bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elesclomol induces cancer cell apoptosis through oxidative stress
Authors: Kirshner Jessica R. , He Suqin , Balasubramanyam Vishwasenani , Kepros Jane , Yang Chin-Yu , Zhang Mei , Du Zhenjian , Barsoum James , Bertin John 
Published: August 2008

AbstractElesclomol (formerly STA-4783) is a novel small molecule undergoing clinical evaluation in a pivotal phase III melanoma trial (SYMMETRY). In a phase II randomized, double-blinded, controlled, multi-center trial in 81 patients with stage IV metastatic melanoma, treatment with elesclomol plus paclitaxel showed a statistically significant doubling of progression-free survival time compared with treatment with paclitaxel alone. Although elesclomol displays significant therapeutic activity in the clinic, the mechanism underlying its anticancer activity has not been defined previously. Here, we show that elesclomol induces apoptosis in cancer cells through the induction of oxidative stress. Treatment of cancer cells in vitro with elesclomol resulted in the rapid generation of reactive oxygen species (ROS) and the induction of a transcriptional gene profile characteristic of an oxidative stress response. Inhibition of oxidative stress by the antioxidant N-acetylcysteine blocked the induction of gene transcription by elesclomol. In addition, N-acetylcysteine blocked drug-induced apoptosis, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of elesclomol. Excessive ROS production and elevated levels of oxidative stress are critical biochemical alterations that contribute to cancer cell growth. Thus, the induction of oxidative stress by elesclomol exploits this unique characteristic of cancer cells by increasing ROS levels beyond a threshold that triggers cell death. [Mol Cancer Ther 2008;7(8):2319–27]
Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines
Authors: Zajac Magdalena , Moneo Maria Victoria , Carnero Amancio , Benitez Javier , Martínez-Delgado Beatriz 
Published: August 2008

Abstract
Heat shock protein 90 (Hsp90) is a molecular chaperone involved in folding, assembly, maturation, and stabilization of the client proteins that regulate survival of malignant cells. As previous reports correlate high Hsp90 expression with decreased survival in breast cancer, Hsp90 may be a favorable target for investigational therapy in breast cancer. In our study, we have examined the response of a panel of both BRCA1-null (UACC 3199, HCC 1937, and MBA-MD-436) and BRCA1-wt breast cancer cell lines (MCF-7, MBA-MD-157, and Hs578T) to determine the proteins governing response to Hsp90 inhibitor 17-allyloamino-17-demethoxy-geldanamycin. On treatment with the drug, cells arrested at G2-M phase and entered aberrant mitosis in a BRCA1-dependent manner. Failure to arrest the cells at or before mitosis resulted in formation of micronucleated cells, aberrant segregation of chromosomes, microtubule misalignment, and multicentrosomes, leading in eventual mitotic catastrophe cell death. Our observations show that BRCA1 mediates G2-M transition mainly through chek1 on 17-allyloamino-17-demethoxy-geldanamycin treatment. [Mol Cancer Ther 2008;7(8):2358–66]
High-content imaging characterization of cell cycle therapeutics through in vitro and in vivo subpopulation analysis
Authors: Low Jonathan , Huang Shuguang , Blosser Wayne , Dowless Michele , Burch John , Neubauer Blake , Stancato Louis 
Published: August 2008

Abstract
Although the cycling of eukaryotic cells has long been a primary focus for cancer therapeutics, recent advances in imaging and data analysis allow even further definition of cellular events as they occur in individual cells and cellular subpopulations in response to treatment. High-content imaging (HCI) has been an effective tool to elucidate cellular responses to a variety of agents; however, these data were most frequently observed as averages of the entire captured population, unnecessarily decreasing the resolution of each assay. Here, we dissect the eukaryotic cell cycle into individual cellular subpopulations using HCI in conjunction with unsupervised K-means clustering. We generate distinct phenotypic fingerprints for each major cell cycle and mitotic compartment and use those fingerprints to screen a library of 310 commercially available chemotherapeutic agents. We determine that the cell cycle arrest phenotypes caused by these agents are similar to, although distinct from, those found in untreated cells and that these distinctions frequently suggest the mechanism of action. We then show via subpopulation analysis that these arrest phenotypes are similar in both mouse models and in culture. HCI analysis of cell cycle using data obtained from individual cells under a broad range of research conditions and grouped into cellular subpopulations represents a powerful method to discern both cellular events and treatment effects. In particular, this technique allows for a more accurate means of assessing compound selectivity and leads to more meaningful comparisons between so-called targeted therapeutics. [Mol Cancer Ther 2008;7(8):2455–63]
Relaxin treatment of solid tumors: effects on electric field–mediated gene delivery
Authors: Henshaw Joshua , Mossop Brian , Yuan Fan 
Published: August 2008

Abstract
Pulsed electric fields have been shown to enhance interstitial transport of plasmid DNA (pDNA) in solid tumors in vivo. However, the extent of enhancement is still limited partly due to the collagen component in extracellular matrix. To this end, effects of collagen remodeling on interstitial electrophoresis were investigated by pretreatment of tumor-bearing mice with a recombinant human relaxin (rh-Rlx). In the study, two tumor lines (4T1 and B16.F10) were examined and implanted s.c. to establish two murine models: dorsal skin-fold chamber (DSC) and hind leg. Effects of rh-Rlx on pDNA electrophoresis were measured either directly in the DSC model or indirectly in the hind leg model via reporter gene expression. It was observed that rh-Rlx treatment reduced collagen levels in the hind leg tumors but not in the DSC tumors. The observation correlated with the results from electromobility experiments, where rh-Rlx treatment enhanced transgene expression in 4T1 hind leg tumors but did not increase the electromobility of pDNA in the DSC tumors. In addition, it was observed that pDNA binding to collagen could block its diffusion in collagen gel in vitro. These observations showed that effects of rh-Rlx on the collagen content depended on microenvironment in solid tumors and that rh-Rlx treatment would enhance electric field–mediated gene delivery only if it could effectively reduce the collagen content in collagen-rich tumors. [Mol Cancer Ther 2008;7(8):2566–73]
Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies
Authors: Kurtzberg Joanne , Prasad Vinod K. , Carter Shelly L. , Wagner John E. , Baxter-Lowe Lee Ann , Wall Donna , Kapoor Neena , Guinan Eva C. , Feig Stephen A. , Wagner Elizabeth L. , Kernan Nancy A. 
Published: August 2008

Abstract
Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 × 107 TNC/kg (range, 1.5-23.7) with 3.9 × 107 TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm3 and platelets 50 000/μL) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603.
Plasmin therapy enhances mobilization of HPCs after G-CSF
Authors: Tjwa Marc , Janssens Stefan , Carmeliet Peter 
Published: August 2008

Abstract
The role of proteinases in the mobilization of hematopoietic progenitor cells (HPCs) after granulocyte colony-stimulating factor (G-CSF) remains unclear. Here we report that genetic loss of the plasminogen activator inhibitor Pai-1 or of the plasmin inhibitor α2-antiplasmin increases HPC mobilization in response to G-CSF. Moreover, thrombolytic agents, such as tenecteplase and microplasmin, enhance HPC mobilization in mice and humans. Taken together, these findings identify a novel role for plasmin in augmenting HPC mobilization in response to G-CSF.
Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer
Authors: de Araujo Souza Patricia S , Maciag Paulo C , Ribeiro Karina B , Petzl-Erler Maria Luiza , Franco Eduardo L , Villa Luisa L 
Published: August 2008

AbstractBackgroundPersistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.MethodsWe characterized HPV-16 variants by PCR in 107 ICC cases, which were typed forHLA-DQA1,DRB1andDQB1genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.ResultsEuropean (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association betweenDQB1*05(adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions ofHLA DRB1*1302carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association withDRB1*15was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association betweenDRB1*04and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in theE6gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association betweenDQB1*05and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89).ConclusionOur results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.
Some peace of mind: assessing a pilot intervention to promote mental health among widows of injecting drug users in north-east India
Authors: Kermode Michelle , Devine Alexandra , Chandra Prabha , Dzuvichu Bernice , Gilbert Thomhood , Herrman Helen 
Published: August 2008

Abstract

Background
HIV prevalence in north-east India is high and injecting drug use (IDU) is common. Due to HIV-related deaths there are increasing numbers of IDU widows, many of whom are HIV infected, and experiencing poor health, social isolation, discrimination and poverty, all factors likely to be compromising their mental health. There is increasing recognition of the links between HIV and mental health.

Methods
The aim of this study was to pilot a peer-facilitated, participatory action group (PAG) process and assess the impact of the intervention on the mental health of participants. The intervention consisted of 10 PAG meetings involving 74 IDU widows. Changes in quality of life (WHOQOL-BREF), mental health (GHQ12) and somatic symptoms were assessed. The value of the intervention from the perspective of the participants was captured using a qualitative evaluation method (Most Significant Change).

Results
Participants' quality of life, mental health and experience of somatic symptoms improved significantly over the course of the intervention, and the women told stories reflecting a range of 'significant changes'.

Conclusion
This pilot intervention study demonstrated that a participatory approach to mental health promotion can have a positive impact on the lives of vulnerable women, and the potential to contribute to HIV prevention. Further investigation is warranted.
Evolution of developmental roles of Pax2/5/8paralogs after independent duplication in urochordate and vertebrate lineages
Authors: Bassham Susan , Cañestro Cristian , Postlethwait John H 
Published: August 2008

AbstractBackgroundGene duplication provides opportunities for lineage diversification and evolution of developmental novelties. Duplicated genes generally either disappear by accumulation of mutations (nonfunctionalization), or are preserved either by the origin of positively selected functions in one or both duplicates (neofunctionalization), or by the partitioning of original gene subfunctions between the duplicates (subfunctionalization). The Pax2/5/8 family of important developmental regulators has undergone parallel expansion among chordate groups. After the divergence of urochordate and vertebrate lineages, two rounds of independent gene duplications resulted in thePax2, Pax5, andPax8genes of most vertebrates (the sister group of the urochordates), and an additional duplication provided thepax2aandpax2bduplicates in teleost fish. Separate from the vertebrate genome expansions, a duplication also created twoPax2/5/8genes in the common ancestor of ascidian and larvacean urochordates.ResultsTo better understand mechanisms underlying the evolution of duplicated genes, we investigated, in the larvacean urochordateOikopleura dioica, the embryonic gene expression patterns ofPax2/5/8paralogs. We compared the larvacean and ascidian expression patterns to infer modular subfunctions present in the single pre-duplicationPax2/5/8gene of stem urochordates, and we compared vertebrate and urochordate expression to infer the suite ofPax2/5/8gene subfunctions in the common ancestor of olfactores (vertebrates + urochordates). Expression pattern differences of larvacean and ascidian Pax2/5/8 orthologs in the endostyle, pharynx and hindgut suggest that some ancestral gene functions have been partitioned differently to the duplicates in the two urochordate lineages. Novel expression in the larvacean heart may have resulted from the neofunctionalization of aPax2/5/8gene in the urochordates. Expression of larvaceanPax2/5/8in the endostyle, in sites of epithelial remodeling, and in sensory tissues evokes like functions ofPax2,Pax5andPax8in vertebrate embryos, and may indicate ancient origins for these functions in the chordate common ancestor.ConclusionComparative analysis of expression patterns of chordate Pax2/5/8 duplicates, rooted on the single-copyPax2/5/8gene of amphioxus, whose lineage diverged basally among chordates, provides new insights into the evolution and development of the heart, thyroid, pharynx, stomodeum and placodes in chordates; supports the controversial conclusion that the atrial siphon of ascidians and the otic placode in vertebrates are homologous; and backs the notion thatPax2/5/8functioned in ancestral chordates to engineer epithelial fusions and perforations, including gill slit openings.
Conjugated linoleic acid modulation of risk factors associated with atherosclerosis
Authors: Nakamura Yukiko K , Flintoff-Dye Nichole , Omaye Stanley T 
Published: August 2008

AbstractConjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have resulted in conflicting findings. Both the human and animal study results may be attributed to contrasting doses of CLA, isomers, the coexistence of other dietary fatty acids, length of study, and inter-and/or intra-species diversities. Recent research advances have suggested the importance of CLA isomers in modulating gene expression involved in oxidative damage, fatty acid metabolism, immune/inflammatory responses, and ultimately atherosclerosis. Although the possible mechanisms of action of CLA have been suggested, they have yet to be determined.
Primary squamous cell carcinoma of lung in a 13-year-old boy: a case report
Authors: Wang Jeff F , wang Bo , Jansen Joshua A , Santos Eric E , Sarma Deba P 
Published: August 2008

Abstract
We are reporting a very rare case of primary bronchogenic squamous cell carcinoma (SCC) with bone metastasis in a 13-year-old boy. A brief review of the English literature on this rare neoplasm in childhood is presented.
Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms
Authors: George-Chandy Annie , Trysberg Estelle , Eriksson Kristina 
Published: August 2008

Abstract
Introduction
The tumour necrosis factor (TNF) family ligands BAFF (B-cell activating factor of TNF family) and APRIL (a proliferation-inducing ligand) are essential for B-cell survival and function. Elevated serum levels of BAFF and APRIL have been reported earlier in patients with systemic lupus erythematosus (SLE). Since autoantibody formation in the central nervous system (CNS) is a distinct feature of neuropsychiatric SLE (NPSLE), we have investigated whether NPSLE is associated with an enhanced intrathecal production of APRIL and BAFF.

Methods
Levels of BAFF and APRIL in cerebrospinal fluid (CSF) and serum from healthy controls, SLE patients without CNS involvement, and patients with NPSLE were determined by enzyme-linked immunosorbent assay. Interleukin-6 (IL-6) levels were determined by an IL-6-specific bioassay.

Results
SLE patients had levels of APRIL in CSF that were more than 20-fold higher and levels of BAFF in CSF that were more than 200-fold higher than those of healthy controls. Separate analyses of SLE patients with and without CNS involvement revealed that NPSLE patients had enhanced levels of APRIL in CSF. BAFF and APRIL were likely produced locally in the CNS as CSF and serum levels did not correlate. Moreover, CSF levels of APRIL correlated with BAFF but not with IL-6, suggesting that APRIL and BAFF in the CNS are regulated together but that they are produced independently of IL-6.

Conclusion
To our knowledge this is the first study to show elevated levels of BAFF and APRIL in CSF of SLE patients. APRIL was augmented in NPSLE patients compared with SLE patients without CNS involvement. APRIL and BAFF antagonists breeching the blood-brain barrier therefore could have beneficial effects on SLE patients, in particular patients with NPSLE.
Hydrogen sulfide and oxygen sensing: implications in cardiorespiratory control
Authors: Olson Kenneth R. 
Published: August 2008

SUMMARYAlthough all cells are variously affected by oxygen, a few have the responsibility of monitoring oxygen tensions and initiating key homeostatic responses when PO2 falls to critical levels. These `oxygen-sensing' cells include the chemoreceptors in the gills(neuroepithelial cells), airways (neuroepithelial bodies) and vasculature(carotid bodies) that initiate cardiorespiratory reflexes, oxygen sensitive chromaffin cells associated with systemic veins or adrenal glands that regulate the rate of catecholamine secretion, and vascular smooth muscle cells capable of increasing blood flow to systemic tissues, or decreasing it through the lungs. In spite of intense research, and enormous clinical applicability,there is little, if any, consensus regarding the mechanism of how these cells sense oxygen and transduce this into the appropriate physiological response. We have recently proposed that the metabolism of hydrogen sulfide(H2S) may serve as an `oxygen sensor' in vertebrate vascular smooth muscle and preliminary evidence suggests it has similar activity in gill chemoreceptors. In this proposed mechanism, the cellular concentration of H2S is determined by the simple balance between constitutive H2S production in the cytoplasm and H2S oxidation in the mitochondria; when tissue oxygen levels fall the rate of H2S oxidation decreases and the concentration of biologically active H2S in the tissue increases. This commentary briefly describes the oxygen-sensitive tissues in fish and mammals, delineates the current hypotheses of oxygen sensing by these tissues, and then critically evaluates the evidence for H2S metabolism in oxygen sensing.
The scaling of safety factor in spider draglines
Authors: Ortlepp Christine , Gosline John M. 
Published: August 2008

SUMMARYThis study documents the effect of body mass on the size and strength of draglines produced by the orb-weaving spider Araneus diadematus and the jumping spider Salticus scenicus. Silk samples obtained from individuals spanning the range from first-instar juveniles to gravid adults were tested to determine both the properties of the silk material and the strength and static safety factor of the draglines produced by each individual spider. Analysis of material properties indicates that the tensile strength and extensibility of the silks employed by each species are identical over the entire size range of the species. Analysis of the breaking forces for individual draglines, however, indicates that the draglines scale allometrically with the spider's body mass. For Araneus, breaking force (N) scales with body mass (kg) as Fmax=11.2M0.786, and the static safety factor(SBW=Fmax/Mg) scales as SBW=1.14M–0.214. For Salticus, Fmax=0.363M0.66 and SBW=0.037M–0.34. Thus, static safety factors decrease as these spiders grow, with values falling to 4–6 for adult Araneus and to 1–2 for adult Salticus. Analysis of these results suggests that the safety lines produced by these two species are not able to absorb the impact energy of most falls with a fixed length of pre-existing silk, except in the smallest of the Araneus spiders. It is therefore likely that both spiders must draw new silk from their spinnerets during falls to keep the dynamic loads on their safety-lines below failure levels.