Search results for "Cancer"
showing 10 items of 11546 documents
Pattern of Invasion in Human Pancreatic Cancer Organoids Is Associated with Loss of SMAD4 and Clinical Outcome
2020
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used to observe invasion in organoids from 25 surgically resected human PDAC samples in collagen I. Subsequent lentiviral modification and small-molecule inhibitors were used to investigate the molecular programs underlying invasion in PDAC organoids. When cultured in collagen I, PDAC organoids exhibited two distinct, morphologically defined invasive phenotypes, mesenchymal an…
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…
Abilities of β-Estradiol to interact with chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals and alter the proliferation of pa…
2019
Improving the effects of chemotherapy and reducing the side effects are important goals in cancer research. Various approaches have been examined to enhance the effectiveness of chemotherapy. For example, signal transduction inhibitors or hormonal based approaches have been included with chemo- or radio-therapy. MIA-PaCa-2 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells both express the estrogen receptor (ER). The effects of β-estradiol on the growth of PDAC cells has not been examined yet the ER is expressed in PDAC cells. We have examined the effects of combining β-estradiol with chemotherapeutic drugs, signal transcription inhibitors, natural products and nutraceuticals on PDAC.…
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…
Attachement et parcours de l’aidant face à l’épreuve du cancer
2020
Resume Introduction Depuis le dernier plan cancer 2014–2019, l’evaluation des repercussions de la maladie chez les aidants est devenue essentielle. En effet, la qualite de la relation d’aide participe a la qualite de vie du malade. Dans ce contexte, l’objectif principal de cette etude etait de decrire l’evolution de l’attachement de l’aidant de patients ayant un cancer pendant les trois premieres annees d’accompagnement de la maladie. Methode Les aidants ont ete recrutes dans le cadre de l’etude ICE (Informal Carers of Elderly) et accompagnaient un proche, âge de plus de 60 ans, atteint d’un cancer colorectal, du sein ou de la prostate. Ils ont ete rencontres a domicile dans les trois mois …
High numbers of circulating CD57+ NK cells associate with resistance to HER2-specific therapeutic antibodies in HER2+ primary breast cancer.
2019
Abstract Natural killer (NK) cells can orchestrate effective antitumor immunity. The presence of tumor-infiltrating NK cells in diagnostic biopsies predicts pathologic complete response (pCR) to HER2-specific therapeutic antibodies in patients with primary breast cancer. Here, we analyzed whether diversity in circulating NK cells might influence tumor infiltration and HER2-specific therapeutic antibody efficacy. We found that numbers of circulating CD57+ NK cells inversely correlated with pCR to HER2-specific antibody treatment in patients with primary breast cancer independently of age, traditional clinicopathologic factors, and CD16A 158F/V genotype. This association was uncoupled from th…
Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities
2019
The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its use for cultural and religious rituals in Europe. During the past two decades, scientific investigations provided mounting evidence for the therapeutic potential of frankincense. We conducted a systematic review on the anti-inflammatory and anti-cancer activities of Boswellia species and their chemical ingredients (e.g. 3-O-acetyl-11-keto-β boswellic acid, α- and β-boswellic acids, 11-keto-β-boswellic acid and other boswellic acids, lupeolic acids, incensole, cembrenes, triterpenediol, tirucallic acids, and olibanumols). Frank…