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Boonyaratanakornkit J.B.,University of California at San Francisco | Boonyaratanakornkit J.B.,Dermatology Research | Yue L.,Dermatology Research | Strachan L.R.,University of California at San Francisco | And 8 more authors.
Journal of Investigative Dermatology | Year: 2010

Despite increasing knowledge regarding melanoma-initiating cells (MICs), questions persist regarding the number and phenotypic nature of cells with tumor-generating capability. Evidence for a phenotypically distinct human MIC has been found in NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice. However, a phenotypically distinct human MIC was not found in the NOD/SCIDIl2rg/(NSG) mouse model. The demonstration of a distinct population of human melanoma cells responsible for tumorigenesis and tumor cell self-renewal would provide an important target for new melanoma therapies. In this study, we show a 100-fold range in MIC frequency in human melanoma (1 in 18,000 to 1 in 1,851,000 cells) in the NOD/SCID mouse. In this model, human melanoma cells with high aldehyde dehydrogenase (ALDH) activity were enriched 16.8-fold in tumorigenic cells over unfractionated (UNF) cells, such that 1 in 21,000 cells was a MIC. In the NSG mouse, the ALDH expressing cell population was enriched 100-fold in tumorigenic cells over UNF cells, such that one in four cells was a MIC. Xenograft melanomas that developed from ALDH cells displayed robust self-renewal, whereas those from ALDH cells showed minimal self-renewal in vitro. Thus, ALDH melanoma cells have enhanced tumorigenicity over ALDH cells and superior self-renewal ability. © 2010 The Society for Investigative Dermatology.

This study assessed the bioequivalence, using keratolytic efficacy, of topical preparations studied in humans using adhesive tape stripping and biophysical methods. Ten healthy patients (3 men and 7 women [7 Caucasians and 3 Asians] mean age, 47 years) completed the study. Each coded product was randomly applied to the back according to the designated time of each sample. In addition, an untreated site (normal skin), and an untreated occluded site (chamber only) served as controls. At the end of the application time, each site was rinsed with tap water and then covered with a plastic chamber for 6 hours. Following removal of the chamber, the site was stripped for protein assay and squamometry analysis. This extends previous observations discerning bioequivalence resulting from different active materials with varying mechanism of action and potency on the skin. Results showed no significant difference between tested products. The novel formulations were of equal keratolytic activity to the "standard" (comparator) and hence bioequivalent in keratolytic activity.

Schaller M.,University of Michigan | Ito T.,Nara Medical University | Allen R.M.,University of Michigan | Kroetz D.,University of Michigan | And 9 more authors.
Journal of Leukocyte Biology | Year: 2015

It is well established that the cytokine IL-12 and the transcription factor STAT4, an essential part of the IL-12 signaling pathway, are critical components of the Th1 differentiation process in T cells. In response to pathogenic stimuli, this process causes T cells to proliferate rapidly and secrete high amounts of the cytokine IFN-γ, leading to the Th1 proinflammatory phenotype. However, there are still unknown components of this differentiation pathway. We here demonstrated that the expression of the histone methyltransferase Mll1 is driven by IL-12 signaling through STAT4 in humans and mice and is critical for the proper differentiation of a naïve T cell to a Th1 cell.Once MLL1 is upregulated by IL-12, it regulates the proliferation of Th1 cells. As evidence of this,we showthat Th1 cells fromMll1+/- mice are unable to proliferate rapidly in a Th1 environment in vitro and in vivo. Additionally, upon restimulation with cognate antigen Mll1+/-, T cells do not convert to a Th1 phenotype, as characterized by IFN-γ output. Furthermore, we observed a reduction in IFN-γ production and proliferation in human peripheral blood stimulated with tetanus toxoid by use of a specific inhibitor of the MLL1/menin complex. Together, our results demonstrate that the MLL1 gene plays a previously unrecognized but essential role in Th1 cell biology and furthermore, describes a novel pathway through which Mll1 expression is regulated. © Society for Leukocyte Biology.

Nasir A.,Dermatology Research
Clinical Dermatology Trials 101: A Primer for Dermatologists | Year: 2015

Clinical Dermatology Trials 101 provides dermatologists with a handbook that allows them to become familiar with all aspects of clinical trials. Everything from obtaining the necessary tools and equipment, complying with local, federal, and international guidelines and regulations, and hiring and training staff for the safe and up-to-date conduct of dermatology clinical trials is covered. Written by leading experts in the field, Clinical Dermatology Trials 101 is the only clinical trial how-to available for dermatologists. With skin disease affecting nearly seventy percent of the population over a lifetime, and the rate of development of new drugs and devices for dermatologic use increasing at an exponential rate, there is a tremendous need for training and developing dermatology clinical research facilities to expedite the translation of basic and applied research, from bench to bedside. This is useful for practicing dermatologists, academic dermatologists, dermatology residents, clinical research fellows, dermatology fellows, research scientists, industry dermatologists, and medical students. © Springer International Publishing Switzerland 2015.

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