Superficial x-ray in the treatment of basal and squamous cell carcinomas: a viable option in select patients.

BACKGROUND: Effective nonsurgical modalities are limited in the treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). OBJECTIVE: We sought to evaluate the efficacy and viability of superficial x-ray therapy in the treatment of BCC and SCC in an outpatient setting. METHODS: A retrospective analysis was performed on 1715 histologically confirmed primary cutaneous BCC and SCC treated with superficial x-ray therapy at Dermatology Associates of Tallahassee in Florida between 2000 and 2010. RESULTS: Of the 1715 tumors reviewed during this period, 712 were histologically proven BCC (631 nodular and 81 superficial), 994 were SCC (861 SCC in situ and 133 invasive SCC), and 9 displayed distinct features of both BCC and SCC in the same biopsy specimen. Kaplan-Meier estimates (with 95% confidence intervals) of cumulative recurrence rates of all tumors at 2 and 5 years were 1.9% (1%-2.7%) and 5.0% (3.2%-6.7%), respectively; of BCC at 2 and 5 years were 2% (0.8%-3.3%) and 4.2% (1.9%-6.4%), respectively; and of all SCC at 2 and 5 years were 1.8% (0.8%-2.8%) and 5.8% (2.9%-8.7%), respectively. Tumors on male patients and those with a diameter greater than 2 cm were associated with a statistically significant increase in recurrence likelihood. LIMITATIONS: This study represents only patients treated in 1 dermatology office in North Florida and may not be representative of the general patient population. CONCLUSIONS: Superficial x-ray therapy remains a viable nonsurgical option for the treatment of primary BCC and SCC in patients where surgical intervention is declined, unadvisable, or potentially associated with significant cosmetic or functional limitations.

gp340 promotes transcytosis of human immunodeficiency virus type 1 in genital tract-derived cell lines and primary endocervical tissue.

The human scavenger receptor gp340 has been identified as a binding protein for the human immunodeficiency virus type 1 (HIV-1) envelope that is expressed on the cell surface of female genital tract epithelial cells. This interaction allows such epithelial cells to efficiently transmit infective virus to susceptible targets and maintain viral infectivity for several days. Within the context of vaginal transmission, HIV must first traverse a normally protective mucosa containing a cell barrier to reach the underlying T cells and dendritic cells, which propagate and spread the infection. The mechanism by which HIV-1 can bypass an otherwise healthy cellular barrier remains an important area of study. Here, we demonstrate that genital tract-derived cell lines and primary human endocervical tissue can support direct transcytosis of cell-free virus from the apical to basolateral surfaces. Further, this transport of virus can be blocked through the addition of antibodies or peptides that directly block the interaction of gp340 with the HIV-1 envelope, if added prior to viral pulsing on the apical side of the cell or tissue barrier. Our data support a role for the previously described heparan sulfate moieties in mediating this transcytosis but add gp340 as an important facilitator of HIV-1 transcytosis across genital tract tissue. This study demonstrates that HIV-1 actively traverses the protective barriers of the human genital tract and presents a second mechanism whereby gp340 can promote heterosexual transmission.

HIV envelope binding by macrophage-expressed gp340 promotes HIV-1 infection.

The scavenger receptor cysteine-rich protein gp340 functions as part of the host innate immune defense system at mucosal surfaces. In the genital tract, its expression by cervical and vaginal epithelial cells promotes HIV trans-infection and may play a role in sexual transmission. Gp340 is an alternatively spliced product of the deleted in malignant brain tumors 1 (DMBT1) gene. In addition to its innate immune system activity, DMBT1 demonstrates instability in multiple types of cancer and plays a role in epithelial cell differentiation. We demonstrate that monocyte-derived macrophages express gp340 and that HIV-1 infection is decreased when envelope cannot bind it. Inhibition of infection occurred at the level of fusion of M-, T-, and dual-tropic envelopes. Additional HIV-1 envelope binding molecules, such as dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), mannose-binding lectin, and heparan sulfate, enhance the efficiency of infection of the cells that express them by increasing the local concentration of infectious virus. Our data suggest that gp340, which is expressed by macrophages in vivo, may function to enhance infection in much the same manner. Its expression on tissue macrophages and epithelial cells suggests important new opportunities for HIV-1 pathogenesis investigation and therapy.

Repair of the philtrum: an illustrative case series.

BACKGROUND: Distortion of the philtrum, which lends considerable symmetry to the midface, leads to a poor esthetic outcome. OBJECTIVE: This case series describes reconstructive approaches to six philtral defects after Mohs micrographic surgery. Reconstructive approaches including advancement flaps, full-thickness skin grafts, and second-intention healing are illustrated. Postoperative complications included graft hypertrophy, irregularity of the graft surface, graft color mismatch, tenderness, and slight eclabium, which improved with dermabrasion or intralesional triamcinolone. CONCLUSION: The reasonable success of full-thickness skin grafts demonstrated here provides an additional approach to philtral repairs, especially when combined with traditional advancement flaps.

gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmission.

During sexual transmission of HIV in women, the first cells likely to be infected are submucosal CD4(+) T cells and dendritic cells of the lower genital tract. HIV is segregated from these target cells by an epithelial cell layer that can be bypassed even when healthy and intact. To understand how HIV penetrates this barrier, we identified a host protein, gp340, that is expressed on genital epithelium and binds the HIV envelope via a specific protein-protein interaction. This binding allows otherwise subinfectious amounts of HIV to efficiently infect target cells and allows this infection to occur over a longer period of time after binding. Our findings suggest a mechanism of viral entry during heterosexual transmission where HIV is bound to intact genital epithelia, which then promotes the initial events of infection. Understanding this step in the initiation of infection will allow for the development of tools and methods for blocking HIV transmission.