Cancer Research (CANCER RES )

Publisher: American Association for Cancer Research; International Cancer Research Foundation; William H. Donner Foundation, American Association for Cancer Research


Cancer Research publishes significant, original studies in all areas of basic, clinical, translational, epidemiological, and prevention research devoted to the study of cancer and cancer-related biomedical sciences. Scientific topics include: biochemistry; chemical, physical, and viral carcinogenesis and mutagenesis; clinical investigations including clinical trials; endocrinology; epidemiology and prevention; experimental therapeutics; immunology and immunotherapy including biological therapy; molecular biology and genetics; radiobiology and radiation oncology; tumor biology; and virology. Thus its publication scope covers all subfields of cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.

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  • Website
    Cancer Research website
  • Other titles
    Cancer chemotherapy screening data., Cancer research (Chicago, Ill.), Cancer research
  • ISSN
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  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

American Association for Cancer Research

  • Pre-print
    • Archiving status unclear
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • NIH authors may post author's own version in PubMed Central for release 12 month after publication
    • HHMI, Wellcome Trust, Cancer Research UK and UK Medical Research Council authors may deposit authors own version in UKPMC for release 6 months after publication
    • AACR will deposit on behalf of these authors, if required
    • Authors final version may be deposited on institutional website/ repository if required by institution
    • Published source must be acknowledged
    • Must link to the publisher PDF of article on journal website
  • Classification
    ​ white

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the major limitations of modern cancer vaccine vectors is that, unlike infectious pathogens, to which the immune system has evolved to respond, they are not sufficiently effective in delivering tumor-associated antigens (TAAs) in an immunogenic form to intact professional antigen-presenting cells (APCs) at their anatomic location. To overcome this challenge, we exploited Salmonella Pathogenicity Island 2 (SPI2) and its type III secretion system (T3SS) to deliver a TAA of choice into the cytosol of APCs in situ. We have systematically compared candidate genes from the SPI2 locus of Salmonella typhimurium in the vaccine design, using model antigens and a codon-optimized human TAA, survivin (coSVN). In a screen of 20 SPI2 promoter/effector combinations, the PsifB::sseJ pair demonstrated the maximal potency for antigen translocation in the APC cytosol, presentation to CD8 T cells, and immunogenicity in mice. Therapeutic vaccination with the PsifB::sseJ-coSVN construct (p8032) resulted in CXCR3-dependent tumor infiltration with CD8 T cells, reversal of the CD8:Treg ratio at the tumor site, and potent anti-tumor activity in a CT26 colon carcinoma model. The vaccine’s immunogenicity and anti-tumor potency were further enhanced by co-administration of an NKT-cell ligand, 7WD8-5, which strongly enhanced production of IL-12 and IFNγ in vaccinated mice. Furthermore, therapeutic vaccination with p8032/7WD8-5 resulted in complete tumor regression in an A20 lymphoma model, with the generation of protective memory. Thus, oral antigen delivery via SPI2-encoded T3SS of Salmonella may be the foundation for an effective cancer vaccine platform.
    Cancer Research 09/2014;
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    ABSTRACT: p38 mitogen-activated protein kinase (MAPK) signalling has been implicated in the regulation of processes leading to cancer development and progression. Chronic inflammation is a known risk factor for tumourigenesis, yet the precise mechanism of this association remains largely unknown. The related p38αMAPK (MAPK14) proteins p38γ (MAPK12) and p38δ (MAPK13) were recently shown to modulate the immune response, although their role in tumourigenesis remains controversial and their function in inflammation-associated cancer has not been studied. We analysed the role of p38γ and p38δ in colon cancer associated to colitis, using the azoxymethane/dextran sodium sulphate colitis-associated colon cancer model in wild type (WT), p38γ-, p38δ- and p38γ/δ-deficient (p38γ/δ-/-) mice. We found that p38γ/δ deficiency significantly decreased tumour formation, in parallel with a decrease in proinflammatory cytokine and chemokine production. Analysis of leukocyte populations in p38γ/δ-/- mouse colon showed less macrophage and neutrophil recruitment than in WT mice. Furthermore, WT chimaeric mice with transplanted p38γ/δ-/- bone marrow (BM) had less tumours than WT mice transplanted with WT BM, whereas tumour number was significantly increased in p38γ/δ-/- chimaeric mice with WT BM compared to p38γ/δ-/- mice transplanted with p38γ/δ-/- BM. Together, our results establish that p38γ and p38δ are central to colitis-associated colon cancer formation through regulation of haematopoietic cell response to injury, and validate p38γ and p38δ as potential targets for cancer therapy.
    Cancer Research 09/2014;
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    ABSTRACT: Cancer evolution is a process that is still poorly understood due to the lack of versatile in vivo longitudinal studies. By generating murine Non-Small Cell Lung Cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations and the appearance of naturally occurring intra-tumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the pre-clinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for NSCLC patients.
    Cancer Research 09/2014;
  • Cancer Research 08/2014;
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    ABSTRACT: The JmjC domain histone H3K36me2/me1 demethylase NDY1/KDM2B is overexpressed in various types of cancer. Here we show that knocking down NDY1 in a set of ten cell lines derived from a broad range of human tumors inhibited their anchorage-dependent and anchorage-independent growth by inducing senescence and/or apoptosis in some and by inhibiting G1 progression in all. We further show that the knockdown of NDY1 in mammary adenocarcinoma cell lines decreased the number, size and replating efficiency of mammospheres and downregulated the stem cell markers ALDH and CD44, while upregulating CD24. These findings combined, suggest that NDY1 is required for the self-renewal of cancer stem cells and are in agreement with additional findings showing that, tumor cells in which NDY1 was knocked down undergo differentiation and a higher number of them is required to induce mammary adenocarcinomas, upon orthotopic injection in animals. Mechanistically, NDY1 functions as a master regulator of a set of microRNAs that target several members of the polycomb complexes PRC1 and PRC2 and its knockdown results in the de-repression of these microRNAs and the downregulation of their polycomb targets. Consistent with these observations, NDY1/KDM2B is expressed at higher levels in basal-like triple negative breast cancers and its overexpression is associated with higher rates of relapse after treatment. In addition, NDY1-regulated microRNAs are downregulated in both normal and cancer mammary stem cells. Finally, in primary human breast cancer, NDY1/KDM2B expression correlates negatively with the expression of the NDY1-regulated microRNAs, and positively with the expression of their PRC targets.
    Cancer Research 05/2014;
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    ABSTRACT: Musashi-1 (Msi-1) is a well-established stem cell marker in both normal and malignant colon cells and it acts by positively regulating the Notch pathway through inactivation of Numb, a Notch signalling repressor. To date, the mechanisms of regulation of Msi-1 levels remain largely unknown. Here we investigated the regulation of Msi-1 by Notch signalling in the colorectal cancer cell lines MICOL-14tum and LoVo and in primary cultures of colorectal cancer (CRC) metastases. Stimulation by the Notch ligand DLL4 was associated with an increase of Msi-1 mRNA and protein levels, and this phenomenon was prevented by the addition of antibody neutralizing Notch2/3 but not Notch1. Moreover, forced expression of activated Notch3 increased Msi-1 levels, whereas silencing of Notch3 by shRNA reduced Msi-1 levels in both CRC cells and tumor xenografts. Consistent with these findings, forced Notch3 expression or stimulation by DLL4 increased levels of activated Notch1 in MICOL-14tum and LoVo cells. Finally, treatment of CRC cells with anti-Notch2/3 antibody increased Numb protein while significantly reducing formation of spheroids in both MICOL-14tum cells and primary tumor cultures. This novel feed-forward circuit involving DLL4, Notch3, Msi-1, Numb and Notch1 may be relevant for regulation of Notch signalling in physiological processes as well as in tumor development. With regard to therapeutic implications, Notch3-specific drugs could represent a valuable strategy to limit Notch signaling in the context of colorectal cancers overexpressing this receptor.
    Cancer Research 02/2014;
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    ABSTRACT: Neuroblastoma is a neural crest-derived embryonal malignancy, which accounts for 13% of all pediatric cancer mortality, primarily due to tumor recurrence. Therapy-resistant cancer stem cells are implicated in tumor relapse, but definitive phenotypic evidence of the existence of these cells has been lacking. In this study, we define a highly tumorigenic subpopulation in neuroblastoma with stem cell characteristics, based on the expression of CSF3R, which encodes the receptor for granulocyte colony-stimulating factor (G-CSF). G-CSF receptor positive (aka G-CSFr(+) or CD114(+)) cells isolated from a primary tumor and the NGP cell line by flow cytometry were highly tumorigenic and capable of both self-renewal and differentiation to progeny cells. CD114(+) cells closely resembled embryonic and induced pluripotent stem cells with respect to their profiles of cell cycle, miRNA, and gene expression. In addition, they reflect a primitive undifferentiated neuroectodermal/neural crest phenotype revealing a developmental hierarchy within neuroblastoma tumors. We detected this dedifferentiated neural crest subpopulation in all established neuroblastoma cell lines, xenograft tumors, and primary tumor specimens analyzed. Ligand activation of CD114 by the addition of exogenous G-CSF to CD114(+) cells confirmed intact STAT3 upregulation, characteristic of G-CSF receptor signaling. Together, our data describe a novel distinct subpopulation within neuroblastoma with enhanced tumorigenicity and a stem cell-like phenotype, further elucidating the complex heterogeneity of solid tumors such as neuroblastoma. We propose that this subpopulation may represent an additional target for novel therapeutic approaches to this aggressive pediatric malignancy.
    Cancer Research 07/2013; 73(13):4134.
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    ABSTRACT: Shionogi Carcinoma 115 (SC 115) is an androgen-dependent mouse Iunior, and Chiba subline 2 (CS 2) is its androgen-independent subline which differs from SC 115 in cell size, amount of androgen receptors, and karyotype. To shed light on the mechanism of clonal selection of androgen-independent tumors, mixed tumors with SC 115 and CS 2 were prepared, and growth of these tumors was examined in vivoand in vitro. When the mixed tumor was transplanted in mice, CS 2 showed a predominant growth over SC 115. In a culture of mixed tumor cells, however, CS 2 showed no selective growth advantage. The suppressive interaction which occurred in vivo was due neither to transferable sub stances, nor to some immunologicalfactor(s). It may be, at least partially, attributable to necrosis formation in SC 115, which developed with an increase in the size of the tumor.
    Cancer Research 06/2013;
  • Cancer Research 05/2013;
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    ABSTRACT: Telomeres are repeated DNA sequences that cap the ends of each chromosome. Telomeres are temporally among the earliest genomic sequences to be degraded during apoptosis. We quantified telomeres in cell-free DNA (CF-DNA) in vitro and in vivo. CF-DNA was obtained by differential centrifugation of media or serum to remove intact cells and cellular debris. Telomere sequence in CF-DNA was measured with a quantitative PCR-based assay. We initially studied human breast cancer and brain cancer cell lines in vitro. We found that following treatment with doxorubicin, telomere sequences were rapidly detected in CF-DNA in the media (within 24-48 hours). We call these CF-DNA telomere sequences “extracellular telomeres” (ETs). ETs were preferentially secreted after chemotherapy. The telomere sequence molar fraction in the CF-DNA was up to 50,000-fold higher compared with other genomic sequences such as exons or structural DNA sequences such as alpha-satellite DNA. CF-DNA from the serum of 80 patients with a history of breast cancer and 40 normal female volunteers were analyzed. The patients with a history of metastatic breast cancer (n = 40) had 8-fold higher median value for ETs compared to those with a history of localized breast cancer (p=0.006). 20 normal women had ET levels similar to the local breast cancer patients. We thus hypothesized that the serum extracellular telomere assay could be used as a surrogate marker for in vivo apoptotic cell death. We collected sequential peripheral blood samples of newly diagnosed AML patients with a minimum peripheral circulating blast count of 2500/mm3 or more who received standard induction chemotherapy (anthracycline and cytarabine). These sequential peripheral blood samples were collected before, during and after standard chemotherapy at 12 hours interval for consecutive 21 days. The samples were immediately centrifuged to isolate CF DNA. Subsequently, ETs were quantitatively measured by qPCR telomere assay. In our preliminary data analysis of seven patients, we routinely observed two peaks of ETs about 10- fold higher than baseline that occurred about 2-3 and 4-6 days after initiating standard chemotherapy respectively. We conclude that 1) Telomere DNA is preferentially released from cancer cells in response to chemotherapy-induced apoptosis, 2) ETs can be detected and measured in normal patients and patients with a history of cancer, and 3) ETs are released after chemotherapy in AML patients. We are further investigating the relationship between ETs and other prognostic features in AML including initial white blood cell count, cytogenetics, disease free survival and overall survival.
    Cancer Research 04/2013; 73(8):Abstract 1761.
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    ABSTRACT: Background: Metastatic spread poses the greatest challenge for the management of Prostate Cancer (PCa). Although its frequency at diagnosis of PCa cases is only 4%, it is associated with poor prognosis, with five year survival rates of only 30%. Molecular mechanisms involved in metastatic progression are not completely understood; however, it has been noted that chemokines and their receptors play a key role in the establishment of metastatic lesions. Objective: To compare the mRNA expression profiles of chemokines and their receptors in two human PCa cell lines with different metastatic phenotypes (LNCaP, PC-3) and in a control, normal prostate epithelial cell line (PWR-1E). Methods: We evaluated the expression profiles at the transcript level of chemokines and their receptors in LNCaP, PC-3 and PWR-1E human cell lines using a commercial primer panel (Chemokines SensiMix qPCR Primers Panel©,Origene Technologies), as well as a custom primer panel. The relative quantification of gene expression was determined using the {Delta}{Delta}Ct method with the normal PWR-1E cell line as the reference cell line and normalizing the expression to β-actin, HPRT1 and GAPDH housekeeping genes. Results: Sixteen gene transcripts were overexpressed in PC-3, 13 of which were exclusively overexpressed in this cell line and 3 other genes were up-regulated in both PC-3 and LNCaP cell lines. Of the 13 genes overexpressed in PC-3, 12 were found under-expressed in LNCaP cell line, compared to PWR-1E (CCL2, CCL26, CCL28, CXCL2, CXCL3, CXCL4, CXCL4V1, CXCL6, IL8, CXCL12, CCR10, and CCRL2). Chemokine transcript under-expression was more frequently found in LNCaP than in PC-3 (11 vs 8) and transcripts for genes CCL3, CCL3L1, CCL3L3, CCL27 and DARC were underexpressed in both cell lines. Discussion: Here we describe the differential chemokine expression profile between PCa cell lines with different metastatic potentials. In addition to chemokines/receptors known to play a role in PCa, we have identified the differential expression of chemokine gene transcripts not previously associated with PCa. Conclusions: Differential chemokine expression at the mRNA level was found in association with metastatic phenotypes of PCa cell lines. Additional research is needed to determine mechanisms involved in genic regulation of this profiles and to determine their roles in tumorigenesis and cancer progression in the prostate.
    Cancer Research 04/2013; 73(8).
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    ABSTRACT: Background: Prostate cancer (PCa) is the second most common worldwide neoplasm in men [1]. Proliferative inflammatory atrophy (PIA) is proposed as a "risk factor lesion" as it has an important inflammatory component and the associated oxidative stress has been suggested to have a role in prostatic carcinogenesis [2,3] Objectives: To determine correlations between pathological findings of inflammation and proliferative inflammatory atrophy (PIA), in prostate biopsy specimens and to compare their prevalence in biopsies with and without prostate adenocarcinoma. Methods: A prospective study was conducted between December 2010 and June 2012 in the Hospital Universitario del Caribe, Cartagena, Colombia. Patients referred for transrectal ultrasound-guided prostate needle biopsy for suspected PCa were invited to participle and signed an informed consent. Initial prostate biopsies were examined for the presence of PCa, chronic inflammation and atrophy. The inflammation was scored for grade, localization and extension using the classification system of the CPCRN and IPCN consensus [4]. Atrophy was classified according to "Working Group Classification of Focal Prostate Atrophy Lesions" [5], and grade of atrophy was graduated using categories described by Postma [6]. For statistical analysis we compared parameters between groups with and without PCa. This study was approved for the Ethical Review Board of the participating institutions. Results: 97 patients were included, between the ages of 47 and 87 years (mean age: 68.32, SD: 8.9). Adenocarcinoma was identified in 50 of the 97 (51.5%) biopsies examined. There was a significant age difference between the PCa and benign groups (p=0.0031) and PSA levels were significantly higher in patients with cancer. Inflammation was detected in 95.87% of biopsies. Inflammation grade was significantly different between PCa and benign samples (p=0.038) but extension and localization of inflammation was not different between the groups. PIA was observed in 61 cases (62.8%) of which 23 had PCa. Atrophy grade and type were not different between groups and simple atrophy was the most frequently observed type. Morphological transition PIA-HGPIN was significantly more frequent in PCa group (p=0.0002) Conclusions: Our data provide evidence for a role of PIA as a PCa precursor lesion as we observed a strong association between morphological transition PIA-HGPIN and PCa. As inflammation was observed in the vast majority of patient samples, our analysis did not detect an association with PCa. Likewise, a clear association between atrophy and PCa was not observed.
    Cancer Research 04/2013; 73(8).
  • Cancer Research 04/2013;
  • Cancer Research 04/2013;

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