bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical treatment of basal cell carcinomas using standard postoperative histological assessment
Authors: Walker Patrick , Hill Dudley 
Published: January 2006

SUMMARYSurgical treatment of basal cell carcinomas using postoperative histological assessment is routinely practised in Australia. The efficacy of the procedure depends on key decisions made by the surgeon. The first is case selection that requires an understanding of the limitations of the procedure. The tumour border is then identified and a margin added. The margin selected should achieve the desired balance between incomplete excision rate and mean tissue sacrifice. There is an inverse relationship between these parameters; achieving a 5% incomplete excision rate requires a mean tissue sacrifice of over 4 mm. Factors affecting margin selection are discussed, unfortunately none allows a dramatic reduction in mean tissue sacrifice. The final decision involves interpreting and acting on the histological examination of the excised specimen. Tumour recurrence is rare (less than 2% at 5 years) if the tumour is clear of the surgical margin. The visualized histological margin required to ensure complete excision varies with histological technique and tumour properties. Routine reporting of histological margin in millimetres or horizontal sectioning is recommended. Tumour recurrence averages 38% when the histological margin is involved. The merits of careful clinical follow up of incompletely excised tumours or immediate re‐excision are discussed.
Connective tissue panniculitis in a child with vitiligo and Hashimoto's thyroiditis
Authors: Mirza Basit , Muir James , Peake Jane 
Published: January 2006

SUMMARYA 9‐year‐old girl presented with a 6‐month history of inflamed tender nodules in the pretibial area. These eventually healed leaving depressed areas of atrophy and loss of subcutaneous tissue. Histology showed a predominantly lymphocytic lobular panniculitis, consistent with connective tissue panniculitis. Investigations revealed an elevated thyroid stimulating hormone, elevated thyroid antiperoxidase antibody and a weakly positive antinuclear antibody (titre 1 in 40). She was commenced on hydroxychloroquine 300 mg daily, which resulted in resolution of the panniculitis. She developed focal vitiligo on the thighs. This gradually improved with 0.1% mometasone furoate ointment. The hydroxychloroquine dose was tapered to 200 mg daily after 12 months, then to 100 mg daily after 18 months therapy. Her thyroid autoantibody levels continued to rise and the hydroxychloroquine was increased again to 300 mg daily. She became borderline hypothyroid. Hashimoto's thyroiditis was diagnosed. Thyroxine was instituted with a resultant improvement in her thyroid blood tests. The lipoatrophy has not developed further during 2‐year follow up.
A global model of island biogeography
Authors: Kalmar Attila , Currie David J. 
Published: January 2006

ABSTRACTAim  The goal of our study was to build a global model of island biogeography explaining bird species richness that combines MacArthur and Wilson's area–isolation theory with the species–energy theory.Location  Global.Methods  We assembled a global data set of 346 marine islands representing all types of climate, topography and degree of isolation on our planet, ranging in size from 10 ha to 800,000 km2. We built a multiple regression model with the number of non‐marine breeding bird species as the dependent variable.Results  We found that about 85–90% of the global variance in insular bird species richness can be explained by simple, contemporary abiotic factors. On a global scale, the three major predictors — area, average annual temperature and the distance separating the islands from the nearest continent — all have constraining (i.e. triangular rather than linear) relationships with insular bird species richness. We found that the slope of the species–area curve depends on both average annual temperature and total annual precipitation, but not on isolation. Insular isolation depends not only on the distance of an island from the continent, but also on the presence or absence of other neighbouring islands. Range in elevation — a surrogate for diversity of habitats — showed a positive correlation with bird diversity in warmer regions of the world, while its effect was negative in colder regions. We also propose a global statistical model to quantify the isolation‐reducing effect of neighbouring islands.Main conclusions  The variation in avian richness among islands worldwide can be statistically explained by contemporary environmental variables. The equilibrium theory of island biogeography of MacArthur and Wilson and the species–energy theory are both only partly correct. Global variation in richness depends about equally upon area, climate (temperature and precipitation) and isolation. The slope of the species richness–area curve depends upon climate, but not on isolation, in contrast to MacArthur and Wilson's theory.
Phosphodiesterase Type 5 is Not Upregulated by Tadalafil in Cultures of Human Penile Cells
Authors: Vernet Dolores , Magee Thomas , Qian Ansha , Nolazco Gaby , Rajfer Jacob , Gonzalez-Cadavid Nestor 
Published: January 2006

ABSTRACT

Objective
Tadalafil, a long-acting phosphodiesterase type 5 (PDE5) inhibitor, improves the erectile response by inhibiting cyclic guanosine monophosphate (cGMP) breakdown. Sustained higher levels of cGMP may hypothetically upregulate PDE5 expression and/or activity and lead to tachyphylaxis. We have investigated whether PDE5 upregulation occurs in vitro in cultures of human penile cells subjected to long-term incubation with increasing concentrations of tadalafil in the presence of a nitric oxide (NO) donor.

Methods
Human corpora cavernosa smooth muscle cells (CSMC) and tunica albuginea fibroblasts (TAF) primary cultures were characterized by immunocytochemistry and Western blot, and incubated with graded concentrations of tadalafil for 14 days, adding S-nitroso-N-acetyl penicillamine (SNAP) as an NO donor for the last 24 hours or at time zero, and cGMP levels were measured. Incubations were repeated for 7, 10, and 14 days, in the presence of SNAP, and PDE5 was estimated by Western blot, and at 14 days, by immunocytochemistry combined with quantitative image analysis, and by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Constructs of the human PDE5A promoter expressing luciferase were cloned and transfected into CSMC, and promoter activation by 8-deoxybromo-cGMP (8-Br-cGMP) was measured by luminometry.

Results
Incubations of CSMC with SNAP and tadalafil up to 14 days did not upregulate PDE5 mRNA or protein levels. With TAF, PDE5 protein was also not upregulated despite a slight increase in mRNA levels. PDE5 enzyme activity was unaffected by tadalafil in either CSMC or TAF. No upregulation of the PDE5 promoter was observed with up to 2 mM 8-Br-cGMP.

Conclusions
Long-term incubation of human penile cells with tadalafil at concentrations above the in vitro IC50, and around the in vivo Cmax utilized in the clinical setting, did not upregulate PDE5A expression nor decrease cGMP levels. These data suggest that PDE5 upregulation is unlikely to occur in vivo on long-term tadalafil treatment.
Role of resynchronisation therapy and implantable cardioverter defibrillators in heart failure
Authors: Ellery S , Williams L , Frenneaux M 
Published: January 2006

Abstract
The worldwide prevalence of heart failure is increasing in part because of an aging population. In the developed world, heart failure affects 1%–2% of the general population, accounting for 5% of adult hospital admissions. There is now convincing evidence supporting the beneficial effects of cardiac resynchronisation therapy for the treatment of heart failure. Numerous observational studies, as well as a series of randomised controlled trials, have shown the safety, efficacy, and long term benefits for patients with chronic systolic heart failure who have broad QRS complexes and refractory symptoms despite optimal medical therapy. These studies have consistently found statistically significant improvements in quality of life, New York Heart Association functional class, exercise tolerance, and left ventricular reverse remodelling. Recent evidence suggests that the benefit may at least in part be because of a reduction in mechanical dysynchrony.
INTEGRAL DOMAINS OF THE FORM A + XI[[X]]: PRIME SPECTRUM, KRULL DIMENSION
Authors: HIZEM SANA , BENHISSI ALI 
Published: December 2005

Let A be an integral domain, X an analytic indeterminate over A and I a proper ideal (not necessarily prime) of A. In this paper, we study the ring [Formula: see text] First, we study the prime spectrum of R. We prove that the contraction map: Spec (A[[X]]) → Spec (R); Q ↦ Q ∩ R induces a homeomorphism, for the Zariski's topologies, from {Q ∈ Spec (A[[X]]) | XI[[X]] ⊈ Q} onto {P ∈ Spec (R) | XI[[X]] ⊈ P}. If P ∈ Spec (R) is such that XI[[X]] ⊆ P then there exists p ∈ Spec (A) such that P = p + XI[[X]]. Next, we study the Krull dimension of R. We give a necessary condition for R to be of finite Krull dimension. In particular, if R is of finite dimension then I must be an SFT ideal of A. Then we determine bounds for dim (R). Examples are given to indicate the sharpness of the results. In case I is a maximal ideal of A and A is either a Noetherian ring, SFT Prüfer domain or A[[X]] is catenarian and I SFT, we establish that dim (R) = dim (A[[X]]) = dim (A) + 1. Finally, we examine the possible transfer of the LFD property and the catenarity between the rings A, A[[X]] and R in case I is a maximal ideal of A.
ON LIE INDUCTION AND THE EXCEPTIONAL SERIES
Authors: GRABOWSKI JAN E. 
Published: December 2005

Lie bialgebras occur as the principal objects in the infinitesimalization of the theory of quantum groups — the semi-classical theory. Their relationship with the quantum theory has made available some new tools that we can apply to classical questions. In this paper, we study the simple complex Lie algebras using the double-bosonization construction of Majid. This construction expresses algebraically the induction process given by adding and removing nodes in Dynkin diagrams, which we call Lie induction. We first analyze the deletion of nodes, corresponding to the restriction of adjoint representations to subalgebras. This uses a natural grading associated to each node. We give explicit calculations of the module and algebra structures in the case of the deletion of a single node from the Dynkin diagram for a simple Lie (bi-)algebra. We next consider the inverse process, namely that of adding nodes, and give some necessary conditions for the simplicity of the induced algebra. Finally, we apply these to the exceptional series of simple Lie algebras, in the context of finding obstructions to the existence of finite-dimensional simple complex algebras of types E9, F5 and G3. In particular, our methods give a new point of view on why there cannot exist such an algebra of type E9.
Down-regulation of Hepatoma-Derived Growth Factor Inhibits Anchorage-Independent Growth and Invasion of Non–Small Cell Lung Cancer Cells
Authors: Zhang Jun , Ren Hening , Yuan Ping , Lang Wenhua , Zhang Li , Mao Li 
Published: January 2006

Abstract
We recently reported that a high level of hepatoma-derived growth factor (HDGF) expression in tumors correlates with a high incidence of tumor relapse or distant metastasis and shortened survival time in patients with non–small cell lung cancer (NSCLC). However, the mechanisms of the HDGF-associated aggressive biological behavior are unknown. In this study, we knocked down HDGF expression in NSCLC cells to determine the biological consequences. Transfection with HDGF-specific small interfering RNA (siRNA) resulted in down-regulation of HDGF expression in four NSCLC cell lines. Down-regulation of HDGF resulted in no detectable effect on anchorage-dependent cell growth as determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a microelectronic cell sensor system, and flow cytometry. In contrast, cells transfected with HDGF-siRNA grew more slowly and formed significantly fewer colonies in soft agar than did cells treated with LipofectAMINE alone or transfected with negative control siRNA. In an in vitro invasion assay, significantly fewer cells transfected with HDGF-siRNA than cells treated with LipofectAMINE alone were able to invade across a Matrigel membrane barrier. In an in vivo mouse model, A549 cells treated with HDGF-siRNA grown significantly slower than the cells treated with LipofectAMINE alone or negative control siRNA. Morphologically, HDGF-siRNA–treated tumors exhibited markedly reduced blood vessel formation and increased necrosis, whereas the Ki67 labeling indices were similar in tumors treated with controls. Our results suggest that HDGF is involved in anchorage-independent growth, cell invasion, and formation of neovasculature of NSCLC. These qualities may contribute to the HDGF-associated aggressive biological behavior of NSCLC. (Cancer Res 2006; 66(1): 18–23)
A New IκB Kinase β Inhibitor Prevents Human Breast Cancer Progression through Negative Regulation of Cell Cycle Transition
Authors: Tanaka Akane , Muto Susumu , Konno Masayo , Itai Akiko , Matsuda Hiroshi 
Published: January 2006

Abstract
Constitutive nuclear factor-κB (NF-κB) activity plays a crucial role in the development and progression of lymphoma, leukemia, and some epithelial cancers. Given the contribution of NF-κB in carcinogenesis, a novel approach that interferes with its activity might have therapeutic potential against cancers that respond poorly to conventional treatments. Here, we have shown that a new IκB kinase β inhibitor, IMD-0354, suppressed the growth of human breast cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing apoptosis. In an electrophoretic mobility shift assay and a reporter assay, IMD-0354 abolished the NF-κB activity in MDA-MB-231 cells in a dose-dependent manner. In the cells incubated with IMD-0354, cell cycle arrested at the G0-G1 phase and apoptotic cells were increased. The expression of some cell cycle regulatory molecules and antiapoptotic molecules was suppressed in cells treated with IMD-0354. On the other hand, cyclin-dependent kinase suppressor p27Kip1 was up-regulated by the addition of IMD-0354. Daily administration of IMD-0354 inhibited tumor expansion in immunodeficient mice into which MDA-MB-231 cells were transplanted. These results indicate that NF-κB may contribute to cell proliferation through up-regulation of cell cycle progression; accordingly, inhibition of NF-κB activity might have a therapeutic ability in the treatment of human breast cancers. (Cancer Res 2006; 66(1): 419-26)
Aneuploidy-Dependent Massive Deregulation of the Cellular Transcriptome and Apparent Divergence of the Wnt/β-catenin Signaling Pathway in Human Rectal Carcinomas
Authors: Grade Marian , Ghadimi B. Michael , Varma Sudhir , Simon Richard , Wangsa Danny , Barenboim-Stapleton Linda , Liersch Torsten , Becker Heinz , Ried Thomas , Difilippantonio Michael J. 
Published: January 2006

Abstract
To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P &lt; 1.0e−7) between normal rectal mucosa and rectal carcinomas, 77 genes had a &gt;5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, 18q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas. (Cancer Res 2006; 66(1): 267-82)
Hematopoietic Stem Cells Are Not the Direct Target of Spontaneous Leukemic Transformation in p18INK4C-Null Reconstituted Mice
Authors: Yuan Youzhong , Yu Hui , Boyer Matthew J. , Song Xianmin , Cao Shaonan , Shen Hongmei , Cheng Tao 
Published: January 2006

Abstract
Cell cycle inhibitors are important regulators in normal tissue regeneration and disruption of the regulators are involved in cancer development. Our recent study showed that the absence of the CDK inhibitor p18INK4C (p18) enhances self-renewal of normal hematopoietic stem cell (HSC) in vivo, whereas previous studies by others showed an increased incidence of leukemogenesis in older p18-null mice. Here, we have examined potential leukemogenesis during experimentally induced regeneration of HSC in the absence of p18 in order to gauge the relation between these two processes. Reconstituted mice with p18-deficient HSCs under the condition of repetitive proliferative stress (serial transplantation) were followed for &gt;3 years. T cell leukemia from the p18−/− origin was recapitulated 24 months after secondary transplantation. However, no myeloid leukemia was found in the recipients. The T cell leukemia–initiating cells (mainly in a CD3lo cell subset) did not share the same immunophenotype with normal HSCs and, in fact, the function of HSCs was significantly compromised with decreased abundance in the leukemic mice. Furthermore, we found that the p15 or p16 gene promoters were frequently methylated in the leukemic cells but not in HSCs. Our present study argues against the possibility of overgrowth of p18-null HSCs leading to a leukemic phenotype. The data also support the notion that p18 has an independent role in T cell maintenance such that CD3+CD8+ cells, unlike HSCs, are more accessible to leukemogenic transformation after the loss of p18. (Cancer Res 2006; 66(1): 343-51)
Interleukin-12 Up-Regulates Fas Expression in Human Osteosarcoma and Ewing's Sarcoma Cells by Enhancing Its Promoter Activity
Authors: Zhou Zhichao , Lafleur Elizabeth A. , Koshkina Nadezhda V. , Worth Laura L. , Lester Malisa S. , Kleinerman Eugenie S. 
Published: December 2005

AbstractInterleukin-12 (IL-12) has shown significant antitumor activity in several preclinical animal tumor models. Our previous studies showed that IL-12 inhibited tumor growth in human osteosarcoma and Ewing's sarcoma animal model. Decreased Fas expression in osteosarcoma increased the lung metastatic potential. In this study, we further examined the mechanism of IL-12 antitumor activity and showed that IL-12 significantly increased Fas expression in both human osteosarcoma cells LM7 and Ewing's sarcoma cells TC71. Up-regulation of Fas expression increased their sensitivity to Fas-induced cell apoptosis. Constructs of the Fas promoter linked to a luciferase reporter gene were used to determine the promoter activity. IL-12 increased Fas promoter activity 4.2- and 4.9-fold in TC71 and LM7 cells, respectively. Time course studies have shown that recombinant IL-12 stimulated Fas promoter activity at 2 hours, reached the peak level at 4 hours, and then declined at 24 hours. To investigate whether IL-12 specifically enhanced Fas promoter activity, we determined whether another gene (E1A) was able to stimulate Fas promoter activity. We also evaluated effect of IL-12 on the topoisomerase IIα promoter. The results indicated that E1A but not IL-12 stimulated topoisomerase IIα promoter activity. E1A failed to increase Fas promoter activity. We also found that κB-Sp1 element at position −295 to −286 in Fas promoter was essential for IL-12-induced activation, and nuclear factor-κB transcription factor was activated after IL-12 treatment in TC71 cells. These results indicate that IL-12 up-regulates Fas expression in human osteosarcoma and Ewing's sarcoma by enhancing Fas promoter activity. Understanding this mechanism may lead to new therapeutic approaches for the treatment of sarcoma involving the use of IL-12. (Mol Cancer Res 2005;3(12):685–91)
Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer
Authors: Gelsi-Boyer Véronique , Orsetti Béatrice , Cervera Nathalie , Finetti Pascal , Sircoulomb Fabrice , Rougé Carole , Lasorsa Laurence , Letessier Anne , Ginestier Christophe , Monville Florence , Esteyriès Séverine , Adélaïde José , Esterni Benjamin , Henry Catherine , Ethier Stephen P. , Bibeau Frédéric , Mozziconacci Marie-Joëlle , Charafe-Jauffret Emmanuelle , Jacquemier Jocelyne , Bertucci François , Birnbaum Daniel , Theillet Charles , Chaffanet Max 
Published: December 2005

AbstractIn human carcinomas, especially breast cancer, chromosome arm 8p is frequently involved in complex chromosomal rearrangements that combine amplification at 8p11-12, break in the 8p12-21 region, and loss of 8p21-ter. Several studies have identified putative oncogenes in the 8p11-12 amplicon. However, discrepancies and the lack of knowledge on the structure of this amplification lead us to think that the actual identity of the oncogenes is not definitively established. We present here a comprehensive study combining genomic, expression, and chromosome break analyses of the 8p11-12 region in breast cell lines and primary breast tumors. We show the existence of four amplicons at 8p11-12 using array comparative genomic hybridization. Gene expression analysis of 123 samples using DNA microarrays identified 14 genes significantly overexpressed in relation to amplification. Using fluorescence in situ hybridization analysis on tissue microarrays, we show the existence of a cluster of breakpoints spanning a region just telomeric to and associated with the amplification. Finally, we show that 8p11-12 amplification has a pejorative effect on survival in breast cancer. (Mol Cancer Res 2005;3(12):655–67)
Identification of Mitogen-Activated Protein Kinase Signaling Pathways That Confer Resistance to Endoplasmic Reticulum Stress in Saccharomyces cerevisiae
Authors: Chen Yijun , Feldman Douglas E. , Deng Changchun , Brown James A. , De Giacomo Anthony F. , Gaw Allison F. , Shi Gongyi , Le Quynh T. , Brown J. Martin , Koong Albert C. 
Published: December 2005

Abstract
Hypoxia activates all components of the unfolded protein response (UPR), a stress response initiated by the accumulation of unfolded proteins within the endoplasmic reticulum (ER). Our group and others have shown previously that the UPR, a hypoxia-inducible factor–independent signaling pathway, mediates cell survival during hypoxia and is required for tumor growth. Identifying new genes and pathways that are important for survival during ER stress may lead to the discovery of new targets in cancer therapy. Using the set of 4,728 homozygous diploid deletion mutants in budding yeast, Saccharomyces cerevisiae, we did a functional screen for genes that conferred resistance to ER stress–inducing agents. Deletion mutants in 56 genes showed increased sensitivity under ER stress conditions. Besides the classic UPR pathway and genes related to calcium homeostasis, we report that two additional pathways, including the SLT2 mitogen-activated protein kinase (MAPK) pathway and the osmosensing MAPK pathway, were also required for survival during ER stress. We further show that the SLT2 MAPK pathway was activated during ER stress, was responsible for increased resistance to ER stress, and functioned independently of the classic IRE1/HAC1 pathway. We propose that the SLT2 MAPK pathway is an important cell survival signaling pathway during ER stress. This study shows the feasibility of using the yeast deletion pool to identify relevant mammalian orthologues of the UPR. (Mol Cancer Res 2005;3(12):669–77)