bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Tomato Lycopene and Ketosamine against Rat Prostate Tumorigenesis
Authors: Mossine Valeri V. , Chopra Pankaj , Mawhinney Thomas P. 
Published: June 2008

AbstractPrior investigations on the beneficial effect of dietary processed tomato products and lycopene on prostate cancer risk suggested that lycopene may require the presence of other constituents to exert its chemopreventive potential. We investigated whether ketosamines, a group of carbohydrate derivatives present in dehydrated tomato products, may interact with lycopene against prostate tumorigenesis. One ketosamine, FruHis, strongly synergized with lycopene against proliferation of the highly metastatic rat prostate adenocarcinoma MAT-LyLu cell line in vitro. The FruHis/lycopene combination significantly inhibited in vivo tumor formation by MAT-LyLu cells in syngeneic Copenhagen rats. Energy-balanced diets, supplemented with tomato paste, tomato powder, or tomato paste plus FruHis, were fed to Wistar-Unilever rats (n = 20 per group) treated with N-nitroso-N-methylurea and testosterone to induce prostate carcinogenesis. Survival from carcinogenesis was lowest in the control group (median survival time, 40 weeks) and highest in the group fed the tomato paste/FruHis diet (51 weeks; P = 0.004, versus control). The proportions of dying rats with macroscopic prostate tumors in the control, tomato paste, tomato powder, and tomato paste/FruHis groups were 63% (12 of 19), 39% (5 of 13), 43% (6 of 14), and 18% (2 of 11), respectively. FruHis completely blocked DNA oxidative degradation at &gt;250 μmol/L in vitro, whereas neither ascorbate nor phenolic antioxidants from tomato were effective protectors in this assay. FruHis, therefore, may exert tumor-preventive effect through its antioxidant activity and interaction with lycopene. [Cancer Res 2008;68(11):4384–91]
Epigenetic Silencing of MicroRNA-34b/c and B-Cell Translocation Gene 4 Is Associated with CpG Island Methylation in Colorectal Cancer
Authors: Toyota Minoru , Suzuki Hiromu , Sasaki Yasushi , Maruyama Reo , Imai Kohzoh , Shinomura Yasuhisa , Tokino Takashi 
Published: June 2008

Abstract
Altered expression of microRNA (miRNA) is strongly implicated in cancer, and recent studies have shown that, in cancer, expression of some miRNAs cells is silenced in association with CpG island hypermethylation. To identify epigenetically silenced miRNAs in colorectal cancer (CRC), we screened for miRNAs induced in CRC cells by 5-aza-2′-deoxycytidine (DAC) treatment or DNA methyltransferase knockout. We found that miRNA-34b (miR-34b) and miR-34c, two components of the p53 network, are epigenetically silenced in CRC; that this down-regulation of miR-34b/c is associated with hypermethylation of the neighboring CpG island; and that DAC treatment rapidly restores miR-34b/c expression. Methylation of the miR-34b/c CpG island was frequently observed in CRC cell lines (nine of nine, 100%) and in primary CRC tumors (101 of 111, 90%), but not in normal colonic mucosa. Transfection of precursor miR-34b or miR-34c into CRC cells induced dramatic changes in the gene expression profile, and there was significant overlap between the genes down-regulated by miR-34b/c and those down-regulated by DAC. We also found that the miR-34b/c CpG island is a bidirectional promoter which drives expression of both miR-34b/c and B-cell translocation gene 4 (BTG4); that methylation of the CpG island is also associated with transcriptional silencing of BTG4; and that ectopic expression of BTG4 suppresses colony formation by CRC cells. Our results suggest that miR-34b/c and BTG4 are novel tumor suppressors in CRC and that the miR-34b/c CpG island, which bidirectionally regulates miR-34b/c and BTG4, is a frequent target of epigenetic silencing in CRC. [Cancer Res 2008;68(11):4123–32]
Identification and Characterization of Ovarian Cancer-Initiating Cells from Primary Human Tumors
Authors: Zhang Shu , Balch Curt , Chan Michael W. , Lai Hung-Cheng , Matei Daniela , Schilder Jeanne M. , Yan Pearlly S. , Huang Tim H-M. , Nephew Kenneth P. 
Published: June 2008

Abstract
The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing, nonadherent spheroids previously shown to derive from tissue stem cells. To affirm the existence of OCICs, xenoengraftment of as few as 100 dissociated spheroid cells allowed full recapitulation of the original tumor (grade 2/grade 3 serous adenocarcinoma), whereas &gt;105 unselected cells remained nontumorigenic. Stemness properties of OCICs (under stem cell–selective conditions) were further established by cell proliferation assays and reverse transcription–PCR, demonstrating enhanced chemoresistance to the ovarian cancer chemotherapeutics cisplatin or paclitaxel and up-regulation of stem cell markers (Bmi-1, stem cell factor, Notch-1, Nanog, nestin, ABCG2, and Oct-4) compared with parental tumor cells or OCICs under differentiating conditions. To identify an OCIC cell surface phenotype, spheroid immunostaining showed significant up-regulation of the hyaluronate receptor CD44 and stem cell factor receptor CD117 (c-kit), a tyrosine kinase oncoprotein. Similar to sphere-forming OCICs, injection of only 100 CD44+CD117+ cells could also serially propagate their original tumors, whereas 105 CD44−CD117− cells remained nontumorigenic. Based on these findings, we assert that epithelial ovarian cancers derive from a subpopulation of CD44+CD117+ cells, thus representing a possible therapeutic target for this devastating disease. [Cancer Res 2008;68(11):4311–20]
The Previously Undescribed ZKSCAN3 (ZNF306) Is a Novel “Driver” of Colorectal Cancer Progression
Authors: Yang Lin , Hamilton Stanley R. , Sood Anil , Kuwai Toshio , Ellis Lee , Sanguino Angela , Lopez-Berestein Gabriel , Boyd Douglas D. 
Published: June 2008

Abstract
A relatively new view of colorectal cancer is that its development/progression reflects the contribution of a large set of altered gene products in varying combinations, each providing a “fitness advantage.” In searching for novel contributing gene products using Unigene cluster data mining, we found overrepresentation of expressed sequence tags corresponding to a previously uncharacterized gene (ZKSCAN3) in colorectal tumors. ZKSCAN3 was pursued for several reasons: (a) its sequence similarity with bowl required for Drosophila hindgut development; (b) it lies in a chromosomal region (6p22.1) amplified in colorectal cancer; and (c) its coding sequence predicts tandem C2H2 zinc finger domains present in a class of proteins gaining attention for their role in oncogenesis/tumor progression. Reverse transcription-PCR confirmed overexpression in colorectal tumor tissue compared with adjacent nonmalignant mucosa due in part to gene amplification determined by Southern blotting. Further, immunohistochemistry with an antibody generated to the predicted protein sequence revealed higher ZKSCAN3 expression in invasive compared with noninvasive tumors. Intriguingly, the ZKSCAN3 protein was also expressed in tumors wild-type for genes (APC, p53, K-Ras) commonly targeted in colorectal cancer. ZKSCAN3 knockdown in two independent colon cancer cell lines impaired anchorage-independent growth and orthotopic tumor growth, whereas overexpression in a third cell line had the opposite effect and increased 5-fluorouracil resistance. Liposomal delivery of a ZKSCAN3-targeting small interfering RNA reduced tumorigenicity of orthotopic colon cancer. Thus, the hitherto uncharacterized ZKSCAN3 adds to an expanding set of encoded products contributing to the progression of colorectal cancer. [Cancer Res 2008;68(11):4321–30]
Molecular Interactions between Dying Tumor Cells and the Innate Immune System Determine the Efficacy of Conventional Anticancer Therapies
Authors: Apetoh Lionel , Tesniere Antoine , Ghiringhelli François , Kroemer Guido , Zitvogel Laurence 
Published: June 2008

Abstract
The efficacy of anticancer treatments is mostly assessed by their ability to directly inhibit the proliferation of tumor cells. Recently, we showed that tumor cell death triggered by chemotherapy or radiotherapy initiates an immunoadjuvant pathway that contributes to the success of cytotoxic treatments. The interaction of high mobility group box 1 protein (HMGB1) released from dying tumor cells with Toll-like receptor 4 (TLR4) on dendritic cells was required for the crosspresentation of tumor antigens and the promotion of tumor specific cytotoxic T-cell responses. Breast cancer patients harboring the loss-of-function Asp299Gly polymorphism of TLR4 relapsed earlier after receiving anthracycline-based chemotherapy. These data suggests that HMGB1- and TLR4-dependent immune responses elicited by conventional cancer treatment may increase the probability to achieve a durable therapeutic success. [Cancer Res 2008;68(11):4026–30]
The E2F3-Oncomir-1 Axis Is Activated in Wilms' Tumor
Authors: Kort Eric J. , Farber Leslie , Tretiakova Maria , Petillo David , Furge Kyle A. , Yang Ximing J. , Cornelius Albert , Teh Bin T. 
Published: June 2008

Abstract
Oncomir-1 is an oncogenic cluster of microRNAs (miRNA) located on chromosome 13. Previous in vitro studies showed that it is transcriptionally regulated by the transcription factor E2F3. In this report, we combine expression profiling of both mRNA and miRNAs in Wilms' tumor (WT) samples to provide the first evidence that the E2F3-Oncomir-1 axis, previously identified in cell culture, is deregulated in primary human tumors. Analysis of RNA expression signatures showed that an E2F3 gene signature was activated in all WT samples analyzed, in contrast to other kidney tumors. This finding was validated by immunohistochemistry on the protein level. Expression of E2F3 was lowest in early-stage tumors and highest in metastatic tissue. Expression profiling of miRNAs in WT showed that expression of each measured member of the Oncomir-1 family was highest in WT relative to other kidney tumor subtypes. Quantitative PCR confirmed that these miRNAs were overexpressed in WT relative to normal kidney tissue. These results suggest that the E2F3-Oncomir-1 axis is activated in WT. Our study also shows the utility of integrated genomics combining gene signature analysis with miRNA expression profiling to identify protein-miRNA interactions that are perturbed in disease states. [Cancer Res 2008;68(11):4034–8]
AlkB Homologue 2–Mediated Repair of Ethenoadenine Lesions in Mammalian DNA
Authors: Ringvoll Jeanette , Moen Marivi N. , Nordstrand Line M. , Meira Lisiane B. , Pang Bo , Bekkelund Anders , Dedon Peter C. , Bjelland Svein , Samson Leona D. , Falnes Pål Ø. , Klungland Arne 
Published: June 2008

Abstract
Endogenous formation of the mutagenic DNA adduct 1,N6-ethenoadenine (εA) originates from lipid peroxidation. Elevated levels of εA in cancer-prone tissues suggest a role for this adduct in the development of some cancers. The base excision repair pathway has been considered the principal repair system for εA lesions until recently, when it was shown that the Escherichia coli AlkB dioxygenase could directly reverse the damage. We report here kinetic analysis of the recombinant human AlkB homologue 2 (hABH2), which is able to repair εA lesions in DNA. Furthermore, cation exchange chromatography of nuclear extracts from wild-type and mABH2−/− mice indicates that mABH2 is the principal dioxygenase for εA repair in vivo. This is further substantiated by experiments showing that hABH2, but not hABH3, is able to complement the E. coli alkB mutant with respect to its defective repair of etheno adducts. We conclude that ABH2 is active in the direct reversal of εA lesions, and that ABH2, together with the alkyl-N-adenine-DNA glycosylase, which is the most effective enzyme for the repair of εA, comprise the cellular defense against εA lesions. [Cancer Res 2008;68(11):4142–9]
Focal Adhesion Kinase Expression in Human Neuroblastoma: Immunohistochemical and Real-time PCR Analyses
Authors: Beierle Elizabeth A. , Massoll Nicole A. , Hartwich Joseph , Kurenova Elena V. , Golubovskaya Vita M. , Cance William G. , McGrady Patrick , London Wendy B. 
Published: June 2008

Abstract
Purpose: The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase important in signaling between cells and their extracellular matrix. Studies have shown that FAK expression is up-regulated in several human tumors and is related to tumor progression. We recently found an increase in p125FAK expression in human neuroblastoma cells lines and wished to determine its expression in human neuroblastoma specimens and evaluate for a possible correlation between p125FAK expression and known prognostic factors for neuroblastoma. We hypothesized that p125FAK expression would be up-regulated in advanced human neuroblastomas.
Experimental Design: Using immunohistochemical techniques with monoclonal antibody 4.47 specific for p125FAK expression, we analyzed 70 formalin-fixed, paraffin-embedded human neuroblastoma specimens for p125FAK staining. In addition, real-time PCR was used to determine the abundance of FAK mRNA in 17 matched human neuroblastoma mRNA specimens.
Results: FAK staining was present in 51 of the 70 tumor specimens (73%). Immunohistochemical staining of p125FAK in the ganglion-type tumor cells correlated with advanced International Neuroblastoma Staging System tumor stages and FAK mRNA abundance. In addition, p125FAK staining was significantly increased in stage IV tumors with amplification of the N-MYC oncogene.
Conclusions: These novel findings provide evidence that FAK is expressed by advanced-stage neuroblastoma and provide a rationale for targeting FAK in the treatment of this tumor.
Changes in Tumor Metabolism as Readout for Mammalian Target of Rapamycin Kinase Inhibition by Rapamycin in Glioblastoma
Authors: Wei Liu Hua , Su Helen , Hildebrandt Isabel J. , Phelps Michael E. , Czernin Johannes , Weber Wolfgang A. 
Published: June 2008

Abstract
Purpose: Inhibition of the protein kinase mammalian target of rapamycin (mTOR) is being evaluated for treatment of a variety of malignancies. However, the effects of mTOR inhibitors are cytostatic and standard size criteria do not reliably identify responding tumors. The aim of this study was to evaluate whether response to mTOR inhibition could be assessed by positron emission tomography (PET) imaging of tumor metabolism.
Experiment Design: Glucose, thymidine, and amino acid utilization of human glioma cell lines with varying degrees of sensitivity to mTOR inhibition were assessed by measuring in vitro uptake of [18F]fluorodeoxyglucose ([18F]FDG), [18F]fluorothymidine ([18F]FLT), and [3H]l-tyrosine before and after treatment with the mTOR inhibitor rapamycin. The tumor metabolic activity in vivo was monitored by small-animal PET of tumor-bearing mice. The mechanisms underlying changes in metabolic activity were analyzed by measuring expression and functional activity of enzymes and transporters involved in the uptake of the studied imaging probes.
Results: In sensitive cell lines, rapamycin decreased [18F]FDG and [18F]FLT uptake by up to 65% within 24 hours after the start of therapy. This was associated with inhibition of hexokinase and thymidine kinase 1. In contrast, [3H]l-tyrosine uptake was unaffected by rapamycin. The effects of rapamycin on glucose and thymidine metabolism could be imaged noninvasively by PET. In sensitive tumors, [18F]FDG and [18F]FLT uptake decreased within 48 hours by 56 ± 6% and 52 ± 8%, respectively, whereas there was no change in rapamycin-resistant tumors.
Conclusions: These encouraging preclinical data warrant clinical trials evaluating [18F]FDG and [18F]FLT-PET for monitoring treatment with mTOR inhibitors in patients.
Human High Molecular Weight–Melanoma-Associated Antigen: Utility for Detection of Metastatic Melanoma in Sentinel Lymph Nodes
Authors: Goto Yasufumi , Ferrone Soldano , Arigami Takaaki , Kitago Minoru , Tanemura Atsushi , Sunami Eiji , Nguyen Sandy L. , Turner Roderick R. , Morton Donald L. , Hoon Dave S.B. 
Published: June 2008

AbstractPurpose: Detection of micrometastasis in melanoma-draining lymph nodes is important for staging and prognosis. Immunohistochemical staining (IHC) using S-100p-HMB-45–, and MART-1–specfic antibodies is used for detecting metastases in sentinel lymph nodes (SLN). However, improvement in IHC is needed for melanoma micrometastasis detection.Experimental Design: Paraffin-embedded archival tissue (PEAT) specimens were obtained from 42 non-SLN macrometastases, 42 SLN metastases, and 16 tumor-negative SLNs of 100 melanoma patients who underwent SLN biopsy. PEAT specimens were assessed by IHC with high molecular weight−melanoma-associated antigen (HMW-MAA)–specific monoclonal antibodies (mAb) and with S-100p-, HMB-45–, and MART-1–specific antibodies. Quantitative real-time reverse-transcriptase PCR assay was used for HMW-MAA and MART-1 mRNA detection.Results: Expression frequency and immunostaining intensity were higher for HMW-MAA than MART-1 in nodal macrometastases (P &lt; 0.0001 and P &lt; 0.0001, respectively) and micrometastases (P &lt; 0.0001 and P = 0.004, respectively). All 52 (100%) macrometastases were positive with HMW-MAA–specific mAbs, whereas 43 (83%) were positive with MART-1–specific mAbs. In a comparison analysis, 23 of 23 (100%) micrometastases were HMW-MAA–positive, whereas 21 (91%) and 18 (78%) specimens were S-100p– and HMB-45–positive, respectively. Quantitative real-time reverse-transcriptase PCR analysis of 48 nodal metastases showed HMW-MAA mRNA detection in SLNs with metastases.Conclusions: HMW-MAA is more sensitive and specific than MART-1, S-100p, and HMB-45 for IHC-based detection of SLN micrometastases. SLN PEAT–based detection specificity of melanoma micrometastases can be improved by IHC with HMW-MAA–specific mAbs.
Combination of Docetaxel and Recombinant Vaccine Enhances T-Cell Responses and Antitumor Activity: Effects of Docetaxel on Immune Enhancement
Authors: Garnett Charlie T. , Schlom Jeffrey , Hodge James W. 
Published: June 2008

AbstractPurpose: Taxanes comprise some of the most widely used cancer chemotherapeutic agents. Members of this drug family, including docetaxel, are commonly used to treat breast, prostate, and lung cancers, among others. This study was designed to determine if this taxane has the ability to modulate components of the immune system independent of antitumor activity and to investigate the potential synergistic activities of the combination of docetaxel and vaccine therapy.Experimental Design: We examined the in vivo effects of docetaxel on immune-cell subsets and on the function of CD4+, CD8+, and regulatory T-cell (Treg) populations in response to antigen-specific vaccination. We also examined the antitumor effects of the combination of docetaxel and vaccine in a preclinical model in which docetaxel has no observable effect on tumor growth.Results: These studies show for the first time that (a) docetaxel modulates CD4+, CD8+, CD19+, natural killer cell, and Treg populations in non–tumor-bearing mice; (b) unlike cyclophosphamide, docetaxel does not inhibit the function of Tregs; (c) docetaxel enhances CD8+ but not CD4+ response to CD3 cross-linking; (d) docetaxel given after vaccination provides optimal enhancement of immune response to recombinant viral vaccines; (e) docetaxel combined with recombinant viral vaccine is superior to either agent alone at reducing tumor burden; and (f) docetaxel plus vaccine increases antigen-specific T-cell responses to antigen in the vaccine, as well as to cascade antigens derived from the tumor.Conclusions: These findings suggest potential clinical benefit for the combined use of docetaxel and recombinant cancer vaccines.
Involvement of Hepcidin in the Anemia of Multiple Myeloma
Authors: Sharma Sanjai , Nemeth Elizabeta , Chen Yi-Hsiang , Goodnough Julia , Huston Alissa , Roodman G.D. , Ganz Tomas , Lichtenstein Alan 
Published: June 2008

Abstract
Purpose: Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma.
Experimental Design: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-α, and IL-1β were studied in newly diagnosed myeloma patients. In vitro hepcidin induction assay was assessed by real-time PCR assay.
Results: Pretreatment urinary hepcidin levels in 44 patients with stage III multiple myeloma were 3-fold greater than normal controls. In the subset of multiple myeloma patients without renal insufficiency (n = 27), a marked inverse correlation was seen between hemoglobin at diagnosis and urinary hepcidin level (P = 0.014) strongly supporting a causal relationship between up-regulated hepcidin expression and anemia. The urinary hepcidin also significantly (P &lt; 0.05) correlated with serum ferritin and C-reactive protein, whereas its correlation with serum IL-6 levels was of borderline significance (P = 0.06). Sera from 14 multiple myeloma patients, with known elevated urinary hepcidin, significantly induced hepcidin mRNA in the Hep3B cells, whereas normal sera had no effect. For 10 patients, the ability of anti-IL-6 and anti-IL-6 receptor antibodies to prevent the serum-induced hepcidin RNA was tested. In 6 of these patients, hepcidin induction was abrogated by the anti-IL-6 antibodies, but in the other 4 patients, the neutralizing antibodies had no effect.
Conclusions: These results indicate hepcidin is up-regulated in multiple myeloma patients by both IL-6-dependent and IL-6-independent mechanisms and may play a role in the anemia of multiple myeloma.
Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors
Authors: Prasad Nijaguna B. , Somervell Helina , Tufano Ralph P. , Dackiw Alan P.B. , Marohn Michael R. , Califano Joseph A. , Wang Yongchun , Westra William H. , Clark Douglas P. , Umbricht Christopher B. , Libutti Steven K. , Zeiger Martha A. 
Published: June 2008

Abstract
Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as “suspicious” or “indeterminate.” Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions.
Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician.
Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription–PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription–PCR data.
Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.