International Journal of Cancer

Cover image for Vol. 139 Issue 1

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

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

Impact Factor: 5.085

ISI Journal Citation Reports © Ranking: 2014: 31/211 (Oncology)

Online ISSN: 1097-0215


  1. 1 - 68
  1. Mini Reviews

    1. Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy

      Keiran S.M. Smalley, Inna V. Fedorenko, Rajappa S. Kenchappa, Solmaz Sahebjam and Peter A. Forsyth

      Article first published online: 30 APR 2016 | DOI: 10.1002/ijc.30147

  2. Cancer Epidemiology

    1. Irregular menses predicts ovarian cancer: Prospective evidence from the Child Health and Development Studies

      Piera M. Cirillo, Erica T. Wang, Marcelle I. Cedars, Lee-may Chen and Barbara A. Cohn

      Article first published online: 29 APR 2016 | DOI: 10.1002/ijc.30144

      What's new?

      The lack of specific early symptoms in ovarian cancer, aggressiveness of some of the histopathologic subtypes and need for more effective screening and treatment strategies are evidenced by a dismal 5-year survival rate for all stages. While several studies have reported ovarian cancer associations with menstrual cycle variability, the findings are inconsistent. This study provides the first prospective evidence that women with irregular menstrual cycles are at higher risk of ovarian cancer. Discovering high-risk phenotypes such as irregular menstruation creates opportunities to find novel early biomarkers, refine clinical screening protocols and potentially develop new risk reduction strategies for ovarian cancer.

  3. Infectious Causes of Cancer

    1. Clonal deleted latent membrane protein 1 variants of Epstein-Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment

      Mohamad Adnan Halabi, Arnaud Jaccard, Rémi Moulinas, Racha Bahri, Hazar Al Mouhammad, Nour Mammari, Jean Feuillard and Sylvie Ranger-Rogez

      Article first published online: 29 APR 2016 | DOI: 10.1002/ijc.30128

      What's new?

      Extranodal natural killer/T-cell lymphoma (NK/TL) is a rare and highly aggressive cancer. Epstein-Barr virus (EBV) has been found in all cases of NK/TL studied so far. In this study, the authors found that the EBV LMP1 gene contains a small deletion in all biopsies from European patients. In patients who achieved complete remission, however, the wild-type form of LMP1 became more common during treatment. Monitoring EBV strains may thus provide a useful tool for assessing treatment efficacy in NK/TL.

  4. Letters to the Editor

  5. Tumor Markers and Signatures

    1. MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer

      Emne Ali Abdallah, Marcello Ferretti Fanelli, Virgílio Souza, e Silva, Marcelo Calil Machado Netto, José Luiz Gasparini Junior, Daniel Vilarim Araújo, Luciana Menezes Mendonça Ocea, Marcilei Eliza Cavicchioli Buim, Milena Shizue Tariki, Vanessa da Silva Alves, Victor Piana de Andrade, Aldo Lourenço Abbade Dettino, Celso Abdon Lopes de Mello and Ludmilla Thomé Domingos Chinen

      Article first published online: 28 APR 2016 | DOI: 10.1002/ijc.30082

      What's new?

      Wouldn't it be nice to know right away when a patient's cancer becomes drug-resistant? New results suggest that a molecular marker, MRP1, on circulating tumor cells could provide just such a tip. These authors studied patients with metastatic colorectal cancer who were receiving irinotecan therapy. They tested the patients' circulating tumor cells for various marker proteins, and when the cells carried MRP1, irinotecan resistance was more likely.

  6. Cancer Therapy and Prevention

    1. Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

      Louise T. Thomsen, Christian Dehlendorff, Jette Junge, Marianne Waldstrøm, Doris Schledermann, Kirsten Frederiksen and Susanne K. Kjaer

      Article first published online: 26 APR 2016 | DOI: 10.1002/ijc.30104

      What's new?

      Testing for human papillomavirus (HPV) DNA in women with atypical squamous cells of undetermined significance (ASC-US) is widely implemented in cervical cancer screening, despite suboptimal specificity. An emerging alternative is HPV mRNA testing, though few prospective studies have compared HPV mRNA and DNA testing for ASC-US triage. Here, in a cohort of 13,729 women, a commercial mRNA test for five different HPV types was found to be more specific but far less sensitive for high-grade cervical intraepithelial neoplasia than widely used HPV DNA tests. The authors conclude that five-type HPV mRNA testing is not optimal for ASC-US triage.

  7. Cancer Epidemiology

    1. Is human herpesvirus 8 infection more common in men than in women? Systematic review and meta-analysis

      Lorin Begré, Eliane Rohner, Sam M. Mbulaiteye, Matthias Egger and Julia Bohlius

      Article first published online: 26 APR 2016 | DOI: 10.1002/ijc.30129

      What's new?

      All forms of Kaposi sarcoma are more common in men than in women but the association of gender with human herpesvirus 8 (HHV8) status is less clear. In this meta-analysis of existing data, the authors found that men from sub-Saharan Africa, where HHV-8 is endemic, were more likely to be HHV-8 seropositive than women. This association was only found in sub-Saharan Africa and did not apply to boys in the same region, raising the question of sexual transmission and hormonal status as additional factors in Kaposi sarcoma development.

    2. CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case–control study within a large-scale population-based prospective study

      Akihisa Hidaka, Shizuka Sasazuki, Keitaro Matsuo, Hidemi Ito, Hadrien Charvat, Norie Sawada, Taichi Shimazu, Taiki Yamaji, Motoki Iwasaki, Manami Inoue, Shoichiro Tsugane and for the JPHC Study Group

      Article first published online: 26 APR 2016 | DOI: 10.1002/ijc.30130

      What's new?

      The study of association between CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk was done in recent several meta-analyses. However, most individual studies are retrospective, and their sample sizes are small. Although neither gene–gene nor gene–environment interactions were significant, the CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population.

  8. Tumor Immunology and Microenvironment

    1. IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients

      Rushikesh Sudam Patil, Sagar Umesh Shah, Shailesh Vinayak Shrikhande, Mahesh Goel, Rajesh Prabhakar Dikshit and Shubhada Vivek Chiplunkar

      Article first published online: 26 APR 2016 | DOI: 10.1002/ijc.30134

      What's new?

      Human T cells expressing γδ-TCR exhibit potent anti-tumor activity and are potential candidates for cell-based therapies. Evidence however also exists of the ability of γδ-TCR cells to suppress anti-tumor responses, making deeper insight necessary for the successful clinical application of γδT cell-based immunotherapies. This study identified IL17-producing γδT cells (Tγδ17) as a pro-tumorigenic subtype of γδT cells associated with poor survival in gallbladder cancer (GBC) patients. Tγδ17 cells infiltrate the tumor bed via CXCL9-CXCR3 axis and IL17 induces pro-angiogenic factors in GBC cells. Tγδ17 may be considered as a predictive biomarker in GBC, opening up new avenues for targeted therapies.

  9. Cancer Therapy and Prevention

    1. Randomized phase II trial of TEGAFIRI (tegafur/uracil, oral leucovorin, irinotecan) compared with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) in patients with unresectable/recurrent colorectal cancer

      Kohei Shigeta, Hirotoshi Hasegawa, Koji Okabayashi, Masashi Tsuruta, Yoshiyuki Ishii, Takashi Endo, Hiroki Ochiai, Takayuki Kondo and Yuko Kitagawa

      Article first published online: 23 APR 2016 | DOI: 10.1002/ijc.30127

      What's new?

      This study was the first to evaluate the safety and efficacy of a new combination therapy called TEGAFIRI. This therapy combines one of the most common chemotherapy agents in Europe and Japan, the oral fluoropyramidine UFT/LV, and combines it with irinotecan. They compared TEGAFIRI with the combination of 5-FU/LV and irinotecan, called FOLFIRI, in patients with metastatic colorectal cancer who had not been treated before. They found no difference in progression-free survival between patients treated with either therapy. Further, they showed that the side effects of TEGAFIRI were no worse than those from FOLFIRI.

  10. Molecular Cancer Biology

    1. h-Prune is associated with poor prognosis and epithelial–mesenchymal transition in patients with colorectal liver metastases

      Masakazu Hashimoto, Tsuyoshi Kobayashi, Hirotaka Tashiro, Koji Arihiro, Akira Kikuchi and Hideki Ohdan

      Article first published online: 21 APR 2016 | DOI: 10.1002/ijc.30118

      What's new?

      Once colorectal cancer spreads to the liver, it becomes much more deadly, despite advances in treatment. Could there be a way to predict survival for these cancers? These authors investigated the protein h-prune, which is associated with tumor aggressiveness. When they analyzed specimens of colorectal liver tumor metastases, they found h-prune in 28% of cases, and these had poorer survival than patients whose tumors lacked h-prune. In cell culture, h-prune promoted cell motility and boosted production of proteins involved in metastasis, while in mice it increased tumor invasiveness. Thus, h-prune could be a valuable prognostic tool or therapeutic target.

  11. Tumor Markers and Signatures

    1. Elevated expression of the centromere protein-A(CENP-A)-encoding gene as a prognostic and predictive biomarker in human cancers

      Xia Sun, Pier-Luc Clermont, Wenlin Jiao, Cheryl D. Helgason, Peter W. Gout, Yuzhuo Wang and Sifeng Qu

      Article first published online: 21 APR 2016 | DOI: 10.1002/ijc.30133

      What's new?

      Elevated expression of Centromere protein-A (CENP-A), a histone-H3 variant with a regulatory role in cell division, has been associated with cancer progression. Using publicly available databases, this study demonstrates that elevated CENP-A expression is coupled to malignant progression of numerous types of cancer. In particular, it can be used as a critically needed biomarker for (i) poor patient prognosis and (ii) predicting the response of breast cancer patients to taxane-based chemotherapy.

  12. Cancer Epidemiology

    1. Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden

      Caroline Simberg-Danell, Johan Lyth, Eva Månsson-Brahme, Margareta Frohm-Nilsson, John Carstensen, Johan Hansson and Hanna Eriksson

      Article first published online: 19 APR 2016 | DOI: 10.1002/ijc.30103

      What's new?

      Little is known about cutaneous malignant melanoma and its prognosis among immigrants in Europe. This study aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. The results demonstrate that higher disease stage at diagnosis and nodular melanoma subtype were associated with melanoma in immigrants from Southern Europe. The melanoma-specific survival was significantly decreased among women from former Yugoslavia compared to Swedish-born women. Overall, however, the melanoma-specific survival did not differ significantly between Swedish-born patients and foreign-born patients or second generation immigrants. This information may improve prevention and early detection-programs.

  13. Molecular Cancer Biology

    1. RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy

      Hiroki Osumi, Eiji Shinozaki, Mitsukuni Suenaga, Satoshi Matsusaka, Tsuyoshi Konishi, Takashi Akiyoshi, Yoshiya Fujimoto, Satoshi Nagayama, Yosuke Fukunaga, Masashi Ueno, Yoshihiro Mise, Takeaki Ishizawa, Yosuke Inoue, Yu Takahashi, Akio Saiura, Hirohumi Uehara, Mingyon Mun, Sakae Okumura, Nobuyuki Mizunuma, Yoshio Miki and Toshiharu Yamaguchi

      Article first published online: 19 APR 2016 | DOI: 10.1002/ijc.30106

      What's new?

      Previous studies have demonstrated a relationship between clinical outcomes following curative resection for colorectal cancer and gene mutations of the EGFR pathway. However, so far no studies have focused on metastatic colorectal cancer (mCRC) patients with metastasectomy. The aim of this study was thus to evaluate the relationship between gene mutations of the EGFR pathway and clinical outcomes following metastasectomy in mCRC patients. The results show that RAS mutation predicts shorter overall survival after metastasectomy in patients with metastatic colorectal cancer. No association between recurrence free survival and gene mutation of the EGFR pathway was observed.

  14. Cancer Epidemiology

    1. Changes over time in the impact of gene-expression profiles on the administration of adjuvant chemotherapy in estrogen receptor positive early stage breast cancer patients: A nationwide study

      A. Kuijer, C.A. Drukker, S.G. Elias, C.H. Smorenburg, E.J. Th. Rutgers, S. Siesling and Th. van Dalen

      Article first published online: 19 APR 2016 | DOI: 10.1002/ijc.30132

      What's new?

      In the Netherlands, gene-expression profiling was introduced in 2004 to help guide decisions about the administration of adjuvant chemotherapy in patients with early-stage estrogen receptor-positive breast cancer. Since then, indications for adjuvant chemotherapy have broadened beyond the results of gene-expression profiling to include the majority of early-stage breast cancer patients. This study shows that since 2004, the number of Dutch patients eligible for adjuvant chemotherapy has increased by 13 percent. Despite broader clinical guidelines, however, over time gene-expression profile use appears to be associated with more consistent use of adjuvant chemotherapy and high adherence rates.

    2. Patients' perceptions of mortality risk for localized prostate cancer vary markedly depending on their treatment strategy

      Friederike Kendel, Lukas Helbig, Konrad Neumann, Jan Herden, Carsten Stephan, Mark Schrader and Wolfgang Gaissmaier

      Article first published online: 19 APR 2016 | DOI: 10.1002/ijc.30123

      What's new?

      Patients with localized prostate cancer typically must choose between invasive treatments, like radical prostatectomy (RP), and less-invasive strategies, including active surveillance (AS). It is probable that the strategy chosen is the one patients think is most likely to minimize risk of death. However, communicating risk probabilities to patients is a great challenge. Here, men on AS and after RP were asked to rate the risk of dying from localized prostate cancer. The results show that all men, irrespective of the chosen treatment, overestimated prostate cancer mortality risk by 20–50 absolute percentage points. The findings indicate a need for better patient education.

    3. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study

      Jianguang Ji, Bengt Zöller, Jan Sundquist and Kristina Sundquist

      Article first published online: 19 APR 2016 | DOI: 10.1002/ijc.30126

      What's new?

      Several microRNAs located on the human X chromosome have roles in cancer, suggesting that abnormalities in X chromosome number or structure can affect cancer risk. This longitudinal study in Sweden explored the risk of solid and hematological malignancy in women with Turner syndrome (X chromosome monosomy) and men with Klinefelter syndrome (two or more X chromosomes). Solid tumor incidence was increased in Turner syndrome patients but decreased in patients with Klinefelter syndrome. Though the mechanism remains unknown, the posited role of X chromosome disorders in solid tumor etiology may be associated with the loss or dysfunction of immune-related genes.

    4. Trends in oral cavity cancer incidence, mortality, survival and treatment in the Netherlands

      Boukje A.C. van Dijk, Marieke T. Brands, Sandra M.E. Geurts, Matthias A.W. Merkx and Jan L.N. Roodenburg

      Article first published online: 18 APR 2016 | DOI: 10.1002/ijc.30107

      What's new?

      Many studies have analyzed the epidemiology of “head and neck cancer”—or of “oral and oropharyngeal cancer”—combined. However, these categories are heterogeneous with regard to aetiology, treatment, and prognosis. In this Dutch study, the authors analyzed specific incidence, mortality and relative survival rates for oral cavity cancer (OCC). They found an increase in OCC incidence as well as mortality, while mortality rates have declined for most other cancers. The increasing incidence and intensive follow-up required for oral cavity cancer will be a challenge to future health care resources.

    5. Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?

      Marcin R. Lener, Rodney J. Scott, Wojciech Kluźniak, Piotr Baszuk, Cezary Cybulski, Anna Wiechowska-Kozłowska, Tomasz Huzarski, Tomasz Byrski, Józef Kładny, Sandra Pietrzak, Agnieszka Soluch, Anna Jakubowska and Jan Lubiński

      Article first published online: 18 APR 2016 | DOI: 10.1002/ijc.30116

      What's new?

      The genetic and molecular mechanisms that lead to pancreatic cancer are still poorly understood. In this study, the authors examined founder mutations that are known to be associated with several types of cancer in Poland. They found that a particular mutation in NBS1 was associated with a significant increase in the risk of pancreatic cancer. Screening for this mutation may therefore help identify people who are at risk for pancreatic cancer in Poland and probably other Slavic populations.

  15. Cancer Therapy and Prevention

    1. First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors

      Caterina Vivaldi, Chiara Caparello, Gianna Musettini, Giulia Pasquini, Silvia Catanese, Lorenzo Fornaro, Monica Lencioni, Alfredo Falcone and Enrico Vasile

      Article first published online: 18 APR 2016 | DOI: 10.1002/ijc.30125

      What's new?

      Standard first-line therapy for advanced pancreatic cancer centers on FOLFIRINOX, a combination regimen using 5-fluorouracil, irinotecan, oxaliplatin, and gemcitabine plus nabpaclitaxel. The regimen's increased adverse effects, however, warrant investigation of alternative drug combinations. Here, modified Gruppo Oncologico Nord Ovest FOLFOXIRI (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) was found to produce survival results similar to those of FOLFIRINOX in patients with pancreatic cancer. The modified FOLFOXIRI regimen also compared favorably with FOLFIRINOX in terms of gastrointestinal adverse events. Prognostic factors were identified, enabling FOLFOXIRI-treated patients to be stratified into subgroups with different survival outcomes.

  16. Mini Review

    1. Molecular basis and current strategies of therapeutic arginine depletion for cancer

      Livingstone Fultang, Ashley Vardon, Carmela De Santo and Francis Mussai

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30051

  17. Molecular Cancer Biology

    1. Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer

      Andreas Seeber, Gerold Untergasser, Gilbert Spizzo, Luigi Terracciano, Alessandro Lugli, Armin Kasal, Florian Kocher, Normann Steiner, Guido Mazzoleni, Guenther Gastl and Dominic Fong

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30099

      What's New?

      Two novel cell-adhesion molecules, the full-length variant EpCAMMF and the truncated variant EpCAMMT, which is characterized by proteolytic cleavage of the EpCAM intracellular domain (EpICD), were recently identified on the membrane of human epithelial tumor cells. EpICD loss at the membrane is correlated with poor prognosis in pancreatic and breast cancers. Whether EpCAMMT expression, which possibly leads to EpICD loss, similarly influences tumor behavior, however, is unknown. The authors of the present study investigated the expression of EpCAMMF and EpCAMMT in colorectal cancer patients. The findings reveal an association between EpCAMMT expression, aggressive tumor behavior, and poor outcome in colorectal cancer.

  18. Cancer Epidemiology

    1. Epidemiologic evidence of slow growing, nonprogressive or regressive breast cancer: A systematic review

      Nereo Segnan, Silvia Minozzi, Paola Armaroli, Michela Cinquini, Cristina Bellisario, Marien González-Lorenzo, Silvia Gianola and Antonio Ponti

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30105

      What's new?

      The advance of breast cancer (BC) care depends heavily on mitigating overdiagnosis and overtreatment. However, reaching that goal requires greater understanding of the natural history of BC, including the occurrence and features of slowly developing breast tumors. Here, a summary of data from the literature on regressing or not progressing BCs suggests that numerous clinically insignificant ductal lesions are included among ductal carcinoma in situ BCs. Furthermore, about 10% of invasive BCs remain asymptomatic during life, being detected only on autopsy, and about 20% of patients, left untreated, would survive five years after diagnosis.

  19. Mini Reviews

  20. Cancer Epidemiology

    1. Smoking in pregnancy and risk of cancer among young children: A population-based study

      Julia E. Heck, Zuelma A. Contreras, Andrew S. Park, Tom B. Davidson, Myles Cockburn and Beate Ritz

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30111

      What's New?

      Women who smoke during pregnancy may be putting their unborn offspring at risk of childhood cancer, though few prospective population-based studies have explored the relationship. The authors of the present study aligned data on childhood cancers recorded in the California Cancer Registry with information on maternal smoking status obtained from medical record review. Maternal smoking was positively associated with retinoblastoma and glial tumors. A slight increase in risk of astrocytoma was also observed. For gliomas, the risk from maternal smoking was similar across trimesters, whereas risk for retinoblastoma increased steadily from one trimester to the next.

    2. Obesity, weight gain, and ovarian cancer risk in African American women

      Elisa V. Bandera, Bo Qin, Patricia G. Moorman, Anthony J. Alberg, Jill S. Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, Ellen Funkhouser, Edward S. Peters, Ann G. Schwartz, Paul Terry and Joellen M. Schildkraut

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30115

      What's new?

      While obesity can raise a woman's risk for certain types of cancer, menopausal status and hormone therapy significantly influence those associations. Moreover, in the case of ovarian cancer, racial/ethnic associations may also be at play, though links with adiposity remain obscure for African American women, a group disproportionately affected by obesity in the United States. Here, analyses of data from the U.S. population-based African American Cancer Epidemiology Study reveal a strong association between high adiposity and increased ovarian cancer risk, particularly among postmenopausal women. The findings highlight the importance of weight control in reducing ovarian cancer risk among African American women.

  21. Cancer Therapy and Prevention

    1. A novel approach for targeted elimination of CSPG4-positive triple-negative breast cancer cells using a MAP tau-based fusion protein

      Manal Amoury, Radoslav Mladenov, Thomas Nachreiner, Anh-Tuan Pham, Dmitrij Hristodorov, Stefano Di Fiore, Wijnand Helfrich, Alessa Pardo, Georg Fey, Michael Schwenkert, Theophilus Thepen, Fabian Kiessling, Ahmad F. Hussain, Rainer Fischer, Katharina Kolberg and Stefan Barth

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30119

      What's New?

      New therapies for triple-negative breast cancer (TNBC) are urgently needed. It would be ideal if such a therapy could specifically target TNBC cells. In this study, the authors engineered a fusion protein composed of an antibody fragment that binds to TNBC cells, plus a protein called MAP tau that kills these proliferating cells. This cytolytic fusion protein caused tumor regression in mice carrying human TNBC tumors. These results indicate that this novel molecule may be a promising immunotherapy for TNBC.

  22. Tumor Immunology and Microenvironment

    1. Induction of antigen-specific TH9 immunity accompanied by mast cell activation blocks tumor cell engraftment

      Aws Abdul-Wahid, Marzena Cydzik, Aaron Prodeus, Mays Alwash, Mile Stanojcic, Megan Thompson, Eric H.-B. Huang, John E. Shively, Scott D. Gray-Owen and Jean Gariépy

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30121

      What's new?

      The vast majority of cancer deaths are the result of metastasis, yet the integration of circulating tumor cells at sites distant from the tumor of origin remains largely unexplored from the view of therapeutics. A vaccine capable of neutralizing circulating tumor cells, however, could be key to preventing or delaying metastasis, according to this study. A carcinoembryonic antigen (CEA)-based vaccine with a focused response against the IgV-like N domain successfully generated a CEA-specific TH9 response that blocked the establishment of metastatic tumor nodules in mice. This alternate tumor-eradication mechanism could aid the development of metastasis-preventing immunotherapies.

  23. Cancer Epidemiology

    1. Sex hormones and the risk of keratinocyte cancers among women in the United States: A population-based case–control study

      Lawrence F. Kuklinski, Michael S. Zens, Ann E. Perry, Anala Gossai, Heather H. Nelson and Margaret R. Karagas

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30072

      What's new?

      Rates of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) appear to be rising faster in women than in men. The question is, why? In this study, the authors found that both oral contraception (OC) and hormone replacement therapy (HRT) were associated with an increased risk of these keratinocyte cancers, as well as with more aggressive subtypes of BCC. These results suggest that careful surveillance and early identification of skin lesions is especially important among women who have used synthetic sex steroids

  24. Cancer Therapy and Prevention

    1. Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer

      Ping Wang, Byunghee Yoo, Sarah Sherman, Pinku Mukherjee, Alana Ross, Pamela Pantazopoulos, Victoria Petkova, Christian Farrar, Zdravka Medarova and Anna Moore

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30098

      What's new?

      During treatment, cancer cells often undergo molecular changes long before tumor morphology changes. Biomarkers to detect these changes could enhance therapy by allowing earlier analysis. In this study in mice, the authors developed a non-invasive technique for imaging cellular levels of the tumor antigen uMUC1, which is overexpressed in more than 50% of all cancers. They found that uMUC1 expression drops when pancreatic cancer begins to respond to therapy. This imaging technique may allow the early assessment of tumor response and prognosis.

  25. Cancer Epidemiology

    1. Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda

      Silvia Franceschi, M. Chantal Umulisa, Ugyen Tshomo, Tarik Gheit, Iacopo Baussano, Vanessa Tenet, Tshokey Tshokey, Maurice Gatera, Fidele Ngabo, Pierre Van Damme, Peter J.F. Snijders, Massimo Tommasino, Alex Vorsters and Gary M. Clifford

      Article first published online: 15 APR 2016 | DOI: 10.1002/ijc.30092

      What's New?

      The self-collection of urine for human papillomavirus (HPV) testing is a potential alternative to cervical sampling for the monitoring of HPV prevalence and HPV vaccination effectiveness in women. The present study indicates that urine surveys could be especially useful in Bhutan and Rwanda, which were among the first countries in Asia and Africa to implement school-based HPV vaccination programmes. First-void urine samples yielded evidence for lower prevalence of HPV types 6, 11, 16, and 18 in vaccinated versus unvaccinated female students ages 18 to 20. Women in this age group often are reluctant to undergo examination for cervical cytology.

    2. Analgesic use and risk of renal cell carcinoma: A case-control, cohort and meta-analytic assessment

      Sara Karami, Sarah E. Daughtery, Kendra Schwartz, Faith G. Davis, Julie J. Ruterbusch, Sholom Wacholder, Barry I. Graubard, Sonja I. Berndt, Jonathan N. Hofmann, Mark P. Purdue, Lee E. Moore and Joanne S. Colt

      Article first published online: 9 APR 2016 | DOI: 10.1002/ijc.30108

      What's new?

      Analgesics, taken for pain relief or to reduce fever, are the most commonly consumed medications in the world. Could these drugs influence the risk of kidney cancer? This paper examined the effect of aspirin, acetaminophen and non-aspirin NSAIDs on renal cell carcinoma risk. The authors analyzed data from a case-control study and a cohort study, as well as a meta-analytic review. Findings for aspirin and NSAIDs use were null; but, acetaminophen use was associated with increased RCC risk.

    3. The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations

      Hyuna Sung, Philip S. Rosenberg, Wan-Qing Chen, Mikael Hartman, Wei-yen Lim, Kee Seng Chia, Oscar Wai-Kong Mang, Lapah TSE, William F. Anderson and Xiaohong R. Yang

      Article first published online: 9 APR 2016 | DOI: 10.1002/ijc.30095

      What's new?

      Increasing breast cancer risk among Asian women can be explained by birth cohort effects, though trends by age in multiple populations have not been fully described or formally tested. Here, standard descriptive epidemiology and age-period-cohort comparative analyses show that rising cohort-specific breast cancer rates in Chinese populations reduced the historical gap in breast cancer incidence between Chinese women and U.S. non-Hispanic white women. The most rapid increase was observed in regions and age groups with the lowest baseline rates. The findings suggest that Westernization-related risk factors differentially influence breast cancer risk in populations of older and younger Chinese women.

  26. Cancer Therapy and Prevention

    1. The clinical value of HPV genotyping in triage of women with high-risk-HPV-positive self-samples

      Renée M.F. Ebisch, Gabriëlle M. de Kuyper–de Ridder, Remko P. Bosgraaf, Leon F.A.G. Massuger, Joanna IntHout, Viola M.J. Verhoef, Daniëlle A.M. Heideman, Peter J.F. Snijders, Chris J.L.M. Meijer, Folkert J. van Kemenade, Johan Bulten, Albert G. Siebers, Ruud L.M. Bekkers and Willem J.G. Melchers

      Article first published online: 7 APR 2016 | DOI: 10.1002/ijc.30090

      What's new?

      Western countries increasingly consider testing for an infection with a high-risk human papilloma virus (HPV) as primary cervical cancer screening method, and replace conventional cytology. However, high-risk HPV testing cannot distinguish between transient and persistent infections, and a triage strategy is therefore necessary. Here the authors show that triage of hrHPV positive women by cytology testing can be improved by adjusting its threshold and combining it with genotyping of high-risk HPV16/18.

    2. Invention of a novel photodynamic therapy for tumors using a photosensitizing PI3K inhibitor

      Yushi Hayashida, Yuka Ikeda, Koichi Sawada, Katsuhisa Kawai, Takuma Kato, Yoshiyuki Kakehi and Nobukazu Araki

      Article first published online: 6 APR 2016 | DOI: 10.1002/ijc.30097

      What's new?

      Photodynamic therapy is an alternative cancer treatment modality in which patients are administered a photosensitizing drug that preferentially accumulates in tumor cells. Here, using live-cell imaging, the authors demonstrate that XL147-treated PC3 prostate cancer cells are rapidly injured by 430 nm light illumination. New anticancer drug XL147 has previously been developed as a pan-class I PI3K inhibitor. Marked reactive oxygen species (ROS) production was found in the cytoplasm of XL147-treated PC3 prostate cancer cells when illuminated, suggesting such XL147 cytotoxicity may be attributed to ROS. This study will potentially open up new possibilities for photodynamic therapy using existing anticancer drugs.

  27. Cancer Epidemiology

    1. Polymorphisms in DNA repair genes, traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence

      Irina Mordukhovich, Jan Beyea, Amy H. Herring, Maureen Hatch, Steven D. Stellman, Susan L. Teitelbaum, David B. Richardson, Robert C. Millikan, Lawrence S. Engel, Sumitra Shantakumar, Susan E. Steck, Alfred I. Neugut, Pavel Rossner Jr., Regina M. Santella and Marilie D. Gammon

      Article first published online: 6 APR 2016 | DOI: 10.1002/ijc.30079

      What's new?

      Polycyclic aromatic hydrocarbons are known carcinogens generated by vehicular traffic. They damage DNA by forming adducts or inducing oxidative stress. Here the authors examined the association between traffic exposure and breast cancer incidence while taking into account different DNA repair genotypes. Cancer risks were elevated in women carrying certain DNA repair variants especially when some variants were combined. These findings may help identify women who are particularly susceptible to the carcinogenic effects of traffic pollution on the breast.

  28. Tumor Markers and Signatures

    1. Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging

      Nobuhiko Onda, Masayuki Kimura, Toshinori Yoshida and Makoto Shibutani

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30102

      What's new?

      Near-infrared fluorescence imaging with indocyanine green (ICG) is a valuable approach to cancer detection and can potentially facilitate the complete removal of tumor tissue during surgery. Little is known, however, about the cellular mechanism underlying ICG-based tumor visualization. Here, tumor imaging by ICG is linked to nonspecific tissue delivery with subsequent preferential uptake and retention of the agent by tumor cells. Preferential uptake was associated with ICG cell membrane-binding and the expanded role of clathrin-dependent endocytosis in tumor cells. The findings suggest that the clinical utility of tumor imaging by ICG is based on elevated endocytic activity.

  29. Cancer Epidemiology

    1. Is the prevalence of colonic neuroendocrine tumors increased in patients with inflammatory bowel disease?

      Lauranne A.A.P. Derikx, Wouter-Michiel A.M. Vierdag, Wietske Kievit, Steven Bosch, Frank Hoentjen and Iris D. Nagtegaal

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30096

      What's new?

      Patients with inflammatory bowel disease (IBD) may bear an increased risk to develop neuroendocrine tumors (NET). In this study, we determined a NET prevalence rate ratio (PRR) between 2.8 and 4.1 for IBD patients compared to the general population. Higher NET PRR were found for other patients who frequently undergo gastrointestinal surgery compared with IBD (diverticulitis, odds ratio 5.52; ischemia, odds ratio 1.97). This suggests that the increased NET prevalence for IBD compared with the general population might be attributed to a high rate of incidental NET identified during surgery.

  30. Tumor Markers and Signatures

    1. Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma

      Casey J. Rowe, Fiona Tang, Maria Celia B. Hughes, Mathieu P. Rodero, Maryrose Malt, Duncan Lambie, Andrew Barbour, Nicholas K. Hayward, B. Mark Smithers, Adele C. Green and Kiarash Khosrotehrani

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30085

      What's new?

      Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics, and carries rare but significant morbidity. In a study based on a cohort of melanoma patients with locally advanced disease, the authors show that the use of clinicopathological factors and established routine and accessible immunohistochemical markers can be combined in a score that is highly predictive of melanoma prognosis. This score remained highly predictive in sentinel lymph node negative patients, suggesting its potential to be applied in a clinical setting immediately.

  31. Cancer Epidemiology

    1. The relationship between cancer incidence, stage and poverty in the United States

      Francis P. Boscoe, Kevin A. Henry, Recinda L. Sherman and Christopher J. Johnson

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30087

      What's new?

      How does poverty impact cancer diagnoses? New data indicates that people living in poverty are more likely to be diagnosed with later-stage cancer. Building on previous studies of socioeconomic status and cancer, this study adds information about cancer stage at diagnosis. The authors show that in poorer populations, more cancers are diagnosed at later stages, while affluent populations get many more early-stage diagnoses. Reducing poverty, then, should help reduce the number of late-stage, less treatable cancers.

  32. Research Articles

    1. Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases

      Inger Marie Løes, Heike Immervoll, Halfdan Sorbye, Jon-Helge Angelsen, Arild Horn, Stian Knappskog and Per Eystein Lønning

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30089

      What's new?

      Preliminary evidence suggests that poor outcome after liver resection in metastatic colorectal cancer (CRC) is predicted by mutations in KRAS and BRAF and by intra-individual heterogeneity involving copy number alterations that vary from one metastatic lesion to the next. Little is known, however, about the clinical implications of intra-individual mutation heterogeneity in CRC. Here, in a comparison of KRAS and BRAF wild-type status, mutational homogeneity, and mutational heterogeneity, mutation heterogeneity was found to be the strongest predict or of reduced disease-specific survival following liver resection in metastatic CRC. Knowledge of intra-individual mutation heterogeneity in KRAS and BRAF in CRC could facilitate therapeutic decisions.

  33. Mini Reviews

    1. ALDH1A3, a metabolic target for cancer diagnosis and therapy

      Jiang-Jie Duan, Jiao Cai, Yu-Feng Guo, Xiu-Wu Bian and Shi-Cang Yu

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30091

  34. Infectious Causes of Cancer

    1. Antibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men

      Huachun Zou, Sepehr N. Tabrizi, Andrew E. Grulich, Jane S. Hocking, Suzanne M. Garland, Catriona S. Bradshaw, Alyssa M. Cornall, Christopher K. Fairley and Marcus Y. Chen

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30093

      What's new?

      Antibody responses can protect from repeat infections with high-risk human papilloma virus (HPV), but their development after anal infection is less well studied. Here the authors examine HPV antibody responses (genotypes 6, 11, 16 and 18) following incident anal or penile infection within a cohort of teenage men who have sex with men in the very early stages of their sexual careers. The data uncover different likelihoods for antibody responses depending on viral genotype and the site of infection.

  35. Cancer Epidemiology

    1. Colorectal cancer risk and nitrate exposure through drinking water and diet

      Nadia Espejo-Herrera, Esther Gràcia-Lavedan, Elena Boldo, Nuria Aragonés, Beatriz Pérez-Gómez, Marina Pollán, Antonio J. Molina, Tania Fernández, Vicente Martín, Carlo La Vecchia, Cristina Bosetti, Alessandra Tavani, Jerry Polesel, Diego Serraino, Inés Gómez Acebo, Jone M. Altzibar, Eva Ardanaz, Rosana Burgui, Federica Pisa, Guillermo Fernández-Tardón, Adonina Tardón, Rosana Peiró, Carmen Navarro, Gemma Castaño-Vinyals, Victor Moreno, Elena Righi, Gabriella Aggazzotti, Xavier Basagaña, Mark Nieuwenhuijsen, Manolis Kogevinas and Cristina M. Villanueva

      Article first published online: 4 APR 2016 | DOI: 10.1002/ijc.30083

      What's new?

      Nitrate ingested in food and water can react with amines and amides in the gastrointestinal tract, leading to the formation of N-nitroso compounds (NOCs), which are carcinogenic in animals. In humans, nitrate and several NOCs are probable carcinogens. The aim of the present investigation, a case–control study in Europe, was to examine links between nitrate intake and colorectal cancer (CRC). The findings indicate that CRC risk is increased for waterborne nitrate intake at levels below current international guidelines, particularly in subgroups with other risk factors. Nitrate intake from animal sources was further associated with increased rectal cancer risk.

    2. You have full text access to this OnlineOpen article
      Lung cancer in never smokers in the UK Million Women Study

      Kirstin Pirie, Richard Peto, Jane Green, Gillian K. Reeves, Valerie Beral and for the Million Women Study Collaborators

      Article first published online: 31 MAR 2016 | DOI: 10.1002/ijc.30084

      What's new?

      What causes lung cancer in people who don't smoke? Because it's rare, researchers have a hard time teasing out exactly what factors contribute. Thanks to the Million Women Study, these authors were able to collect data from more than 634,000 women who had never smoked, of whom 1469 (0.2%) developed lung cancer. They analyzed 34 different characteristics, including lifestyle, medical, and socioeconomic factors, in relation to lung cancer status. Of the 34 risk factors, 3 showed a statistical connection with lung cancer: non-white race, taller stature, and asthma requiring treatment.

    3. You have full text access to this OnlineOpen article
      Cause-specific long-term mortality in survivors of childhood cancer in Switzerland: A population-based study

      Matthias Schindler, Ben D. Spycher, Roland A. Ammann, Marc Ansari, Gisela Michel, Claudia E. Kuehni and for the Swiss Paediatric Oncology Group (SPOG)

      Article first published online: 30 MAR 2016 | DOI: 10.1002/ijc.30080

      What's new?

      As survivors of childhood cancer age, they are more likely to die prematurely than their peers. The causes of early death, however, are not fully understood, particularly for recently diagnosed children, who may benefit from newer treatment strategies. This study shows that for at least three decades after diagnosis, childhood cancer survivors suffer increased mortality. Disease recurrence initially accounts for the greatest proportion of deaths but is supplanted over time by late treatment-related toxicities, including second cancers. The findings draw attention to the significance of lifelong follow-up among survivors of childhood cancer, especially for high-risk individuals.

  36. Cancer Genetics and Epigenetics

    1. Characterization of functionally active gene fusions in human papillomavirus related oropharyngeal squamous cell carcinoma

      Theresa Guo, Daria A. Gaykalova, Michael Considine, Sarah Wheelan, Aparna Pallavajjala, Justin A Bishop, William H. Westra, Trey Ideker, Wayne M Koch, Zubair Khan, Elana J. Fertig and Joseph A. Califano

      Article first published online: 30 MAR 2016 | DOI: 10.1002/ijc.30081

      What's new?

      The Cancer Genome Atlas (TCGA), a national sequencing project to investigate genetic changes in cancer, predicted the presence of nearly 14,000 gene fusion events in head and neck squamous cell carcinoma (HNSCC). Now, a major challenge is to determine which of those fusions are functionally relevant. Here, in an independent cohort of human papillomavirus (HPV)-positive oropharyngeal SCCs, some 282 gene fusions, 10 of which overlapped with previous TCGA findings, were identified by RNA sequencing. While fusions were limited to a small number of tumors, fusion-associated changes in gene expression were pervasive. Moreover, gene expression analyses illuminated potential functional roles for identified fusions.

    2. Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 9q22.33 and 14q13.3 detects novel candidate functional SNPs in Europeans from metropolitan France and Melanesians from New Caledonia

      Catherine Tcheandjieu, Fabienne Lesueur, Marie Sanchez, Dominique Baron-Dubourdieu, Anne-Valerie Guizard, Claire Mulot, Pierre Laurent-Puig, Claire Schvartz, Therese Truong and Pascal Guenel

      Article first published online: 30 MAR 2016 | DOI: 10.1002/ijc.30088

      What's new?

      People of Melanesian descent in the South Pacific have an especially high risk of differentiated thyroid cancer (DTC). Certain genetic loci are thought to increase DTC risk. In this case-control, SNP fine-mapping study, the authors compared those candidate loci in Europeans and Melanesians in France and New Caledonia. They found that certain novel SNP variants may be worth investigating further for their role in DTC risk.

  37. Cancer Epidemiology

    1. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women

      Yang Yang, Jing Gao, Hong-Lan Li, Wei Zheng, Gong Yang, Wei Zhang, Xiao Ma, Yu-Ting Tan, Nathaniel Rothman, Yu-Tang Gao, Wong-Ho Chow, Xiao-Ou Shu and Yong-Bing Xiang

      Article first published online: 30 MAR 2016 | DOI: 10.1002/ijc.30086

      What's new?

      Hepatitis B surface antigen (HBsAg) is a hallmark of infection with hepatitis B virus, the chronic presence of which greatly increases a person's risk of liver cancer. Serum titers of HBsAg vary markedly between individuals, however, and it remains uncertain whether different HBsAg levels are associated with liver cancer risk. In this study of male and female population-based cohorts in Shanghai, China, a positive dose-response relationship was observed between HBsAg levels and liver cancer risk. Risk increased most steeply in men, such that men with high HBsAg titers were most likely to develop liver cancer.

  38. Cancer Therapy and Prevention

    1. Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer

      Sujit K. Bhutia, Birendra Behera, Durgesh Nandini Das, Subhadip Mukhopadhyay, Niharika Sinha, Prashanta Kumar Panda, Prajna Paramita Naik, Samir K. Patra, Mahitosh Mandal, Siddik Sarkar, Mitchell E. Menezes, Sarmistha Talukdar, Tapas K. Maiti, Swadesh K. Das, Devanand Sarkar and Paul B. Fisher

      Article first published online: 30 MAR 2016 | DOI: 10.1002/ijc.30055

      What's new?

      The growing need for new drugs to combat cancer has been paralleled by increasing interest in the clinical potential of natural products. Among those products are plant lectins, several of which have been shown in preclinical studies to have potent antitumor effects. The present paper suggests that the plant lectin Abrus agglutinin (AGG) can be added to that list of naturally occurring, potent cancer-fighting substances. In human breast cancer cells, AGG promoted apoptosis and exerted anti-angiogenic effects. Its antitumor activity was associated with AKT-dependent ROS generation and with inhibition of IGFBP-2, a pro-angiogenic factor.

  39. Tumor Markers and Signatures

    1. Nuclear expression of Y-box binding protein-1 is associated with poor prognosis in patients with pancreatic cancer and its knockdown inhibits tumor growth and metastasis in mice tumor models

      Kentaro Shinkai, Kenji Nakano, Lin Cui, Yusuke Mizuuchi, Hideya Onishi, Yoshinao Oda, Satoshi Obika, Masao Tanaka and Mitsuo Katano

      Article first published online: 29 MAR 2016 | DOI: 10.1002/ijc.30075

      What's New?

      The objective of this study was to investigate the possible implication of Y-box-binding protein-1 (YB-1) in the aggressiveness and prognosis of pancreatic ductal adenocarcinoma (PDAC) and its potential as a therapeutic target. The results suggest a correlation between nuclear YB-1 expression and poor prognosis. The involvement of YB-1 signaling in tumor growth and PDAC invasiveness was verified by in vitro and in vivo experiments using RNAi manipulation. This study for the first time demonstrates that YB-1 may contribute to the aggressive characteristics and unfavorable outcomes of PDAC, with YB-1-targeting emerging as a potential therapy against the refractory disease.

  40. Tumor Immunology and Microenvironment

    1. Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

      Lorena Consolino, Dario Livio Longo, Walter Dastrù, Juan Carlos Cutrin, Daniela Dettori, Stefania Lanzardo, Salvatore Oliviero, Federica Cavallo and Silvio Aime

      Article first published online: 29 MAR 2016 | DOI: 10.1002/ijc.30073

      What's New?

      The formation of new blood vessels is a crucial step in tumor growth and progression. In this study, the authors used an imaging method called DCE-MRI to study tumor angiogenesis in a mouse model of breast cancer. They saw a significant increase in DCE-MRI biomarkers during malignant transformation. This “angiogenic switch” coincided with an increase in vessel permeability and plasma volume, and histology confirmed that the number of microvessels had increased. These results suggest that DCE-MRI may be a valuable tool for early, non-invasive detection of breast cancer.

  41. Cancer Epidemiology

    1. Hypertension, use of antihypertensive medications, and risk of epithelial ovarian cancer

      Tianyi Huang, Elizabeth M. Poole, A. Heather Eliassen, Olivia I. Okereke, Laura D. Kubzansky, Anil K. Sood, John P. Forman and Shelley S. Tworoger

      Article first published online: 25 MAR 2016 | DOI: 10.1002/ijc.30066

      What's new?

      Antihypertensive drugs lower blood pressure by acting through various mechanisms, some of which may be relevant to cancer. Yet, despite widespread use of antihypertensive medications, whether the drugs impact cancer risk remains disputed. Here, in two large prospective U.S. cohorts, current and long-term use of thiazide diuretics was associated with a significantly increased risk of ovarian cancer. By contrast, no association was detected between ovarian cancer risk and hypertension, nor was an association observed for beta-blockers, which have been shown experimentally to inhibit ovarian tumor growth. The findings could have important implications for ovarian cancer prevention.

  42. Cancer Therapy and Prevention

    1. Hyperthermia adds to trabectedin effectiveness and thermal enhancement is associated with BRCA2 degradation and impairment of DNA homologous recombination repair

      Dominique Harnicek, Eric Kampmann, Kirsten Lauber, Roman Hennel, Ana Sofia Cardoso Martins, Yang Guo, Claus Belka, Simone Mörtl, Eike Gallmeier, Roland Kanaar, Ulrich Mansmann, Tomas Hucl, Lars H. Lindner, Wolfgang Hiddemann and Rolf D. Issels

      Article first published online: 25 MAR 2016 | DOI: 10.1002/ijc.30070

      What's new?

      Trabectedin kills tumor cells by binding to DNA and inducing double-strand breaks. An impaired DNA repair mechanism makes a tumor more susceptible to trabectedin treatment, and heat inactivates certain proteins involved in DNA double-strand break repair. The authors found that heat improves trabectedin-induced cell death in sarcoma cell lines. This enhancement results from the degradation of BRCA2, they conclude: on-demand inhibition of DNA repair by heat is a promising strategy to improve effectiveness of trabectedin.

  43. Mini Reviews

  44. Molecular Cancer Biology

    1. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma

      Melanie Ruf, Holger Moch and Peter Schraml

      Article first published online: 25 MAR 2016 | DOI: 10.1002/ijc.30077

      What's new?

      Interactions between programmed cell death-1 (PD-1) receptor and its ligand PD-L1 serve to inhibit T-cell responses, protecting against autoimmunity. In cancer, however, aberrant PD-L1 expression facilitates tumor escape from immune surveillance, making the ligand a potential anticancer drug target. The present study identifies a mechanism underlying the role of PD-L1 in clear cell renal cell carcinoma (ccRCC). In ccRCC cell lines, PD-L1 upregulation was found to be hypoxia-inducible factor (HIF)-dependent and driven predominantly by the HIF2α subunit, which accumulates in ccRCC as a result of Von Hippel-Lindau protein inactivation. Combined PD-L1/HIF inhibition could be of therapeutic relevance in ccRCC.

  45. Tumor Markers and Signatures

    1. Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer

      Maria Rosaria Galdiero, Paolo Bianchi, Fabio Grizzi, Giuseppe Di Caro, Gianluca Basso, Andrea Ponzetta, Eduardo Bonavita, Marialuisa Barbagallo, Silvia Tartari, Nadia Polentarutti, Alberto Malesci, Gianni Marone, Massimo Roncalli, Luigi Laghi, Cecilia Garlanda, Alberto Mantovani and Sébastien Jaillon

      Article first published online: 24 MAR 2016 | DOI: 10.1002/ijc.30076

      What's new?

      While inflammatory cells are common in the tumor microenvironment, the associations of specific cell types with tumor development and disease progression are unclear. This is true particularly in the case of tumor-associated neutrophils (TAN), for which previous reports have identified conflicting roles in tumor progression. The present study links TAN density in colorectal cancer (CRC) tissues with patient outcome, indicating that TANs are an important component of tumor-infiltrating inflammatory cell populations in this disease. The prognostic relevance of TANs in CRC was influenced by disease stage and 5-fluorouracil-based chemotherapy, with higher TAN density associated with better therapeutic response.

    2. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism

      Rui Batista, Adriana Cruvinel-Carloni, João Vinagre, Joana Peixoto, Telmo A. Catarino, Nathalia Cristina Campanella, Weder Menezes, Aline Paixão Becker, Gisele Caravina de Almeida, Marcus M. Matsushita, Carlos Clara, Luciano Neder, Marta Viana-Pereira, Mrinalini Honavar, Lígia Castro, José Manuel Lopes, Bruno Carvalho, Rui Manuel Vaz, Valdemar Máximo, Paula Soares, Manuel Sobrinho-Simões, Rui Manuel Reis and Jorge Lima

      Article first published online: 24 MAR 2016 | DOI: 10.1002/ijc.30057

      What's new?

      Cancer cells avoid senescence in part by reactivating telomerase (TERT), a ribonucleoprotein that replenishes shortening telomeres. Here, the authors discover a positive association between TERT promoter mutations and unfavorable prognosis in glioblastoma patients from Portuguese and Brazilian origin. This association was only observed in patients with a specific allelic background (AA) in a TERT polymorphism (rs2853669) recently linked to enhanced TERT mRNA levels. The authors recommend considering the allelic status of rs2853669 when assessing the prognostic value of TERT promoter mutations in glioblastoma patients.

  46. Mini Reviews

    1. Eurogin Roadmap 2015: How has HPV knowledge changed our practice: Vaccines

      Julia M.L. Brotherton, Mark Jit, Patti E. Gravitt, Marc Brisson, Aimée R. Kreimer, Sara I. Pai, Carole Fakhry, Joseph Monsonego and Silvia Franceschi

      Article first published online: 22 MAR 2016 | DOI: 10.1002/ijc.30063

      What's new?

      Ten years since the licensing of HPV vaccines, evidence of their efficacy, safety, and potential cost-effectiveness has continued to grow; we have also seen the fruit of efforts to develop vaccines that target a broader number of HPV types. Despite efforts to decrease vaccine price, the implementation of HPV vaccination worldwide remains a considerable challenge on account of insufficient political commitment, competing priorities in poor countries, and remaining problems with vaccine hesitancy.

  47. Cancer Genetics and Epigenetics

    1. Exome sequencing of oral squamous cell carcinoma in users of Arabian snuff reveals novel candidates for driver genes

      Nezar Noor Al-hebshi, Shiyong Li, Akram Thabet Nasher, Maged El-Setouhy, Rashad Alsanosi, Jan Blancato and Christopher Loffredo

      Article first published online: 18 MAR 2016 | DOI: 10.1002/ijc.30068

      What's new?

      The mutational landscape of oral cancer seems to differ depending on the environmental exposure associations. However, there has been no attempt to assess differences in genetic alterations by type of tobacco exposure. This study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty candidate novel driver genes were identified, some of which previously implicated in other cancer types. The majority of these driver genes were amplified and may thus be targetable with drugs. The findings broaden our understanding of the genetic basis of oral cancer.

  48. Tumor Markers and Signatures

    1. LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients

      Andreas Mock, Christoph Geisenberger, Christian Orlik, Rolf Warta, Christian Schwager, Christine Jungk, Céline Dutruel, Lea Geiselhart, Dieter Weichenhan, Manuela Zucknick, Ann-Katrin Nied, Sara Friauf, Janina Exner, David Capper, Christian Hartmann, Bernd Lahrmann, Niels Grabe, Jürgen Debus, Andreas von Deimling, Odilia Popanda, Christoph Plass, Andreas Unterberg, Amir Abdollahi, Peter Schmezer and Christel Herold-Mende

      Article first published online: 18 MAR 2016 | DOI: 10.1002/ijc.30069

      What's new?

      The mechanisms underlying long-term patient survival in primary IDH1 wild-type/non-G-CIMP glioblastoma need to be further elucidated. Currently, MGMT promoter methylation is the only established molecular prognosticator in IDH1 wild-type glioblastoma multiforme (GBM). Here, the authors identified promoter hypermethylation of the so far undescribed gene locus LOC283731 to be associated with improved survival. LOC283731 promoter methylation is the first epigenetic biomarker after MGMT to be thoroughly tested in multiple independent study sets consisting of IDH1 wild-type patients uniformly treated with radiochemotherapy post maximal safe surgery. LOC283731 promoter hypermethylation has the potential to be established as a novel MGMT-independent GBM prognosticator.

  49. Mini Review

    1. You have full text access to this OnlineOpen article
      Roles of N-Myc and STAT interactor in cancer: From initiation to dissemination

      Hawley C. Pruitt, Daniel J. Devine and Rajeev S. Samant

      Article first published online: 11 MAR 2016 | DOI: 10.1002/ijc.30043

  50. Cancer Epidemiology

    1. Home-based HPV self-sampling improves participation by never-screened and under-screened women: Results from a large randomized trial (iPap) in Australia

      Farhana Sultana, Dallas R. English, Julie A. Simpson, Kelly T. Drennan, Robyn Mullins, Julia M.L. Brotherton, C. David Wrede, Stella Heley, Marion Saville and Dorota M. Gertig

      Article first published online: 10 MAR 2016 | DOI: 10.1002/ijc.30031

      What's new?

      For women who have not had a recent Pap test, self-sampling for human papillomavirus (HPV) can potentially improve participation in cervical cancer screening. The present study emphasizes the degree to which home-based HPV self-sampling can increase participation, particularly among women never previously screened. More than three times as many never-screened women participated in self-sampling compared to the number who underwent Pap testing as a result of traditional invitation or reminder strategies. Among never-screened and under-screened women who tested positive for high-risk HPV types via self-sampling, more than four-fifths subsequently underwent Pap testing or appropriate clinical investigation.

  51. Mini Reviews

    1. Biomarkers in bladder cancer: A metabolomic approach using in vitro and ex vivo model systems

      Daniela Rodrigues, Carmen Jerónimo, Rui Henrique, Luís Belo, Maria de Lourdes Bastos, Paula Guedes de Pinho and Márcia Carvalho

      Article first published online: 23 FEB 2016 | DOI: 10.1002/ijc.30016

  52. Mini Review

    1. Single-cell profiling approaches to probing tumor heterogeneity

      Bee Luan Khoo, Parthiv Kant Chaudhuri, Naveen Ramalingam, Daniel Shao Weng Tan, Chwee Teck Lim and Majid Ebrahimi Warkiani

      Article first published online: 16 FEB 2016 | DOI: 10.1002/ijc.30006

  53. Molecular Cancer Biology

    1. Ninjurin1 suppresses metastatic property of lung cancer cells through inhibition of interleukin 6 signaling pathway

      Yeong-Su Jang, Ju-Hee Kang, Jong Kyu Woo, Hwan Mook Kim, Jong-Ik Hwang, Sang-Jin Lee, Ho-Young Lee and Seung Hyun Oh

      Article first published online: 16 FEB 2016 | DOI: 10.1002/ijc.30021

      What's new?

      The cell-adhesion molecule Ninj1 is overexpressed in human cancers, but its role in metastasis has been unclear. In this study of an in vivo model of lung cancer, the authors found that Ninj1 acts as a “metastasis suppressor gene” in human lung-cancer cells. When Ninj1 was blocked, cancer cell migration, invasion, and metastasis increased. Conversely, overexpression of Ninj1 reduced metastasis, and this was due to inhibition of the IL-6/STAT3 signaling pathway. Further study of Ninj1 might, therefore, lead to useful therapeutic applications in cancer treatment.

  54. Cancer Therapy and Prevention

    1. Cardiovascular medication after cancer at a young age in Finland: A nationwide registry linkage study

      A.E. Kero, L.M. Madanat-Harjuoja, L.S. Järvelä, N. Malila, J. Matomäki and P.M. Lähteenmäki

      Article first published online: 12 DEC 2015 | DOI: 10.1002/ijc.29943

      What's new?

      Children and young adults who survive cancer should remain vigilant against cardiovascular complications according to this report. The authors investigated how often young cancer patients began purchasing cardiovascular medications compared with their cancer-free siblings. They showed that the cancer patients went on cardiovascular medications, especially anticoagulants, far more often than their siblings. Thus, these findings suggest that screening for cardiovascular disease should be emphasized after cancer at a young age. This study may help doctors craft individualized follow-up schedules after early onset cancer.


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