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1.
Thorax ; 70(12): 1202-4, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26123659

RESUMEN

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease. Progressive airflow limitation, pneumothorax and angiomyolipoma-related bleeding are major morbidities. As treatments are available for these complications, we prospectively audited loss of FEV1 (ΔFEV1), pneumothorax and angiomyolipoma bleeding against clinical standards over 4 years at the UK Clinical Centre. ΔFEV1 for these patients is lower than previously reported and rates of pneumothorax and angiomyolipoma haemorrhage are low. This suggests that real-time analysis of clinical data with targeted interventions can reduce morbidity in LAM. These measures could be applied as quality standards to compare the emerging LAM clinical networks worldwide.


Asunto(s)
Protocolos Clínicos , Linfangioleiomiomatosis/terapia , Femenino , Humanos , Linfangioleiomiomatosis/epidemiología , Linfangioleiomiomatosis/fisiopatología , Neumotórax/epidemiología , Pronóstico , Indicadores de Calidad de la Atención de Salud , Pruebas de Función Respiratoria , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Resultado del Tratamiento
2.
Eur J Hum Genet ; 32(8): 887-894, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38802529

RESUMEN

In a subset of patients with renal tumours, multiple primary lesions may occur. Predisposition to multiple primary renal tumours (MPRT) is a well-recognised feature of some inherited renal cancer syndromes. The diagnosis of MPRT should therefore provoke a thorough assessment for clinical and genetic evidence of disorders associated with predisposition to renal tumourigenesis. To better define the clinical and genetic characteristics of MPRT, a systematic literature review was performed for publications up to 3 April 2024. A total of 7689 patients from 467 articles were identified with MPRT. Compared to all patients with renal cell carcinoma (RCC), patients with MPRT were more likely to be male (71.8% versus 63%) and have an earlier age at diagnosis (<46 years, 32.4% versus 19%). In 61.1% of cases MPRT were synchronous. The proportion of cases with similar histology and the proportion of cases with multiple papillary renal cell carcinoma (RCC) (16.1%) were higher than expected. In total, 14.9% of patients with MPRT had a family history of cancer or were diagnosed with a hereditary RCC associated syndrome with von Hippel-Lindau (VHL) disease being the most common one (69.7%), followed by Birt-Hogg-Dubé (BHD) syndrome (14.2%). Individuals with a known or likely genetic cause were, on average, younger (43.9 years versus 57.1 years). In rare cases intrarenal metastatic RCC can phenocopy MPRT. We review potential genetic causes of MPRT and their implications for management, suggest an approach to genetic testing for individuals presenting with MPRT and considerations in cases in which routine germline genetic testing does not provide a diagnosis.


Asunto(s)
Neoplasias Renales , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/diagnóstico , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/patología , Enfermedad de von Hippel-Lindau/complicaciones
3.
Cancer Immunol Immunother ; 61(5): 615-28, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22021067

RESUMEN

4-1BB ligation co-stimulates T cell activation, and agonistic antibodies have entered clinical trials. Natural killer (NK) cells also express 4-1BB following activation and are implicated in the anti-tumour efficacy of 4-1BB stimulation in mice; however, the response of human NK cells to 4-1BB stimulation is not clearly defined. Stimulation of non-adherent PBMC with OVCAR-3 cells expressing 4-1BB ligand (4-1BBL) or IL-12 resulted in preferential expansion of the NK cell population, while the combination 4-1BBL + IL-12 was superior for the activation and proliferation of functional NK cells from healthy donors and patients with renal cell or ovarian carcinoma, supporting long-term (21 day) NK cell proliferation. The expanded NK cells are predominantly CD56(bright), and we show that isolated CD56(dim)CD16(+) NK cells can switch to a CD56(bright)CD16(-) phenotype and proliferate in response to 4-1BBL + IL-12. Whereas 4-1BB upregulation on NK cells in response to 4-1BBL required 'help' from other PBMC, it could be induced on isolated NK cells by IL-12, but only in the presence of target (OVCAR-3) cells. Following primary stimulation with OVCAR-3 cells expressing 4-1BBL + IL-12 and subsequent resting until day 21, NK cells remained predominantly CD56(bright) and retained both high cytotoxic capability against K562 targets and enhanced ability to produce IFNγ relative to NK cells in PBMC. These data support the concept that NK cells could contribute to anti-tumour activity of 4-1BB agonists in humans and suggest that combining 4-1BB-stimulation with IL-12 could be beneficial for ex vivo or in vivo expansion and activation of NK cells for cancer immunotherapy.


Asunto(s)
Ligando 4-1BB/inmunología , Interleucina-12/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Neoplasias/inmunología , Neoplasias/patología , Ligando 4-1BB/biosíntesis , Ligando 4-1BB/genética , Antígeno CD56/inmunología , Procesos de Crecimiento Celular/genética , Procesos de Crecimiento Celular/inmunología , Línea Celular Tumoral , Femenino , Proteínas Ligadas a GPI/inmunología , Humanos , Interferón gamma/inmunología , Interleucina-12/biosíntesis , Interleucina-12/genética , Leucocitos Mononucleares/inmunología , Activación de Linfocitos , Neoplasias/genética , Fenotipo , Receptores de IgG/inmunología , Regulación hacia Arriba
4.
Onkologie ; 32(1-2): 44-6, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19209019

RESUMEN

BACKGROUND: Collecting duct carcinoma (CDC) is a rare and aggressive variant of renal cell carcinoma (RCC), which has poor response to cytokine therapy and chemotherapy. Introduction of tyrosine kinase inhibitors (TKIs), in particular sorafenib and sunitinib, is changing the treatment paradigm for management of RCC. However, patients with CDC have been excluded from the majority of randomised trials involving the use of TKIs. CASE REPORT: Our patient with metastatic CDC was treated with sorafenib, and demonstrated an excellent response, both clinically and radiologically. She continues on sorafenib treatment with minimal toxicity, and has demonstrated a progression-free survival exceeding 13 months. CONCLUSIONS: This is the first reported case of a patient with CDC responding to sorafenib treatment. Therefore, the role of sorafenib in the management of metastatic CDC needs prospective evaluation.


Asunto(s)
Bencenosulfonatos/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Neoplasias Renales/tratamiento farmacológico , Piridinas/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Células Renales/diagnóstico , Humanos , Neoplasias Renales/diagnóstico , Metástasis Linfática , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Sorafenib , Resultado del Tratamiento
5.
Eur Urol ; 75(1): 63-71, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30274699

RESUMEN

BACKGROUND: There is no effective intravesical second-line therapy for non-muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. OBJECTIVE: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION: Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND LIMITATIONS: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. CONCLUSIONS: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. PATIENT SUMMARY: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.


Asunto(s)
Antineoplásicos/uso terapéutico , Vacuna BCG/uso terapéutico , Mitomicina/uso terapéutico , Recurrencia Local de Neoplasia/terapia , Terapia por Radiofrecuencia , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Anciano , Anciano de 80 o más Años , Carcinoma in Situ/patología , Carcinoma in Situ/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
6.
Urol Ann ; 10(3): 270-279, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30089985

RESUMEN

INTRODUCTION: Nephrometric scores are used to predict perioperative and postoperative complications, with no uniform results in the current literature. MATERIALS AND METHODS: A retrospective study of 141 patients in a single center who underwent open partial nephrectomy between June 2006 and 2016 for T1a and T1b renal tumor was conducted. Univariate and multivariate analyses were used to evaluate the correlations between preoperative aspects and dimensions used for an anatomical (PADUA) and radius exophytic/endophytic nearness anterior/posterior location (RENAL) scores and their components with pre-, peri-, and post-operative parameters. Linear regression (F-tests) and logical regression models were used to test for significance of the association and predictability of outcomes. RESULTS: Total RENAL score (P = 0.032), its components R (P = 0.004), E (P = 0.022), L (P = 0.011), and total PADUA score (P = 0.016) were significantly associated with ischemic time. In postoperative complications, the PADUA components: sinus line location (P = 0.008), lateral/medial rim score (P = 0.029), and collecting system score (P = 0.006) showed significance. None of the variables showed correlation with operation time and change in estimated glomerular filtration rate (eGFR). On multivariate analysis, sinus line location and gender (P = 0.012) showed significance in predicting eGFR changes and RENAL score component: A (P = 0.049) was significant in predicting estimated blood loss. Both RENAL and PADUA components were significantly associated with hospital length of stay. CONCLUSION: Both RENAL and PADUA scores showed important correlation in predicting outcomes. We further demonstrated the importance of knowing the individual components of the scores, which can independently give outcome predictions. The scoring systems can still be improved and standardized for broad clinical use with larger cohort and multicenter-based studies.

7.
Cancer Res ; 76(8): 2314-26, 2016 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-26921326

RESUMEN

The structure and molecular signature of tumor-associated vasculature are distinct from those of the host tissue, offering an opportunity to selectively target the tumor blood vessels. To identify tumor-specific endothelial markers, we performed a microarray on tumor-associated and nonmalignant endothelium collected from patients with renal cell carcinoma (RCC), colorectal carcinoma, or colorectal liver metastasis. We identified a panel of genes consistently upregulated by tumor blood vessels, of which melanoma cell adhesion molecule (MCAM) and its extracellular matrix interaction partner laminin alpha 4 (LAMA4) emerged as the most consistently expressed genes. This result was subsequently confirmed by immunohistochemical analysis of MCAM and LAMA4 expression in RCC and colorectal carcinoma blood vessels. Strong MCAM and LAMA4 expression was also shown to predict poor survival in RCC, but not in colorectal carcinoma. Notably, MCAM and LAMA4 were enhanced in locally advanced tumors as well as both the primary tumor and secondary metastases. Expression analysis in 18 different cancers and matched healthy tissues revealed vascular MCAM as highly specific in RCC, where it was induced strongly by VEGF, which is highly abundant in this disease. Lastly, MCAM monoclonal antibodies specifically localized to vessels in a murine model of RCC, offering an opportunity for endothelial-specific targeting of anticancer agents. Overall, our findings highlight MCAM and LAMA4 as prime candidates for RCC prognosis and therapeutic targeting. Cancer Res; 76(8); 2314-26. ©2016 AACR.


Asunto(s)
Carcinoma de Células Renales/irrigación sanguínea , Neoplasias Renales/irrigación sanguínea , Laminina/metabolismo , Animales , Antígeno CD146/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/terapia , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/terapia , Ratones , Metástasis de la Neoplasia , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/farmacología
8.
Nat Commun ; 6: 6336, 2015 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-25790038

RESUMEN

Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only ~10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches.


Asunto(s)
Carcinoma de Células Renales/genética , Cromosomas/ultraestructura , Neoplasias Renales/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/química , Mapeo Cromosómico , Variaciones en el Número de Copia de ADN , Exoma , Exones , Femenino , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Filogenia , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN
9.
Orphanet J Rare Dis ; 9: 151, 2014 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-25277108

RESUMEN

BACKGROUND: LAM is a rare disease of women categorised by lung cysts and lymphatic abnormalities. The disease occurs sporadically or associated with Tuberous Sclerosis Complex (TSC-LAM). Angiomyolipoma, a benign tumour, prone to haemorrhage, occurs mostly in the kidneys in many of these patients. Treatment guidelines exist for angiomyolipoma in patients with TSC but the natural history of angiomyolipoma in sporadic LAM has not been studied. AIMS: To document the natural history of angiomyolipoma in a national cohort of patients with sporadic LAM to inform tumour screening and surveillance protocols. METHODS: Demographic data, clinical features, lung function and tumour size were obtained from clinical records of patients attending the National Centre for LAM in Nottingham, UK. RESULTS: 122 patients with definite or probable LAM by European Respiratory Society criteria were identified. One hundred and seven had sporadic LAM, of which 53 (50%) had at least one angiomyolipoma. In patients with sporadic LAM presentation of angiomyolipoma preceded or followed onset of lung symptoms by up to 11 and 38 years respectively. Mean tumour size was 28 mm (range 5-140 mm) at presentation and growth was 1.8 mm/yr (95% C.I. 0.42-3.82) thereafter. Eleven patients with sporadic LAM had had a nephrectomy due to angiomyolipoma bleeding. The need for intervention did not differ between those with TSC-LAM and sporadic LAM. CONCLUSIONS: Patients with LAM have a high prevalence of symptomatic angiomyolipoma which can present at any time. Angiomyolipoma in sporadic-LAM have a similar risk of bleeding to those with TSC. All patients should be screened for angiomyolipoma at diagnosis of lung disease by MRI scanning and the tumours require continuous monitoring.


Asunto(s)
Angiomiolipoma/fisiopatología , Linfangioleiomiomatosis/fisiopatología , Adulto , Angiomiolipoma/diagnóstico , Estudios de Cohortes , Humanos , Persona de Mediana Edad
11.
Eur Urol ; 61(2): 385-94, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22079021

RESUMEN

BACKGROUND: Evidence suggests that some patients with renal cell carcinoma (RCC) respond to immunomodulatory therapies that activate T lymphocytes. A prerequisite for effective T cell therapy is efficient targeting of effector T cells to the tumour site, yet the molecular basis of T cell recruitment to RCC is unknown. Furthermore, some T cells that naturally infiltrate this cancer are regulatory T cells (Tregs) that may suppress antitumour immune responses. OBJECTIVE: Determine the mechanisms of effector and regulatory T cell recruitment to RCC to allow targeted therapy that promotes local anti-tumour immunity. DESIGN, SETTING, AND PARTICIPANTS: Tumour-infiltrating and peripheral blood T cells were collected from 70 patients undergoing nephrectomy for RCC. MEASUREMENTS: T cells were analysed by multicolour flow cytometry for expression of 19 chemokine receptors and 7 adhesion molecules. Receptors that were expressed at higher levels on tumour-infiltrating lymphocytes (TILs) compared with matched peripheral blood lymphocytes (PBLs) were analysed further for their ability to mediate migration responses in TILs and for expression of corresponding ligands in tumour tissue. RESULTS AND LIMITATIONS: Three chemokine receptors-CCR5, CXCR3, and CXCR6-were significantly overexpressed on TILs compared with matched PBLs (n=16 cases) and were capable of promoting migration in vitro. Their corresponding ligands CCL4-5, CXCL9-11, and CXCL16 were all detected in RCC tissue. However, since they were present in all cases studied, it was not possible to correlate ligand expression with levels of T cell infiltration. Foxp3(+) Tregs were enriched within TILs compared with matched PBLs and expressed high levels of CCR5, CXCR3, and CXCR6, as well as CCR6, the ligand for which (CCL20) was detectable in RCC tissue. CONCLUSIONS: Our data support a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into RCC tissue and, together with CCR6, in the recruitment of Tregs.


Asunto(s)
Carcinoma de Células Renales/inmunología , Neoplasias Renales/inmunología , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Receptores CCR5/inmunología , Receptores CCR6/inmunología , Receptores CXCR3/inmunología , Receptores de Quimiocina/inmunología , Receptores Virales/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Movimiento Celular/inmunología , Femenino , Citometría de Flujo/métodos , Factores de Transcripción Forkhead/inmunología , Humanos , Masculino , Persona de Mediana Edad , Receptores CXCR6 , Linfocitos T/inmunología
13.
J Urol ; 176(6 Pt 1): 2518-22; discussion 2522, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17085147

RESUMEN

PURPOSE: There is little consensus regarding long-term followup of renal function in patients who undergo urinary diversion. We established the usefulness of combined serial isotopic glomerular filtration rate measurement and diuresis renography in the early identification of patients at risk for deterioration of renal function following ileal conduit diversion. MATERIALS AND METHODS: A total of 340 patients with ileal conduit diversion who were followed between 1990 and 2000 were identified. We analyzed data on 178 patients who had more than 4 years of followup. Renal function was assessed by serial estimation of serum creatinine, isotopic glomerular filtration rate and diuresis renographic measurements. RESULTS: Of the patients 52 (29%) demonstrated a worsening glomerular filtration rate. Mean followup +/- SEM was 8.2 +/- 0.4 years (range 4 to 30) and 67% of patients had more than 6 years of followup. In this group we found that hypertension, recurrent urinary sepsis and an initial post-diversion glomerular filtration rate of less than 50 ml per minute per 1.73 m were prevalent risk factors. Hypertension was an independent predictor of a decreased glomerular filtration rate in this group. Of 52 patients with a deteriorating glomerular filtration rate 19 had type II or IIIb curves on followup renography, of whom 13 underwent revision surgery. Renal function subsequently stabilized or improved in this group. CONCLUSIONS: Of patients with an ileal conduit 29% have renal function deterioration in the long term. No surgical cause for glomerular filtration rate deterioration was found in 18%. Important predisposing factors in nonobstructed cases were hypertension, recurrent urinary sepsis and a glomerular filtration rate of less than 50 ml per minute per 1.73 m. Hypertension was an independent predictor of a decreased glomerular filtration rate in the group with worsening glomerular filtration rates. In 11% of patients deterioration was due to upper tract obstruction. This was identifiable using renography and the glomerular filtration rate. A type IIIb curve was an early indicator of obstruction.


Asunto(s)
Tasa de Filtración Glomerular , Riñón/fisiopatología , Renografía por Radioisótopo , Radiofármacos , Tecnecio Tc 99m Mertiatida , Derivación Urinaria , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/cirugía , Creatinina/sangre , Cistectomía , Humanos , Riñón/diagnóstico por imagen , Persona de Mediana Edad , Periodo Posoperatorio , Radiografía , Neoplasias de la Vejiga Urinaria/cirugía , Enfermedades Urológicas/etiología
14.
Cytometry A ; 54(2): 89-99, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12879455

RESUMEN

BACKGROUND: Prostate stem cells, responsible for the development, maturation, and function of the prostate, have been implicated in the aetiology of both benign prostate hyperplasia (BPH) and prostate cancer (CaP). However, research has been hampered by the lack of a definitive stem cell marker. We have adapted the protocol for differential Hoechst 33342 uptake by hemopoietic stem cells to enable isolation of putative stem cells from the prostate. METHODS: Prostate epithelial cells isolated from prostate tissue obtained from patients with BPH after transurethral resection of the prostate were stained with Hoechst 33342. The Hoechst 33342 Red/Blue flow cytometry profile was then determined. Hoechst 33342 and Pyronin Y staining was used to determined the cell cycle status. RESULTS: A verapamil-sensitive side population (SP) can be isolated from primary prostate tissue accounting for 1.38% +/- 0.07% of prostate epithelial cells. Cell cycle analysis of this SP population revealed that the majority of SP cells are in either G0 (12.38 +/- 0.31%) or G1 (63.19 +/- 2.13%). CONCLUSIONS: The Hoechst 33342 dye efflux protocol can be adapted for the isolation of a SP from primary prostate tissue.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Citometría de Flujo/métodos , Próstata/citología , Células Madre/citología , Bencimidazoles/farmacocinética , Bloqueadores de los Canales de Calcio/farmacología , Ciclo Celular , Células Epiteliales/citología , Colorantes Fluorescentes/farmacología , Fase G1 , Células Madre Hematopoyéticas/citología , Humanos , Queratinas/metabolismo , Antígenos Comunes de Leucocito/biosíntesis , Masculino , Fenotipo , Propidio/farmacología , Fase de Descanso del Ciclo Celular , Verapamilo/farmacología
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