Aromatase was purified from term human placenta by immuno-affinity chromatography in a highly active form. It was complexed with androstenedione and crystallized at 4 °C in the oxidized high-spin ferric state of the haem iron with poly(ethylene glycol) 4000 as the precipitant. The space group was P3221 and the unit cell parameters are a =b =140.2 Å, c =119.3 Å, α = β =90°, γ =120°, having one aromatase molecule in the asymmetric unit. Diffraction data at about 100 K were collected initially at the Cornell High Energy Synchrotron Source (CHESS) and then to 2.90 Å resolution at the Advanced Photon Source, Argonne National Laboratory, with glycerol as a cryoprotectant. Two data sets at the Fe absorption edge were also collected at the CHESS. The structure was solved by the molecular replacement method coupled with Bijvoet difference Fourier synthesis for identifying the correct solution. Model building and refinement were performed with Coot and Refmac5, respectively. The final model contained 452 amino acid residues; 44 N-terminal and 7 C-terminal residues could not be built because of weakness of their electron densities. The final R factor for all reflections between 38 and 2.90 Å resolution was 0.214, and the R-free value was 0.244. The r.m.s. deviations of bond lengths and angles from ideal values were 0.009 Å and 1.32°, respectively. The average isotropic thermal factor for all atoms was 77.3 Å2. There were only two violations in the backbone torsion angle Ramachandran plot, both in the loop regions. The oxyferryl Fe(IV)=O moiety was generated by adding an oxygen atom to Fe with the modelling software MOE (Chemical Computing Group) The exemestane molecule was built into the active site by superimposing it on the experimentally derived androstenedione atomic positions with MOE.
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Exemestane
Exemestane
Exemestane is a steroidal aromatase inhibitor used to treat hormone-receptor positive breast cancer in postmenopausal women.
It works by blocking the enzyme aromatase, which is responsible for converting androgens into estrogens.
Exemestane has been shown to be effective in reducing the risk of recurrence and improving overall survival in early-stage breast cancer patients.
Researchers can use PubCompare.ai's AI-driven platform to optimize research protocols for Exemestane and enhance the reproducibility of their findings.
The platform helps identify the most effective approaches by comparing protocols from literature, preprints, and patents, streamlining the research process and providing more reliable resutls.
It works by blocking the enzyme aromatase, which is responsible for converting androgens into estrogens.
Exemestane has been shown to be effective in reducing the risk of recurrence and improving overall survival in early-stage breast cancer patients.
Researchers can use PubCompare.ai's AI-driven platform to optimize research protocols for Exemestane and enhance the reproducibility of their findings.
The platform helps identify the most effective approaches by comparing protocols from literature, preprints, and patents, streamlining the research process and providing more reliable resutls.
Most cited protocols related to «Exemestane»
Amino Acids
Anabolism
Androstenedione
Aromatase
Asthenia
Cells
Chromatography, Affinity
Cryoprotective Agents
Electrons
exemestane
Glycerin
Heme
Homo sapiens
Iron
Oxygen
Placenta
polyethylene glycol 4000
Reflex
R Factors
Vertebral Column
Anastrozole
Biopsy
BLOOD
Cell Nucleus
Diploid Cell
exemestane
Formalin
Freezing
Immunohistochemistry
INDEL Mutation
Letrozole
MLL protein, human
Mutation
Neoplasms
Operative Surgical Procedures
Point Mutation
Surgeons
START Trial A patients were randomised to either 50 Gy in 25 fractions (control group) or 41·6 Gy in 13 fractions or 39 Gy in 13 fractions (experimental schedules). All regimens were administered over 5 weeks to eliminate treatment time as a variable. This treatment involved five fractions per week in the control group and five treatments per fortnight (Monday, Wednesday, Friday one week, Tuesday and Thursday the next week) in each of the two experimental schedules.
Randomisation was arranged via telephone at the Clinical Trials and Statistics Unit at the Institute of Cancer Research (ICR-CTSU), Sutton, UK, where patient details were recorded and treatment was allocated. Randomisation was not blinded. Computer-generated random permuted blocks were used as the method of allocation, with patients stratified by hospital, type of surgery (breast conserving surgery or mastectomy), and intention to give a tumour bed boost dose or not. Use of adjuvant systemic treatment was recorded, with a requirement of at least a 2-week gap between exposure to chemotherapy and radiotherapy.
Patients lay in a supine treatment position. The planning target volume was defined as the whole breast with a 1 cm margin to palpable breast tissue; where regional radiotherapy was indicated, the planning target volume was supraclavicular nodes with or without axillary chain with a 1 cm margin. The decision to give regional radiotherapy was made before randomisation and was only used in 14% of patients (table 1 ). In two patients prescribed radiotherapy to the breast and supraclavicular fossa and randomised to the 41·6 Gy schedule, the total dose administered to the supraclavicular fossa was reduced to 39 Gy because of the sensitivity of brachial plexus to fraction size. Most patients were treated with 6 MV x-rays, although treatment with higher energies or cobalt γ-rays was allowed after discussion with the START Trial radiotherapy quality assurance team. Planning protocols were specified at the time of notification of participation into the study and had to conform to the minimum quality criteria described in the START Trial A protocol. Planning protocols varied slightly between centres, but within each centre they were identical in each fractionation group. Doses were prescribed to international reference points.11 Departments were required to have a protocol specifying whether patients who had breast-conserving surgery would receive a boost to the tumour bed, and to use an electron field of appropriate energy to deliver 10 Gy in five daily fractions to the 100% isodose after initial radiotherapy.
The principal endpoints specified in the protocol were local-regional relapse, normal tissue effects, and quality of life. Local-regional tumour relapse was defined as local relapse in breast or chest wall, and regional relapse in ipsilateral axilla or supraclavicular fossa if it had been within an irradiated target volume. Any ipsilateral regional relapse outside the radiotherapy target volume was excluded from the analysis of local-regional relapse. Normal tissue effects in the breast, arm, and shoulder were assessed by photographic comparison with baseline, patient self-reported assessments, and physician assessments. Other endpoints were disease-free and overall survival, second primary cancers, and health economic consequences. Disease-free survival was defined as time to any breast cancer-related event (local-regional or distant relapse, contralateral breast cancer, or death from breast cancer). Data relating to five key breast normal tissue effects from the patient quality of life self-assessments are presented here. Separate papers will present the full analysis of all self-assessments and physician assessments of normal tissue effects, and of quality of life. Cases of ischaemic heart disease, symptomatic rib fracture, and symptomatic lung fibrosis were recorded during follow-up; incidence with and without confirmation of diagnosis (eg, using imaging and further investigation) was included. Brachial plexopathy was reported if damage to the brachial plexus was suspected and the patient had symptoms of pain, parasthesia, numbness, or other sensory symptoms (graded on a 4-point scale). Suspected cases of brachial plexopathy were subject to confirmation by neurophysiological assessment and MRI.
Patients were reviewed every year for tumour relapse and radiotherapy-induced normal tissue effects. Clinical data were recorded on pre-printed case report forms and sent to the coordinating clinical trials office at the ICR-CTSU, Sutton, UK. Photographs were taken at baseline (post-surgery and pre-radiotherapy) and then at 2 and 5 years to assess changes to the breast based on change in size, shrinkage, and shape, and scored on a 3-point graded scale. Changes in breast appearance (photographic) were scored by three observers blind to patient identity, treatment allocation, and year of follow-up, and a final agreed score reached by consensus. The assessment of change in breast appearance from photographs was fully validated in the pilot study.7 (link) Breast size and surgical deficit were both defined from the baseline photographs by the same three observers applying 3-point graded scales. Quality of life data were obtained using standardised questionnaires19 (link), 20 (link), 21 (link), 22 (link) at baseline and at 6 months, 1, 2, and 5 years. Post-baseline quality of life questionnaires included an additional four protocol-specific items relating to changes in the affected breast after radiotherapy (skin changes in the area of the affected breast, overall change in breast appearance, firmness to touch of the affected breast, and reduction in size of the affected breast). Of these four items, patients who had had mastectomy only rated change in skin appearance after radiotherapy. Details of the quality of life study protocol and baseline data have been published elsewhere.10 (link)
The trial was coordinated by the ICR-CTSU, Sutton, UK. The trial was overseen by a Steering Committee of several independent experts joined by members of the ICR-CTSU, START Trial Management Group, and representatives of the funding bodies (as observers). The Trial Management Group was responsible for the day-to-day management of the trial, and the emerging safety and efficacy data was reviewed regularly by the Independent Data Monitoring Committee. Central statistical monitoring of data was done by ICR-CTSU, supplemented by selected on-site source document verification.
Randomisation was arranged via telephone at the Clinical Trials and Statistics Unit at the Institute of Cancer Research (ICR-CTSU), Sutton, UK, where patient details were recorded and treatment was allocated. Randomisation was not blinded. Computer-generated random permuted blocks were used as the method of allocation, with patients stratified by hospital, type of surgery (breast conserving surgery or mastectomy), and intention to give a tumour bed boost dose or not. Use of adjuvant systemic treatment was recorded, with a requirement of at least a 2-week gap between exposure to chemotherapy and radiotherapy.
Patients lay in a supine treatment position. The planning target volume was defined as the whole breast with a 1 cm margin to palpable breast tissue; where regional radiotherapy was indicated, the planning target volume was supraclavicular nodes with or without axillary chain with a 1 cm margin. The decision to give regional radiotherapy was made before randomisation and was only used in 14% of patients (
Demographic and clinical characteristics at randomisation of the 2236 patients in START Trial A
| 50 Gy in 25 fractions n=749 (%) | 41·6 Gy in 13 fractions n=750 (%) | 39 Gy in 13 fractions n=737 (%) | |||
|---|---|---|---|---|---|
| Age (years) | |||||
| 20–29 | 5 (0·7) | 4 (0·5) | 3 (0·4) | 12 (0·5) | |
| 30–39 | 38 (5·1) | 40 (5·3) | 38 (5·2) | 116 (5·2) | |
| 40–49 | 116 (15·5) | 136 (18·1) | 129 (17·5) | 381 (17·0) | |
| 50–59 | 280 (37·4) | 283 (37·7) | 286 (38·8) | 849 (38·0) | |
| 60–69 | 215 (28·7) | 192 (25·6) | 194 (26·3) | 601 (26·9) | |
| 70–79 | 87 (11·6) | 85 (11·3) | 78 (10·6) | 250 (11·2) | |
| 80− | 8 (1·1) | 10 (1·3) | 9 (1·2) | 27 (1·2) | |
| Mean (SD) | 57·6 (10·5) | 57·0 (10·7) | 57·1 (10·5) | 57·2 (10·6) | |
| Time from surgery to randomisation (weeks); median (IQR) [range] | 8·8 (5·3–20·8) [0·4–71·3] | 9·4 (5·9–20·2) [1·0–50·3] | 9·3 (5·4–21·1) [1·1–53·6] | 9·1 (5·4–20·7) [0·4–71·3] | |
| Primary surgery | |||||
| Breast conserving surgery | 631 (84·2) | 641 (85·5) | 628 (85·2) | 1900 (85·0) | |
| Mastectomy | 118 (15·8) | 109 (14·5) | 109 (14·8) | 336 (15·0) | |
| Histological type | |||||
| Invasive ductal | 581 (77·6) | 585 (78·0) | 584 (79·2) | 1750 (78·3) | |
| Invasive lobular | 88 (11·7) | 95 (12·7) | 83 (11·3) | 266 (11·9) | |
| Mixed ductal/lobular | 21 (2·8) | 17 (2·3) | 17 (2·3) | 55 (2·5) | |
| Other | 57 (7·6) | 51 (6·8) | 52 (7·1) | 160 (7·2) | |
| Not known | 2 (0·3) | 2 (0·3) | 1 (0·1) | 5 (0·2) | |
| Pathological node status | |||||
| Positive | 222 (29·6) | 197 (26·3) | 224 (30·4) | 643 (28·8) | |
| Negative | 514 (68·6) | 536 (71·5) | 497 (67·4) | 1547 (69·2) | |
| Not known (no axillary surgery) | 12 (1·6) | 17 (2·3) | 15 (2·0) | 44 (2·0) | |
| Not known (missing data) | 1 (0·1) | 0 (0·0) | 1 (0·2) | 2 (0·1) | |
| Tumour size (cm) | |||||
| <1 | 24 (3·2) | 26 (3·5) | 24 (3·3) | 74 (3·3) | |
| 1− | 362 (48·3) | 347 (46·3) | 355 (48·2) | 1064 (47·6) | |
| 2− | 202 (27·0) | 203 (27·1) | 198 (26·9) | 603 (27·0) | |
| 3− | 156 (20·8) | 169 (22·5) | 157 (21·3) | 482 (21·6) | |
| Not known | 5 (0·7) | 5 (0·7) | 3 (0·3) | 13 (0·6) | |
| Tumour grade | |||||
| 1 | 157 (21·0) | 150 (20·0) | 149 (20·2) | 456 (20·4) | |
| 2 | 369 (49·3) | 379 (50·5) | 368 (49·9) | 1116 (49·9) | |
| 3 | 212 (28·3) | 207 (27·6) | 210 (28·5) | 629 (28·1) | |
| Not known (not applicable) | 11 (1·5) | 10 (1·3) | 6 (0·8) | 27 (1·2) | |
| Not known | 0 (0·0) | 4 (0·6) | 4 (0·5) | 8 (0·4) | |
| Adjuvant therapy | |||||
| None | 52 (6·9) | 53 (7·1) | 67 (9·1) | 172 (7·7) | |
| Tamoxifen/no chemotherapy | 416 (55·5) | 418 (55·7) | 376 (51·0) | 1210 (54·1) | |
| Chemotherapy/no tamoxifen | 86 (11·5) | 77 (10·3) | 82 (11·1) | 245 (11·0) | |
| Tamoxifen+chemotherapy | 173 (23·1) | 187 (25·0) | 188 (25·5) | 548 (24·5) | |
| Other endocrine therapy | 17 (2·3) | 13 (1·7) | 17 (2·3) | 47 (2·1) | |
| Not known | 5 (0·7) | 2 (0·2) | 7 (0·9) | 14 (0·6) | |
| Lymphatic treatment | |||||
| None | 8 (1·1) | 14 (1·9) | 13 (1·8) | 35 (1·6) | |
| Surgery/no radiotherapy | 610 (81·4) | 636 (84·8) | 620 (84·1) | 1866 (83·5) | |
| Radiotherapy/no surgery | 3 (0·4) | 4 (0·5) | 2 (0·3) | 9 (0·4) | |
| Surgery+radiotherapy | 119 (15·9) | 95 (12·7) | 95 (12·9) | 309 (13·8) | |
| Not known | 9 (1·2) | 1 (0·1) | 7 (0·9) | 17 (0·8) | |
| Boost (BCS patients only) | n=631 | n=641 | n=628 | n=1900 | |
| Yes | 381 (60·4) | 391 (61·0) | 380 (60·5) | 1152 (60·6) | |
| No | 242 (38·3) | 249 (38·8) | 241 (38·4) | 732 (38·5) | |
| Not known | 8 (1·3) | 1 (0·2) | 7 (1·1) | 16 (0·8) | |
| From baseline photographs | n=413 | n=421 | n=416 | n=1250 | |
| Breast size | |||||
| Small | 43 (10·4) | 47 (11·2) | 41 (9·9) | 131 (10·5) | |
| Medium | 294 (71·2) | 324 (77·0) | 322 (77·4) | 940 (75·2) | |
| Large | 76 (18·4) | 50 (11·9) | 53 (12·7) | 179 (14·3) | |
| Surgical deficit | |||||
| Small | 232 (56·2) | 235 (55·8) | 249 (59·9) | 716 (57·3) | |
| Medium | 142 (34·4) | 146 (34·7) | 132 (31·7) | 420 (33·6) | |
| Large | 39 (9·4) | 40 (9·5) | 35 (8·4) | 114 (9·1) | |
BCS=breast-conserving surgery.
Lobular and other histological types.
Other endocrine therapies include combinations of tamoxifen/anastrozole/letrozole/exemestane/goserelin, mostly within randomised trials.
The principal endpoints specified in the protocol were local-regional relapse, normal tissue effects, and quality of life. Local-regional tumour relapse was defined as local relapse in breast or chest wall, and regional relapse in ipsilateral axilla or supraclavicular fossa if it had been within an irradiated target volume. Any ipsilateral regional relapse outside the radiotherapy target volume was excluded from the analysis of local-regional relapse. Normal tissue effects in the breast, arm, and shoulder were assessed by photographic comparison with baseline, patient self-reported assessments, and physician assessments. Other endpoints were disease-free and overall survival, second primary cancers, and health economic consequences. Disease-free survival was defined as time to any breast cancer-related event (local-regional or distant relapse, contralateral breast cancer, or death from breast cancer). Data relating to five key breast normal tissue effects from the patient quality of life self-assessments are presented here. Separate papers will present the full analysis of all self-assessments and physician assessments of normal tissue effects, and of quality of life. Cases of ischaemic heart disease, symptomatic rib fracture, and symptomatic lung fibrosis were recorded during follow-up; incidence with and without confirmation of diagnosis (eg, using imaging and further investigation) was included. Brachial plexopathy was reported if damage to the brachial plexus was suspected and the patient had symptoms of pain, parasthesia, numbness, or other sensory symptoms (graded on a 4-point scale). Suspected cases of brachial plexopathy were subject to confirmation by neurophysiological assessment and MRI.
Patients were reviewed every year for tumour relapse and radiotherapy-induced normal tissue effects. Clinical data were recorded on pre-printed case report forms and sent to the coordinating clinical trials office at the ICR-CTSU, Sutton, UK. Photographs were taken at baseline (post-surgery and pre-radiotherapy) and then at 2 and 5 years to assess changes to the breast based on change in size, shrinkage, and shape, and scored on a 3-point graded scale. Changes in breast appearance (photographic) were scored by three observers blind to patient identity, treatment allocation, and year of follow-up, and a final agreed score reached by consensus. The assessment of change in breast appearance from photographs was fully validated in the pilot study.7 (link) Breast size and surgical deficit were both defined from the baseline photographs by the same three observers applying 3-point graded scales. Quality of life data were obtained using standardised questionnaires19 (link), 20 (link), 21 (link), 22 (link) at baseline and at 6 months, 1, 2, and 5 years. Post-baseline quality of life questionnaires included an additional four protocol-specific items relating to changes in the affected breast after radiotherapy (skin changes in the area of the affected breast, overall change in breast appearance, firmness to touch of the affected breast, and reduction in size of the affected breast). Of these four items, patients who had had mastectomy only rated change in skin appearance after radiotherapy. Details of the quality of life study protocol and baseline data have been published elsewhere.10 (link)
The trial was coordinated by the ICR-CTSU, Sutton, UK. The trial was overseen by a Steering Committee of several independent experts joined by members of the ICR-CTSU, START Trial Management Group, and representatives of the funding bodies (as observers). The Trial Management Group was responsible for the day-to-day management of the trial, and the emerging safety and efficacy data was reviewed regularly by the Independent Data Monitoring Committee. Central statistical monitoring of data was done by ICR-CTSU, supplemented by selected on-site source document verification.
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Everolimus
exemestane
Hormones
Hypersensitivity
Neoplasm Metastasis
Patients
Safety
The Wellness After Breast Cancer (WABC) Study is a cross-sectional study conducted between March 2008 and July 2009 at the Rowan Breast Cancer Center of the Abramson Cancer Center of the University of Pennsylvania (Philadelphia, PA, USA). Eligibility criteria included postmenopausal status (≥12 months of amenorrhea), history of histologically-confirmed hormone receptor-positive breast cancer, AJCC stages 0 to III, and exposure to a third-generation aromatase inhibitor (anastrozole, letrozole, or exemestane). Additional eligibility criteria included completion of all chemotherapy and/or radiotherapy at least one month prior to enrollment, approval of the patient's primary oncologist, and ability to provide informed consent. Research assistants screened medical records and approached potential patients for enrollment at their regular follow-up appointments. After informed consent was obtained, each participant completed a self-administered survey. Peripheral blood was collected; whole blood and serum samples were banked at -80°C for genetic and biomarker analysis, respectively. The study was approved by the Institutional Review Board of the University of Pennsylvania.
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Anastrozole
Aromatase Inhibitors
Biological Markers
BLOOD
Eligibility Determination
Ethics Committees, Research
exemestane
Hormones
Letrozole
Malignant Neoplasm of Breast
Oncologists
Patients
Pharmacotherapy
Radiotherapy
Serum
Sorbus
Most recents protocols related to «Exemestane»
Morning fasting serum samples were frozen at baseline and final visit (day before surgery) and stored in aliquots at −80 °C until assayed, and freeze and thawed cycles were avoided. Serum adiponectin and leptin were measured using an automated immunoassay platform called ELLA (ProteinSimple, Bio-techne, Minneapolis, MN, USA). The platform is based on a microfluidic technology that allows the performance of automated enzyme-linked immunoassays without manual steps45 (link). The inter-assay coefficient of variation of our in-house prepared pooled serum sample was 6.6% for adiponectin and 5.4% for leptin. Sex hormone binding globulin (SHBG) serum levels were measured by a chemiluminescent immunoassay designed for the IDS-iSYS Multi-Discipline Automated System (Immunodiagnostic Systems Limited, United Kingdom), having a lower limit of detection (LLOQ) of 0.30 nmol/L. Insulin was measured by a chemiluminescent microparticle immunoassay technology designed for the ARCHITECT automated instrument (Abbott Diagnostics), having an analytical sensitivity below 1.0 μU/mL. The inter-assay coefficient of variation of ARCHITECT controls (3 different levels) for insulin was below 1.7% and our in-house pooled serum control was 3.7% (mean concentration: 5.2 μU/mL). At baseline and final visits, glucose concentrations were determined locally at each participating center. We applied the homeostasis model assessment (HOMA) as a surrogate index of insulin sensitivity, obtained by the formula [fasting insulinemia (mU/L) × glycemia (mmol/L)]/22.5.
Serum concentrations of estradiol, estrone, exemestane, and 17-hydroxy-exemestane were determined simultaneously using a highly sensitive, previously described assay46 (link). In short, samples were spiked with isotope-labeled internal standard and extracted with hexane: methyl tert-butyl ether and hexane: isopropyl alcohol in an automated procedure using a Hamilton Star robot. Extracts were reconstituted and analyzed by LC-MS/MS. The LLOQs were 0.8 pmol/L (estradiol), 0.2 pmol/L (estrone), 13 pmol/L (exemestane), and 8 pmol/L (17-hydroxy-exemestane). Arbitrary values of 0.4 pmol/L for estradiol (n = 70), 0.15 pmol/L for estrone (n = 7), 6.5 pmol/L for exemestane (n = 16); 4 pmol/L for 17-OH-exemestane (n = 38); were assigned to levels below LLOQ. The formula used was LLOQ/2.
Testosterone and androstenedione were analyzed using a previously published method47 (link). Shortly described, serum samples were spiked with isotope-labeled IS and extracted with ethyl acetate: hexane (80:20). The supernatant was transferred to a new vial and washed with ammonium formate buffer. The organic phase was transferred to a new vial and evaporated under nitrogen gas. Samples were reconstituted and analyzed using LC-MS/MS. The LC-MS/MS system was comprised of a 1290 UPLC system (Agilent) and an API 5500 (SCIEX). The column used was a Zorbax C18. The mobile phases were water and acetonitrile with 0.1% formic acid. The LLOQ was 0.1 nmol/L for testosterone and 0.2 nmol/L for androstenedione.
Serum concentrations of estradiol, estrone, exemestane, and 17-hydroxy-exemestane were determined simultaneously using a highly sensitive, previously described assay46 (link). In short, samples were spiked with isotope-labeled internal standard and extracted with hexane: methyl tert-butyl ether and hexane: isopropyl alcohol in an automated procedure using a Hamilton Star robot. Extracts were reconstituted and analyzed by LC-MS/MS. The LLOQs were 0.8 pmol/L (estradiol), 0.2 pmol/L (estrone), 13 pmol/L (exemestane), and 8 pmol/L (17-hydroxy-exemestane). Arbitrary values of 0.4 pmol/L for estradiol (n = 70), 0.15 pmol/L for estrone (n = 7), 6.5 pmol/L for exemestane (n = 16); 4 pmol/L for 17-OH-exemestane (n = 38); were assigned to levels below LLOQ. The formula used was LLOQ/2.
Testosterone and androstenedione were analyzed using a previously published method47 (link). Shortly described, serum samples were spiked with isotope-labeled IS and extracted with ethyl acetate: hexane (80:20). The supernatant was transferred to a new vial and washed with ammonium formate buffer. The organic phase was transferred to a new vial and evaporated under nitrogen gas. Samples were reconstituted and analyzed using LC-MS/MS. The LC-MS/MS system was comprised of a 1290 UPLC system (Agilent) and an API 5500 (SCIEX). The column used was a Zorbax C18. The mobile phases were water and acetonitrile with 0.1% formic acid. The LLOQ was 0.1 nmol/L for testosterone and 0.2 nmol/L for androstenedione.
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Palbociclib was administered orally, once daily for 21 consecutive days, followed by a 7-day rest (28-day cycle). Everolimus and exemestane were administered orally, once daily for 28 consecutive days (28-day cycle). During phase Ib, participants were treated with increasing/decreasing doses of palbociclib and everolimus to establish the MTD/RP2D for both drugs in the context of the P-E-E combination. The starting dose of palbociclib was 100 mg, which was increased to 125 mg. The starting dose of everolimus was 5 mg, which was increased to 10 mg. Only one of the two study drugs was escalated/de-escalated at a time. If patients developed toxicity to 5 mg everolimus, de-escalation to 2.5 mg was allowed. Palbociclib doses below 100 mg were not explored. Exemestane was maintained at 25 mg. Patients were observed for dose-limiting toxicity (DLT) events, which were defined as adverse events or abnormal laboratory values with a reasonably possible relationship to the study medication(s).
The RP2D for the combination was determined to be palbociclib 100 mg + everolimus 5 mg + exemestane 25 mg20 (link). This dose was used throughout phase IIa. During phase IIa, patients were evaluated for response every 8 weeks according to RECIST 1.1 criteria48 (link). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes were used.
The RP2D for the combination was determined to be palbociclib 100 mg + everolimus 5 mg + exemestane 25 mg20 (link). This dose was used throughout phase IIa. During phase IIa, patients were evaluated for response every 8 weeks according to RECIST 1.1 criteria48 (link). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes were used.
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Exemestane (anhydrous form) was granted as a gift sample by Coral
Drugs Private Limited (New Delhi, India). Genistein was a gift sample
provided by DSM Nutritional Products Europe Ltd. Phospholipid (Lipoid
S 100) was a gift sample generously offered by Lipoid GmbH, Germany.
Cholesterol was gifted by Central Drug House Pvt Ltd. Delhi. Chitosan
was obtained from Sigma-Aldrich (St. Louis, MO). Tween 80 was procured
from Mana Scientific Products, Hyderabad, Telangana. Distilled deionized
water was prepared with the Milli-Q water purification system (Millipore,
Bedford, MA). MCF-7 cells were obtained from the National Centre for
Cell Science, Pune, India. All additional solvents, compounds, and
reagents used in the entire methods were of analytical grade.
Drugs Private Limited (New Delhi, India). Genistein was a gift sample
provided by DSM Nutritional Products Europe Ltd. Phospholipid (Lipoid
S 100) was a gift sample generously offered by Lipoid GmbH, Germany.
Cholesterol was gifted by Central Drug House Pvt Ltd. Delhi. Chitosan
was obtained from Sigma-Aldrich (St. Louis, MO). Tween 80 was procured
from Mana Scientific Products, Hyderabad, Telangana. Distilled deionized
water was prepared with the Milli-Q water purification system (Millipore,
Bedford, MA). MCF-7 cells were obtained from the National Centre for
Cell Science, Pune, India. All additional solvents, compounds, and
reagents used in the entire methods were of analytical grade.
We presented median values and interquartile ranges of serum exemestane, 17-OH-exemestane, circulating estrogens, androgen metabolites, adipokines, insulin and HOMA index and tumor Ki-67 index at baseline and changes from baseline to post-treatment, by arms and BMI. Patients were categorized as obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2). The decision to use 30 instead of 25 as a cut-off was based on the proportion of women with obesity higher than expected. From a clinical point of view, the implications of obesity appear more relevant than those of overweight. A supplementary table 3 illustrates the median and interquartile ranges of drug, estradiol, and Ki-67 according to all three BMI categories. Differences at baseline were evaluated by Wilcoxon rank tests. Differences by arms of changes in time were evaluated through ANCOVA models adjusted for baseline values, BMI, and age. The normal distribution of residuals from the full model was graphically checked. Predicted and observed Ki-67 absolute change values were plotted against the % change of serum estradiol by arms and BMI. We also compared the proportions of participants having an absolute decrease in tumor Ki-67 index of at least 3% at the surgery by treatment arms with Chi-square tests. This 3% threshold in Ki-67 decrease after short-term neoadjuvant tamoxifen was shown to be predictive of recurrence-free survival and overall survival16 (link). Adjustment for multiple testing was not carried out given the exploratory nature of the subgroup analyses by BMI
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Data come from a randomized, double-blind, global, multicenter study (NCT00065325) [30] (link) comparing the efficacy and tolerability of fulvestrant to exemestane after prior nonsteroidal aromatase inhibitor therapy in women who are postmenopausal with hormone receptor-positive (HR+) advanced or metastatic breast cancer. Inclusion required women to have a World Health Organization (WHO) performance status of 0 to 2, a life expectancy of at least three months, and at least one measurable or assessable lesion. Exclusion criteria included the presence of life-threating metastatic visceral disease, brain or leptomeningeal metastases, prior exposure to fulvestrant or exemestane, extensive radiation or cytotoxic therapy within the last four weeks, or a history of bleeding diathesis or need for long-term anticoagulation [30] (link). Patients (n = 693) across 138 worldwide centers were randomized 1:1 to either fulvestrant (n = 351) or exemestane (n = 342). All randomized patients who completed at least one FACT-GP5 assessment (n = 618) were included in the current analyses. Further details about the original study can be found in Chia et al. [30] (link).
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Exemestane is a laboratory product manufactured by Merck Group. It is a steroidal aromatase inhibitor, a type of enzyme that plays a role in the production of estrogen. Exemestane is used in various research and development applications, but its core function is to inhibit the aromatase enzyme.
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Letrozole is a laboratory equipment product manufactured by Merck Group. It is a selective aromatase inhibitor, which is a class of compounds that block the enzyme aromatase, responsible for the conversion of androgens into estrogens.
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Acetonitrile is a colorless, volatile, flammable liquid. It is a commonly used solvent in various analytical and chemical applications, including liquid chromatography, gas chromatography, and other laboratory procedures. Acetonitrile is known for its high polarity and ability to dissolve a wide range of organic compounds.
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Exemestane is a laboratory product used as an enzyme inhibitor. It functions by inhibiting the aromatase enzyme, which is responsible for the conversion of androgens to estrogens. This product is intended for research and development purposes only.
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Pooled human liver cytosol (HLC) is a laboratory product that contains the soluble fraction of human liver cells. It provides a source of various enzymes and proteins found naturally in the human liver.
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The CFX384 real-time PCR machine is a high-performance instrument designed for quantitative PCR (qPCR) analysis. It features a 384-well format and can perform real-time detection and analysis of nucleic acid samples. The core function of the CFX384 is to enable precise and reliable quantification of target DNA sequences in a variety of sample types.
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Aromasin is a laboratory equipment product manufactured by Pfizer. It is designed to perform essential functions in scientific research and analysis. The core function of Aromasin is to provide a reliable and controlled environment for various experiments and testing procedures. Further details on the specific intended use of this product are not available.
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The Acquity UPLC BEH C18 column is a reversed-phase liquid chromatography column designed for ultra-high-performance liquid chromatography (UPLC) applications. The column features a sub-2 μm bridged ethylene hybrid (BEH) particle technology that provides efficient and high-resolution separations.
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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.
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Formic acid is a clear, colorless liquid chemical compound used in various industrial and laboratory applications. It is the simplest carboxylic acid, with the chemical formula HCOOH. Formic acid has a pungent odor and is highly corrosive. It is commonly used as a preservative, pH adjuster, and analytical reagent in laboratory settings.
More about "Exemestane"
Exemestane, a steroidal aromatase inhibitor, is a widely used medication for the treatment of hormone receptor-positive breast cancer in postmenopausal women.
This AI-driven drug plays a critical role in blocking the enzyme aromatase, which is responsible for converting androgens into estrogens - a key process in the development and progression of certain breast cancers.
Researchers can leverage PubCompare.ai's innovative platform to optimize their research protocols for Exemestane and enhance the reproducibility of their findings.
The platform empowers researchers to identify the most effective approaches by conducting intelligent comparisons of protocols from the literature, preprints, and patents.
This streamlined process helps researchers save time and resources, while providing more reliable and actionable results.
Beyond Exemestane, the PubCompare.ai platform can also be utilized to explore other related compounds, such as Letrozole, another aromatase inhibitor commonly used in breast cancer treatment.
Additionally, the platform can assist with the analysis of various analytical techniques, including the use of Acetonitrile, Pooled human liver cytosol (HLC), and the CFX384 real-time PCR machine, which are often employed in the study of Exemestane and related drugs.
By harnessing the power of this AI-driven platform, researchers can unlock new insights and drive advancements in the field of breast cancer treatment.
The platform's ability to compare and identify the most effective protocols for Exemestane, Aromasin (the brand name for Exemestane), and other related compounds, can lead to more reliable and reproducible research outcomes, ultimately benefiting patients and advancing the fight against this devastating disease.
To further enrich the research process, researchers may also explore the use of other relevant compounds, such as Tamoxifen, a selective estrogen receptor modulator (SERM), and Formic acid, a common additive in liquid chromatography-mass spectrometry (LC-MS) analysis of Exemestane and related drugs.
By leveraging the PubCompare.ai platform and combining it with a comprehensive understanding of Exemestane and related compounds, researchers can streamline their workflow, enhance the reproducibility of their findings, and contribute to the ongoing progress in the field of breast cancer treatment.
This AI-driven drug plays a critical role in blocking the enzyme aromatase, which is responsible for converting androgens into estrogens - a key process in the development and progression of certain breast cancers.
Researchers can leverage PubCompare.ai's innovative platform to optimize their research protocols for Exemestane and enhance the reproducibility of their findings.
The platform empowers researchers to identify the most effective approaches by conducting intelligent comparisons of protocols from the literature, preprints, and patents.
This streamlined process helps researchers save time and resources, while providing more reliable and actionable results.
Beyond Exemestane, the PubCompare.ai platform can also be utilized to explore other related compounds, such as Letrozole, another aromatase inhibitor commonly used in breast cancer treatment.
Additionally, the platform can assist with the analysis of various analytical techniques, including the use of Acetonitrile, Pooled human liver cytosol (HLC), and the CFX384 real-time PCR machine, which are often employed in the study of Exemestane and related drugs.
By harnessing the power of this AI-driven platform, researchers can unlock new insights and drive advancements in the field of breast cancer treatment.
The platform's ability to compare and identify the most effective protocols for Exemestane, Aromasin (the brand name for Exemestane), and other related compounds, can lead to more reliable and reproducible research outcomes, ultimately benefiting patients and advancing the fight against this devastating disease.
To further enrich the research process, researchers may also explore the use of other relevant compounds, such as Tamoxifen, a selective estrogen receptor modulator (SERM), and Formic acid, a common additive in liquid chromatography-mass spectrometry (LC-MS) analysis of Exemestane and related drugs.
By leveraging the PubCompare.ai platform and combining it with a comprehensive understanding of Exemestane and related compounds, researchers can streamline their workflow, enhance the reproducibility of their findings, and contribute to the ongoing progress in the field of breast cancer treatment.