bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maspin Retards Cell Detachment via a Novel Interaction with the Urokinase-Type Plasminogen Activator/Urokinase-Type Plasminogen Activator Receptor System
Authors: Yin Shuping , Lockett Jaron , Meng Yonghong , Biliran Hector , Blouse Grant E. , Li Xiaohua , Reddy Neelima , Zhao Zimin , Lin Xinli , Anagli John , Cher Michael L. , Sheng Shijie 
Published: April 2006

Abstract
It is well documented that tumor suppressive maspin inhibits tumor cell invasion and extracellular matrix remodeling. Maspin is a cytosolic, cell surface–associated, and secreted protein in the serine protease inhibitor superfamily. Although several molecules have been identified as candidate intracellular maspin targets, the extracellular maspin target(s) remains elusive. Although maspin does not directly inhibit urokinase-type plasminogen activator (uPA) activity, we have shown evidence that maspin may block the pericellular proteolysis mediated by cell surface–associated uPA. In the current study, maspin significantly inhibited the Ca2+ reduction–induced detachment of DU145 cells. This maspin effect was associated with increased and sustained levels of mature focal adhesion contacts (FAC). We noted that maspin (a) colocalized with uPA and uPA receptor (uPAR), (b) enhanced the interaction between uPAR and low-density lipoprotein receptor related protein, and (c) induced rapid internalization of uPA and uPAR. The maspin effects on surface-associated uPA and uPAR required the interaction between uPA and uPAR. Further biochemical and biophysical analyses revealed that maspin specifically bound to pro-uPA with a deduced Kd of 270 nmol/L and inhibited the plasmin-mediated pro-uPA cleavage. Interestingly, substitution of maspin p1′ site Arg340 in the reactive site loop (RSL) with alanine not only abolished the binding to pro-uPA but also diminished the maspin effects on pro-uPA cleavage and cell detachment. These data show an important role of maspin RSL in regulating the uPA/uPAR–dependent cell detachment. Together, our data led to a new hypothesis that maspin may stabilize mature FACs by quenching localized uPA/uPAR complex before uPA activation. (Cancer Res 2006; 66(8): 4173-81)
Antitumor Activity of a Small-Molecule Inhibitor of Human Silent Information Regulator 2 Enzymes
Authors: Heltweg Birgit , Gatbonton Tonibelle , Schuler Aaron D. , Posakony Jeff , Li Hongzhe , Goehle Sondra , Kollipara Ramya , DePinho Ronald A. , Gu Yansong , Simon Julian A. , Bedalov Antonio 
Published: April 2006

Abstract
SIRT1 and other NAD-dependent deacetylases have been implicated in control of cellular responses to stress and in tumorigenesis through deacetylation of important regulatory proteins, including p53 and the BCL6 oncoprotein. Hereby, we describe the identification of a compound we named cambinol that inhibits NAD-dependent deacetylase activity of human SIRT1 and SIRT2. Consistent with the role of SIRT1 in promoting cell survival during stress, inhibition of SIRT1 activity with cambinol during genotoxic stress leads to hyperacetylation of key stress response proteins and promotes cell cycle arrest. Treatment of BCL6-expressing Burkitt lymphoma cells with cambinol as a single agent induced apoptosis, which was accompanied by hyperacetylation of BCL6 and p53. Because acetylation inactivates BCL6 and has the opposite effect on the function of p53 and other checkpoint pathways, the antitumor activity of cambinol in Burkitt lymphoma cells may be accomplished through a combined effect of BCL6 inactivation and checkpoint activation. Cambinol was well tolerated in mice and inhibited growth of Burkitt lymphoma xenografts. Inhibitors of NAD-dependent deacetylases may constitute novel anticancer agents. (Cancer Res 2006; 66(8): 4368-77)
Heat Shock Protein 70 Neutralization Exerts Potent Antitumor Effects in Animal Models of Colon Cancer and Melanoma
Authors: Schmitt Elise , Maingret Loic , Puig Pierre-Emmanuel , Rerole Anne-Laure , Ghiringhelli François , Hammann Arlette , Solary Eric , Kroemer Guido , Garrido Carmen 
Published: April 2006

Abstract
When overexpressed, the stress protein heat shock protein 70 (HSP70) increases the oncogenic potential of cancer cells in rodent models. HSP70 also prevents apoptosis, thereby increasing the survival of cells exposed to a wide range of otherwise lethal stimuli. These protective functions of HSP70 involve its interaction with and neutralization of the adaptor molecule apoptotic protease activation factor-1, implicated in caspase activation, and the flavoprotein apoptosis-inducing factor (AIF), involved in caspase-independent cell death. We have shown previously that a peptide containing the AIF sequence involved in its interaction with HSP70 (ADD70, amino acids 150-228) binds to and neutralizes HSP70 in the cytosol, thereby sensitizing cancer cells to apoptosis induced by a variety of death stimuli. Here, we show that expression of ADD70 in tumor cells decreases their tumorigenicity in syngeneic animals without affecting their growth in immunodeficient animals. ADD70 antitumorigenic effects are associated with an increase in tumor-infiltrating cytotoxic CD8+ T cells. In addition, ADD70 sensitizes rat colon cancer cells (PROb) and mouse melanoma cells (B16F10) to the chemotherapeutic agent cisplatin. ADD70 also shows an additive effect with HSP90 inhibition by 17-allylamino-17-demethoxygeldanamycin in vitro. Altogether, these data indicate the potential interest of targeting the HSP70 interaction with AIF for cancer therapy. (Cancer Res 2006; 66(8): 4191-7)
Inhibition of p38 by Vitamin D Reduces Interleukin-6 Production in Normal Prostate Cells via Mitogen-Activated Protein Kinase Phosphatase 5: Implications for Prostate Cancer Prevention by Vitamin D
Authors: Nonn Larisa , Peng Lihong , Feldman David , Peehl Donna M. 
Published: April 2006

Abstract
Although numerous studies have implicated vitamin D in preventing prostate cancer, the underlying mechanism(s) remains unclear. Using normal human prostatic epithelial cells, we examined the role of mitogen-activated protein kinase phosphatase 5 (MKP5) in mediating cancer preventive activities of vitamin D. Up-regulation of MKP5 mRNA by 1,25-dihydroxyvitamin-D3 (1,25D) was dependent on the vitamin D receptor. We also identified a putative positive vitamin D response element within the MKP5 promoter that associated with the vitamin D receptor following 1,25D treatment. MKP5 dephosphorylates/inactivates the stress-activated protein kinase p38. Treatment of prostate cells with 1,25D inhibited p38 phosphorylation, and MKP5 small interfering RNA blocked this effect. Activation of p38 and downstream production of interleukin 6 (IL-6) are proinflammatory. Inflammation and IL-6 overexpression have been implicated in the initiation and progression of prostate cancer. 1,25D pretreatment inhibited both UV- and tumor necrosis factor α–stimulated IL-6 production in normal cells via p38 inhibition. Consistent with inhibition of p38, 1,25D decreased UV-stimulated IL-6 mRNA stabilization. The ability of 1,25D to up-regulate MKP5 was maintained in primary prostatic adenocarcinoma cells but was absent in metastases-derived prostate cancer cell lines. The inability of 1,25D to regulate MKP5 in the metastasis-derived cancer cells suggests there may be selective pressure to eliminate key tumor suppressor functions of vitamin D during cancer progression. These studies reveal MKP5 as a mediator of p38 inactivation and decreased IL-6 expression by 1,25D in primary prostatic cultures of normal and adenocarcinoma cells, implicating decreased prostatic inflammation as a potential mechanism for prostate cancer prevention by 1,25D. (Cancer Res 2006; 66(8): 4516-24)
Detection of Recurrent Copy Number Loss at Yp11.2 Involving TSPY Gene Cluster in Prostate Cancer Using Array-Based Comparative Genomic Hybridization
Authors: Vijayakumar Sapna , Hall Devon C. , Reveles Xavier T. , Troyer Dean A. , Thompson Ian M. , Garcia Dawn , Xiang RuiHua , Leach Robin J. , Johnson-Pais Teresa L. , Naylor Susan L. 
Published: April 2006

Abstract
Prostate cancer is the second leading cause of cancer deaths among American men. The loss of Y chromosome has been frequently observed in primary prostate cancer as well as other types of cancer. Earlier, we showed that introduction of the human Y chromosome suppresses the in vivo tumorigenicity of the prostate cancer cell line PC-3. To further characterize the Y chromosome, we have developed a high-density bacterial artificial chromosome (BAC) microarray containing 178 BAC clones from the human Y chromosome. BAC microarray was used for array comparative genomic hybridization on prostate cancer samples and cell lines. The most prominent observation on prostate cancer specimens was a deletion at Yp11.2 containing the TSPY tandem gene array. Out of 36 primary prostate tumors analyzed, 16 (44.4%) samples exhibited loss of TSPY gene copies. Notably, we observed association between the number of TSPY copies in the blood and the incidence of prostate cancer. Moreover, PC-3 hybrids with an intact Yp11.2 did not grow tumors in nude mice, whereas PC-3 hybrids with a deletion at Yp11.2 grew tumors in nude mice. (Cancer Res 2006; 66(8): 4055-64)
Genetic Polymorphisms of Interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and Risk of Prostate Cancer
Authors: Michaud Dominique S. , Daugherty Sarah E. , Berndt Sonja I. , Platz Elizabeth A. , Yeager Meredith , Crawford E. David , Hsing Ann , Huang Wen-Yi , Hayes Richard B. 
Published: April 2006

Abstract
Chronic intraprostatic inflammation is suspected to play a role in the pathogenesis of prostate cancer. Polymorphisms in cytokine genes can influence inflammation and immune response and may be related to the risk of prostate cancer. Four common single nucleotide polymorphisms (SNPs) in the genes encoding interleukin-1B (IL-1B), IL-6, and IL-8 were assessed in 503 prostate cancer cases and 652 controls, and three SNPs in IL-10 were assessed in an additional 817 prostate cancer cases and 1,190 controls (for a total of 1,320 prostate cancer cases and 1,255 controls). Cases and controls were selected from the on-going Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and were frequency matched on age, ethnicity, time-period since initial screening, and date of blood draw. Single-locus analyses were conducted using conditional logistic regression. In addition, we did a haplotype analysis for the three IL-10 SNPs tested. Overall, no associations were detected between the seven polymorphisms in the four cytokine genes examined in this study and prostate cancer risk. Further stratifying by use of nonsteroidal anti-inflammatory drugs did not modify the associations. Findings were similar for early or advanced prostate cancers. Similarly, we observed no association between the major IL-10 haplotypes and the risk of prostate cancer. At least seven common polymorphisms in genes of inflammatory cytokines IL-1B, IL-6, IL-8, and IL-10 do not seem to play a role in the risk of prostate cancer. (Cancer Res 2006; 66(8): 4525-30)
Combined cDNA Array Comparative Genomic Hybridization and Serial Analysis of Gene Expression Analysis of Breast Tumor Progression
Authors: Yao Jun , Weremowicz Stanislawa , Feng Bin , Gentleman Robert C. , Marks Jeffrey R. , Gelman Rebecca , Brennan Cameron , Polyak Kornelia 
Published: April 2006

Abstract
To identify genetic changes involved in the progression of breast carcinoma, we did cDNA array comparative genomic hybridization (CGH) on a panel of breast tumors, including 10 ductal carcinoma in situ (DCIS), 18 invasive breast carcinomas, and two lymph node metastases. We identified 49 minimal commonly amplified regions (MCRs) that included known (1q, 8q24, 11q13, 17q21-q23, and 20q13) and several uncharacterized (12p13 and 16p13) regional copy number gains. With the exception of the 17q21 (ERBB2) amplicon, the overall frequency of copy number alterations was higher in invasive tumors than that in DCIS, with several of them present only in invasive cancer. Amplification of candidate loci was confirmed by quantitative PCR in breast carcinomas and cell lines. To identify putative targets of amplicons, we developed a method combining array CGH and serial analysis of gene expression (SAGE) data to correlate copy number and expression levels for each gene within MCRs. Using this approach, we were able to distinguish a few candidate targets from a set of coamplified genes. Analysis of the 12p13-p12 amplicon identified four putative targets: TEL/ETV6, H2AFJ, EPS8, and KRAS2. The amplification of all four candidates was confirmed by quantitative PCR and fluorescence in situ hybridization, but only H2AFJ and EPS8 were overexpressed in breast tumors with 12p13 amplification compared with a panel of normal mammary epithelial cells. These results show the power of combined array CGH and SAGE analysis for the identification of candidate amplicon targets and identify H2AFJ and EPS8 as novel putative oncogenes in breast cancer. (Cancer Res 2006; 66(8): 4065-78)
Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions
Authors: Helfer Brooke , Boswell Bernard C. , Finlay Darren , Cipres Angel , Vuori Kristiina , Bong Kang Tae , Wallach David , Dorfleutner Andrea , Lahti Jill M. , Flynn Daniel C. , Frisch Steven M. 
Published: April 2006

Abstract
Significant caspase-8 activity has been found in normal and certain tumor cells, suggesting that caspase-8 possesses an alternative, nonapoptotic function that may contribute to tumor progression. In this article, we report that caspase-8 promotes cell motility. In particular, caspase-8 is required for the optimal activation of calpains, Rac, and lamellipodial assembly. This represents a novel nonapoptotic function of caspase-8 acting at the intersection of the caspase-8 and calpain proteolytic pathways to coordinate cell death versus cell motility signaling. (Cancer Res 2006; 66(8): 4273-8)
Targeting Oncogenes to Improve Breast Cancer Chemotherapy
Authors: Christensen Laura A. , Finch Rick A. , Booker Adam J. , Vasquez Karen M. 
Published: April 2006

Abstract
Despite recent advances in treatment, breast cancer remains a serious health threat for women. Traditional chemotherapies are limited by a lack of specificity for tumor cells and the cell cycle dependence of many chemotherapeutic agents. Here we report a novel strategy to help overcome these limitations. Using triplex-forming oligonucleotides (TFOs) to direct DNA damage site-specifically to oncogenes overexpressed in human breast cancer cells, we show that the effectiveness of the anticancer nucleoside analogue gemcitabine can be improved significantly. TFOs targeted to the promoter region of c-myc directly inhibited gene expression by ∼40%. When used in combination, specific TFOs increased the incorporation of gemcitabine at the targeted site ∼4-fold, presumably due to induction of replication-independent DNA synthesis. Cells treated with TFOs and gemcitabine in combination showed a reduction in both cell survival and capacity for anchorage-independent growth (∼19% of untreated cells). This combination affected the tumorigenic potential of these cancer cells to a significantly greater extent than either treatment alone. This novel strategy may be used to increase the range of effectiveness of antitumor nucleosides in any tumor which overexpresses a targetable oncogene. Multifaceted chemotherapeutic approaches such as this, coupled with triplex-directed gene targeting, may lead to more than incremental improvements in nonsurgical treatment of breast tumors. (Cancer Res 2006; 66(8): 4089-94)
Prevention of Azoxymethane-Induced Colon Cancer by Combination of Low Doses of Atorvastatin, Aspirin, and Celecoxib in F 344 Rats
Authors: Reddy Bandaru S. , Wang Chung Xiou , Kong Ah-Ng , Khor Tin Oo , Zheng Xi , Steele Vernon E. , Kopelovich Levy , Rao Chinthalapally V. 
Published: April 2006

Abstract
Preclinical and clinical studies have provided evidence that aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of these agents may induce side effects in ostensibly normal individuals. Combining low doses of agents may be an effective way to increase their efficacy and minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib, and aspirin, given individually at high dose levels and in combination at lower doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once weekly for 2 weeks), groups of male F 344 rats were fed the AIN-76A diet or AIN-76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm aspirin. Rats were killed 42 weeks later, and colon tumors were processed histopathologically and analyzed for cell proliferation and apoptosis immunohistochemically. Administration of these agents individually and in combination significantly suppressed the incidence and multiplicity of colon adenocarcinomas. Low doses of these agents in combination inhibited colon carcinogenesis more effectively than when they were given individually at higher doses. Inhibition of colon carcinogenesis by these agents is associated with the inhibition of cell proliferation and increase in apoptosis in colon tumors. These observations are of clinical significance because this can pave the way for the use of combinations of these agents in small doses against colon cancer. (Cancer Res 2006; 66(8): 4542-6)
Antibody-Maytansinoid Conjugates Are Activated in Targeted Cancer Cells by Lysosomal Degradation and Linker-Dependent Intracellular Processing
Authors: Erickson Hans K. , Park Peter U. , Widdison Wayne C. , Kovtun Yelena V. , Garrett Lisa M. , Hoffman Karen , Lutz Robert J. , Goldmacher Victor S. , Blättler Walter A. 
Published: April 2006

Abstract
Antibody-drug conjugates are targeted anticancer agents consisting of a cytotoxic drug covalently linked to a monoclonal antibody for tumor antigen–specific activity. Once bound to the target cell-surface antigen, the conjugate must be processed to release an active form of the drug, which can reach its intracellular target. Here, we used both biological and biochemical methods to better define this process for antibody-maytansinoid conjugates. In particular, we examined the metabolic fate in cells of huC242-maytansinoid conjugates containing either a disulfide linker (huC242-SPDB-DM4) or a thioether linker (huC242-SMCC-DM1). Using cell cycle analysis combined with lysosomal inhibitors, we showed that lysosomal processing is required for the activity of antibody-maytansinoid conjugates, irrespective of the linker. We also identified and characterized the released maytansinoid molecules from these conjugates, and measured their rate of release compared with the kinetics of cell cycle arrest. Both conjugates are efficiently degraded in lysosomes to yield metabolites consisting of the intact maytansinoid drug and linker attached to lysine. The lysine adduct is the sole metabolite from the thioether-linked conjugate. However, the lysine metabolite generated from the disulfide-linked conjugate is reduced and S-methylated to yield the lipophilic and potently cytotoxic metabolite, S-methyl-DM4. These findings provide insight into the mechanism of action of antibody-maytansinoid conjugates in general, and more specifically, identify a biochemical mechanism that may account for the significantly enhanced antitumor efficacy observed with disulfide-linked conjugates. (Cancer Res 2006; 66(8): 4426-33)
Comparison of Model-Produced and Observed Microwave Radiances and Estimation of Background Error Covariances for Hydrometeor Variables within Hurricanes
Authors: Amerault Clark , Zou Xiaolei 
Published: April 2006

Abstract
A radiative transfer model was updated to better simulate Special Sensor Microwave Imager (SSM/I)–observed brightness temperatures in areas of high ice concentration. The difference between the lowest observed and model-produced brightness temperatures at 85 GHz has been reduced from over 100 K to roughly 20 K. Probability distribution functions of model-produced and SSM/I-observed brightness temperatures show that the model overestimates the areas of precipitation, but overall matches the SSM/I observations quite well.
Estimates of vertical background error covariance matrices and their inverses were calculated for all hydrometeor variables (both liquid and frozen). For cloud and rainwater, the largest values in the matrices are located in the lower levels of the atmosphere, while the largest values in the cloud ice, snow, and graupel matrices are in the upper levels of the atmosphere. The inverse background matrices can be used as weightings for hydrometeor variables in assimilation experiments involving rain-affected observations.
Brecht in America, 1935
Authors: Baxandall Lee 
Published: April 2006

Bert Brecht set out in 1935 on his first voyage to America. He sailed on
a dingy, if not black, freighter, from Denmark, where he lived during
several years of exile from Hitler's Germany. His destination: New York and
the opportunity to collaborate in a production of The
Mother at the Theatre Union, the most famous American
socialist theatre.
Brecht had had few chances to see his work done since his emigration. He
worked with productions in Copenhagen and Paris, but the reputation of
American left theatre stood much higher, with enthusiastic theatre groups in
dozens of large and small cities seeking good “social plays,” in response to
the depression crisis. Friedrich Wolf, a fellow German emigre playwright,
declared sweepingly in International Literature
that New York left theatre was “without exaggeration the strongest and most
outstanding outpost of the Left Theatre in all the capitalist countries.”
(Wolf's Sailors ofCattaro was being done at
Theatre Union.) Brecht had doubts.
Marta Minujin’s “Simultaneity in Simultaneity”
Authors: Kirby Michael 
Published: April 2006

Simultaneity in Simultaneity, presented in Buenos Aires, Argentina, on 24 October, 1966, by Marta Minujin was probably the first performance piece in history to make use of several coordinated mass media. In part of the work, each “spectator” was alone in his own home: relatively few perceived every dimension of the performance, but aspects of it were available to anyone with a radio or television set.The piece which eventually became Simultaneity in Simultaneity was originally conceived as part of an intercontinental presentation. At the same time that Minujin's work was being done in Argentina, Allan Kaprow in the United States and Wolf Vostell in Germany were to do performances. The three had talked of making use of the telstar communications satellite to transmit video material from one part of the performance to another, of flying performers from one country to another so that they could appear in person in more than one “section,” etc. This original plan was not carried through when both Kaprow and Vostell failed to realize their segments, but it determined some of Minujin's imagery, and, eventually, provoked an interesting juxtapositioning of “truth” and “falsity” in art.