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1.  Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis 
Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size—a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P < 0.05) and the vehicle (50% decrease; P < 0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies.
PMCID: PMC3957859  PMID: 24342632
2.  Topical Chemotherapy in Cutaneous T-cell Lymphoma: Positive Results of a Randomized, Controlled, Multi-center Trial Testing the Efficacy and Safety of a Novel 0.02% Mechlorethamine Gel in Mycosis Fungoides 
JAMA dermatology (Chicago, Ill.)  2013;149(1):25-32.
Evaluate the efficacy & safety of a novel 0.02% mechlorethamine (MCH) gel in mycosis fungoides (MF).
Multi-center, randomized, observer-blinded, active controlled trial, comparing 0.02% MCH gel with 0.02% MCH compounded ointment. MCH was applied once daily for up to 12 months. Tumor response and adverse events (AEs) were assessed every month (months 1–6) and every 2 months (months 7–12). Serum drug levels were drawn on a subset of subjects.
Academic medical and/or cancer centers
260 Stage IA-IIA MF patients who had not used topical MCH within 2 years and were naïve to prior use of topical carmustine therapy.
Main Outcome Measures
Response rates (RRs) of all subjects based on primary (composite assessment of index lesion severity - CAILS) and secondary (modified severity weighted assessment tool (mSWAT) and time to response analyses) clinical endpoints.
RR for MCH gel and ointment were 59% vs. 48% by CAILS and 46.9% vs. 46.2% by mSWAT, respectively. The ratio of CAILS RR of MCH gel to ointment was 1.23 (CI: 0.97–1.55), which met the pre-specified criterion for non-inferiority. Time to response demonstrated superiority of MCH gel to ointment (p<0.012). No drug-related serious AEs were seen. Twenty percent (20%) of enrolled patients on gel and 17% on ointment withdrew due to drug-related skin irritation. No systemic absorption of the study medication was detected.
These results demonstrate the safety and efficacy of a novel 0.02% MCH gel in the treatment of MF patients.
Clinical Trial Registration
PMCID: PMC3662469  PMID: 23069814
3.  FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system 
Nucleic Acids Research  2010;39(Database issue):D111-D117.
FlyFactorSurvey ( is a database of DNA binding specificities for Drosophila transcription factors (TFs) primarily determined using the bacterial one-hybrid system. The database provides community access to over 400 recognition motifs and position weight matrices for over 200 TFs, including many unpublished motifs. Search tools and flat file downloads are provided to retrieve binding site information (as sequences, matrices and sequence logos) for individual TFs, groups of TFs or for all TFs with characterized binding specificities. Linked analysis tools allow users to identify motifs within our database that share similarity to a query matrix or to view the distribution of occurrences of an individual motif throughout the Drosophila genome. Together, this database and its associated tools provide computational and experimental biologists with resources to predict interactions between Drosophila TFs and target cis-regulatory sequences.
PMCID: PMC3013762  PMID: 21097781
4.  Activated Notch4 Inhibits Angiogenesis: Role of β1-Integrin Activation 
Molecular and Cellular Biology  2002;22(8):2830-2841.
Notch4 is a member of the Notch family of transmembrane receptors that is expressed primarily on endothelial cells. Activation of Notch in various cell systems has been shown to regulate cell fate decisions. The sprouting of endothelial cells from microvessels, or angiogenesis, involves the modulation of the endothelial cell phenotype. Based on the function of other Notch family members and the expression pattern of Notch4, we postulated that Notch4 activation would modulate angiogenesis. Using an in vitro endothelial-sprouting assay, we show that expression of constitutively active Notch4 in human dermal microvascular endothelial cells (HMEC-1) inhibits endothelial sprouting. We also show that activated Notch4 inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis in the chick chorioallantoic membrane in vivo. Activated Notch4 does not inhibit HMEC-1 proliferation or migration through fibrinogen. However, migration through collagen is inhibited. Our data show that Notch4 cells exhibit increased β1-integrin-mediated adhesion to collagen. HMEC-1 expressing activated Notch4 do not have increased surface expression of β1-integrins. Rather, we demonstrate that Notch4-expressing cells display β1-integrin in an active, high-affinity conformation. Furthermore, using function-activating β1-integrin antibodies, we demonstrate that activation of β1-integrins is sufficient to inhibit VEGF-induced endothelial sprouting in vitro and angiogenesis in vivo. Our findings suggest that constitutive Notch4 activation in endothelial cells inhibits angiogenesis in part by promoting β1-integrin-mediated adhesion to the underlying matrix.
PMCID: PMC133705  PMID: 11909975
5.  Increased Expression of Cyclin D2 during Multiple States of Growth Arrest in Primary and Established Cells 
Molecular and Cellular Biology  1998;18(6):3163-3172.
Cyclin D2 is a member of the family of D-type cyclins that is implicated in cell cycle regulation, differentiation, and oncogenic transformation. To better understand the role of this cyclin in the control of cell proliferation, cyclin D2 expression was monitored under various growth conditions in primary human and established murine fibroblasts. In different states of cellular growth arrest initiated by contact inhibition, serum starvation, or cellular senescence, marked increases (5- to 20-fold) were seen in the expression levels of cyclin D2 mRNA and protein. Indirect immunofluorescence studies showed that cyclin D2 protein localized to the nucleus in G0, suggesting a nuclear function for cyclin D2 in quiescent cells. Cyclin D2 was also found to be associated with the cyclin-dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest. Cyclin D2-CDK2 complexes increased in amounts but were inactive as histone H1 kinases in quiescent cells. Transient transfection and needle microinjection of cyclin D2 expression constructs demonstrated that overexpression of cyclin D2 protein efficiently inhibited cell cycle progression and DNA synthesis. These data suggest that in addition to a role in promoting cell cycle progression through phosphorylation of retinoblastoma family proteins in some cell systems, cyclin D2 may contribute to the induction and/or maintenance of a nonproliferative state, possibly through sequestration of the CDK2 catalytic subunit.
PMCID: PMC108898  PMID: 9584157

Results 1-5 (5)