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Tamoxifen

Tamoxifen is a selective estrogen receptor modulator (SERM) used in the treatment and prevention of estrogen receptor-positive breast cancer.
It works by blocking the effects of estrogen in breast tissue, inhibiting tumor growth.
Tamoxifen is commonly prescribed as an adjuvant therapy following surgery or radiation, and can also be used to reduce the risk of breast cancer in high-risk individuals.
This powerful medication has been extensively studied, with a wealth of research available on its efficacy, safety, and optimal use.
PubCompare.ai can help streamline your Tamoxifen research by locating the best protocols from literature, preprints, and patents, while utilizing AI-driven comparisons to enhance reproducibility and accuarcy.
Leveraging this tool can help you achieve better results in your Tamoxifen-related studies.

Most cited protocols related to «Tamoxifen»

1
Tamoxifen-Induced Cre Recombination
Cited 408 times
Tamoxifen was prepared by first dissolving in ethanol (20 mg/500 μl) and mixing this solution with 980 μl corn oil for a final concentration of 20 mg/ml. Ethanol was then removed with a heated speed vacuum. Mice containing CreERT2 that were ~2 months old were injected with approximately 200 μl tamoxifen solution (200 mg/kg) once a day over 5 days. Animals were monitored for adverse effects, and if these became apparent, treatment was stopped. One week after treatment ended, animals were processed as described below for ISH or localization of XFP.
Madisen L., Zwingman T.A., Sunkin S.M., Oh S.W., Zariwala H.A., Gu H., Ng L.L., Palmiter R.D., Hawrylycz M.J., Jones A.R., Lein E.S, & Zeng H. (2009). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nature neuroscience, 13(1), 133-140.
Publication 2009
Aftercare Animals Corn oil Ethanol Mice, House Tamoxifen Vacuum
2
Tamoxifen-Induced Cre Recombination
Cited 372 times
Tamoxifen was prepared by first dissolving in ethanol (20 mg/500 μl) and mixing this solution with 980 μl corn oil for a final concentration of 20 mg/ml. Ethanol was then removed with a heated speed vacuum. Mice containing CreERT2 that were ~2 months old were injected with approximately 200 μl tamoxifen solution (200 mg/kg) once a day over 5 days. Animals were monitored for adverse effects, and if these became apparent, treatment was stopped. One week after treatment ended, animals were processed as described below for ISH or localization of XFP.
Madisen L., Zwingman T.A., Sunkin S.M., Oh S.W., Zariwala H.A., Gu H., Ng L.L., Palmiter R.D., Hawrylycz M.J., Jones A.R., Lein E.S, & Zeng H. (2009). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nature neuroscience, 13(1), 133-140.
Publication 2009
Aftercare Animals Corn oil Ethanol Mice, House Tamoxifen Vacuum
3
Genetic Manipulation and Melanoma Induction in Mice
Cited 77 times
BRafCA, Tyr::CreER and Ptenlox4-5 mice were genotyped as previously described 17 (link),20 (link),24 (link). Cre-mediated conversion of BRafCA to BRafVE and the deletion of exons 4 and 5 of Pten were assessed by PCR as previously described. Topical administration of 4-hydroxytamoxifen (4-HT) was performed by preparing a 25-50mg/ml (65-130mM) solution of 4-HT (70% Z-isomer, Sigma) in DMSO and applying enough solution to wet the right ear, right flank and tail with a small paint brush on post-natal days 2, 3, and 4. For localized melanoma induction on the back skin, adult (6-8 weeks of age) mice were treated topically with 1-2 μl of 1.9mg/ml (5mM) 4-HT at 6-8 weeks of age using a similar protocol. Generalized induction in adult mice was performed by intra-peritoneal injection of 1mg of tamoxifen/40g mouse on 3 consecutive days. In this case tamoxifen was prepared as a 10mg/ml suspension in peanut oil. PD352901 was dissolved in 0.5%(w/v) Hydroxy-propyl-methylcellulose, 0.2%(v/v) Tween 80 (Sigma) and administered to mice daily by oral gavage at a dose of 12.5mg/kg. Rapamycin (LC Laboratories, Woburn, MA) was suspended in 0.5%(w/v) methylcellulose and administered to mice daily by oral gavage at a dose of 7.5mg/kg. Control animals in the melanoma prevention studies were administered with the relevant solvent. Tissues were prepared for analysis as previously described 17 (link),20 (link)
Dankort D., Curley D.P., Cartlidge R.A., Nelson B., Karnezis A.N., Damsky WE J.r., You M.J., DePinho R.A., McMahon M, & Bosenberg M. (2009). BRafV600E cooperates with Pten silencing to elicit metastatic melanoma. Nature genetics, 41(5), 544-552.
Publication 2009
Administration, Topical Adult Animals Deletion Mutation Exons Familial Atypical Mole-Malignant Melanoma Syndrome hydroxytamoxifen Hypromellose Injections, Intraperitoneal Isomerism Melanoma Methylcellulose Mice, House Peanut Oil PTEN protein, human Sirolimus Solvents Sulfoxide, Dimethyl Tail Tamoxifen Tissues Tube Feeding Tween 80
4
Monocyte Trafficking in Tumor Metastasis
Cited 61 times
Monocytes trafficking into primary tumors and their metastases were studied by adoptive transfer of mouse (Ly6C/Gr1+ or Ly6C/Gr1−) or human (CD14+CD16+ and CD16−) monocytes using MMTV-PyMT autochthonous, human and mouse experimental metastasis and human orthotopic tumor models. Monocytes and macrophages were recovered by enzymatic disaggregation of the tumors followed by FACS analysis. To test mechanisms behind monocyte recruitment and the effect of inhibition of this trafficking on metastasis anti-mouse or human neutralizing CCL2 antibodies or Ccr2 null mutant mice were used. In order to ablate VEGF expression in monocytes a myeloid specific (Csf1r promoter) tamoxifen inducible Cre expressing strain was crossed with VEGFflox/flox mice and gene ablation induced by tamoxifen. Effects of monocyte depletion on tumor cell extravasation using Met-1, a FVB PyMT tumor derived metastatic cell line, was determined using an ex vivo intact lung imaging system and an in vitro extravasation assay.
Qian B.Z., Li J., Zhang H., Kitamura T., Zhang J., Campion L.R., Kaiser E.A., Snyder L.A, & Pollard J.W. (2011). CCL2 recruits inflammatory monocytes to facilitate breast tumor metastasis. Nature, 475(7355), 222-225.
Publication 2011
Adoptive Transfer Antibodies, Neutralizing Biological Assay CCL2 protein, human Cell Line, Tumor Cells Enzymes Gene, c-fms Genes Homo sapiens Lung Macrophage Mice, Knockout Monocytes Mouse mammary tumor virus Mus Neoplasm Metastasis Neoplasms Psychological Inhibition Strains Tamoxifen Vascular Endothelial Growth Factors
5
Monocyte Trafficking in Tumor Metastasis
Cited 61 times
Monocytes trafficking into primary tumors and their metastases were studied by adoptive transfer of mouse (Ly6C/Gr1+ or Ly6C/Gr1−) or human (CD14+CD16+ and CD16−) monocytes using MMTV-PyMT autochthonous, human and mouse experimental metastasis and human orthotopic tumor models. Monocytes and macrophages were recovered by enzymatic disaggregation of the tumors followed by FACS analysis. To test mechanisms behind monocyte recruitment and the effect of inhibition of this trafficking on metastasis anti-mouse or human neutralizing CCL2 antibodies or Ccr2 null mutant mice were used. In order to ablate VEGF expression in monocytes a myeloid specific (Csf1r promoter) tamoxifen inducible Cre expressing strain was crossed with VEGFflox/flox mice and gene ablation induced by tamoxifen. Effects of monocyte depletion on tumor cell extravasation using Met-1, a FVB PyMT tumor derived metastatic cell line, was determined using an ex vivo intact lung imaging system and an in vitro extravasation assay.
Qian B.Z., Li J., Zhang H., Kitamura T., Zhang J., Campion L.R., Kaiser E.A., Snyder L.A, & Pollard J.W. (2011). CCL2 recruits inflammatory monocytes to facilitate breast tumor metastasis. Nature, 475(7355), 222-225.
Publication 2011
Adoptive Transfer Antibodies, Neutralizing Biological Assay CCL2 protein, human Cell Line, Tumor Cells Enzymes Gene, c-fms Genes Homo sapiens Lung Macrophage Mice, Knockout Monocytes Mouse mammary tumor virus Mus Neoplasm Metastasis Neoplasms Psychological Inhibition Strains Tamoxifen Vascular Endothelial Growth Factors

Most recents protocols related to «Tamoxifen»

1
Spontaneous HNSCC Model and Therapy
The Bmi1CreER; RosatdTomato mice received drinking water with 4NQO for 16 weeks to allow HNSCC to develop, followed by normal drinking water for 6 weeks, to form a spontaneous model of HNSCC. The mice were randomly divided into groups at 22 weeks. Before sacrificing the mice, they were given tamoxifen to label Bmi1+ CSCs. For the treatment assay, Bmi1CreER; RosatdTomato mice were divided randomly into the indicated groups, and injected with the indicated ASO PVT1 (10 nM, Integrated Biotech Solutions Co., Ltd, Shanghai, China) and ASO NC over the whole mouse tongue by twice-weekly subcutaneous injection for 4 weeks. For combination therapy, mice were intraperitoneally injected with anti-PD1 (BioXcell, Lebanon, NH, USA, 200 μg/mouse twice per week). After mice were sacrificed, the cervical lymph nodes and tongues were removed, and the lesion surface areas were calculated. For histological investigation and immunostaining, longitudinally cut tongues (dorsal/ventral) and intact lymph nodes were fixed overnight in 4% paraformaldehyde and paraffin-embedded. 10 sections of 5 mm thick tissue blocks were cut, and they were then stained with hematoxylin and eosin (HE). The SCC number was counted and regions were measured [8 (link)]. The following criteria were used to grade the invasiveness of the HNSCC: showing signs of normal or epithelial dysplasia appearance (grade 1); distinct invasion, unclearness of the basement membrane, drop and diffuse infiltration into the superficial portion of the muscle layer (grade 2); loss of the basement membrane; extensive invasion into deep muscle layer (grade 3). To examine cervical lymph node metastasis of HNSCC, the sections of cervical lymph nodes were immunostained with anti-PCK antibodies.
Qin Z., Zhang W., Liu S., Wang Y., Peng X, & Jia L. (2023). PVT1 inhibition stimulates anti-tumor immunity, prevents metastasis, and depletes cancer stem cells in squamous cell carcinoma. Cell Death & Disease, 14(3), 187.
Full text: Click here
Publication 2023
Anti-Antibodies Biological Assay Bladder Detrusor Muscle BMI1 protein, human Combined Modality Therapy Eosin Lymph Node Metastasis Membrane, Basement Mice, House Neck Neoplasm, Intraepithelial Nodes, Lymph Paraffin paraform PVT1 long-non-coding RNA, human Squamous Cell Carcinoma of the Head and Neck Subcutaneous Injections Tamoxifen Tissues Tongue
2
Angiotensin II-Induced Gene Expression
The effects of αv knockout on gene expression were examined at 6 weeks after tamoxifen injection followed or not by a 4-week treatment with Ang II. Anaesthesia was induced by isoflurane inhalation at 3.5% in 1 L/min oxygen, and then maintained at 1.5% in 1 L/min oxygen during the intervention. Angiotensin II was administered at 1.5 mg/kg/day for 28 days via subcutaneous Alzet osmotic minipumps (Charles River, L’Arbresle, France). Prior to pump implantation, mice were conditioned to tail-cuff blood pressure measurement using a computerized mouse tail-cuff sphygmomanometer (Hatteras Instruments, Inc., NC, USA). Systolic arterial pressure (SAP) and heart rate (HR) were measured on the day of surgery and on day 28 prior to euthanasia. Mice were euthanized via exsanguination under isoflurane anaesthesia (1.5% in 1 L/min oxygen). Carotid arteries were used for morphological and histological analyses and thoracic aorta for all other parameters. It is generally accepted including our previous studies that changes in gene and/or protein expression are similar in these two main conductance arteries.14 (link),15 (link)
Li Z., Belozertseva E., Parlakian A., Bascetin R., Louis H., Kawamura Y., Blanc J., Gao-Li J., Pinet F., Lacy-Hulbert A., Challande P., Humphrey J.D., Regnault V, & Lacolley P. (2023). Smooth muscle αv integrins regulate vascular fibrosis via CD109 downregulation of TGF-β signalling. European Heart Journal Open, 3(2), oead010.
Publication 2023
Anesthesia Angiotensin II Arteries Carotid Arteries Determination, Blood Pressure Euthanasia Exsanguination Gene Expression Genes Inhalation Isoflurane Mus Osmosis Ovum Implantation Oxygen Proteins Rate, Heart Rivers Sphygmomanometers Surgery, Day Systolic Pressure Tail Tamoxifen Thoracic Aorta
3
Inducible Deletion of Integrin αv in Smooth Muscle Cells
SM22-CreERT2(ki) transgenic mice have been described previously.12 (link)Itgavflox/flox mice were obtained from A. Lacy-Hulbert13 (link) and maintained on a C57BL/6 background. Itgavflox/flox mice were crossed with SM22-CreERT2(ki) mice to generate SM22-CreERT2(ki)/Itgavflox/flox double-transgenic mice. All mice (male and female) were genotyped by PCR as described previously.12 (link),13 (link) At 8–10 months of age, Itgavflox/flox/SM22-CreERT2(ki)/+ mice were injected intraperitoneally with 1 mg of tamoxifen in 100 µL of peanut oil for 3 days to generate αvSMKO mice. Itgavflox/flox littermates injected for 3 days with tamoxifen were used as controls. All experiments were performed 4–6 weeks after tamoxifen injection. Mice were housed in a temperature- and humidity-controlled facility with a 12 h light/day cycle and given free access to standard rodent chow and water. All animal work was conducted in accordance with French regulations and experimental guidelines of the European Community, and the protocols were approved by the local Animal Ethics Committee of the University of Lorraine, France.
Li Z., Belozertseva E., Parlakian A., Bascetin R., Louis H., Kawamura Y., Blanc J., Gao-Li J., Pinet F., Lacy-Hulbert A., Challande P., Humphrey J.D., Regnault V, & Lacolley P. (2023). Smooth muscle αv integrins regulate vascular fibrosis via CD109 downregulation of TGF-β signalling. European Heart Journal Open, 3(2), oead010.
Publication 2023
Animal Ethics Committees Animals Females Humidity Males Mice, Laboratory Mice, Transgenic Peanut Oil Rodent Tamoxifen
4
Tonotopic Labeling of Auditory Neurons
For auditory stimulation, mice at P16–P30 were housed in a custom soundproof box, and received sound stimulation as illustrated in Figure 1A. After three quiet hours, continuous sound was delivered for 6 h at ∼90 dB using BioSigRP software (Tucker-Davis Technologies). A 15-kHz tone of 20-ms duration with 2-ms rise and fall time was presented at a rate of 41 Hz (leaving 4.4-ms gaps). The sound was produced by a PC sound card, processed by RZ6 Multi-I/O Processer (Tucker-Davis Technologies), and delivered via a speaker (Ignite) mounted directly above the animals. The sound was paused for no more than 5 min after the first 3 h to administer an intraperitoneal injection of 160 mg/kg Tamoxifen or 50 mg/kg 4-OHT. Tamoxifen was first dissolved in absolute EtOH, then diluted 1/10 by volume with sunflower oil followed by 2-h sonication or overnight nutation, and stored at 4°C in the dark for up to one week. 4-OHT was first dissolved in absolute EtOH at 20 mg/ml, and diluted with Chen oil (a 1:4 mixture of castor oil:sunflower seed oil) to 10 mg/ml for injection (Guenthner et al., 2013 (link)). After sound stimulation, mice were kept in quiet for another 3 h before returning to their home cage, and killed 4–5 d later for experiments. This protocol has been shown to produce tonotopic labeling in DCN and VCN from TRAP mice crossed with the Ai14 reporter line (Guenthner et al., 2013 (link)). The time line is consistent with the time window determined by the pharmacodynamics of 4-OHT in mice (Robinson et al., 1991 (link)).
Ma Y., Shu W.C., Lin L., Cao X.J., Oertel D., Smith P.H, & Jackson M.B. (2023). Imaging Voltage Globally and in Isofrequency Lamina in Slices of Mouse Ventral Cochlear Nucleus. eNeuro, 10(3), ENEURO.0465-22.2023.
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Publication 2023
4,17 beta-dihydroxy-4-androstene-3-one Acoustic Stimulation Animals Castor oil Ethanol Injections, Intraperitoneal Mice, House Oil, Sunflower Sound Tamoxifen TimeLine
5
Adoptive Transfer and Immunization Assay
Adoptive transfers were performed by intravenous injection of 5 × 103 Igλ-enriched B1-8 B cells into the retro-orbital plexus of anesthetized mice. Mice were immunized the following day. All immunizations were performed using NP-CGG (Biosearch Technologies) resuspended at 1 mg/ml in D-PBS and mixed 50:50 volumetrically with Alhydrogel (Accurate Chemical and Scientific). Mice were injected subcutaneously with 20 μl of this solution (10 μg of NP-CGG per injection) in each ear. At endpoint, the facial LNs from each side were pooled for analysis (see figure legends for various timepoints).
Unmodified αIgE (clone R1E4; produced by hybridoma culture as described below), αIgE with a mutated Fc-receptor binding domain (clone R1E4; Cedarlane), or control rat γ globulin were diluted in D-PBS to a concentration of 0.3 mg/ml and injected intravenously to achieve a final dose of 3.25 mg/kg. For the experiment shown, mouse γ globulin (Jackson ImmunoResearch) was used as a control whereas in previous experiments that the presented data are representative of rat γ globulin was used as a control.
Tamoxifen was dissolved at 50 mg/ml in corn oil (Sigma-Aldrich) by shaking at 56°C for several hours. Approximately 100 μl/mouse was delivered by intraperitoneal injection to achieve a dose of 200 mg/kg.
Wade-Vallance A.K., Yang Z., Libang J.B., Robinson M.J., Tarlinton D.M, & Allen C.D. (2023). B cell receptor ligation induces IgE plasma cell elimination. The Journal of Experimental Medicine, 220(4), e20220964.
Publication 2023
Adoptive Transfer Alhydrogel B-Lymphocytes Clone Cells Corn oil Face Fc Receptor gamma-Globulin Hybridomas Immunization Injections, Intraperitoneal Mice, House NP 10 Tamoxifen

Top products related to «Tamoxifen»

1
Tamoxifen by Merck Group
Sourced in United States, Germany, Sao Tome and Principe, United Kingdom, Switzerland, Macao, China, Australia, Canada, Japan, Spain, Belgium, France, Italy, New Zealand, Denmark
Tamoxifen is a drug used in the treatment of certain types of cancer, primarily breast cancer. It is a selective estrogen receptor modulator (SERM) that can act as both an agonist and antagonist of the estrogen receptor. Tamoxifen is used to treat and prevent breast cancer in both men and women.
2
Corn oil by Merck Group
Sourced in United States, Germany, Sao Tome and Principe, Italy, Canada, Japan, India, France, United Kingdom, Belgium
Corn oil is a versatile laboratory product derived from the kernels of corn. It serves as a useful medium for various applications in the scientific and research fields. The oil's core function is to provide a consistent and reliable source of lipids for experimental purposes.
3
4 hydroxytamoxifen by Merck Group
Sourced in United States, Germany, United Kingdom, Australia, Israel, Spain, France, Macao, China
4-hydroxytamoxifen is a laboratory reagent used in scientific research. It is a metabolite of the anti-cancer drug tamoxifen. The core function of 4-hydroxytamoxifen is to serve as a tool for researchers to investigate cellular processes and pathways.
4
Fetal bovine serum (fbs) by Thermo Fisher Scientific
Sourced in United States, China, United Kingdom, Germany, Australia, Japan, Canada, Italy, France, Switzerland, New Zealand, Brazil, Belgium, India, Spain, Israel, Austria, Poland, Ireland, Sweden, Macao, Netherlands, Denmark, Cameroon, Singapore, Portugal, Argentina, Holy See (Vatican City State), Morocco, Uruguay, Mexico, Thailand, Sao Tome and Principe, Hungary, Panama, Hong Kong, Norway, United Arab Emirates, Czechia, Russian Federation, Chile, Moldova, Republic of, Gabon, Palestine, State of, Saudi Arabia, Senegal
Fetal Bovine Serum (FBS) is a cell culture supplement derived from the blood of bovine fetuses. FBS provides a source of proteins, growth factors, and other components that support the growth and maintenance of various cell types in in vitro cell culture applications.
5
4 oh tamoxifen by Merck Group
Sourced in United States, Germany, Sao Tome and Principe
4-OH tamoxifen is a laboratory reagent. It is a metabolite of the drug tamoxifen. 4-OH tamoxifen is used in research applications, but its specific function and intended use are not provided in this response.
6
Dimethyl sulfoxide (dmso) by Merck Group
Sourced in United States, Germany, United Kingdom, China, Italy, Sao Tome and Principe, France, Macao, India, Canada, Switzerland, Japan, Australia, Spain, Poland, Belgium, Brazil, Czechia, Portugal, Austria, Denmark, Israel, Sweden, Ireland, Hungary, Mexico, Netherlands, Singapore, Indonesia, Slovakia, Cameroon, Norway, Thailand, Chile, Finland, Malaysia, Latvia, New Zealand, Hong Kong, Pakistan, Uruguay, Bangladesh
DMSO is a versatile organic solvent commonly used in laboratory settings. It has a high boiling point, low viscosity, and the ability to dissolve a wide range of polar and non-polar compounds. DMSO's core function is as a solvent, allowing for the effective dissolution and handling of various chemical substances during research and experimentation.
7
Sunflower seed oil by Merck Group
Sourced in United States, Germany
Sunflower seed oil is a versatile liquid extracted from the seeds of the sunflower plant. It is a common ingredient in various laboratory applications due to its neutral taste and light color.
8
C57bl 6j by Jackson ImmunoResearch
Sourced in United States, Montenegro, Germany, United Kingdom, Japan, China, Canada, Australia, France, Colombia, Netherlands, Spain
C57BL/6J is a mouse strain commonly used in biomedical research. It is a common inbred mouse strain that has been extensively characterized.
9
Penicillin streptomycin by Thermo Fisher Scientific
Sourced in United States, Germany, United Kingdom, China, Canada, France, Japan, Australia, Switzerland, Israel, Italy, Belgium, Austria, Spain, Gabon, Ireland, New Zealand, Sweden, Netherlands, Denmark, Brazil, Macao, India, Singapore, Poland, Argentina, Cameroon, Uruguay, Morocco, Panama, Colombia, Holy See (Vatican City State), Hungary, Norway, Portugal, Mexico, Thailand, Palestine, State of, Finland, Moldova, Republic of, Jamaica, Czechia
Penicillin/streptomycin is a commonly used antibiotic solution for cell culture applications. It contains a combination of penicillin and streptomycin, which are broad-spectrum antibiotics that inhibit the growth of both Gram-positive and Gram-negative bacteria.
10
C57bl 6j mice by Jackson ImmunoResearch
Sourced in United States, Montenegro, Japan, Canada, United Kingdom, Germany, Macao, Switzerland, China
C57BL/6J mice are a widely used inbred mouse strain. They are a commonly used model organism in biomedical research.

More about "Tamoxifen"

Tamoxifen, a selective estrogen receptor modulator (SERM), is a powerful medication widely used in the treatment and prevention of estrogen receptor-positive breast cancer.
This medication works by blocking the effects of estrogen in breast tissue, effectively inhibiting tumor growth.
Tamoxifen is commonly prescribed as an adjuvant therapy following surgery or radiation, and can also be used to reduce the risk of breast cancer in high-risk individuals.
The efficacy, safety, and optimal use of Tamoxifen have been extensively studied, providing a wealth of research on this topic. 4-Hydroxytamoxifen (4-OH Tamoxifen) is an active metabolite of Tamoxifen, and has been studied for its potential therapeutic applications.
Corn oil and Sunflower seed oil are often used as vehicles for Tamoxifen administration in research studies, while DMSO (Dimethyl sulfoxide) is a commonly used solvent.
Fetal Bovine Serum (FBS) is a commonly used supplement in cell culture media, and may be used in conjunction with Tamoxifen in in vitro studies.
The C57BL/6J mouse strain is a widely used model in Tamoxifen-related research, often in combination with Penicillin/Streptomycin antibiotics.
PubCompare.ai, an AI-driven platform, can help streamline your Tamoxifen research by locating the best protocols from literature, preprints, and patents, while utilizing AI-driven comparisons to enhance reproducibility and accuarcy.
Leveraging this tool can help you achieve better results in your Tamoxifen-related studies.