bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues
Authors: Sisirak Vanja , Vey Nelly , Vanbervliet Béatrice , Duhen Thomas , Puisieux Isabelle , Homey Bernhard , Bowman Edward P. , Trinchieri Giorgio , Dubois Bertrand , Kaiserlian Dominique , Lira Sergio A. , Puisieux Alain , Blay Jean-Yves , Caux Christophe , Bendriss-Vermare Nathalie 
Published: September 2011

AbstractAbsent in peripheral tissues during homeostasis, human plasmacytoid dendritic cells (pDCs) are described in inflamed skin or mucosa. Here, we report that, unlike blood pDCs, a subset of tonsil pDCs express functional CCR6 and CCR10, and their respective ligands CCL20 and CCL27are detected in inflamed epithelia contacting blood dendritic cell antigen 2+ pDCs. Moreover, pDCs are recruited to imiquimod-treated skin tumors in WT but not CCR6-deficient mice, and competitive adoptive transfers reveal that CCR6-deficient pDCs are impaired in homing to inflamed skin tumors after intravenous transfer. On IL-3 culture, CCR6 and CCR10 expression is induced on human blood pDCs that become responsive to CCL20 and CCL27/CCL28, respectively. Interestingly, unlike myeloid DC, blood pDCs initially up-regulate CCR7 expression and CCL19 responsiveness on IL-3 ± CpG-B and then acquire functional CCR6 and CCR10. Finally, IL-3–differentiated CCR6+ CCR10+ pDCs secrete high levels of IFN-α in response to virus. Overall, we propose an unexpected pDCs migratory model that may best apply for mucosal-associated lymphoid tissues. After CCR7-mediated extravasation into lymphoid tissues draining inflamed epithelia, blood pDCs may be instructed to up-regulate CCR6 and/or CCR10 allowing their homing into inflamed epithelia (in mucosae or skin). At this site, pDCs can then produce IFN-α contributing to pathogen clearance and/or local inflammation.
Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling
Authors: Wey Shiuan , Luo Biquan , Tseng Chun-Chih , Ni Min , Zhou Hui , Fu Yong , Bhojwani Deepa , Carroll William L. , Lee Amy S. 
Published: September 2011

AbstractTraditionally, GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors; thus, its role in the development of hematologic malignancies remains to be determined. To directly elucidate the requirement of GRP78 in leukemogenesis, we created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. Strikingly, heterozygous knockdown of GRP78 in PTEN null mice is sufficient to restore the hematopoietic stem cell population back to the normal percentage and suppress leukemic blast cell expansion. AKT/mTOR activation in PTEN null BM cells is potently inhibited by Grp78 heterozygosity, corresponding with suppression of the PI3K/AKT pathway by GRP78 knockdown in leukemia cell lines. This is the first demonstration that GRP78 is a critical effector of leukemia progression, at least in part through regulation of oncogenic PI3K/AKT signaling. In agreement with PI3K/AKT as an effector for cytosine arabinoside resistance in acute myeloid leukemia, overexpression of GRP78 renders human leukemic cells more resistant to cytosine arabinoside-induced apoptosis, whereas knockdown of GRP78 sensitizes them. These, coupled with the emerging association of elevated GRP78 expression in leukemic blasts of adult patients and early relapse in childhood leukemia, suggest that GRP78 is a novel therapeutic target for leukemia.
β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos
Authors: Wu Yi-Ting , Lin Che Yi , Tsai Ming-Yuan , Chen Yi-Hua , Lu Yu-Fen , Huang Chang-Jen , Cheng Chao-Min , Hwang Sheng-Ping L 
Published: September 2011

Abstract

Background
β-Lapachone has antitumor and wound healing-promoting activities. To address the potential influences of various chemicals on heart development of zebrafish embryos, we previously treated zebrafish embryos with chemicals from a Sigma LOPAC1280™ library and found several chemicals including β-lapachone that affected heart morphogenesis. In this study, we further evaluated the effects of β-lapachone on zebrafish embryonic heart development.

Methods
Embryos were treated with β-lapachone or dimethyl sulfoxide (DMSO) at 24 or 48 hours post fertilization (hpf) for 4 h at 28°C. Heart looping and valve development was analyzed by whole-mount in situ hybridization and histological analysis. For fractional shortening and wall shear stress analyses, AB and Tg (gata1:DsRed) embryos were recorded for their heart pumping and blood cell circulations via time-lapse fluorescence microscopy. Dextran rhodamine dye injection into the tail reticular cells was used to analyze circulation. Reactive oxygen species (ROS) was analyzed by incubating embryos in 5-(and 6-)-chloromethyl-2',7'-dichloro-dihydrofluorescein diacetate (CM-H2DCFDA) and recorded using fluorescence microscopy. o-Dianisidine (ODA) staining and whole mount in situ hybridization were used to analyze erythrocytes. TUNEL assay was used to examine DNA fragmentation.

Results
We observed a linear arrangement of the ventricle and atrium, bradycardia arrhythmia, reduced fractional shortening, circulation with a few or no erythrocytes, and pericardial edema in β-lapachone-treated 52-hpf embryos. Abnormal expression patterns of cmlc2, nppa, BMP4, versican, and nfatc1, and histological analyses showed defects in heart-looping and valve development of β-lapachone-treated embryos. ROS production was observed in erythrocytes and DNA fragmentation was detected in both erythrocytes and endocardium of β-lapachone-treated embryos. Reduction in wall shear stress was uncovered in β-lapachone-treated embryos. Co-treatment with the NQO1 inhibitor, dicoumarol, or the calcium chelator, BAPTA-AM, rescued the erythrocyte-deficiency in circulation and heart-looping defect phenotypes in β-lapachone-treated embryos. These results suggest that the induction of apoptosis of endocardium and erythrocytes by β-lapachone is mediated through an NQO1- and calcium-dependent pathway.

Conclusions
The novel finding of this study is that β-lapachone affects heart morphogenesis and function through the induction of apoptosis of endocardium and erythrocytes. In addition, this study further demonstrates the importance of endocardium and hemodynamic forces on heart morphogenesis and contractile performance.
Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan
Authors: Chen Chien-Yuan , Sheng Wang-Huei , Cheng Aristine , Chen Yee-Chun , Tsay Woei , Tang Jih-Luh , Huang Shang-Yi , Chang Shan-Chwen , Tien Hwei-Fang 
Published: September 2011

Abstract

Background
Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.

Method
A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.

Results
Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.

Conclusions
Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.
A case of bilateral self-induced keratoconus in a patient with tourette syndrome associated with compulsive eye rubbing: case report
Authors: Kandarakis Artemios , Karampelas Michael , Soumplis Vasileios , Panos Christos , Makris Nikolaos , Kandarakis Stylianos , Karagiannis Dimitrios 
Published: September 2011

Abstract

Background
Tourette syndrome is a neurologic disorder that is characterized by repetitive muscle contractions that produce stereotyped movements or sounds. Approximately 50% of individuals with TS also exhibit obsessive-compulsive behaviors including eye rubbing. We report a case of bilateral self-induced keratoconus in a patient with TS, associated with compulsive eye rubbing.

Case presentation
A 35-year-old man was first seen in our clinic as an outpatient due to rapid deterioration of vision in his right eye associated with pain and tearing, over a period of one month. Slit lamp biomicroscopy of the right eye showed a central stromal scar due to corneal hydrops. Clinical examination and corneal topography of the left eye were normal. Six months later the patient developed corneal hydrops of his left eye. During the following examinations his vision continued to deteriorate in both eyes, while a central stromal scar was forming in his left cornea. Four years after the initial examination the patient's visual acuity was no light perception in the right eye and counting fingers at 33 cm in the left eye. His right eye was phthisic.

Conclusions
Our patient developed a rapidly progressing bilateral corneal ectasia and phthisis of his right eye during a time period of 4 years. This unusual pattern suggests that the patient's compulsive behavior compromised both of his corneas and led to bilateral keratoconus.
Initial clinical experience with a novel vertebral augmentation system for treatment of symptomatic vertebral compression fractures: A case series of 26 consecutive patients
Authors: Korovessis Panagiotis , Repantis Thomas , Miller Larry E , Block Jon E 
Published: September 2011

Abstract

Background
Minimally invasive vertebral augmentation procedures are widely used to treat vertebral compression fractures although procedural polymethylmethacrylate cement leakage remains common. We report herein our initial experience with a novel vertebral augmentation technique designed to treat symptomatic vertebral osteoporotic fractures and osteolytic metastases with minimal cement extravasation.

Methods
Forty-two vertebral fractures were identified in 26 consecutive patients (mean age 74 ± 9 years). All patients were treated with a novel percutaneous vertebral augmentation device (Kiva® VCF Treatment System, Benvenue Medical, Santa Clara, CA, USA). Indications for surgery included recent (≤ 3 months) symptomatic osteoporotic vertebral fracture (n = 34) and pathologic vertebral fractures (e.g. metabolic bone disease, myeloma, metastasis) (n = 8) located between T10 and S1. Patient outcomes were evaluated pre-treatment and at 2- and 6-month follow-up visits. Postoperative cement extravasation was assessed with computed tomography. Patient-reported back pain was quantified using an 11-point numeric scale. Back-specific functional disability was self-reported with the Oswestry Disability Index on a 0 to 100% scale.

Results
No cases of intraoperative hypotension, respiratory disturbance, neurological deterioration, infection, or death were observed. There were 2 (4.8%) levels where anterior cement leakage was visible radiographically in patients with osteolyses. No intracanal leakage was observed. Back pain scores improved 71% (p < 0.001) from pre-treatment to the 6-month follow-up. Back function improved 56% from baseline to 6 months (p < 0.001).

Conclusions
The initial clinical experience with the Kiva® System demonstrated significant improvements in back pain and function with minimal and clinically insignificant procedural cement leakage.
Does Glycine max leaves or Garcinia Cambogiapromote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial
Authors: Kim Ji-Eun , Jeon Seon-Min , Park Ki Hun , Lee Woo Song , Jeong Tae-Sook , McGregor Robin A , Choi Myung-Sook 
Published: September 2011

Abstract

Background
Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles.

Methods
Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants.

Results
EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group.

Conclusions
Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.
Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells
Authors: Yang Mei , Chen Jingqi , Su Fang , Yu Bin , Su Fengxi , Lin Ling , Liu Yujie , Huang Jian-Dong , Song Erwei 
Published: September 2011

Abstract

Background
Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.

Results
We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.

Conclusions
We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.
Abolished adherence alters signaling pathways in phorbol ester-induced human U937 cells
Authors: Otte Anna , Mandel Katharina , Reinstrom Gesche , Hass Ralf 
Published: September 2011

Abstract
Phorbol ester (TPA) treatment of human U937 myeloid leukemia cells is associated with increasing adherence and monocyte-like maturation whereby the role of β2 integrin-mediated attachment for subsequent growth properties and the differentiation program remains unclear. Here, stably-transfected U937 cells with a pMTH1 vector containing the β2 integrin gene of CD11b in antisense orientation (asCD11b-U937) demonstrated a significantly reduced proliferative capacity in contrast to control vector transfectants (pMTH1-U937) or wild-type U937 cells. Phorbol ester exposure induced adherence and growth arrest in more than 90% of pMTH1-U937 and wild-type U937 cells after 72 h. In contrast, TPA-treated asCD11b-U937 failed to attach and the proliferation continued in more than 30% of the cells. Moreover, increased apoptosis appeared in asCD11b-U937 after TPA induction in contrast to pMTH1-U937 cells. In addition, non-specific inhibition of adherence on an agarose surface demonstrated internucleosomal DNA fragmentation in both, pMTH1-U937 and asCD11b-U937 after TPA treatment indicating a functional relationship between abolished adherence, regulation of proliferation and induction of apoptosis. Western blot analysis revealed differences in the expression levels and altered phosphorylation patterns of Pyk-2, pp60src and p42/p44 MAP kinases between pMTH1-U937 and asCD11b-U937 following TPA exposure which was also substantiated by Pyk-2 immunoprecipitation. These findings suggested that induced adherence predominantly mediated by a functional CD11b/CD18 integrin in U937 cells is involved in the activation of downstream signaling kinases and contributes to cell cycle regulation and apoptosis during monocytic maturation.
Different patterns of NF-κB and Notch1 signaling contribute to tumor-induced lymphangiogenesis of esophageal squamous cell carcinoma
Authors: Su Chunhua , Chen Zhenguang , Luo Honghe , Su Yihua , Liu Wangkai , Cai Lie , Wang Tao , Lei Yiyan , Zhong Beilong 
Published: September 2011

AbstractBackgroundLymph node involvement and tumor-induced lymphangiogenesis appear as the earliest features of esophageal squamous cell carcinoma (ESCC), although the molecular regulatory mechanisms involved have remained unclear. Our aim was to investigate the contribution of NF-κB and Notch1 signaling to lymph node involvement and tumor-induced lymphangiogenesis in ESCC.Material and methodsNF-κB and Notch1 expression in 60 tissue samples of ESCC were assessed by immunohistochemical staining. The correlations of NF-κB and Notch1 with lymph node involvement, lymphatic vessel density (LVD), podoplanin, and vascular endothelial growth factor-C (VEGF-C) were further evaluated to determine the association of NF-κB and Notch1 expression with tumor-induced lymphangiogenesis.ResultsChi-square tests revealed that NF-κB and Notch1 expression in ESCC tissues were significant associated with lymph node metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF-κB, but weak expression of Notch1, was observed in tumor tissues with lymph nodes involvement (P< 0.05 for both). The mean histoscores of LVD, podoplanin, and VEGF-C staining were higher in high-NF-κB-expressing tissue than in low-expressing tissue (P< 0.05 for each). In contrast, the mean histoscores of LVD and VEGF-C staining were lower in high-Notch1-expressing tissue than in low-expressing tissue (P< 0.05 for both). A multiple factors analysis of LVD and VEGF-C further demonstrated that LVD and VEGF-C status were significantly correlated with NF-κB and Notch1 expression in tumors. NF-κB and Notch1 expression were also significantly inversely correlated (P< 0.05).ConclusionThese results suggest that different patterns of NF-κB and Notch1 signaling contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC, and reveal that up-regulation of NF-κB is associated with down-regulation of Notch1 in tumor tissue.
erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines
Authors: Knowlden Janice M , Gee Julia MW , Barrow Denise , Robertson John F , Ellis Ian O , Nicholson Robert I , Hutcheson Iain R 
Published: September 2011

Abstract
Introduction
Recently we reported that insulin receptor substrate 1 (IRS-1), classically an adaptor protein for the insulin-like growth factor type I receptor (IGF-IR), associates with the epidermal growth factor receptor in oestrogen receptor (ER)-positive (ER+) tamoxifen-resistant breast cancer cells. In this study, we examined whether IRS-1 also associates with another erbB receptor family member, erbB3, and what impact this might have on IGF-IR signalling in three ER+ breast cancer cell lines.

Methods
Immunoprecipitation and Western blot analysis were utilised to examine the potential association between erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells in the absence and presence of the erbB3/4 ligand heregulin β1 (HRGβ1). Subsequently, the impact of a selective IGF-IR/IR inhibitor 4-anilino-5-bromo-2-[4-(2-hydroxy-3-(N, N-dimethylamino)propoxy)anilino]pyrimidine on this association and HRGβ1 signalling was assessed in these cell lines. Immunohistochemical analysis of a small cohort of ER+ breast cancer patient samples was also performed to determine the potential clinical relevance of this novel interaction.

Results
Immunoprecipitation and Western blot analysis revealed an interaction between erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells, with HRGβ1 significantly enhancing this recruitment and promoting IRS-1 phosphorylation at Y612. IRS-1 participates in erbB3 signalling in MCF-7 and T47D cells as IRS-1 knockdown impaired HRGβ1 signalling. Importantly, recruitment of IRS-1 by erbB3 reduced IRS-1 association with IGF-IR in MCF-7 and T47D cells, whilst blockade of IGF-IR-enhanced erbB3-IRS-1 interaction and sensitised both cell lines to HRGβ1, allowing HRGβ1 to override IGF-IR blockade. Consequently, suppression of IRS-1 signalling enhanced the effects of IGF-IR inhibition in these cells. This novel interaction may have clinical relevance, as immunohistochemical analysis of a small ER+ breast tumour series revealed significant positive correlations between phosphorylated IRS-1 Y612 expression and total erbB3, phosphorylated Akt and Ki-67 expression.

Conclusions
IRS-1 can be recruited to IGF-IR and erbB3 in ER+ breast cancer cells, and this provides an adaptive resistance mechanism when these receptors are targeted individually. Consequently, cotargeting IGF-IR and either erbB3 or IRS-1 should prove to be a more effective strategy for the treatment of ER+ breast cancer.