Cancer Medicine

Cover image for Vol. 4 Issue 2

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 - 56
  1. Original Research

    1. You have full text access to this OnlineOpen article
      HER2 as a target in invasive urothelial carcinoma

      Joaquim Bellmunt, Lillian Werner, Aristotle Bamias, André P. Fay, Rachel S. Park, Markus Riester, Shamini Selvarajah, Justine A. Barletta, David M. Berman, Silvia de Muga, Marta Salido, Enrique Gallardo, Federico Rojo, Elizabeth A. Guancial, Richard Bambury, Stephanie A. Mullane, Toni K. Choueiri, Massimo Loda, Edward Stack and Jonathan Rosenberg

      Article first published online: 26 FEB 2015 | DOI: 10.1002/cam4.432

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      The association between HER2 status and overall survival (OS) in UC remains unclear. HER2 positivity may not only be a biomarker for more aggressive disease but also a potential therapeutic target. We report that HER2 overexpression or amplification in the primary tumor did not predict OS in patients with metastatic UC. Further trials in genomically screened patients are needed to assess HER2-targeted therapies in UC.

    2. You have full text access to this OnlineOpen article
      Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma

      Giselle L. Saulnier Sholler, Jeffrey P. Bond, Genevieve Bergendahl, Akshita Dutta, Julie Dragon, Kathleen Neville, William Ferguson, William Roberts, Don Eslin, Jacqueline Kraveka, Joel Kaplan, Deanna Mitchell, Nehal Parikh, Melinda Merchant, Takamaru Ashikaga, Gina Hanna, Pamela Jean Lescault, Ashley Siniard, Jason Corneveaux, Matthew Huentelman and Jeffrey Trent

      Article first published online: 26 FEB 2015 | DOI: 10.1002/cam4.436

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      This study demonstrates the feasibility and safety of a novel approach to guide treatment decisions which utilizes tumor genomic profiling to create individualized treatment plans for children with relapsed/refractory neuroblastoma. The average time from biopsy to genomic profiling and report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and clinical benefit was seen in 64% of patients as stabilization of disease or partial response.

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      Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors

      Khalid Al-Efraij, Mohammed A. Aljama and Hagen Fritz Kennecke

      Article first published online: 26 FEB 2015 | DOI: 10.1002/cam4.435

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      This retrospective analysis examined if higher than approved doses of octeotride long-acting release (O-LAR) might successfully mitigate symptoms in neuroendocrine tumors (NETs) patients that remain symptomatic in spite of standard doses of LAR by evaluating the association between dose escalation of O-LAR, symptom control, tumor markers (chromogranin A and 5-hydoxyindoacetate), and radiological progression of the tumors. In our study, we found that higher doses of O-LAR are associated with improved symptom control in NET patients. The variability in tumor marker levels in response to O-LAR dose escalation may indicate that tumor marker levels may not be an accurate assessment of therapeutic efficacy.

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      Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK

      Diletta Fontana, Monica Ceccon, Carlo Gambacorti-Passerini and Luca Mologni

      Article first published online: 26 FEB 2015 | DOI: 10.1002/cam4.413

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      ALK is a tyrosine kinase receptor involved both in ALCL and NSCLC. Patients affected by these diseases are treated with the ALK inhibitor crizotinib, but patients relapsed after treatment due to crizotinib conferring resistance point mutations selection. Activities of four second-generation ALK inhibitors on crizotinib-resistant mutants are reported.

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      Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer

      Kishore R. Rollakanti, Sanjay Anand and Edward V. Maytin

      Article first published online: 25 FEB 2015 | DOI: 10.1002/cam4.361

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      Preconditioning of breast cancer cutaneous tumors with Vitamin D3 (1,25 dihydroxyvitamin D3; Vit D) increases the cytotoxic, tumor-specific effects of aminolevulinate-based photodynamic therapy (PDT). This novel combination approach offers a potential new way to treat breast cancer metastasis and achieve better efficacy with fewer complications than standard treatment modalities.

    6. You have full text access to this OnlineOpen article
      BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma

      Lauren E. Henke, John D. Pfeifer, Changquing Ma, Stephanie M. Perkins, Todd DeWees, Samir El-Mofty, Jeffrey F. Moley, Brian Nussenbaum, Bruce H. Haughey, Thomas J. Baranski, Julie K. Schwarz and Perry W. Grigsby

      Article first published online: 25 FEB 2015 | DOI: 10.1002/cam4.417

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      The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC.

  2. Reviews

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      Pancreatic cancer and FOLFIRINOX: a new era and new questions

      Robert De W. Marsh, Mark S. Talamonti, Matthew Harold Katz and Joseph M. Herman

      Article first published online: 19 FEB 2015 | DOI: 10.1002/cam4.433

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      This is a review of the revolution in pancreatic cancer care since the advent of FOLFIRINOX chemotherapy. It addresses the common issues which arise when using this therapy and then explores some of the challenging questions which have now been raised as we seek to move forward. A systematic review of the current literature for all relevant articles and meeting abstracts has been performed to derive the data, and the significant personal experience of the authors in treating this disease has been used to analyze the information. It is intended both as a review of the current knowledge and as a discussion of short- and long-term challenges building on what we have learned.

  3. Original Research

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      Id3 induces an Elk-1–caspase-8-dependent apoptotic pathway in squamous carcinoma cells

      You-Shin Chen, Joseph Aubee, Kyle A. DiVito, Hengbo Zhou, Weiyi Zhang, Fen-Pi Chou, Cynthia M. Simbulan-Rosenthal and Dean S. Rosenthal

      Article first published online: 18 FEB 2015 | DOI: 10.1002/cam4.427

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      Id3 is shown to regress squamous cell carcinoma xenografts through induction of apoptosis. This molecular pathway is mediated through Elk-1, caspase-8, and caspase-3. This pathway is dependent on the HLH and C-terminal domains of Id3.

    2. You have full text access to this OnlineOpen article
      Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells

      Karolina Weiner-Gorzel, Eugene Dempsey, Malgorzata Milewska, Aloysius McGoldrick, Valerie Toh, Aoibheann Walsh, Sinead Lindsay, Luke Gubbins, Aoife Cannon, Daniel Sharpe, Jacintha O'Sullivan, Madeline Murphy, Stephen F. Madden, Malcolm Kell, Amanda McCann and Fiona Furlong

      Article first published online: 15 FEB 2015 | DOI: 10.1002/cam4.409

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      In this manuscript, we describe the role of the microRNA miR-433 in the induction of cellular senescence, by the downregulation of cyclin-dependent kinase 6. Interestingly, we show that high miR-433 expressing cells can induce a senescence bystander effect in neighboring cells in nonautonomous manner. Crucially, our bioinformatic analysis demonstrates that miR-433 has a pivotal role in the regulation of the cell cycle, and therefore contributing to mediate chemoresistance to paclitaxel in ovarian cancer cells.

    3. You have full text access to this OnlineOpen article
      Induction therapy with cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (ETPF) in patients with resectable nonmetastatic stage III or IV squamous cell carcinoma of the oropharynx. A GERCOR phase II ECHO-07 study

      Benoist Chibaudel, Roger Lacave, Marine Lefevre, Patrick Soussan, Martine Antoine, Sophie Périé, Jean-Baptiste Belloc, Alain Banal, Sébastien Albert, Frédéric Chabolle, Philippe Céruse, Philippe Baril, Michel Gatineau, Martin Housset, Rachel Moukoko, Magdalena Benetkiewicz, Aimery de Gramont, Franck Bonnetain and Jean Lacau St Guily

      Article first published online: 14 FEB 2015 | DOI: 10.1002/cam4.408

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      This phase II study reports a clinical and radiological complete response of 22% and a primary tumor overall response rate of 58% for ETPF in patients with moderately advanced squamous cell carcinoma of the oropharynx. The schedule of ETPF evaluated in this study cannot be recommended at this dosage.

    4. You have full text access to this OnlineOpen article
      A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study

      Hisanori Shoji, Masahiko Motegi, Kiyotaka Osawa, Noriyuki Okonogi, Atsushi Okazaki, Yoshitaka Andou, Takayuki Asao, Hiroyuki Kuwano, Takeo Takahashi and Kyoji Ogoshi

      Article first published online: 9 FEB 2015 | DOI: 10.1002/cam4.431

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      The standardization of radiofrequency hyperthermia using an 8 MHz radiofrequency capacitive heating device can be established as a potential new treatment for rectal cancer concomitant with chemoradiation therapy. This new combined modality provides another potential treatment in patients with rectal cancer.

  4. Commentary

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      Rare childhood cancers—an increasing entity requiring the need for global consensus and collaboration

      Rishi S. Kotecha, Ursula R. Kees, Catherine H. Cole and Nicholas G. Gottardo

      Article first published online: 9 FEB 2015 | DOI: 10.1002/cam4.426

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      Rare childhood cancers have not benefited to the same extent from the gains that have been made for their frequently occurring counterparts. In recent years, this gap has been recognized and a number of vehicles now exist to improve outcome, including rare tumor groups, disease-specific registries, and clinics. The multitude of approaches has allowed significant progress, however, this framework is limited by patient number and is not inclusive for every type of rare childhood cancer. These shortcomings can be overcome by a single global unified approach to the study of rare childhood tumors.

  5. Original Research

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      Prevalence of renal impairment and use of nephrotoxic agents among patients with bone metastases from solid tumors in the United States

      Jorge Arellano, Rohini K. Hernandez, Sally W. Wade, Kristina Chen, Melissa Pirolli, David Quach, Jane Quigley, Alexander Liede and Vahakn B. Shahinian

      Article first published online: 8 FEB 2015 | DOI: 10.1002/cam4.403

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      In patients with bone metastases secondary to solid tumors, the 5-year prevalence was 43% for renal impairment (RI) and 71% for chronic kidney disease among evaluable RI patients. Whenever possible, treatments that are potentially less damaging for the kidney should be considered for patients with or predisposed to RI.

    2. You have full text access to this OnlineOpen article
      Cellular localization of CIP2A determines its prognostic impact in superficial spreading and nodular melanoma

      Vivi Ann Flørenes, Elisabeth Emilsen, Hiep Phuc Dong, Mette Førsund, Ruth Holm and Ana Slipicevic

      Article first published online: 7 FEB 2015 | DOI: 10.1002/cam4.425

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      Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel important oncogene contributing to cancer progression through regulation of PP2A, cMYC and AKT. This study shows for the first time that in a histologically defined subset of melanoma tumors CIP2A has a distinct, complex function associated with better prognosis. Still, melanoma cell lines with intrinsic resistance to BRAFV600E inhibitors are highly sensitive to CIP2A downregulation, suggesting that targeting CIP2A might be a good therapeutic alternative for this subset of patients.

    3. You have full text access to this OnlineOpen article
      Cervical cancer screening with clinic-based Pap test versus home HPV test among Somali immigrant women in Minnesota: a pilot randomized controlled trial

      Barrett Sewali, Kolawole S. Okuyemi, Asli Askhir, Jerome Belinson, Rachel I. Vogel, Anne Joseph and Rahel G. Ghebre

      Article first published online: 4 FEB 2015 | DOI: 10.1002/cam4.429

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      Cervical cancer is more common in the Somali immigrant population than the general population in the United States (US). Among the participants in the human papilloma virus (HPV) test group, 21 (67.7%) completed the test compared to seven (21.8%) participants in the Pap test group. The use of a self-sampling HPV kit has the potential to increase cervical cancer screening in under-served communities in the US.

    4. You have full text access to this OnlineOpen article
      Detection of tumor ALK status in neuroblastoma patients using peripheral blood

      Valérie Combaret, Isabelle Iacono, Angela Bellini, Stéphanie Bréjon, Virginie Bernard, Aurélien Marabelle, Carole Coze, Gaelle Pierron, Eve Lapouble, Gudrun Schleiermacher and Jean Yves Blay

      Article first published online: 4 FEB 2015 | DOI: 10.1002/cam4.414

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      In the present report, by targeting the F1174 and R1275 hotspots of ALK gene and using the droplet digital PCR system, we demonstrate that ALK mutations are detectable in cell-free plasma DNA from neuroblastoma patients showing a high risk of relapse. This assay offers a reliable, noninvasive blood test to assess ALK mutational status at F1174 and R1275 hotspots and should help the clinicians to identify patients showing an ALK mutation in particular when no tumor tissue is available.

    5. You have full text access to this OnlineOpen article
      The B subunit of Escherichia coli enterotoxin helps control the in vivo growth of solid tumors expressing the Epstein–Barr virus latent membrane protein 2A

      Beatrice Ondondo, Lee Faulkner, Neil A. Williams, Andrew J. Morgan and David J. Morgan

      Article first published online: 2 FEB 2015 | DOI: 10.1002/cam4.380

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      Previous studies showed that the B subunit of Escherichia coli enterotoxin (EtxB), causes rapid internalization and processing of membrane-bound Epstein–Barr Virus (EBV) latent membrane protein 2A (LMP2A) antigen on EBV-infected B cells, and facilitates loading of processed-LMP2A peptides onto MHC class I. This redirected trafficking/delivery of LMP2A to the MHC class I machinery enhances recognition and killing by LMP2A-specific cytotoxic T-lymphocytes (CTL) in vitro. In this report, we demonstrate that direct administration of EtxB into LMP2A tumors not only significantly delayed the onset of tumor growth in vivo, but moreover caused regression of some tumors; thus demonstrating the strong immunomodulatory potential of EtxB in enhancing antitumor immunity in EBV-associated cancers.

    6. You have full text access to this OnlineOpen article
      PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer

      Gilles Manceau, Laetitia Marisa, Valérie Boige, Alex Duval, Marie-Pierre Gaub, Gérard Milano, Janick Selves, Sylviane Olschwang, Valérie Jooste, Michè le Legrain, Delphine Lecorre, Dominique Guenot, Marie-Christine Etienne-Grimaldi, Sylvain Kirzin, Laurent Martin, Come Lepage, Anne-Marie Bouvier and Pierre Laurent-Puig

      Article first published online: 2 FEB 2015 | DOI: 10.1002/cam4.370

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      By using fresh frozen tissue samples from two large independent cohorts with a total of 826 stage I–III colon cancers (CCs), we found that patients with PIK3CA-mutated microsatellite stable tumors experienced a significant increased 5-year relapse-free survival and overall survival compared with those without PIK3CA mutation. Our study suggests that PIK3CA mutations could be used as a favorable prognostic biomarker in the adjuvant setting for CC.

  6. Reviews

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      Current trends in the etiology and diagnosis of HPV-related head and neck cancers

      Ryan C. Chai, Duncan Lambie, Mukesh Verma and Chamindie Punyadeera

      Article first published online: 1 FEB 2015 | DOI: 10.1002/cam4.424

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      The current review summarizes the epidemiology of human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC) and the disease burden, the infectious cycle of HPV, the roles of viral oncoproteins, E6 and E7, and the downstream cellular events that lead to malignant transformation. We also reviewed the current regimes and novel noninvasive methods of HPV detection.

  7. Original Research

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      Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph+ALL04

      Atsushi Manabe, Hirohide Kawasaki, Hiroyuki Shimada, Itaru Kato, Yuichi Kodama, Atsushi Sato, Kimikazu Matsumoto, Keisuke Kato, Hiromasa Yabe, Kazuko Kudo, Motohiro Kato, Tomohiro Saito, Akiko M. Saito, Masahito Tsurusawa and Keizo Horibe

      Article first published online: 31 JAN 2015 | DOI: 10.1002/cam4.383

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      Imatinib, which was produced as a prototype molecular targeting drug, was expected to become a major component in the treatment of children with Ph+ALL, however, the optimal timing and duration of its use was not established 10 years ago. In response, we conducted a nationwide clinical trial to investigate the use of imatinib as a single agent “bridge” between intensive chemotherapy and transplantation, utilizing serial molecular measurements of minimal residual disease (MRD). Forty-two patients were enrolled and a decrease in the amount of MRD or the ability to maintain negative MRD was observed in most patients. In addition, 4-year-overall survival was favorable at 78%, although all the patients were treated with transplantation.

    2. You have full text access to this OnlineOpen article
      HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case–control study

      Violet Kayamba, Allen C. Bateman, Akwi W. Asombang, Aaron Shibemba, Kanekwa Zyambo, Themba Banda, Rose Soko and Paul Kelly

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.434

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      Human immunodeficiency virus (HIV) infection and exposure to domestic and cigarette smoke are risk factors for esophageal squamous cell carcinoma. Human papillomavirus (HPV) infection does not appear to explain this relationship with HIV. HPV immunization is unlikely to prevent the apparent increase in esophageal cancers in young Zambian adults.

    3. You have full text access to this OnlineOpen article
      Sequential occurrence of dyspnea at the end of life in palliative care, according to the underlying cancer

      Frédéric Guirimand, Marine Sahut d'izarn, Lucy Laporte, Marie Francillard, Jean-François Richard and Philippe Aegerter

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.419

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      Extracted data for 3621 cancer patients who died after more than 6 days in the palliative care hospital. Dyspnea occurred in 47% of these patients. Cancers were classified into three groups according to the frequency of dyspnea: low frequency (brain: 27%), high frequency (thorax and ENT: 63%) and intermediate frequency (others: 43%). Dyspnea was classified according to the timing of the first episode: during the last 4 days of life (exclusively terminal dyspnea: ETD) or earlier (more precocious dyspnea). The frequency of ETD (8–10%) was independent of the site of the primary cancer, unlike that of more precocious dyspnea (18–54%).

    4. You have full text access to this OnlineOpen article
      Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells

      Ryo Yamashita, Mitsuo Sato, Tomohiko Kakumu, Tetsunari Hase, Naoyuki Yogo, Eiichi Maruyama, Yoshitaka Sekido, Masashi Kondo and Yoshinori Hasegawa

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.412

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      Previous studies suggested oncogenic roles of miR-221 and miR-222 microRNAs in lung cancer, and thus they are believed to function solely as oncogenes in lung cancer. However, by analyzing multiple lung cancer cell lines with diverse genetic alterations, we here show that miR-221 and miR-222 function also as tumor suppressors, as demonstrated by their growth suppressive and chemosensitizing effects, warranting testing their potential as novel therapeutics for lung cancer.

  8. Reviews

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      Part I: cancer in Sudan—burden, distribution, and trends breast, gynecological, and prostate cancers

      Amany Elamin, Muntaser E. Ibrahim, Dafalla Abuidris, Kamal Eldin H. Mohamed and Sulma Ibrahim Mohammed

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.378

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      Despite the growing burden of cancer worldwide, it continues to receive low priority in Africa, across the continent and specifically in Sudan. This review is the first of four papers that focuses on cancer, its distribution and trend as well as the risk factors most common in Sudan.

  9. Original Research

    1. You have full text access to this OnlineOpen article
      Warburg effect regulated by amphiregulin in the development of colorectal cancer

      Sung Ouk Nam, Fusanori Yotsumoto, Kohei Miyata, Satoshi Fukagawa, Hiromi Yamada, Masahide Kuroki and Shingo Miyamoto

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.416

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      We focused on MLX, which binds to carbohydrate response elements (ChoREs) involved in glucose metabolism. Transcriptional regulation of AREG expression by the MLX. ChiP analysis of MLX binding to the AREG promoter.

    2. You have full text access to this OnlineOpen article
      ANGPTL3 is a novel biomarker as it activates ERK/MAPK pathway in oral cancer

      Tomoyoshi Koyama, Katsunori Ogawara, Atsushi Kasamatsu, Atsushi Okamoto, Hiroki Kasama, Yasuyuki Minakawa, Ken Shimada, Hidetaka Yokoe, Masashi Shiiba, Hideki Tanzawa and Katsuhiro Uzawa

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.418

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      Despite comprehensive treatments, patient with advanced oral squamous cell carcinoma (OSCC) usually reveals poor prognosis. The authors have shown a predictive relevance of ANGPTL3 expression status in future patients with OSCC. Thus, it would be interesting to design clinical studies to elucidate the predictive relevance of ANGPTL3 expression status in future patients with OSCC because advanced OSCC cases have been divided into two groups, those with favorable and unfavorable prognoses.

    3. You have full text access to this OnlineOpen article
      Quality of life and disease understanding: impact of attending a patient-centered cancer symposium

      Leslie Padrnos, Amylou C. Dueck, Robyn Scherber, Pamela Glassley, Rachel Stigge, Donald Northfelt, Joseph Mikhael, Annette Aguirre, Robert M. Bennett and Ruben A. Mesa

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.422

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      A comprehensive cancer patient-centered symposium comprised a broad population was surveyed on quality of life, symptoms, and disease-specific knowledge before and after completed the symposium. This study revealed that a patient symposium, as an educational intervention improves a solid knowledge base amongst attendees regarding their disease, increases knowledge in symptom management, but may be insufficient to impact quality of life as a single intervention.

    4. You have full text access to this OnlineOpen article
      Impact of weight change during neoadjuvant chemotherapy on pathologic response in triple-negative breast cancer

      Jean Bao, Nicholas Borja, Madhu Rao, James Huth, A. Marilyn Leitch, Aeisha Rivers, Rachel Wooldridge and Roshni Rao

      Article first published online: 30 JAN 2015 | DOI: 10.1002/cam4.388

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      Weight change during neoadjuvant chemotherapy for triple-negative breast cancer did not change the rate of pathologic complete response, nor impact reduction in Ki-67 levels. This may reflect the nature of this subtype of breast cancer that is less responsive to the hormonal effects that adipose tissue exerts on cancer cell proliferation. Opportunities exist to stratify the response across socioeconomic, age, and race-based cohorts.

    5. You have full text access to this OnlineOpen article
      FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma

      Tatsuya Nishi, Hiroyuki Takahashi, Miki Hashimura, Tsutomu Yoshida, Yasutaka Ohta and Makoto Saegusa

      Article first published online: 29 JAN 2015 | DOI: 10.1002/cam4.423

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      FilGAP, a Rho GTPase-activating protein (GAP), may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular follicular lymphoma.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

  10. 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.

  11. 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.

  12. Short Reports

    1. You have full text access to this OnlineOpen article
      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.

  13. Original Research

    1. You have full text access to this OnlineOpen article
      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).

  14. Reviews

    1. You have full text access to this OnlineOpen article
      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.

  15. 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.

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      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.

  16. 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.

  17. Original Research

    1. You have full text access to this OnlineOpen article
      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.

  18. 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.

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