Current pharmaceutical design
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Pancreatic cancer is characterized by its intrinsic resistance to cytotoxic agents. But the underlying molecular mechanism is unclear. Studies demonstrate that angiogenesis, presence of highly resistant cancer stem cells (CSCs), dysregulation of cell cycle and apoptosis are main aspects of mechanisms of pancreatic cancer chemoresistance. ⋯ Conceivably, the dysregulation of Wnt/β-catenin signaling pathway is involved in pancreatic cancer chemoresistance. Though researchers have proven it in some other cancer types, however, there is no direct evidence for this reasoning in pancreatic cancer. Designing effective experiment setups to define the function and mechanism of Wnt/β-catenin signaling in pancreatic cancer chemoresistance and subsequently targeting the signaling to improve the sensitivity of chemotherapy in pancreatic cancer require a full understanding of the molecular mechanisms of Wnt/β-catenin signaling pathway in angiogenesis, maintaining of highly resistant CSCs, regulation of cell cycle and apoptosis in pancreatic cancer.
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Lenalidomide is a second generation immunomodulatory agent (IMiD), which currently represents the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndrome (MDS) patients with deletion (5q). Lenalidomide has unique activity with a high transfusion independence rate observed in this subset of patients. ⋯ We highlight the mechanism of action and the recent advances in understanding the biology of del (5q) MDS. We also explore its potential use and the efforts to further improve its activity in non-del (5q) MDS.
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Central nervous system pericytes have critical and complex inductive, structural, and regulatory roles interacting with other cell types of the neurovascular unit, especially endothelial cells and astrocytes. Pericyte-endothelial interactions are particularly prominent for blood-brain barrier (BBB) maintenance, with profound effects on basement membrane and endothelial tight junction structure and function. ⋯ Stem cell characteristics of pericytes imply an important regenerative role following stroke. Pericytes thus appear to orchestrate multiple critical functions in stroke, involving blood flow, permeability, and repair of the neurovascular unit.
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Hyperglycemia is associated with increased mortality and morbidity in critically ill patients. Surgical patients commonly develop hyperglycemia related to the hypermetabolic stress response, which increases glucose production and causes insulin resistance. Although hyperglycemia is associated with worse outcomes, the treatment of hyperglycemia with insulin infusions has not provided consistent benefits. ⋯ Patients with diabetes mellitus experience chronic hyperglycemia and often require more intensive perioperative glucose management. When diabetic patients are evaluated before surgery, appropriate management of oral hypoglycemic agents is necessary as several of these agents warrant special consideration. Current recommendations for perioperative glucose management from national societies are varied, but, most suggest that tight glucose control may not be beneficial, while mild hyperglycemia appears to be well-tolerated.
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The development of antimicrobial treatments for respiratory pathogens in cystic fibrosis (CF) has been an integral component to the increased survival of CF patients over the past fifty years. Despite significant treatment advances, however, respiratory failure secondary to chronic bacterial pulmonary infection remains the primary cause of death in CF patients. The purpose of this review is to discuss emerging pathogens (other than Pseudomonas) in CF by describing the characteristics of the organism, their clinical significance in CF, their mechanisms of antimicrobial resistance and the current treatment approaches including newer pharmaceutical modalities. This review will focus on the following pathogens: Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, methicillin-resistant Staphylococcus aureus and nontuberculous mycobacteria The goal is to familiarize the reader with the challenges in treating pulmonary infections in CF caused by multi-drug resistant pathogens and to highlight some of the newer pharmaceutical treatments that are currently the focus of intense research.