Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium

Background High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Methods Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Results Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p < 0.0001). Furthermore, all CD133 + pOC patients were International Federation of Gynaecology and Obstetrics (FIGO)-stage III/IV (p < 0.0001) and had significantly worse progression-free interval (PFI) (p = 0.04) and overall survival (OS) (p = 0.02). On multivariate analysis, CD133/ALDH1 coexpression in pOCs was identified as independent prognostic factor for PFI (HR: 1.64; 95% CI: 1.03–2.60; p = 0.036) and OS (HR: 1.71; 95% CI: 1.01–2.88; p = 0.045). Analysis on 52 pts patients with known somatic BRCA status revealed that BRCA mutations did not influence CSC biomarker expression. Conclusions The study showed that CD133/ALDH1 expression impacts HGSOC patients' survival and first suggests that CSCs might undergo phenotypic change during the disease course similarly to non stem-like cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status

Characterisation of tumor microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact. An OCTIPS Consortium study.

Background: High-grade serous ovarian cancer (HGSOC) intratumoural vasculature evolution remains unknown. The study investigated changes in tumour microvessel density (MVD) in a large cohort of paired primary and recurrent HGSOC tissue samples and its impact on patients’ clinico-pathological outcome. Methods: A total of 222 primary (pOC) and recurrent (rOC) intra-patient paired HGSOC were assessed for immunohistochemical expression of angiogenesis-associated biomarkers (CD31, to evaluate MVD, and VEGF-A). Expression profiles were compared between pOCs and rOCs and correlated with patients' data. Results: High intratumoural MVD and VEGF-A expression were observed in 75.7% (84/111) and 20.7% (23/111) pOCs, respectively. MVDhighand VEGF(+)samples were detected in 51.4% (57/111) and 20.7% (23/111) rOCs, respectively. MVDhigh/VEGF(+)co-expression was found in 19.8% (22/111) and 8.1% (9/111) of pOCs and rOCs, respectively (p = 0.02). Pairwise analysis showed no significant change in MVD (p = 0.935) and VEGF-A (p = 0.121) levels from pOCs to rOCs. MVDhighpOCs were associated with higher CD3(+)(p = 0.029) and CD8(+)(p = 0.013) intratumoural effector TILs, while VEGF(+)samples were most frequently encountered among BRCA-mutated tumours (p = 0.019). Multivariate analysis showed VEGF and MVD were not independent prognostic factors for OS. Conclusions: HGSOC intratumoural vasculature did not undergo significant changes during disease progression. High concentration of CD31(+)vessels seems to promote recruitment of effector TILs. The study also provides preliminary evidence of the correlation between VEGF-positivity and BRCA status

Efficiency of Multiparticulate Delivery Systems Loaded with Flufenamic Acid Designed for Burn Wound Healing Applications

Burns are soft tissue injuries that require particular care for wound healing. Current tissue engineering approaches are aimed at identifying the most efficient treatment combinations to restore the tissue properties and function by using adapted scaffolds or delivery platforms for tissue repair and regeneration by triggering molecules. To reduce the inflammation associated with skin burns, the addition of an anti-inflammatory factor in these scaffolds would greatly increase the quality of the therapy. Therefore, this study is aimed at obtaining and validating a novel multiparticulate system based on a collagen matrix with controlled delivery of flufenamic acid anti-inflammatory drug for burn wound healing applications. In this work, we have characterized the properties and biocompatibility of these multiparticulate drug delivery systems (MDDS) and we have demonstrated their efficiency against burns and soft tissue lesions, particularly when the drug was microencapsulated, and thus with a controlled release. This study contributes to the advancement in therapy of burns and burn wound healing applications

Research and Science Today No. 2(4)/2012

RESEARCH AND SCIENCE TODAY is a biannual science journal established in 2011. The journal is an informational platform that publishes assessment articles and the results of various scientific research carried out by academics. We provide the authors with the opportunity to create and/or perfect their science writing skills. Thus, each issue of the journal (two per year and at least two supplements) will contain professional articles from any academic field, authored by domestic and international academics. The goal of this journal is to pass on relevant information to undergraduate, graduate, and post-graduate students as well as to fellow academics and researchers; the topics covered are unlimited, considering its multi-disciplinary profile. Regarding the national and international visibility of Research and Science Today, it is indexed in over 30 international databases (IDB) and is present in over 200 online libraries and catalogues; therefore, anybody can easily consult the articles featured in each issue by accessing the databases or simply the website

Research and Science Today No. 1(5)/2013

RESEARCH AND SCIENCE TODAY is a biannual science journal established in 2011. The journal is an informational platform that publishes assessment articles and the results of various scientific research carried out by academics. We provide the authors with the opportunity to create and/or perfect their science writing skills. Thus, each issue of the journal (two per year and at least two supplements) will contain professional articles from any academic field, authored by domestic and international academics. The goal of this journal is to pass on relevant information to undergraduate, graduate, and post-graduate students as well as to fellow academics and researchers; the topics covered are unlimited, considering its multi-disciplinary profile. Regarding the national and international visibility of Research and Science Today, it is indexed in over 30 international databases (IDB) and is present in over 200 online libraries and catalogues; therefore, anybody can easily consult the articles featured in each issue by accessing the databases or simply the website

Research and Science Today No. 2(6)/2013

RESEARCH AND SCIENCE TODAY is a biannual science journal established in 2011. The journal is an informational platform that publishes assessment articles and the results of various scientific research carried out by academics. We provide the authors with the opportunity to create and/or perfect their science writing skills. Thus, each issue of the journal (two per year and at least two supplements) will contain professional articles from any academic field, authored by domestic and international academics. The goal of this journal is to pass on relevant information to undergraduate, graduate, and post-graduate students as well as to fellow academics and researchers; the topics covered are unlimited, considering its multi-disciplinary profile. Regarding the national and international visibility of Research and Science Today, it is indexed in over 30 international databases (IDB) and is present in over 200 online libraries and catalogues; therefore, anybody can easily consult the articles featured in each issue by accessing the databases or simply the website