bluuebunny/crossref_metadata_2025 huggingface dataset:
A New ZnII Tweezer Pyridine‐Naphthalene System – An Off‐On‐Off System Working in a Biological pH Window
Authors: Aucejo Ricardo , Alarcón Javier , García‐España Enrique , Llinares José M. , Marchin Katherine L. , Soriano Conxa , Lodeiro Carlos , Bernardo M. Alexandra , Pina Fernando , Pina João , Seixas de Melo J.
Published: September 2005

The synthesis, protonation behaviour and Zn2+ coordination chemistry of a new photoactive polyamine exhibiting “off‐on‐off” fluorescence is presented. Addition of Zn2+ reduces the width of the fluorescence window, which is centred around physiological pH, and sharply enhances the emission intensity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Anions of 1,3,5‐Benzenetricarboxylic and Heptanedioic Acids Serving as Bridges between Dimolybdenum(V) Metal–Metal Bonded Units: Preparation and Structural Characterization of Dinuclear and Tetranuclear Complexes
Authors: Modec Barbara , Brenčič Jurij V.
Published: September 2005

(PyH)5[MoOCl4(H2O)]3Cl2 and (PyH)[MoOBr4] reacted with the anions of 1,3,5‐benzenetricarboxylic acid (btcH3) and heptanedioic acid (hdaH2) to afford a series of novel carboxylato complexes based on the {Mo2O4}2+ structural core: (PyH)4[Mo2O4Cl4(μ2‐btcH2)]Cl (1), (PyH)4[Mo2O4Br4(μ2‐btcH2)]Br (2), [(Mo2O4Py3)2(μ3‐btcH)2]·6Py (3), (PyH)6[(Mo2O4Cl4)2(μ4‐hda)]·2CH3CN (4), and (PyH)10[(Mo2O4Cl4)2(μ4‐hda)][MoOCl5]Cl2 (5) {Py = pyridine, C5H5N; PyH+ = pyridinium cation, C5H5NH+; btcH2– = (HOOC)2C6H3COO–; btcH2– = (HOOC)C6H3(COO)22– and hda2– = –OOC(CH2)5COO–}. A pair of isostructral compounds 1 and 2 contains dinuclear anions [Mo2O4X4(μ2‐btcH2)]3– (X = Cl, Br) in which the btcH2– ligand is bonded to the {Mo2O4}2+ core via one carboxylate group in a syn‐syn bidentate bridging manner. In 3, two btcH2– ligands link two {Mo2O4}2+ cores into a loop‐like structure. Each btcH2– ligand is coordinated via two carboxylate groups, with one in the syn‐syn bidentate bridging manner and with another in a monodentate manner. The linkage of two dinuclear subunits was also realized in [(Mo2O4Cl4)2(μ4‐hda)]6–, the anion in 4 and 5, where both carboxylate groups of the hda2– ligand bind in the syn‐syn bidentate‐bridging manner to {Mo2O4}2+ cores. The title compounds were characterized by X‐ray crystallography and infrared spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
New Chiral Building Blocks and Branched 1,6‐Anhydro Sugars from Regio‐ and Stereoisomeric Černý Epoxides
Authors: Krohn Karsten , Gehle Dietmar , Flörke Ulrich
Published: September 2005

The tandem epoxide→allyl alcohol rearrangement–cuprate cross‐coupling previously described for the Černý epoxide 1, to yield the allyl alcohol 2, was extended to the regioisomeric epoxy‐tosylate 3, to yield allyl alcohol 4, and to the stereoisomeric epoxide 5 to afford the allyl alcohols of type 6. Further transformation of the products from this new two‐step one‐pot reaction afforded regio‐ and stereodiverse branched 1,6‐anhydrosugars of potential use as building blocks in natural product synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Molecular Selective Binding of Pyridinium Guest Ions by Water‐Soluble Calix[4]arenes
Authors: Liu Yu , Yang En‐Cui , Chen Yong , Guo Dong‐Sheng , Ding Fei
Published: September 2005

The complex stability constants (KS) and thermodynamic parameters (ΔG°, ΔH°, and TΔS°) for 1:1 intermolecular complexation of water‐soluble calix[4]arene tetrasulfonate (CAS) and thiacalix[4]arene tetrasulfonate (TCAS) with pyridinium guest ions 1–10 have been determined by means of titration calorimetry in an acidic buffer solution (pH = 2.0) at 298.15 K, and their binding modes have been investigated by NMR spectroscopy. Possessing a smaller cavity and a higher π electron density than TCAS, CAS affords the stronger binding abilities for all guests examined, giving an exciting molecular selectivity of up to 354 for the 2,6‐dimethylpyridine/2,6‐pyridinedicarboxylic acid pair. The high binding affinities, attributed to the favorable enthalpic gains, are comprehensively discussed from the viewpoint of π–π stacking, electronic effect and size‐fit relationship between host and guest. The thermodynamic parameters that have been obtained, together with the NMR results, jointly demonstrate that the position, number, and type of substituent groups introduced onto the guest molecule are the key factors controlling the structural‐energetics correlation for the molecular selective binding of water‐soluble calixarenes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A New Modular and Practical Methodology for the Synthesis of 4‐ or 3‐Substituted Phenyl C‐Nucleosides
Authors: Hocek Michal , Pohl Radek , Klepetářová Blanka
Published: September 2005

A novel efficient and practical approach to the synthesis of 4‐ or 3‐substituted phenyl C‐nucleosides has been developed. It consists in coupling of protected halogenose 1 with bromophenylmagnesium bromides followed by acid mediated epimerization to prepare 4‐ or 3‐bromophenyl C‐nucleoside intermediates. Their Pd‐catalyzed cross‐coupling reactions with diverse organometallics followed by deprotection afforded the title nucleoside analogues. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Information rate bounds in common‐mode aided wireline communications
Authors: Magesacher Thomas , Ödling Per , Börjesson Per Ola , Shamai (Shitz) Shlomo
Published: September 2005

Communication over the copper twisted‐pair channel is performed by transmitting and receiving differential‐mode (DM) signals. In this paper, we extend the conventional DM receiver scheme by incorporating the common‐mode (CM) signal, which is strongly correlated with the DM signal and can be extracted at the end of every wire pair. The wireline channel, including the CM receive signal, is modelled as a Gaussian vector (multiple‐input multiple‐output) channel with memory and an arbitrary number of disturbers that introduce interference which can be correlated both temporally and spatially. We investigate the potential of CM‐aided reception in terms of information rate for single‐user digital subscriber line systems (xDSL) operating on a single pair. Numerical results of information rate calculations using measured channel data are presented. The achievable information rate of the twisted‐pair channel when incorporating the CM signal in practically relevant example scenarios can exceed the information rate of the conventional DM channel by a factor of up to two. Copyright © 2005 AEIT.
Promoting organizational learning inhigher education to achieve equity in educational outcomes
Authors: Bauman Georgia L.
Published: September 2005

This chapter describes a project in which teams of faculty, administrators, and staff from fourteen colleges and universities engaged in organizational learning for the purposes of identifying and improving inequitable educational outcomes for African American and Latino students.
Community service as learning
Authors: Anderson Jodi L.
Published: September 2005

This chapter uses the conceptual framework of a learning organization to make a case for how a theory might enrich organizational practice in the field of higher education.
Organizational learning through knowledge workers and infomediaries
Authors: Milam John
Published: September 2005

Knowledge management is defined and compared to information management and the institutional research function. In order to promote learning, new tools such as learning histories are needed, mistakes must be valued, and dissatisfaction recognized as part of the learning process.
Modeling learning: The role of leaders
Authors: Ramaley Judith A. , Holland Barbara A.
Published: September 2005

What follows is the Portland State University story, a reflection on change as a scholarly act within a learning community using techniques from organizational learning.
Organizational learning: A tool for diversity and institutional effectiveness
Authors: Smith Daryl G. , Parker Sharon
Published: September 2005

Organizational learning, along with a framework for diversity, is an effective approach for campuses seeking sustained institutional change with regard to diversity.
Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice
Authors: Wang Shixuan , Coleman Elaine J. , Pop Laurentiu M. , Brooks Kimberly J. , Vitetta Ellen S. , Niederkorn Jerry Y.
Published: September 2005

We have shown that administration of a novel anti‐CD54 monoclonal antibody (UV3) results in long‐term survival of SCID mice bearing human myeloma xenografts. Previous studies have demonstrated a link between the expression of CD54 and the progression of uveal melanoma. Our study assessed the expression of CD54 on 7 human uveal melanoma cell lines and 3 cell lines established from uveal melanoma metastases. In vivo studies examined the efficacy of systemic and local administration of UV3 antibody on the progression of uveal melanoma cells transplanted either heterotopically or orthotopically into SCID mice. Five of the 7 primary uveal melanoma cell lines and all 3 of the metastases cell lines expressed CD54. Intraperitoneal injection of either IgG or F(ab′)2 fragments of UV3 significantly inhibited the growth of subcutaneous and intraocular melanomas. Subconjunctival injection of either IgG or F(ab′)2 fragments of UV3 produced a significant reduction in the growth of intraocular melanomas, even if the antibody was administered after the appearance of intraocular tumors. The results indicate that both primary and metastatic human uveal melanoma cells express CD54. The marked inhibition of intraocular and subcutaneous uveal melanoma progression suggests that UV3 antibody is a promising therapeutic agent for further evaluation in patients with uveal melanoma. This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma. © 2005 Wiley‐Liss, Inc.
DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients
Authors: Wynter Coral V.A. , Kambara Takeshi , Walsh Michael D. , Leggett Barbara A. , Young Joanne , Jass Jeremy R.
Published: September 2005

Colorectal adenomas have traditionally been regarded as homogeneous. The aim of our study was to identify molecular features that may differentiate sporadic adenomas from familial adenomas such as Familial Adenomatous Polyposis (FAP) and Multiple Adenoma patients. DNA methylation was tested at Methylated IN Tumor (MINT) loci (1,2,12,31) and the CpG promoter region of genes MLH1, HPP1, MGMT, p14ARF and p16INK4a in FAP‐associated adenomas (33) from 5 patients with a known APC mutation (Group 1, FAP), adenomas (29) from 4 Multiple Adenoma patients (Group 2 Multiple), adenomas (14) from 3 patients with sporadic colorectal cancers showing high microsatellite instability (Group 3, MSI‐H) and adenomas (16) from 7 patients, with sporadic colorectal cancers showing microsatellite stable or low level instability (Group 4, MSS/MSI‐L). Aberrant Crypt Foci (ACFs), Hyperplastic Polyps (HPs) and cancers were also examined for methylation status as well as K‐ras mutation. Multiple Adenoma patients were examined for germline polymorphisms in the base excision repair gene, MYH. The familial syndrome, FAP ‐associated adenomas showed a significantly low frequency of MINT methylation (15.5%,) compared to sporadic MSS/MSI‐L‐associated adenomas (35.5%). Group 3 (MSI‐H) adenomas were different in that many showed serration and a high level of methylation (57.1%). Group 2, Multiple Adenoma cases, resembled sporadic MSS/MSI‐L‐associated adenomas. However the promoter regions of key genes, MGMT, p14ARF and p16INK4a were methylated to a greater extent than MINTs in both sporadic and familial adenomas. Genetic profiling of adenomas supports the concept that adenomas belonging to familial syndromes pursue a different pathway to tumorigenesis than their sporadic counterpar/ts from their earliest formation. © 2005 Wiley‐Liss, Inc.
Loss of intercellular adhesion activates a transition from low‐ to high‐grade human squamous cell carcinoma
Authors: Margulis Alexander , Zhang Weitian , Alt‐Holland Addy , Pawagi Sujata , Prabhu Padmaja , Cao Jian , Zucker Stanley , Pfeiffer Laurence , Garfield Jacqueline , Fusenig Norbert E. , Garlick Jonathan A.
Published: September 2005

The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E‐cadherin‐mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell‐cell adhesion was disrupted in early‐stage epithelial tumor cells (HaCaT‐II‐4) through expression of a dominant‐negative form of E‐cadherin (H‐2Kd‐Ecad). Three‐dimensional human tissue constructs harboring either H‐2Kd‐Ecad‐expressing or control II‐4 cells (pBabe, H‐2Kd‐EcadΔC25) were cultured at an air‐liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H‐2Kd‐Ecad‐expressing tumors demonstrated a switch to a high‐grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high‐grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 γ2 chain. When II‐4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E‐cadherin‐deficient cells detached, migrated as single cells and expressed N‐cadherin. Function‐blocking studies demonstrated that this migration was matrix metalloproteinase‐dependent, as GM‐6001 and TIMP‐2, but not TIMP‐1, could block migration. Gene expression profiles revealed that E‐cadherin‐deficient II‐4 cells demonstrated increased expression of proteases and cell‐cell and cell‐matrix proteins. These findings showed that loss of E‐cadherin‐mediated adhesion plays a causal role in the transition from low‐ to high‐grade squamous cell carcinomas and that the absence of E‐cadherin is an important prognostic marker in the progression of this disease. © 2005 Wiley‐Liss, Inc.
Occupational physical activity and risk of adenocarcinomas of the esophagus and stomach
Authors: Vigen Cheryl , Bernstein Leslie , Wu Anna H.
Published: September 2005

Physical activity may have a role in many cancers, but little is known about its effect on esophageal and gastric adenocarcinoma risk. We investigated occupational physical activity and esophageal and gastric adenocarcinoma risk in a population‐based, case‐control study including 212 esophageal, 264 gastric cardia and 389 distal gastric cancer cases, and 1,330 controls in Los Angeles County. Lifetime occupational histories were obtained during in‐person interviews, and total lifetime occupational activity (Total Activity Index) was calculated using US Census job codes classified as sedentary, or moderately or highly physically active. Average Annual Activity Index was a per‐year Total Activity Index counterpart. Unconditional logistic regression was used to calculate odds ratios, 95% confidence intervals and trend tests adjusting for gender, race, age, birthplace, education, smoking, body mass index (BMI) and number of years worked. Esophageal adenocarcinoma risk tended to decrease with increasing Total Activity Index (OR = 0.67, 95% CI = 0.38,1.19 for highest versus lowest quartile), but neither gastric cardia nor distal gastric cancer was associated with the Total Activity Index. This inverse association held for esophageal adenocarcinoma (OR = 0.61, 95% CI = 0.38,0.99 for highest vs. lowest quartile) and modest associations were observed for gastric cardia (OR = 0.76, 95% CI = 0.49,1.18) and distal gastric cancer (OR = 0.77, 95% CI = 0.52,1.14) when based on Average Annual Activity Index before age 65 years. Analyses stratified by gender, race, age, BMI, education and years worked provided similar results. We found a modest protective effect of Total Activity Index on esophageal adenocarcinoma. Future studies with more complete information on occupational and recreational physical activity are needed to confirm and further investigate the suggested protective effect of physical activity on these tumor types. © 2005 Wiley‐Liss, Inc.
Vascular endothelial growth factor‐D is a survival factor for human breast carcinoma cells
Authors: Akahane Manabu , Akahane Takemi , Matheny Shannon L. , Shah Amy , Okajima Eijiro , Thorgeirsson Unnur P.
Published: September 2005

Vascular endothelial growth factor‐D (VEGF‐D) stimulates growth of vascular and lymphatic endothelial cells by signaling through the tyrosine kinase receptors KDR (VEGFR‐2) and Flt‐4 (VEGFR‐3). In the present study, we examined the effects of VEGF‐D on apoptosis in human MCF‐7 and MDA‐MB‐231 breast carcinoma cells. Because VEGF‐D was not expressed constitutively in vitro, stable VEGF‐D transfectants were produced. The VEGF‐D‐expressing MCF‐7 and MDA‐MB‐231 lines displayed resistance to apoptosis induced by hypoxia, staurosporin and cycloheximide. Increased Bcl‐2 expression, decreased homogenous caspase activities and inhibition of poly(ADP‐ribose) polymerase cleavage were associated with inhibition of apoptosis in VEGF‐D‐expressing clones. Also, caspase‐3 activation was suppressed in the VEGF‐D expressing MDA‐MB‐231 clone. The antiapoptotic effect of VEGF‐D in vitro was recapitulated in vivo using VEGF‐D‐expressing MDA‐MB‐231 xenografts. The lack of VEGFR‐2 protein expression by Western blot and ineffectiveness of a neutralizing VEGFR‐2 antibody in eliminating the antiapoptotic effects of VEGF‐D suggest a different and yet unknown signaling mechanism. Our findings indicate that VEGF‐D has a novel function as a survival factor of breast carcinoma cells in addition to its established functions as an angiogenic and lymphangiogenic factor. © 2005 Wiley‐Liss, Inc.
Vascular endothelial growth factor–regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases
Authors: Wang Feng‐qiang , So John , Reierstad Scott , Fishman David A.
Published: September 2005

Vascular endothelial growth factor (VEGF) expression is elevated in primary ovarian tumors and metastases. We examined the effect of VEGF on epithelial ovarian cancer (EOC) in vitro invasion and migration and underlying mechanisms. Using the Matrigel invasion assay and colloidal gold phagokinetic track assay, we found that VEGF induced EOC DOV13 invasion and migration in a matrix metalloproteinase (MMP)–dependent manner. Using Western blotting, we show that VEGF, at 20–80 ng/ml, induced secretion of pro‐MMP‐7 and pro‐MMP‐9 and activation of pro‐MMP‐2 in DOV13 conditioned medium in a concentration‐dependent manner. However, gelatinolytic activity and total MMP‐7 protein in DOV13 conditioned medium reached the maximum upon VEGF treatment at 20–40 ng/ml and decreased at higher‐concentration VEGF treatment (80 ng/ml), as shown by DQ‐gelatin degradation assay and ELISA. In addition to the effect on MMP secretion/activation, VEGF stimulated secretion of TIMP‐2; and blocking TIMP‐2 activity by an anti‐TIMP‐2 MAb significantly increased VEGF (80 ng/ml)–induced DOV13 invasion (p < 0.05), suggesting that VEGF may regulate MMP‐2 activity in DOV13 conditioned medium through TIMP‐2. Using real‐time PCR, we found that VEGF, at 20 ng/ml, significantly increased the expression of VEGFR‐1 and VEGFR‐2 by approximately 4‐fold and 31‐fold, respectively, compared to untreated control (p < 0.05). However, the inducing effect of VEGF on VEGFR‐2 expression and the internal expression of VEGF121 in DOV13 cells decreased with increasing of VEGF concentration, suggesting the existence of a negative feedback regulatory mechanism. In summary, our results indicate that VEGF may regulate EOC invasion and migration through VEGFR‐mediated secretion and activation of MMPs. © 2005 Wiley‐Liss, Inc.
CB694, a novel antimitotic with antitumor activities
Authors: Weiderhold Kimberly N. , Randall‐Hlubek Deborah A. , Polin Lisa A. , Hamel Ernest , Mooberry Susan L.
Published: September 2005

During the course of a mechanism‐based screening program aimed at identifying new antimitotic agents, a novel microtubule depolymerizing piperazine derivative, 1‐(5‐chloro‐2‐methoxybenzoyl)‐4‐(3‐chlorophenyl) piperazine, was identified. The compound, designated CB694, caused inhibition of proliferation of a wide range of cancer cell lines, with an average IC50 of 85 nM. A multidrug‐resistant cell line was sensitive to inhibition by CB694, suggesting that this compound is a poor substrate for transport by P‐glycoprotein. CB694 caused formation of abnormal mitotic structures in HeLa cells. Specifically, CB694 caused a concentration‐dependent increase in bipolar spindles with lagging chromosomes and, with slightly higher concentrations, formation of multipolar mitotic spindles. These mitotic abnormalities occurred at concentrations that did not cause significant changes in the appearance or quantity of interphase microtubules. Coincident with the formation of abnormal mitotic spindles, CB694 caused G2/M arrest. CB694 inhibited the assembly of purified tubulin with an IC50 of 2.3 μM. Colchicine binding was strongly inhibited by CB694, suggesting that it binds to tubulin at the colchicine site. Bcl‐2 phosphorylation and activation of ERK and JNK and caspase 3‐dependent cleavage of PARP were observed in MDA‐MB‐435 cells treated with CB694. CB694 caused phosphorylation of Aurora A within 8 hr of treatment, and increases in Aurora A protein levels were coincident with mitotic accumulation. The efficacy of CB694 against a syngeneic murine transplantable solid tumor, Mammary 16/C, was also evaluated. CB694 was well tolerated and showed antitumor activity. © 2005 Wiley‐Liss, Inc.
The steroid receptor RNA activator protein is expressed in breast tumor tissues
Authors: Chooniedass‐Kothari Shilpa , Hamedani Mohammad Kariminia , Troup Sandy , Hubé Florent , Leygue Etienne
Published: September 2005

The steroid receptor RNA activator (SRA) was originally described as the first functional noncoding RNA able to specifically coactivate the activity of steroid receptors. We previously demonstrated the existence in breast cancer cell lines of new SRA isoforms that, as opposed to the first cloned SRA RNA, encode for a 236–amino acid protein, SRAP. To investigate the possible implications of the coding SRA RNA and SRAP expression on breast cancer progression, we examined by Western blot analysis 74 primary breast tumors of patients subsequently treated with tamoxifen. Patients whose primary tumors were positive for SRAP expression (n = 24) had a significantly (Kaplan‐Meier survival curve p = 0.047) lower likelihood of dying from recurrent disease than SRAP‐negative patients (n = 50). We generated 2 cell lines, SRAP‐V5‐High.A and SRAP‐V5‐High.B, by stably overexpressing SRAP in the estrogen receptor‐positive MCF‐7 breast cancer cell line. Transient transfection experiments, performed using a luciferase reporter gene under the control of an estrogen‐responsive element, revealed decreased sensitivity to estradiol but no additional sensitivity to tamoxifen in SRAP‐overexpressing cells. Overall, our data suggest that the presence of both coding SRA RNA and its corresponding SRAP modifies the activity of estrogen receptor in breast cancer cells and that SRAP could be a new clinical marker for breast cancer. Further studies are needed to define the respective mechanisms of action and the roles of SRA RNA and protein in breast tumorigenesis and tumor progression. © 2005 Wiley‐Liss, Inc.
Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis
Authors: Wu Jian‐Yu , Vlastos Anne‐Therese , Pelte Marie‐Françoise , Caligo Maria‐Adelaide , Bianco Andrea , Krause Karl‐Heinz , Laurent Geoffrey J. , Irminger‐Finger Irmgard
Published: September 2005

Mutations in tumor‐suppressor gene BARD1 have been found in inherited and spontaneous breast, ovarian and uterine cancers. BARD1 plays a critical role in DNA repair and ubiquitination as binding partner of BRCA1, with which it colocalizes to nuclear dots. Independently of BRCA1, BARD1 can induce p53‐dependent apoptosis in response to genotoxic stress. Therefore, BARD1 or p53 might be defective in cancer cells spared from apoptosis. We investigated BARD1 and p53 expression in ovarian, breast and non‐small‐cell lung cancers. BARD1 expression was highly upregulated and cytoplasmic in most cancer cells, while weak nuclear staining was observed in the surrounding normal tissue. Maximal BARD1 expression was associated with the most malignant ovarian cancer, clear cell carcinoma. In breast cancer, BARD1 expression was correlated with poor differentiation and large tumor size, established factors of poor prognosis, as well as short disease‐free survival. In contrast to breast and ovarian cancers, no correlation of BARD1 expression with either grade or stage could be determined for lung cancer. RT‐PCR, performed on 10 ovarian cancers, revealed absence of the 5′ portion of the BARD1 transcript in 7 tumors, and sequencing of the remaining 3 identified a missense mutation (A1291G) resulting in an amino acid change of glutamine 406 to arginine. These data suggest that genetic and epigenetic changes might lead to elevated cytoplasmic expression of BARD1 and that cytoplasmic BARD1 might be a poor prognostic factor for breast and ovarian cancers. © 2005 Wiley‐Liss, Inc.
Regulation of prostate cell collagen receptors by malignant transformation
Authors: Mirtti Tuomas , Nylund Camilla , Lehtonen Janika , Hiekkanen Heikki , Nissinen Liisa , Kallajoki Markku , Alanen Kalle , Gullberg Donald , Heino Jyrki
Published: September 2005

Cell adhesion receptors, including the integrin‐type collagen receptors (α1β1, α2β1, α10β1 and α11β1) participate in cancer progression and invasion. Quantitative RT‐PCR indicated that all 4 receptors are abundantly expressed in sarcoma‐derived cell lines, whereas most carcinoma‐derived cells express α1β1 and α2β1 only. This was surprising because α11β1 has been connected previously to the progression of lung adenocarcinomas. To test the hypothesis that α11 expression may not persist in cultured cancer cells we analyzed fresh tissue samples of 104 total prostatectomies, keeping in mind that prostate cancer cell lines showed negligible α11 mRNA levels. In prostate α2 expression was significantly lower in poorly differentiated carcinomas when compared to benign lesions (p = 0.0331). In immunohistochemistry the protein levels of α2 integrin decreased significantly (p = 0.0001) and the protein levels of α11 subunit increased significantly (p = 0.029) with the increasing grade of carcinoma. Thus α11β1 may replace α2β1 during tumor progression. Our observations support the idea that α11β1 may be expressed in tumors but the corresponding cell lines may lose the expression of this integrin. Previous studies have shown that in cell culture androgen receptor (AR) controls α2β1 expression. We measured AR mRNA levels and the number of AR positive nuclei in the prostate samples and the results showed a significant correlation between α2β1 and AR. Androgen receptors may control the mechanisms regulating integrin expression in prostate. © 2005 Wiley‐Liss, Inc.
Steroid hormone receptors and coregulators in endocrine‐resistant and estrogen‐independent breast cancer cells
Authors: Sarvilinna Nanna , Eronen Heli , Miettinen Susanna , Vienonen Annika , Ylikomi Timo
Published: September 2005

Resistance to hormonal therapy is often a problem in the treatment of breast cancer patients. It has been suggested that resistance could be explained by altered nuclear hormone receptor or coregulator levels or inappropriately increased agonist activity of selective estrogen receptor modulator (SERM). To test these hypotheses, we have established novel MCF‐7 cell line‐derived in vitro models of anti‐estrogen‐ and progestin‐resistant and estrogen‐independent breast cancer by long‐term culture in the presence of toremifene and medroxyprogesterone acetate (MPA) and in the absence of estradiol, respectively. Using cell growth and multiprobe ribonuclease protection assays, the expression of 5 nuclear hormone receptors and 9 coregulators as well as the alterations in the cell proliferation and target gene transcription in response to hormonal treatments were studied. Progesterone receptor (PR) expression was decreased and silencing mediator for retinoid acid and thyroid hormone receptors (SMRT) and amplified in breast cancer‐1 (AIB1) expression increased in anti‐estrogen‐resistant cells. Estrogen caused PR and ERβ upregulation in all cell lines, but we did not observe increased agonist activity of anti‐estrogen measured by regulation of these estrogen target genes. Basal ERα levels and estrogenic growth response were decreased and p300/CBP‐associated factor (pCAF) and AIB1 upregulated by estrogen in progestin‐resistant cells, but coregulator levels were unchanged. Estrogen‐independent cells were still estrogen‐responsive and PR, nuclear receptor corepressor (N‐CoR) and SMRT expression was increased whereas steroid receptor coactivator‐1 (SRC‐1a) and CBP‐related protein p300 (p300) expression decreased. Their growth was inhibited by toremifene, but estradiol was able to abrogate this effect, which might have interesting clinical implications concerning the use of postmenopausal hormone replacement therapy. © 2005 Wiley‐Liss, Inc.
Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine
Authors: Iizuka Yukihiko , Kojima Hidefumi , Kobata Tetsuji , Kawase Takeshi , Kawakami Yutaka , Toda Masahiro
Published: September 2005

Despite several ongoing clinical trials of immunotherapies against glioma, few glioma‐specific antigens recognized by cytotoxic T lymphocytes (CTLs) have been identified. We recently demonstrated that intratumoral inoculation with herpes simplex virus (HSV) as a cancer vaccine activates tumor‐specific CTLs. To identify glioma antigens recognized by CTLs, we used the HSV cancer vaccine to vaccinate mice harboring a syngeneic mouse glioma cell line, GL261. From the splenocytes of the immunized mice, we generated an H‐2Db‐restricted CTL line, GCL‐1, that was specific for GL261. Then, a cDNA expression library generated from GL261 was screened with GCL‐1, and a new gene encoding glioma antigen, GARC‐1, was isolated. Sequence analysis revealed that the GARC‐1 gene isolated from GL261 had a point mutation causing an amino acid change (Asp to Asn at position 81). T‐cell epitope analysis revealed that the mutated peptide GARC‐177–85 (AALLNKLYA) but not the wild‐type peptide (AALLDKLYA), was recognized by GCL‐1. These results suggest that HSV cancer vaccination may be a useful method for inducing tumor‐specific CTLs and identifying tumor antigens. Furthermore, this GL261/GARC‐1 murine glioma model may be useful for the development of immunotherapy for brain tumors. © 2005 Wiley‐Liss, Inc.
Cancer risk among Danish women with cosmetic breast implants
Authors: Friis Søren , Hölmich Lisbet R. , McLaughlin Joseph K. , Kjøller Kim , Fryzek Jon P. , Henriksen Trine F. , Olsen Jørgen H.
Published: September 2005

The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10–15 years after breast implantation. We extended follow‐up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow‐up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973–95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0–1.4), during a mean follow‐up period of 14.4 years (range = 0–30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5–1.0), and an increased risk of non‐melanoma skin cancer (SIR = 2.1; 95% CI = 1.5–2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non‐melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8–1.2). With respect to other site‐specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non‐melanoma skin cancer of 1.1 (95% CI = 0.8–1.6), 0.7 (95% CI = 0.4–1.3) and 1.5 (95% CI = 0.8–2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non‐melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants. © 2005 Wiley‐Liss, Inc.
The Brn‐3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells
Authors: Samady Laila , Faulkes David J. , Budhram‐Mahadeo Vishwanie , Ndisang Daniel , Potter Eyck , Brabant Georg , Latchman David S.
Published: September 2005

The Brn‐3b transcription factor has been shown to be overexpressed in human breast cancer cells and contributes toward cell growth regulation. Using micro‐arrays, more than 50 cancer‐related genes regulated by Brn‐3b in human breast cancer cells have been identified. For example, Brn‐3b activates the cell cycle regulator CDK4 that provides a mechanism by which Brn‐3b controls the growth of breast cancer cells. Here, we show that Brn‐3b regulates plakoglobin (γ‐catenin), a member of the catenin family involved in cell‐cell adhesion and signal transduction. Brn‐3b expression inversely correlates with plakoglobin expression at both mRNA and protein levels in breast cancer cell lines and human breast biopsies. In contrast, no significant correlation was observed between Brn‐3b expression and β‐catenin, or between Brn‐3b expression and E‐cadherin expression. Brn‐3b represses the plakoglobin promoter via a Brn‐3 consensus binding site contained within the region −965 to −593 relative to the transcriptional start site. Both repression of the promoter and binding of Brn‐3b are lost when this site is mutated. To our knowledge, this is the first time that a Brn‐3b POU family transcription factor has been shown to regulate a member of the catenin family, which provides insight into the molecular mechanisms by which Brn‐3b expression may favour breast cancer progression and tumor invasion. © 2005 Wiley‐Liss, Inc.
Cancer risk among patients with multiple sclerosis: A population‐based register study
Authors: Nielsen Nete Munk , Rostgaard Klaus , Rasmussen Søren , Koch‐Henriksen Nils , Storm Hans H. , Melbye Mads , Hjalgrim Henrik
Published: September 2005

Cancer occurrence in patients with multiple sclerosis (MS) has been little studied, but associations with brain tumours, breast cancer, Hodgkin lymphoma and nasopharyngeal carcinoma have been suggested. We took advantage of population‐based registers of MS and cancer to assess the risk of cancer following diagnosis of MS. Patients registered in the Danish Multiple Sclerosis Register were linked with the Danish Cancer Register to obtain information on cancer occurrence. The ratio of the observed to the number of expected cancers based on population‐based incidence rates, i.e., the standardised incidence ratio (SIR), served as measure of the relative cancer risk. A database comprising all Danish women born after April 1, 1935, with information on all live‐born children, was used in the analyses of breast cancer to adjust for reproductive factors. Overall 1,037 cancers were observed in 11,817 MS patients during 153,875 person‐years of follow‐up vs. an expected number of 1,098 (SIR = 0.94 [95% confidence interval CI: (0.89–1.00)]. The risk of brain tumours and Hodgkin lymphoma was not increased. A 16% overall reduced cancer risk in men with MS was explained by reduced numbers of cancers of the digestive, respiratory and genital organs. Though the overall cancer risk was not increased [SIR = 1.01(0.94–1.09), n = 676], female MS patients had an increased risk of breast cancer [SIR = 1.21 (1.05–1.39), n = 193]. Adjusting for parity and age at first child delivery did not change this risk estimate materially. In general MS patients are not at increased risk of cancer. Women with MS, however, seem to have a small excess risk of breast cancer, which cannot be attributed to reduced parity or delayed first child birth. © 2005 Wiley‐Liss, Inc.
Associations between 5,10‐methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: A case‐control study in an Indian population
Authors: Wang Jingwen , Gajalakshmi Vendhan , Jiang Jing , Kuriki Kiyonori , Suzuki Sadao , Nagaya Teruo , Nakamura Seiichi , Akasaka Susumu , Ishikawa Hideki , Tokudome Shinkan
Published: September 2005

Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case‐control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28–2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86–2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09–0.81) and rectal cancer (OR = 0.43, 95% CI 0.23–0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09–0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86–6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73–3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram‐years) may be also associated with colon or rectal cancer risk. © 2005 Wiley‐Liss, Inc.
Carrier frequency of mutation 657del5 in the NBS1 gene in a population of polish pediatric patients with sporadic lymphoid malignancies
Authors: Chrzanowska Krystyna H. , Piekutowska‐Abramczuk Dorota , Popowska Ewa , Gładkowska‐Dura Małgorzata , Małdyk Jadwiga , Syczewska Małgorzata , Krajewska‐Walasek Małgorzata , Goryluk‐Kozakiewicz Bożenna , Bubała Halina , Gadomski Artur , Gaworczyk Anna , Kazanowska Bernarda , Kołtan Andrzej , Kuźmicz Marta , Luszawska‐Kutrzeba Teresa , Maciejka‐Kapuścińska Lucyna , Stolarska Małgorzata , Stefańska Katarzyna , Sznurkowska Katarzyna , Wakulińska Anna , Wieczorek Maria , Szczepański Tomasz , Kowalczyk Jerzy
Published: September 2005

Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non‐Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48–1.85, 95% confidence interval 1.18–2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence. © 2005 Wiley‐Liss, Inc.
Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas
Authors: Pimenta Flávio J. , Gomes Dawidson A. , Perdigão Paolla F. , Barbosa Alvimar A. , Romano‐Silva Marco A. , Gomez Marcus V. , Aldaz C. Marcelo , De Marco Luiz , Gomez Ricardo S.
Published: September 2005

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, representing ˜90% of all oral carcinomas and accounting for 3–5% of all malignancies. The WWOX gene (WW‐domain containing oxidoreductase) is a candidate tumor suppressor gene located at 16q23.3–24.1, spanning the second most common fragile site, FRA16D. In this report, the role of the WWOX gene was investigated in 20 tumors and 10 normal oral mucosas, and we demonstrated an altered WWOX gene in 50% (10/20) of OSCCs. Using nested RT‐PCR, mRNA transcription was altered in 35% of the tumors, with the complete absence of transcripts in 2 samples as well as absence of exons 6–8 (2 tumors), exon 7 (1 tumor), exon 7 and exon 6–8 (1 tumor) and partial loss of exons 8 and 9 (1 tumor). To determine if the aberrant transcripts were translated, Western blots were performed in all samples; however, only the normal protein was detected. By immunohistochemistry, a reduction in Wwox protein expression was observed, affecting 40% of the tumors when compared with normal mucosa. In addition, a novel somatic mutation (S329F) was found. The presence of alterations in mRNA transcription correlated with the reduced expression of Wwox protein in the tumors. These results show that the WWOX gene is frequently altered in OSCC and may contribute to the carcinogenesis processes in oral cancer. © 2005 Wiley‐Liss, Inc.
Promoter hypermethylation of the potential tumor suppressor DAL‐1/4.1B gene in renal clear cell carcinoma
Authors: Yamada Daisuke , Kikuchi Shinji , Williams Yuko N. , Sakurai‐Yageta Mika , Masuda Mari , Maruyama Tomoko , Tomita Kyoichi , Gutmann David H. , Kakizoe Tadao , Kitamura Tadaichi , Kanai Yae , Murakami Yoshinori
Published: September 2005

Renal clear cell carcinoma (RCCC) is a malignant tumor with poor prognosis caused by the high incidence of metastasis to distal organs. Although metastatic RCCC cells frequently show aberrant cytoskeletal organization, the underlying mechanism has not been elucidated. DAL‐1/4.1B is an actin‐binding protein implicated in the cytoskeleton‐associated processes, while its inactivation is frequently observed in lung and breast cancers and meningiomas, suggesting that 4.1B is a potential tumor suppressor. We studied a possible involvement of 4.1B in RCCCs and evaluated it as a clinical indicator. 4.1B protein was detected in the proximal convoluted tubules of human kidney, the presumed cell of origin of RCCC. On the other hand, loss or marked reduction of its expression was observed in 10 of 19 (53%) renal cell carcinoma (RCC) cells and 12 of 19 (63%) surgically resected RCCC by reverse transcription‐PCR. Bisulfite sequencing or bisulfite SSCP analyses revealed that the 4.1B promoter was methylated in 9 of 19 (47%) RCC cells and 25 of 55 (45%) surgically resected RCCC, and inversely correlated with 4.1B expression (p < 0.0001). Aberrant methylation appeared to be a relatively early event because more than 40% of the tumors with pT1a showed hypermethylation. Furthermore, 4.1B methylation correlated with a nuclear grade (p = 0.017) and a recurrence‐free survival (p = 0.0036) and provided an independent prognostic factor (p = 0.038, relative risk 10.5). These results indicate that the promoter methylation of the 4.1B is one of the most frequent epigenetic alterations in RCCC and could predict the metastatic recurrence of the surgically resected RCCC. © 2005 Wiley‐Liss, Inc.
Increase in skin cancer screening during a community‐based randomized intervention trial
Authors: Aitken Joanne F. , Youl Philippa H. , Janda Monika , Lowe John B , Ring Ian T. , Elwood Mark
Published: September 2005

Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community‐based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3‐year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross‐sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole‐body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole‐body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women ≥50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self‐examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole‐body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered. © 2005 Wiley‐Liss, Inc.