Yi-Hua Liao

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.

Pattern of Skin Diseases in a Geriatric Patient Group in Taiwan: A 7-Year Survey from the Outpatient Clinic of a University Medical Center

Background: Geriatric health care has become a worldwide concern, but relatively few statistical studies are available about geriatric skin diseases. Moreover, no information exists regarding skin disorders among the elderly population in Taiwan that has become a geriatric country. Objective: To determine the characteristic pattern and the prevalence of various skin disorders for the elderly who visited the National Taiwan University in the last 7 years. Methods: Using a database from the Dermatology Outpatient Clinic of the National Taiwan University Hospital, 1993–1999 file, we conducted a retrospective cross-sectional study by evaluating the age, proportion, and gender of each specific cutaneous disease category, χ2 tests were used for analyzing statistical significance. The analysis supplied odds ratios and 95% confidence intervals. Results: A total of 16,924 patients aged 65 years and older, which constituted 11% of the total patients seen at the Clinic of Dermatology from 1993 through 1999, were studied. The male to female ratio was 1.3 to 1. The most common cutaneous disorder in the elderly was dermatitis (58.7%), followed by fungal infections (38.0%), pruritus (14.2%), benign tumors (12.8%), and viral infections (12.3%). Cutaneous malignant tumors were found in 2.1%. Basal cell carcinoma occurred in 29.8%, actinic keratosis in 22.4%, Bowen’s disease in 13.3% and squamous cell carcinoma 13.3%. Interestingly, our cases of extramammary Paget’s disease showed a male predominance. Most melanomas were acral lentiginous melanoma located on the soles. The prevalence of common diseases in elderly patients compared with those outpatients of less than 65 years showed a 3-fold increased risk for pruritus. Moreover, the pattern of geriatric skin diseases in Taiwan was significantly different from Western countries. Conclusion: The prevalence of skin diseases in elderly patients emphasizes the importance of health education in geriatric people in Taiwan concerning appropriate use of emollients, proper foot care, sun protection and early detection of skin cancers.

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.

Optical biopsy of fixed human skin with backward-collected optical harmonics signals

Harmonics-based optical microscopy has been widely applied in biomedical researches due to its noninvasiveness to the studied biomaterials. Due to momentum conservation consideration, most previous studies collect harmonics generation signals in a forward geometry, especially for third harmonic generation signals. However, the adopted forward transmission type geometry is not feasible for future clinical diagnosis. In this paper, first virtual biopsy based on backward propagating optical higher harmonics, combining second harmonic and third harmonic, is demonstrated in the fixed human skin specimens. In our study, third harmonic generation can provide morphologic information including the distribution of basal cells while second harmonic generation can provide distribution of collagen fibers in dermis. Therefore, this technique is ideal for future noninvasive in vivo skin disease examination without dye.

Increased expression of the natural killer cell inhibitory receptor CD94/NKG2A and CD158b on circulating and lesional T cells in patients with chronic plaque psoriasis

Background  Psoriasis is a common inflammatory cutaneous disorder characterized by activated T‐cell infiltration. T lymphocytes bearing natural killer cell receptors (NKRs) have been suggested to play an important role in the pathogenesis of psoriasis. However, the expression pattern of activating and inhibitory NKRs on T lymphocytes from psoriatic patients and its significance in psoriasis needs further study.

Optical signal degradation study in fixed human skin using confocal microscopy and higher-harmonic optical microscopy

Confocal and nonlinear optical microscopies have been applied for dermatological studies because of their capability to provide sub-surface three-dimensional images with sub-microm spatial resolutions. Optical signal degradation as the imaging plane being moved toward deeper regions in skin specimens is the key factor that limits the observation depth for the laser scanning based linear or nonlinear imaging modalities. In this article, we studied the signal degradation in fixed human skin specimens using reflection confocal microscopy and higher-harmonic optical microscopy based on a Cr:forsterite femtosecond laser centered at 1230-nm. By analyzing the optical properties through these linear and nonlinear imaging modalities, we found that the optical signal degradation in the studied human skin specimen is dominated by the distortion of the point spread function.

Quantitative analysis of intrinsic skin aging in dermal papillae by in vivo harmonic generation microscopy

Chronological skin aging is associated with flattening of the dermal-epidermal junction (DEJ), but to date no quantitative analysis focusing on the aging changes in the dermal papillae (DP) has been performed. The aim of the study is to determine the architectural changes and the collagen density related to chronological aging in the dermal papilla zone (DPZ) by in vivo harmonic generation microscopy (HGM) with a sub-femtoliter spatial resolution. We recruited 48 Asian subjects and obtained in vivo images on the sun-protected volar forearm. Six parameters were defined to quantify 3D morphological changes of the DPZ, which we analyzed both manually and computationally to study their correlation with age. The depth of DPZ, the average height of isolated DP, and the 3D interdigitation index decreased with age, while DP number density, DP volume, and the collagen density in DP remained constant over time. In vivo high-resolution HGM technology has uncovered chronological aging-related variations in DP, and sheds light on real-time quantitative skin fragility assessment and disease diagnostics based on collagen density and morphology.

Determination of chronological aging parameters in epidermal keratinocytes by in vivo harmonic generation microscopy

Skin aging is an important issue in geriatric and cosmetic dermatology. To quantitatively analyze changes in keratinocytes related to intrinsic aging, we exploited a 1230 nm-based in vivo harmonic generation microscopy, combining second- and third-harmonic generation modalities. 52 individuals (21 men and 31 women, age range 19–79) were examined on the sun-protected volar forearm. Through quantitative analysis by the standard algorithm provided, we found that the cellular and nuclear size of basal keratinocytes, but not that of granular cells, was significantly increased with advancing age. The cellular and nuclear areas, which have an increase of 0.51 μm2 and 0.15 μm2 per year, respectively, can serve as scoring indices for intrinsic skin aging.

Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate‐to‐severe plaque psoriasis in Taiwan: results of an open‐label, single‐arm pilot study

Background  No clinical trial of efalizumab has been conducted in Asia.

Optical Biopsy of Human Skin with Backward-Collected Optical Harmonics Signals

Combining backward-collected second- and third-harmonic signals, noninvasive optical biopsy of human skin is demonstrated. With backward collection geometry and energy-conservation characteristic of harmonic generations, this technique is ideal for future noninvasive clinical skin disease diagnosis