bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of programmed cell death 4 expression marks adenoma‐carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer
Authors: Mudduluru Giridhar , Medved Fabian , Grobholz Rainer , Jost Camela , Gruber Anette , Leupold Joerg H. , Post Stefan , Jansen Aaron , Colburn Nancy H. , Allgayer Heike 
Published: September 2007

AbstractBACKGROUND.Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma‐carcinoma sequence, 2) to support phosphorylated Akt (pAkt)‐mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer.METHODS.Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow‐up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses.RESULTS.A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan‐Meier analysis (using the Mantel‐Cox log‐rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease‐specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease‐specific or overall survival.CONCLUSIONS.To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues. Cancer 2007. Published 2007 by the American Cancer Society.
Descriptive nomograms of adjuvant radiotherapy use and patterns of care analysis for stage I and II endometrial adenocarcinoma: A surveillance, epidemiology, and end results population study
Authors: Lee Christopher M. , Szabo Aniko , Shrieve Dennis C. , Macdonald O. Kenneth , Tward Jonathan D. , Skidmore Thomas B. , Gaffney David K. 
Published: September 2007

AbstractBACKGROUND.Although endometrial cancer remains the most common gynecologic malignancy in the United States, differing approaches to adjuvant radiotherapy treatment for early disease exist within the medical community because of the lack of a national consensus.METHODS.The authors studied patterns of adjuvant care for stage I and II endometrial adenocarcinoma using a large United States population database. A retrospective analysis was conducted from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute from 1988 to 2002, and 26,923 women with American Joint Committee on Cancer stage I and II endometrial adenocarcinoma were selected. The following prognostic factors were analyzed: age, race, stage, grade, year of diagnosis, SEER registry location, and use and type of postoperative radiotherapy (RT). Adjuvant RT was coded as none, external‐beam RT (EBRT), brachytherapy (BR), or a combination of the 2 (EBRT + BR).RESULTS.Higher tumor grade and stage led to greater use of RT. The odds ratio (OR) for adjuvant RT was 3.4 for stage IB versus stage IA and 51.8 for stage IC/II versus stage IA. The effect of grade depended on stage: for stages IA and IB, the OR was 2.9 for grade 2 versus grade 1 and 11.7 for grade 3/4 versus grade 1; whereas, for stage IC/II, the OR was 1.5 for grade 2 versus grade 1 and 2.0 for grade 3/4 versus grade 1. Within stage I, increasing substage and grade increased the odds of EBRT with or without BR compared with BR alone. Race did not effect the choice of therapy (all P > .1). Geographic location had a significant effect on overall RT use and therapy choice.CONCLUSIONS.To the authors' knowledge, this was the largest patterns of care analysis to date of adjuvant RT in patients with stage I and II endometrial adenocarcinoma. The current study revealed that there is significant diversity in the use of adjuvant RT across the United States, and the results reflected the absence of a national consensus on adjuvant treatment for early‐stage disease. Cancer 2007. © 2007 American Cancer Society.
Interleukin‐6 and its receptor in cancer
Authors: Hong David S. , Angelo Laura S. , Kurzrock Razelle 
Published: September 2007

AbstractInterleukin‐6 (IL‐6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL‐6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL‐6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL‐6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL‐6 are observed in almost every type of tumor studied and predict a poor outcome. Furthermore, elevated IL‐6 levels are associated strongly with several of the striking phenotypic features of cancer. Several molecules have been developed recently that target the biologic function of IL‐6. Early results in the clinic suggest that this strategy may have a significant salutary impact on diverse tumors. The field of cytokine research has yielded a deep understanding of the fundamental role of IL‐6 and its receptor in health and disease. Therapeutic targeting of IL‐6 and its receptor in cancer has strong biologic rationale, and there is preliminary evidence suggesting that targeting of the IL‐6 system may be beneficial in the treatment of cancer. Cancer 2007. © 2007 American Cancer Society.
Surviving colorectal cancer
Authors: Schneider Eric C. , Malin Jennifer L. , Kahn Katherine L. , Ko Clifford Y. , Adams John , Epstein Arnold M. 
Published: September 2007

AbstractBACKGROUND.The number of long‐term survivors after a cancer diagnosis is increasing, yet relatively few studies have addressed survivors' reported symptoms beyond the initial year after diagnosis.METHODS.The symptom reports of 474 survivors of colon and rectal cancer from 5 US metropolitan areas were collected during 2002‐2003 as part a larger study of the quality of care for patients with cancer diagnosed in 1998. The relation between the prevalence of reported symptoms and prior treatments received was analyzed, adjusting statistically for other patient characteristics.RESULTS.Sixty‐nine percent of the survivors had colon cancer and 31% had rectal cancer. The most commonly reported symptoms were “fatigue” (23%), “negative feelings about body appearance” (14%), “diarrhea” (13%), and “constipation” (7%). Higher percentages of respondents attributed health effects to cancer or its treatment including “worry about health” (24%), “physical discomfort” (19%), and “activity limitations” (15%). In general, prior treatment was not associated with symptom prevalence. However, radiation therapy recipients and patients that received a diverting ostomy were more likely than others to report some of the symptoms we studied. Attribution of health effects to disease or treatment did not vary by prior treatment except that recipients of radiation therapy were more likely than others to report limitations in their activities (30% vs 10%; P = .003).CONCLUSIONS.Among colorectal cancer survivors the prevalence of symptoms at 4 years was low and relatively comparable to published estimates for the general population, but some survivors continue to attribute health effects to cancer or its treatment. Cancer 2007. © 2007 American Cancer Society.
Zone‐specific remodeling of tumor blood vessels affects tumor growth
Authors: Tilki Derya , Kilic Nerbil , Sevinc Sema , Zywietz Friedrich , Stief Christian G. , Ergun Suleyman 
Published: September 2007

AbstractBACKGROUND.Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet.METHODS.By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones.RESULTS.The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of α‐smooth‐muscle‐actin (α‐SMA)‐positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for αvβ3‐integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative.CONCLUSIONS.The results indicate a zone‐specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging. Cancer 2007. © 2007 American Cancer Society.
Reproductive history, infertility treatment, and the risk of acute leukemia in children with down syndrome
Authors: Puumala Susan E. , Ross Julie A. , Olshan Andrew F. , Robison Leslie L. , Smith Franklin O. , Spector Logan G. 
Published: September 2007

AbstractBACKGROUND.Children with Down syndrome (DS) have from 10 to 20 times the risk of developing acute leukemia than the general pediatric population. There is mixed evidence for associations between reproductive history or infertility and acute leukemia among children without DS.METHODS.The authors conducted a case‐control study of acute leukemia among children with DS to investigate possible risk factors in this population. From 1997 to 2002, 158 children aged <20 years with DS who had a diagnosis of acute leukemia (97 children with acute lymphoblastic leukemia [ALL] and 61 children with acute myeloid leukemia [AML]) were enrolled at Children's Oncology Group (COG) institutions. Controls with DS (n = 173) were selected from the cases' primary care clinic and frequency matched to cases on age. Telephone interviews were conducted with mothers of cases and controls assessing reproductive history, infertility, and infertility treatment.RESULTS.Null results were observed overall and by subtype for reproductive factors, including previous pregnancy outcomes and contraceptive use, and for most infertility outcomes. There was an increased risk of AML among children with DS whose parents had ever tried for ≥1 year to become pregnant (odds ratio [OR], 2.22; 95% confidence interval [95% CI], 1.14–4.33). A 1‐year increase in maternal age also was associated with AML (OR, 1.06; 95% CI, 1.01–1.12).CONCLUSIONS.Although the questionnaire was limited in this area, the results suggested that the risk for AML may be raised in children with DS because of infertility. In that the risk of infertility, along with having a child with DS, increase with age, these results warrant more research. Cancer 2007. © 2007 American Cancer Society.
Interrogation of Single Synthetic Polymer Chains and Polysaccharides by AFM‐Based Force Spectroscopy
Authors: Giannotti Marina I. , Vancso G. Julius 
Published: September 2007

AbstractThis contribution reviews selected mechanical experiments on individual flexible macromolecules using single‐molecule force spectroscopy (SMFS) based on atomic force microscopy. Focus is placed on the analysis of elasticity and conformational changes in single polymer chains upon variation of the external environment, as well as on conformational changes induced by the mechanical stress applied to individual macromolecular chains. Various experimental strategies regarding single‐molecule manipulation and SMFS testing are discussed, as is theoretical analysis through single‐chain elasticity models derived from statistical mechanics. Moreover, a complete record, reported to date, of the parameters obtained when applying the models to fit experimental results on synthetic polymers and polysaccharides is presented.
Two‐Photon Microscopy and Spectroscopy of Lanthanide Bioprobes
Authors: D'Aléo Anthony , Pompidor Guillaume , Elena Bénédicte , Vicat Jean , Baldeck Patrice L. , Toupet Loïc , Kahn Richard , Andraud Chantal , Maury Olivier 
Published: September 2007

AbstractThe linear and non‐linear photophysical properties of tris‐dipicolinate europium and terbium complexes (absorption, emission, lifetime, luminescence induced by two‐photon absorption) are studied in the crystalline state as well as in protein derivative crystals and compared to those in solution. Upon laser irradiation at 532 nm, luminescence of terbium is induced by a two‐photon antenna effect, whereas luminescence of europium results from one‐photon absorption in forbidden f–f transitions. Finally, linear and two‐photon microscopy imaging experiments on biological and bio‐inspired crystals are performed. These first proof‐of‐concept experiments open the way for the development of time‐resolved non‐linear microscopy that should combine the advantages of lanthanide luminescence (long lifetime, sharp emission bands, insensitivity to oxygen) with those of confocal biphotonic excitation (near‐IR excitation, 3D resolution and reduced photodamage).
Convergence and extension movements affect dynamic notochord‐somite interactions essential for zebrafish slow muscle morphogenesis
Authors: Yin Chunyue , Solnica‐Krezel Lilianna 
Published: September 2007

AbstractDuring vertebrate gastrulation, convergence and extension (C&E) movements shape and position the somites that form the fast and slow muscles. In zebrafish knypek;trilobite non‐canonical Wnt mutants, defective C&E movements cause misshapen somites and reduction of slow muscle precursors, the adaxial cells. Here, we demonstrate essential roles of C&E in slow muscle morphogenesis. During segmentation, the adaxial cells change shapes and migrate laterally to form slow muscles at the myotome surface. Using confocal imaging techniques, we show that the adaxial cells undergo three‐step shape changes, including dorsoventral elongation, anterior‐ward rotation, and anteroposterior elongation. The adaxial cells in knypek;trilobite double mutants maintain prolonged contact with the notochord and fail to rotate anteriorly. Such a defect was suppressed by physical removal of their notochord or by introducing wild‐type notochord cells into the mutant. We propose that in the double mutants, impaired C&E movements disrupt notochord development, which impedes the adaxial cell shape changes. Developmental Dynamics 236:2742–2756, 2007. © 2007 Wiley‐Liss, Inc.
Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets
Authors: Goto Yutaka , Nomura Masatoshi , Tanaka Kimitaka , Kondo Akiyo , Morinaga Hidetaka , Okabe Taijirou , Yanase Toshihiko , Nawata Hajime , Takayanagi Ryoichi , Li En 
Published: September 2007

AbstractSignaling through activin type IIB receptor (ActRIIB) has been shown to regulate the axial formation and the development of foregut‐derived organs such as the pancreas in mice. Here, we provide genetic evidence that ActRIIB and Smad2 genes cooperatively regulated asymmetrical patterning of the thoracic organs and pancreas development in mice. The loss of one allele of Smad2 on ActRIIB−/− background resulted in the increased severity of ActRIIB−/− phenotypes, including right pulmonary isomerism and complex cardiac malformations, and resulted in 100% frequency of death soon after birth. Of interest, 14% of compound heterozygous ActRIIB+/−Smad2+/− mice exhibited the ActRIIB−/− phenotypes and died soon after birth. In the pancreas, hypoplastic islets were found not only in ActRIIB−/− but also in Smad2+/− mice. A more severe phenotype was also found in ActRIIB+/−Smad2+/− mice. As well, these mutant mice exhibited impaired glucose tolerance in a gene dosage‐sensitive manner. This genetic evidence strongly suggested that ActRIIB and Smad2 function in the same signaling pathway to regulate axial patterning and pancreas islet formation by means of a threshold mechanism. Developmental Dynamics 236:2865–2874, 2007. © 2007 Wiley‐Liss, Inc.
Imaging the migrating border cell cluster in living Drosophila egg chambers
Authors: Tekotte Hille , Tollervey David , Davis Ilan 
Published: September 2007

AbstractCell migration is a key process in animal development and central to the spread of cancer. Border cell migration in Drosophila egg chambers is an excellent general model for cell migration, but lacks techniques for studying this process in living cells. Here, we describe a simple and effective method of preparing egg chambers in halocarbon oil. The movement and behavior of the migrating border cells can reproducibly be followed in up to 25 egg chambers simultaneously by time‐lapse microscopy using a variety of green fluorescent protein markers on a widefield microscope over a period of 4 hr. Our studies reveal a remarkably linear migration route of the border cell cluster and highly dynamic activity within their cluster. Migrating cells rapidly alter their relative positions and generate transient protrusions. These activities are likely to play key roles in the mechanism of migration and cannot readily be analyzed using fixed samples. Developmental Dynamics 236:2818–2824, 2007 © 2007 Wiley‐Liss, Inc.
Serial cloning of pigs by somatic cell nuclear transfer: Restoration of phenotypic normality during serial cloning
Authors: Cho Seong‐Keun , Kim Jae‐Hwan , Park Jong‐Yi , Choi Yun‐Jung , Bang Jae‐Il , Hwang Kyu‐Chan , Cho Eun‐Jeong , Sohn Sea‐Hwan , Uhm Sang Jun , Koo Deog‐Bon , Lee Kyung‐Kwang , Kim Teoan , Kim Jin‐Hoi 
Published: September 2007

AbstractSomatic cell nuclear transfer (scNT) is a useful way to create cloned animals. However, scNT clones exhibit high levels of phenotypic instability. This instability may be due to epigenetic reprogramming and/or genomic damage in the donor cells. To test this, we produced transgenic pig fibroblasts harboring the truncated human thrombopoietin (hTPO) gene and used them as donor cells in scNT to produce first‐generation (G1) cloned piglets. In this study, 2,818 scNT embryos were transferred to 11 recipients and five G1 piglets were obtained. Among them, a clone had a dimorphic facial appearance with severe hypertelorism and a broad prominent nasal bridge. The other clones looked normal. Second‐generation (G2) scNT piglets were then produced using ear cells from a G1 piglet that had an abnormal nose phenotype. We reasoned that, if the phenotypic abnormality of the G1 clone was not present in the G2 and third‐generation (G3) clones, or was absent in the G2 clones but reappeared in the G3 clones, the phenotypic instability of the G1 clone could be attributed to faulty epigenetic reprogramming rather than to inherent/accidental genomic damage to the donor cells. Blastocyst rates, cell numbers in blastocyst, pregnancy rates, term placenta weight and ponderal index, and birth weight between G1 and G2 clones did not differ, but were significantly (P < 0.05) lower than control age‐ and sex‐matched piglets. Next, we analyzed global methylation changes during development of the preimplantation embryos reconstructed by donor cells used for the production of G1 and G2 clones and could not find any significant differences in the methylation patterns between G1 and G2 clones. Indeed, we failed to detect the phenotypic abnormality in the G2 and G3 clones. Thus, the phenotypic abnormality of the G1 clone is likely to be due to epigenetic dysregulation. Additional observations then suggested that expression of the hTPO gene in the transgenic clones did not appear to be the cause of the phenotypic abnormality in the G1 clones and that the abnormality was acquired by only a few of the G1 clone's cells during its gestational development. Developmental Dynamics 236:3369–3382, 2007. © 2007 Wiley‐Liss, Inc.
Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development
Authors: Wu Xunwei , Li Shaohua , Chrostek‐Grashoff Anna , Czuchra Aleksandra , Meyer Hannelore , Yurchenco Peter D. , Brakebusch Cord 
Published: September 2007

AbstractTo study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42‐null embryonic stem cells and analyzed peri‐implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane, but exhibited defects of cell polarity, cell–cell junctions, survival, and cavitation. These defects corresponded to a decreased phosphorylation and membrane localization of aPKC, a reduced phosphorylation of GSK3β, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3β seem to contribute to cell polarization and cell–cell contacts. In contrast, EBs expressing dominant‐negative (dn) PKCζ mimicked well the phenotype of Cdc42‐null EBs, suggesting a major role of aPKC in mediating cell polarization downstream of Cdc42. Finally, aggregation experiments with endodermal cell lines suggested that Cdc42 might affect formation of adherens and tight junctions by PKCζ‐dependent regulation of the protein levels of p120 catenin and E‐cadherin. Developmental Dynamics 236:2767–2778, 2007. © 2007 Wiley‐Liss, Inc.