Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis

Phosphatidylserine released from apoptotic cells in tumor induces M2‐like macrophage polarization through the PSR‐STAT3‐JMJD3 axis

(2022) Xiao Liang et al.   Cancer Communications

PRP4 Induces Epithelial–Mesenchymal Transition and Drug Resistance in Colon Cancer Cells via Activation of p53

(2022) Salman Ul Islam et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

(2022) Qinghua Wu et al.   Journal of Hematology & Oncology

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

(2022) Dominique Farge et al.   LANCET ONCOLOGY

The potential applications of microparticles in the diagnosis, treatment, and prognosis of lung cancer

(2022) Yu Liu et al.   Journal of Translational Medicine

Aberrant Factors of Fibrinolysis and Coagulation in Pancreatic Cancer

(2021) Lianghua Fang et al.   OncoTargets and Therapy

Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

(2021) Mark P. Ward et al.   Molecular Cancer

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

(2021) Wolfgang M. J. Obermann et al.   Frontiers in Cell and Developmental Biology

Tumor-derived microparticles promote the progression of triple-negative breast cancer via PD-L1-associated immune suppression

(2021) Cong Li et al.   CANCER LETTERS

Roles of Microvesicles in Tumor Progression and Clinical Applications

(2021) Shuangli Zhu et al.   International Journal of Nanomedicine

Extracellular vesicle interactions with the external and internal exposome in mediating carcinogenesis

(2021) Priyakshi Kalita-de Croft et al.   MOLECULAR ASPECTS OF MEDICINE

Breast cancer stromal clotting activation (Tissue Factor and thrombin): A pre‐invasive phenomena that is prognostic in invasion

(2020) Hudhaifah Shaker et al.   Cancer Medicine

A Comprehensive Picture of Extracellular Vesicles and Their Contents. Molecular Transfer to Cancer Cells

(2020) Ancuta Jurj et al.   Cancers

Phosphatidylserine exposure in living cells

(2020) Hye-Won Shin et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

Mechanism of tumor cells escaping from immune surveillance of NK cells

(2020) Zhe Ge et al.   IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY

Proinflammatory S100A8 Induces PD-L1 Expression in Macrophages, Mediating Tumor Immune Escape

(2020) Zhengshuo Li et al.   JOURNAL OF IMMUNOLOGY

MiR-301a transcriptionally activated by HIF-2α promotes hypoxia-induced epithelial-mesenchymal transition by targeting TP63 in pancreatic cancer

(2020) Kun-Dong Zhang et al.   WORLD JOURNAL OF GASTROENTEROLOGY

A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma

(2020) Sabna Rajeev Krishnan et al.   Blood Cancer Journal

Interplay between platelets and coagulation

(2020) Yaqiu Sang et al.   BLOOD REVIEWS

Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology

(2020) Wei Hu et al.   Molecular Cancer

Cytoskeletal Crosstalk in Cell Migration

(2020) Shailaja Seetharaman et al.   TRENDS IN CELL BIOLOGY

Tumor‐derived microparticles in tumor immunology and immunotherapy

(2020) Jingwei Ma et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Midkine Is a Potential Therapeutic Target of Tumorigenesis, Angiogenesis, and Metastasis in Non-Small Cell Lung Cancer

(2020) Dong Hoon Shin et al.   Cancers

Novel antiplatelet strategies targeting GPVI, CLEC-2 and tyrosine kinases

(2020) Maan H. Harbi et al.   PLATELETS

Potential Roles of Tumor Cell- and Stroma Cell-Derived Small Extracellular Vesicles in Promoting a Pro-Angiogenic Tumor Microenvironment

(2020) Nils Ludwig et al.   Cancers

The functional role of integrins during intra- and extravasation within the metastatic cascade

(2019) Greta Sökeland et al.   Molecular Cancer

PD-L1 Expression in Circulating Tumor Cells Increases during Radio(chemo)therapy and Indicates Poor Prognosis in Non-small Cell Lung Cancer

(2019) Yang Wang et al.   Scientific Reports

Phosphorylation-mediated activation of mouse Xkr8 scramblase for phosphatidylserine exposure

(2019) Takaharu Sakuragi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Vessel co-option in cancer

(2019) Elizabeth A. Kuczynski et al.   Nature Reviews Clinical Oncology

Neoantigen-directed immune escape in lung cancer evolution

(2019) Rachel Rosenthal et al.   NATURE

VEGF in Signaling and Disease: Beyond Discovery and Development

(2019) Rajendra S. Apte et al.   CELL

Thrombin signaling promotes pancreatic adenocarcinoma through PAR-1-dependent immune evasion

(2019) Yi Yang et al.   CANCER RESEARCH

Microvesicles and chemokines in tumor microenvironment: mediators of intercellular communications in tumor progression

(2019) Xiaojie Bian et al.   Molecular Cancer

The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues

(2019) Elena Campello et al.   BRITISH JOURNAL OF CANCER

Thrombosis Risk Associated with Head and Neck Cancer: A Review

(2019) Pierre Haen et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β

(2019) Jie Chen et al.   Cellular & Molecular Immunology

Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents

(2019) Garrido-Navas et al.   Cells

Bacterial Endotoxin Activates the Coagulation Cascade through Gasdermin D-Dependent Phosphatidylserine Exposure

(2019) Xinyu Yang et al.   IMMUNITY

Surgical Stress Increases Circulating Low-Density Neutrophils Which May Promote Tumor Recurrence

(2019) Yuko Kumagai et al.   JOURNAL OF SURGICAL RESEARCH

Squeezing in a Meal: Myosin Functions in Phagocytosis

(2019) Sarah R. Barger et al.   TRENDS IN CELL BIOLOGY

Epithelial Mesenchymal Transition in Tumor Metastasis

(2018) Vivek Mittal   Annual Review of Pathology-Mechanisms of Disease

Matrix metalloproteinase-2: A key regulator in coagulation proteases mediated human breast cancer progression through autocrine signaling

(2018) Kaushik Das et al.   BIOMEDICINE & PHARMACOTHERAPY

Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents

(2018) Xiaohong Ruby Xu et al.   BLOOD

The Platelet Lifeline to Cancer: Challenges and Opportunities

(2018) Monika Haemmerle et al.   CANCER CELL

Targeting HIF-2α as therapy for advanced cancers

(2018) Thanabal Murugesan et al.   DRUG DISCOVERY TODAY

Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma

(2018) Ruixia Huang et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Shedding light on the cell biology of extracellular vesicles

(2018) Guillaume van Niel et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression

(2018) Eduard Willms et al.   Frontiers in Immunology

Mechanisms of Immune Evasion and Immune Modulation by Lymphoma Cells

(2018) Thomas Menter et al.   Frontiers in Oncology

Substrates of P4-ATPases: beyond aminophospholipids (phosphatidylserine and phosphatidylethanolamine)

(2018) Hye-Won Shin et al.   FASEB JOURNAL

HIF-2α promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways

(2018) Yuanyuan Yan et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Role of platelets and platelet receptors in cancer metastasis

(2018) Martin Schlesinger   Journal of Hematology & Oncology

Tissue factor-bearing microparticles and inflammation: a potential mechanism for the development of venous thromboembolism in cancer

(2017) K. Date et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

(2017) Yuan Jiang et al.   MOLECULAR CANCER RESEARCH

Dabigatran Potentiates Gemcitabine-Induced Growth Inhibition of Pancreatic Cancer in Mice

(2017) Kun Shi et al.   MOLECULAR MEDICINE

miR-200a targets Gelsolin: A novel mechanism regulating secretion of microvesicles in hepatocellular carcinoma cells

(2017) Ya Xu et al.   ONCOLOGY REPORTS

Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy

(2017) Tianchi Yu et al.   YONSEI MEDICAL JOURNAL

Phospholipid flippase ATP11C is endocytosed and downregulated following Ca2+-mediated protein kinase C activation

(2017) Hiroyuki Takatsu et al.   Nature Communications

Platelets reduce anoikis and promote metastasis by activating YAP1 signaling

(2017) Monika Haemmerle et al.   Nature Communications

Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer

(2016) Mitsuro Kanda et al.   ANNALS OF SURGICAL ONCOLOGY

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

(2016) Marek Z. Wojtukiewicz et al.   CANCER AND METASTASIS REVIEWS

Monocyte Induction of E-Selectin–Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade

(2016) Irina Häuselmann et al.   CANCER RESEARCH

Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease and cancer

(2016) R B Birge et al.   CELL DEATH AND DIFFERENTIATION

The biology and function of exosomes in cancer

(2016) Raghu Kalluri   JOURNAL OF CLINICAL INVESTIGATION

Clinical Significance and Roles in Angiogenesis of Circulating Microparticles in Oral Cancer

(2016) J.G. Ren et al.   JOURNAL OF DENTAL RESEARCH

Surface Phosphatidylserine Is Responsible for the Internalization on Microvesicles Derived from Hypoxia-Induced Human Bone Marrow Mesenchymal Stem Cells into Human Endothelial Cells

(2016) Xiaojuan Wei et al.   PLoS One

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression

(2016) Ruihua Ma et al.   OncoImmunology

The polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis

(2015) K. F. Nickel et al.   BLOOD

The origin and concentration of circulating microparticles differ according to cancer type and evolution: A prospective single-center study

(2015) Diane Mege et al.   INTERNATIONAL JOURNAL OF CANCER

RASA3 is a critical inhibitor of RAP1-dependent platelet activation

(2015) Lucia Stefanini et al.   JOURNAL OF CLINICAL INVESTIGATION

Elevated Level of Circulating Platelet-derived Microparticles in Oral Cancer

(2015) J.G. Ren et al.   JOURNAL OF DENTAL RESEARCH

Administered circulating microparticles derived from lung cancer patients markedly improved angiogenesis, blood flow and ischemic recovery in rat critical limb ischemia

(2015) Jiunn-Jye Sheu et al.   Journal of Translational Medicine

Downregulation of Integrins in Cancer Cells and Anti-Platelet Properties Are Involved in Holothurian Glycosaminoglycan-Mediated Disruption of the Interaction of Cancer Cells and Platelets in Hematogenous Metastasis

(2015) Wenhui Qian et al.   JOURNAL OF VASCULAR RESEARCH

Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

(2015) Michael Schnoor et al.   MEDIATORS OF INFLAMMATION

Cancer Patient–Derived Circulating Microparticles Enhance Lung Metastasis in a Rat Model: Dual-Source CT, Cellular, and Molecular Studies

(2015) Sheung-Fat Ko et al.   MOLECULAR IMAGING AND BIOLOGY

IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis

(2015) Seth B. Coffelt et al.   NATURE

Tissue Factor: Old and New Links with Cancer Biology

(2015) Henri Versteeg   SEMINARS IN THROMBOSIS AND HEMOSTASIS

Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium

(2015) Subrahmanya D. Vallabhapurapu et al.   Oncotarget

Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis

(2015) Mohit Kumar Jolly   Frontiers in Oncology

Neutrophil extracellular traps in cancer progression

(2014) Jonathan Cools-Lartigue et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Thrombin conducts epithelial-mesenchymal transition via protease-activated receptor-1 in human gastric cancer

(2014) TADAYOSHI OTSUKI et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Tissue factor in tumor microenvironment: a systematic review

(2014) Xiao Han et al.   Journal of Hematology & Oncology

Bavituximab plus paclitaxel and carboplatin for the treatment of advanced non-small-cell lung cancer

(2014) Raghunadharao Digumarti et al.   LUNG CANCER

Effects of the HIF-1α and NF-κB loop on epithelial-mesenchymal transition and chemoresistance induced by hypoxia in pancreatic cancer cells

(2014) ZHUO-XIN CHENG et al.   ONCOLOGY REPORTS

Platelets guide the formation of early metastatic niches

(2014) M. Labelle et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Involvement of Platelet-Derived Microparticles in Tumor Progression and Thrombosis

(2014) Soraya Mezouar et al.   SEMINARS IN ONCOLOGY

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

(2014) Le-Xing Yu et al.   Nature Communications

Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response

(2013) E. M. Battinelli et al.   BLOOD

Platelet-Derived Nucleotides Promote Tumor-Cell Transendothelial Migration and Metastasis via P2Y2 Receptor

(2013) Dagmar Schumacher et al.   CANCER CELL

VEGF in Tumor Progression and Targeted Therapy

(2013) Vladimir P. Chekhonin et al.   CURRENT CANCER DRUG TARGETS

D-pinitol Inhibits Prostate Cancer Metastasis through Inhibition of αVβ3 Integrin by Modulating FAK, c-Src and NF-κB Pathways

(2013) Tien-Huang Lin et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ARF1 regulates the Rho/MLC pathway to control EGF-dependent breast cancer cell invasion

(2013) Sabrina Schlienger et al.   MOLECULAR BIOLOGY OF THE CELL

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(2013) Ching-Fong Liao et al.   MOLECULAR MEDICINE

Epithelial-mesenchymal transition and migration of prostate cancer stem cells is driven by cancer-associated fibroblasts in an HIF-1α/β-catenin-dependent pathway

(2013) Yong Luo et al.   MOLECULES AND CELLS

Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel

(2013) Mattia Malvezzi et al.   Nature Communications

Cancer-associated thrombosis

(2013) G. C. Connolly et al.   Hematology-American Society of Hematology Education Program

A Kunitz-type FXa inhibitor affects tumor progression, hypercoagulable state and triggers apoptosis

(2012) Janaína Souza Ventura et al.   BIOMEDICINE & PHARMACOTHERAPY

Tissue factor expression determines tumour cell coagulation kinetics

(2012) J. WELSH et al.   International Journal of Laboratory Hematology

Recent agents targeting HIF-1α for cancer therapy

(2012) Yaozhong Hu et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

GITR Ligand Provided by Thrombopoietic Cells Inhibits NK Cell Antitumor Activity

(2012) T. Placke et al.   JOURNAL OF IMMUNOLOGY

Immuno-PET of Tissue Factor in Pancreatic Cancer

(2012) H. Hong et al.   JOURNAL OF NUCLEAR MEDICINE

Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials

(2012) Peter M Rothwell et al.   LANCET

RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells

(2012) B Li et al.   ONCOGENE

Cooperation of protease-activated receptor 1 and integrin ανβ5 in thrombin-mediated lung cancer cell invasion

(2012) LINGYUN ZHU et al.   ONCOLOGY REPORTS

TLR4 signaling induces the release of microparticles by tumor cells that regulate inflammatory cytokine IL-6 of macrophages via microRNA let-7b

(2012) Dapeng Li et al.   OncoImmunology

The relationship between tissue factor and cancer progression: insights from bench and bedside

(2011) Y. W. van den Berg et al.   BLOOD

Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis

(2011) Michel S Beausoleil et al.   BMC CANCER

Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer

(2011) A Lecharpentier et al.   BRITISH JOURNAL OF CANCER

Direct Signaling between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis

(2011) Myriam Labelle et al.   CANCER CELL

Tissue Factor-Activated Coagulation Cascade in the Tumor Microenvironment Is Critical for Tumor Progression and an Effective Target for Therapy

(2011) Y. Liu et al.   CANCER RESEARCH

Platelet-Derived MHC Class I Confers a Pseudonormal Phenotype to Cancer Cells That Subverts the Antitumor Reactivity of Natural Killer Immune Cells

(2011) T. Placke et al.   CANCER RESEARCH

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Phase I Safety and Pharmacokinetic Study of Bavituximab, a Chimeric Phosphatidylserine-Targeting Monoclonal Antibody, in Patients with Advanced Solid Tumors

(2011) D. E. Gerber et al.   CLINICAL CANCER RESEARCH

PAR1 plays a role in epithelial malignancies: Transcriptional regulation and novel signaling pathway

(2011) Rachel Bar-Shavit et al.   IUBMB LIFE

Critical Role of the β-Subunit CDC50A in the Stable Expression, Assembly, Subcellular Localization, and Lipid Transport Activity of the P4-ATPase ATP8A2

(2011) Jonathan A. Coleman et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

(2011) Anke S. Lonsdorf et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

New Aryl Hydrocarbon Receptor Homology Model Targeted To Improve Docking Reliability

(2011) Ilaria Motto et al.   Journal of Chemical Information and Modeling

Tissue factor and cell signalling in cancer progression and thrombosis

(2011) W. RUF et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Circulating Tumor Cells from Patients with Advanced Prostate and Breast Cancer Display Both Epithelial and Mesenchymal Markers

(2011) A. J. Armstrong et al.   MOLECULAR CANCER RESEARCH

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

(2011) Bin-Zhi Qian et al.   NATURE

Evaluation of the safety, pharmacokinetics and treatment effects of an ανβ3integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases

(2010) Mark A ROSENTHAL et al.   Asia-Pacific Journal of Clinical Oncology

Growth Factors in Induction of Epithelial-Mesenchymal Transition and Metastasis

(2010) Nur Akmarina B.M. Said et al.   CELLS TISSUES ORGANS

Thrombin induces platelet activation in the absence of functional protease activated receptors 1 and 4 and glycoprotein Ib-IX-V

(2010) Paolo Lova et al.   CELLULAR SIGNALLING

12-Lipoxygenase and the regulation of hypoxia-inducible factor in prostate cancer cells

(2010) Sriram Krishnamoorthy et al.   EXPERIMENTAL CELL RESEARCH

Microvesicles: mediators of extracellular communication during cancer progression

(2010) V. Muralidharan-Chari et al.   JOURNAL OF CELL SCIENCE

Aspirin Intake and Survival After Breast Cancer

(2010) Michelle D. Holmes et al.   JOURNAL OF CLINICAL ONCOLOGY

Sequential Binding of  v 3 and ICAM-1 Determines Fibrin-Mediated Melanoma Capture and Stable Adhesion to CD11b/CD18 on Neutrophils

(2010) P. Zhang et al.   JOURNAL OF IMMUNOLOGY

Microparticles in Cancer

(2010) Janusz Rak   SEMINARS IN THROMBOSIS AND HEMOSTASIS

Procoagulant mechanisms in tumour cells

(2009) Anna Falanga et al.   BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY

Platelet-Derived Transforming Growth Factor-  Down-Regulates NKG2D Thereby Inhibiting Natural Killer Cell Antitumor Reactivity

(2009) H.-G. Kopp et al.   CANCER RESEARCH

ARF6-Regulated Shedding of Tumor Cell-Derived Plasma Membrane Microvesicles

(2009) Vandhana Muralidharan-Chari et al.   CURRENT BIOLOGY

The enterocyte microvillus is a vesicle-generating organelle

(2009) Russell E. McConnell et al.   JOURNAL OF CELL BIOLOGY

A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth

(2009) Binzhi Qian et al.   PLoS One

Alternatively spliced tissue factor induces angiogenesis through integrin ligation

(2009) Y. W. van den Berg et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Tissue Factor Regulation by Epidermal Growth Factor Receptor and Epithelial-to-Mesenchymal Transitions: Effect on Tumor Initiation and Angiogenesis

(2008) C. C. Milsom et al.   CANCER RESEARCH

The role of adherens junctions and VE-cadherin in the control of vascular permeability

(2008) E. Dejana et al.   JOURNAL OF CELL SCIENCE

Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function

(2008) J. S. PALUMBO et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Modulation of the antitumor immune response by complement

(2008) Maciej M Markiewski et al.   NATURE IMMUNOLOGY

Thrombin up-regulates vascular endothelial growth factor in experimental gliomas

(2008) Ying Xu et al.   NEUROLOGICAL RESEARCH