RESUMO
In patients with prostate cancer (PCa), serum prostate-specific antigen (PSA) is a useful marker for evaluating the effects of androgen deprivation therapy (ADT). Intuitively, most urologists expect that a more rapid PSA decline in response to ADT would be positively associated with extended survival. Recently, we have reported that prolonged gradual serum PSA decline after ADT is strongly associated with favorable prognosis in PCa patients, however, the mechanism remains unknown. We investigated the role of fibroblasts in serum PSA decline after ADT. We performed in vitro experiments using androgen-sensitive, androgen receptor (AR)-positive prostate epithelial cell lines (LNCaP, 22Rv1, and RWPE-1 cells), commercially available prostate stromal cells (PrSC), and primary cultures of prostate fibroblasts (pcPrFs). In LNCaP and 22Rv1 cells, PSA production was increased by co-culture with fibroblasts under androgen-deprived conditions. In an in vivo model using LNCaP cells, serum PSA declined rapidly after ADT becoming undetectable within 14 days in mice inoculated with LNCaP cells alone. In contrast, when LNCaP cells were co-inoculated with fibroblasts, serum PSA levels were still high on 14 days post ADT and did not drop to undetectable levels until 21 days post ADT. Tumor volumes and Ki67 labeling indices were not altered between days 14 and 21 post ADT in mice inoculated with LNCaP cells; however, those in mice inoculated with LNCaP cells plus fibroblasts decreased gradually. PSA protein was detected in all tumors on 21 days post ADT by immunohistochemical staining. Microvessel densities were higher on 14 days post ADT for tumors from mice inoculated with LNCaP cells plus fibroblasts as compared with LNCaP cells alone. In summary, co-inoculation of fibroblasts with LNCaP cells prolonged serum PSA decline after ADT and enhanced the efficacy of ADT. Prolonged serum PSA decline may indicate the presence of protective fibroblasts that preserve the AR dependence of PCa cells, improving treatment efficacy.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Fibroblastos/fisiologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/etiologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/patologiaRESUMO
PURPOSE: To retrospectively evaluate the clinical outcomes of radiofrequency (RF) ablation for the treatment of unresectable adrenal metastasis. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and informed consent to perform adrenal RF ablation was obtained from all patients. From February 2005 through May 2014, 35 patients (25 men and 10 women; mean age, 64.7 years ± 9.6; age range, 39-82 years) underwent RF ablation to treat 41 metastatic adrenal tumors from lung cancer (n = 15), renal cell carcinoma (n = 9), colorectal cancer (n = 5), hepatocellular carcinoma (n = 4), and other tumors (n = 2). Tumors ranged in size from 1.2 to 8.2 cm (mean, 3.3 cm ± 1.6). The diagnosis was established mainly on the basis of radiologic findings. Adrenal arterial embolization was combined with RF ablation in 12 of the 35 patients (34%). Technical success, safety, local tumor progression, and survival were evaluated. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate prognostic factors. RESULTS: There were 48 completed sessions with planned procedures and treatment protocols with no mortality and a major complication rate of 8.3% (four of 48 sessions). Tumor enhancement disappeared after initial adrenal RF ablation in 33 of the 35 patients (94%). Local tumor progression developed in eight of the 35 patients (23%); two patients received repeated RF ablation, resulting in adrenal tumor control in 27 of the 35 patients (77%) at the last follow-up (mean, 30.1 months ± 27.5; range 1.2-96.8 months). The 1-, 3-, and 5-year overall survival rates were 75% (95% confidence interval [CI], 61%, 90%), 34% (95% CI: 17%, 52%), and 30% (95% CI: 13%, 48%), respectively, with a median survival time of 26.0 months. Existence of extra-adrenal tumors (P = .005) and age of 65 years or older (P = .04) were significant indicators of a poor prognosis. CONCLUSION: Adrenal RF ablation is a feasible and useful method for controlling adrenal metastases and offers patients opportunities for improved survival.
Assuntos
Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias das Glândulas Suprarrenais/cirurgia , Ablação por Cateter/métodos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Poor oral health is associated with an increased risk of dementia in the elderly. One possible pathway linking these two phenomena is lacunar infarction, a potential cause of dementia. An association between poor oral health and an increased risk of ischaemic stroke has been recognised through the oral infection-inflammation pathway. However, little is known about whether poor oral health is associated with the progression of lacunar infarction. OBJECTIVE: We examined the association between variables related to oral health and lacunar infarction, as detected by magnetic resonance imaging (MRI). METHODS: A total of 110 subjects (52 men, 58 women), aged 27-76 years, who visited our periodontology clinic participated in this study. The subjects underwent dental radiography, periodontal examinations and brain MRI. One experienced specialist in cardiovascular disease and one experienced neurosurgeon determined the number of lacunar infarctions on brain MRI. Periodontologists performed clinical periodontal examinations. Variables related to oral health were determined from the radiographs by an oral radiologist. Information on the subjects' lifestyles and disease histories were obtained using a structured questionnaire and confirmed by clinical records. Adjacent categories logit regression analysis with backward elimination was used to determine variables associated with three groups based on the number of lacunar infarctions. RESULTS: Of the 110 subjects, 61 had lacunar infarctions. Nineteen had multiple (≥7) lesions. Aging (p = 0.0004), increased time spent in physical activity per day (p = 0.042), the presence of hypertension (p = 0.006), the absence of hyperlipidaemia (p = 0.045), the presence of diabetes mellitus (p = 0.025) and low alveolar bone height (p = 0.026) were significantly associated with an increased number of lacunar infarctions in the final regression model. The significance of hyperlipidaemia and alveolar bone height disappeared in an unadjusted model. An increased pocket depth, which indicates current periodontal disease progression, tended to be associated with an increased number of lacunar infarctions (p = 0.058). This tendency did not disappear in an unadjusted model. CONCLUSION: Our results suggest that lacunar infarction may be associated with current periodontal disease in Japanese adults.
Assuntos
Saúde Bucal , Acidente Vascular Cerebral Lacunar/etiologia , Adulto , Fatores Etários , Idoso , Povo Asiático , Demência/etiologia , Complicações do Diabetes/etiologia , Feminino , Humanos , Hipertensão/complicações , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/complicações , Fatores de Risco , Acidente Vascular Cerebral Lacunar/diagnóstico , Acidente Vascular Cerebral Lacunar/epidemiologia , Perda de Dente/complicaçõesRESUMO
A 48-year-old married woman complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Flexible cystoscopy revealed many yellowish, nodular masses at the paries posterior of the urinary bladder, and cold-punch biopsy proved it to be amyloidosis. Serum amyloid protein A (SAA) was high, and suggested systemic amyloidosis. Renal biopsy and colon fiberscopy did not reveal any abnormalities. We therefore diagnosed a primary localized amyloidosis of the urinary bladder. Transurethral resection and dimethyl sulfoxide (DMSO) infusion therapy are used to treat amyloidosis of the urinary bladder. However there is no definite cure for amyloidosis of the urinary bladder. Therefore we selected DMSO occlusive dressing technique therapy. After 5 years of therapy, there was no evidence of a recurrence of amyloidosis.
Assuntos
Amiloidose/tratamento farmacológico , Dimetil Sulfóxido/administração & dosagem , Curativos Oclusivos , Doenças da Bexiga Urinária/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The purpose of this study was to evaluate the association between clinical manifestations of occlusal trauma of the teeth and maximum signal intensity of periodontal ligament space on MRI. METHODS: 20 subjects (males: 9, females: 11, mean age: 35.9 ± 14.0 years, range: 22-65 years) participated in this study. Subjective symptoms of bruxism, tooth mobility, fremitus, occlusal contact area, occlusal force, widening of the periodontal ligament space, and thickening of the lamina dura were defined as clinical manifestations of occlusal trauma. The total number of clinical manifestations was used to evaluate the degree of clinical occlusal trauma, with a score of 7 indicating the highest degree of occlusal trauma. The maximum signal intensity in the periodontal ligament space was evaluated by a specific T2 weighted MRI sequence: IDEAL image. RESULTS: Spearman's rank correlation between the total clinical occlusal trauma score and maximum signal intensity in the periodontal ligament space was 0.529 for all teeth, 0.517 for anterior teeth, and 0.396 for molar teeth (p < 0.001 for all). CONCLUSIONS: A significant correlation between the degree of occlusal trauma and the signal intensity of the periodontal ligament space suggests a new potential MRI-based method for objectively determining occlusal trauma.
Assuntos
Oclusão Dentária Traumática , Dente , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Ligamento Periodontal/diagnóstico por imagem , Ligamento Periodontal/patologia , Oclusão Dentária Traumática/complicações , Oclusão Dentária Traumática/diagnóstico por imagem , Força de Mordida , Imageamento por Ressonância MagnéticaRESUMO
The patient was a 74-year-old man. Computed tomography (CT) detected a right renal tumor with paraaortic lymph node swelling. Radical nephrectomy and left lymphadenectomy were performed in September 2008. Interferon-alpha (6 million international units three times per week) was administered as adjuvant therapy. Due to the development of side effects, including fatigue, the patient's immunotherapy was discontinued after 6 months. Radiofrequency ablation for pulmonary metastasis was performed 9 months after surgery. A nodular pedunculated tumor was detected on the posterior wall of the urinary bladder by CT, and transurethral resection was performed 18 months after nephrectomy/lymphadenectomy. Since the pathological diagnosis of the bladder tumor was clear cell carcinoma, that tumor was thought to have originated from the renal cell carcinoma. We have summarized 43 cases of bladder metastasis of renal cell carcinoma in Japanese patients, including ours.
Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias da Bexiga Urinária/secundário , Idoso , Carcinoma de Células Renais/terapia , Humanos , Excisão de Linfonodo , Masculino , Nefrectomia , Neoplasias da Bexiga Urinária/terapiaRESUMO
A 58-year-old man, received polypectomy to evaluate the polyp of sigmoid colon. Pathological examination of the specimen revealed non-invasive adenocarcinoma. Systemic work up including abdominal computed tomography (CT) demonstrated a bladder tumor 11 x 18 mm in diameter associated with left obturator lymph node swelling (16 x 14 mm). In the preoperative staging, this nodule was suspected to be lymph node metastasis, even though both cancers were diagnosed to be early stage. Transurethral resection of bladder tumor (TUR-Bt) and lymph node open biopsy were performed. The final diagnosis of bladder tumor was pTa, urothelial cancer grade 2 and low grade. The nodule had originated from the obturator nerve itself, and pathological diagnosis demonstrated benign schwannoma. To the best of our knowledge, this is the 14th report of benign schwannoma of the obturator nerve in Japan.
Assuntos
Metástase Linfática/patologia , Neoplasias Primárias Múltiplas/patologia , Neurilemoma/patologia , Nervo Obturador , Neoplasias do Sistema Nervoso Periférico/patologia , Neoplasias da Bexiga Urinária/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 33-year-old male complained of poor vision and visited the ophthalmology department of our hospital. Right iridoncus suspected as a metastatic nodule, was found. A systemic examination was done. Abdominal computed tomographic (CT) scan showed an enhanced mass in the right scrotum, 15 mm in diameter and enlargement of iliac lymph nodes. Chest CT scan demonstrated bilateral enlargement of mediastinal lymph nodes and enlargement of lymph nodes above the collarbone. Since malignant lymphoma or testicular malignancy was suspected, right orchiectomy was planned. A hard and nodular mass at the head of the epididymis, completely separated from the testis, was recognized. Only open biopsy was done, because no malignancy was found by the intraoperative biopsy. Pathological findings of the epididymal tissue revealed non-caseating epithelioid cell granulomas. Sarcoidosis was diagnosed based on pathological findings and systemic evaluations. Steroid ocular instillation therapy was started. To the best of our knowledge, this is the 18th report of epididymis sarcoidosis in Japan.
Assuntos
Epididimo , Doenças dos Genitais Masculinos/patologia , Sarcoidose/patologia , Adulto , Humanos , MasculinoRESUMO
An 11-year-old female consulted our department with complaints of urinary incontinence and pyuria. She had had a cloacal repair 7 years ago. The radiograph showed four stones in the pelvis. Magnetic resonance imaging showed two diverticula next to the urethra and several low intensity masses in one diverticulum were regarded as stones. Voiding cystourethrography showed normal urinary bladder contraction, although there were residual urine in the diverticula. Preoperatively, these stones were thought to be formed as a result of the long-standing residual urine. Cystourethroscopy showed that the two diverticula existed within the proximal area of the urethral sphincter and four white stones were found in them. Transurethral cystolithotripsy was performed and a surgical staple was found in the core of each stone. The surgical staples had been used for the cloacal repair and they had migrated into the bladder resulted in stone formation. To the best of our knowledge, this is the first report of bladder stones caused by the migration of surgical staples into the bladder after cloacal repair.
Assuntos
Cloaca/cirurgia , Migração de Corpo Estranho/complicações , Suturas , Cálculos da Bexiga Urinária/etiologia , Criança , Divertículo/complicações , Feminino , Humanos , Complicações Pós-Operatórias , Doenças Uretrais/complicaçõesRESUMO
A 47-year-old female presented to a clinic complaining of right back pain. A CT scan revealed a right retroperitoneal mass and she was referred to our department for further evaluation. Contrast-enhanced CT and MRI revealed a right retroperitoneal mass (6 cm) in the hilum of the right kidney that invaded the right renal vein and inferior vena cava (IVC). Suspecting a tumor arising from retroperitoneal tissues involving the right renal vein and IVC, the decision was made to excise the tumor with the right kidney, renal vein, and a portion of the IVC. The histologic findings indicated that the tumor was a leiomyosarcoma originating from the renal vein wall. The tumor cells were spindle-shaped and stained positive for desmin, caldesmon and HHF35. The post-operative course was uneventful and she was recurrence-free 20 months after surgery. In addition to presenting a case of a leiomyosarcoma of the renal vein, a short review of the literature is provided.
RESUMO
BACKGROUND: In nonmuscle invasive bladder cancer patients, prediction of pTa and pT1 bladder cancer recurrence and progression must be established. Micropapillary structures have been defined as small clusters of invasive cancer cells having features of the epithelial-mesenchymal transition. Since the stromal microenvironment helps to induce the epithelial-mesenchymal transition, interactions between cancer cells and stroma should be closely examined to predict the tumorigenic phenotype of human bladder cancer cells. MATERIALS AND METHODS: To investigate differences in the responsiveness of cancer cells to stroma, we combined 3 established human bladder cancer cell lines (high-grade T24 and UM-UC-3 cells, and low-grade papillary RT4 cells) with fetal rat mesenchyme. RESULTS: Among 3 bladder cancer cell lines, the expression profiles of p63 isoforms were distinct, i.e., p63γ in T24 cells, p63ß in UM-UC-3 cells, and p63α in RT4 cells. Tumors formed by T24 cells combined with fetal mesenchyme formed micropapillary-like structures, whereas those formed by T24 cells alone did not. T24 cells combined with fetal mesenchyme showed poor differentiation, e.g., innumerable chromatic atypia in the nuclei, higher levels of chromatic condensation, and increased nucleoli. In contrast, both UM-UC-3 and RT4 cells combined with fetal mesenchyme did not form micropapillary-like structures. Ki-67 and p63 labeling indices were significantly elevated by combining fetal mesenchyme with T24 cells but not with the others. CONCLUSIONS: By mixing cancer cells with fetal mesenchyme, our data demonstrated that formation of micropapillary-like structures may predict the tumorigenic phenotype of invasive bladder cancer cells. Taken together, distinct expression profiles of p63 isoforms may predict poor outcomes in invasive bladder cancer.
Assuntos
Carcinogênese , Carcinoma de Células de Transição/patologia , Transição Epitelial-Mesenquimal/fisiologia , Mesoderma , Neoplasias da Bexiga Urinária/patologia , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Técnicas de Cocultura , Feto , Humanos , Proteínas de Membrana/metabolismo , Fenótipo , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells. METHODS: The effects of combination treatment with DTX plus naftopidil were analyzed using two animal models of LNCaP cells plus PrSC xenografts (sub-renal capsule grafting) and PC-3 xenografts (intratibial injection). RESULTS: Combination treatment with DTX plus naftopidil significantly inhibited cell growth in LNCaP cells compared with DTX alone. Analysis of the cooperativity index (CI) showed that combination treatment exhibited additive effects on DTX-induced growth inhibition in LNCaP cells. In contrast, combination treatment showed more than an additive (synergistic) effect on DTX-induced apoptosis in LNCaP and PC-3 cells. In LNCaP cells plus PrSC xenografts, combination treatment showed synergistic effects on DTX-induced apoptosis. The synergistic effects of naftopidil on DTX-induced apoptosis were also observed in PC-3 xenografts. CONCLUSIONS: Our results demonstrated that additive naftopidil treatment in combination with DTX increased the efficacy of DTX for the treatment of LNCaP and PC-3 tumors in vivo. Thus, additive naftopidil treatment showed a synergistic effect on DTX-induced apoptosis in PCa cells in vitro and in vivo, suggesting that this treatment approach may yield improved clinical benefits compared with DTX alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Naftalenos/farmacologia , Piperazinas/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Taxoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Docetaxel , Sinergismo Farmacológico , Humanos , Masculino , Camundongos , Camundongos Nus , Naftalenos/administração & dosagem , Piperazinas/administração & dosagem , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Distribuição Aleatória , Taxoides/administração & dosagem , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Clinically, radiotherapy (RT) often leads to the development of prostate cancer (PCa) resistance because of protective responses in cancer cells. One of the mechanisms includes the upregulation of RT-induced antioxidant enzymes. Thus, combination therapy with RT and certain pharmaceutical drugs targeting antioxidant enzymes may be ideal for increasing the efficacy of RT with minimum side effects. Naftopidil is a subtype-selective α1D-adrenoceptor antagonist used for the treatment of benign prostatic hyperplasia (BPH). In our drug repositioning study, naftopidil showed not only unique growth-inhibitory effects but also AKT phosphorylation-inhibitory effects in PC-3 human PCa cells. Here, we examined the efficacy of additive naftopidil treatment in combination with RT in PC-3 cells. METHODS: The effects of combination therapy with RT plus naftopidil were analyzed using an animal model of PC-3 xenografts in BALB/c nude mice. The expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD) was evaluated by western blotting. RESULTS: Combination therapy with RT plus naftopidil induced a more efficacious delay in PC-3 xenograft tumor growth as compared with monotherapy with naftopidil or RT. In PC-3 tumors, combination therapy with RT plus naftopidil suppressed the upregulation of RT-induced MnSOD expression. In vitro, neither AKT inhibitor IV nor naftopidil directly altered MnSOD expression. Upregulation of RT-induced MnSOD expression was markedly suppressed by combination treatment with RT plus AKT inhibitor IV or naftopidil. CONCLUSIONS: These results suggest that additive naftopidil treatment in combination with RT may increase the efficacy of RT for the treatment of PCa.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Naftalenos/uso terapêutico , Piperazinas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Quimiorradioterapia , Terapia Combinada , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: The aim of this study was to clarify the changes, using magnetic resonance (MR) images, in the masseter muscles caused by low-level static contraction. STUDY DESIGN: Ten healthy male volunteers were enrolled in the study. The MR scans were performed before, immediately after, and 10 minutes after low-level static contraction. Two imaging sequences were acquired: a diffusion-weighted image and an iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) image. The apparent diffusion coefficient (ADC), the signal-to-noise ratio (SNR), and the thicknesses of the right and left masseter muscles were examined. RESULTS: The ADC and SNR immediately after exercise were significantly higher than those before exercise and 10 minutes after exercise. The muscles were significantly thicker immediately after exercise than before exercise and 10 minutes after exercise. CONCLUSION: We confirmed the presence of edema in the masseter muscles caused by low-level static contraction using MR images.