Cancer Medicine

Cover image for Vol. 5 Issue 9

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

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

Impact Factor: 2.915

ISI Journal Citation Reports © Ranking: 2015: 107/213 (Oncology)

Online ISSN: 2045-7634

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  1. 1 - 33
  1. Original Research

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      The full blood count as a biomarker of outcome and toxicity in ipilimumab-treated cutaneous metastatic melanoma

      Leila Khoja, Eshetu G. Atenafu, Arnoud Templeton, Ye Qye, Mary Anne Chappell, Sam Saibil, David Hogg, Marcus O. Butler and Anthony M. Joshua

      Version of Record online: 29 SEP 2016 | DOI: 10.1002/cam4.878

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      Neutrophil lymphocyte ratios (NLR) is an independent prognostic marker at baseline and during ipilimumab treatment in metastatic melanoma patients.

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      Chemokine CXCL1 may serve as a potential molecular target for hepatocellular carcinoma

      Ke-qi Han, Hui Han, Xue-qun He, Lei Wang, Xiao-dong Guo, Xue-ming Zhang, Jie Chen, Quan-gang Zhu, Hua Nian, Xiao-feng Zhai and Ma-wei Jiang

      Version of Record online: 28 SEP 2016 | DOI: 10.1002/cam4.843

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      We identified several chemokine genes that may play important roles in the tumor microenvironment of hepatocellular carcinoma (HCC). These results provide new insights into human HCC and may ultimately improve early HCC diagnosis as well as lead to the discovery of innovative therapeutic approaches for HCC.

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      Geraniol suppresses prostate cancer growth through down-regulation of E2F8

      Sanghoon Lee, Yu Rang Park, Su-Hwa Kim, Eun-Jung Park, Min Ji Kang, Insuk So, Jung Nyeo Chun and Ju-Hong Jeon

      Version of Record online: 28 SEP 2016 | DOI: 10.1002/cam4.864

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      Geraniol exerts chemotherapeutic activity against cancer. Microarray analysis from geraniol-treated prostate cancer cells identified that E2F8 is a specific target molecule that regulates geraniol-specific cell cycle signatures. E2F8 is required for growth of prostate cancer cells by regulating G2/M progression. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer patients and is associated with poor prognosis. Our study provides potential role of E2F8 in prostate cancer biology and therapeutics.

  2. Commentary

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      Screening mammography: sparing the emperor's blushes

      Saroj Niraula

      Version of Record online: 28 SEP 2016 | DOI: 10.1002/cam4.859

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      Screening mammography is controversial. Emerging data show minimal benefits with this procedure, if any, in terms of duration of survival. However, mammography is associated with substantial harms. This commentary analyses evidence on screening mammography from various aspects.

  3. Original Research

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      The use of adjuvant chemotherapy for pancreatic cancer varies widely between hospitals: a nationwide population-based analysis

      Maikel J. Bakens, Lydia G. van der Geest, Magreet van Putten, Hanneke W. van Laarhoven, Geert-Jan Creemers, Marc G. Besselink, Valery E. Lemmens, Ignace H. de Hingh and for the Dutch Pancreatic Cancer Group

      Version of Record online: 27 SEP 2016 | DOI: 10.1002/cam4.921

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      The use of adjuvant chemotherapy in the Netherlands significantly differed between pancreatic centers. Elderly patients and patients with TNM stage I disease were less likely to undergo adjuvant treatment. Adjuvant chemotherapy prolonged survival in this study.

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      Regression in thin melanoma is associated with nodal recurrence after a negative sentinel node biopsy

      Jill C. Rubinstein, Gang Han, Laura Jackson, Kaleigh Bulloch, Stephan Ariyan, Deepak Narayan, Bonnie G. Rothberg and Dale Han

      Version of Record online: 27 SEP 2016 | DOI: 10.1002/cam4.922

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      Prognostic markers for nodal metastasis in thin melanoma patients are debated. In this single institution study looking at factors predictive of nodal disease in thin melanoma patients, regression was not correlated with nodal metastasis, but it was correlated with a false-negative sentinel lymph node biopsy. Patients with thin melanoma and regression may need more intensive surveillance after a negative sentinel lymph node biopsy (SLNB).

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      Quantitative diagnosis of HER2 protein expressing breast cancer by single-particle quantum dot imaging

      Minoru Miyashita, Kohsuke Gonda, Hiroshi Tada, Mika Watanabe, Narufumi Kitamura, Takashi Kamei, Hironobu Sasano, Takanori Ishida and Noriaki Ohuchi

      Version of Record online: 26 SEP 2016 | DOI: 10.1002/cam4.898

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      Overexpression of human epidermal growth factor receptor 2 (HER2) is a major cause of breast cancer, and therefore precise diagnosis of its protein expression level is important. We developed a new immunohistochemical technique with quantum dot-conjugated anti-HER2 antibody using single-particle imaging. The quantitative diagnosis of HER2-expression level was strongly related to its gene amplification, and analysis correlating both factors suggested that the immunohistochemical score is a strong predictive factor for therapy.

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      Evaluating IPMN and pancreatic carcinoma utilizing quantitative histopathology

      Evan S. Glazer, Hao Helen Zhang, Kimberly A. Hill, Charmi Patel, Stephanie T. Kha, Michael L. Yozwiak, Hubert Bartels, Nellie N. Nafissi, Joseph C. Watkins, David S. Alberts and Robert S. Krouse

      Version of Record online: 26 SEP 2016 | DOI: 10.1002/cam4.923

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      Retrospective quantitative histopathological analysis of pancreatic lesions was performed to classify pancreatic tissues as chronic pancreatitis (CP), intraductal papillary mucinous neoplasms (IPMN), and pancreatic carcinoma (PC). Classification accuracy with six unique nuclear features yields a quantitative measure of uncertainty in a given classification and provides a means of distinguishing among patients with CP, IPMN, and PC.

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      CCL2 as a potential therapeutic target for clear cell renal cell carcinoma

      Ryuichiro Arakaki, Toshinari Yamasaki, Toru Kanno, Noboru Shibasaki, Hiromasa Sakamoto, Noriaki Utsunomiya, Takayuki Sumiyoshi, Shinsuke Shibuya, Tatsuaki Tsuruyama, Eijiro Nakamura, Osamu Ogawa and Tomomi Kamba

      Version of Record online: 26 SEP 2016 | DOI: 10.1002/cam4.886

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      Antiangiogenic-targeted therapies are used for treatment of advanced renal cell carcinoma. Our clinical data, corroborated by xenograft models, suggest that CCL2 is involved in tumor progression and may serve as novel therapeutic target for clear cell renal cell carcinoma.

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      Clinical significance and functional validation of PPA1 in various tumors

      Dehong Luo, Guanwen Wang, Wenzhi Shen, Shuangtao Zhao, Wei Zhou, Lin Wan, Liying Yuan, Shuang Yang and Rong Xiang

      Version of Record online: 26 SEP 2016 | DOI: 10.1002/cam4.894

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      PPA1 expression is significantly higher in many tumors, especially those of lung and ovarian origin, which suggests that PPA1 plays an important role in carcinogenesis and in the development of some tumors.

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      D2-resected stage IIIc gastric cancer patients benefit from adjuvant chemoradiotherapy

      Jin Peng, Yuehua Wei, Fuxiang Zhou, Jing Dai, Yahua Zhong, Conghua Xie, Yue'e Qin, Jun Gong, Bin Xiong and Yunfeng Zhou

      Version of Record online: 26 SEP 2016 | DOI: 10.1002/cam4.873

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      Adjuvant chemoradiotherapy in gastric cancer patients with D2 resection was well tolerated. Stage IIIc patients can benefit from adjuvant chemoradiation.

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      Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers

      Marco Lucioni, Emilio Berti, Luca Arcaini, Giorgio A. Croci, Aldo Maffi, Catherine Klersy, Gaia Goteri, Carlo Tomasini, Pietro Quaglino, Roberta Riboni, Mariarosa Arra, Elena Dallera, Vieri Grandi, Mauro Alaibac, Antonio Ramponi, Sara Rattotti, Maria Giuseppina Cabras, Silvia Franceschetti, Giulio Fraternali-Orcioni, Nicola Zerbinati, Francesco Onida, Stefano Ascani, Maria Teresa Fierro, Serena Rupoli, Marcello Gambacorta, Pier Luigi Zinzani, Nicola Pimpinelli, Marco Santucci and Marco Paulli

      Version of Record online: 26 SEP 2016 | DOI: 10.1002/cam4.865

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      This article deals with a series of 161 cases of primary cutaneous, nonmarginal zone B-cell lymphoma (BCL), which we retrospectively reviewed. We were able to identify a subset of cases, which we classified as primary cutaneous diffuse large BCL, not otherwise specified, displaying intermediate features—both histologic and clinical—between primary cutaneous follicular and “leg type” lymphoma. We also highlighted the relevance of immunohistochemical characterization—particularly the definition of the histogenic profile and BCL2/MYC expression—as well as of detection of BCL2 translocation in identifying prognostic subsets.

    9. You have full text access to this OnlineOpen article
      HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

      Sara Nicolás-Párraga, Carolina Gandini, Ville N. Pimenoff, Laia Alemany, Silvia de Sanjosé, F. Xavier Bosch, Ignacio G. Bravo and on behalf of the RIS HPV TT and HPV VVAP study groups

      Version of Record online: 21 SEP 2016 | DOI: 10.1002/cam4.870

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      We communicate a comprehensive description of human papillomavirus (HPV)16 variants in anogenital cancers in Europe, Central/South America, and Asia and quantify the contributions of anatomy and geography. Prevalence values of HPV16 variants are largely the same independently of the geographical origin and anatomical location of the lesion, with the only exception of anal cancers in Asia. Geographic dispersal with humans and tissue adaptation are not major driving forces in the evolution of HPV16, the most oncogenic HPV.

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      Clinical implication of Keap1 and phosphorylated Nrf2 expression in hepatocellular carcinoma

      Jiang Chen, Yaojun Yu, Tong Ji, Rui Ma, Mingming Chen, Gaofeng Li, Feibo Li, Qiong Ding, Qingsong Kang, Diyu Huang, Xiao Liang, Hui Lin and Xiujun Cai

      Version of Record online: 20 SEP 2016 | DOI: 10.1002/cam4.788

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      Oxidative stress has a crucial clinical significance on patients in a variety of tumors. However, there has been no comprehensive analysis of the role and clinical significance of oxidative stress markers Keap1 and pNrf2 expression in hepatocellular carcinoma (HCC). We found that reduced expression of cytoplasmic Keap1 and positive expression of nuclear pNrf2 of cancer cells may be associated with poor clinical outcome and worse prognosis.

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      Recombinant canstatin inhibits VEGF-A-induced lymphangiogenesis and metastasis in an oral squamous cell carcinoma SCC-VII animal model

      Jeon Hwang-Bo, Jong-Hwa Park, Mun Gyeong Bae and In Sik Chung

      Version of Record online: 20 SEP 2016 | DOI: 10.1002/cam4.866

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      Tumor-induced lymphangiogenesis is an attractive target for developing therapeutics to restrict the metastatic spread of oral squamous cell carcinoma (SCC). Recombinant canstatin exhibited in vivo antilymphangiogenic effects to suppress tumor growth and lung metastasis of oral SCC. Recombinant canstatin inhibited lymphangiogenesis via suppression of vascular endothelial growth factor (VEGF)-A/vascular endothelial growth factor receptors (VEGFR)-1 and -2 signaling. These findings suggest that recombinant canstatin has a high potential to treat oral SCC-induced tumor and prevent lymphatic metastasis.

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      Survival benefit of gastrectomy for gastric cancer with peritoneal carcinomatosis: a propensity score-matched analysis

      Xiuwen Geng, Hao Liu, Tian Lin, Yanfeng Hu, Hao Chen, Liying Zhao, Tingyu Mou, Xiaolong Qi, Jiang Yu and Guoxin Li

      Version of Record online: 20 SEP 2016 | DOI: 10.1002/cam4.877

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      The gastrectomy plus chemotherapy plus hyperthermic intraperitoneal chemotherapy (HIPEC) modality showed a significant survival benefit for gastric adenocarcinoma, particularly in those with P1 and P2 diseases. These results may shed light on the role of adjuvant surgery on the treatment of stage IV gastric cancer with peritoneal carcinomatosis.

    13. You have full text access to this OnlineOpen article
      ZNF703 Overexpression may act as an oncogene in non-small cell lung cancer

      Onur Baykara, Nejat Dalay, Kamil Kaynak and Nur Buyru

      Version of Record online: 20 SEP 2016 | DOI: 10.1002/cam4.847

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      Although amplification of the ZNF703 gene has been associated with different types of cancer so far there are no studies in the literature investigating the gene in lung cancer. In this study we analyze the expression of the gene in matched tumor and normal tissue samples from patients with non-small cell lung cancer. Our study is the first report in the literature investigating the expression rate and role of ZNF703 in non-small cell lung cancer (NSCLC). Our results indicate that ZNF703 functions as an oncogene in NSCLC and exerts its effect partly by activating the Akt/mTOR pathway.

    14. You have full text access to this OnlineOpen article
      Associations between cancer and Alzheimer's disease in a U.S. Medicare population

      Daryl Michal Freedman, Jincao Wu, Honglei Chen, Ralph W. Kuncl, Lindsey R. Enewold, Eric A. Engels, Neal D. Freedman and Ruth M. Pfeiffer

      Version of Record online: 14 SEP 2016 | DOI: 10.1002/cam4.850

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      Using Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data, we evaluated cancer risks following Alzheimer's disease (AD) in a large case-control study as well as AD risk after cancer in a cohort study. We also evaluated cancer in relation to automobile injuries, which are unlikely to be biologically related, to explore potential study biases. We found that cancer risks were similarly modestly reduced after both AD and automobile injuries, suggesting biases against detecting cancer in persons with unrelated medical conditions. In addition, there was a slightly lower AD risk in cancer survivors, which may reflect under-diagnosis of AD in those with a serious illness.

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      Symptom clusters and survival in Portuguese patients with advanced cancer

      Pedro C. Barata, Alice Cardoso, Maria P. Custodio, Marta Alves, Ana L. Papoila, Barbosa António and Peter G. Lawlor

      Version of Record online: 13 SEP 2016 | DOI: 10.1002/cam4.860

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      Three clinically meaningful symptom clusters were identified in patients with advanced cancer. The neuro-psycho-metabolic cluster and the presence of two or more symptom clusters were associated with a poorer survival prognosis.

    16. You have full text access to this OnlineOpen article
      Partial splenic embolization to permit continuation of systemic chemotherapy

      Jose Hugo M. Luz, Paula M. Luz, Edson Marchiori, Leonardo A. Rodrigues, Hugo R. Gouveia, Henrique S. Martin, Igor M. Faria, Roberto R. Souza, Roberto de Almeida Gil, Alexandre de M. Palladino, Karina B. Pimenta and Henrique S. de Souza

      Version of Record online: 9 SEP 2016 | DOI: 10.1002/cam4.856

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      Partial splenic embolization is an excellent option in the management of thrombocytopenia, enabling the resumption of systemic chemotherapy with minimal procedure-related morbidity.

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      Antimetastatic activity of novel ruthenium (III) pyridine complexes

      Liwei Gu, Xiaodong Li, Qingsen Ran, Chen Kang, Canghai Lee and Jianying Shen

      Version of Record online: 7 SEP 2016 | DOI: 10.1002/cam4.826

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      The ruthenium (III)-pyridine complexes, G26b and G94a, which is derived from NAMI-A, could strongly reduce the occurrence and development of lung metastases in mice when kept a slower Ru elimination, which prolonged contact with the metastatic cells in the lungs. The ruthenium (III)-pyridine complexes had coped better than well-studied NAMI-A.

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      Dabigatran antagonizes growth, cell-cycle progression, migration, and endothelial tube formation induced by thrombin in breast and glioblastoma cell lines

      Fabrizio Vianello, Luisa Sambado, Ashley Goss, Fabrizio Fabris and Paolo Prandoni

      Version of Record online: 7 SEP 2016 | DOI: 10.1002/cam4.857

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      Advanced malignancy often correlates with activation of the coagulation system, termed cancer coagulopathy, which is associated with increased mortality rates. Thrombin, the main effector of the coagulation cascade, has been shown to affect cancer progression by activation of PAR-1. We show that the direct thrombin inhibitor dabigatran antagonizes proliferation, migration, and proangiogenetic effects of thrombin in tumor cells.

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      Up-regulation of mir-10b predicate advanced clinicopathological features and liver metastasis in colorectal cancer

      Hong Jiang, Jijun Liu, Yingtao Chen, Chong Ma, Baosong Li and Tao Hao

      Version of Record online: 4 SEP 2016 | DOI: 10.1002/cam4.789

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      miR-10b expression was also found correlated with advanced stage (P < 0.0001), lymph node metastasis (P = 0.025), venous infiltration (P = 0.007), poorer differentiation (P = 0.002), and served as an independent prognostic factor of poor overall survival (P < 0.0001).

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      A -1573T>C SNP within the human TRAIL promoter determines TRAIL expression and HCC tumor progression

      Katja Piras-Straub, Khaleda Khairzada, Peri Kocabayoglu, Andreas Paul, Guido Gerken and Kerstin Herzer

      Version of Record online: 31 AUG 2016 | DOI: 10.1002/cam4.854

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      We investigated sequences of the TRAIL promoter from a large number of human hepatocellular carcinoma (HCCs), observing a SNP (single-nucleotide polymorphism) within a GATA-1-binding site which is related to a loss-of-function of the corresponding GATA-1 site, resulting in a reduced TRAIL expression and increased tumor cell migration. This is the first report on a SNP in the TRAIL promoter segment with implications for the regulation of TRAIL, and thus, with predictive value for HCC development.

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      AFAP1-AS1 is upregulated and promotes esophageal squamous cell carcinoma cell proliferation and inhibits cell apoptosis

      Hong-lei Luo, Ming-de Huang, Jia-ni Guo, Rui-hua Fan, Xiao-tian Xia, Jing-dong He and Xiao-fei Chen

      Version of Record online: 30 AUG 2016 | DOI: 10.1002/cam4.848

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      AFAP1-AS1 is upregulated in esophageal squamous cell carcinoma and AFAP1-AS1 could promote esophageal squamous cell carcinoma cell's proliferation and inhibit cell apoptosis.

    22. You have full text access to this OnlineOpen article
      Significance of delayed primary excision in localized nonmetastatic adult head and neck rhabdomyosarcoma

      Kenya Kobayashi, Fumihiko Matsumoto, Makoto Kodaira, Taisuke Mori, Naoya Murakami, Akihiko Yoshida, Daisuke Maki, Masanori Teshima, Masahiko Fukasawa, Jun Itami, Masahiro Asai and Seiichi Yoshimoto

      Version of Record online: 26 AUG 2016 | DOI: 10.1002/cam4.855

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      Delayed primary excision might contribute to the improvement of local control in head and neck adult rhabdomyosarcoma. Poor response to induction chemotherapy is a risk factor for local recurrence.

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      Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma

      Zhengbo Song, Xinmin Yu and Yiping Zhang

      Version of Record online: 23 AUG 2016 | DOI: 10.1002/cam4.852

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      PIK3CA mutation of lung adenocarcinoma was commonly concurrent with other driver genes. PIK3CA mutation was associated with reduced progression-free survival of EGFR-TKIs treatment and shorter overall survival.

    24. You have full text access to this OnlineOpen article
      The histological characteristics and clinical outcomes of lung cancer in patients with combined pulmonary fibrosis and emphysema

      Meng Zhang, Akihiko Yoshizawa, Satoshi Kawakami, Shiho Asaka, Hiroshi Yamamoto, Masanori Yasuo, Hiroyuki Agatsuma, Masayuki Toishi, Takayuki Shiina, Kazuo Yoshida, Takayuki Honda and Ken-ichi Ito

      Version of Record online: 21 AUG 2016 | DOI: 10.1002/cam4.858

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      The histology of lung cancer in patients with combined pulmonary fibrosis and emphysema (LC-CPFE) is poorly understood. Our results indicate that LC-CPFE has a distinct histological phenotype, can arise from the dysplastic epithelium, and is associated with poor survival outcomes.

    25. You have full text access to this OnlineOpen article
      Patients with ROS1 rearrangement-positive non-small-cell lung cancer benefit from pemetrexed-based chemotherapy

      Zhengbo Song, Haiyan Su and Yiping Zhang

      Version of Record online: 20 AUG 2016 | DOI: 10.1002/cam4.809

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      This study determined 34 patients with ROS1 rearrangement positive from 1750 samples with lung cancer. They found PFS of pemetrexed-based chemotherapy in ROS1-positive patients is longer than ROS1-negative and the TS mRNA level was lower in patients with ROS1-positive than in ROS1-negative patients.

    26. You have full text access to this OnlineOpen article
      Analysis of prognostic factors for pancreatic head cancer according to para-aortic lymph node

      Jian-yu Lin, Xing-mao Zhang, Jian-tiao Kou, Hua Fa, Xin-xue Zhang, Yang Dai and Qiang He

      Version of Record online: 19 AUG 2016 | DOI: 10.1002/cam4.853

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      There were few reports on analysis of prognostic factors for pancreatic head cancer according to para-aortic lymph node. Different prognostic factors for pancreatic cancer had been confirmed by our study.

    27. You have full text access to this OnlineOpen article
      Analysis of predictability of F-18 fluorodeoxyglucose-PET/CT in the recurrence of papillary thyroid carcinoma

      Suk Kyeong Kim, Young So, Hyun Woo Chung, Young Bum Yoo, Kyung Sik Park, Tae Sook Hwang, Bokyung Kim and Won Woo Lee

      Version of Record online: 19 AUG 2016 | DOI: 10.1002/cam4.867

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      FDG (fluorodeoxyglucose)-avid papillary thyroid carcinomas showed worse pathological prognostic factors. Lymph node metastasis was the only predictor of papillary thyroid carcinoma (PTC) recurrence. Preoperative FDG-PET/CT may play a potential role for the prediction of papillary thyroid carcinoma recurrence.

  4. Reviews

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      The pivotal role of mammalian target of rapamycin inhibition in the treatment of patients with neuroendocrine tumors

      Alexandria T. Phan and Bhuvanesh Dave

      Version of Record online: 18 AUG 2016 | DOI: 10.1002/cam4.742

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      Mammalian target of rapamycin (mTOR) and components of the mTOR pathway play pivotal roles in neuroendocrine tumor (NET) pathogenesis. mTOR inhibition as backbone therapy within the NET treatment landscape is an ongoing focus. Data evaluating the clinical benefits of agents targeting mTOR and related pathways (alone and in combination) in the treatment of patients with pancreatic NET continues to emerge, and many of the findings to date are encouraging.

  5. Review Articles

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      The hedgehog pathway in triple-negative breast cancer

      Joyce G. Habib and Joyce A. O'Shaughnessy

      Version of Record online: 18 AUG 2016 | DOI: 10.1002/cam4.833

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      Given the increasingly recognized role of aberrant Hedgehog signaling in breast tumorigenesis as a whole and TNBC in particular, we sought to review all relevant preclinical data and provide a concise summary of the mechanisms of Hedgehog signaling in this breast cancer subtype. Further, we extend our review to recent findings of both established and potential crosstalk with other key signaling pathways which may potentially impact the efficacy of agents targeting the Hedgehog pathway in TNBC.

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