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1.
Nat Commun ; 12(1): 4878, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385447

RESUMO

A postprandial increase of translation mediated by eukaryotic Initiation Factor 6 (eIF6) occurs in the liver. Its contribution to steatosis and disease is unknown. In this study we address whether eIF6-driven translation contributes to disease progression. eIF6 levels increase throughout the progression from Non-Alcoholic Fatty Liver Disease (NAFLD) to hepatocellular carcinoma. Reduction of eIF6 levels protects the liver from disease progression. eIF6 depletion blunts lipid accumulation, increases fatty acid oxidation (FAO) and reduces oncogenic transformation in vitro. In addition, eIF6 depletion delays the progression from NAFLD to hepatocellular carcinoma, in vivo. Mechanistically, eIF6 depletion reduces the translation of transcription factor C/EBPß, leading to a drop in biomarkers associated with NAFLD progression to hepatocellular carcinoma and preserves mitochondrial respiration due to the maintenance of an alternative mTORC1-eIF4F translational branch that increases the expression of transcription factor YY1. We provide proof-of-concept that in vitro pharmacological inhibition of eIF6 activity recapitulates the protective effects of eIF6 depletion. We hypothesize the existence of a targetable, evolutionarily conserved translation circuit optimized for lipid accumulation and tumor progression.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Fatores de Iniciação de Peptídeos/genética , Biossíntese de Proteínas/genética , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Clofazimina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Progressão da Doença , Inativação Gênica , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , Fatores de Iniciação de Peptídeos/antagonistas & inibidores , Fatores de Iniciação de Peptídeos/metabolismo
2.
J Clin Med ; 10(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073544

RESUMO

Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.

3.
Transl Lung Cancer Res ; 10(5): 2368-2377, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164284

RESUMO

Since the National Lung Screening Trial in 2011 showed a 20% reduction in lung cancer mortality using annual low-dose computed tomography (LDCT), several randomised controlled trials and studies have been started in Europe. These include the Italian lung study (ITALUNG), the Dutch-Belgian lung cancer screening trial (NELSON), the UK lung cancer screening trial (UKLS), the Detection and screening of early lung cancer with novel imaging technology (DANTE), the Danish lung cancer screening trial (DLCST), the German lung cancer screening intervention trial (LUSI), the Multicentric Italian lung detection trial (MILD) and the CT screening for lung cancer study (COSMOS). As a result of the increasing number of screening trials and the growing utilization of LDCT, the high detection of subsolid nodules is an increasingly important clinical problem. In the last few years, several guidelines have been published and providing guidance on the optimal management of subsolid nodules, but many controversies still exist. Follow-up imaging plays an important role in clinical assessment and subsequent management of this particular type of lung nodules, since they can be transient inflammatory lesions, and if persistent they can be both benign lesions or lung cancers of variable clinical behaviour. However, the vast majority of subsolid nodules retain an indolent course over many years. The aim of this review is to present a European perspective in management of screening detected subsolid nodules.

4.
Front Med (Lausanne) ; 8: 664529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968968

RESUMO

Purpose: To evaluate the performance of artificial neural networks (aNN) applied to preoperative 18F-FDG PET/CT for predicting nodal involvement in non-small-cell lung cancer (NSCLC) patients. Methods: We retrospectively analyzed data from 540 clinically resectable NSCLC patients (333 M; 67.4 ± 9 years) undergone preoperative 18F-FDG PET/CT and pulmonary resection with hilo-mediastinal lymphadenectomy. A 3-layers NN model was applied (dataset randomly splitted into 2/3 training and 1/3 testing). Using histopathological reference standard, NN performance for nodal involvement (N0/N+ patient) was calculated by ROC analysis in terms of: area under the curve (AUC), accuracy (ACC), sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV). Diagnostic performance of PET visual analysis (N+ patient: at least one node with uptake ≥ mediastinal blood-pool) and of logistic regression (LR) was evaluated. Results: Histology proved 108/540 (20%) nodal-metastatic patients. Among all collected data, relevant features selected as input parameters were: patients' age, tumor parameters (size, PET visual and semiquantitative features, histotype, grading), PET visual nodal result (patient-based, as N0/N+ and N0/N1/N2). Training and testing NN performance (AUC = 0.849, 0.769): ACC = 80 and 77%; SE = 72 and 58%; SP = 81 and 81%; PPV = 50 and 44%; NPV = 92 and 89%, respectively. Visual PET performance: ACC = 82%, SE = 32%, SP = 94%; PPV = 57%, NPV = 85%. Training and testing LR performance (AUC = 0.795, 0.763): ACC = 75 and 77%; SE = 68 and 55%; SP = 77 and 82%; PPV = 43 and 43%; NPV = 90 and 88%, respectively. Conclusions: aNN application to preoperative 18F-FDG PET/CT provides overall good performance for predicting nodal involvement in NSCLC patients candidate to surgery, especially for ruling out nodal metastases, being NPV the best diagnostic result; a high NPV was also reached by PET qualitative assessment. Moreover, in such population with low a priori nodal involvement probability, aNN better identify the relatively few and unexpected nodal-metastatic patients than PET analysis, so supporting the additional aNN use in case of PET-negative images.

5.
Epidemiol Prev ; 45(1-2): 72-81, 2021.
Artigo em Italiano | MEDLINE | ID: mdl-33884845

RESUMO

OBJECTIVES: to define the most frequent health pathways of cases affected by malignant pleural mesothelioma according to those suggested and evaluated by the most recent specific guidelines. DESIGN: epidemiological descriptive study. SETTING AND PARTICIPANTS: 100 cases histologically or cytologically well defined during 2015-2017 are extracted from the archive of two Regional Mesothelioma Registries: in Tuscany Region (Central Italy) they are randomly extracted, while in Lombardy Region (Northern Italy) cases treated by a highly-specialized health centre are collected. MAIN OUTCOME MEASURES: frequency of the diagnostic and therapeutic procedures; development and application of the checklist with evaluation of the duration of some phases of the predefined pathway. RESULTS: all hospital medical records were collected only for 34 cases in Tuscany and 20 cases in Lombardy. The health examinations were supplied according to each case's health condition and it was not possible to define one or more structured and standardized pathways. The pre-diagnostic phase has a variable duration according to the initial health condition of the patient, also for his/her comorbidity, and to the hospital where he/she was hospitalized at first. The examinations in outpatient services (medical examinations, blood chemistry tests and radiological examinations) are several, but they are specially requested during the pre-diagnostic phase and during the period of chemotherapy. The checklist applied to a subset of Tuscan cases shows a large variation of the length of the pre-diagnostic phase (6-330 days), of the time interval between diagnosis and reporting to mesothelioma registry (1-200 days), and of the survival time (8 days - alive at 31.12.2019). CONCLUSIONS: to obtain the best health pathways for malignant pleural mesotheliomas, it is necessary a strong network among the health regional services with a clinical multiprofessional coordination located in hospitals characterized by a long experience on these cases, and with an active regional monitoring on all clinical, psychological, epidemiological, and legal aspects of the pathway. The regional mesothelioma registries could give a high contribution thanks to their epidemiological skills which are necessary for the monitoring.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Feminino , Acesso aos Serviços de Saúde , Humanos , Itália/epidemiologia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/epidemiologia , Mesotelioma/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/terapia
6.
Lung Cancer ; 154: 29-35, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33610120

RESUMO

BACKGROUNDS: Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. METHODS: The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan - Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. RESULTS: 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29-53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00-1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45-1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 - 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21-3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. CONCLUSIONS: Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
7.
Ann Surg Oncol ; 28(2): 676-684, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32720046

RESUMO

BACKGROUND: This study aimed to identify the results of the quality assessment and the learning curve of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK). METHODS: The study retrospectively reviewed the data of 400 consecutive patients with esophageal cancer who underwent RAMIE-MK by a single surgeon from November 2015 to March 2019. Cumulative summation analysis of the learning curve was performed. The patients were divided into decile cohorts of 40 cases to minimize demographic deviations and to maximize the power of detecting statistically significant changes in performance. RESULTS: The 90-day mortality rate for all the patients was 0.5% (2 cases). The authors' experience was divided into the ascending phase (40 cases), the plateau phase (175 cases), and the descending phase (185 cases). After 40 cases, significant improvements in operative time (328 vs. 251 min; P = 0.019), estimated blood loss (350 vs. 200 ml; P = 0.031), and conversion rates (12.5% vs. 2.5%; P < 0.001) were observed. After 80 cases, a decrease in the rates of anastomotic leakage (22.5% vs. 8.1%; P = 0.001) and vocal cord palsy (31.3% vs. 18.4%; P = 0.024) was observed. The number of harvested lymph nodes increased after 40 cases (13 vs. 23; P < 0.001), especially for lymph nodes along the recurrent laryngeal nerve (3.0 vs. 6.0; P < 0.001). CONCLUSIONS: The learning phase of RAMIE-MK consists of 40 cases, and quality outcomes can be improved after 80 procedures. Several turning points related to the optimization of surgical outcomes can be used as benchmarks for surgeons performing RAMIE-MK.


Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Curva de Aprendizado , Estudos Retrospectivos
8.
Dev Comp Immunol ; 109: 103697, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32330465

RESUMO

The transition from a naïve to an effector T cell is an essential event that requires metabolic reprogramming. We have recently demonstrated that the rapid metabolic changes that occur following stimulation of naïve T cells require the translation of preexisting mRNAs. Here, we provide evidence that translation regulates the metabolic asset of effector T cells. By performing ribosome profiling in human CD4+ Th1 cells, we show that the metabolism of glucose, fatty acids and pentose phosphates is regulated at the translational level. In Th1 cells, each pathway has at least one enzyme regulated at the translational level and selected enzymes have high translational efficiencies. mRNA expression does not predict protein expression. For instance, PKM2 mRNA is equally present in naïve T and Th1 cells, but the protein is abundant only in Th1. 5'-untranslated regions (UTRs) may partly account for this regulation. Overall we suggest that immunometabolism is controlled by translation.

9.
Clin Lung Cancer ; 21(5): e417-e422, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32276869

RESUMO

INTRODUCTION: Surgical resection with minimally invasive approach is the gold standard for both definitive diagnosis and treatment of solitary pulmonary nodules (SPNs); however, it can be difficult to pinpoint small, deep, or subsolid nodes without palpating lung parenchyma. The primary endpoint of this study is showing that radioguided surgery is a cost-effective strategy to improve the effectiveness of video-thoracoscopic localization/resection of SPNs/ground-glass opacities (GGOs). Secondary endpoints are analyzing the morbidity of this technique and tips and tricks to better manage this method. METHODS: SPN smaller than 20 mm and/or with a distance from the visceral pleura ≥5 mm underwent minimally invasive resection after computed tomography-guided injection of a solution composed of 0.1/0.2 mL of 99Tc-labeled human serum albumin microspheres and 0.1 mL of nonionic contrast. In the operating theater, a collimated probe connected to a gamma ray detector allowed localization of the target area. RESULTS: Between 1997 and 2018, a total of 451 patients with SPN/GGO underwent minimally invasive surgery with a radioguided technique at our hospital. The mean SPN diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-29 mm). The mean time to a localizing nodule was 3 minutes (range, 1-5 minutes). No significant injection-related complications were reported; only 3.3% of patients (15 of 451) developed pneumothorax. Both 30- to 60-day and 90-day mortality were 0%. The rate of postoperative complications was 2.53% (prolonged air leak). The conversion rate to thoracotomy was 1.55% (7 of 451). CONCLUSIONS: Our 20-year experience shows that radioguided thoracoscopic surgery is a safe and feasible strategy to treat suspicious SPN/GGO, with a success rate of 98%.

10.
Cells ; 9(1)2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936702

RESUMO

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible.


Assuntos
Fatores de Iniciação de Peptídeos/metabolismo , Biossíntese de Proteínas , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Linhagem Celular , Nucléolo Celular/efeitos dos fármacos , Nucléolo Celular/metabolismo , Sobrevivência Celular , Ensaio de Imunoadsorção Enzimática , Humanos , Iniciação Traducional da Cadeia Peptídica/efeitos dos fármacos , Polirribossomos/efeitos dos fármacos , Polirribossomos/metabolismo , Ligação Proteica/efeitos dos fármacos , Puromicina/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes
11.
Q J Nucl Med Mol Imaging ; 64(3): 291-298, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-30654605

RESUMO

BACKGROUND: Solitary pulmonary nodules detected during follow-up in patients with previous cancer history have a high probability of malignancy being either a metachronous lung cancer or a metastasis. This distinction represents a crucial issue in the perspective of "personalized medicine," implying different treatments and prognosis. Aim, to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in distinguishing whether solitary pulmonary nodules are metachronous cancers or metastases and the relationship between the nodule's characteristics and their nature. METHODS: From a single-institution database, we retrospectively selected all patients with a previous cancer history who performed 18F-FDG PET/CT to evaluate pulmonary nodules detected during follow-up, ranging from 5 mm to 40 mm, and histologically diagnosed as malignant. RESULTS: Between September 2009 and August 2017, 127 patients (80 males; mean age=70.2±8.5years) with 127 malignant nodules were included: 103/127 (81%) metachronous cancers, 24/127 (19%) metastases. In both groups, PET/CT provided good and equivalent detection rate of malignancy (81% vs. 83%). No differences between metachronous cancers and metastases were found in: patient's age (70.3±8.1 years vs. 69.5±9.7years), gender (males=63.1% vs. 62.5%), interval between previous cancer diagnosis and nodules' detection (median time=4years vs. 4.5years), location (right-lung=55% vs. 54%; upper-lobes=64% vs. 67%; central-site=31% vs. 25%), size (median size=17mm vs. 19.5mm), 18F-FDG standardized uptake value (median SUVmax=5.2 vs. 5.9). CONCLUSIONS: In oncological patients, despite its high detection rate, 18F-FDG PET/CT, as well as any other clinico-anatomical features, cannot distinguish whether a malignant solitary pulmonary nodule is a metachronous lung cancer or a metastasis, supporting the need of histological differential diagnosis.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
12.
Int J Colorectal Dis ; 35(2): 371-372, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31838578

RESUMO

The original version of this article, unfortunately, contained an error. In Fig. 2 - panel d, incorrect image was published and this is now presented correctly in this article.

13.
Int J Colorectal Dis ; 35(1): 9-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31686201

RESUMO

BACKGROUND: Pulmonary metastasectomy is considered a potentially curative treatment for selected patients with metastatic colorectal cancer (CRC). Several prognostic factors have been analysed, but to date, it is still not well defined which is the optimal resection margin during lung metastasectomy (LM). This study analyses the long-term results and prognostic factors after LM in CRC patients with particular attention to the resection margins. Primary endpoint of this study is to assess the correlation between resection margins and long-term outcomes. METHODS: Observational cohort study on all proven cases of CRC lung metastases (2000-2016) resected with curative intent in a single centre. RESULTS: The series included 210 consecutive patients (M/F 133/77) with a mean age of 65.4 (± 9.96) years, 75% (159/210) of them with a solitary metastasis. Mean size of metastasis was 2.57 cm (± 1.45). One hundred sixty-eight patients underwent wedge resections (80%) and lymphadenectomy was carried out in 90 cases (42.9%). With a mean follow-up of 56 months (range 5-192), we observed a 1-, 3- and 5-year overall survival (OS) of 95%, 74% and 54%, respectively. The patients were divided into three groups according to the resection margin distance from the tumour: (a) ≥ 2 cm (145 cases); (b) < 2, ≥ 1 cm (37 cases); and (c) < 1 cm (12 cases). The OS was significantly different between the three groups (p = 0,020); univariate and multivariate analyses showed that a narrow resection margin was an independent prognostic factor of worse survival (p = 0.006 and HR 3.4 p = 0.009). CONCLUSIONS: Long-term survival of patients after LM is strongly associated with a greater distance between the lesion and the resection margin.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Margens de Excisão , Metastasectomia , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Análise Multivariada , Prognóstico , Fatores de Tempo
15.
Front Oncol ; 9: 763, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482063

RESUMO

Background: Adjuvant chemotherapy after resection of colorectal cancer (CRC) lung metastases may reduce recurrences and improve survival. The choice of best candidates for adjuvant chemotherapy in this setting is controversial, especially when a single lung metastases (SLM) is resected. The aim of this study is to evaluate the risk of recurrence after radical resection for single lung metastasis from CRC. Patients and methods: Demographic, clinical, and pathological data were retrospectively collected for patients radically operated on for single pulmonary metastasis from CRC in 4 centers. Survival was computed by Kaplan-Meyer methods. Chi-square, log-rank test, and for multivariate analysis, Cox-regression and binary logistic regression were used when indicated. Results: The sample consisted of 344 patients, mean age 65 yrs. Overall 5 yrs survival was 61.9%. Recurrence occurred in 113 pts (32.8%). At univariate analysis, age > 70 (p = 0.046) and tumor size > 2 cm (p = 0.038) were predictive of the worst survival chance, while synchronous lung metastasis (p = 0.039), previous resection of extrathoracic metastasis (p = 0.017), uptake at FDG-PET scan (p = 0.006) and short (<12 months) disease-free interval (DFI) prior to lung metastasectomy (p = 0.048) were risk factors for recurrence. At multivariate analysis, only high CEA (>4 ng/mL) was associated with worst survival (HR: 4.3, p = 0.014), while prior abdominal surgery (HR: 3, p = 0.033), PET positivity (HR: 2.7, p = 0.041), and DFI > 12 months (HR: 0.14, p < 0.001) confirmed to predict recurrence of disease. Conclusions: Surgical resection of solitary lung metastases from CRC is associated with prolonged survival. High value of CEA, PET positivity, previous extrathoracic resected metastasis, and short (<12 months) DFI were found to be predictive of death or disease recurrence and might identify in this scenario patients at higher risk which could potential benefit of chemotherapy.

16.
Dev Biol ; 455(1): 100-111, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283922

RESUMO

During development, ribosome biogenesis and translation reach peak activities, due to impetuous cell proliferation. Current models predict that protein synthesis elevation is controlled by transcription factors and signalling pathways. Developmental models addressing translation factors overexpression effects are lacking. Eukaryotic Initiation Factor 6 (eIF6) is necessary for ribosome biogenesis and efficient translation. eIF6 is a single gene, conserved from yeasts to mammals, suggesting a tight regulation need. We generated a Drosophila melanogaster model of eIF6 upregulation, leading to a boost in general translation and the shut-down of the ecdysone biosynthetic pathway. Indeed, translation modulation in S2 cells showed that translational rate and ecdysone biosynthesis are inversely correlated. In vivo, eIF6-driven alterations delayed Programmed Cell Death (PCD), resulting in aberrant phenotypes, partially rescued by ecdysone administration. Our data show that eIF6 triggers a translation program with far-reaching effects on metabolism and development, stressing the driving and central role of translation.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Ecdisona/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Iniciação de Peptídeos/genética , Biossíntese de Proteínas/genética , Animais , Animais Geneticamente Modificados , Apoptose/genética , Linhagem Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Discos Imaginais/crescimento & desenvolvimento , Discos Imaginais/metabolismo , Fatores de Iniciação de Peptídeos/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Surg Oncol ; 28: 223-227, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851905

RESUMO

OBJECTIVE(S): Robotic lobectomy is becoming a widespread surgical procedure in NSCLC treatment, but data on oncologic outcomes is still lacking. The aim of this study was to analyze long term oncologic results of robotic lobectomy for non small lung cancer. METHODS: Clinical records of consecutive NSCLC patients underwent robotic major surgery, between January 2010 and December 2015, were collected and analyzed. RESULTS: We analyzed data of 212 patients (127 male and 85 female), with a median age of 66.3 years. The median follow-up time was 40.3 months (range 4-83). The median disease free survival was 66.3 months. Free disease survival stage-correlated was 75.6 months for stage I, 42.3 months for stage II, 51.2 months for stage III and 10.3 months for stage IV. The median overall survival was 78.6 months. Overall survival stage-correlated was 82 months for stage I, 73.5 months for stage II, 61.4 months for stage III and 41.3 months for stage IV. CONCLUSIONS: This study suggests high safety level, positive post-operative and oncologic outcomes for patients NSCLC underwent robotic major surgery, also in advanced stages.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/mortalidade , Procedimentos Cirúrgicos Robóticos/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Sci Rep ; 9(1): 3536, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837581

RESUMO

Pulmonary sarcomatoid carcinomas (PSC) are a rare group of lung cancer with a median overall survival of 9-12 months. PSC are divided into five histotypes, challenging to diagnose and treat. The identification of PSC biomarkers is warranted, but PSC molecular profile remains to be defined. Herein, a targeted whole transcriptome analysis was performed on 14 PSC samples, evaluated also for the presence of the main oncogene mutations and rearrangements. PSC expression data were compared with transcriptome data of lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC) from The Cancer Genome Atlas. Deregulated genes were used for pathway enrichment analysis; the most representative genes were tested by immunohistochemistry (IHC) in an independent cohort (30 PSC, 31 LUAD, 31 LUSC). All PSC cases were investigated for PD-L1 expression. Thirty-eight genes deregulated in PSC were identified, among these IGJ and SLMAP were confirmed by IHC. Moreover, Forkhead box signaling and Fanconi anemia pathways were specifically enriched in PSC. Finally, some PSC harboured alterations in genes targetable by tyrosine kinase inhibitors, as EGFR and MET. We provide a deep molecular characterization of PSC; the identification of specific molecular profiles, besides increasing our knowledge on PSC biology, might suggest new strategies to improve patients management.


Assuntos
Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência
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