• Hypericum beanii
• anti-inflammatory activity
• chemical constituents
• xanthones

• Mice
• Xanthones/pharmacology
• Xanthones/chemistry
• Xanthones/isolation & purification
• Animals
• RAW 264.7 Cells
• Nitric Oxide/metabolism
• Nitric Oxide/biosynthesis
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/chemistry
• Cyclooxygenase 2/metabolism
• Cyclooxygenase 2/genetics
• Macrophages/drug effects
• Macrophages/metabolism
• Interleukin-6/metabolism
• Interleukin-6/genetics
• Interleukin-6/biosynthesis
• Tumor Necrosis Factor-alpha/metabolism
• Interleukin-1beta/metabolism
• Interleukin-1beta/genetics
• Hypericum/chemistry
• Lipopolysaccharides/pharmacology
• Plant Extracts/pharmacology
• Plant Extracts/chemistry

• NO. 32270424 the National Natural Science Foundation of China
• 2022xkjT045 the Scientific Research Platform Improvement Project of Anhui Medical University
• KJ2020A0775 the University natural science research project of Anhui province
• KJ2019A1301 the University natural science research project of Anhui province

• central nervous system
• general anesthesia
• perioperative neurocognitive disorder
• peripheral inflammation
• preventive strategies

• MitoSOX Red
• fluorescence microscopy
• metformin
• oxidative stress
• sulindac
• superoxide
• time-lapse imaging

• Humans
• Sulindac/pharmacology
• Sulindac/therapeutic use
• Lung Neoplasms/drug therapy
• Superoxides
• Pharmaceutical Preparations
• Time-Lapse Imaging
• Cell Line, Tumor
• Microscopy, Fluorescence
• Metformin/pharmacology
• Metformin/therapeutic use

• R15 EY031533 NEI NIH HHS
• EY031533 NIH HHS

• COX-2 inhibitors
• Cyclooxygenase
• anticancer
• cardiovascular
• homeostatic
• secondary metabolites

• cutaneous neoplasia
• equine
• melanocytic tumors

• enzyme
• fluorescent probe
• near-infrared

• Biomarkers
• Fluorescent Dyes
• Optical Imaging/methods

• 22077055 National Natural Science Foundation of China
• 20JR5RA311 Natural Science Foundation of Gansu Province

The repurposing strategy of converting nimesulide from an anti-fever drug to an anti-cancer agent by modifying its main structure targeting HSP27 is gaining great attention these days. The goal of this study focuses on synthesizing a new nimesulide derivative with new ligands that have biological anti-cancer activities in different cancer models using the in-vitro assay. Nimesulide derivative L1 was synthesized, characterized by 1H NMR, 13C NMR, FTIR, melting point, mass spectra, and TGA analysis. A single crystal was diffracted and showed colorless block group P-1. The results revealed that L1 demonstrates potent anti-cancer activity with lung (H292), ovarian (SKOV3), and breast (SKBR3) cancer cell lines in-vitro models with IC₅₀ values below 8.8 µM.

Myeloid-derived suppressor cells (MDSCs) are one of the main suppressive cell population of the immune system. They play a pivotal role in the establishment of the tumor microenvironment (TME). In the context of cancers or other pathological conditions, MDSCs can differentiate, expand, and migrate in large quantities during circulation, inhibiting the cytotoxic functions of T cells and NK cells. This process is regulated by ROS, iNOS/NO, arginase-1, and multiple soluble cytokines. The definition of MDSCs and their phenotypes in humans are not as well represented as in other organisms such as mice, owing to the absence of the cognate molecule. However, a comprehensive understanding of the differences between different species and subsets will be beneficial for clarifying the immunosuppressive properties and potential clinical values of these cells during tumor progression. Recently, experimental evidence and clinical investigations have demonstrated that MDSCs have a close relationship with poor prognosis and drug resistance, which is considered to be a leading marker for practical applications and therapeutic methods. In this review, we summarize the remarkable position of MDSCs in solid tumors, explain their classifications in different models, and introduce new treatment approaches to target MDSCs to better understand the advancement of new approaches to cancer treatment.

• Animals
• Disease Models, Animal
• Humans
• Immunotherapy
• Models, Biological
• Myeloid-Derived Suppressor Cells/pathology
• Neoplasms/immunology
• Neoplasms/pathology
• Neoplasms/therapy

• aspirin
• colorectal cancer
• ibuprofen
• incident adenoma
• recurrent adenoma

• Adenoma/diagnosis
• Adenoma/epidemiology
• Adenoma/prevention & control
• Aged
• Aspirin/therapeutic use
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/prevention & control
• Early Detection of Cancer
• Female
• Humans
• Ibuprofen/therapeutic use
• Incidence
• Male
• Prospective Studies

• K07 CA230182 NCI NIH HHS
• T32 DK067872 NIDDK NIH HHS

• IL6
• PDIA3
• STAT3
• glioma
• microglia
• punicalagin

• Adult
• Aged
• Aged, 80 and over
• Brain Neoplasms/genetics
• Brain Neoplasms/pathology
• Cells, Cultured
• Cohort Studies
• Disease Progression
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Glioblastoma/genetics
• Glioblastoma/pathology
• Humans
• Macrophage Activation/genetics
• Macrophages/metabolism
• Macrophages/pathology
• Macrophages/physiology
• Male
• Microglia/metabolism
• Microglia/pathology
• Microglia/physiology
• Middle Aged
• Protein Disulfide-Isomerases/genetics
• Protein Disulfide-Isomerases/metabolism
• Tumor Microenvironment/genetics

• aspirin
• duration-risk relation
• meta-analysis
• neoplasm
• risk factor

• Biomarkers
• Epigenesis, Genetic
• Humans
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/mortality
• Non-alcoholic Fatty Liver Disease/physiopathology
• Prognosis
• RNA, Untranslated/blood
• RNA, Untranslated/genetics

• Phytochemistry
• chemical methods
• chromatographic
• partitioned
• phytoconstituents

The need for increasingly personalized medicine solutions (precision medicine) and quality medical treatments, has led to a growing demand and research for image-guided therapeutic solutions. Positron emission tomography (PET) is a powerful imaging technique that can be established using complementary imaging systems and selective imaging agents—chemical probes or radiotracers—which are drugs labeled with a radionuclide, also called radiopharmaceuticals. PET has two complementary purposes: selective imaging for diagnosis and monitoring of disease progression and response to treatment. The development of selective imaging agents is a growing research area, with a high number of diverse drugs, labeled with different radionuclides, being reported nowadays. This review article is focused on the use of pyrazoles as suitable scaffolds for the development of ¹⁸F-labeled radiotracers for PET imaging. A brief introduction to PET and pyrazoles, as key scaffolds in medicinal chemistry, is presented, followed by a description of the most important [¹⁸F]pyrazole-derived radiotracers (PET tracers) that have been developed in the last 20 years for selective PET imaging, grouped according to their specific targets.

• PET probes
• fluorine-18
• imaging pharmaceuticals
• positron emission tomography (PET)
• pyrazoles
• radionuclides

• aspirin
• colorectal neoplasm
• digestive tract neoplasm
• dose
• duration
• meta-analysis
• risk factor

Rumex japonicus Houtt. (RJ) is widely distributed in Korea, Japan, and China. The root of RJ has traditionally been used to treat constipation, jaundice, hematemesis, dysfunctional uterine bleeding, and gastrointestinal diseases. According to recent studies, plants of the genus Rumex have beneficial functionalities such as anti-microbial, antioxidative, and anti-inflammatory effects. Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, is a chronic inflammatory disease characterized by an abnormal immune response and epithelial barrier dysfunction. This study evaluates the protective effect of RJ against dextran sulfate sodium (DSS)-induced colitis.

Male 8-week-old C57BL/6 N mice were treated with methanolic extract of RJ for 14 days, and DSS-induced groups were administered 2.5% DSS for last 7 days. After sacrifice, the length and weight of the colon were measured, and colon sections were subjected to H&E staining, immunohistochemistry and Western blotting to investigate the changes of inflammatory cytokines, tight junction and apoptosis-related factors.

The colon of DSS-treated mouse was significantly shorter and heavier than the normal mouse. Moreover, DSS exposure induced an increase of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, occludin, zonula occludens-1, p21, p53 and Bcl-2, and decreased the expressions of IL-10, claudin-2 and cleaved caspase-3 in the colon tissue. These DSS-induced changes were inhibited by RJ treatment.

Our results indicate that RJ effectively suppresses DSS-induced colitis by protecting tight junction connections in the colonic tissue. We therefore infer that RJ has the potential as a medicine or ingredient for treating colitis.

• Colitis
• Cytokine
• Inflammation
• Rumex japonicas
• Tight junction

• GBM
• clinical trial
• glioblastoma multiforme
• glioma
• metformin

• ATF3
• adipocyte
• cancer
• glucose metabolism
• immunity

• Activating Transcription Factor 3/genetics
• Activating Transcription Factor 3/metabolism
• Adipocytes/metabolism
• Adipocytes/pathology
• Animals
• Endoplasmic Reticulum Stress/physiology
• Energy Metabolism/physiology
• Homeostasis/physiology
• Humans
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology

• Anti-Inflammatory Agents, Non-Steroidal
• Aspirin
• Bile Duct Neoplasms
• Bile Ducts, Intrahepatic
• Cholangiocarcinoma
• Humans

• cluster of differentiation 133
• cyclooxygenase-2
• prostaglandin E2
• renal cell carcinoma
• sunitinib resistance

• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Aspirin/therapeutic use
• Bile Duct Neoplasms/epidemiology
• Bile Duct Neoplasms/prevention & control
• Cholangiocarcinoma/epidemiology
• Cholangiocarcinoma/prevention & control
• Humans
• Risk Factors

• Anti-inflammatory activity
• Antitumor activity
• Cyclooxygenase-2 inhibition
• Nimesulide analogues
• Synthetic approaches

• immunometabolism
• myeloid-derived suppressor cells (MDSCs)
• tumor immunity
• tumor microenvironment
• tumor-associated macrophages (TAMs)

• immunometabolism
• myeloid-derived suppressor cells (MDSCs)
• tumor immunity
• tumor microenvironment
• tumor-associated macrophages (TAMs)

• Animals
• CD11b Antigen/metabolism
• Cell Differentiation
• Cell Line, Tumor
• Cellular Reprogramming
• Cytokines/metabolism
• Humans
• Immunity
• Macrophages/immunology
• Metformin/metabolism
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Myeloid Cells/immunology
• Myeloid-Derived Suppressor Cells/immunology
• Osteosarcoma/immunology
• Oxidative Phosphorylation
• Th1 Cells/immunology
• Th2 Cells/immunology
• Tumor Microenvironment

Emergence of drug-resistant cancer phenotypes is a challenge for anti-cancer therapy. Cancer stem cells are identified as one of the ways by which chemoresistance develops.

We investigated the anti-inflammatory combinatorial treatment (DA) of doxorubicin and aspirin using a preclinical microfluidic model on cancer cell lines and patient-derived circulating tumour cell clusters. The model had been previously demonstrated to predict patient overall prognosis.

We demonstrated that low-dose aspirin with a sub-optimal dose of doxorubicin for 72 h could generate higher killing efficacy and enhanced apoptosis. Seven days of DA treatment significantly reduced the proportion of cancer stem cells and colony-forming ability. DA treatment delayed the inhibition of interleukin-6 secretion, which is mediated by both COX-dependent and independent pathways. The response of patients varied due to clinical heterogeneity, with 62.5% and 64.7% of samples demonstrating higher killing efficacy or reduction in cancer stem cell (CSC) proportions after DA treatment, respectively. These results highlight the importance of using patient-derived models for drug discovery.

This preclinical proof of concept seeks to reduce the onset of CSCs generated post treatment by stressful stimuli. Our study will promote a better understanding of anti-inflammatory treatments for cancer and reduce the risk of relapse in patients.

Glioblastoma remains a fatal diagnosis. Previous research has shown that metformin, which is an inhibitor of complex I of the respiratory chain, may inhibit some brain tumor initiating cells (BTICs), albeit at dosages that are too high for clinical use. Here, we explored whether a combined treatment of metformin and diclofenac, which is a non-steroidal anti-inflammatory drug (NSAID) shown to inhibit glycolysis by interfering with lactate efflux, may lead to additive or even synergistic effects on BTICs (BTIC-8, -11, -13 and -18) and tumor cell lines (TCs, U87, and HTZ349). Therefore, we investigated the functional effects, including proliferation and migration, metabolic effects including oxygen consumption and extracellular lactate levels, and effects on the protein level, including signaling pathways. Functional investigation revealed synergistic anti-migratory and anti-proliferative effects of the combined treatment with metformin and diclofenac on BTICs and TCs. Signaling pathways did not sufficiently explain synergistic effects. However, we observed that metformin inhibited cellular oxygen consumption and increased extracellular lactate levels, indicating glycolytic rescue mechanisms. Combined treatment inhibited metformin-induced lactate increase. The combination of metformin and diclofenac may represent a promising new strategy in the treatment of glioblastoma. Combined treatment may reduce the effective doses of the single agents and prevent metabolic rescue mechanisms. Further studies are needed in order to determine possible side effects in humans.

• BTICs
• diclofenac
• glioma
• lactate
• metformin

• Apoptotic markers
• antioxidant
• MAPK
• myeloperoxidase
• cyclooxygenase-2

• 1,2-Dimethylhydrazine/toxicity
• Animals
• Antioxidants/pharmacology
• Apoptosis/drug effects
• Berberine/pharmacology
• Carcinogens/toxicity
• Cell Proliferation/drug effects
• Colonic Neoplasms/chemically induced
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/pathology
• Inflammation Mediators/metabolism
• Male
• Rats

In a variety of experimental models, dietary phytochemicals have been demonstrated to exhibit pronounced and versatile bioactivities. Importantly, the possibility of such phytochemicals for human application has been supported in part by epidemiological surveys, which have demonstrated that frequent ingestion of vegetables and fruits containing abundant phytochemicals lowers the risk of onset of various diseases. However, the action mechanisms underlying those dietary phytochemical activities remain to be fully elucidated. For example, even though the anti-oxidant effects of natural polyphenols have long received widespread attention from food scientists, their roles in and contribution to those bioactivities remain controversial because of their poor bioavailability, resulting in extremely low concentrations in the bloodstream. Meanwhile, another important question is why phytochemicals have beneficial effects for animals, including humans, since they are biosynthesized by plants as compounds necessary for adaptation to environmental stress. In regard to that fundamental question, we recently reported novel and unique mechanisms of action of zerumbone, a sesquiterpene with anti-inflammatory and chemopreventive properties. This agent was found to partially exhibit bioactivity through its non-specific interactions with cellular proteins. More strikingly, a non-specific protein binding action of zerumbone was revealed to partially contribute to its anti-inflammatory functions via activation of heat shock factor 1. The present review article highlights and introduces our recent findings regarding the proteo-stress-mediated mechanisms of this phytochemical, along with the concept of hormesis.

• hormesis
• mechanism
• protein quality control
• target molecule
• zerumbone

• Cancer stem cells
• DNA hypermethylation
• De novo synthesis
• Embryonic stem cells
• Epigenetic silencing
• Epithelial–mesenchymal transition (EMT)
• Glycolipid enriched microdomain (GEM)
• Glycosynapse
• Hematogenous metastasis
• Histone modification
• Hypoxia inducible factor (HIF)
• Incomplete synthesis
• MicroRNA
• Scavenger pathway

• adenomas
• biology
• cancer
• colitis
• food
• inflammation
• long-chain carboxychromanol
• medicine
• tocopherol
• tocotrienol

• Animals
• Antineoplastic Agents/pharmacology
• Carcinogenesis/drug effects
• Chromans/pharmacology
• Humans
• Neoplasms/prevention & control
• Neoplasms/therapy
• Signal Transduction/drug effects
• Tocopherols/pharmacology
• Vitamin E/analogs & derivatives
• Vitamin E/pharmacology
• Vitamins/pharmacology
• gamma-Tocopherol/pharmacology

• Combination index
• Hyaluronic acid
• Ibuprofen
• Paclitaxel
• Solid lipid nanoparticle

• PET imaging
• celecoxib
• colorectal carcinoma
• cyclooxygenase-2
• indomethacin

• biomarkers
• body mass index
• cancer risk
• pancreatic cancer
• prostaglandin E2 metabolite

• breast cancer
• case-control study
• cruciferous vegetable
• risk association
• self-reported consumption

• K07 CA148888 NCI NIH HHS

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Cause of Death
• Celecoxib/administration & dosage
• Diphosphonates/administration & dosage
• Disease-Free Survival
• Early Termination of Clinical Trials
• Follow-Up Studies
• Gonadotropin-Releasing Hormone/agonists
• Gonadotropin-Releasing Hormone/antagonists & inhibitors
• Humans
• Imidazoles/administration & dosage
• Lymphatic Metastasis
• Male
• Middle Aged
• Orchiectomy
• Proportional Hazards Models
• Prostate-Specific Antigen/blood
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/surgery
• Survival Rate
• Time Factors
• Zoledronic Acid

• 22744 Cancer Research UK
• 12518 Cancer Research UK
• 3804 Cancer Research UK
• MC_UU_12023/20 Medical Research Council
• 10588 Cancer Research UK

The aim of the present study was to investigate the role of autophagy in celecoxib-induced apoptosis in human hormone-insensitive prostate cancer cell line PC3 cells and to explore the underlying molecular mechanism leading to autophagic activation. A cell viability assay was applied to investigate the effect of various concentrations of celecoxib (0, 40, 60, 80, 100 and 120 µmol/l) on PC3 cells for 24 and 48 h, respectively. The 50% inhibitory concentration of celecoxib for 24 h was chosen for subsequent experiments. Annexin V-fluorescein isothiocyanate/propidium iodide double staining flow cytometry, as well as caspase 3 and poly (ADP-ribose) polymerase proteins detected by western blotting, were applied to analyze cellular apoptosis induced by celecoxib. Ultrastructural cellular changes observed by transmission electron microscopy and the level of LC-3 II and P62 detected by western blotting were used to determine the activation of autophagy. It was demonstrated that celecoxib induced apoptosis and activated autophagy in PC3 cells in a dose- and time-dependent manner. Furthermore, flow cytometry and western blotting were applied to elucidate whether the role of autophagy in celecoxib-induced apoptosis is protective or destructive. Blockade of autophagy markedly increased apoptosis, suggesting that celecoxib-activated autophagy was cytoprotective. Additionally, c-jun-N-terminal kinase (JNK) was demonstrated to have a role in autophagic activation, and suppression of JNK was able to reduce autophagy and increase apoptosis. In conclusion, the results of the present study indicate that celecoxib induces apoptosis in PC3 cells; however, celecoxib also activates JNK-mediated autophagy, which exerts cytoprotective effects in prostate cancer PC3 cells. Blockade of autophagy via the JNK-mediated pathway may provide a promising strategy for prostate cancer therapy.

• apoptosis
• autophagy
• cyclooxygenase-2
• prostate cancer

MicroRNAs (miRNAs) regulate disease-relevant metabolic pathways. However, most current pathway identification methods fail to consider miRNAs in addition to genes when analyzing pathways. We developed a powerful method called Subpathway-GMir to construct miRNA-regulated metabolic pathways and to identify miRNA-mediated subpathways by considering condition-specific genes, miRNAs, and pathway topologies. We used Subpathway-GMir to analyze two liver hepatocellular carcinomas (LIHC), one stomach adenocarcinoma (STAD), and one type 2 diabetes (T2D) data sets. Results indicate that Subpathway-GMir is more effective in identifying phenotype-associated metabolic pathways than other methods and our results are reproducible and robust. Subpathway-GMir provides a flexible platform for identifying abnormal metabolic subpathways mediated by miRNAs, and may help to clarify the roles that miRNAs play in a variety of diseases. The Subpathway-GMir method has been implemented as a freely available R package.

• cancer
• mRNA
• microRNA
• pathway identification
• regulation

• Aged
• Aspirin/therapeutic use
• Bile Duct Neoplasms/epidemiology
• Bile Duct Neoplasms/prevention & control
• Case-Control Studies
• Cholangiocarcinoma/epidemiology
• Cholangiocarcinoma/prevention & control
• Cohort Studies
• Cyclooxygenase Inhibitors/therapeutic use
• Female
• Humans
• Male
• Middle Aged
• Minnesota/epidemiology
• Risk Factors

• R01 CA165076 NCI NIH HHS
• UL1 TR000135 NCATS NIH HHS
• P30 CA015083 NCI NIH HHS
• P30 DK084567 NIDDK NIH HHS
• N01 CA015083 NCI NIH HHS

• Animals
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Colorectal Neoplasms/prevention & control
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors/adverse effects
• Cyclooxygenase Inhibitors/pharmacology
• Cyclooxygenase Inhibitors/therapeutic use
• Epidemiologic Studies
• Humans
• Isoenzymes/antagonists & inhibitors
• Membrane Proteins
• Prostaglandin-Endoperoxide Synthases
• Randomized Controlled Trials as Topic

• Animals
• Cyclooxygenase 2
• Dog Diseases/metabolism
• Dogs
• Hemangiosarcoma/metabolism
• Hemangiosarcoma/veterinary
• Histiocytic Disorders, Malignant/metabolism
• Immunohistochemistry/veterinary
• Mast-Cell Sarcoma/metabolism
• Prostaglandin-Endoperoxide Synthases/metabolism

• Adenocarcinoma/enzymology
• Adenocarcinoma/veterinary
• Animals
• Carcinoma/enzymology
• Carcinoma/veterinary
• Cyclooxygenase 2/metabolism
• Dog Diseases/enzymology
• Dogs
• Female
• Gene Expression Regulation, Neoplastic
• Immunohistochemistry/veterinary
• Mammary Neoplasms, Animal/enzymology

Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts₂O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [¹⁸F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [¹⁸F]F⁻ (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/μmol (EOS) based on decay-corrected calculations. Ex-vivo analysis of [¹⁸F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [¹⁸F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro-environments.

• Inflammation
• NSAIDs
• cyclooxygenase
• molecular imaging

• COX-1 and COX-2
• Inhibitors
• Isoindolines
• LS-SVM
• MLR

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit several pathways in experimental models of breast carcinogenesis, but epidemiological evidence remains insufficient to support their use for breast cancer prevention. We examined the association between use of NSAIDs and breast cancer risk in a prospective cohort.

The Sister Study is a prospective cohort study of women who had a sister(s) with breast cancer. As of December 2013, 2118 incident breast cancers were ascertained from 50,884 women enrolled between 2003 and 2009. Lifetime history of NSAID use was estimated from self-reported data in pill-years, with 1 pill per week for a year equivalent to 1 pill-year. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer in relation to pill-years of use for different NSAIDs, with adjustment for potential confounders.

In the full cohort, although there was some evidence that use of non-aspirin, non-COXib NSAIDs was associated with lower breast cancer risk, there was little evidence of overall association for most categories of NSAID use. Among postmenopausal women NSAID use was not associated with reduced risk of breast cancer. However, among premenopausal women there was significantly reduced risk for any NSAID (HR_4vs1 = 0.66, 95 % CI: 0.50–0.87) and specifically for aspirin (HR_4vs1 = 0.57, 95 % CI: 0.33–0.98), with small, but non-significant reductions in risk for other drug classes.