Jeng-Wei Tjiu

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.

Prediction of heat-induced collagen shrinkage by use of second harmonic generation microscopy

Collagen shrinkage associated with denaturation from thermal treatment has a number of important clinical applications. However, individualized treatment is hindered by the lack of reliable noninvasive methods to monitor the process of collagen denaturation. We investigate the serial changes of collagen denaturation from thermal treatment of rat tail tendons at 58 degrees C by use of second harmonic generation (SHG) microscopy. We find that rat tail tendon shrinks progressively from 0 to 9 min of thermal treatment, and remains unchanged in length upon further thermal treatment. The SHG intensity also decreases from 0 to 9 min of thermal treatment and becomes barely detectable from further thermal treatment. Collagen shrinkage and the SHG intensity are well correlated in a linear model. In addition, SHG imaging reveals a tiger-tail-like pattern of collagen denaturation. The bands of denatured collagen progressively widen from increased thermal treatment and completely replace the adjacent bands of normal collagen after 9 min of thermal treatment. Our results show that collagen denaturation in rat tail tendon from thermal treatment is inhomogeneous, and that SHG intensity can be used to predict the degree of thermally induced collagen shrinkage. With additional development, this approach has the potential to be used in biomedical applications.

SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda

Background  Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP‐1 (lymphocyte antigen 6/urokinase‐type plasminogen activator receptor related protein‐1). SLURP‐1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T‐cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T‐cell function as well as a derangement of epidermal homeostasis.

Infiltrating macrophage count: a significant predictor for the progression and prognosis of oral squamous cell carcinomas in Taiwan.

Infiltrating macrophage count (IMC) is found to correlate with the progression and prognosis of many human cancers.

Full-depth epidermis tomography using a Mirau-based full-field optical coherence tomography

With a Gaussian-like broadband light source from high brightness Ce(3+):YAG single-clad crystal fiber, a full-field optical coherence tomography using a home-designed Mirau objective realized high quality images of in vivo and excised skin tissues. With a 40 × silicone-oil-immersion Mirau objective, the achieved spatial resolutions in axial and lateral directions were 0.9 and 0.51 μm, respectively. Such a high spatial resolution enables the separation of lamellar structure of the full epidermis in both the cross-sectional and en face planes. The number of layers of stratum corneum and its thickness were quantitatively measured. This label free and non-invasive optical probe could be useful for evaluating the water barrier of skin tissue in clinics. As a preliminary in vivo experiment, the blood vessel in dermis was also observed, and the flowing of the red blood cells and location of the melanocyte were traced.

Cell death detection by quantitative three-dimensional single-cell tomography.

Ultrahigh-resolution optical coherence tomography (UR-OCT) has been used for the first time to our knowledge to study single-cell basal cell carcinoma (BCC) in vitro. This noninvasive, in situ, label-free technique with deep imaging depth enables three-dimensional analysis of scattering properties of single cells with cellular spatial resolution. From three-dimensional UR-OCT imaging, live and dead BCC cells can be easily identified based on morphological observation. We developed a novel method to automatically extract characteristic parameters of a single cell from data volume, and quantitative comparison and parametric analysis were performed. The results demonstrate the capability of UR-OCT to detect cell death at the cellular level.

Digital infarcts showing microangiopathy in adult dermatomyositis suggest severe pulmonary involvement and poor prognosis

after the chemotherapy. Raynaud’s phenomenon and digital pitting scars were seen in two and one cases, respectively. The ANA was positive in three of the patients, although no case had scleroderma-specific autoantibodies. In seven patients, skin sclerosis was limited to the extremities, while only one showed skin sclerosis of the trunk as well as the extremities. The atypical distribution of skin involvement without sclerodactyly was specific for our case. Two cases showed morphoea-like plaques. None of the patients had a visceral involvement. Eight of nine cases had minimal persistent scleroderma after withdrawal of the drugs and additional treatments, including oral corticosteroids. Thus, the small incidence of Raynaud’s phenomenon, digital pitting scars and ANA, and the absence of visceral involvement are characteristics of bleomycinor peplomycin-induced scleroderma. Although the pathogenesis of bleomycinor peplomycininduced pulmonary and dermal fibrosis is still unknown, numerous examinations have disclosed several aspects of its mechanism. In normal human dermal fibroblasts, bleomycin enhances the synthesis of type I collagen. In rat lung fibroblasts, bleomycin stimulates pro-a1(I) collagen promoter through the transforming growth factor (TGF)-b response element. Bleomycin or peplomycin enhances reactive oxygen intermediate (ROI) generation from macrophages and polymorphonuclear leucocytes, which provokes inflammation, resulting in tissue fibrosis. Bleomycin or peplomycin induces cytokines such as interleukin-1b and TGF-b, which activate macrophages and polymorphonuclear leucocytes to produce ROI and stimulate dermal fibroblasts to generate collagen, respectively. In addition, cutaneous collagenolytic activity is decreased in animal models treated with bleomycin. Moreover, bleomycin is concentrated in the lung and skin in several species because of the very low activity of the bleomycin-inactivating enzyme, bleomycin hydrolase, in these tissues, which clearly explains the organ-specific adverse effects of bleomycin or peplomycin. In summary, we report the first case of peplomycin-induced scleroderma. Considering the widespread use of bleomycin or peplomycin, it is possible that this type of bleomycin or peplomycin complication may occur more frequently than recognized. Therefore, the history of exposure to chemicals or drugs should be investigated in patients with scleroderma.

Nephrogenic systemic fibrosis developed after recovery from acute renal failure: gadolinium as a possible aetiological factor.

© 2008 The Authors JEADV 2009, 23, 317–368 Journal compilation

Macular amyloidosis presenting in an incontinentia pigmenti-like pattern with subepidermal blister formation.

© 2008 The Authors 635 JEADV 2008, 22, 616–650 Journal compilation

Investigation of influences of the paraformaldehyde fixation and paraffin embedding removal process on refractive indices and scattering properties of epithelial cells

Abstract. The scattering properties and refractive indices (RI) of tissue are important parameters in tissue optics. These parameters can be determined from quantitative phase images of thin slices of tissue blocks. However, the changes in RI and structure of cells due to fixation and paraffin embedding might result in inaccuracies in the estimation of the scattering properties of tissue. In this study, three-dimensional RI distributions of cells were measured using digital holographic microtomography to obtain total scattering cross sections (TSCS) of the cells based on the first-order Born approximation. We investigated the slight loss of dry mass and drastic shrinkage of cells due to paraformaldehyde fixation and paraffin embedding removal processes. We propose a method to compensate for the correlated changes in volume and RI of cells. The results demonstrate that the TSCS of live cells can be estimated using restored cells. The percentage deviation of the TSCS between restored cells and live cells was only −8%. Spatially resolved RI and scattering coefficients of unprocessed oral epithelium ranged from 1.35 to 1.39 and from 100 to 450  cm−1, respectively, estimated from paraffin-embedded oral epithelial tissue after restoration of RI and volume.