There is an unmet need for novel non-invasive prognostic molecular tumour markers for breast cancer (BC). Accumulating evidence shows that miR-155 plays a pivotal role in tumorigenesis. Generally, miR-155 is considered an oncogenic miRNA promoting tumour growth, angiogenesis and aggressiveness of BC. Therefore, many researchers have focused on its use as a prognostic biomarker and therapeutic target. However, its prognostic value for BC patients remains controversial. To address this issue, the present systematic review aims to summarize the available evidence and give a picture of a prognostic significance of miR-155 in BC pathology. All eligible studies were searched on PubMed and EMBASE databases through various search strategies. Starting from 289 potential eligible records, data were examined from 28 studies, comparing tissue and circulating miR-155 expression levels with clinicopathological features and survival rates in BC patients. We discuss the pitfalls and challenges that need to be assessed to understand the power of miR-155 to respond to real clinical needs, highlighting the consistency, robustness or lack of results obtained to sate in translating this molecule to clinical practice. Our paper suggests that the prognostic role of miR-155 in the management of BC needs to be further verified.
Abstract PED (phosphoprotein enriched in diabetes) is a death‐effector domain (DED) family member with a broad anti‐apoptotic action. PED inhibits the assembly of the death‐inducing signalling complex (DISC) of death receptors following stimulation. Recently, we reported that the expression of PED is increased in breast cancer cells and determines the refractoriness of these cells to anticancer therapy. In the present study, we focused on the role of PED in non‐small cell lung cancer (NSCLC), a tumour frequently characterized by evasion of apoptosis and drug resistance. Immunohistochemical analysis of a tissue microarray, containing 160 lung cancer samples, indicated that PED was strongly expressed in different lung tumour types. Western blotting performed with specimens from NSCLC‐affected patients showed that PED was strongly up‐regulated (>6 fold) in the areas of tumour compared to adjacent normal tissue. Furthermore, PED expression levels in NSCLC cell lines correlated with their resistance to tumour necrosis factor related apoptosis‐inducing ligand (TRAIL)‐induced cell death. The involvement of PED in the refractoriness to TRAIL‐induced cell death was investigated by silencing PED expression in TRAIL‐resistant NSCLC cells with small interfering (si) RNAs: transfection with PED siRNA, but not with cFLIP siRNA, sensitized cells to TRAIL‐induced cell death. In conclusion, PED is specifically overexpressed in lung tumour tissue and contributes to TRAIL resistance.
The aim of this study was to evaluate the value of CA15-3 for the diagnostic integration of molecular imaging findings performed with hybrid positron emission tomography and computed tomography (PETCT) technology. We retrospectively selected 45 patients with a median age of 60 years (range 39–85 years) and a previous history of breast cancer (BC) who had already been treated with surgery and other treatments. Three measurements of CA15-3 were collected within 1 year before PETCT examination, at 6–9 months 3–6 months and 0–3 months before PETCT. The prolonged clinical outcome or imaging follow-up was used to define disease relapse. An increase in tumor marker value was compared with PETCT findings and disease relapse. Sensitivity and specificity for both tests were calculated with respect to clinical outcome. Disease relapse was detected in 16 out of 45 BC patients. CA15-3 and PETCT showed 75% sensitivity with a specificity percentage of 76% for CA15-3 and 79% for PETCT. Serum CA15-3 expression levels were significantly higher in BC patients with multiple metastatic sites with hepatic involvement. Analysis of serial CA15-3 serum levels showed an increase in CA15-3 3–6 months before PETCT could identify BC patients at risk for relapse (AUC = 0.81). Moreover, patients receiving anti-hormonal or chemotherapy medications with negative PETCT and positive CA15-3 relapsed after a median time of 158 days compared to patients who were negative for both tests and who were free from disease for at least 1 year. Our results showed that serial increases in CA15-3 can be used to predict positive PETCT results in BC patients during follow-up. Increased levels of CA15-3 may be considered an early warning sign in patients needing accurate molecular imaging investigations, as they are at higher risk of recurrence. In cases of elevated levels, multiple lesions or liver involvement may exist. Also, patients receiving chemotherapeutic or anti-hormonal treatment who have negative PETCT scans and increased CA15-3 serum levels should be considered at risk for relapse, because the CA15-3-linked biochemical signal of the presence of a tumor can predict positive metabolic imaging.
Abstract Leukemic cells originate from the malignant transformation of undifferentiated myeloid/lymphoid hematopoietic progenitors normally residing in bone marrow. As the precise molecular mechanisms underlying this heterogeneous disease are yet to be disclosed, the identification and the validation of novel actors in leukemia is of extreme importance. Here, we show that KCTD15, a member of the emerging class of KCTD ((K)potassium Channel Tetramerization Domain containing) proteins, is strongly upregulated in patients affected by B-cell type acute lymphoblastic leukemia (B-ALL) and in continuous cell lines (RS4;11, REH, TOM-1, SEM) derived from this form of childhood leukemia. Interestingly, KCTD15 downregulation induces apoptosis and cell death suggesting that it has a role in cellular homeostasis and proliferation. In addition, stimulation of normal lymphocytes with the pokeweed mitogen leads to increased KCTD15 levels in a fashion comparable to those observed in proliferating leukemic cells. In this way, the role of KCTD15 is likely not confined to the B-ALL pathological state and extends to activation and proliferation of normal lymphocytes. Collectively, data here presented indicate that KCTD15 is an important and hitherto unidentified player in childhood lymphoid leukemia, and its study could open a new scenario for the identification of altered and still unknown molecular pathways in leukemia.
Abstract Background . Chronic liver diseases (CHDs) are an important public health issue. The presence of significant fibrosis is a hallmark for liver disease staging and prognosis. Aims . To develop a non-invasive score that can discriminate between patients with or without fibrosis in the aim to avoid liver biopsy. Methods . Forty patients with CHDs who received liver biopsy to stage fibrosis and 12 normal subjects performed also share wave elastography (SWE) and ELF-test. We chose two different outcome for histological fibrosis (F0-F1 vs F2-F4) and (F0-F2 vs F3-F4). ELF-test and SWE were independent predictors, categorized using ROC analysis. Two scores called SCORE1 and SCORE2 were devised. Results . The discriminatory values for SCORE1 were SWE>5.62 kPa and ELF-test >9.33 and for SCORE2 were SWE>7.04 kPa and ELF-test 9.33. SCORE1 specificity was 91.7% (CI 77.5-98.2%), significatively greater than obtained using SWE 63.9% (CI 46.2-79.2%; p=0.0013) or ELF-test 83.3% (CI 67.2-93.6%; p=0.1760) separately. SCORE2 specificity was 95.2% (CI 83.8-99.4%). This value was not-significatively greater than obtained using SWE or ELF-test 81.0% (CI 65.9-91.4%; p=0.0921) separately. Conclusion . SWE and ELF-test can be performed for non-invasive staging of liver fibrosis. Their use grouped in a single score increase the specificity for the prediction of histological fibrosis stage.
Abstract Background The aim of the present review is to discuss how the promising field of biobanking can support health care research strategies. As the concept has evolved over time, biobanks have grown from simple biological sample repositories to complex and dynamic units belonging to large infrastructure networks, such as the Pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Biobanks were established to support scientific knowledge. Different professional figures with varied expertise collaborate to obtain and collect biological and clinical data from human subjects. At same time biobanks preserve the human and legal rights of each person that offers biomaterial for research. Methods A literature review was conducted in April 2019 from the online database PubMed, accessed through the Bibliosan platform. Four primary topics related to biobanking will be discussed: (i) evolution, (ii) bioethical issues, (iii) organization, and (iv) imaging. Results Most biobanks were founded as local units to support specific research projects, so they evolved in a decentralized manner. The consequence is an urgent needing for procedure harmonization regarding sample collection, processing, and storage. Considering the involvement of biomaterials obtained from human beings, different ethical issues such as the informed consent model, sample ownership, veto rights, and biobank sustainability are debated. In the face of these methodological and ethical challenges, international organizations such as BBMRI play a key role in supporting biobanking activities. Finally, a unique development is the creation of imaging biobanks that support the translation of imaging biomarkers (identified using a radiomic approach) into clinical practice by ensuring standardization of data acquisition and analysis, accredited technical validation, and transparent sharing of biological and clinical data. Conclusion Modern biobanks permit large-scale analysis for individuation of specific diseases biomarkers starting from biological or digital material (i.e., bioimages) with well-annotated clinical and biological data. These features are essential for improving personalized medical approaches, where effective biomarker identification is a critical step for disease diagnosis and prognosis.
