Search results for "TOC"
showing 10 items of 14693 documents
Current treatment options for HER2-positive breast cancer patients with brain metastases
2020
Abstract Brain metastases (BMs) are frequently associated with HER2+ breast cancer (BC). Their management is based on a multi-modal strategy including both local treatment and systemic therapy. Despite therapeutic advance, BMs still have an adverse impact on survival and quality of life and the development of effective systemic therapy to prevent and treat BMs from HER2 + BC represents an unmet clinical need. Trastuzumab-based therapy has long been the mainstay of systemic therapy and over the last two decades other HER2-targeted agents including lapatinib, pertuzumab and trastuzumab emtansine, have been introduced in the clinical practice. More recently, novel agents such as neratinib, tuc…
Prognostic Significance of Focal Adhesion Kinase in Node-Negative Breast Cancer.
2017
<b><i>Background:</i></b> Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays an important role as a mediator of cell migration, invasion, proliferation and survival. Conflicting results for the prognostic role of FAK in breast cancer (BC) prompted us to determine its impact. <b><i>Methods:</i></b> Patients with node-negative BC entered this retrospective study. FAK expression was determined by immunohistochemistry (n = 335). The prognostic impact of FAK was examined with Cox regression analyses and Kaplan-Meier estimation in the whole cohort as well as in different molecular subtypes. <b><i>Results:</i>&l…
Contribution of the Cancer Stem Cell Phenotype to Hepatocellular Carcinoma Resistance
2017
The cancer stem cell (CSC) hypothesis is an increasingly accepted concept in cancer research that provides a plausible explanation for the considerable phenotypic and molecular heterogeneities observed in hepatocellular carcinoma (HCC) which hampers therapeutic progress. The hypothesis infers that CSCs share functional properties similar to adult stem cells, such as self-renewal and differentiation capacity, and are exclusively responsible for tumor evolution. By definition, CSCs are held responsible not only for tumor initiation and progression but also acquisition of chemoresistance and the fueling of relapse after therapy. Therefore, the CSC model has significant implications both for tr…
Is immunohistochemical evaluation of p16 in oropharyngeal cancer enough to predict the HPV positivity?
2016
Abstract Aim Our goal was to determine the expression levels of p16 in the cohort of the OPSCC patients and evaluation of the pathological and clinical differences between these two groups including patients’ survival. Background HPV infection is the main causative factor of oropharyngeal cancer (OPSCC). Identification of HPV status in OPSCC requires positive evaluation of viral DNA integration into host cell however, p16 accumulation in the proliferating cell layers has been accepted as an alternative marker for HPV infection. Material and Methods The IHC staining for p16 has been performed in tumor tissue from 382 OPSCC patients. The sample was considered positive based on more than 70% o…
Pharmacogenomics and the treatment of acute myeloid leukemia.
2016
Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous malignancy that is primarily treated with combinations of cytarabine and anthracyclines. Although this scheme remains effective in most of the patients, variability of outcomes in patients has been partly related with their genetic variability. Several pharmacogenetic studies have analyzed the impact of polymorphisms in genes encoding transporters, metabolizers or molecular targets of chemotherapy agents. A systematic review on all eligible studies was carried out in order to estimate the effect of polymorphisms of anthracyclines and cytarabine pathways on efficacy and toxicity of AML treatment. Other emerging gene…
Consistency in biomarkers expression between matched tissue microarray cores from primary gallblader and ovarian cancers
2019
Introduction. Tissue microarray (TMA) technique has been widely used, especially in immunohistochemical assays of new prognostic and predictive markers. The main objections raised by its opponents are the small amount of sampled material and the associated risk of inadequate assessment of analysed expression, resulting from the potential heterogeneity of tumour tissue. Material and methods. This study evaluated the compatibility of biomarker expression in two independent tissue cores, 1.5 mm in diameter, obtained by TMA technique from patients with gallbladder cancer (ERb, cytoPgR, HER2, CTGF) and ovarian cancer (PTEN, BCL2, PIK3CA, IGF1R). Comparison of the expression of individual biomark…
A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients
2019
Background Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Methods Epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K arra…
5-Fluorouracil and recombinant alpha interferon-2a in the treatment of advanced colorectal carcinoma: a dose optimization study
1990
A dose optimization study was carried out with the aim of identifying the maximally tolerated dose of recombinant alpha interferon-2a (raIFN-2a) in combination with 5-fluorouracil (5FU). 5FU was given at the dose of 750 mg/m2 over a 4-hour infusion on day 1- - greater than 5 followed by 750 mg/m2 weekly i.v. bolus. Recombinant aIFN-2a was started at 3 x 10(6) IU subcutaneously three times/week. 12 patients with advanced colorectal carcinoma were included in the study. 10 patients had previously received chemotherapy for advanced disease. Severe fatigue, most likely attributable to rIFN, was the dose-limiting toxicity. The dosage of raIFN-2a could not be further escalated above 12 x 10(6) IU…
Virulence of Streptococcus mutans: An intrafamilial cohort study on transmission of genotypes
2020
Background The main aims of this cohort study were to measure the intrafamilial risk of transmission, sharing and stability of the most virulent S. mutans genotypes. Material and Methods A total of 392 clinical isolates of S. mutans obtained from caries-active adults and genotyped to evaluate their transmissibility over time. After extraction of the chromosomal DNA, PCR were performed to detect the genes involved in the production of GbpA (gbpA) and mutacin types I, II, III and IV (mutAI, mutAII, mutAIII and mutAIV). Results The gbpA, mutAI, mutAII, mutAIII and mutAIV genes were detected in 77.3, 12.5, 51, 16.6 and 89.8% of S. mutans isolates, respectively. The virulence of S. mutans was as…
Can Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
2019
The unprecedented clinical activity of checkpoint blockade in several types of cancers has formally demonstrated that anti-tumor immune responses are crucial in cancer therapy. Durable responses seen in patients treated with immune checkpoint inhibitors (ICI) show that they can trigger the establishment of long-lasting immunologic memory. This beneficial outcome is however achieved for a limited number of patients. In addition, late relapses are emerging suggesting the development of acquired resistances that compromise the anticancer efficacy of ICI. How can this be prevented through combination therapies? We here review the functions of immune checkpoints, the successes of ICI in treating…