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International Journal of Cancer

Cover image for Vol. 133 Issue 10

15 November 2013

Volume 133, Issue 10

Pages 2263–2510

  1. Mini Reviews

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

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma (pages 2284–2295)

      Alissa Michelle Go Wong, Kar Lok Kong, Leilei Chen, Ming Liu, Aikha Melissa Go Wong, Cailei Zhu, Janice Wing-hang Tsang and Xin-Yuan Guan

      Version of Record online: 13 JUL 2013 | DOI: 10.1002/ijc.28252

      What's new?

      Calcium has been involved in diverse cellular processes associated with cancer development. Despite growing evidence for the potential tumor suppressive properties of CACNA2D3—an auxiliary member of the alpha-2/delta subunit family of the voltage-dependent calcium channel complex—the mechanism underlying its role in Nasopharyngeal Carcinoma (NPC) remains unclear. Here the authors demonstrate for the first time that CACNA2D3-mediated increase in intracellular calcium activates NLK via the Wnt/Ca2+ non-canonical Wnt pathway. The observed epigenetic silencing of CACNA2D3 may also be required for accumulated β-catenin to effectively activate Wnt-associated oncogenes known to promote apoptosis evasion, cell proliferation, invasion, metastasis, and epithelial-to-mesynchemal transition.

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      The metastatic microenvironment: Lung-derived factors control the viability of neuroblastoma lung metastasis (pages 2296–2306)

      Shelly Maman, Liat Edry-Botzer, Orit Sagi-Assif, Tsipi Meshel, Weirong Yuan, Wuyuan Lu and Isaac P. Witz

      Version of Record online: 14 JUN 2013 | DOI: 10.1002/ijc.28255

      What's new?

      Factors in the microenvironment of distant organs are key suspects in the process of cancer progression, possibly determining whether circulating tumor cells that arrive to secondary organs become dormant or give rise to metastatic lesions. This report sheds new light on the role of the secondary organ microenvironment, specifically concerning the fate of metastatic neuroblastoma cells. Its central finding, that in mice factors derived from the lungs restrain neuroblastoma cells, particularly micrometastatic neuroblastoma cells, could facilitate the identification of novel anticancer therapies that aim to eradicate micrometastasis and/or prevent its progression to metastatic lesions.

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      Induction of CaSR expression circumvents the molecular features of malignant CaSR null colon cancer cells (pages 2307–2314)

      Navneet Singh and Subhas Chakrabarty

      Version of Record online: 8 JUN 2013 | DOI: 10.1002/ijc.28270

      What's new?

      Expression of the calcium sensor receptor (CaSR) coincides with colonic epithelial cell differentiation, its expression intensifying as stem cells migrate from the depths of colonic crypts. When CaSR expression is lost, a highly malignant phenotype of colon cancer ensues. This study demonstrates that the malignant CaSR null phenotype can be circumvented by induction of CaSR expression and function in CaSR null cells. CaSR expression was found to be driven by methylation and demethylation of the CaSR gene promoter. The findings could have clinical implications, with CaSR inactivation serving as a marker of colon carcinogenesis.

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      Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen-1 and nidogen-2 (pages 2315–2324)

      Estefanía Martino-Echarri, Rubén Fernández-Rodríguez, Francisco Javier Rodríguez-Baena, Antonio Barrientos-Durán, Antoni X. Torres-Collado, María del Carmen Plaza-Calonge, Suyapa Amador-Cubero, Javier Cortés, Louise E. Reynolds, Kairbaan M. Hodivala-Dilke and Juan Carlos Rodríguez-Manzaneque

      Version of Record online: 13 JUN 2013 | DOI: 10.1002/ijc.28271

      What's new?

      The extracellular milieu is a complex and dynamic environment, and certain proteases within it may play a role in tumor suppression. Of particular interest is the protease ADAMTS1, which this study indicates is a key tumor inhibitor in the extracellular matrix. In mice, increased ADAMTS1 was correlated with increased proteolysis of nidogens in the vascular basement membrane and decreased vessel density in tumors. Conversely, the protease was downregulated and nidogen proteolysis partially inhibited, with implications for vessel integrity, in human breast cancer specimens. The findings suggest that protease interactions with specific substrates are of functional importance in the tumor microenvironment.

  3. Cancer Genetics

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      Genetic variants in C-type lectin genes are associated with colorectal cancer susceptibility and clinical outcome (pages 2325–2333)

      Shun Lu, Melanie Bevier, Stefanie Huhn, Juan Sainz, Jesus Lascorz, Barbara Pardini, Alessio Naccarati, Ludmila Vodickova, Jan Novotny, Kari Hemminki, Pavel Vodicka and Asta Försti

      Version of Record online: 29 MAY 2013 | DOI: 10.1002/ijc.28251

      What's new?

      The identification of new risk and prognostic biomarkers brings the prospect of individualized medicine ever closer. That promise is illustrated here, with the discovery of novel genetic variants in three C-type lectin genes, CD209, MBL2, and REG4, which previously have been implicated in colorectal carcinogenesis and prognosis. Genotyping of 15 C-type lectin single nucleotide polymorphisms uncovered a total of 34 variants in regulatory and coding regions of the three genes. Variants in two of the genes, CD209 and REG4, were linked to colorectal cancer risk and prognosis, respectively, suggesting that they may be of clinical value.

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      Matriptase-2 gene (TMPRSS6) variants associate with breast cancer survival, and reduced expression is related to triple-negative breast cancer (pages 2334–2340)

      Hanna Tuhkanen, Jaana M. Hartikainen, Ylermi Soini, Gloria Velasco, Reijo Sironen, Timo K. Nykopp, Vesa Kataja, Matti Eskelinen, Veli-Matti Kosma and Arto Mannermaa

      Version of Record online: 4 JUN 2013 | DOI: 10.1002/ijc.28254

      What's new?

      The discovery of gene variants linked to breast cancer risk and disease outcome could help improve treatment strategies. This study is the first to show that variants in matriptase-2 (TMPRSS6), a transmembrane serine protease that is essential for the regulation of systemic iron levels, are related to breast cancer prognosis. The investigation, carried out in a Finnish population, reveals that matriptase-2 gene expression declines as breast tumors progress. Marked reductions in expression were detected in triple-negative breast cancers, which are associated with particularly low survival rates, opening the way to new therapeutic opportunities for this clinically important group.

  4. Infectious Causes of Cancer

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      Early gene expression changes by Epstein-Barr virus infection of B-cells indicate CDKs and survivin as therapeutic targets for post-transplant lymphoproliferative diseases (pages 2341–2350)

      Michele Bernasconi, Seigo Ueda, Patricia Krukowski, Beat C. Bornhauser, Kristin Ladell, Marcus Dorner, Juerg A. Sigrist, Cristina Campidelli, Roberta Aslandogmus, Davide Alessi, Christoph Berger, Stefano A. Pileri, Roberto F. Speck and David Nadal

      Version of Record online: 29 MAY 2013 | DOI: 10.1002/ijc.28239

      What's new?

      Lymphoproliferative diseases associated with Epstein-Barr virus (EBV) infection cause morbidity and mortality in bone marrow and solid organ transplant recipients. Here the authors analyzed the early molecular events leading to B-cell transformation following EBV infection. They demonstrated in vitro, 72 hours post-infection when B-cell hyperproliferation starts, the up-regulation of cell cycle-related genes (CDKs) and of the apoptosis inhibitor survivin. Treatment with specific CDK or survivin inhibitors led to EBV-transformed B-cell death. Importantly, survivin over-expression was also found in EBV-positive post-transplant diffuse large B-cell lymphomas, suggesting that inhibition of CDKs or survivin could represent a potential therapy for EBV-associated lymphoproliferative diseases.

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      Frequent detection of human cytomegalovirus in neuroblastoma: A novel therapeutic target? (pages 2351–2361)

      Nina Wolmer-Solberg, Ninib Baryawno, Afsar Rahbar, Dieter Fuchs, Jenny Odeberg, Chato Taher, Vanessa Wilhelmi, Jelena Milosevic, Abdul-Aleem Mohammad, Tommy Martinsson, Baldur Sveinbjörnsson, John Inge Johnsen, Per Kogner and Cecilia Söderberg-Nauclér

      Version of Record online: 13 JUL 2013 | DOI: 10.1002/ijc.28265

      What's new?

      Relapse and invasiveness of neuroblastoma, a frequently fatal cancer of early childhood, may be linked to the presence of human cytomegalovirus (HCMV), one of the most common congenital viral infections known. In this study, HCMV was observed in primary neuroblastoma tumors and in six neuroblastoma cell lines. Although no infectious virus was isolated from tumors, the HCMV-specific drug valganciclovir significantly reduced viral protein expression and tumor cell growth both in vitro and in vivo. The results suggest that HCMV may be important in the pathogenesis of neuroblastoma and that antiviral therapy may represent a possible future treatment option for affected children. We have shown that all examined primary neuroblastoma tumors and six neuroblastoma cell lines were infected with HCMV, but no infectious virus was isolated from tumors. The HCMV-specific drug Valganciclovir significantly reduced viral protein expression and tumor cell growth in vitro and in vivo. Thus, HCMV may be important in the pathogenesis of neuroblastoma and anti-viral therapy may provide a novel treatment option for children with neuroblastoma.

  5. Tumor Immunology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      αv-Integrin isoform expression in primary human tumors and brain metastases (pages 2362–2371)

      Alexander Vogetseder, Svenja Thies, Barbara Ingold, Patrick Roth, Michael Weller, Peter Schraml, Simon L. Goodman and Holger Moch

      Version of Record online: 10 JUN 2013 | DOI: 10.1002/ijc.28267

      What's new?

      Cilengitide, a specific integrin-inhibitor is in a Phase III trial in glioblastoma. Anti-integrin agents might conceivably also be a therapeutic option for patients with brain metastasis. We investigated the expression of αvβ3, αvβ5, αvβ6 and αvβ8 integrins in various primary malignancies and metastases to brain. We found a significant stronger αv-integrin expression in brain metastases. These αv integrins could therefore be potential therapeutic targets for patients with brain metastasis. As cancer patients live longer due to improved primary tumor treatment, the prevalence of brain metastases has increased. Here the authors examined the promise of integrins, a family of cell surface glycoproteins involved in cell motility, attachment and invasion, as potential pharmacological targets in brain metastases. By comparing the expression levels of αvβ3, αvβ5, αvβ6 and αvβ8 integrins in various primary malignancies and metastases to the brain, they found a significantly stronger expression in brain metastases, especially of αvβ3 and αvβ8 integrins. Cilengitide, a specific integrin-inhibitor, is currently in late clinical trials for the treatment of glioblastoma, and the authors speculate that αv integrins may also play specific pathogenetic functions in brain metastases that might be exploited therapeutically.

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      Endothelial plasticity governs the site-specific leukocyte recruitment in hepatocellular cancer (pages 2372–2382)

      Olga Salnikova, Kai Breuhahn, Natalie Hartmann, Jan Schmidt and Eduard Ryschich

      Version of Record online: 10 JUN 2013 | DOI: 10.1002/ijc.28268

      What's new?

      Blood vessels deep within many types of tumors undergo changes that reduce the “recruitment” of leukocytes into the tumor. In this study, the authors compared endothelial cells from hepatocellular cancer (HCC) tumors with normal liver endothelial cells. The HCC cells showed altered expression of many molecular markers and inflammatory cytokines. In vitro, however, these HCC cells reverted to a normal phenotype. The authors propose a mechanism that connects endothelial cell plasticity and a specific pattern of leukocyte infiltration in HCC. These results may suggest new immunotherapeutic approaches against HCC tumors.

  6. Early Detection and Diagnosis

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      Molecular diagnosis of endometrial cancer from uterine aspirates (pages 2383–2391)

      Cristina Perez-Sanchez, Eva Colas, Silvia Cabrera, Orlando Falcon, Angel Sanchez-del-Río, Enrique García, Luis Fernández-de-Castillo, Juan Carlos Muruzabal, Elena Alvarez, Gabriel Fiol, Carmen González, Rafael Torrejón, Eloy Moral, Miriam Campos, Manuel Repollés, Ramon Carreras, Jesus Jiménez-López, Jordi Xercavins, Elena Aibar, Alvaro Perdones-Montero, Eric Lalanne, Marta Palicio, Tamara Maes, Elisabet Rosell-Vives, Carlos Nieto, Alicia Ortega, Nuria Pedrola, Marta Llauradó, Marina Rigau, Andreas Doll, Miguel Abal, Jordi Ponce, Antonio Gil-Moreno and Jaume Reventós

      Version of Record online: 21 JUN 2013 | DOI: 10.1002/ijc.28243

      What's new?

      Many studies report biomarker discovery using omics approaches, but few survive the translation into clinically validated diagnostic assays. Using previously identified biomarkers, here the authors set to improve the early diagnosis of endometrial cancer (EC) based on minimally invasive samples: endometrial aspirates. Current sensitivity and failure rate of histological diagnosis limit the success of aspirate-based diagnosis and subsequent hysteroscopy is often necessary. The authors developed and clinically validated a novel molecular test, which increases the efficacy, sensitivity and negative predictive value of aspirate-based diagnosis and has the potential to reduce the average time and cost for EC diagnosis.

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      Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature (pages 2392–2397)

      Ola Ghatnekar, Roland Andersson, Marianne Svensson, Ulf Persson, Ulrika Ringdahl, Paula Zeilon and Carl A.K. Borrebaeck

      Version of Record online: 10 JUN 2013 | DOI: 10.1002/ijc.28256

      What's new?

      Pancreatic cancer often kills because its diffuse symptoms mean it may go undetected until it has reached a dangerous stage. What would it be worth to detect it earlier? The authors of this paper developed a framework to identify and analyze under what conditions a pancreatic screening test is cost-effective. They evaluated cost, test accuracy, and expected life-gains among various risk groups. Their calculations showed that the cost-effectiveness depended on the incidence of pancreatic cancer within the population. Certain risk groups, such as newly diagnosed diabetics, could be screened at an acceptable cost, they conclude.

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      CD133 expression in circulating tumor cells from breast cancer patients: Potential role in resistance to chemotherapy (pages 2398–2407)

      Rosa Nadal, F. Gabriel. Ortega, Marta Salido, Jose A. Lorente, Maria Rodríguez-Rivera, Miguel Delgado-Rodríguez, Marta Macià, Ana Fernández, Josep M. Corominas, J. Luis García-Puche, Pedro Sánchez-Rovira, Francesc Solé and M. Jose Serrano

      Version of Record online: 6 JUL 2013 | DOI: 10.1002/ijc.28263

      What's new?

      Despite advances in breast cancer treatments, primary and acquired resistance to cancer therapies remains a challenge. Here the authors looked at the expression of CD133—a glycoprotein associated with stem cell and migratory properties and vasculogenic mimicry—in circulating tumor cells (CTCs) of non-metastatic patients. CD133 was widely expressed, particularly in patients with luminal tumors before they received treatment. A relative enrichment was detected in non-luminal tumor subtypes following systemic therapy, suggesting a potential role of CD133+ CTCs in chemoresistance. Characterization of CD133 in CTCs might help to develop new therapeutic approaches targeting cancer stem cells and tumor vasculature.

  7. Epidemiology

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      Risk factors for false positive and for false negative test results in screening with fecal occult blood testing (pages 2408–2414)

      Inge Stegeman, Thomas R. de Wijkerslooth, Esther M. Stoop, Monique van Leerdam, M. van Ballegooijen, Roderik A. Kraaijenhagen, Paul Fockens, Ernst J. Kuipers, Evelien Dekker and Patrick M. Bossuyt

      Version of Record online: 25 JUN 2013 | DOI: 10.1002/ijc.28242

      What's new?

      Fecal immunochemical testing (FIT) is used as a non-invasive triaging test for colonoscopy in screening programs for colorectal-cancer (CRC). In this study, the authors examined whether certain subgroups of people have an increased risk of inaccurate FIT results. They found that men, smokers and regular NSAID users had higher rates of false-positive results, while the chances of having a false negative FIT are higher in smokers and in people at advanced age. Sensitivity was also lower in women. These results may be useful for improving CRC screening strategies.

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      Tubal ligation, hysterectomy and epithelial ovarian cancer in the New England Case–Control Study (pages 2415–2421)

      Megan S. Rice, Megan A. Murphy, Allison F. Vitonis, Daniel W. Cramer, Linda J. Titus, Shelley S. Tworoger and Kathryn L. Terry

      Version of Record online: 9 JUL 2013 | DOI: 10.1002/ijc.28249

      What's new?

      Tubal ligation and hysterectomy are generally known to lower ovarian cancer risk. However, little is known whether this risk reduction is influenced by the details of the surgical procedures or by the tumor histology. In this large case-control study, the authors show that tubal ligation was associated with a 18% reduced risk in ovarian cancer with strongest effects in endometrioid tumors and among women who underwent the procedure after the last childbirth. No overall association with simple hysterectomy was observed but hysterectomy with unilateral oophorectomy lowered the risk by 35%, underscoring the benefit of the procedure in the prevention of ovarian cancer.

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      A population-based prospective study of energy-providing nutrients in relation to all-cause cancer mortality and cancers of digestive organs mortality (pages 2422–2428)

      Maria Argos, Stephanie Melkonian, Faruque Parvez, Muhammad Rakibuz-Zaman, Alauddin Ahmed, Yu Chen and Habibul Ahsan

      Version of Record online: 29 MAY 2013 | DOI: 10.1002/ijc.28250

      What's new?

      Cancer incidence and deaths are projected to increase in the coming years, mostly in developing countries. The amount of protein and fat in the diet has been associated with risk of digestive cancers in wealthy countries, but not in low income countries such as Bangladesh. The authors collected data on people's dietary habits and compared this with mortality over about 9 years. They found that protein consumption is associated with higher risk of death from digestive cancers among rural-dwelling Bangladeshis.

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      Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study (pages 2429–2443)

      Raul Zamora-Ros, Veronika Fedirko, Antonia Trichopoulou, Carlos A. González, Christina Bamia, Elisabeth Trepo, Ute Nöthlings, Talita Duarte-Salles, Mauro Serafini, Lea Bredsdorff, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Guy Fagherazzi, Florence Perquier, Marie-Christine Boutron-Ruault, Verena Katzke, Annekatrin Lukanova, Anna Floegel, Heiner Boeing, Pagona Lagiou, Dimitrios Trichopoulos, Calogero Saieva, Claudia Agnoli, Amalia Mattiello, Rosario Tumino, Carlotta Sacerdote, H. Bas Bueno-de-Mesquita, Petra H.M. Peeters, Elisabete Weiderpass, Dagrun Engeset, Guri Skeie, Marcial Vicente Argüelles, Esther Molina-Montes, Miren Dorronsoro, María José Tormo, Eva Ardanaz, Ulrika Ericson, Emily Sonestedt, Malin Sund, Rikard Landberg, Kay-Tee Khaw, Nicholas J. Wareham, Francesca L. Crowe, Elio Riboli and Mazda Jenab

      Version of Record online: 4 JUN 2013 | DOI: 10.1002/ijc.28257

      What's new?

      Coffee, tea, fruits and vegetables, and certain other foods may protect against hepatocellular carcinoma (HCC), thanks to their antioxidant ingredients. This study lends fresh support to that idea, revealing specifically that dietary flavanols, which possess antioxidant activity, could play a favourable role in HCC prevention. Dietary antioxidant capacity from coffee intake in particular was found to be inversely associated with HCC risk, though statistical significance was lost after exclusion of the first two years of follow-up. Assessment of the bioavailability of flavonoids and other antioxidants is needed to confirm links between antioxidant intake and HCC risk.

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      Familial risk of childhood cancer and tumors in the li-fraumeni spectrum in the utah population database: Implications for genetic evaluation in pediatric practice (pages 2444–2453)

      Karen Curtin, Ken R. Smith, Alison Fraser, Richard Pimentel, Wendy Kohlmann and Joshua D. Schiffman

      Version of Record online: 12 JUN 2013 | DOI: 10.1002/ijc.28266

      What's new?

      Childhood cancer, although relatively rare compared to adulthood cancers, is the leading cause of death in children up to 14 years of age. Little is known about the hereditary components of the disease. Using a large population-based genealogical database in the US state Utah, Curtin and colleagues report that children with cancer have an increased risk for positive cancer family history as compared to controls. Siblings of patients diagnosed before age five have a 3.6-fold childhood cancer risk. Notably, a second report in this issue of IJC also investigated risks associated with childhood cancer and shows an increased risk of adulthood cancer in relatives of children with cancer (Neale et al.). A resulting clinical recommendation is that a three-generation family history be collected and updated for all pediatric patients, and that families with clusters of several cancers are referred to genetic counseling.

  8. Cancer Therapy

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of multimodality therapy response (pages 2454–2463)

      M. Odenthal, E. Bollschweiler, P.P. Grimminger, W. Schröder, J. Brabender, U. Drebber, A.H. Hölscher, R. Metzger and D. Vallböhmer

      Version of Record online: 3 JUN 2013 | DOI: 10.1002/ijc.28253

      What's new?

      Combining multiple modes of treatment is increasingly the standard of care in advanced esophageal cancer. However, while meta-analyses have indicated that patients with major histopathologic response may benefit from neoadjuvant regimens, predictive markers to determine patient response are missing. Here, the expression of a subset of microRNAs, identified from a panel of miRNAs in esophageal tumor specimens collected before and after neoadjuvant therapy, was found to be significantly reduced following treatment. Two markers in particular, miR-192 and miR-194, may be potential pre-therapeutic indicators of major histopathologic regression in esophageal cancer.

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      Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells (pages 2464–2472)

      Marta Vives, Mireia M. Ginestà, Kristina Gracova, Mariona Graupera, Oriol Casanovas, Gabriel Capellà, Teresa Serrano, Berta Laquente and Francesc Viñals

      Version of Record online: 4 JUN 2013 | DOI: 10.1002/ijc.28259

      What's new?

      Although the effectiveness and rationale of chemotherapy regimens at the maximum tolerated dose have long been questioned, there is a lack of preclinical data to validate the potential of alternative administration schedules. Here the authors report indications that standard chemotherapy at the maximum tolerated dose followed by metronomic maintenance administration, known as the chemo-switch schedule, could be a useful clinical strategy for treating various tumours with different drugs. They also demonstrate the chemo-switch treatment to be a multi-targeted schedule inhibiting angiogenesis, cancer stem cells, and tumour dissemination. This study paves the way for a generalised use of the chemo-switch schedule.

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      Estrogen and insulin-like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice (pages 2473–2482)

      Hexiao Tang, Yongde Liao, Liqiang Xu, Chao Zhang, Zhaoguo Liu, Yu Deng, Zhixiao Jiang, Shengling Fu, Zhenguang Chen and Sheng Zhou

      Version of Record online: 12 JUN 2013 | DOI: 10.1002/ijc.28262

      What's new?

      The present study demonstrated for the first time that estrogen and insulin-like growth factor-1 (IGF-1) can synergistically promote the development of lung adenocarcinoma in mice. Such effect might be attributed to the activation of the MAPK and AKT signaling pathways, with the key molecules ERβ1, ERβ2, and IGF-1R playing important roles. The results further revealed that the combined use of estrogen receptor (ER) and IGF-1R inhibitors may suppress lung adenocarcinoma growth to a greater extent than either inhibitor alone. Blocking multiple targets in the estrogen and IGF-1 signaling pathways may thus have substantial therapeutic potential in lung cancer.

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      Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established solid tumors and increase nanoparticle delivery (pages 2483–2492)

      Xinping Fu, Armando Rivera, Lihua Tao and Xiaoliu Zhang

      Version of Record online: 11 JUL 2013 | DOI: 10.1002/ijc.28269

      What's new?

      Immunological tolerance of tumor cells is a major obstacle to efficient cancer prevention and treatment. Engrafting T cells with chimeric antigen receptors (CARs) increases the number of high-affinity tumor-specific T cells in an attempt to tackle tumor tolerance therapeutically. Current CAR strategies exclusively target tumor cells, but here the authors report the construction of eCAR that targets tumor blood vessels instead thus overcoming the difficulty of CAR-modified T cells to penetrate tumor parenchyma. They show that T cells engrafted with eCAR (T-eCAR) can efficiently lyse umbilical vein endothelial cells and that its in vivo administration results in significant tumor shrinkage. Moreover, delivery of T-eCAR together with nanoparticles increases the tumor deposition of the latter, pointing to a new combinatorial strategy for selective anticancer drug delivery.

  9. Short Reports

    1. Top of page
    2. Mini Reviews
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Infectious Causes of Cancer
    6. Tumor Immunology
    7. Early Detection and Diagnosis
    8. Epidemiology
    9. Cancer Therapy
    10. Short Reports
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      Mortality risk in former smokers with breast cancer: Pack-years vs. smoking status (pages 2493–2497)

      Nazmus Saquib, Marcia L. Stefanick, Loki Natarajan and John P. Pierce

      Version of Record online: 29 MAY 2013 | DOI: 10.1002/ijc.28241

      What's new?

      Once you have cancer, it's too late to quit smoking—or is it? Some studies have shown that people who quit smoking at the time they are diagnosed can still improve their survival. These conclusions may be misleading, however, by grouping heavy smokers together with occasional smokers in a single category. In this study, the authors expanded on the basic categories of “former” or “current” smoker. Those who had smoked for 20 years or more did indeed show increased breast cancer specific mortality, even though no increased risk appeared when patients were categorized by current smoking status alone.

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      Long-term treatment with Sitagliptin, a dipeptidyl peptidase-4 inhibitor, reduces colon carcinogenesis and reactive oxygen species in 1,2-dimethylhydrazine-induced rats (pages 2498–2503)

      Angelo Pietro Femia, Laura Raimondi, Giulia Maglieri, Maura Lodovici, Edoardo Mannucci and Giovanna Caderni

      Version of Record online: 29 MAY 2013 | DOI: 10.1002/ijc.28260

      What's new?

      The enzyme dipeptidyl peptidase-4 (DPP4) rapidly degrades insulin-stimulating incretin hormones, making its inhibition an appealing strategy for the treatment of type 2 diabetes mellitus and possibly colon cancer. The DPP4 inhibitor sitagliptin is of particular interest, though its role in colon carcinogenesis is unclear. Here, chemopreventive administration of sitagliptin in rats, at doses comparable to those used in therapeutic settings for humans with diabetes, was found to reduce precancerous colon lesions and to lower levels of reactive oxygen species in the blood. The findings warrant further investigation of sitagliptin in human chemoprevention trials for colon cancer.

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      Tumor necrosis factor alpha induces Warburg-like metabolism and is reversed by anti-inflammatory curcumin in breast epithelial cells (pages 2504–2510)

      Roger A. Vaughan, Randi Garcia-Smith, Jonathan Dorsey, Jeffrey K. Griffith, Marco Bisoffi and Kristina A. Trujillo

      Version of Record online: 10 JUN 2013 | DOI: 10.1002/ijc.28264

      What's new?

      Oncogene expression can reprogram cell metabolism. In fact, most cancer cells have altered metabolism—specifically, increased aerobic glycolysis. Indirect evidence indicates that this type of altered metabolism may play an important role in tumorigenesis linked to inflammation. However, it wasn't known whether chronic inflammation can directly reprogram cell metabolism. In this study of normal and malignant breast epithelial cells, the authors found that the inflammatory cytokine TNF-α can indeed directly induce metabolic changes, similar to those produced by oncogene expression. The study also found that this effect can be blocked by the natural dietary compound curcumin.

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