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1.
J Transl Med ; 20(1): 436, 2022 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-36180872

RESUMEN

BACKGROUND: The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma. METHODS: Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb-IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment. RESULTS: Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28-0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29-0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005). CONCLUSIONS: This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents.


Asunto(s)
Melanoma , Receptor de Muerte Celular Programada 1 , Cetirizina/farmacología , Cetirizina/uso terapéutico , Humanos , Interferón gamma/uso terapéutico , Macrófagos/metabolismo , Melanoma/genética , Estudios Retrospectivos
2.
Radiol Med ; 127(2): 183-190, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34958441

RESUMEN

PURPOSE: To assess efficacy and safety of cone beam computed tomography (CBCT) in the radiofrequency ablation (RFA) of osteoid osteoma (OO) in children and adolescents, and to compare technical success, clinical success, radiation dose and procedure duration time of CBCT guidance to conventional computed tomography (CT) guidance. MATERIALS AND METHODS: Between 2015 and 2019, 53 consecutive percutaneous RFA were performed on pediatric patients with CBCT or conventional CT guidance, respectively, in 24 and 29 children and adolescents with 24-month follow-up. Dose area product (DAP) and dose length product (DLP) were recorded, respectively, for CBCT and conventional CT and converted to effective doses (ED). RESULTS: CBCT and conventional CT groups were similar in terms of patient age and weight, tumor size and tumor location. Technical success was achieved in all cases. Primary clinical success was 91.67% (22/24) for the CBCT group and 89.66% (26/29) for the conventional CT group. Mean DAP was 64.75Gycm2 (range 6.0-266.7). Mean DLP was 972.62mGycm (range 337-2344). ED was significantly lower in the CBCT group compared to the conventional CT group (0.34 mSv vs. 5.53 mSv, p = 0.0119). Procedure duration time was not significantly longer in the CBCT group (102.25 min vs. 92.34 min, p = 0.065). No major complication was registered. Minor complications were observed in 4 patients (2 in CBCT; 2 in conventional CT). CONCLUSIONS: Compared to conventional CT guidance, CBCT guidance for percutaneous OO ablation shows similar technical and clinical success rates, with reduced radiation dose and equivalent procedure duration time. This technique helps sparing dose exposure to pediatric patients.


Asunto(s)
Tomografía Computarizada de Haz Cónico/métodos , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/cirugía , Dosis de Radiación , Ablación por Radiofrecuencia/métodos , Radiografía Intervencional/métodos , Adolescente , Femenino , Humanos , Masculino , Resultado del Tratamiento
3.
Curr Heart Fail Rep ; 18(4): 191-199, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34181210

RESUMEN

PURPOSE OF REVIEW: Oncological treatments are known to induce cardiac toxicity, but the impact of new-onset cancer in patients with pre-existing HF remains unknown. This review focuses on the epidemiology, pathophysiological mechanisms, and clinical implications of HF patients who develop malignancies. RECENT FINDINGS: Novel findings suggest that HF and cancer, beside common risk factors, are deeply linked by shared pathophysiological mechanisms. In particular, HF itself may enhance carcinogenesis by producing pro-inflammatory cytokines, and it has been suggested that neurohormonal activation, commonly associated with the failing heart, might play a pivotal role in promoting neoplastic transformation. The risk of malignancies seems to be higher in HF patients compared to the general population, probably due to shared risk factors and common pathophysiological pathways. Additionally, management of these patients represents a challenge for clinicians, considering that the co-existence of these diseases significantly worsens patients' prognosis and negatively affects therapeutic options for both diseases.


Asunto(s)
Insuficiencia Cardíaca , Neoplasias , Cardiotoxicidad , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Pronóstico , Factores de Riesgo
4.
Eur J Nucl Med Mol Imaging ; 45(10): 1721-1730, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29516130

RESUMEN

PURPOSE: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. METHODS: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. RESULTS: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976. CONCLUSIONS: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.


Asunto(s)
Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica , Neoplasias Hepáticas/radioterapia , Hígado/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Embolización Terapéutica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Seguridad , Análisis de Supervivencia , Adulto Joven
5.
Med Lav ; 109(6): 471-477, 2018 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-30556537

RESUMEN

BACKGROUND: Following recent epidemiological studies, which showed tissue reactions from ionizing radiation at significantly lower doses, the 2013/59 EURATOM Directive of 5th December 2013 lowered the limit on the equivalent dose to the eye lens from 150 mSv to 20 mSv per year. Therefore, as a precautionary measure, it is considered appropriate to perform a timely dose monitoring by using specific dosimeters. OBJECTIVES: Analysis of the current state of the eye lens exposures during interventional procedures. The survey aimed at assessing the degree of information available to the exposed workers as regards lowering the dose limit in Interventional Radiology departments of some hospitals in Campania (Southern Italy). METHODS: The equivalent dose was assessed, over a period of 90 days, using specific Hp dosimeters(3), placed sideways with regard to prescription eye glasses. The level of awareness of the new dose limit among operators was assessed using a questionnaire. RESULTS: The values of the equivalent dose to the lens of the eye for the I and II Operators were found to be <150 mSv/year but for the I Operator a value of 54 mSv/year was obtained, ie higher than 20 mSv/year, that is the new limit of the equivalent dose according to 2013/59 EURATOM. The initial results of the questionnaire from 52 exposed workers, of which 46 (88%) were from exposure category A and 6 (12%) from category B, showed a low level of information (19%). CONCLUSIONS: The results highlight not only the importance of using specific devices for individual protection but also the importance of the level of training and information the exposed medical staff are given concerning the new regulations.


Asunto(s)
Cristalino , Exposición Profesional , Exposición a la Radiación , Protección Radiológica , Humanos , Cristalino/efectos de la radiación , Dosis de Radiación , Radiología Intervencionista
6.
Bioinformatics ; 32(17): 2672-80, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27162187

RESUMEN

MOTIVATION: Vaccines represent the most effective and cost-efficient weapons against a wide range of diseases. Nowadays new generation vaccines based on subunit antigens reduce adverse effects in high risk individuals. However, vaccine antigens are often poor immunogens when administered alone. Adjuvants represent a good strategy to overcome such hurdles, indeed they are able to: enhance the immune response; allow antigens sparing; accelerate the specific immune response; and increase vaccine efficacy in vulnerable groups such as newborns, elderly or immuno-compromised people. However, due to safety concerns and adverse reactions, there are only a few adjuvants approved for use in humans. Moreover, in practice current adjuvants sometimes fail to confer adequate stimulation. Hence, there is an imperative need to develop novel adjuvants that overcome the limitations of the currently available licensed adjuvants. RESULTS: We developed a computational framework that provides a complete pipeline capable of predicting the best citrus-derived adjuvants for enhancing the immune system response using, as a target disease model, influenza A infection. In silico simulations suggested a good immune efficacy of specific citrus-derived adjuvant (Beta Sitosterol) that was then confirmed in vivoAvailability: The model is available visiting the following URL: http://vaima.dmi.unict.it/AdjSim CONTACT: francesco.pappalardo@unict.it; fp@francescopappalardo.net.


Asunto(s)
Adyuvantes Inmunológicos , Citrus , Sistema Inmunológico , Vacunas contra la Influenza , Anciano , Antígenos , Predicción , Humanos , Huésped Inmunocomprometido , Recién Nacido , Modelación Específica para el Paciente
7.
Cancer Med ; 13(4): e6892, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38457226

RESUMEN

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Anciano , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Heterogeneidad Genética , Pronóstico
8.
J Hepatol ; 59(4): 753-61, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23707371

RESUMEN

BACKGROUND & AIMS: The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. METHODS: Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. RESULTS: Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. CONCLUSIONS: Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.


Asunto(s)
Carcinoma Hepatocelular/terapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Embolización Terapéutica/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Microesferas , Persona de Mediana Edad , Radiofármacos/administración & dosificación , Radiofármacos/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/efectos adversos
9.
Sci Rep ; 13(1): 22531, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110463

RESUMEN

The adoption of high-fidelity models in multidisciplinary design optimization (MDO) permits to enhance the identification of superior design configurations, but would prohibitively rise the demand for computational resources and time. Multifidelity Bayesian Optimization (MFBO) efficiently combines information from multiple models at different levels of fidelity to accelerate the MDO procedure. State-of-the-art MFBO methods currently meet two major limitations: (i) the sequential adaptive sampling precludes parallel computations of high-fidelity models, and (ii) the search scheme measures the utility of new design evaluations only at the immediate next iteration. This paper proposes a Non-Myopic Multipoint Multifidelity Bayesian Optimization (NM3-BO) algorithm to sensitively accelerate MDO overcoming the limitations of standard methods. NM3-BO selects a batch of promising design configurations to be evaluated in parallel, and quantifies the expected long-term improvement of these designs at future steps of the optimization. Our learning scheme leverages an original acquisition function based on the combination of a two-step lookahead policy and a local penalization strategy to measure the future utility achieved evaluating multiple design configurations simultaneously. We observe that the proposed framework permits to sensitively accelerate the MDO of a space vehicle and outperforms popular algorithms.

10.
Front Oncol ; 13: 1077794, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37324013

RESUMEN

Cholangiocarcinoma (CCA) is a rare cancer originating from the biliary epithelium and accounts for about 3% of all gastrointestinal malignancies. Unfortunately, the majority of patients are not eligible for surgical resection at the time of diagnosis, because of the locally advanced stage or metastatic disease. The overall survival time of unresectable CCA is generally less than 1 year, despite current chemotherapy regimens. Biliary drainage is often required as a palliative treatment for patients with unresectable CCA. Recurrent jaundice and cholangitis tend to occur because of reobstruction of the biliary stents. This not only jeopardizes the efficacy of chemotherapy, but also causes significant morbidity and mortality. Effective control of tumor growth is crucial for prolonging stent patency and consequently patient survival. Recently, endobiliary radiofrequency ablation (ERFA) has been experimented as a treatment modality to reduce tumor mass, and delay tumor growth, extending stent patency. Ablation is accomplished by means of high-frequency alternating current which is released from the active electrode of an endobiliary probe placed in a biliary stricture. It has been shown that tumor necrosis releases intracellular particles which are highly immunogenic and activate antigen-presenting cells, enhancing local immunity directed against the tumor. This immunogenic response could potentially enhance tumor suppression and be responsible for improved survival of patients with unresectable CCA who undergo ERFA. Several studies have demonstrated that ERFA is associated with an increased median survival of approximately 6 months in patients with unresectable CCA. Furthermore, recent data support the hypothesis that ERFA could ameliorate the efficacy of chemotherapy administered to patients with unresectable CCA, without increasing the risk of complications. This narrative review discusses the results of the studies published in recent years and focuses on the impact that ERFA could have on overall survival of patients with unresectable cholangiocarcinoma.

11.
Cancers (Basel) ; 15(6)2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36980713

RESUMEN

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as "oligometastatic disease" (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.

12.
Hepatology ; 54(3): 868-78, 2011 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-21618574

RESUMEN

UNLABELLED: A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. CONCLUSION: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options.


Asunto(s)
Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/radioterapia , Radioisótopos de Itrio/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Embolización Terapéutica/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Microesferas , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
13.
Front Oncol ; 12: 1088962, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36713525

RESUMEN

Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor. PIK3CA is the main significant mutated gene after PTEN alterations. Overall, over 90% of endometrioid tumors have activating PI3K molecular alterations that suggests its critical role in the EC pathogenesis. Thus, the dysregulation of PI3K pathway represents an attractive target in EC treatment. Herein, we report a radiological and clinically meaningful response to a selective PIK3 inhibitor in a patient with extensively pre-treated advanced endometrioid EC harboring a somatic activating PIK3CA hotspot mutation. These evidences provide the rational for translational strategies of the PI3K inhibition and could support the clinical usefulness of PIK3CA genotyping in advanced EC. To our knowledge, this is the first clinical case of PIK3CA-mutated EC successfully treated with alpelisib.

14.
Front Immunol ; 13: 953115, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36119020

RESUMEN

Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called "kynurenine (Kyn) pathway", which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC.


Asunto(s)
Neoplasias Endometriales , Quinurenina , Biomarcadores , Neoplasias Endometriales/terapia , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Quinurenina/metabolismo , Triptófano/metabolismo
15.
PLoS One ; 16(3): e0248589, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33735214

RESUMEN

PURPOSE: To assess efficacy and safety of imaging-guided radiofrequency ablation (RFA) of Osteoid Osteoma (OO) in both typical and atypical sites. METHODS AND MATERIALS: Between January 2014 and March 2019, 102 consecutive percutaneous RFA were performed and retrospectively reviewed. The procedures were performed using a RFA bipolar ablation system (Covidien, exposed tip of 0.7-1cm), under Computed Tomography (CT) guidance or using a navigation system (Masmec) under CT and Cone Beam CT (CBCT) guidance. Patients were followed up over 24 months. Clinical success and recurrences were considered on the base of established criteria. In patients with clinical failure and/or imaging evidence of relapse, retreatment was considered. RESULTS: Administered power per-procedure was ≤8 W (mean temperature, 90°C). The pre-procedure average value of visual analog scale (VAS) was 8.33+/-0.91. Primary and secondary success rate 96.08% (98/102) and100% (102/102), respectively. No major complication was described. Technical success was proved in every patient by CT scan acquisition after needle positioning. Relapse and tumour location were significantly correlated (p-value = 0.0165). The mean dose-length product was 751.55 mGycm2. Advanced bone healing was noted in 68 lesions after 1y-follow up and in 86 lesions after 2y-follow up. CONCLUSION: Imaging-guided percutaneous RFA is a highly effective technique for OO, both in typical and atypical sites. CT or CBCT guidance, navigation systems and operator experience grant the technical success, which is the most crucial parameter affecting outcome.


Asunto(s)
Neoplasias Óseas/terapia , Dolor en Cáncer/terapia , Recurrencia Local de Neoplasia/epidemiología , Osteoma Osteoide/terapia , Ablación por Radiofrecuencia/métodos , Adolescente , Adulto , Neoplasias Óseas/complicaciones , Neoplasias Óseas/diagnóstico , Dolor en Cáncer/diagnóstico , Dolor en Cáncer/etiología , Tomografía Computarizada de Haz Cónico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Osteoma Osteoide/complicaciones , Osteoma Osteoide/diagnóstico , Dimensión del Dolor/estadística & datos numéricos , Ablación por Radiofrecuencia/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
16.
Thorac Cancer ; 11(2): 443-446, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31876364

RESUMEN

Solitary fibrous tumor (SFT) of the pleura is a rare neoplasm which is challenging for clinicians to treat and radiologists to diagnose. Herein, we report a case of recurrence of SFT of the pleura in a 77-year-old patient which was diagnosed and surgically treated on the first occasion in 2005. The patient had a recurrence in 2016 which was treated and then six months later, he again experienced chest pain and a further local recurrence was found. Taking into consideration the age and comorbidities of the patient, CT-guided percutaneous microwave-thermal ablation was preferrable to surgery and a safe and highly effective local ablative technique with few side-effects.


Asunto(s)
Técnicas de Ablación/efectos adversos , Hipertermia Inducida/efectos adversos , Microondas/efectos adversos , Recurrencia Local de Neoplasia/etiología , Tumor Fibroso Solitario Pleural/cirugía , Técnicas de Ablación/instrumentación , Anciano , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Pronóstico , Tumor Fibroso Solitario Pleural/patología
17.
Infect Agent Cancer ; 15(1): 69, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33292365

RESUMEN

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS "Fondazione Pascale" in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

18.
Anticancer Drugs ; 20(10): 893-900, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19752718

RESUMEN

Metastatic renal cell carcinoma (RCC) is notoriously chemoresistant; up until recently, immunotherapy (in particular interferon-alpha) has represented the treatment of choice. The understanding of the biology of RCC has resulted in the development of targeted therapies. In particular, multikinase inhibitors (sunitinib, sorafenib, axitinib, pazopanib), antivascular endothelial growth factor agents (bevacizumab), and mammalian target of rapamycin inhibitors (temsirolimus, everolimus) now have a role in the approach to different subsets of RCC. Sunitinib is indicated for the first-line therapy of metastatic RCC as a consequence of a positive phase III trial versus interferon-alpha; sorafenib is now registered for the second-line treatment of RCC, which was earlier treated with cytokine as a consequence of a positive phase III trial versus placebo. Bevacizumab is also indicated in the first-line treatment of metastatic RCC given in combination with interferon-alpha as a consequence of two positive phase III trials. Temsirolimus, unlike the other agents, has also shown activity in poor-prognosis patients, and is now the treatment of choice in previously untreated poor-prognosis RCC as a single agent. Everolimus can be considered as the best therapeutic option in patients with RCC pretreated with targeted agents as a consequence of a positive phase III study versus best supportive care. Markers for appropriate treatment selection, combined use of targeted agents, treatment of special histologies, and adjuvant and neoadjuvant setting represent important special issues to be dealt with in future studies.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Biomarcadores Farmacológicos , Protocolos Clínicos , Ensayos Clínicos como Asunto , Sistemas de Liberación de Medicamentos , Humanos , Modelos Biológicos , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas/metabolismo , Serina-Treonina Quinasas TOR , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
20.
PLoS One ; 14(5): e0216935, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31141552

RESUMEN

PURPOSE: Portal vein thrombosis (PVT) is generally recognized as a prognostic factor in HCC. Our purpose is to assess and compare the survival of patients with PVT and without PVT, after Y-90 Trans-Arterial Radio-Embolization (TARE) of unresectable HCC, unresponsive to other loco-regional treatments. MATERIALS AND METHODS: Between November 2005 and November 2012, Y-90 resin-based TARE was performed in an IRB-approved prospective protocol, on 89 patients with unresectable HCC. 33/89 patients had PVT, the remaining 56 were resistant-to-cTACE or underwent TARE as a downstaging therapy. All patients were studied with Multi-Detector Computed Tomography (MDCT), angiography, 99mTc-MAA-scintigraphy and liver biopsy. Gastro-duodenal artery was embolized in most cases. Proton-Pump Inhibitors were administered to prevent gastritis and ulcers. χ2 test with Yates correction and log rank test were used to compare the two proportions and Kaplan-Meier survival curves, respectively. RESULTS: The average activity administered was 1.7 ± 0.4 GBq. After the treatment, CTCAE grade 2 adverse events occurred in 46% (41/89) patients: in particular, fever and abdominal pain were found in 25 and 16 patients, respectively. No major side-effect was observed. According to mRECIST criteria, partial response or complete response was found in 70% of patient three months after the treatment, and in 90.5% nine months after the treatment. No significant difference was found in survival of patients with PVT compared to those without PVT (p-value = 0.672). A complete regression of PVT was observed in almost half patients (13/27, 48.1%). CONCLUSIONS: Portal vein invasion does not affect survival in advanced stage HCC-patients undergoing TARE using Y-90 resin-based microspheres. Y90 procedure is associated with regression of portal vein tumor thrombus.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Trombosis de la Vena/terapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/mortalidad , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Masculino , Microesferas , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Estadificación de Neoplasias , Vena Porta/diagnóstico por imagen , Vena Porta/patología , Vena Porta/efectos de la radiación , Pronóstico , Cintigrafía , Análisis de Supervivencia , Trombosis de la Vena/complicaciones , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/mortalidad
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