Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success.

Venous thromboembolism and prostate cancer: what about genetic markers?

To review the existing literature concerning the relationship between venous thromboembolism (VTE) and prostate cancer (PC) and explore the putative biological and clinical implications of VTE genetic markers on PC patients by screening the PubMed database. Considering the roles of VTE genome-wide association studies-identified genetic determinants in disease development in the general population, these variants might also underlie the susceptibility for PC-related VTE. Therefore, they could help to identify those with a positive benefit-to-harm ratio for thromboprophylaxis approaches during cancer therapy management, thereby improving patient's prognosis.

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.

Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity.

Ovarian cancer is the second most common gynaecologic malignancy and the main cause of death from gynaecologic cancer, due to late diagnosis and chemoresistance. Studies have reported the role of cysteine in cancer, by contributing for hydrogen sulphide (HS) generation and as a precursor of glutathione (GSH). However, the role of cysteine in the adaptation to hypoxia and therapy response remains unclear.

Modulation of membrane properties of lung cancer cells by azurin enhances the sensitivity to EGFR-targeted therapy and decreased β1 integrin-mediated adhesion.

In lung cancer, the Epidermal Growth Factor Receptor (EGFR) is one of the main targets for clinical management of this disease. The effectiveness of therapies toward this receptor has already been linked to the expression of integrin receptor subunit β1 in NSCLC A549 cells. In this work we demonstrate that azurin, an anticancer therapeutic protein originated from bacterial cells, controls the levels of integrin β1 and its appropriate membrane localization, impairing the intracellular signaling cascades downstream these receptors and the invasiveness of cells.

Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models.

Currently there is an effort toward the development of in vitro cancer models more predictive of clinical efficacy. The onset of advanced analytical tools and imaging technologies has increased the utilization of spheroids in the implementation of high throughput approaches in drug discovery. Agitation-based culture systems are commonly proposed as an alternative method for the production of tumor spheroids, despite the scarce experimental evidence found in the literature.

The influence of gait cadence on the ground reaction forces and plantar pressures during load carriage of young adults.

Biomechanical gait parameters--ground reaction forces (GRFs) and plantar pressures--during load carriage of young adults were compared at a low gait cadence and a high gait cadence. Differences between load carriage and normal walking during both gait cadences were also assessed. A force plate and an in-shoe plantar pressure system were used to assess 60 adults while they were walking either normally (unloaded condition) or wearing a backpack (loaded condition) at low (70 steps per minute) and high gait cadences (120 steps per minute).

In-shoe plantar pressures and ground reaction forces during overweight adults' overground walking.

Purpose: Because walking is highly recommended for prevention and treatment of obesity and some of its biomechanical aspects are not clearly understood for overweight people, we compared the absolute and normalized ground reaction forces (GRF), plantar pressures, and temporal parameters of normal-weight and overweight participants during overground walking.

Method: A force plate and an in-shoe pressure system were used to record GRF, plantar pressures (foot divided in 10 regions), and temporal parameters of 17 overweight adults and 17 gender-matched normal-weight adults while walking.

Results: With high effect sizes, the overweight participants showed higher absolute medial-lateral and vertical GRF and pressure peaks in the central rearfoot, lateral midfoot, and lateral and central forefoot.

High-throughput molecular profiling of a P-cadherin overexpressing breast cancer model reveals new targets for the anti-cancer bacterial protein azurin.

Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels.

Influence of pressure-relief insoles developed for loaded gait (backpackers and obese people) on plantar pressure distribution and ground reaction forces.

The aims of this study were to test the effects of two pressure relief insoles developed for backpackers and obese people on the ground reaction forces (GRF) and plantar pressure peaks during gait; and to compare the GRF and plantar pressures among normal-weight, backpackers, and obese participants. Based on GRF, plantar pressures, and finite element analysis two insoles were manufactured: flat cork-based insole with (i) corkgel in the rearfoot and forefoot (SLS1) and with (ii) poron foam in the great toe and lateral forefoot (SLS2). Gait data were recorded from 21 normal-weight/backpackers and 10 obese participants.

The bacterial protein azurin impairs invasion and FAK/Src signaling in P-cadherin-overexpressing breast cancer cell models.

P-cadherin overexpression occurs in about 30% of all breast carcinomas, being a poor prognostic factor for breast cancer patients. In a cellular background of wild-type E-cadherin, we have previously shown that its expression promotes invasion, motility and migration of breast cancer cells due to the induced secretion of metalloproteases (MMPs) to the extracellular medium and to the concomitant shedding of a pro-invasive soluble form of this protein (sP-cad). Azurin is secreted by Pseudomonas aeruginosa and induces in vitro and in vivo cytotoxicity after its preferential penetration in human cancer cells relative to normal cells.

Ground reaction forces and plantar pressure distribution during occasional loaded gait.

This study compared the ground reaction forces (GRF) and plantar pressures between unloaded and occasional loaded gait. The GRF and plantar pressures of 60 participants were recorded during unloaded gait and occasional loaded gait (wearing a backpack that raised their body mass index to 30); this load criterion was adopted because is considered potentially harmful in permanent loaded gait (obese people). The results indicate an overall increase (absolute values) of GRF and plantar pressures during occasional loaded gait (p < 0.

[Evaluation of the performance of three spacers].

Introduction: Several aspects are known to influence the drug distribution within the low respiratory tract, with particular emphasis on those related to the inhalation device. The aim of this work was to assess the performance of three spacers in the drug release, and also the quantity of active agent deposited inside these devices.

Materials And Methods: In order to evaluate the behaviour of particles in suspension delivered through the Ventilan®HFA inhaler coupled to three different spacers (Volumatic®, AeroChamber MAX® and NebuChamber®) the Multistage Liquid Impinger (MSLI) was used, according to the Portuguese Pharmacopoeia.