bluuebunny/crossref_metadata_2025_split huggingface dataset:
PI3K class IB controls the cell cycle checkpoint promoting cell proliferation in hepatocellular carcinoma
Authors: Dituri Francesco , Mazzocca Antonio , Lupo Luigi , Edling Charlotte E. , Azzariti Amalia , Antonaci Salvatore , Falasca Marco , Giannelli Gianluigi 
Published: July 2011

AbstractAlterations of the cell cycle checkpoint frequently occur during hepatocarcinogenesis. Dysregulation of the phosphatidylinositol‐3‐kinases (PI3K) signaling pathway is believed to exert a potential oncogenic effect in hepatocellular carcinoma (HCC), ultimately promoting tumor cell proliferation. However, the impact of PI3K on cell cycle regulation remains unclear. We used a combined loss‐ and gain‐of‐function approach to address the involvement of p110γ in HCC cell proliferation, apoptosis and the cell cycle. We also investigated the correlation between p110γ and Ki‐67 in 24 HCC patients. Finally, we analyzed the expression levels of p110γ and cell cycle regulators in HCC tissues. We found that PI3K class IB, but not class IA, is required for HCC cell proliferation. In particular, we found that knock‐down of p110γ inhibits cell proliferation because of an arrest of the cell cycle in the G0‐G1 phase. This effect is associated with an altered expression of proteins regulating the cell cycle progression, including p21, and with an increased apoptosis. By contrast, we found that ectopic expression of p110γ promotes HCC cell proliferation. Tissues analysis performed in HCC patients showed a positive correlation between the expression of p110γ and Ki‐67, a marker of proliferation, and, even more importantly, that p21 expression is up‐regulated in HCC patients with a lower p110γ expression. Our results emphasize the role of p110γ as a promoter of HCC proliferation and unveil an important cell cycle regulation function of this molecule.
Epigenetic regulation by decitabine of melanoma differentiation in vitro and in vivo
Authors: Alcazar Oscar , Achberger Susan , Aldrich Wayne , Hu Zhenbo , Negrotto Soledad , Saunthararajah Yogen , Triozzi Pierre 
Published: July 2011

AbstractApoptosis genes, such as TP53 and p16/CDKN2A, that mediate responses to cytotoxic chemotherapy, are frequently nonfunctional in melanoma. Differentiation may be an alternative to apoptosis for inducing melanoma cell cycle exit. Epigenetic mechanisms regulate differentiation, and DNA methylation alterations are associated with the abnormal differentiation of melanoma cells. The effects of the deoxycytidine analogue decitabine (5‐aza‐2′‐deoxycytidine), which depletes DNA methyl transferase 1 (DNMT1), on melanoma differentiation were examined. Treatment of human and murine melanoma cells in vitro with concentrations of decitabine that did not cause apoptosis inhibited proliferation accompanied by cellular differentiation. A decrease in promoter methylation, and increase in expression of the melanocyte late‐differentiation driver SOX9, was followed by increases in cyclin‐dependent kinase inhibitors (CDKN) p27/CDKN1B and p21/CDKN1A that mediate cell cycle exit with differentiation. Effects were independent of the TP53, p16/CDKN2A and also the BRAF status of the melanoma cells. Resistance, when observed, was pharmacologic, characterized by diminished ability of decitabine to deplete DNMT1. Treatment of murine melanoma models in vivo with intermittent, low‐dose decitabine, administered sub‐cutaneously to limit high peak drug levels that cause cytotoxicity and increase exposure time for DNMT1 depletion, and with tetrahydrouridine to decrease decitabine metabolism and further increase exposure time, inhibited tumor growth and increased molecular and tumor stromal factors implicated in melanocyte differentiation. Modification of decitabine dose, schedule and formulation for differentiation rather than cytotoxic objectives inhibits the growth of melanoma cells in vitro and in vivo.
Molecular history of Richter syndrome: origin from a cell already present at the time of chronic lymphocytic leukemia diagnosis
Authors: Rossi Davide , Spina Valeria , Forconi Francesco , Capello Daniela , Fangazio Marco , Rasi Silvia , Martini Maurizio , Gattei Valter , Ramponi Antonio , Larocca Luigi M. , Bertoni Francesco , Gaidano Gianluca 
Published: July 2011

AbstractRichter syndrome (RS) represents the transformation of chronic lymphocytic leukemia to aggressive lymphoma. We explored intraclonal diversification (ID) of immunoglobulin genes in order to (i) follow the evolutionary history of the RS clone (ii) compare the role of ID in clonally related RS vs. clonally unrelated cases. Most (10/11, 90.9%) clonally related RS stem from the predominant clone observed at CLL diagnosis. One single RS had a transformation pattern compatible with sequential evolution from a secondary CLL subclone. Once RS transformation had occurred, all secondary CLL subclones disappeared and were substituted by the dominant RS clone with its own descendants. These observations suggest that genetic lesions associated with RS transformation are acquired by a cell belonging to the original CLL clone, rather than being progressively accumulated by later CLL subclones. Accordingly, most (9/11, 81.1%) clonally related RS harbored a genetic lesion disrupting TP53 that was already present, though at subclonal levels, in 5/11 (45.5%) samples of the paired CLL phase. A fraction of clonally related RS switched off ID (4/11, 36.4%) or reduced the levels of ID (5/11, 45.4%) at transformation. Conversely, all clonally unrelated RS harbored ID and were characterized by a significantly higher mutation frequency compared to clonally related RS (median: 1.18 × 10−3
vs. 0.13 × 10‐3; p =0.002). These data indicate that (i) clonally related RS stems from a cell that is already present within the initial CLL clone and (ii) clonally unrelated and clonally related RS are biologically distinct disorders also in terms of antigen affinity maturation.
The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression
Authors: Eom Bang Wool , Jo Min Jung , Kook Myeong‐Cherl , Ryu Keun Won , Choi Il Ju , Nam Byung‐Ho , Kim Young‐Woo , Lee Jun Ho 
Published: July 2011

AbstractSOX group F genes are important regulators of angiogenesis and lymphangiogenesis. The aim of the present study was to examine the relationships between Sox group F expression and clinicopathological factors in gastric cancer. Three hundred and fifteen gastric cancer tissues and the corresponding normal gastric tissue were obtained from the tumor bank at the National Cancer Center, Korea. SOX group F mRNA levels in these tissues were evaluated by reverse transcriptase polymerase chain reaction (RT‐PCR). The serum levels of SOX 18 proteins in 219 gastric cancer patients and in 30 healthy volunteers were also measured by enzyme‐linked immunosorbent assay. Furthermore, immunohistochemistry (IHC) was performed on 679 gastric cancer tissues and the clinicopathological characteristics, as well as the survival rates of SOX 18 positive and negative gastric cancers were compared. RT‐PCR showed that SOX group F mRNA was increased in the gastric cancer tissues compared to the normal gastric tissues (p < 0.001, respectively). The serum levels of SOX 18 protein were also increased in gastric cancer patients compared to healthy volunteers. IHC showed that of the 679 gastric cancer cases, 177 (26.1%) were positive for SOX 18 expression in their tumor stroma, and the frequencies of both lymphovascular invasion and lymph node metastases were higher in the SOX 18 positive than in the negative group. Both the 5‐year survival and the recurrence‐free survival were shorter for SOX 18 positive tumors (p = 0.023 and 0.012, respectively). SOX 18 expression might be a prognostic tumor marker and a potential therapeutic target in gastric cancer.
A four‐gene methylation marker panel as triage test in high‐risk human papillomavirus positive patients
Authors: Eijsink J.J.H. , Lendvai Á. , Deregowski V. , Klip H.G. , Verpooten G. , Dehaspe L. , de Bock G.H. , Hollema H. , van Criekinge W. , Schuuring E. , van der Zee A.G.J. , Wisman G.B.A. 
Published: July 2011

AbstractCervical neoplasia‐specific biomarkers, e.g. DNA methylation markers, with high sensitivity and specificity are urgently needed to improve current population‐based screening on (pre)malignant cervical neoplasia. We aimed to identify new cervical neoplasia‐specific DNA methylation markers and to design and validate a methylation marker panel for triage of high‐risk human papillomavirus (hr‐HPV) positive patients. First, high‐throughput quantitative methylation‐specific PCRs (QMSP) on a novel OpenArray™ platform, representing 424 primers of 213 cancer specific methylated genes, were performed on frozen tissue samples from 84 cervical cancer patients and 106 normal cervices. Second, the top 20 discriminating methylation markers were validated by LightCycler® MSP on frozen tissue from 27 cervical cancer patients and 20 normal cervices and ROCs and test characteristics were assessed. Three new methylation markers were identified (JAM3, EPB41L3 and TERT), which were subsequently combined with C13ORF18 in our four‐gene methylation panel. In a third step, our methylation panel detected in cervical scrapings 94% (70/74) of cervical cancers, while in a fourth step 82% (32/39) cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and 65% (44/68) CIN2+ were detected, with 21% positive cases for ≤CIN1 (16/75). Finally, hypothetical scenario analysis showed that primary hr‐HPV testing combined with our four‐gene methylation panel as a triage test resulted in a higher identification of CIN3 and cervical cancers and a higher percentage of correct referrals compared to hr‐HPV testing in combination with conventional cytology. In conclusion, our four‐gene methylation panel might provide an alternative triage test after primary hr‐HPV testing.
Co‐expression of hepatocyte growth factor and c‐Met predicts peritoneal dissemination established by autocrine hepatocyte growth factor/c‐Met signaling in gastric cancer
Authors: Toiyama Yuji , Yasuda Hiromi , Saigusa Susumu , Matushita Kouhei , Fujikawa Hiroyuki , Tanaka Koji , Mohri Yasuhiko , Inoue Yasuhiro , Goel Ajay , Kusunoki Masato 
Published: July 2011

AbstractEpithelial–mesenchymal transition (EMT) promotes and facilitates migration and invasion of epithelial tumor cells. EMT is induced by factors such as hepatocyte growth factor (HGF). This study aimed to establish whether the HGF/c‐Met pathway is associated with gastric cancer metastasis; especially peritoneal dissemination. HGF and c‐Met expression and EMT‐related molecules were evaluated using real‐time PCR and immunohistochemistry. The role of the HGF/c‐Met pathway in EMT and anoikis was determined, and kinase inhibitor SU11274 was tested for its ability to block HGF‐induced biological effects. In HGF−/c‐Met+ gastric cancer cells, recombinant HGF promoted an EMT phenotype that was characterized by morphology, impaired E‐cadherin and induction of vimentin. HGF promoted cell growth, invasiveness and migration and inhibition of anoikis. SU11274 blocked HGF‐induced EMT and biological effects in vitro. In HGF+/c‐Met+ gastric cancer cells, HGF did not affect the biological outcome of EMT and anoikis, but SU11274 exerted the same inhibitory effects as in HGF−/c‐Met+ cells. In vivo, HGF+/c‐Met+ gastric cancer cells only established peritoneal dissemination and SU11274 inhibited tumor growth. Clinically, HGF expression was significantly correlated with c‐Met expression in gastric cancer. Increased HGF and c‐Met had a significant association with poor prognosis and predicted peritoneal dissemination. We demonstrated that the HGF/c‐Met pathway induces EMT and inhibition of anoikis in gastric cancer cells. Co‐expression of HGF and c‐Met has the potential to promote peritoneal dissemination in gastric cancer. Blockade of the autocrine HGF/c‐Met pathway could be clinically useful for the treatment of peritoneal dissemination in gastric cancer.
Knockdown of metallopanstimulin‐1 inhibits NF‐κB signaling at different levels: The role of apoptosis induction of gastric cancer cells
Authors: Yang Zhong‐Yin , Qu Ying , Zhang Qing , Wei Min , Liu Chuan‐Xu , Chen Xue‐Hua , Yan Min , Zhu Zheng‐Gang , Liu Bing‐Ya , Chen Guo‐Qiang , Wu Ying‐Li , Gu Qin‐Long 
Published: July 2011

AbstractThe ribosomal protein S27 (metallopanstimulin‐1, MPS‐1) has been reported to be a multifunctional protein, with increased expression in a number of cancers. We reported previously that MPS‐1 was highly expressed in human gastric cancer. Knockdown of MPS‐1 led to spontaneous apoptosis and repressed proliferation of human gastric cancer cells in vitro and in vivo. However, how does MPS‐1 regulate these processes is unclear. Here we performed microarray and pathway analyses to investigate possible pathways involved in MPS‐1 knockdown‐induced apoptosis in gastric cancer cells. Our results showed that knockdown of MPS‐1 inhibited NF‐κB activity by reducing phosphorylation of p65 at Ser536 and IκBα at Ser32, inhibiting NF‐κB nuclear translocation, and down‐regulating its DNA binding activity. Furthermore, data‐mining the Gene‐Regulatory‐Network revealed that growth arrest DNA damage inducible gene 45β (Gadd45β), a direct NF‐κB target gene, played a critical role in MPS‐1 knockdown‐induced apoptosis. Over‐expression of Gadd45β inhibited MPS‐1 knockdown‐induced apoptosis via inhibition of JNK phosphorylation. Taken together, these data revealed a novel pathway, the MPS‐1/NF‐κB/Gadd45β signal pathway, played an important role in MPS‐1 knockdown‐induced apoptosis of gastric cancer cells. This study sheds new light on the role of MPS‐1/NF‐κB in apoptosis and the possible use of MPS‐1 targeting strategy in the treatment of gastric cancer.
Developmental evolution of the insect retina: insights from standardized numbering of homologous photoreceptors
Authors: Friedrich Markus , Wood Emily J. , Wu Meng 
Published: July 2011

AbstractThe canonical number of eight photoreceptors and their arrangement in the ommatidia of insect compound eyes is very conserved. However significant variations exist in selective groups, such as the Lepidoptera and Hymenoptera, which independently evolved additional photoreceptors. For this and historical reasons, heterogeneous labeling conventions have been in use for photoreceptor subtypes, despite developmentally and structurally well‐defined homologies. Extending earlier efforts, we introduce a universal photoreceptor subtype classification key that relates to the Drosophila numbering system. Its application is demonstrated in major insect orders, with detailed information on the relationship to previous conventions. We then discuss new insights that result from the improved understanding of photoreceptor subtype homologies. This includes evidence of functionally imposed ground rules of differential opsin expression, the underappreciated role of R8 as ancestral color receptor, the causes and consequences of parallel R7 photoreceptor addition in Hymenoptera and Lepidoptera, and the ancestral subfunctionalization of outer photoreceptors cells, which may be only developmentally recapitulated in Drosophila. We conclude with pointing out the need for opsin expression data from a wider range of insect orders. J. Exp. Zool. (Mol. Dev. Evol.) 316:484–499, 2011. © 2011 Wiley Periodicals, Inc.
Spring temperature variability in northern Fennoscandia AD 1693–2011
Authors: Loader Neil J. , Jalkanen Risto , Mccarroll Danny , Moberg Anders 
Published: July 2011

AbstractA reconstruction of spring (April–May) temperature for northern Fennoscandia developed from the Tornionjoki (Tornio river) long cryophenological record of ice break‐up dates, back to AD 1693, is presented. The record is strongly climatically sensitive and explains 67% of the variance in the instrumental data over the last 150 years. The record exhibits a stepped decrease in the duration of the river's ice cover by 14 days, equivalent to an increase in April–May mean temperature of approximately 2.5°C over the last three centuries. The relationship between the date of ice break‐up, and accumulated daily mean temperatures (>0°C) is investigated. Uncertainty in the observation of ice break‐up is also considered in addition to the potential of this time series for regional climate model validation. Copyright © 2011 John Wiley & Sons, Ltd.
Physico‐chemical and toxicological assessment of liquid wastes from olive processing‐related industries
Authors: Pierantozzi Pierluigi , Zampini Catiana , Torres Mariela , Isla María I , Verdenelli Romina A , Meriles José M , Maestri Damián 
Published: July 2011

AbstractBACKGROUND: In the last few years, agricultural uses of waste waters from olive processing‐related industries have been gaining interest mainly with a view to composting or bio‐fertilizers. The present work examines physico‐chemical, toxicological and geno‐toxicological properties of three liquid wastes, namely olive mill wastewater (OMWW), olive wet husk and olive brine. The effect of OMWW spreading on soil microbial activity and biomass was also evaluated.RESULTS: Data from Artemia salina and Lactuca sativa toxicity tests indicated high levels of lethality, and inhibitory effects on seed germination and seedling growth of all olive wastes. The genotoxicity assays using Allium cepa tests showed contrasting results. At high concentrations, olive wastes caused inhibition or suppression of mitosis. However, they did not produce induced anaphase aberrations. Data on reversion of Salmonella thyphimurium strains using the Ames test indicated that the olive wastes did not present mutagenic activity. Results from the field experiment showed that OMWW at a 500 m3 ha−1 had the highest values of both soil microbial activity and biomass after 3 months of the amendment application.CONCLUSION: This work adds new data for environmental risk assessment of olive industrial wastes. Direct use of olive wastes for agricultural purposes should be limited owing to their possible chemotoxic, phytotoxic and antimicrobial effects. Copyright © 2011 Society of Chemical Industry
Effects of freeze‐dried Mitsuokella jalaludinii culture and Natuphos® phytase supplementation on the performance and nutrient utilisation of broiler chickens
Authors: Lan Ganqiu , Abdullah Norhani , Jalaludin Syed , Ho Yin Wan 
Published: July 2011

AbstractBACKGROUND: Phytate‐bound phosphorus (P) in poultry diets is poorly available to chickens. Hence exogenous phytase is often added to their diets. Mitsuokella jalaludinii is a rumen bacterial species that produces high phytase activity. In this study the effects of freeze‐dried active M. jalaludinii culture (FD‐AMJC) and Natuphos® phytase (phytase N) supplementations on the growth performance and nutrient utilisation of broiler chickens fed a low‐available P (aP) diet were evaluated.RESULTS: Supplementation of FD‐AMJC or phytase N to the low‐aP diet improved the feed intake, feed conversion rate, body weight gain, dry matter (DM) digestibility and P, Ca and Mn retention, increased the tibia bone ash content, Ca and P concentrations in tibia DM and P and Zn concentrations in plasma and reduced the P excretion of broiler chickens. However, the feed conversion rate, P and Ca retention, DM digestibility and reduction of P excretion were better with FD‐AMJC than phytase N supplementation. Supplementation of FD‐AMJC to the low‐aP diet also improved the apparent metabolisable energy value of the diet, Cu and Zn retention and crude protein digestibility, but phytase N supplementation did not.CONCLUSION: FD‐AMJC supplementation was more efficient in improving nutrient utilisation and reducing P excretion in chickens than phytase N supplementation. Copyright © 2011 Society of Chemical Industry
Method validation for the determination of propellant components by Soxhlet extraction and gas chromatography/mass spectrometry
Authors: Fryš Ondřej , Bajerová Petra , Eisner Aleš , Mudruňková Martina , Ventura Karel 
Published: July 2011

AbstractA fast, sensitive, and accurate GC/MS method for the quantification of aliphatic nitroesters (ethylene glycol dinitrate, nitroglycerin, and triethylene glycol dinitrate) and aromatic amines (diphenylamine, 2‐nitrodiphenylamine, and triphenylamine) in propellants was developed and validated. This method comprises a Soxhlet extraction step with dichloromethane, followed by separation on a capillary column MDN‐5. Ionization of the analytes is carried out using electron ionization. The limit of quantification of the method was 1% w/w for aliphatic nitroesters and 0.1% w/w for aromatic amines (diphenylamine and triphenylamine). Values of repeatability and reproducibility for analyzed compounds were smaller than values of the maximum allowed tolerances of the Horwitz‐equation RSDmax and 2/3 RSDmax. Values of accuracy for selected compounds were below the acceptable threshold of 15% for all tested levels in the range of calibration curve excepting the lowest concentration of calibration curve for nitroglycerin and aromatic amines. During the validation of method, temperature instability in injection port of gas chromatograph and column was observed for 2‐nitrodiphenylamine. Hence, it follows worse results of accuracy and linearity and 2‐nitrodiphenylamine was not validated successfully.
Hot-topic debate on kidney function: Renal-sparing approaches are beneficial
Authors: Durand François 
Published: July 2011

Key Points
1. Renal function is frequently compromised in candidates for transplantation with advanced cirrhosis. These patients frequently have chronic and irreversible kidney changes at the time of transplantation.
2. The accumulated incidence of chronic renal failure is high in liver transplant recipients. Chronic renal failure has a deleterious impact on the outcome.
3. Calcineurin inhibitor (CNI)–based immunosuppression is highly effective at preventing rejection. However, CNI nephrotoxicity has a central role in the occurrence of chronic renal failure.
4. Renal function impairment frequently occurs within the first year after transplantation. Once renal function is significantly impaired [glomerular filtration rate (GFR) < 60 mL/minute/1.73 m2], any intervention is unlikely to result in a return to normal renal function. Early interventions are needed to prevent chronic and irreversible kidney injury.
5. De novo CNI minimization has been proven to be effective at reducing the rate of impaired renal function after transplantation. The reduction in the CNI doses should be offset by the addition of mycophenolate mofetil or enteric-coated mycophenolate sodium.
6. Delayed CNI minimization in patients with established renal insufficiency may result in a significant improvement in the GFR, even though the increase in the GFR after minimization is generally modest.
7. Mammalian target of rapamycin (mTOR) inhibitors are considered nonnephrotoxic immunosuppressive agents. They may be an option for improving renal function in liver transplant recipients. However, not all patients with renal dysfunction benefit from a switch to mTOR inhibitors. In addition, the benefits in terms of renal function should be balanced against specific side effects.
8. New immunosuppressive agents without intrinsic nephrotoxicity are currently under development for solid organ transplantation. These agents could help to reduce the burden of impaired renal function in transplantation in the near future.