Current Pharmaceutical Design - Volume 21, Issue 21, 2015

Vitamin D, beyond its classical roles in the regulation of calcium and phosphorus homeostasis and bone metabolism, has been implicated in multiple pathological processes, including progression from inflammation to cancer development and also involvement in autoimmune diseases as well as cardiovascular disorders. In this review, we shall discuss the different roles of vitamin D and its therapeutic targets in different ga Read More

Gastrointestinal (GI) tract cancers account for a significant proportion of human malignancies. While classical multistep carcinogenesis is characterized by the stochastic accumulation of genetic mutations, additional extrinsic factors can also contribute to tumor promotion. Inflammation plays a critical role in cancers of the GI tract, for which the two major etiological factors are tissue injuries and altered mic Read More

Gastrointestinal (G-I) cancers are one of the most common malignant tumors worldwide. Symptoms relate to the organ affected in the G-I tract are non-specific, making early detection and effective treatment difficult to achieve. Epithelial-mesenchymal transition (EMT), a reversible and dynamical process, can disperse cells in embryos, form mesenchymal cells in injured tissues, and regulate embryonic stem cell different Read More

Peroxisome proliferator-activated receptorδ (PPARδ) belongs to the PPARs receptor family including PPARα, PPARδ, and PPARγ. PPARδ is a ligand-activated transcription factor that plays a critical role in regulating cancer progression. PPARδ-linked tumorigenesis was first identified in colorectal cancer, which is demonstrated by the following evidences, so PPARε is a potential drug target for colorectal cancer. In contrast, some o Read More

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in males and the second in females worldwide. Accumulating evidence has demonstrated that patients with chronic inflammation in bowels have an increased risk to develop CRC. Various inflammatory cells and mediators produced during chronic inflammation are orchestrated through different molecular signaling pathways and lead to the formation of a Read More

Collectively, cancers of the gastrointestinal (GI) tract (including the esophagus, stomach, duodenum, colon, rectum, liver, gall bladder and bile ducts) are the most prevalent and deadly worldwide. A common denominator in the pathogenesis of these GI tract cancers is chronic inflammation, as evidenced by the fact that sufferers of inflammatory bowel disease (IBD) are significantly more susceptible to colon cancer than healt Read More

Ibuprofen is a non-steroidal anti-inflammatory drug of generalized use with over-thecounter availability. Population-based studies have provided evidence that its long-term use is associated with a 30-60% decrease in the risk of developing major types of cancer. Initially, the underlying molecular mechanism was thought to be exclusively dependent on its inhibitory effect on cyclooxygenase activity, which is involved in th Read More

Chronic inflammation increases the risk of developing cancer. For example, patients with severe and prolonged inflammatory bowel disease, particularly ulcerative colitis, have a significantly higher risk of developing colorectal cancer. Serine proteases coordinating the coagulation cascade and immune cell proteases play important roles in regulating the inflammatory response through their actions on protease-activated re Read More

Ulcers in the stomach, duodenum, ileum/jejunum and colon may look alike grossly and microscopically, but they have very different etiologies and pathogenesis. Unfortunately, there is virtually no etiologic treatment for any of these lesions which are also accompanied by limited or extensive inflammation. This article reviews four groups of new antiulcer drugs discovered and patented in our lab in Boston and Long Beach/Irvin Read More

We herein reviewed the mechanism underlying the gastric hyperemic response following barrier disruption, with a focus on cyclooxygenase (COX) isozymes, prostaglandin (PG) E2, and capsaicin-sensitive afferent neurons. Mucosal damage was induced by exposing the stomach to 20 mM taurocholate (TC) with 50 mM HCl. The TC treatment disrupted surface epithelial cells, and then increased acid back-diffusion and mucos Read More

Hydrogen sulfide has potent anti-inflammatory and cytoprotective properties. In the gastrointestinal tract, hydrogen sulfide contributes significantly to mucosal defence and responses to injury. This includes promotion of resolution of inflammation and healing. Inhibition of hydrogen sulfide synthesis increases the susceptibility of the gastrointestinal mucosa to injury and delays healing processes. The beneficial effects of hydr Read More

Chronic inflammation plays important roles in the initiation and development of various cancers, particularly gastrointestinal cancer. Cancer is characterized by stepwise accumulation of genetic and epigenetic alterations of genes. As a high risk factor for cancer, chronic inflammatory response produces great amount of mediators, including cytokines, reactive oxygen and nitrogen species, proteinases, which can induc Read More

Inflammation is a beneficial response that can remove pathogens, repair injured tissue and restore homeostasis to damaged tissues and organs. However, increasing evidence indicate that chronic inflammation plays a pivotal role in tumor development, as well as progression, metastasis, and resistance to chemotherapy. We will review the current knowledge regarding the contribution of inflammation to epithelial mesenchyma Read More

It is necessary to use more effective and safer therapies to treat the increasing prevalence of metabolic diseases. The evidence from several studies indicates that FGF21 which acts as an endocrine hormone can induce beneficial influence to metabolism without apparent adverse effects. Thus, the pharmacologic and physiologic actions of FGF21 play a key role in controlling substrate utilization and energy balance. Recentl Read More

Protein-protein interactions (PPIs) are becoming highly attractive targets for drug discovery. Motivated by the rapid accumulation of PPI data in public database and the success stories concerning the targeting of PPIs, a machine-learning method based on sequence and structure properties was developed to access the druggability of PPIs. Here, a comprehensive non-redundant set of 34 druggable and 122 less druggable PPI Read More