bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of Psoriasin for non-small cell lung cancer patients and its biological impact on lung cancer cell functions
Authors: Hu Mu , Ye Lin , Ruge Fiona , Zhi Xiuyi , Zhang Lijian , Jiang Wen G 
Published: December 2012

Abstract

Background
Psoriasin (S100A7) is a member of the S100 gene family. Alteration of Psoriasin expression has previously been reported to play an important role in cancer aggressive behaviour. The current study sought to investigate the level of Psoriasin expression at the mRNA level in a cohort of patients with non-small cell lung cancer (NSCLC), the association with clinical implication and outcomes, and the molecular and cellular impact of the protein on lung cancer cells.

Methods
Fresh frozen NSCLC cell carcinoma tissues, along with matched normal tissues were obtained from 83 NSCLC patients who received curative resection from January 2003 to December 2011. The expression of Psoriasin in the NSCLC specimens was assessed using both quantitative real time PCR (QPCR) and immunochemical staining. Knockdown and forced expression of Psoriasin in NSCLC cell lines were carried out using constructed plasmid vectors carrying either ribozyme transgenes targeting human Psoriasin or full-length coding sequence, respectively. The effect of Psoriasin on the functions of NSCLC cells was determined using a variety of in vitro cell function assays.

Results
Higher mRNA levels of Psoriasin were observed in tumour tissues when compared to both the paired normal background tissues and none paired normal tissues (p = 0.0251 and 0.0195). The mRNA level of Psoriasin was found to be higher in the squamous carcinoma (P=0.035). Higher Psoriasin expression is associated with poor prognosis. The cell function tests had supportive results to the clinical findings. Over-expression of Posriasin in lung cancer cells (SK-MES-1) resulted in an increase in in vitro growth and invasiveness. In contrast, Psoriasin knockdown suppressed cell growth and invasion (P<0.05), but increased cell adhesion (P<0.05).

Conclusions
Psoriasin expression is increased in lung cancer, more specifically in lung squamous carcinoma compared with adenocarcinoma, and is associated with poor prognosis. Psoriasin plays crucial roles in regulating the growth and invasion of lung cancer cells.
The impact of secondary hyperparathyroidism on the efficacy of antiresorptive therapy
Authors: Kincse Gyöngyvér , Varga József , Somogyi Péter , Szodoray Péter , Surányi Péter , Gaál János 
Published: December 2012

Abstract

Background
The aim of the present study was to assess whether the efficacy of bisphosphonate treatment is influenced by PTH levels measured in newly diagnosed osteoporotic patients and to identify the threshold value, beyond which PTH level negatively influences therapeutic efficacy.

Methods
One hundred and thirty-eight osteoporotic patients were enrolled into the study. All subjects underwent laboratory screening, bone densitometry with DEXA, and x-ray imaging. The changes in bone density were evaluated after a mean follow-up period of 13.37 ± 1.29 months. Correlation analysis was performed on the clinical data of patients, the percentage changes of BMD values, and the PTH levels measured at the beginning of study, using SPSS software.

Results
The mean age of the subjects was 64.82 ± 10.51 years, and the female-to-male ratio was 116/22. Baseline BMD value measured with AP DEXA scanning was 0.854 ± 0.108 g/cm2 in the L1-4 vertebrae and 0.768 ± 0.115 g/cm2 in the left femoral neck. By the end of the follow-up period, these values changed to 0.890 ± 0.111 g/cm2 and 0.773 ± 0.111 g/cm2, respectively. We found a statistically significant, negative correlation between PTH levels and the percentage changes of lumbar BMD values measured at the end of the follow-up (correlation coefficient R2 = 0.121, p < 0.0001). The analysis of frequency histograms suggested that negative effects on bone might be expected above a PTH level of 60 pg/mL (7.3 pmol/L).

Conclusion
Our findings imply that a baseline PTH level over 60 ng/mL can reduce the efficacy of bisphosphonate treatment.
Sentinel lymph node biopsy in melanoma: Our 8-year clinical experience in a single French institute (2002–2009)
Authors: Biver-Dalle Caroline , Puzenat Eve , Puyraveau Marc , Delroeux Delphine , Boulahdour Hatem , Sheppard Frances , Pelletier Fabien , Humbert Philippe , Aubin François 
Published: December 2012

Abstract

Background
Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma.

Methods
A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation.

Results
The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients.

Conclusion
Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.
Prakriti (Ayurvedic concept of constitution) and variations in platelet aggregation
Authors: Bhalerao Supriya , Deshpande Tejashree , Thatte Urmila 
Published: December 2012

Abstract

Background
Ayurveda, the Indian traditional system of medicine describes a unique concept “prakriti”, genetically determined, categorising the population into several subgroups based on phenotypic characters like appearance, temperament and habits. The concept is claimed to be useful in predicting an individual’s susceptibility to a particular disease, prognosis of that illness and selection of therapy. The present study was carried out to study if the platelet aggregatory response and its inhibition by aspirin varied in the different prakriti subtypes.

Methods
After obtaining Institutional Ethics Committee permission, normal healthy individuals of either sex between the age group 18 to 30 years were recruited in the study. Their prakriti evaluation was done using a standardized validated questionnaire (TNMC Prakriti 2004). Their Platelet Rich Plasma was incubated with either aspirin [2.5micro-mole (μM) and 5μM] or distilled water as control for three minutes after which the aggregatory response to 5μM Adenosine Diphosphate (ADP) was measured over a period of 7 minutes.

Results
We observed that in the study population of normal healthy participants (n= 137), ADP-induced maximal platelet aggregation (MPA) was highest among the Vata-pitta prakriti individuals [Median (range), 83.33% (52.33-96)] as compared to the other prakriti types and these individuals responded better to lower dose of aspirin compared to other prakriti types.

Conclusions
Our results suggest that identifying the prakriti may help in individualising therapy or predicting proneness to a disease.
Inhibition of lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by chloroform fraction of Cudrania tricuspidata in RAW 264.7 macrophages
Authors: Yang Gabsik , Lee Kyungjin , Lee Mihwa , Ham Inhye , Choi Ho-Young 
Published: December 2012

Abstract

Background

Cudrania tricuspidata extract is an important traditional herbal remedy for tumors, inflammation, gastritis, and liver damage and is predominantly used in Korea, China, and Japan. However, the anti-inflammatory effects of the extract have not yet been conclusively proved.

Methods
In this study, we investigated the effects of the CHCl3 fraction (CTC) of a methanol extract of C. tricuspidata on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophage cells and mouse peritoneal macrophages, and the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in RAW 264.7 macrophage cells.

Results
We observed that the protein expression levels of inducible NO synthase and COX-2 enzymes were markedly inhibited by CTC in a concentration-dependent manner. In addition, CTC reduced the production of TNF-α, IL-1β, and IL-6 in the LPS-stimulated RAW 264.7 macrophage cells.

Conclusions
Our results show that the C. tricuspidata extract could modulate macrophage-mediated inflammatory functions such as the overproduction of cytokines, NO, and PGE2. The CTC was found to be the active fraction in this context.
Evaluation of iron and manganese-coated pumice application for the removal of as(v) from aqueous solutions
Authors: Far Leila Babaie , Souri Bubak , Heidari Masoumeh , Khoshnavazi Roshan 
Published: December 2012

Abstract
Arsenic contamination of water has been recognized as a serious environmental issue and there are reports on its epidemiological problems to human health. The objective of this study was to evaluate the performances of iron-coated pumice and manganese-coated pumice as the adsorbents for removing arsenate from aqueous solutions. The effect of various parameters such as adsorbent dose, contact time, pH and initial concentration on removal efficiency of arsenate were evaluated in batch mode. The data obtained from the kinetic studies were analyzed using kinetic models of pseudo-first-order and pseudo-second-order. In addition, two isotherm models of Freundlich and Langmuir were used to fit the experimental data. The results showed that the optimum dosage of iron-coated pumice and manganese-coated pumice for arsenate removal were 40 and 80 g/L whereas the adsorption process reached equilibrium after 80 and 100 min, respectively. The maximum removal efficiency of arsenate using the two adsorbents were both recorded in pH=3 as the removal efficiency gradually declined following every increase in pH values of the solution. Iron-coated pumice also showed to have high removal efficiency when the initial concentration of arsenate was high while the low concentration of arsenate was efficiently removed by manganese-coated pumice. Moreover, it was depicted that the adsorption kinetics by both adsorbents followed pseudo-second order equation and the uptake data of arsenate were well fitted with Langmuir isotherm model. Therefore, it could be concluded that iron and manganese-coated pumice could be considered as suitable adsorbents for arsenate removal from aqueous solutions.
Pegylated interferon α enhances recovery of memory T cells in e antigen positive chronic hepatitis B patients
Authors: Liu Yong Zhe , Hou Feng Qin , Ding Peng , Ren Yuan Yuan , Li Shi Hong , Wang Gui Qiang 
Published: December 2012

AbstractBackgroundInterferons (IFNs) are a group of cytokines commonly used in the clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic effects are highly correlated with recovery of host antiviral immunity. Clearance of hepatitis B virus (HBV) is mediated partially by activated functional memory T cells. The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-α (IFN-α) therapy and to identify new biomarkers for predicting antiviral immune responses.MethodsPeripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-α at week 0 (baseline) and week 24. Co-expression of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a subset of CD127 and CXCR4 positive memory T cells were assessed. In addition, perforin, granzyme B, and interferon-γ (IFN-γ) expressions were also analyzed by flow cytometric analysis after intracytoplasmic cytokine staining (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-γ expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated.ResultsAt week 24, PD-1 and CD244 expression in CD8 memory T cells were down-regulated (P < 0.05,P < 0.05, respectively), along with decreased HBV DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8 and CD4 memory T cells was up-regulated (P < 0.05,P < 0.05, respectively), especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory T cells after pegylated IFN-α treatment (P < 0.05), which was inversely correlated with HBV DNA loads (r = −0.47,P = 0.001). The responders had a higher IFN-γ expression in memory T cells than the non-responders did after HBV antigen re-stimulationin vitro.ConclusionPegylated IFN-α treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. The expressions of CXCR4 and CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome of treatment.
Carbon nanoparticles induce ceramide- and lipid raft-dependent signalling in lung epithelial cells: a target for a preventive strategy against environmentally-induced lung inflammation
Authors: Peuschel Henrike , Sydlik Ulrich , Grether-Beck Susanne , Felsner Ingo , Stöckmann Daniel , Jakob Sascha , Kroker Matthias , Haendeler Judith , Gotić Marijan , Bieschke Christiane , Krutmann Jean , Unfried Klaus 
Published: December 2012

Abstract

Background
Particulate air pollution in lung epithelial cells induces pathogenic endpoints like proliferation, apoptosis, and pro-inflammatory reactions. The activation of the epidermal growth factor receptor (EGFR) is a key event responsible for signalling events involving mitogen activated protein kinases specific for these endpoints. The molecular events leading to receptor activation however are not well understood. These events are relevant for the toxicological evaluation of inhalable particles as well as for potential preventive strategies in situations when particulate air pollution cannot be avoided. The current study therefore had the objective to elucidate membrane-coupled events leading to EGFR activation and the subsequent signalling cascade in lung epithelial cells. Furthermore, we aimed to identify the molecular target of ectoine, a biophysical active substance which we described to prevent carbon nanoparticle-induced lung inflammation.

Methods
Membrane signalling events were investigated in isolated lipid rafts from lung epithelial cells with regard to lipid and protein content of the signalling platforms. Using positive and negative intervention approaches, lipid raft changes, subsequent signalling events, and lung inflammation were investigated in vitro in lung epithelial cells (RLE-6TN) and in vivo in exposed animals.

Results
Carbon nanoparticle treatment specifically led to an accumulation of ceramides in lipid rafts. Detailed analyses demonstrated a causal link of ceramides and subsequent EGFR activation coupled with a loss of the receptor in the lipid raft fractions. In vitro and in vivo investigations demonstrate the relevance of these events for carbon nanoparticle-induced lung inflammation. Moreover, the compatible solute ectoine was able to prevent ceramide-mediated EGFR phosphorylation and subsequent signalling as well as lung inflammation in vivo.

Conclusion
The data identify a so far unknown event in pro-inflammatory signalling and contribute to the understanding of particle cell interaction and therefore to risk identification and risk assessment of inhalable xenobiotics. Moreover, as this cellular reaction can be prevented by the well tolerated substance ectoine, a molecular preventive strategy for susceptible persons against airway inflammation is proposed.
Clinical outcome for patients with dedifferentiated chondrosarcoma: a report of 9 cases at a single institute
Authors: Yokota Kazuya , Sakamoto Akio , Matsumoto Yoshihiro , Matsuda Shuichi , Harimaya Katsumi , Oda Yoshinao , Iwamoto Yukihide 
Published: December 2012

Abstract

Background
Dedifferentiated chondrosarcomas consist of two distinguishable components: low-grade chondrosarcoma components and high-grade dedifferentiated components.

Materials and methods
Nine cases (4 males, 5 females) of dedifferentiated chondrosarcoma were treated in our institute. The average age was 58.6 (range, 37–86) years. The tumor location was the long bone in 7 cases (femur, n=5; humerus, n=1; tibia, n=1) and the pelvic bone in 2 cases. The average time from appearance of symptoms to treatment was 9.4 (range, 1–40) months.

Results and discussion
On plain radiographs, matrix mineralization was seen in all 9 cases (100%). Bone destruction was observed in 5 of 9 cases (56%), while pathological fracture was seen in one femur case (11%). Lung metastasis was observed in all cases (initially in 5 cases; during the treatment course in 4 cases). Surgery was performed in 8 cases, with local recurrence occurring in 2 of those cases (time to recurrence, 2 and 10 months). Chemotherapy was administered in 4 cases, but did not result in significant improvement. All 9 cases died of lung metastases, with a median survival time of 10 (range, 3.4-18.8) months. The presence of initial metastasis at diagnosis was a significant unfavorable prognostic factor.

Conclusion
The prognosis of dedifferentiated chondrosarcoma is dismal. With the lack of convincing evidence of the benefit of chemotherapy, complete surgical excision is the initial recommended treatment.
Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection
Authors: Tamayev Robert , Akpan Nsikan , Arancio Ottavio , Troy Carol M , D’Adamio Luciano 
Published: December 2012

Abstract

Background
Mutations in either Aβ Precursor protein (APP) or genes that regulate APP processing, such as BRI2/ITM2B and PSEN1/PSEN2, cause familial dementias. Although dementias due to APP/PSEN1/PSEN2 mutations are classified as familial Alzheimer disease (FAD) and those due to mutations in BRI2/ITM2B as British and Danish dementias (FBD, FDD), data suggest that these diseases have a common pathogenesis involving toxic APP metabolites. It was previously shown that FAD mutations in APP and PSENs promote activation of caspases leading to the hypothesis that aberrant caspase activation could participate in AD pathogenesis.

Results
Here, we tested whether a similar mechanism applies to the Danish BRI2/ITM2B mutation. We have generated a genetically congruous mouse model of FDD, called FDDKI, which presents memory and synaptic plasticity deficits. We found that caspase-9 is activated in hippocampal synaptic fractions of FDDKI mice and inhibition of caspase-9 activity rescues both synaptic plasticity and memory deficits.

Conclusion
These data directly implicate caspase-9 in the pathogenesis of Danish dementia and suggest that reducing caspase-9 activity is a valid therapeutic approach to treating human dementias.
New analogues of 13-hydroxyocatdecadienoic acid and 12-hydroxyeicosatetraenoic acid block human blood platelet aggregation and cyclooxygenase-1 activity
Authors: Hirz Taghreed , Khalaf Ali , El-Hachem Nehme , Mrad May F , Abdallah Hassan , Créminon Christophe , Grée René , Merhi Raghida Abou , Habib Aïda , Hachem Ali , Hamade Eva 
Published: December 2012

Abstract

Background
Thromboxane A2 is derived from arachidonic acid through the action of cyclooxygenases and thromboxane synthase. It is mainly formed in blood platelets upon activation and plays an important role in aggregation. Aspirin is effective in reducing the incidence of complications following acute coronary syndrome and stroke. The anti-thrombotic effect of aspirin is obtained through the irreversible inhibition of cyclooxygenases. Analogues of 12-hydroxyeicosatetraenoic acid and 13-hydroxyocatdecadienoic acid were shown previously to modulate platelet activation and to block thromboxane receptors.

Results and discussion
We synthesized 10 compounds based on the structures of analogues of 12-hydroxyeicosatetraenoic acid and 13-hydroxyocatdecadienoic acid and evaluated their effect on platelet aggregation triggered by arachidonic acid. The structure activity relationship was evaluated. Five compounds showed a significant inhibition of platelet aggregation and highlighted the importance of the lipidic hydrophobic hydrocarbon chain and the phenol group. Their IC50 ranged from 7.5 ± 0.8 to 14.2 ± 5.7 μM (Mean ± S.E.M.). All five compounds decreased platelet aggregation and thromboxane synthesis in response to collagen whereas no modification of platelet aggregation in response to thromboxane receptor agonist, U46619, was observed. Using COS-7 cells overexpressing human cyclooxygenase-1, we showed that these compounds are specific inhibitors of cyclooxygenase-1 with IC50 ranging from 1.3 to 12 μM. Docking observation of human recombinant cyclooxygenase-1 supported a role of the phenol group in the fitting of cyclooxygenase-1, most likely related to hydrogen bonding with the Tyr 355 of cyclooxygenase-1.

Conclusions
In conclusion, the compounds we synthesized at first based on the structures of analogues of 12 lipoxygenase metabolites showed a role of the phenol group in the anti-platelet and anti-cyclooxygenase-1 activities. These compounds mediate their effects via blockade of cyclooxygenase-1.
A novel monoclonal antibody of human stem cell factor inhibits umbilical cord blood stem cell ex vivo expansion
Authors: Fan Jie , Ding Xinxin , Jiang Yongping 
Published: December 2012

Abstract
Stem cell factor (SCF) activates hematopoietic stem cell (HSC) self-renewal and is being used to stimulate the ex vivo expansion of HSCs. The mechanism by which SCF supports expansion of HSCs remains poorly understood. In cord blood ex vivo expansion assays, a newly produced anti-SCF monoclonal antibody (clone 23C8) was found to significantly inhibit the expansion of CD34+ cells. This antibody appears to bind directly to a part of SCF that is critical for biological activity toward expansion of CD34+ cells, which is located in the first 104 amino acids from the NH2-terminus.