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1.
Int J Urol ; 31(3): 194-207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38113344

RESUMO

This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/terapia , Carcinoma de Células de Transição/patologia , Japão/epidemiologia
2.
Int J Urol ; 30(8): 649-657, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37130800

RESUMO

OBJECTIVE: To assess the impact of radical nephroureterectomy on postoperative renal function in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively evaluated 645 patients with UTUC treated with radical nephroureterectomy between January 2000 and May 2022. The primary outcome was the rate of postoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 . Secondary outcomes included the rate of eGFR decline, identification of factors related to eGFR decline, and the impact of comorbidities (diabetes or cardiovascular disease) on postoperative eGFR at 1 year. RESULTS: The median preoperative and postoperative eGFR levels were 55.6 and 43.3 mL/min/1.73 m2 , respectively. The rate of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 was 40.9% and 9.0%, respectively. The median decline in eGFR after surgery was 25.1%. The presence of preoperative unilateral hydronephrosis and eGFR <60 mL/min/1.73 m2 was significantly associated with a low decline of postoperative eGFR and poor survival. The impact of the presence of comorbidities on postoperative eGFR at 1 year was significant (p < 0.001). CONCLUSION: Impaired renal function is prevalent in patients with UTUC. The rate of patients with postoperative eGFR ≥60 mL/min/1.73 m2 was 9.0%. The presence of preoperative renal impairment was significantly related to a low decline in postoperative eGFR and poor survival. The presence of comorbidities had a significant effect on eGFR decline 1 year after radical nephroureterectomy.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Insuficiência Renal , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Nefrectomia/efeitos adversos , Neoplasias Renais/complicações , Rim/cirurgia , Rim/fisiologia , Neoplasias Ureterais/cirurgia
3.
World J Urol ; 39(3): 847-853, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32419054

RESUMO

PURPOSE: To explore associations between the gut microbiome and overactive bladder (OAB) with daily urinary urgency among individuals reporting this diagnosis within a single community. METHODS: This cross-sectional study surveyed 1113 individuals who participated in the Iwaki Health Promotion Project in Japan. OAB was defined as urinary urgency at least once per week and an Overactive Bladder Symptom Score (OABSS) of ≥ 3. OAB with urinary urgency at least once a day was defined as daily urgency. The gut microbiomes were assessed by next-generation sequencing of 16S rRNA genes extracted from fecal samples. The participants were divided into two groups: OAB-daily urgency and non-OAB. Cases were selected for inclusion on the basis of 1:1 propensity score matching; we assigned 58 individuals to each group (23 men and 35 women) for our analysis. RESULTS: Individuals reporting OAB with daily urinary urgency demonstrated a lower bacterial diversity between individuals (Bray-Curtis distance 0.48 vs. 0.53, P < 0.001); the results cluster differently in the non-OAB groups. The relative abundance of genus Bifidobacterium was significantly lower among those reporting daily urgency (2.41% vs. 4.23%, P = 0.014). By contrast, the relative abundance of genus Faecalibacterium (9.25% vs. 6.26%, P = 0.006) was significantly higher in this group. CONCLUSION: We observed significant differences in gut microbial contents and specific bacterial genera in association with OAB with daily urgency. Further study will be necessary to assess causal relationships between the gut microbiome and OAB.


Assuntos
Microbioma Gastrointestinal , Bexiga Urinária Hiperativa/etiologia , Transtornos Urinários/etiologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
World J Urol ; 39(1): 169-175, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32193653

RESUMO

PURPOSE: To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. METHODS: This cross-sectional study analyzed 1024 subjects who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. OAB was assessed using the Overactive Bladder Symptom Score (OABSS). OAB was defined as an occurrence of urinary urgency at least once a week and an OABSS of ≥ 3. We assessed serum 5-HT levels, laboratory data, and comorbidities of each participants. Participants' mental health status was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. The association of serum 5-HT levels and OAB was analyzed by multivariable logistic regression analysis. RESULTS: This study included 394 men and 630 women. Of those, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and CES-D score. Participants' serum 5-HT levels in the OAB group were significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P < 0.001). Multivariable analysis showed that age (odds ratio [OR]; 1.06, 95% confidence interval [CI]; 1.04-1.08, P < 0.001) and log serum 5-HT level (OR; 0.25, 95% CI; 0.10-0.68, P = 0.006) were independently associated with OAB. CONCLUSIONS: Lower serum 5-HT levels could independently be associated with the presence of OAB. Further study is necessary to elucidate a possible causal relationship between serum 5-HT levels and OAB.


Assuntos
Serotonina/sangue , Bexiga Urinária Hiperativa/sangue , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Vida Independente , Japão , Masculino , Pessoa de Meia-Idade
5.
Int J Clin Oncol ; 25(2): 362-369, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31655941

RESUMO

BACKGROUND: We investigated the association between the pretreatment quality of life (QOL) and overall survival (OS) in patients with urothelial carcinoma (UC), as the influence of pretreatment QOL on prognosis remains unclear in patients with localized and metastatic UC. METHODS: Between June 2013 and May 2019, we retrospectively investigated 205 patients with UC who received radical cystectomy or nephroureterectomy for non-metastatic UC (M0 group) or systemic chemotherapy for metastatic UC (M1 group). Patients answered the European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (QLQ-C30) before the treatments. Patients were stratified into two groups: QOL high and low according to the optimal cutoff scores which were defined by receiver operating characteristic curve. Inverse probability of treatment weighting (IPTW)-adjusted multivariate Cox regression analyses were performed to investigate the clinical implication of pretreatment QOL score on OS in patients with UC. RESULTS: The number of patients in the M0 and M1 groups was 125 and 80, respectively. Optimal cutoff values in global, fatigue, pain, appetite loss, physical, and role scores were < 50, > 33, > 33, > 16, < 80, and < 67, respectively. IPTW-adjusted multivariate Cox regression analyses revealed that appetite loss score indicated a significantly poorer OS in the M1 group. No significant association of QOL with OS was observed in the M0 group. CONCLUSION: Pretreatment QOL of appetite loss may predict poor prognosis of patients with metastatic UC.


Assuntos
Apetite , Qualidade de Vida , Neoplasias Urológicas/terapia , Idoso , Cistectomia , Fadiga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefroureterectomia , Prognóstico , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia
6.
Cancer Sci ; 110(8): 2573-2589, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31145522

RESUMO

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA normalized by prostate volume (LDN-PSAD). We retrospectively measured LDN-PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop-PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN-PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN-PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN-PSA and LDN-PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop-PSA cohort, LDN-PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc-glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution ("The Study about Carbohydrate Structure Change in Urological Disease"; approval no. 2014-195).


Assuntos
Lactose/análogos & derivados , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Glicosilação , Humanos , Lactose/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Antígeno Prostático Específico , Curva ROC , Estudos Retrospectivos , Carga Tumoral/fisiologia
7.
J Sex Med ; 16(12): 1922-1929, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31522986

RESUMO

INTRODUCTION: Although physical activity is associated with a decreased risk of erectile dysfunction (ED), the association of ED with physical function remains unclear. AIM: To investigate the relationship between gait function and ED in a community-dwelling population. METHODS: This cross-sectional study analyzed 324 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. ED was assessed with the 5-Item International Index of Erectile Function (IIEF-5). The participants were divided into 2 groups: low IIEF-5 score (≤16) and high IIEF-5 score (>16). We evaluated physical function, including gait function and grip strength. Gait function was evaluated by 10-meter gait speed and 2-step score (the ratio of the maximum length of 2 strides to height). We assessed daily physical activity, comorbidities, mental status, and laboratory data. The association between physical function and a low IIEF-5 score was analyzed by multivariate logistic regression analysis. MAIN OUTCOME MEASURE: The main outcome measure was to assess whether gait function was an independent indicator for erectile dysfunction. RESULTS: Of 324 men, 154 (48%) had a low IIEF-5 score. Grip strength, 2-step score, and 10-meter gait speed in the low IIEF-5 group were significantly inferior to those in the high IIEF-5 group. Multivariate analysis showed that the 2-step score (odds ratio = 0.08), age, and total testosterone were independently associated with a low IIEF-5. CLINICAL IMPLICATIONS: This study may motivate clinicians to investigate predictive values of physical function for ED. STRENGTHS & LIMITATIONS: The strength of this study was the use of simple, objective, and feasible tests for gait function to assess its association with ED. The limitations of this study were selection bias, regional bias, and nature of the cross-sectional study. CONCLUSIONS: Of the gait functional tests, not the 10-meter gait speed but 2-step score was an independent indicator for the presence of ED. Okamoto T, Hatakeyama S, Imai A, et al. The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan. J Sex Med 2019; 16:1922-1929.


Assuntos
Disfunção Erétil/fisiopatologia , Marcha , Nível de Saúde , Adulto , Estudos Transversais , Humanos , Japão , Masculino , Pessoa de Meia-Idade
8.
Breed Sci ; 67(3): 320-326, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28744186

RESUMO

'Nagasaki Kogane' is a new potato variety bred from a cross between 'Saikai 35' as a female parent and 'Saikai 33' as a male. 'Saikai 35' is resistant to bacterial wilt, contains the H1 and Rychc genes for resistance to the potato cyst nematode (PCN) and potato virus Y (PVY), respectively, and has high carotenoid content, while 'Saikai 33' has large and high-yielding tubers and is resistant to both bacterial wilt and PCN. The carotenoid content of 'Nagasaki Kogane' is higher than that of 'Dejima', a common double cropping variety. The taste quality of steamed 'Nagasaki Kogane' is comparable to that of 'Inca-no-mezame' tubers, which has high levels of carotenoid, and superior to 'Nishiyutaka', another popular double cropping variety. 'Nagasaki Kogane' is suitable for French fries, because its tuber has high starch content. The marketable yield of 'Nagasaki Kogane' was higher than that of 'Inca-no-mezame' in spring cropping, although it was lower than that of 'Nishiyutaka' in double cropping regions. 'Nagasaki Kogane' tubers are larger on average than 'Inca-no-mezame' tubers in spring cropping. Moreover, the 'Nagasaki Kogane' variety is resistant to PCN and PVY, and exhibits a high level of resistance to bacterial wilt.

9.
Int J Mol Sci ; 18(2)2017 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28134773

RESUMO

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.


Assuntos
Biomarcadores Tumorais/sangue , Lectinas de Plantas/metabolismo , Polissacarídeos/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Receptores de N-Acetilglucosamina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biópsia , Glicosilação , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Prognóstico , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Curva ROC , Fatores de Risco
10.
Int J Mol Sci ; 18(8)2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28786963

RESUMO

We determined if the serum N-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine N-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The N-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/imunologia , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Transplante de Rim/efeitos adversos , Doadores Vivos , Polissacarídeos/sangue , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto Jovem
11.
Int J Mol Sci ; 18(12)2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29210993

RESUMO

The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained-from 339 healthy volunteers (HV)-controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , Imunoglobulinas/metabolismo , Processamento de Proteína Pós-Traducional , Neoplasias da Bexiga Urinária/sangue , Idoso , Carcinoma/patologia , Estudos de Casos e Controles , Feminino , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
12.
Rinsho Byori ; 65(2): 210-217, 2017 02.
Artigo em Japonês | MEDLINE | ID: mdl-30762989

RESUMO

Prostate cancer (PCa) is now the most common male malignant tumor in both Japan and Western countries. Prostate-specific antigen (PSA) has been widely used for the early detection of PCa; however, it is not an ideal biomarker due to its low specificity. Aberrant glycosylation is closely associated with malignant transformation and cancer progression. Recent advances in glycobiology techniques can be applied to the development of novel biomarkers for PCa. We previously identified PCa-associated aberrant glycosylation on PSA, that is, α2,3-linked sialylation as an additional terminal N-glycan on free PSA(S2,3PSA). We then developed a new assay system for the measurement of S2,3PSA utilizing the µTAS method. The area under the curve (AUC) for the detection of PCa with the %S2,3PSA ratio was significantly better than that with total PSA. Another urgent issue in clinical practice for PCa is the over-treatment of patients with a low malignant potential, as aggressive treatment is not necessary. To overcome this problem, it is essential to develop a useful tool for the measurement of the malignant potential. Core2 ,ß-1,6-N-acetylglucosaminyltransferase-1 (GCNT1, C2GnT) is a key enzyme that forms core 2-branched 0-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression with the clinicopathological status of PCa. GCNT1- negative patients were associated with significantly better PSA-free survival compared with GCNT1-positive patients. Furthermore, we established new methods for GCNT1 detection using urine samples of PCa patients. Immunoblotting was used to examine post-digital rectal examination (DRE) urine from PCa patients. Over 90% of GCNT1-positive PCa patients with high concentrations of serum PSA showed extracapsular extension in prostatectomy specimens. In conclusion, the clinical application of glycobiology techniques is a promising approach to develop novel biomarkers for PCa.


Assuntos
Biomarcadores Tumorais , Polissacarídeos , Antígeno Prostático Específico , Neoplasias da Próstata , Biomarcadores Tumorais/sangue , Glicosilação , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico
13.
Cancer Sci ; 107(3): 359-68, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26678556

RESUMO

Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I-branching N-acetylglucosaminyltransferase (GCNT2) converts linear i-antigen to I-branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin-embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2-positive cells were significantly lesser in organ-confined disease than in that with extra-capsular extensions, and GCNT2-negative tumors were associated with significantly better prostate-specific antigen-free survival compared with GCNT2-positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 regulated the expression of cell surface I-antigen on the O-glycan and glycolipid. Moreover, I-antigen-bearing glycolipids were subject to α5ß1 integrin-fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT2 expression is closely associated with invasive potential of PCa.


Assuntos
Integrina alfa5beta1/metabolismo , N-Acetilglucosaminiltransferases/fisiologia , Neoplasias da Próstata/enzimologia , Linhagem Celular Tumoral , Movimento Celular , Intervalo Livre de Doença , Fibronectinas/metabolismo , Humanos , Masculino , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
14.
Biochem Biophys Res Commun ; 470(1): 150-156, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26768364

RESUMO

INTRODUCTION: To avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 ß-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression. METHODS: Paraffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1. RESULTS: GCNT1 expression correlated with D' Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. CONCLUSIONS: GCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.


Assuntos
Biomarcadores Tumorais/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Idoso , Intervalo Livre de Doença , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Próstata/epidemiologia , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade
15.
EMBO J ; 30(15): 3173-85, 2011 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-21712812

RESUMO

The O-glycan branching enzyme, core2 ß-1,6-N-acetylglucosaminyltransferase (C2GnT), forms O-glycans containing an N-acetylglucosamine branch connected to N-acetylgalactosamine (core2 O-glycans) on cell-surface glycoproteins. Here, we report that upregulation of C2GnT is closely correlated with progression of bladder tumours and that C2GnT-expressing bladder tumours use a novel strategy to increase their metastatic potential. Our results showed that C2GnT-expressing bladder tumour cells are highly metastatic due to their high ability to evade NK cell immunity and revealed the molecular mechanism of the immune evasion by C2GnT expression. Engagement of an NK-activating receptor, NKG2D, by its tumour-associated ligand, Major histocompatibility complex class I-related chain A (MICA), is critical to tumour rejection by NK cells. In C2GnT-expressing bladder tumour cells, poly-N-acetyllactosamine was present on core2 O-glycans on MICA, and galectin-3 bound the NKG2D-binding site of MICA through this poly-N-acetyllactosamine. Galectin-3 reduced the affinity of MICA for NKG2D, thereby severely impairing NK cell activation and silencing the NK cells. This new mode of NK cell silencing promotes immune evasion of C2GnT-expressing bladder tumour cells, resulting in tumour metastasis.


Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Evasão da Resposta Imune , Células Matadoras Naturais/imunologia , N-Acetilglucosaminiltransferases/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Polissacarídeos/metabolismo , Neoplasias da Bexiga Urinária/imunologia , Galectina 3/metabolismo , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/enzimologia
16.
BMC Urol ; 15: 32, 2015 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-25887125

RESUMO

BACKGROUND: Clinical benefit of axitinib as a first line agent to treat patients with metastatic renal cell carcinoma (mRCC), or locally advanced renal cell carcinoma (RCC) have not been clearly demonstrated. The aim of this study was to evaluate the efficacy and safety of axitinib as first-line therapy in Japanese patients with locally advanced RCC or mRCC. METHODS: In this retrospective study, we focused on eighteen patients who underwent first-line therapy with axitinib between May 2012 and May 2014 at Hirosaki University. Axitinib was orally administered at a dose of 10 mg daily. Progression-free survival (PFS) was the primary endpoint, while secondary endpoints included overall response rate (ORR) and adverse events (AEs). RESULTS: All patients had histologically proven clear cell RCC. The median duration of the administration of axitinib was 10.8 months. According to the response evaluation criteria for solid tumors, five patients (27.8%) achieved a partial response and nine (50%) had stable disease. The 1-year PFS rate was 84.4%, and the median PFS was 20.4 months (95% confidence interval, 17.5 - 21.7). No serious AEs were reported during the study, and there were no toxicity-related deaths. CONCLUSIONS: In the current study, axitinib showed acceptable oncological outcomes and favorable safety profile as first-line therapy for locally advanced RCC or mRCC in treatment-naïve Japanese patients. Thus, first-line therapy with axitinib may provide a feasible option for treatment of advanced RCC or mRCC patients.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Axitinibe , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/secundário , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Estudos Retrospectivos , Resultado do Tratamento
17.
Breed Sci ; 65(1): 3-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25931976

RESUMO

The potato (Solanum tuberosum L.) is cultivated all year round in Japan by using four types of cropping: summer and winter croppings, and double cropping in spring and fall. In each cropping season, growth conditions such as temperature, day length, and growing period, differ drastically; thus, different cultivars adapted to each environment are required. Breeding stations are located in both summer cropping areas and double cropping areas, and cultivars suitable for each cropping system are developed. The required cultivars differ according to cropping type and according to use such as table use, food processing, and starch production. The qualities necessary for each purpose differ and are therefore evaluated accordingly. Improvements in pest and disease resistance and in yield abilities are important as common breeding targets for all purposes. To develop potato cultivars that meet different needs, breeders have continued efforts to improve these traits. In this review, we introduce our approaches to developing new potato cultivars. We also discuss problems predicted in the future and introduce our efforts on broadening genetic diversity.

18.
Angew Chem Int Ed Engl ; 54(23): 6847-51, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25907312

RESUMO

A single-strand arylene-vinylene precursor containing four phenylene and three naphthylene units linked together with six vinylene spacers undergoes helical folding via sextuple photocyclization to give a [16]helicene core in a single step. The phenylene and naphthylene units are arranged in the precursor such that unfavorable side reactions (anthracene or benzoperylene formation) are avoided, and this is the key to the success of the one-step synthesis of [16]helicene, which is the longest [n]helicene that has been synthesized to date.

19.
Biochem Biophys Res Commun ; 448(4): 390-6, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24814705

RESUMO

INTRODUCTION: We previously identified prostate cancer (PCa)-associated aberrant glycosylation of PSA, where α2,3-linked sialylation is an additional terminal N-glycan on free PSA (S2,3PSA). We then developed a new assay system measuring S2,3PSA using a magnetic microbead-based immunoassay. We compared the diagnostic accuracy of conventional PSA and percent-free PSA (%fPSA) tests. METHODS: We used MagPlex beads to measure serum S2,3PSA levels using anti-human fPSA monoclonal antibody (8A6) for capture and anti-α2,3-linked sialic acid monoclonal antibody (HYB4) for detection. We determined the cutoff values in a training test and measured serum S2,3PSA levels in 314 patients who underwent biopsy, including 138 PCa and 176 non-PCa patients with PSA of <10.0 ng/ml. Serum S2,3PSA levels were presented as mean fluorescence intensity (MFI). Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of total PSA, %fPSA, and S2,3PSA. RESULTS: We determined an MFI cutoff value of 1130 with a sensitivity of 95.0% and specificity of 72.0% for the diagnosis of PCa in the training test. In the validation study, the area under the curve for the detection of PCa with S2,3PSA was 0.84, which was significantly higher than that with PSA or %fPSA. CONCLUSIONS: Although the present study is small and preliminary, these results suggest that the measurement of serum S2,3PSA using a magnetic microbead-based immunoassay may improve the accuracy of early detection of PCa and reduce unnecessary prostate biopsy.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Detecção Precoce de Câncer , Glicosilação , Humanos , Separação Imunomagnética/métodos , Separação Imunomagnética/estatística & dados numéricos , Calicreínas/química , Calicreínas/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/química , Antígeno Prostático Específico/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo
20.
Hinyokika Kiyo ; 60(11): 579-82, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25511947

RESUMO

A 34-year-old man presented with left inguinal discomfort. Digital rectal examination revealed an enlarged nodular prostate. Computed tomography showed an enlarged prostate invading the bladder and rectum. A histological examination of transrectal prostatic needle biopsy specimens revealed sarcoma of the prostate. He received three courses of neoadjuvant arterial injection chemotherapy consisting of adriamycin (30 mg/m2) and cisplatin (70 mg/m2). Total pelvic excenteration was perfomed. Histopathological examination of the tumor revealed leiomyosarcoma of the prostate. He remains alive 11 months after the operation without recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leiomiossarcoma/terapia , Terapia Neoadjuvante , Exenteração Pélvica , Neoplasias da Próstata/terapia , Adulto , Biópsia , Cisplatino/administração & dosagem , Exame Retal Digital , Doxorrubicina/administração & dosagem , Humanos , Injeções Intra-Arteriais , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/patologia , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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