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This article presents a case study of a 10-year-old girl with gray-brown patches in the axillary and inguinal folds. The girl had been unsuccessfully treated with topical cream and oral medication for a presumed tinea infection. Further examination revealed gray-brown macules and patches in the affected areas, as well as perifollicular pigment deposits. Biopsies confirmed the diagnosis of lichen planus pigmentosus inversus (LPPI). LPPI is a rare variant of lichen planus characterized by asymptomatic or mildly itchy pigmented lesions in skin folds. Treatment options include topical corticosteroids or calcineurin inhibitors. [Extracted from the article]

In non-small cell lung cancer (NSCLC), activating mutations in the epidermal growth factor receptor (EGFR) induce sensitivity to EGFR tyrosine kinase inhibitors. Despite impressive clinical responses, patients ultimately relapse as a reservoir of drugtolerant cells persist, which ultimately leads to acquired resistance mechanisms. We performed an unbiased high-throughput siRNA screen to identify proteins that abrogate the response of EGFR-mutant NSCLC to EGFR-targeted therapy. The deubiquitinase USP13 was a top hit resulting from this screen. Targeting USP13 increases the sensitivity to EGFR inhibition with small molecules in vitro and in vivo. USP13 selectively stabilizes mutant EGFR in a peptidase-independent manner by counteracting the action of members of the Cbl family of E3 ubiquitin ligases. We conclude that USP13 is a strong mutant EGFR-specific cotarget that could improve the treatment efficacy of EGFR-targeted therapies [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate histological changes in torn (0.5-27 weeks after injury) and osteoarthritic (OA) knee menisci versus normal menisci after PAS-AB, SAF-O-FG, and immunostaining for CD34, CD31, and smooth muscle actin (SMA). Cell layers in the superficial zone and the cell density in the deep zone of the menisci were counted. In the superficial zone of normal menisci, cells expressing CD34 were demonstrated. CD34+ CD31− cells were absent in OA menisci and disappeared in torn menisci as a function of time. In contrast, an increase of SMA+ cells combined with an increase of cell layers was observed in the superficial zone of torn menisci. SMA+ cells were absent in normal and OA menisci. The predominant tissue type in torn menisci evolved from fibrocartilage-like to fibrous-like tissue as a function of time, whereas in OA menisci it became cartilage-like. The response of the superficial zone was reflected by the decrease of CD34+ and the increase of SMA+ cells in torn menisci and the transformation of a fibrous-like into a cartilage-like surface layer in OA menisci. These results potentially illustrate the contribution of CD34+ cells to the homeostasis of meniscus tissue. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:800-808, 2012 [ABSTRACT FROM AUTHOR]

Balla P, Moskovszky L, Sapi Z, Forsyth R, Knowles H, Athanasou N A, Szendroi M, Kopper L, Rajnai H, Pinter F, Petak I, Benassi M S, Picci P, Conti A & Krenacs T (2011) Histopathology 59, 376-389 Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone Aims: Epidermal growth factor receptor (EGFR) is implicated in bone remodelling. The aim was to determine whether EGFR protein expression contributes to the aggressiveness and recurrence potential of giant cell tumour of bone (GCTB), an osteolytic primary bone tumour that can exhibit markedly variable clinical behaviour. Methods and results: Immunohistochemical analysis on tissue microarrays (TMA) of 231 primary, 97 recurrent, 17 metastatic and 26 malignant GCTBs was performed using TMA analysis software and whole digital slides allowing validated scoring. EGFR expression was restricted to neoplastic stromal cells and was significantly more frequent in recurrent (71 of 92; 77%) than in non-recurrent GCTBs (86 of 162; 53%) ( P = 0.002); and in clinicoradiologically aggressive (31 of 43; 72%) than latent (27 of 54; 50%) cases ( P = 0.034). Detecting phosphotyrosine epitopes pY1068 and -pY1173 indicated active EGFR signalling, and finding EGFR ligands EGF and transforming growth factor-α restricted to cells of the monocytic lineage suggested paracrine EGFR activation in stromal cells. In functional studies EGF supported proliferation of GCTB stromal cells, and the addition of EGF and macrophage-colony stimulating factor promoted osteoclastogenesis. Conclusion: In GCTB, EGFR signalling in neoplastic stromal cells may contribute to disease progression through promoting stromal cell proliferation and osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Telomeres, the ends of eukaryotic chromosomes, have been the subject of intense investigation over the last decade. As telomere dysfunction has been associated with ageing and developing cancer, understanding the exact mechanisms regulating telomere structure and function is essential for the prevention and treatment of human cancers and age-related diseases. The mechanisms by which cells maintain telomere lengthening involve either telomerase or the alternative lengthening of the telomere pathway, although specific mechanisms of the latter and the relationship between the two are as yet unknown. Many cellular factors directly (TRF1/TRF2) and indirectly (shelterin-complex, PinX, Apollo and tankyrase) interact with telomeres, and their interplay influences telomere structure and function. One challenge comes from the observation that many DNA damage response proteins are stably associated with telomeres and contribute to several other aspects of telomere function. This review focuses on the different components involved in telomere maintenance and their role in telomere length homeostasis. Special attention is paid to understanding how these telomere-associated factors, and mainly those involved in double-strand break repair, perform their activities at the telomere ends. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a medical research study which investigated the expression profiles of blood monocytes with CD14/CD33 markers in giant cell tumor of bone. The monocytes were shown to be programmed as pre-osteoclasts. The expression of markers has been shown on mononuclear rounded cells. Researchers believe that osteoclastogenesis is not an exclusive result of fusion of intratumoral CD14+ mononuclear cells. They note the possibility for new therapies using CD33-modulated osteoclastogenesis.