Polymeric nanocapsules prevent oxidation of core-loaded molecules: evidence based on the effects of docosahexaenoic acid and neuroprostane on breast cancer cells proliferation

Background

Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive molecules to specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs from inactivation upon interaction with the body and to ensure the release to the target. However, the mechanism of improved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellular levels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidity and mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it has been suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidant agents.

Methods

The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative medium was evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and of the non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions.

Results

DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) and enhanced by the pro-oxidant hydrogen peroxide that confirms that DHA has to be oxidized to exert its anti-proliferative properties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F_4t-neuroprostane, a bioactive, non-enzymatic oxygenated metabolite of DHA known to play a major role in the prevention of cardiovascular diseases. DHA-loaded nanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H₂O₂ maintained the inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of 4(RS)-4-F_4t-neuroprostane that is more hydrophilic than DHA.

Conclusion

Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites. They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not the sole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability, and control the release of bioactive fatty acids following their lipophilicities.

     

Extent of Primary Breast Cancer Surgery: Standards and Individualized Concepts

Surgery is still a main therapeutic option in breast cancer treatment. Nowadays, methods of resection and reconstruction vary according to different tumors and patients. This review presents and discusses standards of care and arising questions on how radical primary breast cancer surgery should be according to different clinical situations. In most early breast cancer patients, breast conservation is the method of choice. The discussion on resection margins is still controversial as different studies show conflicting results. Modified radical mastectomy is the standard in locally advanced breast cancer patients, although there are different promising approaches to spare skin or even the nipple-areola complex. A sentinel node biopsy is the standard of care in clinically node-negative invasive breast cancer patients, whereas the significance of axillary lymphonodectomy seems to be questioned through a number of different findings. Although there are interesting findings to modify surgical approaches in very young or elderly breast cancer patients, it will always be an individualized approach if we do not adhere to current guidelines. Up to date, there are no special surgical procedures in BRCA mutation carriers or patients of high-risk families.     

Recommendations for managing patients with diabetes mellitus in cardiopulmonary rehabilitation: an American Association of Cardiovascular and Pulmonary Rehabilitation statement

Diabetes mellitus is a highly prevalent condition in patients participating in cardiopulmonary rehabilitation. However, research and subsequent guidelines specifically applicable to patients with diabetes, participating in cardiopulmonary rehabilitation, are limited. Recognizing this limitation, the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) initiated this statement, with the goal of developing a template that incorporated recommendations provided in the AACVPR Core Components and the American Association of Diabetes Educators 7 Self-Care Behaviors. This statement describes key processes regarding evaluation, interventions, and expected outcomes in each of the core components for the management of patients with diabetes in a cardiopulmonary rehabilitation program.     

Risks of nonchromosomal birth defects,small-for-gestational age birthweight,and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth

Journal of Assisted Reproduction and Genetics - Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks’ gestation are associated with reductions...     

Decision tool to improve the quality of care in rheumatoid arthritis

Objective

Despite the importance of achieving tight control, many patients with rheumatoid arthritis (RA) are not effectively treated with disease‐modifying antirheumatic drugs. The objective of this study was to develop a decision support tool to inform RA patients with ongoing active disease about the risks and benefits related to biologic therapy.

Methods

We developed a balanced, web‐based, decision support tool. Options, values, and probabilistic information were described using theoretically supported formulations. We conducted a pre‐/posttest study to assess preliminary evidence of the tool's efficacy in improving knowledge related to biologics, clarity of values, willingness to take a biologic, and informed choice.

Results

We interviewed 104 subjects (mean age 62 years, 84% women, 87% white, and median duration of RA 8 years). Knowledge (coded on a 0–20 scale) and willingness to take a biologic (coded on a 0–10 scale) significantly increased after viewing the tool (mean differences 2.3 and 1.4, respectively; P < 0.0001 for both). Perceived knowledge and values clarity (coded on 0–100 scales) also significantly improved (mean differences 20.4 and 20.8, respectively; P < 0.0001 for both). The proportion of subjects making an informed value‐concordant choice increased substantially from 35% to 64%.

Conclusion

A tool designed to effectively communicate the risks and benefits associated with biologic therapy increased knowledge, patient willingness to escalate care, and the likelihood of making an informed choice. The results of this study support the need for a clinical trial to examine the impact of the tool in clinical practice.