1,721,126 research outputs found
Molecular characterization and targeted therapeutic approaches in breast cancer
Full text linkDespite the wide improvements in breast cancer (BC) detection and adjuvant treatment, BC is still responsible for approximately 40,000 deaths annually in the United States. Novel biomarkers are fundamental to assist clinicians in BC detection, risk stratification, disease subtyping, prediction of treatment response, and surveillance, allowing a more tailored approach to therapy in both primary and metastatic settings. In primary BC, the development of molecular profiling techniques has added prognostic and predictive information to conventional biomarkers - estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Moreover, the application of next-generation sequencing and reverse-phase protein microarray methods in the metastatic setting holds the promise to further advance toward a personalized management of cancer. The improvement in our understanding on BC biology associated with the study of the genomic aberrations characterizing the most common molecular subtypes allows us to explore new targets for drug development. Finally, the integration of cancer stem cell-targeted therapies and immune therapies in future combination regimens increases our chances to successfully treat a larger proportion of women with more aggressive and resistant metastatic disease. This article reviews the current state of novel biological markers for BC, the evidence to demonstrate their clinical validity and utility, and the implication for therapeutic targeting
CTCs in metastatic breast cancer
No full textCirculating tumor cells (CTCs), enumerated by the Food and Drugs Administration-cleared CellSearch® system, are an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) in metastatic breast cancer (MBC) patients. Several published papers demonstrated the poor prognosis for MBC patients who presented basal CTC count ≥5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. Randomized clinical trials are ongoing to demonstrate whether CTCs detected by CellSearch® may help to guide treatments in MBC patients and improve prognosis. Moreover, the ability to perform molecular characterization of CTCs might identify a new druggable target in MBC patients. For example, the RT-PCR-based approach AdnaTest BreastCancerSelectTM showed a high discordance rate in receptor expression between the primary tumors and CTCs. Theoretically, the phenotypic analysis of CTCs can represent a "liquid" biopsy of breast tumor that is able to identify a new potential target against the metastatic disease. © 2012 Springer-Verlag Berlin Heidelberg
Blood-Based Diagnostics in Solid Tumors: An Overview
No full textThe application of patient-specific genetic information and molecular tumor characteristics enables the selection of treatment strategies for individual patients, improving the therapeutic efficacy and expanding the scope of personalized medicine. Emerging evidence from clinical research provides demonstration that the genetic landscape of any given tumor will dictate its sensitivity or resistance profile to anticancer agents. Nevertheless, the inter-and intra-tumor genetic heterogeneity can be a substantial impediment to the successful clinical application of this approach. Since acquired drug resistance is common during the course of the disease, there is an urgent need to monitor tumor evolution. On these bases, the importance of molecular re-characterization of metastatic disease has been prospectively confirmed and has been recently acknowledged in the clinical guidelines for the management of advanced malignancies. Nevertheless, obtaining serial samples of metastatic tissue is impractical and complicated by spatial heterogeneity, sampling bias, and invasive procedures. An attractive alternative to overcome these limitations is represented by the analysis of peripheral blood sample as a “liquid biopsy.” Blood draws can easily be performed serially; thus blood would be an ideal compartment for detection of prognostic and predictive biomarkers. Nowadays, the principal sources for liquid biopsies are represented by cells and intracellular materials that are released by the tumor mass and are swept away by the bloodstream, such as CTCs, ctDNA, and exosomes. This book provides an overview of the technological approaches to perform and enhance the strategy and the principal applications in clinical practice of “liquid biopsy.
Clinical utility of measuring circulating tumor cells in metastatic breast cancer
No full textDespite significant improvements in screening, early diagnosis, and adjuvant treatment of breast cancer, some women still develop metastatic disease.1 Metastatic breast cancer (MBC) remains an incurable condition, and its treatment is considered palliative; nevertheless, the selection of appropriate treatments is generally associated with survival prolongation.2,3 Moreover, our increasing knowledge of the biology of the disease and the availability of targeted therapies have improved significantly the prognosis of some subsets of patients, such as women with amplification of the erbb2 oncogene.4The use of novel technologies to accurately assess disease status can theoretically provide the possibility of better prognostic stratification for patients with MBC, which should also contribute to better treatment outcomes in this condition. However, measurement of serum tumour marker levels and extensive radiological monitoring of women with a history of primary breast cancer have failed to detect early recurrences and have not provided any survival benefit when tested in large prospective studies.5,6The detection of circulating tumour cells (CTCs) in MBC has been shown to be reliable, sensitive, reproducible, and predictive of prognosis and early treatment response.7 A multicenter prospective trial demonstrated that the level of CTCs in patients with MBC who have measurable disease is a powerful predictor of progression-free and overall survival. In that trial patients with > 5 CTCs per 7.5 ml of blood (a prospectively identified cut-off level) had significantly shorter progression-free and overall survival durations compared to those with < 5 CTCs per 7.5 ml of blood. The continue monitoring of CTCs predicted for disease outcome as early as 3 weeks, therefore indicating the benefit of treatments. Furthermore, in a multivariate analysis, the level of CTCs had a predictive value independent of the line and type of therapy, time to metastasis, site of recurrence (visceral vs. nonvisceral), and hormone receptor statu
Risk of ipsilateral lung cancer after postmastectomy radiotherapy and smoking: does the possible triumph over the actual?
No full textAcute Ischemia/Hypoxia in Rat Hippocampal Neurons Activates Nuclear Ubiquitin and Alters Chromatin and DNA
No full textCTC enumeration and characterization: Moving toward personalized medicine
Full text linkThe primary cause of tumor-related death in breast cancer (BC) is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. The enumeration of circulating tumor cells (CTCs) represents an effective prognostic and predictive biomarker, which is able to monitor efficacy of adjuvant therapies, detect early development of (micro)metastases and at last, assess therapeutic responses of advanced disease earlier than traditional imaging methods. Moreover, since repeated tissue biopsies are invasive, costly and not always feasible, the assessment of tumor characteristics on CTCs, by a peripheral blood sample as a 'liquid biopsy', represents an attractive opportunity. The implementation of molecular and genomic characterization of CTCs could contribute to improve the treatment selection and thus, to move toward more personalized treatments. This review describes the current state of the art on CTC detection strategies, the evidence to demonstrate their clinical validity, and their potential impact for both future clinical trial design and, decision-making process in our daily practice
Automated Electrorotation to Reveal Dielectric Variations Related to HER-2/neu Overexpression in MCF-7 Sublines
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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