bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-21: an oncomir on strike in prostate cancer
Authors: Folini Marco , Gandellini Paolo , Longoni Nicole , Profumo Valentina , Callari Maurizio , Pennati Marzia , Colecchia Maurizio , Supino Rosanna , Veneroni Silvia , Salvioni Roberto , Valdagni Riccardo , Daidone Maria Grazia , Zaffaroni Nadia 
Published: January 2010

Abstract

Background
Aberrant expression of microRNAs, small non-coding RNA molecules that post-transcriptionally repress gene expression, seems to be causatively linked to the pathogenesis of cancer. In this context, miR-21 was found to be overexpressed in different human cancers (e.g. glioblastoma, breast cancer). In addition, it is thought to be endowed with oncogenic properties due to its ability to negatively modulate the expression of tumor-suppressor genes (e.g. PTEN) and to cause the reversion of malignant phenotype when knocked- down in several tumor models. On the basis of these findings, miR-21 has been proposed as a widely exploitable cancer-related target. However, scanty information is available concerning the relevance of miR-21 for prostate cancer. In the present study, we investigated the role of miR-21 and its potential as a therapeutic target in two prostate cancer cell lines, characterized by different miR-21 expression levels and PTEN gene status.

Results
We provide evidence that miR-21 knockdown in prostate cancer cells is not sufficient per se i) to affect the proliferative and invasive potential or the chemo- and radiosensitivity profiles or ii) to modulate the expression of the tumor-suppressors PTEN and Pdcd4, which in other tumor types were found to be regulated by miR-21. We also show that miR-21 is not differently expressed in carcinomas and matched normal tissues obtained from 36 untreated prostate cancer patients subjected to radical prostatectomy.

Conclusions
Overall, our data suggest that miR-21 is not a central player in the onset of prostate cancer and that its single hitting is not a valuable therapeutic strategy in the disease. This supports the notion that the oncogenic properties of miR-21 could be cell and tissue dependent and that the potential role of a given miRNA as a therapeutic target should be contextualized with respect to the disease.
Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score
Authors: Gencer Baris , Vaucher Paul , Herzig Lilli , Verdon François , Ruffieux Christiane , Bösner Stefan , Burnand Bernard , Bischoff Thomas , Donner-Banzhoff Norbert , Favrat Bernard 
Published: January 2010

Abstract

Background
Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care.

Methods
Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group.

Results
The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increasing with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%.

Conclusions
This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.
Down-Regulation of Toll-Like Receptor 4 Gene Expression by Short Interfering RNA Attenuates Bone Cancer Pain in a Rat Model
Authors: Lan Liu Si , Ping Yang Jian , Na Wang Li , Miao Jiang , Cheng Qiu Qiao , Ni Ma Zhen , Lei Liu , Fang Li Cai , Guang Ren Chun , Jin Zhou , Wei Li 
Published: January 2010

Background: This study demonstrates a critical role in CNS innate immunity of the microglial Toll-like receptor 4 (TLR4) in the induction and maintenance of behavioral hypersensitivity in a rat model of bone cancer pain with the technique of RNA interference (RNAi). We hypothesized that after intramedullary injection of Walker 256 cells (a breast cancer cell line) into the tibia, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. Results: We assessed tactile allodynia and spontaneous pain in female Sprague-Dawley (SD) rats after intramedullary injection of Walker 256 cells into the tibia. In a complementary study, TLR4 small interfering RNA (siRNA) was administered intrathecally to bone cancer pain rats to reduce the expression of spinal TLR4. The bone cancer pain rats treated with TLR4 siRNA displayed significantly attenuated behavioral hypersensitivity and decreased expression of spinal microglial markers and proinflammatory cytokines compared with controls. Only intrathecal injection of TRL4 siRNA at post-inoculation day 4 could prevent initial development of bone cancer pain; intrathecal injection of TRL4 siRNA at post-inoculation day 9 could attenuate, but not completely block, well-established bone cancer pain. Conclusions: TLR4 might be the main mediator in the induction of bone cancer pain. Further study of this early, specific, and innate CNS/microglial response, and how it leads to sustained glial/neuronal hypersensitivity, might lead to new therapies for the prevention and treatment of bone cancer pain syndromes.
Effects of Parecoxib and Fentanyl on Nociception-Induced Cortical Activity
Authors: Peng Yuan-Zhi , Li Xiao-Xi , Wang Ying-Wei 
Published: January 2010

Background: Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist) and parecoxib (a selective cyclooxygenase-2 inhibitor) on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals) were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results: Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG) desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity), while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion: Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.
The Roles of iPLA2, TRPM8 and TRPA1 in Chemically Induced Cold Hypersensitivity
Authors: Gentry Clive , Stoakley Natalie , Andersson David A , Bevan Stuart 
Published: January 2010

Background: The cooling agents menthol and icilin act as agonists at TRPM8 and TRPA1. In vitro, activation of TRPM8 by icilin and cold, but not menthol, is dependent on the activity of a sub-type of phospholipase A2, iPLA2. Lysophospholipids (e.g. LPC) produced by PLA2 activity can also activate TRPM8. The role of TRPA1 as a primary cold sensor in vitro is controversial, although there is evidence that TRPA1 plays a role in behavioural responses to noxious cold stimuli. In this study, we have investigated the roles of TRPM8 and TRPA1 and the influence of iPLA2 on noxious cold sensitivities in naïve animals and after local administration of menthol, icilin and LPC. The roles of the channels in cold sensitivity were investigated in mice lacking either TRPM8 ( Trpm8−/−) or TRPA1 ( Trpa1−/−). Results: Intraplantar administration of icilin evoked a dose-dependent increase in sensitivity to a 10°C stimulus that was inhibited by iPLA2 inhibition with BEL. In contrast the cold hypersensitivities elicited by intraplantar menthol and LPC were not inhibited by BEL treatment. BEL had no effect on basal cold sensitivity and mechanical hypersensitivities induced by the TRPV1 agonist, capsaicin, and the P2X3 agonist α,β-methylene ATP. Both Trpm8−/− and Trpa1−/− mice showed longer latencies for paw withdrawal from a 10°C stimulus than wild-type littermates. Cold hypersensitivities induced by either icilin or LPC were absent in Trpm8−/− mice but were retained in Trpa1−/− mice. In contrast, cold hypersensitivity evoked by menthol was present in Trpm8−/− mice but was lost in Trpa1−/− mice. Conclusions: The findings that iPLA2 inhibition blocked the development of cold hypersensitivity after administration of icilin but failed to affect menthol-induced hypersensitivity agree well with our earlier in vitro data showing a differential effect of iPLA2 inhibition on the agonist activities of these agents. The ability of LPC to induce cold hypersensitivity supports a role for iPLA2 in modulating TRPM8 activity in vivo. Studies on genetically modified mice demonstrated that the effects of icilin and LPC were mediated by TRPM8 and not TRPA1. In contrast, menthol-induced cold hypersensitivity was dependent on expression of TRPA1 and not TRPM8.
Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation
Authors: Nicodemo Alexander A , Pampillo Macarena , Ferreira Lucimar T , Dale Lianne B , Cregan Tamara , Ribeiro Fabiola M , Ferguson Stephen SG 
Published: January 2010

Abstract
Group I metabotropic glutamate receptors (mGluRs) are coupled via Gαq/11 to the activation of phospholipase Cβ, which hydrolyzes membrane phospholipids to form inositol 1,4,5 trisphosphate and diacylglycerol. This results in the release of Ca2+ from intracellular stores and the activation of protein kinase C. The activation of Group I mGluRs also results in ERK1/2 phosphorylation. We show here, that the proline-rich tyrosine kinase 2 (Pyk2) interacts with both mGluR1 and mGluR5 and is precipitated with both receptors from rat brain. Pyk2 also interacts with GST-fusion proteins corresponding to the second intracellular loop and the distal carboxyl-terminal tail domains of mGluR1a. Pyk2 colocalizes with mGluR1a at the plasma membrane in human embryonic kidney (HEK293) cells and with endogenous mGluR5 in cortical neurons. Pyk2 overexpression in HEK293 results in attenuated basal and agonist-stimulated inositol phosphate formation in mGluR1 expressing cells and involves a mechanism whereby Pyk2 displaces Gαq/11 from the receptor. The activation of endogenous mGluR1 in primary mouse cortical neuron stimulates ERK1/2 phosphorylation. Treatments that prevent Pyk2 phosphorylation in cortical neurons, and the overexpression of Pyk2 dominant-negative and catalytically inactive Pyk2 mutants in HEK293 cells, prevent ERK1/2 phosphorylation. The Pyk2 mediated activation of ERK1/2 phosphorylation is also Src-, calmodulin- and protein kinase C-dependent. Our data reveal that Pyk2 couples the activation mGluRs to the mitogen-activated protein kinase pathway even though it attenuates mGluR1-dependent G protein signaling.
Ultrastaging of lymph node in uterine cancers
Authors: Bézu Corinne , Coutant Charles , Ballester Marcos , Feron Jean-Guillaume , Rouzier Roman , Uzan Serge , Daraï Emile 
Published: January 2010

Abstract

Background
Lymph node status is an important prognostic factor and a criterion for adjuvant therapy in uterine cancers. While detection of micrometastases by ultrastaging techniques is correlated to prognosis in several other cancers, this remains a matter of debate for uterine cancers. The objective of this review on sentinel nodes (SN) in uterine cancers was to determine the contribution of ultrastaging to detect micrometastases.

Methods
Review of the English literature on SN procedure in cervical and endometrial cancers and histological techniques including hematoxylin and eosin (H&E) staining, serial sectioning, immunohistochemistry (IHC) and molecular techniques to detect micrometastases.

Results
In both cervical and endometrial cancers, H&E and IHC appeared insufficient to detect micrometastases. In cervical cancer, using H&E, serial sectioning and IHC, the rate of macrometastases varied between 7.1% and 36.3% with a mean value of 25.8%. The percentage of women with micrometastases ranged from 0% and 47.4% with a mean value of 28.3%. In endometrial cancer, the rate of macrometastases varied from 0% to 22%. Using H&E, serial sectioning and IHC, the rate of micrometastases varied from 0% to 15% with a mean value of 5.8%. In both cervical and endometrial cancers, data on the contribution of molecular techniques to detect micrometastases are insufficient to clarify their role in SN ultrastaging.

Conclusion
In uterine cancers, H&E, serial sectioning and IHC appears the best histological combined technique to detect micrometastases. Although accumulating data have proved the relation between the risk of recurrence and the presence of micrometastases, their clinical implications on indications for adjuvant therapy has to be clarified.
MALT lymphoma of the rectum, presenting with rectal prolapsus: a case report
Authors: Ersoz Feyzullah , Toros Ahmet Burak , Bektas Hasan , Ozcan Ozhan , Koc Oguz , Arikan Soykan 
Published: January 2010

AbstractUp to now, there have been only a few reported cases of Mucosa-associated lymphoid tissue (MALT) lymphomas arising in the rectum. Its clinical presentation is indistinguishable from that of rectal carcinoma but the treatment is apparently different. Symptoms of primary lymphomas involving the rectum include; anorexia, weight loss, change in bowel habits, obstruction, and bleeding. These symptoms are not disease specific and can be seen in many other gastrointestinal disorders. Patients with polypoid masses may present with obstruction symptoms. In this rare case, a female patient admitted to the emergency service with prolapsus of a rectal mass.The optimal treatment of rectal MALT lymphoma is not well defined yet, given the rarity of the disease. Surgical resection of the localized lesion and following adjuvant chemotherapy has proved to be an effective treatment option. However, a close and long-lasting follow-up is important.
Cellular zinc homeostasis is a regulator in monocyte differentiation of HL-60 cells by 1α,25-dihydroxyvitamin D3
Authors: Dubben Svenja , Hönscheid Andrea , Winkler Katja , Rink Lothar , Haase Hajo 
Published: January 2010

Abstract
A decrease of free cellular zinc promotes monocyte differentiation of HL-60 cells by alleviating zinc-mediated inhibition of adenylate cyclase.
It was reported previously that zinc-deficient mice show impaired lymphopoiesis. At the same time, monocyte numbers in these animals are increased, indicating a negative impact of zinc on monocyte development. Here, we investigate the role of zinc homeostasis in the differentiation of myeloid precursors into monocytes. Reduced gene expression of several zinc transporters, predominantly from the Zip family, was observed during 1α, 25-dihydroxyvitamin D3 (1,25D3)-induced differentiation of HL-60 cells. This was accompanied by a reduction of intracellular-free zinc, measured by FluoZin-3. Amplifying this reduction with the zinc chelator TPEN or zinc-depleted cell-culture medium enhanced 1,25D3-induced expression of monocytic surface markers CD11b and CD14 on HL-60, THP-1, and NB4 cells. In contrast, differentiation of NB4 cells to granulocytes was not zinc-sensitive, pointing toward a specific effect of zinc on monocyte differentiation. Further, monocyte functions, such as TNF-α secretion, phagocytosis, and oxidative burst, were also augmented by differentiation in the presence of TPEN. The second messenger cAMP promotes monocyte differentiation. We could show that zinc inhibits the cAMP-synthesizing enzyme adenylate cyclase, and chelation of zinc by TPEN increases cAMP generation after stimulation with the adenylate cyclase activator forskolin. Based on our in vitro results and the in vivo observations from the literature, we suggest a model in which the intracellular-free zinc concentration limits AC activity, and the decrease of zinc after 1,25D3 treatment promotes differentiation by relieving AC inhibition. Thus, cellular zinc homeostasis acts as an endogenous modulator of monocyte differentiation.
CFTR-mediated halide transport in phagosomes of human neutrophils
Authors: Painter Richard G , Marrero Luis , Lombard Gisele A , Valentine Vincent G , Nauseef William M , Wang Guoshun 
Published: January 2010

Abstract
CFTR transports chloride anions necessary for HOCl production and optimal microbicidal activity in human neutrophil phagosomes.
Chloride serves as a critical component of innate host defense against infection, providing the substrate for MPO-catalyzed production of HOCl in the phagosome of human neutrophils. Here, we used halide-specific fluorescent sensors covalently coupled to zymosan particles to investigate the kinetics of chloride and iodide transport in phagosomes of human neutrophils. Using the self-ratioable fluorescent probe specific for chloride anion, we measured chloride dynamics within phagosomes in response to extracellular chloride changes by quantitative fluorescence microscopy. Under the experimental conditions used, normal neutrophils showed rapid phagosomal chloride uptake with an initial influx rate of 0.31 ± 0.04 mM/s (n=5). GlyH-101, a CFTRinh, decreased the rate of uptake in a dose-dependent manner. Neutrophils isolated from CF patients showed a significantly slower rate of chloride uptake by phagosomes, having an initial influx rate of 0.043 ± 0.012 mM/s (n=5). Interestingly, the steady-state level of chloride in CF phagosomes was ∼26 mM, significantly lower than that of the control (∼68 mM). As CFTR transports chloride as well as other halides, we conjugated an iodide-sensitive probe as an independent approach to confirm the results. The dynamics of iodide uptake by neutrophil phagosomes were monitored by flow cytometry. CFTRinh172 blocked 40–50% of the overall iodide uptake by phagosomes in normal neutrophils. In a parallel manner, the level of iodide uptake by CF phagosomes was only 20–30% of that of the control. Taken together, these results implicate CFTR in transporting halides into the phagosomal lumen.
Utility of Various Functional and Anatomic Imaging Modalities for Detection of Ectopic Adrenocorticotropin-Secreting Tumors
Authors: Zemskova Marina S. , Gundabolu Bhaskar , Sinaii Ninet , Chen Clara C. , Carrasquillo Jorge A. , Whatley Millie , Chowdhury Iffat , Gharib Ahmed M. , Nieman Lynnette K. 
Published: January 2010

AbstractContext: Because ectopic ACTH-secreting (EAS) tumors are often occult, improved imaging is needed.Objective: Our objective was to evaluate the utility of [111In-DTPA-d-Phe]pentetreotide scintigraphy [octreotide (OCT)] imaging at 6 mCi [low OCT (LOCT)] and 18 mCi [high OCT (HOCT)], [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) and [18F]l-3,4-dihydroxyphenylalanine (F-DOPA)-PET scans, computed tomography (CT), and magnetic resonance imaging (MRI).Design and Setting: The study was a prospective evaluation at a clinical research center.Patients: Forty-one subjects participated, 30 (17 female) with resected EAS tumors and 11 (three female) with occult EAS, based on inferior petrosal sinus sampling results and imaging studies.Intervention: Intervention included CT and MRI of neck, chest, abdomen, LOCT (with or without HOCT) and FDG- or F-DOPA-PET without CT every 6–12 months.Main Outcome Measure: Tumor identification was the main outcome measure.Results: Most recent results were analyzed. Eighteen patients had tumor resected on the first visit; otherwise, surgery occurred 33 ± 25 (9–99) months later. Tumor size was 1.9 ± 1.7 (0.8–8.0) cm; 83% were intrathoracic. CT, MRI, LOCT, HOCT, FDG-PET, and F-DOPA-PET had sensitivities per patient of 93% [95% confidence interval (CI) = 79–98%], 90% (95% CI = 74–96%), 57% (95% CI = 39–73%), 50% (95% CI = 25–75%), 64% (95% CI = 35–85%), and 55% (95% CI = 28–79%) and positive predictive values (PPV) per lesion of 66, 74, 79, 89, 53, and 100%, respectively. LOCT and PET detected only lesions seen by CT/MRI; abnormal LOCT or F-DOPA-PET improved PPV of CT/MRI. By modality, the fraction of patients with one or more false-positive findings was 50% by CT, 31% by MRI, 18% by L/HOCT, and 18% by FDG-PET. Eight occult EAS patients had 64 ± 58 (9–198) months follow-up; others had none.Conclusions: High sensitivity and PPV suggest thoracic CT/MRI plus LOCT scans for initial imaging, with lesion confirmation by two modalities.
Investigations on the power losses and thermal behaviour of rolling element bearings
Authors: Pouly F , Changenet C , Ville F , Velex P , Damiens B 
Published: January 2010

Temperature levels and distributions in rolling element bearings (REBs) depend on many parameters such as load, rotational speed, lubricant, etc. In this context, the understanding of power loss and heat generation mechanisms is a major issue especially for REBs operating at high speeds, since they largely control the component behaviour, its capacity to operate at high temperatures, and ultimately its integrity. It is commonly accepted that the power losses in high-speed bearings can be divided into (a) sliding friction losses in the contacts between the rolling elements and races, (b) sliding friction losses (Couette flow) at the cage/race and cage/rolling elements contacts, (c) oil churning losses for splash and dip lubrication. However, there is no general agreement about two other sources namely rolling friction and drag forces, but it seems that whatever the chosen model be the resulting total power losses are equivalent. In the present study, a thermal network approach is presented in order to estimate the temperatures at different locations within a thrust angular ball bearing. Several power loss distributions inside the REBs are considered and their influences on different power losses and on temperatures along with the important role of the oil—air mixture are highlighted.