RESUMEN
BACKGROUND: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). PATIENTS AND METHODS: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). RESULTS: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). CONCLUSIONS: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients.
Asunto(s)
Neoplasias Encefálicas , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Neoplasias Renales/patología , Estudios Retrospectivos , Pronóstico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundarioRESUMEN
BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Nivolumab/farmacología , Nivolumab/uso terapéutico , Ipilimumab/farmacología , Ipilimumab/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
PURPOSE: The aim of this study was to evaluate the clinical outcomes of patients treated with anatomic medial patellofemoral ligament (MPFL) reconstruction with and without tibial tuberosity osteotomy (TTO). Correlations between patient's age, gender, pre-injury physical activity and the achieved results were investigated as secondary endpoints. METHODS: An observational retrospective study with prospective collected data was performed. Inclusion criteria were: treatment with anatomic MPFL reconstruction with gracilis tendon according to SchÓ§ttle's technique performed between 2011 and 2017; associated TTO as unique accessory procedure; skeletal joint maturity; a minimum follow-up of 12 months after surgery. Clinical outcomes were assessed with the Kujala, Lysholm and Tegner scores. RESULTS: Forty patients (42 knees) were included, 64% of them underwent TTO. The Kujala score significantly improved from 47.4 ± 17.6 preoperatively to 89.4 ± 13.6 postoperatively (p < 0.01). The average Lysholm score was 45.6 ± 20.5 preoperatively: it showed a significant increase to 89.8 ± 12.8 postoperatively (p < 0.01). Pre-injury mean Tegner was 5.9 ± 1.8, while it dropped to 3.0 ± 1.6 after injury. After surgery, Tegner resulted 4.9 ± 1.6. Forty-three percent of patients regained the pre-injury sport activity level. Redislocation rate was 2.4%. CONCLUSION: Anatomic MPFL reconstruction allows excellent patellar stability recovery, knee functionality improvement, return to Activities of Daily Living and a low redislocation rate. Better results were achieved in younger (under 30 years old) and higher sports activity-level subjects. The TTO association provided clinical results comparable to isolated MPFL reconstructions, suggesting that the two procedures can be safely accomplished together without affecting the positive outcomes. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Inestabilidad de la Articulación , Luxación de la Rótula , Ligamento Rotuliano , Articulación Patelofemoral , Humanos , Adulto , Inestabilidad de la Articulación/cirugía , Luxación de la Rótula/cirugía , Articulación Patelofemoral/cirugía , Estudios Retrospectivos , Estudios Prospectivos , Actividades Cotidianas , Ligamentos Articulares/cirugía , Osteotomía/métodos , Ligamento Rotuliano/cirugíaRESUMEN
The Sardinian and Sicilian Channels are considered hotspots of biodiversity and key ecological passages between Mediterranean sub-basins, but with significant knowledge gaps about marine mammal presence and potential threats they face. Using data collected between 2013 and 2019 along fixed transects, inter and intra-annual cetacean index of abundance was assessed. Habitat suitability, seasonal hot spots, and risk exposure for plastic were performed using the Kernel analysis and the Biomod2 R-package. 661 sightings of 8 cetacean species were recorded, with bottlenose and striped dolphins as the most sighted species. The north-eastern pelagic sector, the coastal waters and areas near ridges resulted the most suitable habitats for these species. The risk analysis identified the Tunis, Palermo, and Castellammare gulfs and the Egadi Island as areas of particular risk of plastic exposure. The study represents a great improvement for cetacean knowledge in this region and contributes to the development of effective conservation strategies.
Asunto(s)
Cetáceos , Plásticos , Animales , Biodiversidad , Ecosistema , Mar MediterráneoRESUMEN
Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-up data.Methods: The phase II RESORT trial randomized patients to sorafenib or observation within 12 weeks from surgery. RFS was the primary endpoint.Results: We analyzed 68 patients (32 in sorafenib and 36 in the observation arm), randomized between November 2012 and November 2017. Eighty-one percent in the sorafenib arm and 80% in the observation arm had one metastasis . At a median follow-up of 42 months (interquartile range 31-58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42-76%) at 24 and 44% (95% CI 30-65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34-71%) at 24 and 32% (95% CI 18-57%) at 48 months (p = 0.342;HR 1.35;95% CI 0.72-2.54). Forty-seven percent and 37.5% of the patients in the two arms, respectively, are disease free. The site of relapses was independent of the previous metastasectomy site.Expert commentary: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients should be considered in order to potentially improve survival.Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480.
Asunto(s)
Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Metastasectomía/métodos , Sorafenib/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Neoplasias Renales/patología , Recurrencia Local de Neoplasia , ProbabilidadRESUMEN
Mucilaginous aggregates produced by planktonic or benthic algae are considered ecological threats to marine systems. The study evaluated the effects of the spread of benthic mucilaginous aggregates on the structure of coralligenous assemblages. The assemblage and the quality of a site subjected to a benthic mucilage bloom were compared to those of two reference sites using a Before/After-Control/Impact (BACI) design. Results showed the α and ß-diversity, ESCA and COARSE quality ecological indices and the cover of encrusting algae and bryozoans were lower at the impact site after the mucilage event than at the control sites and at the impact site before the mucilage event. An opposite pattern was observed for the necrosis of gorgonians and the cover of algal turf. This study describes for the first time the impacts of ephemeral mucilage blooms on the whole coralligenous assemblage, identifying a further threat of this habitat and the need of adequate monitoring programs.
Asunto(s)
Antozoos/fisiología , Arrecifes de Coral , Microalgas/fisiología , Plancton/fisiología , Animales , EcosistemaRESUMEN
A modified version of the ALien Biotic IndEX (ALEX) has been recently proposed to evaluate biological invasions in macroalgal assemblages. ALEX was applied in a Marine Protected Area where a recreational-fishing port is present testing the following hypotheses: ALEX increases with the distance from the port, it changes between the two directions off the port and it changes among three different habitats: Cystoseira beds, algal turf and dead matte of the seagrass Posidonia oceanica. A total of 78 native macroalgal taxa and 4 introduced species were found, the Chlorophyta Caulerpa cylindracea and the Rhodophyta Apoglossum gregarium, Acrothamnion preissii and Womersleyella setacea. All study sites were in high quality status highlighting that the assemblages investigated were at an early stage of NIS invasion. However, ALEX detected different values among conditions and habitats within the MPA, suggesting a local dynamics of NIS spread and different resistance to invasion of the investigated habitats.
Asunto(s)
Monitoreo del Ambiente/métodos , Especies Introducidas/tendencias , Agua de Mar/química , Algas Marinas/crecimiento & desarrollo , Biodiversidad , Ecosistema , Italia , Algas Marinas/clasificación , Navíos , Estaciones de TransporteRESUMEN
INTRODUCTION: Even if different surgical approaches for total knee arthroplasty are well known since decades, the standard medial parapatellar incision remains the most common one; general agreement about significant advantages with minimally invasive techniques is lacking. Furthermore, the surgical stress effect on the organism has always been analyzed through blood inflammatory parameters. This study aim was to compare the standard and subvastus approaches, using the salivary cortisol in particular as measure for systemic surgery-related stress. METHODS: Fifteen operations were performed in a consecutive series; clinical (Knee Society Knee Scoring System., a questionnaire score, range of motion, tourniquet time, intra-operative bleeding) and biochemical factors (salivary and hematic cortisol, C-reactive protein, muscular creatine phosphokinase levels) were evaluated. The final follow-up was at two months after the operation. RESULTS: No significant differences were observed in most of the parameters; however, the subvastus group had a sharper and earlier functional improvement trend than the standard one. On the other side, it increased the CPK levels significantly. CONCLUSIONS: In our experience, the medial subvastus approach, firstly associated with greater surgical stress, has then been characterized by a more favorable functional improvement trend. Moreover, the salivary cortisol measurement has proved to be a non-invasive and reliable method to evaluate the systemic surgery-related stress.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Herida Quirúrgica/metabolismo , Anciano , Biomarcadores , Pérdida de Sangre Quirúrgica , Proteína C-Reactiva/análisis , Forma MM de la Creatina-Quinasa/sangre , Femenino , Humanos , Hidrocortisona/análisis , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Tempo Operativo , Osteoartritis de la Rodilla/cirugía , Estudios Prospectivos , Recuperación de la Función , Saliva/química , Estrés Fisiológico , Resultado del TratamientoRESUMEN
BACKGROUND: The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. PATIENTS AND METHODS: This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. RESULTS: From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33-83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1-7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4-58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). CONCLUSIONS: The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.
Asunto(s)
Androstadienos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Everolimus/administración & dosificación , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de NeoplasiasRESUMEN
INTRODUCTION: Isolated patellofemoral (PF) arthritis is rare, and there is no complete agreement about the best surgical treatment. The operative treatments are total knee arthroplasty and patellofemoral replacement (PFR). The incidence of many early complications of PF arthroplasty has decreased with the introduction of newer designs. Nowadays, the main cause of revision surgery is the progression of tibiofemoral osteoarthritis. In the past, PF arthroplasty was contraindicated in patients with evidence of osteoarthritis or pain in medial or lateral tibiofemoral compartments. The improvement in implant designs and surgical techniques has allowed the addition of a monocompartmental arthroplasty for the medial or lateral tibiofemoral compartment. In this work, we evaluate our first experience with PF arthroplasty and its combination with unicompartmental knee arthroplasty. MATERIALS AND METHODS: From May 2014 to March 2016, we treated 14 patients. An isolated PF arthroplasty was performed in six knees (five patients), and a combined PF and unicompartmental knee arthroplasty was performed in nine cases. We observed a significant improvement in the clinical and functional Knee Society Scores (KSSs) after surgery in our patients. RESULTS: We obtained good results in our cases both for clinical and functional KSSs. Patellar clunk was recorded in one case. DISCUSSION AND CONCLUSION: We are going toward a new attitude in which partial osteoarthritic changes could be treated with partial resurfacing prosthetic solutions such as unicompartmental, bi-unicompartmental or PFR alone, or unicompartmental combined, which respects the cruciates and achieves maximal bone preservation, which is vital, particularly, for young patients.
RESUMEN
BACKGROUND: Total knee arthroplasty gives excellent objective results. Nevertheless, the subjective findings do not match the normal knee perception: Often, it depends on patellar pain onset. In this study, we analyzed clinical and radiological items that can affect resurfaced patellar tracking, and role of a patella-friendly femoral component and patellar size on patellar pain onset. MATERIALS AND METHODS: Thirty consecutive patients were implanted using the same-cemented posterior-stabilized TKA associated with patella resurfacing. Fifteen patients were implanted using a classical femoral component, while another 15 patients were implanted using a patella-friendly femoral component. The statistical analysis was set to detect a significant difference (p < 0.05) in clinical and radiological outcomes related to several surgical parameters. Clinical and functional outcomes were recorded using the Knee Society Scoring System (KSS) and patellar pain with the Burnett questionnaire. RESULTS: Mean follow-up was 25 months. KSS results were excellent in both groups. Group 2 (patella-friendly femoral model) reached a higher percentage of 100 points in the clinical and functional KSS, but there was no statistical difference. Also, no statistical differences for Burnett Questionnaire results were recorded. We had one case of patellar clunk syndrome in the standard femoral component group and one poor result in the second group. Postoperative radiographic measurements evidenced no statistical differences in both groups. In group 1 (classical femoral component), better significant result (p < 0.05) war recorded at clinical evaluation according to the Knee Society Scoring System (KSS) in case of wider patellar component resurfaced. CONCLUSIONS: The present study reveals no statistically significant difference in the incidence of anterior knee pain between classical and "patella-friendly" femoral components. With the particular type of implant design utilized in this study, when the classical femoral component is used, bigger patellar implant sizes (38 and 41 mm) showed superior clinical outcome.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla/cirugía , Dimensión del Dolor , Dolor Postoperatorio , Rótula , Articulación Patelofemoral , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/instrumentación , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Estudios de Seguimiento , Humanos , Prótesis de la Rodilla , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Dimensión del Dolor/métodos , Dolor Postoperatorio/etiología , Rótula/patología , Articulación Patelofemoral/patología , Diseño de Prótesis , Rango del Movimiento Articular , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Since its first detection in Sardinia (Italy), Tuta absoluta (Meyrick) has been reported as a major pest of greenhouse tomatoes. In recent years, however, a tendency toward a progressive reduction of tomato borer infestation levels has been observed. The reasons behind this decline are probably diverse, including both the increase in growers' ability to manage the pest and the adaptation of native predators and parasitoids to the new prey/host. In order to assess the species composition of the parasitoid complex associated with T. absoluta larvae in Sardinian greenhouse tomatoes, a two-year (2010/11) survey was conducted in one of the island's major horticultural areas (Pula, Cagliari). An estimate of the levels of parasitism caused by native wasps was also carried out. The occurrence of larval parasitoids of T. absoluta was detected in approximately half of the crops monitored. The average parasitism rate recorded in tomato plants infested by tomato borer larvae was 1.3%. Moreover, while no parasitism was observed in 76.4% of the samples collected, only 3.0% of the samples showed a parasitism rate exceeding 10%. The highest rates were recorded in spring and summer, with a peak in July (4.8%). Of 159 adult parasitoids recovered from infested leaves, 62.9% were found to belong to a Necremnus sp. near artynes (Walker), 34.6% to a Necremnus sp. near tidius (Walker), and 2.5% to Neochrysocharis formosa (Westwood) (Hymenoptera: Eulophidae). These results show that some native parasitoids have adapted to T. absoluta in the study area. Although parasitoid abundance in tomato crops appeared to be low, their contribution for the control of tomato borer infestation could possibly be enhanced through the application of conservation biological control measures.
Asunto(s)
Mariposas Nocturnas/fisiología , Enfermedades de las Plantas/parasitología , Solanum lycopersicum/parasitología , Avispas/crecimiento & desarrollo , Animales , Femenino , Italia , Larva/crecimiento & desarrollo , Masculino , Control Biológico de Vectores , Enfermedades de las Plantas/prevención & control , Estaciones del AñoAsunto(s)
Heterópteros/crecimiento & desarrollo , Mariposas Nocturnas/fisiología , Control Biológico de Vectores/métodos , Enfermedades de las Plantas/prevención & control , Solanum lycopersicum/parasitología , Animales , Femenino , Larva/crecimiento & desarrollo , Masculino , Enfermedades de las Plantas/parasitologíaRESUMEN
Coastal habitats play a major role as nurseries for many fish species; however, they are also submitted to pollutants and oxygen fluctuations. Fry's concept of metabolic scope for activity was used to evaluate the effect of polychlorinated biphenyls (PCBs) on the aerobic metabolism in juvenile common sole (0-1 year old). Aerobic metabolic scope (AMS) in control and PCB-contaminated fish via food pathway was determined using respirometry techniques. Furthermore, the hypoxia tolerance in control and PCB-contaminated fish was evaluated by assessing their critical oxygen concentration (O(2crit)). Our results showed that while PCB-contaminated fish were able to maintain a constant AMS and O(2crit), PCBs tend to affect their aerobic metabolism by acting on maximal oxygen consumption (MO(2max)) in hypoxia and standard metabolic rate, but only at the highest PCB concentration between 30 and 60 days of exposure. In conclusion, we can hypothetise that the tested PCB-exposures may not impair the tolerance to hypoxia and the survival of common sole in their natural environment.
Asunto(s)
Metabolismo Energético/efectos de los fármacos , Exposición a Riesgos Ambientales , Peces Planos/metabolismo , Bifenilos Policlorados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Aerobiosis/efectos de los fármacos , Animales , Hígado/efectos de los fármacos , Oxígeno/metabolismoRESUMEN
Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients' outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.
Asunto(s)
Neoplasias de la Mama/fisiopatología , Regulación Neoplásica de la Expresión Génica , Proteínas de Filamentos Intermediarios/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas del Tejido Nervioso/genética , Nestina , Fenotipo , Pronóstico , Receptores de Estrógenos/inmunologíaRESUMEN
The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.
Asunto(s)
Biomarcadores Farmacológicos/análisis , Inhibidores Enzimáticos/uso terapéutico , Neoplasias/tratamiento farmacológico , Inhibidores de las Quinasa Fosfoinosítidos-3 , Antineoplásicos/uso terapéutico , Biomarcadores Farmacológicos/metabolismo , Ensayos Clínicos como Asunto , Humanos , Modelos Biológicos , Mutación/fisiología , Neoplasias/genética , Neoplasias/metabolismo , Proteína Oncogénica v-akt/antagonistas & inhibidores , Proteína Oncogénica v-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Long-term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent relapses. This 12-month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE). METHODS: During the initial open-label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of < or =2 was achieved, the patient entered the disease control period (DCP) and was randomized to either proactive tacrolimus (n = 116) or vehicle ointment (n = 108) twice weekly for 12 months. Exacerbations were treated with 0.1% tacrolimus ointment b.i.d. until an IGA < or =2 was regained, then randomized treatment was restarted. The primary endpoint was the number of DEs during the DCP that required a substantial therapeutic intervention. RESULTS: Proactive tacrolimus 0.1% ointment application significantly reduced the number of DEs requiring substantial therapeutic intervention (median difference 2; P < 0.001; Wilcoxon rank sum test), the percentage of DE treatment days (median difference: 15.2%; P < 0.001; Wilcoxon rank sum test) and increased the time to first DE (median 142 vs 15 days; P < 0.001; stratified log-rank test). The adverse event profile was similar for the two treatment approaches. CONCLUSION: A 12-month, twice weekly proactive tacrolimus ointment application was an effective treatment in most study patients which prevented, delayed and reduced the occurrence of AD exacerbations.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Tacrolimus/administración & dosificación , Adulto , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Pomadas , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Several surgical techniques have been proposed for the treatment of piebaldism. These procedures, however, are poorly suited for the treatment of large leucodermal lesions, can cause scars and require multiple donor sites. Recently, it has been reported that autologous cultured epidermis induces scarless repigmentation of large vitiligo lesions, using a single small donor site. OBJECTIVES: To induce permanent repigmentation of large achromic lesions in patients suffering from piebaldism by means of autologous cultured epidermal grafts using a rapid, simple and non-invasive surgical procedure. METHODS: Six patients with piebaldism were enrolled in this study. Achromic epidermis was removed by means of appropriately set erbium:YAG laser and autologous cultured epidermal grafts were applied on to the recipient bed. Melanocyte content was evaluated by 3,4-dihydroxyphenylalanine reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. RESULTS: Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45% (2791.5 cm2 repigmented/2924.2 cm2 transplanted). CONCLUSIONS: Autologous cultured epidermal grafts induce permanent and complete repigmentation of piebald lesions, in the absence of scars. Erbium:YAG laser surgery is a rapid and precise tool for disepithelialization, hence allowing treatment of large piebald lesions during a single surgical operation.
Asunto(s)
Queratinocitos/trasplante , Terapia por Láser/métodos , Piebaldismo/terapia , Pigmentación de la Piel/fisiología , Adolescente , Adulto , Células Cultivadas , Niño , Terapia Combinada/métodos , Epidermis/fisiopatología , Femenino , Humanos , Masculino , Piebaldismo/fisiopatología , Piebaldismo/cirugía , Trasplante AutólogoRESUMEN
A pilot study was conducted to assess the tolerability and the effect on host immunity of a post-surgery adjuvant treatment of melanoma patients with an anti-angiogenic agent, Tamoxifen (TAM, 20 mg/die p.o., daily), combined with immunomodulating cytokines, i.e. recombinant interleukin-2 (IL-2, 4 MUI/m2 s.c., day 8,10,12) and alpha-2b-interferon (IFN, 3 MUI/m2 i.m., day 15,17,19), starting a new cycle on day 21, for a total of 12 cycles. Fifty patients (pts) entered into the study, 27 males and 23 females with a median age of 55 years (range 25-75), performance status (ECOG) 0 with melanoma stage IIA (12 patients), stage IIB (28 patients), stage III (10 patients). Preliminary in vitro studies showed that TAM does not interfere with up-regulation of natural immunity induced by IFN, IL-2, or IFN + IL-2 in normal peripheral blood mononuclear cells (MNC). The clinical study indicates that the protocol was well tolerated. Increase of NK and LAK activity of patient MNC was observed on day 15. The mean disease-free interval was 10 months and 40 pts were alive at 5 years of follow-up. Further investigations should be performed to test effectiveness of this protocol in a randomized study.