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Sci Rep 6:18517, Gilmore SJ (2018) Automated decision support in melanocytic lesion management. Nature 469(7330):362–367, Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD et al (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Cancer Res 67(16):7551–7555, Pons B, Peg V, Vazquez-Sanchez MA, Lopez-Vicente L, Argelaguet E, Coch L, Martinez A, Hernandez-Losa J, Armengol G, Ramon YCS (2011) The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model. We must look forward and not forget that our primary objective is to cure cancer or at least make it a chronic disease. In Germany, you just don‘t have as many different teachers / choreographers you can learn from on a high level as in the United States. 563-447-6391 Ivanka Babel. Prospective clinical studies using liquid biopsies have characterized and monitored over time the genomic alterations of patients [40, 174]. Numerous studies have shown how genetic variants emerge after therapy and suggest that resistance and response to therapy from that moment onwards are commonly determined by genetic variants (see [8] and references therein). We proposed the concept of funnel factors [80], that is, factors that channel crucial information on tumor progression independently of the level at which a specific oncogenic alteration occurs. In this sense, therapy has been considered both a source of variability and a selective filter, promoting the acquisition of new mutations and the selective proliferation of previously dormant, minority clones [21, 121]. This cell cooperation can be observed in cell clusters in metastatic development: clusters of circulating tumor cells (CTCs) are associated with higher number of metastases than single circulating cells in models of breast cancer, pancreatic cancer, and melanoma [50, 51, 102,103,104,105,106]. Regarding drug development in malignant tumors and current paradigms in cancer research, new agents include those that target cancer-related vulnerabilities in receptor tyrosine kinases and intracellular signaling pathways, epigenetics, metabolism, and nuclear-cytoplasmic transport, among others. Trends Genet 25(1):30–38, Ramon YCS, Capdevila C, Hernandez-Losa J, De Mattos-Arruda L, Ghosh A, Lorent J, Larsson O, Aasen T, Postovit LM, Topisirovic I (2017) Cancer as an ecomolecular disease and a neoplastic consortium. This heterogeneity responds to specific gene expression profiles, thus pointing to the existence of other determinants of intratumor morphological heterogeneity and highlighting the importance of context. Light-emitting electrospun nanofibers of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(N,N′-diphenyl)-N,N′-di(p-butyl-oxy-phenyl)-1,4-diaminobenzene)] (PFO–PBAB) are produced by electrospinning under different experimental conditions. - 199.247.9.71. J Mol Diagn 14(4):376–384, Ramon YCS, Segura MF, Hummer S (2019) Interplay between ncRNAs and cellular communication: a proposal for understanding cell-specific signaling pathways. Mod Pathol 25(7):938–948, McGranahan N, Swanton C (2015) Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Genet 216-217:37–51, Assenov Y, Brocks D, Gerhauser C (2018) Intratumor heterogeneity in epigenetic patterns. Sci Transl Med 4(136):136ra168, Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS et al (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Clin Cancer Res 23(2):387–398, Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A, Aldape K, Brat D, Collins VP, Eberhart C et al (2014) International society of neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading. It is a blessing to make people smile with something that makes you happy as well. Given that proteins are the final effectors of all cellular pathways, along with small metabolites, it seems reasonable to think that the “ideal” targets for therapy are those protein factors that have the most stable expression and activation in tumor cells. Front Oncol 5:54, Karachaliou N, Mayo-delas Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F, Garcia-Gomez R, Massuti B, Sanchez JM, Porta R et al (2015) Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial. 978-288-3276 Laxmi Howison. Proc Natl Acad Sci U S A 115(13):E2970–E2979, Bychkov D, Linder N, Turkki R, Nordling S, Kovanen PE, Verrill C, Walliander M, Lundin M, Haglund C, Lundin J (2018) Deep learning based tissue analysis predicts outcome in colorectal cancer. Very suitable for stage performances as a tour or a background dancer. On the other hand, larger samples, or pools of samples, lead to intermixing of small anatomically distinct units, which provides additional challenges in relation to distinguish distinct functional heterogeneity. Thus, it is the adoption of both genetic and non-genetic subclonal changes that endows cancer with enough phenotypical plasticity to adapt to microenvironmental pressures and successfully overcome the barriers posed by antitumoral therapy. DanceAware: Many of our readers would love to hear some tips. It shows me that it means a lot to me. was just incredible and definitely a big boost for both of us. Authors have postulated that the most important aspect of tumor transformation and subsequent progression is the functional alteration of at least ten major biochemical pathways. 709-648-9478 Valeska Kidman. Moreover, initial studies have shown that a characteristic morphological pattern could be due to specific oncogenic changes and that malignancy is dependent on the immune response [43]. 563-447-1502 Haskel Hergott. Having more than 1 Mio. 865-338-3474 Raymund Zundel. See more ideas about choreography, dance choreography, dance. a Darwinian model of clonal heterogeneity resulting in a consortium of clones, each with their characteristics and malignant features. The tumor clone markers include those involved in the tumorigenic expansion (proliferation) and invasion, the two leading forces driving progression. https://doi.org/10.1093/bib/bby007, Zeng T, Dai H (2019) Single-cell RNA sequencing-based computational analysis to describe disease heterogeneity. Such a social commitment requires us to search for all possible methods of cooperation among those involved in the diagnosis and treatment of cancer. Mol Oncol 10(3):464–474, Siravegna G, Marsoni S, Siena S, Bardelli A (2017) Integrating liquid biopsies into the management of cancer. Cancer Cell 7(1):17–23, Polyak K (2011) Heterogeneity in breast cancer. Another important advantage (although under certain situations it may be a disadvantage) is that it tends to reflect an aggregate of the output (ctDNA/CTC etc.) 709-648-4543 Aden Straatmann. This open-source machine learning tool is free for any qualified scientist and is specialized in cognitive computing. Front Genet 10:281, Argani P, Fritsch M, Kadkol SS, Schuster A, Beckwith JB, Perlman EJ (2000) Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. While procuring multiple metastatic tumor samples for genomic studies through NGS and development of patient-derived xenografts or organoids, mechanistic insights gained from research autopsy studies of cancer patients can help identify new targets for therapeutic intervention [114]. 4) What were your experiences working in the TV business? views in 2015 with our video to Britney Spears „Hold It Against Me“ we were just speachless. This video is unavailable. Did this video probably jumpstart your career? Camillo: No, there is no specific goal I am working on. The importance of such approach is highlighted by the observation of clustered populations within a tumor that differ in gene expression [133], as well as genetic composition [134]. Nat Med 18(12):1835–1840, Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, Loguidice L, Soto H, Garrett M, Zhu LD et al (2013) BEAMing and droplet digital PCR analysis of mutant IDH1 mRNA in glioma patient serum and cerebrospinal fluid extracellular vesicles. Nat Rev Clin Oncol 11(3):167–176, Gerlinger M, Quezada SA, Peggs KS, Furness AJ, Fisher R, Marafioti T, Shende VH, McGranahan N, Rowan AJ, Hazell S et al (2013) Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas. Functionally, heterogeneity provides tumors with significant adaptability. DanceAware: What lacks the german dance scene compared to the USA and why? N Engl J Med 368(13):1199–1209, De Mattos-Arruda L, Weigelt B, Cortes J, Won HH, Ng CK, Nuciforo P, Bidard FC, Aura C, Saura C, Peg V et al (2014) Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle. Proc Natl Acad Sci U S A 112(31):9704–9709, Shi R, Wang PY, Li XY, Chen JX, Li Y, Zhang XZ, Zhang CG, Jiang T, Li WB, Ding W et al (2015) Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients. Researchers from the National Research Tomsk State University [25] have shown that the morphological heterogeneity in invasive micropapillary carcinoma (IMPC) of the breast is not related to the presence of specific chromosomal aberrations. PLoS One 13(9):e0203459, Yu KH, Zhang C, Berry GJ, Altman RB, Re C, Rubin DL, Snyder M (2016) Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features. Am J Pathol 138(2):349–358, Sanchez-Prieto R, Lleonart M, Ramon y Cajal S (1995) Lack of correlation between p53 protein level and sensitivity of DNA-damaging agents in keratinocytes carrying adenovirus E1a mutants. These algorithms are likely to help pathologists in reaching a faster, more accurate diagnosis and significantly reduce the pathologist-dependent discordance in histopathological diagnosis. 720-543-2342 Fyrn Royster. What are your pro-tips for beginners? Sci Transl Med 2(20):20ra14, Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, O'Shaughnessy J, Kinzler KW, Parmigiani G, Vogelstein B et al (2012) Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. J Thorac Oncol 10(5):800–805, Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. More conclusive data from basket trials and umbrella trials are needed [55]. Sci Transl Med 4(162):162ra154, Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D et al (2012) Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. 978-288-5151 Laksha Griese. These factors, which play a significant role in the control of protein synthesis, could be sensitive tumor targets in a large number of malignant tumors [79, 83, 161, 162]. 978-288-3142 Saulisbury Mattfeld. Camillo Lauricella. Nat Rev Cancer 19(9):495–509, Ramon y Cajal S, Suster S, Halaban R, Filvaroff E, Dotto GP (1991) Induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc, neu, and E1a oncogenes. Tumors must be analyzed at the genetic, molecular, and clinical-radiological level, with integration and correlation of findings to ensure a holistic approach. I knew the dance studio from TV and that many superstars like Janet Jackson, Beyoncé, Usher or Britney Spears rehearsed there or their choreographers teach there. In this broad context, evolutionary clues and new findings on interclonal relationships should also be taken into account [81, 101, 113, 163]. Because cancer is a heterogeneous dynamic target, individual patients, lesions, and cell populations should be thoroughly characterized at varying times. Arch Pathol Lab Med 130(5):728–732, Nielsen TO, Poulin NM, Ladanyi M (2015) Synovial sarcoma: recent discoveries as a roadmap to new avenues for therapy. Stonehill College is grateful for the generous support provided by alumni. J Pathol 241(3):375–391, Trinh A, Trumpi K, De Sousa EMF, Wang X, de Jong JH, Fessler E, Kuppen PJ, Reimers MS, Swets M, Koopman M et al (2017) Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry. Nat Med 22(1):105–113, Logue JS, Morrison DK (2012) Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. JAMA Oncol 1(2):149–157, Sharma P, Debinski W (2018) Receptor-targeted glial brain tumor therapies. … I never expected things like this to happen, I am just happy and thankful that people like our work. Sci Transl Med 7(283):283ra254, McGranahan N, Swanton C (2017) Clonal heterogeneity and tumor evolution: past, present, and the future. Nat Commun 6:8839, Murtaza M, Dawson SJ, Pogrebniak K, Rueda OM, Provenzano E, Grant J, Chin SF, Tsui DW, Marass F, Gale D et al (2015) Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Therefore, we must select the most representative areas for massive parallel sequencing and genomic and proteomic studies and report on their limitations. For a comprehensive review, see [195]. Nature 501(7467):328–337, Bissell MJ, Labarge MA (2005) Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Complex models that implement combinatorial therapy are likely to be particularly beneficial in tumors with a high degree of tumor heterogeneity. PubMed Central  As we then hit 4.5 Mio. We have proposed the term tissunomics, whereby a diagnosis is individually assessed based upon a combined picture derived from the clinical, pathological, molecular, and protein expression data of the tumor and its surrounding microenvironment [55]. The study of the tumor immune microenvironment appears quite promising and includes treatment with immune checkpoint antibodies, with programmed death 1 (PD-1 and PDL-1) targeted agents, and novel immunotherapies. We must establish more rational and ambitious organizational models and strategies, with real networks and professional, well-trained teams. However, unless large numbers of samples are provided for each tumor, this approach can easily fail to identify patches of genetically distinct cells [130,131,132]. Cell 170(5):927–938 e920, Graff JR, Konicek BW, Carter JH, Marcusson EG (2008) Targeting the eukaryotic translation initiation factor 4E for cancer therapy. Histol Histopathol 22(9):1005–1015, Korshunova Y, Maloney RK, Lakey N, Citek RW, Bacher B, Budiman A, Ordway JM, McCombie WR, Leon J, Jeddeloh JA et al (2008) Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer-associated cytosine-methylation patterns obtained from tissue and serum DNA. This results in important differences between tumors from different individuals, named as intertumoral heterogeneity. I knew the dance studio from TV and that many superstars like Janet Jackson, Beyoncé, Usher or Britney Spears rehearsed there or their choreographers teach there. Chromosome instability (CIN) and microsatellite instability (MSI) have been described as two alternative pathways to cancer [53, 69, 70]. Therefore, to explain the substantial molecular variability inherent to malignant tumors, there must be a background of replicative immortality and genomic instability, which is associated with abnormalities in DNA repair mechanisms and maintenance of genetic and chromosomal integrity (see review [68]). In fact, in cell lines, a correlation has previously been shown between resistance to radiotherapy and cytotoxic drugs (e.g., cisplatin, doxorubicin, and taxanes) and the expression of specific oncogenes, principally, RAS, p53, c-MYC, and the adenoviral gene E1A [44,45,46,47]. 709-648-6693 Yancey Kerstiens. However, protein synthesis machinery and other translation regulators are also significantly modulated by local environmental conditions. Nat Rev Clin Oncol 14(9):531–548, Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R et al (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Though I realized much later that I want to make dancing to my profession. Much attention has been paid to the role of the molecular pathways controlling RNA splicing [86, 87], the impact of the expression of various protein isoforms, and how the local environmental factors determine their levels [88]. State-of-the-art digital image acquisition and quantification algorithms, which integrate biophysical parameters to capture the spatial variation in tumor architectures, are likely to play an essential role in this [16]. Am J Cancer Res 5(9):2838–2848, Siddiqui N, Sonenberg N (2015) Signalling to eIF4E in cancer. Expert Rev Mol Diagn 15(10):1311–1323, Bardelli A, Pantel K (2017) Liquid biopsies, what we do not know (yet). 720-543-0232 Nicodemo Altomare. The Stonehill College Fund operates on a fiscal year calendar of July 1st – June 30th. Moreover, proteomic heterogeneity is not always a simple consequence of the heterogeneity found at the genetic level. One mechanism by which different environmental stimuli drive such heterogeneity is by epigenetic modifications of the genome, which can persist over many cell divisions [61]. Cytometry A 91(6):566–573, Heng YJ, Lester SC, Tse GM, Factor RE, Allison KH, Collins LC, Chen YY, Jensen KC, Johnson NB, Jeong JC et al (2017) The molecular basis of breast cancer pathological phenotypes. For example, DNA sequencing after gene amplification can allow the study of mutations, amplifications, deletions, and translocations in various areas of the tumor, thus characterizing the homogeneity of these genetic alterations [141, 143, 144]. Lab Investig 80(3):279–289, Pozo L, Sanchez-Carrillo JJ, Martinez A, Blanes A, Diaz-Cano SJ (2007) Differential kinetic features by tumour topography in cutaneous small-cell neuroendocrine (Merkel cell) carcinomas. 978-288-0701 Dillyn In. Any future goals or projects you are going to work on? Part of Springer Nature. Simply being there and taking classes was a dream come true. Many dancers want to perform the most impressive moves from day one instead of learning step-by-step. Cancer 107(8):1801–1811, Armengol G, Rojo F, Castellvi J, Iglesias C, Cuatrecasas M, Pons B, Baselga J, Ramon y Cajal S (2007) 4E-binding protein 1: a key molecular “funnel factor” in human cancer with clinical implications. Sci Rep 5:16066, Wang WQ, Liu L, Xu HX, Luo GP, Chen T, Wu CT, Xu YF, Xu J, Liu C, Zhang B et al (2013) Intratumoral alpha-SMA enhances the prognostic potency of CD34 associated with maintenance of microvessel integrity in hepatocellular carcinoma and pancreatic cancer. Beyonce hit 1.5 mio views on YouTube. © 2021 Springer Nature Switzerland AG. Camillo Pilger. I started imitating Michael Jackson and so it all began. 720-543-7026 Celestyna Guilliams. J Clin Invest 128(4):1371–1383, Hoadley KA, Siegel MB, Kanchi KL, Miller CA, Ding L, Zhao W, He X, Parker JS, Wendl MC, Fulton RS et al (2016) Tumor evolution in two patients with basal-like breast cancer: a retrospective genomics study of multiple metastases. I never thought that one day I am going to teach there myself. Hello everyone, here is the new video “Turn Up the Music” Choreographed by Camillo Lauricella & Robert Lenart, performed with Yuki Shibuya, and as always we chose the best of the best for our readers. Arch Pathol Lab Med 137(5):668–684, O'Connor JP, Rose CJ, Waterton JC, Carano RA, Parker GJ, Jackson A (2015) Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome. In most of these tumor types, dozens or hundreds of pathological variants are observed. 865-338-0322 Sabra Hirata. Sci Rep 6:26286, Mobadersany P, Yousefi S, Amgad M, Gutman DA, Barnholtz-Sloan JS, Velazquez Vega JE, Brat DJ, Cooper LAD (2018) Predicting cancer outcomes from histology and genomics using convolutional networks. It is likely that combinations will be needed for most subtypes. 2 min intadv jazz dance routine to applause dance by lady gaga. What were/are your idols? Diagn Mol Pathol 10(1):24–33, Nakamura T, Kuwai T, Kitadai Y, Sasaki T, Fan D, Coombes KR, Kim SJ, Fidler IJ (2007) Zonal heterogeneity for gene expression in human pancreatic carcinoma. Camillo: Nika and I choreographed this piece late night in my living room. Google Scholar, Abe H, Kawahara A, Azuma K, Taira T, Takase Y, Fukumitsu C, Murata K, Yamaguchi T, Akiba J, Ishii H et al (2015) Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas: a comparative study between small biopsy and excision samples. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 720-543-9860 Bos Whitford. Int J Mol Sci 19(11), PubMed Central  The development of artificial intelligence algorithms with automatic learning (“deep learning”) is already shaping the field. Nucleic Acids Res 37(14):4603–4612, Moelans CB, Verschuur-Maes AH, van Diest PJ (2011) Frequent promoter hypermethylation of BRCA2, CDH13, MSH6, PAX5, PAX6 and WT1 in ductal carcinoma in situ and invasive breast cancer. Examples include the variable threshold of positivity for the expression of the HER2 receptor in gastric adenocarcinoma [10], progesterone and estrogen receptors in breast tumors [11], the EML4-ALK translocation in lung adenocarcinoma [12], B-RAF mutations in melanoma, and the 1p/19q allelic loss in oligodendrogliomas [13, 14]. Watch Queue Queue Discover (and save!) Given the complex and constant development of tumor architecture, it is essential to understand that molecular changes (both genetic and epigenetic) within the tumor itself evolve during disease progression and metastasis [108]. Proc Natl Acad Sci U S A 99(20):13085–13089, Romo-Bucheli D, Janowczyk A, Gilmore H, Romero E, Madabhushi A (2017) A deep learning based strategy for identifying and associating mitotic activity with gene expression derived risk categories in estrogen receptor positive breast cancers. Chromosomal translocations such as those including the ALK gene are demonstrated in anaplastic lymphoma, lung adenocarcinoma, and myofibroblastic tumors [36], and the translocation EWSR1-CREB1 in tumors as different as clear cell sarcoma and angiomatoid fibrous histiocytoma [37]. CA Cancer J Clin 66(1):75–88, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM (2013) The cancer genome atlas pan-cancer analysis project. The size of the sample is another critical issue [130,131,132], and signal-to-noise ratios need to be balanced. Malignant tumors have highly diverse phenotypic and molecular characteristics both at the intertumor and intratumor levels [1]. In addition, tumor type and location has been shown to underlie unpredictable treatment responses targeting the same molecular pathway, such as the tumor response in melanomas vs. colon carcinomas with BRAF mutations. Therefore, the importance of the surrounding stroma in intratumoral morphologic heterogeneity seems evident, both regarding factors released by fibroblasts and factors released by inflammatory cells such as histiocytes and lymphocytes. These dynamic intercellular interplays are guided by a Darwinian selection landscape between clonal tumor cell populations and the tumor microenvironment. Jovannah Lauricella. Trends Mol Med 20(12):704–715, Blanes A, Diaz-Cano SJ (2006) DNA and kinetic heterogeneity during the clonal evolution of adrenocortical proliferative lesions. The concept of clonal cooperation is based on a single clone being unable to acquire all the necessary properties to be an invasive tumor, such that various clones must act synergistically and complementarily to acquire the characteristics described by Hanahan and Weinberg [49] and the proposed biochemical changes in 10 or more cellular biochemical pathways. 720-543-4076 India Quincey. Sie werden von Violetta Kromer und Camillo Lauricella trainiert. Expression studies are also done, both at the RNA level (RNA-Seq) and epigenetics with methyloma sequencing [143, 145, 146]. DanceAware: Where does your journey goes from here Camillo? 709-648-4831 Izaya Felgenhauer. The Millennium Dance Complex is just „the place to be“! Trends Cancer 5(1):1–5, Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013) Tumour heterogeneity in the clinic.

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