Search results for "Research"
showing 10 items of 25967 documents
Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants i…
2020
Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform…
Pancreatic Ductal Adenocarcinoma (PDAC) Organoids: The Shining Light at the End of the Tunnel for Drug Response Prediction and Personalized Medicine.
2020
Simple Summary Pancreatic ductal adenocarcinoma (PDAC) causes massive medical problems because of late diagnosis and limited responsiveness to standard chemotherapeutic treatments. This makes PDAC one of the major causes of death by cancer. To address this problem, novel tools for early diagnosis and therapy are needed. The recent development of PDAC organoids, which represent micro-scale mini-tumors, offers promising new options for personalized drug-testing based on primary PDAC patient material. This overview article summarizes and discusses the current state-of-the-art in exploiting the organoid technology to improve clinical management of PDAC. Abstract Pancreatic ductal adenocarcinoma…
Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to …
2019
This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13-1.88, p = 0.004; HR, 2.65; 95% CI, 1.79-3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05-2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that E…
High BCR-ABL/GUS(IS) levels at diagnosis of chronic phase CML are associated with unfavorable responses to standard-dose imatinib
2017
Abstract Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses. Experimental Design: We correlated BCR–ABL/GUSIS and BCR–ABL/ABL transcripts at diagnosis with the outcome—defined by the 2013 European LeukemiaNet recommendations—of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR–ABL/GUSIS and BCR–ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transform…
Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer.
2017
Background/Aim: Chemo-radiation currently serves as first-line therapy of advanced and recurrent head and neck cancer, while new chemotherapy regimens are emerging. However, response rates to any treatment are difficult to predict and underlie broad variation. This study shows the development of a standardized, high-throughput in vitro assay to assess patients' individual response to therapy regimens as a future tool for personalized tumor therapy. Materials and Methods: Viability and proliferation analyses after chemo +/- radiation treatment of single spheroids (low adhesion plates/Hanging Drop (HD)) were generated from head and neck squamous cell carcinoma (HNSCC) cell lines and primary h…
Abstract P1-19-08: Neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer: Updated results from t…
2020
Abstract Background: HER2 mutations define a subset of metastatic breast cancers (MBCs) with a unique mechanism of oncogenic addiction to HER2 signaling. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has been shown to have encouraging clinical activity when combined with fulvestrant in HER2-mutant, hormone receptor-positive (HR+) MBC [Smyth et al. SABCS 2018]. Genomic analyses suggest that acquired resistance to neratinib may occur by the acquisition of additional HER2 alterations, which may amplify HER2 pathway signaling [Won et al. AACR 2019]. We therefore explored whether dual HER2-targeted therapy may improve clinical benefit in this setting. Here we describe initial res…
Features associated with melanoma metastasis in Latvia
2020
Cutaneous melanoma (CM) is the most aggressive form of skin cancer, exhibits an increasing incidence worldwide and has a high potential to develop metastasis. The current study aimed to identify a set of parameters that may aid in predicting the probability and timing of the onset of CM metastasis. A retrospective analysis was performed using the archive data of 2,026 patients with CM that were treated at the Riga East University Hospital Latvian Oncology Centre, which is the largest oncological hospital in the country, between 1998 and 2015. A case-control study design was employed, where patients with metastasis (n=278) were used as the cases and patients without metastasis were used as t…
Semiquantitative evaluation of lymph-vascular space invasion in patients affected by endometrial cancer: Prognostic and clinical implications.
2020
Objectives: The interpretation of lymph-vascular space invasion (LVSI) is usually qualitative, as presence or absence. The aim of this study is to investigate the prognostic role of LVSI in patients affected by endometrial cancer, when evaluated with a semiquantitative analysis. Methods: This retrospective multicentre study enrolled patients who received a histologically confirmed diagnosis of endometrial cancer. The assessment of LVSI was semiquantitative in accordance with the three-tiered scoring system (absent, focal and diffuse). Results: Among 1258 patients with surgical-stage endometrial cancer, LVSI has been found in 32.8% of cases (n = 412), whose 12.7% (n = 160) were focal, and 20…
Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: A look into the …
2021
In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and inve…
Radiomics predicts survival of patients with advanced non-small cell lung cancer undergoing PD-1 blockade using Nivolumab
2019
Immune checkpoint blockade is an emerging anticancer strategy, and Nivolumab is a human mAb to PD-1 that is used in the treatment of a number of different malignancies, including non-small cell lung cancer (NSCLC), kidney cancer, urothelial carcinoma and melanoma. Although the use of Nivolumab prolongs survival in a number of patients, this treatment is hampered by high cost. Therefore, the identification of predictive markers of response to treatment in patients is required. In this context, PD-1/PDL1 blockade antitumor effects occur through the reactivation of a pre-existing immune response, and the efficacy of these effects is strictly associated with the presence of necrosis, hypoxia an…