International Journal of Cancer

Cover image for Vol. 137 Issue 1

Early View (Online Version of Record published before inclusion in an issue)

Editor-in-Chief: Professor Peter Lichter, DKFZ, Germany

Impact Factor: 5.007

ISI Journal Citation Reports © Ranking: 2013: 34/203 (Oncology)

Online ISSN: 1097-0215


  1. 1 - 100
  2. 101 - 184
  1. Cancer Therapy

    1. ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors

      Ping Zhang, Mark C. de Gooijer, Levi C.M. Buil, Jos H. Beijnen, Gang Li and Olaf van Tellingen

      Article first published online: 24 APR 2015 | DOI: 10.1002/ijc.29566

  2. Epidemiology

    1. Assessing individual risk for high-risk colorectal adenoma at first-time screening colonoscopy

      Yin Cao, Bernard A. Rosner, Jing Ma, Rulla M. Tamimi, Andrew T. Chan, Charles S. Fuchs, Kana Wu and Edward L. Giovannucci

      Article first published online: 23 APR 2015 | DOI: 10.1002/ijc.29533

      What's New?

      Population screening has dramatically reduced mortality rates for colorectal cancer (CRC) in the U.S. However, colonoscopy is expensive, and healthcare resources need to be more efficiently allocated. In this study, the authors developed and validated a comprehensive risk-assessment tool for high-risk colorectal adenoma. This tool, which includes a list of risk factors, may allow first-line colorectal cancer screening to identify people who are at increased risk. These people could then be encouraged to undergo colonoscopy, and to alter their behavior and lifestyle factors to lower their risk.

  3. Cancer Genetics

    1. Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

      Veronika Mancikova, Raquel Cruz, Lucía Inglada-Pérez, Ceres Fernández-Rozadilla, Iñigo Landa, José Cameselle-Teijeiro, Catuxa Celeiro, Susana Pastor, Antonia Velázquez, Ricard Marcos, Victor Andía, Cristina Álvarez-Escolá, Amparo Meoro, Francesca Schiavi, Giuseppe Opocher, Inés Quintela, Juan Ansede-Bermejo, Clara Ruiz-Ponte, Pilar Santisteban, Mercedes Robledo and Angel Carracedo

      Article first published online: 22 APR 2015 | DOI: 10.1002/ijc.29557

      What's new?

      Thyroid cancer shows the highest genetic susceptibility among all cancers with non-Mendelian hereditability. The authors performed a two-step association study involving 1820 cases and 2410 controls in Europe and identify the 9q22 locus near the FOXE1 locus as the most important low-penetrance variation in thyroid cancer. In addition, novel variations at 10q26.12 and 6q14.1 were found associated with risk of the disease in a population-specific manner, underscoring how genetic heterogeneity among populations influences thyroid cancer susceptibility.

  4. Epidemiology

    1. Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta-analysis of epidemiologic studies

      Ting-Ting Gong, Qi-Jun Wu, Yong-Lai Wang and Xiao-Xin Ma

      Article first published online: 22 APR 2015 | DOI: 10.1002/ijc.29561

      What's new?

      How does obesity confer an increase in endometrial cancer risk? Some studies have suggested that adipokines could be involved, in particular, adiponectin, leptin, and the ratio between the two. Adiponectin is generally associated with anti-diabetic and anti-inflammatory actions, while leptin contributes to cell proliferation and metastasis. In this study, the authors collected the existing literature on adiponectin, leptin, and endometrial cancer risk, and analyzed the combined data. They conclude that increased circulating adiponectin or decreased leptin, or a higher A/L ratio, corresponds to a reduced risk of endometrial cancer.

    2. Coffee intake and the risk of colorectal adenoma: The colorectal adenoma study in Tokyo

      Sanjeev Budhathoki, Motoki Iwasaki, Taiki Yamaji, Shizuka Sasazuki and Shoichiro Tsugane

      Article first published online: 21 APR 2015 | DOI: 10.1002/ijc.29390

      What's new?

      The presence of cancer-fighting compounds in coffee is of considerable interest to the understanding of colorectal cancer etiology. But data on the relationship between coffee intake and colorectal adenoma is limited, and studies have arrived at varying conclusions. In the present analysis of the coffee-drinking habits of 1,435 individuals, coffee intake was found to be inversely associated with the risk of proximal and distal colon adenoma, precursors of malignant disease. The association was evident particularly in individuals with single and small adenomas. The findings support the idea that coffee consumption helps defend against colorectal carcinogenesis.

  5. Early Detection and Diagnosis

    1. Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma

      Yang Wen, Jing Han, Jianguo Chen, Jing Dong, Yongxiang Xia, Jibin Liu, Yue Jiang, Juncheng Dai, Jianhua Lu, Guangfu Jin, Jiali Han, Qingyi Wei, Hongbing Shen, Beicheng Sun and Zhibin Hu

      Article first published online: 21 APR 2015 | DOI: 10.1002/ijc.29544

      What's new?

      Half of all deaths from hepatocellular carcinoma (HCC) occur in China. But while early detection of the disease could improve survival, preclinical diagnostic biomarkers are lacking. Using tissue and plasma samples from HCC patients and plasma samples from prospective cohorts, the authors of this study evaluated the diagnostic and predictive potential of miRNAs. A panel of eight miRNAs dysregulated during HCC development successfully distinguished HCC patients from controls, while a panel of four miRNAs was found to have preclinical potential. The newly described miRNA panels could aid in the detection of HCC before the disease is otherwise clinically apparent.

  6. Epidemiology

    1. You have full text access to this OnlineOpen article
      Prevalence of incidental prostate cancer: A systematic review of autopsy studies

      Katy J.L. Bell, Chris Del Mar, Gordon Wright, James Dickinson and Paul Glasziou

      Article first published online: 21 APR 2015 | DOI: 10.1002/ijc.29538

      What's new?

      Before symptoms of prostate cancer manifest clinically, many men die of other causes. Yet, prostate screening, particularly in older men, frequently turns out positive, resulting in overdiagnosis and overtreatment. This meta-analysis of published autopsy studies shows that incidental prostate cancer increases with age and with the use of sensitive screening strategies, especially in older men. Among men whose prostate cancers are designated “favorable-risk,” active surveillance and subsequent biopsy can result in reclassification with higher-grade cancer, purely by chance. The potential for the detection of clinically irrelevant, incidental prostate cancer is high, indicating a need for improved screening strategies.

  7. Carcinogenesis

    1. Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm

      Chao Zhang, Xiangmei Chen, Hui Liu, Hui Li, Wei Jiang, Wenting Hou, Michael A. McNutt, Fengmin Lu and Gang Li

      Article first published online: 21 APR 2015 | DOI: 10.1002/ijc.29548

      What's New?

      Although tumor-associated fetal protein AFP has demonstrated utility as a clinical tumor marker, the significance of intracellular AFP remains unclear. This study set to explore the role of cytoplasmic AFP during hepatitis B virus (HBV)-induced carcinogenesis. The results show that HBx promotes transcription of AFP by acting on two elements in the regulatory region of the AFP gene. As a consequence, transcription of the tumor suppressor gene GADD45α is suppressed, through the disruption of RAR signaling. Cytoplasmic AFP is thus not only a histochemical biomarker for human hepatoma but also an intracellular signal molecule and potential participant in HBx-induced hepatocarcinogenesis.

  8. Epidemiology

    1. Postmenopausal hormone therapy–also use of estradiol plus levonorgestrel-intrauterine system is associated with an increased risk of primary fallopian tube carcinoma

      Virpi Koskela-Niska, Eero Pukkala, Heli Lyytinen, Olavi Ylikorkala and Tadeusz Dyba

      Article first published online: 21 APR 2015 | DOI: 10.1002/ijc.29549

      What's New?

      Primary fallopian tube carcinoma (PFTC) is a rare disease of unknown etiology. Among the suspected risk factors is postmenopausal hormone therapy, regimens of which are linked to ovarian cancer, a disease closely related to PFTC. In this analysis of data from the Finnish Cancer Registry and Prescription Register, both sequential estradiol-progestin therapy and the combined use of estradiol and a levonorgestrel-releasing-intrauterine system were associated with increased PFTC risk among women age 50 or older. Risk rose significantly after the regimens had been used for five years or longer. The study supports the idea of hormonal involvement in PFTC.

  9. Letter to the Editor

    1. microRNA regulation in cancer: One arm or two arms?

      Ramkrishna Mitra, Jingchun Sun and Zhongming Zhao

      Article first published online: 20 APR 2015 | DOI: 10.1002/ijc.29512

  10. Epidemiology

    1. F2RL3 methylation, lung cancer incidence and mortality

      Yan Zhang, Ben Schöttker, José Ordóñez-Mena, Bernd Holleczek, Rongxi Yang, Barbara Burwinkel, Katja Butterbach and Hermann Brenner

      Article first published online: 17 APR 2015 | DOI: 10.1002/ijc.29537

      What's new?

      Methylation of F2RL3 is linked to both current and lifetime smoking exposure, making it a potentially valuable marker for the assessment of lung cancer risk. This population-based prospective cohort study strengthens that potential, showing that F2RL3 hypomethylation, as measured in blood samples, is strongly predictive of lung cancer incidence and mortality. The association was significant regardless of whether F2RL3 methylation was considered alone or in combination with smoking status or pack-years. It was particularly strong in individuals aged 65 or older.

    2. Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC)

      Sepideh Saadatmand, Inge-Marie Obdeijn, Emiel J. Rutgers, Jan C. Oosterwijk, Rob A. Tollenaar, Gwendolyn H. Woldringh, Elisabeth Bergers, Cornelis Verhoef, Eveline A. Heijnsdijk, Maartje J. Hooning, Harry J. de Koning and Madeleine M. Tilanus-Linthorst

      Article first published online: 17 APR 2015 | DOI: 10.1002/ijc.29534

      What's New?

      Adding MRI to annual mammography screening improves early breast cancer detection in women with familial risk or BRCA1/2 mutation. The impact of MRI screening on metastasis free survival remains unknown, however. For ethical reasons, all of the relevant studies so far have had a non-randomized design. To address this issue, here the authors compare breast cancer patients in the largest prospective MRI Screening Study (MRISC) with controls matched for risk group, year of diagnosis, and age at diagnosis. Annual screening with MRI and mammography improves breast cancer specific metastasis free survival significantly in women with BRCA1 mutation or familial predisposition.

  11. Cancer Cell Biology

    1. Combined targeting of high-mobility group box-1 and interleukin-8 to control micrometastasis potential in gastric cancer

      Hye Won Chung, Sunphil Jang, Hoguen Kim and Jong-Baeck Lim

      Article first published online: 16 APR 2015 | DOI: 10.1002/ijc.29539

      What's New?

      Treatment failure in gastric cancer frequently is attributed to micrometastasis, a clinically undetectable process. But indications of potential micrometastasis formation may be evident in early tumor development. Here, serum levels of high-mobility group box-1 (HMGB1), a suspected pre-invasion epithelial-to-mesenchymal transition (EMT)-activation factor, were increased throughout early gastric carcinogenesis. HMGB1 overexpression correlated with increased expression of multiple EMT markers and resulted in enhanced IL-8 secretion and promotion of EMT activation. Silencing of HMGB1 and IL-8 produced antitumor effects with reductions in tumor growth. Combined HMGB1-IL-8 targeting may effectively control micrometastasis in gastric cancer.

  12. Epidemiology

    1. Implementation of HPV-testing for cervical cancer screening in programmatic contexts: The Jujuy demonstration project in Argentina

      Silvina Arrossi, Laura Thouyaret, Rosa Laudi, Oscar Marín, Josefina Ramírez, Melisa Paolino, Rolando Herrero and Alicia Campanera

      Article first published online: 15 APR 2015 | DOI: 10.1002/ijc.29530

      What's new?

      DNA testing for human papillomavirus (HPV) is rapidly becoming the preferred test for cervical cancer screening programs. But few studies have evaluated implementation strategies or program performance. Here, both implementation and performance are described for a recently introduced program for routine HPV-testing in the province of Jujuy, Argentina. The report details the year-long planning and implementation phase, during which fundamental components, including guidelines and outreach strategies, were developed. Analyses show that the program's main screening goals were fulfilled in its first year. The program's success inspired the rollout of HPV-testing to other Argentinian provinces.

  13. Carcinogenesis

    1. Mutant p53 expression in fallopian tube epithelium drives cell migration

      Suzanne M. Quartuccio, Subbulakshmi Karthikeyan, Sharon L. Eddie, Daniel D. Lantvit, Eoghainín Ó hAinmhire, Dimple A. Modi, Jian-Jun Wei and Joanna E. Burdette

      Article first published online: 11 APR 2015 | DOI: 10.1002/ijc.29528

      What's new?

      Ovarian cancer is the gynecological cancer with the highest mortality but the question remains, which cell type is involved in its development. The authors explore the role of a mutation in the p53 tumor suppressor (R273H) in fallopian tube epithelium cells (FTE) connecting the ovaries and the uterus. While the mutation was insufficient to drive cellular transformation, migration of FTE was significantly increased, a process not observed with ovarian surface epithelium cells traditionally associated with ovarian cancer.  The authors speculate that this phenotype might support the spread of cancer cells from the fallopian tube to organs in the peritoneal cavity including the ovaries.

  14. Epidemiology

    1. You have full text access to this OnlineOpen article
      High nevus counts confer a favorable prognosis in melanoma patients

      Simone Ribero, John R. Davies, Celia Requena, Cristina Carrera, Daniel Glass, Ramon Rull, Sergi Vidal-Sicart, Antonio Vilalta, Lucia Alos, Virtudes Soriano, Pietro Quaglino, Victor Traves, Julia A. Newton-Bishop, Eduardo Nagore, Josep Malvehy, Susana Puig and Veronique Bataille

      Article first published online: 11 APR 2015 | DOI: 10.1002/ijc.29525

      What's new?

      Having a lot of pigmented skin lesions known as naevi or moles is a known risk factor for melanoma, but is it also a bad prognostic marker for melanoma patients? The authors looked at the impact of nevus counts on melanoma survival in more than 2000 patients and found the opposite: high nevus counts were associated with favorable prognostic markers and a higher 5- and 10-year survival rate. These findings point to biological factor associated with high nevus count that may confer improved survival and may be exploited therapeutically in the future.

  15. Cancer Therapy

    1. Treatment of melanoma with a serotype 5/3 chimeric oncolytic adenovirus coding for GM-CSF: Results in vitro, in rodents and in humans

      Simona Bramante, Johanna K. Kaufmann, Ville Veckman, Ilkka Liikanen, Dirk M. Nettelbeck, Otto Hemminki, Lotta Vassilev, Vincenzo Cerullo, Minna Oksanen, Raita Heiskanen, Timo Joensuu, Anna Kanerva, Sari Pesonen, Sampsa Matikainen, Markus Vähä-Koskela, Anniina Koski and Akseli Hemminki

      Article first published online: 11 APR 2015 | DOI: 10.1002/ijc.29536

      What's new?

      Oncolytic viruses hold great potential in cancer therapy, particularly for their ability to carry genes that encode molecules capable of stimulating immunity against cancer. In this study, the authors evaluated an oncolytic adenovirus that carries the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF), with positive results for the treatment of melanoma. The GM-CSF-expressing virus successfully produced an antitumor immune response, evidenced in cells by the differentiation of human monocytes into macrophages and in animals by the eradication of melanoma xenografts. In human melanoma patients, the treatment was well-tolerated and demonstrated promising antitumor activity, warranting further clinical investigation.

  16. Epidemiology

    1. Cervical cancer prevented by screening: Long-term incidence trends by morphology in Norway

      Stefan Lönnberg, Bo Terning Hansen, Tor Haldorsen, Suzanne Campbell, Kristina Schee and Mari Nygård

      Article first published online: 11 APR 2015 | DOI: 10.1002/ijc.29541

      What's new?

      Estimates indicate that cervical cancer incidence has decreased by half since the expansion of cytology screening in the 1970s in Norway. The decline has been attributed to the prevention of squamous cell carcinoma. This study shows, however, that screening has impacted cervical cancer burden beyond the overall observed reduction in incidence. Analysis of more than 50 years of incidence trends by cancer morphology reveals that the actual proportion of cervical cancers prevented by screening in Norway was 68%, considerably larger than previous figures. The difference is attributed to an increase in the background risk of cervical adenocarcinoma.

  17. Early Detection and Diagnosis

    1. The clinical utility of serum anti-Müllerian hormone in the follow-up of ovarian adult-type granulosa cell tumors—A comparative study with inhibin B

      Anniina Färkkilä, Sanna Koskela, Saara Bryk, Henrik Alfthan, Ralf Bützow, Arto Leminen, Ulla Puistola, Juha S. Tapanainen, Markku Heikinheimo, Mikko Anttonen and Leila Unkila-Kallio

      Article first published online: 11 APR 2015 | DOI: 10.1002/ijc.29532

      What's new?

      More than a quarter of patients in remission with adult-type granulosa cell tumor (AGCT), a rare ovarian cancer, relapse within a decade after diagnosis, making long-term follow-up critical to patient survival. Here, the objective was to validate the use of anti-Müllerian hormone (AMH) and inhibin B in the detection of primary and recurrent AGCT. In some 560 serum samples from 123 AGCT patients, the markers were found to serve equally well alone but were especially powerful when combined. Thus, while either AMH or inhibin B can be monitored, their combined use may improve the detection of recurrent AGCT.

  18. Cancer Cell Biology

    1. Targeting FAK scaffold functions inhibits human renal cell carcinoma growth

      Claire Béraud, Valérian Dormoy, Sabrina Danilin, Véronique Lindner, Audrey Béthry, Mazène Hochane, Catherine Coquard, Mariette Barthelmebs, Didier Jacqmin, Hervé Lang and Thierry Massfelder

      Article first published online: 9 APR 2015 | DOI: 10.1002/ijc.29522

      What's new?

      Clear cell renal cell carcinoma (CCC) is notorious for its therapeutic resistance, a problem that continues despite advances in drug development. Improvements in CCC survival may now depend on the development of innovative approaches, such as disruption of the scaffolding activities of focal adhesion kinase (FAK). Here, loss of FAK was found to dramatically reduce CCC cell growth, migration, and invasion and to inhibit tumor growth. Mechanistic analyses indicated that FAK acts through kinase-independent scaffolding properties to promote renal tumorigenesis, rather than through kinase activity, as in other cancers.

  19. Letters to the Editor

  20. Cancer Cell Biology

    1. You have full text access to this OnlineOpen article
      Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles

      Eyra Marien, Michael Meister, Thomas Muley, Steffen Fieuws, Sergio Bordel, Rita Derua, Jeffrey Spraggins, Raf Van de Plas, Jonas Dehairs, Jens Wouters, Muralidhararao Bagadi, Hendrik Dienemann, Michael Thomas, Philipp A. Schnabel, Richard M. Caprioli, Etienne Waelkens and Johannes V. Swinnen

      Article first published online: 7 APR 2015 | DOI: 10.1002/ijc.29517

      What's new?

      Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant.

  21. Tumor Immunology

    1. Glioblastoma-derived extracellular vesicles modify the phenotype of monocytic cells

      Jeroen de Vrij, S.L. Niek Maas, Kitty M.C. Kwappenberg, Rosalie Schnoor, Anne Kleijn, Lennard Dekker, Theo M. Luider, Lot D. de Witte, Manja Litjens, Miriam E. van Strien, Elly M. Hol, Jerome Kroonen, Pierre A. Robe, Martine L. Lamfers, Marco W. Schilham and Marike L.D. Broekman

      Article first published online: 7 APR 2015 | DOI: 10.1002/ijc.29521

      What's New?

      The prognosis of patients with glioblastoma multiforme (GBM) remains dismal. GBM tumors can modify the immune response, both locally and systemically, which contributes to the aggressive nature of the disease. In this study, the authors found that GBM-derived extracellular vesicles (EVs) were able to modify the phenotypes of immune cells such as microglia and blood-derived monocytes in ways that made them more tumor-supportive. Changes included altered cytokine secretion by macrophages and increased expression of Membrane type 1-matrix metalloproteinase (MT1-MMP) by microglia. These results suggest that blocking GBM-derived EVs may have therapeutic potential.

  22. Cancer Genetics

    1. Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer

      Ismail Hosen, P. Sivaramakrishna Rachakonda, Barbara Heidenreich, Petra J. de Verdier, Charlotta Ryk, Gunnar Steineck, Kari Hemminki and Rajiv Kumar

      Article first published online: 7 APR 2015 | DOI: 10.1002/ijc.29526

      What's New?

      The identification of recurrent somatic mutations in bladder cancer opens the door to the development of new prognostic and therapeutic tools. Here, the TERT promoter mutations in conjunction with a common variant, rs2853669, define a subset of patients with increased risk of recurrence and poor survival. Mutations in FGFR3, in contrast, were not independently associated with either disease recurrence or overall survival. Tumors with mutations in FGFR3 or the TERT promoter carried shorter telomeres than those without mutations. The findings highlight the prognostic potential of TERT mutations and reveal a possible etiological role for telomere biology in bladder cancer.

  23. Mini Reviews

  24. Early Detection and Diagnosis

    1. Expression of mucin 1 possessing a 3′-sulfated core1 in recurrent and metastatic breast cancer

      Hiroko Ideo, Yuji Hinoda, Kohei Sakai, Ikue Hoshi, Shigeru Yamamoto, Masaaki Oka, Kazunari Maeda, Noriko Maeda, Shoichi Hazama, Junko Amano and Katsuko Yamashita

      Article first published online: 7 APR 2015 | DOI: 10.1002/ijc.29520

      What's new?

      The cancer antigen 15-3 (CA15-3) assay has been widely used for the detection of breast cancer recurrence; however, its sensitivity and specificity are inadequate. Here, the authors developed a lectin-sandwich immunoassay (Gal4/MUC1) using a 3′-sulfated core1-specific galectin-4 and a MUC1 monoclonal antibody. They found that MUC1 possessing a 3′-sulfated core1 (3Score1-MUC1) was expressed in the blood streams of patients with recurrent and/or metastatic breast cancer. The positive ratio of the Gal4/MUC1 assay was higher than that of the CA15-3 assay, especially in the relapsed or metastatic breast cancer. The study thus suggests the Gal4/MUC1 assay as an excellent alternative to CA15-3.

  25. Cancer Cell Biology

    1. Expression of nuclear matrix proteins binding matrix attachment regions in prostate cancer. PARP-1: New player in tumor progression

      Paola Barboro, Nicoletta Ferrari, Matteo Capaia, Andrea Petretto, Sandra Salvi, Simona Boccardo and Cecilia Balbi

      Article first published online: 6 APR 2015 | DOI: 10.1002/ijc.29531

      What's new?

      Higher-order chromatin organization in the cell nucleus is regulated by interactions between nuclear matrix (NM) proteins and matrix attachment regions (MARs). In tumors, however, MAR-binding proteins are subject to dysregulation. In the present analysis of tissues from prostate cancer patients, the number of NM proteins bound to MAR sequences was found to decrease as tumor aggressiveness increased. Tumor progression was associated with increasing expression of the nuclear protein PARP-1. PARP inhibition in androgen-independent PC3 cells mitigated the aggressive tumor phenotype, suggesting that the protein's role in chromatin remodeling could be important in the design of new prostate cancer therapies.

  26. Epidemiology

    1. Comparison of anthropometric measures as predictors of cancer incidence: A pooled collaborative analysis of 11 Australian cohorts

      Jessica L. Harding, Jonathan E. Shaw, Kaarin J. Anstey, Robert Adams, Beverley Balkau, Sharon L. Brennan-Olsen, Tom Briffa, Timothy M.E. Davis, Wendy A. Davis, Annette Dobson, Leon Flicker, Graham Giles, Janet Grant, Rachel Huxley, Matthew Knuiman, Mary Luszcz, Robert J. MacInnis, Paul Mitchell, Julie A. Pasco, Christopher Reid, David Simmons, Leon Simons, Andrew Tonkin, Mark Woodward, Anna Peeters and Dianna J. Magliano

      Article first published online: 6 APR 2015 | DOI: 10.1002/ijc.29529

      What's New?

      The accumulation of excess fat around the abdomen is a well-known risk factor for cardiovascular and metabolic diseases and is associated with a variety of cancers. While measures that reflect central adiposity, namely waist circumference (WC) and waist-to-hip ratio (WHR), are strongly associated with cardiometabolic disease risk, their ability to predict cancer risk is unclear. In this study, overall cancer risk and risk of colorectal and obesity-related cancers were associated with multiple anthropometric measures—not only WC or WHR. An exception was prostate cancer, which was not significantly associated with any anthropometric marker.

  27. Carcinogenesis

    1. Reciprocal repression between TUSC7 and miR-23b in gastric cancer

      Peng Qi, Mi-die Xu, Xiao-Han Shen, Shu-Juan Ni, Dan Huang, Cong Tan, Wei-Wei Weng, Wei-Qi Sheng, Xiao-Yan Zhou and Xiang Du

      Article first published online: 6 APR 2015 | DOI: 10.1002/ijc.29516

      What's new?

      Long noncoding RNA expression could predict gastric cancer survival, new data suggest. It's been shown previously that these transcripts can function as tumor suppressors, and in this paper the authors investigate lncRNAs in gastric cancer. First, they identified lncRNAs that were expressed differently in cancer cells than healthy ones. By performing a cohort analysis they showed that patients with one particular lncRNA, called TUSC7, had a greater chance of survival. They then demonstrated that p53 regulates TUSC7 transcription, and that TUSC7 represses miR-23b, which spurs cell growth. Thus, TUSC7 may act as a tumor suppressor.

  28. Early Detection and Diagnosis

    1. High preoperative levels of serum glypican-3 containing N-terminal subunit are associated with poor prognosis in patients with hepatocellular carcinoma after partial hepatectomy

      Yukihiro Haruyama, Kenji Yorita, Tetsuji Yamaguchi, Sachiko Kitajima, Jun Amano, Toshihiko Ohtomo, Akinobu Ohno, Kazuhiro Kondo and Hiroaki Kataoka

      Article first published online: 6 APR 2015 | DOI: 10.1002/ijc.29518

      What's new?

      Glypican-3 (GPC3), a glycoprotein that is overexpressed on the cell surface of hepatocellular carcinoma (HCC) cells, is an emerging candidate for novel molecular target therapies. Identification of patients with high GPC3 expression levels in HCC cells, which has been shown to have prognostic value, may become helpful when using GPC3-targeting therapies. Here, the authors develop a novel ELISA essay to quantify serum GPC3 N-terminal subunit antigen (sGPC3N) in patients and determine its correlation to histological GPC3 expression and prognosis after curative partial hepatectomy. The data revealed for the first time that pre-operative sGPC3N level serves as an independent prognostic biomarker.

  29. Letter to the Editor

    1. Authors’ response to Letter to the Editor

      Kyriaki Papantoniou, Gemma Castaño-Vinyals, Javier Llorca, Marina Pollan and Manolis Kogevinas

      Article first published online: 2 APR 2015 | DOI: 10.1002/ijc.29523

  30. Cancer Cell Biology

    1. Sialidase NEU3 contributes neoplastic potential on colon cancer cells as a key modulator of gangliosides by regulating Wnt signaling

      Kohta Takahashi, Masahiro Hosono, Ikuro Sato, Keiko Hata, Tadashi Wada, Kazunori Yamaguchi, Kazuo Nitta, Hiroshi Shima and Taeko Miyagi

      Article first published online: 1 APR 2015 | DOI: 10.1002/ijc.29527

      What's new?

      Although abnormal up-regulation of the sialidase NEU3 may play a role in colon cancer promotion and progression, the mechanisms behind its malignant activity remain unclear. This study shows that NEU3 expression is closely associated with Wnt/β-catenin signaling. In colon cancer cells, NEU3 expression was linked to tumorigenic potential and was found to influence the expression of stem- and Wnt-related genes. NEU3 activation of Wnt signaling was mediated via LRP6 phosphorylation and β-catenin activation. Wnt-mediated sphere formation was abrogated by NEU3 silencing, indicating that regulation of Wnt/β-catenin signaling by NEU3 is critical for colon carcinogenesis.

  31. Short Reports

    1. You have full text access to this OnlineOpen article
      Physical activity, alcohol consumption, BMI and smoking status before and after prostate cancer diagnosis in the ProtecT trial: Opportunities for lifestyle modification

      Lucy E. Hackshaw-McGeagh, Chris M. Penfold, Eleanor Walsh, Jenny L. Donovan, Freddie C. Hamdy, David E. Neal, Mona Jeffreys, Richard M. Martin, J. Athene Lane and the ProtecT Study Group

      Article first published online: 1 APR 2015 | DOI: 10.1002/ijc.29514

      What's new?

      Does cancer diagnosis lead individuals to consider making healthy lifestyle changes? These authors studied men diagnosed with prostate cancer to find out whether they changed their activity level, alcohol consumption, body mass index, or smoking habits after being diagnosed with prostate cancer. They found that some men increased their activity level and/or decreased their alcohol consumption, but not all. As making positive lifestyle changes may improve prognosis, it's worth looking for ways to encourage newly diagnosed patients to make healthy changes.

  32. Cancer Cell Biology

    1. Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications

      Yi-Jen Liao, Cheng-Chieh Fang, Chia-Hung Yen, Shih-Ming Hsu, Chung-Kwe Wang, Shiu-Feng Huang, Yu-Chih Liang, Ying-Yu Lin, Yu-Tseng Chu and Yi-Ming Arthur Chen

      Article first published online: 24 MAR 2015 | DOI: 10.1002/ijc.29507

      What's new?

      The hunt for new markers and treatments in hepatocellular carcinoma (HCC) has opened the door to the development of novel strategies that promise to improve patient outcome. Here, that promise is highlighted by Niemann-Pick disease type C2 (NPC2), which is identified as a potential prognostic marker and therapeutic target in HCC. In liver cancer cells and in patients, NPC2 downregulation was associated with various clinicopathologic features, including vascular invasion, enhanced cell proliferation, and tumor growth. In patients, decreased NPC2 was associated with decreased survival. In mice, treatment with NPC2, delivered via adeno-associated virus 8, suppressed spontaneous HCC development.

  33. Mini Reviews

    1. Biological relevance of Hsp90-binding immunophilins in cancer development and treatment

      Gisela I. Mazaira, María F. Camisay, Sonia De Leo, Alejandra G. Erlejman and Mario D. Galigniana

      Article first published online: 24 MAR 2015 | DOI: 10.1002/ijc.29509

    2. You have full text access to this OnlineOpen article
      Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation

      Alejandra Martinez de Pinillos Bayona, Caroline M. Moore, Marilena Loizidou, Alexander J. MacRobert and Josephine H. Woodhams

      Article first published online: 23 MAR 2015 | DOI: 10.1002/ijc.29510

  34. Epidemiology

    1. Twenty-years experience with de novo metastatic breast cancer

      Laura Cortesi, Angela Toss, Claudia Cirilli, Luigi Marcheselli, Barbara Braghiroli, Federica Sebastiani and Massimo Federico

      Article first published online: 23 MAR 2015 | DOI: 10.1002/ijc.29503

      What's new?

      Despite the approval of increasingly advanced drugs for metastatic breast cancer, the absolute benefits of such agents remain unclear, fueling questions about whether their effects justify their rising costs. This study suggests that new agents, such as trastuzumab, LH-RH analogues, and aromatase inhibitors, are in fact contributing to improvements in overall prognosis, specifically for “de novo” breast cancer. Evaluation of outcomes of metastatic breast cancer among women in revealed significant improvement in overall survival for de novo" disease from 2002 until 2009, a window of time coincident with the introduction and growing use of new agents.

  35. Cancer Cell Biology

    1. Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells

      Kateřina Kratochvílová, Peter Horak, Milan Ešner, Karel Souček, Dietmar Pils, Mariam Anees, Erwin Tomasich, František Dráfi, Veronika Jurtíková, Aleš Hampl, Michael Krainer and Petr Vaňhara

      Article first published online: 21 MAR 2015 | DOI: 10.1002/ijc.29502

      What's New?

      While epigenetic silencing of the tumor suppressor candidate 3 (TUSC3) gene is associated with poor outcome in ovarian cancer, the molecular role of TUSC3 in ovarian malignancies is unknown. In this study, loss of TUSC3 expression in ovarian cancer cells was associated with alterations in endoplasmic reticulum (ER) ultrastructure, as well as with alterations in ER stress signaling. TUSC3 silencing was further associated with the loss of epithelial phenotype and epithelial-to-mesenchymal transition. In mice, loss of TUSC3 promoted massive tumor growth of ovarian cancer cells. The results establish TUSC3 as a novel tumor suppressor in ovarian cancer.

  36. Cancer Genetics

    1. Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease

      María Asunción García-González, Luis Bujanda, Enrique Quintero, Santos Santolaria, Rafael Benito, Mark Strunk, Federico Sopeña, Concha Thomson, Angeles Pérez-Aisa, David Nicolás-Pérez, Elizabeth Hijona, Patricia Carrera-Lasfuentes, Elena Piazuelo, Pilar Jiménez, Jesús Espinel, Rafael Campo, Marisa Manzano, Fernando Geijo, María Pellise, Manuel Zaballa, Ferrán González-Huix, Jorge Espinós, Llúcia Titó, Luis Barranco, Roberto Pazo-Cid and Angel Lanas

      Article first published online: 19 MAR 2015 | DOI: 10.1002/ijc.29500

      What's new?

      Susceptibility to Helicobacter pylori infection-related disease differs by ethnic group, and there are vast divergences in disease outcome, specifically for duodenal ulcer (DU) and gastric cancer (GC). Those differences may be explained in part by genetic variations, including differences in allele frequencies of rs2294008, a polymorphism of the PSCA gene. In this study of a Spanish Caucasian population, the rs2294008 T allele was found to be associated with increased GC risk, particularly diffuse-type GC, and with reduced DU risk. A significant link was uncovered between the rs2294008 T allele and worse overall survival in patients with diffuse-type GC.

  37. Mini Reviews

  38. Early Detection and Diagnosis

    1. The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer

      Sven Wach, Omar Al-Janabi, Katrin Weigelt, Kersten Fischer, Thomas Greither, Marios Marcou, Gerit Theil, Elke Nolte, Hans-Juergen Holzhausen, Robert Stöhr, Verena Huppert, Arndt Hartmann, Paolo Fornara, Bernd Wullich and Helge Taubert

      Article first published online: 18 MAR 2015 | DOI: 10.1002/ijc.29505

      What's new?

      Prostate cancer (PCa) sheds cells, genetic fragments, and proteins into the bloodstream that can be used as quantitative biomarkers for diagnosis, staging, prognostication, and monitoring. This study suggests that serum levels of soluble urokinase plasminogen activator receptor (suPAR) and miR-375 are both useful as diagnostic biomarkers. High serum level of suPAR is also significantly associated with poor disease-specific survival, and the combination of miR-375/suPAR levels is significantly correlated with 10-year overall and disease-specific survival in patients. suPAR and the combination of suPAR with miR-375 may thus have a prognostic impact, indicating the potential value of combining protein and miRNA biomarkers.

  39. Epidemiology

    1. Mortality after exposure to polychlorinated biphenyls and polychlorinated dibenzofurans: A meta-analysis of two highly exposed cohorts

      Ming-Chieh Li, Pau-Chung Chen, Pei-Chien Tsai, Masutaka Furue, Daisuke Onozuka, Akihito Hagihara, Hiroshi Uchi, Takesumi Yoshimura and Yue Leon Guo

      Article first published online: 16 MAR 2015 | DOI: 10.1002/ijc.29504

  40. Short Report

    1. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma

      Shripad Joshi, Christian Wels, Christine Beham-Schmid, Mizuho Fukunaga-Kalabis, Sheri L. Holmen, Marcus Otte, Meenhard Herlyn, Maria Waldhoer and Helmut Schaider

      Article first published online: 16 MAR 2015 | DOI: 10.1002/ijc.29506

      What's new?

      Human cytomegalovirus (HCMV) can influence oncogenic processes, an ability that may stem from the activities of HMCV-encoded proteins. The HCMV-encoded G-protein-coupled receptor US28, for example, promotes tumorigenesis via disturbance of signaling pathways. But US28 also can induce cell death, an alternate effect explored in the present study. In human melanoma cells, the apoptosis-inducing properties of US28 were discovered to be mediated through the G-protein subunit Gα13. Differences in Gα13 expression in melanoma cells and tissue governed susceptibility to US28 apoptosis induction. The results suggest that Gα13 availability dictates the US28 cell death-inducing effect.

  41. Epidemiology

    1. Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population-based cohort study of 32,308 one-year survivors

      Thorgerdur Gudmundsdottir, Jeanette F. Winther, Sofie de Fine Licht, Trine G. Bonnesen, Peter H. Asdahl, Laufey Tryggvadottir, Harald Anderson, Finn Wesenberg, Nea Malila, Henrik Hasle, Jørgen H. Olsen and on behalf of the ALiCCS study group

      Article first published online: 14 MAR 2015 | DOI: 10.1002/ijc.29468

      What's new?

      The long-term effects of cancer treatment in childhood cancer survivors can be serious, and more research is needed to fully investigate the relationship between treatment and chronic disease in aging survivors. This retrospective population-based cohort study focused on cardiovascular late effects among childhood cancer survivors in the five Nordic countries. Survivors were found to be at significantly increased risk for cardiovascular disease throughout their lives. Relative risk was highest for heart failure, valvular dysfunction, and cerebrovascular diseases. Overall, survivors had a twofold increased lifetime risk for hospitalization for cardiovascular disease.

  42. Carcinogenesis

    1. Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway

      Miki Ito, Shinichi Kanno, Katsuhiko Nosho, Yasutaka Sukawa, Kei Mitsuhashi, Hiroyoshi Kurihara, Hisayoshi Igarashi, Taiga Takahashi, Mami Tachibana, Hiroaki Takahashi, Shinji Yoshii, Toshinao Takenouchi, Tadashi Hasegawa, Kenji Okita, Koichi Hirata, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto and Yasuhisa Shinomura

      Article first published online: 13 MAR 2015 | DOI: 10.1002/ijc.29488

      What's new?

      Changes in the microbial community in the human gut may contribute to colorectal cancer (CRC). Of particular interest are changes in populations of Fusobacterium nucleatum, which previous work has shown to be abundant in CRC tissues. In this study, F. nucleatum was detected in CRCs, as well as in premalignant lesions with elevated CpG island methylator phenotype status. In sessile serrated adenomas, F. nucleatum increased steadily from the sigmoid colon to the cecum, supporting the existence of a colorectal continuum. F. nucleatum may become increasingly abundant with histological grade and may influence CRC progression.

  43. Cancer Genetics

    1. Epigenetic silencing of miR-708 enhances NF-κB signaling in chronic lymphocytic leukemia

      Constance Baer, Christopher C. Oakes, Amy S. Ruppert, Rainer Claus, Soo-Zin Kim-Wanner, Daniel Mertens, Thorsten Zenz, Stephan Stilgenbauer, John C. Byrd and Christoph Plass

      Article first published online: 13 MAR 2015 | DOI: 10.1002/ijc.29491

      What's new?

      Mechanisms by which microRNAs (miRNAs) become deregulated in chronic lymphocytic leukemia (CLL) are largely unknown, but for miR-708, a potential tumor suppressor, aberrant promoter methylation may be at fault. Here, miR-708 overexpression was associated with IKKβ repression and impaired expression of genes targeted by NF-κB. Regulation of miR-708 in CLL occurred at a distal enhancer element, where elevated enhancer methylation was correlated with reduced miR-708 expression. Increased miR-708 methylation was found primarily in CLL patients with poor prognosis. The findings shed light on a possible functional connection between an epigenetic mark and regulation of a highly disease-relevant pathway.

  44. Cancer Cell Biology

    1. FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors

      Bettina Schwamb, Robert Pick, Sara Beatriz Mateus Fernández, Kirsten Völp, Jan Heering, Volker Dötsch, Susanne Bösser, Jennifer Jung, Rasa Beinoraviciute-Kellner, Josephine Wesely, Inka Zörnig, Matthias Hammerschmidt, Matthias Nowak, Roland Penzel, Kurt Zatloukal, Stefan Joos, Ralf Joachim Rieker, Abbas Agaimy, Stephan Söder, KMarie Reid-Lombardo, Michael L. Kendrick, Michael R. Bardsley, Yujiro Hayashi, David T. Asuzu, Sabriya A. Syed, Tamas Ordog and Martin Zörnig

      Article first published online: 12 MAR 2015 | DOI: 10.1002/ijc.29498

      What's new?

      The emergence of drug resistance is a major problem in gastrointestinal stromal tumors (GISTs), where tumor cell escape appears in many instances to be associated with acquired resistance to apoptosis. Here, a protein known as FAM96A was found to bind to apoptotic peptidase activating factor 1 (APAF1) and to be profoundly reduced in most GISTs. When FAM96A expression was re-established in cells, tumor sensitivity to apoptosis increased. In xenograft and allograft murine models, tumor growth slowed with FAM96A re-expression. Hence, FAM96A may have a tumor-suppressive role in GISTs. Knowledge of its function could aid the development of novel GIST therapies.

  45. Early Detection and Diagnosis

    1. You have full text access to this OnlineOpen article
      Thymidylate synthase expression in circulating tumor cells: A new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients

      Emne Ali Abdallah, Marcello Ferretti Fanelli, Marcilei Eliza Cavicchioli Buim, Marcelo Calil Machado Netto, José Luiz Gasparini Junior, Virgílio Souza e Silva, Aldo Lourenço Abbade Dettino, Natalia Breve Mingues, Juliana Valim Romero, Luciana Menezes Mendonça Ocea, Bruna Maria Malagoli Rocha, Vanessa Silva Alves, Daniel Vilarim Araújo and Ludmilla Thomé Domingos Chinen

      Article first published online: 11 MAR 2015 | DOI: 10.1002/ijc.29495

      What's new?

      Currently, the common treatment strategy for metastatic colorectal cancer patients is 5-Fluorouracil-based chemotherapy, which shows high efficacy in a subset of patients. Even those patients, however, can experience disease progression due to 5-FU resistance. There are indications that the DNA replication and repair enzyme thymidylate synthase (TYMS) may be involved. Here, the authors set to measure circulating tumor cells levels and search for TYMS staining to correlate these findings with clinical outcome. The results suggest that circulating tumor cells represent a powerful tool to follow up 5-FU resistance in metastatic colorectal cancer patients in real time, by TYMS expression analysis.

  46. Mini Reviews

    1. Receptor tyrosine kinase inhibitors: Are they real tumor killers?

      Andreas K.A. Gaumann, Friedemann Kiefer, Joachim Alfer, Sven A. Lang, Edward K. Geissler and Georg Breier

      Article first published online: 11 MAR 2015 | DOI: 10.1002/ijc.29499

  47. Cancer Therapy

    1. Engagement of signaling pathways of protease-activated receptor 2 and μ-opioid receptor in bone cancer pain and morphine tolerance

      Yanju Bao, Yebo Gao, Wei Hou, Liping Yang, Xiangying Kong, Honggang Zheng, Conghuang Li and Baojin Hua

      Article first published online: 10 MAR 2015 | DOI: 10.1002/ijc.29497

      What's New?

      Cancer patients frequently suffer great pain, and though morphine can help, the dose must continually increase to continue delivering the same pain relief. These authors investigated a molecular signaling pathway that transmits pain in rats carrying human cancers. They found high levels of the protein PAR2 in the spinal cord, revving up its downstream signaling pathway and increasing the rats' sensitivity to pain. When they blocked PAR2, they observed less activity in the downstream pathway and alleviated the excess sensitivity. The PAR2 blocker also reduced the rats' tolerance to morphine, which could prove very useful in treating cancer pain.

    2. You have full text access to this OnlineOpen article
      Antitumor effect of antitissue factor antibody-MMAE conjugate in human pancreatic tumor xenografts

      Yoshikatsu Koga, Shino Manabe, Yoshiyuki Aihara, Ryuta Sato, Ryo Tsumura, Hikaru Iwafuji, Fumiaki Furuya, Hirobumi Fuchigami, Yuki Fujiwara, Yohei Hisada, Yoshiyuki Yamamoto, Masahiro Yasunaga and Yasuhiro Matsumura

      Article first published online: 9 MAR 2015 | DOI: 10.1002/ijc.29492

      What's new?

      Tissue factor (TF) triggers normal blood coagulation, and is also highly expressed in various types of tumor, including pancreatic, malignant glioma, and gastric cancer. In this study, the authors developed a new antibody-drug conjugate (ADC) consisting of an anti-TF monoclonal antibody linked to monomethyl auristatin E (MMAE). The ADC accumulated selectively within tumors, and caused significant suppression of tumor growth in vivo. Because it penetrates tumors via their leaky vasculature, but is too large to pass through normal vessel walls, this ADC may provide a promising therapeutic strategy.

  48. Infectious Causes of Cancer

    1. A natural HIV p17 protein variant up-regulates the LMP-1 EBV oncoprotein and promotes the growth of EBV-infected B-lymphocytes: Implications for EBV-driven lymphomagenesis in the HIV setting

      Debora Martorelli, Elena Muraro, Katy Mastorci, Jessica Dal Col, Damiana Antonia Faè, Chiara Furlan, Cinzia Giagulli, Francesca Caccuri, Marco Rusnati, Simona Fiorentini, Antonino Carbone, Arnaldo Caruso and Riccardo Dolcetti

      Article first published online: 9 MAR 2015 | DOI: 10.1002/ijc.29494

      What's new?

      Although it is well established that individuals afflicted with HIV infection are at risk to develop Hodgkin as well as Non-Hodgkin lymphoma, the exact molecular relationship between HIV and a frequently co-infecting oncogenic γ-herpesvirus, Epstein Barr Virus (EBV), remains unclear. Here the authors provide evidence that by up-regulating the chemokine receptor CXCR2, EBV renders B lymphocytes permissive to the growth-promoting effects of the HIV matrix protein p17, especially a natural variant called S75X. p17 binding to CXCR2 in turn upregulates the expression of the EBV-encoded oncogene LMP-1 promoting the proliferation of EBV-infected B cells and demonstrating a bidirectional molecular interplay between HIV p17 and EBV LMP-1 proteins in the development of EBV-driven lymphomas during HIV infection.

  49. Cancer Therapy

    1. Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab

      Line S. Tarpgaard, Ib J. Christensen, Gunilla Høyer-Hansen, Ida K. Lund, Tormod K. Guren, Bengt Glimelius, Halfdan Sorbye, Kjell M. Tveit, Hans Jørgen Nielsen, José M. A. Moreira, Per Pfeiffer and Nils Brünner

      Article first published online: 9 MAR 2015 | DOI: 10.1002/ijc.29476

      What's new?

      The spread of malignant cells in metastatic colorectal cancer is facilitated by urokinase plasminogen activator receptor (uPAR), a membrane-anchored protein with multiple cleaved forms, some of which circulate in the blood. This study shows that one of those forms, uPAR(I-III)+(II-III), is a prognostic biomarker in metastatic colorectal cancer, being associated specifically with short overall survival. Furthermore, patients with KRAS wild-type tumors and low levels of soluble uPAR(I-III)+(II-III) benefited more from FLOX (fluorouracil, folinate, and oxaliplatin) and cetuximab treatment regimens than patients with high suPAR levels. The findings suggest that suPAR influences therapeutic response, particularly to the EGFR inhibitor cetuximab.

  50. Early Detection and Diagnosis

    1. Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls

      Lei Dong, Peng Qi, Mi-Die Xu, Shu-Juan Ni, Dan Huang, Qing-Hua Xu, Wei-Wei Weng, Cong Tan, Wei-Qi Sheng, Xiao-Yan Zhou and Xiang Du

      Article first published online: 9 MAR 2015 | DOI: 10.1002/ijc.29484

      What's new?

      Certain long noncoding RNAs (lncRNAs) may be involved in oncogenesis or tumor suppression, raising questions about their potential service as cancer biomarkers. The authors of the present study systematically assessed the diagnostic value of serum-detectable lncRNAs for gastric cancer (GC) patients. Reverse transcription, quantitative PCR resulted in the identification of a GC-associated three-lncRNA signature centering on CUDR, LSINCT-5 and PTENP1. The three-lncRNA signature successfully distinguished between early-stage GC patients and healthy subjects. The findings warrant further investigation of the clinical utility of serum lncRNAs in the detection of early-stage GC.

  51. Short Reports

    1. Association between height and thyroid cancer risk: A meta-analysis of prospective cohort studies

      Zhaohai Jing, Xu Hou, Ying Liu, Shengli Yan, Robin Wang, Shihua Zhao and Yangang Wang

      Article first published online: 9 MAR 2015 | DOI: 10.1002/ijc.29487

      What's new?

      The taller a person is, the greater his or her risk for thyroid cancer may be, although not all studies on the subject have reached that same conclusion. To gain a clearer picture of the relationship between height and thyroid cancer, the present meta-analysis took into consideration data from 15 prospective cohort studies. The findings of the analysis corroborate the existence of an association, whereby thyroid cancer risk increases with increasing height, in both men and women. Although the mechanistic basis for the association awaits elucidation, pathways centering on insulin-like growth factor-1 (IGF-1), which influences growth, are implicated.

    2. Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma

      Aziz Zaanan, Jae Myung Park, David Tougeron, Shengbing Huang, Tsung-Teh Wu, Nathan R. Foster and Frank A. Sinicrope

      Article first published online: 9 MAR 2015 | DOI: 10.1002/ijc.29496

      What's new?

      Patients with nonmetastatic rectal cancer routinely receive chemotherapy and radiation before surgery. However, a predictive marker for the efficacy of chemoradiation is lacking. Here, the authors show that the essential autophagy protein Beclin 1 –known to protect against radiation-induced DNA damage– could be such a predictive marker. In locally advanced rectal cancer patients, high-level Beclin 1 expression in pretreatment tumor tissues was associated with a significantly reduced rate of tumor downstaging after chemoradiation and vice versa, supporting a new role of Beclin 1 as a clinical biomarker.

  52. Cancer Cell Biology

    1. O6-methylguanine DNA methyltransferase repairs platinum-DNA adducts following cisplatin treatment and predicts prognoses of nasopharyngeal carcinoma

      Shang Hung Chen, Ching Chuan Kuo, Chien Feng Li, Chun Hei Antonio Cheung, Tsui Chun Tsou, Huai Chih Chiang, Yun Ning Yang, Shin Lun Chang, Li Ching Lin, Hsin Yi Pan, Kwang Yu Chang and Jang Yang Chang

      Article first published online: 6 MAR 2015 | DOI: 10.1002/ijc.29486

      What's new?

      Although commonly used in human cancers, the efficacy of cisplatin (CDDP) is limited by drug resistance. This study finds the DNA-repair protein O6-methylguanine–DNA methyltransferase (MGMT) to play an important role in altering the cellular cytotoxicity of CDDP in nasopharyngeal carcinoma cells. Notably, MGMT proteins bind to CDDP-induced DNA damage and are subsequently degraded via the ubiquitin-mediated proteasome system. Furthermore, high MGMT expression predicts shorter prognosis for nasopharyngeal carcinoma patients treated with CDDP-based concurrent chemoradiotherapy. These findings suggest that MGMT is a significant determinant of the efficacy of CDDP and a promising therapeutic target, especially in patients with nasopharyngeal carcinoma.

  53. Cancer Therapy

    1. Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib

      Qiaoli Zhao, Nadine Kretschmer, Rudolf Bauer and Thomas Efferth

      Article first published online: 6 MAR 2015 | DOI: 10.1002/ijc.29483

      What's new?

      Patients with glioblastoma can fight back with EGFR inhibitors, such as erlotinib, but drug resistance hobbles their usefulness over the long term. Now, researchers may have found a wingman for these EGFR inhibitors. The natural naphthoquinone shikonin also kills cancer cells, and in this study, the authors investigated whether the addition of various different shikonins could boost the efficacy of erlotinib. Shikonin, they found, also inhibits EGFR signaling, and when used in combination, the two agents halted EGFR phosphorylation and killed tumor cells far more effectively than either alone.

  54. Tumor Immunology

    1. Modulatory effects of adiponectin on the polarization of tumor-associated macrophages

      Jiao Peng, Julia Y. Tsang, Derek H. Ho, Ruizhong Zhang, Haitao Xiao, Daxu Li, Jiang Zhu, Fenghua Wang, Zhaoxiang Bian, Vincent C. Lui, Aimin Xu, Paul K. Tam, Jonathan R. Lamb, Huimin Xia and Yan Chen

      Article first published online: 4 MAR 2015 | DOI: 10.1002/ijc.29485

      What's New?

      The localization and function of tumor-associated macrophages (TAMs) in adult tumors are well documented. However, less is known of their presence in pediatric tumors. Here, the authors report for the first time that TAM accumulation is positively associated with adiponectin (APN) expression in infantile rhabdomyosarcoma. Using a murine MN/MCA1 sarcoma model to investigate the mechanisms of this association, they demonstrate that APN deficiency restricts tumor growth, which correlates with a reduction in the number of TAMs. Furthermore, they reveal that APN deficiency allows TAMs to adopt a M1-like phenotype by down-regulating the p38 MAPK signaling pathway.

  55. Short Reports

    1. Epstein-Barr virus infection induces miR-21 in terminally differentiated malignant B cells

      Eleni Anastasiadou, Neha Garg, Rachele Bigi, Shivangi Yadav, Antonio Francesco Campese, Caterina Lapenta, Massimo Spada, Laura Cuomo, Annalisa Botta, Filippo Belardelli, Luigi Frati, Elisabetta Ferretti, Alberto Faggioni and Pankaj Trivedi

      Article first published online: 4 MAR 2015 | DOI: 10.1002/ijc.29489

      What's new?

      Epstein-Barr virus (EBV) infection is ubiquitous in human populations, but the virus association with plasma cell malignancies is frequent in immunocompromised individuals. Furthermore, the mechanisms by which EBV may influence neoplastic transformation in such individuals remain unclear. Here, in multiple myeloma cell lines, EBV infection was found to induce the expression of miR-21, a microRNA which is frequently overexpressed in tumors. MiR-21 induction was associated with downregulation of p21, and EBV-infected cells readily produced tumors in SCID mice. The findings suggest that knowledge of miRNA profiles could be of diagnostic and therapeutic relevance in EBV associated plasmacytoid malignancies.

  56. Cancer Therapy

    1. Circulating tumor cells as a longitudinal biomarker in patients with advanced chemorefractory, RAS-BRAF wild-type colorectal cancer receiving cetuximab or panitumumab

      Valeria Musella, Filippo Pietrantonio, Eleonora Di Buduo, Roberto Iacovelli, Antonia Martinetti, Elisa Sottotetti, Ilaria Bossi, Claudia Maggi, Maria Di Bartolomeo, Filippo de Braud, Maria Grazia Daidone and Vera Cappelletti

      Article first published online: 4 MAR 2015 | DOI: 10.1002/ijc.29493

      What's new?

      Antibodies against epidermal growth factor receptor (EGFR) can effectively treat certain colorectal cancers, but inevitably some patients' tumors prove resistant. In this paper, the authors investigated circulating tumor cells (CTCs) before and during treatment. Half the patients had CTCs before treatment began, which did not seem to correlate with the patients' response to treatment. Those patients who developed CTCs early in treatment, however, had shorter survival times than those who acquired them later. Thus, checking for the presence of CTCs early in treatment could help predict treatment response.

  57. Tumor Immunology

    1. NKT cells act through third party bone marrow-derived cells to suppress NK cell activity in the liver and exacerbate hepatic melanoma metastases

      Leila Sadegh, Peter W. Chen, Joseph R. Brown, Zhiqiang Han and Jerry Y. Niederkorn

      Article first published online: 27 FEB 2015 | DOI: 10.1002/ijc.29480

      What's new?

      Natural killer T (NKT) cells are a distinct population of T cells with the characteristics of both innate and adaptive immunity whose role in the development of liver metastases from intraocular melanomas requires further clarification. Here, using a mouse model, the authors find that NKT cells in the liver cross-regulate liver NK cells by upregulating IL-10 receptor on the surface of NK cells and by stimulating IL-10 production by bone marrow-derived liver cells. NKT cell impairment of NK cell activity is limited to the liver and occurs only in mice harboring liver metastases.

  58. Epidemiology

    1. Asthma and risk of lethal prostate cancer in the Health Professionals Follow-Up Study

      Elizabeth A. Platz, Charles G. Drake, Kathryn M. Wilson, Siobhan Sutcliffe, Stacey A. Kenfield, Lorelei A. Mucci, Meir J. Stampfer, Walter C. Willett, Carlos A. Camargo Jr and Edward Giovannucci

      Article first published online: 27 FEB 2015 | DOI: 10.1002/ijc.29463

      What's new?

      The way in which the immune system responds to allergens may play a role in the development of prostate cancer. Hence, to better understand prostate malignancies, the authors of the present study focused on potential associations with asthma and hayfever, which are mediated via TH2 pathways. Men who had been diagnosed with asthma had a reduced risk for both lethal and fatal prostate cancer, whereas men diagnosed with hayfever 30 or more years in the past were at slightly increased risk for the disease. The reason for the difference in risk between asthma and hayfever was unclear.

    2. Dietary and biomarker estimates of fatty acids and risk of colorectal cancer

      Allison M. Hodge, Elizabeth J. Williamson, Julie K. Bassett, Robert J. MacInnis, Graham G. Giles and Dallas R. English

      Article first published online: 27 FEB 2015 | DOI: 10.1002/ijc.29479

      What's new?

      While there is considerable evidence that diet is associated with colorectal cancer (CRC) risk, the associations for specific fatty acids remain unclear. Here, the authors prospectively examine associations between dietary intake estimates or plasma phospholipids (PPL) estimates of fatty acids and incident CRC. PPL saturated fat (SF) is positively associated with incident CRC and dietary SF with rectal cancer, while long chain n-3 fats are inversely associated with both. Following guidelines to limit red and processed meat would help reduce saturated fatty acids intake; the adverse association with linoleic acid, found in margarines and vegetable oils, requires further confirmation.

  59. Cancer Genetics

    1. Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma

      Guilherme Augusto Silva Nogueira, Gustavo Jacob Lourenço, Camila Borges Martins Oliveira, Fernando Augusto Lima Marson, Leisa Lopes-Aguiar, Ericka Francislaine Dias Costa, Tathiane Regine Penna Lima, Vitor Teixeira Liutti, Frederico Leal, Vivian Castro Antunes Santos, José Augusto Rinck-Junior and Carmen Silvia Passos Lima

      Article first published online: 26 FEB 2015 | DOI: 10.1002/ijc.29435

      What is new?

      Not all smokers get cancer: the disease results from a combination of environmental and genetic factors. Mutations that hamper DNA repair could contribute, and in this paper the authors investigated four such variants. These polymorphisms, they found, could triple the risk of head and neck cancer. Among smokers, the effect was even more pronounced. Thus, these DNA mismatch repair alleles could be useful for predicting patient outcomes.

    2. The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses

      Soo Young Kim, Yoon Young Choi, Ji Yeong An, Hyun Beak Shin, Ara Jo, Hyeji Choi, Sang Hyuk Seo, Hui-Jae Bang, Jae-Ho Cheong, Woo Jin Hyung and Sung Hoon Noh

      Article first published online: 26 FEB 2015 | DOI: 10.1002/ijc.29449

      What's new?

      The frequency of microsatellite instability (MSI) in gastric cancer is associated with prognosis, with high frequency (MSI-H) generally linked to good prognosis. Importantly, however, the ability of MSI frequency to predict patient outcome in gastric cancer may be influenced by chemotherapy. The authors of the present study tested that hypothesis by analyzing data on stage II and stage III gastric cancer patients who underwent gastrectomy. The prognostic benefits conferred by MSI-H status were found to be significantly reduced among patients who received chemotherapy following surgery. Certain clinico-pathological characteristics also modified the association of MSI-H with gastric cancer prognosis.

  60. Epidemiology

    1. Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort

      Renée T. Fortner, Jennifer Ose, Melissa A. Merritt, Helena Schock, Anne Tjønneland, Louise Hansen, Kim Overvad, Laure Dossus, Françoise Clavel-Chapelon, Laura Baglietto, Heiner Boeing, Antonia Trichopoulou, Vassiliki Benetou, Pagona Lagiou, Claudia Agnoli, Amalia Mattiello, Giovanna Masala, Rosario Tumino, Carlotta Sacerdote, H.B(as). Bueno-de-Mesquita, N. Charlotte Onland-Moret, Petra H. Peeters, Elisabete Weiderpass, Inger Torhild Gram, Eric J Duell, Nerea Larrañaga, Eva Ardanaz, María-José Sánchez, M-D Chirlaque, Jenny Brändstedt, Annika Idahl, Eva Lundin, Kay-Tee Khaw, Nick Wareham, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Marc J. Gunter, Elio Riboli and Rudolf Kaaks

      Article first published online: 26 FEB 2015 | DOI: 10.1002/ijc.29471

      What's new?

      Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

    2. Advance and stagnation in the treatment of patients with lymphoma and myeloma: Analysis using population-based cancer registry data in Japan from 1993 to 2006

      Dai Chihara, Hidemi Ito, Koji Izutsu, Masakazu Hattori, Yoshikazu Nishino, Akiko Ioka, Tomohiro Matsuda and Yuri Ito

      Article first published online: 26 FEB 2015 | DOI: 10.1002/ijc.29477

      What's new?

      Do advances in diagnosing and treating cancer translate into real improvements in survival among the population? These authors set out to measure improvements in survival using Japanese population-based cancer registry data from 1993 to 2006. Good news for those diagnosed with Hodgkin lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma: relative survival has improved significantly for those cancers since 1993. They could detect no improvement in survival rates, however, for peripheral T-cell lymphoma, adult T-cell leukemia/lymphoma, or multiple myeloma, suggesting that there remains need for new strategies for treating those cancers.

  61. Tumor Immunology

    1. CD4+ T cells in chronic autoantigenic stimulation in MGUS, multiple myeloma and Waldenström's macroglobulinemia

      Frank Neumann, Michael Pfreundschuh, Klaus D. Preuss, Claudia Schormann, Carsten Zwick, Niels Murawski and Boris Kubuschok

      Article first published online: 26 FEB 2015 | DOI: 10.1002/ijc.29478

      What's new?

      Chronic autoantigenic stimulation involving hyperphosphorylated paratag-7 (pP-7) is thought to play a role in monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). However, paraproteins against P-7 bind to both the hyperphosphorylated and wild-type forms. The present study suggests that autoantigenic stimulation may be mediated by autoimmunity involving T-helper cells. T-helper responses specific for pP-7 were detected in 9 out of 14 with MGUS, MM, or WM. The pP-7 carrier state and a pP-7-presenting HLA-DR subtype appeared to be required for the specific T-helper response.

  62. Cancer Cell Biology

    1. FOXP3 suppresses breast cancer metastasis through downregulation of CD44

      Cun Zhang, Yujin Xu, Qiang Hao, Shuning Wang, Hong Li, Jialin Li, Yuan Gao, Meng Li, Weina Li, Xiaochang Xue, Shouzhen Wu, Yingqi Zhang and Wei Zhang

      Article first published online: 25 FEB 2015 | DOI: 10.1002/ijc.29482

      What's New?

      FOXP3 is an X-linked tumor suppressor gene that influences mammary carcinogenesis by acting as a transcriptional repressor of breast cancer oncogenes such as SKP2 and HER2. The present study examined the role of FOXP3 in breast cancer metastasis. In vivo and in vitro experiments demonstrated that FOXP3 inhibited breast cancer cell adhesion, invasion and metastasis, while study on the molecular mechanism revealed that FOXP3 inhibited breast cancer metastasis by down-regulating CD44 expression directly.

  63. Epidemiology

    1. Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence

      Angeline S. Andrew, Carmen J. Marsit, Alan R. Schned, John D. Seigne, Karl T. Kelsey, Jason H. Moore, Laurent Perreard, Margaret R. Karagas and Lorenzo F. Sempere

      Article first published online: 25 FEB 2015 | DOI: 10.1002/ijc.29413

      What's new?

      About half a million people in the United States are living with a history of urothelial carcinoma, the most common form of bladder cancer. Many of those patients will experience disease recurrence, screening for which poses a significant challenge for patient management. In the present study, increased levels of a marker known as miR-34a were associated with a decreased risk of tumor recurrence. Functions for miR-34a that are consistent with a tumor suppressive role were identified in vitro. The findings suggest that miR-34a may be of value in the surveillance of urothelial carcinoma, having both prognostic and therapeutic potential.

  64. Cancer Therapy

    1. NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma—Very good response predominantly in patients with intestinal type tumors

      Christoph Schulz, Frank Kullmann, Volker Kunzmann, Martin Fuchs, Michael Geissler, Ursula Vehling-Kaiser, Heribert Stauder, Axel Wein, Salah-Eddin Al-Batran, Thomas Kubin, Claus Schäfer, Sebastian Stintzing, Clemens Giessen, Dominik Paul Modest, Karsten Ridwelski and Volker Heinemann

      Article first published online: 25 FEB 2015 | DOI: 10.1002/ijc.29403

      What's New?

      The benefit of perioperative chemotherapy in gastroesophageal cancer is well documented. However, only half of the patients receive postoperative therapy raising the question whether the benefit rests mainly on the preoperative part of the treatment. Here, the authors present the results of a multicenter study that tested the effect of intensified preoperative chemotherapy. They find that this treatment resulted in a high complete pathological response rate (20%), especially in patients with a specific tumor type involving chronic inflammation supporting further studies into patient selection as well as dosage optimization for future standard treatment.

  65. Mini Reviews

  66. Epidemiology

    1. Red blood cell folate and plasma folate are not associated with risk of incident colorectal cancer in the Women's Health Initiative observational study

      Marian L. Neuhouser, Ting-Yuan David Cheng, Shirley A.A. Beresford, Elissa Brown, Xiaoling Song, Joshua W. Miller, Yingye Zheng, Cynthia A. Thomson, James M. Shikany, Mara Z. Vitolins, Thomas Rohan, Ralph Green and Cornelia M. Ulrich

      Article first published online: 24 FEB 2015 | DOI: 10.1002/ijc.29453

      What's new?

      Poor intake of the B-vitamin folate has been associated with increased risk of colorectal cancer (CRC). However, some studies suggest that very high intakes of folate may increase CRC risk. Given that certain foods are now fortified with folic acid in the U.S., it's important to ascertain whether fortification might increase CRC risk in the general population. In this large study of folate status, the authors found no evidence that folate fortification increases the risk of CRC.

  67. Letters to the Editor

  68. Letter to the Editor

  69. Cancer Cell Biology

    1. Interaction between bone marrow stromal cells and neuroblastoma cells leads to a VEGFA-mediated osteoblastogenesis

      Josephine H. HaDuong, Laurence Blavier, Sanjeev K. Baniwal, Baruch Frenkel, Jemily Malvar, Vasu Punj, Richard Sposto and Yves A. DeClerck

      Article first published online: 21 FEB 2015 | DOI: 10.1002/ijc.29465

      What's new?

      Wandering cancer cells often find bone marrow a hospitable place to settle down and start a new tumor. The tumor cells accelerate bone cell turnover, which releases physiological factors that feed the tumor cell, promoting a vicious cycle. What mechanism drives this? This paper shows that neuroblastoma cells team up with the cytokine BMP-4 to spur bone marrow mesenchymal cells to become osteoblasts. They also need to bump up production of VEGFA, suggesting that blocking VEGFA production could hinder bone metastasis.

  70. Mini Reviews

    1. Roles of the Hippo pathway in lung development and tumorigenesis

      Benjamin Yeung, Jihang Yu and Xiaolong Yang

      Article first published online: 21 FEB 2015 | DOI: 10.1002/ijc.29457

  71. Cancer Cell Biology

    1. Podoplanin-expressing cancer-associated fibroblasts lead and enhance the local invasion of cancer cells in lung adenocarcinoma

      Shinya Neri, Genichiro Ishii, Hiroko Hashimoto, Takeshi Kuwata, Kanji Nagai, Hiroshi Date and Atsushi Ochiai

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29464

      What's new?

      The protein podoplanin helps tumors push into the surrounding tissue, and thus may be a useful target for slowing down the disease. Cancer-associated fibroblasts (CAFs) communicate with cancer cells and assist with invasion. In this paper, the authors report that CAFs expressing podoplanin boosted the efficiency of a lung tumor's invasion of the matrix. Knocking down podoplanin, furthermore, reduced the invasiveness of both the CAFs and the tumor cells. Finally, the authors showed that this activity relied on the Rho-ROCK pathway, and treatment with a ROCK inhibitor stifled the cells' ability to invade.

  72. Early Detection and Diagnosis

    1. The impact of stratifying by family history in colorectal cancer screening programs

      Simon Lucas Goede, Linda Rabeneck, Iris Lansdorp-Vogelaar, Ann G. Zauber, Lawrence F. Paszat, Jeffrey S. Hoch, Jean H.E. Yong, Frank van Hees, Jill Tinmouth and Marjolein van Ballegooijen

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29473

      What's new?

      One of the first population-based screening programs for colorectal cancer (CRC) to offer colonoscopy for individuals with a family history of the disease is Canada's ColonCancerCheck. The present study estimated the long-term effects of the program, to 2038, via microsimulation modeling. Compared with a program based on guaiac fecal occult blood testing (gFOBT) alone, the family history-based program was projected to prevent 40% more deaths. The incorporation of family history-based colonoscopy into CRC screening was estimated to increase demand for the procedure by 93%.

  73. Epidemiology

    1. Hyperemesis gravidarum and maternal cancer risk, a scandinavian nested case-control study

      Kathrine F. Vandraas, Andrej M. Grjibovski, Nathalie C. Støer, Rebecca Troisi, Olof Stephansson, Anne Gulbech Ording, Siri Vangen, Tom Grotmol and Åse V. Vikanes

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29475

      What's new?

      Women who experience hyperemesis gravidarum during pregnancy may have an altered risk of cancer later in life, but results have been inconsistent. In this large case-control study, the authors found that hyperemesis was inversely associated with lung, cervical, rectal, and overall cancer risk. However, the condition was also associated with an increased risk of thyroid cancer. These results suggest that further research is needed in order to identify potential mechanisms for these associations, as hyperemesis is one of the most common complications of early pregnancy.

    2. Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers

      Harald zur Hausen and Ethel-Michele de Villiers

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29466

      What's new?

      While the association between human papilloma virus (HPV) infection and cervical cancer is well established, viral causes for other common cancers remain less clear. Here, Prof. Harald zur Hausen, the former editor-in-chief of IJC, and Prof. Ethel-Michele de Villiers summarize intriguing epidemiological data linking dairy cattle and milk consumption with colon and breast cancer. A possible connection with recently isolated episomally persisting circular single-stranded DNA, presumably of viral origin, is also being discussed. This analysis may increase attention to species-specific infectious factors present in dairy cattle meat, serum or milk that, if confirmed, could contribute to the pathogenesis of common cancers like colon and breast cancer.

    3. Sotalol, but not digoxin is associated with decreased prostate cancer risk: A population-based case–control study

      Kalle J. Kaapu, Janne Ahti, Teuvo L. J. Tammela, Anssi Auvinen and Teemu J. Murtola

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29470

      What's new?

      The antiarrhythmic drug digoxin triggers apoptosis in prostate cancer cells, and recent research suggests that the drug may even reduce prostate cancer risk. In the present population-based case-control study, which included data on more than 25,000 Finnish men, digoxin and other antiarrhythmic drugs, with the exception of sotalol, were found to have no impact on prostate cancer risk. By contrast, sotalol, which possesses both beta-blocker and K+-channel inhibitor activity, was inversely associated with overall risk and risk of advanced prostate cancer. If validated, sotalol may prove to be of greater relevance to prostate cancer prevention than digoxin.

  74. Cancer Therapy

    1. Engineered adenoviruses combine enhanced oncolysis with improved virus production by mesenchymal stromal carrier cells

      Katharina Hammer, Adam Kazcorowski, Li Liu, Michael Behr, Peter Schemmer, Ingrid Herr and Dirk M. Nettelbeck

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29442

      What's new?

      MSCs, possessing tumor-homing properties, have been developed as “carrier cells” for improved delivery of oncolytic viruses to tumors, as required in patients. This study demonstrates for the first time that engineering post-entry steps of oncolytic virus replication, in addition to cell entry, can dramatically increase the virus dose released by MSCs. The engineered viruses improved replication in both MSCs and cancer cells, thus representing promising agents for future cancer treatment by carrier cell-mediated viral oncolysis.

  75. Early Detection and Diagnosis

    1. Individual patient risk stratification of high-risk neuroblastomas using a two-gene score suited for clinical use

      Kristoffer von Stedingk, Katleen De Preter, Jo Vandesompele, Rosa Noguera, Ingrid Øra, Jan Koster, Rogier Versteeg, Sven Påhlman, David Lindgren and Håkan Axelson

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29461

      What's new?

      Children with highly aggressive neuroblastoma respond in different ways to intense, high-risk treatments. For those children whose tumors show little or no response, such treatments can be particularly harmful. With prognostic gene-expression signatures, however, it may be possible to tailor therapeutic strategies to individual patients. The present study describes a gene-expression signature based on two genes, DKC1 and PAFAH1B1, which are associated with poor prognosis and good prognosis, respectively. The two-gene analysis was performed across qPCR and array platforms and was applicable to high-risk patients, potentially enabling early identification of patients who require changes in treatment regimens.

  76. Cancer Genetics

    1. You have full text access to this OnlineOpen article
      Modeling HLA associations with EBV-positive and -negative Hodgkin lymphoma suggests distinct mechanisms in disease pathogenesis

      Paul C.D. Johnson, Karen A. McAulay, Dorothy Montgomery, Annette Lake, Lesley Shield, Alice Gallagher, Ann-Margaret Little, Anila Shah, Steven G.E. Marsh, G. Malcolm Taylor and Ruth F. Jarrett

      Article first published online: 20 FEB 2015 | DOI: 10.1002/ijc.29467

      What's new?

      Strong evidence exists for associations between HLA alleles and classical Hodgkin lymphoma (cHL). Analysis is however complicated by the linkage disequilibrium within the MHC region and data suggesting that associations with Epstein-Barr virus (EBV)-positive and negative cHL are distinct. In the largest study to date to investigate associations between EBV-stratified cHL subgroups and directly typed HLA alleles, the authors extend associations with EBV-positive cHL to novel HLA class II alleles, which are associated with decreased disease risk. For EBV-negative disease, the class II SNP rs6903608 remains the strongest predictor of risk after adjusting for the effects of common HLA alleles.

  77. Epidemiology

    1. Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study

      G. Buckland, N. Travier, J.M. Huerta, H.B.(as) Bueno-de-Mesquita, P.D. Siersema, G. Skeie, E. Weiderpass, D. Engeset, U. Ericson, B. Ohlsson, A. Agudo, I. Romieu, P. Ferrari, H. Freisling, S. Colorado-Yohar, K. Li, R. Kaaks, V. Pala, A.J. Cross, E. Riboli, A. Trichopoulou, P. Lagiou, C. Bamia, M.C. Boutron-Ruault, G. Fagherazzi, L. Dartois, A.M. May, P.H. Peeters, S. Panico, M. Johansson, B. Wallner, D. Palli, T.J. Key, K.T. Khaw, E. Ardanaz, K. Overvad, A. Tjønneland, M. Dorronsoro, M.J. Sánchez, J.R. Quirós, A. Naccarati, R. Tumino, H. Boeing and C.A. Gonzalez

      Article first published online: 13 FEB 2015 | DOI: 10.1002/ijc.29411

      What's new?

      Several modifiable lifestyle factors, including smoking status, alcohol consumption, diet quality and weight, have been independently associated with gastric cancer. Behavioral patterns often cluster, however, “lifestyle scores” can be used to analyse overlapping risk factors. In this study, the authors used a “healthy-lifestyle index” to evaluate the combined effects of all of the above factors on the risk of developing gastric cancer (GC). They found that following a healthy lifestyle dramatically decreases the burden of gastric cancer.

  78. Short Reports

    1. Analysis of circulating tumor cells derived from advanced gastric cancer

      Kosei Toyoshima, Akira Hayashi, Masahide Kashiwagi, Naoko Hayashi, Masaaki Iwatsuki, Takatsugu Ishimoto, Yoshifumi Baba, Hideo Baba and Yoshikazu Ohta

      Article first published online: 13 FEB 2015 | DOI: 10.1002/ijc.29455

      What's new?

      Circulating tumor cells (CTCs) are found in the peripheral blood of metastatic cancer patients, and may offer prognostic biomarkers for several types of cancer. In this study, the authors evaluated whether CTCs from advanced gastric cancer patients are actually tumorigenic. Injecting peripheral blood mononuclear cells (PBMCs) from these patients into mice produced tumors, while PBMCs from healthy volunteers did not. CTCs from gastric cancer patients may thus offer a potential therapeutic target, as well as a tool for further investigation.

  79. Cancer Cell Biology

    1. Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women

      Tony K.H. Chung, Paul Van Hummelen, Paul K.S. Chan, Tak Hong Cheung, So Fan Yim, Mei Y. Yu, Matthew D. Ducar, Aaron R. Thorner, Laura E. MacConaill, Graeme Doran, Chandra Sekhar Pedamallu, Akinyemi I. Ojesina, Raymond R.Y. Wong, Vivian W. Wang, Samuel S. Freeman, Tat San Lau, Joseph Kwong, Loucia K.Y. Chan, Menachem Fromer, Taymaa May, Michael J. Worley Jr., Katharine M. Esselen, Kevin M. Elias, Michael Lawrence, Gad Getz, David I. Smith, Christopher P. Crum, Matthew Meyerson, Ross S. Berkowitz and Yick Fu Wong

      Article first published online: 13 FEB 2015 | DOI: 10.1002/ijc.29456

      What's new?

      Cervical cancer is almost always associated with infections with human papilloma virus (HPV) but additional genetic mutations are required for carcinogenesis. Here the authors performed whole-exome sequencing in Hong Kong women and identified several novel recurrently mutated genes in cervical adenocarcinomas that were not present in normal adjacent tissue. Notably, HPV sequences were detected in several tumors pointing to chromosomal integration of the virus. These studies may support the development of targeted molecular therapies of cervical cancer patients in East Asia and other parts of the world.

  80. Epidemiology

    1. Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)

      Fulvio Ricceri, Francesca Fasanelli, Maria Teresa Giraudo, Sabina Sieri, Rosario Tumino, Amalia Mattiello, Liliana Vagliano, Giovanna Masala, J. Ramón Quirós, Noemie Travier, María-José Sánchez, Nerea Larranaga, María-Dolores Chirlaque, Eva Ardanaz, Anne Tjonneland, Anja Olsen, Kim Overvad, Jenny Chang-Claude, Rudolf Kaaks, Heiner Boeing, Françoise Clavel-Chapelon, Marina Kvaskoff, Laure Dossus, Antonia Trichopoulou, Vassiliki Benetou, George Adarakis, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Malin Sund, Anne Andersson, Signe Borgquist, Salma Butt, Elisabete Weiderpass, Guri Skeie, Kay-Tee Khaw, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Marc Gunter, Mai Kadi, Elio Riboli, Paolo Vineis and Carlotta Sacerdote

      Article first published online: 13 FEB 2015 | DOI: 10.1002/ijc.29462

      What's new?

      For the first time, researchers have used cohort data to show that people who survive breast cancer have a higher risk of developing another cancer later. By collecting data on 10,000 breast cancer patients over 11 years, these authors calculated a 30% boost in the patients' risk of developing a second primary malignancy, particularly colorectal cancer, lymphoma, melanoma, endometrial cancer, and kidney cancer. These findings, plus the data they collected on risk factors such as age, smoking, body mass index, and others, will help guide clinicians in screening procedures and follow up care for breast cancer patients.

  81. Early Detection and Diagnosis

    1. Diagnostic accuracy of VIA and HPV detection as primary and sequential screening tests in a cervical cancer screening demonstration project in India

      Partha Basu, Srabani Mittal, Dipanwita Banerjee, Priyanka Singh, Chinmay Panda, Sankhadeep Dutta, Ranajit Mandal, Pradip Das, Jaydip Biswas, Richard Muwonge and Rengaswamy Sankaranarayanan

      Article first published online: 12 FEB 2015 | DOI: 10.1002/ijc.29458

      Whats's new?

      Rather than conventional Pap-smear cytology, visual inspection after acetic acid application, or VIA, and human papillomavirus (HPV) detection tests have been recommended for screening women in low- and middle-income countries for cervical cancer. In this large demonstration project in India, the authors used both techniques, in order to compare their accuracy and to assess triaging scenarios. They found that triaging VIA-positive women with a hybrid capture II (HC-II) assay for HPV would considerably improve the positive predictive value, and allow detection of cervical cancers at an earlier, treatable stage.

  82. Epidemiology

    1. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

      Annika Steffen, José-Maria Huerta, Elisabete Weiderpass, H.B(as). Bueno-de-Mesquita, Anne M. May, Peter D. Siersema, Rudolf Kaaks, Jasmine Neamat-Allah, Valeria Pala, Salvatore Panico, Calogero Saieva, Rosario Tumino, Alessio Naccarati, Miren Dorronsoro, Emilio Sánchez-Cantalejo, Eva Ardanaz, J. Ramón Quirós, Bodil Ohlsson, Mattias Johansson, Bengt Wallner, Kim Overvad, Jytte Halkjær, Anne Tjønneland, Guy Fagherazzi, Antoine Racine, Françoise Clavel-Chapelon, Tim J. Key, Kay-Tee Khaw, Nick Wareham, Pagona Lagiou, Christina Bamia, Antonia Trichopoulou, Pietro Ferrari, Heinz Freisling, Yunxia Lu, Elio Riboli, Amanda J. Cross, Carlos A. Gonzalez and Heiner Boeing

      Article first published online: 9 FEB 2015 | DOI: 10.1002/ijc.29432

      What's new?

      While mainly general obesity, as measured by body mass index, has been investigated in relation to gastric and esophageal cancer, the effect of a large waist on these cancer sites is unknown. In this article, the authors report results of extensive analysis of measured anthropometry, including measures of general (BMI) and abdominal obesity (waist circumference), collected by the European Prospective Investigation into Cancer and Nutrition (EPIC). They show that general obesity is not a risk factor for esophageal and gastric cancer, while waist circumference strongly increases risk of esophageal cancer and may potentially be related to gastric cardia cancer.

  83. Mini Review

    1. The role of stromal fibroblasts in lung carcinogenesis: A target for chemoprevention?

      Jagdish Mahale, Gintare Smagurauskaite, Karen Brown, Anne Thomas and Lynne M. Howells

      Article first published online: 6 FEB 2015 | DOI: 10.1002/ijc.29447

  84. Epidemiology

    1. Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

      Katharina Nimptsch, Krasimira Aleksandrova, Heiner Boeing, Jürgen Janke, Young-Ae Lee, Mazda Jenab, So Yeon Kong, Konstantinos K. Tsilidis, Elisabete Weiderpass, Bas H. Bueno-De-Mesquita, Peter D. Siersema, Eugène H.J.M. Jansen, Antonia Trichopoulou, Anne Tjønneland, Anja Olsen, Chunsen Wu, Kim Overvad, Marie-Christine Boutron-Ruault, Antoine Racine, Heinz Freisling, Verena Katzke, Rudolf Kaaks, Pagona Lagiou, Dimitrios Trichopoulos, Gianluca Severi, Alessio Naccarati, Amalia Mattiello, Domenico Palli, Sara Grioni, Rosario Tumino, Petra H. Peeters, Ingrid Ljuslinder, Hanna Nyström, Jenny Brändstedt, María-José Sánchez, Aurelio Barricarte Gurrea, Catalina Bonet Bonet, María-Dolores Chirlaque, Miren Dorronsoro, José Ramón Quirós, Ruth C. Travis, Kay-Tee Khaw, Nick Wareham, Elio Riboli, Marc J. Gunter and Tobias Pischon

      Article first published online: 5 FEB 2015 | DOI: 10.1002/ijc.29448

      What's new?

      Fetuin-A is a liver protein associated with insulin resistance, but with no defined role yet in colorectal cancer. In this prospective study, the authors uncover a modest linear association between fetuin-A levels and higher risk of colorectal cancer, but this was only observed in male participants. In addition, no association was observed between fetuin-A variants and colorectal cancer risk in a Mendelian randomization analysis, arguing against a direct role of fetuin-A in colorectal carcinogenesis.

  85. Mini Review

    1. Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?

      Ji-Won Jung, Nana H. Overgaard, Michael T. Burke, Nicole Isbel, Ian H. Frazer, Fiona Simpson and James W. Wells

      Article first published online: 5 FEB 2015 | DOI: 10.1002/ijc.29450

  86. Cancer Cell Biology

    1. NOXIN as a cofactor of DNA polymerase-primase complex could promote hepatocellular carcinoma

      Zhuang-Zhuang Zhang, Jian Huang, Yu-Ping Wang, Bing Cai and Ze-Guang Han

      Article first published online: 5 FEB 2015 | DOI: 10.1002/ijc.29451

      What's new?

      DNA copy number amplification mechanism which contributes to the activation of oncogenesis one of the most common genetic aberrations found in human hepatocellular carcinoma (HCC). Here, the authors found that NOXIN overexpression, as a result of genomic DNA gain or amplification, promotes HCC tumorigenesis by accelerating DNA synthesis and cell cycle progression. The data also indicate that NOXIN functions as a cofactor of the DNA polymerase-primase complex by associating with DNA polymerase α. This study for the first time suggests NOXIN as a potential oncogene for HCC and provides new insight in how oncogenes may contribute to HCC.

  87. Epidemiology

    1. Overdiagnosis by mammographic screening for breast cancer studied in birth cohorts in The Netherlands

      T.M. Ripping, A.L.M. Verbeek, J. Fracheboud, H.J. de Koning, N.T. van Ravesteyn and M.J.M. Broeders

      Article first published online: 5 FEB 2015 | DOI: 10.1002/ijc.29452

      What's new?

      The extent of overdiagnosis of breast cancer associated with screening by mammography remains uncertain. The absence of ideal study cohorts is to blame, but an optimal quantitative secondary approach has also been lacking. Here, overdiagnosis was quantified from mammographic screening data in birth cohorts using an age-period-cohort model that included variables for multiple rounds of screening. The approach allowed the same women to be followed over time, thereby eliminating the possibility of overestimation. With the model, the estimated combined overdiagnosis of invasive breast cancer and ductal carcinoma in situ was found to range from 14% to 22%.

      Key words: mammographic screening, breast cancer, overdiagnosis, The Netherlands, birth cohort

  88. Letter to the Editor

    1. Authors' response to Letter to the Editor

      Manolis Kogevinas and Kyriaki Papantoniou

      Article first published online: 5 FEB 2015 | DOI: 10.1002/ijc.29460

  89. Cancer Therapy

    1. Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma

      Keun-Yeong Jeong, Eun-Jung Lee, Su Jin Kim, Seung-Hyun Yang, Young Chul Sung and Jinsil Seong

      Article first published online: 5 FEB 2015 | DOI: 10.1002/ijc.29428

      What's new?

      Mesenchymal stem cells (MSCs) are promising gene-delivery vehicles, with the potential to improve antitumor effects when used in combination with existing therapies. In the present study, the combined use of interleukin (IL)-12-expressing MSCs (MSCs/IL-12) and radiation therapy increased antitumor activity in murine metastatic hepatoma, a model that is representative of human metastatic hepatocellular carcinoma (HCC), which affects nearly half of HCC patients. Treatment with MSCs/IL-12 resulted in increased IL-12 expression in tumor cells and immune cell proliferation. Immune cell cytotoxicity, evidenced by increased apoptotic activity, appeared to play a role in MSCs/IL-12 augmentation of antitumor effects.


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