the preparation also had a more substantial inhibitory effect on tumor cells, and subsequent apoptosis assays and cell cycle analyses further confirmed its enhanced anti-tumor effect. Results of pharmacokinetic experiments confirmed that the vesicle system could significantly extend the blood circulation time of tanshinone IIA, and the larger area under the curve indicated that the preparation had a better drug effect. Thus, the results of biodistribution experiments confirmed the in vivo liver targeting ability of this preparation. Niosomes designed in this manner are expected to be a safe and effective drug delivery system for liver cancer therapy.


Asunto(s)
Abietanos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma Hepatocelular/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Galactosa/administración & dosificación , Neoplasias Hepáticas/metabolismo , Abietanos/farmacocinética , Animales , Antineoplásicos Fitogénicos/farmacocinética , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos/fisiología , Galactosa/farmacocinética , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Liposomas , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Ratones , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
19.
Zhongguo Zhong Yao Za Zhi ; 46(2): 478-487, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645137

RESUMEN

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.


Asunto(s)
Medicamentos Herbarios Chinos , Neoplasias Hepáticas , Adyuvantes Farmacéuticos , Mezclas Complejas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Trametes
20.
J Biomed Nanotechnol ; 17(1): 18-36, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33653494

RESUMEN

Multidrug resistance (MDR) is a key to the ineffectiveness of hepatocellular carcinoma (HCC) chemotherapy. Oxaliplatin (OXA), as one of the first-line chemotherapeutic drugs for HCC, abnormally activates the PI3K/AKT/mTOR signaling pathway and DNA damage repair pathway (NHEJ and HR), causing drug resistance and consequnet compromised efficacy. Herein, we developed a hollow polydopamine nanoparticle (H-PDA)-based nano-delivery system (O/P-HP) that contained OXA and a dual PI3K/mTOR inhibitor PKI-587 with complementary effects for combating drug resistance in cancer chemotherapy. The hollow structure of H-PDA endowed O/P-HP with high loading efficiencies of OXA and PKI-587-up to 49.6% and 7.0%, respectively. In addition, benefiting from the intracellular delivery of H-PDA as well as the highly concentrated drugs therein, O/P-HP inhibited the proliferation of OXA-resistant HR cells, resulting in a cell viability of only 17.63%. These values were significantly superior to those with OXA single-agent treatment and treatment with free OXA in combination with PKI-587. We examined the intrinsic mechanisms of the combination therapy: O/PHP had excellent anti-cancer effects via the simultaneous upstream and downstream action to re-sensitize HR cells to chemotherapy; OXA induced strong apoptosis via the direct platinum lesions on DNA molecules, while PKI-587 normalized the abnormally activated PI3K/AKT/mTOR signaling pathway and DNA damage repair pathway (NHEJ and HR) that could attenuate the effectiveness of OXA, thus resulting in inhibition of cell proliferation, migration and DNA repair enzyme activity and the augment of apoptotic effects. Such combination therapy, with simultaneous upstream and downstream action, may be a strategy for minimizing resistance for anti-cancer treatments.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Preparaciones Farmacéuticas , Apoptosis , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Indoles , Neoplasias Hepáticas/tratamiento farmacológico , Morfolinas , Oxaliplatino , Fosfatidilinositol 3-Quinasas , Polímeros , Triazinas
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