bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARMS Depletion Facilitates UV Irradiation–Induced Apoptotic Cell Death in Melanoma
Authors: Liao Yi-Hua , Hsu Su-Ming , Huang Pei-Hsin 
Published: December 2007

Abstract
Tumor cells often aberrantly reexpress molecules that mediate proper embryonic development for advantageous growth or survival. Here, we report that ankyrin repeat-rich membrane spanning (ARMS), a transmembrane protein abundant in the developing and adult neural tissues, is overexpressed in melanoma, a tumor ontogenetically originating from neural crest. Immunohistochemical study of 79 melanocytic lesions showed significantly increased expression of ARMS in primary malignant melanomas (92.9%) and metastatic melanoma (60.0%) in comparison with benign nevocellular nevi (26.7%). To investigate the role of ARMS in melanoma formation, murine B16F0 melanoma cells with stable knockdown of ARMS were established by RNA interference. Down-regulation of ARMS resulted in significant inhibition of anchorage-independent growth in soft agar and restrictive growth of melanoma in severe combined immunodeficient mice. Importantly, depletion of ARMS facilitated UVB-induced apoptosis in melanoma cells through inactivation of mitogen-activated protein kinase/extracellular signal–regulated kinase (ERK) kinase (MEK)/ERK. Addition of MEK inhibitor PD98059 further sensitized ARMS-depleted melanoma cells to UVB-induced apoptosis, whereas constitutively active MEK rescued ARMS-depleted cells from apoptosis. We further showed that BRAF, a downstream signaling molecule of ARMS in ERK pathway, is not mutated as a constitutively active form in acral lentiginous melanoma; in contrast, BRAFT1799A mutation, which leads to constitutive activation of ERK signaling, was detected in 57.1% of superficial spreading melanoma. Our study suggests that overexpression of ARMS per se serves as one mechanism to promote melanoma formation by preventing stress-induced apoptotic death mediated by the MEK/ERK signaling pathway, especially in acral lentiginous melanoma, most of which does not harbor BRAF mutation. [Cancer Res 2007;67(24):11547–56]
Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2
Authors: Varchetta Stefania , Gibelli Nadia , Oliviero Barbara , Nardini Elena , Gennari Roberto , Gatti Giovanna , Silva Luzemira Santos , Villani Laura , Tagliabue Elda , Ménard Sylvie , Costa Alberto , Fagnoni Francesco F. 
Published: December 2007

Abstract
Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis of circulating mononuclear cells in 18 patients. ADCC was induced by trastuzumab therapy in 15 of 18 patients (83%). Inability to develop ADCC in three patients did not depend on inadequate levels of trastuzumab because further increase in its concentration in vitro was ineffective. Rather, susceptibility to develop ADCC was fairly predicted by test with trastuzumab before therapy and was correlated to the number of lymphocytes coexpressing CD16 and CD56. Phenotypic analysis at the end of ADCC evaluating down-regulation of CD16, and up-regulation of CD69 and CD107a, confirmed that natural killer (NK) cells and CD56+ T cells were involved in productive engagement of trastuzumab. Also, the killing efficiency of CD16+ lymphocytes was influenced by 158 V/F polymorphism of FcγRIII (CD16), whereas variations of CD247 on NK cells were consistent with trends between ADCC before and after therapy. Complete pathologic response was observed in one patient showing ADCC of outstanding intensity, whereas four cases of partial response showed intermediate ADCC; none of the three patients unable to mount ADCC had significant tumor regression. These data indicate that quantity and lytic efficiency of CD16+ lymphocytes are major factors for ADCC induction by trastuzumab, and confirm that breast cancer responses to short-term trastuzumab monotherapy may depend on involvement of the ADCC mechanism. [Cancer Res 2007;67(24):11991–9]
Oncogenic BARD1 Isoforms Expressed in Gynecological Cancers
Authors: Li Lin , Ryser Stephan , Dizin Eva , Pils Dietmar , Krainer Michael , Jefford Charles Edward , Bertoni Francesco , Zeillinger Robert , Irminger-Finger Irmgard 
Published: December 2007

Abstract
BARD1 is required for protein stability and tumor suppressor functions of BRCA1, which depend on the ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. The NH2-terminal RING domains of both proteins act as interaction modules and form a ubiquitin ligase, which has functions in DNA repair, cell cycle checkpoint regulation, and mitosis. Interestingly, up-regulated expression of truncated BARD1 isoforms was found to be associated with poor prognosis in breast and ovarian cancers and, in a hormonally regulated fashion, in the human cytotrophoblast, a cell type with properties reminiscent of cancer cells. We therefore performed reverse transcription-PCR to determine the structure of BARD1 isoforms in cell lines derived from hormone-dependent and hormone-independent cancers. We found a specific combination of isoforms, generated by differential splicing and alternative transcription initiation, mostly lacking the BRCA1 interaction domain, in gynecologic but not hematologic cancer cell lines. To investigate the prevalence of BARD1 isoforms in tumors, we applied immunohistochemistry to ovarian cancers, using antibodies distinguishing full-length BARD1 and isoforms. Expression of NH2 terminally truncated BARD1 was correlated with advanced stage of cancer, and expression of spliced isoforms was typical for clear cell carcinoma, the ovarian cancer with worst prognosis, suggesting a role of BARD1 isoforms in cancer progression. To challenge this hypothesis, we silenced BARD1 isoforms in ovarian cancer cells that lacked wild-type BARD1 by siRNA interference, which led to a complete proliferation arrest. Thus, BARD1 isoform expression is required for cancer cell proliferation, which is compatible with the notion that BARD1 isoforms act as cancer maintenance genes. [Cancer Res 2007;67(24):11876–85]
Effects of Dietary Energy Restriction on Gene Regulation in Mammary Epithelial Cells
Authors: Zhu Zongjian , Jiang Weiqin , McGinley John N. , Price Jennifer M. , Gao Bifeng , Thompson Henry J. 
Published: December 2007

Abstract
The objective of this study was to determine whether dietary energy restriction (DER) affects the pattern of gene expression in three interrelated energy metabolism pathways: glycolysis, gluconeogenesis, and the citric acid cycle. Mammary carcinogenesis was initiated by the i.p. injection of female Sprague-Dawley rats with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight. Five days following 1-methyl-1-nitrosourea administration, animals were fed ad libitum or 80% or 60% of the ad libitum intake. Epithelial cells were harvested from histologically confirmed adenocarcinomas (adenocarcinoma epithelial cell; ACEC) and uninvolved mammary gland (mammary gland epithelial cells; MGEC) via laser capture microdissection, whereas isolated RNA was arrayed on Affymetrix R230 2.0 genome chips. Principal components analysis revealed complete separation of the patterns of gene expression between ACEC versus MGEC. Further examination of the data set revealed an up-regulated pattern of expression in the ACEC of genes involved in glycolysis, whereas gluconeogenesis was suppressed. In general, genes involved in the citric acid cycle were not differentially expressed; however, pyruvate dehydrogenase expression was down-regulated and lactate dehydrogenase expression was increased in ACEC versus MGEC. Collectively, the observed patterns of expression were consistent with the Warburg effect. DER exerted no effect on the Warburg pattern of gene expression or on other aspects of these energy metabolism pathways. These findings imply that efforts to target the Warburg effect for cancer prevention are mechanistically distinct from those modulated by DER and provide a rationale for the combination of approaches that target basic defects in energy metabolism and energy-sensing pathways for the prevention of breast cancer. [Cancer Res 2007;67(24):12018–25]
Human Cancer Cells Commonly Acquire DNA Damage during Mitotic Arrest
Authors: Dalton W. Brian , Nandan Mandayam O. , Moore Ryan T. , Yang Vincent W. 
Published: December 2007

AbstractThe mitotic checkpoint is a mechanism that arrests the progression to anaphase until all chromosomes have achieved proper attachment to mitotic spindles. In cancer cells, satisfaction of this checkpoint is frequently delayed or prevented by various defects, some of which have been causally implicated in tumorigenesis. At the same time, deliberate induction of mitotic arrest has proved clinically useful, as antimitotic drugs that interfere with proper chromosome-spindle interactions are effective anticancer agents. However, how mitotic arrest contributes to tumorigenesis or antimitotic drug toxicity is not well defined. Here, we report that mitotic chromosomes can acquire DNA breaks during both pharmacologic and genetic induction of mitotic arrest in human cancer cells. These breaks activate a DNA damage response, occur independently of cell death, and subsequently manifest as karyotype alterations. Such breaks can also occur spontaneously, particularly in cancer cells containing mitotic spindle abnormalities. Moreover, we observed evidence of some breakage in primary human cells. Our findings thus describe a novel source of DNA damage in human cells. They also suggest that mitotic arrest may promote tumorigenesis and antimitotic toxicity by provoking DNA damage. [Cancer Res 2007;67(24):11487–92]
Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation
Authors: Hong Jung Wan , Lee In-Hyun , Kwak Young Hak , Park Young Taek , Sung Ha Chin , Kwon Ick Chan , Chung Hesson 
Published: December 2007

AbstractPaclitaxel is indispensable in treating human cancers. Due to poor drug solubility and efflux systems in the gastrointestinal tract, peroral delivery of paclitaxel has been a significant challenge. We developed a mucoadhesive oral formulation (DHP107) that can directly and effectively deliver paclitaxel to intestinal endothelial cells without concomitant use of P-glycoprotein inhibitors. Here, we evaluated the tissue distribution of paclitaxel, the antitumor efficacy and the absorption mechanism of DHP107. DHP107, which contains 10 mg/mL of paclitaxel in a mixture of monoolein, tricarprylin, and Tween 80 was administered p.o. to female BALB/c mice at a 50 mg/kg dose. Diluted Taxol was administered via bolus tail-vein injection at 10 mg/kg as a control. Blood and tissue samples were harvested at various time points and analyzed by high-performance liquid chromatography. Tissue sections were observed using light microscopy after immunohistochemical and Oil Red O staining. By day 27, tumor volume after DHP107 and Taxol treatments was one-third of that in the untreated group. After p.o. administration, paclitaxel was widely distributed in various organs (Tmax = 2 h), especially liver, spleen, and lung. DHP107 was effectively absorbed through the intestinal lipid transport system. DHP107 changed spontaneously into &lt;100-μm droplets and micelles in the intestine, which in turn adhered to mucoepithelial cells, were absorbed via lipid uptake mechanism, and formed lipid bodies in the epithelium. Paclitaxel in DHP107 was effectively absorbed through the gastrointestinal tract via lipid uptake mechanism and was distributed in various tissues. The detailed uptake mechanism is currently under investigation. [Mol Cancer Ther 2007;6(12):3239–47]
Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma
Authors: Christensen James G. , Zou Helen Y. , Arango Maria E. , Li Qiuhua , Lee Joseph H. , McDonnell Scott R. , Yamazaki Shinji , Alton Gordon R. , Mroczkowski Barbara , Los Gerrit 
Published: December 2007

Abstract
A t(2;5) chromosomal translocation resulting in expression of an oncogenic kinase fusion protein known as nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) has been implicated in the pathogenesis of anaplastic large-cell lymphoma (ALCL). PF-2341066 was recently identified as a p.o. bioavailable, small-molecule inhibitor of the catalytic activity of c-Met kinase and the NPM-ALK fusion protein. PF-2341066 also potently inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells (mean IC50 value, 24 nmol/L). In biochemical and cellular screens, PF-2341066 was shown to be selective for c-Met and ALK at pharmacologically relevant concentrations across a panel of &gt;120 diverse kinases. PF-2341066 potently inhibited cell proliferation, which was associated with G1-S–phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells (IC50 values, ∼30 nmol/L) but not ALK-negative lymphoma cells. The induction of apoptosis was confirmed using terminal deoxyribonucleotide transferase–mediated nick-end labeling and Annexin V staining (IC50 values, 25–50 nmol/L). P.o. administration of PF-2341066 to severe combined immunodeficient-Beige mice bearing Karpas299 ALCL tumor xenografts resulted in dose-dependent antitumor efficacy with complete regression of all tumors at the 100 mg/kg/d dose within 15 days of initial compound administration. A strong correlation was observed between antitumor response and inhibition of NPM-ALK phosphorylation and induction of apoptosis in tumor tissue. In addition, inhibition of key NPM-ALK signaling mediators, including phospholipase C-γ, signal transducers and activators of transcription 3, extracellular signal-regulated kinases, and Akt by PF-2341066 were observed at concentrations or dose levels, which correlated with inhibition of NPM-ALK phosphorylation and function. Collectively, these data illustrate the potential clinical utility of inhibitors of NPM-ALK in treatment of patients with ALK-positive ALCL. [Mol Cancer Ther 2007;6(12):3314–22]
Zoledronic acid inhibits osteosarcoma growth in an orthotopic model
Authors: Dass Crispin R. , Choong Peter F.M. 
Published: December 2007

Abstract
Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. Its efficacy in osteosarcoma has not been convincingly proved in a clinically relevant model for the disease. In vitro, ZOL decreased osteosarcoma cell proliferation, mainly due to an increase in apoptosis in a dose-dependent fashion. There was a decrease in cell migration at ≥10 μmol/L concentrations, but invasion was inhibited at a much lower dose of 0.1 μmol/L. Reverse transcription-PCR showed that ZOL overall caused an increased expression of osteocalcin and decreased expression of alkaline phosphatase, osteopontin, osteonectin, and vascular endothelial growth factor, with no change in expression of osteoprotegerin. ZOL administration s.c. twice weekly at 0.12 mg/kg to SaOS-2 tumor–bearing mice resulted in primary tumor growth inhibition, reduction in lung metastases, and dramatic decrease in osteolysis. Furthermore, in the ZOL cohort, there was a clear reduction in the number of osteoclasts in bone exposed to tumor and a lower tumor vessel density. These data point to the adjuvant potential of ZOL in the management of osteosarcoma not only for its antiosteolytic properties but also for its ability to directly halt tumor cell growth and metastasis via its effects on viability, invasion, differentiation, and angiogenesis. [Mol Cancer Ther 2007;6(12):3263–70]
Hermeneutic knowledge: Dialogue between experiences
Authors: Georgii-Hemming Eva 
Published: December 2007

This article discusses the need for theoretical analysis in narrative music education research. Stories we hear are not simply accounts of individual experiences. They are also part of cultural narratives, socially and historically located. For the purpose of increased and in-depth understanding in narrative studies there must be an analysis of how a person's life relates to phenomena such as time, culture, society and gender. In order to bring to light unconscious pre-understandings, hidden conventions and ideologies it is necessary to problematize the text on different levels of abstraction. One way of enriching narrative work is through the incorporation of hermeneutics.i Hermeneutics offers dialogue-based interpretations of meaningful phenomena in the life world. If we understand narrative as a form of knowledge, both narrative and hermeneutics refer to the same fundamental characteristics of our individual and social existence: historicity and interaction, or dialogue, between experiences.
Construction and characterization of an expressed sequenced tag library for the mosquito vector Armigeres subalbatus
Authors: Mayhew George F , Bartholomay Lyric C , Kou Hang-Yen , Rocheleau Thomas A , Fuchs Jeremy F , Aliota Matthew T , Tsao I-Yu , Huang Chiung-Yen , Liu Tze-Tze , Hsiao Kwang-Jen , Tsai Shih-Feng , Yang Ueng-Cheng , Perna Nicole T , Cho Wen-Long , Christensen Bruce M , Chen Cheng-Chen 
Published: December 2007

AbstractBackgroundThe mosquito,Armigeres subalbatus, mounts a distinctively robust innate immune response when infected with the nematodeBrugia malayi, a causative agent of lymphatic filariasis. In order to mine the transcriptome for new insight into the cascade of events that takes place in response to infection in this mosquito, 6 cDNA libraries were generated from tissues of adult female mosquitoes subjected to immune-response activation treatments that lead to well-characterized responses, and from aging, naïve mosquitoes. Expressed sequence tags (ESTs) from each library were produced, annotated, and subjected to comparative analyses.ResultsSix libraries were constructed and used to generate 44,940 expressed sequence tags, of which 38,079 passed quality filters to be included in the annotation project and subsequent analyses. All of these sequences were collapsed into clusters resulting in 8,020 unique sequence clusters or singletons. EST clusters were annotated and curated manually within ASAP (A Systematic Annotation Package for Community Analysis of Genomes) web portal according to BLAST results from comparisons to Genbank, and theAnopheles gambiaeandDrosophila melanogastergenome projects.ConclusionThe resulting dataset is the first of its kind for this mosquito vector and provides a basis for future studies of mosquito vectors regarding the cascade of events that occurs in response to infection, and thereby providing insight into vector competence and innate immunity.
Sequence analysis of Plasmodium falciparum cytochrome b in multiple geographic sites
Authors: Ekala Marie-Thérèse , Khim Nimol , Legrand Eric , Randrianarivelojosia Milijaona , Jambou Ronan , Fandeur Thierry , Menard Didier , Assi Serge-Brice , Henry Marie-Claire , Rogier Christophe , Bouchier Christiane , Mercereau-Puijalon Odile 
Published: December 2007

Abstract

Background
The antimalarial drug atovaquone specifically targets Plasmodium falciparum cytochrome b (Pfcytb), a mitochondrial gene with uniparental inheritance. Cases of resistance to atovaquone associated with mutant Pfcytb have been reported, justifying efforts to better document the natural polymorphism of this gene. To this end, a large molecular survey was conducted in several malaria endemic areas where atovaquone was not yet in regular use.

Methods
The polymorphism of the Pfcytb was analysed by direct sequencing of PCR products corresponding to the full length coding region. Sequence was generated for 671 isolates originating from three continents: Africa (Senegal, Ivory Coast, Central African Republic and Madagascar), Asia (Cambodia) and South America (French Guiana).

Results
Overall, 11 polymorphic sites were observed, of which eight were novel mutations. There was a large disparity in the geographic distribution of the mutants. All isolates from Senegal, Central African Republic and Madagascar displayed a Camp/3D7 wild type Pfcytb sequence, as did most samples originating from Cambodia and Ivory Coast. One synonymous (t759a at codon V253V) and two non-synonymous (t553g and a581g at codons F185V and H194R, respectively) singletons were detected in Ivory Coast. Likewise, two synonymous (a126t and c793t at codons -T42T and L265L, respectively) singletons were observed in Cambodia. In contrast, seven mutated sites, affecting seven codons and defining four mutant haplotypes were observed in French Guiana. The wild type allele was observed in only 14% of the French Guiana isolates. The synonymous c688t mutation at position L230L was highly prevalent; the most frequent allele was the c688t single mutant, observed in 84% of the isolates. The other alleles were singletons (a126t/a165c, a4g/a20t/a1024c and a20t/t341c/c688t corresponding to T42T/S55S, N2D/N71I/I342L, N71I/L114S/L230L, respectively" please replace with ' corresponding to T42T/S55S, N2D/N71I/I342L and N71I/L114S/L230L, respectively). The codon 268 polymorphisms associated with atovaquone resistance were not observed in the panel the isolates studied. Overall, the wild type PfCYTb protein isoform was highly predominant in all study areas, including French Guiana, suggesting stringent functional constraints.

Conclusion
These data along with previously identified Pfcytb field polymorphisms indicate a clustering of molecular signatures, suggesting different ancestral types in South America and other continents. The absence of mutations associated with most atovaquone-proguanil clinical failures indicates that the atovaquone-proguanil association is an interesting treatment option in the study areas.
Lung inflammation following a single exposure to swine barn air
Authors: Gamage Lakshman Nihal Angunna , Charavaryamath Chandrashekhar , Swift Trisha Lee , Singh Baljit 
Published: December 2007

Abstract

Background
Exposure to swine barn air is an occupational hazard. Barn workers following an eight-hour work shift develop many signs of lung dysfunction including lung inflammation. However, the in situ cellular and molecular mechanisms responsible for lung dysfunction induced following exposure to the barn air remain largely unknown. Specifically, the recruitment and role of pulmonary intravascular monocytes/macrophages (PIMMs), which increase host susceptibility for acute lung inflammation, remain unknown in barn air induced lung inflammation. We hypothesized that barn exposure induces recruitment of PIMMs and increases susceptibility for acute lung inflammation with a secondary challenge.

Methods
Sprague-Dawley rats were exposed either to the barn or ambient air for eight hours and were euthanized at various time intervals to collect blood, broncho-alveolar lavage fluid (BALF) and lung tissue. Subsequently, following an eight hour barn or ambient air exposure, rats were challenged either with Escherichia coli (E. coli) lipopolysaccharide (LPS) or saline and euthanized 6 hours post-LPS or saline treatment. We used ANOVA (P < 0.05 means significant) to compare group differences.

Results
An eight-hour exposure to barn air induced acute lung inflammation with recruitment of granulocytes and PIMMs. Granulocyte and PIMM numbers peaked at one and 48 hour post-exposure, respectively.
Secondary challenge with E. coli LPS at 48 hour following barn exposure resulted in intense lung inflammation, greater numbers of granulocytes, increased number of cells positive for TNF-α and decreased amounts of TGF-β2 in lung tissues. We also localized TNF-α, IL-1β and TGF-β2 in PIMMs.

Conclusion
A single exposure to barn air induces lung inflammation with recruitment of PIMMs and granulocytes. Recruited PIMMs may be linked to more robust lung inflammation in barn-exposed rats exposed to LPS. These data may have implications of workers exposed to the barn air who may encounter secondary microbial challenge.