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International Journal of Cancer

Cover image for Vol. 133 Issue 5

1 September 2013

Volume 133, Issue 5

Pages 1023–1269

  1. Mini Reviews

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
    1. You have free access to this content
      Utility of subtyping intestinal metaplasia as marker of gastric cancer risk. A review of the evidence (pages 1023–1032)

      Carlos A. González, José M. Sanz-Anquela, Javier P. Gisbert and Pelayo Correa

      Article first published online: 5 FEB 2013 | DOI: 10.1002/ijc.28003

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      Folic acid supplementation and cancer risk: A meta-analysis of randomized controlled trials (pages 1033–1041)

      Xianhui Qin, Yimin Cui, Lin Shen, Ningling Sun, Yan Zhang, Jianping Li, Xin Xu, Binyan Wang, Xiping Xu, Yong Huo and Xiaobin Wang

      Article first published online: 15 FEB 2013 | DOI: 10.1002/ijc.28038

  2. Carcinogenesis

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      In vivo efficacy of melanoma internal radionuclide therapy with a 131I-labelled melanin-targeting heteroarylcarboxamide molecule (pages 1042–1053)

      Françoise Degoul, Michèle Borel, Nathalie Jacquemot, Sophie Besse, Yves Communal, Florence Mishellany, Janine Papon, Frédérique Penault-Llorca, Denise Donnarieix, Michel Doly, Lydia Maigne, Elisabeth Miot-Noirault, Anne Cayre, Jacques Cluzel, Nicole Moins, Jean-Michel Chezal and Mathilde Bonnet

      Article first published online: 18 MAR 2013 | DOI: 10.1002/ijc.28103

      What's new?

      Currently, there is no effective treatment for disseminated melanoma. In this study, the authors found that a 131I-labelled heteroarylcarboxamide molecule called [131I]ICF01012 was effective in killing melanoma cells in an in vivo mouse model, with low toxicity. Molecular analyses of treated tumors revealed features consistent with a tumor-cell death mechanism of mitotic catastrophe. This targeted radionuclide therapy (TRT) offers a promising alternative to conventional therapeutic agents.

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      Chemopreventive effect of a novel oleanane triterpenoid in a chemically induced rodent model of breast cancer (pages 1054–1063)

      Anupam Bishayee, Animesh Mandal, Roslin J. Thoppil, Altaf S. Darvesh and Deepak Bhatia

      Article first published online: 29 MAR 2013 | DOI: 10.1002/ijc.28108

      What's new?

      Due to the long-term toxicity of prophylactic treatments for breast cancer such as tamoxifen and raloxifene, new chemopreventive therapies that have acceptable efficacy and toxicity profiles are urgently needed. In this study, the authors investigated whether a novel triterpenoid called “methyl amooranin” (AMR-Me) could prevent chemically-induced mammary tumors in rats. They found that AMR-Me exerted a striking chemopreventive effect, suppressing tumor-cell proliferation and inducing apoptosis. AMR-Me may thus represent a less toxic alternative for chemoprevention of breast cancer.

  3. Cancer Cell Biology

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating KDM1A (pages 1064–1073)

      Kristina Althoff, Anneleen Beckers, Andrea Odersky, Pieter Mestdagh, Johannes Köster, Isabella M. Bray, Kenneth Bryan, Jo Vandesompele, Frank Speleman, Raymond L. Stallings, Alexander Schramm, Angelika Eggert, Annika Sprüssel and Johannes H. Schulte

      Article first published online: 7 MAR 2013 | DOI: 10.1002/ijc.28091

      What's new?

      The protein KDM1A is strongly expressed in neuroblastomas. Overexpression of this protein correlates with poor patient prognosis, as does reduced expression of the microRNA miR-137. In this study, the authors examined whether miR-137 might act as a tumor suppressor in neuroblastoma, via the down-regulation of KDM1A. Their data led them to conclude that miR-137 does directly target KDM1A mRNA levels in neuroblastoma cells. In addition, increasing the expression of miR-137 resulted in increased apoptosis and decreased cell proliferation of neuroblastoma cells. This may provide a promising therapeutic strategy for aggressive neuroblastomas.

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      Gene silencing of the BDNF/TrkB axis in multiple myeloma blocks bone destruction and tumor burden in vitro and in vivo (pages 1074–1084)

      Li-Sha Ai, Chun-Yan Sun, Ya-Dan Wang, Lu Zhang, Zhang-Bo Chu, You Qin, Fei Gao, Han Yan, Tao Guo, Lei Chen, Di Yang and Yu Hu

      Article first published online: 8 MAR 2013 | DOI: 10.1002/ijc.28116

      What's new?

      The recent association of brain-derived neurotrophic factor (BDNF) with bone disease in multiple myeloma could have important therapeutic implications, though how the factor exerts its effects has remained unclear. Here, binding of multiple myeloma-derived BDNF to tyrosine receptor kinase B (TrkB) on osteoblasts was linked to increased RANKL and decreased OPG expression, thereby tipping the balance of these essential mediators of osteoclastogenesis toward increased bone resorption. Antisense inhibition of endogenous BDNF in multiple myeloma cells prevented bone destruction, angiogenesis, and tumor burden in vivo.

  4. Cancer Genetics

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      Polymorphisms in the VEGFA promoter are associated with susceptibility to hepatocellular carcinoma by altering promoter activity (pages 1085–1093)

      Xiaopan Wu, Zhenhui Xin, Wei Zhang, Jia Wu, Kangmei Chen, Huifen Wang, Xilin Zhu, Liping Pan, Zhuo Li, Hui Li and Ying Liu

      Article first published online: 7 MAR 2013 | DOI: 10.1002/ijc.28109

      What's new?

      Genetic variations in vascular endothelial growth factor A (VEGFA) have been implicated in susceptibility to certain cancers and may explain the factor's involvement in tumor growth and metastasis. Here, two single nucleotide polymorphisms (SNPs), rs833601 and rs 1570360, identified in the promoter region of the VEGFA gene were found to be strongly associated with hepatitis B virus-related hepatocellular carcinoma (HCC) in Han Chinese populations. HCC patients were observed to have elevated VEGFA transcription, suggesting that the SNPs may contribute to HCC susceptibility by altering promoter activity.

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      Xeroderma pigmentosum genes and melanoma risk (pages 1094–1100)

      K. Paszkowska-Szczur, R.J. Scott, P. Serrano-Fernandez, A. Mirecka, P. Gapska, B. Górski, C. Cybulski, R. Maleszka, M. Sulikowski, L. Nagay, J. Lubinski and T. Dębniak

      Article first published online: 13 MAR 2013 | DOI: 10.1002/ijc.28123

      What's new?

      Frequent mutation of the nucleotide excision repair (NER) system in both malignant melanoma and the inherited skin disease Xeroderma pigmentosum (XP) has led to speculation about whether XP may influence melanoma risk. Here, haplotype analysis of seven XP genes (XPA-XPG) in a Polish population uncovered a significant association between an XPC haplotype and decreased risk of malignant melanoma. Modest associations were also found for two XPD haplotypes. The findings contribute to the growing body of evidence that has implicated XPC and XPD polymorphisms as factors in melanoma susceptibility.

  5. Infectious Causes of Cancer

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      Can clinical tests help monitor human papillomavirus vaccine impact? (pages 1101–1106)

      Elissa Meites, Carol Lin, Elizabeth R. Unger, Martin Steinau, Sonya Patel, Lauri E. Markowitz and Susan Hariri

      Article first published online: 13 MAR 2013 | DOI: 10.1002/ijc.28115

      What's new?

      The impact of human papillomavirus (HPV) immunization on cervical cancer incidence in populations of vaccinated women may not be apparent for decades, complicating evaluation of the early effectiveness of HPV vaccination programs. Evidence presented here indicates that it may be possible to do this by performing HPV-type analysis on cervical specimens, since one of the earliest measurable effects of HPV vaccine in a population should be a reduction in specific HPV types. The triage of cervical specimens for HPV typing based on results of a clinical HPV test such as the digene hybrid capture 2 (HC-2) could complement existing cervical cancer screening programs and reduce overall testing costs, and therefore may be appealing for use in low-resource settings.

  6. Tumor Immunology

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity (pages 1107–1118)

      Toshimitsu Ohashi, Takashi Akazawa, Mitsuhiro Aoki, Bunya Kuze, Keisuke Mizuta, Yatsuji Ito and Norimitsu Inoue

      Article first published online: 16 MAR 2013 | DOI: 10.1002/ijc.28114

      What's new?

      Contrary to their usual protective function, immune cells can also enhance tumor progression, invasion and metastasis. In this study, the authors found that when lactic acid is secreted by tumor cells, it can play two independent roles in promoting tumor development: First, it inhibits the immune response by increasing arginase-1 expression in myeloid cells. Secondly, it induces inflammation within the tumor microenvironment by activating the IL-23/IL-17 pathway. The authors then found that dichloroacetate (DCA) can suppress both the inflammatory and immunosuppressive effects of lactic acid. DCA may therefore improve the effectiveness of anti-tumor immunotherapy.

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      Whole blood interferon-γ levels predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer (pages 1119–1125)

      Takeshi Ishikawa, Satoshi Kokura, Naoyuki Sakamoto, Tetsuya Okayama, Masahiro Endo, Reiko Tsuchiya, Manabu Okajima, Tatsuzo Matsuyama, Satoko Adachi, Kazuhiro Kamada, Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Takashi Ando, Kazuko Uno, Yuji Naito and Toshikazu Yoshikawa

      Article first published online: 29 MAR 2013 | DOI: 10.1002/ijc.28117

      What's new?

      The study addresses a critical challenge in immune-based treatments of cancers: finding an easily accessible blood test that can predict a patient's responsiveness to treatment. The authors tested various cytokine and T cell parameters in patients afflicted with pancreatic cancer after receiving adoptive T cell therapy. They find that changes in whole blood interferon-gamma (IFN-γ) levels were independent variables predicting overall survival. Although a whole blood IFN-γ assay is considered a “nonspecific” immunological test, it faithfully reflected the patients' actual immune responses and should be especially valuable in situations where the relevant target antigen of the adoptively transferred T cells is not known. By combining measurements of whole blood IFN-γ with antigen-specific immunological assays, the authors hope to even better predict clinical outcome in cancer immunotherapy.

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      The combination therapy of α-galactosylceramide and 5-fluorouracil showed antitumor effect synergistically against liver tumor in mice (pages 1126–1134)

      Hiroshi Aketa, Tomohide Tatsumi, Keisuke Kohga, Hinako Tsunematsu, Satoshi Aono, Satoshi Shimizu, Takahiro Kodama, Takatoshi Nawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Atsushi Hosui, Takuya Miyagi, Naoki Hiramatsu, Tatsuya Kanto, Norio Hayashi and Tetsuo Takehara

      Article first published online: 13 MAR 2013 | DOI: 10.1002/ijc.28118

      What's new?

      α-Galactosylceramide (α-GalCer) is effective against metastatic liver tumors in mice. In this study, the authors evaluated the antitumor effect of a combination therapy of α-GalCer plus 5-FU. They found that the combination therapy produced synergistic antitumor effects against liver tumors of colon cancer cells in mice, by both increasing the activation of natural killer (NK) cells and enhancing the sensitivity of the cancer cells to those NK cells. This combination may therefore represent a promising new chemo-immunotherapy against metastatic liver cancer.

  7. Early Detection and Diagnosis

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: Array-based DNA methylation and expression profiling (pages 1135–1142)

      Yong-June Kim, Hyung-Yoon Yoon, Ji Sang Kim, Ho Won Kang, Byung-Dal Min, Seon-Kyu Kim, Yun-Sok Ha, Isaac Yi Kim, Keun Ho Ryu, Sang-Cheol Lee and Wun-Jae Kim

      Article first published online: 16 MAR 2013 | DOI: 10.1002/ijc.28121

      What's new?

      Many patients with non-muscle invasive bladder cancer (NMIBC) are at high risk of disease recurrence and progression after primary treatment. Clinicians thus have to develop both cost-effective, non-invasive surveillance protocols for low-risk patients and more aggressive approaches to identify high-risk refractory cancers. This study used microarray-based methylation and expression profiling to identify novel prognostic methylation markers associated with clinicopathological tumor characteristics and disease outcomes. The presented candidate genes are the first methylation-based prognostic indicators for NMIBC. Epigenetic markers could be valuable tools for stratifying heterogeneous bladder cancer patient populations into risk groups, which in turn could help guide clinical decisions.

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      Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells (pages 1143–1152)

      Dhwanil Damania, Hemant K. Roy, Dhananja Kunte, Jean A. Hurteau, Hariharan Subramanian, Lusik Cherkezyan, Nela Krosnjar, Maitri Shah and Vadim Backman

      Article first published online: 1 APR 2013 | DOI: 10.1002/ijc.28122

      What's new?

      Ovarian cancer is frequently fatal because it is not detected until it has progressed to late-stage metastatic disease, and new techniques for early detection are sorely needed. Sometimes, apparently normal cells can undergo changes similar to the cancer cells, in a phenomenon called “field carcinogenesis.” In these instances, multiple cancers arise in different sites within the same region. In this paper, the authors employ a novel technique, partial wave spectroscopy (PWS) to detect ovarian field carcinogenesis by looking for nanoscale changes in the architecture of endometrial and cervical cells. This report signifies the first demonstration that PWS nanocytology can detect cellular structures at such a small scale. Using this technique to detect ovarian field carcinogenesis could represent a minimally invasive approach to early intervention for ovarian cancer.

  8. Epidemiology

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: The Norwegian Women and Cancer (NOWAC) cohort study (pages 1153–1163)

      Christine L. Parr, Anette Hjartåker, Eiliv Lund and Marit B. Veierød

      Article first published online: 29 MAR 2013 | DOI: 10.1002/ijc.28101

      What's new?

      Whether certain regions within the colon are more susceptible than others to cancer associated with the intake of red and processed meat has remained unclear. As this study of more than 84,500 women in Norway suggests, however, there exists little difference. Increased risk of colorectal cancer at all subsites, including the distal and proximal colon and the rectum, was associated with the consumption of 60 or more grams of processed meat per day. Cooking methods and intake of red meat and chicken, on the other hand, were not linked to increased risk.

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      Anal squamous intraepithelial lesions are frequent among young HIV-infected men who have sex with men followed up at the Spanish AIDS Research Network Cohort (CoRIS-HPV) (pages 1164–1172)

      Cristina González, Montserrat Torres, Amparo Benito, Jorge del Romero, Carmen Rodríguez, María Fontillón, Mónica Trastoy, Pompeyo Viciana, Julia del Amo, Marta Ortiz, Beatriz Hernández-Novoa and on behalf of the CoRIS-HPV Study Group

      Article first published online: 7 MAR 2013 | DOI: 10.1002/ijc.28102

      What's new?

      Anal squamous intraepithelial lesions (SILs) have been implicated as a risk factor for anal cancer in HIV-positive men who have sex with men (MSM), and now, as detailed in this report, it appears that their development is associated with high risk (HR) human papillomavirus (HPV) genotype burden. Analysis of patients enrolled in the Spanish AIDS Research Network Cohort (CoRIS) revealed a seven-fold increase in SIL risk for HIV-positive MSM who had five or more detectable HR-HPV genotypes. The findings could influence the development of SIL screening programs.

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      Marriage, cohabitation and incidence trends of invasive penile squamous cell carcinoma in Denmark 1978–2010 (pages 1173–1179)

      Constance J. Ulff-Møller, Jacob Simonsen and Morten Frisch

      Article first published online: 7 MAR 2013 | DOI: 10.1002/ijc.28107

      What's new?

      Infection with HPV is a risk factor for penile squamous cell carcinoma. Since HPV infection is sexually acquired, sexual and marital history might also influence risk of penile cancer. In this paper, the authors investigated the relationship between living arrangements and invasive penile cancer among Danish men for a 33-year period. Unmarried, divorced and widowed men had higher risk of penile cancer than married men, they found, and those living alone had higher risk than those cohabitating with an opposite-sex partner. Greater sexual instability, measured by the number of partners a man had lived with, increased the risk of penile cancer.

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      Increased risk for cancer among offspring of women with fertility problems (pages 1180–1186)

      Marie Hargreave, Allan Jensen, Isabelle Deltour, Louise A. Brinton, Klaus K. Andersen and Susanne K. Kjaer

      Article first published online: 25 MAR 2013 | DOI: 10.1002/ijc.28110

      What's new?

      Do children born after fertility treatment have a higher risk of cancer? In this report, the authors conducted a cohort study measuring how often children born from infertile mothers developed cancer. People whose mothers had fertility problems had a higher risk of cancer in childhood and young adulthood than those born to mothers without fertility problems. This study is the largest cohort study to date to measure this risk, and if these risk estimates are accurate, indicate about 13 additional cancer cases per 100,000 exposed individuals.

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      Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study (pages 1187–1196)

      Mark E. Scott, Yurii B. Shvetsov, Pamela J. Thompson, Brenda Y. Hernandez, Xuemei Zhu, Lynne R. Wilkens, Jeffrey Killeen, Dien D. Vo, Anna-Barbara Moscicki and Marc T. Goodman

      Article first published online: 16 MAR 2013 | DOI: 10.1002/ijc.28119

      What's new?

      While most human papillomavirus (HPV) infections clear within a few months or years, the 5–10% of women with persistent infections remain at an elevated risk of cervical intraepithelial neoplasia (CIN) 3 or cervical cancer. The mechanisms underlying HPV infection clearance are unclear. This longitudinal study found that proinflammatory, Type-1, and regulatory cytokines were elevated in women with a non-transient HPV infection, underscoring the long-term commitment of local immune mediators to viral eradication. The relative duration of infection was accounted for through examination of the association of cytokine expression with the clearance of incident, rather than prevalent, cervical HPV infection.

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      Kaposi sarcoma trends in Uganda and Zimbabwe: A sustained decline in incidence? (pages 1197–1203)

      Karima Chaabna, Freddie Bray, Henry R. Wabinga, Eric Chokunonga, Margaret Borok, Philippe Vanhems, David Forman and Isabelle Soerjomataram

      Article first published online: 8 MAR 2013 | DOI: 10.1002/ijc.28125

      What's new?

      The incidence of Kaposi sarcoma (KS) increased dramatically in Uganda and Zimbabwe following the rise of HIV/AIDS in Sub-Saharan Africa. Since the 1990s, however, KS incidence among men under age 50 has declined significantly in both countries, according to this analysis of cancer registry data. The declines paralleled the decrease in HIV/AIDS prevalence, which occurred following the implementation of prevention programs and scale-up of antiretroviral therapy coverage.

  9. Cancer Therapy

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: A randomized, double-blind, hypothesis-generating study (pages 1204–1213)

      Giuseppe Stragliotto, Afsar Rahbar, Nina Wolmer Solberg, Anders Lilja, Chato Taher, Abiel Orrego, Birgitta Bjurman, Charlotte Tammik, Petra Skarman, Inti Peredo and Cecilia Söderberg-Nauclér

      Article first published online: 13 MAR 2013 | DOI: 10.1002/ijc.28111

      What's new?

      An exciting new connection has emerged between human cytomegalovirus infection and glioblastoma multiforme, the most deadly primary brain tumor with a mean overall survival of 15 months. The authors assessed the effect of antiviral Valganciclovir treatment in glioblastoma patients in a randomized hypothesis-generating study. Tumor growth was hampered and survival was longer in patients treated with Valganciclovir for >6 months. Because Valganciclovir is not curative and antiviral treatment during the study was only transient, the authors propose larger randomised trials to evaluate the effect of long-term Valganciclovir treatment in glioblastoma patients.

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      Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer (pages 1214–1221)

      Anuj Goenka, Luc G.T. Morris, Shyam S. Rao, Suzanne L. Wolden, Richard J. Wong, Dennis H. Kraus, Nisha Ohri, Jeremy Setton, Benjamin H. Lok, Nadeem Riaz, Borys R. Mychalczak, Heiko Schoder, Ian Ganly, Jatin P. Shah, David G. Pfister, Michael J. Zelefsky and Nancy Y. Lee

      Article first published online: 29 MAR 2013 | DOI: 10.1002/ijc.28120

      What's new?

      Traditionally, most patients with head and neck cancer and nodal metastases who are treated with chemoradiotherapy undergo a neck dissection after treatment in order to remove residual metastatic disease in the neck. However, not all of these patients' necks actually harbor residual disease. In fact, emerging data now reveals that patients who experience a complete response after chemoradiation therapy have a very low rate of residual disease identified in the neck. Furthermore, a PET/CT scan obtained after treatment is a highly accurate predictor of whether there will be any residual disease in neck lymph nodes. These findings have led many to hypothesize that patients achieving a complete response might not require post-treatment neck dissections. The current study now presents the first comprehensive analysis of a large, uniform cohort of node-positive head and neck cancer patients undergoing observation of the neck rather than neck dissection, provided that PET/CT indicates that a complete response after chemoradiation has been achieved. The rate of recurrence in these observed patients was very low, indicating that head and neck cancer patients experiencing a PET/CT-confirmed complete response after chemoradiation therapy can be safely observed, rather than undergoing neck dissection.

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      Dual mTORC1 and mTORC2 inhibitor Palomid 529 penetrates the Blood–Brain Barrier without restriction by ABCB1 and ABCG2 (pages 1222–1233)

      Fan Lin, Levi Buil, David Sherris, Jos H. Beijnen and Olaf van Tellingen

      Article first published online: 1 APR 2013 | DOI: 10.1002/ijc.28126

      What's new?

      The oncogenic activation of the mTOR pathway is crucial for tumor development in most cancer types, including primary central nervous tumors. This is the first pharmacokinetic evaluation of Palomid 529, a novel dual mTORC1/2 inhibitor. The results show that Palomid 529 is the first targeted agent being able to penetrate the blood-brain barrier without restriction by two dominant drug efflux transporters, P-glycoprotein (ABCB1) and Breast Cancer Resistant Protein (ABCG2). This finding is in marked contrast to many novel targeted agents that are currently under development and whose brain penetration is markedly impaired by drug efflux transporters (e.g. vemurafinib, cederanib, etc.).

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      Inhibition of the renin–angiotensin system improves physiological outcomes in mice with mild or severe cancer cachexia (pages 1234–1246)

      Kate T. Murphy, Annabel Chee, Jennifer Trieu, Timur Naim and Gordon S. Lynch

      Article first published online: 16 MAR 2013 | DOI: 10.1002/ijc.28128

      What's new?

      Cachexia, the progressive weakening of skeletal muscle which often accompanies cancer, can affect response to chemotherapy and worsen outcomes. The resulting failure of respiratory and cardiac muscle contributes to mortality. The renin-angiotensin (RAS) hormone system is boosted in various conditions associated with muscle weakness, including certain cancers, suggesting that inhibiting it could alleviate cachexia. In this report, the authors tested whether an inhibitor of angiotensin converting enzyme (ACE) could enhance skeletal muscle function in mice. The ACE inhibitor improved mobility and strength in mice with both mild and severe cachexia. It also reduced respiratory muscle fatigue. Based on these results, this ACE inhibitor could prove useful to treat the muscle wasting that accompanies cancer.

  10. Short Reports

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
    8. Early Detection and Diagnosis
    9. Epidemiology
    10. Cancer Therapy
    11. Short Reports
    12. Letters to the Editor
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      Male circumcision decreases high-risk human papillomavirus viral load in female partners: A randomized trial in Rakai, Uganda (pages 1247–1252)

      Mitzie-Ann Davis, Ronald H. Gray, Mary K. Grabowski, David Serwadda, Godfrey Kigozi, Patti E. Gravitt, Fred Nalugoda, Stephen Watya, Maria J. Wawer, Thomas C. Quinn and Aaron A.R. Tobian

      Article first published online: 7 MAR 2013 | DOI: 10.1002/ijc.28100

      What's new?

      Infection with human papillomavirus is linked to cervical cancer. Previous studies have shown that women married to circumcised men have lower rates of cervical cancer, but whether or not this is related to lower HPV load has never been reported. In this study, the authors measured HPV infection in HIV-negative women with circumcised and uncircumcised male partners. They found that HPV viral load was indeed lower in women whose male partners had been circumcised.

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      Impact of chemotherapy on activated protein C-dependent thrombin generation—Association with VTE occurrence (pages 1253–1258)

      Mario Roselli, Patrizia Ferroni, Silvia Riondino, Sabrina Mariotti, Anastasia Laudisi, Matteo Vergati, Francesco Cavaliere, Raffaele Palmirotta and Fiorella Guadagni

      Article first published online: 16 MAR 2013 | DOI: 10.1002/ijc.28104

      What's new?

      Chemotherapy has been associated with an increased risk of venous thromboembolism (VTE). However, the prevalence of coagulation abnormalities or VTE occurrence as a consequence of different anti-cancer agents is largely uncharacterized. Here the authors find that use of platinum-based regimens is responsible for induction of an acquired thrombophilic condition (resistance to the anti-coagulant Activated Protein C) and represents a predictor for VTE even after adjustment for other risk factors. Monitoring coagulation changes during the first chemotherapy cycle, more than the determination of a single point measurement at baseline, might also help to identify patients susceptible of developing VTE during treatment.

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      KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy (pages 1259–1265)

      Emanuele Valtorta, Sandra Misale, Andrea Sartore-Bianchi, Iris D. Nagtegaal, François Paraf, Calogero Lauricella, Valentina Dimartino, Sebastijan Hobor, Bart Jacobs, Cristiana Ercolani, Simona Lamba, Elisa Scala, Silvio Veronese, Pierre Laurent-Puig, Salvatore Siena, Sabine Tejpar, Marcella Mottolese, Cornelis J.A. Punt, Marcello Gambacorta, Alberto Bardelli and Federica Di Nicolantonio

      Article first published online: 16 MAR 2013 | DOI: 10.1002/ijc.28106

      What's new?

      Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR) are one of the therapeutic options for metastatic colorectal cancer, but they are effective only in a small subset of patients. Here the authors determined the prevalence of KRAS gene amplification in a large dataset of colorectal cancer samples and assessed the possible predictive role of KRAS gene copy number status in response to anti-EGFR treatment. The data show that amplification of the KRAS oncogene occurs in a small fraction of KRAS wild-type cases and that KRAS amplification is causally associated with resistance to anti-EGFR treatment.

  11. Letters to the Editor

    1. Top of page
    2. Mini Reviews
    3. Carcinogenesis
    4. Cancer Cell Biology
    5. Cancer Genetics
    6. Infectious Causes of Cancer
    7. Tumor Immunology
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    1. You have free access to this content
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      The challenges of understanding cancer of unknown primary (pages 1268–1269)

      Kari Hemminki, Matias Riihimäki, Kristina Sundquist and Akseli Hemminki

      Article first published online: 7 MAR 2013 | DOI: 10.1002/ijc.28098

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