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2.
Biochem Biophys Res Commun ; 590: 117-124, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-34974299

RESUMO

The association between type 2 diabetes mellitus and prostate cancer is still under investigation, and the relationship between hyperinsulinemia and prostate cancer stem-like cells (CSCs) is elusive. Here, we investigated the function of insulin/AKT signaling in prostate CSCs. We isolated prostate CSCs as aldehyde dehydrogenase 1-high (ALDH1high) cells from the human prostate cancer 22Rv1 cell line using an ALDEFLUOR assay and established several ALDH1high and ALDH1low clones. ALDH1high clones showed high ALDH1 expression which is a putative CSC marker; however, they showed heterogeneity regarding tumorigenicity and resistance to radiation and chemotherapy. Interestingly, all ALDH1high clones showed lower phosphorylated AKT (Ser473) (pAKT) levels than the ALDH1low clones. PI3K/AKT signaling is a key cell survival pathway and we analyzed radiation resistance under AKT signaling activation by insulin. Insulin increased pAKT levels in ALDH1high and ALDH1low cells; the fold increase rate of pAKT was higher in ALDH1high cells than in ALDH1low cells. Insulin induced resistance to radiation and chemotherapy in ALDH1high cells, and the increased levels of pAKT induced by insulin were significantly related to radiation resistance. These results suggest that ALDH1 suppresses baseline pAKT levels, but AKT can be activated by insulin, leading to treatment resistance.


Assuntos
Aldeído Desidrogenase/metabolismo , Insulina/farmacologia , Neoplasias da Próstata/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação , Transdução de Sinais , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Neoplasias da Próstata/patologia
3.
Cancer Immunol Immunother ; 71(4): 905-918, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34491407

RESUMO

Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy to block programmed death-1 and cytotoxic T-lymphocyte antigen 4, but the response rate for ICIs is still low and tumor cell heterogeneity is considered to be responsible for resistance to immunotherapy. Tumor-infiltrating lymphocytes (TILs) have an essential role in the anti-tumor effect of cancer immunotherapy; however, the specificity of TILs in renal cell carcinoma (RCC) is elusive. In this study, we analyzed a 58-year-old case with clear cell RCC (ccRCC) with the tumor showing macroscopic and microscopic heterogeneity. The tumor was composed of low-grade and high-grade ccRCC. A tumor cell line (1226 RCC cells) and TILs were isolated from the high-grade ccRCC lesion, and a TIL clone recognized a novel neoantigen peptide (YVVPGSPCL) encoded by a missense mutation of the tensin 1 (TNS1) gene in a human leukocyte antigen-C*03:03-restricted fashion. The TNS1 gene mutation was not detected in the low-grade ccRCC lesion and the TIL clone did not recognized low-grade ccRCC cells. The missense mutation of TNS1 encoding the S1309Y mutation was found to be related to cell migration by gene over-expression. These findings suggest that macroscopically and microscopically heterogenous tumors might show heterogenous gene mutations and reactivity to TILs.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Linfócitos T CD8-Positivos , Carcinoma de Células Renais/patologia , Humanos , Imunoterapia , Neoplasias Renais/patologia , Linfócitos do Interstício Tumoral , Pessoa de Meia-Idade
4.
PLoS One ; 16(6): e0253646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166439

RESUMO

PURPOSE: Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly across the world. During the pandemic, physicians in our hospital have had to respond both to the issue of treating the patients and the increasing domestic burden associated with social disruption. The purpose of this study was to assess how much the burden on our doctors, especially female doctors, was increasing. MATERIAL AND METHODS: The Physicians' Career Support Committee in Sapporo Medical University conducted a questionnaire survey. The questionnaire inquired about a wide range of subjects with regard to working style and family life during the first and second waves of the COVID-19 pandemic, and was sent to all medical/dental physicians working in Sapporo Medical University. RESULTS: A total of 266 (42.7%) physicians in our hospital responded to our questionnaire and the data for 264 data were analyzed. The total numbers of males, females, and others, including those who did not want to specify, were 178 (67.4%), 82 (31.0%), and 4 (1.5%), respectively. Among them, 62 (23.5%) and 23 (8.7%) answered that their domestic burden was slightly or markedly increased. The increase in the domestic burden showed a significant difference between genders (p = 0.04). Even after correction for background differences using multivariate analysis, being female (p<0.001), having child dependents (p<0.001), and treating COVID-19 patients (p = 0.03) were significantly related to an increased domestic burden. Regarding family style, 58.1% of the physician-fathers were from two-income families (i.e., families with both parents in employment), and they answered that their partner mainly cared for the children. In contrast, 97.3% of physician-mothers were from two-income families, and 94.6% of the physician-mothers had to take care of children by themselves. CONCLUSION: Physician-mothers are caught in a dilemma between an increased home burden and clinical duties in the hospital, with a significantly higher ratio than physician-fathers during the pandemic. As we showed, female doctors could have not continued their careers and take responsible positions in the same way as male doctors. This is a social risk in the timing of a crisis, such as a pandemic.


Assuntos
COVID-19 , Mães , Pandemias , Médicas , SARS-CoV-2 , Inquéritos e Questionários , Mulheres Trabalhadoras , Adulto , Idoso , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade
5.
Hinyokika Kiyo ; 67(4): 125-132, 2021 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-34107607

RESUMO

Gender equality is one of the most important issues in the promotion of diversity. The participation status of female urologists in academic activities has not been clarified. In the present study, we analyzed a total of 10,288 articles published by 58,914 authors in Acta Urologica Japonica since the first issue in 1955 to the present. The author's gender was determined by an application program interface for gender estimation in combination with independent manual confirmation by two researchers. The increasing rate (⊿person/⊿year) of female authors was as low as 0.067 in 1955-79, but increased to 0.400 in 1980-2000 and 0.814 in 2001-20. Over the time periods, the annual total numbers of female authors (person/year) showed an increasing trend from 3.2 in 1955-79 to 16.3 in 1980-2000 and 26.0 in 2001-20. The numbers of female author individuals, the ratio of female authors to all authors and the ratio of publications by female first author to all publications also showed similar trends. These results suggest that gender equality is becoming more prevalent in the academic field of urology. The methods and data of this study are considered to be useful for the promotion of gender equality in the academic field of urology for the future.


Assuntos
Urologia , Autoria , Bibliometria , Feminino , Equidade de Gênero , Humanos , Fatores de Tempo
6.
Biochem Biophys Res Commun ; 552: 128-135, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33744760

RESUMO

Previously, we investigated gene expression in a high aldehyde dehydrogenase 1 expression (ALDH1high) population of urothelial carcinoma (UC) cells as UC cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) and found that NRG1 expression was upregulated in ALDH1high cells. NRG1 is a trophic factor that contains an epidermal growth factor (EGF)-like domain that signals by stimulating ERBB receptor tyrosine kinases and the cytoplasmic domain. NRG1 has been determined to be involved in frequent gene fusions with other partners in several malignancies and has a role in carcinogenesis through the NRG1 EGF-like domain and its cognitive receptor ERBBs. We thus aimed to elucidate the function of NRG1 in UC CSCs/CICs in this study. Both NRG1α and NRG1-ß1 were preferentially expressed in ALDH1high cells compared with ALDH1low cells; however, siRNA experiments revealed that NRG1-ß1 but not NRG1-α has a role in sphere formation. The EGF-like domain of NRG1 had a role in sphere formation of UC cells to some extent but was not essential. The intracellular domain of NRG1 did not have a role in sphere-formation. Inhibition of γ-secretase suppressed sphere formation. These findings indicate that cleavage of NRG1-ß1 by γ-secretase plays an important role in UC CSC/CIC proliferation; however, the downstream targets of NRG1-ß1 remain elusive.


Assuntos
Secretases da Proteína Precursora do Amiloide/genética , Células-Tronco Neoplásicas/metabolismo , Neuregulina-1/genética , Esferoides Celulares/metabolismo , Neoplasias Urológicas/genética , Urotélio/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neuregulina-1/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Presenilina-2/genética , Presenilina-2/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Urológicas/metabolismo , Urotélio/patologia
7.
Hinyokika Kiyo ; 67(1): 47-51, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33535298

RESUMO

A 53-year-old man was diagnosed with prostate cancer with multiple bone metastasis. Therefore androgen deprivation therapy was initiated. After treatment with denosumab injection for bone metastasis, hypocalcemia and hypophosphatemia occurred. Despite treatment for hypocalcemia with vitamin D and calcium lactate,his serum calcium and phosphate levels were refractory to treatment. The etiology of hypophosphatemia was investigated,and the level of serum fibroblast growth factor 23 (FGF23) was abnormally elevated. Three months after the first measurement of FGF23,the patient died of prostate cancer. Severe hypophosphatemia is a typical manifestation of tumor-induced hypophosphatemic osteomalacia (TIO),which is a paraneoplastic condition, mediated by FGF23 overexpression in most cases. His osteoblastic metastasis,however,did not meet the disease criteria of osteomalacia. Several reports have suggested that excessive FGF23 may mediate both severe hypophosphatemia and aggressive castrationresistant prostate cancer characteristics. Management of serum FGF23 may be a novel therapeutic strategy for castration-resistant prostate cancer with hypophosphatemia.


Assuntos
Hipocalcemia , Hipofosfatemia , Neoplasias da Próstata , Antagonistas de Androgênios , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Hipofosfatemia/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico
8.
Oncotarget ; 8(17): 28826-28839, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28418868

RESUMO

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub-population of cancer cells that are endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs could be isolated as high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh cells and investigated the molecular aspects. ALDH1high cells showed greater sphere-forming ability and higher tumor-initiating ability in immune-deficient mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in ALDH1high cells. cDNA microarray analysis revealed that an ionotropic glutamate receptor glutamate receptor, ionotropic, kainate 2 (GRIK2) was expressed in ALDH1high cells at a higher level than that in ALDH1low cells. GRIK2 gene knockdown by siRNAs decreased the sphere-forming ability and invasion ability, whereas GRIK2 overexpression increased the sphere-forming ability, invasion ability and tumorigenicity, indicating that GRIK2 has a role in the maintenance of CSCs/CICs. Immunohistochemical staining revealed that higher levels of GRIK2 and ALDH1 expression were related to poorer prognosis in urinary tract carcinoma cases. The findings indicate that GRIK2 has a role in the maintenance of urothelial CSCs/CICs and that GRIK2 and ALDH1 can be prognosis prediction markers for urinary tract carcinomas.


Assuntos
Isoenzimas/metabolismo , Células-Tronco Neoplásicas/patologia , Receptores de Ácido Caínico/metabolismo , Retinal Desidrogenase/metabolismo , Neoplasias Urológicas/genética , Urotélio/patologia , Família Aldeído Desidrogenase 1 , Animais , Carcinogênese , Linhagem Celular Tumoral , Autorrenovação Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Prognóstico , RNA Interferente Pequeno/genética , Receptores de Ácido Caínico/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor de GluK2 Cainato
9.
Jpn J Clin Oncol ; 46(11): 1026-1030, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27576436

RESUMO

OBJECTIVES: The aim of this study was to evaluate the additional benefit of 3 Tesla magnetic resonance imaging for neurovascular bundle preservation in radical prostatectomy. METHODS: We retrospectively evaluated patients who underwent 3 T magnetic resonance imaging followed by radical prostatectomy from April 2010 through February 2014 in our university. A total of 50 patients (100 prostate sides) were included in the study. The algorithm previously we described and magnetic resonance imaging findings were considered for the decision on neurovascular bundle preservation. A tumor adjacent to the neurovascular bundle or with extracapsular extension of a posterolateral lesion of the prostate on magnetic resonance imaging was considered a contraindication for nerve-sparing radical prostatectomy. Two experienced radiologists evaluated the magnetic resonance imaging findings. Patients who received neoadjuvant hormonal therapy were excluded. All patients underwent ultrasound-guided prostate biopsy with at least 10 cores. RESULTS: Overall, 60 of the 100 neurovascular bundles were preserved according to an algorithm that consisted of the clinical stage, prostate specific antigen, Gleason score and a positive biopsy core in the apex of the prostate. Considering magnetic resonance imaging findings together with the algorithm, six neurovascular bundles were not preserved. The accuracy of predicting a positive surgical margin only by the algorithm was 56 of 60 neurovascular bundle (93.3%). When adding magnetic resonance imaging, the accuracy was 50 of 54 neurovascular bundle (92.3%). CONCLUSIONS: 3 T magnetic resonance imaging provided no additional benefit to our algorithm for neurovascular bundle preservation.

10.
Anticancer Res ; 35(1): 413-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25550581

RESUMO

We previously found that prostate cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) express hepatocyte growth factor (HGF) and that the HGF/c-MET proto-oncogene product (c-MET) signal has a role in the maintenance of prostate CSCs/CICs in an autocrine fashion. HGF is, thus, a novel marker for prostate CSCs/CICs. We hypothesized that high expression of HGF might be related to early recurrence of prostate cancer after radical prostatectomy, and the purpose of the present study was to evaluate the relationship between expression of HGF in prostate tissues and biochemical recurrence after radical prostatectomy. One hundred-one patients with prostate cancer who underwent open or laparoscopic radical prostatectomy from November 2008 to October 2011 with an adequate prostate-specific antigen (PSA) follow-up period, were investigated. Immunohistochemical staining of HGF was compared to biochemical recurrence after radical prostatectomy. Patients with tumors exhibiting HGF positivity of 5% or more had a significantly shorter biochemical recurrence-free period than that of patients whose tumor HGF positivity was less than 5% (p=0.001). In multivariate Cox regression, preoperative PSA and HGF positivity were independent predictors of biochemical recurrence following prostatectomy. Our finding suggests a direct link between expression of HGF, a novel prostate marker of CSCs/CICs, and biochemical recurrence after radical prostatectomy in patients with prostate cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/metabolismo , Modelos de Riscos Proporcionais , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proto-Oncogene Mas , Curva ROC , Estudos Retrospectivos
11.
Nihon Rinsho ; 72(12): 2229-33, 2014 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-25518363

RESUMO

The cancer stem cell (CSC) hypothesis shows that tumors contain a reservoir of self-renewing cells that maintain the tumor. Such cancer cells were first identified in leukemia in the 1990s. These cells appear to be resistant to various therapies and can survive to repopulate the tumor. Therefore, this concept has important therapeutic implications for recurrence and metastasis. In this review, we introduce the CSC hypothesis and the origin, method of identification and functions of prostate CSCs. In addition, we review the therapeutic challenges of targeting prostate CSCs.


Assuntos
Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/patologia , Animais , Biomarcadores Tumorais/metabolismo , Reprogramação Celular , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia
12.
Clin Dev Immunol ; 2013: 262967, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24363758

RESUMO

We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88, a member of the inhibitor of apoptosis protein family, recognized by CD8+cytotoxic T lymphocytes (CTL). In a phase I clinical trial of survivin-2B80-88 vaccination for metastatic urothelial cancer (MUC), we achieved clinical and immunological responses with safety. Moreover, our previous study indicated that interferon alpha (IFN α ) enhanced the effects of the vaccine for colorectal cancer. Therefore, we started a new phase I clinical trial of survivin-2B80-88 vaccination with IFN α for MUC patients. Twenty-one patients were enrolled and no severe adverse event was observed. HLA-A24/survivin-2B80-88 tetramer analysis and ELISPOT assay revealed a significant increase in the frequency of the peptide-specific CTLs after vaccination in nine patients. Six patients had stable disease. The effects of IFN α on the vaccination were unclear for MUC. Throughout two trials, 30 MUO patients received survivin-2B80-88 vaccination. Patients receiving the vaccination had significantly better overall survival than a comparable control group of MUO patients without vaccination (P = 0.0009). Survivin-2B80-88 vaccination may be a promising therapy for selected patients with MUC refractory to standard chemotherapy. This trial was registered with UMIN00005859.


Assuntos
Vacinas Anticâncer/imunologia , Proteínas Inibidoras de Apoptose/imunologia , Interferon-alfa/uso terapêutico , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , Vacinas de Subunidades Antigênicas/imunologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer/efeitos adversos , Feminino , Humanos , Proteínas Inibidoras de Apoptose/efeitos adversos , Proteínas Inibidoras de Apoptose/química , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Fragmentos de Peptídeos/imunologia , Prognóstico , Survivina , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Vacinas de Subunidades Antigênicas/efeitos adversos
13.
Cancer Sci ; 104(4): 431-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23320511

RESUMO

Prostate cancer cells include a small population of cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) that have roles in initiation and progression of the cancer. Recently, we isolated prostate CSCs/CICs as aldehyde dehydrogenase 1-highh (ALDH1(high) ) cells using the ALDEFLUOR assay; however, the molecular mechanisms of prostate CSCs/CICs are still elusive. Prostate CSCs/CICs were isolated as ALDH1(high) cells using the ALDEFLUOR assay, and the gene expression profiles were analyzed using a cDNA microarray and RT-PCR. We found that prostate CSCs/CICs expressed higher levels of growth factors including hepatocyte growth factor (HGF). Hepatocyte growth factor protein expression was confirmed by enzyme linked immunosorbent assay and Western blotting. On the other hand, c-MET HGF receptor was expressed in both CSCs/CICs and non-CSCs/CICs at similar levels. Hepatocyte growth factor and the supernatant of myofibloblasts derived from the prostate augmented prostasphere formation in vitro, and prostasphere formation was inhibited by an anti-HGF antibody. Furthermore, c-MET gene knockdown by siRNA inhibited the prostasphere-forming ability in vitro and tumor-initiating ability in vivo. Taken together, the results indicate that HGF secreted by prostate CSCs/CICs and prostate myofibroblasts has a role in the maintenance of prostate CSCs/CICs in an autocrine and paracrine fashion.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Transplante Heterólogo
14.
Mod Pathol ; 26(1): 117-24, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22899292

RESUMO

Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumor-initiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P=0.014), pathological N stage (P=0.005) and ALDH1 expression (P=0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (P<0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/metabolismo , Isoenzimas/biossíntese , Retinal Desidrogenase/biossíntese , Fatores de Transcrição SOXB1/biossíntese , Neoplasias Urológicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Família Aldeído Desidrogenase 1 , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Retinal Desidrogenase/análise , Fatores de Transcrição SOXB1/análise , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia
15.
Virchows Arch ; 462(1): 101-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23179762

RESUMO

Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p < 0.001), lymphovascular invasion (p = 0.022) and poor survival with an estimated 5-year CSS probability of 54 % for tumors with nuclear expression of survivin vs. 73 % for those without nuclear expression of survivin (hazard ratio = 2.19; 95 % confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67 %, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/mortalidade , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Urológicas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/metabolismo , Feminino , Humanos , Pelve Renal/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Taxa de Sobrevida , Survivina , Ureter/patologia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/metabolismo
16.
J Urol ; 188(1): 294-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22608744

RESUMO

PURPOSE: Prostate cancer cells include a small population of cancer stem-like/cancer initiating cells, which have roles in cancer initiation and progression. Recently aldehyde dehydrogenase activity was used to isolate stem cells of various cancer and normal cells. We evaluated the aldehyde dehydrogenase activity of the human prostate cancer cell line 22Rv1 (ATCC®) with the ALDEFLUOR® assay and determined its potency as prostate cancer stem-like/cancer initiating cells. MATERIALS AND METHODS: The human prostate cancer cell line 22Rv1 was labeled with ALDEFLUOR reagent and analyzed by flow cytometry. ALDH1(high) and ALDH1(low) cells were isolated and tumorigenicity was evaluated by xenograft transplantation into NOD/SCID mice. Tumor sphere forming ability was evaluated by culturing in a floating condition. Invasion capability was evaluated by the Matrigel™ invasion assay. Gene expression profiling was assessed by microarrays and reverse transcriptase-polymerase chain reaction. RESULTS: ALDH1(high) cells were detected in 6.8% of 22Rv1 cells, which showed significantly higher tumorigenicity than ALDH1(low) cells in NOD/SCID mice (p < 0.05). Gene expression profiling revealed higher expression of the stem cell related genes PROM1 and NKX3-1 in ALDH1(high) cells than in ALDH1(low) cells. ALDH1(high) cells also showed higher invasive capability and sphere forming capability than ALDH1(low) cells. CONCLUSIONS: Results indicate that cancer stem-like/cancer initiating cells are enriched in the ALDH1(high) population of the prostate cancer cell line 22Rv1. This approach may provide a breakthrough to further clarify prostate cancer stem-like/cancer initiating cells. To our knowledge this is the first report of cancer stem-like/cancer initiating cells of 22Rv1 using the aldehyde dehydrogenase activity assay.


Assuntos
Regulação Neoplásica da Expressão Gênica , Isoenzimas/genética , Células-Tronco Neoplásicas/metabolismo , Próstata/enzimologia , Neoplasias da Próstata/genética , RNA Neoplásico/genética , Retinal Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Isoenzimas/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Experimentais , Células-Tronco Neoplásicas/patologia , Próstata/patologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Retinal Desidrogenase/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Int J Clin Oncol ; 17(1): 63-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21607828

RESUMO

BACKGROUND: The aim of this study was to evaluate the distribution of lymph node metastasis in extended lymphadenectomy for patients with bladder cancer. METHODS: We analyzed 31 patients who underwent extended lymphadenectomy at radical cystectomy for bladder cancer between April 2008 and February 2010. Specimens were evaluated as 14 separate packages from predesignated anatomical locations. The lymph node mapping was prospectively registered. RESULTS: The median lymph node count was 37 (range 19-68). Ten (32%) patients had lymph node metastasis. The positive rates at each lymph node site were 0% at the left internal iliac, 13% at the left obturator, 3.2% at the left external iliac, 6.5% at the right internal iliac, 10% at the right obturator, 16% at the right external iliac, 3.2% at the left common iliac, 3.2% at the right common iliac and 6.5% at the presacral node. No lymph node metastasis was detected in the Cloquet, paracaval, aortocaval or paraaortic nodes. One (3.2%) patient had a skip metastasis from the left obturator to the presacral node. CONCLUSIONS: Extended lymphadenectomy provides more accurate lymph node staging. We suggest that it is better to perform lymphadenectomy at least below the aortic bifurcation including the presacral node.


Assuntos
Carcinoma/patologia , Carcinoma/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistectomia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Artéria Mesentérica Inferior , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Bexiga Urinária/patologia , Urotélio/patologia
18.
Int J Urol ; 19(3): 273-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22168748

RESUMO

We reported a new technique for closure of the renal parenchyma in laparoscopic partial nephrectomy, shortening the suturing time. Between 2009 and 2011, 41 patients with renal masses 4 cm or smaller in diameter underwent transabdominal laparoscopic partial nephrectomy by a single surgeon in a single institution. The sutures were carried out using 2-0 vicryl CT-1 with a 1.2 × 1.2 cm piece of felt, and both sutures were temporarily held using a Hem-o-lok. After all sutures (median 3) were completed, they were sequentially fixed by sliding the Hem-o-lok, and then locked using the Lapra-Ty. The median times for suturing the renal parenchyma and ischemic time were 13 min and 28 min, respectively. The arrangement of the wound and hemostasis were good. No patients developed urinoma or postoperative bleeding.


Assuntos
Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Técnicas de Sutura , Suturas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Técnicas de Sutura/efeitos adversos , Fatores de Tempo
19.
Int J Urol ; 18(9): 653-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21790792

RESUMO

OBJECTIVES: The diagnostic value of 3.0-Tesla magnetic resonance imaging (MRI) for prostate cancer remains to be determined. The aim of the present study was to assess the features of prostate cancer detectable by prebiopsy 3.0-Tesla MRI. METHODS: From January 2007 through to December 2008, 116 patients who were examined by prebiopsy 3.0-Tesla MRI underwent radical prostatectomy for localized prostate cancer. Prostate specimens were examined to see whether the largest cancer area was the same as the area indicated on the MRI. Univariate and multivariate logistic regression analyses were conducted to identify variables predictive of agreement between MRI and histopathological findings. RESULTS: Sixty-six (56.9%) patients were suspected of having prostate cancer on the basis of MRI findings. In 49 of these patients (74.2%), it was considered that there was agreement between the abnormal area on the MRI and the index tumor. Univariate analysis revealed that there were significant differences in abnormal digital rectal examination, capsular penetration, the diameter of the index tumor of the radical prostatectomy specimen, and the Gleason scores of the biopsy and radical prostatectomy specimens. Multivariate analysis revealed that the Gleason score of the radical prostatectomy specimen was associated with the accurate detection of the prostate cancer by MRI (P = 0.0177). CONCLUSIONS: In conclusion, 3.0-Tesla MRI tends to accurately diagnose prostate cancer with high tumor burden and aggressiveness. Multimodal examination (T2-weighted imaging, dynamic contrast-enhanced imaging, and diffusion-weighted imaging) is recommended for the diagnosis of prostate cancer using 3.0-Tesla MRI.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Gradação de Tumores/métodos , Cuidados Pré-Operatórios/métodos , Neoplasias da Próstata/patologia , Idoso , Biópsia , Imagem de Difusão por Ressonância Magnética/normas , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/normas , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/normas , Prostatectomia , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos Testes , Estudos Retrospectivos
20.
Int J Urol ; 17(5): 492-5, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20415710

RESUMO

Among 294 patients who underwent laparoscopic radical prostatectomy (LRP), five (1.7%) developed complications such as rectal injury (RI) and rectourethral fistula (RUF). In four patients, the RI was immediately repaired by placing two layers of uninterrupted sutures without fecal diversion. The RI in two of these four patients were diagnosed using a transrectally inserted Hegar uterine dilator (26 mm). The remaining patients, who presented with RUF as the primary manifestation, were conservatively managed, and the fistulas closed spontaneously. Most of the RI detected during the operation were managed with primary fistula closure without fecal diversion. In some cases of postoperative RUF, spontaneous closure may occur while the patient is waiting for surgical repair.


Assuntos
Complicações Intraoperatórias/cirurgia , Laparoscopia/efeitos adversos , Prostatectomia/efeitos adversos , Reto/lesões , Reto/cirurgia , Idoso , Humanos , Complicações Intraoperatórias/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Fístula Retal/diagnóstico , Fístula Retal/cirurgia , Remissão Espontânea , Fístula Urinária/diagnóstico , Fístula Urinária/cirurgia
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