Tackling the tumor microenvironment - how can complex tumor models aid oncology drug development?

Introduction: Identifying effective cancer drugs remains an inefficient process. Drug efficacy in traditional preclinical cancer models translates poorly into therapy in the clinic. Implementation of preclinical models that incorporate the tumor microenvironment (TME) is needed to improve selection of active drugs prior to clinical trials.

Exploring Metabolic Signatures of Ex Vivo Tumor Tissue Cultures for Prediction of Chemosensitivity in Ovarian Cancer.

Predicting patient response to treatment and the onset of chemoresistance are still major challenges in oncology. Chemoresistance is deeply influenced by the complex cellular interactions occurring within the tumor microenvironment (TME), including metabolic crosstalk. We have previously shown that ex vivo tumor tissue cultures derived from ovarian carcinoma (OvC) resections retain the TME components for at least four weeks of culture and implemented assays for assessment of drug response.

Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models.

The current standard preclinical oncology models are not able to fully recapitulate therapeutic targets and clinically relevant disease biology, evidenced by the 90% attrition rate of new therapies in clinical trials. Three-dimensional (3D) culture systems have the potential to enhance the relevance of preclinical models. However, the limitations of currently available cellular assays to accurately evaluate therapeutic efficacy in these models are hindering their widespread adoption.

Fighting S. aureus catheter-related infections with sophorolipids: Electing an antiadhesive strategy or a release one?

Staphylococcus aureus medical devices related-infections, such as blood stream catheter are of major concern. Their prevention is compulsory and strategies, not prone to the development of resistance, to prevent S. aureus biofilms on catheter surfaces (e.

Seeking faster, alternative methods for glycolipid biosurfactant characterization and purification.

Biosurfactants have been investigated as potential alternatives for synthetic surfactants in several areas, for example, in environmental and pharmaceutical fields. In that regard, extensive research has been carried out with sophorolipids and rhamnolipids that also present various biological properties with therapeutic significance. These biosurfactants are obtained as complex mixtures of slightly different molecules, and thus when studying these microbial glycolipids, the ability to identify and purify the produced compounds is of extreme importance.

Improving the Anti-inflammatory Response via Gold Nanoparticle Vectorization of CO-Releasing Molecules.

CO-releasing molecules (CORMs) have been widely studied for their anti-inflammatory, antiapoptotic, and antiproliferative effects. CORM-3 is a water-soluble Ru-based metal carbonyl complex, which metallates serum proteins and readily releases CO in biological media. In this work, we evaluated the anti-inflammatory and wound-healing effects of gold nanoparticles-CORM-3 conjugates, AuNPs@PEG@BSA·Ru(CO), exploring its use as an efficient CO carrier.

Patient-derived ovarian cancer explants: preserved viability and histopathological features in long-term agitation-based cultures.

Ovarian carcinoma (OvC) remains a major therapeutic challenge due to its propensity to develop resistance after an initial response to chemotherapy. Interactions of tumour cells with the surrounding microenvironment play a role in tumour survival, invasion capacity and drug resistance. Cancer models that retain tissue architecture and tumour microenvironment components are therefore essential to understand drug response and resistance mechanisms.

Prenatal or Childhood Serum Levels of Vitamin D and Dental Caries in Paediatric Patients: A Systematic Review.

Purpose: To assess the association between low prenatal or childhood levels of 25-hydroxyvitamin D (25(OH) D) and dental caries experience in children.

Materials And Methods: PubMed, B-On, Web of Science, Scopus, and Cochrane Library databases were searched. The inclusion criteria were randomised controlled trials, cohort and cross-sectional studies published between 1998 and 2019; caries outcomes expressed as prevalence or based on the decayed missing and filled index for primary and permanent teeth/surfaces; and vitamin D levels assessed by laboratory analysis.

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect).

Combination of chemotherapy and Au-nanoparticle photothermy in the visible light to tackle doxorubicin resistance in cancer cells.

Despite great advances in the fight against cancer, traditional chemotherapy has been hindered by the dose dependent adverse side effects that reduce the usable doses for effective therapy. This has been associated to drug resistance in tumor cells that often cause relapse and therapy failure. These drawbacks have been tackled by combining different therapeutic regiments that prevent drug resistance while decreasing the chemotherapy dose required for efficacious ablation of cancer.

Nanoparticles-Emerging Potential for Managing Leukemia and Lymphoma.

Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles (NPs) possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. , NPs enhance the therapeutic efficacy of anticancer agents when compared with conventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance.

Photothermal enhancement of chemotherapy in breast cancer by visible irradiation of Gold Nanoparticles.

Photothermal Therapy (PTT) impact in cancer therapy has been increasing due to the enhanced photothermal capabilities of a new generation of nanoscale photothermal agents. Among these nanoscale agents, gold nanoshells and nanorods have demonstrated optimal properties for translation of near infra-red radiation into heat at the site of interest. However, smaller spherical gold nanoparticles (AuNPs) are easier to produce, less toxic and show improved photoconversion capability that may profit from the irradiation in the visible via standard surgical green lasers.

Paroxysmal Sympathetic Hyperactivity: An Old but Unrecognized Condition.

Unlabelled: Patients who survive a traumatic brain injury (TBI) can sometimes experience symptoms of excessive sympathetic discharge. Despite being known about for more than 60 years, the diagnostic criteria for this condition have only recently been defined under the name "paroxysmal sympathetic hyperactivity". Failure to recognize this syndrome leads to excessive costs, prolonged hospital stays and delayed recovery for TBI patients.

Three Synchronous Tumors Discovered in SIADH Investigation.

Unlabelled: Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a common cause of euvolemic hyponatremia which has many possible etiologies such as tumors (mainly lung cancers). We present a case of a 79-year old women hospitalized due to microcytic anemia with transfusion need and hyponatremia due to SIADH. Three primary tumors without known metastasis were discovered.

Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer-The Case for Combined Delivery?

Gene therapy arises as a great promise for cancer therapeutics due to its potential to silence genes involved in tumor development. In fact, there are some pivotal gene drivers that suffer critical alterations leading to cell transformation and ultimately to tumor growth. In this vein, gene silencing has been proposed as an active tool to selectively silence these molecular triggers of cancer, thus improving treatment.

First occurrence of cylindrospermopsin in Portugal: a contribution to its continuous global dispersal.

Cylindrospermopsin (CYN) was found to occur in Portugal for the first time. In this study CYN values varied from a minimum of 1.4 μg L to a maximum of 12 μg L detected through HPLC technique and confirmed by LC-MS method.

Health information technology implementation - impacts and policy considerations: a comparison between Israel and Portugal.

The use of Information and Communications Technology (ICT) in health systems is increasing worldwide. While it is assumed that ICT holds great potential to make health services more efficient and grant patients more empowerment, research on these trends is at an early stage. Building on a study of the impact of ICT on physicians and patients in Israel, a Short Term Scientific Mission (STSM) sponsored by COST Net in conjunction with CIES/ISCTE IUL (Portugal) facilitated a comparison of ICT in health in Israel and Portugal.

A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study.

Objective: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients.

Methods: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years.

The effect of care pathways for hip fractures: a systematic overview of secondary studies.

The aim of this paper was to perform a systematic overview of secondary literature studies on care pathways (CPs) for hip fracture (HF). The online databases MEDLINE-PubMed, Ovid-EMBASE, CINAHL-EBSCO-host, and The Cochrane Library were searched. A total of six papers, corresponding to six secondary studies, were included but only four secondary studies were HF-specific and thus assessed.

Quality indicators for in-hospital management of exacerbation of chronic obstructive pulmonary disease: results of an international Delphi study.

Aim: To report a Delphi study that was conducted to select process and outcome indicators that are relevant to study quality of care and impact of care pathways for patients hospitalized with exacerbation of chronic obstructive pulmonary disease.

Background: Management of patients hospitalized with exacerbation of chronic obstructive pulmonary disease is suboptimal and outcomes are poor. To evaluate the impact of care pathways properly, relevant indicators need to be selected.

The impact of care pathways for patients with proximal femur fracture: rationale and design of a cluster-randomized controlled trial.

Background: Proximal femur fracture (PFF) is associated with considerable morbidity and mortality. The European Quality of Care Pathway (EQCP) study on PFF (NCT00962910) was designed to determine how care pathways (CP) for hospital treatment of PFF affect consistency of care, adherence to evidence-based key interventions, and clinical outcome.

Methods/design: An international cluster-randomized controlled trial (cRCT) will be performed in Belgium, Ireland, Italy and Portugal.