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International Journal of Cancer

Cover image for Vol. 132 Issue 6

15 March 2013

Volume 132, Issue 6

Pages 1235–1485

  1. Editorial

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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  2. Special Section Papers

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Cellular reprogramming and cancer development (pages 1240–1248)

      Katsunori Semi, Yutaka Matsuda, Kotaro Ohnishi and Yasuhiro Yamada

      Version of Record online: 17 DEC 2012 | DOI: 10.1002/ijc.27963

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    4. You have full text access to this OnlineOpen article
  3. Carcinogenesis

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      20(S)-protopanaxadiol-aglycone downregulation of the full-length and splice variants of androgen receptor (pages 1277–1287)

      Bo Cao, Xichun Liu, Jing Li, Shuang Liu, Yanfeng Qi, Zhenggang Xiong, Allen Zhang, Thomas Wiese, Xueqi Fu, Jingkai Gu, Paul S. Rennie, Oliver Sartor, Benjamin R. Lee, Clement Ip, Lijuan Zhao, Haitao Zhang and Yan Dong

      Version of Record online: 20 AUG 2012 | DOI: 10.1002/ijc.27754

      What's new?

      This is the first report on 20(S)-protopanaxadiol-aglycone as an effective agent to downregulate the expression and activity of the full-length androgen receptor and its constitutively-active splice variants in prostate cancer. It is also the first to show the in vivo efficacy of 20(S)-protopanaxadiol-aglycone against androgen-receptor-expressing prostate tumors. Considering the critical roles of androgen receptor and its splice variants in disease progression, our findings suggest that 20(S)-protopanaxadiol-aglycone is a promising agent for prostate cancer intervention.

  4. Cancer Cell Biology

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Contribution of Na+,HCO3-cotransport to cellular pH control in human breast cancer: A role for the breast cancer susceptibility locus NBCn1 (SLC4A7) (pages 1288–1299)

      Ebbe Boedtkjer, José M.A. Moreira, Marco Mele, Pernille Vahl, Vera T. Wielenga, Peer M. Christiansen, Vibeke E.D. Jensen, Stine F. Pedersen and Christian Aalkjaer

      Version of Record online: 7 SEP 2012 | DOI: 10.1002/ijc.27782

      What's new?

      Genome-wide association studies have linked the Na+,HCO3-cotransporter NBCn1 (SLC4A7) to human breast cancer. The Danish researchers show that NBCn1 expression is upregulated in human breast carcinomas and metastases. Furthermore, they identify Na+,HCO3-cotransport as a major mechanism of acid extrusion critical for intracellular pH control in human primary breast carcinomas. These data implicate NBCn1 in the pathophysiology of breast cancer and may provide clues to future therapeutic strategies.

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      Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression (pages 1300–1310)

      Benjamin Otto, Katharina Gruner, Christina Heinlein, Florian Wegwitz, Peter Nollau, Bauke Ylstra, Klaus Pantel, Udo Schumacher, Lars O. Baumbusch, José Ignacio Martin-Subero, Reiner Siebert, Christoph Wagener, Thomas Streichert, Wolfgang Deppert and Genrich V. Tolstonog

      Version of Record online: 26 SEP 2012 | DOI: 10.1002/ijc.27783

      What's new?

      The expression of oncogenes in transgenic mice is a useful tool for simplifying the study of tumor progression at the molecular level. In this study, the authors analyzed WAP-T transgenic mice, which are prone to both low- and high-grade mammary tumors. They found that the high-grade tumors featured recurrent amplification of the proto-oncogene Met locus, as well as increased expression of an active Met receptor. The results of this analysis suggest that low-grade and high-grade tumors originate independently in separate progenitor cells, rather than a single tumor progressing from one to the other.

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      Transcription factors link mouse WAP-T mammary tumors with human breast cancer (pages 1311–1322)

      Benjamin Otto, Thomas Streichert, Florian Wegwitz, Heidrun Gevensleben, Kristin Klätschke, Christoph Wagener, Wolfgang Deppert and Genrich V. Tolstonog

      Version of Record online: 13 DEC 2012 | DOI: 10.1002/ijc.27941

      What's new?

      Mouse models are an important tool for studying the molecular mechanisms that lead to cancer in humans. However, it is still a challenging task to determine whether murine models truly correlate to human disease. In this study, the authors used bioinformatics to compare the differential expression of specific transcription factors (TFs) in WAP-T mouse and human breast tumors. The patterns of TF expression were indeed similar, suggesting a parallel evolution of different tumor phenotypes from distinct subsets of progenitors. These results underscore the importance of TFs as common cross-species denominators in the regulatory networks underlying mammary carcinogenesis.

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      Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response (pages 1323–1332)

      Louise Ming, Niall M. Byrne, Sarah Nicole Camac, Christopher A. Mitchell, Claire Ward, David J. Waugh, Stephanie R. McKeown and Jenny Worthington

      Version of Record online: 23 NOV 2012 | DOI: 10.1002/ijc.27796

      What's new?

      Standard androgen-deprivation therapy (ADT) can induce profound and persistent hypoxia within prostate-cancer tumors. Unfortunately, hypoxia can actually result in more aggressive tumors in many types of cancer. In this study, the authors found that combined treatment with ADT and the drug AQ4N (banoxantrone) improves primary tumor control and reduces metastatic spread in a mouse xenograft model of prostate cancer. (In hypoxic conditions AQ4N is reduced to AQ4, a highly cytotoxic compound.) These results provide proof of principle for targeting hypoxic cells in the treatment of prostate cancer.

  5. Cancer Genetics

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Loss of pSer2448-mTOR expression is linked to adverse prognosis and tumor progression in ERG-fusion-positive cancers (pages 1333–1340)

      Julia Müller, Arne Ehlers, Lia Burkhardt, Hüseyin Sirma, Thomas Steuber, Markus Graefen, Guido Sauter, Sarah Minner, Ronald Simon, Thorsten Schlomm and Uwe Michl

      Version of Record online: 30 AUG 2012 | DOI: 10.1002/ijc.27768

      What's new?

      While the phosphorylation of mammalian target of rapamycin (mTOR) has been implicated in prostate cancer, its clinical significance is largely unknown. Here, loss of phosphorylation of mTOR at serine 2448 was linked to adverse features of prostate cancer, including deletion of phosphatase and tensin homolog (PTEN), which occurs in 20-70 percent of cases. The data suggest that pSer2448-mTOR expression could be used to identify patients who would benefit from anti-mTOR-based therapies.

  6. Tumor Immunology

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer (pages 1341–1350)

      Yung-Chang Lin, Jayashri Mahalingam, Jy-Ming Chiang, Po-Jung Su, Yu-Yi Chu, Hsin-Yi Lai, Jian-He Fang, Ching-Tai Huang, Cheng-Tang Chiu and Chun-Yen Lin

      Version of Record online: 18 SEP 2012 | DOI: 10.1002/ijc.27784

      What's new?

      Activated T regulatory (Treg) cells suppress the immune response, and can interfere with immunological attacks on cancer cells. This study examined levels of Treg cells in human colorectal cancer, and found that cancer tissue and peripheral blood contained more activated Treg cells than healthy tissue. Also, the presence of activated Treg cells correlated with tumor metastases, suggesting these cells might be an important key to improving immune therapeutic strategies.

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      Impact of chemotherapeutic agents on the immunostimulatory properties of human 6-sulfo LacNAc+ (slan) dendritic cells (pages 1351–1359)

      Rebekka Wehner, Anna Bitterlich, Nicole Meyer, Anja Kloß, Knut Schäkel, Michael Bachmann and Marc Schmitz

      Version of Record online: 16 NOV 2012 | DOI: 10.1002/ijc.27786

      What's new?

      Evidence suggests that immune cells can contribute to the outcome of chemotherapy. In addition, it has been shown that some anti-tumor drugs affect the activity of immune cells such as dendritic cells (DCs), which play a crucial role in the immune response against tumors. In this study, the authors found that doxorubicin and vinblastine impair the immune-stimulating activity of a subclass of human DCs, while methotrexate, mitomycin C, and paclitaxel had no effect. These results may have implications for the design of treatment modalities for tumor patients that combine immunotherapeutic strategies and chemotherapy.

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      NY-ESO-1 antigen-reactive T cell receptors exhibit diverse therapeutic capability (pages 1360–1367)

      Daniel Sommermeyer, Heinke Conrad, Holger Krönig, Haike Gelfort, Helga Bernhard and Wolfgang Uckert

      Version of Record online: 14 SEP 2012 | DOI: 10.1002/ijc.27792

      What's new?

      The cancer-testis antigen NY-ESO-1 is expressed on many solid and hematological cancers but rarely in normal tissues and if so, in immune-privileged germ cells. To test its therapeutic potential as a target for immunotherapies, the authors characterized three different NY-ESO-1-specific T cell receptors, which were isolated from T cell clones generated by autologous and allogeneic approaches. They find considerable differences in TCR behavior towards MHC-associated NY-ESO-1 peptides, underscoring that multiple functional parameters of TCR-transgenic T cells have to be thoroughly characterized prior to clinical application of NY-ESO-1 directed immunotherapies.

  7. Early Detection and Diagnosis

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Novel prognostic protein markers of resectable pancreatic cancer identified by coupled shotgun and targeted proteomics using formalin-fixed paraffin-embedded tissues (pages 1368–1382)

      Tatsuyuki Takadate, Tohru Onogawa, Tetsuya Fukuda, Fuyuhiko Motoi, Takashi Suzuki, Kiyonaga Fujii, Makoto Kihara, Sayaka Mikami, Yasuhiko Bando, Shimpei Maeda, Kazuyuki Ishida, Takashi Minowa, Nobutaka Hanagata, Hideo Ohtsuka, Yu Katayose, Shinichi Egawa, Toshihide Nishimura and Michiaki Unno

      Version of Record online: 14 SEP 2012 | DOI: 10.1002/ijc.27797

      What's new?

      While the search for biomarkers for particular cancers has often focused on mRNA, protein profiles may actually be more accurate. In addition, mRNA levels can't detect the activation of key signaling molecules in protein networks. In this study of pancreatic cancer, the authors used a novel strategy combining “global shotgun proteomics” using mass spectrometry (MS), and targeted “selected reaction monitoring” (SRM). They found that patients whose tumors expressed the proteins ECH1, OLFM4, STML2 and GTR1 had significantly worse outcomes. These proteins may thus have prognostic significance, and may also suggest new therapeutic targets.

  8. Epidemiology

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark (pages 1383–1388)

      Luise Winkel Idorn, Elisabeth Thieden, Peter Alshede Philipsen and Hans Christian Wulf

      Version of Record online: 6 AUG 2012 | DOI: 10.1002/ijc.27734

      What's new?

      The positive association of socioeconomic status (SES) with cutaneous malignant melanoma (CMM) is intriguing but poorly understood. Here, using home gardens as an indicator of high SES, dosimetry data and sun exposure diaries revealed that Danish people who have home gardens expose themselves to the sun more frequently. Additionally, data from Danish registers showed that those with a home garden are at increased risk of CMM of the trunk and extremities. The findings suggest that SES influences recreational sun behavior and skin cancer risk, in part by providing easier access to sunny areas.

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      Intake of trans fatty acids from partially hydrogenated vegetable and fish oils and ruminant fat in relation to cancer risk (pages 1389–1403)

      Ida Laake, Monica H. Carlsen, Jan I. Pedersen, Elisabete Weiderpass, Randi Selmer, Bente Kirkhus, Inger Thune and Marit B. Veierød

      Version of Record online: 12 AUG 2012 | DOI: 10.1002/ijc.27737

      What's new?

      The unfavorable effects of trans fatty acids (TFAs) on cardiovascular disease risk factors have been studied extensively, but whether these substances also influence risk factors related to other diseases, particularly cancer, is poorly understood. Here, intake of TFA from partially hydrogenated fish oils, but not from partially hydrogenated vegetable oils, was associated with increased cancer risk. While the carcinogenic mechanism is unclear, the results support the idea that different sources of TFA have distinct affects on cancer risk.

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      Italian mediterranean index and risk of colorectal cancer in the Italian section of the EPIC cohort (pages 1404–1411)

      Claudia Agnoli, Sara Grioni, Sabina Sieri, Domenico Palli, Giovanna Masala, Carlotta Sacerdote, Paolo Vineis, Rosario Tumino, Maria Concetta Giurdanella, Valeria Pala, Franco Berrino, Amalia Mattiello, Salvatore Panico and Vittorio Krogh

      Version of Record online: 7 AUG 2012 | DOI: 10.1002/ijc.27740

      What's new?

      The Mediterranean diet has been associated with beneficial effects on cancer risk. Here, in the first prospective study to assess the relationship between Mediterranean diet and colorectal cancer risk in a European country, high adherence to the diet was found to protect against the disease, with the exception of proximal colon cancer. The findings reveal that a diet high in fruits, vegetables, and pulses, which are rich in dietary fiber, may reduce colorectal cancer risk.

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      Elevated methylation of HPV16 DNA is associated with the development of high grade cervical intraepithelial neoplasia (pages 1412–1422)

      Lisa Mirabello, Mark Schiffman, Arpita Ghosh, Ana C. Rodriguez, Natasa Vasiljevic, Nicolas Wentzensen, Rolando Herrero, Allan Hildesheim, Sholom Wacholder, Dorota Scibior-Bentkowska, Robert D. Burk and Attila T. Lorincz

      Version of Record online: 20 AUG 2012 | DOI: 10.1002/ijc.27750

      What's new?

      Although most cervical cancers are caused by human papillomavirus type 16 (HPV16), infection with HPV16 generally doesn't lead to cancer. Biomarkers that could help clinicians distinguish between HPV infections that will clear spontaneously, and those that will progress to cervical precancer, would thus be very useful. In this study, the authors found that DNA methylation of particular CpG sites in the HPV16 genome may provide a valuable diagnostic biomarker for precancerous cervical lesions. It may also provide a reasonable predictive marker for infections that are likely to lead to such lesions in the future.

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      Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia (pages 1423–1428)

      Nicholas de Klerk, Helman Alfonso, Nola Olsen, Alison Reid, Jan Sleith, Lyle Palmer, Geoffrey Berry and AW (Bill) Musk

      Version of Record online: 16 AUG 2012 | DOI: 10.1002/ijc.27758

      What's new?

      Familial clustering has long been observed in cases of malignant mesothelioma but it was difficult to separate increased exposure of families to asbestos at home from genetic factors. The Wittenoom cohorts in Australia are unique because they provide thorough estimates of asbestos exposure levels for families of workers, allowing a realistic differentiation between genetic and environmental risks. The authors find a 1.9-fold increase in risk for blood relatives, consistent with a small but potentially important genetic component to mesothelioma.

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      Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008—A Swedish population-based study (pages 1429–1438)

      Britta Krynitz, Gustaf Edgren, Bernt Lindelöf, Eva Baecklund, Christina Brattström, Henryk Wilczek and Karin E. Smedby

      Version of Record online: 28 AUG 2012 | DOI: 10.1002/ijc.27765

      What's new?

      After an organ transplant, the immune system must be permanently suppressed, to allow the foreign organ to survive in the body. With the immune system stifled, viruses that cause cancer have a much easier time of it, and transplant recipients are known to have increased cancer risk. The present study examined more than 10,000 organ transplant recipients over a 20-year period to determine their risk of various cancers, including skin cancer, which had not been included in previous studies. They found that the risk of squamous cell carcinoma shot up 100-fold overall, while the risk of other cancers doubled. These detailed estimates of risk over time will greatly assist doctors working with these transplant patients.

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      Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk (pages 1439–1450)

      Beatrice A. Boucher, Michelle Cotterchio, Laura N. Anderson, Nancy Kreiger, Victoria A. Kirsh and Lilian U. Thompson

      Version of Record online: 18 SEP 2012 | DOI: 10.1002/ijc.27769

      What's new?

      Our study is the first to evaluate breast cancer risk and the use of several botanical supplements identified by isoflavone content, as well as differences by menopausal and tumor hormone receptor status. We also uniquely examined multiple variables relevant to daily and long-term isoflavone exposure through supplements. Findings suggest that isoflavone supplements are associated with reduced postmenopausal breast cancer risk, and contribute to an important debate around risk associations of isoflavone supplements versus foods.

  9. Cancer Therapy

    1. Top of page
    2. Editorial
    3. Special Section Papers
    4. Carcinogenesis
    5. Cancer Cell Biology
    6. Cancer Genetics
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
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      Telomerase-specific oncolytic adenoviral therapy for orthotopic hepatocellular carcinoma in HBx transgenic mice (pages 1451–1462)

      Wei-Hsiang Lin, Shiou-Hwei Yeh, Wan-Jen Yang, Kun-Huei Yeh, Toshiyoshi Fujiwara, Aisuke Nii, Stanley Shi-Chung Chang and Pei-Jer Chen

      Version of Record online: 23 NOV 2012 | DOI: 10.1002/ijc.27770

      What's new?

      More than 95 percent of hepatocellular carcinomas (HCCs) are associated with telomerase reverse transcriptase (hTERT) activation, which promotes cell immortality. In this study, the adenovirus Telomelysin demonstrated specific oncolytic activity in HCC cells with elevated hTERT. In addition, in mice with orthotopically growing HCC xenografts, the adenovirus slowed tumor growth, despite the generation of an immune response. The results suggest that Telomelysin may be useful in the treatment of HCC.

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      A novel role for junctional adhesion molecule-A in tumor proliferation: Modulation by an anti-JAM-A monoclonal antibody (pages 1463–1474)

      Liliane Goetsch, Jean-François Haeuw, Charlotte Beau-Larvor, Alexandra Gonzalez, Laurence Zanna, Martine Malissard, Anne-Marie Lepecquet, Alain Robert, Christian Bailly, Matthieu Broussas and Nathalie Corvaia

      Version of Record online: 13 DEC 2012 | DOI: 10.1002/ijc.27772

      What's new?

      Discovering novel therapeutic targets is a crucial challenge in oncology research. In this study, the authors used a functional approach, seeking monoclonal antibodies that could inhibit cancer-cell proliferation. They injected whole cancer cells into mice, screened the resulting monoclonals in vitro, then used proteomic analysis to identify the target antigens. A monoclonal antibody against the tight-junction protein JAM-A was able to slow the growth of xenograft human tumours in mice. This approach may aid the search for new antibody-based therapies against various cancers.

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      Role and pharmacologic significance of cytochrome P-450 2D6 in oxidative metabolism of toremifene and tamoxifen (pages 1475–1485)

      Juhyun Kim, Christopher C. Coss, Christina M. Barrett, Michael L. Mohler, Casey E. Bohl, Chien-Ming Li, Yali He, Karen A. Veverka and James T. Dalton

      Version of Record online: 14 SEP 2012 | DOI: 10.1002/ijc.27794

      What's new?

      Toremifene and tamoxifen are widely used in the treatment of metastatic breast cancer, but the potential effect on their pharmacologic activity of genetic variations in the enzymes responsible for their metabolism is not fully understood. In this study, variations in activity of the enzyme CYP2D6 were associated with significant differences in the metabolism of tamoxifen, but not toremifene. The variations may alter plasma concentrations of active tamoxifen metabolites, leading to unexpected toxicities and drug-drug interactions.

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