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International Journal of Cancer

Cover image for Vol. 135 Issue 2

15 July 2014

Volume 135, Issue 2

Pages 253–518, E1–E4

  1. Mini Review

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
    1. You have free access to this content
      The network of P-glycoprotein and microRNAs interactions (pages 253–263)

      Vanessa Lopes-Rodrigues, Hugo Seca, Diana Sousa, Emília Sousa, Raquel T. Lima and M. Helena Vasconcelos

      Version of Record online: 17 OCT 2013 | DOI: 10.1002/ijc.28500

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  2. Cancer Cell Biology

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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      Tumor-derived microparticles induce bone marrow-derived cell mobilization and tumor homing: A process regulated by osteopontin (pages 270–281)

      Ella Fremder, Michal Munster, Anat Aharon, Valeria Miller, Svetlana Gingis-Velitski, Tali Voloshin, Dror Alishekevitz, Rotem Bril, Stefan J. Scherer, David Loven, Benjamin Brenner and Yuval Shaked

      Version of Record online: 13 JAN 2014 | DOI: 10.1002/ijc.28678

      What's new?

      Cytotoxic drugs may actually increase angiogenesis, which could explain why tumor growth sometimes rebounds after chemotherapy. We know that proangiogenic bone-marrow-derived cells (BMDCs) are involved in this process, but how are they mobilized? In this study, the authors examined the role of tumor-derived microparticles (TMPs). They found that TMPs are altered following exposure of tumor cells to chemotherapy, which enables them to trigger proangiogenic BMDCs to rapidly mobilize and home to treated tumor sites. This effect is mediated in part by osteopontin.

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      Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17β-estradiol biosynthesis in endometrial carcinoma microenvironment (pages 282–294)

      Qi Che, Bin-Ya Liu, Yun Liao, Hui-Juan Zhang, Ting-Ting Yang, Yin-Yan He, Yu-Hong Xia, Wen Lu, Xiao-Ying He, Zheng Chen, Fang-Yuan Wang and Xiao-Ping Wan

      Version of Record online: 6 JAN 2014 | DOI: 10.1002/ijc.28679

      What's new?

      Aromatase expression and activity may contribute to malignancy and poor survival in endometrial carcinoma, but specific aromatase regulators in the endometrial tumor microenvironment are unknown. According to this study, an important aromatase regulator may be IL-6, owing to a positive feedback loop in which IL-6 is induced by estrogen in cancer cells and stimulates aromatase expression in intratumoral stromal cells, thereby promoting estrogen biosynthesis in situ. Inhibition of IL-6 with an anti-IL-6 receptor antibody attenuated both aromatase expression in stromal cells and estrogen concentration in coculture systems of cancer cells and stromal cells. The results were confirmed in an orthotopic endometrial carcinoma mouse model.

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      Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts (pages 295–307)

      Shinichiro Miyazaki, Hirotoshi Kikuchi, Ichirota Iino, Takashi Uehara, Tomohiko Setoguchi, Takeshi Fujita, Yoshihiro Hiramatsu, Manabu Ohta, Kinji Kamiya, Kyoko Kitagawa, Masatoshi Kitagawa, Satoshi Baba and Hiroyuki Konno

      Version of Record online: 6 JAN 2014 | DOI: 10.1002/ijc.28686

      What's new?

      Antibodies against vascular endothelial growth factor (VEGF) are used in the treatment of colorectal cancer, but tumors may become resistant to them. In this study, anti-VEGF antibodies were found to effectively suppress the growth of cecal tumors at day 14 in a colorectal cancer xenograft mouse model. At day 35, however, indications of drug resistance emerged. Intratumoral hypoxia induced by treatment played an important role in regulating multiple processes that accelerated the malignant potential of colon cancers. The data may explain the molecular mechanism behind the limited clinical effectiveness of anti-VEGF antibodies.

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      Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation (pages 308–318)

      Kanako Shinjo, Yoriko Yamashita, Eiko Yamamoto, Shinya Akatsuka, Nozomi Uno, Akihiro Kamiya, Kaoru Niimi, Yuka Sakaguchi, Tetsuro Nagasaka, Takashi Takahashi, Kiyosumi Shibata, Hiroaki Kajiyama, Fumitaka Kikkawa and Shinya Toyokuni

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/ijc.28692

      What's new?

      Ovarian cancer is the most lethal gynecologic malignancy, with clear celladenocarcinoma of the ovary (OCCA) having a particularly poor prognosis due to high chemoresistance. Chromobox homolog 7 (CBX7) is a polycomb group transcriptional repressor whose role in human cancer remains controversial. Here, the authors showed for the first time that CBX7 expression is related to worse prognosis in OCCA. Furthermore, knockdown of CBX7 in vitro induced apoptosis in OCCA cell lines, possibly via regulation of the TRAIL-pathway. The findings thus indicate CBX7 as a good prognostic marker, andthe TRAIL-pathway as a potential target for OCCA diagnosis and therapy.

  3. Cancer Genetics

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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      Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease (pages 319–334)

      Takashi Sato, Eri Arai, Takashi Kohno, Yoriko Takahashi, Sayaka Miyata, Koji Tsuta, Shun-ichi Watanabe, Kenzo Soejima, Tomoko Betsuyaku and Yae Kanai

      Version of Record online: 13 JAN 2014 | DOI: 10.1002/ijc.28684

      What's new?

      While genetic abnormalities are well studied in human cancers, epigenetic changes, especially in the early stages of carcinogenesis, remain largely unknown. Here, the authors perform a genome-wide analysis focusing on DNA methylation profiles in “normal” lung tissue adjacent to lung adenocarcinomas. Using single-CpG-resolution Infinium assays, they identify distinct DNA methylation profiles clustering with specific risk factors such as cigarette smoking, inflammation and chronic obstructive pulmonary disease. The authors speculate that these epigenetic profiles detected in the neighboring cells may influence the aggressiveness of tumors developing in individual patients and may thus help predict disease outcome.

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      Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai (pages 335–347)

      Roman Corral, Juan Pablo Lewinger, David Van Den Berg, Amit D. Joshi, Jian-Min Yuan, Manuela Gago-Dominguez, Victoria K. Cortessis, Malcolm C. Pike, David V. Conti, Duncan C. Thomas, Christopher K. Edlund, Yu-Tang Gao, Yong-Bing Xiang, Wei Zhang, Yu-Chen Su and Mariana C. Stern

      Version of Record online: 13 JAN 2014 | DOI: 10.1002/ijc.28693

      What's new?

      DNA repair plays a vital role in maintaining DNA integrity in bladder epithelial cells exposed to carcinogens from tobacco smoke. As a result, genetic variations in DNA repair genes could modify bladder cancer risk. Here, analysis of 28 genes that participate in four DNA repair pathways suggests that certain variants in base excision repair and nucleotide excision repair genes may contribute to bladder cancer formation specifically in Chinese populations. Gene-by-environment interaction analyses that included non-Hispanic whites and Chinese suggest that double strand breaks might be the most detrimental type of tobacco-induced DNA damage leading to bladder cancer.

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      MicroRNA expression profiles distinguish liposarcoma subtypes and implicate miR-145 and miR-451 as tumor suppressors (pages 348–361)

      Caroline M.M. Gits, Patricia F. van Kuijk, Moniek B.E. Jonkers, Antonius W.M. Boersma, Marcel Smid, Wilfred F. van Ijcken, Jean-Michel Coindre, Fréderic Chibon, Cornelis Verhoef, Ron H.J. Mathijssen, Michael A. den Bakker, Jaap Verweij, Stefan Sleijfer and Erik A.C. Wiemer

      Version of Record online: 16 JAN 2014 | DOI: 10.1002/ijc.28694

      What's new?

      Although rare, liposarcomas have a high mortality rate. These tumors fall into four categories, with different characteristics and prognosis. It's tremendously helpful when treating the disease to identify the tumor type, but that's still a laborious process. Could there be a simple molecular test? In this paper, the authors hoped miRNA might be the key. They tested microRNA expression and found that miRNA expression varied enough among subtypes to accurately identify a particular tumor. In addition, they showed that boosting the levels of certain underexpressed miRNAs in the tumor cells will slow tumor growth, suggesting a possible avenue for therapy.

  4. Tumor Immunology

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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      The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas (pages 362–370)

      Joanna Szkandera, Armin Gerger, Bernadette Liegl-Atzwanger, Gudrun Absenger, Michael Stotz, Joerg Friesenbichler, Slave Trajanoski, Tatjana Stojakovic, Katharina Eberhard, Andreas Leithner and Martin Pichler

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/ijc.28677

      What's new?

      With increasing evidence of the involvement of inflammation and coagulation in cancer progression and metastases, inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools. This study reports for the first time that the pre-operative lymphocyte/monocyte (L/M) ratio represents a novel independent prognostic factor for prediction of clinical outcome in soft tissue sarcoma (STS) patients. This easily determinable biomarker might be helpful in improving individual risk assessment and patient stratification. Furthermore, supplementing the Kattan nomogram–a well-established postoperative prognostic model that predicts sarcoma-specific death–with the L/M ratio improved the predictive ability of such prognostic tool.

  5. Early Detection and Diagnosis

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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      Improving the TNM classification: Findings from a 10-year continuous literature review (pages 371–378)

      Colleen Webber, Mary Gospodarowicz, Leslie H. Sobin, Christian Wittekind, Frederick L. Greene, Malcolm D. Mason, Carolyn Compton, James Brierley and Patti A Groome

      Version of Record online: 15 JAN 2014 | DOI: 10.1002/ijc.28683

      What's new?

      The Union for International Cancer Control's TNM classification undergoes periodic revisions to incorporate current knowledge of anatomic extent of disease and its relationship with patient management and prognosis. This article describes the results of an annual literature review process that was implemented in 2002 to inform revisions to the classification. Since that time, more than 770 articles have been reviewed, with the number of articles reviewed increasing over time, reflecting growing research interest in cancer staging and new developments in cancer diagnosis. The report suggests that the literature review process has enhanced recent changes to the TNM classification.

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      A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients (pages 379–390)

      Crescenzo D'Alterio, Antonio Avallone, Fabiana Tatangelo, Paolo Delrio, Biagio Pecori, Laura Cella, Alessia Pelella, Francesco Paolo D'Armiento, Chiara Carlomagno, Franco Bianco, Lucrezia Silvestro, Roberto Pacelli, Maria Napolitano, Rosario Vincenzo Iaffaioli and Stefania Scala

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/ijc.28689

      What's new?

      Approximately one-third of patients with locally advanced rectal cancer (LARC) develop distant metastases. To gain further insight into LARC biology, the authors of the present study evaluated the chemokine axis CXCR4-CXCL12-CXCR7 in poor-responder, neoadjuvant treated LARC patients. Axis expression was found to be an extremely powerful tool for the identification of patients with high risk of relapse, who are also ideal subjects for adjuvant therapy. CXCR4 and CXCR7 specifically were two of five variables that constituted the optimal multivariable predictive model for relapse free survival. Moreover, the CXCR4-CXCL12-CXCR7 axis is a suitable therapeutic target.

  6. Epidemiology

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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      Coffee and green tea consumption is associated with upper aerodigestive tract cancer in Japan (pages 391–400)

      Isao Oze, Keitaro Matsuo, Daisuke Kawakita, Satoyo Hosono, Hidemi Ito, Miki Watanabe, Shunzo Hatooka, Yasuhisa Hasegawa, Masayuki Shinoda, Kazuo Tajima and Hideo Tanaka

      Version of Record online: 17 DEC 2013 | DOI: 10.1002/ijc.28653

      What's new?

      Coffee and green tea are both thought to protect against cancer; both contain anti-carcinogenic compounds, including caffeine and antioxidants. However, both drinks are generally consumed hot, and damage caused by hot drinks may contribute to esophageal cancer. In this study, the authors investigated the link between coffee and tea consumption and aerodigestive tract cancers. They found that people who drank 3 or more cups of coffee per day were less likely to develop upper aerodigestive tract cancers, while those who drank green tea had a higher risk.

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      Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk—Results from the EPIC cohort study (pages 401–412)

      Vincent K. Dik, H. B(as) Bueno-de-Mesquita, Martijn G.H. Van Oijen, Peter D. Siersema, Cuno S.P.M. Uiterwaal, Carla H. Van Gils, Fränzel J.B. Van Duijnhoven, Stéphane Cauchi, Loic Yengo, Philippe Froguel, Kim Overvad, Bodil H. Bech, Anne Tjønneland, Anja Olsen, Marie-Christine Boutron-Ruault, Antoine Racine, Guy Fagherazzi, Tilman Kühn, Daniele Campa, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Eleni Peppa, Eleni Oikonomou, Domenico Palli, Sara Grioni, Paolo Vineis, Rosaria Tumino, Salvatore Panico, Petra H.M. Peeters, Elisabete Weiderpass, Dagrun Engeset, Tonje Braaten, Miren Dorronsoro, María-Dolores Chirlaque, María-José Sánchez, Aurelio Barricarte, Raul Zamora-Ros, Marcial Argüelles, Karin Jirström, Peter Wallström, Lena M. Nilsson, Ingrid Ljuslinder, Ruth C. Travis, Kay-Tee Khaw, Nick Wareham, Heinz Freisling, Idlir Licaj, Mazda Jenab, Marc J. Gunter, Neil Murphy, Dora Romaguera-Bosch and Elio Riboli

      Version of Record online: 21 DEC 2013 | DOI: 10.1002/ijc.28655

      What's new?

      Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk.

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      Host characteristics, sun exposure, indoor tanning and risk of squamous cell carcinoma of the skin (pages 413–422)

      Marit B. Veierød, Elisabeth Couto, Eiliv Lund, Hans-Olov Adami and Elisabete Weiderpass

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/ijc.28657

      What's new?

      Indoor tanning devices are known to increase the risk of malignant melanoma, but their impact on the risk of squamous cell carcinoma (SCC) of the skin is unclear. In this large, population-based, prospective cohort study, the authors found that skin sensitivity to acute sun exposure was the most important host risk factor for SCC, and that the use of indoor tanning devices was indeed associated with an increased risk of SCC. They conclude that the use of indoor tanning devices should therefore be discouraged.

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      Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health Study cohort (pages 423–431)

      Hannah Arem, Steve C. Moore, Yikyung Park, Rachel Ballard-Barbash, Albert Hollenbeck, Michael Leitzmann and Charles E. Matthews

      Version of Record online: 18 DEC 2013 | DOI: 10.1002/ijc.28659

      What's new?

      Despite evidence that physical activity reduces risk of multiple chronic diseases, including cancer, as much as one-third of the U.S. population is inactive. In this study, the authors explored associations between pre-diagnosis physical activity and cancer mortality. They found that higher pre-diagnosis leisure-time physical activity is associated with a decreased risk of overall cancer mortality, and particularly mortality from cancers of the colon, liver, lung, and non-Hodgkin's lymphoma.

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      Trends in the incidence of cancer in Kampala, Uganda 1991–2010 (pages 432–439)

      Henry R. Wabinga, Sarah Nambooze, Phoebe Mary Amulen, Catherine Okello, Louise Mbus and Donald Maxwell Parkin

      Version of Record online: 27 FEB 2014 | DOI: 10.1002/ijc.28661

      What's new?

      Little information is available on trends in cancer incidence from sub-Saharan Africa. To help rectify that situation, the authors of the present study examined cancer incidence trends over a 20-year period in Kyadondo County, which includes Kampala, the capital of Uganda, using data from the Kampala Cancer Registry. Some trends were expected, such as an increase in cancers associated with Western lifestyles. Other trends, however, such as a lack of decline in cancers of the cervix, esophagus, and stomach, which are associated with poverty, were surprising. In addition, HIV-related cancers showed only modest or no recent decline.

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      Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort (pages 440–452)

      Xavier Castellsagué, Michael Pawlita, Esther Roura, Núria Margall, Tim Waterboer, F. Xavier Bosch, Silvia de Sanjosé, Carlos Alberto Gonzalez, Joakim Dillner, Inger T. Gram, Anne Tjønneland, Christian Munk, Valeria Pala, Domenico Palli, Kay-Tee Khaw, Ruanne V. Barnabas, Kim Overvad, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Rudolf Kaaks, Annekatrin Lukanova, Annika Steffen, Antonia Trichopoulou, Dimitrios Trichopoulos, Eleni Klinaki, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H. B(as) Bueno-de-Mesquita, Petra H. Peeters, Eiliv Lund, Elisabete Weiderpass, J. Ramón Quirós, María-José Sánchez, Carmen Navarro, Aurelio Barricarte, Nerea Larrañaga, Johanna Ekström, Maria Hortlund, David Lindquist, Nick Wareham, Ruth C. Travis, Sabina Rinaldi, Massimo Tommasino, Silvia Franceschi and Elio Riboli

      Version of Record online: 6 JAN 2014 | DOI: 10.1002/ijc.28665

      What's New?

      Limited data are available from prospective studies concerning the role of past exposure to human papillomavirus (HPV) and other infections in cervical carcinogenesis. This study assessed associations between cervical cancer and pre-cancer and serological markers of exposure to mucosal and cutaneous HPVs, Chlamydia trachomatis (CT), Chlamydia pneumonia, human herpes virus-2 (HHV-2), and polyomaviruses using a nested case-control design within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations were found for mucosal HPVs, CT, and HHV-2. A greater number of sexually transmitted diseases further raised the risk of cervical cancer.

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      Smoking as a major risk factor for cervical cancer and pre-cancer: Results from the EPIC cohort (pages 453–466)

      Esther Roura, Xavier Castellsagué, Michael Pawlita, Noémie Travier, Tim Waterboer, Núria Margall, F. Xavier Bosch, Silvia de Sanjosé, Joakim Dillner, Inger T. Gram, Anne Tjønneland, Christian Munk, Valeria Pala, Domenico Palli, Kay-Tee Khaw, Ruanne V. Barnabas, Kim Overvad, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Rudolf Kaaks, Annekatrin Lukanova, Annika Steffen, Antonia Trichopoulou, Dimitrios Trichopoulos, Eleni Klinaki, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, H. B(as) Bueno-de-Mesquita, Petra H. Peeters, Eiliv Lund, Elisabete Weiderpass, M. Luisa Redondo, María-José Sánchez, Maria-José Tormo, Aurelio Barricarte, Nerea Larrañaga, Johanna Ekström, Maria Hortlund, David Lindquist, Nick Wareham, Ruth C. Travis, Sabina Rinaldi, Massimo Tommasino, Silvia Franceschi and Elio Riboli

      Version of Record online: 6 JAN 2014 | DOI: 10.1002/ijc.28666

      What's new?

      Tobacco smoking is a cited cause of cervical cancer, but whether it causes cervical malignancy independent of human papillomavirus (HPV) infection is unclear. Here, strong associations were found between most measures of tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3/carcinoma in situ and invasive cervical cancer, after taking into account past exposure to HPV infection. Quitting smoking was associated with a 2-fold risk reduction. The findings confirm the role of tobacco smoking in cervical carcinogenesis and show that quitting the habit has important benefits for cancer protection.

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      pT4 stage II and III colon cancers carry the worst prognosis in a nationwide survival analysis. Shepherd's local peritoneal involvement revisited (pages 467–478)

      P. Snaebjornsson, V.M.H. Coupe, L. Jonasson, G.A. Meijer, N.C. van Grieken and J.G. Jonasson

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/ijc.28676

      What's new?

      Lymph node status is considered to be the single most important determinant of prognosis in colon cancer, supporting the standard four-tiered TNM and Dukes staging systems. This study indicates, however, that pT4, the most advanced category for local invasion, is equally as important as positive lymph nodes in determining colon cancer prognosis. The findings suggest that the survival impact of pT4a versus pT4b depends on how the categories are defined and that lymphatic invasion and poor differentiation are not useful as high-risk stage II variables.

  7. Cancer Therapy

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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      Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019 (pages 479–491)

      Donatella Vecchio, Antonio Daga, Elisa Carra, Daniela Marubbi, Gabriella Baio, Carlo E. Neumaier, Stefano Vagge, Renzo Corvò, Maria Pia Brisigotti, Jean Louis Ravetti, Annalisa Zunino, Alessandro Poggi, Samantha Mascelli, Alessandro Raso and Guido Frosina

      Version of Record online: 8 JAN 2014 | DOI: 10.1002/ijc.28680

      What's new?

      Glioblastoma multiforme is a highly infiltrative brain tumor resistant to radiation. Here, the authors report that inhibition of Ataxia Telangiectasia Mutated (ATM) protein, a key regulator of the DNA damage checkpoint response, improves the efficacy of ionizing radiation against radio-resistant glioblastoma-initiating cells, primary human cell lines isolated from grade IV gliomas. The response to the ATM inhibitor KU-60019 correlated with low expression levels of tumor protein p53 (wild type or mutant) and high expression levels of phosphatidylinositol 3-kinase and was tested after intracranial application in mice with orthotopic tumors. The study supports emerging evidence that KU-60019 may improve radiotherapy of high-grade gliomas.

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      Radiosensitization by combining an aurora kinase inhibitor with radiotherapy in hepatocellular carcinoma through cell cycle interruption (pages 492–501)

      Zhong-Zhe Lin, Chia-Hung Chou, Ann-Lii Cheng, Wei-Lin Liu and Jason Chia-Hsien Cheng

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/ijc.28682

      What's new?

      Inhibitors of Aurora kinases, key molecules in the maintenance of accurate cell cycling and genomic stability, have emerged as promising new antitumor agents. Here, the authors examined whether the pan-Aurora kinase inhibitor VE-465 sensitizes hepatocellular carcinomas (HCC) to radiation. Radiation is often suboptimal in HCC and increases the risk of metastasis. They show that combination of VE-465 with radiation results in synergistic inhibition of survival of HCC cell lines and the enhanced suppression of tumor growth in mice. These studies are promising but the authors caution that a careful analysis of malignant and neighboring nonmalignant tissue is required to conclusively evaluate the radiosensitizing effects of VE-465.

  8. Short Reports

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
    1. You have free access to this content
      Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy (pages 502–507)

      Heinz H. Schmeiser, Joëlle L. Nortier, Rajinder Singh, Gonçalo Gamboa da Costa, Jacques Sennesael, Elisabeth Cassuto-Viguier, Damien Ambrosetti, Sandrine Rorive, Agnieszka Pozdzik, David H. Phillips, Marie Stiborova and Volker M. Arlt

      Version of Record online: 14 JAN 2014 | DOI: 10.1002/ijc.28681

      What's new?

      Aristolochic acid (AA), present in Aristolochia-derived herbal drugs frequently used in traditional Chinese medicine, can cause aristolochic acid nephropathy and urothelial cancer. The true extent of AA exposure is unknown as reliable biomarkers are missing. This study demonstrates that premutagenic AA-DNA adducts, specifically 7-(deoxyadenosin-N6-yl)-aristolactam I adducts, have an exceptionally long-term persistence in the renal DNA of aristolochic acid nephropathy patients and thus can serve as biomarkers to assess exposure to AA, even decades later.

  9. Reviewers List

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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  10. Errata

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    10. Reviewers List
    11. Errata
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    2. You have free access to this content
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