Frontiers in Molecular Medicine
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2674-0095

2021 ◽  
Vol 1 ◽  
Author(s):  
Morgan Williamson ◽  
Naima Moustaid-Moussa ◽  
Lauren Gollahon

Metabolic diseases are becoming more common and more severe in populations adhering to western lifestyle. Since metabolic conditions are highly diet and lifestyle dependent, it is suggested that certain diets are the cause for a wide range of metabolic dysfunctions. Oxidative stress, excess calcium excretion, inflammation, and metabolic acidosis are common features in the origins of most metabolic disease. These primary manifestations of “metabolic syndrome” can lead to insulin resistance, diabetes, obesity, and hypertension. Further complications of the conditions involve kidney disease, cardiovascular disease, osteoporosis, and cancers. Dietary analysis shows that a modern “Western-style” diet may facilitate a disruption in pH homeostasis and drive disease progression through high consumption of exogenous acids. Because so many physiological and cellular functions rely on acid-base reactions and pH equilibrium, prolonged exposure of the body to more acids than can effectively be buffered, by chronic adherence to poor diet, may result in metabolic stress followed by disease. This review addresses relevant molecular pathways in mammalian cells discovered to be sensitive to acid - base equilibria, their cellular effects, and how they can cascade into an organism-level manifestation of Metabolic Syndromes. We will also discuss potential ways to help mitigate this digestive disruption of pH and metabolic homeostasis through dietary change.


2021 ◽  
Vol 1 ◽  
Author(s):  
Timothy Crook ◽  
Darshana Patil ◽  
Rajnish Nagarkar ◽  
Andrew Gaya ◽  
Nicholas Plowman ◽  
...  

Background: Angiogenic factors are commonly activated in solid tumors and present a viable therapeutic target. However, anticancer treatment with angiogenesis inhibitors (AGI) is limited to a few cancers, mostly as monotherapy and not selected based on molecular indications. We aimed to determine whether patient-specific combination regimens with AGI and other anticancer agents when selected based on multi-analyte tumor interrogation (ETA: Encyclopedic Tumor Analysis) can expand the scope of AGIs in advanced refractory solid organ cancers with improved treatment responses.Methods: We evaluated treatment outcomes in 60 patients with advanced, refractory solid organ cancers who received ETA-guided combination regimens of AGI with other targeted, endocrine or cytotoxic agents. Radiological evaluation of treatment response was followed by determination of Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS).Results: Among the 60 patients, Partial Response (PR) was observed in 28 cases (46.7%), Stable Disease (SD) was observed in 29 cases (48.3%) and Disease Progression (PD, within 60 days) was observed in 3 cases (5.0%). The ORR was 46.7% and DCR was 95.0%. At the most recent follow-up the median PFS (mPFS) was 5.0 months and median OS (mOS) was 8.9 months. There were no Grade 4 therapy related adverse events or treatment related deaths.Conclusion: ETA-guided patient-specific combination regimens with AGI and other anti-neoplastic agents, can yield improved outcomes over AGI monotherapy. Trial Registration: Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011,808. LIQUID IMPACT ID CTRI/2019/02/017,548.


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