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  • American Association for Cancer Research (AACR)  (11)
  • 1
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    Plasma Carotenoid- and Retinol-Weighted Multi-SNP Scores and Risk of Breast Cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 22, No. 5 ( 2013-05-01), p. 927-936
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 22, No. 5 ( 2013-05-01), p. 927-936
    Abstract: Background: Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in β-carotene 15,15′-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. Methods: We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. Results: Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk [OR (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores = 1.04 (0.94–1.16) for β-carotene, 1.08 (0.98–1.20) for α-carotene, 1.04 (0.94–1.16) for β-cryptoxanthin, 0.95 (0.87–1.05) for lutein/zeaxanthin, and 0.92 (0.83–1.02) for retinol]. Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. Conclusions: Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. Impact: Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer. Cancer Epidemiol Biomarkers Prev; 22(5); 927–36. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-13-0017
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 2
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    Abstract 4934: Modified SWATH MS analysis of serine hydrolase activity in lung adenocarcinoma
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4934-4934
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4934-4934
    Abstract: Lung cancer, especially adenocarcinoma as the most common subtype, is still the most deadly human cancers. Therefore biomarker discovery for implementation of individualised therapies remains of utmost importance. Serine hydrolases (SHs), one of the largest enzyme families, have previously been shown to be implicated in the development of lung cancers. Activity-based protein profiling (ABPP) is a proteomic method that uses active site-directed chemical probes to selectively target the active form of the subsets of the enzymes in question, and then by a combination of a streptavidin-biotin enrichment step and mass spectrometry quantifies the catalytically active amount of the enzyme molecule. In this project, we monitored both forms of serine hydrolase, the catalytically active and inactive, in a patient cohort of lung adenocarcinoma biopsies. For this purpose, we combined the activity-based proteomics for serine hydrolase and SWATH mass spectrometry (MS), which ensures highly reproducible protein quantification in a large panel of clinical samples. Twenty four lung biopsies of long- and short surviving patients with stage IIIA adenocarcinomas and their normal tissue counterparts were available as OCT-embedded tissue. Although OCT represents a non-reactive compound used to preserve tissue morphology in long-term sample storage, this substance is incompatible with mass spectrometry measurements. We optimized and developed an OCT clean-up protocol compatible with enzyme-substrate binding of activity-based chemical probes and the targeted portion of the active enzyme. To prevent digestion on streptavidin beads and MS spectra contamination, we used the reproducible and accurate SWATH MS to indirectly measure the active enzyme form in the biopsy-extract solution which had earlier been depleted for all active enzyme molecules by precipitation with chemical probes attached to the beads. We identified over 4000 lung tissue proteins from a few milligrams of OCT-embedded biopsies, and confirmed good data quality for further SH enzyme quantification. In addition to the analysis of total proteome, 278 distinct proteins were identified on the parallel streptavidin bead samples, with chemical probes being used to deplete the active enzyme from the biopsy-extract. Each SWATH experiment reported the percentage of active enzyme form through the indirectly measured ratio between the inactive SHs (sample depleted for active SHs) and the total SHs (non-depleted sample). We detected around 80 enzymes with the active form comparably measured in all three independent experiments, which amount generally accounted for between 5-55% of the total enzyme concentration. We conclude that with the modified protocol compatible with OCT-embedded tissue biopsies the combination of ABPP and SWATH-MS enables highly reproducible protein quantification in biomarker discovery. Citation Format: Tatjana Sajic, Stephan Arni, Walter Weder, Rudolf Aebersold, Sven Hillinger. Modified SWATH MS analysis of serine hydrolase activity in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4934.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-4934
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 3
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    Abstract OT-04-03: Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. OT-04-03-OT-04-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. OT-04-03-OT-04-03
    Abstract: Background Main weaknesses of neoadjuvant chemotherapy (NACT) to avoid axillary dissection (ALND) in patients with clinically node-positive breast cancer are frequent failure of achieving nodal pathologic complete response (pCR) and administration of chemotherapy even though not indicated otherwise in many cases. Tailored axillary surgery (TAS) was designed to selectively remove positive nodes and omit ALND in patients with clinically node-positive breast cancer either in the upfront surgery setting or in case of residual nodal disease after neoadjuvant therapy, which distinguishes this trial from all others ongoing and published. Trial design In this international, multi-center, phase-III, non-inferiority randomized controlled trial, including 61 study sites from six countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS only followed by regional nodal irradiation including the full axilla. TAS consists of selective removal of the sentinel lymph nodes (SLNs) and all palpably suspicious findings, thereby tailoring the extent of axillary surgery to the extent of axillary disease, followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. All patients undergo adjuvant whole-breast irradiation after breast conserving surgery and chest wall irradiation after mastectomy. Inclusion of internal mammary nodes is recommended irrespective of treatment arm. ClinicalTrials.gov Identifier: NCT03513614. Inclusion criteria - Clinically node-positive breast cancer (all molecular subtypes allowed) - Node-positivity palpable or detectable only by imaging at time of initial diagnosis - Newly diagnosed or isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT. - In case of prior neoadjuvant treatment: residual disease (including residual ITCs) confirmed by pathology at the time of surgery - Clipping of sampled axillary lymph node Exclusion criteria - Absence of clip in the specimen radiography - Palpable disease left behind in the axilla after TAS - No SLN identified in the axilla Specific aims To test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival (DFS) of clinically node-positive breast cancer patients. Secondary objective is to test if quality of life is significantly better with TAS and axillary radiotherapy compared to ALND. Statistical methods With type I error 5% and power 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio (HR) of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm), including one interim analysis for efficacy/futility after 20% of the required events have occurred. The sample size needed is 1500 patients (750 per arm). The HR and one-sided 95% confidence interval will be calculated using a Cox regression model based on the per-protocol set. Present accrual and target accrual The trial was activated on 31 July 2018 and the first patient was randomized on 07 August 2018. As of 03 July 2020, 291 patients have been randomized. Accrual is currently running according to protocol and is planned until end of 2023 with the primary endpoint analysis expected in 2029. Contact information Prof. Dr. Walter Paul Weber, University Hospital Basel; Tel: +41 61 328 61 49; Walter.Weber@usb.ch Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihály Újhelyi, Christian Kurzeder, Loïc Lelièvre, Christoph Tausch, Daniel Egle, Jörg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-04-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-OT-04-03
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 4
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    A Common 8q24 Variant in Prostate and Breast Cancer from a Large Nested Case-Control Study
    American Association for Cancer Research (AACR) ; 2007
    In:  Cancer Research Vol. 67, No. 7 ( 2007-04-01), p. 2951-2956
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 7 ( 2007-04-01), p. 2951-2956
    Abstract: Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rs1447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 × 10−13). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 × 10−13). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an ORAC = 1.34 (99% confidence intervals, 1.19–1.50) and carriers with two copies of the minor allele had an ORAA = 1.86 (99% confidence intervals, 1.30–2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result. [Cancer Res 2007;67(7):2951–6]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-06-3591
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 5
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    Abstract P6-12-06: Shared decision making (SDM) in routine care treatment of breast cancer patients - A survey of patients following surgery
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. P6-12-06-P6-12-06
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P6-12-06-P6-12-06
    Abstract: Introduction: The aim of shared decision making (SDM) is a treatment decision in which patients are meaningfully involved. Many preference-sensitive decisions have to be made in breast cancer treatment and little is known about the implementation of SDM. We therefore investigated the process of SDM in routine care treatment. Methods: All breast cancer patients who underwent surgery in four German breast centers between 07/2016 and 07/2018 were invited to take part. The experienced decision-making process was assessed using the German version of the 9-item SDM questionnaire (PEF-FB-9). Furthermore, satisfaction with care with focus on patient participation was assessed using the ZAPA questionnaire. PEF-FB-9 and ZAPA items were summed up and transformed into a total score ranging from 0 to 100. The higher the total score the higher the experienced degree of participation and satisfaction, respectively. Participants were asked to separately rate decision-making consultations with their inpatient hospital doctors, outpatient gynecologists, outpatient oncologists and primary care providers (PCP). In addition, satisfaction with decision, participation preferences as well as other items for the complete decision process were queried. Results: Of 1,068 approached patients, 563 with a median age of 62 (31-92) filled in the survey (response rate: 53%). 81% had breast conserving surgery, 19% mastectomy. Consultations were assessed most often for hospital doctors (n=484). Gynecologists (n=270), oncologists (n=174) and PCP (n=64) were evaluated less often. Hospital doctors (mean (M): 75, standard deviation (SD): 22) and oncologists (M: 74, SD: 22) achieved the highest PEF-FB-9 scores indicating the highest degree of SDM. Gynecologists and PCP were rated almost as good with mean scores of 71 (SD: 23) and 69 (SD: 28), respectively. The mean score for all groups of doctors was 74 (SD: 21), less than 4% of patients reported SDM scores & lt;25. The values for satisfaction with decision were distributed as follows: PCP (M: 90, SD: 16), hospital doctors (M: 89, SD: 16), oncologists (M: 89, SD: 17), gynecologists (M: 85, SD: 22). Conclusions: Overall, patients reported to have experienced SDM in many situations where treatment decisions were necessary. Patients were quite satisfied with the quality of information and their participation in medical decisions. However, we do not know whether non-respondents might have had different experiences regarding their treatment decision-making. Citation Format: Rudolf Weide, Isabelle Scholl, Jan Dünnebacke, Marcus Schmidt, Arno Franzen, Walter Ernst, Ilhan Saka, Heike Spaderna, Stefan Feiten. Shared decision making (SDM) in routine care treatment of breast cancer patients - A survey of patients following surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-12-06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-P6-12-06
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 6
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    The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 26, No. 9 ( 2017-09-01), p. 1360-1369
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 26, No. 9 ( 2017-09-01), p. 1360-1369
    Abstract: Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360–9. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-17-0246
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 7
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    Abstract 5101: Biomarker identification in non-small cell lung cancer (NSCLC) with activity-based proteomics
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 5101-5101
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 5101-5101
    Abstract: Background: Lung cancer is the leading cause of all cancer related deaths and treatment is still suboptimal. Novel biomarkers with a reliable predictive significance which may additionally represent therapeutic targets are therefore of utmost importance. In biomarker discovery studies transcript or protein abundances are typically compared in normal versus disease states. However, crucial changes in enzymatic activities remain undetected. Based on the work of Prof. Cravatt and others, activity-based proteomics has become a promising option to circumvent this limitation. This study aims to establish a robust and high throughput activity-based proteomics platform and to investigate the role of serine hydrolase activity profiles as prognostic biomarkers in lung cancer. Methods: A fluorophosphate derivate (CAS-Number: 353754-93-5) was used to covalently target serine hydrolases in proteomes derived from human lung adenocarcinoma biopsies and corresponding normal lung tissues (tumor cell content: & gt;50%, TNM-stage: I-IV). Tagged proteins were subsequently affinity purified and analyzed using a directed mass spectrometry based approach (LTQ-FTMS, Thermo Finnigan). Data were qualitatively analyzed using the Mascot 2.2 search engine and Progenesis LC-MS version 2.5 (Nonlinear Dynamics) was employed for relative quantification. Results: The strategy described above results in the simultaneous qualitative and quantitative analysis of serine hydrolase activities in complex proteomes, thereby representing a valid alternative to activity-based proteomics approaches described so far. The analysis of 40 pairs of fresh frozen malignant and corresponding normal lung tissues in combination with clinical follow-up data led to the identification of two biomarker candidates that have previously not been associated with lung cancer. Conclusion & Outlook: Based on the results obtained in this study we conclude that activity-based proteomics represents a powerful strategy in the seek for novel biomarker candidates in human lung adenocarcinoma. Future research will involve data validation with additional samples from our tumor bank using advanced quantitative Multiple Reaction Monitoring (MRM) technology. Liu, Y., Patricelli, M.P. & Cravatt, B.F. Activity-based protein profiling: the serine hydrolases. Proceedings of the National Academy of Sciences of the United States of America 96, 14694-14699 (1999). Jessani, N., et al. A streamlined platform for high-content functional proteomics of primary human specimens. Nature methods 2, 691-697 (2005). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5101. doi:10.1158/1538-7445.AM2011-5101
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-5101
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 8
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    Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 17 ( 2016-09-01), p. 5103-5114
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 17 ( 2016-09-01), p. 5103-5114
    Abstract: Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-15-2980
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 9
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    Abstract 3795: Novel and selective MELK kinase inhibitors active in breast cancer cell lines
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3795-3795
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3795-3795
    Abstract: Maternal Embryonic Leucine zipper Kinase (MELK) is a serine-threonine kinase implicated in stem cell renewal, override of cell cycle checkpoints, pre-mRNA splicing and resistance to apoptosis, while MELK gene expression levels correlate inversely with poor prognosis in breast cancer, prostate cancer and glioblastoma patients. Moreover, recent findings underlie the oncogenic role of this kinase in triple negative breast cancer (TNBC), a category of high-grade, invasive tumors which lack expression of estrogen receptor (ER) and progesterone receptor (PR) and HER2 amplification and which is resistant to current cytotoxic and targeted therapies. Furthermore, they are highly heterogeneous with respect to genomic alterations, and common therapeutic targets are lacking, although substantial evidence implicates dysregulated kinase signaling. Here, we describe the preclinical characterization of novel, potent and selective ATP-competitive MELK kinase inhibitors identified by means of high-throughput screening of the NMS proprietary compound collection. Leading compounds possess biochemical activity against MELK in the nanomolar range with high selectivity against a panel of 60 further kinases representative of the human kinome. Amongst human tumor cell lines tested in 2-dimensional colony outgrowth assays, marked sensitivity was observed in breast cancer cell lines, with sub-micromolar anti-proliferative activity. This effect was accompanied by dose-dependent induction of apoptosis and by modulation of cellular biomarkers, consistent with a MELK-dependent mechanism of action. Overall, these data provide further evidence that MELK is a promising biological target for the development of novel anticancer therapies. Citation Format: Patrizia Carpinelli, Marisa Montemartini, Nadia Amboldi, Dario Ballinari, Sabrina Cribioli, Marina Ciomei, Riccardo Colombo, Stefania Re Depaolini, Nilla Avanzi, Giulia Canevari, Walter Ceccarelli, Helena Posteri, Maria Gabriella Brasca, Daniele Donati, Eduard Rudolf Felder, Antonella Isacchi, Arturo Galvani, Alessia Montagnoli. Novel and selective MELK kinase inhibitors active in breast cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3795.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-3795
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 10
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    Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 11 ( 2010-11-01), p. 2877-2887
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 11 ( 2010-11-01), p. 2877-2887
    Abstract: Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins. Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in & gt;5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium. Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P & lt; 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers. Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women. Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes. Cancer Epidemiol Biomarkers Prev; 19(11); 2877–87. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-10-0507
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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