Cancer Medicine

Cover image for Vol. 4 Issue 1

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

Edited By: Qingyi Wei, M.D., Ph.D.

Online ISSN: 2045-7634

VIEW

  1. 1 - 41
  1. Original Research

    1. You have full text access to this OnlineOpen article
      Effects of human arylamine N-acetyltransferase I knockdown in triple-negative breast cancer cell lines

      Jacky M. Tiang, Neville J. Butcher and Rodney F. Minchin

      Article first published online: 28 JAN 2015 | DOI: 10.1002/cam4.415

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      Human arylamine N-acetyltransferase I (NAT1) has been associated with risk of some cancers due to its role in the metabolism of carcinogens. Recently, inhibition of NAT1 was shown to affect cancer cell growth and survival. Here, the authors report for the first time that NAT1 is associated with lamellipodia and the filopodia extensions in breast cancer cells. Furthermore, knockdown of NAT1 results in a loss of filopodia and a decrease in invasion both in vitro and in vivo.

    2. You have full text access to this OnlineOpen article
      Variability in the reported management of pulmonary metastases in osteosarcoma

      Onita Bhattasali, Andrea T. Vo, Michael Roth, David Geller, R. Lor Randall, Richard Gorlick and Jonathan Gill

      Article first published online: 28 JAN 2015 | DOI: 10.1002/cam4.407

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      In this study, we present the results of a survey of the membership of the Connective Tissue Oncology Society, regarding the management of pulmonary metastases in patients with osteosarcoma. We found variability in the management of pulmonary nodules within and among different specialties treating patients with osteosarcoma. There is a paucity of data on the practice patterns in this entity.

    3. You have full text access to this OnlineOpen article
      Years of life lived with disease and years of potential life lost in children who die of cancer in the United States, 2009

      Peter M. de Blank, Quinn T. Ostrom, Chaturia Rouse, Yingli Wolinsky, Carol Kruchko, Joanne Salcido and Jill S. Barnholtz-Sloan

      Article first published online: 27 JAN 2015 | DOI: 10.1002/cam4.410

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      Using the National Vital Statistics System (NVSS) mortality data and the Surveillance, Epidemiology and End Results (SEER) incidence-based mortality data, we calculated estimates of the years of potential life lost (YPLL) for the most common types of childhood cancer in the United States in 2009, as well as specific brain and CNS tumor histologies. We found that childhood brain and CNS tumors are the largest contributor to YPLL for children under 20, followed by leukemia. We also propose a new measure, years of life lived with disease (YLLD), that measures the total years from diagnosis to death for those that die due to their cancer and suggest that this presents a new measure to measure the impact of disease on a population, as well as to gauge success in tumors that are rapidly fatal.

    4. You have full text access to this OnlineOpen article
      Using topical imiquimod for the management of positive in situ margins after melanoma resection

      Amrita S. Pandit, Erik J. Geiger, Stephan Ariyan, Deepak Narayan and Jennifer Nam Choi

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.402

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      The current standard of care for melanoma in situ is wide excision with 5–10 mm margins, though several other nonsurgical therapies have been described. Positive histological margins showing melanoma in situ after initial wide local resection of melanoma is a common clinically challenging scenario, particularly in sites of chronic sun exposure. Imiquimod 5% cream can be used as an alternative treatment for residual margin involvement with melanoma in situ after initial local excision, and is associated with high clinical and histopathologic clearance rates.

    5. You have full text access to this OnlineOpen article
      Risk of second malignancies in patients with early-stage classical Hodgkin's lymphoma treated in a modern era

      Melissa H. LeMieux, Abhishek A. Solanki, Usama Mahmood, Steven J. Chmura and Matthew Koshy

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.405

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      Our analysis suggests that in patients treated with radiation therapy for stage I or II Hodgkin's lymphoma, treatment prior to 2000 had a slightly higher risk of second malignancy compared to treatment in 2000 and later. Further studies, with longer follow-up of patients treated in the modern era are needed to confirm these findings.

    6. You have full text access to this OnlineOpen article
      Cutaneous squamous cell carcinoma in norway 1963–2011: increasing incidence and stable mortality

      Trude E. Robsahm, Per Helsing and Marit B. Veierød

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.404

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      In this study of squamous cell carcinoma (SCC) incidence, mortality, and survival rates in the whole Norwegian population over 50 years (1963–2011), strong increasing incidence rates were found in all age groups >30 years, in both females and males. The findings underline an increasing need for treatment resources, especially considering aging of the population, and call for creation of particular guidelines for primary prevention of SCC.

  2. Short Reports

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      Rates of complete diagnostic testing for patients with acute myeloid leukemia

      Tara L. Lin, Travis Williams, Jianghua He, Omar S. Aljitawi, Siddhartha Ganguly, Sunil Abhyankar, Allan Fleming, Heather Male and Joseph P. McGuirk

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.406

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      In addition to cytogenetics, additional molecular markers of prognosis have been identified and incorporated into the management of patients with acute myeloid leukemia (AML). We hypothesized that rates of molecular testing would be higher in an academic center versus community sites. Rates of molecular testing in AML were higher in an academic center versus community sites in the 5 years following the World Health Organization revised classification of AML.

  3. Original Research

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      S-adenosylmethionine blocks osteosarcoma cells proliferation and invasion in vitro and tumor metastasis in vivo: therapeutic and diagnostic clinical applications

      Surabhi Parashar, David Cheishvili, Ani Arakelian, Zahid Hussain, Imrana Tanvir, Haseeb Ahmed Khan, Moshe Szyf and Shafaat A. Rabbani

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.386

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      These studies provide a possible mechanism for the role of DNA demethylation in the development of and metastasis of OS to provide a rationale for the use of hypermethylation therapy OS patients and identify new targets for monitoring OS development and progression.

    2. You have full text access to this OnlineOpen article
      Clinical benefit in recurrent glioblastoma from adjuvant NovoTTF-100A and TCCC after temozolomide and bevacizumab failure: a preliminary observation

      Eric T. Wong, Edwin Lok and Kenneth D. Swanson

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.421

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      We treated a series of patients with NovoTTF-100A and bevacizumab alone or in combination with a regimen consisting of 6-thioguanine, lomustine, capecitabine and celecoxib. Compared to the former cohort, the latter cohort exhibited a trend for prolonged overall survival, with one experiencing an objective response with a 50% reduction in tumor size on magnetic resonance imaging despite possessing a larger tumor size at baseline and more severe neurologic dysfunction than the median for either group.

    3. You have full text access to this OnlineOpen article
      Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies

      Andrew P. Stein, Adam D. Swick, Molly A. Smith, Grace C. Blitzer, Robert Z. Yang, Sandeep Saha, Paul M. Harari, Paul F. Lambert, Cheng Z. Liu and Randall J. Kimple

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.387

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      No clinically validated predictive biomarkers for head and neck squamous cell carcinoma (HNSCC) exist. Utilizing a mouse xenograft model generated from HNSCC cell lines, we demonstrate both unique and established relationships including low excision repair cross-complementation group 1 (ERCC1), low phospho-Akt/low phospho-ERK, and high total epidermal growth factor receptor (EGFR) being associated with cisplatin sensitivity, cetuximab sensitivity, and radiation resistance, respectively. This protocol can be applied to other model systems and provide guidance for the proper validation of putative predictive biomarkers for clinical usage.

    4. You have full text access to this OnlineOpen article
      Development and validation of the functional assessment of cancer therapy–antiangiogenesis subscale

      Karen Kaiser, Jennifer L. Beaumont, Kimberly Webster, Susan E. Yount, Lynne I. Wagner, Timothy M. Kuzel and David Cella

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.385

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      Side effects from anti-angiogenesis therapies may impact health-related quality of life and can result in dose reductions, delays or discontinuation of therapy. The Functional Assessment of Cancer Therapy (FACT) -Anti-Angiogenesis Subscale was developed and validated to enhance treatment decision-making and side effect management for patients receiving anti-angiogenesis therapies.

    5. You have full text access to this OnlineOpen article
      Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell carcinoma

      Nicolas F. Schlecht, Miriam Ben-Dayan, Nicole Anayannis, Roberto A. Lleras, Carlos Thomas, Yanhua Wang, Richard V. Smith, Robert D. Burk, Thomas M. Harris, Geoffrey Childs, Thomas J. Ow, Michael B. Prystowsky and Thomas J. Belbin

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.374

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      Heat Map of the 22 CpG molecular panel distinguishing HPV-positive from HPV-negative OPSCC. Patient identifiers, presence of HPV16 DNA and RNA (top), and p16 immunohistochemistry (bottom) status for each patient are shown. Illumina TargetID for each CpG loci is indicated at the right. DNA hypermethylation (tumor to corresponding normal) is shown in red; DNA hypomethylation is indicated by green.

    6. You have full text access to this OnlineOpen article
      Clinical outcomes associated with evolving treatment modalities and radiation techniques for base-of-tongue carcinoma: thirty years of institutional experience

      Leechuan Andy Chen, Christopher J. Anker, Jason P. Hunt, Luke O. Buchmann, Kenneth F. Grossmann, Kenneth Boucher, Li-Ming Christine Fang, Dennis C. Shrieve and Ying J. Hitchcock

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.364

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      Over the past 30 years, curative treatment modalities for locally advanced base-of-tongue carcinomas at our institution have evolved from surgery to definitive radiotherapy to definitive chemoradiotherapy. Radiation techniques have evolved from external beam radiation therapy plus interstitial brachytherapy to intensity modulated radiation therapy with simultaneous integrated boost. Clinical outcomes associated with evolving treatment modalities and radiation techniques demonstrate excellent locoregional control and survival with modern techniques.

  4. Short Reports

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      Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

      Muhammad A. Mir, Samith T. Kochuparambil, Roshini S. Abraham, Vilmarie Rodriguez, Matthew Howard, Amy P. Hsu, Amie E. Jackson, Steven M. Holland and Mrinal M. Patnaik

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.384

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      Guanine-adenine-thymine-adenine 2 (GATA2) mutation results in a newly described syndrome of familial myelodysplastic syndrome/acute myeloid leukemia, human papillomavirus infections and MonoMAC syndrome. Hematopoietic stem cell transplant (HSCT) and supportive care are mainstay of treatment.

  5. Original Research

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      Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

      Manabu Shigeoka, Naoki Urakawa, Mari Nishio, Nobuhisa Takase, Soken Utsunomiya, Hiroaki Akiyama, Yoshihiro Kakeji, Takahide Komori, Yu-ichiro Koma and Hiroshi Yokozaki

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.401

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      We previously suggested that CD204 was a useful marker for tumor-associated macrophages (TAMs) of esophageal squamous cell carcinoma (ESCC). Here, we discovered that within the ESCC microenvironment not only cancer cells but also TAMs expressed cysteine-rich, angiogenic inducer, 61 (Cyr61), induced by conditioned media of ESCC cells. Levels of Cyr61 expression were associated with CD204+ macrophage infiltration in ESCC tissue. Cyr61 promoted CD204 expression and the migration of macrophages via MEK/ERK pathway in vitro.

    2. You have full text access to this OnlineOpen article
      Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients

      Brenda Y. Hernandez, Lynne R. Wilkens, Loïc Le Marchand, David Horio, Clayton D. Chong and Lenora W. M. Loo

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.375

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      The relationship of (insulin-like growth factor) IGF1, IGF1R, IGFBP2 (IGF-binding proteins2), and IGFBP3 expression in breast tumor tissue with survival was examined in a multiethnic population. In Native Hawaiian patients, IGFBP2 and IGFBP3, and IGF1R expression were predictors of poor survival. No association of IGF-axis protein expression and survival was observed in Japanese or Caucasian patients.

    3. You have full text access to this OnlineOpen article
      Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

      Amy Schell, Jessica Ley, Ningying Wu, Kathryn Trinkaus, Tanya Marya Wildes, Loren Michel, Wade Thorstad, Hiram Gay, James Lewis, Jason Rich, Jason Diaz, Randal C. Paniello, Brian Nussenbaum and Douglas R. Adkins

      Article first published online: 26 JAN 2015 | DOI: 10.1002/cam4.382

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      This study is a historical comparison of different taxane-based induction regimens in HNSCC. Disease-specific survival (DSS) and OS were compared between APF-C & TPF-C. T and N classification and smoking history were similar between the two groups. In p16+ OPSCC, 2-year DSS was 100% with APF-C and 74.6% with TPF-C (P = 0.0019). In p16+ OPSCC, 2-year OS was 94.1% with APF-C and 74.6% with TPF-C (P = 0.013).

  6. Reviews

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      CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations

      Luis H. Camacho

      Article first published online: 25 JAN 2015 | DOI: 10.1002/cam4.371

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      Ipilimumab indirectly targets the tumor by stimulating the patient's immune system to recognize and destroy cancer cells and has demonstrated a survival benefit for patients treated in different clinical trials, now exceeding 4 years in some cases. Most patients (84.8%) experience a drug-related adverse event (AE) of any grade, most of these are of low toxicity grade, and a majority these events can be managed following established guidelines.

  7. Original Research

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      The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells

      Hirokazu Hirakawa, Hiroshi Fujisawa, Aya Masaoka, Miho Noguchi, Ryoichi Hirayama, Momoko Takahashi, Akira Fujimori and Ryuichi Okayasu

      Article first published online: 13 JAN 2015 | DOI: 10.1002/cam4.377

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      The combination of Hsp90 inhibitor with heavy-ion irradiation provided effective tumor control in vitro and in vivo with human cancer cells. This study can offer a new attractive alternative for solid tumor treatment.

    2. You have full text access to this OnlineOpen article
      Aberrant DNA hypermethylation reduces the expression of the desmosome-related molecule periplakin in esophageal squamous cell carcinoma

      Takeshi Otsubo, Teruki Hagiwara, Miwa Tamura-Nakano, Takuhito Sezaki, Oki Miyake, Chihaya Hinohara, Toshio Shimizu, Kazuhiko Yamada, Taeko Dohi and Yuki I. Kawamura

      Article first published online: 12 JAN 2015 | DOI: 10.1002/cam4.369

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      A desmosomal protein preplakin (PPL) is reduced in esophageal squamous cell carcinoma (ESCC). Here, we first report DNA methylation of PPL in ESCC and that PPL plays significant role in desmosome formation, squamous cell stratifying, adhesion to extracellular matrix and delayed migration.

    3. You have full text access to this OnlineOpen article
      PIAS3 expression in squamous cell lung cancer is low and predicts overall survival

      Rime Abbas, Karen S. McColl, Adam Kresak, Michael Yang, Yanwen Chen, Pingfu Fu, Gary Wildey and Afshin Dowlati

      Article first published online: 9 JAN 2015 | DOI: 10.1002/cam4.372

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      PIAS3, an endogenous inhibitor of STAT3 activity, demonstrates low expression in squamous cell lung cancer tumors and predicts poor survival. Restoration of PIAS3 expression in squamous lung cancer cells inhibited cell growth by inducing apoptosis and may therefore represent a therapeutic strategy benefiting a subgroup of squamous cell lung cancer patients.

  8. Methods

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      Open pipelines for integrated tumor genome profiles reveal differences between pancreatic cancer tumors and cell lines

      Jeremy Goecks, Bassel F. El-Rayes, Shishir K. Maithel, H. Jean Khoury, James Taylor and Michael R. Rossi

      Article first published online: 4 JAN 2015 | DOI: 10.1002/cam4.360

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      We describe open, reproducible data analysis pipelines that create an integrated genomic profile of a cancer and use the profile to find mutations associated with disease and potentially useful drugs. These pipelines analyze high-throughput cancer exome and transcriptome sequence data together with public databases to find mutations and drugs. The pipelines are integrated into the popular Web platform Galaxy and available for use at http://usegalaxy.org/cancer.

  9. Original Research

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      Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute

      John D. Hainsworth, Dana S. Thompson, John A. Bismayer, Victor G. Gian, William M. Merritt, Robert C. Whorf, Lindsey H. Finney and B. Stephens Dudley

      Article first published online: 31 DEC 2014 | DOI: 10.1002/cam4.376

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      The purpose of this study was to compare the efficacy and toxicity of standard first-line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. The addition of sorafenib to standard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first-line treatment of advanced epithelial ovarian cancer.

    2. You have full text access to this OnlineOpen article
      Sex differences in bladder cancer pathology and survival: analysis of a population-based cancer registry

      Masayoshi Zaitsu, Satoshi Toyokawa, Akiko Tonooka, Fumiaki Nakamura, Takumi Takeuchi, Yukio Homma and Yasuki Kobayashi

      Article first published online: 23 DEC 2014 | DOI: 10.1002/cam4.379

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      There are sex differences in the epidemiological characteristics of bladder cancer. Female patients have less favorable pathology and survival than male patients.

    3. You have full text access to this OnlineOpen article
      Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

      Hiroaki Kimura, Norio Yamamoto, Toshiharu Shirai, Hideji Nishida, Katsuhiro Hayashi, Yoshikazu Tanzawa, Akihiko Takeuchi, Kentaro Igarashi, Hiroyuki Inatani, Shingo Shimozaki, Takashi Kato, Yu Aoki, Takashi Higuchi and Hiroyuki Tsuchiya

      Article first published online: 23 DEC 2014 | DOI: 10.1002/cam4.373

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      Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during combination chemotherapy for bone and soft tissue sarcoma patients. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron administration for CINV.

    4. You have full text access to this OnlineOpen article
      A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma

      Ragini Kudchadkar, Scott Ernst, Bartosz Chmielowski, Bruce G. Redman, Joyce Steinberg, Anne Keating, Fei Jie, Caroline Chen, Rene Gonzalez and Jeffrey Weber

      Article first published online: 23 DEC 2014 | DOI: 10.1002/cam4.363

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      YM155 is a first-in-class agent that suppresses surviving. Though YM155 combined with docetaxel was generally well-tolerated in this study, it showed limited efficacy in the treatment of metastatic melanoma.

    5. You have full text access to this OnlineOpen article
      Reproducibility of Her2/neu scoring in gastric cancer and assessment of the 10% cut-off rule

      Hans-Michael Behrens, Viktoria S. Warneke, Christine Böger, Nele Garbrecht, Eva Jüttner, Wolfram Klapper, Micaela Mathiak, Ilske Oschlies, Ursula Rudolph, Christiane Stuhlmann-Laeisz, David Trick, Christoph Röcken and Peter Hufnagl

      Article first published online: 16 DEC 2014 | DOI: 10.1002/cam4.365

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      We studied the reproducibility of Her2/neu scoring in gastric cancer and its effect on the application of Trastuzumab, especially when the ratio of stained tumor is around the cutoff limit of 10%. It was demonstrated that the stained tumor ratio cannot be reliably determined. Thus stained tumor ratios around 10% may lead to erratic decisions whether to apply a Trastuzumab therapy. Therefore we propose to reconsider the 10% cutoff limit.

    6. You have full text access to this OnlineOpen article
      Smoking and mortality after breast cancer diagnosis: the health and functioning in women study

      Monika Izano, William A. Satariano, Robert A. Hiatt and Dejana Braithwaite

      Article first published online: 16 DEC 2014 | DOI: 10.1002/cam4.359

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      Long-term smoking was associated with reduced survival in women with breast cancer. Survival decreased with increasing smoking intensity.

  10. Reviews

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      Ectokinases as novel cancer markers and drug targets in cancer therapy

      Garif Yalak and Viola Vogel

      Article first published online: 14 DEC 2014 | DOI: 10.1002/cam4.368

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      The concentrations of several ectokinases are significantly increased in body fluids from cancer patients and might serve as future tumor markers. Furthermore, the sudden release of intracellular content increases extracellular ATP levels, thereby transiently allowing kinases to phosphorylate extracellular matrix (ECM) proteins.

  11. Original Research

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      Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

      Julia C. Meier, Bernard Haendler, Henrik Seidel, Philip Groth, Robert Adams, Karl Ziegelbauer, Bertolt Kreft, Georg Beckmann, Anette Sommer and Charlotte Kopitz

      Article first published online: 10 DEC 2014 | DOI: 10.1002/cam4.354

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      This article shows for the first time that the cytokine growth differentiation factor 15 (GDF15) is involved in carboplatin resistance in ovarian cancer. Evidences were shown by a whole-genome expression analysis and statistical testing with linear model analysis of the short-term and long-term carboplatin-treated ovarian cancer model A2780 and its resistant variant A2780cis in vitro and in vivo. Interestingly, GDF15 may contribute to chemoresistance by maintaining a stem-like cancer phenotype via basal p27-upregulation and the alteration of p16 as well as p53 protein expression.

    2. You have full text access to this OnlineOpen article
      Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer

      Justin S. Gundara, JingTing Zhao, Anthony J. Gill, James C. Lee, Leigh Delbridge, Bruce G. Robinson, Catriona McLean, Jonathan Serpell and Stan B. Sidhu

      Article first published online: 8 DEC 2014 | DOI: 10.1002/cam4.355

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      (A) western blot of apoptosis and autophagy markers 48 h post TT cell transfection with miR-9-3p or negative control; (B) quantified densitometry results of 2A; (C) western blot of apoptosis and autophagy markers 48h post MZ-CRC-1 cell transfection with miR-9-3p or negative control; (D) quantified densitometry results of 2C (#: P < 0.05). These results indicate that autophagy is a tumor cell survival mechanism in medullary thyroid carcinoma (MTC) that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease.

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      Setting up a wide panel of patient-derived tumor xenografts of non–small cell lung cancer by improving the preanalytical steps

      Marius Ilie, Manoel Nunes, Lydia Blot, Véronique Hofman, Elodie Long-Mira, Catherine Butori, Eric Selva, Ana Merino-Trigo, Nicolas Vénissac, Jérôme Mouroux, Patricia Vrignaud and Paul Hofman

      Article first published online: 3 DEC 2014 | DOI: 10.1002/cam4.357

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      We established a patient-derived NSCLC xenograft collection, regardless of the time required and the distance between the clinic and the animal facilities. This large PDX collection recapitulates the histopathology and molecular diversity of NSCLC and provides stable and reliable preclinical models for human lung cancer research.

    4. You have full text access to this OnlineOpen article
      Zerumbone increases oxidative stress in a thiol-dependent ROS-independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation

      Amit Deorukhkar, Niharika Ahuja, Armando-Lopez Mercado, Parmeswaran Diagaradjane, Uma Raju, Nalini Patel, Pranshu Mohindra, Nga Diep, Sushovan Guha and Sunil Krishnan

      Article first published online: 1 DEC 2014 | DOI: 10.1002/cam4.367

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      Though sesquiterpene zerumbone has been shown to have antiproliferative and anticarcinogenic activities in colorectal cancer (CRC); no reports document its potential for and mechanism of CRC radiosensitization. Our studies, for the first time show potent radiosensitizing properties of zerumbone in CRC cells, and also for the first time report zerumbone's ability to enhance radiation-induced DNA damage. This study suggests a novel cellular glutathione-dependent mechanism of radiosensitization that is independent of reactive oxygen species generation.

    5. You have full text access to this OnlineOpen article
      Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells

      Naoki Sato, Masao Maeda, Mai Sugiyama, Satoko Ito, Toshinori Hyodo, Akio Masuda, Nobuyuki Tsunoda, Toshio Kokuryo, Michinari Hamaguchi, Masato Nagino and Takeshi Senga

      Article first published online: 1 DEC 2014 | DOI: 10.1002/cam4.366

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      SNW1, EFTUD2, and SNRNP200 are critical regulators for RNA splicing. SNW1 directly associates with EFTUD2 and SNRNP200, and inhibition of the SNW1 association promotes apoptosis o breast cancer cells.

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      Induction of Ras by SAF-1/MAZ through a feed-forward loop promotes angiogenesis in breast cancer

      Alpana Ray and Bimal K. Ray

      Article first published online: 30 NOV 2014 | DOI: 10.1002/cam4.362

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      Onnogenic Ras activates SAF-1/MAZ which in turn induces expression of Ras allowing high level of Ras protein in cancer cells. Together, these cellular events promote angiogenesis via induction of VEGF expression.

  12. Reviews

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      Systematic review of sleep disorders in cancer patients: can the prevalence of sleep disorders be ascertained?

      Julie L. Otte, Janet S. Carpenter, Shalini Manchanda, Kevin L. Rand, Todd C. Skaar, Michael Weaver, Yelena Chernyak, Xin Zhong, Christele Igega and Carol Landis

      Article first published online: 30 NOV 2014 | DOI: 10.1002/cam4.356

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      Studies of sleep and cancer focus on specific types of symptoms of poor sleep, and there are no published prevalence studies that focus on underlying sleep disorders. Challenging the current paradigm of the way sleep is studied in cancer could produce better clinical screening tools for use in oncology clinics leading to better triaging of patients with sleep complaints to sleep specialists, and overall improvement in sleep quality.

  13. Original Research

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      Primary care physician characteristics associated with cancer screening: a retrospective cohort study in Ontario, Canada

      Aisha K. Lofters, Ryan Ng and Rebecca Lobb

      Article first published online: 27 NOV 2014 | DOI: 10.1002/cam4.358

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      This study identified primary care physician characteristics associated with cancer screening for their eligible patients. In multivariable analyses, physicians who attended medical schools in certain parts of the world were less likely to screen their patients than Canadian graduates. South Asian patients were the most vulnerable to under-screening.

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      Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer

      Kevin M. Schuler, Brooke S. Rambally, Megan J. DiFurio, Brante P. Sampey, Paola A. Gehrig, Liza Makowski and Victoria L. Bae-Jump

      Article first published online: 21 NOV 2014 | DOI: 10.1002/cam4.353

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      Metformin significantly reduced proliferation, as assessed by Ki-67 staining, in a preoperative window study in obese endometrial cancer patients, with parallel effects on inhibition of the mTOR pathway. Differences were found in the metabolic effects of metformin in the serum and endometrial tumors of responders versus nonresponders to treatment, including increased lipolysis, fatty acid oxidation, and glycogen metabolism in responders. This study provides support for therapeutic clinical trials of metformin in this obesity-driven disease.

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      Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo−/− mice

      Elizabeth J. Campbell, Margreet C. M. Vissers, Stephanie Bozonet, Arron Dyer, Bridget A Robinson and Gabi U. Dachs

      Article first published online: 29 OCT 2014 | DOI: 10.1002/cam4.349

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      The ability of dietary vitamin C to act as a preventative agent for cancer is of considerable public interest. We show that restoration from adequate to optimal vitamin C levels can reduce tumor growth in an animal which models the human vitamin C dependency. This study provides a mechanistic insight into the role of vitamin C in tumor biology, and provides evidence in vivo of a direct involvement of vitamin C in gene regulation via the transcription factor HIF-1.

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      Vismodegib, an antagonist of hedgehog signaling, directly alters taste molecular signaling in taste buds

      Hyekyung Yang, Wei-na Cong, Jeong Seon Yoon and Josephine M. Egan

      Article first published online: 29 OCT 2014 | DOI: 10.1002/cam4.350

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      Vismodegib, an inhibitor of hedgehog (hh) signaling, is the first oral medicine approved by the US Food and Drug Administration for the treatment of adults with advanced basal-cell carcinoma and, interestingly, patients on vismodegib treatment often report distortion in taste perception (dysgeusia). The processing of taste begins with molecular events at the surface membrane of modified epithelial-derived taste cells and sonic hh (Shh) plays a critical role in development and maintaining of taste papillae in rodents. In this study, we demonstrate that vismodegib treatment causes alteration in taste cell turnover and expression of taste sensing machinery in taste cells, suggesting that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds.

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      Establishment of new predictive markers for distant recurrence of colorectal cancer using lectin microarray analysis

      Kentaro Nakajima, Masafumi Inomata, Hidekatsu Iha, Takahiro Hiratsuka, Tsuyoshi Etoh, Norio Shiraishi, Kenji Kashima and Seigo Kitano

      Article first published online: 29 OCT 2014 | DOI: 10.1002/cam4.342

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      This report evaluates the usefulness of lectin microarray profiling identifying a novel predictive marker for distant recurrence in colorectal cancer. Increased Agaricus bisporus (ABA)-binding signals in cancer tissues compared with those in the normal epithelium were significantly associated with distant recurrence both in learning and validation setting. Tumor/normal ratio of ABA may be used as a new predictive biomarker for distant recurrence of curatively resected colorectal cancer.

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