Current Pharmaceutical Design - Volume 25, Issue 28, 2019

Breast cancer is a complex heterogeneous disease that is categorized into several histological and genomic subtypes with relevant prognostic and therapeutical implications. Such diversity requires a multidisciplinary approach for a comprehensive treatment that will involve surgeons, radiotherapists and medical oncologists. Breast cancer is classified as either local (or locoregional), which stands for 90-95% of cases, or metastatic, representing 5% of cases. The management of breast cancer will be determined by the stage of the disease. The treatment of local breast cancer is based on surgery and/or radiotherapy. Systemic breast cancer requires chemotherapy and/or endocrine and/or biological therapy.

Introduction: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. Method: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. Results: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. Conclusion: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

Opioid-free anesthesia is revolutionizing anesthetic practices for its potential benefits in selected patients. Opioid-free anesthesia represents a step forward in anesthetic practice as it has been suggested to provide potential clinical benefits for selected patients. Opioid-free anesthesia spares the use of opioids and involves the administration of multiple adjuvant anesthetics, which may have an impact on cancer progression. All this have added to the growing interest in the immune response to anesthetics, making opioid-free anesthesia a promising avenue for future research. Assessing the role of anesthetics in immunomodulation in the surgical setting is challenging, and results are often contradictory. Indeed, there is a scarcity of data of studies on humans, which hinder the interpretation of results. However, promising evidence has been published that cancer progression can be delayed by the administration of specific anesthetic agents.

Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis. This narrative review highlights earlier and more recent in vitro, in vivo and human retrospective studies that yield conflicting results as to the immune-modulatory effects of morphine on tumor biology. The article examines and explains the discrepancies with regards to the seemingly opposite results of morphine in the tumor milieu. The results of both, earlier studies that demonstrated procarcinogenic effects versus the data of more recent refined rodent studies that yielded neutral or even anti-carcinogenic effects are presented here. Until the results of prospective randomized controlled trials are available to clarify this important question, it is currently not warranted to support opiophobia and opioids continue to constitute a pivotal role in the pain management of cancer patients.

Background: Based on animal data only, some clinicians have adopted propofol-based anesthesia for cancer surgery with the aim of increased survival. Objective: Our objective is to verify or refute the hypothesis that survival increases after cancer surgery with propofol compared with sevoflurane for anesthesia maintenance. This aim deserves a large-scale randomized study. The primary hypothesis is an absolute increase of minimum 5%-units in 1- and 5-year survival with propofol- based anesthesia for breast or colorectal cancer after radical surgery, compared with sevoflurane-based anesthesia. Method: Ethics and medical agency approvals were received and pre-study registrations at clinicaltrial.gov and EudraCT were made for our now ongoing prospective, randomized, open-label, multicenter study. A power analysis based on a retrospective study, including a safety margin for drop outs, resulted in a total requirement of 8,000 patients. The initial inclusion period constituted a feasibility phase with an emphasis on the functionality of the infrastructure at the contributing centers and at the monitoring organization, as well as on protocol adherence. Conclusion: The infrastructure and organization work smoothly at the different contributing centers. Protocol adherence is good, and the monitors are satisfied. We expect this trial to be able to either verify or refute that propofol is better than sevoflurane for cancer surgery.

Background: Cancer is the major public health problem in developing countries. The treatment of cancer requires a multimodal approach and chemotherapy is one of them. Chemotherapeutic drug is administered to cancer patients in the form of a formulation which is prepared by mixing an active ingredient (drug) with the excipient. The role of excipient in a formulation is to regulate the release, bio-distribution, and selectivity of drug within the body. Methods: In this context, selectivity of an anticancer formulation is achieved through two mechanisms like passive and active targeting. The passive targeting of a formulation is generally through enhanced permeation retention (EPR) effect which is dictated by physical properties of the carrier such as shape and size. On the contrary, active targeting means surface functionalization of excipient with target-specific ligands and/or receptors to increase its selectivity. Results: Over the past several decades, remarkable progress has been made in the development and application of an engineered excipient or carrier to treat cancer more effectively. Especially nanoparticulate systems composed of metal/liposomes/polymeric material/proteins have received significant attention in the rational design of anticancer drug formulations; for example, therapeutic agents have been integrated with nanoparticles of optimal sizes, shapes and surface properties to improve their solubility, circulation half-life, and bio-distribution. In this review article, recent literature is included to discuss the role of physicochemical properties of excipients in achieving tumour targeting through passive and active approaches. Conclusion: The selection of an excipient/carrier and targeting ligand plays a very important role in rational design and development of anticancer drug formulations.

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

Chitosan is a cationic polysaccharide and multi-potential polymer with the ability to interact with other natural and synthetic polyanionic/polymeric compounds, with or without a cross-linking agent. It has been able to composite nano-microparticles with a variety of features. This compound has the ability to carry quercetin, as an anti-tumor subject, through the various epithelial systems and release in the sustained and controlled state to the target site. This paper reviews published studies on detailed physicochemical properties of chitosan and quercetin in the fight against the tumor. This also focused on how the chitosan polymer interacts with other polymeric and polyanion species in order to improve its efficiency to make a more suitable capsule or matrix for a variety of drugs, especially quercetin, in oral delivery systems.

Background: The lipid profile is associated with metabolic diseases in overweight and obese individuals. Quercetin treatment is suggested to reduce the risk factors for obesity. Objective: The aim of the literature meta-analysis was to determine the range of doses of quercetin administration on plasma lipid levels in overweight and obese human subjects. Methods: Articles searched on EMBASE, PubMed, Cochrane Library, and Web of Science through March 20, 2019, were reviewed independently using predetermined selection criteria. The Cochrane collaboration’s tool for assessing risk of bias was used to assess the quality of the included trials. Heterogeneity was measured using Cochran's Q test and the I-square (I2) statistic. Data were pooled using a random-effects model and the standardized mean difference (SMD) was considered for measuring the overall effect size. Results: Of 176 articles reviewed, 9 randomized clinical trials were selected based on the inclusion criteria. The pooled results for the effect of quercetin administration on LDL-cholesterol (SMD: -002; 95% CI: -0.15–0.11), HDL-cholesterol (SMD: -0.06; 95% CI: -0.19–0.07), triglycerides (SMD: 0.05; 95% CI: -0.08–0.18), and total cholesterol (SMD: 0.04; 95% CI: -0.09–0.17) were not significantly different from the control group results. Quercetin administration at doses of ≥250 mg/day (SMD: -0.58 ; 95% CI: -0.94–-0.22) and total dose ≥14,000 mg (SMD: -0.58 ; 95% CI: -0.94–-0.22) significantly reduced LDL levels; however, HDL-cholesterol, triglycerides, and total cholesterol levels remained unchanged (p > 0.05). Conclusion: Quercetin administration does not affect plasma lipid levels in overweight and obese individuals. However, it significantly reduces LDL-cholesterol levels at doses of ≥250 mg/day and total dose ≥14000 mg.