Genital basal cell carcinoma, a different pathogenesis from sun-exposed basal cell carcinoma? A case-control study of 30 cases.

BACKGROUND: Genital basal cell carcinoma (BCC) accounts for <1% of all BCCs. We aimed to elucidate the pathogenesis of genital BCC. METHODS: We retrospectively evaluated cases of pathologically diagnosed genital BCC between 1990 and 2016 in an Asian tertiary referral center. The control group was composed of consecutive cases, from 2016, of BCCs occurring in sun-exposed areas. Presence of human papillomavirus (HPV) was evaluated by polymerase chain reaction (PCR). Immunohistochemical p16 and p53 staining was performed and analyzed. RESULTS: We found 33 genital BCCs (33/1837, 1.8%) over 26 years. The mean follow-up duration was 30.0 ± 33.2 months. Genital BCCs had a larger size (14.05 vs 8.92 mm, P = 0.014), more common presence of ulcers (61.3% vs 32.0%, P = 0.035), shorter epidermal p53 clone (0.33 vs 1.20 mm, P = 0.007), and high p53 expression levels. Most cases (29/30, 96.7%) showed negative or faint spotty p16 staining. Patient age, tumor depth, presence of pigment, or histology subtype did not differ significantly. Thirty genital BCCs were negative for HPV. CONCLUSIONS: HPV infection is mostly likely not involved in genital BCC pathogenesis. A greater level of p53 expression in genital BCCs implicates pathways other than ultraviolet (UV)-specific p53 mutations in their pathogenesis.

The pathological spectrum and clinical correlation of pigmented purpuric dermatosis-A retrospective review of 107 cases.

BACKGROUND: Various pathological findings have been reported in pigmented purpuric dermatosis, but their clinical significance remains unclear. METHODS: We retrospectively reviewed demographics, clinical presentations, pathological patterns and concurrent systemic diseases among biopsy-confirmed cases of pigmented purpuric dermatosis. RESULTS: A total of 107 cases were ascertained. Five major pathological patterns were identified: lichenoid (45/107, 42.1%), perivascular (40/107, 37.4%), interface (11/107, 10.3%), spongiotic (7/107, 6.5%) and granulomatous (4/107, 3.7%). Lymphocytic vasculitis was present in 17 patients (15.9%), and Langerhans cell microabscess was seen in 4 (3.7%). Nine patients had partial features mimicking mycosis fungoides but none were confirmed. The lichenoid, perivascular and spongiotic patterns correlated to lichen aureus, Schamberg and eczematoid clinical variants, respectively. The interface pattern was associated with a higher risk of coincident autoimmune diseases (18.2%, P = .0280) and gout (27.3%, P = .0180). CONCLUSIONS: This study described the wide pathological spectrum of pigmented purpuric dermatosis among Asians. Physicians should be aware about the clinical and pathological variations to facilitate diagnosis.

Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation.

The human S100 calcium-binding protein A11 (S100A11) is a member of the S100 protein family. Once S100A11 proteins bind to calcium ions at EF-hand motifs, S100A11 changes its conformation, promoting interaction with target proteins. The receptor for advanced glycation end products (RAGE) consists of three extracellular domains, including the V domain, C1 domain, and C2 domain. In this case, the V domain is the target for mutant S100A11 (mS100A11) binding. RAGE binds to the ligands, resulting in cell proliferation, cell growth, and several signal transduction cascades. We used NMR and fluorescence spectroscopy to demonstrate the interactions between mS100A11and RAGE V domain. The tranilast molecule is a drug used for treating allergic disorders. We discovered that the RAGE V domain and tranilast would interact with mS100A11 by using (1)H-(15)N HSQC NMR titrations. According to the results, we obtained two binary complex models from the HADDOCK program, S100A11-RAGE V domain and S100A11-tranilast, respectively. We overlapped two binary complex models with the same orientation of S100A11 homodimer and demonstrated that tranilast would block the binding site between S100A11 and the RAGE V domain. We further utilized a water-soluble tetrazolium-1 assay to confirm this result. We think that the results will be potentially useful in the development of new anti-cancer drugs.

Kinetic and thermodynamic analysis of Candida antarctica lipase B-catalyzed alcoholytic resolution of (R,S)-ß-butyrolactone in organic solvents.

Optically pure (R)-ß-butyrolactone as an important chiral building block in the syntheses of various biologically active compounds and biodegradable polymers was prepared from (R,S)-ß-butyrolactone through kinetic resolution. Candida antarctica lipase B (CALB) with a high enantiomeric ratio of 198 enantioselectively catalyzed the ring opening of the racemate with methanol in methyl tert-butyl ether at 45 °C and yielded the remaining (R)-ß-butyrolactone. A detailed kinetic analysis indicated that methanol and (R)- and (S)-methyl ester all acted as competitive inhibitors for the enzyme. Comparisons of the theoretical and experimental conversions for both enantiomers were further made and elucidated. The thermodynamic analysis implied the enantiomer discrimination for the transition states of both enantiomers to be entropy-driven in the temperature range investigated. Moreover, preliminary results from the lipase reusability, feed-batch operation, and remaining substrate recovery were addressed.