ABSTRACT
Depth of invasion, a quantifier of vertical growth, is a major cutaneous melanoma staging factor. Stromal penetrance requires pericellular proteolysis regulated by the serine protease and matrix metalloproteinase cascades. The serine protease inhibitor SERPINE1, a poor prognosis biomarker in various cancers, promotes tumor progression likely by titrating the extent and local of plasmin-initiated matrix remodelling. SERPINE1 in human melanoma was assessed using tissue arrays that included primary/metastatic tumors and normal skin. SERPINE1 was basal layer-restricted in the normal epidermis. SERPINE1 immunoreactivity was evident in 27/28 primary (96%) and 24/26 metastatic tumors (92%); cutaneous metastases (80%) had significantly elevated SERPINE1 levels compared with low signals characteristic of lymph node lesions. Moderate SERPINE1 expression was a general finding in primary melanoma, whereas reduced or increased SERPINE1 immunolocalization typified metastatic deposits. The amplitude of SERPINE1 expression may impact melanoma site-specific dissemination, with cutaneous metastases representing a high-SERPINE1 tumor subtype.
Subject(s)
Biomarkers, Tumor/metabolism , Melanoma/metabolism , Melanoma/secondary , Plasminogen Activator Inhibitor 1/metabolism , Skin Neoplasms/metabolism , Epidermis/metabolism , Humans , Immunohistochemistry , Lymphatic Metastasis , Skin Neoplasms/pathology , Skin Neoplasms/secondaryABSTRACT
Acanthosis nigricans is a dermatosis characterized by thickened, hyperpigmented plaques, typically of the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize acanthosis nigricans; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of acanthosis nigricans and its clinical implications and management.
Subject(s)
Acanthosis Nigricans , Acanthosis Nigricans/diagnosis , Acanthosis Nigricans/drug therapy , Acanthosis Nigricans/epidemiology , Acanthosis Nigricans/etiology , Acanthosis Nigricans/pathology , Acanthosis Nigricans/radiotherapy , Adolescent , Calcitriol/analogs & derivatives , Calcitriol/pharmacology , Child , Disease Susceptibility , Ethnicity/genetics , Female , Fish Oils/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Insulin-Like Growth Factor I/physiology , Low-Level Light Therapy , Male , Neoplasms/complications , Prevalence , Receptor Protein-Tyrosine Kinases/physiology , Retinoids/therapeutic useABSTRACT
Onychomatricoma is a rare nail tumor with a distinctive architecture. Proximally, there are serum-filled invaginations of nail matrix epithelium into the stroma, and distally, dermal protrusions perforate the nail plate. Because other matrical tumors of follicular and odontogenic origin express nuclear beta-catenin, we examined the expression of cadherin/catenin proteins in this onychomatricoma case. The patient presented with a toenail yellow streak, and the biopsy revealed an onychomatricoma. E-cadherin and beta-catenin were at the cell membrane in the epithelial invaginations. P-cadherin was restricted to basal cells. In contrast to other matrical tumors, nuclear beta-catenin was not present. These results suggest that onychomatricoma may lack the transcriptional activating role of beta-catenin that characterizes follicular and odontogenic matrical tumors. This is the first report on the expression of cadherin/ catenin cell-cell adhesion proteins in this rare nail tumor.
Subject(s)
Cadherins/metabolism , Nail Diseases/pathology , Nails/pathology , Skin Neoplasms/pathology , beta Catenin/metabolism , Biomarkers, Tumor/metabolism , Female , Fluorescent Antibody Technique, Direct , Humans , Immunoenzyme Techniques , Middle AgedABSTRACT
Pharmaceutical companies and their representatives attempt to influence the practice of medicine by giving gifts. Gifts, even those of trivial monetary value, impart a sense of obligation that conflicts with the provider's primary responsibility to the patient. Providers are less likely than their patients and peers to believe that gifts change their own prescribing habits, making them vulnerable to manipulation by industry. Providers who interact with drug reps must exercise caution to prevent compromise of the patient-physician relationship.
Subject(s)
Conflict of Interest , Drug Industry/ethics , Ethics, Medical , Gift Giving/ethics , Attitude of Health Personnel , Commerce/ethics , Humans , Interprofessional Relations/ethics , Physician-Patient RelationsABSTRACT
Polyglycolic acid (PGA) is commonly used as a scaffold for tissue engineering. Recent studies utilized PGA as a scaffold for vascular tissue engineering using bovine and porcine smooth muscle cells (SMCs). In engineered vessels, the SMCs displayed high rates of mitosis and dedifferentiation in areas where PGA fragments were present. We hypothesized that PGA breakdown products, sequestered within a SMC vessel at the conclusion of culture, led to increased proliferation and dedifferentiation of vascular SMCs. To test this hypothesis, the current study assessed possible means by which PGA breakdown products could lead to changes in SMC phenotype. SMCs grown in high concentrations of PGA breakdown products showed, by Western blotting, decreased expression of calponin, a marker for SMC differentiation. The same was true for SMCs grown in glycolic acid (GA), which also showed decreased expression of proliferating cell nuclear antigen (PCNA), a marker for SMC proliferation. In contrast, cells grown in varying amounts of NaCl or HCl showed little change in differentiation. We conclude that, independent of acidity or osmolality, plausible products of PGA degradation appear to induce dedifferentiation of porcine SMCs in vitro. Because of dedifferentiation and decreased mitosis, commercially available PGA may not represent an optimal scaffold for vascular tissue engineering.