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1.
Sci Rep ; 9(1): 14245, 2019 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-31578391

RESUMEN

The possibility of p-wave pairing in superconductors has been proposed more than five decades ago, but has not yet been convincingly demonstrated. One difficulty is that some p-wave states are thermodynamically indistinguishable from s-wave, while others are very similar to d-wave states. Here we studied the self-field critical current of NdFeAs(O,F) thin films in order to extract absolute values of the London penetration depth, the superconducting energy gap, and the relative jump in specific heat at the superconducting transition temperature, and find that all the deduced physical parameters strongly indicate that NdFeAs(O,F) is a bulk p-wave superconductor. Further investigation revealed that single atomic layer FeSe also shows p-wave pairing. In an attempt to generalize these findings, we re-examined the whole inventory of superfluid density measurements in iron-based superconductors and show quite generally that single-band weak-coupling p-wave superconductivity is exhibited in iron-based superconductors.

2.
Lupus ; 28(1): 133-136, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30486727

RESUMEN

Toxoplasma is a common parasite worldwide that mainly affects the brain, lungs and eyes. Although toxoplasmic encephalitis is a lethal disease without treatment, past case reports show most patients with systemic lupus erythematosus who developed toxoplasmic encephalitis were misdiagnosed and treated as neuropsychiatric systemic lupus erythematosus, which led to unfavorable outcomes. We herein describe a case of disseminated toxoplasmosis affecting all the above organs with atypical symptoms, which developed with exacerbation of systemic lupus erythematosus. She had initially manifested with retinochoroiditis without vitritis, mild cognitive impairment and an isolated lung mass. These are completely different from the classic symptoms of toxoplasmosis that have been reported in patients with HIV infection and/or those after hematopoietic transplantation. Our case, together with previously reported cases, suggests the manifestation of toxoplasmosis that develops in systemic lupus erythematosus patients can be different from that seen in conventional cases and varies between individual patients. Our case highlights both the difficulty in and the importance of diagnosing toxoplasmosis in patients with systemic lupus erythematosus and provides helpful information to identify this rare, devastating, yet treatable disease.


Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Infecciones Oportunistas/complicaciones , Toxoplasmosis Cerebral/complicaciones , Toxoplasmosis Cerebral/diagnóstico , Adulto , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/diagnóstico por imagen , Vasculitis por Lupus del Sistema Nervioso Central/complicaciones , Imagen por Resonancia Magnética , Oftalmoscopios , Tomografía Computarizada por Rayos X
3.
Eur J Gynaecol Oncol ; 37(1): 117-21, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27048122

RESUMEN

INTRODUCTION: Malignant lymphoma of the female genital tract is quite rare and its presentation may resemble that of other, more common tumors, causing confusion for clinicians. CASE HISTORY: The authors report three patients with a non-Hodgkin lymphoma (NHL) involving the female genital tract: two cases involved the ovary and one involved the uterus. In all patients, the genital tract was the initial site of clinical presentation of a B cell lymphoma. One patient was diagnosed postoperatively and subsequently received chemotherapy; the other two patients were diagnosed by imaging-guided biopsy and were successfully managed by chemotherapy without resection surgery. Two patients were alive, without evidence of disease, and one patient was alive with disease at their most recent follow-up visit. CONCLUSION: The authors' experience emphasizes that lymphoma should be in the differential diagnosis of pelvic gynecological malignancies, and its clinical, biological, and radiological signs must be actively sought. Imaging-guided biopsy should be performed to avoid unnecessary surgery.


Asunto(s)
Neoplasias de los Genitales Femeninos/patología , Linfoma no Hodgkin/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad
4.
Br J Cancer ; 112(3): 547-55, 2015 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-25562433

RESUMEN

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.


Asunto(s)
Movimiento Celular , Liposarcoma Mixoide/patología , Macrófagos/patología , Animales , Células Cultivadas , Receptores ErbB/metabolismo , Factor de Crecimiento Similar a EGF de Unión a Heparina/metabolismo , Humanos , Ratones , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Células U937
5.
Eur J Gynaecol Oncol ; 35(4): 443-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25118489

RESUMEN

In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/terapia , Quimioradioterapia/efectos adversos , Leucemia Mieloide Aguda/etiología , Neoplasias Hepáticas/terapia , Síndromes Mielodisplásicos/etiología , Neoplasias Primarias Secundarias/etiología , Neoplasias Ováricas/terapia , Neoplasias de las Glándulas Suprarrenales/secundario , Anciano , Neoplasias Óseas/secundario , Carboplatino/administración & dosificación , Infarto Cerebral/etiología , Resultado Fatal , Femenino , Humanos , Neoplasias Hepáticas/secundario , Células Neoplásicas Circulantes , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación
6.
Clin Exp Obstet Gynecol ; 40(3): 377-80, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24283169

RESUMEN

In recent years, Shimane University Hospital has begun to see patients with pelvic inflammatory disease (PID) which has become severe and chronic after insufficient conservative treatment in primary or secondary medical care facilities. Serious chronic tubo-ovarian abscess (TOA) is complicated by intraperitoneal inflammatory adhesions to surrounding organs, so that it is difficult to determine the original anatomical position of organs at surgery. Forcible synechotomy can result in damage to the adhering organs and insufficient drainage after surgery can cause recurrence of inflammation. In order to increase the chances for a successful surgical treatment, careful preparation, such as preoperative administration of antibiotics and ureteral stent insertion are necessary. In addition, the chances for recurrence of inflammation can be lessened by thorough intraperitoneal irrigation and insertion of a drainage tube.


Asunto(s)
Absceso/cirugía , Enfermedades de las Trompas Uterinas/cirugía , Enfermedades del Ovario/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento
7.
Br J Cancer ; 108(4): 836-47, 2013 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-23462806

RESUMEN

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.


Asunto(s)
Neoplasias Óseas/metabolismo , Osteosarcoma/metabolismo , Proteína 1 de Unión a la Caja Y/metabolismo , Adolescente , Adulto , Animales , Neoplasias Óseas/mortalidad , Ciclo Celular/genética , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular , Niño , Ciclina A/metabolismo , Ciclina D1/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Osteosarcoma/mortalidad , Pronóstico , ARN Interferente Pequeño/farmacología , Proteína 1 de Unión a la Caja Y/antagonistas & inhibidores , Proteína 1 de Unión a la Caja Y/genética , Adulto Joven
8.
Br J Cancer ; 107(2): 300-7, 2012 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-22653145

RESUMEN

BACKGROUND: This study examined the clinical significance of NAC1 and the expression level of its potential downstream target fatty acid synthase (FASN) in ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a potential therapeutic target. METHODS: NAC1 and FASN expression and NACC1 gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridisation, and clinical data collected by a retrospective chart review. C75, a FASN inhibitor, was used to assess whether this pathway represented a therapeutic target in OCCC. RESULTS: High NAC1 expression was most frequent in clear cell tumours (40.0%:24/60). NACC1 gene amplification was identified in none of the 58 OCCCs. The frequency of NACC1 gene amplification was significantly higher in the high-grade serous histology than in the clear cell histology (P<0.01). NAC1 expression was significantly correlated with FASN expression in both OCCC samples and OCCC cell lines. Either high NAC1 expression or high FASN expression significantly correlated with shorter progression-free and overall survival (P=0.002 and 0.0048). NAC1 overexpression stimulated FASN expression, and NAC1 silencing using siRNA decreased FASN expression in OCCC cell lines. Profound growth inhibition was observed in C75-treated carcinoma cells with FASN overexpression when compared with the response in carcinoma cells without FASN expression. CONCLUSION: These findings indicate that NAC1/FASN overexpression is critical to the growth and survival of a subset of OCCC. The FASN silencing by the C75-induced phenotypes depends on the expression status of the targeted cell line. Therefore, NAC1/FASN pathway-targeted therapy may benefit selected OCCC patients.


Asunto(s)
Adenocarcinoma de Células Claras/metabolismo , Ácido Graso Sintasas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas Represoras/metabolismo , Adenocarcinoma de Células Claras/enzimología , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patología , Línea Celular Tumoral , Supervivencia sin Enfermedad , Ácido Graso Sintasas/antagonistas & inhibidores , Ácido Graso Sintasas/genética , Femenino , Amplificación de Genes , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Inmunohistoquímica , Terapia Molecular Dirigida , Proteínas de Neoplasias/genética , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Proteínas Represoras/genética , Estudios Retrospectivos , Transducción de Señal
9.
Br J Cancer ; 105(3): 420-7, 2011 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-21730982

RESUMEN

BACKGROUND: The aim of this study was to investigate the patterns of epidermal growth factor receptor (EGFR) overexpression, EGFR gene amplification, and the presence of activating mutations in the tyrosine kinase domain of this gene in squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas of the uterine cervix. METHODS: The EGFR expression, amplification, and mutation in cervical carcinomas were assessed by immunohistochemistry, fluorescence in situ hybridisation, and PCR-SSCP, respectively, and correlated with clinical data collected by a retrospective chart review. A functional assessment was performed by inactivating EGFR in cervical cancer cells with the potent inhibitor AG1478. RESULTS: Immunohistochemical analysis revealed that 6 out of 59 (10.2%) cervical squamous cell carcinomas showed significant amplification of the EGFR locus, whereas none of the 52 adeno/adenosquamous cell carcinomas had detectable EGFR amplification (P<0.05). The EGFR amplification significantly correlated with shorter overall survival (P=0.001) in cervical squamous cell carcinomas. Multivariate analysis showed that EGFR gene amplification was an independent prognostic factor for overall survival (P=0.011). None of the squamous cell carcinomas (0%: 0 out of 32) had detectable oncogenic mutations in EGFR exons 18 through 21. The frequencies of KRAS and BRAF mutations were very low in both squamous and adeno/adenosquamous cell carcinomas. Sensitivity of cervical cancer cells to AG1478 depended on the presence of EGFR overexpression. AG1478-induced EGFR inactivation in cell lines with EGFR overexpression significantly suppressed tumour development and progression in a mouse xenograft model. CONCLUSION: Our data suggest that EGFR signalling is important in a subset of cervical squamous cell carcinomas and that anti-EGFR therapy may benefit patients who carry the 7p11.2 amplicon in their tumours.


Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Amplificación de Genes , Genes erbB-1 , Mutación , Neoplasias del Cuello Uterino/genética , Adenocarcinoma/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinoma de Células Escamosas/mortalidad , Niño , Preescolar , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Femenino , Humanos , Ratones , Ratones Desnudos , Persona de Mediana Edad , Terapia Molecular Dirigida , Quinazolinas , Tirfostinos/farmacología , Regulación hacia Arriba , Neoplasias del Cuello Uterino/mortalidad
10.
Clin Exp Obstet Gynecol ; 38(1): 33-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21485722

RESUMEN

OBJECTIVE: To compare microwave endometrial ablation (MEA) using a new curved applicator with conventional surgical procedures in 26 patients with menorrhagia. STUDY DESIGN: Ten patients received MEA and 16 patients received conventional surgical procedures. Using a visual analog scale (VAS). MEA patients rated their menorrhagia, dysmenorrhea, and feelings of satisfaction from the procedure. The patients' intraoperative blood loss, operating time, and length of hospital stay were compared. RESULTS: Following MEA, the VAS scores were significantly decreased in the MEA patients for menorrhagia (p < 0.0001) and dysmenorrhea (p = 0.0002). The average VAS score regarding feelings of satisfaction for MEA was 8.9 (full score = 10). Mean blood loss, operating time, and mean length of hospital stay were significantly decreased in the MEA group compared to the conventional surgical procedure group (p < 0.0001). CONCLUSION: MEA successfully controlled menorrhagia and achieved a high rate of satisfaction among patients.


Asunto(s)
Técnicas de Ablación Endometrial/métodos , Menorragia/cirugía , Microondas/uso terapéutico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Dimensión del Dolor , Satisfacción del Paciente
11.
Eur J Gynaecol Oncol ; 31(5): 586-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21061810

RESUMEN

Exaggerated placental site is defined as a non-neoplastic trophoblastic lesion featuring exuberant infiltration into the endometrium and myometrium by intermediate trophoblasts and syncytiotrophoblasts. Exaggerated placental site can occur following normal or ectopic pregnancy, abortion, or hydatidiform mole. We encountered a case of reactive exaggerated placental site seven months following normal pregnancy that clinically mimicked placental site trophoblastic tumor. Few reports have described the clinical course, histopathology and differential diagnosis of exaggerated placental site; we present our patient's case together with histopathological observations and review of related literature.


Asunto(s)
Enfermedad Trofoblástica Gestacional/patología , Imagen por Resonancia Magnética , Tumor Trofoblástico Localizado en la Placenta/patología , Trofoblastos/patología , Enfermedades Uterinas/patología , Adulto , Gonadotropina Coriónica/sangre , Diagnóstico Diferencial , Femenino , Enfermedad Trofoblástica Gestacional/diagnóstico por imagen , Humanos , Embarazo , Tumor Trofoblástico Localizado en la Placenta/sangre , Tumor Trofoblástico Localizado en la Placenta/diagnóstico por imagen , Trofoblastos/diagnóstico por imagen , Ultrasonografía , Enfermedades Uterinas/sangre , Enfermedades Uterinas/diagnóstico por imagen
12.
Br J Cancer ; 103(3): 370-81, 2010 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-20606682

RESUMEN

BACKGROUND: Ewing's sarcoma family of tumours (ESFT) is a malignant small round-cell tumour of the bone and soft tissues. It is characterised by a strong tendency to invade and form metastases. The microenvironment of the bone marrow is a large repository for many growth factors, including the basic fibroblast growth factor (bFGF). However, the role of bFGF in the invasive and metastatic phenotype of ESFT has not been investigated. METHODS: The motility and invasion of ESFT cells were assessed by a wound-healing assay, chemotaxis assay, and invasion assay. The expression and activation of FGF receptors (FGFRs) in ESFT cell lines and clinical samples were detected by RT-PCR, western blotting, and immunohistochemistry. The morphology of ESFT cells was investigated by phase-contrast microscopy and fluorescence staining for actin. Activation of Rac1 was analysed by a pull-down assay. RESULTS: bFGF strongly induced the motility and invasion of ESFT cells. Furthermore, FGFR1 was found to be expressed and activated in clinical samples of ESFT. Basic FGF-induced cell motility was mediated through the FGFR1-phosphatidylinositol 3-kinase (PI3K)-Rac1 pathway. Conditioned medium from bone marrow stromal cells induced the motility of ESFT cells by activating bFGF/FGFR1 signalling. CONCLUSION: The bFGF-FGFR1-PI3K-Rac1 pathway in the bone microenvironment may have a significant role in the invasion and metastasis of ESFT.


Asunto(s)
Médula Ósea/fisiología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Invasividad Neoplásica , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Proteína de Unión al GTP rac1/genética , Médula Ósea/fisiopatología , Línea Celular Tumoral , Movimiento Celular/fisiología , Citoesqueleto/patología , Activación Enzimática , Factor de Crecimiento Epidérmico/farmacología , Humanos , Osteosarcoma/genética , Osteosarcoma/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Reacción en Cadena de la Polimerasa , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Proteínas Recombinantes/farmacología , Cicatrización de Heridas , Proteína de Unión al GTP rac1/metabolismo
13.
J Food Sci ; 75(1): E39-45, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20492164

RESUMEN

The influence of the feed liquid temperature of the spray drying was investigated on the particle morphology (vacuole size and shell thickness of hollow particle) and the stability of encapsulated d-limonene. The feed liquid was the mixture of d-limonene emulsified in a wall material of blending gum arabic (GA) and maltodextrin (MD) at the mass ratio of 1 : 2, and the liquid temperature was varied from 40 to 80 degrees C. The percentage of the hollow particle in the spray-dried powder was over 40% and slightly increased with the rising of the feed temperature. Hollow particles have shells of different thickness, which was estimated from the image with a confocal laser scanning microscope (CLSM). The shell thickness increased with the increase in the feed temperature. This finding was qualitatively supported by scanning electron microscopy (SEM) images of the fractured particles. In addition, release and oxidation stability of encapsulated d-limonene were measured at constant temperature and humidity. The powder at high temperature of feed has higher stability for release and oxidation of d-limonene than that at a lower feed temperature. The result may partly be attributed to the increase of the shell thickness of the particle at a higher feed temperature. The thicker shell wall possibly served as the barrier of the flavor release and the diffusion of oxygen and moisture from the surrounding environment.


Asunto(s)
Ciclohexenos/química , Terpenos/química , Anticarcinógenos/química , Cápsulas , Desecación/métodos , Estabilidad de Medicamentos , Emulsiones , Limoneno , Microscopía Confocal , Aceites , Tamaño de la Partícula , Polvos/química , Solubilidad , Propiedades de Superficie , Termodinámica
14.
J Eur Acad Dermatol Venereol ; 23(6): 668-72, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19250332

RESUMEN

We investigated the level of telomerase activity (TA) in 17 specimens of non-genital Bowen's disease (BD) and in 14 specimens of skin without sun exposure (non-exposed skin) using a non-isotopic PCR-based telomeric repeat amplification protocol (TRAP) assay. Expression of human telomerase reverse transcriptase (hTERT; the catalytic subunit of telomerase) was also evaluated by immunochemistry in the non-genital BD tissues. Moderate to high levels of TA were detected in 41.2% of 17 non-genital BD specimens (P = 0.001). In contrast, TA was not evident in non-exposed skin. Recently, nucleolin was reported to be associated with hTERT, so we used this antibody instead of hTERT antibody. Immunohistochemistry showed that nucleolin expression was associated with high TA levels in non-genital BD. Our results also revealed differences of TA levels among non-genital BD specimens. High levels of TA in those specimens were not age related. Five out of 7 specimens (71.4%) with moderate to high TA levels were from sun-exposed sites, while the remaining 10 specimens with low levels of TA were from non-exposed sites. These results suggested that cellular DNA damage caused by ultraviolet irradiation might be associated with an increase of TA in non-genital BD. Among non-genital BD specimens, 4 out of 17 (23.5%) showed high levels of TA (median relative TA value: 79.8%; P = 0.003), which might be associated with immortalization or transformation to invasive squamous cell carcinoma.


Asunto(s)
Enfermedad de Bowen/enzimología , Telomerasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
15.
Eur J Gynaecol Oncol ; 29(5): 518-22, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19051826

RESUMEN

BACKGROUND: Pleomorphic rhabdomyosarcoma (RMS) of gynecologic origin is an exceedingly rare, highly malignant tumor. Only a few cases have been reported in the last decades. CASE REPORT: A 60-year-old postmenopausal woman presented with a high LDH level of unknown origin. Ultimately, she was diagnosed with pleomorphic RMS. She underwent total hysterectomy, bilateral salpingo-oophorectomy, left pelvic and paraaortic lymphadenectomy and partial omentectomy. Surgery was followed by systemic chemotherapy and pelvic irradiation. Unfortunately, the patient did not respond to treatment. Her disease course correlated with the fluctuation of plasma LDH levels. Ultimately she died within 20 months of the diagnosis. CONCLUSION: It is important to have better insight and to set a standard multimodal treatment for adult RMS. In addition, plasma LDH levels can be considered as a prognostic marker for RMS, particularly in advanced stage.


Asunto(s)
L-Lactato Deshidrogenasa/sangre , Rabdomiosarcoma/patología , Neoplasias Uterinas/patología , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Rabdomiosarcoma/sangre , Rabdomiosarcoma/fisiopatología , Neoplasias Uterinas/sangre , Neoplasias Uterinas/fisiopatología
16.
Br J Cancer ; 99(12): 2020-8, 2008 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-19018267

RESUMEN

This study examined the status of KRAS and BRAF mutations, in relation to extracellular signal-regulated protein kinase (ERK) activation in 58 ovarian carcinomas to clarify the clinicopathological and prognostic significance of KRAS/BRAF mutations. Somatic mutations of either KRAS or BRAF were identified in 12 (20.6%) out of 58 ovarian carcinomas. The frequency of KRAS/BRAF mutations in conventional serous high-grade carcinomas (4.0% : 1/25) was significantly lower than that in the other histological type (32.3% : 10/31). Phosphorylated ERK1/2 (p-ERK1/2) expression was identified in 18 (38.2%) out of 45 ovarian carcinomas. KRAS/BRAF mutation was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage I, II (P<0.001), and p-ERK1/2 (P<0.001). No significant correlations between KRAS/BRAF mutations or p-ERK1/2 expression and overall survival were found in patients with ovarian carcinoma treated with platinum and taxane chemotherapy (P=0.2460, P=0.9339, respectively). Next, to clarify the roles of ERK1/2 activation in ovarian cancers harbouring KRAS or BRAF mutations, we inactivated ERK1/2 in ovarian cancer cells using CI-1040. Cl-1040 is a compound that selectively inhibits MAP kinase kinase (MEK), an upstream regulator of ERK1/2, and thus prevents ERK1/2 activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated cancer cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. This was evident in both in vitro and in vivo studies. The findings in this study indicate that an activated ERK1/2 pathway is critical to tumour growth and survival of ovarian cancers with KRAS or BRAF mutations. Furthermore, they suggest that the CI-1040-induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian cancers. Therefore, ovarian cancer patients with KRAS or BRAF mutations may benefit from CI-1040 treatment.


Asunto(s)
Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Animales , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular , Activación Enzimática , Femenino , Humanos , Ratones , Ratones Desnudos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación/genética , Neoplasias Ováricas/patología , Fosforilación , Pronóstico , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , Especificidad por Sustrato , Tasa de Supervivencia , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas ras/metabolismo
17.
Int J Gynecol Cancer ; 18(6): 1371-6, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18217963

RESUMEN

Alkylating agents have strong leukemogenic potential. There are a number of recent acute myeloid leukemia (t-AML) cases related to previous paclitaxel exposure. These leukemias tend to be of aggressive subtypes with long-latency periods. Unlike previously reported cases, the present case was of the secondary acute megakaryoblastic myeloid leukemia (AML M7) subtype. Additionally, it did not harbor a translocation in chromosome 19. A 73-year-old woman was diagnosed with t-AML M7 with antecedent myelodysplasia. Leukemia followed a second induction of paclitaxel- and carboplatin-based chemotherapy for recurrent ovarian cancer. Her second induction began 25 months after completion of her first course of chemotherapy. The increased incidence of postpaclitaxel leukemia suggests a probable role for paclitaxel as a leukemogenic agent. It highlights the importance of assessing for leukemia risk factors prior to beginning paclitaxel therapy.


Asunto(s)
Carboplatino/uso terapéutico , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Mieloide Aguda/complicaciones , Síndromes Mielodisplásicos/inducido químicamente , Síndromes Mielodisplásicos/complicaciones , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Femenino , Humanos , Cariotipificación , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/patología , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/patología
18.
Exp Clin Endocrinol Diabetes ; 115(7): 417-22, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17647137

RESUMEN

Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. While, although physical exercise is useful for improving insulin sensitivity, the effect of physical exercise on adiponectin and adiponectin receptors are still unclear. In present study, we investigated whether acute exercise affects the plasma adiponectin concentration and expression of adiponectin receptor in skeletal muscle and liver in healthy mice C57BL/6. Following an acute exercise, plasma glucose, insulin, FFA, and adiponectin were measured. The mRNA levels of AdipR1 and AdipoR2 were also analyzed. Although acute exercise did not significantly change plasma adiponectin concentration at 2 hours or 18 hours after the exercise compared with control group, the expression levels of AdipoR1 significantly increased in both skeletal muscle (2H: 1.2-fold, p=0.0423, 18H: 1.4-fold, p=0.0006) and liver (2H: 1.3-fold, p=0.0448) compared with control group. In contrast, the level of AdipoR2 mRNA was decreased in skeletal muscle (18H: 0.8-fold, p=0.027) and liver (2H: 0.9-fold, p=0.1551) compared with control group. Additionally, the transcription factor Foxo1 mRNA expression level was also significantly increased in skeletal muscle (2H: 10-fold, p=0.0001, 18H: 3-fold, p=0.0424) and liver (2H: 2-fold, p=0.002, 18H: 2-fold, p=0.0014) compared with control group by the acute exercise. These findings suggest that acute exercise affects the expression level of adiponectin receptors, and an increase of Foxo1 expression might be relative to regulate adiponectin receptors.


Asunto(s)
Regulación de la Expresión Génica , Condicionamiento Físico Animal/fisiología , Receptores de Superficie Celular/genética , Adiponectina/sangre , Animales , Análisis Químico de la Sangre , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Esfuerzo Físico/fisiología , Receptores de Adiponectina , Receptores de Superficie Celular/metabolismo
19.
Br J Cancer ; 90(6): 1204-10, 2004 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-15026802

RESUMEN

Ovarian tumours of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas. These tumours are often associated with a significantly better prognosis than ovarian carcinomas. However, a subset of these tumours can progress and become lethal. In order to seek sensitive diagnostic tools for monitoring patients after surgical operation, we performed a genome-wide scan for loss of heterozygosity (LOH) in 41 mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reportedly associated with ovarian carcinoma. In addition, we assessed whether clinicopathological parameters, microvessel density, Ki-67 labeling index, apoptotic index or p53 overexpression would be useful for predicting the postoperative outcome of LMP patients. Of the 116 markers examined, 19q12 and Xq11-12 showed significant correlation between postoperative progression-free survival time and LOH status (P<0.05). Patients with a high Ki-67 labeling index had a significantly poorer progression-free survival time than those with lower levels (P=0.042). Other clinicopathological factors and immunohistochemical analysis had no correlation with progression-free survival time in this series of patients. When the combination of LOH at 19q12 and/or Xq11-12 was assessed using Cox's regression analysis, patients with tumours that showed LOH at these positions were at greatest risk of progression (P=0.0073). These findings suggest that the identification of LOH at 19q12 and/or Xq11-12 in former mucinous LMP sites should alert the clinician to the presence of a potentially aggressive lesion in the coelomic epithelium, even if a distinction between second primary tumours or recurrence could not be determined.


Asunto(s)
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Cromosomas Humanos Par 19 , Cromosomas Humanos X , Marcadores Genéticos , Pérdida de Heterocigocidad , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Repeticiones de Microsatélite , Persona de Mediana Edad , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo
20.
J Clin Neurosci ; 9(6): 659-63, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12604278

RESUMEN

To determine the clinical significance of dynamic magnetic resonance imaging (MRI) for pituitary adenomas, we analyzed sequential enhancement patterns of pituitary adenomas and factors contributing to these sequential patterns. Dynamic MRI was performed in 67 patients with pituitary adenomas and compared to conventional imaging. Subjects were classified into four categories according to the sequential enhancement patterns of the adenomas. Factors supposed to correlate with enhancement pattern, such as secreting hormone, tumor size, microscopically examined vascularity and arterial involvement, and intraoperatively observed texture of the adenomas, were examined among the groups. Adenomas inclined to have late enhancement patterns were relatively small compared to those with early patterns. Tumors with very early enhancement patterns were significantly more fibrous than those with the other three patterns. The factors that contribute to sequential enhancement patterns remain unclear. None the less, scrutinizing the dynamic sequential pattern may provide useful information about the probable texture of the tumor.


Asunto(s)
Adenoma/patología , Neoplasias Hipofisarias/patología , Adolescente , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hipófisis/patología
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