Adv Exp Med Biol
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Cancer immunotherapy is emerging as the most promising novel strategy for cancer treatment. Cancer immunotherapy is broadly categorized into three forms: immune checkpoint modulation, adoptive cell transfer, and cancer vaccine. Immune checkpoint blockade is demonstrated as the most clinically effective treatment with low immune-related adverse events (irAE). ⋯ Breast cancers such as triple negative breast cancer and HER-2 negative breast cancer respond to immune checkpoint blockade therapy due to their high immunogenicity. PD-1/PD-L1 blockade has just received FDA approval as a standard cancer therapy for solid tumors such as breast cancer. Development of immune checkpoint blockade focuses on two directions: one is to identify proper biomarkers of immune checkpoint blockade in breast cancer, and the other is to combine therapies with PD-1/PD-L1 blockade antibodies to achieve optimal clinical outcomes.
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Inter-individual variability in response to pharmacotherapy has provoked a higher demand to personalize medical decisions. As the field of pharmacogenomics has served to translate personalized medicine from concept to practice, the contribution of the "omics" disciplines to the era of precision medicine seems to be vital in improving therapeutic outcomes. Although we have observed significant advances in the field of genomics towards personalized medicine , the field of proteomics-with all its capabilities- is still in its infancy towards the area of personalized precision medicine. ⋯ However, other applications in proteomics such as "individual" proteome sequencing with its signature PTMs, have not been fully investigated as compared to the achievements in the genomics discipline This infers that proteomics research work has promising potential, yet to be discovered, in the precision medicine and comprises a major component of the personalized medicine infrastructure as it allows individual characterization of disease at the protein level. To conclude, the field of proteomics-based personalized medicine is still in its infancy compared to genomics field due to several technical and instrumentation-based obstacles; however, we anticipate to have this initiative leading in the coming future. This chapter will discuss briefly how neuroproteomics can impact personalized medicine in the fields of neurodegenerative disorders particularly in Alzheimer's disease and brain injury .
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Hypertension remains the most important risk factor for cardiovascular disease. If antihypertensive drugs choice is well guided today, blood pressure (BP) target still a subject of controversies. Residual risk is matter of debate and the lower- the better dogma is come back again regarding to data reported from recent trials. ⋯ In diabetic patients, SBP target should be less than 140 mmHg according to ACCORD trial. However, for patients with protein-creatinine ratio >500 mg/g (albumin-creatinine ratio > 300 mg/g), with or without diabetes, lower SBP target should be proposed for renal protection aiming SBP < 130 mmHg as recommended by KDIGO guidelines. In patients at low or intermediate risk, without cardiovascular disease, SBP should start to be treated when SBP is above 140 mmHg, and when treated, target BP should be less than 140 mmHg as reported by HOPE-3 trial.
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Two major guide-line committees (JNC-8 and NICE UK) have dropped beta-blockers as first-line therapy in the treatment of hypertension. Also, recent meta-analyses (that do not take age into account) have concluded that beta-blockers are inappropriate first-line agents in the treatment of hypertension. This review seeks to shed some light on the "rights and wrongs" of such actions and conclusions. ⋯ Primary/essential hypertension in younger/middle-age is underpinned by high sympathetic nerve activity. In this age-group high resting heart rates and high plasma norepinephrine levels (independent of blood pressure) are linked to premature cardiovascular events and death. Thus, anti-hypertensive agents that increase sympathetic nerve activity ie diuretics, dihydropyridine calcium blockers, and ARBs, are inappropriate first-line choices in this younger age-group. Beta-blockers perform well vs randomised placebo and other antihypertensive agents regarding reduced risk of death/stroke/myocardial infarction in younger (<60 years) hypertensive subjects, and are a reasonable first-line choice of therapy (certainly in men). These facts should be reflected in the recommendations of guideline committees around the world.
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Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. ⋯ In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.