Nerve Growth Factor and the Role of Inflammation in Tumor Development.

Nerve growth factor (NGF) plays a dual role both in inflammatory states and cancer, acting both as a pro-inflammatory and oncogenic factor and as an anti-inflammatory and pro-apoptotic mediator in a context-dependent way based on the signaling networks and its interaction with diverse cellular components within the microenvironment. This report aims to provide a summary and subsequent review of the literature on the role of NGF in regulating the inflammatory microenvironment and tumor cell growth, survival, and death. The role of NGF in inflammation and tumorigenesis as a component of the inflammatory system, its interaction with the various components of the respective microenvironments, its ability to cause epigenetic changes, and its role in the treatment of cancer have been highlighted in this paper.

Nerve Growth Factor and Autoimmune Diseases.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.

NGF and BDNF in pediatrics syndromes.

Neurotrophins (NTs) as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play multiple roles in different settings including neuronal development, function and survival in both the peripheral and the central nervous systems from early stages. This report aims to provide a summary and subsequent review of evidences on the role of NTs in rare and non-common pediatric human diseases associated with changes in neurodevelopment. A variety of diseases has been analyzed and many have been linked to NTs neurobiological effects, including chronic granulomatous disease, hereditary sensory and autonomic neuropathy, Duchenne muscular dystrophy, Bardet-Biedl syndrome, Angelman syndrome, fragile X syndrome, trisomy 16, Williams-Beuren syndrome, Prader-Willi syndrome, WAGR syndrome, fetal alcohol spectrum disorders, Down syndrome and Klinefelter Syndrome. NTs alterations have been associated with numerous pathologic manifestations including cognitive defects, behavioral abnormalities, epilepsy, obesity, tumorigenesis as well as muscle-skeletal, immunity, bowel, pain sensibility and cilia diseases. In this report, we discuss that further studies are needed to clear a possible therapeutic role of NTs in these still often uncurable diseases.

Characteristic Hallmarks of Aging and the Impact on Carcinogenesis.

Evidence shows that there is a synergistic, bidirectional association between cancer and aging with many shared traits. Age itself is a risk factor for the onset of most cancers, while evidence suggests that cancer and its treatments might accelerate aging by causing genotoxic and cytotoxic insults. Aging has been associated with a series of alterations that can be linked to cancer: i) genomic instability caused by DNA damage or epigenetic alterations coupled with repair errors, which lead to progressive accumulation of mutations; ii) telomere attrition with possible impairment of telomerase, shelterin complex, or the trimeric complex (Cdc13, Stn1 and Ten1 - CST) activities associated with abnormalities in DNA replication and repair; iii) altered proteostasis, especially when leading to an augmented proteasome, chaperon and autophagy-lysosome activity; iv) mitochondrial dysfunction causing oxidative stress; v) cellular senescence; vi) stem cells exhaustion, intercellular altered communication and deregulated nutrient sensing which are associated with microenvironmental modifications which may facilitate the subsequential role of cancer stem cells. Nowadays, anti-growth factor agents and epigenetic therapies seem to assume an increasing role in fighting aging-related diseases, especially cancer. This report aims to discuss the impact of age on cancer growth.

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents.

Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells' growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.

Can Cerebral Near-infrared Spectroscopy Predict Cerebral Ischemic Events in Neurosurgical Patients? A Narrative Review of the Literature.

Cerebral near-infrared spectroscopy (NIRS) is considered a valuable noninvasive modality for cerebral oxygenation monitoring during cardiovascular surgery and cardiac arrest. We assessed the capability of cerebral NIRS to predict cerebral desaturation and the related neurological outcomes in neurosurgical patients. A literature search in different electronic medical databases was performed from inception to January 2018. A total of 286 citations were found and finally 48 studies were retrieved, only 7 of these were eligible and included for review. A meta-analysis was not feasible because of high heterogeneity of patients' groups, different NIRS techniques used in the studies and different outcome criteria selected. The qualitative assessment showed controversial data on the threshold value of cerebral near-infrared spectroscopy used for detecting cerebral ischemia in neurosurgical patients. The evidence on the selected studies is not strong enough, at the moment, to recommend cerebral NIRS as a mandatory monitor to detect cerebral deoxygenation able to predict the future neurological outcome in neurosurgical patients. Further studies are needed to validate a threshold value for cerebral ischemia and the relationship between NIRS-detected cerebral desaturation and clinical outcome in the neurosurgical population.

Prevention and Treatment of Postoperative Pain after Lumbar Spine Procedures: A Systematic Review.

BACKGROUND AND OBJECTIVE: In the past 2 decades, in developed countries, spine procedures (surgical and percutaneous) had the highest absolute increase in case volume trend. The optimal approach to prevent and treat postoperative pain is continuously evolving. This systematic literature review presents evidence on safety and efficacy of pharmacological and nonpharmacological therapies to prevent and treat postoperative pain after lumbar spine procedures. DATABASES AND DATA TREATMENT: Publications listed in PUBMED and EMBASE were considered to identify randomized clinical trials suitable for inclusion in this systematic review. Key words for literature search were selected, with authors' agreement, using the PICOS approach (participants, interventions, comparisons, outcomes, and study design). RESULTS: Fifty-nine randomized clinical trials (involving a total of 4,238 patients, with ages ranging from 18 to 86 years) published between January 2012 and September 2017 were retrieved. Data are presented according to the timing of therapy administration. CONCLUSION AND RECOMMENDATIONS: Clinical evidence on perioperative pain management in patients undergoing spine procedures have significantly evolved after the review published in 2012. The aim of this systematic review was to report the latest evidence published. These include the preoperative use of dexamethasone, which was shown to be able to reduce pain at mobilization but not to reduce pain at rest or total morphine consumption; the use of gabapentinoids as part of a multimodal analgesic approach; and the safety and effectiveness of the intraoperative use of ketamine, dexketoprofen, and tramadol. Finally, electrical nerve stimulation is gaining interest and is potentially suitable for clinical needs.