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1.
Gan To Kagaku Ryoho ; 50(11): 1215-1218, 2023 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-38056878

RESUMO

A 56-year-old woman was diagnosed with advanced rectal cancer, with tumor invasion to the sacrum and levator muscle of the anus and multiple lymph node metastasis. After construction of an artificial anus, chemotherapy was started. However, tumor invasion and the cancer pain progressed. Finally, she was hospitalized for pain control; an anesthesiologist planned to insert an epidural catheter. The epidural catheter was placed at the L5-S1 interspace, and continuous administration of 0.2% ropivacaine was started. Cancer pain in the buttocks improved quickly. Therefore, an epidural catheter with a subcutaneous port was placed to prevent catheter-related infection after a long period. The postoperative course was uneventful, and she was discharged from the hospital on the 10th day postoperatively. She could receive home medical care and pain control treatment in an outpatient clinic. Finally, she died due to progression of the rectal cancer, 3 months after placement of the epidural catheter with the subcutaneous port. Some patients with advanced rectal cancer develop cancer pain even though they are sufficiently treated with opioids or palliative radiation therapy. Here, we describe the case of a patient with locally advanced rectal cancer, treated with an epidural catheter with a subcutaneous port for cancer pain that was difficult to manage with opioids alone.


Assuntos
Analgesia Epidural , Dor do Câncer , Cateteres Venosos Centrais , Segunda Neoplasia Primária , Neoplasias Retais , Feminino , Humanos , Pessoa de Meia-Idade , Analgésicos Opioides/uso terapêutico , Analgesia Epidural/efeitos adversos , Dor/etiologia , Neoplasias Retais/complicações , Neoplasias Retais/tratamento farmacológico , Cateteres Venosos Centrais/efeitos adversos
2.
Surg Case Rep ; 8(1): 163, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048264

RESUMO

BACKGROUND: Superior mesenteric artery (SMA) syndrome denotes a mechanical duodenal obstruction between the SMA and aorta. Total parenteral or enteral nutrition is the treatment of choice. However, surgical intervention is indicated if the patient's condition does not improve with conservative treatment. Here, we describe a case of SMA syndrome with dysphagia treated by laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy. CASE PRESENTATION: A 64-year-old man was admitted to another hospital because of appetite loss and vomiting. There, he was diagnosed as having superior mesenteric artery (SMA) syndrome after appropriate investigation. He had had a cerebral infarction at age 57 years, since which he had lived in social housing because of complications of that infarction. A nasogastric tube was inserted into the third portion of the duodenum beyond the constricted section. He was discharged 2 months after admission his condition having improved. He was subsequently referred to our hospital for gastrostomy because the nasogastric tube had been in place for a long time and his condition had not improved. Additionally, gastrostomy was needed as a route for enteral nutrition because he had dysphagia, which had persisted despite attempts at rehabilitation, restricting his food intake to small amounts. Computed tomography (CT) revealed compression of the third portion of the duodenum between the SMA and aorta. After obtaining informed consent, we planned an operative procedure. We performed laparoscopic gastrojejunostomy under general anesthesia, followed by laparoscopic-assisted percutaneous endoscopic gastrostomy. The operation time was 156 min and there was little blood loss. Contrast radiography on postoperative day 3 revealed no evidence of leakage or stenosis. Enteral nutrition via the gastrostomy was started. He was discharged from our hospital on the 27th postoperative day. The gastrostomy was well tolerated and there has been no evidence of recurrence of SMA syndrome during follow-up. CONCLUSION: Gastrostomy is often performed to provide a route for administering enteral nutrition in patients with dysphagia. Development of SMA syndrome in patients with dysphagia necessitates operative management of the obstruction. Here, we describe a case of SMA syndrome with dysphagia treated by laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy.

3.
Surg Case Rep ; 8(1): 12, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038069

RESUMO

BACKGROUND: Because of the coronavirus disease 2019 (COVID-19) pandemic, preoperative screenings for COVID-19 infection are often performed in many institutions. Some patients are diagnosed with COVID-19 infection by antigen tests or polymerase chain reaction (PCR) testing for COVID-19, even if they have no symptoms, such as fever or respiratory symptoms. We herein describe a patient with gastric cancer who underwent distal gastrectomy 6 weeks after recovering from COVID-19 infection diagnosed by preoperative PCR. CASE PRESENTATION: An 86-year-old man was transferred to our hospital because of hematemesis and melena. A hemorrhagic gastric ulcer was found in the lesser curvature of the antrum by emergency endoscopy. Endoscopic hemostasis was performed, and he was discharged after recovery. A tumor-like lesion in the lesser curvature of the antrum was found on repeat endoscopy and was diagnosed as well-differentiated adenocarcinoma by biopsy. There was no evidence of lymph node metastasis or distant metastasis; therefore, we planned radical surgery. However, he was diagnosed with COVID-19 infection by preoperative PCR screening. Although he had no symptoms, such as fever or respiratory symptoms, he was hospitalized because of his advanced age. He was discharged 10 days after admission, and repeat COVID-19 PCR was negative. We planned radical surgery for the stomach tumor 6 weeks after recovery from the COVID-19 infection. A PCR-negative COVID-19 status was confirmed again before hospitalization. Open distal gastrectomy with Billroth I reconstruction was performed. We avoided ultrasonic scalpels and used a Crystal Vision 450D surgical smoke evacuator (I.C. Medical, Inc., Phoenix, AZ, USA) to reduce intraoperative surgical smoke. The postoperative course was uneventful. CONCLUSION: Because of the COVID-19 pandemic, some patients are diagnosed with COVID-19 infection by preoperative antigen tests or PCR, even if they have no symptoms. If possible, elective surgery should be performed 4 to 6 weeks after recovery from COVID-19 infection to maximize safety. Moreover, surgeons must consider intraoperative surgical smoke.

4.
Surg Case Rep ; 6(1): 177, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32700198

RESUMO

BACKGROUND: Despite improved surgical techniques and perioperative management, anastomotic leakage (AL) after esophageal cancer surgery remains a potential complication. In most cases, spontaneous healing upon proper drainage is observed, but sometimes, AL results in intractable enterocutaneous fistulas. We here report a case of intractable enterocutaneous fistula caused by post-esophagectomy AL and successfully treated by scopolamine ointment and negative pressure wound therapy (NPWT). CASE PRESENTATION: A 77-year-old man underwent thoracoscopic subtotal esophagectomy with 3-field lymph node dissection, followed by gastric tube reconstruction through the posterior mediastinal route. On the 6th postoperative day, AL was identified, forming an enterocutaneous fistula. Initially, conservative treatment was performed, but the fistula failed to close. We hypothesized that the substantial amount of exudate might be hampering fistula closure. Scopolamine ointment was used to reduce the amount of fluid. NPWT was also initiated to promote wound healing. Approximately 3 weeks after the beginning of the treatment, the fistula closed; oral intake became possible, and the patient was discharged from the hospital without any symptoms. CONCLUSIONS: The combination of scopolamine ointment and NPWT may be regarded as one effective treatment option for intractable enterocutaneous fistula due to AL after esophagectomy.

5.
Int Surg ; 99(4): 463-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25058785

RESUMO

Our report concerns a 64-year-old man with a small-intestinal gastrointestinal stromal tumor (GIST), which was successfully treated with single-incision laparoscopic surgery (SILS). Small-bowel endoscopy detected a submucosal tumor located approximately 10 cm from the ligament of Treitz in the wall of the proximal jejunum. Contrast-enhanced computed tomography revealed a tumor (diameter, 4 cm) containing high- and low-density areas in the proximal jejunum. On 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET), the tumor demonstrated intense FDG uptake (maximum standard uptake value, 3.82), whereas it displayed high signal intensity on diffusion-weighted magnetic resonance images. No metastatic lesions were observed. The patient was diagnosed with a jejunal GIST. Wedge resection of the jejunum was performed using the SILS procedure. The tumor was histopathologically diagnosed as a low-grade malignant GIST. SILS is a useful resection technique for small-intestinal GIST.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Neoplasias Intestinais/cirurgia , Intestino Delgado , Laparoscopia/métodos , Meios de Contraste , Endoscopia Gastrointestinal , Fluordesoxiglucose F18 , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
6.
Rare Tumors ; 5(3): e30, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24179642

RESUMO

Intraductal papillary neoplasms of the bile duct (IPNB) is the collective term used to refer to papillary bile duct tumors, mucin producing bile duct tumors, and cystic bile duct tumors. Pathologically, these tumors may be considered a highly differentiated adenocarcinoma or a tumor of borderline malignant potential. IPNB is classified into one of four variants based on cell differentiation. The rarest, oncocytic, is characterized by oxyphilic granular cytoplasm and no mucous cell differentiation. The patient, a 59-year old man, was admitted with a complaint of abdominal fullness and a 30×25 cm cystic mass in the right hepatic lobe demonstrated on computed tomography (CT). The mass had no malignant features on CT or magnetic resonance imaging; however, a portion was FDG avid on (18)F-fluorodeoxyglucose positron emission tomography scan (FDG-PET). A fenestration operation was performed for the presumed diagnosis of a hepatic cyst. Pathological examination of the cyst contents demonstrated some atypical cells suspicious for malignancy. After eight months of observation, abnormal FDG uptake was again observed at the residual cyst. A partial hepatectomy was performed to excise the cyst. Pathological examination demonstrated adenocarcinoma in situ derived from an oncocytic IPNB variant. Following the resection, the patient remained disease free for 40 months. This is an extremely rare case of an oncocytic variant of IPNB that was difficult to distinguish clinically from a solitary hepatic cyst.

7.
Int Surg ; 98(4): 330-3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24229019

RESUMO

We report on a case of ileal lipoma that prolapsed into the ascending colon and was resected by laparoscopy-assisted surgery. A 31-year-old male Japanese patient was admitted to our hospital because of hematochezia and anemia. Colonoscopy revealed a pedunculated polyp arising from the ileum. The surface was covered with slightly edematous mucosa. Abdominal computed tomography showed a low-density mass in the ascending colon. A diagnosis of pedunculated ileal lipoma with intussusception was made, and laparoscopy-assisted surgery was performed. The intussusception was reducted by resection of the lipoma. The surgical specimen was a 40 × 30 × 25 mm round tumor with a long stalk 11 cm in length. Microscopic examination of the specimen revealed ileal lipoma. Laparoscopic surgery is recommended for benign tumors of the small intestine because it is minimally invasive.


Assuntos
Doenças do Ceco/etiologia , Doenças do Ceco/cirurgia , Neoplasias do Íleo/complicações , Neoplasias do Íleo/cirurgia , Intussuscepção/etiologia , Intussuscepção/cirurgia , Laparoscopia/métodos , Lipoma/complicações , Lipoma/cirurgia , Adulto , Doenças do Ceco/diagnóstico , Colonoscopia , Diagnóstico Diferencial , Humanos , Neoplasias do Íleo/diagnóstico , Intussuscepção/diagnóstico , Lipoma/diagnóstico , Masculino , Tomografia Computadorizada por Raios X
8.
Int Surg ; 97(3): 230-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23113851

RESUMO

A 58-year-old female with hepatitis C was referred to our hospital after computed tomography (CT) revealed a tumor in the right lobe of her liver. After thorough examination, tumor thrombosis was detected on the main trunk of the portal vein, and we decided to administer a combination of subcutaneous interferon-alfa and intra-arterial 5-fluorouracil. However, after 2 cycles of treatment, this regimen was ineffective, and thus cisplatin (CDDP) was added for the third cycle. On completion of 5 treatment cycles, the tumor and portal vein tumor thrombosis were not detected by CT or (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography. Hence, chemotherapy was considered effective and stopped. Two years after chemotherapy, Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) levels were within normal limits. Combination therapies have been recognized recently, and judging from the above case, the addition of CDDP to the combination regimen can prove beneficial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Interferon-alfa/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Células Neoplásicas Circulantes/patologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Injeções Subcutâneas , Pessoa de Meia-Idade , Veia Porta
9.
Int Surg ; 97(2): 145-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23343338

RESUMO

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is one of the IgG4-related systemic sclerosing diseases and responds well to steroid therapy. A 58-year-old male was admitted with hilar bile duct stenosis revealed by computed tomography. We performed percutaneous transhepatic right portal vein embolization (PTPE) and scheduled a right hepatectomy because a hilar cholangiocarcinoma was first suspected. However, there was no cytologic evidence of malignancy and serum IgG4 was elevated. Steroid therapy was initiated after PTPE. There was no evidence of bile duct stenosis after 4 weeks. Improving diagnostic technique, IgG4-SC was diagnosed and treated with steroid therapy. In some cases, we couldn't deny the malignancy and performed unnecessary resection. We recommend that steroid administration while waiting for the liver volume to increase after PTPE is useful. The therapy aids in the diagnosis of bile duct stenosis, which has value for a hilar bile duct limit type of IgG4-SC, as in the case reported here.


Assuntos
Anti-Inflamatórios , Colangite Esclerosante/diagnóstico , Imunoglobulina G/sangue , Prednisolona , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Colangite Esclerosante/sangue , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico
10.
Int Surg ; 96(2): 153-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22026308

RESUMO

We present a successfully treated case of mixed ductal-endocrine carcinoma of the pancreas complicated by right renal cell carcinoma. The patient had no symptoms, and laboratory data were close to the normal range. Enhanced computed tomography demonstrated a marked enhanced tumor, which appeared to be an endocrine tumor, at the pancreas uncus. We performed pyrolus-preserving pancreaticoduodenectomy, regional lymph node resection, and right nephrectomy. Histologically and immunohistochemically, the pancreas tumor had both a ductal (exocrine) and an endocrine component. The renal tumor was a typical clear cell carcinoma. A diagnosis of synchronous double cancer was made. As demonstrated in previously published reports, this type of mixed tumor has malignant potential for invasive ductal carcinoma. We propose that mixed ductal-endocrine carcinoma of the pancreas should be treated by surgical resection with a sufficient surgical margin and regional lymph node resection to improve the patient's prognosis.


Assuntos
Carcinoma Neuroendócrino/patologia , Carcinoma Ductal Pancreático/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pancreáticas/patologia , Idoso , Carcinoma Neuroendócrino/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma de Células Renais/cirurgia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Neoplasias Renais/cirurgia , Linfonodos/cirurgia , Masculino , Nefrectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Prognóstico
11.
Clin Exp Metastasis ; 28(4): 367-76, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21331750

RESUMO

Pancreatic cancer demonstrates a strong resistance to anticancer drugs, presumably due to its resistance to drug induced apoptosis. Although gemcitabine (GEM) might be partially effective for treating advanced pancreatic cancer, its efficacy is still less than satisfactory. Galectin-3 (gal-3), a member of the ß-galactoside-binding protein family, is a multifunctional protein with roles in tumor cell adhesion, proliferation, differentiation, angiogenesis, metastasis, and apoptosis. We have utilized gal-3 small interfering RNA (siRNA) to probe whether gal-3 regulates anticancer drug-induced apoptosis in pancreatic cancer cells. We found that Gal-3 siRNA augmented GEM- and cisplatin-induced apoptosis in pancreatic cancer cell lines in vitro. Mitochondrial depolarization induction was increased in gal-3-silenced cells after GEM treatment, resulting in activation of caspase-9, but not caspase-8. Akt phosphorylation was significantly downregulated in gal-3- silenced cells in association with apoptosis. Moreover, intratumoral administration of gal-3 siRNA increased the GEM sensitivity of tumor xenografts produced by subcutaneous inoculation of pancreatic cancer cells into nude mice. These results suggest that gal-3 might provide a novel therapeutic target in pancreatic cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Galectina 3/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Interferência de RNA , Animais , Apoptose/genética , Desoxicitidina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/patologia , Transfecção , Células Tumorais Cultivadas , Gencitabina
12.
J Hepatol ; 43(5): 823-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16085335

RESUMO

BACKGROUND/AIMS: The expression level of the activin betaC subunit is high in normal liver and reduces after partial hepatectomy, but its function is controversial. METHODS: To determine the role of the betaC subunit during liver regeneration, we overexpressed the betaC subunit gene in the liver by infusing adenovirus vector encoding the flag-tagged betaC subunit into the portal vein. Adenovirus vector encoding the beta-galactosidase was also infused as a control. Seventy percent hepatectomy was performed 4 days after the infection. RESULTS: Approximately 20% of hepatocytes expressed the flag-tagged betaC subunit at the time of hepatectomy and approximately 50% of hepatocytes expressed the betaC subunit 3 days after hepatectomy. In betaC-infected liver, bromodeoxyuridine labeling was significantly greater at 24 and 48 h after partial hepatectomy compared with the control liver. Consistent with this observation, the liver regeneration rate was significantly greater in betaC-transfected liver at 72 and 96 h after hepatectomy. Many of the bromodeoxyuridine-positive nuclei were observed in or by the betaC-transfected hepatocytes. CONCLUSIONS: These results indicate that liver regeneration is accelerated in betaC-overexpressing liver. The betaC subunit may function to promote replication of hepatocytes during liver regeneration.


Assuntos
Adenoviridae/metabolismo , Hepatectomia , Hepatócitos/metabolismo , Subunidades beta de Inibinas/metabolismo , Regeneração Hepática , Adenoviridae/genética , Animais , Dimerização , Hepatócitos/citologia , Subunidades beta de Inibinas/química , Subunidades beta de Inibinas/genética , Masculino , Tamanho do Órgão , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Ratos , Ratos Wistar
13.
Endocr J ; 52(2): 169-75, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15863943

RESUMO

To investigate the function of the beta(C) and beta(E) subunits of activin, we overexpressed these subunits in AML12 cells, a normal hepatocyte cell line, using adenovirus vector. Overexpression of the beta(C) subunit increased [3H]thymidine incorporation and the cell number. In contrast, both [3H]thymidine incorporation and the cell number were reduced in the beta(E) overexpressing cells. When AML cells overexpressing the beta(E) subunit were cultured in medium containing 1% serum for 48 h, many of the cells died by apoptosis, whereas cells overexpressing the beta(C) subunit or beta-galactosidase survived in the same condition. To examine dimer formation, the beta(C) and beta(E) subunits were expressed in AML12 cells. In these cells, the beta(C) homodimer, the beta(E) homodimer and the beta(C)-beta(E) heterodimer were detected. When the expression level of the beta(E) subunit was increased, formation of the beta(E) homodimer was increased, while formation of the beta(C)-beta(E) heterodimer was slightly reduced. Overexpression of the beta(E) subunit did not significantly affect the formation of the beta(C) homodimer. These results indicate that the beta(C) and beta(E) subunits form homo- and heterodimers, and that the functions of the two subunits are quite different.


Assuntos
Hepatócitos/fisiologia , Subunidades beta de Inibinas/fisiologia , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , DNA/biossíntese , Fragmentação do DNA , Dimerização , Expressão Gênica , Marcação In Situ das Extremidades Cortadas , Subunidades beta de Inibinas/genética , Camundongos , Camundongos Transgênicos , Transfecção , Fator de Crescimento Transformador alfa/genética
14.
Am J Physiol Endocrinol Metab ; 287(2): E247-54, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15039147

RESUMO

We assessed the function of the beta(C)-subunit of activin in hepatocytes. We studied the effect of conditioned medium of Chinese hamster ovary (CHO) cell line stably expressing the beta(C) gene (CHO-beta(C)) on growth of AML12 hepatocytes. We also examined the effect of recombinant activin C and transfection of the beta(C) gene by using adenovirus vector. CHO-beta(C) secreted activin C, a homodimer of the beta(C), as well as precursors of the beta(C). The conditioned medium of CHO-beta(C) increased both [(3)H]thymidine incorporation and the cell number in AML12 cells. It also supported survival of AML12 cells in a serum-free condition. Recombinant human activin C also increased both [(3)H]thymidine incorporation and the number of AML12 cells. Transfection of AML12 cells with the beta(C)-subunit led to the stimulation of [(3)H]thymidine incorporation. Analysis of the conditioned medium revealed that the beta(C)-subunit formed a heterodimer with the endogenous beta(A), the formation of which was dependent on the amount of beta(C) expressed. Recombinant activin C did not affect the binding of (125)I-activin A to its receptor or follistatin. These results indicate that activin C stimulates growth of AML12 cells. The beta(C)-subunit modifies the function of the beta(A)-subunit by multiple mechanisms.


Assuntos
Hepatócitos/metabolismo , Subunidades beta de Inibinas/fisiologia , Animais , Células CHO/metabolismo , Divisão Celular/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Cricetinae , Cricetulus , Meios de Cultivo Condicionados/metabolismo , Hepatócitos/citologia , Humanos , Subunidades beta de Inibinas/biossíntese , Camundongos , Conformação Proteica , Proteínas Recombinantes , Transfecção
15.
Endocrinology ; 145(6): 2753-9, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15001548

RESUMO

The present study was conducted to examine the role of activin A in the activation of cultured rat hepatic stellate cells (HSC). HSC expressed mRNA for the beta(A)-subunit of activin and the type I and II activin receptors. TGF-beta increased the mRNA expression of the beta(A)-subunit of activin as well as the release of the beta(A) dimer, activin A. Exogenous activin A activated HSC and increased the expression of alpha-smooth muscle actin and collagen. Exogenous follistatin, an antagonist of activin A, blocked not only the effect of activin A but also the effect of TGF-beta on the expression of type I collagen. Similarly, follistatin inhibited TGF-beta-induced secretion of collagen from HSC. Additionally, the effect of TGF-beta was markedly reduced in HSC overexpressing the dominant-negative type II activin receptor. In contrast, the effect of activin A on the collagen production was not affected in HSC overexpressing the dominant-negative type II TGF-beta receptor. In conclusion, an autocrine factor activin A mediates part of the action of TGF-beta on the production of collagen in HSC. The results also suggest that follistatin may be useful for the treatment of hepatic fibrosis.


Assuntos
Ativinas/fisiologia , Colágeno/biossíntese , Hepatócitos/metabolismo , Subunidades beta de Inibinas/fisiologia , Proteínas , Fator de Crescimento Transformador beta/fisiologia , Receptores de Ativinas Tipo I/metabolismo , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Ativinas/metabolismo , Ativinas/farmacologia , Animais , Células Cultivadas , Folistatina/farmacologia , Genes Dominantes , Humanos , Subunidades beta de Inibinas/metabolismo , Subunidades beta de Inibinas/farmacologia , Ratos , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia
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