Hsien-Ching Chiu

Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction

Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells.

Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 Cases

OBJECTIVE To investigate the clinical and pathologic features of patients with drug reaction with eosinophilia and systemic symptoms (DRESS) in Taiwan. DESIGN Case series and retrospective analysis. SETTING A medical referral center in Northern Taiwan. PATIENTS Sixty cases of DRESS occurring from June 1998 to May 2008. MAIN OUTCOME MEASURES Clinical characteristics for specific drugs and important prognostic factors in DRESS. RESULTS Patients ranged in age from 6 to 90 years (mean age, 51 years). The female to male ratio was 1.3 to 1. The most common culprit drugs were allopurinol, phenytoin, and dapsone. Exanthematous eruption was the most common skin manifestation, but purpurae and blisters were also observed. Hepatic (80%), renal (40%), and pulmonary (33%) involvement were also common. The overall mortality rate was 10%. Allopurinol-induced DRESS was characterized by preceding chronic renal insufficiency and frequent renal involvement. Pancytopenia indicated a poor prognosis. CONCLUSIONS Drug reaction with eosinophilia and systemic symptoms has a variable clinical presentation, and its definition requires clarification. It may be a heterogeneous syndrome with some particular patterns related to different drugs. Early diagnosis and prompt discontinuation of offending drug regimens are essential.

Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency

Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using 3H-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. We also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells. Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination. Supportive of this finding, we found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.

Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: A retrospective cohort study from Taiwan

BACKGROUND The development of autoimmune sequelae is one of the characteristic features of drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome; however, the incidence of sequelae and prognosis of patients with DRESS are unknown. OBJECTIVE We sought to investigate the incidence of sequelae, including less well-known sequelae, and long-term prognosis in patients with DRESS/drug-induced hypersensitivity syndrome. METHODS A retrospective cohort study was conducted at a medical center in northern Taiwan using a DRESS/drug-induced hypersensitivity syndrome database. Patients who were followed up for at least 1 year were included in the study. RESULTS Nine patients died before interview, whereas 43 patients completed a specially designed questionnaire. The overall cumulative incidence of long-term sequelae was 11.5% (6 of 52 patients). Four patients developed autoimmune diseases, specifically Graves disease (n = 2), type 1 diabetes mellitus (n = 1), and autoimmune hemolytic anemia (n = 1). Alopecia areata was also noted in 1 of the 2 patients with Graves disease. The other 2 patients developed renal failure after visceral involvement and required lifetime hemodialysis. LIMITATIONS Our study included a small number of patients. Further, viral studies were not performed. CONCLUSION The sequelae of DRESS can be divided into 2 major types that appear to occur in different age groups: young patients tend to develop autoimmune diseases, whereas elderly patients are more vulnerable to end-organ failure.

Self-assembly of dermal papilla cells into inductive spheroidal microtissues on poly(ethylene-co-vinyl alcohol) membranes for hair follicle regeneration

Self-aggregation is key to hair follicle (HF) induction ability of dermal papilla (DP) cells and neogenesis of HF can be achieved by transplanting DP microtissues. However, there is currently lack of a suitable system that allows efficient production of DP microtissues and analysis of DP self-aggregation in vitro. We demonstrate that, at a higher seeding cell density, poly(ethylene-co-vinyl alcohol) (EVAL) membranes facilitate DP self-assembly into many compact spheroidal microtissues that are able to induce new HFs. This self-assembling process is associated with an enhanced cell movement and a declined cell-substrate adhesivity on EVAL. A compromised cell growth is also revealed on EVAL. On the contrary, a more adherent surface allows faster cell expansion but maintains DP cells in a flat morphology. Dynamically, cell migration, intercellular collision and intercellular adhesion contribute to DP microtissue formation on EVAL. Our results suggest that, for large-scale production of DP microtissues for HF regeneration, an adhesive surface is needed for quick cell expansion and a biomaterial with a lower adhesivity is required for self-aggregation. In addition, this system can be a model for investigation of DP self-aggregation in vitro.

Transformation between Kaposiform Hemangioendothelioma and Tufted Angioma

Kaposiform hemangioendothelioma and tufted angioma are viewed as two separate disease entities in the current classification of vascular tumors. However, the concurrence of features of both vascular tumors in the same specimen of some patients raises the question whether these tumors exist on a continuum. Herein, we report a dynamic transformation between both tumors within a single patient, which suggests they are two variants of the same vascular tumor.

Hydroa vacciniforme-like primary cutaneous CD8-positive T-cell lymphoma

An 8‐year‐old Taiwanese girl had a 6‐month history of a relapsing papulovesicular eruption on her face that resembled hydroa vacciniforme (HV). Histologically, there was a dense infiltration of large atypical lymphocytic cells expressing CD8. TCR‐γ gene rearrangement study revealed a monoclonal band present in the DNA extracted from the specimen. A diagnosis of CD8+ cutaneous T‐cell lymphoma (CTCL) was made. The patient was treated with Chinese herbal drugs and her skin lesions waxed and waned. At this writing, 11 months after establishment of the diagnosis, the skin lesions have been limited to the facial area and no definite evidence of systemic involvement is noted. To our knowledge, this is the first case of CD8+ primary CTCL with clinical features resembling HV.

Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel.

Docetaxel (Taxotere®), a semisynthetic taxoid, acts as an antimicrotubule agent and is considered to have great potential in the treatment of non‐small cell lung cancer, advanced breast cancer, ovarian cancer and some other tumours. Well‐recognized side‐effects include dose‐limiting neutropenia, fluid retention, myalgia, neuropathy, hypersensitivity reaction, alopecia, mucositis, nail changes and cutaneous reactions such as acral erythema. We describe a unique docetaxel‐induced cutaneous reaction presenting as fixed erythematous plaque(s) unrelated to extravasation or previous skin injury; histopathological studies were performed in three of the four cases.

Comparison of cutaneous tolerance and efficacy of calcitriol 3 μg g−1 ointment and tacrolimus 0·3 mg g−1 ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial

Background Two nonsteroidal topical agents, calcitriol and tacrolimus, have been reported to be effective and safe for psoriatic lesions on sensitive areas. However, no comparative studies between calcitriol and tacrolimus have been reported.

Subcutaneous fat necrosis of the newborn complicating hypothermic cardiac surgery

A newborn male infant developed subcutaneous fat necrosis (SCFN) with extensive calcification, 1 week after hypothermic cardiac surgery. The lesions resolved spontaneously, without sequelae, within 10 weeks. Five cases of SCFN occurring after induced hypothermia, used as an adjuvant in cardiac surgery, have been reported to date in the English literature. Our description of a sixth case re‐emphasizes hypothermia as one possible cause of SCFN of the newborn.