bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma
Authors: Baiocchi Robert A. , Alinari Lapo , Lustberg Mark E. , Lin Thomas S. , Porcu Pierluigi , Li Xiaobai , Johnston Jeffrey S. , Byrd John C. , Blum Kristie A. 
Published: December 2010

AbstractBACKGROUND:In vitro studies in mantle cell lymphoma (MCL) cell lines and patient‐derived cells have demonstrated synergistic apoptosis with combined rituximab and bortezomib (R‐bortezomib) compared with single‐agent bortezomib. Therefore, the authors of this report evaluated R‐bortezomib in a preclinical model and in a phase 2 clinical trial.METHODS:A Hu‐MCL‐severe combined immunodeficiency (SCID) model engrafted with the Jeko cell line was treated with R‐bortezomib, bortezomib, or rituximab. Twenty‐five patients with relapsed follicular lymphoma (n = 11) and MCL (n = 14) received 375 mg/m2 rituximab on Days 1 and 8 and 1.3 to 1.5 mg/m2 bortezomib on Days 1, 4, 8, and 11 every 21 days for a median of 3 cycles (range, 1‐5 cycles).RESULTS:R‐bortezomib resulted in a statistically significant improvement in overall survival in Hu‐MCL‐SCID mice. In the clinical trial, the overall response rate was 40% in all 25 patients, 55% in patients with follicular lymphoma, and 29% in patients with MCL. The estimated 2‐year progression‐free survival (PFS) rate was 24% (95% confidence interval [CI], 10%‐53%) in all patients and 60% (95% CI, 20%‐85%) in responding patients. Thirteen patients (52%) developed grade 3 neurotoxicity, which consisted of constipation/ileus, sensory or motor neuropathy, or orthostatic hypotension. Patients who were heterozygous for the CD32a (Fcγ receptor IIa) 131 histidine (H) to arginine (R) polymorphism had a significantly decreased PFS (P = .009) after R‐bortezomib compared with HH and RR homozygotes.CONCLUSIONS:R‐bortezomib had significant activity in patients with relapsed or refractory follicular lymphoma and MCL, although an unexpectedly high incidence of grade 3 neurologic toxicity was a potential limiting factor with this combination. Cancer 2011. © 2010 American Cancer Society.
Induction of MUC5AC mucin by conjugated bile acids in the esophagus involves the phosphatidylinositol 3‐kinase/protein kinase C/activator protein‐1 pathway
Authors: Song Shumei , Byrd James C. , Guha Sushovan , Liu Kai‐Feng , Koul Dimpy , Bresalier Robert S. 
Published: December 2010

AbstractBACKGROUND:Bile reflux contributes to the development of esophageal injury and neoplasia. The mucin 5AC (MUC5AC) is absent in the normal squamous epithelium of the esophagus but is strongly expressed in Barrett esophagus (BE). The objective of this study was to determine whether and how bile acids influence the expression of MUC5AC in the esophagus.METHODS:MUC5AC expression was studied by immunohistochemistry and immunoblotting in human tissues, in tissues from a rat model of BE, and in SKGT‐4 cultured esophageal epithelial cells. MUC5AC transcription was studied by real‐time polymerase chain reaction and transient transfection assays.RESULTS:MUC5AC was absent from normal squamous epithelium but was present in 100% of Barrett specimens and in 61.5% of human esophageal adenocarcinoma tissues that were examined. MUC5AC protein expression was induced to a greater degree by conjugated bile acids than by unconjugated bile acids, and this occurred at the transcriptional level. In the rat reflux model, MUC5AC mucin was expressed abundantly in tissues of BE stimulated by duodenoesophageal reflux. Conjugated bile acids induced AKT phosphorylation in SKGT‐4 cells but had no effect on extracellular signal‐regulated protein kinases 1 and 2, c‐Jun N‐terminal kinase, or protein‐38 kinase phosphorylation. The phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 and a dominant‐negative protein kinase C (AKT) construct prevented the induction of MUC5AC by conjugated bile acids. Transactivation of AP‐1 by conjugated bile acids coincided with MUC5AC induction, and cotransfection with a dominant‐negative activator protein‐1 (AP‐1) vector decreased MUC5AC transcription and its induction.CONCLUSIONS:Conjugated bile acids in the bile refluxate contribute to MUC5AC induction in the esophagus. This occurs at the level of transcription and involves activation of the PI3K/AKT/AP‐1 pathway. Cancer 2011. © 2010 American Cancer Society.
Additive effect on survival of Raf kinase inhibitor protein and signal transducer and activator of transcription 3 in high‐grade glioma
Authors: Maresch Judith , Birner Peter , Zakharinov Mikhail , Toumangelova‐Uzeir Kalina , Natchev Sevdalin , Guentchev Marin 
Published: December 2010

AbstractBACKGROUND:Animal studies have shown cooperative contribution of the Ras/Raf/MAPK and PI3K/Akt/mTOR signaling pathways in glioblastoma formation. However, this joint action has not yet been confirmed in human studies.METHODS:The expression of Raf kinase inhibitory protein (RKIP) was examined in 159 patients with high‐grade and low‐grade gliomas and correlated with previously obtained data on the activation of signal transducer and activator of transcription 3 (STAT3), a downstream effector of the PI3K/Akt/mTOR signaling pathway.RESULTS:RKIP expression was associated with a longer overall survival in high‐grade glioma cases without showing a direct or inverse correlation with tyrosine‐705 phosphorylation of STAT3 (pSTAT3). Notably, RKIP‐positive and pSTAT3 negative cases demarcate a patients group with exceptionally long survival, exceeding the prognostic impact of each single marker.CONCLUSIONS:The results of this study indicated that 1) RKIP expression correlates with tumor grade and is a marker for good prognosis in high‐grade gliomas; 2) RKIP expression and lack of pSTAT3 have a cumulative prognostic impact; and 3) RKIP and pSTAT3 are likely to operate independently to influence survival. These findings represented the first human evidence of an additive effect of 2 distinct signaling pathways in high‐grade glioma, suggesting that simultaneous inhibition of multiple pathways should be considered as a treatment strategy for these patients. Cancer 2011. © 2010 American Cancer Society.
Incidence of gastric involvement in patients with nongastrointestinal extranodal marginal zone lymphoma
Authors: Mazloom Ali , Rodriguez Alma , Ha Chul S. , Medeiros L. Jeffery , Wogan Christine , Shihadeh Ferial , Allen Pamela , Fowler Nathan , Dabaja Bouthaina 
Published: December 2010

AbstractBACKGROUND:The current study was conducted to determine the incidence of gastric involvement in patients presenting with extranodal marginal zone lymphoma (MZL) outside the gastrointestinal (GI) tract and to identify clinical or laboratory parameters that predict gastric involvement in such cases.METHODS:The records of 121 consecutive patients who presented with non‐GI extranodal MZL and had undergone esophagogastroduodenoscopy (EGD) as part of their initial workup were retrospectively reviewed. The authors assessed the presence of occult gastric MZL in these patients and possible associations with demographic characteristics; anatomic site of initial presentation; Helicobacter pylori (H. pylori) infection; Zubrod score; International Prognostic Index (IPI); B symptoms; and serum lactate dehydrogenase, hemoglobin, albumin, and β2‐microglobulin levels.RESULTS:The median age at diagnosis of non‐GI MZL was 59 years. The most common primary tumor sites were the salivary/parotid gland (32 patients), ocular adnexa (26 patients), skin (19 patients), and lung (17 patients). Twenty‐two patients (18%) were found to have gastric involvement on EGD. Using logistic regression analysis, factors found to be associated with gastric involvement included: high IPI score (odds ratio [OR], 3.70; P = .03), female sex (OR, 6.50; P = .02), serum β2‐microglobulin level of ≥2.5 mg/L (OR, 3.69; P = .02), and involvement of the aerodigestive mucosal/glandular tissue (OR, 4.50; P = .004). On multivariate logistic analysis, aerodigestive mucosal/glandular sites, H. pylori infection, and an elevated β2‐microglobulin level were found to be associated with gastric involvement.CONCLUSIONS:Routine EGD is recommended for patients with non‐GI MZL, particularly those with primary aerodigestive mucosal/glandular tissue involvement or those with a high IPI, female sex, elevated serum β2‐microglobulin level, or H. pylori infection regardless of the primary tumor site. Cancer 2011. © 2010 American Cancer Society.
Early hypofractionated salvage radiotherapy for postprostatectomy biochemical recurrence
Authors: Kruser Tim J. , Jarrard David F. , Graf Andrew K. , Hedican Sean P. , Paolone David R. , Wegenke John D. , Liu Glenn , Geye Heather M. , Ritter Mark A. 
Published: December 2010

AbstractBACKGROUND:Postprostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5 to 8 weeks of treatment. The authors report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy.METHODS:A total of 108 consecutive patients were treated with salvage radiation therapy to 65 grays (Gy) in 26 fractions of 2.5 Gy. Median follow‐up was 32.4 months. Median presalvage prostate‐specific antigen (PSA) was 0.44 (range, 0.05‐9.50). Eighteen (17%) patients received androgen deprivation after surgery or concurrently with radiation.RESULTS:The actuarial freedom from biochemical failure for the entire group at 4 years was 67% ± 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients, whose median follow‐up was longer at 43 months. One acute grade 3 genitourinary toxicity occurred, with no acute grade 3 gastrointestinal and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (P = .006), PSA doubling time ≤12 months (P = .03), perineural invasion (P = .06), and negative margins (P = .06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (P = .057) and negative margins (P = .088) retained an association with biochemical failure.CONCLUSIONS:Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1‐½ to 3 weeks relative to other treatment schedules commonly used, produces low rates of toxicity, and demonstrates encouraging efficacy at 4 to 5 years. Hypofractionation may provide a convenient, resource‐efficient, and well‐tolerated salvage approach for the estimated 20,000 to 35,000 US men per year experiencing biochemical recurrence after prostatectomy. Cancer 2011. © 2010 American Cancer Society.
Chemical Shift Tensors in Isomers of Adenine: Relation to Aromaticity of Purine Rings?
Authors: Maliňáková Kateřina , Novosadová Lucie , Pipíška Matej , Marek Radek 
Published: December 2010

AbstractThe 13C and 15N chemical shift tensors are measured, calculated, and compared for three N‐benzyladenine isomers with an attempt to characterize differences in electron distribution in the purine ring related to the position of the substituent. Furthermore, the aromaticity of the purine rings is evaluated on the basis of nucleus‐independent chemical shifts, and variations among the isomers are discussed. Both parameters indicate significant differences between the electronic properties of the N3‐substituted compound and the N7/N9 pair of structures, which can be viewed more generally as the reason for the different stabilities of the individual tautomers.
Generation of a novel rtTA transgenic mouse to induce time‐controlled, tissue‐specific alterations in Pax2‐expressing cells
Authors: Burger Alexa , Koesters Robert , Schäfer Beat W. , Niggli Felix K. 
Published: December 2010

AbstractThe paired‐box transcription factor Pax2 plays a major role in early development of the kidney and the central nervous system. It is expressed in the metanephric mesenchyme of the developing kidney, at the midbrain‐hindbrain boundary and the anlagen of the inner ear. The early expression of Pax2, especially in the developing kidney, prompted us to use this locus as a novel genetic tool to introduce temporally‐controlled expression of transgenes. We generated a transgenic Pax2‐rtTA mouse strain through genetic recombineering using a large BAC clone which drives expression of TetO‐controlled transgenes upon doxycycline treatment in natively Pax2‐expressing tissues. We show that expression of a TetO‐responsive lacZ gene is tightly regulated by addition of doxycycline and can be detected in all Pax2‐expressing tissues. Our transgenic Pax2‐rtTA mouse thus represents a suitable tool to study the cell fates and molecular pathways in Pax2‐positive tissues during development, such as the kidney. We further propose that the Pax2‐rtTA tool has great potential to induce time‐controlled, tissue‐specific alterations for tumorigenic transformation of Pax2‐expressing cells for generating in vivo tumor models, such as Wilms tumor. genesis 49:797–802, 2011. © 2011 Wiley‐Liss, Inc.
A Bifunctional Diketimine Ligand for Secondary Building Blocks: Formation of a 2D Copper–Zinc Coordination Polymer
Authors: Rousset Élodie , Whitehorne Todd J. J. , Baslon Valérie , Reber Christian , Schaper Frank 
Published: December 2010

AbstractCondensation of 3‐(aminomethyl)pyridine with acetylacetone in the presence of 2 equiv. of HCl affordedN,N′‐bis(3‐pyridylmethyl)‐2‐amino‐4‐imino‐pent‐2‐ene, nacnacCH2PyH, a diketimine with pendant pyridine donors.Under the same conditions, 2‐ and 4‐(aminomethyl)pyridine afforded the respective 1‐(2‐pyridyl)‐ and 1‐(4‐pyridyl)‐2,4‐dimethylpyrrol. The heteroleptic complex (nacnacCH2Py)(nacnacBn)Zn was obtained upon reaction of nacnacCH2PyH with nacnacBnZnEt. Combining 2 equiv. of this ligand with ZnEt2 afforded the homoleptic complex nacnacCH2Py2Zn. The latter forms a 2D coordination polymer upon reaction with [Cu(NCMe)4][PF6], which shows short‐lived luminescence at ambient temperature. The coordination polymer and complex (nacnacCH2Py)(nacnacBn)Zn were characterised by single‐crystal X‐ray diffraction.
Palm oil analysis in adulterated sesame oil using chromatography and FTIR spectroscopy
Authors: Rohman Abdul , Man Yaakob B. Che 
Published: December 2010

AbstractThis study highlights the application of two analytical techniques, namely GC‐FID and FTIR spectroscopy, for analysis of refined‐bleached‐deodorized palm oil (RBD‐PO) in adulterated sesame oil (SeO). Using GC‐FID, the profiles of fatty acids were used for the evaluation of SeO adulteration. The increased concentrations of palmitic and oleic acids together with the decreased levels of stearic, linoleic, and linolenic acids with the increasing contents of RBD‐PO in SeO can be used for monitoring the presence of RBD‐PO in SeO. Meanwhile, FTIR spectroscopy combined with multivariate calibration of partial least square (PLS) has been successfully developed for the detection and quantification of RBD‐PO in SeO using the combined frequencies of 3040–2995, 1660–1654, and 1150–1050 cm−1. The values of coefficient of determination (R2) for the relationship between actual versus FTIR‐calculated values of RBD‐PO in SeO and root mean square error of calibration (RMSEC) obtained are 0.997 and 1.32% v/v, respectively. In addition, using three factors, the root mean square error of prediction (RMSEP) value obtained using the developed PLS calibration model is relatively low, i.e., 1.83% v/v.Practical Application: The adulteration practice is commonly encountered in fats and oils industry. It involves the replacement of high value edible oils such as sesame oil with the lower ones like palm oil. Gas chromatography and FTIR spectroscopy can be used as reliable and accurate analytical techniques for detection and quantification of palm oil in sesame oil.
Conjugate Addition of 2‐Acetylindole Enolates to Unsaturated Oxazolopiperidone Lactams: Enantioselective Access to the Tetracyclic Ring System of Ervitsine
Authors: Amat Mercedes , Checa Begoña , Llor Núria , Pérez Maria , Bosch Joan 
Published: December 2010

AbstractThe stereochemical outcomes of the conjugate addition reactions of 2‐acetylindole enolates to the unsaturated phenylglycinol‐derived oxazolopiperidone lactams 1a–f have been studied. After reduction of the 2‐acylindole carbonyl group, the Michael adduct cis‐6 underwent a Lewis acid‐promoted intramolecular α‐amidoalkylation, leading enantioselectively to the tetracyclic ring system of the indole alkaloid ervitsine.
Direct Synthesis of Organic Azides from Primary Amines with 2‐Azido‐1,3‐dimethylimidazolinium Hexafluorophosphate
Authors: Kitamura Mitsuru , Yano Masakazu , Tashiro Norifumi , Miyagawa Satoshi , Sando Mitsuyoshi , Okauchi Tatsuo 
Published: December 2010

AbstractOrganic azides were prepared from primary amines in high yields by metal‐free diazo transfer with 2‐azido‐1,3‐dimethylimidazolinium hexafluorophosphate, which is a stable, crystalline solid that is easy to handle.
Sensitivity enhancement of fluorescence detection in CE by coupling and conducting excitation light with tapered optical fiber
Authors: Yang Xiupei , Huo Feng , Yuan Hongyan , Zhang Bo , Xiao Dan , Choi Martin M. F. 
Published: December 2010

AbstractThis paper reports the enhancement of sensitivity of detection for in‐column fiber optic‐induced fluorescence detection system in CE by tapered optical fiber (TOF). Two types of optical fiber, TOF and conventional cylindrical optical fiber (COF), were employed to construct the CE (TOF‐CE and COF‐CE) and were compared for sensitivity to riboflavin (RF). The fluorescence intensities from a RF sample with excitation light sources and fibers at various coupling angles were investigated. The fluorescence signal from TOF‐CE was ca. ten times that of COF‐CE. In addition, the detection performance of four excitation light source‐fiber configurations including Laser‐TOF, Laser‐COF, LED‐TOF, and LED‐COF were compared. The LODs for RF were 0.21, 0.82, 0.80, and 7.5 nM, respectively, for the four excitation light source–fiber configurations. The results demonstrate that the sensitivity obtained by LED‐TOF is close to that of Laser‐COF. Both Laser‐TOF and LED‐TOF can greatly improve the sensitivity of detection in CE. TOF has the major attribute of collecting and focusing the excitation light intensity. Thus, the sensitivity obtained by LED‐TOF without focusing lens is just same as that of LED‐COF with a focusing lens. This demonstrates that the CE system can be further simplified by eliminating the focusing lens for excitation light. LED‐TOF‐CE and LED‐COF‐CE system were applied to the separation and determination of RF in real sample (green tea), respectively. The tapered fiber optic‐induced fluorescence detection system in CE is an ideal tool for trace analysis.
The Berelekh quest: A review of forty years of research in the mammoth graveyard in northeast Siberia
Authors: Pitulko Vladimir V. 
Published: December 2010

AbstractThe Berelekh mammoth graveyard became known following its first scientific description in 1947. Both the “graveyard” and the “archaeological site” were investigated in the early 1970s, and then systematic investigations ended. This article reviews all the available data from a range of sources and provides a complete set of the 36 14C dates so far obtained for the Berelekh geoarchaeological complex. The host deposits of the Berelekh bone bed (or mammoth graveyard) accumulated between 14,000 and 11,000 14C yr B.P., with the most intensive accumulation of bones around 12,300 14C yr B.P. There is almost no chronological overlap between the “graveyard” and “archaeological site” at the same location. Episodes of human habitation near the bone bed, which produced the Late Palaeolithic Berelekh archaeological site, were related to the exploitation of natural mass mammoth accumulation, which was a valuable source of raw material, such as ivory and long bones. The youngest mammoth remains date to 11,800 14C yr B.P. and have no cultural relation to the Dyuktai archaeological culture. © 2010 Wiley Periodicals, Inc.
Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics
Authors: Mensa Laura , Crespo Gonzalo , Gastinger Matthew J. , Kabat Juraj , Pérez-del-Pulgar Sofía , Miquel Rosa , Emerson Suzanne U. , Purcell Robert H. , Forns Xavier 
Published: December 2010

Abstract

Liver transplantation (LT) is a unique model to study hepatitis C virus (HCV) entry into hepatocytes. Recent

in vitro

studies suggest significant changes in the expression of the HCV receptors claudin-1 and occludin after HCV infection. Our aims were: (1) to characterize claudin-1 and occludin expression in grafts from LT recipients and (2) to explore their potential influence on early HCV kinetics and their changes after HCV infection. We included 42 HCV-infected LT recipients and 19 uninfected controls. Claudin-1 and occludin were detected in paraffin-embedded liver biopsies obtained during reperfusion and 3 and 12 months after LT. HCV receptors were characterized by confocal immunofluorescence microscopy; quantification and colocalization studies were performed with dedicated software. Claudin-1 and occludin expression were restricted to the apical pole of hepatocytes. There was a significant correlation between the amount of scavenger receptor B1 at the time of reperfusion and the HCV-RNA decay during the first 24 hours following LT (

r

= 0.55,

P

= 0.007). Similarly, there was a significant correlation between the levels of claudin and occludin and the slope of HCV-RNA increase during the first week after LT (

r

= 0.63,

P

= 0.005). Occludin and claudin-1 levels increased significantly 12 months after LT (

P

= 0.03 and

P

= 0.007, respectively). The expression pattern of both proteins, however, remained unchanged, colocalizing strongly (60%-94%) at the apical membrane of hepatocytes.

Conclusions.

HCV receptor levels at the time of LT seem to modulate early HCV kinetics. Hepatitis C recurrence after LT was associated with increased levels of claudin-1 and occludin in the hepatocyte cell membrane, although it did not alter their localization within the tight junctions. (Hepatology 2011;.)
Innate Immunity and Primary Biliary Cirrhosis: Activated Invariant Natural Killer T Cells Exacerbate Murine Autoimmune Cholangitis and Fibrosis §Δ
Authors: Wu Si-Jie , Yang Yao-Hsu , Tsuneyama Koichi , Leung Patrick S.C. , Illarionov Petr , Gershwin Eric M. , Chuang Ya-Hui 
Published: December 2010

Abstract

Murine models of autoimmunity allow the study of the earliest events in disease pathogenesis. Our laboratory has developed a xenobiotic induced model of primary biliary cirrhosis (PBC) following immunization of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA), an antigen selected following quantitative structure-activity relationship analysis of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the immunodominant autoantigen of PBC. Recent data in humans with PBC has suggested that a major component of liver pathology is due to activation of innate immunity. We took advantage of our 2-OA-BSA model and immunized mice with and without the addition of α-galactosylceramide (α-GalCer), an invariant natural killer T cell activator. Importantly, we report herein that 2-OA-BSA-immunized mice exposed to α-GalCer develop a profound exacerbation of their autoimmune cholangitis, including significant increases in CD8+ T-cell infiltrates, portal inflammation, granuloma formation, and bile duct damage. Furthermore, such mice produce increased levels of antimitochondrial antibodies and have evidence of fibrosis, a feature not previously reported in the murine models of PBC.

Conclusion:

Our data suggests a primary role of innate immunity in the exacerbation of autoimmune cholangitis and also become a logical explanation for the recurrence of PBC following liver transplantation in the absence of major histocompatability complex compatibility. We submit that PBC begins with loss of tolerance to PDC-E2 and a multilineage antimitochondrial response in which autoreactive CD8+ T cells are critical. However, the perpetuation of disease and its exacerbation will also be modulated by innate immune mechanisms. (Hepatology 2011;)