Matricellular Proteins Produced by Melanocytes and Melanomas: In Search for Functions

Matricellular proteins are modulators of cell-matrix interactions and cellular functions. The group includes thrombospondin, osteopontin, osteonectin/SPARC, tenascin, disintegrins, galectins and CCN proteins. The production of matricellular proteins such as osteopontin, SPARC or tenascin is highly upregulated in melanoma and other tumors but little is known about their functions in tumor growth, survival, and metastasis. The distribution pattern of CCN3 differs from most other matricellular proteins, such that it is produced abundantly by normal melanocytes, but is not significantly expressed in melanoma cells. CCN3 is known to inhibit melanocyte proliferation and stimulate adhesion to collagen type IV, the main component of the basement membrane. CCN3 has a unique role in securing adhesion of melanocytes to the basement membrane distinct from other melanoma-produced matricellular proteins which act as de-adhesive molecules and antagonists of focal adhesion. Qualitative and quantitative changes in matricellular protein expression contribute to melanoma progression similar to the E-cadherin to N-cadherin class switch, allowing melanoma cells to escape from keratinocyte control

KDM1A microenvironment, its oncogenic potential, and therapeutic significance

The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators). In this review, we discuss the microenvironment of KDM1A in cancer progression that enables this protein to activate or repress target gene expression, thus making it an important epigenetic modifier that regulates the growth and differentiation potential of cells. A detailed analysis of the mechanisms underlying the interactions between KDM1A and the associated complexes will help to improve our understanding of epigenetic regulation, which may enable the discovery of more effective anticancer drugs

Reducing necrotizing enterocolitis in very low birth weight infants using quality-improvement methods

OBJECTIVE: Due to a rise in necrotizing enterocolitis (NEC, stage ≥2) among very low birth weight (VLBW, birth weight <1500g) infants from 4% in 2005-6 to 10% in 2007-8, we developed and implemented quality improvement (QI) initiatives. The objective was to evaluate the impact of QI initiatives on NEC incidence in VLBW infants. STUDY DESIGN: In September 2009 we developed a NEC QI multidisciplinary team that conducted literature reviews and reviewed practices from other institutions to develop a feeding protocol, which was implemented in December 2009. The team tracked intervention compliance and occurrence of NEC stage ≥2. In May 2010 we reviewed our nasogastric tube practice and relevant literature to develop a second intervention that reduced nasogastric tube indwelling time. The infants were divided into three groups: baseline (Jan 2008-Nov 2009, n219), QI phase 1 (Dec 2009-May 2010, n62), and QI phase 2 (June 2010-Nov 2011, n170). RESULT: The NEC incidence did not decrease after implementation of the feeding protocol in QI phase 1 (19.4%), but did decline significantly after changing nasogastric tube management in QI phase 2 (2.9%). Multivariable logistic regression analysis demonstrated a significant relationship between QI phase and the incidence of NEC. CONCLUSION: QI initiatives were effective in decreasing NEC incidence in our high human milk-feeding NICU. Nasogastric tube bacterial contamination may have contributed to our peak in NEC incidence