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1.
Cancer Immunol Immunother ; 69(4): 663-675, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31980914

RESUMO

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Proteínas de Membrana/imunologia , Neoplasias/imunologia , Proteína Adaptadora de Sinalização NOD2/imunologia , Receptor Toll-Like 9/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antineoplásicos/sangue , Anticorpos Antineoplásicos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/administração & dosagem , Linhagem Celular Tumoral , Feminino , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neoplasias/patologia , Neoplasias/terapia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Receptor Toll-Like 9/metabolismo , Vacinação/métodos
2.
BMC Cancer ; 20(1): 606, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600281

RESUMO

BACKGROUND: Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE). METHODS: MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Informed consent was obtained from individuals prior to study enrolment. RESULTS: In total, 585 samples in 21 tumour types were evaluated between June 2009 and March 2018. The positive expression rates of these CT antigens were as follows: MAGE-A4, 34.6% (range, 30.7-38.7); NY-ESO-1, 21.0% (range, 17.2-25.1); and SAGE, 21.8% (range, 18.5-25.4). The MAGE-A4 antigen was expressed in 54.9% of oesophageal cancers, 37.5% of head and neck cancers, 35.0% of gastric cancers and 34.2% of ovarian cancers; the NY-ESO-1 antigen was expressed in 28.6% of lung cancers, 25.3% of oesophageal cancers and 22.6% of ovarian cancers; and the SAGE antigen was expressed in 35.3% of prostate cancers, 32.9% of oesophageal cancers and 26.3% of ovarian cancers. The most common tumour type in this study was oesophageal cancer. MAGE-A4, NY-ESO-1 and SAGE antigen expression were assessed in 214 oesophageal cancer samples, among which 24 (11.2%) were triple-positive, 58 (27.1%) were positive for any two, 59 (27.6%) were positive for any one, and 73 (34.1%) were triple negative. CONCLUSIONS: Oesophageal cancer exhibited a relatively high rate of CT antigen mRNA expression positivity.


Assuntos
Antígenos de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/imunologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo
3.
Carcinogenesis ; 37(6): 583-588, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26992901

RESUMO

Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms. Here, we conducted a matched case-control study to investigate whether ALDH2 and ADH1B polymorphisms influence BCa risk associated with alcohol drinking. Cases were 74 BCa patients and controls were 740 first-visit outpatients without cancer at Aichi Cancer Center Hospital between January 2001 and December 2005. Odds ratio (OR), 95% confidence interval (CI) and gene-environment interaction were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results showed that ALDH2 Glu/Lys was associated with a significantly increased risk of BCa compared with Glu/Glu (OR 2.03, 95% CI 1.14-3.62, P = 0.017). In contrast, ALDH2 Glu/Lys showed no increase in risk among the stratum of never drinkers compared with Glu/Glu, indicating a gene-environment interaction. ADH1B His/Arg had an OR of 1.98 (1.20-3.24, P = 0.007) compared with His/His. ADH1B Arg+ showed a similar OR and 95% CI. Individuals with ALDH2 Glu/Lys and ADH1B Arg+ had the highest risk of BCa compared with ALDH2 Glu/Glu and ADH1B His/His [OR 4.00 (1.81-8.87), P = 0.001].


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Hinyokika Kiyo ; 62(9): 495-500, 2016 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-27760976

RESUMO

A 69-year-old man was referred to our hospital with the chief complaint of a painless right scrotal swelling gradually increasing in size during the past 10 years. Testicular tumor markers were within the normal range. Ultrasonography showed an intrascrotal homogeneous mass. Computed tomography and magnetic resonance imaging revealed an inguinal mass, which mainly consisted of fat signal area and partially well enhanced in vascular density. Pre-surgical diagnosis was liposarcoma of spermatic cord estimated by radiographic examination and resection of the right intrascrotal tumor with high inguinal orchitectomy was performed. Histopathological diagnosis revealed well-differentiated liposarcoma. No recurrence phenomenon has been observed after 12 months without any adjuvant therapy. This case is the 129th report of intrascrotal liposarcoma in the Japanese literature.


Assuntos
Neoplasias dos Genitais Masculinos/cirurgia , Lipossarcoma/cirurgia , Cordão Espermático/cirurgia , Idoso , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Humanos , Lipossarcoma/diagnóstico por imagem , Masculino , Cordão Espermático/diagnóstico por imagem , Resultado do Tratamento
5.
J Med Genet ; 51(8): 530-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24919509

RESUMO

BACKGROUND: Prostate-specific antigen (PSA) is a useful marker for prostate cancer (PCa) and is widely used for screening of PCa. Previous studies have shown that genetic components influence the levels of PSA, and some of these genetic components would lead to better diagnostic sensitivity and specificity to PCa. However, genetic studies for PSA from Asian countries are limited. Our aim was to identify genetic components influencing PSA levels in the Japanese population using genome-wide association study (GWAS) and to analyse whether genetic components would lead to better screening abilities of PCa. METHODS: We performed a GWAS comprising 1086 male subjects using 303 283 single nucleotide proteins, followed by a replication study of 1302 subjects. PSA levels were quantified by chemiluminescence immunoassay method. Quantitative linear regression analysis was performed to assess genetic components of PSA levels. A total of 413 subjects with prostate biopsies were analysed to examine whether genetic determinants would improve diagnostic ability. RESULTS: Rs16856139 in SLC45A3, the same region as the previous Chinese study, showed an overall significant association with PSA levels (p=2.4×10(-11)) along with rs1058205 in KLK3. In silico analysis revealed significant association between rs16856139 and expression of SLC45A3. Genetic scores of PSA showed a dose-dependent decrease of area under curve (AUC) of PCa and successfully subgrouped the individuals with significantly different AUC (p≤0.0097). CONCLUSIONS: Rs16856139, associated with the expression of SLC45A3, is significantly associated with the levels of PSA in the Japanese population. Classification of subjects based on PSA genetic determinants would improve screening ability of PSA to detect PCa.


Assuntos
Povo Asiático/genética , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/genética , Estudo de Associação Genômica Ampla , Humanos , Japão , Masculino , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Curva ROC
6.
Urol Int ; 95(4): 452-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26430904

RESUMO

OBJECTIVES: The Gleason score (GS) is the primary classification of clinical risk in prostate cancer (PCa). Here, we estimated the factors predictive of accordance of local and central pathologist-dependent GS and clinical risk classification in an increased number of cases. METHODS: Between January 2009 and December 2013, 388 patients were diagnosed with PCa by 80 independent pathologists from local communities and were referred to our hospital. Validation of the GS with needle-core biopsy specimens was carried out by a single central pathologist, and clinical risk, according to the D'Amico risk classification, was determined. Discrepancies between the GS and risk classification, based on the GS estimated by the local or central pathologist, were reviewed, and predictive factors for accordance of clinical risk classification were estimated. RESULTS: When pathological results were compared, 59.5% of cases were given concordant GSs by local and central pathologists. A significant discrepancy existed in the classification of intermediate risk (p < 0.0001). Multivariate analysis indicated that local pathologist-dependent GS7, lower prostate-specific antigen (≤ 10 ng/ml), and lower T stage (T1 or T2a) were significant predictive factors for discordance with the central pathologist-dependent risk classification. CONCLUSION: Review of bioptic GSs by central pathologists affected discrepancies in risk classification in patients with PCa.


Assuntos
Gradação de Tumores/métodos , Patologia Clínica/métodos , Próstata/patologia , Neoplasias da Próstata/classificação , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia com Agulha de Grande Calibre , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos
7.
Nagoya J Med Sci ; 77(4): 637-46, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26663942

RESUMO

The purposes of this study on prostate cancer are to demonstrate the time course of International Prostate Symptom Score (IPSS) after intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) and to examine the factor associated with the IPSS change. This study included 216 patients treated with IMRT between 2006 and 2010. Patients were evaluated in three groups according to baseline IPSS as defined by the American Urological Association classification, where IPSSs of 0 to 7, 8 to 19, and 20 to 35 represent mild (n = 124), moderate (n = 70), and severe (n = 22) symptom groups, respectively. The average IPSSs ± standard deviation at baseline vs. those at 24 months after IMRT were 3.5 ± 2.1 vs. 5.1 ± 3.6 in the mild group (P < 0.001), 12.6 ± 3.4 vs. 10.0 ± 6.0 in the moderate group (P = 0.0015), and 23.8 ± 2.9 vs. 14.4 ± 9.1 in the severe group (P < 0.001). Among factors of patient and treatment characteristics, age, IPSS classification, pretreatment GU medications, and positive biopsy rates were associated with the IPSS difference between baseline and 24 months (P = 0.023, < 0.001, 0.044, and 0.028, respectively). In conclusion, patients with moderate to severe urinary symptoms can exhibit improvement in urinary function after IMRT, whereas patients with mild symptoms may have slightly worsened functions. Age, baseline IPSS, GU medications, and tumor burden in the prostate can have an effect on the IPSS changes.

8.
Radiology ; 270(1): 292-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23925272

RESUMO

PURPOSE: To compare clinical outcomes of radiofrequency (RF) ablation retrospectively with those after radical nephrectomy in patients with stage T1b renal cell carcinoma (RCC). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. From June 2002 to March 2012, 60 patients (mean age, 65.2 years; age range, 39-86 years) with a single RCC measuring 4.1-7.0 cm (stage T1b) underwent RF ablation (n = 21) or radical nephrectomy (n = 39). Selective renal artery embolization was performed before RF ablation in eight patients. The overall, RCC-related, and disease-free survival rates, the percentage decrease in the glomerular filtration rate (GFR), and safety were compared by using the log-rank (survival), paired and Student t (GFR), and Fisher exact (safety) tests. RESULTS: The overall survival rate was significantly lower in the RF ablation group than in the radical nephrectomy group (48% vs 97% at 10 years, respectively; 95% confidence interval [CI]: 12.4%, 76.7% vs 78.2%, 99.5%; P < .009). The RCC-related survival rate (94% [95% CI: 62.6%, 99.1%] with RF ablation vs 100% with radical nephrectomy at 10 years) and the disease-free survival rate (88% [95% CI: 59.2%, 96.9%] with RF ablation vs 84% [95% CI: 60.6%, 94.3%] with radical nephrectomy at 10 years, P = .99) were comparable between the two groups. No treatment-related deaths occurred. Although major complication rates were similar between the two patient groups (8.0% [two of 25 patients] vs 5.1% [two of 39 patients], P = .61), the percentage decrease in the GFR was significantly lower in the RF ablation group than in the radical nephrectomy group at the last follow-up (12.5% ± 23.4 vs 32.3% ± 20.8, respectively; P < .003). CONCLUSION: RF ablation is a safe procedure for patients at substantial surgical risk for radical nephrectomy, providing comparable RCC-related and disease-free survival and preserving renal function.


Assuntos
Carcinoma de Células Renais/cirurgia , Ablação por Cateter , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Embolização Terapêutica , Feminino , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Hinyokika Kiyo ; 59(10): 673-6, 2013 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-24262710

RESUMO

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-Idade
10.
Gan To Kagaku Ryoho ; 40(11): 1497-501, 2013 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-24231702

RESUMO

BACKGROUND: Bone metastases from renal cell carcinoma(RCC)are almost osteolytic and often cause pathological fractures. The objective of this study was to assess the efficacy of radiotherapy and zoledronic acid in patients with bone metastases from RCC. METHODS: We retrospectively analyzed 12 patients with bone metastases from RCC. Of these patients, 5 were treated with radiotherapy(RT group)and 7 were treated with a combination of radiotherapy and zoledronic acid(RT+Z group). We analyzed the radiological changes in the bone metastases and evaluated the response rate, survival rate, and skeletal-related event(SRE)rate. RESULTS: Radiologically, 2 patients showed progressive disease(PD), 3 showed stable disease( SD), 1 showed partial response(PR), and 1 showed complete response(CR)in the RT group(response rate: 28.6%). In the RT+Z group, 1 patient showed PD, 3 showed PR, and 1 showed CR(response rate: 80.0%). CONCLUSIONS: With regard to radiological changes, the response rate was higher in the RT group than in the RT+Z group, but the survival rate did not differ significantly between the 2 groups. SREs were less frequent in the RT+Z group than in the RT group.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/terapia , Carcinoma de Células Renais/patologia , Quimiorradioterapia , Difosfonatos/uso terapêutico , Neoplasias Renais/patologia , Adulto , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Jpn J Clin Oncol ; 42(6): 534-40, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22438406

RESUMO

OBJECTIVE: To evaluate long-term clinical outcomes in cT1c-T3a prostate cancer patients following delayed-combined androgen blockade therapy. METHODS: From January 2001 to December 2004, 92 cT1c-T3a prostate cancer cases were enrolled. Medical castration and anti-androgen treatment were used sequentially as delayed-combined androgen blockade therapy. Time to prostate-specific antigen biochemical failure was estimated, and risk factors for prostate-specific antigen biochemical failure were evaluated. RESULTS: The average patient age was 76.4 years (range, 59-91 years), the median observation period was 52.8 months (range, 26-106.6 months) and the median pre-treatment prostate-specific antigen level was 14 ng/ml (range, 3.68-492 ng/ml). The TNM classification distribution was as follows: T1c, n= 27; T2a, n = 39; T2b, n = 20; and T3a, n = 6. In the multivariate analysis, Gleason's score ≥8 (P < 0.05; hazard ratio, 3.02), prostate-specific antigen nadir >1.4 ng/ml (P = 0.001; hazard ratio, 8.76) and a half-life of the prostate-specific antigen level >1.2 months (P < 0.005; hazard ratio, 6.3) during the initial 6 months of luteinizing hormone-releasing hormone agonist monotherapy were significant independent risk factors for prostate-specific antigen biochemical failure with luteinizing hormone-releasing hormone agonist monotherapy. The high-risk group, which had at least one of these three risk factors, had a shorter time to prostate-specific antigen biochemical failure than the low-risk group, during luteinizing hormone-releasing hormone agonist monotherapy (P < 0.0001). For the total delayed-combined androgen blockade therapy observation period, the free-prostate-specific antigen biochemical failure rate was 88.3% at 5 years. Only a maintenance period following luteinizing hormone-releasing hormone agonist monotherapy (P < 0.005; hazard ratio, 16.8) was revealed to be a significant independent risk factor for prostate-specific antigen biochemical failure with total delayed-combined androgen blockade. CONCLUSIONS: The free-prostate-specific antigen biochemical failure rate of delayed-combined androgen blockade therapy in our study was as valuable as those in other androgen deprivation therapy of previous reports.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Anilidas/administração & dosagem , Esquema de Medicação , Gosserrelina/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leuprolida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Nitrilas/administração & dosagem , Razão de Chances , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Compostos de Tosil/administração & dosagem , Falha de Tratamento , Resultado do Tratamento
12.
Int J Urol ; 19(8): 729-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22515572

RESUMO

OBJECTIVE: To assess the incidence of benign renal lesions in our Japanese clinical experience with surgical resection. METHODS: A total of 411 renal masses harvested by radical or partial nephrectomy between January 1991 and April 2011 at our institution were retrospectively assessed. The incidence of benign lesions in 1-cm increments in diameter was determined, and a logistic regression model was used to assess relationships between the incidence of benign lesions and other factors. RESULTS: Histological examination confirmed a total of 18 (4.4%) benign lesions. The incidence of benign lesions was 42.8% for nodules <1 cm and 10.0% for nodules 1 to <2 cm. In contrast, the incidence of benign lesions in each 1-cm increment between 2 and 6 cm was 4.1-4.9%. The incidence of benign lesions 2 to <4 cm was 4.8% and of benign nodules ≥6 cm was just 0-1.0%. The incidence of benign lesions ≥2 cm (3.5%) was significantly lower than that of masses <2 cm (16.2%; P < 0.001). Multivariate analysis showed that female gender (odds ratio 3.68) and smaller mass size (<2 cm; odds ratio 4.84) were significant predictors for benign lesions. CONCLUSIONS: The incidence of benign lesions among renal masses ≥2 cm in diameter was found to be much lower than previously reported. This should be taken into account when designing strategies for the management of suspicious small renal masses.


Assuntos
Carcinoma de Células Renais/epidemiologia , Neoplasias Renais/epidemiologia , Rim/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Neoplasias Renais/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Hinyokika Kiyo ; 58(5): 231-5, 2012 May.
Artigo em Japonês | MEDLINE | ID: mdl-22767276

RESUMO

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/terapia
14.
Cancer Diagn Progn ; 2(3): 345-350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530651

RESUMO

BACKGROUND/AIM: We investigated pre-operative factors for predicting whether renal masses are benign in order to facilitate the selection of optimal candidates for pre-operative biopsy. PATIENTS AND METHODS: We evaluated 278 patients with renal masses suspected to be clinically T1 or T2 renal cell carcinoma. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, tumor size, and blood tests, were utilized to predict which lesions were benign. RESULTS: Twenty-five lesions (9.0%) were benign. Multivariate analysis showed that female sex [odds ratio (OR)=2.92, p=0.016], serum albumin ≥4.3 g/dl (OR=3.50, p=0.013), and tumor size <23 mm (OR=3.96, p=0.002) were significant independent factors for benign renal masses. The incidence of benign lesions in cases with all three factors (female sex, higher serum albumin, and smaller tumor size) was 4 of 16 (25.0%), which was significantly higher (p=0.037) than that in all cases (25/278; 9.0%). CONCLUSION: Relatively high pre-operative serum albumin levels may be a predictor of benign lesions when associated with female sex and smaller tumor size.

15.
IJU Case Rep ; 5(6): 442-445, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36341181

RESUMO

Introduction: Prostate cancer with a microsatellite instability-high or mismatch repair-deficient status is not common. Few reports of the response to pembrolizumab in metastatic castration-resistant prostate cancer in a real-world setting have been reported. This case report describes a dramatic response to pembrolizumab after initial pseudoprogression in a patient with microsatellite instability-high metastatic castration-resistant prostate cancer. Case presentation: A 70-year-old man was administered pembrolizumab for metastatic castration-resistant prostate cancer after the genetic evaluation of lymphadenectomy revealed a microsatellite instability-high status. His general condition dramatically improved after pseudoprogression. His favorable condition has been maintained for 1 year since the final dose. Conclusion: We experienced a case of dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer. In patients with metastatic castration-resistant prostate cancer and the microsatellite instability-high/mismatch repair-deficient phenotype, a few months follow-up is necessary to evaluate the efficacy of pembrolizumab.

16.
Differentiation ; 80(2-3): 82-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20638776

RESUMO

Transforming growth factor-α (TGFα) promotes cell proliferation by binding to the epidermal growth factor receptor (EGFR). TGFα and EGFR overexpression have been reported in various human cancers. However, whether TGFα induces cancer by itself is unknown in urogenital organs. To investigate whether TGFα overexpression induces carcinogenesis in urogenital organs, we analyzed the phenotypes of urogenital organs in male TGFα transgenic (TG) mice of the CD1 strain. Urogenital organs including the kidney, bladder, prostate, seminal vesicles, testes, and epididymis were isolated from 4- to 48-week-old TGFα TG and wild-type (WT) CD1 mice. Prostates were separated into anterior prostate (AP), dorsolateral prostate (DLP), and ventral prostate (VP). Neither tumor formation nor epithelial hyperplasia was observed in the TGFα TG mouse urogenital organs that we have investigated. Histopathologically, in prostate, we found an increased number of p63-positive basal epithelial cells in the TGFα TG mice AP and DLP. There was no morphological change in the stromal component, such as hypercellular stroma or fibrosis. However, bladder weight was greater in TGFα TG mice than that in WT mice, and distended bladders were observed macroscopically in 19 of 20 TGFα TG mice over 20 weeks of age. Ki67 labeling index was increased significantly in the TGFα TG mouse urethral epithelium, whereas neither epithelial hyperplasia nor hypertrophy was observed. In conclusion, our results suggest that TGFα overexpression in mouse urogenital organs alone may not be responsible for tumor formation and epithelial hyperplasia, but is involved in bladder outlet obstruction.


Assuntos
Fator de Crescimento Transformador alfa/genética , Sistema Urogenital/embriologia , Animais , Sequência de Bases , Primers do DNA , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase
17.
Microsurgery ; 31(7): 564-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21769925

RESUMO

We present a case of successful operative management of an iatrogenic rectourethral fistula with a pedicled vastus lateralis musculofascial flap. The fistula was created during radical prostatectomy operation. During the operation, it was deemed possible to spare this patient from a diverting colostomy and primarily repair a rectal injury. Postoperatively, however, a rectourethral fistula occurred, which was confirmed on retrograde urethrogram. A first attempt failed to close the fistula utilizing the transanal rectal flap advancement technique. A novel technique was attempted using a pedicled vastus lateralis musculofascial flap. This is the first report to our knowledge of repairing a rectourethral fistula with a pedicled vastus lateralis musculofascial flap.


Assuntos
Complicações Intraoperatórias , Prostatectomia/efeitos adversos , Fístula Retal/cirurgia , Retalhos Cirúrgicos , Doenças Uretrais/cirurgia , Fístula Urinária/cirurgia , Idoso , Humanos , Masculino , Fístula Retal/etiologia , Doenças Uretrais/etiologia , Fístula Urinária/etiologia
18.
Biol Pharm Bull ; 33(4): 721-4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20410614

RESUMO

Zoledronic acid (ZDA) is commonly prescribed to treat and prevent skeletal complications in patients with multiple myeloma or bone metastases. Although hypocalcemia often develops by ZDA, there is little information about the risk factors for hypocalcemia mediated by ZDA. This study was conducted to assess the risk of ZDA-mediated hypocalcemia. We retrospectively reviewed the records of patients receiving ZDA in Mie University Hospital. The subjects were divided into two groups on the basis of whether hypocalcemia developed (19 patients) or not (30 patients). We compared patients' baseline characteristics between the two groups. The patients with hypocalcemia had lower albumin-adjusted serum calcium concentrations (median 9.2 mg/dl) before ZDA administration than the patients without hypocalcemia (median 9.8 mg/dl) (p< 0.01). Multivariate analysis revealed that an adjusted serum calcium concentration lower than 9.5 mg/dl before ZDA administration was an independent risk factor significantly contributing to the development of hypocalcemia (odds ratio 22.0, p< 0.01). Furthermore, the patients receiving corticosteroid had increased risk of ZDA mediated hypocalcemia (odds ratio 11.9, p<0.05). On the other hand, the patients with prostate cancer had a reduced risk for hypocalcemia after ZDA administration (odds ratio 0.06, p<0.05). In conclusion, a lower serum calcium concentration and co-administration of corticosteroid increased the risk of hypocalcemia after ZDA administration, while patients with prostate cancer might have a small risk of this incidence. These findings should provide useful information regarding the monitoring of serum calcium concentration in cancer patients receiving ZDA.


Assuntos
Corticosteroides/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Cálcio/sangue , Difosfonatos/efeitos adversos , Hipocalcemia/induzido quimicamente , Imidazóis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/sangue , Difosfonatos/uso terapêutico , Feminino , Humanos , Hipocalcemia/sangue , Imidazóis/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de Risco , Ácido Zoledrônico
20.
Int J Clin Oncol ; 15(4): 376-81, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20333430

RESUMO

OBJECTIVE: To evaluate the efficacy and toxicity of third-line gemcitabine monotherapy (Gem) in patients with platinum-resistant advanced urothelial cancer (UC). PATIENTS AND METHODS: From July 2005 to March 2009, 13 patients were enrolled. All patients had previously received methotrexate, vinblastine, doxorubicin, and cisplatin as first-line therapy. Second-line therapy consisted of paclitaxel/carboplatin (Pca) therapy: paclitaxel (175 mg/m(2)) followed by carboplatin (area under the curve = 5) was intravenously infused on day 1 of each 21-day cycle. Following Pca failure, Gem was given as third-line treatment: gemcitabine (1,000 mg/m(2)) was intravenously administered on days 1, 8, and 15 of each 28-day cycle. All patients were eligible for toxicity assessment. Survival curves were produced using the Kaplan-Meier method. RESULTS: An average of 3.2 Gem cycles (range, 1-8 cycles) were given. Following Gem treatment, overall response rates were 0% CR, 7.7% PR (n = 1), 53.8% SD (n = 7), and 38.5% PD (n = 5). Grade 3-4 toxicities included anemia (31%), neutropenia (31%), and thrombocytopenia (31%). One case experienced grade 3-4 hepatic dysfunction during treatment with Gem. Low-grade alopecia was observed in all 13 patients (100%). Median time to progression and overall survival was 2 and 7.3 months, respectively, following Gem. The 1- and 2-year overall survival rate was 30.8% and 15.3%, respectively, for Gem. CONCLUSION: Gem as third-line therapy was performed safely with good tolerability in platinum-resistant advanced UC, even though the efficacy was very limited.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Neoplasias Urológicas/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Salvação , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/secundário , Urotélio/patologia , Gencitabina
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