Determinants of metastatic competency in colorectal cancer

The delicate balance of macrophages in colorectal cancer; their role in tumour development and therapeutic potential

(2017) R. Braster et al.   IMMUNOBIOLOGY

ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

(2016) E. Van Cutsem et al.   ANNALS OF ONCOLOGY

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients

(2016) Niels Halama et al.   CANCER CELL

Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases after Surgical Stress

(2016) Samer Tohme et al.   CANCER RESEARCH

Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT

(2016) Srinivas Malladi et al.   CELL

The Basis of Oncoimmunology

(2016) A. Karolina Palucka et al.   CELL

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters

(2016) Paul W. Tetteh et al.   Cell Stem Cell

A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis

(2016) Masayuki Fujii et al.   Cell Stem Cell

Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1 + Tumor-Associated Neutrophils through CCL15-CCR1 Axis

(2016) Takamasa Yamamoto et al.   CLINICAL CANCER RESEARCH

Immune and Stromal Classification of Colorectal Cancer Is Associated with Molecular Subtypes and Relevant for Precision Immunotherapy

(2016) Etienne Becht et al.   CLINICAL CANCER RESEARCH

IFN  gene/cell therapy curbs colorectal cancer colonization of the liver by acting on the hepatic microenvironment

(2016) M. Catarinella et al.   EMBO Molecular Medicine

Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives

(2016) Markus Moehler et al.   EUROPEAN JOURNAL OF CANCER

Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability

(2016) Bernhard Mlecnik et al.   IMMUNITY

The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis

(2016) Yoshiro Itatani et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis

(2016) Yu Zhang et al.   MOLECULAR CARCINOGENESIS

Metastatic colonization by circulating tumour cells

(2016) Joan Massagué et al.   NATURE

Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis

(2016) Boris Strilic et al.   NATURE

Ten years of anti-vascular endothelial growth factor therapy

(2016) Napoleone Ferrara et al.   NATURE REVIEWS DRUG DISCOVERY

The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis

(2016) Bernhard Mlecnik et al.   Science Translational Medicine

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

(2016) Jeanne Tie et al.   Science Translational Medicine

The Immune Revolution in Gastrointestinal Tumours: Leading the Way or Just Following?

(2016) Marco Puzzoni et al.   Targeted Oncology

TNIK inhibition abrogates colorectal cancer stemness

(2016) Mari Masuda et al.   Nature Communications

Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling

(2016) So-Young Hwang et al.   Cell Reports

Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

(2016) Marios Giannakis et al.   Cell Reports

Global cancer statistics, 2012

(2015) Lindsey A. Torre et al.   CA-A CANCER JOURNAL FOR CLINICIANS

The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: A systematic review

(2015) H.C. van Wyk et al.   CANCER TREATMENT REVIEWS

Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity

(2015) Michael S. Rooney et al.   CELL

DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts

(2015) David Roulois et al.   CELL

Co-migration of colon cancer cells and CAFs induced by TGFβ1 enhances liver metastasis

(2015) Idoia Gonzalez-Zubeldia et al.   CELL AND TISSUE RESEARCH

Loss of SMAD4 Promotes Colorectal Cancer Progression by Accumulation of Myeloid-Derived Suppressor Cells through the CCL15-CCR1 Chemokine Axis

(2015) S. Inamoto et al.   CLINICAL CANCER RESEARCH

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach

(2015) Moisés Blanco-Calvo et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The interaction of anticancer therapies with tumor-associated macrophages

(2015) Alberto Mantovani et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Unknown

(2015) Jennifer Hardingham et al.   MOLECULAR MEDICINE

The genomic landscape of response to EGFR blockade in colorectal cancer

(2015) Andrea Bertotti et al.   NATURE

Sequential cancer mutations in cultured human intestinal stem cells

(2015) Jarno Drost et al.   NATURE

Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

(2015) Alexandre Calon et al.   NATURE GENETICS

Stromal contribution to the colorectal cancer transcriptome

(2015) Claudio Isella et al.   NATURE GENETICS

A Big Bang model of human colorectal tumor growth

(2015) Andrea Sottoriva et al.   NATURE GENETICS

The consensus molecular subtypes of colorectal cancer

(2015) Justin Guinney et al.   NATURE MEDICINE

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

(2015)   NEW ENGLAND JOURNAL OF MEDICINE

Targeting the TGFβ pathway for cancer therapy

(2015) Cindy Neuzillet et al.   PHARMACOLOGY & THERAPEUTICS

IL-33 activates tumor stroma to promote intestinal polyposis

(2015) Rebecca L. Maywald et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The future of immune checkpoint therapy

(2015) P. Sharma et al.   SCIENCE

Targeting LGR5 + cells with an antibody-drug conjugate for the treatment of colon cancer

(2015) Melissa R. Junttila et al.   Science Translational Medicine

Immune evasion in cancer: Mechanistic basis and therapeutic strategies

(2015) Dass S. Vinay et al.   SEMINARS IN CANCER BIOLOGY

Plasticity within stem cell hierarchies in mammalian epithelia

(2015) Paul W. Tetteh et al.   TRENDS IN CELL BIOLOGY

Humanized anti-hepatocyte growth factor (HGF) antibody suppresses innate irinotecan (CPT-11) resistance induced by fibroblast-derived HGF

(2015) Jong Kyu Woo et al.   Oncotarget

Cancer vaccines

(2015) L. H. Butterfield   BMJ-British Medical Journal

ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy

(2015) Mattheus C.B. Wielenga et al.   Cell Reports

CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function

(2015) Eunyoung Chun et al.   Cell Reports

Cancer vaccines

(2015) L. H. Butterfield   BMJ-British Medical Journal

Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: Tumor budding as oncotarget

(2015)   Oncotarget

PDGF receptor-α promotes TGF-β signaling in hepatic stellate cells via transcriptional and posttranscriptional regulation of TGF-β receptors

(2014) Chunsheng Liu et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Serum levels of hepatocyte growth factor and epiregulin are associated with the prognosis on anti-EGFR antibody treatment in KRAS wild-type metastatic colorectal cancer

(2014) N Takahashi et al.   BRITISH JOURNAL OF CANCER

Serpins Promote Cancer Cell Survival and Vascular Co-Option in Brain Metastasis

(2014) Manuel Valiente et al.   CELL

Evolution of the Cancer Stem Cell Model

(2014) Antonija Kreso et al.   Cell Stem Cell

Metastatic Stem Cells: Sources, Niches, and Vital Pathways

(2014) Thordur Oskarsson et al.   Cell Stem Cell

CD44v6 Is a Marker of Constitutive and Reprogrammed Cancer Stem Cells Driving Colon Cancer Metastasis

(2014) Matilde Todaro et al.   Cell Stem Cell

CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis

(2014) Hideyo Hirai et al.   CLINICAL & EXPERIMENTAL METASTASIS

IL-22+CD4+ T Cells Promote Colorectal Cancer Stemness via STAT3 Transcription Factor Activation and Induction of the Methyltransferase DOT1L

(2014) Ilona Kryczek et al.   IMMUNITY

Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information

(2014) Mireia Berdiel-Acer et al.   Molecular Oncology

Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH

(2014) Jelena Urosevic et al.   NATURE CELL BIOLOGY

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche

(2014) Hayley Davis et al.   NATURE MEDICINE

Can we safely target the WNT pathway?

(2014) Michael Kahn   NATURE REVIEWS DRUG DISCOVERY

TGF-beta in CAF-mediated tumor growth and metastasis

(2014) A. Calon et al.   SEMINARS IN CANCER BIOLOGY

Hallmarks in colorectal cancer: Angiogenesis and cancer stem-like cells

(2014) Muriel Mathonnet   WORLD JOURNAL OF GASTROENTEROLOGY

Epidemiological transition of colorectal cancer in developing countries: Environmental factors, molecular pathways, and opportunities for prevention

(2014) Faraz Bishehsari   WORLD JOURNAL OF GASTROENTEROLOGY

Promotion of Colorectal Cancer Invasion and Metastasis through Activation of NOTCH–DAB1–ABL–RHOGEF Protein TRIO

(2014) Masahiro Sonoshita et al.   Cancer Discovery

The Vigorous Immune Microenvironment of Microsatellite Instable Colon Cancer Is Balanced by Multiple Counter-Inhibitory Checkpoints

(2014) Nicolas J. Llosa et al.   Cancer Discovery

Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1

(2013) Jia Lu et al.   CANCER CELL

Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically

(2013) Tracy L. Putoczki et al.   CANCER CELL

Targeting the Tumor Microenvironment: From Understanding Pathways to Effective Clinical Trials

(2013) H. Fang et al.   CANCER RESEARCH

Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients

(2013) Mercedes Herrera et al.   CANCER SCIENCE

The Intestinal Crypt, A Prototype Stem Cell Compartment

(2013) Hans Clevers   CELL

Mechanisms Governing Metastatic Dormancy and Reactivation

(2013) Filippo G. Giancotti   CELL

Continuous Clonal Labeling Reveals Small Numbers of Functional Stem Cells in Intestinal Crypts and Adenomas

(2013) Sarah Kozar et al.   Cell Stem Cell

Lgr5+ Stem Cells Are Indispensable for Radiation-Induced Intestinal Regeneration

(2013) Ciara Metcalfe et al.   Cell Stem Cell

Loss of SMAD4 From Colorectal Cancer Cells Promotes CCL15 Expression to Recruit CCR1+ Myeloid Cells and Facilitate Liver Metastasis

(2013) Yoshiro Itatani et al.   GASTROENTEROLOGY

Mechanism of Action of Conventional and Targeted Anticancer Therapies: Reinstating Immunosurveillance

(2013) Laurence Zitvogel et al.   IMMUNITY

Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition

(2013) Paul Roepman et al.   INTERNATIONAL JOURNAL OF CANCER

Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: A systematic review and meta-analysis

(2013) Mu-Xing Li et al.   INTERNATIONAL JOURNAL OF CANCER

IQGAP1 suppresses TβRII-mediated myofibroblastic activation and metastatic growth in liver

(2013) Chunsheng Liu et al.   JOURNAL OF CLINICAL INVESTIGATION

Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A

(2013) Fiorenza Lotti et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer

(2013) Eva Budinska et al.   JOURNAL OF PATHOLOGY

Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours

(2013) Jérôme Galon et al.   JOURNAL OF PATHOLOGY

Intestinal label-retaining cells are secretory precursors expressing Lgr5

(2013) Simon J. A. Buczacki et al.   NATURE

Microenvironmental regulation of tumor progression and metastasis

(2013) Daniela F Quail et al.   NATURE MEDICINE

Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions

(2013) Felipe De Sousa E Melo et al.   NATURE MEDICINE

A colorectal cancer classification system that associates cellular phenotype and responses to therapy

(2013) Anguraj Sadanandam et al.   NATURE MEDICINE

Self-renewal as a therapeutic target in human colorectal cancer

(2013) Antonija Kreso et al.   NATURE MEDICINE

Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer

(2013) C. Feig et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cancer Genome Landscapes

(2013) B. Vogelstein et al.   SCIENCE

Tumor Endothelial Cells

(2013) A. C. Dudley   Cold Spring Harbor Perspectives in Medicine

Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value

(2013) Laetitia Marisa et al.   PLOS MEDICINE

Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines

(2012) Andreas Schlicker et al.   BMC Medical Genomics

Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation

(2012) Alexandre Calon et al.   CANCER CELL

Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

(2012) Douglas Hanahan et al.   CANCER CELL

MUC1 Vaccine for Individuals with Advanced Adenoma of the Colon: A Cancer Immunoprevention Feasibility Study

(2012) T. Kimura et al.   Cancer Prevention Research

Intratumor Heterogeneity: Evolution through Space and Time

(2012) C. Swanton   CANCER RESEARCH

Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties

(2012) Sarah Schwitalla et al.   CELL

Molecular Pathways: Targeting the TGF-  Pathway for Cancer Therapy

(2012) A. L. Smith et al.   CLINICAL CANCER RESEARCH

Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer

(2012) Kei Shinagawa et al.   INTERNATIONAL JOURNAL OF CANCER

Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

(2012) Eric Van Cutsem et al.   JOURNAL OF CLINICAL ONCOLOGY

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

(2012) Anirudh Prahallad et al.   NATURE

Clonal evolution in cancer

(2012) Mel Greaves et al.   NATURE

Recurrent R-spondin fusions in colon cancer

(2012) Somasekar Seshagiri et al.   NATURE

Comprehensive molecular characterization of human colon and rectal cancer

(2012)   NATURE

Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting

(2012) Hirokazu Matsushita et al.   NATURE

Expression of tumour-specific antigens underlies cancer immunoediting

(2012) Michel DuPage et al.   NATURE

Dll1+ secretory progenitor cells revert to stem cells upon crypt damage

(2012) Johan H. van Es et al.   NATURE CELL BIOLOGY

β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer

(2012) Stephan P Tenbaum et al.   NATURE MEDICINE

Targeting the TGFβ signalling pathway in disease

(2012) Rosemary J. Akhurst et al.   NATURE REVIEWS DRUG DISCOVERY

Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer

(2012) A. Kreso et al.   SCIENCE

Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas

(2012) A. G. Schepers et al.   SCIENCE

Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E 2 Signaling

(2012) Hua-Jung Li et al.   Cancer Discovery

Inflammation-Induced Endothelial-to-Mesenchymal Transition

(2011) Florian Rieder et al.   AMERICAN JOURNAL OF PATHOLOGY

Molecular Genetics of Colorectal Cancer

(2011) Eric R. Fearon   Annual Review of Pathology-Mechanisms of Disease

A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells

(2011) S. Solito et al.   BLOOD

Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling

(2011) Masahiro Sonoshita et al.   CANCER CELL

Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases Are Prognostic for Response to Chemotherapy

(2011) N. Halama et al.   CANCER RESEARCH

Tumor Metastasis: Molecular Insights and Evolving Paradigms

(2011) Scott Valastyan et al.   CELL

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Distinct Types of Tumor-Initiating Cells Form Human Colon Cancer Tumors and Metastases

(2011) Sebastian M. Dieter et al.   Cell Stem Cell

The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse

(2011) Anna Merlos-Suárez et al.   Cell Stem Cell

Role of dendritic cells in progression and clinical outcome of colon cancer

(2011) Maya V. Gulubova et al.   INTERNATIONAL JOURNAL OF COLORECTAL DISEASE

Clinical Significance of Circulating Tumor Cells, Including Cancer Stem-Like Cells, in Peripheral Blood for Recurrence and Prognosis in Patients With Dukes' Stage B and C Colorectal Cancer

(2011) Hisae Iinuma et al.   JOURNAL OF CLINICAL ONCOLOGY

Single-cell dissection of transcriptional heterogeneity in human colon tumors

(2011) Piero Dalerba et al.   NATURE BIOTECHNOLOGY

Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs

(2011) Thordur Oskarsson et al.   NATURE MEDICINE

The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations

(2011) K. S. Yan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cancer Immunoediting: Integrating Immunity's Roles in Cancer Suppression and Promotion

(2011) R. D. Schreiber et al.   SCIENCE

HGF Rescues Colorectal Cancer Cells from EGFR Inhibition via MET Activation

(2010) D. Liska et al.   CLINICAL CANCER RESEARCH

Bone Morphogenetic Protein 4 Induces Differentiation of Colorectal Cancer Stem Cells and Increases Their Response to Chemotherapy in Mice

(2010) Ylenia Lombardo et al.   GASTROENTEROLOGY

Mesenchymal stem cells enhance growth and metastasis of colon cancer

(2010) Kei Shinagawa et al.   INTERNATIONAL JOURNAL OF CANCER

Immune evasion of microsatellite unstable colorectal cancers

(2010) Matthias Kloor et al.   INTERNATIONAL JOURNAL OF CANCER

Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

(2010) Jo Eyles et al.   JOURNAL OF CLINICAL INVESTIGATION

Transmission of donor melanoma by organ transplantation

(2010) Dirk C Strauss et al.   LANCET ONCOLOGY

Wnt activity defines colon cancer stem cells and is regulated by the microenvironment

(2010) Louis Vermeulen et al.   NATURE CELL BIOLOGY

Inactivation of chemokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model

(2010) T. Kitamura et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein- 

(2010) M. Kraman et al.   SCIENCE

TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression

(2010) Li Yang et al.   TRENDS IN IMMUNOLOGY

Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN

(2009) Zvi G. Fridlender et al.   CANCER CELL

The kinase TNIK is an essential activator of Wnt target genes

(2009) Tokameh Mahmoudi et al.   EMBO JOURNAL

Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation

(2009) Alberto Mantovani et al.   HUMAN IMMUNOLOGY

Improved Overall Survival With Oxaliplatin, Fluorouracil, and Leucovorin As Adjuvant Treatment in Stage II or III Colon Cancer in the MOSAIC Trial

(2009) Thierry André et al.   JOURNAL OF CLINICAL ONCOLOGY

Role of bone marrow-derived cells in colon cancer: lessons from mouse model studies

(2009) Makoto Mark Taketo   JOURNAL OF GASTROENTEROLOGY

TGFβ Primes Breast Tumors for Lung Metastasis Seeding through Angiopoietin-like 4

(2008) David Padua et al.   CELL

Crypt stem cells as the cells-of-origin of intestinal cancer

(2008) Nick Barker et al.   NATURE

Comparative lesion sequencing provides insights into tumor evolution

(2008) S. Jones et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity

(2008) L. Vermeulen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA