International Journal of Cancer

Cover image for Vol. 134 Issue 4

15 February 2014

Volume 134, Issue 4

Pages 747–1012, E1–E2

  1. Mini Reviews

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
  2. Cancer Cell Biology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer (pages 755–764)

      Carolina Bizama, Felipe Benavente, Edgardo Salvatierra, Ana Gutiérrez-Moraga, Jaime A. Espinoza, Elmer A. Fernández, Iván Roa, Guillermo Mazzolini, Eduardo A. Sagredo, Manuel Gidekel and Osvaldo L. Podhajcer

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28405

      What's new?

      The present study aimed to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analysis of the low-abundance transcriptome. Aberrant cancer-specific intracellular pathways such as the wnt/hedgehog and the PI3K and genes like CTBP1 were identified. Most of the differentially expressed low-abundance transcripts were not detected when the whole transcriptome was analyzed. CTBP1 was further identified as a novel target for sensitization of gastric cancer cells to chemotherapeutic drugs that have shown limited effectiveness in the clinics. The study of the low-abundance transcriptome might help to improve response to mainstay treatments and develop novel therapies.

    2. Expression of TLR9 in tumor-infiltrating mononuclear cells enhances angiogenesis and is associated with a worse survival in lung cancer (pages 765–777)

      Laure Belmont, Nathalie Rabbe, Martine Antoine, Dominique Cathelin, Christophe Guignabert, Jonathan Kurie, Jacques Cadranel and Marie Wislez

      Article first published online: 4 SEP 2013 | DOI: 10.1002/ijc.28413

      What's new?

      In the quest to bring the body's own immune defenses to bear against cancer, researchers have investigated the receptor TLR9, a toll-like receptor that initiates a cascade of immune responses. Although activating TLR9 provided a boost to chemotherapy in animal models, further trials showed no benefit over chemotherapy alone. The current study compared lung cancer in mice with and without TLR9 inactivation. The authors found that expressing TLR9 promoted angiogenesis and cancer progression, and reduced survival. Perhaps understanding how TLR9 boosts angiogenesis can help refine its development as an anti-cancer agent.

    3. Paracrine activation of hepatic stellate cells in platelet-derived growth factor C transgenic mice: Evidence for stromal induction of hepatocellular carcinoma (pages 778–788)

      Jocelyn H. Wright, Melissa M. Johnson, Masami Shimizu-Albergine, Renay L. Bauer, Brian J. Hayes, James Surapisitchat, Kelly L. Hudkins, Kimberly J. Riehle, Simon C. Johnson, Matthew M. Yeh, Theodor K. Bammler, Richard P. Beyer, Debra G. Gilbertson, Charles E. Alpers, Nelson Fausto and Jean S. Campbell

      Article first published online: 16 SEP 2013 | DOI: 10.1002/ijc.28421

      What's new?

      Hepatocellular carcinoma (HCC) is a deadly disease, with a small percentage of patients qualifying for liver resection or transplantation, the only potentially curative treatments. Improvements in treatment and prevention, however, may be possible through a better understanding of how cirrhosis predisposes individuals to HCC. This study implicates platelet derived growth factor-C (PDGF-C) as a possible driver of stromal changes that lead to epithelial neoplasia in the liver. In transgenic mice, hepatic PDGF-C expression altered the liver microenvironment, promoting carcinogenesis. The transgenic PDGF-C pre-clinical HCC model may be useful for testing novel therapies that target the hepatic tumor microenvironment.

    4. Gene expression profile of A549 cells from tissue of 4D model predicts poor prognosis in lung cancer patients (pages 789–798)

      Dhruva K. Mishra, Chad J. Creighton, Yiqun Zhang, Don L. Gibbons, Jonathan M. Kurie and Min P. Kim

      Article first published online: 3 SEP 2013 | DOI: 10.1002/ijc.28428

      What's new?

      This study aimed to investigate whether a previously-developed ex vivo lung cancer 4D model—which forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern—is a better mimic of the natural history of lung cancer growth in patients. The authors found that the 4D model leads to change in gene expression in the human lung cancer A549 cell line that correlates with poor survival in patients. Since patients with larger tumors have a worse rate of survival, the 4D model may be a good mimic of natural progression of tumor growth.

  3. Carcinogenesis

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. A novel role of the tumor suppressor GNMT in cellular defense against DNA damage (pages 799–810)

      Yi-Cheng Wang, Wei-Li Lin, Yan-Jun Lin, Feng-Yao Tang, Yi-Ming Chen and En-Pei Isabel Chiang

      Article first published online: 5 OCT 2013 | DOI: 10.1002/ijc.28420

      What's new

      Commonly absent in hepatocellular carcinoma is the liver protein glycine N-methyltransferase (GNMT), a proposed tumor suppressor. While GNMT and its role in preventing tumor formation have been studied extensively, this study reveals a hitherto unknown mechanism by which the protein may participate in tumor suppression. In knockout mice and engineered cell lines, GNMT deletion led to DNA damage in conditions of folate depletion. Furthermore, its overexpression not only improved cellular methylation kinetics but also enhanced DNA synthesis and repair, in both in vitro and in vivo model systems.

  4. Cancer Genetics

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. miR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene (pages 811–821)

      Chung-Ji Liu, Wilma Grace Shen, Shih-Yuan Peng, Hui-Wen Cheng, Shou-Yen Kao, Shu-Chun Lin and Kuo-Wei Chang

      Article first published online: 8 OCT 2013 | DOI: 10.1002/ijc.28358

      What's new?

      Head and neck squamous cell carcinoma (HNSCC) is a prevalent disease for which survival has not improved over the last decades. Here, the authors found that miR-134 was highly expressed in HNSCC tumor tissues. High miR-134 expression was associated with nodal metastasis and mortality in patients and acted as an independent predictor of poor survival. Mouse studies confirmed the role of miR-134 expression in tumorigenesis and cervical lymph node metastasis. miR-134 was found to target the WWOX tumor suppressor in HNSCC cells, suggesting that anti-miR-134 or WWOX induction strategies could serve as a potential intervention against HNSCC genesis or metastasis.

    2. Genetic variants in fas signaling pathway genes and risk of gastric cancer (pages 822–831)

      Paula L. Hyland, Shih-Wen Lin, Nan Hu, Han Zhang, Lemin Wang, Hua Su, Chaoyu Wang, Ti Ding, Ze-Zhong Tang, Jin-Hu Fan, You-Lin Qiao, Xiaoqin Xiong, William Wheeler, Carol Giffen, Kai Yu, Jeff Yuenger, Laurie Burdett, Zhaoming Wang, Stephen J. Chanock, Margaret A. Tucker, Sanford M. Dawsey, Neal D. Freedman, Alisa M. Goldstein, Christian C. Abnet and Philip R. Taylor

      Article first published online: 11 SEP 2013 | DOI: 10.1002/ijc.28415

      What's new?

      The bacteria H. pylori is known to cause gastric cancer, but genetic changes can also contribute, particularly in high-risk populations. Identifying these genetic changes in patients could help clinicians make more accurate prognosis of gastric cancer. These authors looked at variation in genes of the Fas signaling pathway, searching for a connection with GC in a high-risk Chinese population. They found that changes in ten specific genes contributed to GC risk in the population, suggesting further work to investigate the functions of those genes.

    3. Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B-cell-derived mantle cell lymphoma (pages 832–843)

      Stefanie Schneider, Barbara Crescenzi, Markus Schneider, Stefano Ascani, Sylvia Hartmann, Martin-Leo Hansmann, Brunangelo Falini, Cristina Mecucci, Enrico Tiacci and Ralf Küppers

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28422

      What's new?

      When two phenotypically distinct, yet genetically related lymphomas occur in one patient (composite lymphomas), this represents a unique opportunity to study the multistep transformation process in the pathogenesis of B cell lymphomas. Here, the authors present a case consisting of a Hodgkin and a mantle cell lymphoma. The two lymphomas were clonally related and carried the genetic translocation with the cyclin D1 gene translocated into the IGH locus, a characteristic for a mantle cell lymphoma. They further showed an identical TP53 function-impairing mutation, and later independently acquired a TP53 heterozygous deletion (convergent evolution). The authors see this close genetic relationship as evidence for subclonal evolution of a Hodgkin lymphoma from a mantle cell lymphoma.

  5. Infectious Causes of Cancer

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. Prospective study of Merkel cell polyomavirus and risk of Merkel cell carcinoma (pages 844–848)

      Helena Faust, Kristin Andersson, Johanna Ekström, Maria Hortlund, Trude Eid Robsahm and Joakim Dillner

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28419

      What's new?

      Although the DNA of Merkel cell polyomavirus (MCV) is regularly found in most Merkel cell carcinoma tumors, it is also common in healthy skin. The presence of MCV-specific antibodies is higher among Merkel cell carcinoma patients, but the prospective value of this finding has not been formally established. Here, the authors demonstrate that the risk of future Merkel cell carcinoma is increased among subjects with high levels of MCV antibodies, especially in females, thus supporting the model that MCV is etiologically linked to Merkel cell carcinoma.

  6. Tumor Immunology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. Loss of prolyl hydroxylase-2 in myeloid cells and T-lymphocytes impairs tumor development (pages 849–858)

      Soulafa Mamlouk, Joanna Kalucka, Rashim Pal Singh, Kristin Franke, Antje Muschter, Anika Langer, Christiane Jakob, Max Gassmann, Gustavo B. Baretton and Ben Wielockx

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28409

      What's new?

      Here the authors describe the complex role of the oxygen sensor PHD2 in tumor-associated immune cells in a conditional PHD2-deficient mouse line. They demonstrate that the observed reduced tumor volume is a consequence of opposing changes including the drastic down-regulation of numerous pro- as well as anti-tumoral genes and an imbalance between enhanced cell death and greater proliferation of tumor cells. They confined this complex phenotype to the crosstalk of PHD2-deficient myeloid cells and T-lymphocytes. The findings reveal a multifaceted role for PHD2 in hematopoietic lineages during tumor development and might have important implications for the development of tumor therapies.

    2. Therapeutic immunization and local low-dose tumor irradiation, a reinforcing combination (pages 859–872)

      Oana Draghiciu, Mateusz Walczak, Baukje Nynke Hoogeboom, Kees L.M.C. Franken, Kees J.M. Melief, Hans W. Nijman and Toos Daemen

      Article first published online: 4 SEP 2013 | DOI: 10.1002/ijc.28418

      What's new?

      Cancer immunotherapy often fails because of the immunosuppressive environment of the tumor and the lack of infiltration with antigen-specific T cells. This study demonstrates that low-dose tumor irradiation combined with a cancer vaccine can change the intratumoral immune balance in favor of antitumor immune activation. Therapeutic immununization of mice with a Semliki Forest virus-based vector expressing human papilloma virus E6/E7 oncoproteins resulted in an 85-fold increase in the ratio of antitumoral CD8+ T cells to immune suppressive myeloid-derived suppressor cells at the tumor site. This raises the hope that a combination regimen might be a promising strategy to enhance the success of therapeutic tumor vaccination.

    3. Glioma-derived galectin-1 regulates innate and adaptive antitumor immunity (pages 873–884)

      Tina Verschuere, Jaan Toelen, Wim Maes, Françoise Poirier, Louis Boon, Thomas Tousseyn, Thomas Mathivet, Holger Gerhardt, Veronique Mathieu, Robert Kiss, Florence Lefranc, Stefaan W. Van Gool and Steven De Vleeschouwer

      Article first published online: 4 SEP 2013 | DOI: 10.1002/ijc.28426

      What's new?

      Galectin-1 is a glycan-binding protein that plays a major role in the aggressiveness of glioblastomas (GBMs), via a number of different mechanisms. In different types of tumors, galectin-1 has been demonstrated to contribute to tumor-mediated immune evasion. Whether glioma-derived galectin-1 also contributes to glioma-mediated immune evasion is unknown, however. In this study, the authors found that glioma-derived galectin-1 plays an important role in the regulation of myeloid cell accumulation within the tumor microenvironment. They also found that silencing of galectin-1 could improve glioma-bearing mice survival. Intratumoral silencing of galectin-1 may therefore offer a promising adjuvant treatment modality for patients with high-grade glioma.

  7. Early Detection and Diagnosis

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. Structural and functional effects of metastases in rat brain determined by multimodal MRI (pages 885–896)

      Sébastien Serres, Christopher J. Martin, Manuel Sarmiento Soto, Claire Bristow, Emma R. O'Brien, John J. Connell, Alexandre A. Khrapitchev and Nicola R. Sibson

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28406

      What's new?

      Serres et al. have established a model of brain metastasis in the rat that enables serial in vivo MRI studies. They demonstrate differential signal changes across structural and vascular MRI modalities that are associated with either micrometastatic or advanced metastatic growth. The authors also demonstrate the sensitivity of fMRI to early metastatic growth. They propose, therefore, that the use of multimodal MRI may yield greater insight into the stage and progression of brain metastases than single modality MRI.

    2. Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: A follow-up study (pages 897–904)

      Alberto Pacchiarotti, Francesca Ferrari, Paola Bellardini, Francesco Chini, Guido Collina, Paolo Dalla Palma, Bruno Ghiringhello, Vincenzo Maccallini, Fabio Musolino, Giovanni Negri, Roberto Pisa, Ilaria Sabatucci and Paolo Giorgi Rossi

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28407

      What's new?

      Women with low-grade cervical intraepithelial neoplasia 1 (CIN1) detected by positive Pap smear but accompanied by negative colposcopic biopsy present unique challenges for follow-up, especially since CIN1 is known to often regress. The situation could be helped in part through the use of a biomarker for CIN1 progression, such as p16 overexpression. This study shows that p16 has low prognostic sensitivity for patients with CIN2+ (CIN2 or worse) but is associated with elevated risk for these advanced conditions. The data suggest that p16 overexpression may be useful in evaluating the intensity of follow-up needed after a negative colposcopy.

    3. Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method (pages 905–912)

      Ryota Otsubo, Masahiro Oikawa, Hiroshi Hirakawa, Kenichiro Shibata, Kuniko Abe, Tomayoshi Hayashi, Naoe Kinoshita, Kazuto Shigematsu, Toshiko Hatachi, Hiroshi Yano, Megumi Matsumoto, Katsunori Takagi, Tomoshi Tsuchiya, Koichi Tomoshige, Masahiro Nakashima, Hideki Taniguchi, Takeyuki Omagari, Noriaki Itoyanagi and Takeshi Nagayasu

      Article first published online: 16 SEP 2013 | DOI: 10.1002/ijc.28408

      What's new?

      Missed detection of metastases in sentinel lymph node biopsy for node-negative breast cancer, which is notoriously difficult to diagnose, may lead to additional surgeries. So, to improve detection rates, the authors of this study developed a technique known as the semi-dry dot-blot (SDB) method, which employs anti-pancytokeratin antibody to identify cancer cells in lymph node tissue. Clinical results reported here show that the SBD method is accurate at least 98 percent of the time for several malignancies. In nodenegative breast cancer, accuracy was a remarkable 96.6 percent. The short time required for the test could help speed diagnosis.

    4. Evaluation of the impact of a breast cancer awareness program in rural Ghana: A cross-sectional survey (pages 913–924)

      Marisa Mena, Beatrice Wiafe-Addai, Catherine Sauvaget, Ibrahim A. Ali, Seth A. Wiafe, François Dabis, Benjamin O. Anderson, Denis Malvy and Annie J. Sasco

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28412

      What's new?

      Breast cancer awareness programs can bring great benefits for women and the communities they live in. But just how cost-effective these programs are in low-and-middle-income countries, where breast cancer is an increasing public health concern and where outreach can be challenging, has been unclear. Fortunately, the message from this study, which centered on the Ashanti region of Ghana, is that breast cancer awareness programs are paying big dividends for women's knowledge, attitudes, and practice. Women who attended programs not only enjoyed higher knowledge scores than their non-participant counterparts, but also were more likely to perform breast self-examinations.

    5. You have free access to this content
      Presence of disseminated tumor cells in bone marrow correlates with tumor stage and nodal involvement in cervical cancer patients (pages 925–931)

      Tanja Fehm, Malgorzata Banys, Brigitte Rack, Bernadette Jäger, Andreas Hartkopf, Florin-Andrei Taran and Wolfgang Janni

      Article first published online: 14 SEP 2013 | DOI: 10.1002/ijc.28417

      What's new?

      The past decade has seen the rapid development of detection techniques for disseminated tumor cells (DTCs) in solid tumors. While DTCs detection in the bone marrow of breast cancer patients is associated with poor outcome, data on hematogenous tumor cell dissemination in cervical cancer are scarce. This is the largest study on the detection of DTCs in the bone marrow of patients with primary cervical carcinoma. The results show that dissemination into bone marrow is a common phenomenon in cervical cancer and correlates with higher tumor load, but lacks prognostic relevance. Alternative methods may be needed to establish prognostic potential.

  8. Epidemiology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. Epilepsy, anti-epileptic medication use and risk of cancer (pages 932–938)

      Jeanette Kaae, Lisbeth Carstensen, Jan Wohlfahrt, Mads Melbye and Heather Allison Boyd

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28396

      What's new?

      Do anti-epileptic medications increase the risk of cancer? The question has been debated for decades with no clear answer. In this study, the authors used a large Danish registry to tease out the contribution of medication use versus epilepsy alone to cancer rates. Their findings indicate that anti-epileptic medications may not be as strongly carcinogenic as has been feared, and suggest that some aspect of epilepsy itself—or perhaps an etiologic factor common to both epilepsy and cancer—is responsible for the previously observed association between these medications and increased cancer risk.

    2. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer (pages 939–947)

      David Mesher, Isis Dove-Edwin, Peter Sasieni, Hans Vasen, Inge Bernstein, Brigitte Royer-Pokora, Elke Holinski-Feder, Fiona Lalloo, D. Gareth Evans, Anna Forsberg, Annika Lindblom and Huw Thomas

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28397

      What's new?

      About 3-5 percent of colorectal cancer cases are associated with a highly penetrant dominant inherited syndrome. However, established guidelines for the surveillance of Familial Colorectal Cancer (FCC), in which the Polyposis syndromes and Lynch syndrome have been excluded, are lacking. This study suggests that FCC and late-onset FCC (LOFCC) patients should be managed with five-yearly colonoscopies between ages 30 and 40, with more intensive surveillance in individuals who develop multiple or high-risk adenomas. Little evidence was found to support intensive screening before age 30.

    3. Case–case comparison of smoking and alcohol risk associations with Epstein–Barr virus-positive gastric cancer (pages 948–953)

      M. Constanza Camargo, Chihaya Koriyama, Keitaro Matsuo, Woo-Ho Kim, Roberto Herrera-Goepfert, Linda M. Liao, the Eurgast-EPIC Group, Jun Yu, Gabriel Carrasquilla, Joseph J.Y. Sung, Isabel Alvarado-Cabrero, Jolanta Lissowska, Fernando Meneses-Gonzalez, Yashushi Yatabe, Ti Ding, Nan Hu, Philip R. Taylor, Douglas R. Morgan, Margaret L. Gulley, Javier Torres, Suminori Akiba and Charles S. Rabkin

      Article first published online: 28 AUG 2013 | DOI: 10.1002/ijc.28402

      What's new?

      Although the H.pylori bacteria is the primary cause of gastric cancer, in some cases the Epstein-Barr virus also appears to be involved. In this study, the authors compared smoking and alcohol use between patients with EBV-positive and EBV-negative gastric cancers. No association was found with alcohol use, but smokers were more likely to have EBV-positive cancer.

    4. Endometrial thickness and risk of breast and endometrial carcinomas in the prostate, lung, colorectal and ovarian cancer screening trial (pages 954–960)

      Ashley S. Felix, Joel L. Weissfeld, Ruth M. Pfeiffer, Francesmary Modugno, Amanda Black, Lyndon M. Hill, Jerry Martin, Anita S. Sit, Mark E. Sherman and Louise A. Brinton

      Article first published online: 28 AUG 2013 | DOI: 10.1002/ijc.28404

      What's new?

      Endometrial thickness is related to obesity and menopausal hormone use, factors associated with a higher incidence of breast and endometrial carcinomas. Given these associations, the authors of this study investigated whether endometrial thickness was independently associated with incident breast or endometrial carcinoma risk. In a cohort of 1,272 women, an endometrial thickness greater than five millimeters was associated with a two-fold increase in risk for breast carcinoma and a five-fold increase in risk for endometrial carcinoma.

    5. Smoking and smoking cessation in relation to the development of co-existing non-small cell lung cancer with chronic obstructive pulmonary disease (pages 961–970)

      Rihong Zhai, Xiaojin Yu, Yongyue Wei, Li Su and David C. Christiani

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28414

      What's new?

      Non-small cell lung cancer is often associated with co-existing chronic obstructive pulmonary disease. Smoking is a common risk factor for both diseases independently, but here the authors studied how smoking affects the risk to develop the combined disease. They show that ex-smokers and smokers have an ∼5–10-fold higher risk to develop the combined disease as compared to developing cancer alone. Smoking dosage was the most important risk factor for the combined disease, especially in women and among patients with a squamous cell carcinoma subtype, pointing to gender- and cancer subtype specific influences on the combined disease.

    6. Alcohol and smoking and subsequent risk of prostate cancer in Japanese men: The Japan Public Health Center-based prospective study (pages 971–978)

      Norie Sawada, Manami Inoue, Motoki Iwasaki, Shizuka Sasazuki, Taiki Yamaji, Taichi Shimazu and Shoichiro Tsugane

      Article first published online: 4 SEP 2013 | DOI: 10.1002/ijc.28423

      What's new?

      The impact of alcohol consumption or smoking on prostate-cancer risk has been unclear. Using a large, prospective study, the authors investigated the association between these activities and prostate cancer according to stage at diagnosis. They found that alcohol was associated with advanced disease. Both alcohol and smoking were also associated with advanced prostate cancers that were detected by subjective symptoms. These results suggest that abstinence from alcohol and prohibition of smoking might play an important role in the prevention of advanced prostate cancer.

    7. Measuring the health-related quality of life and sexual functioning of patients with rectal cancer: Does type of treatment matter? (pages 979–987)

      Marjan J. Traa, Ricardo G. Orsini, Brenda L. Den Oudsten, Jolanda De Vries, Jan A. Roukema, Sietske J. Bosman, Ralph L. Dudink and Harm J.T. Rutten

      Article first published online: 4 SEP 2013 | DOI: 10.1002/ijc.28430

      What's new?

      The battle against cancer is physically and mentally taxing for many patients and can lead to declines in quality of life. Here, health-related quality of life (HRQOL) data indicates that patients with locally recurrent rectal cancer (LRRC) score worse on Future Perspective and Physical, Social, and Sexual Function measures than healthy individuals and patients with non-advanced disease or locally advanced rectal cancer. Fewer than 50 percent of men and 35 percent of women with the disease were sexually active following operative clinical courses, and only a small number reported the use of aids to improve sexual function.

  9. Cancer Therapy

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha (pages 988–996)

      Rabab M. El Eit, Ahmad N. Iskandarani, Jessica L. Saliba, Mark N. Jabbour, Rami A. Mahfouz, Nizar M.A. Bitar, Hanadi R. El Ayoubi, Ghazi S. Zaatari, Francois-Xavier Mahon, Hugues B. De Thé, Ali A. Bazarbachi and Rihab R. Nasr

      Article first published online: 10 SEP 2013 | DOI: 10.1002/ijc.28427

      What's new?

      The tyrosine kinase inhibitor imatinib has become the standard therapy for Chronic Myeloid Leukemia (CML). However, imatinib is not curative since most patients who discontinue therapy relapse, indicating that leukemia initiating cells are resistant. Here the authors demonstrated that arsenic and interferon alpha (IFN) inhibited the clonogenic activity of human primary CML cells. In a murine CML model, arsenic/IFN sharply diminished transplantation of CML cells, pointing to exhaustion of CML initiating cells. These studies plea for clinical exploration of this combination, knowing that IFN and arsenic have both previously shown clinical activity in CML, alone or in combination with imatinib.

    2. STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in vitro and in vivo (pages 997–1007)

      Melanie Spitzner, Birte Roesler, Christian Bielfeld, Georg Emons, Jochen Gaedcke, Hendrik A. Wolff, Margret Rave-Fränk, Frank Kramer, Tim Beissbarth, Julia Kitz, Jürgen Wienands, B. Michael Ghadimi, Reinhard Ebner, Thomas Ried and Marian Grade

      Article first published online: 3 SEP 2013 | DOI: 10.1002/ijc.28429

      What's new?

      A considerable percentage of rectal cancers are resistant to preoperative chemoradiotherapy, which exposes patients to the potential side effects of both irradiation and chemotherapy without clear benefits. In this study, IL-6-stimulated expression levels of phosphorylated STAT3 were remarkably higher in chemoradiotherapy-resistant colorectal cancer cell lines. RNAi- and small molecule-mediated STAT3 inhibition sensitized to chemoradiotherapy in vitro in a dose-dependent manner, which led to a profound chemoradiotherapy-sensitization in a subcutaneous xenograft model. These results highlight a potential role of STAT3 in treatment resistance, and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to chemoradiotherapy.

  10. Short Reports

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. Exomic landscape of MED12 mutation-negative and -positive uterine leiomyomas (pages 1008–1012)

      Netta Mäkinen, Pia Vahteristo, Ralf Bützow, Jari Sjöberg and Lauri A. Aaltonen

      Article first published online: 29 AUG 2013 | DOI: 10.1002/ijc.28410

      What's new?

      Nearly 70 percent of women develop uterine leiomyomas, or fibroids, by age 50. While benign, these tumors are associated with a high incidence of conditions that adversely affect the pelvis and reproductive system. Despite their prevalence and morbidity, however, little is known about the mechanisms behind uterine leiomyoma formation. Whole exome sequencing of MED12 mutation-negative and mutation-positive uterine leiomyomas performed in this study reveals that these tumors do not carry recurrent mutations in genes other than MED12. The findings suggest that MED12 mutations alone may be sufficient for tumor development and shed light on benign tumorigenesis.

  11. Errata

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Carcinogenesis
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Errata
    1. You have free access to this content
      Erratum (page E1)

      Article first published online: 9 DEC 2013 | DOI: 10.1002/ijc.28459

      This article corrects:

      Reactivation of p53 mutants by p53 reactivation and induction of massive apoptosis in thyroid cancer cells

      Vol. 130, Issue 10, 2259–2270, Article first published online: 14 SEP 2011

    2. You have free access to this content
      Erratum (page E2)

      Article first published online: 9 DEC 2013 | DOI: 10.1002/ijc.28460

      This article corrects:

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