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Cancer Medicine

Cover image for Vol. 1 Issue 2

October 2012

Volume 1, Issue 2

Pages i–ii, 105–288

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. Cancer Biology
    4. Clinical Cancer Research
    5. Cancer Prevention
    1. You have full text access to this OnlineOpen article
      Issue Information (pages i–ii)

      Article first published online: 3 OCT 2012 | DOI: 10.1002/cam4.38

  2. Cancer Biology

    1. Top of page
    2. Issue Information
    3. Cancer Biology
    4. Clinical Cancer Research
    5. Cancer Prevention
    1. Original Research

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      Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations (pages 105–113)

      Nelson K. Y. Wong, Megan Fuller, Sandy Sung, Fred Wong and Aly Karsan

      Article first published online: 18 JUL 2012 | DOI: 10.1002/cam4.18

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      We show that only a subpopulation of cancer stem cells requires Notch signaling for tumor initiation, and demonstrating definitively that there is heterogeneity in the tumor-initiating population. Our results imply the need of developing combination therapy to target cancer stem cells.

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      EGFR targeting monoclonal antibody combines with an mTOR inhibitor and potentiates tumor inhibition by acting on complementary signaling hubs (pages 114–127)

      Roshan James, Siddharth Vishwakarma, Indira V. Chivukula, Chetana Basavaraj, Ramakrishnan Melarkode, Enrique Montero and Pradip Nair

      Article first published online: 1 AUG 2012 | DOI: 10.1002/cam4.21

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      Nimotuzumab, an antibody with intermediate affinity and thereby limited skin toxicity combines synergistically with Sirolimus to inhibit the proliferation of even low EGFR-expressing cells. These molecules affect the complementary signaling hubs of EGFR and mTOR. The mode of action of the drugs is investigated in vitro and in vivo. The results would suggest the feasibility of this drug combination at doses lower than the current therapeutic doses, in cancer patients expressing EGFR differently.

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      Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer (pages 128–140)

      Dan Dayan, Tuula Salo, Sirpa Salo, Pia Nyberg, Sini Nurmenniemi, Daniela Elena Costea and Marilena Vered

      Article first published online: 16 AUG 2012 | DOI: 10.1002/cam4.24

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      The tumor microenvironment (TME) components, inflammatory protumorigenic cells, and cancer-associated fibroblasts (CAFs) were significantly associated with poor clinical outcomes in mobile tongue cancer. Moreover, cultured tongue cancer cells (HSC-3) on a three-dimensional myoma model (mimicking TME) showed the presence of exosomes, epithelial–mesenchymal transition, acquisition of CAF-like phenotype by fibroblasts, and reciprocal interrelations between different cytokines. Collectively, these findings support evidence for crosstalk between cancer cells and TME components, which warrants targeting by new therapies.

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      MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma (pages 141–155)

      Wiyada Kwanhian, Dido Lenze, Julia Alles, Natalie Motsch, Stephanie Barth, Celina Döll, Jochen Imig, Michael Hummel, Marianne Tinguely, Pankaj Trivedi, Viraphong Lulitanond, Gunter Meister, Christoph Renner and Friedrich A. Grässer

      Article first published online: 18 SEP 2012 | DOI: 10.1002/cam4.29

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      The precursor or the mature microRNA miR-142-3p or miR-142-5p was found to be mutated in 20% of diffuse large B-cell lymphoma (DLBCL). Some of the mutations were found to abrogate the function of the microRNA vis-a-vis known targets. We hypothesize that loss-of-function mutations in miR-142 might contribute to the induction or maintenance of DLBCL.

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      Significance of lymphovascular space invasion in epithelial ovarian cancer (pages 156–164)

      Koji Matsuo, Todd B. Sheridan, Kiyoshi Yoshino, Takahito Miyake, Karina E. Hew, Dwight D. Im, Neil B. Rosenshein, Seiji Mabuchi, Takayuki Enomoto, Tadashi Kimura, Anil K. Sood and Lynda D. Roman

      Article first published online: 14 SEP 2012 | DOI: 10.1002/cam4.31

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      The presence of lymphovascular space invasion (LVSI) within the ovarian tumor is an independent predictive indicator of nodal metastasis and associated with a worse prognosis in ovarian cancer. In apparent stage I ovarian cancer, the absence of LVSI was an excellent predictor of negative nodal status.

  3. Clinical Cancer Research

    1. Top of page
    2. Issue Information
    3. Cancer Biology
    4. Clinical Cancer Research
    5. Cancer Prevention
    1. Original Research

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      Coordinate regulation between expression levels of telomere-binding proteins and telomere length in breast carcinomas (pages 165–175)

      Kimberly S. Butler, William C. Hines, Christopher M. Heaphy and Jeffrey K. Griffith

      Article first published online: 24 JUL 2012 | DOI: 10.1002/cam4.14

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      Telomere content assays and quantitative RT-PCR demonstrate that the levels of TRF2, TRF1, TIN2, and POT1 mRNA, but not telomerase reverse transcriptase (TERT) RNA, are inversely correlated with telomere content in breast tumors. Within human breast cancer cell lines, expressions of TRF1, TIN2, and POT1 are upregulated by dexamethasone, suggesting activation of the glucocorticoid receptor, whereas TERT, TRF2, TRF1, TIN2, and POT1 are upregulated by TNF-α, suggesting activation of the NFκB transcription factor. These findings link telomere content in breast tumors to the expression of several telomere-associated proteins previously shown to be negative regulators of telomere length in cell lines and suggest a link between the expressions of the telomere-associated proteins and mediators of stress and inflammation.

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      Epigenetic inactivation of inhibitor of differentiation 4 (Id4) correlates with prostate cancer (pages 176–186)

      Pankaj Sharma, Swathi Chinaranagari, Divya Patel, Jason Carey and Jaideep Chaudhary

      Article first published online: 2 AUG 2012 | DOI: 10.1002/cam4.16

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      Id4, a HLH protein, is highly expressed in normal prostate. Id4 expression is decreased in prostate cancer -Loss of Id4 is due to epigenetic silencing of its promoter

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      Id1 and Id3 expression is associated with increasing grade of prostate cancer: Id3 preferentially regulates CDKN1B (pages 187–197)

      Pankaj Sharma, Divya Patel and Jaideep Chaudhary

      Article first published online: 27 AUG 2012 | DOI: 10.1002/cam4.19

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      In this study we demonstrate that Id3 expression is significantly increased in prostate cancer. At the molecular level, Id3 appears to downregulate the expression of CDKN1B.

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      Analysis of neurosensory adverse events induced by FOLFOX4 treatment in colorectal cancer patients: a comparison between two Asian studies and four Western studies (pages 198–206)

      Kenichi Sugihara, Atsushi Ohtsu, Yasuhiro Shimada, Nobuyuki Mizunuma, Katsushige Gomi, Po-Huang Lee, Aimery de Gramont, Mace L. Rothenberg, Thierry André, Silvano Brienza and Richard M. Goldberg

      Article first published online: 6 AUG 2012 | DOI: 10.1002/cam4.25

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      The cumulative doses of oxaliplatin linked to grade ≥3 NSAEs were higher in Asian patients than in Western patients, whereas those administered during grade escalation of NSAEs in Japanese patients were similar to those in Western patients. The Asian populations accrued to these studies appear to have been less susceptible to the neurotoxicity of oxaliplatin than those enrolled in Western studies.

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      Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer (pages 207–217)

      John Arcaroli, Kevin Quackenbush, Arvind Dasari, Rebecca Powell, Martine McManus, Aik-Choon Tan, Nathan R. Foster, Joel Picus, John Wright, Sujatha Nallapareddy, Charles Erlichman, Manuel Hidalgo and Wells A. Messersmith

      Article first published online: 16 AUG 2012 | DOI: 10.1002/cam4.27

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      We conducted a multicenter phase II clinical trial of saracatinib in gemcitabine-resistant metastatic pancreas cancer patients. Initially, the trial was conducted in unselected patients. Due to lack of a minimum number of patients achieving a 6-month overall survival endpoint in the first 17 patients, the study was amended and a biomarker-driven study based on human tumor explant experiments was conducted. The study was closed due to a low number of biomarker-positive patients, but demonstrates the feasibility of prospective biomarker (DNA) testing study in pancreas cancer.

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      Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer (pages 218–229)

      Maiko Horio, Takuya Kato, Shinji Mii, Atsushi Enomoto, Masato Asai, Naoya Asai, Yoshiki Murakumo, Kiyosumi Shibata, Fumitaka Kikkawa and Masahide Takahashi

      Article first published online: 13 SEP 2012 | DOI: 10.1002/cam4.32

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      Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. Our findings suggest that RET finger protein (RFP) could be a predictive marker for chemoresistance in ovarian cancer patients and also a candidate for a molecular-targeted agent.

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      18-FDG PET/CT assessment of basal cell carcinoma with vismodegib (pages 230–236)

      Curtis A. Thacker, Glen J. Weiss, Raoul Tibes, Lisa Blaydorn, Molly Downhour, Erica White, Jason Baldwin, Daniel D. Von Hoff and Ronald L. Korn

      Article first published online: 17 SEP 2012 | DOI: 10.1002/cam4.33

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      The use of 18-FDG PET/CT in subjects with advanced basal cell carcinoma (BCC) has not been fully explored due to the rarity of disease presentation. This study evaluated PET/CTs from subjects with advanced BCC participating in a phase I dose-escalation clinical trial of vismodegib.

  4. Cancer Prevention

    1. Top of page
    2. Issue Information
    3. Cancer Biology
    4. Clinical Cancer Research
    5. Cancer Prevention
    1. Review

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      Strategies for discovery and validation of methylated and hydroxymethylated DNA biomarkers (pages 237–260)

      Ekaterina Olkhov-Mitsel and Bharati Bapat

      Article first published online: 14 SEP 2012 | DOI: 10.1002/cam4.22

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      This review article describes existing and emerging strategies applied to the discovery and validation of DNA methylation-based biomarkers and describes their most important advantages and limitations. Additionally, recent studies describing the seminal discovery of 5-hydroxymethylation and its significance for methylation marker analyses, and novel detection strategies specific to 5-hydroxymethylation are described. The review covers the large-scale, genome-wide, epigenetic profiling studies used for candidate biomarker discovery and the highly targeted locus-specific assays used for validation of biomarker performance in large independent cohorts.

    2. Original Research

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      Soluble endothelial protein C receptor (sEPCR) is likely a biomarker of cancer-associated hypercoagulability in human hematologic malignancies (pages 261–267)

      Elodie Ducros, Shah Soltan Mirshahi, Anne-Marie Faussat, Pezhman Mirshahi, Sophie Dimicoli, Ruoping Tang, Julia Pardo, Jdid Ibrahim, Jean-Pierre Marie, Amu Therwath, Jeannette Soria and Massoud Mirshahi

      Article first published online: 23 JUL 2012 | DOI: 10.1002/cam4.11

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      Protein C receptor and leukemia-associated hypercoagulability.

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      Differential expression of miRNAs in the serum of patients with high-risk oral lesions (pages 268–274)

      Sara Ann MacLellan, James Lawson, Jonathan Baik, Martial Guillaud, Catherine Fang-Yeu Poh and Cathie Garnis

      Article first published online: 19 JUL 2012 | DOI: 10.1002/cam4.17

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      To our knowledge, this is the first report of global analysis of microRNA expression levels in serum from patients with oral cancer or precancer. In addition, by examining the serum microRNA profiles of patients before and after surgical resection of a given lesion, we have detected microRNA expression profiles that are oral cancer specific. Our results identify several microRNAs with possible utility as biomarkers for detection of early or recurrent oral cancer.

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      Dose-dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin-like growth factor-1 (pages 275–288)

      Leticia M. Nogueira, Jackie A. Lavigne, Gadisetti V. R. Chandramouli, Huaitian Lui, J. Carl Barrett and Stephen D. Hursting

      Article first published online: 6 AUG 2012 | DOI: 10.1002/cam4.23

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      We compared the effects of different levels of calorie restriction (CR), with and without infusion of IGF-1 (a potential mediator of the anticancer effects of CR), on hepatic and mammary gland gene expression and mammary tumor progression. We found (1) several genes and pathways, particularly those associated with macronutrient and steroid hormone metabolism, are associated with the anticancer effects of moderate (30%) CR; (2) mild CR (20%) has little effect on gene expression relative to control, whereas 40% CR modulates metabolic pathways as well as a broad panel of stress-related and DNA damage-related genes, suggesting this level of CR is too severe; and (3) reduced IGF-1 levels can account, at least in part, for many of the effects of CR on metabolism-related gene expression and mammary tumor burden.

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