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1.
Nat Commun ; 11(1): 4858, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978382

RESUMO

Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none of the reported biomarkers for predicting response have been implemented in the clinic. Here we perform a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy (neoadjuvant or first-line) to identify molecular changes associated with treatment response. DNA-based associations with response converge on genomic instability driven by a high number of chromosomal alterations, indels, signature 5 mutations and/or BRCA2 mutations. Expression data identifies the basal/squamous gene expression subtype to be associated with poor response. Immune cell infiltration and high PD-1 protein expression are associated with treatment response. Through integration of genomic and transcriptomic data, we demonstrate patient stratification to groups of low and high likelihood of cisplatin-based response. This could pave the way for future patient selection following validation in prospective clinical trials.


Assuntos
Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Biomarcadores Tumorais , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Metilação de DNA , Tratamento Farmacológico , Instabilidade Genômica , Humanos , Mutação , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Transcriptoma , Neoplasias da Bexiga Urinária/patologia
2.
Anticancer Res ; 40(9): 5221-5227, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878810

RESUMO

BACKGROUND/AIM: Bladder cancer (BLCA, urothelial bladder cancer) is one of the most common malignancies with increasing incidence and mortality worldwide. Poor diagnosis and the limitation of treatment is still an unmet need in clinical practice. γδ T-Cells have been paid increasing attention because of their potent cytotoxicity against tumors. Herein, we investigated the cytolytic effect of γδ T-cells in combination with the chemotherapeutic drug, carboplatin, against BLCA cells. MATERIALS AND METHODS: The standard protocol for the induction and expansion of peripheral blood mononuclear cell-derived γδ T-cells was a zoledronic acid/interleukin-2-based medium system for 2 weeks. The cytotoxicity of γδ T-cells with and without carboplatin against BLCA cells was examined. RESULTS: After incubation, T-cell receptor-positive γδ T-cells showed a natural killer cell-like phenotypic characteristic and dose-dependently increased cytotoxicity against BLCA cells. Interestingly, we found that in advanced BLCA cells, which were more resistant to carboplatin, the cell viability was significantly (p<0.05) reduced in the presence of γδ T-cells. CONCLUSION: Our findings showed that γδ T-cell therapy has potent benefit in cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Carboplatina/farmacologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Neoplasias da Bexiga Urinária/patologia
3.
Anticancer Res ; 40(10): 5861-5868, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988916

RESUMO

AIM: To evaluate our experience with radical radiotherapy and chemotherapy in patients with muscle-invasive bladder cancer. PATIENTS AND METHODS: The study consisted of 27 patients treated with cisplatin-based chemoradiation (CCRT), 48 treated with radiation alone (RT), and 42 with locally advanced disease treated with neoadjuvant chemotherapy and radiation (neoCRT). RESULTS: The incidence of acute grade 3 or more genitourinary (GU) toxicity in the RT, CCRT and neoCRT groups was: 25%, 11% and 19%, respectively (p=0.029). The 3-year freedom from grade 2 or more GU toxicity was: 81%, 89%, 54%, respectively (p=0.36). The long-term outcomes of 3-year local control, overall survival, and disease-free survival were as follows: RT group: 74%, 61% and 55%; CCRT group: 76%, 76% and 56%; neoCRT group: 31%, 43% and 18%, respectively. CONCLUSION: The preferable bladder-conserving approach is CRT, however RT alone might also be an option for appropriately selected patients. NeoCRT for those with locally advanced tumors remain unsatisfactory; adequate selection of patients for radical treatment is of importance.


Assuntos
Cisplatino/uso terapêutico , Músculo Esquelético/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
4.
Cancer Treat Rev ; 89: 102072, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32769039

RESUMO

BACKGROUND: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients. METHODS: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines. Systematic literature reviews were conducted to identify evidence from randomized controlled trials (RCTs) of chemotherapy for patients with previously untreated, unresectable, stage IV UC. Searches included congress databases and articles published between 1990 and 2018. In order to align with the latest treatment paradigms in first-line advanced UC, a focused literature search was conducted to identify evidence supporting immuno-oncology (IO) agents. RESULTS: For advanced UC, guidelines universally recommend cisplatin-based chemotherapy as first-line treatment for eligible patients and carboplatin-based regimens for those unfit to receive cisplatin. Despite the evaluation of a number of different cytotoxic regimens over the years, including triplet combinations, survival outcomes have not improved markedly with chemotherapy. Median overall survival with standard of care chemotherapy is ~13 months. Based on the results of single-arm, phase II studies, recent treatment guidelines have included atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD-1) as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1. However, emerging evidence from RCTs of IO agents, including both cisplatin-eligible and cisplatin-ineligible patients, suggest that survival times exceeding 20 months are possible. CONCLUSIONS: After having reached a plateau with chemotherapy, the treatment landscape for advanced UC is evolving. Survival outcomes for patients with advanced UC are improving with treatment modalities involving IO agents.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Bexiga Urinária/patologia
5.
Life Sci ; 258: 118154, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735882

RESUMO

AIMS: Epithelial-to-mesenchymal transition (EMT) facilitates cell migration and invasion, and contributes to metastasis in bladder cancer. Within the perioperative period, anesthetic such as isoflurane have been found to affect cancer prognosis. In the study, we reported the tumor-promoting effect of isoflurane in bladder cancer. MATERIALS AND METHODS: Human bladder cancer cell lines T24 and BIU-87 were exposed to isoflurane at different concentrations. The immunofluorescent staining of Ki67, Annexin V-FITC/PI staining, Transwell invasion assays and wound-healing assays were performed to assess cell proliferation, apoptosis, invasion and migration. Expressions of EMT markers (E-cadherin, N-cadherin and Vimentin) and metastatic markers (Snail-1, Slug-1 and MMP-2/9) were determined by immunoblotting. Orthotopic tumor models and mice given tail vein injection of T24 cells were developed with or without 4-h exposure to 2% isoflurane. KEY FINDINGS: We found isoflurane promoted bladder cancer cell proliferation, invasion and migration but reduce apoptosis in a concentration-dependent manner. In addition, isoflurane was shown to increase HIF-1α and its nuclear accumulation in bladder cancer cells. HIF-1α knockdown inhibited bladder cancer cell proliferation and delayed EMT, which was reversed in the presence of 4-h exposure to 2% isoflurane. Likewise, we found isoflurane modulated ß-catenin/Notch1 pathways via HIF-1α. In vivo studies showed that isoflurane exposure accelerated formation of orthotopic bladder tumor and promoted hepatic metastases from carcinoma of the bladder. SIGNIFICANCE: Taken together, our study demonstrates that a frequently used anesthetic can exert a protumorigenic effect on bladder cancer. Isoflurane may serve as an important contributory factor to high recurrence following surgery.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Isoflurano/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/induzido quimicamente , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Receptor Notch1/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , beta Catenina/metabolismo
6.
PLoS One ; 15(8): e0237976, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822399

RESUMO

Environmental exposure to arsenite (As3+) has a strong association with the development of human urothelial cancer (UC) and is the 5th most common cancer in men and the 12th most common cancer in women. Muscle invasive urothelial cancer (MIUC) are grouped into basal or luminal molecular subtypes based on their gene expression profile. The basal subtype is more aggressive and can be associated with squamous differentiation, characterized by high expression of keratins (KRT1, 5, 6, 14, and 16) and epidermal growth factor receptor (EGFR) within the tumors. The luminal subtype is less aggressive and is predominately characterized by elevated gene expression of peroxisome proliferator-activated receptor- gamma (PPARγ) and forkhead box protein A1 (FOXA1). We have previously shown that As3+-transformed urothelial cells (As-T) exhibit a basal subtype of UC expressing genes associated with squamous differentiation. We hypothesized that the molecular subtype of the As-T cells could be altered by inducing the expression of PPARγ and/or inhibiting the proliferation of the cells. Non-transformed and As-T cells were treated with Troglitazone (TG, PPARG agonist, 10 µM), PD153035 (PD, an EGFR inhibitor, 1 µM) or a combination of TG and PD for 3 days. The results obtained demonstrate that treatment of the As-T cells with TG upregulated the expression of PPARγ and FOXA1 whereas treatment with PD decreased the expression of some of the basal keratins. However, a combined treatment of TG and PD resulted in a consistent decrease of several proteins associated with the basal subtype of bladder cancers (KRT1, KRT14, KRT16, P63, and TFAP2A). Our data suggests that activation of PPARγ while inhibiting cell proliferation facilitates the regulation of genes involved in maintaining the luminal subtype of UC. In vivo animal studies are needed to address the efficacy of using PPARγ agonists and/or proliferation inhibitors to reduce tumor grade/stage of MIUC.


Assuntos
Arsenitos/farmacologia , Proliferação de Células/efeitos dos fármacos , PPAR gama/metabolismo , Troglitazona/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Queratinas/genética , Queratinas/metabolismo , Camundongos , Camundongos Nus , PPAR gama/agonistas , Quinazolinas/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma/efeitos dos fármacos , Transplante Heterólogo , Regulação para Cima/efeitos dos fármacos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
7.
Asia Pac J Clin Oncol ; 16 Suppl 3: 18-23, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32852900

RESUMO

For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)-based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin-based chemotherapy because of poor performance status and/or other age-related conditions. At the other end of the spectrum, patients with localized non-muscle-invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette-Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune-checkpoint inhibitors has provided viable alternatives in the second-line postplatinum and first-line cisplatin-ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG-unresponsive cases, and for combination treatments that include the newer indoleamine 2,3-dioxygenase-1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.


Assuntos
Imunoterapia/métodos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/tratamento farmacológico , Feminino , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Bexiga Urinária/patologia
8.
Medicine (Baltimore) ; 99(34): e21740, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846796

RESUMO

RATIONALE: A primary primitive neuroectodermal tumor (PNET) is a rare and highly malignant tumor that often occurs in the central nervous system of children and young adults. This tumor is rarely observed in the bladder. PATIENT CONCERNS: In this paper, we describe the case of a 64-year-old man with a PNET of the bladder. He experienced dull pain in the lower left abdomen for 5 months (without any obvious inducement), which gradually became aggravated and intolerable. DIAGNOSES: Partial cystectomy was performed, and a PNET of the bladder, which is extremely rare, was confirmed. INTERVENTIONS: Following cystectomy, the patient's general postoperative state was poor and he could not tolerate chemotherapy. Thus, he was subjected to pelvic radiotherapy for 2 weeks. OUTCOMES: His physical condition did not improve significantly after radiotherapy; however, we still plan to continue it. If the patient's physical condition improves, chemotherapy will be considered. LESSONS: Most cases of PNETs are intravesical or at least mainly endophytic. However, in this case, the mucosal layer was barely involved, and the tumor mainly grew out of the bladder, which is very rare. The present case provides reference for the diagnosis of PNET.


Assuntos
Tumores Neuroectodérmicos Primitivos/patologia , Tumores Neuroectodérmicos Primitivos/terapia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Humanos , Masculino , Pessoa de Meia-Idade
9.
Medicine (Baltimore) ; 99(34): e21768, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846804

RESUMO

BACKGROUND: To compare the efficacy and safety of bipolar and monopolar transurethral resection of bladder tumors (TURBT) in non-muscle invasive bladder cancer (NMIBC) treatment. METHODS: This protocol established in this study has been reported following the preferred reporting items for systematic review and meta-analysis protocols. Web of Science, PubMed, EMBASE, and the Cochrane Library were searched for all randomized controlled trials comparing bipolar TURBT and monopolar TURBT in NMIBC treatment until 31st of June 2020. We will use a combination of Medical Subject Heading and free-text terms with various synonyms to search based on the eligibility criteria. Two investigators independently reviewed the included studies and extracted relevant data. The odds ratio and 95% confidence intervals of were used as effect estimate. I-square (I) test, substantial heterogeneity, sensitivity analysis, and publication bias assessment will be performed accordingly. Stata 15.0 and Review Manger 5.3 are used for meta-analysis and systematic review. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: The results of this review will be widely disseminated through peer-reviewed publications and conference presentations. This evidence may also provide helpful evidence of the efficacy and safety of bipolar and monopolar transurethral resection of TURBT in NMIBC treatment. PROSPERO REGISTRATION NUMBER: CRD42020151997.


Assuntos
Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Humanos , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos/efeitos adversos
10.
PLoS One ; 15(8): e0237070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822394

RESUMO

Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix™) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the RametrixTM screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix™ screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control SurineTM. Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the RametrixTM screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, RametrixTM was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve RametrixTM models and demonstrate clinical relevance, this study demonstrates the ability of the RametrixTM screen to differentiate urine of BCA-positive patients. Molecular signature variances in the urine metabolome of BCA patients included changes in: phosphatidylinositol, nucleic acids, protein (particularly collagen), aromatic amino acids, and carotenoids.


Assuntos
Detecção Precoce de Câncer/métodos , Análise Espectral Raman/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/urina , Cistoscopia , Análise Discriminante , Feminino , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Urinálise/métodos , Neoplasias da Bexiga Urinária/patologia
11.
Parasitol Res ; 119(10): 3145-3164, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748037

RESUMO

Parasites and bacteria have co-evolved with humankind, and they interact all the time in a myriad of ways. For example, some bacterial infections result from parasite-dwelling bacteria as in the case of Salmonella infection during schistosomiasis. Other bacteria synergize with parasites in the evolution of human disease as in the case of the interplay between Wolbachia endosymbiont bacteria and filarial nematodes as well as the interaction between Gram-negative bacteria and Schistosoma haematobium in the pathogenesis of urinary bladder cancer. Moreover, secondary bacterial infections may complicate several parasitic diseases such as visceral leishmaniasis and malaria, due to immunosuppression of the host during parasitic infections. Also, bacteria may colonize the parasitic lesions; for example, hydatid cysts and skin lesions of ectoparasites. Remarkably, some parasitic helminths and arthropods exhibit antibacterial activity usually by the release of specific antimicrobial products. Lastly, some parasite-bacteria interactions are induced as when using probiotic bacteria to modulate the outcome of a variety of parasitic infections. In sum, parasite-bacteria interactions involve intricate processes that never cease to intrigue the researchers. However, understanding and exploiting these interactions could have prophylactic and curative potential for infections by both types of pathogens.


Assuntos
Infecções Bacterianas/complicações , Filarioidea/microbiologia , Doenças Parasitárias/complicações , Schistosoma haematobium/microbiologia , Wolbachia/crescimento & desenvolvimento , Animais , Antibacterianos/uso terapêutico , Artrópodes/microbiologia , Humanos , Parasitos/microbiologia , Probióticos/uso terapêutico , Simbiose , Neoplasias da Bexiga Urinária/microbiologia , Neoplasias da Bexiga Urinária/parasitologia , Neoplasias da Bexiga Urinária/patologia
12.
Anticancer Res ; 40(8): 4787-4793, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727806

RESUMO

BACKGROUND/AIM: Bladder cancer with histological variant (HV) has different morphological features from usual urothelial carcinoma (UC). The aim of this study was to evaluate the oncological outcomes of HV in patients with bladder cancer. PATIENTS AND METHODS: We retrospectively evaluated data from 102 patients with UC of the bladder treated with radical cystectomy between 1998 and 2017. Pathological findings including HV were assigned by one dedicated pathologist. Recurrence-free survival (RFS) and cancer-specific survival (CSS) and overall survival (OS) were estimated by Cox regression models. RESULTS: In total, 26 patients (25.5%) had HV, and the most common variant was squamous differentiation, followed by glandular differentiation and a mixed variant consisted of squamous and glandular differentiation. The presence of HV was associated with RFS and CSS (p=0.018, p=0.036, respectively). CONCLUSION: HV has more aggressive tumor biological features compared to those with pure UC. The presence of HV was associated with poor survival.


Assuntos
Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgia , Cistectomia/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Oncologia/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia
13.
Anticancer Res ; 40(7): 3967-3972, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620639

RESUMO

BACKGROUND/AIM: There is a need to diagnose early bladder cancer by non-invasive tests. This study aimed to explore the clinical value of three non-invasive methods, UBC Rapid, ultrasound (US), and urine cytology, separately and in combination, for the primary diagnosis and surveillance of bladder-cancer. PATIENTS AND METHODS: Urine samples were obtained from 106 patients who presented with symptoms of bladder cancer and patients followed-up after transurethral resection of bladder tumors (TURB). Each patient underwent US, cystoscopy, cytology and UBC Rapid test. The sensitivity and specificity of all methods and combinations were calculated and related to cystoscopy and biopsy. RESULTS: Voided urine samples assayed with UBC Rapid and cytology yielded a sensitivity and specificity of 58.3% and 75.9%, and 57.1% and 98.0%, respectively and for US 76.2% and 98.1%. The combination of all three methods resulted in a sensitivity and specificity of 95.8% and 67.3%, and the combination of UBC Rapid and US, gave a sensitivity of 91.3%, and a specificity of 72.2%, The combination of UBC Rapid and cytology yielded a sensitivity and specificity of 84.6% and 71.2%. CONCLUSION: Combined use of UBC Rapid, US and cytology improved the sensitivity of bladder cancer detection.


Assuntos
Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Citológicas , Técnicas de Diagnóstico Urológico , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Ultrassonografia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urina , Urina/citologia
14.
Bull Cancer ; 107(5S): S49-S55, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620207

RESUMO

Local and systemic immunotherapies are used for the management of bladder cancer in daily practice. BCG has been administered for almost 40 years in patients with non-muscle invasive bladder cancer (NMIBC). Despite its efficacy, disease progression is observed in nearly 30% of patients. Given the antitumor activity of immune checkpoint inhibitors in metastatic setting, these therapies are currently investigated in NMIBC. Pembrolizumab is now approved by the Food and Drug Administration (FDA) for the treatment of patients with BCG-unresponsive, high-risk, NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have not elected to undergo cystectomy. Several phase 3 trials are ongoing to investigate the efficacy of PD(L)1 inhibitors combined with BCG such as ALBAN study in France.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Humanos , Invasividade Neoplásica , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/patologia
15.
Bull Cancer ; 107(5S): eS1-eS7, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32620210

RESUMO

BACKGROUND: The standard treatment in first line of advanced or metastatic urothelial bladder cancer (MBC) is the association of Gemcitabine and Cisplatin (GC). Avelumab, an anti-PD-L1 agent, has recently demonstrated efficacy. The objective is to evaluate the combination of these 3 agents. METHODS: This phase II randomized open-label study, evaluated if GC-avelumab increases response rate and duration of response of patients in 1st line treatment for MBC compared to GC. Severe toxicities should not overlap and be acceptable. The two co-primary end points are the objective response rate and the incidence of severe toxicity after six cycles of treatment. The study will recruit 90 participants, randomized in two arms (1:2), GC (gemcitabine 1 000 mg/m2/j, J1,J8, Cisplatine 70 mg/m2, J1 = J21), and GC-avelumab (10 mg/Kg/3 semaines). Randomization will be stratified on Karnofsky status (≥ 80 % vs. < 80 %) and visceral vs non visceral metastases. The duration of the inclusion period is 24 months, with a duration of participation of each patient of 18 months and a total study duration of 42 months. DISCUSSION: If both efficacy and safety of the association of GC+avelumab are in the range of acceptable through this specific study design, this will support a subsequent randomized phase III study comparing both arms with an overall survival end-point. In addition, the evaluation of predictive parameters to be confirmed (e.g. the impact of tumor PD-L1 expression) or other immunological parameters, may support a selection of the population. NCT number : NCT03324282.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/administração & dosagem , Ensaios Clínicos Fase II como Assunto/métodos , Desoxicitidina/análogos & derivados , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Desoxicitidina/administração & dosagem , Humanos , Invasividade Neoplásica , Estudos Prospectivos , Neoplasias da Bexiga Urinária/patologia
16.
Bull Cancer ; 107(5S): eS8-eS15, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32620213

RESUMO

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in localized muscle-invasive bladder cancer (MIBC). However, 60-70% of patients have residual tumor after NAC. Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination of chemo plus ICI could increase the pCR rate. METHODS/DESIGN: NEMIO is a French open-label randomized phase I/II trial assessing in the neoadjuvant setting the combination of ddMVAC plus durvalumab alone or with tremelimumab: 4 cycles of ddMVAC/2 weeks + 2 cycles of Durvalumab +/- Tremelimumab/4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. Six pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate. Each arm will be expanded to a maximum of 60 pts. The primary endpoint of the safety run-in phase will be the rate of grade 3/4 treatment-related adverse events G3/4 TRAE. The primary endpoint of the phase II will be the pathological response rate and G 3/4 TRAE. Exploratory endpoints will include biomarkers of response and resistance to the combo. A total of 120 patients will be included in 15 French centers and we expect the recruitment to be completed in 2021. DISCUSSION: NEMIO trial will assess for the first time the tolerance and the efficacy of ddMVAC regimen associated with checkpoints inhibitors as neoadjuvant treatment in localized MIBC. NCT number: NCT03549715. Registered on June 8, 2018.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/patologia , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Terapia Neoadjuvante , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Vimblastina/uso terapêutico
17.
PLoS One ; 15(7): e0229193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614890

RESUMO

BACKGROUND: Urine-based diagnostics indicated involvement of oncoprotein 18 (OP18) in bladder cancer. In cell culture models we investigated the role of OP18 for malignant cell growth. METHODS: We analyzed 113 urine samples and investigated two human BCa cell lines as a dual model: RT-4 and ECV-304, which represented differentiated (G1) and poorly differentiated (G3) BCa. We designed specific siRNA for down-regulation of OP18 in both cell lines. Phenotypes were characterized by cell viability, proliferation, and expression of apoptosis-related genes. Besides, sensitivity to cisplatin treatment was evaluated. RESULTS: Analysis of urine samples from patients with urothelial BCa revealed a significant correlation of the RNA-ratio OP18:uroplakin 1A with bladder cancer. High urinary ratios were mainly found in moderately to poorly differentiated tumors (grade G2-3) that were muscle invasive (stage T2-3), whereas samples from patients with more differentiated non-invasive BCa (G1) showed low OP18:UPK1A RNA ratios. Down-regulation of OP18 expression in ECV-304 shifted its phenotype towards G1 state. Further, OP18-directed siRNA induced apoptosis and increased chemo-sensitivity to cisplatin. CONCLUSIONS: This study provides conclusive experimental evidence for the link between OP18-derived RNA as a diagnostic marker for molecular staging of BCa in non-invasive urine-based diagnostics and the patho-mechanistic role of OP18 suggesting this gene as a therapeutic target.


Assuntos
Biomarcadores Tumorais/urina , RNA/urina , Estatmina/genética , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/secundário , Gradação de Tumores , Fenótipo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Estatmina/antagonistas & inibidores , Estatmina/metabolismo , Estatmina/urina , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Uroplaquina Ia/genética
18.
Medicine (Baltimore) ; 99(28): e20825, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664075

RESUMO

INTRODUCTION: Primary bladder mucosa-associated lymphoid tissue (MALT) lymphoma is a rare tumor. To date, the PubMed database contains only 39 English articles covering 63 cases of primary bladder MALT lymphoma. Herein, we report a case of this disease and review the current literature. PATIENT CONCERNS: A 77-year-old woman presented with frequent urination, urinary urgency, and dysuria for 3 years. In the past 3 years, the patient's symptoms recurred and progressively worsened, and she was admitted to the hospital. DIAGNOSIS: A histopathological examination revealed the bladder mass as a tumor with high proliferation of atypical B-lymphocytes. Immunohistochemistry showed positive results for CD20, PAX-5, Ki-67, BCL-2, and CD21 and negative results for CD10, MUM1, TDT, and cyclin D1. These data supported the diagnosis of primary bladder MALT lymphoma. INTERVENTIONS: A transurethral resection of bladder tumor was performed to treat the disease. OUTCOMES: The patient was alive and healthy at the 15-month follow-up. CONCLUSION: Primary bladder MALT lymphoma is a rare disease and can be easily missed or misdiagnosed before achieving a histological confirmation. Surgery may be the best choice for both diagnosis and treatment.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias da Bexiga Urinária/patologia , Transtornos Urinários/etiologia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Cistoscopia/métodos , Feminino , Humanos , Imuno-Histoquímica/métodos , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Transtornos Urinários/fisiopatologia , Adulto Jovem
19.
Br J Radiol ; 93(1114): 20190710, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706981

RESUMO

OBJECTIVE: Limited visibility of post-resection muscle-invasive bladder cancer (MIBC) on CT hinders radiotherapy dose escalation of the residual tumour. Diffusion-weighted MRI (DW-MRI) visualises areas of high tumour burden and is increasingly used within diagnosis and as a biomarker for cancer. DW-MRI could, therefore, facilitate dose escalation, potentially via dose-painting and/or accommodating response. However, the distortion inherent in DW-MRI could limit geometric accuracy. Therefore, this study aims to quantify DW-MRI distortion via imaging of a bladder phantom. METHODS: A phantom was designed to mimic MIBC and imaged using CT, DW-MRI and T2W-MRI. Fiducial marker locations were compared across modalities and publicly available software was assessed for correction of magnetic susceptibility-related distortion. RESULTS: Fiducial marker locations on CT and T2W-MRI agreed within 1.2 mm at 3 T and 1.8 mm at 1.5 T. The greatest discrepancy between CT and apparent diffusion coefficient (ADC) maps was 6.3 mm at 3 T, reducing to 1.8 mm when corrected for distortion. At 1.5 T, these values were 3.9 mm and 1.7 mm, respectively. CONCLUSIONS: Geometric distortion in DW-MRI of a model bladder was initially >6 mm at 3 T and >3 mm at 1.5 T; however, established correction methods reduced this to <2 mm in both cases. ADVANCES IN KNOWLEDGE: A phantom designed to mimic MIBC has been produced and used to show distortion in DW-MRI can be sufficiently mitigated for incorporation into the radiotherapy pathway. Further investigation is therefore warranted to enable individually adaptive image-guided radiotherapy of MIBC based upon DW-MRI.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Imagens de Fantasmas , Radioterapia Guiada por Imagem , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/radioterapia , Marcadores Fiduciais , Humanos , Invasividade Neoplásica , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/patologia
20.
Br J Radiol ; 93(1112): 20200116, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32516554

RESUMO

The distinction of non-muscle-invasive bladder cancer and muscle-invasive bladder cancer is important for the selection of the optimal treatment. Multiparametric MRI (mp-MRI) has been an useful modality for the T staging of bladder cancer, and a systematic evaluation of mp-MRI is needed. The Vesical Imaging Reporting and Data System was designed to standardize the scanning and reporting criteria based on mp-MRI for clinical and research applications. This review briefly describes the method, interpretation, and timing of mp-MRI examinations in the clinical settings. Validation studies of Vesical Imaging Reporting and Data System and future perspectives are also considered.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica/métodos , Estadiamento de Neoplasias/métodos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Humanos , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
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