Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20.592
Filtrar
1.
Medicine (Baltimore) ; 98(42): e17075, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626080

RESUMO

Motion-induced artifacts have been a major drawback in bladder cancer imaging. This study is to evaluate the clinical utility of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) acquisition in improving motion-induced artifacts in T2-weighted (T2W) magnetic resonance imaging (MRI) of bladder cancer at 3T.Sixteen patient MRI exams were included. Using a Likert scale, 2 radiologists independently scored T2W data without and with PROPELLER in terms of artifact severity and tumor visualization. Statistical analysis was done to assess the image quality improvement by PROPELLER and inter-observer variability.Without PROPELLER, the median scores of artifact severity and tumor visualization were 1.5 and 1.5 for reviewer 1, and 2.0 and 2.0 for reviewer 2. With PROPELLER, the scores increased to 3 and 3.5 for reviewer 1, and 3.5 and 3.5 for reviewer 2. Despite the inter-observer variability (κ scores < 0.2), both reviewers found significant improvement in artifacts and visualization (all P < .001).PROPELLER acquisition significantly improved the image quality of T2W-MRI. These initial findings indicate that this technique should be utilized in clinical MRI of the bladder.


Assuntos
Artefatos , Carcinoma de Células de Transição/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Movimento (Física) , Variações Dependentes do Observador , Estudos Prospectivos , Melhoria de Qualidade , Neoplasias da Bexiga Urinária/patologia
2.
Medicine (Baltimore) ; 98(43): e17572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651858

RESUMO

RATIONALE: Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in children with high malignancy. The prognosis of refractory recurrent RMS is extremely poor, and the 5-year survival rate is less than 20%. PATIENT CONCERNS: We reported a 2-year-old male patient with RMS who underwent 3 operations and 2 recurrences while being treated with regular multidisciplinary therapy. DIAGNOSES: A diagnosis of embryonal rhabdomyosarcoma with primary bladder (IIIa, TNM stage 2, and medium risk group) was made. INTERVENTIONS: After repeated recurrence, the patient was treated with chimeric antigen receptor T (CAR-T) cells, which had a safety mechanism and specifically bound the CD56 antigen in the fourth generation. OUTCOMES: The process of CAR-T cell transfusion was smooth, and there were no significant cytokine release syndrome manifestations after reinfusion. The patient was in complete remission at last follow-up visit after 3.5 years. CONCLUSION: CD56-CAR-T cell therapy is a safe and effective approach and may be an option for children with solid tumors who are nonresponsive to conventional radiotherapy and chemotherapy, or are unsuitable for hematopoietic stem cell transplantation.


Assuntos
Antígeno CD56/imunologia , Imunoterapia Adotiva/métodos , Recidiva Local de Neoplasia/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Rabdomiossarcoma/terapia , Neoplasias da Bexiga Urinária/terapia , Pré-Escolar , Seguimentos , Humanos , Masculino , Indução de Remissão , Rabdomiossarcoma/patologia , Neoplasias da Bexiga Urinária/patologia
3.
Pan Afr Med J ; 33: 184, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31565144

RESUMO

We here report a case of bladder urothelial carcinoma, a rare tumor in subjects less than 40 years, as well as our therapeutic experience. The study involved a 37-year old patient with a history of urinary tract infection and of staying at a riparian area (bilharzia) presenting with hypogastralgia and total macroscopic hematuria. Clinical and paraclinical assessment showed voluminous bladder mass suggesting infiltrative tumor without local or distant lymph node or organic involvement. Surgical management was based on resection of bladder tumor and biopsy followed by total cystectomy with substitutive ileal enterocystoplasty. The postoperative course was uneventful. The patient also underwent adjuvant chemotherapy and vitamin B-12 therapy. Clinical and paraclinical assessment, performed after 6 and 12 months, showed no recurrence.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adulto , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Quimioterapia Adjuvante/métodos , Seguimentos , Humanos , Íleo/cirurgia , Masculino , Recidiva Local de Neoplasia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Vitamina B 12/administração & dosagem
4.
Orv Hetil ; 160(42): 1647-1654, 2019 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-31608691

RESUMO

Current advances in molecular techniques and bioinformatics allowed the analysis of complex molecular patterns in various cancers including muscle-invasive bladder cancer. As a consequence, in the last few years numerous gene- and protein expression-based molecular classifications have been recommended. Recently a comprehensive consensus classification for muscle-invasive urothelial bladder cancer has been published, distinguishing 6 subgroups with a potential impact on clinical decision-making. At the same time, the therapeutic landscape of muscle-invasive bladder cancer becomes increasingly differentiated as novel checkpoint inhibitors have been available for cisplatin-ineligible and/or resistant patients. Furthermore, promising results have been obtained with FGFR targeting agents. Therefore, molecular subtyping will probably have a crucial role in individualized therapeutic decision-making in bladder cancer. In the present work, we summarize the evolution, recent advances and potential therapeutic relevance of molecular subclassifications in bladder cancer. Orv Hetil. 2019; 160(42): 1647-1654.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/terapia , Cisplatino/uso terapêutico , Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Urotélio/patologia , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma de Células de Transição/patologia , Terapia Combinada , Humanos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
5.
Medicine (Baltimore) ; 98(36): e16873, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490371

RESUMO

At present, intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is recommended for prophylaxis purposes after transurethral resection of bladder tumor, but has chances of recurrence. Radical cystectomy reduces the risk of recurrence in bladder cancer patients, but may have chances of postoperative complications. The objective of the study was to test the hypothesis that radical cystectomy has overtreatment and definitive BCG immunotherapy has undertreatment in intermediate or high-risk nonmuscle invasive bladder cancer patients. Data regarding biopsies, ultrasound, the computed tomography scan, adopted treatment strategy, treatment-emergent adverse effect, and a follow-up period of 312 patients with confirmed nonmuscle invasive bladder cancer (pTa, pTis, or pT1 stage; intermediate or high-risk cancer) were reviewed. Patients who had received definitive intravesical BCG immunotherapy were included in BCG group (n = 210) and those who underwent radical cystectomy were included in RXC group (n = 87). Clinical decision-making for treatment strategies was evaluated for both groups. Cystitis was frequently observed in all patients who received BCG immunotherapy. In RXC group, ileus was frequently observed in all patients in early days after the operation. During 2 years of the follow-up period, biopsies, ultrasound, and the computed tomography scan reported that BCG group had fewer numbers of negative cancer patients after treatment than the RXC group after surgery (P < .0001). Total expenditure for BCG immunotherapy was higher than radical cystectomy (22,945 ±â€Š945 ¥/patient vs 17,985 ±â€Š545 ¥/patient; P < .0001). Definitive BCG immunotherapy had undertreatment and radical cystectomy had overtreatment for intermediate or high-risk invasive bladder cancer patients (level of evidence III).


Assuntos
Vacina BCG/uso terapêutico , Cistectomia/estatística & dados numéricos , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Adolescente , Adulto , Idoso , Vacina BCG/efeitos adversos , Vacina BCG/economia , Análise Custo-Benefício , Cistectomia/efeitos adversos , Cistectomia/economia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Imunoterapia/economia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores Socioeconômicos , Neoplasias da Bexiga Urinária/patologia , Adulto Jovem
6.
J Cancer Res Clin Oncol ; 145(11): 2649-2661, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529191

RESUMO

PURPOSE: The incidence of Urothelial carcinoma of bladder (UBC) is gradually increasing by changing lifestyle and environment. The development of a tumor has been noted to be accompanied by modifications in the extracellular matrix (ECM) consisting of CD44, hyaluronic acid (HA) and its family members. The importance of CD44 splice variants and HA family members has been studied in UBC. METHODS: The cohort of study included 50 UBC patients undergoing radical cystectomy and 50 healthy subjects. The molecular expression of CD44 and HA family members was determined. Effect of CD44 variant-specific silencing on downstream signaling in HT1376 cells was investigated. Combinatorial treatment of 4-MU (4-methylumbelliferone) with cisplatin or doxorubicin on chemosensitivity was also explored. RESULTS: Higher expression of HA, HAS2, and CD44 was observed in Indian UBC patients which also showed the trend with severity of disease. Splice variant assessment of CD44 demonstrated the distinct role of CD44v3 and CD44v6 in bladder cancer progression. shRNA-mediated downregulation of CD44v3 showed an increase effect on cell cycle, apoptosis and multiple downstream signaling cascade including pAkt, pERK and pSTAT3. Furthermore, 4-MU, an HA synthesis inhibitor, observed to complement the effect of Cisplatin or Doxorubicin by enhancing the chemosensitivity of bladder cancer cells. CONCLUSIONS: Our findings exhibit involvement of CD44 splice variants and HA family members in UBC and significance of 4-MU in enhancing chemosensitivity suggesting their novel therapeutic importance in disease therapeutics.


Assuntos
Processamento Alternativo , Receptores de Hialuronatos/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias da Bexiga Urinária/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Apoptose , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Transcrição STAT3/genética , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
7.
Anticancer Res ; 39(9): 4767-4773, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519577

RESUMO

BACKGROUND/AIM: Rs3824129 is a functional six-nucleotide insertion(I)/deletion(D) polymorphism in the promoter region of caspase 8, an essential apoptosis gene. We aimed to examine the association of this polymorphism with the risk of bladder cancer in the Taiwanese population. MATERIALS AND METHODS: Caspase-8 rs3834129 genotypes were determined and their associations with bladder cancer risk were evaluated among 375 patients and 375 controls by the PCR-RFLP methodology. In addition, the interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were examined. RESULTS: The frequencies of II, ID and DD genotypes for caspase-8 rs3834129 were non-differentially distributed between the two groups (p for trend=0.7187). Analysis of allelic frequency distribution also indicated that the D variant allele was not associated with a risk of bladder cancer. There was no obvious joint interaction between caspase-8 rs3834129 genotypes and smoking, alcohol consumption, and clinical stage and grade. CONCLUSION: Caspase-8 rs3834129 genotypes play a minor role in the personal susceptibility to bladder cancer in Taiwan.


Assuntos
Caspase 8/genética , Predisposição Genética para Doença , Genótipo , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Taiwan , Neoplasias da Bexiga Urinária/patologia
8.
J Cancer Res Clin Oncol ; 145(9): 2261-2271, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31367836

RESUMO

PURPOSE: To investigate the role of sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) in bladder cancer progression and invasion. METHODS: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. RESULTS: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. CONCLUSIONS: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Proteínas Hedgehog/fisiologia , Neoplasias Musculares/secundário , Neoplasias da Bexiga Urinária/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Musculares/metabolismo , Invasividade Neoplásica , Transdução de Sinais/fisiologia , Neoplasias da Bexiga Urinária/metabolismo
9.
Anticancer Res ; 39(8): 4325-4328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366524

RESUMO

BACKGROUND/AIM: The significance of second transurethral resection (TUR), and identification of predictive factors for residual cancer remain unrevealed. This study aimed to find residual cancer and up-staging rates, as well as predictive factors for residual cancer, in patients who undergo second TUR for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent second TURs for NMIBC between 2015 and 2017, were included in the study and their clinicopathological characteristics were analyzed for predictors of residual cancer. RESULTS: Among 143 Japanese patients whose tumors were initially diagnosed as high-risk NMIBC, residual cancers detected at second TURs were, Tis: n=22 (15.4%), Ta: n=15 (10.5%) and T1: n=29 (20.3%). No patients showed up-staging from NMIBC to MIBC. The presence of carcinoma-in situ at initial TUR was an independent risk factor for any residual cancer (Tis, Ta and T1), non-flat residual cancer (Ta and T1), and flat residual cancer (Tis). CONCLUSION: The presence of carcinoma-in situ is suggested to be an independent predictor of residual cancer. This may help guide decisions to perform second TUR.


Assuntos
Carcinoma in Situ/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Cistectomia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Fatores de Risco , Resultado do Tratamento , Uretra/patologia , Uretra/cirurgia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos
10.
Urologe A ; 58(9): 1093-1106, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31399775

RESUMO

Follow-up care of patients with muscle-invasive bladder cancer is subdivided into oncological and functional surveillance. More than 80% of local relapses and distant metastases occur within the first 2 years. Recurrences in the remnant urothelium also occur several years after radical cystectomy. Urinary cytology and a computed tomography (CT) scan of the abdomen and thorax including a urography phase are the standard diagnostics for tumor follow-up. There is no clear evidence for a survival benefit for the detection of asymptomatic vs. symptomatic recurrences. After partial cystectomy or trimodal treatment, there is no established follow-up schedule; however, the relatively high incidence of intravesical recurrences should be considered as there are curative treatment approaches including salvage cystectomy. Functional surveillance, which should be carried out lifelong, encompasses prevention and diagnostics of metabolic complications, urethral/ureteral strictures, problems with the urinary stoma, urinary incontinence, sexual dysfunction and urinary tract infections.


Assuntos
Carcinoma de Células de Transição/patologia , Citodiagnóstico/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Cistectomia , Seguimentos , Humanos
11.
Expert Opin Investig Drugs ; 28(9): 757-770, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31412742

RESUMO

Introduction: The current first line therapy for high grade (HG) non-muscle invasive bladder cancer (NMIBC) is intravesical Bacillus Calmette-Guerin (BCG). Patients who recur or progress despite BCG are recommended to undergo radical cystectomy or participate in clinical trials. There is an urgent need for alternative therapies in the BCG-unresponsive NMIBC realm. Areas covered: We queried clinicaltrials.gov and pubmed.gov for current and recently completed early clinical trials pertaining to investigational agents used for the treatment of BCG-unresponsive NMIBC. These included intravesical chemotherapy, immunotherapy, vaccines, gene therapy, viruses, and agents used with novel drug delivery methods. In this article, we discuss the treatment guidelines for non-muscle invasive bladder cancer and therapeutic approaches under investigation in clinical trials. Expert opinion: The FDA is currently allowing single-arm studies as a pathway for approval in BCG-refractory patients with CIS. Although many agents are currently undergoing testing, none have been approved since Valrubicin. Hopefully, we will identify therapies sufficiently effective and durable to achieve FDA approval. Other considerations in this realm include the use of biomarkers in NMIBC to identify patients who will most likely respond to specific interventions. In addition, as systemic agents such as checkpoint inhibitors, are studied further, a multidisciplinary approach may be needed to treat this subset of patients.


Assuntos
Antineoplásicos/farmacologia , Drogas em Investigação/farmacologia , Neoplasias da Bexiga Urinária/terapia , Animais , Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Biomarcadores Tumorais/metabolismo , Cistectomia/métodos , Sistemas de Liberação de Medicamentos , Drogas em Investigação/administração & dosagem , Humanos , Imunoterapia/métodos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/patologia
12.
Oncol Rep ; 42(4): 1431-1440, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364745

RESUMO

Jumonji domain­containing protein 2A (JMJD2A) has been identified to promote cell proliferation in bladder cancer; however, it remains undetermined whether JMJD2A regulates cell migration and invasion in bladder cancer. The aim of the present study was to further investigate the roles of JMJD2A in bladder cancer. The expression levels of JMJD2A in bladder cancer tissues and cell lines were established by RT­qPCR assays and western blot analysis. Moreover, by gain­ and loss­of­function assays, the effects of JMJD2A on migration and invasion as well as proliferation were investigated in bladder cancer cells. The results revealed that the expression level of JMJD2A was significantly upregulated in bladder cancer tissues and cell lines compared to adjacent non­tumor tissues and a human immortalized bladder urothelial cell line. Kaplan­Meier survival analysis indicated that patients with high JMJD2A expression level had shorter overall survival. Moreover, JMJD2A could promote cell migration and invasion by facilitating epithelial­mesenchymal transition (EMT) in bladder cancer. In addition, it was determined that JMJD2A promoted EMT through regulation of SLUG expression. Collectively, our findings revealed that JMJD2A may act as an oncogene and participate in bladder cancer progression, which provides a promising therapeutic strategy for patients with bladder cancer.


Assuntos
Histona Desmetilases com o Domínio Jumonji/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal , Humanos , Histona Desmetilases com o Domínio Jumonji/biossíntese , Histona Desmetilases com o Domínio Jumonji/genética , Gradação de Tumores , Invasividade Neoplásica , Fatores de Transcrição da Família Snail/genética , Transcrição Genética , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
13.
Cancer Sci ; 110(10): 3235-3243, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368627

RESUMO

Cytology is widely conducted for diagnosis of urothelial bladder cancer; however, its sensitivity is still low. Recent studies show that liquid biopsies can reflect tumor genomic profiles. We aim to investigate whether plasma or urine is more suitable for detecting tumor-derived DNA in patients with early-stage urothelial bladder cancer. Targeted sequencing of 71 genes was carried out using a total of 150 samples including primary tumor, urine supernatant, urine precipitation, plasma and buffy coat from 25 patients with bladder cancer and five patients with cystitis and benign tumor. We compared mutation profiles between each sample, identified tumor-identical mutations and compared tumor diagnostic sensitivities between urine and conventional cytology. We identified a total of 168 somatic mutations in primary tumor. In liquid biopsies, tumor-identical mutations were found at 53% (89/168) in urine supernatant, 48% (81/168) in urine precipitation and 2% (3/168) in plasma. The high variant allele fraction of urine was significantly related to worse clinical indicators such as tumor invasion and cytological examination. Although conventional cytology detected tumor cells in only 22% of non-invasive tumor, tumor diagnostic sensitivity increased to 67% and 78% using urine supernatant and precipitation, respectively. Urine is an ideal liquid biopsy for detecting tumor-derived DNA and more precisely reflects tumor mutational profiles than plasma. Genomic analysis of urine is clinically useful for diagnosis of superficial bladder cancer at early stage.


Assuntos
Biomarcadores Tumorais/urina , Mutação , Análise de Sequência de DNA/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Urina/química , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urina
14.
Cancer Sci ; 110(10): 3315-3327, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385407

RESUMO

Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle-invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony-stimulating factor (GM-CSF) to chemoimmunotherapy with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 105 MBT2 cells s.c. in C3H mice to create a syngeneic animal model of local recurrence (LR). When the tumor diameter reached 12 mm, the mice were allocated randomly as follows: (i) non-treated control (vehicle only); (ii) anti-mPD-L1 monotherapy; (iii) mGM-CSF monotherapy; (iv) anti-mPD-L1 plus mGM-CSF; (v) gemcitabine and cisplatin (GC); (vi) GC plus anti-mPD-L1; (vii) GC plus mGM-CSF; and (viii) GC plus anti-mPD-L1 plus mGM-CSF. After completing 2-week neoadjuvant therapy, tumors were resected for resection margin evaluation and immunohistochemical staining and blood was collected for flow cytometry and ELISA. Operative wounds were sutured, and the operative site was monitored to detect LR. Addition of anti-mPD-L1 and mGM-CSF to neoadjuvant GC chemotherapy enhanced the antitumor effect and reduced positive resection margins (50% vs 12.5%). Combination of GC, anti-mPD-L1, and mGM-CSF resulted in longer LR-free survival and cancer-specific survival compared to those in other groups. These effects involved an immunotherapy-related decrease in oncological properties such as tumor invasion capacity and epithelial-mesenchymal transition. mGM-CSF significantly decreased the accumulation of myeloid-derived suppressor cells in both the blood and tumor microenvironment and blood interleukin-6 levels. Supplementary GM-CSF to neoadjuvant GC plus PD-L1 blockade could decrease LR after radical surgery by immune modulation in the blood and tumor microenvironment.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Recidiva Local de Neoplasia/terapia , Neoplasias da Bexiga Urinária/terapia , Animais , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Terapia Combinada , Cistectomia , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Margens de Excisão , Camundongos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/imunologia , Distribuição Aleatória , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Medicine (Baltimore) ; 98(35): e16576, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464892

RESUMO

OBJECTIVES: G protein-coupled receptor 137 (GPR137) was reported to be associated with several cancers, but its role in bladder cancer has not been reported. The purpose of this study was to evaluate clinical significance of GPR137 in bladder cancer. METHODS: The expressions of GPR137 in pathological tissues and corresponding normal tissues from bladder cancer patients were detected via quantitative real time polymerase chain reaction (qRT-PCR). Western blot was performed to detect GPR137 expression in bladder cancer tissues and adjacent normal tissues. Chi-Squared test analyzed the relationship between GPR137 expression and clinical features of bladder cancer patients. Additionally, Kaplan-Meier method was adopted in estimating overall survival of bladder cancer patients. Prognostic value of GPR137 was evaluated through Cox regression analysis. RESULTS: The expression of GPR137 mRNA and protein in pathological tissues was significantly higher than that in adjacent normal tissues (P < .001). Moreover, similar result was found for bladder cancer patients and healthy controls (P < .001). And GPR137 expression was associated with tumor size (P = .006) and TNM stage (P = .012). The results of Kaplan-Meier analysis suggested that patients with high expression of GPR137 had shorter overall survival time than those with low expression (Log rank test, P = .001). Cox regression analysis indicated that GPR137 could act as an independent biomarker for bladder cancer prognosis (HR = 1.850, 95% CI = 1.272-2.689, P = .001). CONCLUSION: Abnormal expression of GPR137 is associated with bladder cancer and GPR137 is a potential biomarker for the therapy and prognosis of bladder cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Regulação para Cima , Neoplasias da Bexiga Urinária/metabolismo , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Acoplados a Proteínas-G/genética , Análise de Sobrevida , Carga Tumoral , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
16.
Chem Biodivers ; 16(10): e1900334, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31448497

RESUMO

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin. The combination of CER+cDDP inhibited cell migration on T24 cells. CER+cDDP down-regulated MMP-2/9 and p-ERK1/2, while it increased EGFR activity corroborating the observed cell migration inhibition. Down-regulation of Bcl-2 and up-regulation pro-apoptotic Bax and further depletion of the mitochondrial membrane potential (ΔΨm) indicates that mitochondria play a central role in the combination treatment inducing the mitochondrial signaling pathway of apoptosis in T24 cells. Our data showed that the alkaloid cernumidine is worthy of further studies as a chemosensitizing agent to be used in complementary chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ácidos Cafeicos/farmacologia , Guanidinas/farmacologia , Solanum/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Guanidinas/química , Guanidinas/isolamento & purificação , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Folhas de Planta/química , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
17.
Cancer Radiother ; 23(6-7): 732-736, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31400955

RESUMO

When localized, the reference treatment of urothelial, muscle-invasive bladder tumours relies on radical cystectomy with reconstruction by enterocystoplasty if possible or Bricker bypass. Trimodal therapy combining transurethral resection of the tumour followed by concomitant chemotherapy may be considered as a therapeutic alternative to radical cystectomy in well-selected patients with unifocal tumours, stage T2, non-diverticular location, without in situ carcinoma or hydronephrosis and with macroscopically complete transurethral resection. The functional prognosis of the bladder and quality of life should be discussed with the patient as well as the need for salvage surgery for persistent tumour at a 45-Gy dose level, the latter being a highly unfavourable prognosis factor. On the other hand, this trimodal treatment is the reference in case of surgical contraindication. This article details the methods and results of the main series available in the literature in terms of local control, survival, bladder preservation rates and complications, as well as study prospects.


Assuntos
Quimiorradioterapia/métodos , Tratamentos com Preservação do Órgão/métodos , Neoplasias da Bexiga Urinária/terapia , Bexiga Urinária , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Cistectomia/métodos , Humanos , Qualidade de Vida , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia
18.
Medicine (Baltimore) ; 98(32): e16451, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393349

RESUMO

Early diagnose of bladder cancer could lead to good prognosis and high 5-year-survival rate. Among bladder cancer, about 75% patients with were nonmuscle-invasive bladder cancer (NMIBC). Patients were painful and easily get infected during bladder cancer diagnosis, which mainly depends on invasive cystoscopy and low-sensitivity urine exfoliation cytology. Meanwhile, relapse after surgery was also becoming the major problem for patients. Exploring noninvasive, high-sensitivity, and painless method is very important and meaningful for NMIBC treatment.Firstly, we found potential related gene mutation sites for NMIBC by searching COSMIC database and related study. Urinary sediment cells of patients both in normal group (patients with benign) and NMIMC group were collected before and after operation for potential gene mutation site detecting. Meanwhile, the urinary sediment cells of relapse patients and good prognosis people in NMIBC group after surgery were also collected for further Gene mutation detection and NMIBC relapse after surgery prediction.Fourteen genes (152 mutation sites) were selected between 95 NMIBC patients and 67 control patients, which were FGFR3, TP53, PIK3CA, and others. Compared with control group, mutation ratio of above 14 genes was higher in NMIBC group. NMIBC diagnose model was established by 5 times cross-validation and had a good effects, which included the all mutation site in FGFR3, TP53, PIK3CA, ARID1A, STAG2, and KTM2D. On the contrary, the relapse rate was 30.5% among 95 patients for about 1.5-year follow-up time. Compared with control group, smoking rate and tumor grade were higher in relapse group. Meanwhile, mutation rate of FGFR3, TP53, PIK3CA, ERBB3, and TSC1 in relapse group were higher than that in normal group. According to the mutation sites of FGFR3, TP53, PIK3CA, and ERBB3 and the combination of urinary sediment cells genetic mutation and relapse status, a predicted model for NMIBC relapse was also established, which had 90% accuracy.The diagnosed NMIBC model (based on FGFR3, TP53, PIK3CA, ARID1A, STAG2, and KTM2D gene mutation) and predicted relapse model (based on FGFR3, TP53, PIK3CA, and ERBB3 gene mutation) possess high accuracy and would be applied in early diagnose and early predicting relapse of patients.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Proteína Supressora de Tumor p53/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia
19.
J Enzyme Inhib Med Chem ; 34(1): 1380-1387, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401884

RESUMO

Novel sulfonamide-dithiocarbamate hybrids were designed and synthesised via the molecular hybridisation strategy. Among them, compound 13d displayed a potent activity with IC50 values of 0.9, 0.7, 1.9 and 2.6 µM against UM-UC-3, RT-112, RT4 and T24. Compound 13d inhibited the migration and regulated the migration-related markers (E-cadherin, N-cadherin, Vimentin, Snail and Slung) against RT-112 cells in a concentration dependent manner. By the tubulin polymerisation assay in vitro and immunostaining assay, compound 13d was identified as a novel tubulin polymerisation inhibitor. Intragastric administration of compound 13d could inhibit the growth of RT-112 cells in vivo in a xenograft mouse model with the low toxicity, indicating that it may be a leading candidate with antitumor properties to treat bladder cancer.


Assuntos
Antineoplásicos/farmacologia , Sulfonamidas/farmacologia , Moduladores de Tubulina/farmacologia , Neoplasias da Bexiga Urinária/patologia , Animais , Antineoplásicos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectrometria de Massas , Camundongos , Camundongos Nus , Espectroscopia de Prótons por Ressonância Magnética , Sulfonamidas/química , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Medicine (Baltimore) ; 98(27): e16009, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277094

RESUMO

Bladder cancer is one of the most common malignancies of urinary tract. The current study aimed to investigate the role of insulin-like growth factor II messenger RNA binding protein 3 (IMP3) expression in the prognostic evaluation of non-muscle- invasive urothelial carcinoma of the bladder.Immunohistochemistry (IHC) was carried out to examine IMP3 protein expression in specimens from 183 cases of non-muscle-invasive urothelial carcinoma, 20 cases of muscle-invasive urothelial carcinoma and 20 benign tissues adjacent to cancer tissue.The expression of IMP3 was not detected in the adjacent benign tissues. The expression intensity of IMP3 in muscle-invasive samples was significantly higher than that in non-muscle-invasive urothelial carcinoma specimens (P = .008). IMP3 expression was significantly related with advanced tumor stage (P < .001), advanced tumor grade (P = .004), and tumor recurrence (P < .001) in non-muscle-invasive urothelial carcinomas. Kaplan-Meier analysis showed that IMP3-positive patients had much lower disease-free (P < .001), progression-free (P = .002) and metastasis-free (P = .019) survival rates compared with those with IMP3-negative tumors. By multivariable Cox analysis, we also found that IMP3 expression in non-muscle- invasive urothelial carcinomas proved to be an independent unfavorable prognostic factor of disease-free survival (HR: 2.52; 95% CI, 1.39-4.56; P = .002), progression- free survival (HR: 5.19; 95% CI, 1.54-17.46; P = .008) and metastasis-free survival (HR: 4.87; 95% CI, 1.08-22.02; P = .040).Our results demonstrate that the expression of IMP3 in non-muscle- invasive bladder cancer can serve as an independent predictor that will help recognize the subgroup of patients with a high ability to relapse, progress, and metastasize and who might get the maximum benefit from an early and more aggressive treatment strategy.


Assuntos
Carcinoma de Células de Transição/genética , Proteínas de Ligação a RNA/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Modelos de Riscos Proporcionais , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA