1,721,023 research outputs found
BIOMARCATORI CIRCOLANTI E FATTORI CLINICI ASSOCIATI CON LA PROGNOSI NEI PAZIENTI CON CARCINOMA EPATOCELLULARE
Full text linkIl carcinoma epatocellulare (HCC) è uno dei tumori più comuni al mondo e, nonostante i recenti progressi nella sua gestione, è ancora gravato da un'elevata mortalità. La previsione della prognosi nei pazienti con HCC è molto complessa e devono essere considerate diverse variabili (tra cui il carico tumorale, la funzionalità epatica residua e le condizioni cliniche). Allo scopo di stratificare accuratamente la prognosi del paziente, è inoltre necessario identificare biomarcatori circolanti affidabili. Infatti, l'alfa-fetoproteina (AFP), nonostante sia comunemente usata nell'HCC, non è completamente soddisfacente come marcatore prognostico.
L'obiettivo primario di questa tesi è stato quello di valutare alcune molecole coinvolte nello sviluppo e nella progressione dell'HCC, come potenziali biomarcatori prognostici circolanti. In particolare, sono state studiate serpine (squamous cell carcinoma antigen [SCCA]-IgM), molecole di angiogenesi (hypoxia-inducible factor [HIF]-1 and vascular endothelial growth factor [VEGF]), microRNA (miR-21 e miR-122), prostaglandine (prostaglandina E2) e score infiammatori (platelets-to-lymphocytes ratio [PLR] and neutrophils-to-lymphocytes ratio [NLR]). Nella seconda parte della tesi sono stati indagati la sorveglianza, lo stadio tumorale e il trattamento, aspetti clinici essenziali da considerare per il miglioramento della sopravvivenza del paziente.
I risultati ottenuti dimostrano che le molecole valutate sono potenzialmente utili nella stratificazione della prognosi del paziente e meritano una validazione in ampi studi prospettici. Inoltre, i risultati di questa tesi confermano l'importanza centrale della sorveglianza, forniscono il razionale per un'appropriata stadiazione e trattamento di grandi tumori monofocali, mostrano i cambiamenti nel tempo dell’uso e dell’efficacia della chemioembolizzazione transarteriosa, e dimostrano l’efficacia e la sicurezza della capecitabina nel trattamento dell'HCC. In quest’era della medicina personalizzata e di precisione, lo sviluppo di biomarcatori prognostici e predittivi, potenzialmente utili anche nel guidare il trattamento, e un'attenta gestione clinica sono fondamentali per migliorare la sopravvivenza del paziente.Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and, despite recent advances in its management, it is still burdened with high mortality. Prognostic prediction in HCC is very complex and several variables (among which tumor burden, residual liver function and clinical conditions) must be considered. With the aim of accurately stratify patient prognosis, reliable circulating biomarkers are urgently needed. Indeed, alpha-fetoprotein (AFP), despite being commonly used in HCC, is not completely satisfactory in prognostic prediction.
The primary aim of this thesis was to evaluate as potential circulating prognostic biomarkers some molecules involved in HCC development and progression. In particular, serpins (squamous cell carcinoma antigen [SCCA]-IgM), angiogenesis molecules (hypoxia-inducible factor [HIF]-1 and vascular endothelial growth factor [VEGF]), microRNAs (miR-21 and miR-122), prostaglandins (prostaglandin E2) and inflammatory-based scores (platelets-to-lymphocytes ratio [PLR] and neutrophils-to-lymphocytes ratio [NLR]) were investigated. In the second part of the thesis, surveillance, cancer stage and treatment, which are essential clinical aspects to be considered for improving patient survival, were investigated.
The results obtained demonstrate that the biomarkers evaluated are potentially useful in stratifying patient prognosis and deserve a validation in large prospective studies. Moreover, the results of this thesis confirm the central importance of surveillance, provide the rationale for appropriate staging and treatment of large monofocal tumors, show the changes over time of transarterial chemoembolization application and effectiveness, and demonstrate the efficacy and safety of capecitabine in the treatment of HCC. In this personalized and precision medicine era, the development of prognostic and predictive biomarkers, possibly useful also in guiding treatment, and a careful clinical management are fundamental to improve patient survival
Gastric cancer screening in Western countries: A call to action
Full text link: Gastric cancer is a major cause of cancer-related death worldwide, despite the reduction in its incidence. The disease is still burdened with a poor prognosis, particularly in Western countries. The main risk factor is the infection by Helicobacter pylori, classified as a class I carcinogen by the IARC, and It is well-known that primary prevention of gastric cancer can be achieved with the eradication of the infection. Moreover, non-invasive measurement of pepsinogens (PGI and PGI/PGII ratio) allows the identification of patients that should undergo upper gastrointestinal (GI) endoscopy. Gastric non-cardia adenocarcinoma is indeed preceded by a well-defined precancerous process that involves consecutive stages, described for the first time by Correa et al. more than 40 years ago, and patients with advance stages of gastric atrophy/intestinal metaplasia and with dysplastic changes should be followed-up periodically with upper GI endoscopies. Despite these effective screening and surveillance methods, national-level screening campaigns have been adopted only in few countries in eastern Asia (Japan and South Korea). In this review, we describe primary and secondary preventive measures for gastric cancer, discussing the need to introduce screening also in Western countries. Moreover, we propose a simple algorithm for screening that could be easily applied in clinical practice
Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance
Full text linkIn recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with hepatocellular carcinoma (HCC). Following the positive results of the IMbrave150 trial, the combination of atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) became the standard of care frontline treatment for patients with advanced stage HCC. Several other trials evaluated immunotherapy in HCC, demonstrating that ICIs-based regimens are currently the most effective treatment strategies and expanding the therapeutic possibilities. Despite the unprecedent rates of objective tumor response, not all patients benefit from treatment with ICIs. Therefore, in order to select the appropriate therapy as well as to correctly allocate medical resources and avoid unnecessary treatment-related toxicities, there is great interest in identifying the predictive biomarkers of response or resistance to immunotherapy-based regimens. Immune classes of HCC, genomic signatures, anti-drug antibodies, and patient-related factors (e.g., etiology of liver disease, gut microbiota diversity) have been associated to the response to ICIs, but none of the proposed biomarkers have been translated into clinical practice so far. Considering the crucial importance of this topic, in this review we aim to summarize the available data on tumor and clinical features associated with the response or resistance of HCC to immunotherapies
Angiogenesis and Hepatocellular Carcinoma: From Molecular Mechanisms to Systemic Therapies
Full text linkHepatocellular carcinoma (HCC) is the most common primary liver malignancy. The hypervascular nature of the majority of HCCs and the peculiar vascular derangement occurring during liver carcinogenesis underscore the importance of angiogenesis in the development and progression of these tumors. Indeed, several angiogenic molecular pathways have been identified as deregulated in HCC. The hypervascular nature and the peculiar vascularization of HCC, as well as deregulated angiogenic pathways, represent major therapeutic targets. To a large extent, intra-arterial locoregional treatments (transarterial-(chemo)embolization) rely on tumor ischemia caused by embolization of tumor feeding arteries, even though this may represent the “primum movens” of tumor recurrence through the activation of neoangiogenesis. Considering systemic therapies, the currently available tyrosine kinase inhibitors (sorafenib, regorafenib, cabozantinib and lenvatinib) and monoclonal antibodies (ramucirumab and bevacizumab, in combination with the anti-PD-L1, atezolizumab) primarily target, among others, angiogenic pathways. Considering the importance of angiogenesis in the pathogenesis and treatment of liver cancer, in this paper, we aim to review the role of angiogenesis in HCC, addressing the molecular mechanisms, available antiangiogenic therapies and prognostic biomarkers in patients receiving these treatments
Systemic therapies for hepatocellular carcinoma: an evolving landscape
Full text linkIn the last few years, there has been a significant widening of the landscape of systemic therapy for unresectable hepatocellular carcinoma (HCC) patients. After the landmark drug sorafenib, several other molecules have been approved for treatment in first-line (lenvatinib) and second-line (regorafenib, cabozantinib, and ramucirumab) regimens. Very recently, another important step forward has been made with the demonstration that the combination of an anti-programmed death ligand 1 and an anti-vascular endothelial growth factor (atezolizumab + bevacizumab) provides better survival results compared to sorafenib, thus becoming the new paradigm in first-line treatment of HCC. In consideration of this rapidly evolving situation, with the availability of many potential active drugs, the American Society of Clinical Oncology recently published a guideline in order to advise on the selection of systemic treatment options. However, also considering the uncertainties and the unmet needs in the current treatment of patients with advanced liver cancer is mandatory
Efficacy of immunotherapy in hepatocellular carcinoma: Does liver disease etiology have a role?
Full text link: The systemic treatment of hepatocellular carcinoma (HCC) is changing rapidly. After a decade of tyrosine kinase inhibitors (TKIs), as the only therapeutic option for the treatment of advanced HCC, in the last few years several phase III trials demonstrated the efficacy of immune checkpoint inhibitors (ICIs). The combination of the anti-PD-L1 atezolizumab and the anti-vascular endothelial growth factor (VEGF) bevacizumab demonstrated the superiority over sorafenib and currently represents the standard of care treatment for advanced HCC. In addition, the combination of durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) proved to be superior to sorafenib, and in the same trial durvalumab monotherapy showed non-inferiority compared to sorafenib. However, early reports suggest an influence of HCC etiology in modulating the response to these drugs. In particular, a lower effectiveness of ICIs has been suggested in patients with non-viral HCC (in particular non-alcoholic fatty liver disease). Nevertheless, randomized controlled trials available to date have not been stratified for etiology and data suggesting a possible impact of etiology in the outcome of patients managed with ICIs derive from subgroup not pre-specified analyses. In this review, we aim to examine the potential impact of HCC etiology on the response to immunotherapy regimens for HCC
Impact and Novel Perspective of Immune Checkpoint Inhibitors in Patients with Early and Intermediate Stage HCC
Full text linkSIMPLE SUMMARY: The prognostic evaluation and therapeutic management of hepatocarcinoma (HCC) is based on the Barcelona Liver Cancer Clinic (BCLC). In the past years, immunotherapy has become a mainstay of first-line treatment in advanced HCC and further treatment options are underway. Beyond this, the scientific community is more and more focusing on immunotherapeutic approaches in earlier HCC stages. The purpose of this review is to describe the rationale for immunotherapeutic approaches and the studies conducted with immunotherapy in patients with early and intermediate stage HCC. ABSTRACT: Surgery and radiofrequency ablation remain the gold standard to achieve cure in patients with hepatocellular carcinoma (HCC). After a decade in which only sorafenib was available for advanced and metastatic HCC, the emergence of other molecularly targeted drugs and immune checkpoint inhibitors (ICIs) has significantly improved the patients` prognosis. In particular, the use of ICIs has shown promising results and has revolutionized the treatment algorithm in HCC patients. Indeed, preclinical and clinical data have documented a high density of immunosuppressive cells and an increased expression of the programmed death-1 (PD-1) receptor and cytotoxic T-cell associated protein-4 (CTLA-4) in HCC. However, despite these observations, no validated biomarker is available and the molecular groundwork responsible for response to ICIs remains elusive. The anti-CTLA4 monoclonal antibody tremelimumab and the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab were the first ICIs to be tested in HCC. Recently, the combination of the anti-programmed death-ligand 1 (PD-L1) inhibitor atezolizumab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab demonstrated an improvement in patient outcome compared to sorafenib, becoming the standard of care in the frontline setting of advanced disease. Other immunotherapeutic agents such as pembrolizumab or the combination nivolumab-ipilimumab have shown promising results that have to be confirmed in phase III studies. Currently, the combination of different ICIs (i.e., ipilimumab, durvalumab) and anti-angiogenic agents (i.e., regorafenib, lenvatinib) is currently being tested in several trials and will hopefully revolutionize the treatment of HCC. To date, numerous studies are underway evaluating ICIs in adjuvant and neoadjuvant settings to improve survival in early and intermediate stages. Thus, this review focuses on the rationale for ICIs and their potential use for early or intermediate HCC stages
Eosinophilic esophagitis and biologics
No full textEoE incidence and prevalence have sharply increased in the last decade and management of these patients is changing rapidly. Standard regimens as elimination diet, proton pump inhibitors and topical swallowed steroids are not able to achieve remission in all patients. Moreover, loss of efficacy and safety concerns for long-term medical treatments are rising questions. As for other chronic immune-mediated diseases, biologics have been evaluated for treatment of EoE. Several targets in the Th2-mediated inflammatory cascade with eosinophilic mucosal infiltration, have been tested with alternating results. This review provides a comprehensive discussion of the available studies evaluating biologics in EoE and the possible future options most desirable for these patients
- …
