Faculty Bibliography

BACKGROUND:Submissions to medical and scientific journals are vetted by peer review, but peer review itself has been poorly studied until recently. One concern has been that manuscript reviews in which the reviewer is unblinded (e.g. knows author identity) may be biased, with an increased likelihood that the evaluation will not be strictly on scientific merits. OBJECTIVES/OBJECTIVE:The purpose of this study was to compare the outcomes of blinded and unblinded reviews of manuscripts submitted to a single dermatology journal via a randomized multi-rater study. MATERIALS AND METHODS/METHODS:Forty manuscripts submitted to the journal Dermatologic Surgery were assessed by four reviewers, two of whom were randomly selected to be blinded and two unblinded regarding the identities of the manuscripts' authors. The primary outcome measure was the initial score assigned to each manuscript by each reviewer characterized on an ordinal scale of 1-3, with 1 = accept; 2 = revise (i.e. minor or major revisions) and 3 = reject. Subgroup analysis compared the primary outcome measure across manuscripts from U.S. corresponding authors and foreign corresponding authors. The secondary outcome measure was word count of the narrative portion (i.e. comments to editor and comments to authors) of the reviewer forms. RESULTS:There was no significant difference between the scores given to manuscripts by unblinded reviewers and blinded reviewers, both for manuscripts from the U.S. and for foreign submissions. There was also no difference in word count between unblinded and blinded reviews. CONCLUSIONS:It seems, at least in the case of one dermatology journal, that blinding during peer review does not appear to affect the disposition of the manuscript. To the extent that review word count is a proxy for review quality, there appears to be no quality difference associated with blinding.

DNA-damaging agents can induce premature senescence in cancer cells, which contributes to the static effects of cancer. However, senescent cancer cells may re-enter the cell cycle and lead to tumor relapse. Understanding the mechanisms that control the viability of senescent cells may be helpful in eliminating these cells before they can regrow. Treating human squamous cell carcinoma (SCC) cells with the anti-cancer compounds, resveratrol and doxorubicin, triggered p53-independent premature senescence by invoking oxidative stress-mediated DNA damage. This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1. SIRT1 phosphorylation caused concomitant increases in p65/RelA NF-κB acetylation and the expression of an anti-apoptotic Bfl-1/A1. SIRT1 physically interacts with the mTOR-Raptor complex, and a single amino acid substitution in the TOS (TOR signaling) motif in the SIRT1 prevented Ser-47 phosphorylation and Bfl-1/A1 induction. The pharmacologic and genetic inhibition of mTOR, unphosphorylatable S47A, or F474A TOS mutants restored SIRT1 deacetylase activity, blocked Bfl-1/A1 induction, and sensitized prematurely senescent SCC cells for apoptosis. We further show that the treatment of UVB-induced SCCs with doxorubicin transiently stabilized tumor growth but was followed by tumor regrowth upon drug removal in p53(+/-)/SKH-1 mice. The subsequent treatment of stabilized SCCs with rapamycin decreased tumor size and induced caspase-3 activation. These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent SCC cells via Bfl-1/A1 in the absence of functional p53.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue tumor that most commonly presents on the trunk and extremities of adults. It is characterized by low metastatic potential and a favorable prognosis, but extensive subclinical growth can contribute to a high risk of local recurrence. Surgical excision is the first-line treatment, using Mohs micrographic surgery or wide local excision with careful evaluation of the peripheral and deep surgical margins. Adjuvant therapy may be beneficial in patients with unresectable, recurrent, or metastatic DFSP. Historically, adjuvant radiation therapy has been used to reduce the risk of local recurrence when residual disease is present after surgery. The advent of targeted molecular therapies, such as the selective tyrosine kinase inhibitor, imatinib mesylate, has provided new effective and safe options for adjuvant treatment of DFSP.

Sunscreens are an important aspect of photoprotection. Their efficacy in reducing photocarcinogenesis and photoaging is widely documented. Although there are concerns regarding long-term sunscreen safety, the advantages of sunscreen use are far more compelling. In addition, novel technologies and ultraviolet filters are improving the aesthetics and efficacy of modern products.

Surgical treatment remains the standard of care for nonmelanoma skin cancer and is successful for the vast majority of patients with these tumors. The treatment of patients with metastatic or unresectable nonmelanoma skin cancer, however, has until recently been based solely on traditional methods of chemotherapy and radiation. However, these methods have high rates of treatment failure, morbidity, and mortality, and alternative treatment modalities for patients with aggressive or advanced disease are needed. As in other areas of cancer therapeutics, recent research elucidating the molecular basis of cancer development, and the subsequent arrival of targeted molecular inhibitors for cancer therapy, have been met with much excitement. In this review, we seek to illuminate recent developments and future possibilities in the use of targeted molecular inhibitors for treatment of advanced squamous cell carcinoma, basal cell carcinoma, and dermatofibrosarcoma protuberans.

Laminar optical tomography (LOT) is a recently developed technique for depth-resolved in vivo imaging of absorption and fluorescence contrast. Until now, LOT has been implemented in a benchtop configuration, limiting accessibility to tissues and restricting imaging applications. Here we report on LOT implemented through an articulating arm and a fiber optic image bundle allowing flexible imaging for a range of clinical applications. We quantify the performance of these two implementations by imaging a tissue mimicking phantom.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade soft-tissue malignancy associated with a high risk for local recurrence and widespread subclinical extension. Imatinib, a selective tyrosine kinase inhibitor, has been a beneficial adjuvant therapy in patients with unresectable, recurrent, or metastatic DFSP. Because of its characteristic infiltrative growth, effective surgical excision of DFSP may be limited by the risk for disfigurement or functional impairment. In recent cases, neoadjuvant imatinib mesylate therapy has been shown to reduce preoperative tumor size and lessen surgical morbidity associated with the removal of residual DFSP. Use of neoadjuvant imatinib before surgery, however, requires appropriate patient selection and careful weighing of the potential risks and benefits of this treatment.