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2.
Medicine (Baltimore) ; 98(38): e17102, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567946

RESUMO

Combined hepatocellular-cholangiocarcinoma (CHCC) is a rare type of primary liver cancer (PLC). The aim of this study was to investigate the disease characteristics in CHCC patients and compare them with those in hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC).The perioperative and follow-up data of CHCC patients (n = 15), HCC patients (n = 577), and ICC patients (n = 61) were retrospectively analyzed, and the clinicopathological characteristics were compared among these 3 groups.In the CHCC group, the serum level of AFP was significantly higher than that of the ICC group (P = .002), and the CA19-9 level was higher than that of the HCC group (P = .011). The positive rates of CK7 and CK19 expression were higher in CHCC group than in HCC group (both P < .001), while the positive rates of Glypican-3 and Hepatocyte expression were higher in CHCC group than in ICC group (both P < .001). Meanwhile, the CHCC patients were likely to have undergone more MJH/LT than the HCC patients (P = .037) and the ICC patients (P = .011). Macrovascular invasion and lymph node metastasis in the CHCC group were significantly higher but satellite lesions were similar, compared to the HCC group. Both the 1-year disease-free survival (DFS) and the 1-year overall survival (OS) for the CHCC patients were worse than those for the HCC patients. AFP ≥ 400 ng/ml, tumor size ≥5 cm, tumor number ≥2, macro- and microvascular invasion, distant metastasis and positive margin were risk factors for both DFS and OS for the PLC patients. Multivariate analysis also confirmed that ICC and lymph node metastasis were risk factors for DFS and MJH/LT was risk factor for OS.CHCC patients appear to have intermediate clinical characteristics in comparison with the HCC and ICC patients, and the 1-year DFS and OS for the CHCC patients was worse than the HCC patients, but similar to the ICC patients.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Carcinoma Hepatocelular/mortalidade , Colangiocarcinoma/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , China , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia
3.
Anticancer Res ; 39(10): 5393-5401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570434

RESUMO

BACKGROUND/AIM: Local recurrence of hepatocellular carcinoma (HCC) after thermal coagulation therapy may be associated with an aggressive phenotypic change. This study focused on the thermal effects on HCC cells and evaluated the heat shock response and phenotypic changes after heat treatment. MATERIALS AND METHODS: HepG2 and HuH7 cells were used. After heat treatment at 37-50°C for 5-30 min, we assessed their survival rate, induction of heat shock protein (HSP)70 promoter, proliferation rate, induction of the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-related markers. RESULTS: Induction of HSP70 promoter per surviving cell was maximized after 10 min of heat treatment at 48°C. Induction of EMT and CSC-related markers was also observed. CONCLUSION: Sub-lethal heat treatment causes large heat shock response to surviving HCC cells and induce EMT-like and CSC-like phenotypic changes that might contribute to increased aggressiveness.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Resposta ao Choque Térmico/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal/genética , Proteínas de Choque Térmico HSP70/genética , Células Hep G2 , Temperatura Alta , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Taxa de Sobrevida
4.
Anticancer Res ; 39(10): 5639-5643, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570461

RESUMO

BACKGROUND/AIM: Diabetes mellitus (DM) is known as an important risk factor for hepatocellular carcinoma (HCC). However, surgical outcomes in patients with DM and HCC have not been evaluated in detail. PATIENTS AND METHODS: We retrospectively studied 177 patients with type 2 DM who underwent curative hepatectomy for HCC. Surgical outcomes after curative hepatectomy and prognostic factors were evaluated among 75 patients with DM and/or nonalcoholic steatohepatitis (NASH)-related HCC and 102 patients with DM and viral or alcoholic hepatitis (VAH)-related HCC. RESULTS: The 5-year survival rate and 5-year recurrence-free survival rate were significantly higher in the DM and/or NASH-related HCC group (87% and 51%) than in the DM and VAH-related HCC group (68%: p=0.0001 and 26%: p=0.0002). Multivariate analysis showed DM and/or NASH-related HCC to be significant independent prognostic factors for overall survival and recurrence-free survival. CONCLUSION: Patients with DM and/or NASH-related HCC showed more favorable surgical outcomes after hepatectomy in patients with DM and HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
5.
Anticancer Res ; 39(10): 5755-5760, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570478

RESUMO

BACKGROUND/AIM: After primary resection of hepatocellular carcinoma (HCC), the impact of patient's characteristics at the initial hepatectomy, on long-term remnant liver function has not been reported. The aim of this study was to identify factors associated with the deterioration of remnant liver function among patients who developed recurrent HCC. PATIENTS AND METHODS: A total of 51 patients with intrahepatic recurrence after initial hepatic resection for HCC were included. We retrospectively investigated the relation between patient characteristics and the degree of deterioration of remnant liver function upon recurrence. RESULTS: In univariate analysis, significant predictors of deterioration of remnant liver function consisted of preoperative gastro-esophageal varices (p=0.0101), preoperative transcatheter arterial chemoembolization (p=0.0230) and hepatectomy beyond Makuuchi's criteria (p=0.0101). In multivariate analysis, the only significant independent predictor of deterioration of remnant liver function was hepatectomy beyond Makuuchi's criteria (p=0.0498). CONCLUSION: Hepatectomy beyond Makuuchi's criteria at the initial hepatectomy may predict deterioration of remnant liver function upon recurrence of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/patologia , Fígado/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Feminino , Hepatectomia/métodos , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco
6.
Anticancer Res ; 39(9): 4787-4794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519580

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the effects of the macrophage colony-stimulating factor (M-CSF) receptor antagonist on hepatic carcinogenesis in mice. MATERIALS AND METHODS: Mice were injected with diethylnitrosamine (DEN) and treated with M-CSF receptor antagonist GW2580 (GW) or a saline vehicle just after (early treated group) or 2 weeks after (late treated group) DEN injection. Animals were sacrificed after 28 weeks and incidence of tumor was assessed. Isolated Kupffer cells were co-cultured with M-CSF in the presence or absence of GW, and the concentration of VEGF was measured. RESULTS: The incidence of tumors was significantly blunted both in the early- and the late-treated groups. In addition, angiogenesis within the tumor was also suppressed in both groups. The concentration of VEGF increased in Kupffer cells treated with M-CSF compared to those cultured without M-CSF. This increase was blunted by GW. CONCLUSION: M-CSF and its receptor could be novel molecular targets for hepatocellular carcinoma.


Assuntos
Anisóis/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Pirimidinas/farmacologia , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Animais , Biomarcadores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Imuno-Histoquímica , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Carga Tumoral/efeitos dos fármacos
7.
Anticancer Res ; 39(9): 4667-4671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519565

RESUMO

BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS: Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Gene ; 719: 144044, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31400406

RESUMO

OBJECTIVE: Exosomes have been described as a messenger between cells' communication and contain various information (lipids, proteins, mRNAs, microRNAs, LncRNAs). It has been proved that Linc-ROR was enriched in exosomes released by HepG2 cells. Our aim was to investigate whether exosomes released by HepG2 cells could affect the biological behaviors of LO2 cells and whether Linc-ROR played an important role in this process. METHODS: Exosomes-derived from HepG2 cells were isolated and characterized. Real-time PCR assessed expression level of Linc-ROR in specimens of cancerous tissues and carcinoma-adjacent tissues. The Linc-ROR expression level in HepG2, Huh7, SMMC-7721, Bel-7402, LO2 cells and exosomes was detected by real-time PCR. Knockdown the expression of Linc-ROR in HepG2 by using effective siRNA. Cell counting method was used to test LO2 cells proliferative activities. Flow cytometry was performed to quantify the apoptosis rates of LO2 cells cocultured with exosomes. The expression levels of OCT4, NANOG, SOX2, P53 and CD133 were assessed by western blot. RESULTS: Linc-ROR was enriched in exosomes released by HepG2 cells. Exosomes derived from HepG2 cells promoted the proliferation and suppressed the apoptosis of LO2 cells suffering nutrient deficiency. Knockdown the expression of Linc-ROR in HepG2 or LO2 cells could significantly impaired the exosomes' effects on LO2 cells. In addition, the long-term coculture with exosomes would obviously change the biological behaviors of LO2 cells. CONCLUSIONS: Our experiments indicated the HepG2 cells could transfer its Linc-ROR to the LO2 cells via exosomes, then influenced the recipient cells.


Assuntos
Carcinoma Hepatocelular/patologia , Exossomos/metabolismo , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Apoptose , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade
9.
Yonsei Med J ; 60(9): 842-853, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31433582

RESUMO

PURPOSE: Long intergenic non-protein coding RNA 665 (LINC00665) plays a vital role in the development of cancer. Its function in hepatocellular carcinoma (HCC), however, remains largely unknown. MATERIALS AND METHODS: The expressions of LINC00665, miR-186-5p, and MAP4K3 were determined by qRT-PCR. Cell viability and apoptosis were evaluated by MTT and flow cytometry, respectively. Autophagic puncta formation was observed by fluorescence microscopy. Bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and RNA pulldown were performed to identify associations among LINC00665, miR-186-5p, and MAP4K3. Western blot was utilized to examine the expressions of MAP4K3, Beclin-1, and LC3. Tumor growth was evaluated in a xenograft model. RESULTS: Elevations in LINC00665 were observed in HCC tissues and cells. The overall survival of HCC patients with high levels of LINC00665 was shorter than those with low levels. In vitro, LINC00665 depletion inhibited viability and induced apoptosis and autophagy. miR-186-5p interacted with LINC00665 and was downregulated in HCC tissues and cells. Upregulation of miR-186-5p inhibited viability and induced apoptosis and autophagy, which were attenuated by upregulation of LINC00665. MAP4K3 was found to possess binding sites with miR-186-5p and was upregulated in HCC tissues and cells. MAP4K3 depletion inhibited viability and induced apoptosis and autophagy, which were attenuated by miR-186-5p inhibitor. In vivo, miR-186-5p expression was negatively correlated with LINC00665 or MAP4K3 in HCC tissues, while LINC00665 was positively correlated with MAP4K3. LINC00665 knockdown suppressed tumor growth. CONCLUSION: LINC00665 was involved in cell viability, apoptosis, and autophagy in HCC via miR-186-5p/MAP4K3 axis, which may provide a new approach for HCC treatment.


Assuntos
Apoptose/genética , Autofagia/genética , Carcinoma Hepatocelular/patologia , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , Adulto , Idoso , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases , RNA Longo não Codificante/genética , Regulação para Cima
10.
Medicine (Baltimore) ; 98(31): e16660, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374039

RESUMO

INTRODUCTION: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies, only 10% to 20% of HCC patients are surgically resectable as most of the patients are diagnosed at advanced stages at presentation. The efficiencies of transcatheter arterial chemoembolization (TACE), high-intensity focused ultrasound (HIFU), and three-dimensional conformal radiation therapy (3D-CRT) in patients with advanced HCC have been clinically confirmed. We here report a patient with HCC accompanied by venous tumor thrombus, who was treated with the combination of these 3 therapies. The patient survived for 16 months with good quality of life. PATIENT CONCERNS: The patient was a 72-year-old male with a primary multicentric HCC accompanied by tumor thrombus in the right hepatic vein. The patient had the symptoms of abdominal distention and liver pain. He refused sorafenib treatment because of personal reason. DIAGNOSIS: Primary multicentric HCC stage IIIB cT4N0M0, accompanied by tumor thrombus in the right hepatic vein; chronic viral hepatitis B; and hepatitis B virus-related decompensated liver cirrhosis. INTERVENTIONS: TACE + HIFU + 3D-CRT. OUTCOMES: The patient had an overall survival of 16 months with good quality of life. Compared with monotherapy, the combined therapy significantly prolonged patient survival time with improved clinical benefits. CONCLUSION: The combination of TACE, HIFU, and 3D-CRT is safe and effective in the treatment of advanced HCC, which provides a possible comprehensive treatment strategy for advanced HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neoplasias Hepáticas/terapia , Radioterapia Conformacional/métodos , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Terapia Combinada , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Trombose Venosa/etiologia
11.
Medicine (Baltimore) ; 98(31): e16673, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374045

RESUMO

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.


Assuntos
Colangiocarcinoma/radioterapia , Hepatopatias/prevenção & controle , Neoplasias Hepáticas/radioterapia , Lesões por Radiação/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Cisplatino/uso terapêutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/uso terapêutico , Piridinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Adjuvante , Tegafur/uso terapêutico , Tomografia Computadorizada por Raios X
12.
Gene ; 716: 144031, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377314

RESUMO

Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, have been identified as critical regulators of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of circRNAs in HCC are largely unknown. In this study, we identified a novel circRNA, circ-IGF1R, in HCC tumour tissues and cell lines. Circ-IGF1R levels were found to be significantly upregulated in HCC tissues compared with levels in paired peritumoural tissues. The high expression levels of circ-IGF1R in HCC were associated with tumour size. Moreover, knocking down circ-IGF1R with siRNA significantly attenuated cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. Further investigation revealed that PI3K/AKT signalling pathway activation was involved in the oncogenic functions of circ-IGF1R in HCC. Our study suggests that circ-IGF1R may be a potential target for the prevention and treatment of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA/metabolismo , Apoptose , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima
13.
Anticancer Res ; 39(8): 4055-4060, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366487

RESUMO

BACKGROUND/AIM: Tumor-derived exosomes play important roles in tumor metastases. In this report, we observed the fate of tumor-derived exosomes in pancreatic cancer metastatic nude-mouse models using color-coded imaging. MATERIALS AND METHODS: Mia-PaCa-2 human pancreatic cancer cells expressing red fluorescent protein (RFP) were transduced by exosome-specific pCT-CD63-green fluorescent protein (GFP) and injected in the spleen of nude mice. RESULTS: Four weeks after injection of these cells into the spleen, liver metastases developed and tumor-derived exosomes were observed within the metastatic cancer cells and in Kupffer cells. Furthermore, tumor-derived exosomes diffused to bone marrow and lung cells, especially macrophages, without any metastases present. CONCLUSION: In the present study, we visualized the distribution of cancer-derived exosomes for the first time at the cellular level, in a pancreatic-cancer metastatic model.


Assuntos
Linhagem da Célula/genética , Exossomos/genética , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/química , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Proteínas Luminescentes/química , Camundongos , Metástase Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Anticancer Res ; 39(8): 4065-4071, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366489

RESUMO

BACKGROUND: Surgical orthotopic implantation of human colon cancer tissue to the ceca of mice has been used to mimic behavior of cancer in human patients for the development of precision cancer medicine. However, with the current method of serosal surface implantation (SSI) of pieces of human colon cancer tissue, cancer cells are exposed to the peritoneum, which can artificially increase the rate of peritoneal carcinomatosis (PC) during the disease course. The objective of the present study was to introduce a tumor-sealing method (TSM) and compare it with SSI for the ability to produce clinically-relevant metastases without artificial PC. MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm3-sized tumor fragment was sutured to partially torn serosa of the cecum. For TSM, the blind end of the cecum was folded over the tumor fragment and sealed with sutures. At 20 days after implantation, all mice were opened to visualize PC by intravital fluorescence imaging. At necropsy, distant metastasis was investigated using frozen section of whole blocks of organs. RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001). CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.


Assuntos
Carcinogênese/genética , Neoplasias do Colo/patologia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/química , Células HCT116 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos , Metástase Neoplásica , Transplante de Neoplasias/métodos , Imagem Óptica , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Anticancer Res ; 39(8): 4219-4225, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366509

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate surgical outcomes of patients with high-signal intensity (SI) image hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Between 2008 and 2013, 257 HCC patients were retrospectively evaluated. A total of 21 patients were diagnosed as high-SI image HCC, 215 as low-SI image HCC, and 21 patients as mixed (high and low)-SI image HCC in the hepatobiliary (HB) phase of MRI. Five-year overall survival (OS) and recurrence-free survival (RFS) were compared among patient groups. RESULTS: The 5-year OS and RFS rates were significantly higher in patients with high-SI image HCC (100% and 56%) than in patients with low-SI image HCC (71%; p=0.097 and 38%; p=0.0209) and in patients with mixed-SI image HCC (73%; p=0.0329 and 9%; p=0.0021). High-SI image was an independent prognostic factor for OS (relative risk 0.167, p=0.0178) and RFS (relative risk 0.471, p=0.0322) on multivariate analysis. CONCLUSION: Patients with high-SI image HCC showed favorable long-term survival after curative surgery.


Assuntos
Sistema Biliar/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Sistema Biliar/patologia , Carcinoma Hepatocelular/patologia , Meios de Contraste/administração & dosagem , Intervalo Livre de Doença , Feminino , Gadolínio DTPA/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
16.
Anticancer Res ; 39(8): 4315-4324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366523

RESUMO

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metástase Neoplásica/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diagnóstico Diferencial , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
17.
Anticancer Res ; 39(8): 4423-4430, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366540

RESUMO

BACKGROUND/AIM: To evaluate the impact of DEPDC1 expression on patient prognosis after hepatic resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We reviewed data from 75 patients who underwent hepatic resection for HCC between 2004 and 2013. Recurrence at 2 years following resection, which mainly included metastatic recurrence, was defined as late recurrence. RESULTS: DEPDC1 was up-regulated in HCC tissue and in non-tumor tissue of patients with HCC compared to normal liver (p<0.01 and p<0.01, respectively). High expression of DEPDC1 was associated with poor overall, disease-specific, and disease-free survival (p=0.02, p<0.01, and p<0.01, respectively). High DEPDC1 expression was an independent predictor of death and recurrence (p=0.03 and p<0.01, respectively). High expression of DEPDC1 in non-tumor liver was an independent risk factor for late recurrence (p=0.04). CONCLUSION: High expression of DEPDC1 in tumor tissue appears to be associated with tumor progression and poor prognosis.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas Ativadoras de GTPase/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Prognóstico , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
18.
Anticancer Res ; 39(8): 4549-4554, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366558

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. PATIENTS AND METHODS: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. RESULTS: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. CONCLUSION: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Hepatopatia Veno-Oclusiva/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Complicações Pós-Operatórias/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Hepatectomia , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/patologia , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/patologia , Período Pré-Operatório
19.
Presse Med ; 48(7-8 Pt 2): e245-e250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31445698

RESUMO

Embolization and percutaneous ablations became well-established therapeutic options for hepatocellular carcinomas (HCC). All are performed under minimally invasive conditions using imaging guidance. Selection of a technique over another follows guidelines but also patient's status and availability of the techniques. The aim of this review is to present these techniques performed in routine to treat HCC and to report the outcomes.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Cirurgia Assistida por Computador/métodos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/estatística & dados numéricos , Terapia Combinada , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/estatística & dados numéricos , Resultado do Tratamento
20.
Zhonghua Gan Zang Bing Za Zhi ; 27(7): 511-515, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357776

RESUMO

Objective: To comparatively study intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) with reference to clinical features and prognosis in Chinese Han population. Methods: 699 cases of HCC and 170 cases of ICC confirmed by surgical pathological files from 2009 to 2010 were included and followed-up. The differences in demographic characteristics, hepatitis B virus infection, clinical characteristics, biochemical indexes, tumor markers and prognosis of HCC and ICC were analyzed retrospectively by means of paired t-test, analysis of variance, chi-square test and Pearson's correlation coefficient. Results: Among 869 cases of primary liver cancer, HCC and ICC accounted for 80.43% and 19.57%. The old aged (P < 0.001) male incidence of HCC was higher than that of ICC (P < 0.001). The infection rates of hepatitis B virus were 89.84% and 35.88% in HCC and ICC, respectively, and the infection rates of hepatitis B, serum HBsAg postive rate and DNA account in HCC were higher than ICC (P < 0.001). The incidence of liver cirrhosis and hepatic schistosomiasis in HCC was also significantly different from that in ICC (both P < 0.01). Pearson's correlation analysis showed that there was a significant negative correlation between HCC or ICC tumor type and hepatic schistosomiasis (r = -0.018, P < 0.001), and there was a significant positive correlation between HCC and hepatic cirrhosis (r = 0.179, P < 0.001, and r = 0.528, P < 0.001, respectively). However, the proportion of cirrhosis and schistosomiasis in hepatitis B positive ICC cases was not significantly different from that in HCC cases (P > 0.05). Among the biochemical indicators, there were significant differences between HCC and ICC in the abnormal rate of ALT(P < 0.01), AST(P < 0.05), ALP (P < 0.01), GGT (P < 0.01) and TBIL (P < 0.01) while there was no significant difference between ALB and pre-ALB (P > 0.05) in HCC and ICC groups. The content and abnormal rate of alpha-fetoprotein were higher in HCC (P < 0.01), while the content and abnormal rate of carcinoembryonic antigen and carbohydrate antigen 19-9 were higher in ICC (P < 0.01). The 10-year survival rate and median survival time (46.92% and 80.3 months) of HCC were higher than those of ICC (12.57% and 12.4 months) (P < 0.01). Conclusion: In the study population, compared with ICC cases, the old aged male HCC cases are more common and has higher infection rate of hepatitis B virus and cirrhosis, but liver schistosomiasis is less common. The inflammatory damage, secretion and metabolic function of HCC were different from that of ICC cases, while the synthetic reserve function was similar to that of ICC and the prognosis of HCC cases was significantly better. The incidence of cirrhosis and schistosomiasis in ICC cases with positive hepatitis B virus infection was not significantly different from that of HCC cases.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
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