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// Amruta Phatak 1 , Mohammad Athar 2 , James A. Crowell 3 , David Leffel 4 , Brittney-Shea Herbert 1 , Allen E. Bale 5 and Levy Kopelovich 6 1 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA 2 Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA 3 NCI-DCTD-DTP, Bethesda, MD, USA 4 Department of Dermatology, Yale School of Medicine, New Haven, CT, USA 5 Department of Genetics, Yale School of Medicine, New Haven, CT, USA 6 Department of Medicine, Weill Cornell Medical College, New York, NY, USA Correspondence to: Levy Kopelovich, email: kopelovichl@gmail.com Allen E. Bale, email: allen.bale@yale.edu Keywords: Gorlin syndrome; basal cell carcinoma; patched; HH signaling; rapamycin Received: December 09, 2018 Accepted: January 11, 2019 Published: February 15, 2019 ABSTRACT Studies of dominantly heritable cancers enabled insights about tumor progression. BCNS is a dominantly inherited disorder that is characterized by developmental abnormalities and postnatal neoplasms, principally BCCs. We performed an exploratory gene expression profiling of primary cell cultures derived from clinically unaffected skin biopsies of BCNS gene-carriers ( PTCH1 +/- ) and normal individuals. PCA and HC of untreated keratinocytes or fibroblasts failed to clearly distinguish BCNS samples from controls. These results are presumably due to the common suppression of canonical HH signaling in vitro . We then used a relaxed threshold (p-value

BACKGROUND Angiosarcomas are rare tumors. Based on a complete response observed in a patient with angiosarcoma of the scalp treated with paclitaxel in a Phase II trial, the authors treated a cohort of patients with angiosarcoma of the scalp or face with paclitaxel as single agent. METHODS The authors identified nine patients with angiosarcoma of the scalp or face treated at Memorial Sloan-Kettering Cancer Center with paclitaxel between January 1992 and December 1998. Various paclitaxel schedules were used over 1, 3, and 24 hours. RESULTS Of the 9 patients, 8 had major responses (4 partial responses and 4 clinical complete responses) and 1 had a minor response, for a major response rate of 89%. The median duration of response was 5 months (range, 2–13 months). Neutropenia and peripheral neuropathy were the most frequent dose-limiting toxicities. No deaths were attributed to therapy. CONCLUSIONS Paclitaxel as a single agent has substantial activity against angiosarcoma of the scalp or face, even in patients previously treated with chemotherapy or radiation therapy. Further investigation is warranted to define the optimal treatment dose and schedule. Cancer 1999;86:2034–7. © 1999 American Cancer Society.

Background. Tissue-engineered products are usually composed of living cells and their supporting matrices that have been grown in vitro, using a combination of engineering and life sciences principles. Apligraf is a bilayered product composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I bovine collagen. Objective. To evaluate in a prospective, multicentered open study, the effects of tissue therapy with a tissue-engineered skin (Apligraf) with partial or full-thickness excisional wounds. Methods. One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery, usually for skin cancer, and patients were followed for up to one year. Results. The safety results were impressive, with no clinical or laboratory evidence of rejection. Clinically, graft persistence was good to excellent in 77 of 105 (73.3%) of patients at one week, falling to 56.6% and 53.6% at two weeks and one month respectively. Conclusion. To date, this is the largest experience with a tissue-engineered skin product in acute wounds, and this study suggests that tissue therapy may be safe and useful.