Yuko Higashi

Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: Evidence for growth suppression by inhibiting COX-2 expression

Cyclooxygenase (COX)‐2 is one of the rate‐limiting enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Recent studies have shown enhanced expression of COX‐2 in cancer cells of several tissues. We investigated the expression of COX‐2 and prostaglandin (PG) E   2 production in two human skin epidermal cancer cell lines: cutaneous squamous cell carcinoma, HSC‐5, and eccrine carcinoma, EcCa. Both COX‐2 expression and PGE   2 production were significantly enhanced in cancer cell lines compared with the non‐tumorigenic human keratinocyte cell line, HaCaT. In order to determine the role of COX‐2 in the proliferation of HSC‐5 and EcCa, the growth of untreated cells and cells transfected with COX‐2 antisense oligonucleotide was compared using the MTT assay. Transfection with the antisense oligonucleotide suppressed COX‐2 protein expression and significantly inhibited cell growth. The effect of a selective inhibitor of COX‐2, NS398, was compared with the effect of the antisense oligonucleotide in order to see whether COX‐2 expression and prostaglandins have selective effects on cell growth. COX‐2 expression was unchanged by NS398 treatment, whereas NS398 inhibited cell growth to a certain extent. The degree of growth inhibition was greater with the antisense oligonucleotide than with NS398. Our findings indicate that COX‐2 protein expression is enhanced in skin epidermal cancer cells and that COX‐2 plays a pivotal role in regulating cell growth. Furthermore, inhibition of COX‐2 expression had a more significant effect on growth suppression than inhibition of COX‐2 catalytic activity, suggesting the existence of two different signal pathways via COX‐2 in regulating cell growth. Int. J. Cancer 86:667–671, 2000.

Scleroderma en Coup de Sabre with Central Nervous System Involvement

We describe a patient with scleroderma en coup de sabre and central nervous system symptoms. She presented with a linear scleroderma on her left paramedian forehead and scalp and suffered from headaches and dizziness. Axial T2‐weighted MRI showed a 1 cm, high intense signal abnormality in the medial aspect of the left frontal lobe.

Inhibitory effects of 9-cis-retinoic acid and pyrrolidinedithiocarbamate on cyclooxygenase (COX)-2 expression and cell growth in human skin squamous carcinoma cells

We recently demonstrated that the constitutive expression of cyclooxygenase (COX)-2 protein and prostaglandin E(2) (PGE(2)) biosynthesis were significantly enhanced in human skin epidermal cancer cells and that cancer cell growth was effectively inhibited by the suppression of COX-2 expression by transfection with COX-2 antisense oligonucleotide. The purpose of this study was to search for agents which suppress COX-2 expression and examine their effects on cell growth. Since retinoids and antioxidants have been used for chemoprevention of cancers in several tissues, the effects of these agents on COX-2 expression and PGE(2) biosynthesis in skin squamous carcinoma cells were investigated. Treatment with a retinoid (9-cis-retinoic acid (9-cis-RA)) or an antioxidant (pyrrolidinedithiocarbamate (PDTC)) suppressed COX-2 expression and PGE(2) biosynthesis in a concentration-dependent manner. Cell growth was significantly inhibited by 9-cis-RA and PDTC. These results suggest that 9-cis-RA and PDTC may be useful in preventing skin cancer growth and that COX-2 is involved in their protective effects on skin carcinogenesis.

Eosinophilic pustular folliculitis induced by carbamazepine

A 58-year-old man had taken a combination of acetaminophen and carbamazepine for headache and fever. Over the next 2 days, he experienced stomatitis and edematous erythema with papules and pustules on his face, neck, trunk, and extremities. This was diagnosed as a “drug eruption.” His stomatitis improved but his skin eruption persisted. Two months later, examination revealed edema of Eosinophilic pustular folliculitis induced by carbamazepine

9-Cis-retinoic acid exhibits antifibrotic activity via the induction of cyclooxygenase-2 expression and prostaglandin E2 production in scleroderma fibroblasts.

Background.  The pathogenesis of scleroderma (SSc) is not fully understood, and there is no effective treatment for this chronic disease. Retinoic acid (RA) can modulate connective tissue metabolism, exhibit antifibrotic activity and improve the clinical symptoms of patients with SSc. However, the mechanisms by which RA elicits its antifibrotic actions remain to be determined.

Bidens pilosa suppresses interleukin-1β-induced cyclooxygenase-2 expression through the inhibition of mitogen activated protein kinases phosphorylation in normal human dermal fibroblasts

Bidens pilosa (BP) Linn. var. radiata is a plant used in traditional folk medicine. It is clinically effective in various diseases; the pathogenesis of most of these involves cyclooxygenase (COX)‐2. To investigate the mechanism on which the clinical effectiveness of BP is based, we examined its effects on COX‐2 expression and its major product, prostaglandin (PG)E2, under conditions of inflammation. We induced inflammation in normal human dermal fibroblasts with interleukin (IL)‐1β and examined the effects of BP on COX‐2 expression and PGE2 production using Western blotting and competitive enzyme immunoassay, respectively. The functional involvements of mitogen activated protein kinases (MAPK) ERK1/2, p38, and JNK in COX‐2 expression were also examined by Western blotting. IL‐1β‐induced COX‐2 expression was regulated by MAPK pathways, especially by p38. BP inhibited the phosphorylation of MAPKs, COX‐2 expression, and subsequent PGE2 production. The physiological activities and clinical effectiveness of BP observed under diverse conditions may be partly attributable to its ability to inhibit MAPK, mainly p38, activity, COX‐2 expression, and subsequent PGE2 production.

Multicentric castleman disease with cutaneous manifestations : Report of 2 cases and comparison with systemic plasmacytosis

We report 2 patients with multicentric Castleman disease. Both presented with multiple, indurated, hyperpigmented plaques, generalized lymphadenopathy and polyclonal hypergammaglobulinemia. Biopsy specimens showed infiltration of mature plasma cells and lymphocytes in the dermis and lymph nodes. Skin specimens were negative for human herpesvirus 8, latent nuclear antigen 1 and Epstein-Barr virus by in situ hybridization. PCR disclosed clonal T-cell receptor gene rearrangement in the bone marrow cells of 1 patient. We discuss the possible relationship between multicentric Castleman disease and systemic plasmacytosis as well as plasma cell proliferation.

Evaluation of a newly‐developed immunochromatography strip test for diagnosing dermatophytosis

Background  Traditionally, dermatophytosis, a common disease affecting millions of people world‐wide, has been diagnosed by direct microscopy and fungal culture. The immunochromatography (ICG) strip test was recently developed.

Granulomas induced by subcutaneous injection of leuprorelin acetate

Leuprorelin acetate, a chemotherapeutic agent used to treat prostate cancer, is a synthetic luteinizing hormone‐releasing hormone (LHRH) agonist. We report a 75‐year‐old man who presented with several large subcutaneous nodules at the site of leuprorelin acetate injections for his prostatic cancer. A biopsy of the nodules disclosed epithelioid granulomatous inflammation and resulted in a diagnosis of drug‐induced granulomatous reaction to leuprorelin acetate.

A Case of Sarcoidosis Involving the Tongue

Sarcoidosis is a systemic granulomatous disorder which commonly affects the skin. Involvement of the tongue is rare; a review of the previous literature over the last 30 years revealed only six cases of sarcoidosis affecting the tongue. We studied a case of sarcoidosis involving the tongue in a 32‐year‐old Japanese woman with characteristic clinical and pathological findings. She visited our department with a complaint of a tongue lesion of which she had been aware for a month. A diagnosis of sarcoidosis was made for the lesion by clinical and pathological examinations. Oral involvement by sarcoidosis is rare, however this disorder should be considered as a possible cause of intraoral granulomatous lesions.