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Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment

CANCERS (2023)

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Article Cell Biology

Autophagy loss impedes cancer-associated fibroblast activation via downregulating proline biosynthesis

Jingru Bai et al.

Summary: This study reveals that autophagy deficiency in cancer-associated fibroblasts inhibits their activation by impeding proline biosynthesis and collagen production. Autophagy promotes proline biosynthesis through mitophagy-mediated regulation of NADK2. Inhibiting mitophagy can reduce tumor weight in pancreatic ductal adenocarcinoma.

AUTOPHAGY (2023)

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Article Multidisciplinary Sciences

The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis

Lu Han et al.

Summary: Through lineage tracing and single-cell RNA sequencing in mice, this study identifies the splanchnic mesenchyme as the tissue of origin for cancer-associated fibroblasts (CAFs) in pancreatic cancer. The findings shed light on pancreatic morphogenesis and tumorigenesis, and highlight the persistent transcriptional program underlying splanchnic lineage differentiation.

NATURE COMMUNICATIONS (2023)

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Article Oncology

Effi cacy of a Small-Molecule Inhibitor of Kras G12D in Immunocompetent Models of Pancreatic Cancer

Samantha B. Kemp et al.

Summary: This study evaluated the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in PDAC models with an intact immune system. The results showed that MRTX1133 can induce deep tumor regressions and alter the tumor microenvironment, demonstrating its potential as a novel therapy for PDAC patients. Further clinical testing is warranted.

CANCER DISCOVERY (2023)

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Article Biochemistry & Molecular Biology

Photodynamic Stromal Depletion Enhances Therapeutic Nanoparticle Delivery in 3D Pancreatic Ductal Adenocarcinoma Tumor Models

Vida Karimnia et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with obstructed drug delivery and tumor-promoting fibrous stroma. Photodynamic therapy (PDT) has been shown to be feasible and effective for PDAC. This study investigates the ability of photodynamic stromal depletion (PSD) to enhance RNA nanomedicine delivery, and finds that PSD improves the transport of therapeutic nanoparticles and enhances the tumor response to treatment. These findings suggest that PSD could be developed to enhance the delivery of other cancer therapeutics.

PHOTOCHEMISTRY AND PHOTOBIOLOGY (2023)

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Review Cell Biology

Organization, dynamics and mechanoregulation of integrin-mediated cell-ECM adhesions

Pakorn Kanchanawong et al.

Summary: Cell-extracellular matrix (ECM) interactions occur at specialized, multi-protein adhesion complexes, with clustered integrins as the predominant ECM receptors. Progress in characterization of adhesion composition, organization and dynamics in response to force has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2023)

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Article Oncology

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer

Joseph E. Grossman et al.

Summary: This pilot feasibility trial investigated the use of patient-derived organoids (PDOs) to guide personalized therapy for pancreatic ductal adenocarcinoma (PDAC). The study found that the drug sensitivity of PDOs can predict the clinical outcome of patients and is correlated with treatment responses.

CLINICAL CANCER RESEARCH (2022)

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Review Biotechnology & Applied Microbiology

Targeting cancer metabolism in the era of precision oncology

Zachary E. Stine et al.

Summary: In the past century, there have been significant advancements in targeting cancer metabolism, but progress in the past decade has been limited. Some metabolism-based drugs for cancer have been successfully developed and are in clinical trials. However, consideration of the metabolism of non-cancer cells is crucial for successful treatment of cancer.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Review Engineering, Biomedical

Nanomedicine Strategies to Circumvent Intratumor Extracellular Matrix Barriers for Cancer Therapy

Xiaoxuan Xu et al.

Summary: By regulating the physiochemical properties of nanomedicines and remodeling the components and structure of the ECM, intratumor ECM barriers can be effectively overcome, leading to improved drug delivery and anticancer efficacy.

ADVANCED HEALTHCARE MATERIALS (2022)

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Article Cell Biology

Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion

Elizabeth R. Murray et al.

Summary: PKN2 plays a critical role in the differentiation of pancreatic stellate cells into myofibroblast-like cancer-associated fibroblasts. Loss of PKN2 leads to reduced proliferation and contractility of pancreatic stellate cells, as well as a switch from myofibroblast to inflammatory cancer-associated fibroblast phenotype. Furthermore, deletion of PKN2 promotes invasive cancer cell outgrowth and induces more locally invasive pancreatic tumors. The absence of PKN2 in the pancreatic stroma predicts poor outcome in pancreatic and other solid human cancers.

CELL REPORTS (2022)

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Review Biotechnology & Applied Microbiology

Charge reversal nano-systems for tumor therapy

Peng Zhang et al.

Summary: This review comprehensively summarizes the recent advances in charge-reversal nanocarriers, including their roles in cellular uptake, charge-conversion mechanisms in response to specific stimuli, the relationship between chemical structure and charge reversal activity, and commonly used polymeric materials.

JOURNAL OF NANOBIOTECHNOLOGY (2022)

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Review Nanoscience & Nanotechnology

Organelle-level precision with next-generation targeting technologies

Anand Saminathan et al.

Summary: Intracellular organelles are subsystems within a cell that reflect the metabolic state of the cell, and biological pathways can be exploited to target exogenous cargo to specific organelles with nucleic acids as suitable delivery vehicles.

NATURE REVIEWS MATERIALS (2022)

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Article Multidisciplinary Sciences

High-throughput and high-content bioassay enables tuning of polyester nanoparticles for cellular uptake, endosomal escape, and systemic in vivo delivery of mRNA

Yuan Rui et al.

Summary: Nanoparticle-based mRNA therapeutics show great promise, but cellular internalization and endosomal escape pose challenges for cytosolic delivery. Researchers developed a dual nanoparticle uptake and endosomal disruption assay, which can detect cellular internalization and endosomal disruption. The study found that this assay has higher predictive capacity for mRNA delivery compared to conventional polymer and nanoparticle characteristics.

SCIENCE ADVANCES (2022)

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Article Multidisciplinary Sciences

Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors

Rupsa Datta et al.

Summary: The direct interactions between pancreatic stellate cells (PSCs) and cancer cells promote a more oxidized state in cancer cells, overcoming the redox limitations of cell proliferation in pancreatic cancer.

SCIENCE ADVANCES (2022)

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Article Engineering, Biomedical

Towards principled design of cancer nanomedicine to accelerate clinical translation

Mohammad Souri et al.

Summary: Nanotechnology has shown promising results in medical applications, particularly in oncology as drug delivery systems. However, the clinical translation of this technology is challenging. To optimize drug delivery systems for clinical translation, the physicochemical characteristics of nanoparticles can be specified. Researchers have focused on producing biocompatible materials, production technologies, or new formulations to improve efficiency and stability. The effects of design parameters can be studied using various methods. This review summarizes the advances and technologies in cancer nanomedicines for clinical translation and commercialization, as well as the existing challenges and opportunities in the field.

MATERIALS TODAY BIO (2022)

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Article Oncology

Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment

Lenka N. C. Boyd et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a poor prognosis. The tumor microenvironment (TME) of PDAC, characterized by cancer-associated fibroblasts (CAFs), plays a dual role in tumor progression. Understanding the heterogeneity and plasticity of CAFs, as well as their behavior during PDAC progression, is crucial for improving therapeutic strategies for PDAC patients.

SEMINARS IN CANCER BIOLOGY (2022)

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Review Cell Biology

Epigenetic regulation and targeting of ECM for cancer therapy

Romi Gupta

Summary: This mini review discusses epigenetic modifications that regulate the expression of fibrous ECM proteins and glycoproteins and explores the prospects of targeting them for cancer therapy.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2022)

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Article Oncology

Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma

Yasuyuki Mizutani et al.

Summary: Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment. Recent studies have identified a subset of CAFs, called cancer-restraining CAFs (rCAFs), which can suppress cancer progression. This study aims to investigate the efficacy of a combination of the synthetic retinoid AM80 and chemotherapy drugs gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with advanced pancreatic cancer.

BMC CANCER (2022)

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Article Oncology

Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer

Huocong Huang et al.

Summary: Recent studies have identified a unique population of cancer-associated fibroblasts (apCAFs) derived from mesothelial cells, which play a critical role in pancreatic cancer progression. These apCAFs directly induce naive CD4(+) T cells to differentiate into regulatory T cells (Tregs) in an antigen-specific manner.

CANCER CELL (2022)

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Review Cell & Tissue Engineering

Programming hydrogels to probe spatiotemporal cell biology

Taimoor H. Qazi et al.

Summary: This article provides an overview of recent advances in the programming of synthetic hydrogels, which offer precise control over the spatiotemporal properties within cellular microenvironments. It highlights the importance of understanding complex biological processes.

CELL STEM CELL (2022)

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Article Cell Biology

Tackling the effects of extracellular vesicles in fibrosis

Marina Martin-Taboada et al.

Summary: This review outlines the role of extracellular vesicles in fibrosis, focusing on their involvement in adipose tissue and renal fibrosis. The potential of extracellular vesicles as biomarkers and therapeutic tools to prevent fibrosis progression is also discussed.

EUROPEAN JOURNAL OF CELL BIOLOGY (2022)

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Review Biochemistry & Molecular Biology

Application of Ultrasound Combined with Microbubbles for Cancer Therapy

Deepa Sharma et al.

Summary: Cancer, one of the leading causes of death worldwide, poses challenges in treatment due to its metastatic nature. In recent years, ultrasound therapy combined with microbubbles has shown great success in cancer treatment, especially when combined with radiation therapy, chemotherapy, or immunotherapy.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Oncology

Cancer-associated fibroblasts in pancreatic cancer: new subtypes, new markers, new targets

Shinelle Menezes et al.

Summary: This article discusses the conflicting roles of cancer-associated fibroblasts (CAFs) in tumor promotion and suppression, as well as therapeutic strategies. It highlights the heterogeneity of CAF subtypes and their association with patient prognosis and therapy response. Targeting CAF subtypes associated with immunotherapy response may provide new options for pancreatic cancer treatment.

JOURNAL OF PATHOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Emerging therapeutic opportunities for integrin inhibitors

R. J. Slack et al.

Summary: Integrins play crucial roles in cell adhesion and signaling, making them potential therapeutic targets. This review discusses the challenges and development of integrin inhibitors, particularly those targeting integrins with an alpha v-subunit. Opportunities exist for learning from previous trials and exploring new modalities in integrin drug design.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Biochemistry & Molecular Biology

Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics

Tadashi Iida et al.

Summary: Induced expression of the glycosylphosphatidylinositol-anchored protein Meflin in cancer-associated fibroblasts (CAFs) improved chemosensitivity in pancreatic ductal adenocarcinoma (PDAC) in mice. A synthetic retinoid, Am80, effectively induced Meflin expression in CAFs, enhancing PDAC sensitivity to chemotherapy.

ONCOGENE (2022)

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Article Oncology

Mesenchymal Lineage Heterogeneity Underlies Nonredundant Functions of Pancreatic Cancer-Associated Fibroblasts

Erin J. Helms et al.

Summary: This study reveals the origins and functions of distinct cancer-associated fibroblast (CAF) subtypes in pancreatic ductal adenocarcinoma (PDAC). It shows that the abundant and transcriptionally diverse CAF population in PDAC arises from pancreatic stellate cells (PSC), but only a minor subset is derived from PSCs. These PSC-derived CAFs have unique functions in shaping the PDAC microenvironment.

CANCER DISCOVERY (2022)

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Article Oncology

Chemotherapy as a regulator of extracellular matrix-cell communication: Implications in therapy resistance

Jordi Gonzalez-Molina et al.

Summary: The development of most solid cancers involves a process of remodeling of the extracellular matrix (ECM). Chemotherapy can lead to changes in ECM features and communication between ECM and cancer cells. Therapeutic strategies targeting ECM-cell communication are being explored in current clinical trials.

SEMINARS IN CANCER BIOLOGY (2022)

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Review Gastroenterology & Hepatology

Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma

Thomas Lambin et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. The tumoral microenvironment (TME) of PDAC, characterized by fibrosis, hypo microvascular perfusion, and immunosuppression, is a major barrier to effective antitumoral treatment. Locoregional therapies, such as radiofrequency ablation and radiation therapy, hold promise for overcoming these barriers and improving clinical outcomes for PDAC patients.

WORLD JOURNAL OF GASTROENTEROLOGY (2022)

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Review Physics, Applied

Nanomaterials for photothermal and photodynamic cancer therapy

Behzad Nasseri et al.

Summary: This article discusses the significant role of optically sensitive nanomaterials in therapeutic techniques, especially in the applications of photodynamic therapy and photothermal therapy. These treatment modalities can overcome the limitations of conventional protocols and enhance immune system stimulation when combined with immune therapy. Additionally, this review examines the effects of photosensitive nanomaterials in photodynamic therapy and photothermal therapy, focusing on their nature, morphology, and size.

APPLIED PHYSICS REVIEWS (2022)

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Review Physiology

Pancreatic Stellate Cells and Metabolic Alteration: Physiology and Pathophysiology

Shin Hamada et al.

Summary: Pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis and cancer by sensing systemic metabolic changes and altering cell metabolism and microenvironment.

FRONTIERS IN PHYSIOLOGY (2022)

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Review Oncology

A Disintegrin and Metalloproteinase (ADAM) Family-Novel Biomarkers of Selected Gastrointestinal (GI) Malignancies?

Marta Lukaszewicz-Zajac et al.

Summary: ADAM proteins play a crucial role in the pathogenesis of gastrointestinal cancers, potentially affecting patient prognosis. Their significance as potential prognostic biomarkers and therapeutic targets for GI malignancies is promising, but further research is needed for better understanding and treatment strategies.

CANCERS (2022)

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Article Medicine, Research & Experimental

Piezo1-mediated stellate cell activation causes pressure-induced pancreatic fibrosis in mice

Sandip M. Swain et al.

Summary: Pancreatic fibrosis, a complication of chronic pancreatitis and pancreatic cancer, is caused by increased pancreatic duct pressure. Activation of Piezo1 and TRPV4 leads to activation of pancreatic stellate cells, resulting in pressure-induced chronic pancreatitis and fibrosis.

JCI INSIGHT (2022)

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Review Biochemistry & Molecular Biology

Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting

Dongsheng Wen et al.

Summary: This review provides a comprehensive overview of mechanoregulation in fibrosis, covering cellular mechanosensing, intracellular mechanotransduction and processing, and mechanoeffecting. The contents expand beyond cellular mechanisms to include related disorders and current clinical trials, offering insights into the disease and potentially inspiring new approaches for the treatment of tissue fibrosis.

FRONTIERS IN MOLECULAR BIOSCIENCES (2022)

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Review Pharmacology & Pharmacy

Targeting the tumor biophysical microenvironment to reduce resistance to immunotherapy

Tian Zhang et al.

Summary: Immunotherapy based on immune checkpoint inhibitors has become a crucial approach in cancer treatment, but overcoming treatment resistance is a major challenge. The tumor microenvironment (TME) plays a significant role in the pathological behaviors and treatment responses of cancers. This review summarizes five main biophysical cues in the TME that impact immunotherapy resistance and discusses the latest treatment strategies targeting these cues to improve immunotherapy efficacy.

ADVANCED DRUG DELIVERY REVIEWS (2022)

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Article Oncology

Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer

Yang Chen et al.

Summary: Pancreatic cancer cells produce a unique Col1 homotrimer which promotes tumor growth and affects tumor microbiome and immunity. Deletion of Col1 homotrimer improves survival in mice and enhances the efficacy of anti-PD-1 immunotherapy.

CANCER CELL (2022)

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Article Multidisciplinary Sciences

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Han Luo et al.

Summary: This study conducts pan-cancer analysis on 226 samples across 10 solid cancer types, illustrating the commonalities and plasticity of heterogeneous CAFs. It reveals that the activation trajectory of major CAF types is divided into three states, showing distinct interactions with other cell components and correlation with immunotherapy prognosis. Additionally, minor CAF components may originate from other TME components such as endothelial cells and macrophages.

NATURE COMMUNICATIONS (2022)

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Article Chemistry, Multidisciplinary

Stroma-targeted nanoparticles that remodel stromal alignment to enhance drug delivery and improve the antitumor efficacy of Nab-paclitaxel in pancreatic ductal adenocarcinoma models

Dan Wei et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a lethal solid tumor characterized by a specific alignment of the stromal matrix. The alignment of collagen fibers is negatively correlated with pancreatic cancer prognosis. The study proposes a two-step strategy involving pretreatment with nanoparticles delivering inhibitors and subsequent treatment with albumin-bound-paclitaxel to enhance drug penetration and accumulation in PDAC tumors.

NANO TODAY (2022)

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Review Oncology

Good and Bad Stroma in Pancreatic Cancer: Relevance of Functional States of Cancer-Associated Fibroblasts

Ryota Ando et al.

Summary: Recent research has shown that cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) have diverse states and plasticity, which can either suppress or promote cancer progression. These heterogeneous CAFs also affect the sensitivity of PDAC to anticancer therapeutics. Further studies are needed to understand the roles of CAFs in disease progression and to develop therapeutics that modulate the tumor microenvironment in PDAC.

CANCERS (2022)

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Article Medicine, General & Internal

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma

Avital Klein-Brill et al.

Summary: This study compared the two common first-line treatments for metastatic adenocarcinoma of the pancreas, FOLFIRINOX and gemcitabine plus nab-paclitaxel, and found that FOLFIRINOX was associated with improved overall survival and fewer posttreatment complications.

JAMA NETWORK OPEN (2022)

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Article Biology

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

Julia E. Lefler et al.

Summary: Disruption of the STAT3 signaling axis in stromal fibroblasts through genetic ablation of Stat3 slows tumor progression, increases survival, and reshapes the immune-suppressive tumor micro-environment in a PDAC mouse model. Loss of the tumor suppressor PTEN in pancreatic CAFs leads to increased STAT3 phosphorylation and promotes secretion of CXCL1.

LIFE SCIENCE ALLIANCE (2022)

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Article Biochemistry & Molecular Biology

A general chemical principle for creating closure inhibitors

Fu-Yang- Lin et al.

Summary: The failed small-molecule inhibitors of integrins were found to stabilize the high-affinity conformation of the cells. A simple chemical feature that stabilizes the bent-closed conformation of the cells was also discovered.

CELL (2022)

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Article Oncology

Clinical advances and ongoing trials of mRNA vaccines for cancer treatment

Cathrine Lund Lorentzen et al.

LANCET ONCOLOGY (2022)

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Article Multidisciplinary Sciences

Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome

Hua Su et al.

Summary: This study reveals the opposing effects of intact and cleaved collagen I (Col I) in regulating the bioenergetics, tumor growth, and metastasis of pancreatic ductal adenocarcinoma (PDAC) through the tumor microenvironment. Intact Col I inhibits tumor growth, while cleaved Col I promotes tumor growth. Patients with tumors enriched in intact Col I and low levels of related signaling molecules have a longer median survival. These findings shed light on the complex mechanisms of the tumor microenvironment in PDAC and provide new therapeutic targets.

NATURE (2022)

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Article Multidisciplinary Sciences

In situ analysis of nanoparticle soft corona and dynamic evolution

Didar Baimanov et al.

Summary: We developed an in situ Fishing method to monitor the dynamic formation of protein corona on ultra-small chiral Cu2S nanoparticles, allowing direct separation and identification of the corona protein composition. Our method reveals subtle differences in nanoparticle-protein interactions.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling

Lee Shaashua et al.

Summary: Tumors are initiated by mutations in cancer cells and progress through interactions with non-malignant cells of the tumor microenvironment. This study examines how different mutations in cancer cells affect the transcriptional rewiring of cancer-associated fibroblasts (CAFs) in pancreatic cancer. The researchers find that BRCA mutations lead to an increase in a specific subset of immune-regulatory CAFs, mediated by activation of heat-shock factor 1.

NATURE COMMUNICATIONS (2022)

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Article Oncology

Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer

Ashley M. Mello et al.

Summary: Hypoxia plays a crucial role in promoting the inflammatory phenotype in cancer-associated fibroblasts (CAF) in pancreatic ductal adenocarcinoma (PDAC).

ONCOGENESIS (2022)

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Review Chemistry, Multidisciplinary

Rational Nanomedicine Design Enhances Clinically Physical Treatment-Inspired or Combined Immunotherapy

Qiaoqiao Liu et al.

Summary: This paper introduces the use of nanomedicine to enhance immune activation and potential, as well as the efficiency improvement of physical treatment on tumor progression, relapse, and metastasis.

ADVANCED SCIENCE (2022)

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Article Oncology

Multiphasic Heterogeneity of Fibroblasts in the Microenvironment of Pancreatic Ductal Adenocarcinoma: Dissection and the Sum of the Dynamics

Hideaki Ijichi

Summary: Understanding the tumor microenvironment is crucial for overcoming pancreatic ductal adenocarcinoma (PDAC). This article discusses various aspects of the microenvironment, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), immune microenvironment, metabolic properties, microbiome, neural signaling, and the effect of anesthetic drugs. The study found that the PDAC microenvironment is more complicated than expected, with heterogeneity and plasticity resulting from tumor-stromal interactions.

CANCERS (2022)

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Article Biochemistry & Molecular Biology

Mechanobiology of solid tumors

Antonios N. Gargalionis et al.

Summary: Mechanical features of cancer cells play a crucial role in tumor development and progression, with mechanosensory proteins potentially mediating oncogenic signaling and response to chemotherapy. Studying changes in tumor microenvironment and matrix rigidity can offer new anti-cancer strategies.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2022)

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Review Immunology

Antibody-Based Approaches to Target Pancreatic Tumours

Marie Sorbara et al.

Summary: Pancreatic cancer is difficult to detect at an early stage and has limited treatment options due to drug resistance. Monoclonal antibodies show limited efficacy as a monotherapy, but present opportunities for treatment, diagnostics, and imagery.

ANTIBODIES (2022)

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Review Chemistry, Analytical

Recent advances in matrix metalloproteinases-responsive nanoprobes for cancer diagnosis and therapy

Qiuye Wang et al.

Summary: This review systematically summarizes the use of matrix metalloproteinases (MMPs)-responsive nanoprobes for cancer diagnosis and therapy. It covers the classifications of MMPs, their substrates and recognized sequences, and overexpressed tumor types. The advances in trigger mechanism, design principle, and various imaging or therapy modes of MMPs-responsive nanoprobes are also included. Furthermore, the challenges in clinical application and suggestions for future study are analyzed.

REVIEWS IN ANALYTICAL CHEMISTRY (2022)

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Article Oncology

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer

Vanessa Arciero et al.

Summary: This study compared the real-world cost-effectiveness of Gem-Nab and FOLFIRINOX for APC patients in Ontario, Canada. The results showed that patients in the Gem-Nab group had shorter survival and higher total costs compared to the FOLFIRINOX group, indicating that Gem-Nab is likely more costly and less effective than FOLFIRINOX.

JNCI CANCER SPECTRUM (2022)

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Article Endocrinology & Metabolism

Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix

Emily J. Kay et al.

Summary: The study reveals that the newly synthesized proline in CAFs promotes the production of tumor collagen in breast cancer xenografts, and reducing PYCR1 levels can inhibit tumor growth and metastasis. Additionally, the synthesis of collagen and proline in CAFs is epigenetically regulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels.

NATURE METABOLISM (2022)

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Article Materials Science, Biomaterials

A nanomedicine enables synergistic chemo/photodynamic therapy for pancreatic cancer treatment

Liwei Zhu et al.

Summary: In this study, a nanomedicine system was developed for pancreatic cancer treatment, which could release drugs in response to light. Both in vitro and in vivo studies confirmed the tumor inhibition efficacy of this nanomedicine with low toxicity to animals.

BIOMATERIALS SCIENCE (2022)

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Review Oncology

Translational advances in pancreatic ductal adenocarcinoma therapy

Abdel Nasser Hosein et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that is often diagnosed at advanced stages, leading to limited treatment options. Recent advancements in targeted therapy and immunotherapy for different subtypes of PDAC are reviewed in this article, with a focus on the current preclinical and clinical evidence supporting these approaches and the potential of combination treatments.

NATURE CANCER (2022)

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Review Physiology

DIVERSITY AND BIOLOGY OF CANCER-ASSOCIATED FIBROBLASTS

Giulia Biffi et al.

Summary: Efforts to develop anti-cancer therapies have mainly targeted the epithelial compartment, but recent studies have shown the significant influence of cancer-associated fibroblasts (CAFs) in tumor progression. CAFs not only promote cancer cell proliferation, therapy resistance, and immune exclusion, but may also restrain tumor progression in certain contexts. Research on CAFs has focused on their heterogeneity, plasticity, and functions across different cancer types and states, as well as advancements in therapeutic strategies targeting CAFs currently undergoing preclinical and clinical evaluation.

PHYSIOLOGICAL REVIEWS (2021)

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Article Nanoscience & Nanotechnology

Active Targeting Significantly Outperforms Nanoparticle Size in Facilitating Tumor-Specific Uptake in Orthotopic Pancreatic Cancer

William M. MacCuaig et al.

Summary: Active targeting using V7 peptide is superior to nanoparticle size in tumor uptake, with size having a secondary effect on actively targeted nanoparticles. Passive targeting nanoparticles showed no significant effect of size on uptake.

ACS APPLIED MATERIALS & INTERFACES (2021)

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Review Pharmacology & Pharmacy

Ultrasound and microbubbles to beat barriers in tumors: Improving delivery of nanomedicine

Sofie Snipstad et al.

Summary: Nanomedicine has many advantages, but penetrating deep into the tumor stroma remains a challenge. Successful treatment requires overcoming delivery barriers such as crossing the capillary wall.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Article Gastroenterology & Hepatology

Modulation of Cancer-Associated Fibrotic Stroma by An Integrin αvβ3 Targeting Protein for Pancreatic Cancer Treatment

Ravi Chakra Turaga et al.

Summary: ProAgio specifically induces apoptosis in CAPaSC and extends survival in PDAC tumor models, reducing intratumoral insulin-like growth factor 1 levels and enhancing Gem efficacy.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Nrf2 expression in pancreatic stellate cells promotes progression of cancer

Yu Tanaka et al.

Summary: Systemic Nrf2 deletion decreases pancreatic cancer progression in a mutant K-ras/p53-expressing mouse model, with pancreatic stellate cells (PSCs) playing a role in this process. Nrf2-deleted PSCs exhibit lower proliferative and migration capacity, and show reduced growth-stimulating effects on pancreatic cancer cells.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2021)

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Article Engineering, Biomedical

Prodrug nanoparticles rationally integrating stroma modification and chemotherapy to treat metastatic pancreatic cancer

Liying Wang et al.

Summary: The study developed self-assembled prodrug nanoparticles combining a stromal reprogramming inducer, calcipotriol (CAL), and a potent chemotherapeutic agent, 7-Ethyl-10-hydroxycamptothecin (SN38), to effectively treat PDAC. These nanoparticles significantly improved the blood circulation time of CAL and decreased the expression of N-cadherin, collagen, and fibronectin in tumors, demonstrating strong anti-tumor and anti-metastasis effects.

BIOMATERIALS (2021)

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Article Oncology

Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer

Nina G. Steele et al.

Summary: The study reveals that Hedgehog signaling is uniquely activated in fibroblasts in PDAC, with varying levels of elevation in myofibroblastic CAFs compared to inflammatory CAFs. Inhibition of the Hedgehog pathway slows tumor growth, alters the composition of CAF subtypes, and impacts immune cell infiltration, leading to increased immunosuppression.

CLINICAL CANCER RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Spatially confined sub-tumor microenvironments in pancreatic cancer

Barbara T. Grunwald et al.

Summary: Through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models, we identified distinct subTMEs in the human pancreatic tumor microenvironment (TME) that are linked to tumor immunity, subtypes, differentiation, and treatment response. Reactive subTMEs rich in coordinated fibroblast communities were immune hot, while matrix-rich deserted subTMEs harbored fewer activated fibroblasts but showed chemoprotective features. These subTMEs originated in fibroblast differentiation trajectories and produced patient-specific heterogeneity tightly linked to malignant biology.

CELL (2021)

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Article Gastroenterology & Hepatology

Cadherin 11 Promotes Immunosuppression and Extracellular Matrix Deposition to Support Growth of Pancreatic Tumors and Resistance to Gemcitabine in Mice

Ivana Peran et al.

Summary: The study showed that CDH11, expressed by cancer-associated fibroblasts in the pancreatic tumor stroma, plays a critical role in promoting tumor growth and immunosuppression. Knockout or inhibition of CDH11 reduced pancreatic tumor growth, increased response to gemcitabine, and significantly extended survival of mice. Thus, CDH11 may be a potential therapeutic target for pancreatic cancer.

GASTROENTEROLOGY (2021)

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Review Oncology

Targeting hypoxic tumor microenvironment in pancreatic cancer

Jinxin Tao et al.

Summary: Pancreatic cancer, characterized by late diagnosis, early metastasis, and poor prognosis, exhibits high lethality globally. The hypoxic microenvironment in pancreatic cancer has extensive effects on biological behaviors and malignant phenotypes, leading to aggressive progression and therapeutic resistance. Innovative therapies targeting the tumor hypoxic microenvironment show great potential in overcoming treatment resistance and enhancing antitumor efficacy.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Chemistry, Multidisciplinary

Chemo-physical Strategies to Advance the in Vivo Functionality of Targeted Nanomedicine: The Next Generation

Junjie Li et al.

Summary: The text emphasizes the evolution of nanomedicine from biologically inert entities to smarter systems aimed at advancing in vivo functionality. It highlights the importance of focusing on nano-bio interactions and desirable functionality in tissue, cellular, and molecular levels, as well as providing definitive evidence for proof-of-mechanism.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Review Cell Biology

Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Origin, Polarization, Function, and Reprogramming

Sen Yang et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that can only be cured by surgery in its early stages, but recurrence remains a high possibility. Tumor-associated macrophages (TAMs) play a crucial role in PDAC development, promoting tumor behaviors such as tumorigenesis and metastasis.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Article Oncology

Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study

M. Tempero et al.

Summary: This study evaluated the safety and efficacy of first-line ibrutinib plus nab-paclitaxel/gemcitabine treatment in patients with PDAC. Results showed that although there were differences in overall response rates, ibrutinib plus nab-paclitaxel/gemcitabine did not improve overall survival or progression-free survival for patients with PDAC. Additionally, patients in the ibrutinib arm received lower cumulative drug doses.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer

Yang Chen et al.

Summary: The stromal desmoplastic reaction in pancreatic ductal adenocarcinoma involves significant accumulation of type I collagen (Col1). Deletion of Col1 specifically in myofibroblasts accelerates PDAC progression by increasing Cxcl5 expression in cancer cells and promoting recruitment of myeloid-derived suppressor cells. Targeting CXCR2 and CCR2 may help restrain accelerated PDAC progression in the absence of stromal Col1.

CANCER CELL (2021)

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Review Nanoscience & Nanotechnology

The ancillary effects of nanoparticles and their implications for nanomedicine

Evan P. Stater et al.

Summary: Nanoparticles, beyond their engineered functions, can induce specific biological effects, which may have implications for the development and clinical application of nanomedicine.

NATURE NANOTECHNOLOGY (2021)

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Review Biochemistry & Molecular Biology

Targeting Redox Metabolism in Pancreatic Cancer

Nadine Abdel Hadi et al.

Summary: Cell metabolism in cancer cells is reprogrammed to meet their high energy and biosynthetic demands, leading to alterations in redox metabolism and accumulation of reactive oxygen species (ROS). Cancer cells adapt to high ROS levels, contributing to tumorigenesis, metastasis, therapy resistance, and relapse. Combining strategies to increase ROS production and inhibit antioxidant capacity is a promising approach for pancreatic cancer therapy.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Multidisciplinary Sciences

Stiffness of targeted layer-by-layer nanoparticles impacts elimination half-life, tumor accumulation, and tumor penetration

Stephanie M. Kong et al.

Summary: The stiffness of nanoparticles plays a crucial role in drug delivery, affecting circulation time, tumor accumulation, and penetration. Layer-by-layer nanoparticles can modulate stiffness by adjusting the mechanical properties of the core, leading to improved tumor targeting and therapeutic outcomes.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Oncology

Macropinocytosis in Cancer-Associated Fibroblasts Is Dependent on CaMKK2/ARHGEF2 Signaling and Functions to Support Tumor and Stromal Cell Fitness

Yijuan Zhang et al.

Summary: Pancreatic cancer-associated fibroblasts exhibit macropinocytosis triggered by glutamine deficiency, which is potentiated by increased cytosolic Ca2+ levels and dependent on signaling pathways like ARHGEF2 and CaMKK2-AMPK. This process serves as a source of intracellular amino acids for CAF cell fitness and function, while also providing secreted amino acids that promote tumor cell survival. Selective disruption of macropinocytosis in CAFs suppresses PDAC tumor growth, highlighting the crucial role of this process in supporting cancer progression.

CANCER DISCOVERY (2021)

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Article Multidisciplinary Sciences

Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma

J. Alexander et al.

Summary: Pancreatic Ductal Adenocarcinoma (PDAC) has a low five-year survival rate due to fibrotic stromal remodeling process driven by cancer-associated fibroblasts (CAFs). The study reveals that CAF activation and functions are closely related to the palladin iso3 and iso4 proteins, playing a crucial role in sustaining PDAC progression.

SCIENTIFIC REPORTS (2021)

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Article Biotechnology & Applied Microbiology

Targeting Endoglin Expressing Cells in the Tumor Microenvironment Does Not Inhibit Tumor Growth in a Pancreatic Cancer Mouse Model

Mark J. A. Schoonderwoerd et al.

Summary: This study investigated the expression of endoglin on PDAC-CAFs and its impact on PDAC using TRC105. The results showed that although TRC105 efficiently inhibited signaling, it did not decrease tumor growth.

ONCOTARGETS AND THERAPY (2021)

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Article Chemistry, Multidisciplinary

Effect of Matrix-Modulating Enzymes on the Cellular Uptake of Magnetic Nanoparticles and on Magnetic Hyperthermia Treatment of Pancreatic Cancer Models In Vivo

Felista L. Tansi et al.

Summary: The study investigated the impact of matrix-modulating enzymes on the uptake of magnetic nanoparticles by pancreatic cancer cells and their overall influence on magnetic heating and cell death. Results showed that hyaluronidase enhanced the uptake of magnetic nanoparticles, leading to improved thermal treatment outcomes.

NANOMATERIALS (2021)

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Review Chemistry, Multidisciplinary

Tailor-Made Nanomaterials for Diagnosis and Therapy of Pancreatic Ductal Adenocarcinoma

Xi Hu et al.

Summary: Nanomaterials have potential applications in the diagnosis and treatment of PDAC, but a deeper understanding of nano-bio interactions in the microenvironment of PDAC is needed. Detecting potential biomarkers and understanding nano-bio interactions in the tumor microenvironment is crucial for designing effective nanomedicine tailored to PDAC.

ADVANCED SCIENCE (2021)

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Article Biology

Hyaluronic acid fuels pancreatic cancer cell growth

Peter K. Kim et al.

Summary: The rewired metabolism in pancreatic ductal adenocarcinomas is sustained by cancer cells scavenging nutrients from the tumor microenvironment to maintain glycosylation precursor pools. Hyaluronic acid, a carbohydrate polymer in pancreatic tumors, can refuel the hexosamine biosynthetic pathway beyond its structural and signaling roles, providing energy for PDA metabolism.

ELIFE (2021)

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Review Biotechnology & Applied Microbiology

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Ming Jia et al.

Summary: Modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach, and nano-delivery systems have been developed to alter the TME. These systems change the microenvironment in various ways, including depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, and improving the hypoxic environment.

JOURNAL OF NANOBIOTECHNOLOGY (2021)

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Review Cell Biology

The exosome journey: from biogenesis to uptake and intracellular signalling

Sonam Gurung et al.

Summary: Exosomes have vast potential in clinical applications, and understanding their biology is crucial. The processes of exosome biogenesis, transport, and uptake involve numerous influencing factors.

CELL COMMUNICATION AND SIGNALING (2021)

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Article Multidisciplinary Sciences

Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status

Kendelle J. Murphy et al.

Summary: In this study, transient manipulation of focal adhesion kinase in PDAC was visualized using intravital fluorescence imaging, with real-time quantification of cell cycle reporter to improve chemotherapy response. Analysis of different matrices and environmental cues helped to reduce PDAC metastasis.

SCIENCE ADVANCES (2021)

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Article Pharmacology & Pharmacy

Magnetic Fluid Hyperthermia as Treatment Option for Pancreatic Cancer Cells and Pancreatic Cancer Organoids

Julian Palzer et al.

International Journal of Nanomedicine (2021)

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Review Oncology

TGFβ Signaling in the Pancreatic Tumor Microenvironment

Daniel R. Principe et al.

Summary: There is a lack of effective treatment for advanced PDAC patients, but TGF beta pathway inhibitors show promise in enhancing responses to current therapies. TGF beta signaling has complex roles in the pancreatic tumor microenvironment, with both tumor-suppressive and tumorigenic effects. Further research and clinical trials are ongoing to develop TGF beta inhibitors for the treatment of PDAC patients.

CANCERS (2021)

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Review Cell Biology

Fibroblast Memory in Development, Homeostasis and Disease

Thomas Kirk et al.

Summary: Fibroblasts, as the major cell population in connective tissue of organs, play a key role in remodeling the extracellular matrix, but are also recognized as a highly diverse cell population that constantly responds and adapts to their environment.

CELLS (2021)

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Review Oncology

The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies

Vincent M. Perez et al.

Summary: PDAC ECM, primarily consisting of collagens and other proteins, plays a crucial role in influencing tumor growth and microenvironment through biomechanical and biochemical signals, serving as both a barrier and nutrient source for tumors. Understanding the dichotomous nature of ECM in tumor biology has significant implications for therapeutic strategies targeting the PDAC ECM.

FRONTIERS IN ONCOLOGY (2021)

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Review Cell Biology

Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

Beate Guendel et al.

Summary: This review examines the current in vitro models for PDAC, emphasizing the challenges of late diagnosis and treatment resistance in improving patient outcomes. Researchers have established various in vitro and in vivo models for PDAC, with a growing focus on 3D cell culture models like spheroids and organoids.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Pharmacology & Pharmacy

Translating complexity and heterogeneity of pancreatic tumor: 3D in vitro to in vivo models

Marcel A. Heinrich et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type with a complex tumor microenvironment, making treatment challenging. This article provides an overview of recent developments in in vitro and in vivo models aiming to mimic the complexity of PDAC, highlighting the lack of biologically relevant models that resemble the complexity of PDAC.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Article Oncology

Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity

Colin Hutton et al.

Summary: This study used mass cytometry to analyze the stromal composition in murine tissues and tumors, revealing extensive stromal heterogeneity and coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. The research identified two stable and functionally distinct pancreatic fibroblast lineages marked by CD105 expression, with CD105-positive fibroblasts promoting tumor growth and CD105-negative fibroblasts suppressing tumors, dependent on adaptive immunity. These findings highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth.

CANCER CELL (2021)

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Article Oncology

Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression

Chika Iwamoto et al.

Summary: This study found that in PDAC, macrophages derived from bone marrow can partially convert into CAF-like cells, acting as a specific subtype that promotes pancreatic cancer growth and invasion. This conversion may represent a novel therapeutic strategy.

CANCER LETTERS (2021)

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Review Biochemistry & Molecular Biology

Fibroblasts: Origins, definitions, and functions in health and disease

Maksim Plikus et al.

Summary: Fibroblasts are diverse mesenchymal cells that play a role in tissue homeostasis and disease, producing complex extracellular matrix and creating signaling niches. They are transcriptionally and functionally heterogeneous across and within organs, encoding positional information and maintaining distinct cellular progeny. Their unique properties make them poised for tissue repair but can also drive fibrotic disorders if activated aberrantly.

CELL (2021)

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Article Oncology

Gemcitabine/nab-Paclitaxel versus FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer: A propensity score analysis

Jakob M. Riedl et al.

Summary: This study found that FOLFIRINOX and GN have similar effectiveness in the palliative first-line treatment of aPDAC. Despite some differences in patient characteristics between the two groups, survival outcomes remained comparable after weighting the data with propensity scores.

EUROPEAN JOURNAL OF CANCER (2021)

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Article Chemistry, Multidisciplinary

High-throughput evaluation of polymeric nanoparticles for tissue-targeted gene expression using barcoded plasmid DNA

Jayoung Kim et al.

Summary: A new high-throughput method has been developed to evaluate polymeric nanoparticle libraries for tissue-specific gene delivery in vivo. Nanoparticles were found to mainly accumulate in clearance organs, with transfection efficiency not necessarily correlating with tissue accumulation levels. This study validates the effectiveness of the new method in accurately assessing systemic gene delivery.

JOURNAL OF CONTROLLED RELEASE (2021)

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Article Multidisciplinary Sciences

TP53 missense mutations in PDAC are associated with enhanced fibrosis and an immunosuppressive microenvironment

Martino Maddalena et al.

Summary: Missense p53 mutations in PDAC patients can suppress CD8(+) T cell infiltration into tumors and hinder the immune system’s ability to eliminate cancer cells. Silencing mutp53 can reduce tumor size and fibrotic response.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Multidisciplinary Sciences

Inhibition of discoidin domain receptors by imatinib prevented pancreatic fibrosis demonstrated in experimental chronic pancreatitis model

Sapana Bansod et al.

Summary: The study revealed the significant role of DDR1 and DDR2 in chronic pancreatitis, and the use of IMT inhibitor can effectively reduce inflammation and fibrosis, while inhibiting the TGF-beta 1/Smad signaling pathway.

SCIENTIFIC REPORTS (2021)

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Article Biology

Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment

Alba Nicolas-Boluda et al.

Summary: The study found that tumor stiffness is strongly correlated with tumor growth and ECM crosslinking, but negatively correlated with T cell migration. Interfering with collagen stabilization can reduce ECM content and tumor stiffness, improving T cell migration and the efficacy of anti-PD-1 blockade.

ELIFE (2021)

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Review Medicine, General & Internal

Pancreatic Ductal Adenocarcinoma: Relating Biomechanics and Prognosis

Benjamin M. MacCurtain et al.

Summary: PDAC, the most common form of pancreatic cancer, has a poor prognosis. Tumor stiffness and increased tissue heterogeneity, along with current diagnostics, may help predict prognosis and treatment response. Biomechanical changes in PDAC, factors behind these changes, and methods for assessing PDAC biomechanics are discussed in this review.

JOURNAL OF CLINICAL MEDICINE (2021)

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Article Oncology

ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer

Etienne J. Slapak et al.

Summary: Systemic chemotherapy for pancreatic cancer is limited by toxicity-dependent dose restrictions, leading to premature termination of treatment. Targeted drug delivery using a protease-dependent system can reduce collateral toxicity and enhance efficacy by delivering chemotherapy drugs specifically to cancer cells without affecting healthy tissue. This study successfully demonstrated the feasibility of protease-mediated drug release in pancreatic cancer, highlighting the potential of this approach to improve treatment outcomes and reduce side effects.

CANCERS (2021)

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Review Oncology

Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Therapeutic Opportunities and Clinical Challenges

Ashleigh R. Poh et al.

Summary: Macrophages play a crucial role in the pancreatic tumor microenvironment and are associated with poor patient survival. Pre-clinical studies have shown the diverse contributions of macrophages in PDAC development, however, the effectiveness of macrophage-targeting therapies in clinical trials is inconsistent.

CANCERS (2021)

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Review Cell Biology

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

David R. Brigstock

Summary: Fibrosis is characterized by unrelenting deposition of insoluble collagen due to chronic injury, leading to organ dysfunction and increased cancer risk. Extracellular vesicles play important roles in conveying pro-fibrotic signals as well as anti-fibrotic activities in chronic wound environment. EVs in body fluids of fibrotic individuals have potential as fibrosis biomarkers.

CELLS (2021)

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Article Cell Biology

Single-cell analysis of pancreatic ductal adenocarcinoma identifies a novel fibroblast subtype associated with poor prognosis but better immunotherapy response

Yu Wang et al.

Summary: The study investigated the heterogeneity among PDAC patients in terms of CAFs, ductal cancer cells, and immune cells, revealing differences between dense-type and loose-type PDAC. A novel subtype of CAFs, meCAFs, was discovered in loose-type PDAC, playing a critical role in disease progression and response to immunotherapy. This finding highlights the importance of considering intertumoral heterogeneity in PDAC treatment strategies.

CELL DISCOVERY (2021)

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Review Oncology

Regulation of Extracellular Matrix Production in Activated Fibroblasts: Roles of Amino Acid Metabolism in Collagen Synthesis

Emily J. Kay et al.

Summary: This review summarizes the role of cancer associated fibroblasts (CAFs) in regulating ECM production, with a focus on collagen production, at the transcriptional, translational, and post-translational levels, and discusses possible strategies for effectively targeting CAF activation and the formation of a tumor-promoting stroma.

FRONTIERS IN ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

Metabolic pathways fuelling protumourigenic cancer-associated fibroblast functions

Emily J. Kay et al.

Summary: CAFs play crucial roles in supporting tumor growth and progression, engaging in complex metabolic crosstalk with cancer cells. Targeting CAF metabolism may provide strategies for simultaneously targeting tumors and stroma. The rewiring of CAF metabolism regulates protumorigenic functions and maintains CAF activation through epigenetic changes.

CURRENT OPINION IN SYSTEMS BIOLOGY (2021)

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Review Medicine, Research & Experimental

Targeting of promising transmembrane proteins for diagnosis and treatment of pancreatic ductal adenocarcinoma

Vida Mashayekhi et al.

Summary: This review discusses the challenges in the treatment and early diagnosis of pancreatic ductal adenocarcinoma (PDAC), emphasizing the need for more effective and better-tolerated treatment options. It also highlights the discovery of transmembrane proteins that are overexpressed in PDAC cells, which could potentially serve as targets for treatment and diagnosis.

THERANOSTICS (2021)

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Article Chemistry, Multidisciplinary

Comprehensively enhanced delivery cascade by transformable beaded nanofibrils for pancreatic cancer therapy

Qinglin Sheng et al.

Summary: To address the low drug delivery efficiency in tumor therapy, researchers have developed a MMP-2 responsive transformable beaded nanofibril that improves drug penetration and cellular internalization in tumors.

NANOSCALE (2021)

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Review Medicine, Research & Experimental

Metabolic reprogramming of cancer-associated fibroblasts and its effect on cancer cell reprogramming

Zhenzhen Li et al.

Summary: Cancer cells adapt their metabolism to proliferate and survive in harsh environments, with a close relationship between tumor microenvironment and cancer-associated fibroblasts (CAFs) playing key roles in tumor growth and metastasis. CAFs act as major regulators in shaping tumor metabolism, especially through dysregulation of metabolic pathways, influencing cancer cell behavior and response to therapy. The interaction and crosstalk between cancer cells and CAFs contribute to metabolic reprogramming that impacts cancer cell growth and progression.

THERANOSTICS (2021)

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Review Biochemistry & Molecular Biology

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

Li Chen et al.

Summary: Biomimetic nanoparticles (BNPs) integrate biological vectors with functional agents for targeted drug delivery. Natural vectors are deliberately modified to enhance permeability, loading capability, and specificity, making them more effective for delivering contrast agents, chemotherapy drugs, nucleic acids, and genes to target sites.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Biochemistry & Molecular Biology

Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Fanglong Wu et al.

Summary: CAFs play vital roles in cancer progression and their complex signaling pathways with cancer cells are crucial for understanding the development of cancer.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Biochemistry & Molecular Biology

Extracellular matrix and its therapeutic potential for cancer treatment

Jiacheng Huang et al.

Summary: The extracellular matrix (ECM) is a key component of tumors, playing roles in mechanical support, microenvironment modulation, and signaling. Interactions between cancer cells and the tumor microenvironment can lead to ECM stiffness changes and contribute to malignant transformation. Understanding ECM dysregulation in the TME is essential for identifying therapeutic targets for cancer treatment.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Endocrinology & Metabolism

Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism

Ilaria Elia et al.

Summary: The article provides a detailed examination of the complexity of cellular metabolism within the tumor microenvironment, along with potential therapeutic intervention opportunities. Cancer cell metabolism and behavior are regulated by multiple factors, and the metabolic environment within the TME is influenced by various tiers. Understanding the interactions of these tiers reveals unique therapeutic potential for modulating the metabolic profile and function of all cells in the TME.

NATURE METABOLISM (2021)

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Article Anatomy & Morphology

Metalloproteinases and their roles in human cancer

Roopali Roy et al.

ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY (2020)

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Review Nanoscience & Nanotechnology

Physical-, chemical-, and biological-responsive nanomedicine for cancer therapy

Jinfeng Liao et al.

WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY (2020)

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Article Chemistry, Physical

Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions

Danielle Park et al.

NATURE MATERIALS (2020)

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Article Oncology

Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15+ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy

Claudia X. Dominguez et al.

CANCER DISCOVERY (2020)

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Article Cell Biology

Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein

Enyong Dai et al.

AUTOPHAGY (2020)

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Review Oncology

The life cycle of cancer-associated fibroblasts within the tumour stroma and its importance in disease outcome

Elisa D'Arcangelo et al.

BRITISH JOURNAL OF CANCER (2020)

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Article Oncology

Cancer Cell-Derived Matrisome Proteins Promote Metastasis in Pancreatic Ductal Adenocarcinoma

Chenxi Tian et al.

CANCER RESEARCH (2020)

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Article Cell Biology

Extracellular matrix-cell interactions: Focus on therapeutic applications

A. Sainio et al.

CELLULAR SIGNALLING (2020)

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Review Biochemistry & Molecular Biology

Origin and functional heterogeneity of fibroblasts

Valerie S. LeBleu et al.

FASEB JOURNAL (2020)

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Article Oncology

HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA).

Margaret A. Tempero et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Review Immunology

Transforming growth factor-beta in tissue fibrosis

Nikolaos G. Frangogiannis

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Article Chemistry, Multidisciplinary

Metformin-Induced Stromal Depletion to Enhance the Penetration of Gemcitabine-Loaded Magnetic Nanoparticles for Pancreatic Cancer Targeted Therapy

Haijie Han et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2020)

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Article Chemistry, Physical

PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia

Tao Zhang et al.

NANO RESEARCH (2020)

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Article Chemistry, Physical

The entry of nanoparticles into solid tumours

Shrey Sindhwani et al.

NATURE MATERIALS (2020)

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Article Oncology

Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

John D. Martin et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2020)

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Review Cell Biology

Metabolic Regulation of Cell Fate and Function

Shohini Ghosh-Choudhary et al.

TRENDS IN CELL BIOLOGY (2020)

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Article Oncology

Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment

Erin Helms et al.

Cancer Discovery (2020)

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Article Pathology

Discoidin Domain Receptor 1 (DDR1) Is Necessary for Tissue Homeostasis in Pancreatic Injury and Pathogenesis of Pancreatic Ductal Adenocarcinoma

Jeanine M. Ruggeri et al.

AMERICAN JOURNAL OF PATHOLOGY (2020)

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Article Cell Biology

Recent advances in understanding cancer-associated fibroblasts in pancreatic cancer

Huocong Huang et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2020)

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Review Engineering, Biomedical

Tumor extravasation and infiltration as barriers of nanomedicine for high efficacy: The current status and transcytosis strategy

Quan Zhou et al.

BIOMATERIALS (2020)

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Review Polymer Science

The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation

Thai Thanh Hoang Thi et al.

POLYMERS (2020)

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Review Developmental Biology

The extracellular matrix in development

David A. Cruz Walma et al.

DEVELOPMENT (2020)

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Article Chemistry, Multidisciplinary

Size-Tunable Strategies for a Tumor Targeted Drug Delivery System

Wenqi Yu et al.

ACS CENTRAL SCIENCE (2020)

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Review Engineering, Biomedical

Looping In Mechanics: Mechanobiologic Regulation of the Nucleus and the Epigenome

Eric N. Dai et al.

ADVANCED HEALTHCARE MATERIALS (2020)

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Article Instruments & Instrumentation

Challenges in nanomedicine clinical translation

Josbert M. Metselaar et al.

DRUG DELIVERY AND TRANSLATIONAL RESEARCH (2020)

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Review Biochemistry & Molecular Biology

The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

Liam Baird et al.

MOLECULAR AND CELLULAR BIOLOGY (2020)

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Article Nanoscience & Nanotechnology

Hyperthermia affects collagen fiber architecture and induces apoptosis in pancreatic and fibroblast tumor hetero-spheroids in vitro

Susann Piehler et al.

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE (2020)

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Review Oncology

The tumour microenvironment in pancreatic cancer - clinical challenges and opportunities

Won Jin Ho et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2020)

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Review Biotechnology & Applied Microbiology

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of Stealthy Nanomaterials

Riccardo Rampado et al.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2020)

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Review Pharmacology & Pharmacy

Exploiting the dynamics of the EPR effect and strategies to improve the therapeutic effects of nanomedicines by using EPR effect enhancers

Jun Fang et al.

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Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma

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Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

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The vitamin D analogue calcipotriol promotes an anti-tumorigenic phenotype of human pancreatic CAFs but reduces T cell mediated immunity

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Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake

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The extracellular matrix as a key regulator of intracellular signalling networks

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Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness

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Integrin 11 in pancreatic stellate cells regulates tumor stroma interaction in pancreatic cancer

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Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer

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A Stromal Lysolipid-Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression

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ROS-Responsive Polymeric Micelles for Triggered Simultaneous Delivery of PLK1 Inhibitor/miR-34a and Effective Synergistic Therapy in Pancreatic Cancer

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Mathematical modeling in cancer nanomedicine: a review

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Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer A Phase 2 Clinical Trial

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Integrin Regulation of CAF Differentiation and Function

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Integrins as biomechanical sensors of the microenvironment

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In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers

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Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

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Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis

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Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells

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ITGA5 inhibition in pancreatic stellate cells attenuates desmoplasia and potentiates efficacy of chemotherapy in pancreatic cancer

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Single-Stranded DNA-Packaged Polyplex Micelle as Adeno-Associated-Virus-Inspired Compact Vector to Systemically Target Stroma-Rich Pancreatic Cancer

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EMBO MOLECULAR MEDICINE (2019)

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Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma

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IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma

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Extended Exposure to Stiff Microenvironments Leads to Persistent Chromatin Remodeling in Human Mesenchymal Stem Cells

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The Interaction between Laminin-332 and alpha 3 beta 1 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells

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Ultrasound-induced Cavitation enhances the efficacy of Chemotherapy in a 3D Model of Pancreatic Ductal Adenocarcinoma with its microenvironment

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CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

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Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

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WORLD JOURNAL OF ONCOLOGY (2019)

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The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development

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Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution

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Metabolic regulation of dermal fibroblasts contributes to skin extracellular matrix homeostasis and fibrosis

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Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking

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EXPERIMENTAL AND MOLECULAR MEDICINE (2019)

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Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

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Transcytosis - An effective targeting strategy that is complementary to EPR effect for pancreatic cancer nano drug delivery

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Use of nano engineered approaches to overcome the stromal barrier in pancreatic cancer

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Solid Stress Facilitates Fibroblasts Activation to Promote Pancreatic Cancer Cell Migration

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ANNALS OF BIOMEDICAL ENGINEERING (2018)

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Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2018)

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Simultaneous inhibition of hedgehog signaling and tumor proliferation remodels stroma and enhances pancreatic cancer therapy

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Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarcinoma Invasion and Tumor Growth

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Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment

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Block Copolymer Micelles in Nanomedicine Applications

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Extracellular matrix as a driver of progressive fibrosis

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Mechanosensing and fibrosis

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JOURNAL OF CLINICAL INVESTIGATION (2018)

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The fibrotic tumor stroma

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Chemotherapeutic drug delivery by tumoral extracellular matrix targeting

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Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures Into Future Successes

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MOLECULAR CANCER THERAPEUTICS (2018)

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Differences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer

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mRNA vaccines - a new era in vaccinology

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Nanoparticle elasticity directs tumor uptake

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Acid- and reduction-sensitive micelles for improving the drug delivery efficacy for pancreatic cancer therapy

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Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization

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FRONTIERS IN PHARMACOLOGY (2018)

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Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

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CA-A CANCER JOURNAL FOR CLINICIANS (2018)

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Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of IL-37

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CELL PROLIFERATION (2018)

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Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem

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Biologically Targeted Magnetic Hyperthermia: Potential and Limitations

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FRONTIERS IN PHARMACOLOGY (2018)

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Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor

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INTERNATIONAL JOURNAL OF NANOMEDICINE (2018)

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Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles

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NANOSCALE RESEARCH LETTERS (2018)

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FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

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NEW ENGLAND JOURNAL OF MEDICINE (2018)

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TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure

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NATURE COMMUNICATIONS (2018)

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Meeting Abstract Oncology

A phase II pilot trial of nivolumab (N) plus albumin bound paclitaxel (AP) plus paricalcitol (P) plus cisplatin (C) plus gemcitabine (G) (NAPPCG) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC).

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JOURNAL OF CLINICAL ONCOLOGY (2018)

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Negative regulation of TGF-β by AMPK and implications in the treatment of associated disorders

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ACTA BIOCHIMICA ET BIOPHYSICA SINICA (2018)

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Nonmetabolic functions of metabolic enzymes in cancer development

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CANCER COMMUNICATIONS (2018)

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The evolving relationship of wound healing and tumor stroma

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JCI INSIGHT (2018)

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Reengineering the Physical Microenvironment of Tumors to Improve Drug Delivery and Efficacy: From Mathematical Modeling to Bench to Bedside

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TRENDS IN CANCER (2018)

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Functional Polymer Nanocarriers for Photodynamic Therapy

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PHARMACEUTICALS (2018)

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Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery

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CANCER RESEARCH (2018)

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Every step of the way: integrins in cancer progression and metastasis

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ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth

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EMBO MOLECULAR MEDICINE (2017)

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Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors

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MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells

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Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells

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ONCOGENE (2017)

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Article Gastroenterology & Hepatology

Autophagy Is Required for Activation of Pancreatic Stellate Cells, Associated With Pancreatic Cancer Progression and Promotes Growth of Pancreatic Tumors in Mice

Sho Endo et al.

GASTROENTEROLOGY (2017)

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Article Immunology

Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression

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IMMUNITY (2017)

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Article Biochemistry & Molecular Biology

A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis

Shinya Ito et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2017)

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Review Chemistry, Multidisciplinary

Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review

Thiruganesh Ramasamy et al.

JOURNAL OF CONTROLLED RELEASE (2017)

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Article Immunology

Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer

Daniel Ohlund et al.

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Epigenetics in fibrosis

Steven O'Reilly

MOLECULAR ASPECTS OF MEDICINE (2017)

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Mechanistic understanding of nanoparticles' interactions with extracellular matrix: the cell and immune system

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PARTICLE AND FIBRE TOXICOLOGY (2017)

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Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis

Venessa T. Chin et al.

SCIENCE TRANSLATIONAL MEDICINE (2017)

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Review Cell Biology

Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone

Shinya Ito et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2017)

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Novel peptide probes to assess the tensional state of fibronectin fibers in cancer

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NATURE COMMUNICATIONS (2017)

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Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions

Orianne Olivares et al.

NATURE COMMUNICATIONS (2017)

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Desmoplastic Reaction in 3D-Pancreatic Cancer Tissues Suppresses Molecular Permeability

Michiya Matsusaki et al.

ADVANCED HEALTHCARE MATERIALS (2017)

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Article Biology

Matrix-regulated integrin αvβ5 maintains α5β1-dependent desmoplastic traits prognostic of neoplastic recurrence

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ELIFE (2017)

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Article Multidisciplinary Sciences

Tranilast-induced stress alleviation in solid tumors improves the efficacy of chemo- and nanotherapeutics in a size-independent manner

Panagiotis Papageorgis et al.

SCIENTIFIC REPORTS (2017)

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Cancer nanomedicine: progress, challenges and opportunities

Jinjun Shi et al.

NATURE REVIEWS CANCER (2017)

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Understanding the extracellular forces that determine cell fate and maintenance

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Terminating the criminal collaboration in pancreatic cancer: Nanoparticle-based synergistic therapy for overcoming fibroblast induced drug resistance

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The good and the bad collagens of fibrosis - Their role in signaling and organ function

M. A. Karsdal et al.

ADVANCED DRUG DELIVERY REVIEWS (2017)

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Review Biochemistry & Molecular Biology

Drug Discovery and Chemical Biology of Cancer Epigenetics

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CELL CHEMICAL BIOLOGY (2017)

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Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors

Tarun Ojha et al.

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Nrf2 promotes mutant K-ras/p53-driven pancreatic carcinogenesis

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CARCINOGENESIS (2017)

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Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer

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CANCER LETTERS (2017)

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Mechanisms and Barriers in Cancer Nanomedicine: Adressing Challenges, Looking for Solutions

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ACS NANO (2017)

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Preclinical models of pancreatic ductal adenocarcinoma

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JOURNAL OF PATHOLOGY (2016)

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An MMP-2 Responsive Liposome Integrating Antifibrosis and Chemotherapeutic Drugs for Enhanced Drug Perfusion and Efficacy in Pancreatic Cancer

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ACS APPLIED MATERIALS & INTERFACES (2016)

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Editorial Material Chemistry, Multidisciplinary

Stimuli-Responsive Programmed Specific Targeting in Nanomedicine

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ACS NANO (2016)

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PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

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ADVANCED DRUG DELIVERY REVIEWS (2016)

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α-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis

Kai-Hui Sun et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2016)

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Review Biochemistry & Molecular Biology

New photosensitizers for photodynamic therapy

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BIOCHEMICAL JOURNAL (2016)

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Review Biochemical Research Methods

Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer?

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BIOCONJUGATE CHEMISTRY (2016)

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Interstitial Pressure in Pancreatic Ductal Adenocarcinoma Is Dominated by a Gel-Fluid Phase

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BIOPHYSICAL JOURNAL (2016)

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Review Oncology

Key role of pancreatic stellate cells in pancreatic cancer

Srinivasa P. Pothula et al.

CANCER LETTERS (2016)

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Article Oncology

TGFβ Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis

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CANCER RESEARCH (2016)

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Cancer-Associated Fibroblasts in Pancreatic Cancer Are Reprogrammed by Tumor-Induced Alterations in Genomic DNA Methylation

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CANCER RESEARCH (2016)

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Role of hyaluronan in pancreatic cancer biology and therapy: Once again in the spotlight

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NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer

Iok In Christine Chio et al.

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Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation

Christopher J. Tape et al.

CELL (2016)

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Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer

Kohei Horioka et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2016)

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Integrin-mediated mechanotransduction

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JOURNAL OF CELL BIOLOGY (2016)

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Increased fibrosis and impaired intratumoral accumulation of macromolecules in a murine model of pancreatic cancer co-administered with FGF-2

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Analyzing spatiotemporal distribution of uniquely fluorescent nanoparticles in xenograft tumors

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JOURNAL OF CONTROLLED RELEASE (2016)

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To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?

F. Danhier

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Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity

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Diffusion-weighted and dynamic contrast-enhanced MRI of pancreatic adenocarcinoma xenografts: associations with tumor differentiation and collagen content

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Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial

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LANCET (2016)

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Surface charge critically affects tumor penetration and therapeutic efficacy of cancer nanomedicines

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The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery

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Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer

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NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE (2016)

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Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods

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NANOSCALE (2016)

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Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion

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Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities

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Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression

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NATURE MEDICINE (2016)

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Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy

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NATURE MEDICINE (2016)

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Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

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Integrin-based therapeutics: biological basis, clinical use and new drugs

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NATURE REVIEWS DRUG DISCOVERY (2016)

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Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style

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NATURE REVIEWS MOLECULAR CELL BIOLOGY (2016)

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TGF-β: the master regulator of fibrosis

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Stromal Palladin Expression Is an Independent Prognostic Factor in Pancreatic Ductal Adenocarcinoma

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PLOS ONE (2016)

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ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

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IFNγ and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma

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GM-CSF Mediates Mesenchymal-Epithelial Cross-talk in Pancreatic Cancer

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Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120

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CANCER DISCOVERY (2016)

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Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma

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THERANOSTICS (2016)

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Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

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ELIFE (2016)

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NATURE REVIEWS DISEASE PRIMERS (2016)

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The design of reversible hydrogels to capture extracellular matrix dynamics

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Fundamentals of cancer metabolism

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SCIENCE ADVANCES (2016)

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The biology and function of fibroblasts in cancer

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Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis

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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2015)

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The Pathway of Collagen Secretion

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ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 31 (2015)

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Fibroblast activation protein-α-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma

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BMC GASTROENTEROLOGY (2015)

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Ibrutinib Exerts Potent Antifibrotic and Antitumor Activities in Mouse Models of Pancreatic Adenocarcinoma

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CANCER RESEARCH (2015)

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Pulsed High-Intensity Focused Ultrasound Enhances Delivery of Doxorubicin in a Preclinical Model of Pancreatic Cancer

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CANCER RESEARCH (2015)

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Human Pancreatic Cancer Tumors Are Nutrient Poor and Tumor Cells Actively Scavenge Extracellular Protein

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CANCER RESEARCH (2015)

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Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts

Wenjing Pang et al.

CANCER SCIENCE (2015)

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Tissue Transglutaminase Mediated Tumor-Stroma Interaction Promotes Pancreatic Cancer Progression

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CLINICAL CANCER RESEARCH (2015)

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Targeting Acidity in Pancreatic Adenocarcinoma: Multispectral Optoacoustic Tomography Detects pH-Low Insertion Peptide Probes In Vivo

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CLINICAL CANCER RESEARCH (2015)

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SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial

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CLINICAL CANCER RESEARCH (2015)

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Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy

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EMBO MOLECULAR MEDICINE (2015)

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Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer

Daniel V. T. Catenacci et al.

JOURNAL OF CLINICAL ONCOLOGY (2015)

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Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors

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JOURNAL OF CONTROLLED RELEASE (2015)

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Review Oncology

Metabolic reprogramming: the emerging concept and associated therapeutic strategies

Go J. Yoshida

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2015)

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Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Cole R. Drifka et al.

MODERN PATHOLOGY (2015)

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Review Biochemistry & Molecular Biology

Halofuginone - The Multifaceted Molecule

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MOLECULES (2015)

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Tumour exosome integrins determine organotropic metastasis

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NATURE (2015)

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Principles of nanoparticle design for overcoming biological barriers to drug delivery

Elvin Blanco et al.

NATURE BIOTECHNOLOGY (2015)

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Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly

Edward R. Horton et al.

NATURE CELL BIOLOGY (2015)

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Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

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NATURE GENETICS (2015)

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Tranilast: A review of its therapeutic applications

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PHARMACOLOGICAL RESEARCH (2015)

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Anti-PEG immunity: emergence, characteristics, and unaddressed questions

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WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY (2015)

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Review Nutrition & Dietetics

Vitamins in Pancreatic Cancer: A Review of Underlying Mechanisms and Future Applications

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ADVANCES IN NUTRITION (2015)

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Review Biochemistry & Molecular Biology

Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis

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REDOX BIOLOGY (2015)

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Review Oncology

Overview of methods for overcoming hindrance to drug delivery to tumors, with special attention to tumor interstitial fluid

Gianfranco Baronzio et al.

FRONTIERS IN ONCOLOGY (2015)

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Review Chemistry, Medicinal

Stimuli-Responsive Polymeric Nanoparticles for Nanomedicine

Carina I. C. Crucho

CHEMMEDCHEM (2015)

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Review Pharmacology & Pharmacy

Classification of stimuli-responsive polymers as anticancer drug delivery systems

Bita Taghizadeh et al.

DRUG DELIVERY (2015)

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Vasodilator-Stimulated Phosphoprotein Promotes Activation of Hepatic Stellate Cells by Regulating Rab11-Dependent Plasma Membrane Targeting of Transforming Growth Factor Beta Receptors

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HEPATOLOGY (2015)

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Review Pharmacology & Pharmacy

Nanotechnology and tumor microcirculation

Mitsunobu R. Kano

ADVANCED DRUG DELIVERY REVIEWS (2014)

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The Role of Mechanical Forces in Tumor Growth and Therapy

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ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 (2014)

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Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

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BRITISH JOURNAL OF CANCER (2014)

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Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival

Berna C. Oezdemir et al.

CANCER CELL (2014)

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Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma

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CANCER CELL (2014)

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Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy

Mara H. Sherman et al.

CELL (2014)

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Review Chemistry, Multidisciplinary

Smart chemistry in polymeric nanomedicine

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CHEMICAL SOCIETY REVIEWS (2014)

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Review Cell Biology

Diverse functions of matrix metalloproteinases during fibrosis

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DISEASE MODELS & MECHANISMS (2014)

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Review Biochemistry & Molecular Biology

The extracellular matrix modulates the hallmarks of cancer

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EMBO REPORTS (2014)

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Article Gastroenterology & Hepatology

SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice

Albrecht Neesse et al.

GUT (2014)

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Review Pharmacology & Pharmacy

Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting

Masamichi Nakayama et al.

JOURNAL OF DRUG TARGETING (2014)

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Article Medicine, Research & Experimental

MMP-9 Responsive PEG Cleavable Nanovesicles for Efficient Delivery of Chemotherapeutics to Pancreatic Cancer

Prajakta S. Kulkarni et al.

MOLECULAR PHARMACEUTICS (2014)

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Review Biotechnology & Applied Microbiology

Shaping cancer nanomedicine: the effect of particle shape on the in vivo journey of nanoparticles

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NANOMEDICINE (2014)

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Remodelling the extracellular matrix in development and disease

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Stromal response to Hedgehog signaling restrains pancreatic cancer progression

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

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Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

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SCIENTIFIC REPORTS (2014)

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Review Pharmacology & Pharmacy

Fibroblasts in fibrosis: novel roles and mediators

Ryan T. Kendall et al.

FRONTIERS IN PHARMACOLOGY (2014)

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Physicochemical Properties Determine Nanomaterial Cellular Uptake, Transport, and Fate

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ACCOUNTS OF CHEMICAL RESEARCH (2013)

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Review Pharmacology & Pharmacy

The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo

Hiroshi Maeda et al.

ADVANCED DRUG DELIVERY REVIEWS (2013)

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Review Physiology

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

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AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2013)

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Review Biochemistry & Molecular Biology

Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2013)

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Review Biochemical Research Methods

Polymer-based stimuli-responsive nanosystems for biomedical applications

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BIOTECHNOLOGY JOURNAL (2013)

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Dynamic Mast Cell-Stromal Cell Interactions Promote Growth of Pancreatic Cancer

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CANCER RESEARCH (2013)

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Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells

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CANCER RESEARCH (2013)

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Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance

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CHEMICAL SOCIETY REVIEWS (2013)

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Tumor Stromal Architecture Can Define the Intrinsic Tumor Response to VEGF-Targeted Therapy

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CLINICAL CANCER RESEARCH (2013)

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Integrins in mechanotransduction

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CURRENT OPINION IN CELL BIOLOGY (2013)

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Review Rheumatology

Epigenetic regulation of wound healing and fibrosis

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CURRENT OPINION IN RHEUMATOLOGY (2013)

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Nanomaterials for Photohyperthermia: A Review

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CURRENT PHARMACEUTICAL DESIGN (2013)

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Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer

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Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes

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Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia

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Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia

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Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

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Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology

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Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine

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NEW ENGLAND JOURNAL OF MEDICINE (2013)

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CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer

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

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Therapeutic Targeting of Autophagy in Disease: Biology and Pharmacology

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StellaTUM: current consensus and discussion on pancreatic stellate cell research

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The extracellular matrix: A dynamic niche in cancer progression

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Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice

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Robert B. Hamanaka et al.

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Mechanisms of fibrosis: therapeutic translation for fibrotic disease

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NATURE MEDICINE (2012)

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Phage-based molecular probes that discriminate force-induced structural states of fibronectin in vivo

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TGF-β blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma

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Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance

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Overview of the Matrisome-An Inventory of Extracellular Matrix Constituents and Functions

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COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2012)

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A Central Role for RAF→MEK→ERK Signaling in the Genesis of Pancreatic Ductal Adenocarcinoma

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THERAPEUTIC DELIVERY (2012)

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ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 27 (2011)

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Cancer-Stroma Targeting Therapy by Cytotoxic Immunoconjugate Bound to the Collagen 4 Network in the Tumor Tissue

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BIOCONJUGATE CHEMISTRY (2011)

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Pancreatic Stellate Cells Radioprotect Pancreatic Cancer Cells through β1-Integrin Signaling

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CANCER RESEARCH (2011)

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Hedgehog signaling and therapeutics in pancreatic cancer

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CARCINOGENESIS (2011)

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Hallmarks of Cancer: The Next Generation

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CELL (2011)

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Retinoic Acid-Induced Pancreatic Stellate Cell Quiescence Reduces Paracrine Wnt-β-Catenin Signaling to Slow Tumor Progression

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GASTROENTEROLOGY (2011)

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Genetic changes in tumour microenvironments

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Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size

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NATURE NANOTECHNOLOGY (2011)

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Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration

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FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer

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Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

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CURRENT OPINION IN CELL BIOLOGY (2010)

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Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis

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FREE RADICAL BIOLOGY AND MEDICINE (2010)

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New doxorubicin-loaded phospholipid microbubbles for targeted tumor therapy: In-vivo characterization

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NEW ENGLAND JOURNAL OF MEDICINE (2010)

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Phenotype and Genotype of Pancreatic Cancer Cell Lines

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Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma

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Multiscale Measurements Distinguish Cellular and Interstitial Hindrances to Diffusion In Vivo

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Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

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CELL (2009)

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The reverse Warburg effect Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma

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CELL CYCLE (2009)

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Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

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SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients

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Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer

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AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2008)

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NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells

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AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2008)

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ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE (2008)

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Pancreatic stellate cells: Partners in crime with pancreatic cancer cells

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CANCER RESEARCH (2008)

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Sonic Hedgehog Promotes Desmoplasia in Pancreatic Cancer

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Collagen fibril formation - A new target to limit fibrosis

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Cellular and molecular mechanisms of fibrosis

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JOURNAL OF PATHOLOGY (2008)

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LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis

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MOLECULAR CANCER THERAPEUTICS (2008)

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A paracrine requirement for hedgehog signalling in cancer

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Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Nanocarriers as an emerging platform for cancer therapy

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Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts

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CANCER RESEARCH (2007)

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Force-induced unfolding of fibronectin in the extracellular matrix of living cells

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PLOS BIOLOGY (2007)

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Paradoxical roles for lysyl oxidases in cancer - A prospect

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JOURNAL OF CELLULAR BIOCHEMISTRY (2007)

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Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay

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Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma

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The pancreatic stellate cell: a star on the rise in pancreatic diseases

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JOURNAL OF CLINICAL INVESTIGATION (2007)

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MATRIX BIOLOGY (2007)

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Identification of fibroblast heterogeneity in the tumor microenvironment

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CANCER BIOLOGY & THERAPY (2006)

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Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression

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GENES & DEVELOPMENT (2006)

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Degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector

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CANCER RESEARCH (2006)

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Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis

JA McCarroll et al.

GUT (2006)

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Trp53R172H and KraSG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice

SR Hingorani et al.

CANCER CELL (2005)

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Identification of small molecule chemical inhibitors of the collagen-specific chaperone hsp47

CA Thomson et al.

JOURNAL OF MEDICINAL CHEMISTRY (2005)

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Protease-activated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells

A Masamune et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2005)

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Desmoplastic reaction influences pancreatic cancer growth behavior

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Review Oncology

Hyaluronan: From extracellular glue to pericellular cue

BP Toole

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The molecular basis of pancreatic fibrosis - Common stromal gene expression in chronic pancreatitis and pancreatic adenocarcinoma

CE Binkley et al.

PANCREAS (2004)

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SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions

N Sato et al.

ONCOGENE (2003)

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α-smooth muscle actin is crucial for focal adhesion maturation in myofibroblasts

B Hinz et al.

MOLECULAR BIOLOGY OF THE CELL (2003)

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Review Biochemistry & Molecular Biology

The integrin-actin connection, an eternal love affair

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EMBO JOURNAL (2003)

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Rat pancreatic stellate cells secrete matrix metal loproteinases: implications for extracellular matrix turnover

PA Phillips et al.

GUT (2003)

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Article Pharmacology & Pharmacy

Rho kinase inhibitors block activation of pancreatic stellate cells

A Masamune et al.

BRITISH JOURNAL OF PHARMACOLOGY (2003)

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Article Surgery

Pancreatic stellate cell activation and MMP production in experimental pancreatic fibrosis

T Yokota et al.

JOURNAL OF SURGICAL RESEARCH (2002)

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Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension

G Baneyx et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2002)

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Discovery of novel tumor markers of pancreatic cancer using global gene expression technology

CA Iacobuzio-Donahue et al.

AMERICAN JOURNAL OF PATHOLOGY (2002)

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Article Cell Biology

Alpha-smooth muscle actin expression upregulates fibroblast contractile activity

B Hinz et al.

MOLECULAR BIOLOGY OF THE CELL (2001)

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Article Oncology

Pancreatic tumors show high levels of hypoxia

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INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS (2000)

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