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1.
Gan To Kagaku Ryoho ; 47(8): 1221-1224, 2020 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-32829359

RESUMEN

A 44-year-old woman experienced loss of vision and distorted vision in the right eye. After she visited our hospital, she was diagnosed with a right metastatic choroidal tumor. At the age of 35 years, she had undergone surgery for left breast cancer; as recurrence of the breast cancer was suspected, the patient was referred to our department. A CT scan revealed left axillary lymph node swelling, liver metastasis, and lung metastasis. Lymph node needle biopsy was performed under ultrasound guidance, and the pathological findings revealed recurrence of breast cancer. Combination chemotherapy of bevacizumab( BV)plus paclitaxel(PTX)was administered. After chemotherapy, the metastatic lesion had remarkably shrunk, as observed on a CT scan. Optical coherence tomography(OCT)revealed that the tumor was flattened in her right eye. Choroidal metastasis of breast cancer is rare. BV plus PTX therapy was effective for treating choroidal metastasis of breast cancer, and it should be followed by ophthalmological examination over time.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama , Neoplasias de la Coroides , Adulto , Bevacizumab , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/secundario , Neoplasias de la Coroides/tratamiento farmacológico , Femenino , Humanos , Recurrencia Local de Neoplasia , Paclitaxel
2.
Hum Pathol ; 65: 71-78, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28412205

RESUMEN

In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural nodule showing a papillary or nodular proliferation of tumor cells in the dilated pancreatic duct is an indication for resection of IPMN. Solute carrier family 2, facilitated glucose transporter member 1, known as glucose transporter type 1 (SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is correlated with increased 18F-fluorodeoxyglucose (18F-FDG) uptake. We examined SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish malignant/benign tumors. A mural nodule was detected in 80 (44.4%) of the IPMNs, and was detected in 18.6% (13/70) of the IPMN-low (dysplasia) specimens, 36.1% (13/36) of the IPMN-int, 93.3% (28/30) of the IPMN-high, and 59.1% (26/44) of the IPMN-inv (with an associated invasive carcinoma) specimens. The sensitivity for detecting mural nodules was 81.7% by endoscopic ultrasonography, 70% by contrast-enhanced computed tomography and 54% by endoscopic retrograde cholangiopancreatography. SLC2A1/GLUT1 expression in the mural nodules was recognized in the basal and basolateral cytomembrane of tumor cells and was expressed in 15.4% (2/13) of the IPMN-low, 15.4% (2/13) of the IPMN-int, 71.4% (20/28) of the IPMN-high and 84.6% (22/26) of the IPMN-inv groups. The SLC2A1/GLUT1 expression was significantly higher in the IPMN-high and IPMN-inv mural nodules than in those of the IPMN-low and IPMN-int groups. Our findings suggest that SLC2A1/GLUT1 is expressed late in the adenoma-carcinoma sequence during carcinogenesis in IPMN, and SLC2A1/GLUT1 act as therapeutic target for malignant IPMN.


Asunto(s)
Biomarcadores de Tumor/análisis , Transportador de Glucosa de Tipo 1/análisis , Neoplasias Quísticas, Mucinosas y Serosas/química , Neoplasias Pancreáticas/química , Anciano , Biopsia , Colangiopancreatografia Retrógrada Endoscópica , Endosonografía , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico por imagen , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
3.
Lab Invest ; 95(2): 193-206, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25418581

RESUMEN

Anterior gradient 2 (AGR2), a member of the protein disulfide isomerase family, has been implicated in various cancers including pancreatic ductal adenocarcinoma (PDAC) and is known to promote cancer progression. However, the prognostic value of AGR2 expression and the interaction with epithelial-mesenchymal transition (EMT) remain unclear. We investigated the clinical significance of AGR2 and EMT markers in PDAC patients by immunohistochemical analyses. Although AGR2 expression was not observed in normal pancreas, all pancreatic precursor neoplastic lesions were positive for AGR2, even at the earliest stages, including pancreatic intraepithelial neoplasia-1A, AGR2 expression was reduced in 27.7% (54/195 cases) of PDAC patients. AGR2 downregulation correlated with EMT markers (vimentin overexpression and reduced membranous E-cadherin expression), high Union for International Cancer Control stage (P<0.0001), high histological cellular grade (P<0.0001), and adverse outcome (P<0.0001). In vitro, targeted silencing of AGR2 in cancer cells using siRNA reduced cell proliferation, colony formation, cell invasiveness, and migration, but did not alter EMT markers. To confer a more aggressive phenotype and induce EMT in PDAC cells, we co-cultured PDAC cell lines with primary-cultured pancreatic stellate cells (PSCs) and found that AGR2 was downregulated in co-cultured PDAC cells compared with PDAC monocultures. Treatment with transforming growth factor beta-1 (TGF-ß), secreted from PSCs, decreased AGR2 expression, whereas inhibition of TGF-ß signaling using recombinant soluble human TGF-ß receptor type II and TGF-ß-neutralizing antibodies restored AGR2 expression. We conclude that AGR2 downregulation is a useful prognostic marker, induced by EMT, and that secreted TGF-ß from PSCs may partially contribute to AGR2 downregulation in PDAC patients. AGR2 downregulation does not induce EMT or a more aggressive phenotype, but is a secondary effect of these processes in advanced PDAC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Regulación Neoplásica de la Expresión Génica/fisiología , Virus de la Necrosis Pancreática Infecciosa/metabolismo , Proteínas/metabolismo , Western Blotting , Cadherinas/metabolismo , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Ensayo de Unidades Formadoras de Colonias , Cartilla de ADN/genética , Ensayo de Inmunoadsorción Enzimática , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Mucoproteínas , Invasividad Neoplásica/fisiopatología , Proteínas Oncogénicas , Pronóstico , Interferencia de ARN , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/farmacología , Vimentina/metabolismo
4.
J Periodontol ; 86(2): 301-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25272982

RESUMEN

BACKGROUND: Interleukin (IL)-35 plays an important role in immune regulation through the suppression of effector T-cell populations, including T-helper 17 (Th17) cells. Although Th17 cells and IL-17 are involved in the pathogenesis of periodontitis, the level of IL-35 in inflamed periodontal tissues is unclear. Here, IL-35, IL-17, and IL-27 production/expression in gingival crevicular fluid (GCF) and human gingival tissue were investigated. METHODS: GCF samples were collected from buccal (mesial, center, and distal) sites of teeth from patients with chronic periodontitis (CP) and healthy controls and were analyzed by enzyme-linked immunosorbent assay for IL-35 (periodontitis, n = 36; healthy, n = 30) and IL-17 (periodontitis, n = 16; healthy, n = 13). Gingival tissue, including sulcus/pocket epithelium and underlying connective tissue, was collected from an additional 10 healthy participants and 10 patients with CP and were analyzed by quantitative polymerase chain reaction (qPCR) for Epstein Barr virus-induced gene 3 (EBI3), IL12A, and IL17A. IL27p28 was also tested by qPCR. RESULTS: IL-35 and IL-17 were significantly higher in GCF from patients with periodontitis than healthy participants (P <0.01, P <0.05, respectively). In both healthy participants and those with periodontitis, positive correlations were found among IL-35 and probing depth and clinical attachment level (CAL) as well as between IL-17 and CAL. EBI3, IL12A (components of IL-35), and IL17A messenger RNA expression levels were significantly higher in inflamed gingival tissue than in healthy control tissues (P <0.05). IL27p28 was not detected in any sample, suggesting that IL-27 is not produced in large quantities in periodontal tissue. CONCLUSION: IL-35 and IL-17, but not IL-27, may play important roles in the pathogenesis of periodontitis.


Asunto(s)
Periodontitis Crónica/inmunología , Encía/inmunología , Interleucina-17/análisis , Interleucinas/análisis , Adulto , Anciano , Pérdida de Hueso Alveolar/inmunología , Tejido Conectivo/inmunología , Inserción Epitelial/inmunología , Femenino , Líquido del Surco Gingival/inmunología , Humanos , Subunidad p35 de la Interleucina-12/análisis , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , Pérdida de la Inserción Periodontal/inmunología , Índice Periodontal , Bolsa Periodontal/inmunología , Subunidades de Proteína/análisis , Células Th17/inmunología
5.
Virchows Arch ; 465(3): 265-73, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24990300

RESUMEN

A thickened, enhanced cyst wall on imaging examinations is one of the "worrisome features" described in the consensus guidelines for management of intraductal papillary mucinous neoplasm of the pancreas (IPMN). Podoplanin (PDPN) expression by cancer-associated fibroblasts is known to be an indicator of poor prognosis in some types of cancer. We performed immunohistochemical staining for alpha-smooth muscle actin (α-SMA) in IPMN lesions and determined the pathological wall thickness by measuring the thinnest and thickest α-SMA-positive parts of the wall of the largest cyst in each case, and the mean of these two values was recorded as the wall thickness. The thickness of the pathological wall increased with progression from IPMN with low-grade dysplasia to IPMN with an invasive carcinoma. The pathological wall was thicker in IPMN with main duct involvement, nongastric-type IPMN, and IPMN with mural nodules. We also stained for PDPN and assessed the thickness of cyst wall staining as for α-SMA. The thickness of the PDPN-positive cyst wall varied in a pattern similar to the thickness of the α-SMA-positive pathological cyst wall. PDPN-positive stromal fibroblasts in the invasive component of IPMN-IC were evaluated as a ratio to α-SMA-positive fibroblasts. A high ratio (>50 %) of PDPN-positive stromal fibroblasts was a predictor of poor outcome. PDPN expression in the cyst wall correlates with the progression of IPMN. PDPN may be a significant prognostic marker of IPMN-IC.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Carcinoma Ductal Pancreático/patología , Glicoproteínas de Membrana/análisis , Neoplasias Pancreáticas/patología , Actinas/análisis , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/mortalidad , Factor de Crecimiento Transformador beta1/análisis
6.
Histopathology ; 65(3): 389-97, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24931343

RESUMEN

AIMS: Of the recognized precursor lesions of pancreatic adenocarcinoma, pancreatic intraepithelial neoplasia (PanIN) is the most common form. However, little is known about the relationship between the grade of PanIN and prognosis for patients with invasive ductal carcinoma. METHODS AND RESULTS: In 124 patients with invasive ductal carcinoma, we examined the grade and number of PanIN lesions in all slides of resected pancreas. The prevalence rates of PanIN-1A, PanIN-1B, PanIN-2 and PanIN-3 were 86%, 84%, 57% and 30%, respectively. We allocated PanIN-2 and PanIN-3 cases into a PanIN-high group, and cases showing PanIN-1A, PanIN-1B or absence of PanIN into a PanIN-low group. In clinicopathological analysis, PanIN-high status was significantly correlated with the number of PanIN lesions (P < 0.0001). Disease-free and overall survival were statistically better in the PanIN-high group than in the PanIN-low group (P = 0.0005 and P = 0.0003). Univariate and multivariate analyses revealed that tumour size and PanIN-low status were statistically significant factors for a poorer prognosis (P = 0.042 and P = 0.007). CONCLUSIONS: In a pathological examination, it is important to evaluate the grade and number of PanINs in assessing the prognosis of pancreatic cancer.


Asunto(s)
Carcinoma in Situ/patología , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Anciano , Atrofia , Carcinoma Ductal Pancreático/secundario , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico
7.
Int J Oncol ; 45(1): 113-20, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24756180

RESUMEN

Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.


Asunto(s)
Miofibroblastos/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Peritoneales/secundario , Peritoneo/citología , Animales , Línea Celular Tumoral , Movimiento Celular , Células Cultivadas , Humanos , Ratones , Ratones Desnudos , Invasividad Neoplásica/patología , Neoplasias Experimentales , Neoplasias Peritoneales/patología , Peritoneo/patología
8.
Anticancer Res ; 34(1): 69-80, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24403446

RESUMEN

BACKGROUND/AIM: The prognosis for triple-negative breast cancer (TNBC) is poor. In the present study, we evaluated whether NOTCH4 receptor is a potential new therapeutic target for TNBC. MATERIALS AND METHODS: In vitro proliferation and invasiveness were evaluated in TNBC cells with or without small-interfering RNA (siRNA) for NOTCH4, and with or without NOTCH4 plasmid transfection. In vivo, MDA-MB-231 cells with or without NOTCH4 siRNA were subcutaneously implanted into the flank regions of mice. The frequency of nuclear translocation of NOTCH4 was assessed by immunohistochemistry in 21 TNBC samples and 46 non-TNBC samples. RESULTS: NOTCH4 inhibition in TNBC cells reduced proliferation and invasiveness, and NOTCH4 overexpression in TNBC cells increased proliferation and invasiveness. NOTCH4 inhibition reduced tumour volume and tumourigenicity of mouse xenografts. TNBC cells had a higher frequency of nuclear translocation of NOTCH4 than other cells. CONCLUSION: NOTCH4 is a new potential therapeutic target for triple-negative breast cancer.


Asunto(s)
Apoptosis , Proliferación Celular , Proteínas Proto-Oncogénicas/metabolismo , ARN Interferente Pequeño/genética , Receptores Notch/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Animales , Western Blotting , Adhesión Celular , Movimiento Celular , Femenino , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones SCID , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Notch4 , Receptores Notch/antagonistas & inhibidores , Receptores Notch/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo
9.
Pathol Res Pract ; 210(2): 118-22, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24476826

RESUMEN

We herein present a 71-year-old man who underwent pancreatoduodenectomy with the diagnosis of follicular pancreatitis. We could not completely deny malignancy by a preoperative imaging study. Endoscopic ultrasonography-guided fine needle aspiration biopsy demonstrated clusters of benign acinar cells and no proliferation of atypical lymphoid cells or rich plasma cells. Histologically, the prominent lymphoid follicle formation was seen in an ill-defined mass, 15 mm in size, in the pancreatic parenchyma. Duct-centered fibrotic rims were seen in the pancreatic ducts accompanied by mild fibrotic change between the follicles and obliterative phlebitis. No neoplastic epithelial cells were observed in the resected specimen, and infiltrating lymphocytes did not show any morphological atypia and monoclonal proliferation by immunohistochemical staining with B and T cell markers. In addition, we could exclude IgG4-related disease, because plasmacytic cells were rarely positive for IgG4. Although follicular pancreatitis is rare, this mass-forming inflammatory disease (pancreatitis) should be included in the preoperative differential diagnosis of pancreatic cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Pancreáticas/patología , Pancreatitis/patología , Anciano , Biopsia con Aguja Fina , Proliferación Celular , Diagnóstico Diferencial , Humanos , Japón , Linfocitos/metabolismo , Imagen por Resonancia Magnética , Masculino , Páncreas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Pancreatitis/metabolismo , Pancreatitis/cirugía , Células Plasmáticas/metabolismo , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Pancreáticas
10.
Cancer Sci ; 105(3): 272-80, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24438533

RESUMEN

Gallbladder cancer (GBC) is a particularly deadly type of cancer with a 5-year survival rate of only 10%. New effective therapeutic strategies are greatly needed. Recently, we have shown that Hedgehog (Hh) signaling is reactivated in various types of cancer and is a potential therapeutic target. However, little is known about the biological significance of Hh signaling in human GBC. In this study, we determined whether Hh signaling could be a therapeutic target in GBC. The Hh transcription factor Gli1 was detected in the nucleus of GBC cells but not in the nucleus of normal gallbladder cells. The expression levels of Sonic Hh (Shh) and Smoothened (Smo) in human GBC specimens (n = 37) were higher than those in normal gallbladder tissue. The addition of exogenous Shh ligand augmented the anchor-dependent and anchor-independent proliferation and invasiveness of GBC cells in vitro. In contrast, inhibiting the effector Smo decreased the anchor-dependent and anchor-independent proliferation. Furthermore, the suppression of Smo decreased GBC cell invasiveness through the inhibition of MMP-2 and MMP-9 expression and inhibited the epithelial-mesenchymal transition. In a xenograft model, tumor volume in Smo siRNA-transfected GBC cells was significantly lower than in control tumors. These results suggest that Hh signaling is elevated in GBC and may be involved in the acquisition of malignant phenotypes, and that Hh signaling may be a potential therapeutic target for GBC.


Asunto(s)
Neoplasias de la Vesícula Biliar/metabolismo , Proteínas Hedgehog/metabolismo , Receptores Acoplados a Proteínas G/genética , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal , Femenino , Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/terapia , Técnicas de Silenciamiento del Gen , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Trasplante de Neoplasias , ARN Interferente Pequeño/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptor Smoothened , Alcaloides de Veratrum/farmacología
11.
Breast Cancer ; 21(2): 198-201, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22718426

RESUMEN

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been a method of choice for treating breast cancer. Computed tomographic lymphography (CT-LG) provides a view of the sentinel lymph node (SLN) with the detailed lymphatic anatomy preoperatively, and the SLN is easily identified during SLNB. In this article, we examined the usefulness of CT-LG to predict the difficulty of SLNB with the dye method. METHODS: A total of 41 consecutive patients who underwent CT-LG were enrolled in this study. Each CT-LG image was reviewed by one of our co-authors. The images of lymph vessels (LVs) and SLNs were assorted into three categories: not visualized, poorly visualized, and well visualized. The time engaged in SLNB with the dye method was recorded in 30 patients. RESULTS: The time engaged in SLNB between two groups was compared: patients in whom both the SLN and LVs were well visualized (n = 16) and the remaining patients (n = 14). The former required a significantly shorter time than the latter (12.6 ± 4.1 vs. 17.6 ± 6.7 min, respectively; p = 0.025 by Mann-Whitney U test). CONCLUSIONS: Our study clearly demonstrates that the CT-LG findings of well-visualized LVs and SLNs predict the easy access to the stained LVs and SLNs. This information provides several advantages, including the fact that an easy SLNB case can be selected for a doctor with little experience in SLNB, and the volume of dye and/or length of massage can be changed for better identification of stained LVs and SLNs during SLNB.


Asunto(s)
Linfografía/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de la Mama/patología , Medios de Contraste , Femenino , Humanos , Yopamidol , Valor Predictivo de las Pruebas
12.
Mol Cancer ; 12(1): 168, 2013 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-24354864

RESUMEN

BACKGROUND: Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer. METHODS: Expression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+ CAFs and PDPN- CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs. RESULTS: PDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P = 0.0461), vascular invasion (P = 0.0101), tumor size ≥ 3 cm (P = 0.0038), histological grade (P = 0.0344), Union for International Cancer Control classification T stage (P = 0.029), and shorter survival time (P < 0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro. Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs (P < 0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor. CONCLUSIONS: PDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.


Asunto(s)
Carcinoma Ductal Pancreático/metabolismo , Fibroblastos/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Técnicas de Cocultivo , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Modelos de Riesgos Proporcionales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Tumorales Cultivadas
13.
Hum Pathol ; 44(8): 1487-98, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23465281

RESUMEN

Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanINs) are important premalignant lesions of pancreatic cancer. Ezrin is a member of the ezrin, radixin, and moesin protein family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton. We investigated the roles of ezrin during carcinogenesis in IPMN and invasive ductal carcinoma and examined whether ezrin was a prognostic factor. We examined ezrin and phosphorylated ezrin (p-ezrin) expression in 131 IPMNs, 47 PanINs, and 59 invasive ductal carcinomas by immunohistochemical staining. Ezrin and p-ezrin (tyr354) expressions were significantly higher in IPMN with an associated invasive carcinoma, compared with those in IPMN with high-grade dysplasia (P = .03 and P = .0007, respectively). In all grades of PanINs, ezrin and p-ezrin (tyr353) were highly expressed. In patients with invasive ductal carcinoma, the presence of PanIN-2 or PanIN-3 was significantly correlated with positive ezrin and p-ezrin (tyr353) expression of the invasive ductal carcinoma component (P = .01 and P = .0004). The negative p-ezrin (tyr353) expression group of invasive ductal carcinoma showed a significantly worse prognosis than did the positive p-ezrin (tyr353) expression group by survival analysis (P = .04) and was a statistically significant adverse prognostic factor by both univariate and multivariate analyses (P = .048 and P = .015). Ezrin phosphorylation sites differ between the developments of IPMN and PanIN. Although p-ezrin (tyr354) expression in IPMNs is associated with tumor invasion, p-ezrin (tyr353) expression in invasive ductal carcinoma plays an important role not in tumor invasion and metastasis but in the early development of PanINs.


Asunto(s)
Adenocarcinoma Mucinoso/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Papilar/metabolismo , Proteínas del Citoesqueleto/biosíntesis , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Biomarcadores de Tumor/análisis , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Proteínas del Citoesqueleto/análisis , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Fosforilación
14.
Biomaterials ; 31(7): 1546-57, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19962757

RESUMEN

In this study, we tested the potential of UV-photofunctionalized titanium surfaces to overcome compromised bone-titanium integration in a gap healing model. Titanium in rod and disk forms was acid etched and then stored for 4 weeks under dark ambient conditions. Titanium rods with and without UV pretreatment were placed into a rat femur with (contact healing) or without (gap healing) contact with the innate cortical bone. The titanium implants were subjected to a biomechanical push-in test, micro-CT bone morphometry, and surface elemental analysis after 2 weeks of healing. The strength of bone-titanium integration in the gap healing model was one-third of that in the contact healing model. However, UV-treated implants in the gap healing condition produced a strength of bone-titanium integration equivalent to that of untreated implants in the contact healing condition. Bone volume around UV-treated implants was 2- to 3-fold greater than that around the untreated implants in the gap healing model. A bone generation profile drawn along the long axis of the implant exhibited greater contrast between the untreated and UV-treated surfaces in the cortical area than in the bone marrow area. The bone tissue formed on UV-treated implants showed a higher Ca/P ratio than that formed on untreated titanium. The rate of cell proliferation, alkaline phosphatase activity, and calcium deposition in femoral periosteal cells and in bone marrow-derived osteoblasts were greater in cultures on UV-treated titanium disks than in cultures on untreated disks. The UV-enhanced function in periosteal cells was more pronounced when they were co-cultured with bone marrow-derived osteoblasts, indicating a synergistic effect of UV-treated titanium with biological signals from bone marrow-derived osteoblasts. Within the limitation of the model used in this study, UV-photofunctionalized titanium surfaces may overcome the challenging condition of bone-titanium integration without cortical bone support. UV treatment of implants induced marked improvements in the behavior of bone formation and quantity and quality of bone tissue around the implants. These effects may be related to the promoted function of both periosteum- and bone marrow-derived osteogenic cells at the local level around UV-treated titanium surfaces.


Asunto(s)
Huesos/efectos de los fármacos , Huesos/patología , Oseointegración/efectos de los fármacos , Titanio/farmacología , Titanio/efectos de la radiación , Rayos Ultravioleta , Cicatrización de Heridas/efectos de los fármacos , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Células de la Médula Ósea/citología , Proliferación Celular/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/patología , Modelos Animales , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Periostio/citología , Prótesis e Implantes , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie/efectos de los fármacos
15.
Dent Mater ; 26(4): 275-87, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20006380

RESUMEN

OBJECTIVE: There is a great demand for dental implant surfaces to accelerate the process of peri-implant bone generation to reduce its healing time and enable early loading. To this end, an inverse correlation between the proliferation and functional maturation (differentiation) in osteoblasts presents a challenge for the rapid generation of greater amounts of bone. For instance, osteoblasts exhibit faster differentiation but slower proliferation on micro-roughened titanium surfaces. Using a unique micro-nano-hierarchical topography of TiO(2) that mimics biomineralized matrices, this study demonstrates that this challenge can be overcome without the use of biological agents. METHODS: Titanium disks of grade 2 commercially pure titanium were prepared by machining (smooth surface). To create a microtexture with peaks and valleys (micropit surface), titanium disks were acid-etched. To create 200-nm TiO(2) nanonodules within the micropits (nanonodule-in-micropit surface), TiO(2) was sputter-deposited onto the acid-etched surface. Rat bone marrow-derived osteoblasts and NIH3T3 fibroblasts were cultured on machined smooth, micropit, and nanonodule-in-micropit surfaces. RESULTS: Despite the substantially increased surface roughness, the addition of 200-nm nanonodules to micropits increased osteoblast proliferation while enhancing their functional differentiation. In contrast, this nanonodule-in-micropit surface decreased proliferation and function in fibroblasts. SIGNIFICANCE: The data suggest the establishment of cell-selectively functionalized nano-in-micro smart titanium surfaces that involve a regulatory effect on osteoblast proliferation, abrogating the inhibitory mechanism on the micropitted surface, while enhancing their functional differentiation. Biomimetic and controllable nature of this nanonodules-in-micropits surface may offer a novel micro-to-nanoscale hierarchical platform to biologically optimize nanofeatures of biomaterials. Particularly, this micro-nano-hybrid surface may be an effective approach to improve current dental implant surfaces for accelerated bone integration.


Asunto(s)
Materiales Biomiméticos/química , Adhesión Celular , Osteoblastos/citología , Osteoblastos/fisiología , Titanio/química , Células 3T3 , Grabado Ácido Dental , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Colágeno/biosíntesis , Fibroblastos/citología , Ratones , Nanoestructuras , Osteoblastos/metabolismo , Osteocalcina/biosíntesis , Osteopontina/biosíntesis , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie
16.
Dent Mater J ; 25(2): 205-13, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16916219

RESUMEN

Methyl methacrylate (MMA) is the main component of methyl methacrylic resin, which is widely used in dentistry. Previous studies have investigated whether MMA has any adverse effects on growth and gene expression in mouse fibroblast L929 cells. The present study was designed to further understand the effects of MMA by focusing on cDNA microarray data after L929 cells were exposed to MMA. MMA was found to inhibit cell growth and induce detoxification response genes in L929 cells. One of the most highly up-regulated genes was glutathione S-transferase, alpha 1 (Ya) (Gsta1), which has recently been shown to participate in Nrf2 regulation and is considered to be related to detoxification response. Molecular biological data obtained in the present study may therefore provide useful insights into the effects of MMA on living tissue.


Asunto(s)
Materiales Dentales/toxicidad , Inactivación Metabólica/genética , Metilmetacrilato/toxicidad , Animales , Aumento de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Activación Enzimática , Fibroblastos/efectos de los fármacos , Perfilación de la Expresión Génica , Glutatión Transferasa/biosíntesis , Glutatión Transferasa/genética , Concentración 50 Inhibidora , Isoenzimas/biosíntesis , Isoenzimas/genética , Células L , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Regulación hacia Arriba
18.
Gerodontology ; 21(2): 112-9, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15185992

RESUMEN

OBJECTIVE: To evaluate the masticatory performance of elderly people at the age of 80 years. SUBJECTS: A total of 283 individuals of 80 years of age took part in a general and dental health survey. MAIN OUTCOME MEASURES: A dental examination including the number of remaining teeth, occlusion, prostheses, bite force recording, and a questionnaire regarding masticatory performance were recorded. SETTING: Five municipalities (Okazaki city, Tokoname city, Tahara town, Atsumi town and Minami-chita town) in Aichi prefecture, Japan. RESULTS: There were 20 or more teeth in 7.4% subjects, and 44.5% were edentulous. Subjects with no occlusion accounted for 77.4% of the total. Subjects with prostheses accounted for 90.8%. Maximum bite force and masticatory ability score for patients with 20 or more teeth or not wearing prostheses were higher than other groups. The non-wearing prostheses group had a low masticatory ability score. CONCLUSION: Most of the 80-year-old individuals recovered their masticatory ability with the assistance of prostheses. Several individuals with 20 or more remaining teeth or without removable dentures present in both jaws had a high score for bite forces and masticatory abilities.


Asunto(s)
Masticación/fisiología , Pérdida de Diente/fisiopatología , Anciano , Anciano de 80 o más Años , Fuerza de la Mordida , Dentaduras , Femenino , Humanos , Registro de la Relación Maxilomandibular , Masculino , Estadísticas no Paramétricas , Encuestas y Cuestionarios
19.
Nihon Hotetsu Shika Gakkai Zasshi ; 48(5): 713-22, 2004 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-15818004

RESUMEN

PURPOSE: The purpose of this study was to determine the frequency of human papillomavirus(HPV)infections in the oral cavity of middle-aged and elderly dental patients with dentures. METHODS: In this study, 47 patients (20 men and 27 women), aged from 50 to 78 years, were randomly selected from the patients in the Department of Prosthodontics, Aichi-Gakuin University Affiliated Dental Hospital. Oral squamous cells were collected from swabs of the buccal mucosa. For this procedure, informed consent was obtained. Extracted DNA was evaluated for HPV infections by PCR methods, using consensus and specific primers, and direct DNA sequencing analysis. RESULTS: Twenty-four of 47 specimens (51.1%) were positive for HPV DNA. A statistically significant association was not found in the HPV positivity between men and women. The high rate of infection was recognized from 60 or more years old. A statistically significant association was found in the HPV positivity between non-denture wearers and denture wearers. Frequent HPV types in the specimens of all were HPV11, 4 and 16. Frequent HPV types in the specimens of non-denture wearers and denture wearers were HPV4, 11 and HPV11, 16 and 4, respectively. CONCLUSIONS: The results of the present investigation indicate that HPV is present in the oral cavity, especially those of denture wearers, of middle-aged and elderly patients. It is suggested, therefore, that the oral cavity of middle-aged and elderly patients with dentures is a reservoir of HPVs where later HPV-associated diseases, such as oral cancer and other oral lesions, may develop.

20.
Dent Mater J ; 21(1): 53-60, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12046522

RESUMEN

We examined the bactericidal and virucidal effectiveness of a denture cleaner that uses ozone (ozone concentration, 10 ppm) against methicillin-resistant Staphylococcus aureus (MRSA) and T1 phage, respectively. In the bactericidal activity test, with the ozone supply turned on, the number of bacteria was 3.1 x 10(3) CFU/mL at the beginning of the experiment, fell to 1.0 x 10(0) CFU/mL 10 min later, and was 1.0 x 10(0) CFU/mL or less afterwards. In contrast, when the ozone supply was cut off (air bubble only), the number of bacteria was 3.4 x 10(3) CFU/mL at the beginning of the experiment, and had fallen to 3.0 x 10(3) CFU/mL 60 min later (no statistically significant difference). In the virucidal activity test, the number of phages was 1.2 x 10(6) PFU/mL before ozone treatment, fell to about 1/10 of that number 10 min later, and was 6.1 x 10(0) PFU/mL 40 min later. These results indicate that the use of ozone in this denture cleaner is effective against MRSA and viruses.


Asunto(s)
Limpiadores de Dentadura/farmacología , Resistencia a la Meticilina , Oxidantes Fotoquímicos/farmacología , Ozono/farmacología , Staphylococcus aureus/efectos de los fármacos , Fagos T/efectos de los fármacos , Antibacterianos , Antiinfecciosos/farmacología , Antivirales/farmacología , Recuento de Colonia Microbiana , Diseño de Equipo , Humanos , Staphylococcus aureus/crecimiento & desarrollo , Estadística como Asunto , Fagos T/crecimiento & desarrollo
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