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Methotrexate

Methotrexate is a chemotherapeutic agent and immunosuppressant widely used in the treatment of various malignancies, autoimmune disorders, and other conditions.
It inhibits the enzyme dihydrofolate reductase, which is essential for cell division and growth.
Methotrexate has a complex pharmacokinetic profile and can exhibit variable therapeutic responses, necessitating careful optimization of dosage and administration protocols.
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Most cited protocols related to «Methotrexate»

One source of data employed was a large observational cohort of RA outpatients, who were seen on a regular basis, usually every 3 months. At each visit clinical, functional and laboratory core set variables [18 -20 (link)] and disease activity according to the composite scores DAS28 and SDAI were documented. Clinical assessments including joint counts were performed by independent, trained assessors who were not involved in treatment decisions. In July 2004, data on 998 patients followed in our clinics had been entered into the database. Each patient's first visit with complete documentation of clinical data was included to assemble the 'routine' cohort. There were 767 patients with at least one complete observation, and the first of these complete observations was used for the analyses. Of all 5070 patient observations that were initially documented, 2564 (50.6%) had missing data. Among these incomplete observations, 45% (n = 1150) had missing ESR and/or CRP values.
The second source of data was an independent cohort of newly diagnosed RA patients ('inception' cohort), whose visits were documented in the same manner as described above but starting from their first presentation to the clinic. The referral pattern and detailed follow up of these patients were described elsewhere [9 (link),27 (link)]. Radiographs of the hands and feet were obtained every 1–2 years, and were scored using the Larsen method [28 (link)] by a team of two experienced readers; they were presented to the readers in chronological order. Reassessment of a random subgroup of 40 radiographs of hands and feet revealed good agreement (R = 0.86, 95% confidence interval [CI] 0.81–0.91). All patients in the inception cohort received disease-modifying antirheumatic drugs, such as methotrexate, as soon as the diagnosis was made, with a few exceptions in patients who refused to take such therapy immediately.
The demographic and disease activity characteristics of patients in both cohorts are summarized in Table 1. Because several baseline variables were not normally distributed (see below), we present the median along with the first and third quartiles as robust descriptive measures.
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Publication 2005
Antirheumatic Drugs, Disease-Modifying Diagnosis Foot Joints Methotrexate Outpatients Patients Therapeutics X-Rays, Diagnostic
We included all breast cancer patients that were operated on at the Karolinska Hospital from 1 January 1994 to 31 December 1996 (n = 524), identified from the population-based Stockholm–Gotland breast cancer registry established in 1976. Available tumor material was frozen on dry ice or in liquid nitrogen and was stored in -70°C freezers. Figure 1 shows the details of various exclusions leading to the final 159 patients for analysis. The ethical committee at the Karolinska Hospital approved this microarray expression project.
The different reasons for exclusion were not influenced by age at diagnosis (Table 1). The 231 tumors that were not analyzed using expression profiling had a lower mean diameter, had fewer mean affected lymph nodes, and had fewer individuals with recurrent disease at the end of the study period (Table 1). For those excluded for other reasons, there did not seem to be a selection based on age or stage of the disease, compared with those patients included in the study (Table 1).
The Stockholm–Gotland Breast Cancer Registry, supplemented with patient records, were examined for information on the tumor size, the number of retrieved and metastatic axillary lymph nodes, the hormonal receptor status, distant metastases, the site and date of relapse, initial therapy, therapy for possible recurrences, the date and cause of death. Tumor sections from the primary tumors from patients with array profiles were classified using Elston–Ellis grading [18 (link)] by a blinded pathologist (HN).
In the adjuvant setting tamoxifen and/or goserelin is normally used for hormonal treatment, but mostly intravenous cyclophosphamide, methotrexate and 5-fluorouracil (CMF) on days 1 and 8 was used as adjuvant chemotherapy, except in high-risk patients who were offered inclusion in the Scandinavian Breast Group 9401 study [19 (link)]. After primary therapy, patients were recommended to have regular clinical examinations and yearly mammograms, in addition to laboratory and X-ray tests guided by clinical signs and symptoms. Patients were normally followed for 5 years. Patients followed up outside the Karolinska Hospital were tracked using a unique personal identification number. There was no loss to follow-up.
The relapse site, date of relapse, relapse therapy and date of death were ascertained in May 2002. The average follow-up was 6.1 years. Cause of death was coded as death due to breast cancer (including those with distant metastases but dying from other causes), death due to other malignancies and death due to nonmalignant disorders. Through the population-based Swedish Cancer Registry, second primary malignancies were identified.
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Publication 2005
Axilla Breast Chemotherapy, Adjuvant Cyclophosphamide Diagnosis Dry Ice Fluorouracil Freezing Goserelin Malignant Neoplasm of Breast Malignant Neoplasms Mammography Methotrexate Microarray Analysis Neoplasm Metastasis Neoplasms Nitrogen Nodes, Lymph Pathologists Patients Pharmaceutical Adjuvants Physical Examination Precancerous Conditions Radiography Recurrence Relapse Scandinavians Second Primary Cancers Tamoxifen Therapeutics
Fresh frozen breast cancer tissue from every third patient diagnosed and treated between 1991 and 2004 at the Koo Foundation Sun-Yat-Sen Cancer Center (KFSYSCC) were randomly selected for the study. Patients with follow-up periods shorter than three years were excluded, with the exception of those who died of the disease within three years of the initial treatment. In cases of ineligibility, the following sample was selected. The selected tissue samples spanned the major transition periods of adjuvant chemotherapy from CMF (cyclophosphamide, methotrexate and fluorouracil) to CAF (cyclophosphamide, doxorubicin, fluorouracil) and to taxane-based regimens. Four hundred forty seven samples were obtained, but 135 samples were excluded due to insufficient RNA (n = 1), poor RNA quality (n = 116), or unacceptable microarray quality (n = 18). A total of 312 samples were eligible for the study (Cohort 1). Gene expression profiles of an additional 15 lobular breast carcinoma samples, collected between 1999 and 2004 and previously studied, were also included (Cohort 2). All patients were treated by a multidisciplinary team according to the guidelines consistent with the National Comprehensive Cancer Network [18 ]. Following modified radical mastectomy or breast-conserving surgery plus dissection of axillary nodes, patients received radiotherapy, adjuvant chemotherapy, and/or hormonal therapy, if indicated. Neoadjuvant chemotherapy was administered to patients with locally advanced disease. The study was approved by the institutional review board (ID number 20020128A) and ethical approval was obtained from the same board for samples without obtainable informed consent.
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Publication 2011
Axilla Breast-Conserving Surgery Carcinoma, Lobular Chemotherapy, Adjuvant Cyclophosphamide Dissection Doxorubicin Ethics Committees, Research Fluorouracil Freezing Malignant Neoplasm of Breast Malignant Neoplasms Methotrexate Microarray Analysis Modified Radical Mastectomy Neoadjuvant Chemotherapy Patients Radiotherapy taxane Therapeutics Tissues Treatment Protocols
MCF 10A-H2B-mCherry cells were plated at densities that ranged from 156 to 5000 cells per well in 384-well plates using the Multidrop Combi Reagent Dispenser (Thermo Scientific) and grown for 24 hours. Cells were treated with a dilution series of drugs using a D300 Digital Dispenser (Hewlett-Packard) and imaged after drug addition in an Operetta (Perkin Elmer) for high content imaging system equipped with a live-cell chamber over a period of 72 hours.
In the case of methotrexate and oligomycin, 1250 cells were plated in 20–120 µl of media per well, treated with a dilution series of drug, and imaged for 72 hours.
In the case of linsitinib, cells were treated with a dilution series of linsitinib either with or without 10µM batimastat using a D300 Digital Dispenser and imaged in an IncuCyte ZOOM live cell imager (Essen Bioscience) for an additional 72 hours.
In the case of paclitaxel, cells were treated with a dilution series of paclitaxel and 200 nM of NucView 488 caspase 3 substrate (Biotium) using a D300 Digital Dispenser (Hewlett-Packard) and imaged after drug in an IncuCyte ZOOM live cell imager (Essen Bioscience) for an additional 72 hours. For immunofluorescence experiments, cells were grown for 24 hours and then treated with a dilution series of paclitaxel using a D300 Digital Dispenser (Hewlett-Packard) and incubated for 3, 6, 12, and 24 hours. Cells were fixed for 30 min in 3% formaldehyde, permeabilized for 30 min in phosphate buffered saline (PBS) with 0.3% Triton X-100 (Sigma-Aldrich), washed twice in PBS with 0.1% Tween 20 (Sigma-Aldrich; PBS-T), and blocked for 60 min with Odyssey blocking buffer. Anti-active Caspase-3 antibody (BD Biosciences) was diluted 1:1000 in Odyssey blocking buffer and incubated for 16 h at 4°C. Cells were washed three times in PBS-T for 5 min and incubated with Alexa Fluor 488 conjugated goat anti-rabbit secondary antibody for 60 min at room. Cells were washed two times in PBS-T, once with PBS, and stained for 30 min with whole cell stain (Thermo Fisher Scientific) and Hoechst (Thermo Fisher Scientific), and washed three times in PBS.
Publication 2016
alexa fluor 488 Antibodies, Anti-Idiotypic batimastat Cardiac Arrest Caspase Caspase 3 Cells Fingers Formaldehyde Goat Immunofluorescence linsitinib Methotrexate Oligomycins Paclitaxel Pharmaceutical Preparations Phosphates Rabbits Saline Solution Stains Technique, Dilution Triton X-100 Tween 20
Expert panel members used a standardized template (Supplementary Figure 1, available in the online version of this article at http://www3.interscience.wiley.com/journal/76509746/home) to submit 3–5 real-life case scenarios representing patients with early (within 1 year of symptom onset) undifferentiated inflammatory arthritis. These scenarios included all patient information that the experts considered relevant to rule in (positive factors) or out (negative factors) an eventual diagnosis of RA.
Each scenario captured the following patient elements: age and sex, duration of joint pain, duration of joint swelling, average duration of morning stiffness, and distribution of affected joints (swollen and tender joints, indicated on joint homunculi). The expert also provided information on the subsequent disease course, whether or not treatment with methotrexate (MTX) had been initiated at that assessment time point, and the expert’s opinion, using a 5-point Likert scale from 1 (very low probability) to 5 (very high probability), of the probability that the patient would, if untreated, “develop RA.”
Each completed case scenario was assigned a unique name. Two members of the steering committee (TN and GH) selected a subset of 30 case scenarios that best represented the spectrum of probability of RA development. Most of the cases were in the middle 3 probability categories. These 30 scenarios were then simplified and standardized. The submitting expert’s identity, opinion regarding the probability of RA, and information on the subsequent disease course were removed.
Publication 2010
Arthralgia Arthritis Committee Members Diagnosis Disease Progression Joints Methotrexate Patients

Most recents protocols related to «Methotrexate»

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Example 7

The synthesis of the methotrexate conjugates is described in (FIG. 12). A short ethylene diamine spacer may be introduced between methotrexate and the oxidized lipid. 6-Bromomethyl-pteridine-2,4-diamine trihydrobromide (BPT.HBr, 23) may be purchased from Ube Industries and coupled with intermediate 24 to produce 25. Compound 25 may be deprotected from tert-Boc followed by ester hydrolysis to produce amine terminated methotrexate (26). Reductive amination of 26 with ALDO (PE) or (PC) may be performed as described earlier to produce methotrexate prodrugs (27).

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Patent 2024
Amination Amines Anabolism Diamines Esters Ethylenediamines Hydrolysis Lipids Methotrexate Prodrugs Pteridines TERT protein, human
All patients with a record of an allogeneic HSCT between 2006 and 2015 were identified in the Patient Register (n = 2147). This cohort and methods used for identification of cGVHD have been described previously [14 (link)]. Briefly, the following exclusion criteria were applied: absence of a haematological malignancy prior to the HSCT; reused proxy identification numbers; age <18 or >75; and death within 6 months post-HSCT (S1 Fig). cGVHD is commonly defined as occurring onwards of 6 months post-HSCT [16 (link), 17 (link)]. For patients who survived ≥6 months post-HSCT (index date), the 0–6-month follow-up period was therefore 6–12 months post-HSCT. End of follow-up was Dec 31, 2016 (Cancer Register and Patient Register) and Dec 31, 2017 (Prescribed Drug Register and Cause of Death Register). Patient register records were reviewed, and patients were classified as having non-, mild, or moderate-severe cGVHD based on timing and extent of treatments commonly used for cGVHD using criteria developed by the authors (Fig 1) [14 (link)].
Patients were classified as non-cGVHD if, after taper of post-HSCT GvHD prophylaxis immunosuppression, they received neither systemic corticosteroids nor systemic immunosuppressive treatment (including everolimus, cyclosporine, methotrexate, mycophenolate, sirolimus, and tacrolimus) during the entire observation period. In Sweden, GvHD prophylaxis post-HSCT is discontinued by 3 months for matched sibling donors, and by 5 months for matched unrelated donors.
Patients with low-level cGVHD require less intensive immunosuppressive treatment. Based on this rationale, mild cGVHD was defined as patients receiving either corticosteroids or immunosuppressants alone. The following four mild cGVHD groups were defined: 1) patients who received systemic corticosteroid treatment >3 months alone, 2) patients whose last date of systemic corticosteroid treatment ended <3 months before censoring, 3) patients whose last date of systemic corticosteroid treatment ended <6 months before death, and 4) patients who received immunosuppressive treatment only (Fig 1).
Treatment modalities are similar for patients with moderate and severe cGVHD, which meant that it was not possible to separate these two groups. Patients with moderate-severe cGVHD require more intensive treatment than those with mild cGVHD. Based on this rationale, the following three moderate-severe cGVHD groups were defined: 1) patients who received corticosteroid treatment (irrespective of duration) and immunosuppressive treatment, 2) patients who received corticosteroid treatment (irrespective of duration) and extracorporeal photopheresis (ECP), and 3) patients who only received ECP.
Patients were assigned retrospectively to respective groups based on treatment (or not) received.
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Publication 2023
Adrenal Cortex Hormones Cyclosporine Donors Everolimus Hematologic Neoplasms Immunosuppression Immunosuppressive Agents Malignant Neoplasms Methotrexate Patients Pharmaceutical Preparations Photopheresis Sirolimus Tacrolimus Unrelated Donors
This study was approved by the Ethics Committee of Affiliated Tumor Hospital of Xinjiang Medical University and informed consent was obtained from all patients. Inclusion criteria: primary malignant tumor of bone near the knee joint; neoadjuvant chemotherapy is effective; the tumor did not invade the epiphyseal plate; the tumor did not invade important blood vessels and nerves; no infection. Exclusion criteria: pathological fracture; no limb preservation conditions; tumor invading epiphysis. There were 3 male and 2 female patients, the age range was from 8 to 14 years, with an average of 11.6 years. Distal femoral lesions were observed in 2 cases and proximal tibial lesions in 3 cases. All patients underwent X-ray, computed tomography, magnetic resonance imaging, and emission computed tomography examination, and a biopsy was performed after the examination. All cases were common osteosarcomas with no distant metastasis. According to the Enneking staging system, all cases were classified as stage IIB. The distance between the epiphyseal plate and the tumor was >1 cm in all cases. The magnetic resonance imaging image San Julian classification[5 (link)] was applied to classify the lesions. Type I lesions are defined as a distance from the edge of the tumor to the epiphyseal plate >2 cm; for Type II the distance from the edge of the tumor to the epiphyseal plate <2 cm or adjacent; for Type III the epiphyseal plate is partially in contact with the tumor or invaded epiphysis. All cases were classified as San Julian I or San Julian II and the epiphysis could be preserved. All the patients were treated with preoperative neoadjuvant chemotherapy, surgery, and postoperative adjuvant chemotherapy. All lesions were sensitive to preoperative neoadjuvant chemotherapy, and no pathological fractures occurred during chemotherapy. The chemotherapy regimen consisted of cisplatin 100 mg/m2, adriamycin 80 mg/m2, methotrexate 12 g/m2, and ifosfamide 12 g/m2.
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Publication 2023
Adriamycin Biopsy Blood Vessel Bone Cancer Chemotherapy, Adjuvant Cisplatin Epiphyseal Cartilage Epiphyses Ethics Committees, Clinical Femur Ifosfamide Infection Knee Joint Males Methotrexate Neoadjuvant Chemotherapy Neoplasm Metastasis Neoplasms Nervousness Operative Surgical Procedures Osteosarcoma Pathological Fracture Patients Pharmacotherapy Radiography Tibia Tomography, Emission-Computed Treatment Protocols Woman X-Ray Computed Tomography
This was a retrospective claim-based cohort study that utilized longitudinal claims data from the HealthCore Integrated Research Database® (HIRD®) from January 1, 2016 to August 31, 2019. The HIRD® contains data from January 2006 on patient enrollment, inpatient and outpatient medical care, prescription, and health care utilization. It is a large longitudinal medical and pharmacy claims database of health plan members comprising all regions of the US.
The data were accessed and used in full compliance with the relevant provisions of the Health Insurance Portability and Accountability Act. The study was conducted under the research provisions of Privacy Rule 45 CFR 164.514(e). Researchers’ access to claims data was limited to data stripped of identifiers to ensure confidentiality. An Institutional Review Board did not review the study since only this limited data set was accessed. This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Pharmacoepidemiology Practices as well as legal and regulatory requirements.
Adult patients aged ≥ 18 years with CD (International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM] diagnosis codes: K50.x) or UC (ICD-10-CM diagnosis codes: K51.x) who initiated an advanced therapy during the index period of July 1, 2016 through August 31, 2018 were included in the study. Index date was defined as the first observed occurrence of a claim (medical or pharmacy) for any eligible advanced therapy during the index period. For patients who started more than one therapy, only the earliest one observed was used. Included patients were enrolled in commercial, Medicare Advantage, or Medicare Supplemental plus Part D insurance plans for ≥ 6 months before the index date (pre-index period) and ≥ 12 months after index date (follow-up period). Eligible patients were required to have ≥ 2 medical claims for CD or UC from a provider of any specialty at least seven days apart during the study period, of which ≥ 1 claim occurred during the pre-index period.
In this study, advanced therapies for CD included TNFi (adalimumab, certolizumab, infliximab) and non-TNFi (natalizumab, ustekinumab, vedolizumab). For UC, advanced therapies included TNFi (adalimumab, golimumab, infliximab), non-TNFi (vedolizumab; ustekinumab as a potential switcher but not index drug), and other therapies (tofacitinib). Conventional therapies included 5-aminosalicylic acid derivatives (mesalazine and sulfasalazine) and immunosuppressants (azathioprine, methotrexate, mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine).
Patients were excluded if they had claims for ≥ 1 advanced therapy during the 6-month pre-index period to identify new initiators of advanced therapy. Patients who had evidence for other autoimmune diseases including psoriasis, lupus, ankylosing spondylitis, psoriatic arthritis, or rheumatoid arthritis (defined as ≥ 2 claims on different dates for the same disease) were also excluded in order to avoid misclassification of the estimated response rate (e.g., related to non-adherence) due to multiple indications.
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Publication 2023
Adalimumab Adult Ankylosing Spondylitis Arthritis, Psoriatic Autoimmune Diseases Azathioprine Care, Ambulatory Certolizumab Pegol Cyclosporine derivatives Diagnosis Ethics Committees, Research golimumab Health Planning Immunosuppressive Agents Infantile Neuroaxonal Dystrophy Infliximab Inpatient Insurance, Medigap Lupus Vulgaris Mercaptopurine Mesalamine Methotrexate Natalizumab Patient Acceptance of Health Care Patients Pharmaceutical Preparations Psoriasis Rheumatoid Arthritis Sulfasalazine Tacrolimus Therapeutics tofacitinib Ustekinumab vedolizumab
The algorithm to identify inadequate response to index advanced therapy was derived from a claims-based algorithm originally developed by Curtis et al. [16 (link)] and validated for rheumatoid arthritis. The first claim for advanced therapy is set as index date. Some modifications were made to the algorithm for UC and CD. The absence of all criteria listed in Table 1 denoted adequate response (stable disease); presence of one or more of them denoted inadequate response. For example, low index therapy adherence reflects inadequate response. All criteria were calculated based on the 1-year follow-up period for each patient. Details of the algorithm used are presented in Additional file 1: Table S1. In brief, the parameters of the algorithm included low adherence (defined as proportion of days covered [PDC] < 80%), switched/added new advanced therapy/new biologic, added a new conventional therapy, increased dose/frequency of advanced therapy/biologics, addition or dose increase of oral glucocorticoids, used a new pain medication, or had surgery for UC or CD.

Inadequate response criteria evaluated over 1-year follow-up for both Crohn’s disease and ulcerative colitis

Criteria based on the reference algorithm [16 (link)]
 Low adherence to index advanced therapy (defined as proportion of days covered [PDC] < 80%)
 Switch/add non-index advanced therapy
 Add new conventional therapy (methotrexate, sulfasalazine, and others)
 Dose or frequency increase of index advanced therapy (> 20% higher than the index dose)
 Addition or dose increase of oral glucocorticoid
Additional criteria for this study
 Use of pain medication classa not observed at pre-index period
 Use of surgery (Current Procedural Terminology codes for surgery are presented in Additional file 1: Table S2)

aOpioids, nonsteroidal anti-inflammatory drugs, non-narcotic analgesics, neuromodulators (anti-depressants, anticonvulsants, muscle relaxants)

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Publication 2023
Analgesics, Non-Narcotic Anti-Inflammatory Agents, Non-Steroidal Anticonvulsants Biopharmaceuticals Crohn Disease Glucocorticoids Methotrexate Muscle Tissue Neuromodulators Operative Surgical Procedures Pain Patients Pharmaceutical Preparations Rheumatoid Arthritis Sulfasalazine Therapeutics Therapies, Biological Ulcer

Top products related to «Methotrexate»

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Methotrexate is a laboratory reagent manufactured by Merck Group. It is a folic acid analog used in various biochemical and cell culture applications.
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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.
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Cisplatin is a platinum-based medication used as a chemotherapeutic agent. It is a crystalline solid that can be dissolved in water or saline solution for administration. Cisplatin functions by interfering with DNA replication, leading to cell death in rapidly dividing cells.
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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.
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Methotrexate (MTX) is a laboratory product manufactured by Merck Group. It is a chemical compound that inhibits the enzyme dihydrofolate reductase, which is involved in the synthesis of DNA and certain amino acids. MTX is commonly used in research applications to study cellular processes and as a tool in molecular biology experiments.
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Doxorubicin is a cytotoxic medication that is commonly used in the treatment of various types of cancer. It functions as an anthracycline antibiotic, which works by interfering with the DNA replication process in cancer cells, leading to their destruction. Doxorubicin is widely used in the management of different malignancies, including leukemia, lymphoma, and solid tumors.
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L-glutamine is an amino acid that is commonly used as a dietary supplement and in cell culture media. It serves as a source of nitrogen and supports cellular growth and metabolism.
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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.
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Methotrexate is a medication used in the treatment of various medical conditions. It is a folic acid antagonist that inhibits the enzyme dihydrofolate reductase, which is essential for the synthesis of DNA and cell division. Methotrexate is commonly used in the management of cancer, autoimmune disorders, and other inflammatory conditions.
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5-fluorouracil is a laboratory reagent used in scientific research. It is a pyrimidine analog that inhibits the enzyme thymidylate synthase, which is essential for DNA synthesis. 5-fluorouracil is commonly used in cell culture and molecular biology experiments to study cell growth and proliferation.

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Methotrexate, MTX, chemotherapeutic agent, immunosuppressant, dihydrofolate reductase, cell division, growth, PubCompare.ai, research optimization, protocols, literature, preprints, patents, reproducibility, accuracy, intelligent comparisons, effective products, procedures, Fetal Bovine Serum, FBS, Cisplatin, DMSO, Doxorubicin, L-glutamine, Penicillin/streptomycin, 5-fluorouracil