Cancer Medicine

Cover image for Vol. 3 Issue 4

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 - 55
  1. Original Research

    1. You have full text access to this OnlineOpen article
      Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax

      Masaya Higuchi, Masahiko Takahashi, Yuetsu Tanaka and Masahiro Fujii

      Article first published online: 30 AUG 2014 | DOI: 10.1002/cam4.329

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      Human T-cell leukemia virus type 1 (HTLV-1) is an etiological agent of adult T-cell leukemia (ATL). In this study, we show that downregulation of proapoptotic protein Bim augments T-cell transformation by HTLV-1 Tax oncoprotein and contributes to the survival of ATL cells.

  2. Commentary

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      Quadruple wild-type (WT) GIST: defining the subset of GIST that lacks abnormalities of KIT, PDGFRA, SDH, or RAS signaling pathways

      Maria A. Pantaleo, Margherita Nannini, Christopher L. Corless and Michael C. Heinrich

      Article first published online: 27 AUG 2014 | DOI: 10.1002/cam4.325

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      A subset of gastrointestinal stromal tumors (GISTs) lacks mutations in the KIT/platelet-derived growth factor receptor alpha (PDGFRA) or RAS pathways and yet retains an intact succinate dehydrogensase (SDH) complex. We propose that these KIT/PDGFRA/SDH/RAS-P WT GIST tumors be designated as the quadruple wild-type (WT) GIST. Further, molecular and clinicopathological characterization of quadruple WT GIST will help determine their prognosis as well as assist in the optimization of medical management, including clinical test of novel therapies

  3. Original Research

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      Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study

      Eric S. Winer, Howard Safran, Boguslawa Karaszewska, Donald A. Richards, Lee Hartner, Frederic Forget, Rodryg Ramlau, Kirushna Kumar, Bhabita Mayer, Brendan M. Johnson, Conrad A. Messam and Yasser Mostafa Kamel

      Article first published online: 27 AUG 2014 | DOI: 10.1002/cam4.326

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      Eltrombopag, an oral thrombopoietin receptor agonist, was administered in patients receiving treatment with gemcitabine-based therapy. Fewer patients receiving eltrombopag required chemotherapy dose delays and/or reductions compared with those receiving placebo. Eltrombopag was well tolerated with an acceptable safety profile, and will be further tested.

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      Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery

      Karim Tazi, Amanda Hathaway, Cody Chiuzan and Keisuke Shirai

      Article first published online: 27 AUG 2014 | DOI: 10.1002/cam4.315

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      The combination of ipilimumab and SRS for brain metastasis is associated with long survival—comparable to patients without brain metastasis. Treatment of a large number of brain lesions is feasible without significantly impacting performance status.

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      Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer

      Akira Ema, Mina Waraya, Keishi Yamashita, Kenichi Kokubo, Hirosuke Kobayashi, Keika Hoshi, Yoshiko Shinkai, Hiroshi Kawamata, Kazunori Nakamura, Hiroshi Nishimiya, Natsuya Katada and Masahiko Watanabe

      Article first published online: 26 AUG 2014 | DOI: 10.1002/cam4.311

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      We proposed EGFR as the reemerged molecule which explains aggressive mechanism in gastric cancer with high ND. EGFR may be one of the most optimal molecular targets in aggressive gastric cancer which is resistant against the current chemotherapy.

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      Incidence and risk factors for suicide and attempted suicide following a diagnosis of hematological malignancy

      Malin Hultcrantz, Tobias Svensson, Åsa R. Derolf, Sigurdur Y. Kristinsson, Ebba K. Lindqvist, Anders Ekbom, Fredrik Granath and Magnus Björkholm

      Article first published online: 25 AUG 2014 | DOI: 10.1002/cam4.316

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      We assessed the risk of and risk factors for suicide and suicide attempt in patients with hematological malignancies in a large cohort of patients (n = 47,220) and matched controls (n = 235,868) in Sweden. We found the risk of suicide/suicide attempt to be twofold elevated during the first 3 years after diagnosis and the highest risks were observed in patients with multiple myeloma and in patients with a preexisting psychiatric disorder compared to controls. In detailed analysis based on information from medical records, a large proportion of patients who committed suicide were not in a palliative phase which underlines the need for improved psychological support.

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      Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study

      Ilkka Kalliala, Ahti Anttila, Pekka Nieminen, Mervi Halttunen and Tadeusz Dyba

      Article first published online: 21 AUG 2014 | DOI: 10.1002/cam4.300

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      In all, 3530 women were treated for cervical intraepithelial neoplasia (CIN) with 76,000 woman-years of follow-up. Live birth incidence was higher after than before CIN treatment. First pregnancy terminations were more common after the treatment.

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      SIRT1 expression is associated with a poor prognosis, whereas DBC1 is associated with favorable outcomes in gastric cancer

      Akira Noguchi, Keiji Kikuchi, Huachuan Zheng, Hiroyuki Takahashi, Yohei Miyagi, Ichiro Aoki and Yasuo Takano

      Article first published online: 21 AUG 2014 | DOI: 10.1002/cam4.310

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      We evaluated SIRT1, DBC1, acetylated H4K16 (H4K16Ac), acetylated H3K9 (H3K9Ac), and p53 expression by immunohistochemistry (IHC) in 557 cases of gastric cancer to clarify the role of SIRT1 as a histone deacetylase (HDAC) because of clinical trials of HDAC inhibitors as antitumor therapy conducted for gastric cancer. The IHC results revealed that SIRT1 high expression correlated to worse clinico-pathological prognostic factors and related poor prognosis both by univariate and multivariate analyses, by the contrast, DBC1 and H4K16Ac were related to favorable prognostic factors and linked to favorable prognosis by univariate analysis, leading the conclusion that SIRT1 acts as an oncogene and might be a target molecule of HDAC inhibitor treatment for gastric cancer.

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      Molecular subtyping of bladder cancer using Kohonen self-organizing maps

      Edyta M. Borkowska, Andrzej Kruk, Adam Jedrzejczyk, Marek Rozniecki, Zbigniew Jablonowski, Magdalena Traczyk, Maria Constantinou, Monika Banaszkiewicz, Michal Pietrusinski, Marek Sosnowski, Freddie C. Hamdy, Stefan Peter, James W.F. Catto and Bogdan Kaluzewski

      Article first published online: 20 AUG 2014 | DOI: 10.1002/cam4.217

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      We find that Kohonen self-organizing maps (SOMs) are able to stratify tumors according to biological outcomes rather than clinical phenotypes. In our comparison, SOM outperformed hierarchical clustering (its closest competition), suggesting that SOMs may offer a solution to this problem. This work represents the first of its type, in this field.

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      Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment

      Kenichi Miyata, Satoshi Takagi, Shigeo Sato, Hiroshi Morioka, Kiyotaka Shiba, Tamiko Minamisawa, Miho Takami and Naoya Fujita

      Article first published online: 15 AUG 2014 | DOI: 10.1002/cam4.320

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      Almost all highly metastatic tumor cells possess high platelet aggregating abilities. Our identified platelet aggregation-inducing factor Aggrus, also known as podoplanin, could promote pulmonary metastasis by enhancing the embolization of the tumor cells in the blood vasculature. We here generated an anti-Aggrus scFv that could prevent pulmonary metastasis of the Aggrus-expressing tumors.

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      Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia

      Santhosh K. Sadashiv, Christie Hilton, Cyrus Khan, James M. Rossetti, Heather L. Benjamin, Salman Fazal, Entezam Sahovic, Richard K. Shadduck and John Lister

      Article first published online: 15 AUG 2014 | DOI: 10.1002/cam4.321

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      In elderly patients with acute myeloid leukemia, a 7-day regimen of azacitidine 75 mg/m2 demonstrates improved tolerability relative to standard induction chemotherapy, and is approved for the treatment of such patients with bone marrow (BM) blast counts of 20–30%. The findings of this study indicate that, irrespective of BM blast counts, outpatient administration of azacitidine 100 mg/m2 for 5 days every 28 days is well tolerated in elderly patients, and provides comparable efficacy to the approved 7 days of azacitidine 75 mg/m2.

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      Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers

      Margaret E. Wright, Demetrius Albanes, Ann B. Moser, Stephanie J. Weinstein, Kirk Snyder, Satu Männistö and Peter H. Gann

      Article first published online: 15 AUG 2014 | DOI: 10.1002/cam4.319

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      In this molecular epidemiological study, phytanic acid and its primary metabolite pristanic acid—saturated branched-chain fatty acids found predominantly in red meat and dairy products—were not associated with the risk of total or aggressive prostate cancer. Although the direction and magnitude of these associations appeared to depend on serum levels of the antioxidant β-carotene, these findings should be interpreted cautiously as they are likely due to chance.

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      The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling

      Alexander Sankin, Abraham A. Hakimi, Nina Mikkilineni, Irina Ostrovnaya, Mikhail T. Silk, Yupu Liang, Roy Mano, Michael Chevinsky, Robert J. Motzer, Stephen B. Solomon, Emily H. Cheng, Jeremy C. Durack, Jonathan A. Coleman, Paul Russo and James J. Hsieh

      Article first published online: 14 AUG 2014 | DOI: 10.1002/cam4.293

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      Single region genomics of primary kidney cancer leads to underestimation of critical tumor suppressor mutations. On average, analysis of a combination of four distinct tumor regions will yield ~90% of accuracy in detecting the detrimental 3p TSG mutations of clear cell renal cell carcinoma.

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      Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer

      Taofeek K. Owonikoko, Guojing Zhang, Xingming Deng, Michael R. Rossi, Jeffrey M. Switchenko, Gregory H. Doho, Zhengjia Chen, Sungjin Kim, Sandy Strychor, Susan M. Christner, Jan Beumer, Chunyang Li, Ping Yue, Alice Chen, Gabriel L. Sica, Suresh S. Ramalingam, Jeanne Kowalski, Fadlo R. Khuri and Shi-Yong Sun

      Article first published online: 13 AUG 2014 | DOI: 10.1002/cam4.317

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      Veliparib demonstrated a selective potentiation of chemotherapy against small cell lung cancer (SCLC) in vitro. The in vitro selectivity was replicated in vivo with delayed tumor growth observed in the sensitive cell line but not in the insensitive cell line. Veliparib activity was associated with cell sensitivity to cisplatin and modulation of DNA-PKcs.

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      Acetylation-dependent regulation of essential iPS-inducing factors: a regulatory crossroad for pluripotency and tumorigenesis

      Xiangpeng Dai, Pengda Liu, Alan W. Lau, Yueyong Liu and Hiroyuki Inuzuka

      Article first published online: 13 AUG 2014 | DOI: 10.1002/cam4.298

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      Akt regulates the induced pluripotent stem (iPS) process by modulating posttranslational modifications of iPS factors in both direct and indirect manners. Specifically, Akt directly phosphorylates Oct4 to modulate the Oct4/Sox2 heterodimer formation. Furthermore, Akt either facilitates the p300-mediated acetylation of Oct4, Sox2, and Klf4, or stabilizes Klf4 by inactivating GSK3, to indirectly modulate stemness.

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      Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review

      Frédéric Fiteni, Thierry Nguyen, Dewi Vernerey, Marie-Justine Paillard, Stefano Kim, Martin Demarchi, Francine Fein, Christophe Borg, Franck Bonnetain and Xavier Pivot

      Article first published online: 11 AUG 2014 | DOI: 10.1002/cam4.299

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      Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. The results suggest that the Gem/CDDP regimen with cisplatin (25–35 mg/m2) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity.

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      Testicular self-examination and testicular cancer: a cost-utility analysis

      Michael Aberger, Bradley Wilson, Jeffrey M. Holzbeierlein, Tomas L. Griebling and Ajay K. Nangia

      Article first published online: 8 AUG 2014 | DOI: 10.1002/cam4.318

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      Comparing the fiscal effectiveness of a clinical evaluation based on the testicular self-examination to the lifetime risk of testicular cancer, a benefit was demonstrated for advanced-stage disease. Although this benefit was unable to be demonstrated for early detected disease, there remained a 2.4:1 cost benefit ratio.

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      Long-term use of metformin and colorectal cancer risk in type II diabetics: a population-based case–control study

      Majken Cardel, Sara M. Jensen, Anton Pottegård, Trine L. Jørgensen and Jesper Hallas

      Article first published online: 5 AUG 2014 | DOI: 10.1002/cam4.306

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      We performed a nested case–control study restricted to Danish citizens with type II diabetes. The association between long-term metformin use and colorectal cancer (CRC) gave an adjusted odds ratios at 0.83 (95 % CI 0.68–1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.99 for men). There was a significant dose–response association of metformin use >250 defined daily dose (DDD) and for the duration of metformin use >1 year.

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      Mutations in POLE and survival of colorectal cancer patients – link to disease stage and treatment

      Albrecht Stenzinger, Nicole Pfarr, Volker Endris, Roland Penzel, Lina Jansen, Thomas Wolf, Esther Herpel, Arne Warth, Frederick Klauschen, Matthias Kloor, Wilfried Roth, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister and Wilko Weichert

      Article first published online: 1 AUG 2014 | DOI: 10.1002/cam4.305

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      It is currently unclear whether polymerase ɛ (POLE)-mutated colorectal cancers (CRC) define a specific clinical subtype which is associated with a particular outcome. We found (i) that exonuclease domain mutations (EDMs) are more frequent than described previously, (ii) novel POLE EDMs, (iii) POLE EDMs per se do not correlate with BRAF-, KRAS- or CIMP-status or a distinct clinical phenotype including outcome, and (iv) subgroup analysis for patients with POLE mutations in stage III/IV tumors treated with chemotherapy revealed increased mortality. The findings translate pure genetic data in the clinic and suggest that POLE mutations do not define an entirely new clinical CRC-subtype but may have a prognostic or predictive impact whose significance remains to be investigated in future studies.

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      Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4

      Takafumi Jinushi, Yoshihiko Shibayama, Ichiro Kinoshita, Satoshi Oizumi, Masahisa Jinushi, Tadahiro Aota, Toshiyuki Takahashi, Shoichi Horita, Hirotoshi Dosaka-Akita and Ken Iseki

      Article first published online: 1 AUG 2014 | DOI: 10.1002/cam4.309

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      MicroRNA-124-5p may target the tumorigenesis gene, structural maintenance of chromosomes 4 (SMC4), which suggests that the expression of miR-124-5p may be used as biomarkers to determine the prognosis of colorectal cancer patients.

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      A prospective trial comparing FDG-PET/CT and CT to assess tumor response to cetuximab in patients with incurable squamous cell carcinoma of the head and neck

      Douglas Adkins, Jessica Ley, Farrokh Dehdashti, Marilyn J. Siegel, Tanya M. Wildes, Loren Michel, Kathryn Trinkaus and Barry A. Siegel

      Article first published online: 1 AUG 2014 | DOI: 10.1002/cam4.294

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      Computed tomography (CT), the standard method to assess benefit of cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate and short time to progression. In this prospective trial, we show that F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT was better than CT in assessing benefit of single-agent cetuximab in incurable SCCHN.

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      Functional relationship between matrix metalloproteinase-11 and matrix metalloproteinase-14

      Emilie Buache, Robert Thai, Corinne Wendling, Fabien Alpy, Adeline Page, Marie-Pierre Chenard, Vincent Dive, Marc Ruff, Annick Dejaegere, Catherine Tomasetto and Marie-Christine Rio

      Article first published online: 1 AUG 2014 | DOI: 10.1002/cam4.290

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      MMP-11 is a novel substrate of MMP-14. This leads to MMP-11 inactivation, representing therefore one new critical regulatory mechanism to control the extent of pericellular MMP-11 bioavailability. Thus, in addition to the canonical reversible TIMP-dependent process, irreversible MMP inactivation might occur by direct cleavage of the catalytic domain in a MMP-dependent manner.

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      The association between lifetime smoking exposure and breast cancer mortality – results from a Norwegian cohort

      Eivind Bjerkaas, Ranjan Parajuli, Anders Engeland, Gertraud Maskarinec, Elisabete Weiderpass and Inger Torhild Gram

      Article first published online: 30 JUL 2014 | DOI: 10.1002/cam4.304

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      The Association between smoking and breast cancer mortality is not well described in literature, but some recent interesting new papers have been published. We provide interesting new data, especially for the Association between breast cancer mortality and smoking initiation before first childbirth.

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      HPV-positive oropharyngeal squamous cell carcinoma is associated with TIMP3 and CADM1 promoter hypermethylation

      Pauline M. W. van Kempen, Liselotte van Bockel, Weibel W. Braunius, Cathy B. Moelans, Marina van Olst, Rick de Jong, Inge Stegeman, Paul J. van Diest, Wilko Grolman and Stefan M. Willems

      Article first published online: 25 JUL 2014 | DOI: 10.1002/cam4.313

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      HPV-positive and HPV-negative oropharynx squamous cell carcinoma show distinct biological and clinical features. Our study further underscores this diversity by illustrating that HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCCs) also differ epigenetically.

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      Outpatient treatment costs and their potential impact on cancer care

      Takahiro Isshiki

      Article first published online: 24 JUL 2014 | DOI: 10.1002/cam4.308

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      Address points of stomach (orange), liver (green) cancer patients, and the hospital (red).

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      Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

      Kohei Miyata, Fusanori Yotsumoto, Sung Ouk Nam, Takashi Odawara, Sadao Manabe, Toyokazu Ishikawa, Hiroaki Itamochi, Junzo Kigawa, Shuji Takada, Hiroshi Asahara, Masahide Kuroki and Shingo Miyamoto

      Article first published online: 24 JUL 2014 | DOI: 10.1002/cam4.301

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      In this study, we screened for transcription factor(s) that promote HB-EGF expression. Our results indicated that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells.

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      Recurring DNA copy number gain at chromosome 9p13 plays a role in the activation of multiple candidate oncogenes in progressing oral premalignant lesions

      Rebecca Towle, Ivy F. L. Tsui, Yuqi Zhu, Sara MacLellan, Catherine F. Poh and Cathie Garnis

      Article first published online: 24 JUL 2014 | DOI: 10.1002/cam4.307

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      We report a recurrent DNA copy number gain event at chromosome 9p13 that is detectable in the earliest stages of oral premalignancy and is associated with increased progression likelihood for early stage oral lesions (which currently have no clinically viable means of delineating this risk). We find evidence that this alteration event is a product of selection for the activation of multiple oncogenes in parallel, each of which we show to be capable of regulating oral cancer phenotypes.

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      Inhibition of epidermal growth factor signaling by the cardiac glycoside ouabain in medulloblastoma

      Daniel Wolle, Seung Joon Lee, Zhiqin Li, Alisa Litan, Sonali P. Barwe and Sigrid A. Langhans

      Article first published online: 23 JUL 2014 | DOI: 10.1002/cam4.314

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      Aberrant activation of EGFR signaling has been observed in a high percentage of cancers and often is associated with poor outcome but targeted therapy for EGFR/ErbB signaling has remained a challenge due to its complex nature. We now show that the cardiac glycoside ouabain, an inhibitor of Na,K-ATPase, inhibits EGF signaling in medulloblastoma cells and prevents EGF-induced cell migration, a prerequisite for an invasive phenotype in these tumors. Thus, Na,K-ATPase is an attractive target to develop novel therapeutic strategies for cancers with aberrant activation of EGFR signaling.

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      Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer

      Nicholas Willumsen, Cecilie L. Bager, Diana J. Leeming, Victoria Smith, Claus Christiansen, Morten A. Karsdal, David Dornan and Anne-Christine Bay-Jensen

      Article first published online: 18 JUL 2014 | DOI: 10.1002/cam4.303

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      Noninvasive biomarkers reflecting degradation of collagen type I and citrullinated vimentin are highly applicable in the lung cancer setting. In the future, these markers may aid in diagnosing and characterizing patients with lung cancer.

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      Impact of adverse events, treatment modifications, and dose intensity on survival among patients with advanced renal cell carcinoma treated with first-line sunitinib: a medical chart review across ten centers in five European countries

      Camillo Porta, Antonin Levy, Robert Hawkins, Daniel Castellano, Joaquim Bellmunt, Paul Nathan, Ray McDermott, John Wagstaff, Paul Donnellan, John McCaffrey, Francis Vekeman, Maureen P. Neary, Jose Diaz, Faisal Mehmud and Mei Sheng Duh

      Article first published online: 18 JUL 2014 | DOI: 10.1002/cam4.302

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      This study of a large cohort of patients with advanced renal cell carcinoma (RCC) treated with sunitinib in Europe found a significant relationship between adverse events and dose intensity. It also found significant correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival.

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      Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line

      Yi Wang, Yang Jiang, Jun-ichiro Ikeda, Tian Tian, Atsushi Sato, Hiroshi Ohtsu and Eiichi Morii

      Article first published online: 10 JUL 2014 | DOI: 10.1002/cam4.296

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      Histamine increased aldehyde dehydrogenase 1 (ALDH1) high population in endometrioid adenocarcinoma via histamine H1 receptor. As ALDH1 activity is supposed to be a general cancer-initiating cell (CIC) marker, this finding may provide an adjuvant therapeutic approach to eradicate CICs.

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      Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma

      Tadashi Sato, Yohei Suzuki, Takanori Mori, Masahiro Maeda, Masaaki Abe, Okio Hino and Kazuhisa Takahashi

      Article first published online: 10 JUL 2014 | DOI: 10.1002/cam4.297

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      The current study was designed to improve our previous enzyme-linked immunosorbent assay (ELISA) system for measuring N-ERC/mesothelin and to demonstrate the clinical usefulness of the modified ELISA system in patients with suspected pleural mesothelioma. A newly established ELISA system improved the sensitivity and specificity for the diagnosis of pleural mesothelioma in the current cohort compared with our previous system. A new ELISA showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum.

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      Cardiovascular event-free survival after adjuvant radiation therapy in breast cancer patients stratified by cardiovascular risk

      Nneka C. Onwudiwe, Young Kwok, Eberechukwu Onukwugha, John D. Sorkin, Ilene H. Zuckerman, Fadia T. Shaya and C. Daniel Mullins

      Article first published online: 10 JUL 2014 | DOI: 10.1002/cam4.283

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      The objective of this study was to estimate the risk of a cardiovascular event or death associated with modern radiation in breast cancer patients with varying baseline cardiovascular risk. This study showed that elderly women with breast cancer who had preexisting cardiovascular disease and receiving radiation treatment are at a greater risk for the combined outcome in the first 6 months.

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      Volumetric PET/CT parameters predict local response of head and neck squamous cell carcinoma to chemoradiotherapy

      Atsushi Hanamoto, Mitsuaki Tatsumi, Yukinori Takenaka, Toshimitsu Hamasaki, Toshimichi Yasui, Susumu Nakahara, Yoshifumi Yamamoto, Yuji Seo, Fumiaki Isohashi, Kazuhiko Ogawa, Jun Hatazawa and Hidenori Inohara

      Article first published online: 9 JUL 2014 | DOI: 10.1002/cam4.295

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      It is not well established whether pretreatment 18F-FDG PET/CT can predict local response of head and neck squamous cell carcinoma to chemoradiotherapy. Predictive efficacy of pretreatment 18F-FDG PET/CT varies with different primary sites and chosen parameters. Local response of laryngohypopharyngeal cancer is highly predictable by volume-based PET/CT parameters.

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      New prognostic factors and scoring system for patients with skeletal metastasis

      Hirohisa Katagiri, Rieko Okada, Tatsuya Takagi, Mitsuru Takahashi, Hideki Murata, Hideyuki Harada, Tetsuo Nishimura, Hirofumi Asakura and Hirofumi Ogawa

      Article first published online: 9 JUL 2014 | DOI: 10.1002/cam4.292

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      The results of this study identified six significant prognostic factors, including laboratory data, for the patients with skeletal metastasis. With this updated scoring system, life expectancy may be predicted more accurately; thus, a more optimal treatment may be selected.

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      Fatigue in patients with advanced renal cell carcinoma receiving sunitinib on an intermittent versus continuous dosing schedule in a randomized phase II trial

      David Cella, Sally E. Jensen, Elizabeth A. Hahn, Jennifer L. Beaumont, Beata Korytowsky, Helen Bhattacharyya and Robert Motzer

      Article first published online: 9 JUL 2014 | DOI: 10.1002/cam4.286

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      In a randomized trial comparing the sunitinib 4-week on/2-week off schedule to a continuous daily dose schedule, the 4/2 arm was associated with a greater degree of variability in fatigue reflecting a possible “on-off” effect whereby patients receiving the 4/2 schedule reported less fatigue at the beginning of each cycle compared to Day 29. The findings can inform the care for individuals with advanced renal cell carcinoma receiving intermittent dosing of sunitinib.

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      Epidemiology and survivorship of soft tissue sarcomas in adults: a national cancer database report

      Robert M. Corey, Katrina Swett and William G. Ward

      Article first published online: 8 JUL 2014 | DOI: 10.1002/cam4.288

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      The data reported herein contains demographic and survivorship data on 34 distinct soft tissue sarcomas in 63,714 patients. These data are unprecedented in its scope and size and provides an accurate oversight picture of the number of such cases in the USA and the true overall associated survivorship for these entities over the years reported. These data should form a reference baseline for comparisons of future series.

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      Use of percutaneous image-guided coaxial core-needle biopsy for diagnosis of intraabdominal lymphoma

      Ikuo Shimizu, Yoichi Okazaki, Wataru Takeda, Takehiko Kirihara, Keijiro Sato, Yuko Fujikawa, Toshimitsu Ueki, Yuki Hiroshima, Masahiko Sumi, Mayumi Ueno, Naoaki Ichikawa and Hikaru Kobayashi

      Article first published online: 8 JUL 2014 | DOI: 10.1002/cam4.224

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      Percutaneous core-needle biopsy revealed highly effective for diagnosis of intraabdominal lymphomas in comparison to surgical biopsy. It also helps attain immunohistological distinction as well as more timely therapy initiation.

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      Primary squamous cell carcinomas in the thyroid gland: an individual participant data meta-analysis

      Jae Keun Cho, Seung-Hoon Woo, Junoh Park, Min-Ji Kim and Han-Sin Jeong

      Article first published online: 4 JUL 2014 | DOI: 10.1002/cam4.287

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      To better understand the clinical characteristics of primary thyroid squamous cell carcinomas and to identify the prognostic factors, we performed a systematic review and individual participant data meta-analysis. The survival of these patients was ~20% in 3 years, but complete resection of disease correlated with improved survival.

    38. You have full text access to this OnlineOpen article
      Combining the pan-aurora kinase inhibitor AMG 900 with histone deacetylase inhibitors enhances antitumor activity in prostate cancer

      Channing J. Paller, Michel D. Wissing, Janet Mendonca, Anup Sharma, Eugene Kim, Hea-Soo Kim, Madeleine S. Q. Kortenhorst, Stephanie Gerber, Marc Rosen, Faraz Shaikh, Marianna L. Zahurak, Michelle A. Rudek, Hans Hammers, Charles M. Rudin, Michael A. Carducci and Sushant K. Kachhap

      Article first published online: 2 JUL 2014 | DOI: 10.1002/cam4.289

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      Combination therapy consisting of AMG 900, a pan-aurora kinase inhibitor, with the histone deacetylase inhibitors (HDACIs) valproic acid (VPA), and vorinostat (SAHA) was tested in prostate cancer cells. In vitro, the combination had synergistic antitumor activity. In vivo studies indicated decreased tumor growth in mice treated with low-dose AMG 900 and vorinostat compared to either agent alone.

    39. You have full text access to this OnlineOpen article
      Intensity-modulated pelvic radiation therapy and simultaneous integrated boost to the prostate area in patients with high-risk prostate cancer: a preliminary report of disease control

      Biancamaria Saracino, Maria Grazia Petrongari, Simona Marzi, Vicente Bruzzaniti, Gomellini Sara, Stefano Arcangeli, Giorgio Arcangeli, Paola Pinnarò, Carolina Giordano, Anna Maria Ferraro and Lidia Strigari

      Article first published online: 28 JUN 2014 | DOI: 10.1002/cam4.278

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      The treatment of pelvic nodes for high-risk prostate cancer is still controversial. The benefit and safety of whole pelvic irradiation using pelvic intensity-modulated radiation therapy (IMRT) and simultaneous boost to the prostatic area in association with 2-year androgen deprivation therapy (ADT) was evaluated. It was found that simultaneous integrated boost (SIB) technique is a well-tolerated treatment. High disease control in patients with prostate cancer requiring lymph node treatment was achieved.

    40. You have full text access to this OnlineOpen article
      Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis

      Michael Weichhaus, Prabu Segaran, Ashleigh Renaud, Dirk Geerts and Linda Connelly

      Article first published online: 28 JUN 2014 | DOI: 10.1002/cam4.277

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      Breast tumor cells express the protein osteoprotegerin (OPG), but the functional consequences of this are not clear. Here, we show that OPG expression promotes metastasis in triple-negative breast cancer cells.

    41. You have full text access to this OnlineOpen article
      Cancer stem cells and cisplatin-resistant cells isolated from non-small-lung cancer cell lines constitute related cell populations

      Blanca D. Lopez-Ayllon, Veronica Moncho-Amor, Ander Abarrategi, Inmaculada Ibañez de Cáceres, Javier Castro-Carpeño, Cristobal Belda-Iniesta, Rosario Perona and Leandro Sastre

      Article first published online: 24 JUN 2014 | DOI: 10.1002/cam4.291

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      Cisplatin-resistant cells were isolated from H460 and A549 non-small-cell lung cancer cell lines after a single treatment with the drug, simulating patient-treatment protocols. Cancer stem cells were also isolated from these cell lines for comparison. Both cisplatin resistant and stem cells showed increased cisplatin resistance, tumorigenicity, angiogenic, and metastatic capacity. Their gene expression profiles were highly related. Furthermore, the presence of cells with Stem characteristics in patient's surgical samples was related to their sensitivity to cisplatin.

    42. You have full text access to this OnlineOpen article
      Early inflammatory response in epithelial ovarian tumor cyst fluids

      Björg Kristjánsdóttir, Karolina Partheen, Eric T. Fung, Christine Yip, Kristina Levan and Karin Sundfeldt

      Article first published online: 20 JUN 2014 | DOI: 10.1002/cam4.282

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      The majority of epithelial ovarian cancer consists of cysts, the cyst fluid is in direct contact or inside the pathology itself. Inflammation has a central role in all steps of cancer, and we hypothesized and confirmed that inflammatory response could be found in the closeness to the pathology before it presents in the peripheral circulation.

    43. You have full text access to this OnlineOpen article
      CT versus FDG-PET/CT response evaluation in patients with metastatic colorectal cancer treated with irinotecan and cetuximab

      Kristin Skougaard, Helle Hjorth Johannesen, Dorte Nielsen, Jakob Vasehus Schou, Benny Vittrup Jensen, Estrid V. S. Høgdall and Helle Westergren Hendel

      Article first published online: 18 JUN 2014 | DOI: 10.1002/cam4.271

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      Colorectal cancer patients treated with irinotecan and cetuximab were evaluated with both computed tomography (CT) and positron emission tomography (PET/CT). Morphologic and metabolic response agreement was poor. Response Evaluation Criteria in Solid Tumors and Positron Emission Tomography Response Criteria in Solid Tumors response distribution correlated differently with survival.

    44. You have full text access to this OnlineOpen article
      Statin use and its effect on all-cause mortality of melanoma patients: a population-based Dutch cohort study

      Elisabeth Livingstone, Loes M. Hollestein, Myrthe P. P. van Herk-Sukel, Lonneke van de Poll-Franse, Arjen Joosse, Bastian Schilling, Tamar Nijsten, Dirk Schadendorf and Esther de Vries

      Article first published online: 17 JUN 2014 | DOI: 10.1002/cam4.285

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      Statins have demonstrated anticancer effects on melanoma cell lines and in mouse models. In this population-based study, statin use either before or after melanoma diagnosis did not have a significant effect on survival of melanoma patients. Stratification on gender, however, showed a favorable outcome in male statin users compared to nonusers but was unchanged in females.

    45. You have full text access to this OnlineOpen article
      Risk of squamous cell skin cancer after organ transplant associated with antibodies to cutaneous papillomaviruses, polyomaviruses, and TMC6/8 (EVER1/2) variants

      Margaret M. Madeleine, Joseph J. Carter, Lisa G. Johnson, Gregory C. Wipf, Connie Davis, Daniel Berg, Karen Nelson, Janet R. Daling, Stephen M. Schwartz and Denise A. Galloway

      Article first published online: 10 JUN 2014 | DOI: 10.1002/cam4.280

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      Squamous cell skin cancer (SCSC) disproportionately affects organ transplant recipients, and may be related to increased viral replication in the setting of immune suppression after transplant. This study suggests that HPV37, a betapapillomavirus, may play a role in the excess risk of SCSC among transplant recipients.

    46. You have full text access to this OnlineOpen article
      A phase II trial of BAY 43-9006 (sorafenib) (NSC-724772) in patients with relapsing and resistant multiple myeloma: SWOG S0434

      Gordan Srkalovic, Mohamad A. Hussein, Antje Hoering, Jeffrey A. Zonder, Leslie L. Popplewell, Harsha Trivedi, Sandy Mazzoni, Rachel Sexton, Robert Z. Orlowski and Bart Barlogie

      Article first published online: 10 JUN 2014 | DOI: 10.1002/cam4.276

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      Phase II SWOG trial of multityrosine kinase inhibitor, sorafenib, shown to have limited use as a single agent. Based on well-tolerated side effect profile and mechanism of action, future studies should focus on the addition of sorafenib with current therapies.

    47. You have full text access to this OnlineOpen article
      A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

      Gianluca Severi, Liesel M. FitzGerald, David C. Muller, John Pedersen, Anthony Longano, Melissa C. Southey, John L. Hopper, Dallas R. English, Graham G. Giles and John Mills

      Article first published online: 7 JUN 2014 | DOI: 10.1002/cam4.281

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      We evaluated whether a panel of biomarkers (AZGP1, MUC1, NKX3.1, p53, and PTEN), assessed by immunohistochemistry on diagnostic tissue, could predict death from prostate cancer in men with localized disease. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51 and 3.08, P < 0.03), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, P = 0.04). For men with localized disease at diagnosis, assessing the expression of these three proteins in diagnostic tissue could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.

    48. You have full text access to this OnlineOpen article
      African American women's perceptions of cancer clinical trials

      Lindsey Haynes-Maslow, Paul Godley, Lisa Dimartino, Brandolyn White, Janice Odom, Alan Richmond and William Carpenter

      Article first published online: 6 JUN 2014 | DOI: 10.1002/cam4.284

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      Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trials participation among African Americans is significantly lower than among Caucasians. This study engaged focus groups with African American cancer survivors or cancer caregivers. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials.

    49. You have full text access to this OnlineOpen article
      Pharmacovigilance in practice: erythropoiesis-stimulating agents

      Michael Hedenus, Heinz Ludwig, David H. Henry and Eduard Gasal

      Article first published online: 3 JUN 2014 | DOI: 10.1002/cam4.275

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      Pharmacovigilance seeks to advance the safe use of marketed medical products by detecting and assessing potential safety issues and taking appropriate action to balance risks and benefits to patients. The pharmacovigilance process was employed to identify and minimize potential risks of erythropoiesis-stimulating agents (ESAs) used to treat anemia in patients with cancer receiving chemotherapy.

    50. You have full text access to this OnlineOpen article
      T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

      Diana P. English, Stefania Bellone, Carlton L. Schwab, Ileana Bortolomai, Elena Bonazzoli, Emiliano Cocco, Natalia Buza, Pei Hui, Salvatore Lopez, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter E. Schwartz, Thomas J. Rutherford and Alessandro D. Santin

      Article first published online: 2 JUN 2014 | DOI: 10.1002/cam4.274

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      Trastuzumab emtansine (T-DM1) shows significant antitumor effect in epidermal growth factor receptor-2 (HER2)-positive uterine serous carcinoma (USC) cell lines and USC xenografts. T-DM1 may represent a novel treatment option for HER2-positive USC patients harboring disease refractory to chemotherapy and/or unresponsive to trastuzumab.

    51. You have full text access to this OnlineOpen article
      High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas

      Nobuyuki Yanagisawa, Kiyomi Hana, Norihiro Nakada, Masaaki Ichinoe, Wasaburo Koizumi, Hitoshi Endou, Isao Okayasu and Yoshiki Murakumo

      Article first published online: 2 JUN 2014 | DOI: 10.1002/cam4.272

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      In this study, we analyzed LAT1, LAT2, and CD98 expressions in a total of 134 bile duct adenocarcinomas including distal extrahepatic bile duct adenocarcinomas (EHCs), hilar cholangiocarcinomas (HCs), intrahepatic cholangiocarcinomas (ICCs), and ampullary adenocarcinomas (ACs). We found that LAT1 is useful as a significant prognostic marker in bile duct cancer as well as EHC. These results strongly suggest a potential target for future anticancer therapy with its inhibitors.

    52. You have full text access to this OnlineOpen article
      Let-7 microRNA-binding-site polymorphism in the 3′UTR of KRAS and colorectal cancer outcome: a systematic review and meta-analysis

      Scott M. Langevin and Brock C. Christensen

      Article first published online: 2 JUN 2014 | DOI: 10.1002/cam4.279

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      We conducted a meta-analysis of the prognostic significance of the LCS6 let-7-binding-site polymorphism in the 3′UTR of KRAS. We did not find any evidence of association with overall or disease-free survival, or by stage at diagnosis or treatment regimen.

    53. You have full text access to this OnlineOpen article
      Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients

      Kiyoko Takane, Yutaka Midorikawa, Koichi Yagi, Ayako Sakai, Hiroyuki Aburatani, Tadatoshi Takayama and Atsushi Kaneda

      Article first published online: 23 MAY 2014 | DOI: 10.1002/cam4.273

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      Detection of methylation of PPP1R3C alone or in combination with EFHD1 in plasma DNA showed high sensitivity and specificity in colorectal cancer (CRC) patients. They may be useful biomarkers for CRC, especially for detection of early-stage CRCs.

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