MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation.

Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes.

Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma.

T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs.

Macrophage-secreted TGF-β contributes to fibroblast activation and ureteral stricture after ablation injury.

Iatrogenic injury to the healthy ureter during ureteroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-β-mediated scar formation is considered to underlie ureteral stricture, but the cellular sources of this cytokine and the sequelae preceding iatrogenic stricture formation are unknown. Using a swine model of ureteral injury with irreversible electroporation (IRE), we evaluated the cellular sources of TGF-β and scar formation at the site of injury and examined in vitro whether the effects of TGF-β could be attenuated by pirfenidone.

Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous cell carcinoma.

Organ transplant recipients (OTRs) on cyclosporine A (CSA) are prone to catastrophic cutaneous squamous cell carcinoma (SCC). Allograft-sparing, cancer-targeting systemic treatments are unavailable. We have shown increased risk for catastrophic SCC in OTRs via CSA-mediated induction of IL-22.

Pressure and stretch differentially affect proliferation of renal proximal tubular cells.

Renal obstruction is frequently found in adults and children. Mechanical stimuli, including pressure and stretch in the obstructed kidney, contribute to damage; animal models of obstruction are characterized by increased cellular proliferation. We were interested in the direct effects of pressure and stretch on renal tubular cell proliferation.

Linking the degree of virilization in females with congenital adrenal hyperplasia to genotype.

Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations.

Expression of Programmed Cell Death Ligand in Cutaneous Squamous Cell Carcinoma and Treatment of Locally Advanced Disease With Pembrolizumab.

Importance: Limited therapies are available in patients with inoperable locally advanced cutaneous squamous cell carcinoma (cSCC).

Objective: To determine the efficacy of programmed cell death 1 receptor (PD-1) inhibitors in locally advanced cSCC.

Design, Setting, And Participants: A single patient with locally advanced cSCC who declined surgery and radiotherapy underwent treatment with pembrolizumab, an anti-PD-1 antibody, at an academic dermatologic surgery section and cancer center.

Urinary continence outcomes following vaginoplasty in patients with congenital adrenal hyperplasia.

Background: Feminizing genitoplasty techniques have diversified to encompass the spectrum of atypical genitalia in 46,XX congenital adrenal hyperplasia (CAH) patients. However, long-term outcomes evaluating postoperative continence following complex vaginoplasty remain scarce.

Objective: The aim was to review our surgical experience and assess postoperative urinary continence outcomes in CAH patients following complex, primary vaginoplasty.

Interleukin-22 and Cyclosporine in Aggressive Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinomas (SCCs) account for up to 10,000 deaths annually in the United States. Most of the more than 700,000 SCCs diagnosed are cured by excision with clear margins; however, metastasis can occur despite seemingly adequate treatment in some cases. Immune-suppressed organ transplant recipients are 60 to 100 times more likely to develop SCC than immune-competent individuals.

Cyclosporine A immunosuppression drives catastrophic squamous cell carcinoma through IL-22.

Immune-suppressed organ transplant recipients (OTRs) can develop catastrophic squamous cell carcinoma (SCC), characterized by multiple primary tumors, extensive body surface area involvement, or metastases. There are currently no curative systemic therapies available. We previously showed that IL-22 enhances SCC proliferation.

Nerve Sparing Clitoroplasty is an Option for Adolescent and Adult Female Patients with Congenital Adrenal Hyperplasia and Clitoral Pain following Prior Clitoral Recession or Incomplete Reduction.

Purpose: In the past many female patients with congenital adrenal hyperplasia and atypical genitalia were surgically treated with clitoral recession or incomplete reduction of erectile bodies. We report the results of repeat clitoral surgery performed for clitoral pain or enlargement using a nerve sparing reduction clitoroplasty technique.

Materials And Methods: We identified 6 female patients with congenital adrenal hyperplasia who had undergone prior clitoral recession or incomplete reduction elsewhere.

CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking.

Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis.

Gene expression profiling of the leading edge of cutaneous squamous cell carcinoma: IL-24-driven MMP-7.

The precise mechanisms governing invasion at the leading edge of squamous cell carcinoma (SCC) and its subsequent metastasis are not fully understood. We aimed to define the cancer-related molecular changes that distinguish noninvasive tumor from invasive SCC. To this end, we combined laser capture microdissection with complementary DNA (cDNA) microarray analysis.

Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma.

The pathogenesis of BCC is associated with sonic hedgehog (SHH) signaling. Vismodegib, a smoothened inhibitor that targets this pathway, is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required.

An animal explant model for the study of human cutaneous squamous cell carcinoma.

We established a human tissue explant model to facilitate study of cutaneous squamous cell carcinoma. We accomplished this by implanting debulked SCC, from surgical discard, into nude rats. Human SCC remained viable and continued to proliferate for at least 4 weeks and showed evidence of neovascularization.

Increased Tc22 and Treg/CD8 ratio contribute to aggressive growth of transplant associated squamous cell carcinoma.

Immune suppressed organ transplant recipients suffer increased morbidity and mortality from primary cutaneous SCC. We studied tumor microenvironment in transplant-associated SCC (TSCC), immune-competent SCC and normal skin by IHC, IF and RT-PCR on surgical discard. We determined T cell polarization in TSCC and SCC by intracellular cytokine staining of T cell crawl outs from human skin explants.

Understanding dendritic cells and their role in cutaneous carcinoma and cancer immunotherapy.

Dendritic cells (DC) represent a diverse group of professional antigen-presenting cells that serve to link the innate and adaptive immune systems. Their capacity to initiate a robust and antigen-specific immune response has made them the ideal candidates for cancer immunotherapies. To date, the clinical impact of DC immunotherapy has been limited, which may, in part, be explained by the complex nature of DC biology.

CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma.

Objective: To characterize the presence of CD200 and CD200 receptor (CD200R) in the human cutaneous squamous cell carcinoma (SCC) microenvironment and to define a possible role for the CD200 axis in immune evasion by SCC.

Design: Gene expression in SCC vs normal skin was studied. Laser capture microdissection was used to determine differential expression of CD200 in normal skin vs actinic keratosis vs SCC in situ vs invasive SCC.

Langerhans cells from human cutaneous squamous cell carcinoma induce strong type 1 immunity.

Langerhans cells (LCs) are dendritic cells (DCs) localized to the epidermis. They should be the first antigen-presenting cells to encounter squamous cell carcinoma (SCC). The aim of this study was to investigate the ability of LCs isolated from human SCC to induce T-cell proliferation and polarization.

Multiphoton imaging and laser ablation of rodent spermatic cord nerves: potential treatment for patients with chronic orchialgia.

Purpose: Microsurgical denervation of the spermatic cord has been done to treat chronic orchialgia. However, identifying the site of spermatic cord nerves is not feasible with an operating microscope or robotic stereoscope. We used multiphoton microscopy, a novel laser imaging technology, to identify and selectively ablate spermatic cord nerves in the rat.

Mast cells are required for the development of renal fibrosis in the rodent unilateral ureteral obstruction model.

Mast cells are associated with inflammation and fibrosis. Whether they protect against or contribute to renal fibrosis is unclear. Based on our previous findings that mast cells can express and secrete active renin, and that angiotensin (ANG II) is profibrotic, we hypothesized that mast cells play a critical role in tubulointerstitial fibrosis.

Prostaglandin (PG)E2 exhibits antifibrotic activity in vocal fold fibroblasts.

Objectives/hypothesis: Prostaglandin (PG)E2 has been implicated in a variety of disease processes. It has been described as antifibrotic in the lower airway, yet scar-inducing in the skin. We seek to describe the effects of PGE2 on vocal fold fibroblasts and its interactions with transforming growth factor (TGF)-β1.

Cyclooxygenase-2 signaling in vocal fold fibroblasts.

Objectives/hypothesis: Inflammation and its role in a coordinated fibroplastic response, which disrupts the structure of the vocal folds following injury, is critical. Cyclooxygenase-2 (COX-2) is an important enzyme involved in both inflammation and fibrosis; in addition, it is a prime target for therapeutic intervention. We sought to study this pathway in vocal fold fibroblasts to provide a foundation for future interventional studies.