bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor bortezomib
Authors: Liu Feng-Ting , Agrawal Samir G. , Movasaghi Zanyar , Wyatt Peter B. , Rehman Ihtesham U. , Gribben John G. , Newland Adrian C. , Jia Li 
Published: July 2008

Abstract
Dietary flavonoids have many health-promoting actions, including anticancer activity via proteasome inhibition. Bor-tezomib is a dipeptide boronate proteasome inhibitor that has activity in the treatment of multiple myeloma but is not effective in chronic lymphocytic leukemia (CLL). Although CLL cells are sensitive in vitro to bortezomib-induced apoptosis when cultured in medium, the killing activity was blocked when cultured in 50% fresh autologous plasma. Dietary flavonoids, quercetin and myricetin, which are abundant in plasma, inhibited bortezomib-induced apoptosis of primary CLL and malignant B-cell lines in a dose-dependent manner. This inhibitory effect was associated with chemical reactions between quercetin and the boronic acid group, -RB(OH)2, in bortezomib. The addition of boric acid diminished the inhibitory effect of both quercetin and plasma on bortezomib-induced apoptosis. The protective effect was also reduced when myeloma cell lines, but not B-cell lines, were preincubated with quercetin, indicating a direct effect of quercetin on myeloma cells. At high doses, quercetin itself induced tumor cell death. These data indicate that dietary flavonoids limit the efficacy of bortezomib, whereas supplemental inorganic boric acid is able to reverse this. The complex interactions between quercetin, tumor cells, and bortezomib mean caution is required when giving dietary advice to patients.
Comparative transcriptomics of human multipotent stem cells during adipogenesis and osteoblastogenesis
Authors: Scheideler Marcel , Elabd Christian , Zaragosi Laure-Emmanuelle , Chiellini Chiara , Hackl Hubert , Sanchez-Cabo Fatima , Yadav Sunaina , Duszka Kalina , Friedl Gerald , Papak Christine , Prokesch Andreas , Windhager Reinhard , Ailhaud Gerard , Dani Christian , Amri Ez-Zoubir , Trajanoski Zlatko 
Published: July 2008

AbstractBackgroundA reciprocal relationship between bone and fat development in osteoporosis is clinically well established. Some of the key molecular regulators involved in this tissue replacement process have been identified. The detailed mechanisms governing the differentiation of mesenchymal stem cells (MSC) – the key cells involved – are however only now beginning to emerge. In an attempt to address the regulation of the adipocyte/osteoblast balance at the level of gene transcription in a comprehensive and unbiased manner, we performed a large-scale gene expression profiling study using a unique cellular model, human multipotent adipose tissue-derived stem cells (hMADS).ResultsThe analysis of 1606 genes that were found to be differentially expressed between adipogenesis and osteoblastogenesis revealed gene repression to be most prevalent prior to commitment in both lineages. Computational analyses suggested that this gene repression is mediated by miRNAs. The transcriptional activation of lineage-specific molecular processes in both cases occurred predominantly after commitment. Analyses of the gene expression data and promoter sequences produced a set of 65 genes that are candidates for genes involved in the process of adipocyte/osteoblast commitment. Four of these genes were studied in more detail:LXRαand phospholipid transfer protein (PLTP) for adipogenesis, the nuclear receptorCOUP-TF1and one uncharacterized gene,TMEM135for osteoblastogenesis.PLTPwas secreted during both early and late time points of hMADS adipocyte differentiation.LXRα,COUP-TF1, and the transmembrane proteinTMEM135were studied in primary cultures of differentiating bone marrow stromal cells from healthy donors and were found to be transcriptionally activated in the corresponding lineages.ConclusionOur results reveal gene repression as a predominant early mechanism before final cell commitment. We were moreover able to identify 65 genes as candidates for genes controlling the adipocyte/osteoblast balance and to further evaluate four of these. Additional studies will explore the precise role of these candidate genes in regulating the adipogenesis/osteoblastogenesis switch.
Relationship BetweenERCC1Polymorphisms, Disease Progression, and Survival in the Gynecologic Oncology Group Phase III Trial of Intraperitoneal Versus Intravenous Cisplatin and Paclitaxel for Stage III Epithelial Ovarian Cancer
Authors: Krivak Thomas C. , Darcy Kathleen M. , Tian Chunqiao , Armstrong Deborah , Baysal Bora E. , Gallion Holly , Ambrosone Christine B. , DeLoia Julie A. 
Published: July 2008

PurposeWe hypothesized that common polymorphisms in excision repair cross-complementation group 1 (ERCC1), involved in nucleotide excision repair of platinum-induced damage, would be associated with progression-free survival (PFS) and overall survival (OS) in women with optimally resected, stage III epithelial ovarian cancer (EOC) treated with cisplatin and paclitaxel (C+P).Patients and MethodsSingle nucleotide polymorphism analysis was carried out by direct pyrosequencing at two sites (codon 118 and C8092A) in ERCC1 in leukocyte DNA from women who participated in the Gynecologic Oncology Group (GOG) phase III protocol-172 and were randomly assigned to intraperitoneal or intravenous C+P.ResultsERCC1 genotyping was performed in 233 of the 429 women who participated in GOG-172. The genotype distribution at codon 118 was 17% with C/C, 43% with C/T, and 40% with T/T, and the genotype distribution at C8092A was 56% with C/C, 37% with C/A, and 7% with A/A. Adjusted Cox regression analysis revealed that the codon 118 polymorphism in ERCC1 was not significantly associated with disease progression or death. Women with the C8092A C/A or A/A genotypes compared with the C/C genotype had an increased risk of disease progression (hazard ratio [HR] = 1.44; 95% CI, 1.06 to 1.94; P = .018) and death (HR = 1.50; 95% CI, 1.07 to 2.09; P = .018). Median PFS and OS were 6 and 17 months shorter for women with the C8092A C/A or A/A genotypes versus the C/C genotype, respectively.ConclusionAlthough the ERCC1 codon 118 polymorphism does not seem to be associated with clinical outcome, the C8092A polymorphism was an independent predictor of PFS and OS in women with optimally resected EOC.
Pooled Analysis of the Effect of Age on Adjuvant Cisplatin-Based Chemotherapy for Completely Resected Non–Small-Cell Lung Cancer
Authors: Früh Martin , Rolland Estelle , Pignon Jean-Pierre , Seymour Lesley , Ding Keyue , Tribodet Hélène , Winton Timothy , Le Chevalier Thierry , Scagliotti Giorgio V. , Douillard Jean Yves , Spiro Stephen , Shepherd Frances A. 
Published: July 2008

Purpose This pooled analysis was undertaken to assess the efficacy and toxicity of adjuvant cisplatin-based chemotherapy in elderly patients with non–small-cell lung cancer (NSCLC). Methods We used individual patient data from 4,584 patients enrolled onto five trials of cisplatin-based chemotherapy who form the basis for the Lung Adjuvant Cisplatin Analysis (LACE) pooled analysis. Patient and treatment characteristics, overall and event-free survival, cause-specific mortality, chemotherapy toxicity and delivery were compared among three age groups: 3,269 young (71%; < 65), 901 midcategory (20%; 65 to 69), and 414 elderly patients (9%; ≥ 70). Log-rank tests stratified by trials were used with a test for trend to study the effect of chemotherapy on survival according to age. Results The hazard ratio (HR) of death for the young patients was 0.86 (95% CI, 0.78 to 0.94), 1.01 for the midcategory (95% CI, 0.85 to 1.21), and 0.90 for elderly patients (95% CI, 0.70 to 1.16; test for trend: P = .29). The HR for event-free survival was 0.82 for young (95% CI, 0.75 to 0.90), 0.90 for the midcategory (95% CI, 0.76 to 1.06), and 0.87 for elderly patients (95% CI, 0.68 to 1.11; test for trend: P = .42). More elderly patients died from non–lung cancer–related causes (12% young, 19% midcategory, 22% elderly; P < .0001). No differences in severe toxicity rates were observed. Elderly patients received significantly lower first and total cisplatin doses, and fewer chemotherapy cycles (χ2 P < .0001). Conclusion Adjuvant cisplatin-based chemotherapy should not be withheld from elderly patients with NSCLC purely on the basis of age.
Barriers to Enrollment of Elderly Adults in Early-Phase Cancer Clinical Trials
Authors: Basche Michele , Barón Anna E. , Eckhardt S. Gail , Balducci Lodovico , Persky Martha , Levin Adrah , Jackson Nathaniel , Zeng Chan , Vranas Pamela , Steiner John F. 
Published: July 2008

Purpose: To describe patient/family and logistical barriers to participation in university-based, early-phase cancer clinical trials for adults age ≥ 65 years, and to identify influences on their decisions to participate. Participants and Methods: In-person surveys were administered to subjects age ≥ 65 years with advanced tumors who had received prior chemotherapy. Subjects were recruited from private medical oncology practices collaborating with the University of Colorado and Moffitt Cancer Center research networks. Results: Three hundred individuals (51% age 65 to 74 and 49% age 75 or older) responded. Overall, 60% reported one or more barriers to participation in an early-phase trial; logistical barriers such as driving or time demands (34%) or reluctance to be treated at a university center (21%) were most common. Seniors age 75 or older were more reluctant to be treated at a university center (27% v 14%; P = .005), or concerned about loss of continuity with their primary oncologist (24% v 15%, P = .05). Older seniors were also significantly more reluctant than younger seniors to consider treatments with substantial nausea, vomiting, or fatigue. Older and younger seniors differed little in their preferred sources of information; both age groups emphasized the importance of the primary oncologist (100%), a nurse who provides experimental treatment (93%), other patients (83%) or acquaintances who had received experimental treatment (83%). Conclusion: Potential strategies to overcome barriers to enrollment of seniors into early-phase trials include providing more information about trials to community oncologists and prospective enrollees and assisting these individuals in navigating logistical barriers to enrollment.
New insights into the tribology of brake systems
Authors: Ostermeyer G P , Müller M 
Published: July 2008

In spite of remarkable efforts the perfect brake pad in terms of friction performance, wear, noise, and costs has not been found to date. This is mostly because the development is still based on the extensive ‘trial-and-error’ method, as a reliable reproduction or even prediction of those issues is still not possible. A theory regarding the interaction of friction and wear in the interface shows that the tribological behaviour of the system is determined by the growth and destruction of characteristic hard structures (‘patches’) on a mesoscopic length scale. A respective equilibrium of flow taking into account that the main part of the friction power is transmitted by the patches leads to a physically derived dynamic friction law. This paper shows the results that can be gained using this sophisticated law and how it explains several measured phenomena on different timescales. Based on this assumption a cellular automaton model is introduced where the choice of its inner variables and its boundary conditions allows a description of the processes in the interface, as a matter of principle. The paper deals with the formulation of the rules considering the interactions between the patches, friction, wear, and temperature and the resulting dynamic effects. The rules are derived from physical laws and measurements. The occurring timescales according to this model are pointed out and a method towards the problem's simplification with the help of specific algorithms is presented.
microRNAs: a new frontier in kallikrein research
Authors: Yousef George M. 
Published: July 2008

Abstract
microRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression. Rapidly accumulating evidence has revealed that miRNAs are associated with cancer. The human tissue kalli-krein gene family is the largest contiguous family of proteases in the human genome, containing 15 genes. Many kallikreins have been reported as potential tumor markers. In this review, recent bioinformatics and experimental evidence is presented indicating that kallikreins are potential miRNA targets. The available experimental approaches to investigate these interactions and the potential diagnostic and therapeutic applications are also discussed. miRNAs represent a possible regulatory mechanism for controlling kallikrein expression at the post-transcriptional level. Many miRNAs were predicted to target kallikreins and a single miRNA can target more than one kallikrein. Recent evidence suggests that miRNAs can also exert ‘quantitative’ control of kallikreins by utilizing multiple targeting sites in the kallikrein mRNA. More research is needed to experimentally verify the in silico predictions and to investigate the possible role in tumor initiation and/or progression.
Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
Authors: Hollenberg Morley D. , Oikonomopoulou Katerina , Hansen Kristina K. , Saifeddine Mahmoud , Ramachandran Rithwik , Diamandis Eleftherios P. 
Published: July 2008

AbstractProteinases such as thrombin and trypsin can affect tissues by activating a novel family of G protein-coupled proteinase-activated receptors (PARs 1–4) by exposing a ‘tethered’ receptor-triggering ligand (TL). Work with synthetic TL-derived PAR peptide sequences (PAR-APs) that stimulate PARs 1, 2 and 4 has shown that PAR activation can play a role in many tissues, including the gastrointestinal tract, kidney, muscle, nerve, lung and the central and peripheral nervous systems, and can promote tumor growth and invasion. PARs may play roles in many settings, including cancer, arthritis, asthma, inflammatory bowel disease, neurodegeneration and cardiovascular disease, as well as in pathogen-induced inflammation. In addition to activating or disarming PARs, proteinases can also cause hormone-like effects via PAR-independent mechanisms, such as activation of the insulin receptor. In addition to proteinases of the coagulation cascade, recent data suggest that members of the family of kallikrein-related peptidases (KLKs) represent endogenous PAR regulators. In summary: (1) proteinases are like hormones, signaling in a paracrine and endocrine manner via PARs or other mechanisms; (2) KLKs must now be seen as potential hormone-like PAR regulatorsin vivo; and (3) PAR-regulating proteinases, their target PARs, and their associated signaling pathways appear to be novel therapeutic targets.
Functions of KLK4 and MMP-20 in dental enamel formation
Authors: Lu Yuhe , Papagerakis Petros , Yamakoshi Yasuo , Hu Jan C.-C. , Bartlett John D. , Simmer James P. 
Published: July 2008

Abstract
Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory-stage ameloblasts. Enamel protein-cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. KLK4 is secreted by transition- and maturation-stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.
Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
Authors: Smith Robert S. , Gao Lin , Chao Lee , Chao Julie 
Published: July 2008

AbstractAdenovirus-mediated kallikrein delivery has been shown to promote blood vessel growth in the limb under both ischemic and normoperfused conditions. Here we investigated whether a continuous supply of kallikrein and kinin peptide can induce neovascularization in a rat model of hindlimb ischemia. Rats underwent femoral artery ligation and localized injection of tissue kallikrein, bradykinin or B1 receptor agonist, followed by infusion of proteins by osmotic minipump. Regional blood flow was monitored weekly by laser Doppler perfusion imaging. Three weeks after surgery, rats receiving kallikrein and kinins showed a significant increase in the perfusion ratio of ischemic vs. normoperfused limb compared to control rats. Similarly, a microsphere assay showed that kallikrein and kinins significantly increased regional blood flow without altering blood pressure. Moreover, kallikrein and kinins significantly augmented capillary and arteriole densities, as quantified by immunostaining with CD-31 and smooth muscle α-actin. Both tissue kallikrein and bradykinin increased hemoglobin content in Matrigel implants in mice, providing further evidence of the angiogenic properties. Kinins, when delivered subcutaneously via Matrigel in rats, also increased regional perfusion. This is the first demonstration that local application of tissue kallikrein protein or kinin peptide has therapeutic value in the treatment of ischemic disease by promoting neovascularization.
Allantoin as a marker of oxidative stress in human erythrocytes
Authors: Kand'ár Roman , Žáková Pavla 
Published: July 2008

Abstract: Uric acid is the final product of purine metabolism in humans. It was determined that this compound has important antioxidative properties and it may be oxidized to allantoin by various reactive oxygen species. Therefore, the measurement of allantoin may be useful for the determination of oxidative stress in humans.: We measured allantoin and uric acid in human plasma and erythrocytes obtained from patients with chronic renal failure before hemodialysis (n=30) and blood donors (n=30). We used a method based on selective isolation of allantoin from deproteinized plasma and erythrocyte lysate samples on AG 1-X8 resin and its derivatization to glyoxylate-2, 4-dinitrophenylhydrazone. Separation of glyoxylate-2, 4-dinitrophenylhydrazone from interfering substances was achieved on reversed phase HPLC with gradient elution and UV/VIS detection at 360 nm. Uric acid was determined by reversed phase HPLC with UV/VIS detection at 292 nm.: We found significant differences in allantoin and uric acid concentration between the patients with chronic renal failure and the control group both in plasma (20.5±6.5 μmol/L and 323.9±62.9 μmol/L vs. 2.1±1.1 μmol/L and 270.1±62.3 μmol/L, p<0.05) and erythrocytes [82.8±39.1 nmol/g hemoglobin (Hb) and 110.7±28.8 nmol/g Hb vs. 20.1±6.1 nmol/g Hb and 82.1±23.7 nmol/g Hb, p<0.05].: Significant higher levels of allantoin in both plasma and erythrocytes of patients with chronic renal failure indicate that allantoin may be used as a good marker of oxidative stress.Clin Chem Lab Med 2008;46:1270–4.
Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women
Authors: Hübner Ulrich , Alwan Ahmad , Jouma Muhidin , Tabbaa Mohammad , Schorr Heike , Herrmann Wolfgang 
Published: July 2008

Abstract: Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid.: A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined.: Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 μmol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio.: The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion.Clin Chem Lab Med 2008;46:1265–9.
Search for the “missing” α-decay branch in 239Cm
Authors: Qin Zhi , Brüchle W. , Ackermann D. , Eberhardt Klaus , Heßberger F. P. , Jäger E. , Kratz Jens Volker , Kuusiniemi P. , Liebe D. , Münzenberg G. , Nayak Dalia , Novikov Yu. N. , Schädel M. , Schausten B. , Schimpf E. , Semchenkov A. , Sulignano B. , Thörle P. , Wu X.L. 
Published: July 2008

Summary
A search for the α-decay of 239Cm was carried out via the fusion reaction 232Th(12C,5n) 239Cm at GSI, applying nuclear chemistry techniques. The 239Cm α-decay would provide a link between known nuclear masses and α-decay energies measured in the region of the superheavy elements. Three different 12C beam energies were chosen in the present experiments. The α peaks of 238,240Cm were observed clearly at a 12C energy of 74 MeV, while 238Cm disappeared at 70 MeV to provide an undisturbed α-spectrum for a sensitive search of 239Cm decay. No α-events between 6.34 and 6.50 MeV, which could be assigned to 239Cm with confidence, were observed in this experiment. The upper limit of the α-branch of 239Cm was less than 1.0×10−5.
Colpocleisis revisited
Authors: Latthe Pallavi M , Karri Kamakshi , Arunkalaivanan Angamuthu S 
Published: July 2008

Colpocleisis is used to treat advanced pelvic organ prolapse in older women who are too frail for conventional surgery and who are no longer sexually active.
It is quick, easy, effective and associated with low recurrence rates and high patient satisfaction.
Other procedures can be performed concomitantly for stress urinary incontinence and deficient perineum.

Learning objectives:

To understand the indications, alternatives, advantages and procedure of colpocleisis.
To review the available data on effectiveness and complications.

Ethical issues:

Is colpocleisis an appropriate choice in sexually inactive women under 70 years in whom other corrective procedures have failed?

Please cite this article as: Latthe PM, Karri K, Arunkalaivanan AS. Colpocleisis revisited. The Obstetrician & Gynaecologist 2008;10:133–138.
Postnatal affective disorders. Part 1: an introduction
Authors: Oates Margaret 
Published: July 2008

Emotional and behavioural changes affect 50–80% of new mothers between days 3 and 5 of the postnatal period.
Ten percent of all recently‐delivered women develop a depressive illness.
The incidence of puerperal psychosis is 2 per 1000 births.
Women with puerperal psychosis face a 50% risk of serious mental illness at other times in their lives.

Learning objectives:

To learn about the emotional changes following childbirth.
To be aware of the risk factors, clinical features and prognosis of postnatal affective disorders.
To be able to prescribe the appropriate care for women with puerperal psychosis and postnatal depression.

Ethical issues:

Should all women be screened for postnatal mood disorders?

Please cite this article as: Oates M. Postnatal affective disorders. Part 1: an introduction. The Obstetrician & Gynaecologist 2008;10:145–150.