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International Journal of Cancer

Cover image for Vol. 134 Issue 1

1 January 2014

Volume 134, Issue 1

Pages 1–248

  1. Mini Review

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

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
    1. You have free access to this content
      Alternatively spliced tissue factor contributes to tumor spread and activation of coagulation in pancreatic ductal adenocarcinoma (pages 9–20)

      Dusten Unruh, Kevin Turner, Ramprasad Srinivasan, Begüm Kocatürk, Xiaoyang Qi, Zhengtao Chu, Bruce J. Aronow, David R. Plas, Catherine A. Gallo, Holger Kalthoff, Daniel Kirchhofer, Wolfram Ruf, Syed A. Ahmad, Fred V. Lucas, Henri H. Versteeg and Vladimir Y. Bogdanov

      Version of Record online: 26 JUL 2013 | DOI: 10.1002/ijc.28327

      What's new?

      Alternatively spliced tissue factor (asTF) triggers the growth of new blood vessels and is present at elevated levels in certain cancers, indicating that it could play an important role in tumor growth and metastasis. Here, asTF was found to be abundant in human pancreatic ductal adenocarcinoma (PDAC) lesions and stromal monocytes, and its overexpression potentiated PDAC metastasis in vivo. Furthermore, asTF augmented EGFR-linked signaling pathways in PDAC cells and contributed to the coagulant activity of PDAC cells and cell-derived microparticles. The findings suggest that asTF may be a key target for stemming metastatic spread and complications in PDAC.

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      Neogenin1 is a sonic hedgehog target in medulloblastoma and is necessary for cell cycle progression (pages 21–31)

      Luis A. Milla, Andrea Arros, Natalie Espinoza, Marc Remke, Marcel Kool, Michael D. Taylor, Stefan M. Pfister, Brandon J. Wainwright and Verónica Palma

      Version of Record online: 24 JUL 2013 | DOI: 10.1002/ijc.28330

      What's new?

      Abnormal activation of the canonical Sonic Hedgehog (Shh)/Gli pathway has been associated with up to 30% of the human cases of medulloblastoma, which represents the most common malignant primary brain tumor in children. A greater knowledge of the cellular response to Shh pathway activation in the cerebellum is critical for both understanding disease formation and developing new treatments. In this study, the authors identified Neogenin-1 as a novel downstream effector of the Shh pathway that mediates proliferation in both cultured cerebellar progenitors and shh-driven medulloblastoma. The data suggest that targeting Neogenin-1 could offer a promising alternative to current anti-medulloblastoma therapies.

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      Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse (pages 32–42)

      Silke Reinartz, Tim Schumann, Florian Finkernagel, Annika Wortmann, Julia M. Jansen, Wolfgang Meissner, Michael Krause, Anne-Marie Schwörer, Uwe Wagner, Sabine Müller-Brüsselbach and Rolf Müller

      Version of Record online: 19 JUL 2013 | DOI: 10.1002/ijc.28335

      What's new?

      The peritoneal environment plays a critical role in the spread of ovarian cancer, ultimately becoming a malignant ascites, rich in tumor-associated macrophages (TAMs), in advanced stages of disease. TAMs in this context have been implicated in therapy resistance and metastatic spread, though their function remains unclear. Here, TAMs from malignant ascites in patients with serous ovarian carcinoma were found to express a mixed-polarization phenotype and highly variable levels of the surface marker CD163. Elevated CD163 was associated with early disease relapse and increased IL-6 and IL-10 levels. Further investigation of these changes in surface marker expression could provide insight into mechanisms of progression in ovarian cancer.

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      Cancer cells acquire a drug resistant, highly tumorigenic, cancer stem-like phenotype through modulation of the PI3K/Akt/β-catenin/CBP pathway (pages 43–54)

      Kaijie He, Tong Xu, Yucheng Xu, Alexander Ring, Michael Kahn and Amir Goldkorn

      Version of Record online: 5 AUG 2013 | DOI: 10.1002/ijc.28341

      What's new?

      The ability of cancer cells to spontaneously convert to and from a cancer stem-like phenotype may be a major factor in drug resistance and cancer progression. While a mechanistic explanation has been lacking, new findings reported here suggest that this remarkable process is governed by the PI3K/Akt and β-catenin/CBP signaling pathways. Pharmacological inhibition or genetic disruption of molecules in these pathways led to dramatic reductions in the phenotypic plasticity of breast and bladder cancer cells in vitro. The results indicate that the pathways' mitigation could be key to overcoming therapy resistance and disease progression.

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      CD82 regulates STAT5/IL-10 and supports survival of acute myelogenous leukemia cells (pages 55–64)

      Chie Nishioka, Takayuki Ikezoe, Jing Yang, Atsuya Nobumoto, Sayo Kataoka, Masayuki Tsuda, Keiko Udaka and Akihito Yokoyama

      Version of Record online: 27 JUL 2013 | DOI: 10.1002/ijc.28348

      What's new?

      The self-renewal capacity of leukemic stem cells (LSCs), which initiate and maintain acute myelogenous leukemia (AML), is dependent on signal transducer and activator of transcription 5 (STAT5). But while STAT5 is a key therapeutic target for AML, analysis of its function and cooperation with other molecules remains incomplete. Here, the surface protein CD82 was found to positively regulate STAT5/IL-10 signaling in CD34+/CD38 AML cells, suggesting that it is involved in overseeing the survival of this AML cell population. The data indicate that therapeutic disruption of the CD82/STAT5/IL-10 pathway could be key to the eradication of LSCs in AML.

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      Human papillomavirus infections as a marker to predict overall survival in lung adenocarcinoma (pages 65–71)

      Jinn-Li Wang, Chia-Lang Fang, Mey Wang, Ming-Chih Yu, Kuan-Jen Bai, Pei-Chih Lu and H. Eugene Liu

      Version of Record online: 27 JUL 2013 | DOI: 10.1002/ijc.28349

      What's new?

      While smoking is the primary risk factor for lung cancer, one-third of those afflicted have never smoked, indicating that other contributing factors are at work. One such factor, though controversial, may be infection with human papillomavirus (HPV). Here, Taiwanese lung adenocarcinoma patients with HPV infection were found to have significantly better survival, regardless of age, epidermal growth factor receptor (EGFR) mutation status, treatment, or tumor extent. Greatest survival was observed among patients with both HPV infection and EGFR mutation. The findings suggest that HPV may be a prognostic marker in lung adenocarcinoma.

  3. Cancer Genetics

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
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      Ataxia-telangiectasia-mutated protein expression with microsatellite instability in gastric cancer as prognostic marker (pages 72–80)

      Jin Won Kim, Seock-Ah Im, Min A Kim, Hyun Jin Cho, Dae Won Lee, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Hyuk-Joon Lee, Tae-You Kim, Han-Kwang Yang, Woo Ho Kim and Yung-Jue Bang

      Version of Record online: 17 SEP 2013 | DOI: 10.1002/ijc.28245

      What's new?

      ATM is a protein kinase that controls the repair of double-stranded breaks in DNA. Defective ATM has been reported in several types of tumors. Defects in a different type of DNA-repair, mismatch repair, have been associated with microsatellite instability (MSI). In this study, however, the authors confirmed that MSI can also be associated with defective ATM function. In addition, they found that ATM expression plus MSI status may be a useful prognostic biomarker in gastric cancer. These results may be beneficial for further studies of agents that target the DNA-repair pathways controlled by ATM.

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      Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes (pages 81–91)

      Matthew A. Kinseth, Zhenyu Jia, Farahnaz Rahmatpanah, Anne Sawyers, Manuel Sutton, Jessica Wang-Rodriguez, Dan Mercola and Kathleen L. McGuire

      Version of Record online: 13 JUL 2013 | DOI: 10.1002/ijc.28326

      What's new?

      Disparities in prostate cancer incidence and prognosis between African Americans and Caucasians have been attributed to differences in socioeconomic status and access to health care. However, biological and genetic factors may play a role as well. This study, based on pair wise t-tests and multiple linear regression models, describes differential gene expression patterns according to race/ethnicity. Differentially expressed genes tended to be associated with tumor-adjacent stroma. The results further indicate that pathways linked to inflammation and regulation of epithelial-to-mesenchymal transition may underlie the aggressive nature of prostate cancer in African Americans.

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      Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European prospective investigation into cancer-eurgast cohort (pages 92–101)

      Osmel Companioni, Catalina Bonet, Xavier Muñoz, Elisabete Weiderpass, Salvatore Panico, Rosario Tumino, Domenico Palli, Claudia Agnoli, Paolo Vineis, Marie-Christine Boutron-Ruault, Antoine Racine, Françoise Clavel-Chapelon, Ruth C. Travis, Kay-Tee Khaw, Elio Riboli, Neil Murphy, Anne-Claire Vergnaud, Antonia Trichopoulou, Vassiliki Benetou, Dimitrios Trichopoulos, Eiliv Lund, Dorthe Johansen, Björn Lindkvist, Mattias Johansson, Malin Sund, Eva Ardanaz, Emilio Sánchez-Cantalejo, Jose M. Huerta, Miren Dorronsoro, José Ramón Quirós, Anne Tjonneland, Lotte Maxild Mortensen, Kim Overvad, Jenny Chang-Claude, Cosmeri Rizzato, Heiner Boeing, H. Bas Bueno de Mesquita, Peter Siersema, Petra H.M. Peeters, Mattijs E. Numans, Fatima Carneiro, Idlir Licaj, Heinz Freisling, Núria Sala and Carlos A. González

      Version of Record online: 13 AUG 2013 | DOI: 10.1002/ijc.28357

      What's new?

      Variations in immune genes appear to play an important role in determining susceptibility to gastric cancer linked to Helicobacter pylori colonization of gastric mucosa. However, little is known about the influence of variation on anatomical localization and histological subtype of this malignancy. The results of this study first confirm that NOD2 and CD14, which encode proteins that recognize H. pylori lipopolysaccharide and peptidoglycan, are significantly associated with gastric cancer risk and second indicate that NOD2 associates with noncardia and CD14 with cardia gastric cancer. The differential effects of variation on the anatomical localization of disease warrant further investigation.

  4. Tumor Immunology

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
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      Immune escape of cancer cells with beta2-microglobulin loss over the course of metastatic melanoma (pages 102–113)

      Ana B. del Campo, Jon Amund Kyte, Javier Carretero, Svitlana Zinchencko, Rosa Méndez, Gloria González-Aseguinolaza, Francisco Ruiz-Cabello, Steinar Aamdal, Gustav Gaudernack, Federico Garrido and Natalia Aptsiauri

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28338

      What's new?

      In order for immunotherapy to work, tumor cells must first present tumor-associated peptides on their surface via the HLA class I complex. In this chronological study of melanoma progression, the authors suggest that early loss of the beta2-microglobulin (β2m) component of the HLA class I complex allows some tumor cells to evade the immune system. This, in turn, gives these cells a selective advantage for growth, metastasis, and resistance to immunotherapy. β2m/HLA class I expression may thus provide both a biomarker and a therapeutic target in the development of cancer immunotherapy protocols.

  5. Early Detection and Diagnosis

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
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      Decreased Muc5AC expression is associated with poor prognosis in gastric cancer (pages 114–124)

      Sung Mi Kim, Chae Hwa Kwon, Nari Shin, Do Youn Park, Hyun Jung Moon, Gwang Ha Kim and Tae Yong Jeon

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28345

      What's new?

      While various mucins play numerous key roles in carcinogenesis, the functional consequences of Muc5AC expression and the mechanisms underlying its role in gastric cancer remain poorly understood. Here the authors demonstrated that Muc5AC silencing induced increase of gastric cancer cell invasion and migration, identifying PI3K/Akt signaling pathway as a possible mechanism. Low Muc5AC expression was also associated with poor prognosis and predicted aggressiveness in gastric cancer. Muc5AC may thus play a significant role in the invasiveness/migratory capability of gastric cancer cells and could be used as a predictive biomarker for the evaluation of prognosis or aggressiveness in gastric cancer patients.

  6. Epidemiology

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
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      Dietary sources of N-nitroso compounds and bladder cancer risk: Findings from the Los Angeles bladder cancer study (pages 125–135)

      Chelsea E. Catsburg, Manuela Gago-Dominguez, Jian-Min Yuan, J. Esteban Castelao, Victoria K. Cortessis, Malcolm C. Pike and Mariana C. Stern

      Version of Record online: 15 JUL 2013 | DOI: 10.1002/ijc.28331

      What's new?

      The role of diet in bladder cancer is only partially understood. Here the authors investigate the role of dietary sources of N-nitroso compounds (NOCs) in bladder cancer risk, taking into account both ingestion of preformed NOCs as well as the often overlooked role of endogenous NOC formation. NOCs can be formed endogenously from dietary precursors like nitrate, nitrite and amines. Based on a population-based case-control study, the findings support a role for dietary precursors of endogenous NOC formation as risk factors for bladder cancer, suggesting an additional route of carcinogenic exposure in the bladder that deserves consideration and further study.

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      Cross-space-time clustering of childhood cancer in Great Britain: Evidence for a common aetiology (pages 136–143)

      Richard J.Q. McNally, Charles Stiller, Tim J. Vincent and Michael F.G. Murphy

      Version of Record online: 19 JUL 2013 | DOI: 10.1002/ijc.28332

      What's new?

      The clustering of childhood cancers within specific geographical areas of Great Britain between 1969 and 1993 has raised questions about the possible etiological involvement of environmental exposures. Here, cross-space-time clustering analysis was used to explore associations between different childhood cancers diagnosed in the region during the 1ST January 1969 to 31ST December 1993 is a 25-year period. Significant clustering was identified between cases of Hodgkin lymphoma and intracranial and intraspinal embryonal tumors, while marginal clustering was observed between lymphoid leukemia and Hodgkin lymphoma and between lymphoid leukemia and soft tissue sarcoma. The findings support the idea that common etiological factors could explain the clustering of these different cancers.

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      Can resveratrol in wine protect against the carcinogenicity of ethanol? A probabilistic dose-response assessment (pages 144–153)

      Dirk W. Lachenmeier, Rolf Godelmann, Barbara Witt, Kerstin Riedel and Jürgen Rehm

      Version of Record online: 16 SEP 2013 | DOI: 10.1002/ijc.28336

      What's new?

      Resveratrol is a polyphenol found in red wine. Animal studies have suggested that resveratrol might protect wine drinkers from the carcinogenic effects of ethanol, reducing the incidence of cancers linked to alcohol consumption. In this study, the authors quantitatively estimated the resveratrol intake required to achieve a protective effect in humans. They concluded that a wine drinker would need to consume more than 100 glasses of wine per day in order to reach effective dosages of resveratrol, and that assumptions regarding resveratrol's chemoprotective effects with regard to ethanol are therefore invalid.

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      Serum interleukin-6 associated with hepatocellular carcinoma risk: A nested case–control study (pages 154–163)

      Waka Ohishi, John B. Cologne, Saeko Fujiwara, Gen Suzuki, Tomonori Hayashi, Yasuharu Niwa, Masazumi Akahoshi, Keiko Ueda, Masataka Tsuge and Kazuaki Chayama

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28337

      What's new?

      According to previous research, alcohol consumption, obesity, and radiation exposure as well as hepatitis virus infection are all independent risk factors for hepatocellular carcinoma (HCC). Inflammatory markers have also been associated with increased risk of liver cancer, but the evidence is inconsistent. In this nested case-control study in the longitudinal cohort of atomic-bomb survivors, which took into account hepatitis virus infection, lifestyle-related factors, and radiation exposure, elevated IL-6 levels were found to be associated with increased risk of HCC. The findings also indicated that association of IL-6 levels with increased risk of HCC is especially pronounced among subjects with obesity.

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      Prediagnostic plasma testosterone, sex hormone-binding globulin, IGF-I and hepatocellular carcinoma: Etiological factors or risk markers? (pages 164–173)

      Annekatrin Lukanova, Susen Becker, Anika Hüsing, Helena Schock, Veronika Fedirko, Elisabeth Trepo, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Vassiliki Benetou, Dimitrios Trichopoulos, Ute Nöthlings, Anne Tjønneland, Kim Overvad, Laure Dossus, Birgit Teucher, Heiner Boeing, Krasimira Aleksandrova, Domenico Palli, Valeria Pala, Salvatore Panico, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Peter D. Siersema, Petra H.M. Peeters, Jose Ramon Quiros, Eric J. Duell, Esther Molina-Montes, Maria-Dolores Chirlaque, Aurelio Barricarte Gurrea, Miren Dorronsoro, Björn Lindkvist, Dorthe Johansen, Mårten Werner, Malin Sund, Kay-Tee Khaw, Nick Wareham, Timothy J. Key, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Marc J. Gunter, Elio Riboli, Mazda Jenab and Rudolf Kaaks

      Version of Record online: 2 AUG 2013 | DOI: 10.1002/ijc.28342

      What's new?

      Testosterone and insulin-like growth factor-1 (IGF-1) are implicated in the development of hepatocellular carcinoma (HCC), though their involvement may be more complex than previously thought. Here, in a unique study population with low prevalence of hepatitis infections, an association was detected between HCC risk and increased levels of sex hormone binding globulin (SHBG) and IGF-1 prior to diagnosis. Neither testosterone nor IGF-1, however, was found to have an etiological influence in the decade before diagnosis. The results suggest that SHBG and IGF-I should be considered in the clinical evaluation of patients at increased risk of HCC.

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      Incidence of lymphoplasmacytic lymphoma/Waldenström's macroglobulinaemia in Japan and Taiwan population-based cancer registries, 1996–2003 (pages 174–180)

      Masako Iwanaga, Chun-Ju Chiang, Midori Soda, Mei-Shu Lai, Ya-Wen Yang, Yasushi Miyazaki, Keitaro Matsuo, Tomohiro Matsuda and Tomotaka Sobue

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28343

      What's new?

      While identified generally as a rare cancer of B cells, the incidence patterns of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in Asian populations have not been extensively characterized. Here, analysis of data from cancer registries for the period 1996–2003 shows that incidence of LPL/WM among Asians living in Japan and Taiwan is lower than for Asians in the United States and Europe. A trend toward increased incidence, however, was observed in Japan. The overall low incidence for Asians living within their countries of origin warrants further investigation, particularly for environmental and genetic factors that may contribute to this rare disease.

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      Neglected role of hookah and opium in gastric carcinogenesis: A cohort study on risk factors and attributable fractions (pages 181–188)

      Alireza Sadjadi, Mohammad H. Derakhshan, Abbas Yazdanbod, Majid Boreiri, Mahbubeh Parsaeian, Masoud Babaei, Masoomeh Alimohammadian, Fatemeh Samadi, Arash Etemadi, Farhad Pourfarzi, Emad Ahmadi, Alireza Delavari, Farhad Islami, Farshad Farzadfar, Masoud Sotoudeh, Arash Nikmanesh, Behrooz Z. Alizadeh, Geertruida H. de Bock and Reza Malekzadeh

      Version of Record online: 5 AUG 2013 | DOI: 10.1002/ijc.28344

      What's new?

      Gastric cancer strikes Iranian men more often than any other cancer, and previous studies report a connection between gastric cancer and hookah, a traditional smoking device in the region. This study probed the factors associated with precancerous lesions and gastric cancer, including hookah and opium use. They found that both hookah and opium use increased the likelihood of developing cancer, as did high salt intake and cigarette smoking.

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      Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: A case–control observational study based on registry data (pages 189–196)

      Urpo Nieminen, Airi Jussila, Stig Nordling, Harri Mustonen and Martti A. Färkkilä

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28346

      What's new?

      Chronic inflammatory bowel disease (IBD) with ulcerative colitis or Crohn's disease increases risk of colorectal carcinoma (CRC), though the reasons for this are not fully known. Here, analysis of IBD patient data at Helsinki University Central Hospital suggests that patients with severe colon inflammation are at significantly higher risk for dysplasia or CRC compared with patients with mild to moderate or no inflammation. Along with degree of inflammation, duration of IBD also influenced risk. Use of thiopurines and aminosalicylic acid, on the other hand, was linked to a reduction in risk for dysplasia or carcinoma.

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      Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway (pages 197–206)

      Stefan de Vogel, Arve Ulvik, Klaus Meyer, Per Magne Ueland, Ottar Nygård, Stein Emil Vollset, Grethe S. Tell, Jesse F. Gregory III, Steinar Tretli and Tone Bjørge

      Version of Record online: 27 JUL 2013 | DOI: 10.1002/ijc.28347

      What's new?

      The one-carbon metabolic pathway plays a role in carcinogenesis, possibly through involvement with DNA methylation. Circulating choline and vitamin B2 may up the risk of prostate cancer, according to some studies. The urine concentration of sarcosine, a product of choline oxidation, has also been associated with progression of prostate cancer, although subsequent analyses suggest that urine detection may not be good predictor of disease aggressiveness. This study compared serum concentration of sarcosine and various other metabolites with prostate cancer risk. They found that high sarcosine and glycine concentration correlate with modestly reduced risk of prostate cancer, in constrast with previous reports.

  7. Cancer Therapy

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
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      Novel Gemini vitamin D3 analogs: Large structure/function analysis and ability to induce antimicrobial peptide (pages 207–217)

      Ryoko Okamoto, Sigal Gery, Yoshio Kuwayama, Niels Borregaard, Quoc Ho, Rocio Alvarez, Tadayuki Akagi, George Y. Liu, Milan R. Uskokovic and H. Phillip Koeffler

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28328

      What's new?

      The ability of vitamin D3 to stem cancer cell proliferation has inspired investigation of its use as an anticancer agent. Its induction of hypercalcemia, however, has necessitated exploration of less-toxic analogs. Here, 39 vitamin D3 analogs were synthesized and their anticancer activity compared. The analog BXL-01-0126 markedly inhibited the proliferation of cancer cells and the production of cathelicidin antimicrobial peptide (CAMP) in vitro, as well as in a leukemia xenograft mouse model. The findings raise the possibility that vitamin D3 compounds, in addition to their anticancer effects, might also protect against microbial infections in leukemia patients.

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      Antimyeloma activity of NK012, a micelle-forming macromolecular prodrug of SN-38, in an orthotopic model (pages 218–223)

      Osamu Miyazaki, Keiko Sekine, Naoko Nakajima, Eiji Ichimura, Keiko Ebara, Daichi Nagai, Takeshi Onda, Yoshitaka Miyakawa, Kazuya Okamoto and Tomio Morino

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28333

      What's new?

      The prodrug NK012 has been shown to have stronger anti-tumor activity than irinotecan in a broad range of human solid-tumor xenograft models. In this study, the authors evaluated intravenous NK012 in a mouse model of human multiple myeloma (MM). They found that NK012 suppressed tumor-cell proliferation and prolonged survival time, both alone and in combination with bortezomib. NK012 thus shows promise as a therapeutic candidate for the treatment of MM.

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      IPS-1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus (pages 224–234)

      Quan Zhang, Xiaoshuang Xu, Yan Yuan, Xiaocheng Gong, Zedong Chen and Xiangming Xu

      Version of Record online: 24 JUL 2013 | DOI: 10.1002/ijc.28340

      What's new?

      Inactivated Sendai virus (HVJ-E) can directly kill human cancer cells via apoptosis, but the molecular mechanisms aren't fully understood. In this study in a murine melanoma cell line, the authors found that the caspase and MAPK pathways are involved, and that IPS-1 (IFN-β promoter stimulator-1) plays a dual function. In addition, when tumors in live mice were directly injected with the inactivated virus, growth of the tumors was inhibited. These results offer new insights into the selective killing of cancer cells by oncolytic viruses, and suggest new therapeutic targets for inducing apoptosis in cancer cells.

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      Enhanced killing of therapy-induced senescent tumor cells by oncolytic measles vaccine viruses (pages 235–243)

      Timo Weiland, Johanna Lampe, Frank Essmann, Sascha Venturelli, Alexander Berger, Sascha Bossow, Susanne Berchtold, Klaus Schulze-Osthoff, Ulrich M. Lauer and Michael Bitzer

      Version of Record online: 7 AUG 2013 | DOI: 10.1002/ijc.28350

      What's new?

      Therapeutic induction of senescence (TIS) has emerged as a promising cancer treatment strategy with the potential to overcome therapy resistance due to the ability of tumor cells to evade apoptosis. Although senescent cells undergo a permanent cell cycle arrest, they remain metabolically active in vivo, making combination approaches to eliminate them urgently needed. This study provides a proof-of-concept that, despite the profoundly altered phenotype of senescent tumor cells, oncolytic viruses are able to hijack cancer cells after TIS, leading to a destruction of tumor cells. These observations open up a new research field at the crossroads between TIS and virotherapy.

  8. Short Reports

    1. Top of page
    2. Mini Review
    3. Cancer Cell Biology
    4. Cancer Genetics
    5. Tumor Immunology
    6. Early Detection and Diagnosis
    7. Epidemiology
    8. Cancer Therapy
    9. Short Reports
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      Allele-specific imbalance mapping identifies HDAC9 as a candidate gene for cutaneous squamous cell carcinoma (pages 244–248)

      Jessica L. Fleming, Amy M. Dworkin, Dawn C. Allain, Soledad Fernandez, Lai Wei, Sara B. Peters, O. Hans Iwenofu, Katie Ridd, Boris C. Bastian and Amanda Ewart Toland

      Version of Record online: 16 JUL 2013 | DOI: 10.1002/ijc.28339

      What's new?

      While inherited risk factors have been suggested to play a role in cutaneous squamous cell carcinomas (cSCC) in addition to environmental causes, so far few well-validated genetic risk variants exist. Human 7p21 however shows evidence of preferential allelic imbalance (PAI) and copy neutral loss of heterozygosity in cSCCs. 7p21 is orthologous to a mouse skin cancer susceptibility locus, Skts5. Here, candidate genes at Skts5 identified from the mouse were assessed for evidence of PAI in human cSCCs. Multiple variants in HDAC9 were identified that show evidence of allele-specific gains in cSCC, suggesting that HDAC9 may be important in cSCC development.

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