bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of Antiangiogenic and Antimetastatic Activities of the Recombinant Disintegrin Domain of Metargidin
Authors: Trochon-Joseph Véronique , Martel-Renoir Dominique , Mir Lluis M. , Thomaïdis Annick , Opolon Paule , Connault Elisabeth , Li Hong , Grenet Christophe , Fauvel-Lafève Françoise , Soria Jeannette , Legrand Chantal , Soria Claudine , Perricaudet Michel , Lu He 
Published: September 2005

Abstract
Metargidin, a transmembrane protein of the adamalysin family, and integrins, e.g., α5β1 and αv, are preferentially expressed on endothelial cells on angiogenesis. Furthermore, metargidin interacts with these integrins via its disintegrin domain. In this study, recombinant human disintegrin domain (RDD) was produced in Escherichia coli by subcloning its cDNA into the pGEX-2T vector, and the effect of purified RDD on different steps of angiogenesis was evaluated. At concentrations of 2–10 μg/ml, RDD exhibited inhibitory activities in a variety of in vitro functional assays, including endothelial cell proliferation and adhesion on the integrin substrates fibronectin, vitronectin, and fibrinogen. RDD (10 μg/ml) totally abrogated endothelial cell migration and blocked most capillary formation in a three-dimensional fibrin gel. To test RDD efficacy in vivo, the RDD gene inserted into pBi vector containing a tetracycline-inducible promoter was electrotransferred into nude mouse muscle. RDD was successfully synthesized by muscle cells in vivo as shown by immunolabeling and Western blotting. In addition, 78% less MDA-MB-231 tumor growth, associated with strong inhibition of tumor angiogenesis, was observed in athymic mice bearing electrotransferred RDD. Moreover, in the presence of RDD, 74% fewer B16F10 melanoma lung metastases were found in C57BL/6 mice. Taken together, these results identified this RDD as a potent intrinsic inhibitor of angiogenesis, tumor growth, and metastasis, making it a promising tool for use in anticancer treatment.
Pheophorbide a Is a Specific Probe for ABCG2 Function and Inhibition
Authors: Robey Robert W. , Steadman Kenneth , Polgar Orsolya , Morisaki Kuniaki , Blayney Margaret , Mistry Prakash , Bates Susan E. 
Published: September 2005

Abstract
Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2 substrate based on Abcg2−/− knockout mouse studies (J. W. Jonker et al., Proc. Natl. Acad. Sci. USA, 99: 15649–15654, 2002). We developed a functional assay for ABCG2 using PhA and the ABCG2 inhibitor fumitremorgin C. In selected cell lines expressing high levels of P-glycoprotein, multidrug resistance-associated protein 1, or ABCG2, PhA transport was observed only in cells expressing ABCG2. Fumitremorgin C-inhibitable PhA transport was found to correlate with cell surface ABCG2 expression as measured by the anti-ABCG2 antibody 5D3. We found that 100 μm of the cyclin-dependent kinase inhibitor UCN-01 or 1 μm of the P-glycoprotein inhibitor tariquidar inhibited ABCG2-mediated PhA transport. In 4-day cytotoxicity assays, ABCG2-mediated resistance to SN-38 and topotecan was abrogated in ABCG2-transfected HEK-293 cells treated with 1 μm tariquidar, and ABCG2-transfected cells were 6–7-fold resistant to UCN-01. PhA is an ABCG2-specific substrate with potential value in measuring ABCG2 function and expression in clinical samples.
Presence of Simian Virus 40 DNA Sequences in Human Lymphoid and Hematopoietic Malignancies and Their Relationship to Aberrant Promoter Methylation of Multiple Genes
Authors: Shivapurkar Narayan , Takahashi Takao , Reddy Jyotsna , Zheng Yingye , Stastny Victor , Collins Robert , Toyooka Shinichi , Suzuki Makato , Parikh Gunjan , Asplund Sheryl , Kroft Steven H. , Timmons Charles , McKenna Robert W. , Feng Ziding , Gazdar Adi F. 
Published: September 2005

Abstract
The simian polyoma virus SV40 has been detected in specific human tumors including non-Hodgkin’s lymphomas, although a causative role for the virus has not been convincingly demonstrated. Aberrant methylation of CpG islands in promoter regions is a frequent method of silencing tumor suppressor genes (TSGs) in cancers and may be induced by oncogenic viruses. We investigated the relationship between the presence of SV40 or EBV DNA sequences and the methylation profiles for 10 TSGs in 90 cases of non-Hodgkin’s lymphomas/leukemias and 56 control tissues. SV40 sequences were present in 33/90 (37%) non-Hodgkin’s lymphomas/leukemias, and EBV was present in 11/42 (26%) of non-Hodgkin’s lymphomas. We found a highly significant correlation between the presence of SV40 and methylation of seven genes (P values, 0.006 to &lt;0.0001). In lymphomas, there was no relationship between EBV and methylation. Oncogenic viruses and methylation were rarely present in control tissues. We investigated methylation of the same 10 TSGs in peripheral blood mononuclear cells (PBMC) from a healthy volunteer infected with EBV or EBV and SV40. Promoter methylation of CDH1 and CDH13 were noted in dual SV40- and EBV-infected PBMC, and these two genes were also highly significantly correlated to the presence of SV40 sequences in tumors. SV40 infection also resulted in appearance of the lymphoma/leukemia-specific marker, methylated SHP1. Methylation was completely absent in uninfected and EBV-infected PBMC. Our results demonstrate that the presence of SV40 in hematological malignancies is associated with promoter methylation of TSGs and that in all probability, the virus plays a role in tumor pathogenesis.
PrLZ,
a Novel Prostate-Specific and Androgen-Responsive Gene of the TPD52 Family, Amplified in Chromosome 8q21.1 and Overexpressed in Human Prostate Cancer
Authors: Wang Ruoxiang , Xu Jianchun , Saramäki Outi , Visakorpi Tapio , Sutherland William M. , Zhou Jianguang , Sen Buer , Lim So Dug , Mabjeesh Nicola , Amin Mahul , Dong Jin-Tang , Petros John A. , Nelson Peter S. , Marshall Fray F. , Zhau Haiyen E. , Chung Leland W. K. 
Published: September 2005

Abstract
We report a previously unrecognized prostate-specific protein, PrLZ (prostate leucine zipper), a new member of the Tumor Protein D52 (TPD52) family. The gene for PrLZ was localized at chromosome 8q21.1, a locus most frequently amplified in human prostate cancer. Multiple tissue analyses demonstrated PrLZ predominantly in the prostate gland. Although its expression was enhanced by androgens in androgen receptor-expressing cells, PrLZ was detected in all of the human prostate cancer cell lines, regardless of androgen receptor status. Monoclonal anti-PrLZ antibodies were produced and intense immunohistochemical staining of PrLZ was observed in prostate epithelial cells in intraepithelial neoplasia and prostate cancer, whereas lower-level staining was detected in normal and benign epithelial components of the prostate gland. As the only prostate-specific gene identified in the most frequently amplified genomic region in prostate cancer, PrLZ may be the link between chromosome 8q amplification and malignant transformation of the prostate epithelia.
Imatinib Mesylate Is a Potent Inhibitor of the ABCG2 (BCRP) Transporter and Reverses Resistance to Topotecan and SN-38
in Vitro
Authors: Houghton Peter J. , Germain Glen S. , Harwood Franklin C. , Schuetz John D. , Stewart Clinton F. , Buchdunger Elisabeth , Traxler Peter 
Published: September 2005

Abstract
Imatinib mesylate (Gleevec, STI571) is a kinase inhibitor selective for Bcr-Abl, activated c-Kit kinases, and platelet-derived growth factor receptor tyrosine kinase. Imatinib mesylate, similar to many other tyrosine kinase inhibitors (TKIs), such as members of the 4-anilinoquinazoline class, competes for ATP binding. Previously, 4-anilinoquinazoline TKIs have been shown to inhibit the function of the breast cancer resistance-associated drug transporter (ABCG2), reversing resistance to camptothecin derivatives topotecan and SN-38. However, the potential to inhibit ABCG2 for the 2-phenylamino-pyrimidine class of TKIs, exemplified by imatinib mesylate, has not been examined. Here, we show that imatinib mesylate potently reverses ABCG2-mediated resistance to topotecan and SN-38 and significantly increases accumulation of topotecan only in cells expressing functional ABCG2. However, overexpression of ABCG2 does not confer resistance to imatinib mesylate. Furthermore, accumulation and efflux of [14C]imatinib mesylate are unaltered between ABCG2-expressing and non-ABCG2-expressing cells or by ATP depletion. These results suggest that imatinib mesylate inhibits the function of ABCG2 but is not a substrate for this transporter.
Reactive Oxygen Species (ROS), Troublemakers between Nuclear Factor-κB (NF-κB) and c-Jun NH2-terminal Kinase (JNK)
Authors: Zhang Yadong , Chen Fei 
Published: September 2005

Abstract
Nuclear factor-κB (NF-κB) and c-Jun NH2-terminal kinase (JNK) are activated simultaneously under a variety of stress conditions. They also share several common signaling pathways for their activation in response to cytokines or growth factors. Recent studies, however, demonstrated a new form of interplay between these two allies. Inhibition of NF-κB by ikkβ or rela gene deficiency sensitizes stress responses through enhanced or prolonged activation of JNK. Conversely, sustained activation of NF-κB inhibits cytokine-induced JNK activation. The mechanisms of how NF-κB and JNK become rivals for each other are under extensive debate.
Classification of Proliferative Pulmonary Lesions of the Mouse
Authors: Nikitin Alexander Yu. , Alcaraz Ana , Anver Miriam R. , Bronson Roderick T. , Cardiff Robert D. , Dixon Darlene , Fraire Armando E. , Gabrielson Edward W. , Gunning William T. , Haines Diana C. , Kaufman Matthew H. , Linnoila R. Ilona , Maronpot Robert R. , Rabson Alan S. , Reddick Robert L. , Rehm Sabine , Rozengurt Nora , Schuller Hildegard M. , Shmidt Elena N. , Travis William D. , Ward Jerrold M. , Jacks Tyler 
Published: September 2005

AbstractRapid advances in generating new mouse genetic models for lung neoplasia provide a continuous challenge for pathologists and investigators. Frequently, phenotypes of new models either have no precedents or are arbitrarily attributed according to incongruent human and mouse classifications. Thus, comparative characterization and validation of novel models can be difficult. To address these issues, a series of discussions was initiated by a panel of human, veterinary, and experimental pathologists during the Mouse Models of Human Cancers Consortium (NIH/National Cancer Institute) workshop on mouse models of lung cancer held in Boston on June 20–22, 2001. The panel performed a comparative evaluation of 78 cases of mouse and human lung proliferative lesions, and recommended development of a new practical classification scheme that would (a) allow easier comparison between human and mouse lung neoplasms, (b) accommodate newly emerging mouse neoplasms, and (c) address the interpretation of benign and preinvasive lesions of the mouse lung. Subsequent discussions with additional experts in pulmonary pathology resulted in the current proposal of a new classification. It is anticipated that this classification, as well as the complementary digital atlas of virtual histological slides, will help investigators and pathologists in their characterization of new mouse models, as well as stimulate further research aimed at a better understanding of proliferative lesions of the lung.
A Serial Analysis of Gene Expression (SAGE) Database Analysis of Chemosensitivity
Authors: Stein Wilfred D , Litman Thomas , Fojo Tito , Bates Susan E 
Published: September 2005

AbstractDrug sensitivity and resistance has been most extensively studied in cell lines carried in tissue culture. Furthermore, cell lines have been widely used in testing new anticancer agents, despite the widely recognized observation that cell lines are more sensitive to cytotoxic drugs than are their corresponding solid tumors. We used the Serial Analysis of Gene Expression (SAGE) database to identify differences between solid tumors and cell lines, hoping to detect genes that could potentially explain differences in drug sensitivity. SAGE libraries were available for both solid tumors and cell lines from breast, colon, ovarian, pancreatic, and prostate carcinomas and from gliomas and medulloblastomas. Sixty-two genes were identified as overexpressed in tumors. The immune response and complement pathways were the significant common themes, with extracellular matrix (ECM) proteins third. For the 61 genes overexpressed in cell lines, protein synthesis was the dominant theme. We next used the SAGE database to identify genetic differences between tumor types that convey a broad range of survival to the patients that bear them as distant metastases. SAGE gene expression data were correlated with 5-year survivals documented in the SEER (Surveillance, Epidemiology and End-Results) database for patients diagnosed with “distant” or metastatic cancers. These are unlikely to be amenable to surgical resection; therefore, survival here reflects, to some extent, sensitivity to systemic therapy, i.e., chemotherapy. Using survival data as a surrogate of chemotherapy sensitivity, a spectrum can be generated, with testicular cancer at one end and pancreatic cancer at the other. Favorable 5-year survival, despite a distant presentation, correlates with expression of protein synthesis genes. Poor 5-year survival correlates with expression of cell adhesion, cytoskeletal, and ECM genes, a pattern similar to that found to distinguish solid tumors from the more cytotoxin-sensitive cancer cell lines. One interpretation is that resistance to chemotherapy may arise, in part, from the adherent, relatively inert condition (i.e., low in protein synthesis potential) of refractory cancers. Thus, attachment or ECM genes could be targets for anticancer therapy.
Taxane-Mediated Antiangiogenesis
in Vitro
Authors: Ng Sylvia S. W. , Figg William D. , Sparreboom Alex 
Published: September 2005

Abstract
Paclitaxel (Taxol) and docetaxel (Taxotere) have been shown to inhibit angiogenesis at low concentrations that do not affect cancer cell proliferation. Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis. The data show that clinically relevant concentrations of the vehicles and binding proteins nullify the antiangiogenic activity of both taxanes. It is suggested that these agents may need to be used at much higher doses than anticipated for effective antiangiogenic chemotherapy.
Microarray Analysis Reveals Differences in Gene Expression of Circulating CD8+ T Cells in Melanoma Patients and Healthy Donors
Authors: Xu Tong , Shu Chen-Tsen , Purdom Elizabeth , Dang Demi , Ilsley Diane , Guo Yaqian , Weber Jeffrey , Holmes Susan P. , Lee Peter P. 
Published: September 2005

AbstractCirculating T cells from many cancer patients are known to be dysfunctional and undergo spontaneous apoptosis. We used microarray technology to determine whether gene expression differences exist in T cells from melanoma patients versus healthy subjects, which may underlie these abnormalities. To maximize the resolution of our data, we sort purified CD8+ subsets and amplified the extracted RNA for microarray analysis. These analyses show subtle but statistically significant expression differences for 10 genes in T cells from melanoma patients versus healthy controls, which were additionally confirmed by quantitative real-time PCR analysis. Whereas none of these genes are members of the classical apoptosis pathways, several may be linked to apoptosis. To additionally investigate the significance of these 10 genes, we combined them into a classifier and found that they provide a much better discrimination between melanoma and healthy T cells as compared with a classifier built uniquely with classical apoptosis-related genes. These results suggest the possible engagement of an alternative apoptosis pathway in circulating T cells from cancer patients.
Stromal Cell-Derived Factor-1α Promotes Melanoma Cell Invasion across Basement Membranes Involving Stimulation of Membrane-Type 1 Matrix Metalloproteinase and Rho GTPase Activities
Authors: Bartolomé Rubén A. , Gálvez Beatriz G. , Longo Natividad , Baleux Françoise , van Muijen Goos N. P. , Sánchez-Mateos Paloma , Arroyo Alicia G. , Teixidó Joaquin 
Published: September 2005

Abstract
Tissue invasion by tumor cells involves their migration across basement membranes through activation of extracellular matrix degradation and cell motility mechanisms. Chemokines binding to their receptors provide chemotactic cues guiding cells to specific tissues and organs; they therefore could potentially participate in tumor cell dissemination. Melanoma cells express CXCR4, the receptor for the chemokine stromal cell-derived factor-1α (SDF-1α). Using Matrigel as a model, we show that SDF-1α promotes invasion of melanoma cells across basement membranes. Stimulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) activity by SDF-1α was necessary for invasion, involving at least up-regulation in the expression of this metalloproteinase, as detected in the highly metastatic BLM melanoma cell line. Moreover, SDF-1α triggered the activation of the GTPases RhoA, Rac1, and Cdc42 on BLM cells, and expression of dominant-negative forms of RhoA and Rac1, but not Cdc42, substantially impaired the invasion of transfectants in response to SDF-1α, as well as the increase in MT1-MMP expression. Furthermore, CXCR4 expression on melanoma cells was notably augmented by transforming growth factor-β1, a Matrigel component, whereas anti-transforming growth factor-β antibodies inhibited increases in CXCR4 expression and melanoma cell invasion toward SDF-1α. The identification of SDF-1α as a potential stimulatory molecule for MT1-MMP as well as for RhoA and Rac1 activities during melanoma cell invasion, associated with an up-regulation in CXCR4 expression by interaction with basement membrane factors, could contribute to better knowledge of mechanisms stimulating melanoma cell dissemination.
Characterization of the Interaction of Ingenol 3-Angelate with Protein Kinase C
Authors: Kedei Noemi , Lundberg Daniel J. , Toth Attila , Welburn Peter , Garfield Susan H. , Blumberg Peter M. 
Published: September 2005

AbstractIngenol 3-angelate (I3A) is one of the active ingredients in Euphorbia peplus, which has been used in traditional medicine. Here, we report the initial characterization of I3A as a protein kinase C (PKC) ligand. I3A bound to PKC-α in the presence of phosphatidylserine with high affinity; however, under these assay conditions, little PKC isoform selectivity was observed. PKC isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells. In all of the three cell types, I3A inhibited cell proliferation with somewhat lower potency than did PMA. In intact CHO-K1 cells, I3A was able to translocate different green fluorescent protein-tagged PKC isoforms, visualized by confocal microscopy, with equal or higher potency than PMA. PKC-δ in particular showed a different pattern of translocation in response to I3A and PMA. I3A induced a higher level of secretion of the inflammatory cytokine interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. I3A was unable to cause the same extent of association of the C1b domain of PKC-δ with lipids, compared with PMA or the physiological regulator diacylglycerol, and was able to partially block the association induced by these agents, measured by surface plasmon resonance. The in vitro kinase activity of PKC-α induced by I3A was lower than that induced by PMA. The novel pattern of behavior of I3A makes it of great interest for further evaluation.
Marijuana Use and Risk of Oral Squamous Cell Carcinoma
Authors: Rosenblatt Karin A. , Daling Janet R. , Chen Chu , Sherman Karen J. , Schwartz Stephen M. 
Published: September 2005

Abstract
Previous laboratory investigations, case reports, and a hospital-based case-control study have suggested that marijuana use may be a risk factor for squamous cell head and neck cancer. We conducted a population-based case-control study to determine whether marijuana use is associated with the development of oral squamous cell carcinoma (OSCC). Case subjects (n = 407) were 18–65-year-old residents of three counties in western Washington State who were newly diagnosed with OSCC from 1985 through 1995. Control subjects (n = 615), who were similar to the cases with respect to age and sex, were selected from the general population using random-digit telephone dialing. Lifetime histories of marijuana use and exposure to known OSCC risk factors were ascertained using a structured questionnaire. Information on genetic polymorphisms in glutathione S-transferase enzymes was obtained from assays on participant DNA. Odds ratios for associations with features of marijuana use were adjusted for sex, education, birth year, alcohol consumption, and cigarette smoking. A similar proportion of case subjects (25.6%) and control subjects (24.4%) reported ever use of marijuana (adjusted odds ratio, 0.9; 95% confidence interval, 0.6–1.3). There were no trends in risk observed with increasing duration or average frequency of use or time since first or last use. No subgroup defined by known or suspected OSCC risk factors (age, cigarette smoking, alcohol consumption, and genetic polymorphisms) showed an increased risk. Marijuana use was not associated with OSCC risk in this large, population-based study.
Recent Advances in Stress Signaling in Cancer
Authors: Morin Chantale I. , Huot Jacques 
Published: September 2005

Abstract
This meeting brought together some of the world’s leading scientists in the field of stress signaling, apoptosis, and cancer. This resulted in a productive interaction that updated our current knowledge on “Stress Signaling in Cancer.” It comes out that subtle disturbances in cell signaling can be associated with and even lead to cancer. As a corollary, it appears that correcting the signaling defects associated with cancer constitutes a new approach to the treatment and control of neoplastic diseases. The meeting also raised several questions that should be addressed. In particular, it is of the utmost importance to better understand the mechanisms that underlie the specificity of the cellular response with regard to different ligands. For example, why does Gadd45b prevent apoptotic cell death in response to tumor necrosis factor α, whereas it favors apoptosis after transforming growth factor β (E. De Smaele et al., Nature (Lond.), 414: 308–313, 2001; J. Yoo et al., J. Biol. Chem., 278: 43001–43007, 2003). Other questions concern the understanding of the cross-talk mechanisms between different stress and apoptotic pathways and how the strength and the position and timing of a signal may affect different pathways. The next few years of research in this field should be enlightening and fruitful.