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Bone is one of the common sites of metastases from renal cell carcinoma (RCC), however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O) compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1α, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Poroid neoplasm is a skin appendage tumor that has both benign and malignant counterparts. It has traditionally been regarded as of eccrine origin and has four types: intraepidermal poroma (hidroacanthoma simplex), poroma, dermal duct tumor, and poroid hidradenoma. Here we describe the case of a 64-year-old woman who had a verrucous, erythematous to brownish tumor on her left buttock for many years. Histopathology revealed an intra-epidermal poroid tumor with both benign and malignant parts. The benign part had intra-epidermal nests of poroid cells, which were smaller, monomorphic and sharply marginated from adjacent keratinocytes. The malignant part showed similar cell types, but had a higher nuclear/cytoplasmic ratio, pleomorphism, and prominent mitoses. Ductal structures were noted in neoplastic cells and an epithelial membrane antigen stain was strongly positive. Interestingly, peripheral palisading and primitive follicular germ formation were also observed in the neoplasm, which suggests follicular differentiation. We made a final diagnosis of porocarcinoma in situ with follicular differentiation, which may support the folliculosebaceous–apocrine unit theory, but a tumor with such a combination has not been described before. [Copyright &y& Elsevier]

Men with castration-resistant prostate cancer (PCa) frequently develop metastasis in bone. The reason for this association is unclear. We have previously shown that cadherin-11 (also known as OB-cadherin), a homophilic cell adhesion molecule that mediates osteoblast adhesion, plays a role in the metastasis of PCa to bone. Here, we report that androgen-deprivation therapy up-regulates cadherin-11 expression in PCa. In human PCa specimens, immunohistochemical staining showed that 22/26 (85%) primary PCa tumours from men with castration-resistant PCa expressed cadherin-11. In contrast, only 7/50 (14%) androgen-dependent PCa tumours expressed cadherin-11. In the MDA-PCa-2b xenograft animal model, cadherin-11 was expressed in the recurrent tumours following castration. In the PCa cell lines, there is an inverse correlation between expression of cadherin-11 and androgen receptor (AR), and cadherin-11 is expressed in very low levels or not expressed in AR-positive cell lines, including LNCaP, C4-2B4 and VCaP cells. We showed that AR likely regulates cadherin-11 expression in PCa through an indirect mechanism. Although re-expression of AR in the AR-negative PC3 cells led to the inhibition of cadherin-11 expression, depletion of androgen from the culture medium or down-regulation of AR by RNA interference in the C4-2B4 cells or VCaP cells only produced a modest increase of cadherin-11 expression. Promoter analysis indicated that cadherin-11 promoter does not contain a typical AR-binding element, and AR elicits a modest inhibition of cadherin-11 promoter activity, suggesting that AR does not regulate cadherin-11 expression directly. Together, these results suggest that androgen deprivation up-regulates cadherin-11 expression in prostate cancer, and this may contribute to the metastasis of PCa to bone. Our study suggests that therapeutic strategies that block cadherin-11 expression or function may be considered when applying androgen-ablation therapy. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to investigate in a transgenic animal model the cardiac expression and function of a novel extracellular protein SCUBE3 [signal peptide-CUB (complement proteins C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-like domain-containing protein 3]. Methods and results: Real-time quantitative reverse transcriptase (RT)-PCR analysis showed that SCUBE3 is expressed in the ventricular myocardium. Male transgenic (TG) mice overexpressing SCUBE3 appeared normal during development, from birth to adulthood. However, echocardiography and histopathological examination revealed significant cardiac hypertrophy in TG animals as they aged, at 8 months. Interestingly, left-ventricle hypertrophy occurred more rapidly and more severely under pressure overload in TG mice, as compared to age-matched wild-type littermates. Induced SCUBE3 expression, together with elevated transforming growth factor (TGF)-β1 level under pressure overload, may account for the accelerated onset and progression of cardiac hypertrophy in TG mice. Furthermore, biochemical and molecular studies revealed that the carboxyl-terminal portion of SCUBE3 could physically interact with TGF-β1 and promote the TGF-β1-mediated transcriptional activation. Conclusion: This report is the first demonstration that SCUBE3 may play a role in the regulation of cardiac growth and remodeling responses, possibly through the stabilization of the TGF-β1 signaling pathway. [Copyright &y& Elsevier]

We report a 78-year-old woman on hemodialysis who presented with refractory multiple pruritic vesicles and bullae on her trunk and extremities for 2 months. Histopathologic examination of skin biopsy specimen showed subepidermal bullae with many amyloid deposits in the papillary dermis. No evidence of systemic amyloidosis could be found on physical examination. While the initial clinical diagnosis was bullous pemphigoid, the histopathology and direct immunofluorescence result favored hemodialysis-associated amyloidosis. However, immunochemical study for β2-microglobulin was negative. Further hematologic and immunologic work-up revealed the presence of multiple myeloma and that the deposit was AL amyloid. This is the first case of bullous amyloidosis in a hemodialysis patient and should remind dermatologists that bullous amyloidosis should be considered in addition to the usual presentation of porphyria cutanea tarda and pseudoporphyria for bullous dermatosis in the hemodialysis patient. We also suggest that hemodialysis-associated amyloidosis should not be taken for granted in the hemodialysis patient with cutaneous amyloidosis without systemic signs and symptoms. Further testing for other types of amyloid should be performed. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the study was to investigate the protein expression and function of a novel secreted protein in the vascular system, named SCUBE1 for signal peptide, CUB (Complement proteins C1r/C1s, Uegf, and Bmp1) and epidermal growth factor-like (EGF)-like domain containing protein 1. Methods and results: Immunohistochemical analysis demonstrated that the SCUBE1 staining is mainly confined to the intravascular platelet-rich thrombus in vascular tissue samples. While quantitative real-time RT-PCR verified that the SCUBE1 mRNA is expressed in human platelets, numerous immunolocalization techniques revealed that the preformed SCUBE1 protein is stored in the α-granules and translocated to the surface upon platelet stimulation. A smaller SCUBE1 fragment, possibly formed by limited proteolysis after being released from the storage granules, was detected in thrombus lysate by Western blot analysis. Interestingly, deposition of SCUBE1 into the subendothelial matrix of the atherosclerotic plaques was evidenced by immunohistochemistry. In addition, studies of platelet adhesion and ristocetin-induced platelet agglutination showed that fragments containing the amino-terminal EGF-like repeats were able to support platelet adhesion and enhance the ristocetin-induced platelet agglutination, respectively. Conclusion: These data suggest that platelet-derived SCUBE1 could function as a novel adhesive molecule and its matrix-bound and soluble fragments may play critical (patho)physiological roles in cardiovascular biology. [Copyright &y& Elsevier]

Abstract Background and Aims: The existence of gastric metaplasia (GM) of the duodenal mucosa has been considered to be highly related to the recurrence of duodenal ulcers (DU). The aims of this study are to evaluate the usefulness of methylene blue staining in the detection of GM, and to clarify the relationship between GM and the deformity of the duodenal bulb. Methods: Fifteen patients with healed DU and four patients with symptoms of dyspepsia without evidence of ulcers were enrolled into this endoscopic study. During each endoscopy, methylene blue was sprayed evenly on the duodenal bulb, and biopsies were taken from blue-stained and unstained areas. The existence and extent of GM were assessed histologically and grossly. The correlation between duodenal bulb deformity and the extent of GM was also studied. Results: The mean score of methylene blue non-staining (MBNS) was 0, 1.30 ± 0.15, and 3.00 ± 0.00 in group A (non-ulcer patients), group B (patients with healed DU and with normal-shaped bulb) and C (patients with healed DU and with deformed duodenal bulb), respectively; showing significant differences among the groups (P < 0.05 in each). Both the existence and the grading of GM were higher in unstained specimens than in blue-stained specimens (100 vs 16.6%, P < 0.0001 and 3.62 ± 0.09 vs 0.19 ± 0.06, P < 0.001, respectively). Conclusions: Methylene blue non-staining can be applied to investigate the existence and extent of GM in the duodenal bulb accurately. The incidence of GM in the duodenal bulb was higher in patients with healed ulcers than in non-ulcer patients. Patients with deformed duodenal bulbs have a higher extent of GM than those without deformed duodenal bulbs. [ABSTRACT FROM AUTHOR]

In this study, we incorporated silver nanowires (AgNWs) into poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as a hole transport layer (HTL) for inverted perovskite solar cells (PVSCs). The effect of AgNW incorporation on the perovskite crystallization, charge transfer, and power conversion efficiency (PCE) of PVSCs were analyzed and discussed. Compared with neat PEDOT:PSS HTL, incorporation of few AgNWs into PEDOT:PSS can significantly enhance the PCE by 25%. However, the AgNW incorporation may result in performance overestimation due to the lateral charge transfer. The corrosion of AgNWs with a perovskite layer was discussed. Too much AgNW incorporation may lead to defects on the interface between the HTL and the perovskite layer. An extra PEDOT:PSS layer over the pristine PEDOT:PSS-AgNW layer can prevent AgNWs from corrosion by iodide ions. [ABSTRACT FROM AUTHOR]