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BACKGROUND/AIM: The aim of this study was to elucidate the relationship between the progression of bladder cancer (BCa) and TLR4 expression. MATERIALS AND METHODS: The relationship between TLR4 expression and prognosis of BCa patients was analyzed using a publicly available database and immunohistochemical staining of clinical samples. The effect of TLR4 knockdown was also examined on the invasive capabilities of BCa cells. Finally, to investigate the biological function of TLR4, the gene expression profile of TLR4-depleted BCa cells was analyzed by microarray analysis. RESULTS: Expression of TLR4 was inversely associated with prognosis of patients with invasive BCa, and depletion of TLR4 significantly enhanced the invasive capability of BCa cells. Gene expression profiling revealed that depletion of TLR4 led to high expression of epithelial differentiation genes. Furthermore, expression of TLR4 was found to be extremely low in areas of squamous differentiation. CONCLUSION: Low TLR4 expression was correlated with tumor progression.
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Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptor Toll-Like 4/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Diferenciación Celular , Línea Celular Tumoral , Biología Computacional , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , ARN Interferente Pequeño/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. METHODS: We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. RESULTS: MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. CONCLUSIONS: These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscle-invasive BCa.
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Anilidas/farmacología , Regulación Neoplásica de la Expresión Génica , Factor de Crecimiento de Hepatocito/genética , Metaloproteinasa 1 de la Matriz/genética , Proteínas Proto-Oncogénicas c-met/genética , Piridinas/farmacología , Neoplasias de la Vejiga Urinaria/genética , Vejiga Urinaria/metabolismo , Western Blotting , Recuento de Células , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento de Hepatocito/biosíntesis , Humanos , Metaloproteinasa 1 de la Matriz/biosíntesis , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Análisis por Matrices de Proteínas , Proteínas Proto-Oncogénicas c-met/biosíntesis , ARN Neoplásico/genética , Proteínas Tirosina Quinasas Receptoras , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Castration-resistant prostate cancer (CRPC)-related deaths are increasing worldwide. Therefore, clarification of the mechanisms of hormone-related tumor progression and resistance to anti-androgen drugs is useful in order to develop strategies for appropriate treatment of CRPC. Galectin-3 has been shown to be correlated with tumor progression in a variety of cancer types through the regulation of tumor proliferation, angiogenesis, and apoptosis. MATERIALS AND METHODS: We examined tumor cell invasion and migration using the xCELLigence system. Control LNCaP and galectin-3-expressing LNCaP (LNCaP-Gal-3) cells were cultured with androgen-depleted medium with 5% charcoal-stripped serum. Cells were treated for 24 h with or without dihydrotestosterone alone or combined with MDV3100 and bicalutamide; gene profile was then analyzed by microarray analysis and mRNA expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated tumor growth using spheroids and xenograft tumor growth in a mouse model. RESULTS: In vitro, LNCaP-Gal-3 cells promoted both cell migration and invasion in an androgen-independent manner compared to control LNCaP cells. Galectin-3 also enhanced anchorage-independent growth and xenograft tumor growth even after castration. Importantly, galectin-3 greatly enhanced transcriptional activity of the androgen receptor (AR), especially on treatment with dihydrotestosterone. In microarray and qRT-PCR analyses, galectin-3 increased the expression of several AR-target genes, such as kallikrein-related peptidase 3 (KLK3), and transmembrane protease, serine 2 (TMPRSS2). These AR-target genes were not fully suppressed by anti-androgen drugs such as bicalutamide or MDV3100. Galectin-3 significantly inhibited the effect induced by anti-androgen drugs MDV3100 and bicalutamide, suggesting that galectin-3 may be involved in resistance to anti-androgen drug through enhancement of transcriptional activity of AR and expression of AR-related genes. CONCLUSION: These results suggest that galectin-3 is a potential target molecule for future treatment of anti-androgen drug-resistant prostate cancer.
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Antagonistas de Andrógenos/farmacología , Anilidas/farmacología , Antineoplásicos Hormonales/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Galectina 3/metabolismo , Nitrilos/farmacología , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Compuestos de Tosilo/farmacología , Animales , Benzamidas , Proteínas Sanguíneas , Línea Celular Tumoral , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Galectina 3/genética , Galectinas , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Análisis de Secuencia por Matrices de Oligonucleótidos , Feniltiohidantoína/farmacología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Transcripción Genética/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The flexible ureterorenoscope (URS) and associated devices have developed rapidly. However, despite its therapeutic benefits, URS may be associated with some complications. To the best of our knowledge, there are no studies discussing the complications of flexURS during the learning curve. METHODS: A retrospective review of the records of patients who underwent flexURS from January 2005 to June 2013 was performed. To compare the complications after the introduction of flexURS, patients were divided into four groups based on the surgeon's training experience, that is, based on the number of cases performed by the surgeon. A total of 219 cases underwent flexURS. Groups 1, 2, 3, and 4 included 35, 50, 50, and 84 cases, respectively. The complications were classified using the Clavien system (I-IV). RESULTS: The mean operation time and stone-free rate were significantly different (p < 0.001, p = 0.013, respectively). The total complication rates were 13.6, 10, 8.3, and 3.2%, respectively (p = 0.068). The more the surgeon's experience, the less was the complication rate. Despite our best efforts, the incidence of urosepsis was not reduced (p = 0.902). CONCLUSIONS: To reduce severe complications, it is necessary to have performed about 100 cases. Increased surgeon experience tended to decrease the risk of severe complications, but the incidence of urosepsis was not reduced.
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Cálculos Renales/cirugía , Cálculos Ureterales/cirugía , Ureteroscopios , Ureteroscopía/efectos adversos , Urología/educación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Curva de Aprendizaje , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Riesgo , Sepsis/prevención & control , Uréter/cirugía , Adulto JovenRESUMEN
We report a case of testicular malignant lymphoma in a hemodialysis patient. A 65-year-old man who had been undergoing hemodialysis for 8 years and 10 months consulted our hospital with right testicular enlargement in August 2012. Under a diagnosis of testicular cancer from manipulation test and ultrasonography, high orchiectomy was performed. Computed tomography showed swelling of the retroperitoneal lymph nodes. Histopathological examination revealed diffuse, non-Hodgkin B-cell lymphoma, CD20ï¼. R-CHOP chemotherapy was initiated and retroperitoneal lymph node swelling completely disappeared after 1 cycle of chemotherapy. After completing 2 cycles of chemotherapy, the patient developed interstitial pneumonia, and thus radiotherapy to the retroperitoneal space including the left testis was performed. As of July 2014, the patient remains alive without recurrence.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/terapia , Neoplasias Testiculares/terapia , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Glomerulonefritis por IGA/complicaciones , Humanos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Linfoma de Células B/complicaciones , Masculino , Orquiectomía , Prednisona/administración & dosificación , Prednisona/efectos adversos , Diálisis Renal , Rituximab , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/patología , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
OBJECTIVES: Mineralocorticoid receptor (MR) is known to play physiological and pathophysiological roles in the cardiovascular system, and MR activation directly damages these organs. The aim of this study was to evaluate the expression of MR and 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) in the human penile corpus cavernosum. METHODS: MR and 11ß-HSD2 expression was assayed in human penile tissues, and also in human renal tissues as a positive control. Expressions of MR mRNA and 11ß-HSD2 mRNA were evaluated using reverse transcription polymerase chain reaction (RT-PCR). MR and 11ß-HSD2 were visually identified using immunofluorescence analysis. RESULTS: MR mRNA expression in human penis was confirmed by RT-PCR. On quantitative RT-PCR analysis, 11ß-HSD2 mRNA expression was detected at minimal levels in penile tissue. Immunofluorescence analysis revealed positive staining for MR and negative staining for 11ß-HSD2 in smooth muscle cells of the corpus cavernosum. CONCLUSIONS: This study demonstrated the presence of MR and the absence of 11ß-HSD2 in human penile corpus cavernosum. Considering that MR activation causes various organ damages, MR blockade in human penile corpus cavernosum may have therapeutic benefits. Investigations for the penile effects of MR activation have the potential to provide new treatment approaches for erectile dysfunction.
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Pene/irrigación sanguínea , Receptores de Mineralocorticoides/fisiología , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , Adulto , Anciano , Disfunción Eréctil/tratamiento farmacológico , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Pene/química , ARN Mensajero/análisis , Receptores de Mineralocorticoides/análisis , Receptores de Mineralocorticoides/genéticaRESUMEN
A 61-year-old woman was referred to our department with a diagnosis of left solitary adrenal metastasis from cervical cancer in September 2011. She presented with postmenopausal bleeding in September 2010. The patient received seven courses of paclitaxel (175 mg/m2) and carboplatin (6 mg/GFRï¼25) for stage IV cervical cancer with paraaortic, bilateral common iliac, mediastinal lymph node metastases and left adrenal metastasis from October 2010 to April 2011. Paraaortic radiation (50.4 Gy) was subsequently administered from May 2011 to July 2011. Abdominal nonenhanced computed tomography (CT) revealed a left 26×21 mm adrenal mass with regular margins (attenuation values 53 HU). On enhanced CT, the mass showed heterogeneous enhancement. F fluoro-2-deoxy D-glucose (FDG) positron emission tomography/CT images showed moderately increased FDG-avid uptake in the left adrenal tumor which was high enough to be suspicious of malignant tumor (standardized uptake value max : SUVmax 6.8). There were no other foci of pathologic uptake of FDG in the whole body. The plasma endocrinological examinations was all normal. Left laparoscopic adrenalectomy was performed. The final pathologic evaluation revealed adrenal cortical adenoma.
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Neoplasias de la Corteza Suprarrenal/diagnóstico , Adenoma Corticosuprarrenal/diagnóstico , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Neoplasias del Cuello Uterino/patología , Neoplasias de la Corteza Suprarrenal/secundario , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , RadiofármacosRESUMEN
OBJECTIVES: To analyse the gene-expression level of claudin-7 in urothelial carcinoma (UC) of the urinary bladder, and its relationship with clinicopathological variables. MATERIALS AND METHODS: This study included 68 specimens of UC of the bladder, comprising 35 with non-muscle-invasive (NMI), stage Ta-T1, and 33 with muscle-invasive (MI) tumours, T2-T4, and 26 of normal urothelium (NU). Total RNA was extracted and 1 µg was reverse transcribed using a cDNA kit. RT-PCR was conducted using SYBR Green I dye to examine the expression levels of the target gene (claudin-7) and the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase. Using confocal-laser scanning light microscopy, immunohistochemistry (IHC) was used to validate the RT-PCR data. The correlation between claudin-7 and the clinicopathological variables was assessed. RESULTS: Claudin-7 was down-regulated in UC samples compared to NU samples (P < 0.001). NMI (Ta-T1) tumours had significantly higher claudin-7 expression than MI (⩾pT2) tumours (P = 0.012). There was no significant difference between patients with G1-2 tumours and those with G3 tumours (P = 0.19). There was no significant difference between patients with recurrent NMI UC and those with no recurrence (P = 0.61). IHC showed a lower expression of claudin-7 in the UC samples than NU samples, and in MI UC than in NMI UC. CONCLUSIONS: These results indicate that a reduced expression of claudin-7 correlates with the invasiveness and progression of UC of the urinary bladder. Further studies are needed to validate claudin-7 as a marker for UC.
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OBJECTIVE: To examine plakophilin proteins (Pkp) and 3 expression levels in bladder cancer, in particular their levels during cellular growth and invasion. Pkp is associated with the binding of cadherin to intermediate filaments of the cytoskeleton. METHODS: The relative mRNA and protein expression levels of Pkp2 and 3 in bladder cancer cell lines were determined using quantitative real-time polymerase chain reaction and Western blot analyses. The cellular localization of Pkp2 and 3 proteins in bladder cancer cells was also assayed using immunohistochemistry. The proliferation and invasive activities of bladder cancer cells were evaluated using cell growth and in vitro cell invasion assays, and were compared with those of bladder cancer cells treated with Pkp2 and 3 small interfering RNAs. RESULTS: Pkp2 mRNA and protein levels were elevated, and those of Pkp3 were reduced, in bladder cancer cells that are known to exhibit increased proliferation and invasive activity. Pkp2/3 protein expression was predominantly observed in the cytoplasm of invasive bladder cancer cells and tissues. Pkp2 knockdown inhibited, and Pkp3 knockdown enhanced, invasion of bladder cancer cells, but these knockdowns did not alter cell proliferation. CONCLUSION: We conclude that high Pkp2, and low Pkp3, expression is associated with bladder cancer cell invasion and that neither Pkp2 nor Pkp3 is associated with cell proliferation. We further hypothesize that accumulation of Pkp2 and 3 in the cell cytoplasm, rather than their recruitment to the cell membrane, is related to an increased ability of the tumor to invade and metastasize.
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Regulación Neoplásica de la Expresión Génica , Placofilinas/genética , Neoplasias de la Vejiga Urinaria/genética , Western Blotting , Línea Celular Tumoral/metabolismo , Proliferación Celular , Regulación hacia Abajo , Humanos , Inmunohistoquímica , Microscopía Fluorescente , Invasividad Neoplásica/genética , Placofilinas/metabolismo , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Regulación hacia Arriba , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Overexpression of galectin-3 in a variety of cancer cell lines has been shown to correlate with tumor progression and metastasis. In this study, we investigated the expression of galectin-3 in clear cell renal cell carcinoma (CC-RCC) and evaluated the relationship between galectin-3 expression levels and the clinicopathological features of CC-RCC. Expression of galectin-3 in the kidney cancer cell lines Caki-1, Caki-2, A704, ACHN and KPK-1 were evaluated using western blot analysis, while galectin-3 expression in CC-RCC tissues and normal parenchyma were measured by real-time PCR and immunohistochemistry. We found that galectin-3 was overexpressed in the Caki-1, Caki-2, A704, ACHN and KPK-1 cell lines and that the expression level in CC-RCC was also significantly higher than that in renal parenchyma obtained from the same patient samples (p=0.039). Galectin-3 expression in CC-RCC with distant metastasis was also significantly higher than that in CC-RCC without distant metastasis (p=0.045). In conclusion, we revealed that galectin-3 is highly expressed in CC-RCC, especially in CC-RCC with distant metastasis, suggesting that galectin-3 may serve as a novel target molecule for predicting CC-RCC metastasis.
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Carcinoma de Células Renales/química , Galectina 3/análisis , Neoplasias Renales/química , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Femenino , Galectina 3/genética , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , PronósticoRESUMEN
Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection.
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Adenocarcinoma/patología , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias Endometriales/patología , Laparoscopía , Femenino , Humanos , Persona de Mediana Edad , Sobrevivientes , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To examine actinin-4 expression levels in bladder cancer, in particular its levels during cellular growth and invasion. Actinin-4 is an actin-binding protein that is associated with cell motility and cancer metastasis. METHODS: Relative messenger ribonucleic acid (mRNA) and protein expression of actinin-4 in normal bladder and bladder cancer cell lines was determined by quantitative real-time polymerase chain reaction and Western blot analysis. Actinin-4 expression was also localized in bladder cancer cells and tissues using immunohistochemistry. The growth and invasion activity of bladder cancer cells was evaluated using cell growth and in vitro cell invasion assays, and compared with that of bladder cancer cells treated with actinin-4 small interfering ribonucleic acids. RESULTS: Actinin-4 mRNA and protein levels were elevated in bladder cancer cells that are known to exhibit increased growth and invasion activity. Protein expression was predominantly observed in the cytoplasm of the invasive bladder cancer cells and tissues. Treatment of bladder cancer cell lines with actinin-4 small interfering ribonucleic acids suppressed the invasive potential of the cells, but did not alter their growth. CONCLUSIONS: The current study demonstrates that actinin-4 mRNA and protein levels are elevated in bladder cancer cells lines that exhibit increased growth and invasion activity. In addition, actinin-4 knockdown inhibited invasion of bladder cancer cells, but did not alter their growth. In conclusion, we hypothesize that the accumulation of actinin-4 in the cell cytoplasm is related to an increased susceptibility of tumor invasion and metastasis.
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Actinina/fisiología , Neoplasias de la Vejiga Urinaria/patología , Actinina/análisis , Actinina/biosíntesis , Actinina/genética , Proliferación Celular , Humanos , Invasividad Neoplásica , ARN Mensajero/análisis , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
A 40-year-old woman was referred to our hospital because of pain extending from the left lateral abdomen to the left inferior limb. The abdominal computed tomography (CT) revealed an 8x7x12 cm retroperitoneal serous cystic mass. The serum carcinoembryogenic antigen (CEA) level was slightly elevated to 2.7 ng/ml. Therefore, we suspected it to be malignant, and we performed laparoscopic resection carefully. The retroperitoneal cyst was not adherent to the surrounding tissues and was easily dissected and removed under laparoscopy. Carbohydrale antigen (CA)19-9, CA125 and CEA levels in the fluid were elevated, but a cytology of the fluid was negative and no malignant sign was seen in the cyst wall. To our knowledge, this is the second reported case of retroperitoneal serous cyst resected by laparoscopic surgery in the Japanese literature.
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Quistes/cirugía , Laparoscopía , Adulto , Antígenos de Carbohidratos Asociados a Tumores/sangre , Antígeno Carcinoembrionario/sangre , Quistes/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Espacio RetroperitonealRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors are major regulators of cancer cell growth and metastases. We investigated the association between serum VEGF levels and clinicopathological parameters in bladder cancer patients. We also evaluated the effects of VEGF and its receptor inhibitor on proliferation and invasion in bladder cancer cell lines. METHODS: Serum VEGF levels were measured in 52 patients with bladder cancer and 45 healthy controls. In highly invasive bladder cancer cell lines (T-24, UMUC-3 and J82), we assessed the effect of VEGF on proliferation and invasion of bladder cancer cell lines. The effect of VEGF receptor (VEGFR) tyrosine kinase inhibitor against bladder cancer cell lines was also measured. RESULTS: Serum levels of VEGF were significantly higher in patients with muscular invasive bladder cancer than in patients with superficial bladder cancer (p < 0.005). VEGF increased tumor proliferation in a dose-dependent manner in all cell lines. VEGFR-2 tyrosine kinase inhibitor inhibited proliferation in all three cell lines, and inhibited invasion in T24. CONCLUSIONS: In bladder cancer, the serum VEGF level correlates significantly with muscular invasiveness. This study suggests that VEGF promotes tumor proliferation and invasion through VEGFR-2. VEGF-targeted therapy may be effective in treating invasive bladder cancers.
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Carcinoma de Células Transicionales/patología , Proliferación Celular/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Neoplasias de la Vejiga Urinaria/patología , Factor A de Crecimiento Endotelial Vascular/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Carcinoma de Células Transicionales/sangre , Línea Celular Tumoral , Cinamatos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Vejiga Urinaria/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
Between January 1996 and December 2007, 111 patients with prostate cancer underwent radical prostatectomy, including 34 who received preoperative hormonal therapy. In this study, we reviewed 77 patients who did not undergo neoadjuvant hormonal therapy. The mean age was 65.5 years old and followup time was 40.7 months. The clinical stage was T1c in 60 patients, T2 in 16, and T3 in 1. Prostate specific antigen (PSA) at diagnosis ranged from 3.44 to 46.08 ng/ml (mean 10.18). At our institution, PSA failure after surgery was defined as PSA elevation above 0.2 ng/ml. The pathological stage was pT2 in 59 patients, pT3a in 11, pT3b in 7 and pN + (obturator lymph node) in none. The surgical margin was positive in 29.3% of the pT2 patients and 68.8% of the pT3 patients. Sixteen patients (20.8%) had PSA failure. PSA values at diagnosis and pathological T stage were significantly relevant to PSA failure. Patients with PSA failure underwent radiation therapy or hormonal therapy as a salvage adjuvant therapy. The PSA level was controlled well in majority of the patients. Only one patient died of cancer. In conclusion, 33 out of 111 patients who underwent radical prostatectomy had PSA failure. Sixteen of the 77 patients who were not given neoadjuvant therapy had PSA failure. The significant factors related to PSA failure were PSA values at diagnosis and pathological T stage.
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Biomarcadores de Tumor/sangre , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Terapia Recuperativa , Insuficiencia del TratamientoRESUMEN
With the development of extracorporeal shock wave lithotripsy (ESWL), improved endourologic instrumentation, and medical dissolution therapy, the need for open ureterolithotomy has become less common. Open operation is occasionally necessary when less invasive techniques fail. As in many of the surgical specialties, laparoscopy has become more common in urologic surgery. We recently experienced three cases of ureteral stones, which were treated by laparoscopic ureterolithotomy. The stones were all large and impacted stones. The patients were a 73-year-old man and two 34-year-old men. All procedures were performed by a retroperitoneal approach. We used Roticulator endo mini-shears resourcefully, when we incised the ureteral wall. After surgery, all three patients were stone-free, and hydronephrosis was improved.
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Laparoscopía , Cálculos Ureterales/cirugía , Adulto , Anciano , Humanos , Masculino , UréterRESUMEN
PURPOSE: We analyzed patterns of tumor distribution in radical prostatectomy specimens from patients with repeat biopsies to determine additional appropriate biopsy locations for repeat biopsy. METHODS: Between January 2000 and June 2005, a total of 382 patients underwent transrectal ultrasound-guided prostate biopsy. Of these, 47 patients underwent repeat biopsy. Radical prostatectomy was performed for 7 of 22 cancer-positive cases. The 7 specimens were superimposed to create an idealized prostate gland at 3 levels: apex, mid-prostate, and base. We compared these tumor maps with those from 35 initial biopsy positive patients. RESULTS: Prostate cancer was detected in 22 of 47 patients who underwent repeat biopsy. Tumor mapping showed that tumors detected on repeat biopsy in comparison with tumor maps of initial biopsy were dense at the periurethral area of the apex in prostate. CONCLUSIONS: Additional biopsy cores taken from periurethral area of the apex on repeat biopsy might further enhance the detection of cancers.
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Próstata/patología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Biopsia con Aguja , Predicción , Humanos , Masculino , Antígeno Prostático Específico/sangre , Prostatectomía , ReoperaciónRESUMEN
No adequate serum predictive biomarker currently exists, which can identify the activity of renal cell carcinoma (RCC). We investigate the association of serum hepatocyte growth factor (HGF) and serum vascular endothelial growth factor (VEGF) levels with clinicopathologic parameters in untreated clear cell RCC patients. We measured serum levels of HGF and VEGF in 45 patients with untreated clear cell RCC and 45 healthy controls using an enzyme-linked immunosorbent assay (ELISA). Patients with clear cell RCC had significantly higher serum HGF and VEGF concentrations than healthy subjects: median, 1070.7 versus 728.3 pg/ml (p<0.0001) for HGF; and median, 397.5 versus 245.6 pg/ml (p=0.0003) for VEGF. We found a significant correlation between serum level of HGF and clinical stage and tumor grade. Survival of patients with high serum HGF (>1150 pg/ml) was significantly reduced compared to patients with low serum HGF concentrations (p=0.0044). In patients with nuclear grade 2 or high stage RCC, the higher serum HGF group exhibited significantly lower cause-specific survival (p=0.0087 and p< 0.05, respectively). No significant difference was observed between serum VEGF levels and cause-specific survival rate. Serum HGF might be a diagnostic and prognostic indicator in clear cell RCC, especially for patients with grade 2 or high stage RCC.
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Biomarcadores de Tumor/sangre , Carcinoma de Células Renales/diagnóstico , Factor de Crecimiento de Hepatocito/sangre , Neoplasias Renales/diagnóstico , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
Tight junctions (TJs) are cell-cell adhesive structures that undergo continuous remodeling. We previously demonstrated that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) localized at TJs and mediated the endocytic recycling of the integral TJ protein occludin and the formation of functional TJs. Here, we investigated how JRAB/MICAL-L2 was targeted to TJs. Using a series of deletion mutants, we found the plasma membrane (PM)-targeting domain within JRAB/MICAL-L2. We then identified actinin-4, which was originally isolated as an actin-binding protein associated with cell motility and cancer invasion/metastasis, as a binding protein for the PM-targeting domain of JRAB/MICAL-L2, using a yeast two-hybrid system. Actinin-4 was colocalized with JRAB/MICAL-L2 at cell-cell junctions and linked JRAB/MICAL-L2 to F-actin. Although actinin-4 bound to JRAB/MICAL-L2 without Rab13, the actinin-4-JRAB/MICAL-L2 interaction was enhanced by Rab13 activation. Depletion of actinin-4 by using small interfering RNA inhibited the recruitment of occludin to TJs during the Ca(2+) switch. During the epithelial polarization after replating, JRAB/MICAL-L2 was recruited from the cytosol to cell-cell junctions. This JRAB/MICAL-L2 recruitment as well as the formation of functional TJs was delayed in actinin-4-depleted cells. These results indicate that actinin-4 is involved in recruiting JRAB/MICAL-L2 to cell-cell junctions and forming functional TJs.
Asunto(s)
Actinina/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas de Microfilamentos/metabolismo , Uniones Estrechas/metabolismo , Actinina/genética , Actinas/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Calcio/metabolismo , Línea Celular , Polaridad Celular , Cricetinae , Proteínas del Citoesqueleto/antagonistas & inhibidores , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/genética , Células Epiteliales/citología , Células Epiteliales/metabolismo , Vectores Genéticos , Uniones Intercelulares/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Proteínas de Microfilamentos/genética , Ocludina , Plásmidos/genética , Unión Proteica , Estructura Terciaria de Proteína , ARN Interferente Pequeño/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Eliminación de Secuencia , Transfección , Técnicas del Sistema de Dos Híbridos , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismoRESUMEN
Transverse testicular ectopia (TTE) is an extremely rare congenital anomaly in which both testes descend through the same inguinal canal. We report an 8-month-old male with TTE and hypospadias. To help manage the patient, we conducted laparoscopy to elucidate the anatomy of the spermatic cord of the ectopic testis. On laparoscopy, we clearly identified the spermatic cord of the right ectopic testis. In addition, the laparoscopic guide was helpful when doing the trans-septal orchidopexy, in that the ectopic testis could be precisely discriminated without confusion as to the laterality of the testes. Long-term follow-up at 32 months confirmed that both testes were properly positioned in the scrotum and had a good consistency.