More than any other disease, the complexity of cancer has frustrated the development of effective therapeutics. The varying and evolving landscape of genetic changes between and within tumors and the complex interaction of the cancer cells with the immune system make this disease extremely difficult to simulate. A range of models now exists that better replicate cancers complexity.
Cancer drug candidates sometimes emerge with exceptional promise but ultimately fall short. In the late 1990s, endostatin gained huge prominence and was widely viewed as an exceptional cancer drug candidate. But things didn’t quite work out. Although endostatin is now approved by the FDA, in the West it is largely forgotten, eclipsed by newer treatments. But look East, notably to China, and endostatin is very much at the forefront of cancer therapy, particularly in combination with chemotherapy. Why have its fortunes varied geographically and will it ever make a global impact?
Cell Guidance Systems and Manchester BIOGEL collaborate to launch PODS-PeptiGels for 3D cell culture • PODS-PeptiGels combine two stand-out technologies in a single customisable cell culture environment • Provides researchers with a predictable and controlled system, with potential for long-term experiments and reduced hands-on time
Inflammation is critical for maintaining health, but, paradoxically, can also generate disease: Chronic inflammation is strongly associated with the development of cancer and is also a key driver of the ageing process. In addition, auto-immune diseases, of which there are very many, are debilitating and can lead to high rates of morbidity and mortality. Drugs that are able to specifically target the damaging aspects inflammatory responses whilst leaving critical functions intact can be hugely successful.
Why do some people fall seriously ill and die with Covid whilst others are asymptomatic? A remarkable characteristic of Covid-19 is the way it affects individuals so differently: Around 40% of people infected with SARS-CoV-2 are asymptomatic. A further 40% experience mild, upper respiratory tract symptoms. The remaining 20% develop pneumonia, of which 10% will become hypoxic, leading to critical illness in around 3%. In addition to age, sex and underlying health issues, the ability to deploy key immunomodulatory cytokines has emerged as an important risk factor for mortality.
The calorie-rich environment of the modern world is leading to poorer diets for many people. Excess calories contribute to inflammation throughout the body, early-onset of age-related diseases/mortality and a shorter life expectancy. Extreme calorie restriction, 50% below recommended daily limits, may increase lifespan beyond current levels. However, for many people, this is not a price worth paying. Can drugs allow us to achieve greater longevity without severe calorie restriction?
Diseases that primarily affect the brain, often resulting in dementia, are some of the most prevalent, devastating, and yet poorly treated of all diseases. Despite advances in our knowledge of basic neurosciences, the failure rate for new drugs targeting important central nervous system (CNS) diseases still exceeds most other areas of drug discovery. A significant barrier to drug development for these diseases is presented by the blood-brain barrier (BBB).
Ultracentrifugation is often described as the “gold standard†to isolate or purify extracellular vesicles (EVs) including exosomes. Now, a collaborative EV study led by researchers at Clemson University in South Carolina, has shown that for purification of EVs from urine samples, this gold standard can be improved with a simple modification.
In addition to substrate elasticity (durotaxis) and chemical gradients (chemotaxis), which we explored in previous blog articles, surface topography also impacts cell movement and behavior. Cells develop and function embedded within in a highly complex, and evolving, extracellular matrix (ECM) environment. Various biochemical and biophysical ECM cellular cues and their subsequent cell responses shape the development and homeostasis of tissues. An important component of this extracellular environment, governing cell function and behaviour, is the differing micro-/nanotopographical features.
In a previous article about durotaxis, we discussed how cell movements can be guided by elasticity cues at the cell-substrate interface. Here, we focus on the process of cell migration following biochemical cues and the clinical benefits promised by this developing area of research.
