☆ 4.7 Review

Drug Repurposing for Targeting Myeloid-Derived Suppressor-Cell-Generated Immunosuppression in Ovarian Cancer: A Literature Review of Potential Candidates

PHARMACEUTICS (2023)

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Letter Gastroenterology & Hepatology

Global prediction of primary liver cancer incidences and mortality in 2040

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JOURNAL OF HEPATOLOGY (2023)

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Article Biochemistry & Molecular Biology

Entinostat-Bortezomib Hybrids against Multiple Myeloma

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Article Oncology

Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma

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JAMA Oncology (2023)

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Article Medicine, Research & Experimental

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors

Nicolas Gonzalo Nunez et al.

Summary: In this study, a multi-omics approach was used to characterize the systemic immune compartment of melanoma or non-small cell lung cancer patients before and during immune checkpoint inhibitor (ICI) treatment. Potential predictive biomarkers for ICI-induced immune-related adverse events (irAEs) were identified, including early increase in CXCL9/CXCL10/CXCL11 and interferon-g (IFN-g) 1 to 2 weeks after treatment initiation, as well as early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells.

MED (2023)

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Article Biotechnology & Applied Microbiology

Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer

Senwei Jiang et al.

Summary: This study investigates the potential therapeutic and prognostic roles of CAPG in ovarian cancer. The results indicate that high tumoral expression of CAPG is associated with shorter overall survival. Functional enrichment analysis reveals the involvement of CAPG in inflammatory response, cell adhesion, chemokine and cytokine signaling pathways. CAPG expression is positively correlated with infiltrating levels of Tregs, TAMs, and Texs while being negatively correlated with infiltrating levels of NKTs and neutrophils. These findings suggest that CAPG may contribute to the immunosuppressive tumor microenvironment and tumor progression in ovarian cancer.

DISEASE MARKERS (2022)

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Article Cell Biology

The downregulation of type I IFN signaling in G-MDSCs under tumor conditions promotes their development towards an immunosuppressive phenotype

Yingying Sun et al.

Summary: Tumors can modify myeloid cell differentiation and induce an immunosuppressive microenvironment. Granulocytic myeloid-derived suppressor cells (G-MDSCs), which are immature myeloid cells with immunosuppressive activity, exist in tumor-bearing hosts. This study reveals that the increase of granulocyte colony-stimulating factor (G-CSF) in mouse serum promotes G-MDSCs to obtain immunosuppressive traits in peripheral blood through the PI3K-Akt/mTOR pathway. Additionally, downregulation of type I interferon (IFN-I) signaling in G-MDSCs is a prerequisite for their immunosuppressive effects.

CELL DEATH & DISEASE (2022)

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Review Biochemistry & Molecular Biology

Drug Repurposing in Cancer Therapy: Influence of Patient's Genetic Background in Breast Cancer Treatment

Rafaela Rodrigues et al.

Summary: Cancer is a leading cause of death worldwide, with breast cancer being the most prevalent type in women. Drug resistance poses a major challenge in breast cancer treatment, leading to high mortality rates. Repurposing drugs and conducting further research and clinical trials are important for improving the effectiveness and personalization of breast cancer treatment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Oncology

Preclinical and Clinical Evidence of Lurbinectedin in Ovarian Cancer: Current Status and Future Perspectives

Lucia Musacchio et al.

Summary: Lurbinectedin, a natural marine-based antitumor agent, has shown promising clinical activity and safety in various types of cancer. It inhibits active transcription, causes degradation of RNA polymerase II, and induces DNA breaks, resulting in apoptosis of tumor cells. It also modulates the tumor microenvironment and targets cancer cells with DNA repair deficiency. Lurbinectedin may serve as a valid alternative for patients with platinum-resistant/refractory ovarian cancer.

FRONTIERS IN ONCOLOGY (2022)

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High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure The COVIDICUS Randomized Clinical Trial

Lila Bouadma et al.

Summary: High-dose dexamethasone did not significantly improve 60-day survival in ICU patients with COVID-19-related AHRF. Oxygenation strategies in patients not initially receiving IMV did not significantly modify the 28-day risk of IMV requirement.

JAMA INTERNAL MEDICINE (2022)

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First-in-human phase I study of INCAGN02390, a TIM-3 monoclonal antibody antagonist in patients with advanced malignancies

M. E. Gutierrez et al.

ANNALS OF ONCOLOGY (2022)

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A phase (Ph) I/II trial of the CXCR2 antagonist AZD5069 in combination with enzalutamide (ENZA) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC)

C. Guo et al.

ANNALS OF ONCOLOGY (2022)

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Lurbinectedin shows clinical activity and immune- modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma

Daphne W. Dumoulin et al.

Summary: Lurbinectedin has shown clinical activity in pre-treated patients with SCLC and MPM and its immune-modulatory functions make it a potential platform for immunotherapy combinations.

EUROPEAN JOURNAL OF CANCER (2022)

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Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy

Abdelhakim Bouyahya et al.

Summary: This review provides an overview of the recent developments in the mTOR signaling pathway and its molecular involvement in various human cancer types, as well as the research progress of different mTOR inhibitors and their rational combinations with immunotherapies.

CANCERS (2022)

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Drug repurposing for cancer therapy, easier said than done

Aurora Gonzalez-Fierro et al.

Summary: Drug repurposing for cancer therapy is a hot topic of research with potential advantages of being faster, safer, easier, and cheaper. However, economic barriers are the main challenge in clinical development, hindering the acceptance of repositioned drugs as standard therapy at low cost.

SEMINARS IN CANCER BIOLOGY (2021)

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Understanding the association between metformin plasma concentrations and lactate

Isabelle H. S. Kuan et al.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2021)

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FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer

Sonia Singh et al.

Summary: The FDA granted accelerated approval for lurbinectedin in treating adult patients with metastatic small cell lung cancer on June 15, 2020. This approval represented the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC.

CLINICAL CANCER RESEARCH (2021)

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Meeting Abstract Oncology

A phase I/II study of safety and efficacy of the arginase inhibitor INCB001158 plus chemotherapy in patients (Pts) with advanced biliary tract cancers.

Milind M. Javle et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer

Tyler R. McCaw et al.

Summary: The study found that treatment with the class 1 HDAC inhibitor entinostat can enhance the expression of pathways and genes associated with CD8 T cell cytotoxic function, while downregulating myeloid derived suppressor cell chemoattractants. The suppressive capacity of regulatory T cells within tumors and associated ascites was significantly reduced, reversing the CD8-Treg ratio.

CANCER MEDICINE (2021)

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The systemic treatment of recurrent ovarian cancer revisited

T. Baert et al.

Summary: Treatment approaches for relapsed ovarian cancer have shifted towards patient-oriented biologically driven algorithms. Platinum-based chemotherapy is recommended, while bevacizumab can enhance chemotherapy response and maintenance therapy with a poly(ADP-ribose) polymerase inhibitor may be considered for prolonging efficacy.

ANNALS OF ONCOLOGY (2021)

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Model-informed drug repurposing: A pharmacometric approach to novel pathogen preparedness, response and retrospection

Michael Dodds et al.

Summary: This article discusses the five steps of model-informed drug repurposing (MIDR) and categorizes activities under these steps into three stages. MIDR helps extract more information from emerging data and integrate disparate data into actionable insights.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2021)

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Safety of Dabigatran as an Anticoagulant: A Systematic Review and Meta-Analysis

Ya Zhou et al.

Summary: This study comparing dabigatran with conventional treatments found that dabigatran is not associated with an increased risk of major bleeding, intracranial hemorrhage, fatal adverse reactions, and all-cause mortality, but is linked to a higher risk of gastrointestinal bleeding. Overall, dabigatran may be a suitable alternative to VKAs as an oral anticoagulant, but further research is needed to fully understand its safety profile.

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Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors

Giuseppe Curigliano et al.

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Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)

Kathleen N. Moore et al.

Summary: The study evaluated the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody atezolizumab to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer, showing a significant progression-free survival advantage in the PD-L1-positive population. However, no significant overall survival benefit was observed from atezolizumab in the interim analysis. The most common grade 3 or 4 adverse events were neutropenia, hypertension, and anemia.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Cell Biology

Inhibition of CXCR2 plays a pivotal role in re-sensitizing ovarian cancer to cisplatin treatment

Taciane Barbosa Henriques et al.

Summary: Our study revealed the pivotal role of CXCR2 in ovarian cancer chemoresistance, suggesting the development of lipophilic molecules targeting nuclear CXCR2 as a promising alternative to genetic engineering approaches in combating OC.

AGING-US (2021)

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Dual mTORC1/2 inhibitor AZD2014 diminishes myeloid-derived suppressor cells accumulation in ovarian cancer and delays tumor growth

Ruyu Pi et al.

Summary: High mTORC2 expression level in EOC is associated with poor prognosis, while AZD2014 inhibits tumor growth, reduces peritoneal ascites, and prolongs survival in tumor-bearing mice. In addition, AZD2014 also reduces MDSC accumulation and delays tumor recurrence in EOC models.

CANCER LETTERS (2021)

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Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL)

Stephanie Gaillard et al.

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Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia

Miguel Alejandro Pinzon et al.

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PLOS ONE (2021)

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Model-Informed Repurposing of Medicines for SARS-CoV-2: Extrapolation of Antiviral Activity and Dose Rationale for Paediatric Patients

Federico Romano et al.

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Impact of metformin on survival outcome in ovarian cancer: a nationwide population-based cohort study

Jeong-Yeol Park et al.

Summary: The study found that long-term use of metformin may help reduce all-cause mortality in ovarian cancer patients and is considered a favorable prognostic factor.

JOURNAL OF GYNECOLOGIC ONCOLOGY (2021)

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Update of early phase clinical trials in cancer immunotherapy

Dae Ho Lee

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Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia

Denise Risnik et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2020)

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Opposite Macrophage Polarization in Different Subsets of Ovarian Cancer: Observation from a Pilot Study

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Dual blockade of CXCL12-CXCR4 and PD-1-PD-L1 pathways prolongs survival of ovarian tumor-bearing mice by prevention of immunosuppression in the tumor microenvironment

Yang Zeng et al.

FASEB JOURNAL (2019)

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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A phase II randomized study of avelumab plus entinostat versus avelumab plus placebo in patients (pts) with advanced epithelial ovarian cancer (EOC).

Karen Anne Cadoo et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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NATURE MEDICINE (2019)

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DRUG DISCOVERY TODAY (2019)

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Editorial Material Oncology

PD-Loma: a cancer entity with a shared sensitivity to the PD-1/PD-L1 pathway blockade

Laure Hirsch et al.

BRITISH JOURNAL OF CANCER (2019)

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Combination of mTORC1/2 inhibitor vistusertib plus fulvestrant in vitro and in vivo targets oestrogen receptor-positive endocrine-resistant breast cancer

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Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer

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Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer

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Dexamethasone-Induced Myeloid-Derived Suppressor Cells Prolong Allo Cardiac Graft Survival through iNOS- and Glucocorticoid Receptor-Dependent Mechanism

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Judith A. Seidel et al.

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Reactive Oxygen Species as Regulators of MDSC-Mediated Immune Suppression

Kim Ohl et al.

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ReDO_DB: the repurposing drugs in oncology database

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Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden

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Ascites-derived IL-6 and IL-10 synergistically expand CD14(+)HLA-DR-/low myeloid-derived suppressor cells in ovarian cancer patients

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ONCOTARGET (2017)

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Evaluation of the combination of the dual m-TORC1/2 inhibitor vistusertib (AZD2014) and paclitaxel in ovarian cancer models

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CANCER BIOLOGY & MEDICINE (2017)

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Low-dose glucocorticoids suppresses ovarian tumor growth and metastasis in an immunocompetent syngeneic mouse model

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Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models

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Lurbinectedin (PM01183) plus paclitaxel (P), recommended dose (RD) expansion results with or without the addition of bevacizumab (Bev) in patients (pts) with selected solid tumors

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Arginase Inhibition Improves Microvascular Endothelial Function in Patients With Type 2 Diabetes Mellitus

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Thrombin inhibition and cisplatin block tumor progression in ovarian cancer by alleviating the immunosuppressive microenvironment

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Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs

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Myeloid-Derived Suppressor Cells Enhance Stemness of Cancer Cells by Inducing MicroRNA101 and Suppressing the Corepressor CtBP2

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IMMUNITY (2013)

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Article Oncology

Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies

Gerald S. Falchook et al.

INVESTIGATIONAL NEW DRUGS (2013)

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Article Medicine, Research & Experimental

Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer

Zhiqiang Guo et al.

JOURNAL OF TRANSLATIONAL MEDICINE (2013)

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Review Oncology

Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer

Robert Wesolowski et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2013)

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Article Biotechnology & Applied Microbiology

Celecoxib pathways: pharmacokinetics and pharmacodynamics

Li Gong et al.

PHARMACOGENETICS AND GENOMICS (2012)

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Article Biotechnology & Applied Microbiology

Metformin pathways: pharmacokinetics and pharmacodynamics

Li Gong et al.

PHARMACOGENETICS AND GENOMICS (2012)

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Article Oncology

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Francesco Legge et al.

BMC CANCER (2011)

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Article Oncology

Recent Progress in the Diagnosis and Treatment of Ovarian Cancer

Danijela Jelovac et al.

CA-A CANCER JOURNAL FOR CLINICIANS (2011)

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Article Immunology

IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer

Kevin M. Hart et al.

FRONTIERS IN IMMUNOLOGY (2011)

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Article Oncology

COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function

Joris D. Veltman et al.

BMC CANCER (2010)

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Review Hematology

Venous thromboembolism and prognosis in cancer

Alok A. Khorana

THROMBOSIS RESEARCH (2010)

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Article Pharmacology & Pharmacy

SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor

M. E. Bradley et al.

BRITISH JOURNAL OF PHARMACOLOGY (2009)

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Article Hematology

Pharmacology, Pharmacokinetics, and Pharmacodynamics of Dabigatran Etexilate, an Oral Direct Thrombin Inhibitor

Joachim Stangier et al.

CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS (2009)

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Review Oncology

Role of Tissue Factor in Cancer

Raj S. Kasthuri et al.

JOURNAL OF CLINICAL ONCOLOGY (2009)

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Article Immunology

Myeloid-Derived Suppressor Cells Down-Regulate L-Selectin Expression on CD4+ and CD8+ T Cells

Erica M. Hanson et al.

JOURNAL OF IMMUNOLOGY (2009)

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Article Primary Health Care

Gynecologic Cancers

Amy R. Blair et al.

PRIMARY CARE (2009)

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Article Oncology

Ovarian Tumor-Induced T Cell Suppression Is Alleviated by Vascular Leukocyte Depletion

S. Peter G. Bak et al.

TRANSLATIONAL ONCOLOGY (2009)

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Review Immunology

Myeloid-derived suppressor cells as regulators of the immune system

Dmitry I. Gabrilovich et al.

NATURE REVIEWS IMMUNOLOGY (2009)

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Review Oncology

Tumor escape mechanism governed by myeloid-derived suppressor cells

Srinivas Nagaraj et al.

CANCER RESEARCH (2008)

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Article Immunology

B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer

Yu Liu et al.

CLINICAL IMMUNOLOGY (2008)

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Article Biochemistry & Molecular Biology

Murine ovarian cancer vascular leukocytes require arginase-1 activity for T cell suppression

S. Peter Bak et al.

MOLECULAR IMMUNOLOGY (2008)

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Article Oncology

Expression of chemokine CXCL12 and its receptor CXCR4 in human epithelial ovarian cancer: An independent prognostic factor for tumor progression

Yu-ping Jiang et al.

GYNECOLOGIC ONCOLOGY (2006)

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Article Immunology

Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1

Sonya M. Abraham et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2006)

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Article Oncology

CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells

Rongcun Yang et al.

CANCER RESEARCH (2006)

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Article Oncology

Preoperative serum tissue factor levels are an independent prognostic factor in patients with ovarian carcinoma

LY Han et al.

JOURNAL OF CLINICAL ONCOLOGY (2006)

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Article Multidisciplinary Sciences

Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer

E Sato et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

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Review Oncology

Tumor-induced immune dysfunctions caused by myeloid suppressor cells

V Bronte et al.

JOURNAL OF IMMUNOTHERAPY (2001)

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Review Gastroenterology & Hepatology

Side effects of corticosteroid therapy

AL Buchman

JOURNAL OF CLINICAL GASTROENTEROLOGY (2001)

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