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1.
Carcinogenesis ; 42(4): 631-639, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33367515

RESUMO

The TGF-ß receptor kinase inhibitors (TRKI) have been reported to inhibit tumorigenicity in colon cancer. However, there is no direct evidence showing that these inhibitors function through inhibiting the TGF-ß- mediated tumor-promoting effects in vivo. We established a TGF-ß inducible reporter system by inserting a luciferase reporter gene to the vector downstream of TGF-ß-inducible promoter elements, and transfected it into colon cancer cell lines. TRKIs SB431542 and LY2109761 were used to treat TGF-ß inducible cells in vitro and in vivo. The luciferase activity was induced 5.24-fold by TGF-ß in CT26 inducible cells, while it was marginally changed in MC38 inducible cells lacking Smad4 expression. Temporary treatment of mice with SB431542 inhibited the TGF-ß pathway and TGF-ß induced bioluminescence activity in vivo. Long-term treatment with LY2109761 inhibited tumorigenicity and liver metastasis in vivo in concomitant with reduced luciferase activity in the tumor. In this study, we established a model to monitor the TGF-ß pathway in vivo and to compare the antitumor effects of TRKIs. Based on this novel experimental tool, we provided direct evidences that LY2109761 inhibits tumorigenicity and liver metastasis by blocking the pro-oncogenic functions of TGF-ß in vivo.


Assuntos
Carcinogênese/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Receptores de Fatores de Crescimento Transformadores beta/genética , Fator de Crescimento Transformador beta/genética , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Dioxóis/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirróis/farmacologia , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
2.
Medicine (Baltimore) ; 97(50): e13190, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30557968

RESUMO

RATIONALE: Synchronous gastric carcinoma and hepatocellular carcinoma (HCC) is rare. It is hard to distinguish synchronous HCC from metastatic liver cancer in this condition. The treatment and prognosis is quite different for synchronous HCC of gastric carcinoma and liver metastasis of gastric carcinoma. PATIENT CONCERNS: A 68-year-old man with a chief complaint of epigastric pain for 1 year, accompanied by reflux and belching. The patient was diagnosed with gastric carcinoma (cT4NxM0) and laparoscopy-assisted radical distal gastrectomy was performed. This was followed by chemotherapy of FOLFOX regimen. However, a liver nodule growth was observed after postoperative systemic treatment. DIAGNOSIS: The initial diagnosis was liver metastasis of gastric carcinoma. However after hepatectomy of segment VI and VII as well as thrombectomy of right hepatic vein, histology revealed intermediate to poor differentiated HCC. Hence this case was diagnosed as synchronous gastric carcinoma and HCC. INTERVENTIONS: A preventive transcatheter arterial chemoembolization (TACE) was conducted at 4 weeks after hepatectomy. Another FOLFOX regimen was suggested, but was refused by the patient. OUTCOMES: The patient survived without tumor recurrence for 9 months after the second surgery. LESSONS: Synchronous HCC should be routinely distinguished from gastric carcinoma liver metastasis, especially for patients with hepatitis B virus (HBV) infection. The FOLFOX4 regimen for treating gastric carcinoma liver metastasis may have inhibited the progression of primary HCC in this case. This patient with HCC benefited from liver resection, inspite of hepatic vein tumor thrombosis.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Tratamento Farmacológico/normas , Neoplasias Hepáticas/cirurgia , Neoplasias Gástricas/cirurgia , Idoso , Carcinoma Hepatocelular/complicações , Tratamento Farmacológico/métodos , Eructação/etiologia , Eructação/cirurgia , Gastrectomia/métodos , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Hepatectomia/métodos , Humanos , Masculino
3.
BMC Cancer ; 18(1): 835, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30126375

RESUMO

BACKGROUND: This study explored the effect of liver resection on perioperative circulating tumor cells (CTCs) and found that the prognostic significance of surgery was associated with changes in CTC counts in patients with hepatocellular carcinoma (HCC). METHODS: One hundred thirty-nine patients with HCC were consecutively enrolled. The time-points for collecting blood were one day before operation and three days after operation. CTCs in the peripheral blood were detected by the CellSearch™ System. RESULTS: Both CTC detection incidence and mean CTC counts showed greater increases postoperatively (54%, mean 1.54 cells) than preoperatively (43%, mean 1.13 cells). The postoperative CTC counts increased in 41.7% of patients, decreased in 25.2% of patients and did not change in 33.1% of patients. The increase in postoperative CTC counts was significantly associated with the macroscopic tumor thrombus status. Patients with increased postoperative CTC counts (from preoperative CTC < 2 to postoperative CTC ≥ 2) had significantly shorter disease-free survival (DFS) and overall survival (OS) than did patients with persistent CTC < 2. Patients with persistent CTC levels of ≥2 had the worst prognoses. CONCLUSIONS: Surgical liver resection is associated with an increase in CTC counts, and increased postoperative CTC numbers are associated with a worse prognosis in patients with HCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Células Neoplásicas Circulantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas/métodos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
4.
Ann Vasc Surg ; 48: 251.e5-251.e10, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29221838

RESUMO

BACKGROUND: Aneurysm of splenic artery (SA) which arises from the superior mesenteric artery (SMA) is a very rare condition. The aim of this study was to present our experience with 2 such patients treated by coil embolization. METHODS: A 33-year-old man and a 61-year-old woman were incidentally identified with aneurysms of the SA which arose from the SMA. Endovascular therapy of coil embolization was chosen to treat the aneurysm. RESULTS: Follow-up computed tomography showed no change in the location of the coils and occlusion of majority of the aneurysm sac. The 2 patients have been doing well during a 26-month and 10-month follow-up period, respectively. CONCLUSIONS: Combined with the experience of the previous literature, we think coil embolization can be cost-effective and minimally invasive in selected cases, depending on the morphology and site of the lesion.


Assuntos
Aneurisma/terapia , Embolização Terapêutica/instrumentação , Artéria Mesentérica Superior/anormalidades , Artéria Esplênica/anormalidades , Malformações Vasculares/complicações , Adulto , Idoso , Aneurisma/diagnóstico por imagem , Aneurisma/etiologia , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Pessoa de Meia-Idade , Artéria Esplênica/diagnóstico por imagem , Resultado do Tratamento , Malformações Vasculares/diagnóstico por imagem
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