bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological analysis of 17 primary cutaneous T‐cell lymphoma of the γδ phenotype from Japan
Authors: Takahashi Yuka , Takata Katsuyoshi , Kato Seiichi , Sato Yasuharu , Asano Naoko , Ogino Tetsuro , Hashimoto Kimio , Tashiro Yukie , Takeuchi Shogo , Masunari Taro , Hiramatsu Yasushi , Maeda Yoshinobu , Tanimoto Mitsune , Yoshino Tadashi 
Published: May 2014

Primary cutaneous γδ T‐cell lymphoma (PCGD‐TCL) is an aggressive lymphoma consisting of clonal proliferation of mature activated γδ T‐cells of a cytotoxic phenotype. Because primary cutaneous γδ T‐cell lymphoma is a rare disease, there are few clinicopathological studies. In addition, T‐cell receptor (TCR) γδ cells are typically immunostained in frozen sections or determined by TCRβ negativity. We retrospectively analyzed 17 primary cutaneous T‐cell lymphomas of the γδ phenotype (CTCL‐γδ) in a clinicopathological and molecular study using paraffin‐embedded sections. Among 17 patients, 11 had CTCL‐γδ without subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) features and six had CTCL‐γδ with SPTCL features. Immunophenotypically, some significant differences were found in CD8 and CD56 positivity between our patient series of CTCL‐γδ patients with SPTCL features and SPTCL‐γδ patients described in the previous literature. A univariate analysis of 17 CTCL‐γδ patients showed that being more than 60 years old, presence of visceral organ involvement, and small‐to‐medium cell size were poor prognostic factors. In addition, the 5‐year overall survival rate was 42.4% for the CTCL‐γδ patients without SPTCL features and 80.0% for those with SPTCL features. Consequently, there was a strikingly significant difference in overall survival among SPTCL, CTCL‐γδ with SPTCL features and CTCL‐γδ without SPTCL features (P = 0.0005). Our data suggests that an indolent subgroup may exist in CTCL‐γδ. Studies on more cases, including those from other countries, are warranted to delineate the clinicopathological features and the significance in these rare lymphomas.
Endoscopic findings using narrow‐band imaging to distinguish between basal cell hyperplasia and carcinoma of the pharynx
Authors: Yagishita Atsushi , Fujii Satoshi , Yano Tomonori , Kaneko Kazuhiro 
Published: May 2014

Narrow‐band imaging (NBI) has been reported to be useful for detecting superficial‐type esophageal or head and neck squamous cell carcinoma (SCC), and in the present study we have used NBI to detect non‐carcinomatous lesions, such as basal cell hyperplasia (BCH) accompanied by microvascular irregularities; these non‐carcinomatous lesions were pathologically discriminated from squamous cell carcinoma of the pharynx. The aim of the present study was to clarify the endoscopic characteristics of BCH that contribute to the discrimination of superficial‐type head and neck SCC (HNSCC). We examined the key endoscopic findings capable of distinguishing BCH from SCC using 26 BCH and 37 superficial‐type SCC of the pharynx that had been pathologically diagnosed at our institution between January 2008 and July 2012. The clinicopathological factors were also compared. The size of the BCH lesions was significantly smaller (P < 0.001), and their intervascular transparency was more clearly observed (P < 0.001). Intra‐epithelial papillary capillary loop (IPCL) shapes were less variable and monotonous (P < 0.001), and the distribution of the IPCL was more regular with an interval comparable to that of SCC (P < 0.001), although no significant differences in the sharpness of the lesion border, dilatation of IPCL and tortuosity of the IPCL were seen between the BCH and SCC lesions. This study revealed that BCH was an independent entity in terms of not only pathological findings, but also endoscopic findings observed using NBI, such as the regular distribution of IPCL and the preserved intervascular transparency.
Tumor‐suppressive microRNA‐218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer
Authors: Nishikawa Rika , Goto Yusuke , Sakamoto Shinichi , Chiyomaru Takeshi , Enokida Hideki , Kojima Satoko , Kinoshita Takashi , Yamamoto Noriko , Nakagawa Masayuki , Naya Yukio , Ichikawa Tomohiko , Seki Naohiko 
Published: May 2014

Our recent studies of the microRNA (miRNA) expression signature in prostate cancer (PCa) indicated that miRNA‐218 (miR‐218) was significantly downregulated in clinical specimens, suggesting that miR‐218 might act as a tumor‐suppressive miRNA in PCa. The aim of the present study was to investigate the functional significance of miR‐218 in PCa and to identify novel miR‐218‐regulated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR‐218 in PCa cell lines (PC3 and DU145) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH3 protein 1 (LASP1) is a potential target of miR‐218 regulation. LASP1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR‐218 directly regulated expression of LASP1. Moreover, downregulating the LASP1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP1 was upregulated in cancer tissues. We conclude that loss of tumor‐suppressive miR‐218 enhanced cancer cell migration and invasion in PCa through direct regulation of LASP1. Our data on pathways regulated by tumor‐suppressive miR‐218 provide new insight into the potential mechanisms of PCa oncogenesis and metastasis.
Phase I study of olaratumab in Japanese patients with advanced solid tumors
Authors: Doi Toshihiko , Ma Yan , Dontabhaktuni Aruna , Nippgen Cornelia , Nippgen Johannes , Ohtsu Atsushi 
Published: May 2014

Olaratumab (IMC‐3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet‐derived growth factor receptor‐α with high affinity and blocks ligand binding. This was a single‐center, dose‐escalation, phase I trial of olaratumab in Japanese patients with advanced/refractory solid malignancies. Three to six patients were enrolled into each of three cohorts: Patients received i.v. olaratumab: 10 mg/kg on days 1 and 8 every 3 weeks (cohort 1); 20 mg/kg every 2 weeks (cohort 2); and 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3). Doses were escalated from cohort 1 through cohort 3. The primary objective was to establish the safety and pharmacokinetic profile of olaratumab. Sixteen patients were treated across three cohorts. There were no dose‐limiting toxicities, so the maximum tolerated dose was not reached. The most common olaratumab‐related treatment‐emergent adverse events (TEAEs) were proteinuria (25.0%) and elevated aspartate transaminase (12.5%). One patient (cohort 2) had two olaratumab‐related Grade 3 TEAEs (increased aspartate aminotransferase and tumor hemorrhage); otherwise, olaratumab‐related TEAEs were Grade 1/2. Seven patients (43.8%) had a best response of stable disease. Based on the pharmacokinetic concentration profile of olaratumab, the trough concentrations following single and multiple doses at 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3) and multiple doses at 20 mg/kg every 2 weeks (cohort 2) were above the 155 μg/mL target. Thus, these two doses could represent an acceptable schedule for future trials in Japanese patients. Olaratumab had an acceptable safety profile and was well tolerated.
Distributed expertise: qualitative study of a British network of multidisciplinary teams supporting parents of children with chronic kidney disease
Authors: Swallow V. , Smith T. , Webb N. J. A. , Wirz L. , Qizalbash L. , Brennan E. , Birch A. , Sinha M. D. , Krischock L. , van der Voort J. , King D. , Lambert H. , Milford D. V. , Crowther L. , Saleem M. , Lunn A. , Williams J. 
Published: May 2014

AbstractBackgroundLong‐term childhood conditions are often managed by hospital‐based multidisciplinary teams (MDTs) of professionals with discipline specific expertise of a condition, in partnership with parents. However, little evidence exists on professional–parent interactions in this context. An exploration of professionals' accounts of the way they individually and collectively teach parents to manage their child's clinical care at home is, therefore, important for meeting parents' needs, informing policy and educating novice professionals. Using chronic kidney disease as an exemplar this paper reports on one aspect of a study of interactions between professionals and parents in a network of 12 children's kidney units in Britain.MethodsWe conducted semi‐structured, qualitative interviews with a convenience sample of 112 professionals (clinical‐psychologists, dietitians, doctors, nurses, pharmacists, play‐workers, therapists and social workers), exploring accounts of their parent‐educative activity. We analysed data using framework and the concept of distributed expertise.ResultsFour themes emerged that related to the way expertise was distributed within and across teams: (i) recognizing each other's' expertise, (ii) sharing expertise within the MDT, (iii) language interpretation, and (iv) acting as brokers. Two different professional identifications were also seen to co‐exist within MDTs, with participants using the term ‘we’ both as the intra‐professional ‘we’ (relating to the professional identity) when describing expertise within a disciplinary group (for example: ‘As dietitians we aim to give tailored advice to optimize children's growth’), and the inter‐professional ‘we’ (a ‘team‐identification’), when discussing expertise within the team (for example: ‘We work as a team and make sure we're all happy with every aspect of their training before they go home’).ConclusionsThis study highlights the dual identifications implicit in ‘being professional’ in this context (to the team and to one's profession) as well as the unique role that each member of a team contributes to children's care. Our methodology and results have the potential to be transferred to teams managing other conditions.
Life satisfaction in the transition from care to adulthood: the contribution of readiness to leave care and social support
Authors: Dinisman Tamar 
Published: May 2014

AbstractThis research explores whether readiness to leave care mediates the association between social support – from peers, staff and biological parents – on the verge of leaving care and life satisfaction a year after among young people ageing out of care in Israel. The results represent two waves of a longitudinal study. Two hundred seventy‐two adolescents from residential settings in Israel completed a self‐administered questionnaire shortly before they left care, and one year later, 234 of them were interviewed to assess their life satisfaction. Readiness to leave care was found to mediate the relationship between most social support measurements and life satisfaction. At the same time, the findings also suggest that this mediating effect varies for different types of support and has a lesser amount of influence for profound emotional support than other types of support. These findings highlight the need to include both the preparation to leave care and the reinforcement of emotional support available to young people who aged out of care, before and throughout the transition from care to adulthood.
Quest for the Holy Grail—Is a Unified Approach to the Market Freedoms and European Citizenship Justified?
Authors: de Sousa Pedro Caro 
Published: May 2014

AbstractThe case law of the CJEU on the economic free movement of people has departed from the traditional requirement that a nexus must be established between individual free movement and cross‐border economic activity, which has led to an extension of its scope. It is submitted that concerns with the protection of fundamental rights of European citizens are driving this process, and that the CJEU has sought to protect these fundamental rights through the market freedoms in two ways: by arguing that market freedoms are fundamental right themselves, and/or that European Citizenship has changed their normative underpinnings and status. This Article criticises both lines of argument, and defends a third: that the protection of these fundamental rights must be achieved at European level, if at all, through a conception of European Citizenship able to stand on its own.
SIRT2 as a new player in epigenetic programming of keratinocyte differentiation and a candidate tumor suppressor
Authors: Wang Ming , Yue Zhicao , Paus Ralf , Ramot Yuval 
Published: May 2014

AbstractEpidermal keratinocytes undergo a continuous process of terminal differentiation, which is accompanied by a dramatic change in the expression and composition of keratins. This complex and carefully orchestrated process is regulated by a large number of signal transduction events and transcriptional factors as well as by epigenetic regulatory mechanisms, namely by histone methylation/acetylation and DNA methylation. In a recent issue of Exp Dermatol, Ming et al. provide evidence that sirtuin‐2 (SIRT2), a NAD+‐dependent deacetylase, inhibits the expression of keratin 15 and keratin 19, epidermal stem cell markers, while it stimulates the expression of loricrin, a marker of terminal keratinocyte differentiation. Human skin cancer cells show downregulation of SIRT2, and its deletion increases tumor growth in mice. Overall, these findings suggest that this deacetylase is involved in the epigenetic regulation of keratinocyte differentiation and exerts intracutaneous tumor suppressor functions.
Matricryptins and matrikines: biologically active fragments of the extracellular matrix
Authors: Ricard‐Blum Sylvie , Salza Romain 
Published: May 2014

AbstractNumerous extracellular proteins and glycosaminoglycans (GAGs) undergo limited enzymatic cleavage resulting in the release of fragments exerting biological activities, which are usually different from those of the full‐length molecules. In this review, we define matrikines and matricryptins, which are bioactive fragments released from the extracellular matrix proteins, proteoglycans and GAGs and report their major biological activities. These fragments regulate a number of physiopathological processes including angiogenesis, cancer, fibrosis, inflammation, neurodegenerative diseases and wound healing. The challenges to translate these fragments from molecules biologically active in vitro and in experimental models to potential drugs are discussed in the last part of the review.
Melanoma's high C>T mutation rate: is deamination playing a role?
Authors: Sanchez Margaret I. , Grichnik James M. 
Published: May 2014

AbstractThe majority of melanoma mutations are C>T transitions, and most bear UV signatures. However, other process may contribute to the high C>T mutation rate. Okura et al., have demonstrated immunohistochemical evidence of deaminating enzymes, activation‐induced cytidine deaminase (AID) and apolipoprotein B mRNA‐editing enzyme catalytic polypeptide‐like 3B (APOBEC3B) in melanoma. Both have been implicated in cancer. While further validation is necessary, these findings warrant consideration of a role for deamination in melanomagenesis. Deamination primarily drives C>T transitions. Compared with trunk/extremity melanomas, acral melanomas display a significantly higher percentage of ‘spontaneous’ and ‘AID’ mutation signature events suggesting deamination may be particularly important in this subgroup.
Psoriasis: to treat or to manage?
Authors: Mrowietz Ulrich , Steinz Kirsten , Gerdes Sascha 
Published: May 2014

AbstractThe recognition of psoriasis as a systemic disorder with characteristic skin symptoms and associated diseases has changed treatment concepts substantially. The complexity of psoriasis disease not only requires appropriate therapy but also weight‐loss and smoking cessation programmes as well as trigger factor elimination. The term ‘management’ may better reflect the aim for a holistic approach of disease control. Comorbidity and the presence of psoriatic arthritis are important denominators for drug selection. However, there is a lack of prospective data substantiating a benefit of associated diseases by antipsoriatic therapy. Securing success using treatment goals helps to establish an efficacious therapy and to control inflammation. A regular scoring of disease severity, patients’ quality of life and assessment of other clinically relevant conditions are mandatory to closely follow the disease course. There is debate whether an early treatment may modulate the future course of psoriasis. Concepts of minimal disease activity have not been implemented in psoriasis yet. There is a lack of evidence how long any treatment should be given and when and how to terminate. Finally, outcome tools should specifically be tailored for psoriasis to evaluate disease‐related items as well as the benefit of management from the patient's perspective.
Coming home at last: dermal white adipose tissue
Authors: Schneider Marlon R. 
Published: May 2014

AbstractThe upper part of subcutaneous white adipose tissue (SWAT) is closely associated with the reticular dermis, surrounds hair follicles and is of great importance for a range of skin functions. In this issue of Experimental Dermatology, Driskell and colleagues propose a nomenclature in which the upper SWAT layer is renamed dermal WAT (DWAT), and its cells intradermal adipocytes. Some pros and cons are discussed below.
CD109, a novel TGF‐β antagonist, decreases fibrotic responses in a hypoxic wound model
Authors: Winocour Sebastian , Vorstenbosch Joshua , Trzeciak Alissa , Lessard Lucie , Philip Anie 
Published: May 2014

AbstractExcessive extracellular matrix deposition that occurs in many fibrotic skin disorders such as hypertrophic scarring and scleroderma is often associated with hypoxia. CD109 is a novel TGF‐β co‐receptor and TGF‐β antagonist shown to inhibit TGF‐β‐induced extracellular matrix protein production in vitro. We examined whether CD109 is able to regulate extracellular matrix deposition under low oxygen tension in vivo using transgenic mice overexpressing CD109 in the epidermis. By creating dorsal bipedicle skin flaps with centrally located excisional wounds in these mice and their wild‐type littermates, we generated a novel murine hypoxic wound model. Mice were sacrificed on 7 or 14 days post‐wounding, and tissues were harvested for histological and biochemical analysis. Hypoxic wounds in both transgenic and wild‐type mice showed increased levels of HIF‐1α and delayed wound closure, validating this model in mice. Hypoxic wounds in CD109 transgenic mice demonstrated decreased collagen type 1 and fibronectin expression, and reduced dermal thickness on day 7 post‐wounding as compared to those in wild‐type mice and to non‐hypoxic control wounds. These results suggest that CD109 decreases extracellular matrix production and fibrotic responses during hypoxic wound healing. Manipulating CD109 levels may have potential therapeutic value for the treatment of fibrotic skin disorders associated with poor oxygen delivery.
P2Y2R activation by nucleotides promotes skin wound‐healing process
Authors: Jin Hana , Seo Jihye , Eun So Young , Joo Young Nak , Park Sang Won , Lee Jae Heun , Chang Ki Churl , Kim Hye Jung 
Published: May 2014

AbstractP2Y2R has been shown to be upregulated in a variety of tissues in response to stress or injury and to mediate tissue regeneration through its ability to activate multiple signalling pathways. This study aimed to investigate the role of P2Y2R in the wound‐healing process and the mechanisms by which P2Y2R activation promotes wound healing in fibroblasts. The role of P2Y2R in skin wound healing was examined using a full‐thickness skin wound model in wildtype (WT) and P2Y2R−/− mice and an in vitro scratch wound model in control or P2Y2R siRNA‐transfected fibroblasts. WT mice showed significantly decreased wound size compared with P2Y2R−/− mice at day 14 post‐wounding, and immunohistochemical analysis showed that a proliferation marker Ki67 and extracellular matrix (ECM)‐related proteins VEGF, collagen I, fibronectin and α‐SMA were overexpressed in WT mice, which were reduced in P2Y2R−/− mice. Scratch‐wounded fibroblasts increased ATP release, which peaked at 5 min. In addition, scratch wounding increased the level of P2Y2R mRNA. Activation of P2Y2R by ATP or UTP enhanced proliferation and migration of fibroblasts in in vitro scratch wound assays and were blocked by P2Y2R siRNA. Finally, ATP or UTP also increased the levels of ECM‐related proteins through the activation of P2Y2R in fibroblasts. This study suggests that P2Y2R may be a potential therapeutic target to promote wound healing in chronic wound diseases.
Expression of decorin throughout the murine hair follicle cycle: hair cycle dependence and anagen phase prolongation
Authors: Jing Jing , Wu Xian‐jie , Li Yun‐ling , Cai Sui‐Qing , Zheng Min , Lu Zhong‐Fa 
Published: May 2014

AbstractDecorin is a prototypical member of the small leucine‐rich proteoglycan (SLRP) family, which is involved in numerous biological processes. The role of decorin, as a representative SLRP, in hair follicle morphogenesis has not been elucidated. We present our initial findings on decorin expression patterns during induced murine hair follicle (HF) cycles. It was found that decorin expression is exclusively restricted to the epidermis, outer root sheath and sebaceous glands during the anagen phase, which correlates with the upregulation of decorin mRNA and protein expression in depilated murine dorsal skin. Furthermore, we used a functional approach to investigate the effects of recombinant human decorin (rhDecorin) via cutaneous injection into HFs at various murine hair cycle stages. The local injection of rhDecorin (100 μg/ml) into the hypodermis of depilated C57BL/6 mice at anagen delayed catagen progression. In contrast, rhDecorin injection during the telogen phase caused the premature onset of anagen, as demonstrated by the assessment of the following parameters: (i) hair shaft length, (ii) follicular bulbar diameter, (iii) hair follicle cycling score and (iv) follicular phase percentage. Taken together, our results suggest that decorin may modulate follicular cycling and morphogenesis. In addition, this study also provides insight into the molecular control mechanisms governing hair follicular epithelial–mesenchymal interactions.
Role ofEts‐1 in fibronectin‐derived heparin‐binding domain polypeptides alleviating melanoma cell invasiveness and chemoresistance
Authors: Tang Nanhong , Wang Xiaoqian , Huang Tao , Wu Yong , Chen Yuanzhong 
Published: May 2014

AbstractIn this study, we observed that rhFNHN29 and rhFNHC36, two recombinant heparin‐binding domain polypeptides of fibronectin, suppressed adhesion and invasion ofB16F10 andA375 melanoma cells mediated by integrinαv andα2 in a dose‐dependent manner. Combined with low‐concentration epirubicin (EPI), rhFNHN29 or rhFNHC36 exhibited a synergistic inhibition on the viability and metastasis ofB16F10 cells. Moreover, in the presence of high‐concentration rhFNHN29 or rhFNHC36, theEts‐1 activity and the expression of p‐FAK, p‐Erk1/2 andEts‐1 were notably downregulated inB16F10 cells. Ets‐1 is one of the central regulatory links for rhFNHN29 and rhFNHC36 to suppress the adhesion and invasion of melanoma cells. Combining rhFNHN29 or rhFNHC36 withEPImay be a good way to alleviate invasiveness or chemoresistance in melanoma.