Protein-based therapeutics are considered to be one of the most important classes of pharmaceuticals on the market. The growing need to prolong stability of high protein concentrations in liquid form has proven to be challenging. Therefore, significant effort is being made to design formulations which can enable the storage of these highly concentrated protein therapies for up to 2 years. Currently, the excipient selection approach involves empirical high-throughput screening, but does not reveal details on aggregation mechanisms or the molecular-level effects of the formulations under storage conditions. Computational modelling approaches have the potential to elucidate such mechanisms, and rapidly screen in silico prior to experimental testing. Nuclear Magnetic Resonance (NMR) spectroscopy can also provide complementary insights into excipient–protein interactions. This review will highlight the underpinning principles of molecular modelling and NMR spectroscopy. It will also discuss the advancements in the applications of computational and NMR approaches in investigating excipient–protein interactions.
Breast cancers are the second most common cause of intracranial metastasis, after lung cancer, mostly occurring in brain parenchyma. However, dural metastasis (DM) is a rare site representing only < 1% of all metastasis in breast cancers. Median age of occurrence of DM is after 2–3 years of primary diagnosis. DM is usually associated with other skeletal metastasis and isolated DM in a treated case of breast carcinoma is rarer. We report a case of DM in a 67-year-old female patient previously treated for breast cancer 22 years back. The patient underwent surgical excision for DM followed by whole brain radiation and is on palliative chemotherapy.
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