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1.
World J Gastrointest Oncol ; 14(5): 1057-1064, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35646283

RESUMO

BACKGROUND: Pancreatic accessory spleen (PAS) is an uncommon congenital abnormality of the spleen. Spleen hamartoma (SH) is also rare. Moreover, hamartoma in the PAS has not been reported thus far. We report the first case here. CASE SUMMARY: A 26-year-old male presented with a one-month history of left upper quadrant abdominal pain, and computerized tomography (CT) examination suggested a mass in the pancreas tail. The patient then attended our hospital for diagnosis and treatment. Ultrasonography, CT, and magnetic resonance imaging revealed a solid mass with cystic degeneration growing from the tail of the pancreas. The tumor marker carbohydrate antigen 19-9 (CA19-9) increased to 96.7 U/mL (normal range 0-37 U/mL). An epidermoid cyst in a PAS was considered preoperatively. However, a malignant tumor cannot be ruled out. We performed laparoscopic surgery, and two pancreatic masses were found growing from the pancreatic tail. The two masses were so closely connected that preoperative imaging examinations suggested only one mass. We carefully isolated the masses from the splenic artery and vein. A laparoscopic spleen-preserving distal pancreatectomy was successfully performed. On pathological examination, the masses were well-defined, homogeneous red-tan, 4 × 3, and 4.5 × 1.5 in size, respectively. One of them was cystically degenerated. On microscopical examination, the mass contained unorganized small slit-like vascular channels enclosing red blood cells and lined with plump endothelial cells. No area of cytologic atypia was identified. Focal lymphoid aggregates were found in the intravascular areas. White pulp or fibrosis was not observed. The final diagnosis was pancreatic accessory SH with cystic degeneration. After the operation, CA19-9 was reduced to normal. The patient recovered well, and the 34-mo follow-up period was uneventful. CONCLUSION: Here, we report the first case of pancreatic accessory SH. A laparoscopic spleen-preserving distal pancreatectomy was successfully performed. The patient recovered well and had a good prognosis.

2.
Medicine (Baltimore) ; 101(9): e28874, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244041

RESUMO

RATIONALE: Pancreatic schwannomas are extremely rare and are difficult to diagnose preoperatively. Over the past 50 years, only 96 cases of pancreatic schwannoma have been reported in English literature. Herein, we report a case of pancreatic schwannoma treated with enucleation. PATIENT CONCERNS: A 66-year-old woman visited a local hospital due to ventosities. Ultrasonography and computed tomography revealed a pancreatic mass. She visited our hospital for further diagnosis and treatment. DIAGNOSIS AND INTERVENTIONS: Magnetic resonance imaging revealed a tumor in the pancreatic body, and a solid pseudopapillary tumor was considered preoperatively. During the surgery, a pancreatic mass was found growing in the pancreatic body and tail. A successful tumor enucleation was performed. The mass was 7 × 6 × 3 cm in size with a thin capsule. Pathological examination revealed that the tumor was mainly composed of spindle-shaped cells with a palisading arrangement and no atypia. Both hypercellular and hypocellular areas were visible. Immunohistochemical staining showed that protein S-100 was strongly positive. The tumor was diagnosed as a benign schwannoma originating from the pancreatic body and tail. OUTCOMES: Postoperatively, the patient showed good recovery. During the 24-month follow-up period, the patient remained well and free of complications. LESSONS: Pancreatic schwannomas are extremely rare and difficult to diagnose using imaging examinations. Enucleation is a safe and efficacious treatment for exophytic pancreatic schwannomas.


Assuntos
Neurilemoma/patologia , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia
3.
Medicine (Baltimore) ; 100(2): e24054, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466160

RESUMO

RATIONALE: Primary neuroendocrine tumors (NETs) of the retroperitoneum are extremely rare. The purpose of this case report is to highlight the unusual growth pattern and radiologic features of primary retroperitoneal NETs. PATIENT CONCERNS: A 46-year-old woman was found to have a retroperitoneal cystic and solid mass during a physical checkup. DIAGNOSES: The mass was mainly multiseptated in the cystic portion and had a bead-like, lobulated appearance. The solid portion showed restricted diffusion on diffusion-weighted imaging and obvious homogeneous enhancement. The cystic portion showed ring-like and septal enhancement. The patient was diagnosed with a grade 2 (G2) NET of the retroperitoneum after surgery. INTERVENTIONS: The patient underwent resection of the large retroperitoneal tumor. OUTCOMES: The patient returned 20 months later with tumor recurrence in the retroperitoneum. She was enrolled in a clinical trial for sulfatinib, and the mass was considerably reduced in size after 4 months. During a nearly 1.5-year follow-up, the mass gradually became slightly enlarged. The expression of somatostatin receptor 2 (SSTR2) was detected, and somatuline was administered as the current treatment. LESSONS SUBSECTIONS: When a retroperitoneal mass presents as a well-defined cystic or solid hypervascular mass with a fibrous capsule, a primary retroperitoneal NET should be considered in the differential diagnosis.


Assuntos
Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Retroperitoneais/patologia , Espaço Retroperitoneal/patologia
4.
Pancreas ; 47(6): 732-737, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29851753

RESUMO

OBJECTIVE: The epidermal growth factor receptor is overexpressed in the majority of pancreatic cancer. Epidermal growth factor receptor tyrosine kinase inhibitor erlotinib was approved to treat patients combining with gemcitabine. However, the sensitivity is low. Here, we try to reveal the regulatory role of guanine nucleotide exchange protein 100 (GEP100) in erlotinib sensitivity. METHODS: We investigated the correlation between GEP100 expression and sensitivity to erlotinib in different pancreatic cancer cell lines, followed by examination of the effect of GEP100 on erlotinib sensitivity by establishing the stable knocked-down cell line. The expression level of epithelial mesenchymal transition-related protein was examined by Western blot, and the regulatory mechanism was investigated by short hairpin RNA. Xenograft experiment was also performed in nude mice. RESULTS: We identified a significant correlation between sensitivity to erlotinib and expression of GEP100. GEP100 downregulation increased its sensitivity to erlotinib. E-cadherin short hairpin RNA treatment inhibited this sensitivity. Immunohistochemical staining showed a mutual exclusive expression pattern of GEP100 and E-cadherin in human pancreatic cancer tissues. Xenograft showed that downregulation of GEP100 enhanced the growth inhibition of erlotinib in nude mice. CONCLUSIONS: Our results suggested that GEP100 and E-cadherin have the predictive value for responsiveness to erlotinib in pancreatic cancer.


Assuntos
Regulação para Baixo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Cloridrato de Erlotinib/farmacologia , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Medicine (Baltimore) ; 97(21): e10783, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794760

RESUMO

INTRODUCTION: Ciliated retroperitoneal foregut cysts are rare, and to obtain a preoperative definitive diagnosis of this condition is relatively difficult. In addition, the exact mechanism and formation of ciliated retroperitoneal foregut cysts remains unknown. CASE PRESENTATION: Here, we report a case of a 47-year-old woman who presented with an unusual shaped cystic lesion associated with a patch of solid components between the pancreas and the left kidney, initially misdiagnosed as a cystic pancreatic lesion 5 years previously to presentation at our clinic. During the past years, reports relating to the surveillance of these lesions described that their shapes progressively change while its volumes remain invariably unchanged. We did not observe this phenomenon in any literatures to our knowledge. The patient was diagnosed with ciliated retroperitoneal foregut cyst with remote hemorrhage, after the laparoscopic surgery. CONCLUSIONS: Ciliated retroperitoneal foregut cysts have characteristic manifestations. From this case, we summarized that cysts in the retroperitoneum, associated with a changing shape of the lesion, highly suggest the diagnosis of foregut cysts, which are safe under long-term surveillance.


Assuntos
Gastroenteropatias/diagnóstico , Cisto Pancreático/diagnóstico , Espaço Retroperitoneal/patologia , Trato Gastrointestinal Superior/anormalidades , Cistos , Diagnóstico Diferencial , Feminino , Seguimentos , Gastroenteropatias/cirurgia , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Pâncreas/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Am J Case Rep ; 19: 262-266, 2018 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-29515097

RESUMO

BACKGROUND Multiple lymphomatous polyposis of the gastrointestinal tract can be associated with the B-cell lymphoma variant, mantle cell lymphoma, with most cases having been described in patients who are more than 50 years-of-age. A rare case of multiple lymphomatous polyposis due to mantle cell lymphoma is reported in a 34-year-old man. CASE REPORT A 34-year-old man presented with paroxysmal abdominal pain followed by spontaneous remission, which had been previously diagnosed as gastritis. An episode of ileocecal intussusception occurred, which was confirmed on imaging studies. The diagnosis of multiple lymphomatous polyposis due to mantle cell lymphoma was confirmed following ileocecal resection and histopathology. The patient refused to receive chemotherapy following surgery. Currently, at two-year follow-up, no further abnormality has been found. A review of the literature has shown the importance of endoscopic evaluation in the diagnosis of lymphomatous polyposis. CONCLUSIONS Multiple lymphomatous polyposis due to mantle cell lymphoma has rarely been described in young patients under the age of 50 years. Gastrointestinal endoscopic examination is important for the early diagnosis of multiple lymphomatous polyposis.


Assuntos
Doenças do Íleo/etiologia , Valva Ileocecal , Intussuscepção/etiologia , Linfoma de Célula do Manto/complicações , Adulto , Diagnóstico Diferencial , Humanos , Doenças do Íleo/diagnóstico , Polipose Intestinal , Intussuscepção/diagnóstico , Linfoma de Célula do Manto/diagnóstico , Masculino
7.
Cancer Lett ; 406: 22-26, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28729048

RESUMO

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/análogos & derivados , Metástase Neoplásica/tratamento farmacológico , Compostos Organoplatínicos/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Camptotecina/efeitos adversos , China/epidemiologia , Feminino , Humanos , Irinotecano , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Oxaliplatina , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/epidemiologia , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
8.
BMC Neurol ; 15: 198, 2015 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-26458877

RESUMO

BACKGROUND: Tumor markers are widely applied in clinical practice, however, few serum markers have been found for intracranial tumors. Herein, we firstly report an intracranial epidermoid cyst case with extremely high level of serum CA 199. Furthermore, the relationship between CA 199 level and intracranial epidermoid cyst was closely followed for a long period. CASE PRESENTATION: We report a case of 41-year-old man with a history of 2 months' headache and sudden exacerbation for 3 days. Radiology examination suggested multiple lesions spreading along ventricular system. Laboratory tests showed exceeding increase of serum CA 199. The patient underwent craniotomy and continuous lumber drainage. Post-operative pathology proved a ruptured intracranial epidermoid cyst. MRI scans and serum CA 199 were closely followed up for three years. CONCLUSION: This case suggests an important role of serum CA 199 in the diagnosis and follow-up of intracranial epidermoid cyst. Ruptured intracranial epidermoid cyst should be considered for a sudden onset case with multiple intracranial lesions and dramatically increased serum CA 199.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Neoplasias Encefálicas , Ventriculite Cerebral , Cisto Epidérmico , Adulto , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Ventriculite Cerebral/sangue , Ventriculite Cerebral/diagnóstico , Ventriculite Cerebral/diagnóstico por imagem , Cisto Epidérmico/sangue , Cisto Epidérmico/diagnóstico , Cisto Epidérmico/diagnóstico por imagem , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Ruptura Espontânea
9.
Korean J Radiol ; 16(1): 146-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25598683

RESUMO

OBJECTIVE: To describe the imaging features of pelvic solitary plasmacytoma and to correlate them with the pathologic grade. MATERIALS AND METHODS: A retrospective study was performed on the imaging features of 10 patients with a histological diagnosis of pelvic solitary plasmacytoma. The imaging studies were assessed for bone expansion, cortical destruction, signal intensity/density of soft tissue mass and enhancement manifestations, which were then correlated to the pathologic grade. RESULTS: The imaging features of pelvic solitary plasmacytoma revealed 3 different types: multilocular type (n = 5), unilocular type (n = 2) and complete osteolytic destruction type (n = 3) on computed tomography and MRI. Pathologically, the tumors were classified into low, intermediate and high grades. Features such as multilocular change, perilesional osteosclerosis, slight expansion, local bone cortex disruptions and masses inside bone destruction, often suggest a low-grade solitary plasmacytoma; complete osteolytic destruction, huge soft tissue mass, and osseous defects imply a higher pathologic grade. CONCLUSION: Pelvic solitary plasmacytoma has various imaging manifestations, while a slight expansile osteolytic feature with multilocular change or homogeneous enhancement highly suggests its diagnosis. The distinctive imaging features of pelvic solitary plasmacytoma are well correlated to the pathologic grade.


Assuntos
Neoplasias Pélvicas/patologia , Plasmocitoma/patologia , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Pélvicas/diagnóstico por imagem , Plasmocitoma/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Artigo em Chinês | MEDLINE | ID: mdl-24330879

RESUMO

OBJECTIVE: To investigate the effect of nasal cavity expansion surgery on the abnormal blood supply of the cerebral arterial system. METHODS: Fifty-nine inpatients with abnormal blood supply of cerebral arterial system confirmed by transcranial doppler (TCD) and chronic nasal obstructive diseases were included in this study. All patients accepted nasal cavity expansion surgery and were followed-up with TCD every month after operation until TCD became normal, or up to seven months even if the TCD was still abnormal. SPSS 17.0 software was used to analyze the data. RESULTS: In all 59 patients, there were 164 TCD-abnormal cerebral arteries. Among them, 37 patients(62.71%) with abnormal TCD arteries became normal within 1 to 7 months after operation, 8 patients (13.56 %) got better, but 14 patients (23.73 %) did not improve. CONCLUSIONS: Abnormal blood flow of some cerebral arteries was possibly induced by increasing the activation of sympathetic nervous system around the vertebral arterial system, caused by chronic nasal obstruction. Nasal dilatancy surgery can improve the blood supplement of the cerebral arterial system.


Assuntos
Circulação Cerebrovascular , Ultrassonografia Doppler Transcraniana , Velocidade do Fluxo Sanguíneo , Artérias Cerebrais , Humanos , Cavidade Nasal
11.
J Microbiol Biotechnol ; 23(4): 534-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23568208

RESUMO

The effects of lights with different wavelengths on the growth and the yield of extracellular polysaccharides of Nostoc flagelliforme cells were investigated in a liquid cultivation. N. flagelliforme cells were cultured for 16 days in 500 ml conical flasks containing BG11 culture medium under 27 micromol·m-2·s-1 of light intensity and 25 degrees C on a rotary shaker (140 rpm). The chlorophyll a, phycocyanin, allophycocyanin, and phycoerythrin contents in N. flagelliforme cells under the lights of different wavelengths were also measured. It was found that the cell biomass and the yield of polysaccharide changed with different wavelengths of light. The biomass and the yield of extracellular polysaccharides under the red or violet light were higher than those under other light colors. Chlorophyll a, phycocyanin, and allophycocyanin are the main pigments in N. flagelliforme cells. The results showed that N. flagelliforme, like other cyanobacteria, has the ability of adjusting the contents and relative ratio of its pigments with the light quality. As a conclusion, N. flagelliforme cells favor red and violet lights and perform the complementary chromatic adaptation ability to acclimate to the changes of the light quality in the environment.


Assuntos
Luz , Nostoc/crescimento & desenvolvimento , Nostoc/efeitos da radiação , Polissacarídeos Bacterianos/biossíntese , Biomassa , Meios de Cultura/química , Nostoc/metabolismo , Oxigênio/metabolismo , Pigmentos Biológicos/análise , Temperatura
12.
PLoS One ; 7(8): e43119, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22900095

RESUMO

AIMS: The role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) of pancreatic cancer (PC) is known, however, its mechanism is unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand its mechanism by identifying Gli1 targets in pancreatic cancer cells. METHODS: First, we investigated invasion, migration, and EMT in PC cells transfected with lentiviral Gli1 interference vectors or SHH over-expression vectors in vitro and in vivo. Next, we determined the target gene profiles of Gli1 in PC cells using cDNA microarray assays. Finally, the primary regulatory networks downstream of SHH-Gli1 signaling in PC cells were studied through functional analyses of these targets. RESULTS: Our results indicate there is decreased E-cadherin expression upon increased expression of SHH/Gli1. Migration of PC cells increased significantly in a dose-dependent manner within 24 hours of Gli1 expression (P<0.05). The ratio of liver metastasis and intrasplenic miniature metastasis increased markedly upon activation of SHH-Gli1 signals in nude mice. Using cDNA microarray, we identified 278 upregulated and 59 downregulated genes upon Gli1 expression in AsPC-1 cells. The data indicate that SHH-Gli1 signals promote EMT by mediating a complex signaling network including TGFß, Ras, Wnt, growth factors, PI3K/AKT, integrins, transmembrane 4 superfamily (TM4SF), and S100A4. CONCLUSION: Our results suggest that targeting the molecular connections established between SHH-Gli1 signaling and EMT could provide effective therapies for PC.


Assuntos
Transição Epitelial-Mesenquimal/genética , Proteínas Hedgehog/genética , Proteínas Oncogênicas/genética , Neoplasias Pancreáticas/genética , Transdução de Sinais , Transativadores/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Técnicas de Transferência de Genes , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Nus , Proteínas Oncogênicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Transativadores/metabolismo , Transdução Genética , Proteína GLI1 em Dedos de Zinco
13.
PLoS One ; 7(5): e37854, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22662237

RESUMO

AIMS: Invasion and metastasis are major reasons for pancreatic cancer death and identifying signaling molecules that are specifically used in tumor invasion is of great significance. The purpose of this study was to elucidate the role of GEP100 in pancreatic cancer cell invasion and metastasis and the corresponding molecular mechanism. METHODS: Stable cell lines with GEP100 knocked-down were established by transfecting GEP100 shRNA vector into PaTu8988 cells and selected by puromycin. qRT-PCR and Western blot were performed to detect gene expression. Matrigel-invasion assay was used to detect cancer cell invasion in vitro. Liver metastasis in vivo was determined by splenic injection of indicated cell lines followed by spleen resection. Immunofluorescence study was used to detect the intracellular localization of E-cadherin. RESULTS: We found that the expression level of GEP100 protein was closely related to the invasive ability of a panel of 6 different human pancreatic cancer cell lines. Down-regulation of GEP100 in PaTu8988 cells significantly decreased invasive activity by Matrigel invasion assay, without affecting migration, invasion and viability. The inhibited invasive activity was rescued by over-expression of GEP100 cDNA. In vivo study showed that liver metastasis was significantly decreased in the PaTu8988 cells with GEP100 stably knocked-down. In addition, an epithelial-like morphological change, mimicking a mesenchymal to epithelial transition (MET) was induced by GEP100 down-regulation. The expression of E-cadherin protein was increased 2-3 folds accompanied by its redistribution to the cell-cell contacts, while no obvious changes were observed for E-cadherin mRNA. Unexpectedly, the mRNA of Slug was increased by GEP100 knock-down. CONCLUSION: These findings provided important evidence that GEP100 plays a significant role in pancreatic cancer invasion through regulating the expression of E-cadherin and the process of MET, indicating the possibility of it becoming a potential therapeutic target against pancreatic cancer.


Assuntos
Caderinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Animais , Comunicação Celular , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia
14.
Cell Signal ; 24(2): 524-531, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22033036

RESUMO

Ras is known as an oncogene transferring signals from the plasma membrane. Recent studies have demonstrated that plasma membrane was not the unique platform for Ras signaling. Ras could also be endocytosed and transported to different endomembrane compartments, evoking different signal pathways there. It is of great significance to exploit the unique intracellular trafficking features of different Ras isoforms to develop new anti-Ras drugs. ADP-ribosylation factor 6 (Arf6) was known to mediate one of the clathrin-independent endocytosis (CIE) pathways. The role of Arf6 in K-Ras dynamic remains largely unknown. In this study, we showed that K-RasG12V co-localized with Arf6 at the plasma membrane, and entered the tubular endosomes or protrusions induced by cytochalasin D or aluminum fluoride in the same way as H-RasG12V does. A subcellular fractionation experiment demonstrated that Arf6 siRNA treatment reduced the plasma membrane presence of both endogenous Ras isoforms and inhibited the phosphorylation of Erk triggered by EGF. When co-expressed with Arf6Q67L, both isoforms were sequestered into the large phosphatidylinositol 4,5-biphosphate [PI(4,5)P2]-enriched vacuoles. However, when co-expressed with Arf6T27N, K-RasG12V co-localized with Arf6T27N at the tubular endosomes significantly than H-RasG12V. Immunoprecipitation and GST fusion protein pull-down studies found out for the first time that K-RasG12V interacted with Arf6T27N. Swapping mutation study showed that the above difference was due to different C-termini. Our study indicated that Arf6 was involved in the dynamic regulation of both Ras isoforms.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Membrana Celular/metabolismo , Expressão Gênica , Proteína Oncogênica p21(ras)/metabolismo , Isoformas de Proteínas/metabolismo , Transdução de Sinais/genética , Neoplasias do Colo do Útero/metabolismo , Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP/genética , Compostos de Alumínio/farmacologia , Fracionamento Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Membrana Celular/ultraestrutura , Citocalasina D/farmacologia , Endocitose/genética , Endossomos/genética , Endossomos/metabolismo , Feminino , Fluoretos/farmacologia , Células HeLa , Humanos , Imunoprecipitação , Microscopia Confocal , Proteína Oncogênica p21(ras)/genética , Fosfatidilinositol 4,5-Difosfato/metabolismo , Isoformas de Proteínas/genética , Transporte Proteico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Vacúolos/efeitos dos fármacos , Vacúolos/genética , Vacúolos/metabolismo , Vacúolos/ultraestrutura
16.
Biochem Biophys Res Commun ; 384(3): 352-6, 2009 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-19409876

RESUMO

ADP-ribosylation factor (ARF) like 7 (ARL7, also named ARL4C) is a member of ARL family and recent studies showed that it is involved in the AI-dependent cholesterol secretion process. Yet its biological function remains largely unknown. Using a MALDI-TOF/MS analysis, we identified alpha-tubulin interacted with ARL7. The interaction was confirmed by GST pull-down assay and co-immunoprecipitation in renal carcinoma cell 786-O in which we found the endogenous ARL7 is expressed. This is the second ARL member found interacting with tubulin after ARL8. In addition, ARL7Q72L, a GTP-binding form, promoted the transferrin transport from early endosome to recycling endosome significantly. The above data suggested that ARL7 might modulate the intracellular vesicular transport via interaction with microtubules.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Vesículas Transportadoras/metabolismo , Tubulina (Proteína)/metabolismo , Fatores de Ribosilação do ADP/genética , Linhagem Celular Tumoral , Endossomos , Humanos , Transporte Proteico , RNA Mensageiro/biossíntese
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