bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respective Roles of Serological Status and Blood Specific Antihuman Herpesvirus 8 Antibody Levels in Human Herpesvirus 8 Intrafamilial Transmission in a Highly Endemic Area
Authors: Plancoulaine Sabine , Abel Laurent , Trégouët David , Duprez Renan , van Beveren Monique , Tortevoye Patricia , Froment Alain , Gessain Antoine 
Published: September 2005

Abstract
Transmission of human herpesvirus 8 (HHV-8), the etiological agent of Kaposi’s sarcoma, occurs mainly during childhood in endemic countries and, to a large extent, through intrafamilial contacts. To additionally investigate this familial transmission, and especially the role of plasma anti-HHV–8 antibody titers, we conducted a large survey in a village from Cameroon, Central Africa, including 92 families (608 individuals). Plasma samples were tested for specific IgG directed against HHV-8 lytic antigens by immunofluorescence assay, and titers were determined by 2-fold dilutions. Global HHV-8 seroprevalence was 60%, raising from 32% under 9 years up to a plateau of around 62% between 15 and 40 years. The familial correlation patterns in HHV-8 seropositive/seronegative status showed strong dependence from mother to child and between siblings. In contrast, no familial correlation in anti-HHV–8 antibody levels was observed among infected subjects. In particular, no relationship was observed between the anti-HHV–8 antibody titer of HHV-8 seropositive mothers and the proportion of their HHV-8 seropositive children. Furthermore, a random permutation study of the anti-HHV–8 antibody titers among HHV-8 infected subjects showed that the main risk factor for infection was the HHV-8 serologic status and not the antibody level. In addition, no correlation was found between anti-HHV–8 antibody levels and buffy coat HHV-8 viral loads in a subsample of 95 infected subjects. Overall, these results strongly suggest that, in this highly endemic population from Central Africa, HHV-8 transmission mainly occurs from mother to child and between siblings, and it is independent of plasma antibody levels of HHV-8 infected relatives.
Breast Cancer Cells Isolated by Chemotaxis from Primary Tumors Show Increased Survival and Resistance to Chemotherapy
Authors: Goswami Sumanta , Wang Weigang , Wyckoff Jeffrey B. , Condeelis John S. 
Published: September 2005

Abstract
In this study, we have collected a migratory population of carcinoma cells by chemotaxis to epidermal growth factor-containing microneedles held in the primary tumor. The collected cells were subjected to microarray analysis for differential gene expression. The results show that anti-apoptotic genes are up-regulated and pro-apoptotic genes are down-regulated coordinately in the migratory subpopulation. Induction of apoptosis by doxorubicin, cisplatin, and etoposide in these cells demonstrates that they exhibit a lower drug-induced apoptotic index and lower cell death compared with carcinoma cells of the whole tumor. Our study indicates, for the first time, the capability of using a rat alograft model for evaluating the apoptotic status of a migratory subpopulation of tumor cells and the ability to study their resistance to chemotherapeutic agents directly. In addition, these results indicate that tumor cells that are chemotactic and migratory in response to epidermal growth factor in the primary tumor have a survival advantage over stationary tumor cells.
Physical and Functional Interactions between the Wwox Tumor Suppressor Protein and the AP-2γ Transcription Factor
Authors: Aqeilan Rami I. , Palamarchuk Alexey , Weigel Ronald J. , Herrero Juan J. , Pekarsky Yuri , Croce Carlo M. 
Published: September 2005

Abstract
The WWOX gene encodes a tumor suppressor WW domain-containing protein, Wwox. Alterations of WWOX have been demonstrated in multiple types of cancer, and introduction of Wwox into Wwox-negative tumor cells has resulted in tumor suppression and apoptosis. The Wwox protein contains two WW domains that typically bind proline-rich motifs and mediate protein–protein interactions. Recently, we have described functional cross-talk between the Wwox protein and the p53 homologue, p73. To further explore the biological function of Wwox, we investigated other interacting candidates. In this report, we demonstrate a physical and functional association between AP-2γ transcription factor and the Wwox protein. AP-2γ at 20q13.2 encodes a transcription factor and is frequently amplified in breast carcinoma. We show that Wwox binds to the PPPY motif of AP-2γ via its first WW domain. Alterations of tyrosine 33 in the first WW domain of Wwox or the proline-rich motif in AP-2γ dramatically reduce this interaction. In addition, our results demonstrate that Wwox expression triggers redistribution of nuclear AP-2γ to the cytoplasm, hence suppressing its transactivating function. Our results suggest that Wwox tumor suppressor protein inhibits AP-2γ oncogenic activity by sequestering it in the cytoplasm.
BRAK/CXCL14 Is a Potent Inhibitor of Angiogenesis and a Chemotactic Factor for Immature Dendritic Cells
Authors: Shellenberger Thomas D. , Wang Mary , Gujrati Manu , Jayakumar Arumugam , Strieter Robert M. , Burdick Marie D. , Ioannides Constantin G. , Efferson Clayton L. , El-Naggar Adel K. , Roberts Dianna , Clayman Gary L. , Frederick Mitchell J. 
Published: September 2005

AbstractBRAK/CXCL14 is a CXC chemokine constitutively expressed at the mRNA level in certain normal tissues but absent from many established tumor cell lines and human cancers. Although multiple investigators cloned BRAK, little is known regarding the physiologic function of BRAK or the reason for decreased expression in cancer. To understand the possible significance associated with loss of BRAK mRNA in tumors, we examined the pattern of BRAK protein expression in normal and tumor specimens from patients with squamous cell carcinoma (SCC) of the tongue and used recombinant BRAK (rBRAK) to investigate potential biological functions. Using a peptide-specific antiserum, abundant expression of BRAK protein was found in suprabasal layers of normal tongue mucosa but consistently was absent in tongue SCC. Consistent with previous in situ mRNA studies, BRAK protein also was expressed strongly by stromal cells adjacent to tumors. In the rat corneal micropocket assay, BRAK was a potent inhibitor of in vivo angiogenesis stimulated by multiple angiogenic factors, including interleukin 8, basic fibroblast growth factor, and vascular endothelial growth factor. In vitro, rBRAK blocked endothelial cell chemotaxis at concentrations as low as 1 nmol/L, suggesting this was a major mechanism for angiogenesis inhibition. Although only low affinity receptors for BRAK could be found on endothelial cells, human immature monocyte-derived dendritic cells (iDCs) bound rBRAK with high affinity (i.e., Kd, ∼2 nmol/L). Furthermore, rBRAK was chemotactic for iDCs at concentrations ranging from 1 to 10 nmol/L. Our findings support a hypothesis that loss of BRAK expression from tumors may facilitate neovascularization and possibly contributes to immunologic escape.
CXC Chemokine Receptor 3 Expression by Activated CD8+ T cells Is Associated with Survival in Melanoma Patients with Stage III Disease
Authors: Mullins Irene M. , Slingluff Craig L. , Lee Jae K. , Garbee Courtney F. , Shu Jianfen , Anderson Sara G. , Mayer Melanie E. , Knaus William A. , Mullins David W. 
Published: September 2005

AbstractDespite the presence of tumor Ag-specific CD8+ T cells in the peripheral blood, metastatic melanoma often evades immune-mediated destruction. Even after therapeutic efforts to expand Ag-specific T-cell populations, the correlation between magnitude of response and clinical efficacy has been weak. Because the migratory phenotype of tumor Ag-specific effector T cells may determine their ability for tumor control, we hypothesized that the expression of CC or CXC chemokine receptor (CCR) molecules on activated CD8+ T cells may define phenotypes associated with more effective control of melanoma progression and prolonged survival. In a retrospective evaluation of patient isolates, CCR expression was determined for activated CD8+ T cells derived from the peripheral blood or tumor-involved lymph nodes of 52 patients with stage III or IV metastatic melanoma. In patients with stage III disease, expression of CXCR3 by CD8+CD45RO+ cells was significantly associated with enhanced survival. This was a stage-specific effect, because it was not observed in patients with stage IV disease. In addition, CCR4 and CXCR3 were highly coexpressed and associated with enhanced survival in stage III patients; however, CXCR3 seems to be the dominant receptor associated with clinical outcome. These findings support the hypothesis that the host immune system affects cancer progression and control, and that measures of CCR status of circulating lymphocytes may have prognostic value.
Gene Expression of Parathyroid Tumors
Authors: Haven Carola J. , Howell Viive M. , Eilers Paul H. C. , Dunne Robert , Takahashi Masayuki , van Puijenbroek Marjo , Furge Kyle , Kievit Job , Tan Min-Han , Fleuren Gert Jan , Robinson Bruce G. , Delbridge Leigh W. , Philips Jeanette , Nelson Anne E. , Krause Ulf , Dralle Henning , Hoang-Vu Cuong , Gimm Oliver , Morreau Hans , Marsh Deborah J. , Teh Bin T. 
Published: September 2005

Abstract
Parathyroid tumors are heterogeneous, and diagnosis is often difficult using histologic and clinical features.
We have undertaken expression profiling of 53 hereditary and sporadic parathyroid tumors to better define the molecular genetics of parathyroid tumors. A class discovery approach identified three distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma cluster consisting of sporadic carcinomas and benign and malignant tumors from Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to distinguish between the groups were identified and may serve as diagnostic biomarkers. We demonstrated, by both gene and protein expression, that Histone 1 Family 2, amyloid β precursor protein, and E-cadherin are useful markers for parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether germ-line or somatic, strongly influences the expression pattern of these 3 genes. Cluster 2, characterized by HRPT2 mutations, was the most striking, suggesting that parathyroid tumors with somatic HRPT2 mutation or tumors developing on a background of germ-line HRPT2 mutation follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumors. Furthermore, our findings likely preclude an adenoma to carcinoma progression model for parathyroid tumorigenesis outside of the presence of either a germ-line or somatic HRPT2 mutation. These findings provide insights into the molecular pathways involved in parathyroid tumorigenesis and will contribute to a better understanding, diagnosis, and treatment of parathyroid tumors.
RASSF4/AD037 Is a Potential Ras Effector/Tumor Suppressor of the RASSF Family
Authors: Eckfeld Kristin , Hesson Luke , Vos Michele D. , Bieche Ivan , Latif Farida , Clark Geoffrey J. 
Published: September 2005

Abstract
Activated Ras proteins interact with a broad range of effector proteins to induce a diverse series of biological consequences. Although typically associated with enhanced growth and transformation, activated Ras may also induce growth antagonistic effects such as senescence or apoptosis. It is now apparent that some of the growth-inhibitory properties of Ras are mediated via the RASSF family of Ras effector/tumor suppressors. To date, four members of this family have been identified (Nore1, RASSF1, RASSF2, and RASSF3). We now identify a fifth member of this group, RASSF4 (AD037). RASSF4 shows approximately 25% identity with RASSF1A and 60% identity with RASSF2. RASSF4 binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effector. Overexpression of RASSF4 induces Ras-dependent apoptosis in 293-T cells and inhibits the growth of human tumor cell lines. Although broadly expressed in normal tissue, RASSF4 is frequently down-regulated by promoter methylation in human tumor cells. Thus, RASSF4 appears to be a new member of the RASSF family of potential Ras effector/tumor suppressors.
Activin Type II Receptor Restoration inACVR2-Deficient Colon Cancer Cells Induces Transforming Growth Factor-β Response Pathway Genes
Authors: Deacu Elena , Mori Yuriko , Sato Fumiaki , Yin Jing , Olaru Andreea , Sterian Anca , Xu Yan , Wang Suna , Schulmann Karsten , Berki Agnes , Kan Takatsugu , Abraham John M. , Meltzer Stephen J. 
Published: September 2005

AbstractThe activin type II receptor (ACVR2) gene is a putative tumor suppressor gene that is frequently mutated in microsatellite-unstable colon cancers (MSI-H colon cancers). ACVR2 is a member of the transforming growth factor (TGF)-β type II receptor (TGFBR2) family and controls cell growth and differentiation. SMAD proteins are major intracellular effectors shared by ACVR2 and TGFBR2 signaling; however, additional shared effector mechanisms remain to be explored. To discover novel mechanisms transmitting the ACVR2 signal, we restored ACVR2 function by transfecting wild-type ACVR2 (wt-ACVR2) into a MSI-H colon cancer cell line carrying an ACVR2 frameshift mutation. The effect of ACVR2 restoration on cell growth, SMAD phosphorylation, and global molecular phenotype was then evaluated. Decreased cell growth was observed in wt-ACVR2 transfectants relative to ACVR2-deficient vector-transfected controls. Western blotting revealed higher expression of phosphorylated SMAD2 in wt-ACVR2 transfectants versus controls, suggesting cells deficient in ACVR2 had impaired SMAD signaling. Microarray-based differential expression analysis revealed substantial ACVR2-induced overexpression of genes implicated in the control of cell growth and tumorigenesis, including the activator protein (AP)-1 complex genes JUND, JUN, and FOSB, as well as the small GTPase signal transduction family members, RHOB, ARHE, and ARHGDIA. Overexpression of these genes is shared with TGFBR2 activation. This observed similarity between the activin and TGF-β signaling systems suggests that activin may serve as an alternative activator of TGF-β effectors, including SMADs, and that frameshift mutation of ACVR2 may contribute to MSI-H colon tumorigenesis via disruption of alternate TGF-β effector pathways.
Id2 Drives Differentiation and Suppresses Tumor Formation in the Intestinal Epithelium
Authors: Russell Robert G. , Lasorella Anna , Dettin Luis E. , Iavarone Antonio 
Published: September 2005

Abstract
Oncogenic signals elevate expression of Id2 in multiple tumor types. When deregulated, Id2 inactivates the tumor suppressor proteins retinoblastoma, p107, and p130. Here, we report a novel and unexpected tumor inhibitory function of Id2 in the intestinal epithelium. First, genetic ablation of Id2 in the mouse prevents differentiation and cell cycle arrest of enterocytes at the time of formation of the crypt-villus unit. Later, these developmental abnormalities evolve toward neoplastic transformation with complete penetrance. Id2-null tumors contain severe dysplastic and metaplastic lesions and express aberrant amounts of β-catenin. Thus, our data are the first to establish a direct requirement of basic helix-loop-helix inhibitors in driving differentiation and define an unexpected role for the retinoblastoma-binding protein Id2 in preventing tumor formation.
Endogenous Inhibitors of Nuclear Factor-κB, An Opportunity for Cancer Control
Authors: Chen Fei 
Published: September 2005

AbstractExcessive and prolonged activation of nuclear factor-κB (NF-κB) has been linked to numerous human diseases, especially cancer, because of the elevated expression of genes encoding antiapoptotic proteins, cytokines, chemokines, cell adhesion molecules, and so on. Eukaryotic cells have developed multiple mechanisms to keep this ubiquitous transcription factor in check. In addition to the inhibitor of κB family proteins, a number of endogenous molecules that negatively regulate the activation or activity of NF-κB have been identified. These molecules include A20, CYLD, cyPG15-deoxy-Δ12,14-prostaglandin J2, Foxj1, Twist proteins, and β-arrestins. The extended list of these endogenous inhibitors of NF-κB may provide new opportunities for the development of novel strategies for the intervention of malignant transformation. The question to be asked is how NF-κB is sustained activated in a number of cancers in which so many antagonists are surrounded.
Regulation of Protein Catabolism by Muscle-Specific and Cytokine-Inducible Ubiquitin Ligase E3α-II during Cancer Cachexia
Authors: Kwak Keith S. , Zhou Xiaolan , Solomon Vered , Baracos Vickie E. , Davis James , Bannon Anthony W. , Boyle William J. , Lacey David L. , Han H.Q. 
Published: September 2005

Abstract
The progressive depletion of skeletal muscle is a hallmark of many types of advanced cancer and frequently is associated with debility, morbidity, and mortality. Muscle wasting is primarily mediated by the activation of the ubiquitin-proteasome system, which is responsible for degrading the bulk of intracellular proteins. E3 ubiquitin ligases control polyubiquitination, a rate-limiting step in the ubiquitin-proteasome system, but their direct involvement in muscle protein catabolism in cancer remains obscure. Here, we report the full-length cloning of E3α-II, a novel “N-end rule” ubiquitin ligase, and its functional involvement in cancer cachexia. E3α-II is highly enriched in skeletal muscle, and its expression is regulated by proinflammatory cytokines. In two different animal models of cancer cachexia, E3α-II was significantly induced at the onset and during the progression of muscle wasting. The E3α-II activation in skeletal muscle was accompanied by a sharp increase in protein ubiquitination, which could be blocked by arginine methylester, an E3α-selective inhibitor. Treatment of myotubes with tumor necrosis factor α or interleukin 6 elicited marked increases in E3α-II but not E3α-I expression and ubiquitin conjugation activity in parallel. E3α-II transfection markedly accelerated ubiquitin conjugation to endogenous cellular proteins in muscle cultures. These findings show that E3α-II plays an important role in muscle protein catabolism during cancer cachexia and suggest that E3α-II is a potential therapeutic target for muscle wasting.
Schedule-dependent Inhibition of Hypoxia-inducible Factor-1α Protein Accumulation, Angiogenesis, and Tumor Growth by Topotecan in U251-HRE Glioblastoma Xenografts
Authors: Rapisarda Annamaria , Zalek Jessica , Hollingshead Melinda , Braunschweig Till , Uranchimeg Badarch , Bonomi Carrie A. , Borgel Suzanne D. , Carter John P. , Hewitt Stephen M. , Shoemaker Robert H. , Melillo Giovanni 
Published: September 2005

Abstract
We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1α protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1α protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1α inhibition, topotecan caused a significant tumor growth inhibition associated with a marked decrease of angiogenesis and expression of HIF-1 target genes in tumor tissue. These results provide a compelling rationale for testing topotecan in clinical trials to target HIF-1 in cancer patients.
Nuclear Hormone Receptor NR4A2 Is Involved in Cell Transformation and Apoptosis
Authors: Ke Ning , Claassen Gisela , Yu De-Hua , Albers Aaron , Fan Wufang , Tan Philip , Grifman Mirta , Hu Xiuyuan , DeFife Kristin , Nguy Vivian , Meyhack Bernd , Brachat Arndt , Wong-Staal Flossie , Li Qi-Xiang 
Published: September 2005

Abstract
HeLaHF cells are transformation revertants of cervical cancer HeLa cells and have lost anchorage-independent growth potential and tumorigenicity. Activation of tumor suppressor(s) was implicated previously in this transformation reversion. In this study, expression profiling analysis was carried out to identify potential oncogenes that are down-regulated in HeLaHF cells. We found that all three members of the NR4A1/Nur77/NGFIB orphan nuclear hormone receptor subfamily (NR4A1, NR4A2, and NR4A3) were down-regulated in the HeLaHF revertant. Small interfering RNA-mediated down-regulation of NR4A2 in HeLa cells, either transiently or stably, resulted in reduced anchorage-independent growth that was largely attributable to increased anoikis. Furthermore, down-regulation of NR4A2 as well as NR4A1 promoted intrinsic apoptosis. These phenotypes were also observed in several other experimental cancer cells, suggesting the observed apoptosis suppression is a more general property of NR4A2 and NR4A1. These phenotypes also suggest that the Nur77/NGFIB subfamily of orphan receptors exhibit certain oncogenic functionalities with regards to cell proliferation and apoptosis and could therefore be evaluated as potential cancer therapeutic targets.
Analysis of Gene Expression Patterns and Chromosomal Changes Associated with Aging
Authors: Geigl Jochen B. , Langer Sabine , Barwisch Simone , Pfleghaar Katrin , Lederer Gaby , Speicher Michael R. 
Published: September 2005

Abstract
Age is the largest single risk factor for the development of cancer in mammals. Age-associated chromosomal changes, such as aneuploidy and telomere erosion, may be vitally involved in the initial steps of tumorigenesis. However, changes in gene expression specific for increased aneuploidy with age have not yet been characterized. Here, we address these questions by using a panel of fibroblast cell lines and lymphocyte cultures from young and old age groups. Oligonucleotide microarrays were used to characterize the expression of 14,500 genes. We measured telomere length and analyzed chromosome copy number changes and structural rearrangements by multicolor interphase fluorescence in situ hybridization and 7-fluorochrome multiplex fluorescence in situ hybridization, and we tried to show a relationship between gene expression patterns and chromosomal changes. These analyses revealed a number of genes involved in both the cell cycle and proliferation that are differently expressed in aged cells. More importantly, our data show an association between age-related aneuploidy and the gene expression level of genes involved in centromere and kinetochore function and in the microtubule and spindle assembly apparatus. To verify that some of these genes may also be involved in tumorigenesis, we compared the expression of these genes in chromosomally stable microsatellite instability and chromosomally unstable chromosomal instability colorectal tumor cell lines. Three genes (Notch2, H2AFY2, and CDC5L) showed similar expression differences between microsatellite instability and chromosomal instability cell lines as observed between the young and old cell cultures suggesting that they may play a role in tumorigenesis.