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International Journal of Cancer

Cover image for Vol. 132 Issue 3

1 February 2013

Volume 132, Issue 3

Pages 501–743, E85–E157

  1. Mini Reviews

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

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Nuclear EGFRvIII-STAT5b complex contributes to glioblastoma cell survival by direct activation of the Bcl-XL promoter (pages 509–520)

      Khatri Latha, Ming Li, Vaibhav Chumbalkar, Anupama Gururaj, YeoHyeon Hwang, Sumana Dakeng, Raymond Sawaya, Kenneth Aldape, Webster K. Cavenee, Oliver Bogler and Frank B. Furnari

      Article first published online: 9 JUL 2012 | DOI: 10.1002/ijc.27690

      What's new?

      EGFRvIII (ΔEGFR), characterized by deletion of exons 2-7 in the epidermal growth factor receptor transcript, occurs in more than 25 percent of glioblastomas and is associated with enhanced tumor growth and survival. In this study, EGFRvIII was found to interact with the transcription factor STAT5b, forming a nuclear complex that promoted oncogenesis and treatment resistance in glioblastoma through direct regulation of the anti-apoptotic gene Bcl-XL. These findings may have important implications for the treatment of glioblastoma.

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      α-Catulin downregulates E-cadherin and promotes melanoma progression and invasion (pages 521–530)

      Birgit Kreiseder, Lukas Orel, Constantin Bujnow, Stefan Buschek, Maren Pflueger, Wolfgang Schuett, Harald Hundsberger, Rainer de Martin and Christoph Wiesner

      Article first published online: 14 JUL 2012 | DOI: 10.1002/ijc.27698

      What's new?

      The authors showed for the first time that alpha-catulin is highly expressed in melanoma cells. alpha-catulin knockdown altered the expression of E-cadherin and other genes known to be implicated in melanoma progression. Furthermore, knockdown of alpha-catulin promoted both binding of melanoma cells to keratinocytes and spheroid formation by enhanced E-cadherin expression. The authors also found that alpha-catulin provoked invasion of melanoma cells in a 3D culture assay by up-regulation of the matrix metalloproteinases 2 and 9 and activation of Rho. alpha-catulin may thus represent a key driver of the metastatic process in human melanoma, implicating potential for therapeutic interference.

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      Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer (pages 531–539)

      Päivi Auvinen, Raija Tammi, Veli-Matti Kosma, Reijo Sironen, Ylermi Soini, Arto Mannermaa, Ritva Tumelius, Eliisa Uljas and Markku Tammi

      Article first published online: 20 JUL 2012 | DOI: 10.1002/ijc.27707

      What's new?

      Elevated levels of HER2 occur in more than one-fifth of breast cancers and in vitro appear to result from interactions between the transmembrane receptor CD44 and hyaluronan, a component of the extracellular matrix. New data on these interactions reveals an association between increased hyaluronan and HER2-positivity, characterized in part by intense stromal hyaluronan staining related to obesity and disease relapse. The data suggest that hyaluronan and CD44, which was also linked to relapse, may be of clinical significance in determining breast cancer prognosis.

  3. Cancer Genetics

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Gene expression changes in initiation and progression of oral squamous cell carcinomas revealed by laser microdissection and oligonucleotide microarray analysis (pages 540–548)

      Jun Sumino, Narikazu Uzawa, Norihiko Okada, Ken Miyaguchi, Kaoru Mogushi, Ken-Ichiro Takahashi, Hiroaki Sato, Chieko Michikawa, Yoshimi Nakata, Hiroshi Tanaka and Teruo Amagasa

      Article first published online: 20 JUL 2012 | DOI: 10.1002/ijc.27702

      What's new?

      Oral epithelial dysplasia is a potentially precancerous lesion diagnosed histopathologically. More accurate markers predicting progression to invasive cancer are needed to enable better diagnosis of such lesions and more appropriate selection of aggressive treatment and closer follow-up. This is the first study to demonstrate gene expression changes during oral carcinogenesis using normal epithelial, premalignant, and carcinoma cells from the same oral cancer. The study also examined ISG15 expression at both mRNA and protein level in oral pre-malignant lesions and invasive cancers, demonstrating the association between ISG15 expression status and clinicopathological factors and patients survival.

  4. Infectious Causes of Cancer

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Persistence of newly detected human papillomavirus type 31 infection, stratified by variant lineage (pages 549–555)

      Long Fu Xi, Mark Schiffman, Laura A. Koutsky, Zhonghu He, Rachel L. Winer, Ayaka Hulbert, Shu-Kuang Lee, Yang Ke and Nancy B. Kiviat

      Article first published online: 11 JUL 2012 | DOI: 10.1002/ijc.27689

      What's new?

      HPV31 exists in three different variants, known as group A, B, and C. These variants occur with different frequencies among the different races, and correlate differently with cervical cancer. The authors investigated whether the variants persisted differently depending on the patient's race. They followed the course of HPV31 infection in newly diagnosed women, and found that infections with B variants were most likely to clear up. The A and C variants were equally likely to clear up in Caucasian women, but in African-Americans, the C variant was more persistent.

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      The Rec protein of HERV-K(HML-2) upregulates androgen receptor activity by binding to the human small glutamine-rich tetratricopeptide repeat protein (hSGT) (pages 556–567)

      Kirsten Hanke, Claudia Chudak, Reinhard Kurth and Norbert Bannert

      Article first published online: 14 JUL 2012 | DOI: 10.1002/ijc.27693

      What's new?

      Retroviruses can invade human DNA and cause tumors, and one such culprit is the HERV-K virus subfamily. While healthy cells suppress the retrovirus genes, tumor cells churn out the viral proteins, and attention has recently turned to the HERV-K Rec protein as a possible instigator. In this study, the authors describe a never-before-seen interaction between the HERV-K Rec protein and a cellular androgen receptor inhibitor. As Rec ties up this inhibitor, levels of androgen receptor predictably rise, but expression of other HERV-K genes increases also, suggesting a vicious cycle by which Rec might start the cell rolling toward uncontrolled proliferation and tumor formation.

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      Proteomic analysis of oropharyngeal carcinomas reveals novel HPV-associated biological pathways (pages 568–579)

      Robbert J.C. Slebos, Nico Jehmlich, Brandee Brown, Zhirong Yin, Christine H. Chung, Wendell G. Yarbrough and Daniel C. Liebler

      Article first published online: 20 JUL 2012 | DOI: 10.1002/ijc.27699

  5. Tumor Immunology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Intratracheal and oral administration of SM-276001: A selective TLR7 agonist, leads to antitumor efficacy in primary and metastatic models of cancer (pages 580–590)

      Erina Koga-Yamakawa, Simon J. Dovedi, Masashi Murata, Hiroyuki Matsui, Andrew J. Leishman, John Bell, Douglas Ferguson, Simon P. Heaton, Toshihiro Oki, Hideyuki Tomizawa, Ash Bahl, Haruo Takaku, Robert W. Wilkinson and Hideyuki Harada

      Article first published online: 11 JUL 2012 | DOI: 10.1002/ijc.27691

      What's new?

      Toll-like receptors (TLRs) are expressed on several types of immune cells. They serve to alert the immune system to infection, and stimulate a number of acute immune responses. TLRs are also being investigated for anti-tumour properties. The authors report that a compound called SM-276001 activates the immune system specifically via a TLR called TLR7, and is able to reduce carcinomas in mice. In addition, they found that either oral or tracheal administration of SM-276001 could reduce the frequency of metastasis in a mouse model of ovarian cancer. Thus, this type of compound might provide a valuable adjunct to surgery.

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      Inhibition of GTP cyclohydrolase attenuates tumor growth by reducing angiogenesis and M2-like polarization of tumor associated macrophages (pages 591–604)

      Geethanjali Pickert, Hee-Young Lim, Andreas Weigert, Annett Häussler, Thekla Myrczek, Maximilian Waldner, Sandra Labocha, Nerea Ferreirós, Gerd Geisslinger, Jörn Lötsch, Christoph Becker, Bernhard Brüne and Irmgard Tegeder

      Article first published online: 20 JUL 2012 | DOI: 10.1002/ijc.27706

  6. Early Detection and Diagnosis

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Identification of novel functional and spatial associations between sphingosine kinase 1, sphingosine 1-phosphate receptors and other signaling proteins that affect prognostic outcome in estrogen receptor-positive breast cancer (pages 605–616)

      Jan Ohotski, Joanne Edwards, Beatrix Elsberger, Carol Watson, Clare Orange, Elizabeth Mallon, Susan Pyne and Nigel J. Pyne

      Article first published online: 11 JUL 2012 | DOI: 10.1002/ijc.27692

      What's new?

      Sphingosine kinase-1 (SK1) and sphingosine 1-phosphate (S1P) have been implicated in promoting the survival, growth, and invasiveness of cancer cells. Immunohistochemical investigation of estrogen receptor-positive breast tumors and assessment of clinical outcome revealed that SK1 and S1P expression and subcellular localization, when analyzed in combination with other signaling proteins, yielded distinct associations with prognosis. These biomarker associations could serve an important role in new drug interventions for breast cancer.

  7. Epidemiology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Meat and fish consumption and risk of pancreatic cancer: Results from the European Prospective Investigation into Cancer and Nutrition (pages 617–624)

      Sabine Rohrmann, Jakob Linseisen, Ute Nöthlings, Kim Overvad, Rikke Egeberg, Anne Tjønneland, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Vanessa Cottet, Valeria Pala, Rosario Tumino, Domenico Palli, Salvatore Panico, Paolo Vineis, Heiner Boeing, Tobias Pischon, Verena Grote, Birigit Teucher, Kay-Tee Khaw, Nicholas J. Wareham, Francesca L. Crowe, Ioulia Goufa, Philippos Orfanos, Antonia Trichopoulou, Suzanne M. Jeurnink, Peter D. Siersema, Petra H.M. Peeters, Magritt Brustad, Dagrun Engeset, Guri Skeie, Eric J. Duell, Pilar Amiano, Aurelio Barricarte, Esther Molina-Montes, Laudina Rodríguez, María-José Tormo, Malin Sund, Weimin Ye, Björn Lindkvist, Dorthe Johansen, Pietro Ferrari, Mazda Jenab, Nadia Slimani, Heather Ward, Elio Riboli, Teresa Norat and H. Bas Bueno-de-Mesquita

      Article first published online: 7 JUN 2012 | DOI: 10.1002/ijc.27637

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      Body mass index and survival in patients with renal cell carcinoma: A clinical-based cohort and meta-analysis (pages 625–634)

      Yuni Choi, Bumsoo Park, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Han Yong Choi, Hans-Olov Adami, Jung Eun Lee and Hyun Moo Lee

      Article first published online: 20 JUN 2012 | DOI: 10.1002/ijc.27639

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      Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition (pages 635–644)

      Naomi E. Allen, Paul N. Appleby, Timothy J. Key, H.B. Bueno-de-Mesquita, Martine M. Ros, Lambertus A.L.M. Kiemeney, Anne Tjønneland, Nina Roswall, Kim Overvad, Steffen Weikert, Heiner Boeing, Jenny Chang-Claude, Birgit Teucher, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Domenico Palli, Sabina Sieri, Petra Peeters, Jose Ramón Quirós, Paula Jakszyn, Esther Molina-Montes, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Kay-Tee Khaw, Nick Wareham, Börje Ljungberg, Göran Hallmans, Roy Ehrnström, Ulrika Ericson, Inger Torhild Gram, Christine L. Parr, Antonia Trichopoulou, Tina Karapetyan, Vardis Dilis, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Guy Fagherrazzi, Isabelle Romieu, Marc J. Gunter and Elio Riboli

      Article first published online: 26 JUN 2012 | DOI: 10.1002/ijc.27643

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      Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort (pages 645–657)

      Sabrina Schlesinger, Krasimira Aleksandrova, Tobias Pischon, Veronika Fedirko, Mazda Jenab, Elisabeth Trepo, Paolo Boffetta, Christina C. Dahm, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Guy Fagherazzi, Marie-Christine Boutron-Ruault, Franck Carbonnel, Rudolf Kaaks, Annekatrin Lukanova, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Paolo Vineis, Bueno-de-Mesquita HB, Saskia van den Berg, Petra H.M. Peeters, Tonje Braaten, Elisabete Weiderpass, J. Ramón Quirós, Noémie Travier, María-José Sánchez, Carmen Navarro, Aurelio Barricarte, Miren Dorronsoro, Björn Lindkvist, Sara Regner, Mårten Werner, Malin Sund, Kay-Tee Khaw, Nicholas Wareham, Ruth C. Travis, Teresa Norat, Petra A. Wark, Elio Riboli and Ute Nöthlings

      Article first published online: 13 JUN 2012 | DOI: 10.1002/ijc.27645

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      Evaluation of data quality at the Gambia national cancer registry (pages 658–665)

      Yusuke Shimakawa, Ebrima Bah, Christopher P. Wild and Andrew J. Hall

      Article first published online: 13 JUN 2012 | DOI: 10.1002/ijc.27646

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      Dietary supplement use is not associated with recurrence of colorectal adenomas: A prospective cohort study (pages 666–675)

      Renate C. Heine-Bröring, Renate M. Winkels, Akke Botma, Peter J. Wahab, Adriaan C.I.T.L. Tan, Fokko M. Nagengast, Ben J.M. Witteman and Ellen Kampman

      Article first published online: 20 JUN 2012 | DOI: 10.1002/ijc.27647

      What's new?

      People take vitamins and other dietary supplements for many reasons, but could your supplements be harmful? Heine-Bröring et al. investigated the effects of dietary supplements on colorectal adenomas, to better advise those at risk.

      Colorectal cancer is one of the most common types of cancer in the Western world, and one red flag for clinicians is the presence of colorectal adenomas. Patients who develop these asymptomatic growths have an increased risk of colorectal cancer. As more and more people have begun taking multivitamin supplements, it is important to know how to advise patients with recurrent colorectal adenomas regarding dietary supplements.

      The researchers conducted a cohort study, including 203 dietary supplement users and 362 nonusers, and looked at the relative frequency of colorectal adenomas in each group. Their results showed that taking dietary supplements such as vitamin C, calcium, or multivitamins did not reduce or increase a person's risk of colorectal adenoma recurrence. Use of B-vitamin supplements, however, were associated with an increase in total recurrent colorectal adenomas, but not with recurrent adenomas that showed advanced pathology.

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      Comparability of stage data in cancer registries in six countries: Lessons from the International Cancer Benchmarking Partnership (pages 676–685)

      Sarah Walters, Camille Maringe, John Butler, James D. Brierley, Bernard Rachet and Michel P. Coleman

      Article first published online: 28 JUN 2012 | DOI: 10.1002/ijc.27651

      What's new?

      The way in which “stage at diagnosis” is recorded differs across the world. These variations make it difficult to conduct international comparisons of survival by stage at diagnosis using population-based data. In this study, the authors describe the differences in how cancer stage was recorded in registries from six high-income countries for four common cancers. They also present an approach that allows different staging systems to be reconciled for use in survival analysis and they offer seven recommendations for recording protocols to improve international comparisons of cancer outcomes.

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      Pre-diagnostic alcohol consumption and breast cancer recurrence and mortality: Results from a prospective cohort with a wide range of variation in alcohol intake (pages 686–694)

      Marianne Holm, Anja Olsen, Jane Christensen, Niels T. Kroman, Pernille E. Bidstrup, Christoffer Johansen, Kim Overvad and Anne Tjønneland

      Article first published online: 20 JUN 2012 | DOI: 10.1002/ijc.27652

      What's new?

      This is the first study to investigate both effect and dose-response relationships across a wide range of pre-diagnostic alcohol consumption levels on breast cancer specific outcome measures. The study contributes to the growing, although still limited and inconclusive, evidence of the association between alcohol consumption and breast cancer prognosis. It is therefore highly relevant to both professionals treating patients with breast cancer and those working in the field of breast cancer research.

  8. Cancer Therapy

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Oxidative inhibition of Hsp90 disrupts the super-chaperone complex and attenuates pancreatic adenocarcinoma in vitro and in vivo (pages 695–706)

      Sayantani Sarkar, Devawati Dutta, Suman Kumar Samanta, Kaushik Bhattacharya, Bikas Chandra Pal, Jinping Li, Kaustubh Datta, Chhabinath Mandal and Chitra Mandal

      Article first published online: 9 JUL 2012 | DOI: 10.1002/ijc.27687

      What's new?

      Pancreatic cancer is lethal and often shows resistance to conventional chemotherapy. New drugs and/or combinations of drugs are required for greater efficacy as well as to overcome the observed chemoresistance. Hsp90 is highly expressed in cancerous cells for their survival, making it a potential chemotherapy target. ROS is a critical mediator of apoptosis and can lead to Hsp90 dysfunction. Our data demonstrate the involvement of mahanine-induced ROS in Hsp90 dysfunction which leads to a subsequent disruption of the Hsp90-Cdc37 chaperone complex in pancreatic cancer.

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      Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis (pages 707–716)

      Winnie Lai Ting Kan, Chun Yin, Hong Xi Xu, Gang Xu, Kenneth Kin Wah To, Chi Hin Cho, John Anthony Rudd and Ge Lin

      Article first published online: 11 JUL 2012 | DOI: 10.1002/ijc.27694

      What's new?

      The lack of selectivity among anticancer drugs continues to be a significant barrier in cancer therapeutics. In the present study, guttiferone K, a novel derivative isolated from the tropical evergreen Garcinia cowa, was found to specifically restore the cyclin dependent kinase inhibitors p21Waf1/Cip1 and p27Kip1 and thereby induce G0/G1 cell cycle arrest and apoptosis in colon cancer cells. The findings suggest that guttiferone K is a promising potent and selective anti-tumor drug candidate for colon cancer.

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      A polymer coating applied to Salmonella prevents the binding of Salmonella-specific antibodies (pages 717–725)

      Che-Hsin Lee, Yu-Hsin Lin, Jeng-Long Hsieh, Man-Chin Chen and Wan-Lin Kuo

      Article first published online: 14 JUL 2012 | DOI: 10.1002/ijc.27700

      What's new?

      Salmonella bacteria could make a good tool for delivering anti-tumor treatments, if it can get past the body's immune defenses. The bacteria, which can replicate under anaerobic conditions, preferentially multiply in tumors, where they can bring down the cancer from within, but the process grinds to a halt when the body starts churning out antibodies to round up and eliminate the Salmonella. The authors figured out how to envelop the bacteria with a polymer coating and disguise it from antibodies lurking in the bloodstream, ready to destroy it. In mice, the shielded bacteria evaded immune response and still targeted the tumor, plus showing lower toxicity to the host, suggesting that polymer coated Salmonella could be a very promising avenue for treatment.

  9. Short Reports

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Oncolytic Vaccinia virus safely and effectively treats skin tumors in mouse models of xeroderma pigmentosum (pages 726–731)

      Jan Brun, Douglas J. Mahoney, Fabrice Le Boeuf, Charles Lefebvre, Cina A. Sanaei, Theresa Falls, J. Andrea Mccart and David F. Stojdl

      Article first published online: 28 SEP 2012 | DOI: 10.1002/ijc.27695

      What's new?

      Most of the attacks we use against cancer wind up hitting the host genome pretty hard, as well. In patients with xeroderma pigmentosa, the already-faltering DNA repair system can't cope with traditional genotoxic cancer therapies. In this study, the authors tested whether specially engineered poxviruses could target tumor cells without harming healthy ones. They showed that the virus, a Vaccinia variant, could safely and effectively destroy tumors derived from xeroderma pigmentosa, a development that could be a boon for victims of this rare and devastating condition.

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      Identification of novel driver tumor suppressors through functional interrogation of putative passenger mutations in colorectal cancer (pages 732–737)

      Lu Zhang, Kakajan Komurov, Woodring E. Wright and Jerry W. Shay

      Article first published online: 21 JUL 2012 | DOI: 10.1002/ijc.27705

      What's new?

      Although the field of cancer genomics has produced long lists of mutated genes from many types of cancer, researchers have assumed that most of these are “passenger” mutations that aren't directly involved in tumorigenesis. However, by using RNA interference to inactivate particular genes and mapping their interactions with known “driver” mutations (i.e. those that lead to malignant growth), the authors were able to uncover a number of potential tumor-suppressors among genes that had previously been dismissed. Combining functional assays with biological filters may lead to better predictive models and more potential therapeutic targets than bioinformatics alone.

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      Functional characterization of the novel BRAF complex mutation, BRAFV600delinsYM, identified in papillary thyroid carcinoma (pages 738–743)

      Michiko Matsuse, Norisato Mitsutake, Susumu Tanimura, Tomoo Ogi, Eijun Nishihara, Mitsuyoshi Hirokawa, Cesar S. Fuziwara, Vladimir A. Saenko, Keiji Suzuki, Akira Miyauchi and Shunichi Yamashita

      Article first published online: 21 JUL 2012 | DOI: 10.1002/ijc.27709

      What's new?

      Most papillary thyroid cancer results from mutation in the BRAF gene. Commonly, oncogenic mutations disrupt the inactive form of BRAF, causing it to become “on” all the time, activating the MAPK cascade when it shouldn't. The authors identified a new mutation in BRAF, and they show that this one also ramps up the protein's kinase activity, indiscriminately switching on the MAPK cascade. They also demonstrate that the new mutation transforms cells, suggesting that it could lead to papillary thyroid cancer formation.

  10. Cancer Cell Biology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma (pages E85–E93)

      Luc Bron, Camilla Jandus, Snezana Andrejevic-Blant, Daniel E. Speiser, Philippe Monnier, Pedro Romero and Jean-Paul Rivals

      Article first published online: 3 OCT 2012 | DOI: 10.1002/ijc.27728

      What's new?

      Many types of cancer cells produce cytokines and other molecules that suppress the antitumor immune response. In this study, the authors found that two factors were strongly correlated with an improved prognosis in head and neck squamouscell carcinomas (HNSCCs): the absence of Arginase-II (ARG2) expression by tumor cells, and infiltration of the tumor by regulatory FOXP31 T cells. These findings provide a rationale for therapies that reduce immunosuppression (such as silencing ARG2) in HNSCC. In addition, the authors found that tumor infiltration by FOXP31 T cells may provide a predictive factor for lymph node metastases.

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      Tumor-initiating properties of breast cancer and melanoma cells in vivo are not invariably reflected by spheroid formation in vitro, but can be increased by long-term culturing as adherent monolayers (pages E94–E105)

      Vanessa Kuch, Caroline Schreiber, Wilko Thiele, Viktor Umansky and Jonathan P. Sleeman

      Article first published online: 7 SEP 2012 | DOI: 10.1002/ijc.27785

      What's new?

      Cancer stem cells (CSCs) are regarded as key players in tumor initiation and maintenance but their identity and tumor-forming properties are hard to assess in vitro. The authors performed an extensive cross-comparison of commonly–used methods to define CSCs in laboratory assays. They find that the in vitro methods do not always reliably reflect tumor initiation properties in vivo, underscoring the importance of using multiple methods, in particular in vivo experiments, to demonstrate CSC behavior in a reliable manner.

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      Next-generation RNA sequencing reveals differential expression of MYCN target genes and suggests the mTOR pathway as a promising therapy target in MYCN-amplified neuroblastoma (pages E106–E115)

      Alexander Schramm, Johannes Köster, Tobias Marschall, Marcel Martin, Melanie Schwermer, Kathrin Fielitz, Gabriele Büchel, Matthias Barann, Daniela Esser, Philip Rosenstiel, Sven Rahmann, Angelika Eggert and Johannes H. Schulte

      Article first published online: 26 SEP 2012 | DOI: 10.1002/ijc.27787

      What's new?

      In neuroblastoma, amplification of the MYCN oncogene is associated with a poor prognosis. Now that next-generation sequencing technologies are becoming more affordable, it may soon be possible to identify the mutations underlying individual tumors, and to use that information to develop individualised treatment strategies. In this study, the authors used “RNA deep sequencing” to examine the MYCN-driven transcriptomes of a number of neuroblastomas. Their results suggest that mTOR inhibitors should be further evaluated for the treatment of MYCN-amplified neuroblastoma.

  11. Cancer Genetics

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
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      High-resolution genomic profiling reveals clonal evolution and competition in gastrointestinal marginal zone B-cell lymphoma and its large cell variant (pages E116–E127)

      Lucia Flossbach, Karlheinz Holzmann, Torsten Mattfeldt, Michaela Buck, Karin Lanz, Michael Held, Peter Möller and Thomas F.E. Barth

      Article first published online: 1 SEP 2012 | DOI: 10.1002/ijc.27774

      What's new?

      Evidence that certain small cell and large cell lymphomas have similar gene expression profiles has raised intriguing questions about the genetics of lymphoma. Here, profiling of genetic variations in gastrointestinal lymphomas revealed that large cell lymphomas may arise from small cell lymphomas, with composite cancers of clonally related small and large cells representing a transition state. The findings support the idea that gastrointestinal large cell lymphomas are a distinct subtype of diffuse large B-cell lymphoma.

    2. You have free access to this content
      Genetic polymorphisms in RNA binding proteins contribute to breast cancer survival (pages E128–E138)

      Rohit Upadhyay, Sandhya Sanduja, Vimala Kaza and Dan A. Dixon

      Article first published online: 18 SEP 2012 | DOI: 10.1002/ijc.27789

      What's new?

      RNA-binding proteins control important genes associated with breast cancer pathogenesis through post-transcriptional regulation. The authors identify a new single nucleotide polymorphism in the gene encoding for the mRNA decay factor TTP (ZFP36*2 A>G) that is significantly associated with poor prognosis in patients with breast cancer. This SNP functions to attenuate expression of TTP, allowing for increased expression of pro-inflammatory factors. These results point to ZFP36*2 as a genetic marker that may help identify breast cancer patients at high risk for poor disease outcome.

  12. Infectious Causes of Cancer

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
    1. You have free access to this content
      Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2 (pages E139–E148)

      Hanna Seitz, Markus Schmitt, Gerd Böhmer, Annette Kopp-Schneider and Martin Müller

      Article first published online: 3 OCT 2012 | DOI: 10.1002/ijc.27831

      What's new?

      The L2 capsid protein of human papillomavirus (HPV) contains a cross-neutralizing epitope that is a potential target for novel cervical cancer vaccines. However, while there is concern that natural epitope variants could escape vaccine-induced antibodies, the extent to which this may occur has been unclear. In this analysis, natural variants of different HPV types were isolated, and several of these facilitated antibody escape. Further investigation is needed to ensure the development of effective L2 epitope-targeted vaccines.

  13. Cancer Therapy

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
    11. Cancer Cell Biology
    12. Cancer Genetics
    13. Infectious Causes of Cancer
    14. Cancer Therapy
    1. You have free access to this content
      Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E inhibition (pages E149–E157)

      Patrick A. Mayes, Yan Y. Degenhardt, Andrew Wood, Yana Toporovskya, Sharon J. Diskin, Elizabeth Haglund, Christopher Moy, Richard Wooster and John M. Maris

      Article first published online: 28 SEP 2012 | DOI: 10.1002/ijc.27781

      What's new?

      One goal of current chemotherapy research is to discover drug combinations that have a synergistic effect against malignant tumors. In this study, the authors used a panel of siRNAs to search for compounds that sensitize tumor cells to the small-molecule drug GSK923295, which blocks CENP-E activity. They found that inhibitors of the MEK-ERK signaling pathway yielded potent synergistic activity against various types of cancer cells when combined with GSK923295. This type of combination regimen is therefore a promising therapeutic strategy. The results also revealed that RAS/RAF/MEK signaling can provide a predictive biomarker for sensitivity to GSK923295.

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