Search results for "82"
showing 10 items of 2220 documents
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
2020
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Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—Prevalence and geographic distribution of pathogenic variants in BRCA1/…
2020
Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlini…
The hallmarks of ovarian cancer: proliferation and cell growth
2020
Epithelial ovarian cancer (EOC) is a heterogeneous group of diseases with distinct biological and clinical behaviour. Despite the differences between them, the capability of tumour cells to continuously proliferate and avoid death is maintained among histotypes. This ability is the result of alterations at different levels, causing the deregulation of cell cycle and proliferative-related pathways. Even if the leading role is played by RB and TP53, changes in other molecular pathways are involved in the development of EOC. This ability can be exploited to generate in vitro and in vivo models resembling the conditions of tumour development in a patient. In vivo models, such as patient-derived…
Immunobiology of Uveal Melanoma: State of the Art and Therapeutic Targets
2019
Uveal Melanoma (UM) represents the most common primary intraocular malignant tumor in adults. Although it originates from melanocytes as cutaneous melanoma, it shows significant clinical and biological differences with the latter, including high resistance to immune therapy. Indeed, UM can evade immune surveillance via multiple mechanisms, such as the expression of inhibitory checkpoints (e.g., PD-L1, CD47, CD200) and the production of IDO-1 and soluble FasL, among others. More in-depth understanding of these mechanisms will suggest potential targets for the design of novel and more effective management strategies for UM patients.
Exploiting Gangliosides for the Therapy of Ewing’s Sarcoma and H3K27M-Mutant Diffuse Midline Glioma
2021
Simple Summary Osteosarcoma, Ewing’s sarcoma, and H3K27M-mutant diffuse midline glioma are rare but aggressive malignancies occurring mainly in children. Due to their rareness and often fatal course, drug development is challenging. Here, we repurposed the existing drugs dinutuximab and eliglustat and investigated their potential to directly target or indirectly modulate the tumor cell-specific ganglioside GD2. Our data suggest that targeting and/or modulating tumor cell-specific GD2 may offer a new therapeutic strategy for the above mentioned tumor entities. Abstract The ganglioside GD2 is an important target in childhood cancer. Nevertheless, the only therapy targeting GD2 that is approve…
Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma
2019
Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given the lower miR-155 levels in bortezomib-resistant as compared to sensitive MM cells, we analyzed the p…
Analysis of the Gut Microbiota: An Emerging Source of Biomarkers for Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer
2021
Simple Summary The immune checkpoint blockade (ICB), and concretely the blockade of the PD1/PDL1 axis, has opened up a new standard of treatment for non-small cell lung cancer (NSCLC). However, despite substantial advances in clinical care, many patients still remain refractory to these therapies. Biomarkers such as PD-L1 expression and tumor mutational burden have been associated with ICB efficacy, but the mechanisms underlying variable responses are not yet fully understood. Recently, the differential composition of the gut microbiota was studied as one of the variables accounting for interpatient heterogeneity in ICB responses. To better understand the potential role of the gut microbiot…
Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer
2020
Simple Summary The outcome for patients with rectal cancer has significantly improved over the last thirty years. Previously, local relapses in the pelvis occurred in more than one third of all patients with apparently localized tumors. Total mesorectal excision was the first step to improve local control by reducing local relapses to less than 5%. Preoperative radiation, either short-course or long-course with concurrent administration of chemotherapy, was a second important step for reducing local relapses to a minimum, even in locally advanced tumors where a clean surgical resection was not possible or would not be curative. Magnetic resonance imaging is a very useful tool for locoregion…
Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis
2019
Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study aimed to investigate the contribution of oxidative stress to cancer-induced cachexia in the presence or in the absence of moderate exercise training. Mice bearing the colon C26 carcinoma, either sedentary or exercised, were used. The former showed muscle wasting and redox imbalance, with the activation of an antioxidant response and with upregulation of markers of proteasome-dependent…
More Severe COVID-19 in Patients With Active Cancer: Results of a Multicenter Cohort Study
2021
BackgroundThe aim of the study was to compare coronavirus disease 2019 (COVID-19) severity presentation between oncologic and non-oncologic patients and to evaluate the impact of cancer type and stage on COVID-19 course.MethodsWe performed a multicentre, retrospective study involving 13 COVID-19 Units in Campania region from February to May 2020. We defined as severe COVID-19 presentation the cases that required mechanical ventilation and/or admission to Intensive Care Units (ICU) and/or in case of death.ResultsWe enrolled 371 COVID-19 patients, of whom 34 (9.2%) had a history or a diagnosis of cancer (24 solid, 6 onco-hematological). Oncologic patients were older (p<0.001), had more…