bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous Tumor Evolution Initiated by Loss of pRb Function in a Preclinical Prostate Cancer Model
Authors: Hill Reginald , Song Yurong , Cardiff Robert D. , Van Dyke Terry 
Published: November 2005

Abstract
Because each change in the evolution of a cancer is predicated on the effects of previous events, a full understanding of selective changes and their effect on tumor progression can only be understood in the context of appropriate initiating events. Here, we define the effect of pRb function inactivation in prostate epithelium on both the initiation of prostate cancer and the establishment of selective pressures that lead to diminished Pten function and tumor evolution. Using genetically engineered mice, we show that inactivation of the pRb family proteins (Rb/p107/p130) induces epithelial proliferation and apoptosis and is sufficient to produce prostatic intraepithelial neoplasia (PIN) lesions. Over time, adenocarcinomas develop in all mice with no evidence of neuroendocrine tumors. Apoptosis is dependent on Pten function and not p53, unlike other epithelial cell types tested previously. Consequently, Pten hemizygosity reduces apoptosis by 50%, accelerating progression to adenocarcinomas with heterogeneous composition. Heterogeneity is associated with concurrent Pten haploinsufficiency and focal selective progression to complete Pten loss, which yields distinct tumor properties. Given that this analysis models the apparent timing of highly penetrant events in human prostate cancer, observed effects may recapitulate the natural evolution of prostate cancer development.
Simultaneous Inhibition of EGFR, VEGFR, and Platelet-Derived Growth Factor Receptor Signaling Combined with Gemcitabine Produces Therapy of Human Pancreatic Carcinoma and Prolongs Survival in an Orthotopic Nude Mouse Model
Authors: Yokoi Kenji , Sasaki Takamitsu , Bucana Corazon D. , Fan Dominic , Baker Cheryl H. , Kitadai Yasuhiko , Kuwai Toshio , Abbruzzese James L. , Fidler Isaiah J. 
Published: November 2005

Abstract
Although gemcitabine has been approved as the first-line chemotherapeutic reagent for pancreatic cancer, its response rate is low and average survival duration is still only marginal. Because epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR) modulate tumor progression, we hypothesized that inhibition of phosphorylation of all three on tumor cells, tumor-associated endothelial cells, and stroma cells would improve the treatment efficacy of gemcitabine in an orthotopic pancreatic tumor model in nude mice and prolong survival. We implanted L3.6pl, a human pancreatic cancer cell, in the pancreas of nude mice. We found that tumor-associated endothelial cells in this model highly expressed phosphorylated EGFR, VEGFR, and PDGFR. Oral administration of AEE788, a dual tyrosine kinase inhibitor against EGFR and VEGFR, decreased phosphorylation of EGFR and VEGFR. PDGFR phosphorylation was inhibited by STI571. Although i.p. injection of gemcitabine did not inhibit tumor growth, its combination with AEE788 and STI571 produced &gt;80% inhibition of tumor growth and prolonged survival in parallel with increases in number of tumor cells and tumor-associated endothelial cell apoptosis, decreased microvascular density, decreased proliferation rate, and prolonged survival. STI571 treatment also decreased pericyte coverage on tumor-associated endothelial cells. Thus, inhibiting phosphorylation of EGFR, VEGFR, and PDGFR in combination with gemcitabine enhanced the efficacy of gemcitabine, resulting in inhibition of experimental human pancreatic cancer growth and significant prolongation of survival.
Alternative Splicing of Fibroblast Growth Factor Receptor 3 Produces a Secreted Isoform That Inhibits Fibroblast Growth Factor–Induced Proliferation and Is Repressed in Urothelial Carcinoma Cell Lines
Authors: Tomlinson Darren C. , L'Hôte Corine G. , Kennedy Wendy , Pitt Eva , Knowles Margaret A. 
Published: November 2005

Abstract
Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that play key roles in proliferation, differentiation, and tumorigenesis. FGFR3 was identified as the major family member expressed in both normal human urothelium and cultured normal human urothelial (NHU) cells and was expressed as the IIIb isoform. We also identified a splice variant, FGFR3 Δ8-10, lacking exons encoding the COOH-terminal half of immunoglobulin-like domain III and the transmembrane domain. Previous reports have assumed that this is a cancer-specific splice variant. We showed that FGFR3 Δ8-10 is a normal transcript in NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium expressed high levels of FGFR3 transcripts. In culture, levels were reduced in actively proliferating cells but increased at confluence and as cells approached senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Δ8-10. In bladder tumor cell lines derived from aggressive carcinomas, there were significant alterations in the relative expression of isoforms including an overall decrease in the proportion of FGFR3 Δ8-10 and predominant expression of FGFR3 IIIc in some cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a normal mechanism to generate a transcript that regulates proliferation and in bladder cancer, the ratio of FGFR3 isoforms is significantly altered.
Noninvasive In vivo Detection of Glutathione Metabolism in Tumors
Authors: Thelwall Peter E. , Yemin Avner Y. , Gillian Theresa L. , Simpson Nicholas E. , Kasibhatla Mohit S. , Rabbani Zahid N. , Macdonald Jeffrey M. , Blackband Stephen J. , Gamcsik Michael P. 
Published: November 2005

Abstract
Magnetic resonance spectroscopic imaging has been used to follow glutathione metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in anesthetized rats following infusion of [2-13C]glycine. Using 1H-decoupled 13C magnetic resonance spectroscopy, the appearance of [2-13C]glycine at 42.4 ppm and the subsequent incorporation of this isotope label into the glycyl residue of glutathione at 44.2 ppm can be detected. The identity and relative concentrations of labeled metabolites observed in the in vivo spectrum were confirmed in studies of tissue extracts. The high level of isotopic enrichment and the concentration of glutathione in tumor tissue allow for collection of spatially localized spectra using 13C chemical shift imaging methods. These data provide the first direct images of glutathione in intact tumor tissue and show metabolic heterogeneity. This method may lead to the ability to monitor changes in tumor tissue redox state that may ultimately affect diagnosis, monitoring, and treatment.
BRCA1 and c-Myc Associate to Transcriptionally Repress Psoriasin, a DNA Damage–Inducible Gene
Authors: Kennedy Richard D. , Gorski Julia J. , Quinn Jennifer E. , Stewart Gail E. , James Colin R. , Moore Stephen , Mulligan Karl , Emberley Ethan D. , Lioe Tong F. , Morrison Patrick J. , Mullan Paul B. , Reid George , Johnston Patrick G. , Watson Peter H. , Harkin D. Paul 
Published: November 2005

Abstract
Evidence is accumulating to suggest that some of the diverse functions associated with BRCA1 may relate to its ability to transcriptionally regulate key downstream target genes. Here, we identify S100A7 (psoriasin), S100A8, and S100A9, members of the S100A family of calcium-binding proteins, as novel BRCA1-repressed targets. We show that functional BRCA1 is required for repression of these family members and that a BRCA1 disease–associated mutation abrogates BRCA1-mediated repression of psoriasin. Furthermore, we show that BRCA1 and c-Myc form a complex on the psoriasin promoter and that BRCA1-mediated repression of psoriasin is dependent on functional c-Myc. Finally, we show that psoriasin expression is induced by the topoisomerase IIα poison, etoposide, in the absence of functional BRCA1 and increased psoriasin expression enhances cellular sensitivity to this chemotherapeutic agent. Therefore, we identified a novel transcriptional mechanism that is likely to contribute to BRCA1-mediated resistance to etoposide.
Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary
Authors: Bonome Tomas , Lee Ji-Young , Park Dong-Choon , Radonovich Mike , Pise-Masison Cindy , Brady John , Gardner Ginger J. , Hao Ke , Wong Wing H. , Barrett J. Carl , Lu Karen H. , Sood Anil K. , Gershenson David M. , Mok Samuel C. , Birrer Michael J. 
Published: November 2005

Abstract
Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype.
Negative Regulation of Estrogen Receptor α Transactivation Functions by LIM Domain Only 4 Protein
Authors: Singh Rajesh R. , Barnes Christopher J. , Talukder Amjad H. , Fuqua Suzanne A.W. , Kumar Rakesh 
Published: November 2005

Abstract
LIM domain only 4 (LMO4), a member of the LIM-only family of transcriptional coregulatory proteins, consists of two LIM protein-protein interaction domains that enable it to function as a linker protein in multiprotein complexes. Here, we have identified estrogen receptor α (ERα) and its corepressor, metastasis tumor antigen 1 (MTA1), as two novel binding partners of LMO4. Interestingly, LMO4 exhibited binding with both ERα and MTA1 and existed as a complex with ERα, MTA1, and histone deacetylases (HDAC), implying that LMO4 was a component of the MTA1 corepressor complex. Consistent with this notion, LMO4 overexpression repressed ERα transactivation functions in an HDAC-dependent manner. Accordingly, silencing of endogenous LMO4 expression resulted in a significant increased recruitment of ERα to target gene chromatin, stimulation of ERα transactivation activity, and enhanced expression of ERα-regulated genes. These findings suggested that LMO4 was an integral part of the molecular machinery involved in the negative regulation of ERα transactivation function in breast cells. Because LMO4 is up-regulated in human breast cancers, repression of ERα transactivation functions by LMO4 might contribute to the process of breast cancer progression by allowing the development of ERα-negative phenotypes, leading to increased aggressiveness of breast cancer cells.
MUC1 Oncoprotein Blocks Glycogen Synthase Kinase 3β–Mediated Phosphorylation and Degradation of β-Catenin
Authors: Huang Lei , Chen Dongshu , Liu Derek , Yin Li , Kharbanda Surender , Kufe Donald 
Published: November 2005

AbstractDysregulation of β-catenin is of importance to the development of diverse human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and associates with β-catenin. However, the functional significance of the MUC1-β-catenin interaction is not known. Here, we show that MUC1 increases β-catenin levels in the cytoplasm and nucleus of carcinoma cells. Previous studies have shown that glycogen synthase kinase 3β (GSK3β) phosphorylates β-catenin and thereby targets it for proteosomal degradation. Consistent with the up-regulation of β-catenin levels, our results show that MUC1 blocks GSK3β-mediated phosphorylation and degradation of β-catenin. To further define the interaction between MUC1 and β-catenin, we identified a serine-rich motif (SRM) in the MUC1 cytoplasmic domain that binds directly to β-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUC1 to β-catenin and MUC1-mediated inhibition of β-catenin degradation. Importantly, disruption of the MUC1-β-catenin interaction with the SRM mutant also attenuated MUC1-induced anchorage-dependent and -independent growth and delayed MUC1-mediated tumorigenicity. These findings indicate that MUC1 promotes transformation, at least in part, by blocking GSK3β-mediated phosphorylation and thereby degradation of β-catenin.
Type I Insulin-like Growth Factor Receptor as a Therapeutic Target in Cancer
Authors: Miller Bradley S. , Yee Douglas 
Published: November 2005

Abstract
Data from experimental model systems and population studies have implicated type I insulin-like growth factor receptor (IGF1R) signaling in many different human cancers. Drugs to disrupt IGF1R function have been developed and are now entering clinical trial. This brief review will identify key areas to consider as these clinical trials move forward.
Breeding behaviour and reproduction in the Pampa de Achala toad, Bufo achalensis
Authors: Jofré G.M. , Reading C.J. , di Tada L.E. 
Published: November 2005

AbstractDuring 1999 and 2000 the reproductive behaviour, breeding site characteristics and reproduction of Bufo achalensis were studied mainly at La Ciénaga stream, Pampa de Achala, Argentina, using capture-recapture and skeletochronology methods. Breeding activity occurred from mid-August to mid-September and was explosive. Males and females congregated at night at selected, but scarce, breeding sites, resulting in a patchy distribution of small breeding populations near to the stream source. The sex ratio (♂ : ♀) of the breeding population ranged between 0.65 : 1 and 1.16 : 1. On average, breeding males were larger and older than breeding females. Although most females and males reached sexual maturity at four and five years of age, some bred for the first time at the ages of three and four years respectively. Neither size dependent nor size assortative pairings were found. Male reproductive success was not related to body size (SVL) but was related to the number of nights spent at a breeding site. Females laid between 700-2,390 eggs. Eggs hatched approximately nine days after deposition and larval development was completed in about two months.
A new species of tree frog from the Andes of southeastern Peru (Anura: Hylidae: Hyla)
Authors: De la Riva Ignacio , Chaparro Juan Carlos 
Published: November 2005

AbstractA new species of Hyla is described from cloud forests of the Cosñipata Valley in southern Peru. The new species lacks webbing in hands and has vestigial webbing between toes III and IV, is readily distinguished from any other species of Andean Hyla, and is not clearly assignable to any species group. The new species seems to be a secretive, bromeliad-dweller.
A new species of Diurnal Frog in the genus Crossodactylus Duméril and Bibron, 1841 (Anura, Leptodactylidae) from Southeastern Brazil
Authors: Nascimento Luciana B. , Cruz Carlos A.G. , Feio Renato N. 
Published: November 2005

Abstract
A new species of Crossodactylus, belonging to the C. gaudichaudii species
group, was described from the Municipality of Santa Maria do Salto, in the
Atlantic Rain Forest of the State of Minas Gerais, southeastern Brazil. The
new species was characterised by its: small size; slender body; head being
longer than its width; snout rounded in dorsal view and protruding in
lateral view; skin very granulated on sacral region; males having four to
six keratinized conical spines arranged in a circle on their thumb; inner
tarsal fringe extensively developed; toes extensively fringed on both edges;
and ventral body surface with brownish blotches and short stripes. The
descriptions of advertisement calls and tadpoles are included. Uma nova
espécie de Crossodactylus, pertencente ao grupo de C. gaudichaudii, é
descrita do município de Santa Maria do Salto, na Mata Atlântica do Estado
de Minas Gerais, sudeste do Brasil. A nova espécie é caracterizada pelo
corpo esbelto, cabeça mais longa que larga, focinho arredondado em vista
dorsal e protuso em vista lateral, pele bastante granulada na região sacral,
machos possuindo de quatro a seis espinhos córneos cônicos, dispostos em
círculo no polegar, fimbria tarsal interna bastante desenvolvida, artelhos
bastante fimbriados em ambas as margens e superfície ventral do corpo com
manchas e pequenas faixas amarronzadas. Descrições do canto de anúncio e do
girino são apresentadas.
Efficacy of inguinal palpation for detecting oviductal eggs in Hermann's tortoise, Testudo hermanni
Authors: Bertolero Albert , Marín Aurelio 
Published: November 2005

Abstract
For the first time, inguinal palpation effectively detected calcified
oviductal eggs in a tortoise species. Inguinal palpations for 36 Hermann's
tortoises, from six samples during spring 1999 and spring 2000, were
verified with X-ray radiography. Palpation results did not differ
significantly from radiography results and did not differ between two
independent observers. A logistic regression analysis indicated that
palpation success depended on the presence of oviductal eggs, and not on
observer, year (1999 or 2000) or tortoise age class (young adult or old
adult). The probability of correctly classifying females as gravid or
nongravid through palpation was 78.4%. Although inguinal palpation did not
allow detection of all clutches, it is a simple, inexpensive and effective
means to determine the breeding status of Hermann's tortoise
populations.
Relationships of scincid lizards (Mabuya spp.) from the islands of the Gulf of Guinea based on mtDNA sequence data
Authors: Jesus José , Brehm António , Harris D. James 
Published: November 2005

AbstractRelationships of Mabuya lizards from the islands of the Gulf of Guinea where estimated using partial 12S rRNA, 16S rRNA and cytochrome b mitochondrial gene sequences. Mabuya maculilabris from São Tomé and Principe are discreet monophyletic units, highly divergent from each other and from mainland populations, indicating M. maculilabris may be a species complex. Mabuya affinis from Principe is similarly distinct from mainland populations of this species. The relationships of Mabuya ozorii from Annobon are unclear, but the three species in the Gulf of Guinea islands are not closely related, indicating multiple independent colonization events. The recent proposal to partition Mabuya into four genera is premature, since at least five distinct genetic lineages can be identified.
Use of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Hospital Setting
Authors: Cook Curtiss B. , Boyle Mary E. , Cisar Nancy S. , Miller-Cage Victoria , Bourgeois Peggy , Roust Lori R. , Smith Steven A. , Zimmerman Richard S. 
Published: November 2005

Purpose Individuals whose diabetes is being treated in the outpatient setting via an insulin pump often wish to maintain this therapy during hospitalization. The authors propose guidelines for management of patients on insulin pumps who require a hospital admission. Methods A collaborative interinstitutional task force reviewed current available information regarding the use of insulin pumps in the hospital. Results There was little information in the medical literature on how to manage individuals on established insulin pump therapy during a hospital stay. The task force believed that a policy that promotes patient independence through continuation of insulin pump therapy while ensuring patient safety was possible. A set of contraindications for continued use of pump therapy in the hospital are proposed. A sample patient consent form and order set are presented. Finally, measures that can be used to assess effectiveness of an inpatient insulin pump policy are outlined. Conclusions Patients on established insulin pump therapy do not necessarily have to discontinue treatment while hospitalized. However, clear policies and procedures should be established at the institutional level to guide continued use of the technology in the acute care setting.
I Help You, and You Help Me
Authors: Heisler Michele , Piette John D. 
Published: November 2005

Purpose The feasibility and acceptability of using an Interactive Voice Response (IVR)–based platform to facilitate peer support among older adults with diabetes was evaluated. Methods Diabetes patients with poor glycemic control receiving care at a Veterans' Affairs medical center completed a baseline survey, received rudimentary training, and were matched based on their diabetes-related self-management needs. They were asked to contact their partner weekly using the toll-free IVR calling line. At the completion of the 6-week period, participants completed follow-up surveys and brief telephone interviews. Results Forty of 76 patients screened for eligibility by telephone agreed to participate, and 38 completed the 6-week intervention (50% of eligible patients). More than 80% of the pairs spoke at least once a week for 2 of the 6 weeks of the intervention. A total of 79% of the participants reported that the IVR system was easy to use, and 90% stated that they would be more satisfied with their health care if this type of peer support service were available. Of the participants, 70% found the calls helpful in managing diabetes symptoms, 73% reported that their partner helped them improve their self-care, and 70% stated that they helped their partner do things to stay healthy. There were significant improvements in participants' reported diabetes self-care self-efficacy between baseline and follow-up assessments (P< .01). Qualitative assessments suggested that participants found meaning and positive reinforcement for their own self-care through supporting their partner's efforts to manage diabetes. Conclusions An IVR peer support intervention is feasible, acceptable to patients, and may have positive effects on patients' diabetes self-management and health outcomes that warrant more rigorous evaluation in a randomized trial.