A Perspective on Bone Morphogenetic Proteins: Dilemma behind Cancer- related Responses.

Bone morphogenetic proteins are a center of serious concern and are known to execute various cancer-related issues. The BMP signaling cascades have become more unpredictable as a result of their pleiotropic and risky characteristics, particularly when it comes to cancer responses. This perspective discusses the current therapeutic implications, emphasizes different cellular aspects that impact the failures of the current drug treatments, and speculates on future research avenues that include novel strategies like metabolomic studies and bio-mimetic peptide therapeutics to mitigate cancerous outcomes.

Duality of bone morphogenetic proteins in cancer: A comprehensive analysis.

Over 20 different growth factors belonging to the bone morphogenetic proteins (BMPs) family have been identified, that were initially discovered as growth factors that promote osteogenesis, and play a vital role in bone remodeling and various developmental processes. Numerous studies have explored the aberrance level of BMPs in various cancer types, questioning their role in tumorigenesis. These growth factors have been studied extensively over the decades to define their function during cancer progression and metastasis. Nonetheless, the BMP expression profiles in clinical samples correlate with cancer prognosis. Based on clinical data, various in vitro, and in vivo findings, it has been reported that BMPs have dual roles, that is, they can act as a tumor suppressor, tumor promoter, and both. On contrary, some studies have reported that BMPs have an oncogenic role while others reported their tumor-suppressive role. So, this creates a knowledge gap in the behavior of different types of BMPs. Thus, this review updates and bridges the knowledge gap while considering the dual behavior of various BMPs including BMP-2, 4, 6, 7, 9, and 10. Moreover, the comprehensive analysis provides insight into the role of different BMPs in cancer potential and how the behavior of BMPs alters in the tissue-dependent context in various cancers by modulating canonical SMAD signaling, various noncanonical pathways such as PI3K/AKT, NF-κB, MAPK, STAT, cMYC, cJUN, and so forth. This review also enlightens the role of BMP heterodimers, several ligand-binding proteins (agonists and antagonists), mutational status of BMP receptors, and the tumor microenvironment in relating to the bi-functional aspects of the BMPs in various cancerous tissues by regulating the levels of BMP's canonical and noncanonical signals.

The efficacy of tiotropium as a steroid-sparing agent in severe asthma.

People with severe asthma account for 5% to 10% of all asthmatic patients; however, this small group uses the majority of health care resources. Novel methods are needed to cope with the burden that this minority of patients places on the health care system. A severe asthma clinic patient, who was monitored through the University of Alberta's Virtual Asthma Clinic (Edmonton, Alberta) is presented. Despite optimization of his disease and individualized asthma education (provided by a certified asthma educator), the patient remained on oral glucocorticosteroids (OGS) to control his disease. Following optimization and stabilization, a further reduction in the dose of his OGS by the addition of the long-acting anticholinergic agent tiotropium bromide, was demonstrated. The role of tiotropium as a potential 'steroid-sparing agent' in severe refractory asthma is discussed, noting that if patients who are on OGS are not monitored for active inflammation, they may overuse the amount of prescribed systemic steroids, which can result in long-term steroid-related sequelae.

Preoperative statin use and infection after cardiac surgery: a cohort study.

BACKGROUND: It has been suggested that the routine use of statins preoperatively would reduce the risk of postoperative infection. We conducted this study to explore whether preoperative statin use was associated with infection after cardiac surgery (recipients of which have a higher-than-average risk of postoperative infection). METHODS: We performed secondary analysis of data collected in a prospective cohort study of adults who underwent nontransplant cardiac surgery in a university hospital during the period January 1999 through December 2005. Outcomes were ascertained in a blinded and independent fashion. RESULTS: Of the 7733 patients, 2657 (34%) were taking statins preoperatively; the proportion increased from 16% during 1999-2000 to 53% during 2003-2005 (P < .001, by test for trend). There was no association between preoperative statin use and postoperative infection: 214 statin users (8.1%) versus 425 statin nonusers (8.4%) developed an infection within 30 days after surgery. Factors associated with increased risk of infection after cardiac surgery included diabetes mellitus, heart failure, chronic obstructive pulmonary disease, increasing age, elevated baseline creatinine level, and longer duration of cardiopulmonary bypass but not statin use (adjusted odds ratio, 1.08; 95% confidence interval, 0.89-1.31). CONCLUSIONS: Preoperative statin use was not associated with a reduction in the rate of postoperative infection among patients who underwent cardiac surgery. This lack of apparent benefit for high-risk patients argues against the routine use of statins as a preoperative strategy for lower-risk patients and supports calls for randomized trials to define whether preoperative statin use influences postoperative rates of infection.

Strength of evidence for perioperative use of statins to reduce cardiovascular risk: systematic review of controlled studies.

OBJECTIVE: To determine the strength of evidence underlying recommendations for use of statins during the perioperative period to reduce the risk of cardiovascular events. DESIGN: Systematic review of studies with concurrent control groups. DATA SOURCES: Four electronic databases, the references of identified studies, international experts on perioperative medicine, and the authors of the primary studies. Review methods Two reviewers independently extracted data from studies that reported acute coronary syndromes or mortality in patients receiving or not receiving statins during the perioperative period. MAIN OUTCOME MEASURE: Random effects summary odds ratios for death or acute coronary syndrome during the perioperative period. RESULTS: 18 studies--two randomised trials (n=177), 15 cohort studies (n=799,632), and one case-control study (n=480)--assessed whether statins provide perioperative cardiovascular protection; 12 studies enrolled patients undergoing non-cardiac vascular surgery, four enrolled patients undergoing coronary bypass surgery, and two enrolled patients undergoing various surgical procedures. In the randomised trials the summary odds ratio for death or acute coronary syndrome during the perioperative period with statin use was 0.26 (95% confidence interval 0.07 to 0.99) and the summary odds ratio in the cohort studies was 0.70 (0.57 to 0.87). Although the pooled cohort data provided a statistically significant result, statins were not randomly allocated, results in retrospective studies were larger (odds ratio 0.65, 0.50 to 0.84) than those in the prospective cohorts (0.91, 0.65 to 1.27), and dose, duration, and safety of statin use was not reported. CONCLUSION: The evidence base for routine administration of statins to reduce perioperative cardiovascular risk is inadequate.