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1.
Transl Oncol ; 10(6): 998-1007, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29096248

RESUMEN

Patients who undergo surgical extirpation of a primary liver carcinoma followed by radiotherapy and chemotherapy leading to complete remission are nevertheless known to develop cancerous metastases 3-10 years later. We retrospectively examined the blood sera collected over 8 years from 30 patients who developed bone metastases after the complete remission of liver cancer to identify serum proteins showing differential expression compared to patients without remission. We detected a novel RGD (Arg-Gly-Asp)-containing peptide derived from the C-terminal portion of fibrinogen in the sera of metastatic patients that appeared to control the EMT (epithelial-mesenchymal transition) of cancer cells, in a process associated with miR-199a-3p. The RGD peptide enhanced new blood vessel growth and increased vascular endothelial growth factor levels when introduced into fertilized chicken eggs. The purpose of this study was to enable early detection of metastatic cancer cells using the novel RGD peptide as a biomarker, and thereby develop new drugs for the treatment of metastatic cancer.

2.
Kurume Med J ; 62(1-2): 9-16, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26935441

RESUMEN

We investigated the influence of nocturia and sleep disturbance on health-related quality of life(HRQOL) using the Medical Outcomes Study 8-item Short Form Health Survey (SF-8) in patients with nocturia. We also assessed the effect of therapeutic intervention by means of an anticholinergic agent on the results of the SF-8. One hundred and eighty-four patients who voided at least once per night were surveyed using the SF-8, Overactive Bladder Symptom Score (OABSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). These parameters were also evaluated before and after 12 weeks of imidafenacin treatment in 51 patients with OAB accompanied by nocturia. The SF-8 physical component summary score (PCS) showed a significant decrease as nighttime voiding frequency increased. The mental health component summary score was 47.1 and 47.6 (which were lower than the standard value of 50) in the group with a nighttime frequency of once and ≥3/night, respectively. The SF-8 PCS and 6 subscales were negatively associated with nighttime voiding frequency, while the PSQI global score was positively associated with it. Imidafenacin significantly improved the OABSS, PSQI, and ESS, as well as the SF-8 score. This is the first study using the SF-8 to show that nocturia and sleep disturbance have a major influence on comprehensive HRQOL and that the SF-8 can be used to monitor HRQOL in OAB patients receiving treatment for nocturia.


Asunto(s)
Nocturia/psicología , Calidad de Vida , Trastornos del Sueño-Vigilia/psicología , Sueño , Encuestas y Cuestionarios , Vejiga Urinaria Hiperactiva/psicología , Vejiga Urinaria/fisiopatología , Anciano , Anciano de 80 o más Años , Antagonistas Colinérgicos/uso terapéutico , Femenino , Estado de Salud , Humanos , Imidazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Nocturia/diagnóstico , Nocturia/tratamiento farmacológico , Nocturia/fisiopatología , Valor Predictivo de las Pruebas , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria Hiperactiva/diagnóstico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/fisiopatología , Urodinámica
3.
Low Urin Tract Symptoms ; 8(1): 55-61, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26789544

RESUMEN

OBJECTIVES: To understand the mechanisms underlying ejaculation dysfunction caused by α1A-adrenocetor (AR) antagonists, the effects of α1A-AR antagonists on the contractile responses of the seminal vesicle were investigated. METHODS: Isolated seminal vesicles from guinea pigs were cannulated and pressurized, and the changes in the intraluminal pressure were recorded. Periodic applications of electrical stimulation (ES) caused biphasic increase in the intraluminal pressure, that is, initial and subsequent contractions. The effects of silodosin and tamsulosin, α1A-AR antagonists, on the contractile responses were examined. RESULTS: The ES-induced biphasic contractions were blocked by tetrodotoxin (TTX). Silodosin and tamsulosin suppressed the initial contractions in a dose-dependent manner, while also exerting various inhibitory effects on the subsequent contractions. Increases in the intraluminal pressure facilitated spontaneous phasic contractions. The spontaneous contractions were not affected by TTX or α1A-AR antagonists, but were abolished by nifedipine. CONCLUSIONS: The initial contractions triggered by neuronal excitations were suppressed by silodosin and tamsulosin, suggesting that the ejaculation dysfunction may be attributed to the α1A-AR antagonist-mediated suppression of nerve-evoked contractions in the seminal vesicle. The subsequent contractions may be induced by mechanical stimulation associated with the initial, nerve-evoked contractions. Alternatively, other transmitters may be involved to various degrees in the neuromuscular transmission of the seminal vesicle.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Indoles/farmacología , Contracción Muscular/efectos de los fármacos , Vesículas Seminales/efectos de los fármacos , Sulfonamidas/farmacología , Animales , Cobayas , Masculino , Tamsulosina
4.
Oncol Lett ; 10(2): 822-828, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26622577

RESUMEN

The present study aimed to examine the association between 18F-fluorodeoxyglucose (18F-FDG) uptake and cell proliferation markers; in addition, the correlation between 18F-FDG uptake and biological characteristic in patients with renal cell carcinoma (RCC) was investigated using dual-phase 18F-FDG-positron emission tomography/computed tomography (PET/CT). Dual-phase 18F-FDG PET/CT was performed on 31 RCC patients and the maximum standardized uptake values at 1 h (SUV1) and 2 h (SUV2) as well as the retention index (RI; %) in the primary tumors were calculated. Monoclonal antibodies for Ki-67, minichromosome maintenance 2 (MCM2) and topoisomerase II α (topo II α) were used to assess the expression levels of their respective proteins in excised tumor tissue using immunohistochemistry. The results demonstrated that RI and SUV2 in patients with Stage I/II + grade 1 (G1) RCC were significantly decreased compared with all patients with other stages/grades (RI, P=0.0065; SUV2, P=0.043); in addition, significantly increased uptake and RI were detected in patients with metastases compared with patients without metastases (SUV1, P=0.029; SUV2, P=0.0003; RI, P<0.001). All proliferation markers significantly correlated with RI (Ki-67, r=0.501, P=0.004; MCM2, r=0.359, P=0.047; topo II α, r=0.402, P=0.024), while SUV1 and SUV2 correlated with Ki-67 only. In conclusion, the results of the present study demonstrated that dual-phase 18F-FDG-PET/CT was more useful for predicting cell proliferation in RCC compared with single-phase imaging alone. However, follow-ups are required in order to determine whether dual-phase 18F-FDG-PET/CT provides independent prognostic information.

5.
Acta Histochem ; 117(6): 512-20, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25858530

RESUMEN

The aim of this study is to develop a novel experimental model of the subcutaneous transplantation of fetal urogenital sinus (UGS) into normal and castrated adult male rats for the pathophysiological investigation of the normal and developing prostate. Fetal UGS obtained from 20-day-old male rat embryos was subcutaneously transplanted into 7-week-old normal and castrated male rats. We observed the growth pattern, histopathological characteristics and immunohistochemical localization of cytokeratin 5 (CK 5), cytokeratin 8 (CK 8) and androgen receptor (AR) in the transplanted tissues. Almost all of the transplanted UGS organs gradually increased in weight over time in the non-castrated recipient animals, and the histopathological observations and immunohistochemical analysis of CK 5 and CK 8 revealed that the morphological changes in the tissues were in accordance with the features of normal prostate development. The histological characteristics included glandular epithelial dominant and stromal dominant area, with an increase in the glandular epithelial dominant areas over time and resemblance among a portion of the transplanted tissues within a certain period during the developmental course to the histopathology of human benign prostatic hyperplasia (BPH). The effects of androgens and resemblance in the immunohistochemical localization pattern changes in AR to that observed in the normal differentiating rat prostate were also noted. We conclude that the subcutaneous space provides an adequate microenvironment for UGS growth.


Asunto(s)
Sistema Urogenital/embriología , Animales , Femenino , Feto/metabolismo , Inmunohistoquímica , Masculino , Organogénesis/genética , Organogénesis/fisiología , Embarazo , Ratas , Ratas Sprague-Dawley
6.
Masui ; 64(1): 70-6, 2015 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-25868205

RESUMEN

BACKGROUND: Anesthetic management for cesarean section of patients with placenta previa accreta is challenging. The aim of this retrospective study was to review past placenta previa accreta cases in our hospital to propose a better strategy for anesthetic management for this difficult condition. METHODS: Cases of placenta previa accreta were identified in our anesthesia database. The diagnosis, surgical procedure, amount of blood loss and anesthetic management were reviewed. RESULTS: Eight cases of placenta previa accreta were identified. Four of the eight cases underwent stepwise treatment, and in one of the four cases, intra-aortic balloon occlusion (IABO) was performed. The amount of blood loss in the four cases ranged from 840 to 1,150 ml. The remaining four cases underwent cesarean hysterectomy. The amount of blood loss in the four cases ranged from 2,400 to 5,200 ml. Neuraxial anesthesia alone was planned in four cases, but in two of which anesthesia was converted to general anesthesia due to massive bleeding. CONCLUSIONS: The present retrospective study showed that stepwise treatment and using IABO could be an effective aid for management of plasenta previa accreta. It is necessary to compare the effectiveness of IABO with that of common iliac artery occlusion in reducing the amount of blood loss.


Asunto(s)
Anestesia Obstétrica/métodos , Anestésicos/uso terapéutico , Cesárea , Placenta Previa/cirugía , Adulto , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Histerectomía , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
7.
Int J Urol ; 21(7): 658-63, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24650159

RESUMEN

OBJECTIVE: To analyze clinical and dosimetric factors involved in prostate-specific antigen bounce in patients who underwent permanent implant brachytherapy for localized prostate cancer, and to study the relationships among prostate-specific antigen bounce, age and sexual function. METHODS: Between March 2007 and April 2012, 116 patients with localized prostate cancer underwent permanent implant, iodine-125 brachytherapy. Patients receiving external-beam radiotherapy or who used phosphodiesterase-5 inhibitor pre- or post-treatment were excluded. Prostate-specific antigen bounce was defined as an increase of ≥0.2 ng/mL and ≥0.4 ng/mL above an initial prostate-specific antigen nadir followed by a subsequent decline to or below the initial nadir without treatment. Clinical and dosimetric factors involved in prostate-specific antigen bounce were analyzed using multivariate logistic regression analysis with the forced entry method. RESULTS: The median age was 66 years (range 51-80 years), and prostate-specific antigen bounce on a prostate-specific antigen rise of ≥0.2 ng/mL occurred in 47 of the 116 participants (40.5%). The median period before the prostate-specific antigen bounce was 17.5 months (range 8-36 months). Patients with prostate-specific antigen bounce were younger and had higher sexual function before treatment (P = 0.003) than those who not show prostate-specific antigen bounce. Regression analysis results showed that young age and a high level of pretreatment sexual function were significant predictive factors for prostate-specific antigen bounce (P = 0.028 and P = 0.048). CONCLUSION: Sexual function seems to be associated with a prostate-specific antigen bounce in patients undergoing permanent implant brachytherapy for localized prostate cancer, and it can be preserved after treatment if it is well present before treatment. Highly maintained sexual function after treatment might influence prostate-specific antigen bounce.


Asunto(s)
Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Calicreínas/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/radioterapia , Conducta Sexual/fisiología , Disfunciones Sexuales Fisiológicas/sangre , Anciano , Anciano de 80 o más Años , Eyaculación/fisiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Valor Predictivo de las Pruebas , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Dosis de Radiación , Disfunciones Sexuales Fisiológicas/diagnóstico
8.
PLoS One ; 8(10): e75463, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24116047

RESUMEN

Cancer stem cells (CSC) or cancer stem cell-like cells (CSC-LCs) have been identified in many malignant tumors. CSCs are proposed to be related with drug resistance, tumor recurrence, and metastasis and are considered as a new target for cancer treatment; however, there are only a few reports on CSCs or CSC-LCs in renal cell carcinoma (RCC). Different approaches have been reported for CSC identification, but there are no universal markers for CSC. We used two different approaches, the traditional side population (SP) approach, and the enzymatic (aldehyde dehydrogenase 1 (ALDH1)) approach to identify CSC-LC population in two RCC cell lines, ACHN and KRC/Y. We found that ACHN and KRC/Y contain 1.4% and 1.7% SP cells, respectively. ACHN SP cells showed a higher sphere forming ability, drug resistance, and a slightly higher tumorigenic ability in NOD/SCID mice than Non-SP (NSP) cells, suggesting that cells with CSC-LC properties are included in ACHN SP cells. KRC/Y SP and NSP cells showed no difference in such properties. ALDH1 activity analysis revealed that ACHN SP cells expressed a higher level of activity than NSP cells (SP vs. NSP: 32.7% vs 14.6%). Analysis of ALDH1-positive ACHN cells revealed that they have a higher sphere forming ability, self-renewal ability, tumorigenicity and express higher mRNA levels of CSC-LC property-related genes (e.g., ABC transporter genes, self-replication genes, anti-apoptosis genes, and so forth) than ALDH1-negative cells. Drug treatment or exposure to hypoxic condition induced a 2- to 3-fold increase in number of ALDH1-positive cells. In conclusion, the results suggest that the ALDH1-positive cell population rather than SP cells show CSC-LC properties in a RCC cell line, ACHN.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Isoenzimas/metabolismo , Neoplasias Renales/metabolismo , Células Madre Neoplásicas/metabolismo , Retinal-Deshidrogenasa/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Isoenzimas/genética , Neoplasias Renales/genética , Neoplasias Renales/patología , Células Madre Neoplásicas/patología , Retinal-Deshidrogenasa/genética
9.
Oncol Lett ; 5(3): 793-796, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23426029

RESUMEN

Treating extended prostatic small cell neuroendocrine carcinoma (PSCNC) is extremely difficult and no standard treatment has yet been established. We experienced a case of advanced mixed-type PSCNC in which the patient achieved long-term survival and local control following combined therapy. Locally advanced PSCNC causing lower urinary obstruction was detected during androgen-ablation therapy for stage D2 mixed adenocarcinoma PSCNC. The patient was treated with intra-arterial infusion chemotherapy using a reservoir system and external-beam radiotherapy (EBRT) to the whole pelvis and local tumor. After chemoradiotherapy, the patient's lower urinary obstruction was reduced and did not return during the remaining 40 months of the patient's life. The patient survived for 70 months following the start of the androgen-ablation therapy. The present study reports a useful treatment for advanced mixed-type PSCNC, androgen-ablation therapy and chemoradiotherapy. The present results also suggest that the prognostic factors for advanced mixed-type PSCNC are the sensitivity of the conventional adenocarcinoma to androgen-ablation therapy, degree of metastasis and extent of the small cell neuroendocrine carcinoma component.

10.
Mol Clin Oncol ; 1(1): 112-116, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24649132

RESUMEN

In general, only ≤5% of patients with renal cell carcinoma (RCC) develop paraneoplastic erythropoietin (EPO) overproduction-induced polycythemia. However, a number of reports on EPO-producing RCC are available. The present study aimed to report the first case of a patient demonstrating a therapeutic effect on EPO-producing advanced RCC, subsequent to targeted pre-surgical sunitinib therapy, with a review of the literature. The patient involved was a 62-year-old male who presented with a malformation of the left scrotum. Examination revealed a tumor of 73 mm in diameter along with lymph node metastasis. The histological examination indicated a clear cell RCC containing viable cells as well as hemorrhage and necrosis. EPO in cancer cells was confirmed by immunohistochemistry. Subsequently, a case of EPO-producing RCC with polycythemia was diagnosed. The EPO-producing RCC was successfully treated following targeted presurgical therapy with sunitinib.

11.
Jpn J Radiol ; 30(6): 526-9, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22492471

RESUMEN

We describe a rare case of hematuria and hemospermia associated with pelvic arteriovenous malformation (AVM) in a male patient treated by transcatheter embolization. Understanding AVM hemodynamics contributes to the elucidation of its pathology and improves the outcome of embolization. In the present case, multiple arteriolar components shunted to the initial part of a single dominant outflow vein. Superselective embolization of a draining vein and feeding artery with an n-butyl cyanoacrylate/lipiodol mixture and polyvinyl alcohol particles was effective in terms of shunt disappearance and minimizing the need for subsequent arterial embolization.


Asunto(s)
Malformaciones Arteriovenosas/terapia , Embolización Terapéutica/métodos , Pelvis/irrigación sanguínea , Medios de Contraste , Humanos , Masculino , Pelvis/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
12.
Prostate ; 72(8): 834-45, 2012 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-21932426

RESUMEN

BACKGROUND: Docetaxel-based chemotherapy (DBC) showed limited clinical efficacy for castration-resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC-resistant CRPC patients. METHODS: Twenty DBC-resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC-resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV. RESULTS: Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC-resistant CRPC patients and patients with no prior DBC (log-rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC-resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL-6 levels before vaccination was an unfavorable factor for OS of DBC-resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001-0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068-0.661) by multivariable analysis. CONCLUSIONS: Further clinical study of PPV is recommended for DBC-resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL-6 by combined therapy may provide much better clinical outcome.


Asunto(s)
Antineoplásicos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Orquiectomía , Medicina de Precisión , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/inmunología , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Citocinas/sangre , Progresión de la Enfermedad , Docetaxel , Humanos , Inmunidad Humoral , Interleucina-6/sangre , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/mortalidad , Insuficiencia del Tratamiento , Resultado del Tratamiento
13.
Cancer ; 118(12): 3208-21, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-22071976

RESUMEN

BACKGROUND: Because only a subset of patients show clinical responses to peptide-based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment. METHODS: The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration-resistant prostate cancer patients, who survived for >900 days (long-term survivors, n = 20) or died within 300 days (short-term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray. RESULTS: There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short-term and long-term survivors. Among the 15 up-regulated genes in the short-term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%). CONCLUSIONS: These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines.


Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Perfilación de la Expresión Génica , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Granulocitos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Selección de Paciente , Pronóstico , Neoplasias de la Próstata/sangre
14.
J Infect Chemother ; 18(5): 753-5, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22203121

RESUMEN

Although many treatments have been applied to treat hormone-refractory prostate cancer (HRPC), therapeutic outcome is not altogether satisfactory. In the case of locally recurring HRPC, uncontrolled gross hematuria, dysuria, and scalding are often experienced. We report a patient who improved following intra-arterial infusion of cisplatin (CDDP) and ifosfamide (IFM) to treat urinary retention caused by locally recurring HRPC. After chemotherapy, cancer volume was remarkably reduced and symptoms improved.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Retención Urinaria/tratamiento farmacológico , Cisplatino/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/fisiopatología
15.
Auton Neurosci ; 164(1-2): 27-33, 2011 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-21684817

RESUMEN

We investigated the function and expression pattern of the transient receptor potential melastatin-8 (TRPM8) in urinary bladder afferent neurons from control and bladder outlet obstruction (BOO) rats. BOO was produced and, after six weeks, the effects of intravesical infusion of menthol, the agonist of TRPM8, were investigated using unanesthetized cystometry. The intravesical infusion of menthol produced an increase in the micturition pressure in both sham surgery and BOO rats. In BOO rats, increased basal and threshold pressure and a decreased micturition interval were observed. Next, the population of TRPM8-positive and the co-expression proportion of TRPM8 with neurochemical markers (NF200 or TRPV1) in the bladder afferent neurons were each compared between the control and BOO rats using retrograde tracing and immunohistochemistry. The population of TRPM8-immunoreactive bladder afferent neurons was larger in BOO rats (3.28±0.43%) than in the control rats (1.33±0.18%). However, there were no statistical differences between the control and BOO rats in the co-expression proportion of neither TRPM8-NF200 (84.1±4.3% vs 79.7±2.7%, p=0.41) nor TRPM8-TRPV1 (33.3±3.6% vs 40.8±2.6%, p=0.08) in the bladder afferent neurons. The present results suggest that the neuronal input through TRPM8-positive bladder afferent neurons are augmented after BOO, however, the neurochemical phenotype of the up-regulated TRPM8-positive bladder afferent neurons is not changed after BOO.


Asunto(s)
Células Receptoras Sensoriales/metabolismo , Canales Catiónicos TRPM/biosíntesis , Obstrucción del Cuello de la Vejiga Urinaria/metabolismo , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Vejiga Urinaria/inervación , Vejiga Urinaria/fisiología , Aferentes Viscerales/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Fenotipo , Ratas , Ratas Wistar , Células Receptoras Sensoriales/patología , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/fisiología , Regulación hacia Arriba/fisiología , Vejiga Urinaria/fisiopatología , Obstrucción del Cuello de la Vejiga Urinaria/patología , Aferentes Viscerales/patología , Aferentes Viscerales/fisiopatología
17.
Kurume Med J ; 58(3): 95-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22531125

RESUMEN

Since the introduction of targeted therapy, treatment of metastatic renal cell carcinoma (RCC) has undergone dramatic changes. Responses to targeted therapy within the primary tumor and metastatic lesions are novel findings not seen with immunotherapeutic-based strategies. We report here a case of T4 RCC in which cytoreductive nephrectomy became possible after a neoadjuvant targeted therapy using sunitinib. Our experience with the present case suggests that targeted therapy in the neoadjuvant setting may have a variety of potential applications. Further investigations should be encouraged.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Indoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Pirroles/uso terapéutico , Anciano , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/cirugía , Masculino , Terapia Neoadyuvante , Nefrectomía , Sunitinib , Resultado del Tratamiento
18.
Kurume Med J ; 57(3): 73-80, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21186342

RESUMEN

It is well known that the incidence of urinary stones is higher in men than women. Although it is believed that the lower incidence of urinary stones in women is due to a protective effect of estrogen, the mechanisms remain unclear. To clarify the relation between female sex hormones and stone matrix protein, we examined the interaction of estrogen receptor-α (ERα), estrogen receptor-related receptor-α (ERRα), and stone matrix protein osteopontin (OPN) in a rat hyperoxaluric model and in primary cultured rat kidney cells. Adult female Wistar rats were divided into 6 groups. Groups 1 and 4 consisted of normal females, Groups 2 and 5 consisted of ovariectomized females, and Groups 3 and 6 consisted of ovariectomized females receiving female sex hormone supplements. Groups 1-3 were administered distilled water, while groups 4-6 were administered 0.5% ethyleneglycol (EG). Moreover, rat kidney primary cultured cells were examined after treatment with female sex hormones under various conditions. The expressions of ERα, ERRα and OPN-mRNA in whole kidney and primary cultured cells were examined using Real-Time PCR. The expressions of OPN and ERRα-mRNA were suppressed by ovariectomy. Supplementation with female sex hormones increased the expression of OPN and ERRα-mRNA. In contrast, the expression of ERα-mRNA was increased by ovariectomy and suppressed by supplementation with female sex hormones. The results of the mRNA expression in primary cultured cells matched those in the hyperoxaluric model rats. Although the reason for the difference in expression between ERα and ERRα-mRNA is unclear, estrogen may regulates OPN expression through ERα and/or ERRα, either independently or in combination. Moreover, the decrease of OPN induced by removal of estrogen may increase urinary stones in postmenopausal women.


Asunto(s)
Receptor alfa de Estrógeno/genética , Hiperoxaluria/genética , Osteopontina/genética , Receptores de Estrógenos/genética , Animales , Células Cultivadas , Estradiol/análogos & derivados , Estradiol/farmacología , Femenino , Humanos , Hiperoxaluria/tratamiento farmacológico , Hiperoxaluria/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Ovariectomía , Progesterona/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptor Relacionado con Estrógeno ERRalfa
19.
Cancer Biol Ther ; 10(12): 1266-79, 2010 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-20935522

RESUMEN

To investigate immunological biomarkers to predict overall survival of advanced cancer patients under treatment with personalized peptide vaccination, correlations between overall survival and biomarkers, including cytotoxic T lymphocyte (CTL) and immunoglobulin G (IgG) responses to the vaccinated peptides, were investigated in 500 advanced cancer patients who received personalized peptide vaccination from October 2000 to October 2008. The best clinical response was assessed for in 436 patients, 43 patients (10%) had partial response, 144 patients (33%) had stable disease and 249 patients (57%) had progressive, with a median overall survival of 9.9 months. Both lymphocyte counts prior to the vaccination (P = 0.0095) and increased IgG response (P = 0.0116) to the vaccinated peptides, along with performance status (P < 0.0001), well correlated with overall survival. To confirm the superiority of IgG response to CTL response, the samples from advanced castration-resistant prostate cancer patients who survived more than 900 days (n=20) and those who died within 300 days (n=23) were analyzed further. As a result, both the numbers of peptides, to which increased IgG responses were observed, and the fold increases in IgG levels were significantly higher in long-term survivors (P = 0.000282 and P = 0.00045). In contrast, CTL responses were not statistically different between the two groups. Both lymphocyte numbers and IgG response were thus suggested to be biomarkers of cancer vaccine for advanced cancer patients.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Inmunoglobulina G/sangre , Neoplasias/mortalidad , Neoplasias/terapia , Linfocitos T Citotóxicos/inmunología , Adulto , Anciano , Antígenos de Superficie , Biomarcadores , Femenino , Humanos , Inmunoglobulina G/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Medicina de Precisión , Pronóstico , Antígeno Prostático Específico/inmunología , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Tasa de Supervivencia , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/uso terapéutico
20.
Endocr J ; 57(10): 873-80, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20733268

RESUMEN

Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in the first treatment cycle, and recovered spontaneously. Transient hyperthyroidism was observed during the second or third treatment cycles and was preceded by a rapid increase in thyroglobulin levels. (99m)Tc scintigraphy in the hyperthyroid state showed decreased thyroidal uptake of (99m)TcO(4)(-), suggesting destructive thyroiditis. Hypothyroidism subsequently developed, requiring levothyroxine replacement therapy. Ultrasonography showed a hypoechogenic pattern of the parenchyma and decreased intrathyroidal blood flow. The thyroid glands ultimately became atrophic, which may progress to permanent hypothyroidism. These findings suggest that sunitinib-induced hypothyroidism may occur frequently and may be a consequence of thyroiditis with transient thyrotoxicosis. The marked decrease in thyroid size due to reduced capillary blood flow induced by VEGF receptor inhibition may cause delayed and/or permanent hypothyroidism. Therefore, thyroid function should be monitored in all patients treated with sunitinib.


Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Hipotiroidismo/inducido químicamente , Indoles/efectos adversos , Pirroles/efectos adversos , Glándula Tiroides/efectos de los fármacos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Atrofia , Progresión de la Enfermedad , Femenino , Humanos , Hipertiroidismo/inducido químicamente , Hipertiroidismo/patología , Hipertiroidismo/fisiopatología , Hipotiroidismo/patología , Indoles/uso terapéutico , Japón , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/efectos de los fármacos , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirroles/uso terapéutico , Flujo Sanguíneo Regional/efectos de los fármacos , Sunitinib , Glándula Tiroides/irrigación sanguínea , Glándula Tiroides/patología , Tiroiditis/inducido químicamente , Tirotoxicosis/inducido químicamente , Tirotoxicosis/patología , Tirotoxicosis/fisiopatología
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