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1.
Genet Med ; 23(4): 698-704, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33442023

RESUMEN

PURPOSE: Germline pathogenic variants are estimated to affect 3-5% of renal cell carcinoma (RCC) patients. However, higher mutational prevalence in non-clear cell RCC (non-ccRCC) and advanced disease has been suggested. METHODS: To clarify the prevalence of pathogenic germline variants in metastatic RCC, we sequenced 29 cancer susceptibility genes in 294 unselected metastatic RCC cases plus 21 patients with clinical hereditary features. In 145 tumors, genes frequently mutated in RCC were sequenced and methylation was assessed in selected cases. RESULTS: Germline variants in RCC predisposition genes (FH, VHL) were detected in 1.4% of the unselected metastatic patients, with higher frequency in non-ccRCC versus ccRCC (6.4% and 0.4%; P = 0.0025) and in younger patients (P = 0.036). Among the 315 studied patients, 14% of non-type 1 papillary cases (4 of 28), all metastatic <1 year after diagnosis, carried a FH germline variant with loss of heterozygosity and tumor genome hypermethylation. Variants in other cancer-associated genes (e.g., MUTYH, BRCA2, CHEK2) occurred in 5.1% of the unselected series, with unclear significance for RCC. CONCLUSION: Our findings confirm a high prevalence of pathogenic germline variants in RCC predisposition genes in metastatic non-ccRCC, and highlight that metastatic patients with papillary type 2 or unconventional histologies compatible with FH would benefit from genetic screening.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/genética , Células Germinativas , Mutación de Línea Germinal , Humanos , Neoplasias Renales/epidemiología , Neoplasias Renales/genética , Mutación , Prevalencia
2.
Future Oncol ; 14(1): 41-50, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29232987

RESUMEN

AIM: To report results from the Spanish subset included in the radium-223 international early access program (iEAP). PATIENTS & METHODS: Ninety patients with castration-resistant prostate cancer and bone metastases received radium-223 55 kBq/kg every 4 weeks for six cycles. RESULTS: The median time to disease progression was 8 months and to prostate-specific antigen progression was 4 months. The percentage of patients with ≥50% confirmed declines in prostate-specific antigen was 9%. The median overall survival was 14 months. Grade 3 or 4 treatment emergent adverse events (TEAEs) occurred in 34% of patients (serious TEAEs 28%, TEAEs leading to discontinuation 27%). CONCLUSION: Outcomes of the Spanish subset are consistent with the iEAP. Radium-223 was generally well tolerated with no safety concerns.


Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radioisótopos/administración & dosificación , Radio (Elemento)/administración & dosificación , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/patología , Radioisótopos/efectos adversos , Radio (Elemento)/efectos adversos , España/epidemiología
3.
Am J Transl Res ; 16(5): 1531-1549, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38883349

RESUMEN

Liquid biopsy is an innovative approach that provides a more complete understanding of treatment response and prognosis in monitoring metastatic prostate cancer. It complements invasive tissue biopsy and involves the assessment of various biomarkers in body fluids such as blood, semen, and urine. Liquid biopsy analyzes circulating tumor cells, extracellular vesicles, circulating tumor DNA, and the secretome. This is particularly important given the heterogeneity of prostate cancer and the need for better prognostic biomarkers. Liquid biopsy can personalize the treatment of homonosensitive and castration-resistant metastatic prostate cancer by acting as a predictive and prognostic tool. This review discusses various biomarkers, assay techniques, and potential applications in daily clinical practice, highlighting the exciting possibilities that this emerging field holds for improving patient outcomes.

4.
Eur Urol Oncol ; 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37838555

RESUMEN

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

5.
Gastroenterol Hepatol ; 35(5): 317-20, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22285788

RESUMEN

Verruciform xanthoma (VX) is an uncommon benign lesion of unclear etiology which has only been reported twice before in the esophagus. We describe a 70-year-old male who presented an exophytic esophageal lesion incidentally found upon endoscopy 2.7 years following radiation therapy for unresectable squamous cell carcinoma of the tracheal carina. Histologically, the lesion showed a papillary surface change with numerous foamy histiocytes within the lamina propia papillae. Xanthoma cells were strongly positive for vimentin and CD68 (KP1). Polymerase chain reaction did not demonstrate human papillomavirus (HPV) infection. Our results indicate that esophageal VX is not an HPV-induced lesion and suggest a causal relationship between VX and radiotherapy, as previously noted. Histological differential diagnosis is discussed and emphasis is placed on obtaining adequate biopsy material for accurate diagnosis.


Asunto(s)
Enfermedades del Esófago/etiología , Xantomatosis/etiología , Anciano , Enfermedades del Esófago/patología , Humanos , Masculino , Radioterapia/efectos adversos , Xantomatosis/patología
6.
Anticancer Drugs ; 22 Suppl 1: S15-20, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21173603

RESUMEN

Renal cell cancer (RCC) is a rare disease that accounts for 2-3% of all solid malignancies. Although its etiology is not known, approximately 4% of RCC occurs in the context of complex hereditary syndromes in which the kidney lesions are associated with other manifestations. Therefore, clinical suspicion is essential for proper diagnosis and management. In this review a practical summary to aid treating physicians in the identification of hereditary RCC syndromes, including von Hippel-Lindau syndrome, hereditary papillary RCC, Birt-Hogg-Dubé syndrome, and hereditary leiomyomatosis RCC, is provided. Early recognition of these specific populations will lead to better care, correct surveillance, and, in the near future, to personalized treatment taking advantage of underlying genetic defects.


Asunto(s)
Síndrome de Birt-Hogg-Dubé/diagnóstico , Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico , Leiomiomatosis/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Enfermedad de von Hippel-Lindau/diagnóstico , Síndrome de Birt-Hogg-Dubé/genética , Síndrome de Birt-Hogg-Dubé/patología , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Femenino , Humanos , Riñón/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Leiomiomatosis/genética , Leiomiomatosis/patología , Masculino , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Síndrome , Resultado del Tratamiento , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/patología
7.
J Health Organ Manag ; ahead-of-print(ahead-of-print)2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34464035

RESUMEN

PURPOSE: This study aims to elucidate the health care organization, management and policy barriers and facilitators associated with implementation of an evidence-based health promotion intervention in primary care centers in the Basque Country, Spain. DESIGN/METHODOLOGY/APPROACH: Seven focus groups were conducted with 49 health professionals from six primary care centers participating in the Prescribing Healthy Life program. Text was analyzed using the Consolidated Framework for Implementation Research (CFIR) focusing on those constructs related to health care organization, management and policy. FINDINGS: The health promotion intervention was found to be compatible with the values of primary care professionals. However, professionals at all centers reported barriers to implementation related to: (1) external policy and incentives, (2) compatibility with existing workflow and (3) available resources to carry out the program. Specific barriers in these areas related to lack of financial and political support, consultation time constraints and difficulty managing competing day-to-day demands. Other barriers and facilitators were related to the constructs networks and communication, culture, relative priority and leadership engagement. A set of six specific barrier-facilitator pairs emerged. ORIGINALITY/VALUE: Implementation science and, specifically, the CFIR constructs were used as a guide. Barriers and facilitators related to the implementation of a health promotion program in primary care were identified. Healthcare managers and policy makers can modify these factors to foster a more propitious implementation environment. These factors should be appropriately monitored, both in pre-implementation phases and during the implementation process, in order to ensure effective integration of health promotion into the primary care setting.


Asunto(s)
Atención a la Salud , Atención Primaria de Salud , Personal de Salud , Promoción de la Salud , Humanos , Investigación Cualitativa
8.
J Pers Med ; 11(8)2021 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-34442392

RESUMEN

Primary care is especially well positioned to address prevention of non-communicable diseases. However, implementation of health promotion activities such as personalized dietary advice is challenging. The study aim was to understand barriers and facilitators of the personalized dietary advice component of a lifestyle intervention in primary care, as perceived by health center professionals and program participants. Thirteen focus groups were conducted with 49 professionals and 47 participants. Audio recordings were transcribed. Professional group text was coded using the Consolidated Framework for Implementation Research (CFIR). Participant group text was coded via an inductive approach with thematic analysis. Across most CFIR domains, both barriers and facilitators were equally present, except for 'characteristics of individuals', which were primarily facilitators. Intervention characteristics was the most important domain, with barriers in design and packaging (e.g., the ICT tool) and complexity. Facilitators included high evidence strength and quality, adaptability, and relative advantage. Participants described the importance of more personalized advice, the value of follow-up with feedback, and the need to see outcomes. Both professionals and patients stated that primary care was the place for personalized dietary advice intervention, but that lack of time, workload, and training were barriers to effective implementation. Implementation strategies targeting these modifiable barriers could potentially increase intervention adoption and intervention effectiveness.

9.
Eur Urol ; 75(3): 368-373, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30773204

RESUMEN

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR]=1.61, 95% confidence interval [CI]=1.08-2.39, p=0.018), but not PFS (HR=1.04, 95% CI 0.74-1.46, p=0.8) or PSA response (odds ratio=1.14, 95% CI=0.65-1.99, p=0.7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naïve, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.16, 95% CI=0.06-0.46, p<0.001) and PFS (HR=0.31, 95% CI=0.12-0.80, p=0.02). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal patients (HR=1.93, 95% CI=1.19-3.12, p=0.008) and a suggestion favoring docetaxel for AR-gained patients (HR=0.53, 95% CI=0.24-1.16, p=0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained could benefit from docetaxel. This treatment selection merits prospective evaluation in a randomized trial. PATIENT SUMMARY: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker.


Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Androstenos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Docetaxel/uso terapéutico , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/sangre , Antagonistas de Andrógenos/efectos adversos , Androstenos/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas , Docetaxel/efectos adversos , Humanos , Calicreínas/sangre , Masculino , Metástasis de la Neoplasia , Nitrilos , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/efectos adversos , Supervivencia sin Progresión , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/genética , España , Factores de Tiempo
10.
J Clin Virol ; 109: 50-56, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30500488

RESUMEN

BACKGROUND: Our study focuses on the role that human Cytomegalovirus (CMV) genotypes play in the development of disease. OBJECTIVES: (1) To analyze the frequency of various genotype envelope proteins (gB, gH) in a group of solid organ transplant (SOT) recipients; (2) to assess their correlation with CMV disease; (3) to study the association between any of the genotypes and viral loads. STUDY DESIGN: A retrospective observational study conducted by analyzing CMV gB and gH genotypes detected with real-time polymerase chain reaction (PCR)-specific assays in 162 CMV-positive blood samples from 62 SOT recipients. Demographic, clinical, and microbiological data were recorded. RESULTS: Mixed gB genotypes were associated with viral syndrome (70%, p = .004), earlier presentation of symptoms (48.27 ± 27.03 versus 74.33 ± 47.25 days, respectively, p = .001), and higher median of the plasma viral load log10 (UI/ml) than infection with a single genotype (p = .004). Furthermore, the gB3 genotype was detected more frequently in patients who presented with asymptomatic viremia (77.27%, p < .0001). The gH1 genotype was more frequent (65%) in patients who presented with asymptomatic viremia (p = .003), and it caused infection later than gH2 or the mixed genotype (84.88 ± 48.10 versus 57.91 ± 39.18 days, respectively, p < .001). CONCLUSIONS: Patients who presented mixed gB genotypes more frequently developed clinical manifestations and earlier, higher, plasma viral loads. The detection of gB and gH genotypes by real-time PCR can provide relevant information to stratify the risk of SOT recipients to develop symptomatic infection by CMV.


Asunto(s)
Infecciones por Citomegalovirus/virología , Citomegalovirus/genética , Receptores de Trasplantes , Proteínas del Envoltorio Viral/genética , Adulto , Citomegalovirus/clasificación , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/complicaciones , ADN Viral/sangre , ADN Viral/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Análisis de Secuencia de ADN , Carga Viral
11.
Eur Urol Focus ; 3(4-5): 430-436, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28753791

RESUMEN

BACKGROUND: Markers able to predict the response to antiangiogenics in metastatic clear cell renal cell carcinoma (ccRCC) are not available. The development of new treatment options like immunotherapy are reaching the clinic; therefore, predictors of benefit from these different available treatments are increasingly needed. OBJECTIVE: In this study, we prospectively assessed the association of circulating endothelial cells (CECs) in peripheral blood with long-term benefit from first-line treatment in ccRCC. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study was designed involving 13 institutions of the Spanish Oncology Genitourinary Group. Adult patients diagnosed with advanced ccRCC who had achieved response or disease stabilization after 3 mo on first-line therapy were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: CECs were isolated from peripheral blood, captured with ferrofluids coated with monoclonal antibodies directed against the CD146 antigen, and assessed centrally with an automated standardized system. CECs were defined as 4',6-diamidino-2-phenylindole+, CD105+, and CD45-. Blood samples were systematically taken every 6 wk for 15 mo or until tumor progression, whichever occurred first. Clinical data were externally monitored at all centers. RESULTS AND LIMITATIONS: From August 9, 2011, to January 17, 2013, 75 patients were enrolled in the study. Patients with baseline CECs above the median showed a significantly longer progression-free survival than those with low CECs (22.2 mo vs 12.2 mo) with a hazard ratio of 2.5 (95% confidence interval: 1.2-5.3, p=0.016). There was no difference between CEC levels at baseline and at tumor progression (medians of 50 CECs/4ml and 52 CECs/4ml, respectively). CONCLUSIONS: Under antiangiogenic treatment, the detection of higher CEC levels is associated with clinical benefit in terms of progression-free survival in ccRCC. PATIENT SUMMARY: Antiangiogenics are the cornerstone of treatment in kidney cancer. Since they target endothelial rather than tumor cells, we studied the correlation between levels of circulating endothelial cells in peripheral blood and long-term benefit in patients on antiangiogenic therapy. Higher levels were associated with long-term benefit, suggesting that this determination could help to separate best responders from those who could require a more intensive approach.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Antígeno CD146/metabolismo , Recuento de Células/métodos , Endoglina/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos
12.
Transplantation ; 82(1): 30-5, 2006 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-16861938

RESUMEN

BACKGROUND: The role of valganciclovir in the prevention of cytomegalovirus (CMV) disease in high-risk seropositive transplant patients is not known. METHODS: We prospectively followed 301 seropositive solid organ transplant recipients to assess the efficacy and safety of valganciclovir (VGCV) in the prevention of CMV disease in high-risk patients. Asymptomatic patients with an antigenemia test >or=25 positive cells/2x10(5) polymorphonuclear cells received valganciclovir 900 mg twice a day as preemptive therapy until resolution of antigenemia (minimum 14 days). Additionally, patients treated with antilymphocytic drugs for more than 6 days received prophylaxis with VGCV 900 mg once a day during 90 days. Mean follow-up was 14 months (range 6-20 months). RESULTS: Thirty-eight patients received VGCV; 24 as preemptive therapy and 14 due to the use of antilymphocytic drugs. No patient developed CMV disease during the follow-up. Viral load (antigenemia) decreased a mean of 78% from baseline after 7 days of VGCV therapy (P=0.024) and 98% at day 14 (P=0.029). Two patients showed a relapse of the antigenemia test >or=25 positive cells and were successfully treated with a repeated course of VGCV. Leukopenia (<2500/mm3) developed in 3/24 (12.5%) recipients in the preemptive therapy group and required to discontinuing the drug in one of them. CONCLUSIONS: VGCV is safe and highly efficacious in the prevention of CMV disease in high-risk seropositive organ transplant recipients.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/análogos & derivados , Trasplante de Órganos , Adolescente , Adulto , Antígenos Virales/sangre , Antivirales/efectos adversos , Niño , Citomegalovirus/inmunología , Femenino , Ganciclovir/efectos adversos , Ganciclovir/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Valganciclovir
13.
J Gynecol Oncol ; 27(1): e7, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26463438

RESUMEN

OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.


Asunto(s)
Cistadenocarcinoma Seroso/genética , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/genética , Factores de Transcripción/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinoma Epitelial de Ovario , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Pronóstico , Factores de Transcripción/biosíntesis , Células Tumorales Cultivadas
14.
JCI Insight ; 1(10): e86051, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27699216

RESUMEN

The majority of metastatic renal cell carcinoma (RCC) patients are treated with tyrosine kinase inhibitors (TKI) in first-line treatment; however, a fraction are refractory to these antiangiogenic drugs. MicroRNAs (miRNAs) are regulatory molecules proven to be accurate biomarkers in cancer. Here, we identified miRNAs predictive of progressive disease under TKI treatment through deep sequencing of 74 metastatic clear cell RCC cases uniformly treated with these drugs. Twenty-nine miRNAs were differentially expressed in the tumors of patients who progressed under TKI therapy (P values from 6 × 10-9 to 3 × 10-3). Among 6 miRNAs selected for validation in an independent series, the most relevant associations corresponded to miR-1307-3p, miR-155-5p, and miR-221-3p (P = 4.6 × 10-3, 6.5 × 10-3, and 3.4 × 10-2, respectively). Furthermore, a 2 miRNA-based classifier discriminated individuals with progressive disease upon TKI treatment (AUC = 0.75, 95% CI, 0.64-0.85; P = 1.3 × 10-4) with better predictive value than clinicopathological risk factors commonly used. We also identified miRNAs significantly associated with progression-free survival and overall survival (P = 6.8 × 10-8 and 7.8 × 10-7 for top hits, respectively), and 7 overlapped with early progressive disease. In conclusion, this is the first miRNome comprehensive study, to our knowledge, that demonstrates a predictive value of miRNAs for TKI response and provides a new set of relevant markers that can help rationalize metastatic RCC treatment.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Tasa de Supervivencia
15.
Mol Oncol ; 9(2): 422-36, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25454820

RESUMEN

Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; Padj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 6/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Ováricas/terapia , Tasa de Supervivencia
16.
Gac Sanit ; 27(3): 241-7, 2013.
Artículo en Español | MEDLINE | ID: mdl-22943976

RESUMEN

OBJECTIVE: To analyze information needs and search strategies among women with breast cancer in Spain. An additional aim was to explore how the internet, as a source of health information, influences the autonomy and active management of this disease among patients. The research was conducted in 2010 and 2011. METHOD: This study forms part of a broader qualitative study that focuses on describing patients' experiences of breast cancer and the trajectory of the disease, with the aim of creating a platform of integrated information resources for patients, relatives and healthcare professionals (PyDEsalud: http://www.pydesalud.com). We carried out 41 in-depth, semi-structured interviews with breast cancer patients in different stage of the disease, who were aged between 32 and 69 years. The interviewees' were selected by intentional sampling, which included 15 Spanish regions. The field work was carried out from June to August, 2010. The interviews were recorded on videotape or audio. Based on patients' narratives of their disease, a thematic-inductive analysis was performed of the information gathered. RESULTS: The findings show the importance of the internet as a source of health information. Moreover, the internet is a resource that is able to promote the empowerment process among patients and, consequently, to aid improvement in disease management. CONCLUSIONS: Users need access to web sites with high quality health information, adapted to their needs and objectives.


Asunto(s)
Neoplasias de la Mama/psicología , Conducta en la Búsqueda de Información , Internet/estadística & datos numéricos , Adulto , Anciano , Neoplasias de la Mama/terapia , Terapia Combinada , Información de Salud al Consumidor , Escolaridad , Femenino , Humanos , Persona de Mediana Edad , Poder Psicológico , Investigación Cualitativa , España
17.
Clin Transl Oncol ; 14(6): 413-22, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22634529

RESUMEN

Chemotherapy-induced nausea and vomiting (CINV) is a major determinant of quality of life in cancer patients. In addition, the perceptions that oncology professionals have about CINV quite often do not coincide with reality. Antineoplastic agents and their combinations can be categorised according to their emetogenic level, and this categorisation is helpful for classifying the severity of CINV and treating it. All CINV treatment guidelines emphasise the need to administer prophylaxis to patients who receive highly or moderately emetogenic chemotherapy. With the introduction of NK1 receptor antagonists, the control of acute and delayed CINV after highly or moderately emetogenic chemotherapy schedules has improved in the great majority of patients. NK1 receptor antagonists have been demonstrated to improve the control of CINV in all risk subgroups of patients.


Asunto(s)
Antineoplásicos/efectos adversos , Náusea/inducido químicamente , Vómitos/inducido químicamente , Antieméticos/administración & dosificación , Antineoplásicos/uso terapéutico , Humanos , Náusea/tratamiento farmacológico , Náusea/fisiopatología , Vómitos/tratamiento farmacológico , Vómitos/fisiopatología
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