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Statistical analysis
dysplasia
ESOPHAGEAL CANCER, DYSPLASIA
Summary statistics for continuous variables (means and standard deviations) and categorical variables (counts and proportions) were presented for both the intervention and control groups. An aggregate of the compliance for all 12 weeks for each individual was obtained by dividing 100/12 for example, 100% compliance if ...
PMC9939163
RESULTS
PMC9939163
Study participants
esophageal cancer, D) Muscle mass
OESOPHAGEAL CANCER
Patient enrolment was consecutive and lasted from January 2016 to August 2020. A total of 243 survivors from the OSCAR study were assessed for eligibility. Of them, 233 met the inclusion criteria, but 72 declined to participate. The remaining 161 participants (69.1% of those eligible) were randomly assigned to either t...
PMC9939163
Hand grip strength
esophageal cancer
OESOPHAGEAL CANCER
Among the 70 patients with completed measures in the control group, two patients had missing values for hand grip strength and hence were not included in the final analysis (Figure Differences in primary outcomes between baseline and post‐intervention for the two allocation groups of the Swedish nationwide randomized c...
PMC9939163
Lower extremity strength
From those who had completed measures in the control group (
PMC9939163
Muscle mass
Among the participants with complete end of study measures in the intervention group (
PMC9939163
DISCUSSION
esophageal cancer, lower extremity muscle strength, muscle mass
ESOPHAGEAL CANCER, RECRUITMENT, OESOPHAGEAL CANCER
This trial demonstrated that a specially designed 12‐week home‐based PA program improved lower extremity muscle strength among patients having undergone surgery for esophageal cancer 1‐year earlier, while no influence on hand grip strength or muscle mass was identified.Some methodological strengths and weaknesses of th...
PMC9939163
FUNDING INFORMATION
ALF, Cancer
CANCER
This work is supported by the Swedish Cancer Society 180685, the Swedish Research Council 2017–01744, the Swedish Research Council for Health, Workinglife and Welfare 2017–00812, The Cancer Research Funds of Radiumhemmet 171103 and Region Stockholm (ALF) LS 2018–1157. Pernilla Lagergren is supported by the NIHR Imperia...
PMC9939163
CONFLICT OF INTEREST
The authors declare no conflict of interest.
PMC9939163
ETHICAL APPROVAL STATEMENT
Ethical approval was granted by the Regional Ethical Review Board in Stockholm, Sweden (Dnrs: 2015/2142–32; 2016/1696–32/1; 2018/1447–32).
PMC9939163
CONSENT TO PARTICIPATE
Written and oral information was given, and informed consent was collected from all participants by the research nurse before the randomization envelope was opened.
PMC9939163
TRIAL REGISTRATION
PMC9939163
ACKNOWLEDGMENTS
We acknowledge patients of the PA study for their valuable participation and our Surgical Care Science patient research partnership group for valuable inputs on the study.
PMC9939163
DATA AVAILABILITY STATEMENT
The data sets generated and/or analyzed in the current study will not be publicly available due to the ethical review act but will be available from the principal investigators of the study on reasonable request.
PMC9939163
REFERENCES
PMC9939163
2. Materials and Methods
PMC10346321
2.1. Study Design and Participants
chronic non-communicable diseases, amenorrhea
VASODILATION, CARDIOVASCULAR DISEASES
A randomized trial conducted on 48 individuals compared the effects of resveratrol supplementation (500 mg/day) and energy restriction (1000 kcal/day) for 30 days on SIRT1 and vascular reactivity parameters. The study participants were 24 postmenopausal women (01 years of natural amenorrhea) and 24 men aged 55 to 65, a...
PMC10346321
2.2. Biochemical Analysis
Laboratory tests were performed with biological samples collected after a 12-h fast. Serum samples were obtained after collecting venous blood in tubes without an anticoagulant and centrifuged for 20 min at 1800G (Eppendorf, Hamburg, Germany). Citrated blood samples were centrifuged for 10 min at 200×
PMC10346321
2.3. Sirtuin 1 Assessment
SIRT1 serum concentration was determined using an ELISA kit (Uscn Life Science, Wuhan, Hubei, China). Serum samples, before and after interventions, were analyzed in duplicate and in the same ELISA plate using the Multiscan FC plate reader (Thermo Scientific, Waltham, MA, USA), with a coefficient of variation of 12%, a...
PMC10346321
2.4. Resveratrol Purity and Formulation Analysis
The resveratrol administered to participants was obtained from a compounding pharmacy (Buenos Aires Pharmacy, São Paulo, Brazil). The purity of the product supplied was analyzed by capillary electrophoresis using a Proteome Lab PA800 (Beckman Coulter, Fullerton, CA, USA) at the Laboratory of Capillary Chromatography an...
PMC10346321
2.5. Vascular Reactivity Assessment
Endothelium-dependent flow-mediated vasodilation
VASODILATION
Endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent vasodilation (NMD) were assessed according to a previous guideline [
PMC10346321
2.6. Statistical Analyses
REGRESSIONS
The sample size of 48 patients, with 24 subjects per treatment arm, was determined to yield a power of 80% with a 5% significance level to detect a 30% difference in Sirt1 serum concentrations. Participants were randomly assigned in a 1:1 ratio using computer-generated numbers to include participants in the resveratrol...
PMC10346321
3. Results
REGRESSIONS
Baseline and post-intervention data are described in At the end of the study, individuals in the energy restriction group had a significant reduction in weight (When comparing groups, there was a statistically significant difference between the changes (∆) in weight (Both interventions increased serum SIRT1 (Correlatio...
PMC10346321
4. Discussion
cerebral ischemic stress
VASODILATION, CARDIOVASCULAR DISEASES, INFLAMMATION, OXIDATIVE STRESS, ENDOTHELIAL DYSFUNCTION
The main results of our study showed that 30 days of energy restriction, i.e., a 1000 kcal diet, or 500 mg daily resveratrol supplementation similarly increased circulating SIRT1 and decreased plasma noradrenaline. Plasma noradrenaline reduction was correlated with higher baseline circulating SIRT1. After the intervent...
PMC10346321
Author Contributions
Conceptualization, A.d.P.M. and G.H.F.G.; Methodology, A.d.P.M.; Validation, A.d.P.M.; Data collection, A.R., M.F.d.S.G., S.D.A., C.M.C.S. and A.d.P.M.; Data analysis, A.d.P.M. and G.H.F.G.; Writing—Original draft preparation, A.d.P.M., G.H.F.G., K.L.K. and N.F.d.O.F.; Writing—review and editing, A.d.P.M. and G.H.F.G.;...
PMC10346321
Institutional Review Board Statement
HEART
The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Heart Institute of University of São Paulo Medical School (protocol code CAAE:00788012.8.0000.0068).
PMC10346321
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC10346321
Data Availability Statement
Not applicable.
PMC10346321
Conflicts of Interest
The authors declare no conflict of interest.
PMC10346321
References
AD
VASODILATION
Research protocol design.Clinical and biochemical characteristics of the participants at baseline and post-treatment.Data are presented as median (interquartile range—IQR). *: Comparison of intra-groups post–pre-tests. **: Comparison between groups at baseline. Significant values are bold.Comparison of the median diffe...
PMC10346321
1. Introduction
Obesity, obesity, death, breast cancer, Breast cancer, Smartphone-Based Cancer, deaths, Cancer
OBESITY, OBESITY, BREAST CANCER, BREAST CANCER, SECONDARY, CANCER
Breast cancer prevalence has increased globally, with 12.2% of breast cancer cases identified in China. Obesity and unhealthy lifestyles are major risk factors for breast cancer. We conducted a randomized control trial to assess the feasibility and evaluate the preliminary effect of the Smartphone-Based Cancer and Obes...
PMC10218157
2. Materials and Methods
DISEASE, RECRUITMENT
This pilot study used a randomized control trial design. The social cognitive theory (SCT) [Women who met the inclusion criteria from two community health centers in Changsha, Hunan Province, China, were invited to this study and randomized to either the SCOPE or control programs. Inclusion criteria included (1) being ...
PMC10218157
2.1. Intervention Contents
Obesity, WeChat-based, Cancer
OBESITY, BREAST CANCER, DISEASE, CANCER
Fitbit tracker. All participants received a Fitbit Alta HRTwelve modules. Modules were sent via WeChat. Participants received 12 weekly, culturally appropriate, evidence-based educational modules along with tailored tips and messages via WeChat. Each module includes an educational session/information that lasts less th...
PMC10218157
2.2. Control Group
The control group received a Fitbit Alta HR
PMC10218157
2.3. Data Collection and Measures
obesity, Diabetes
OBESITY, BREAST CANCER, CREST, DIABETES
Data were collected at baseline, 3 months, and 6 months. The research assistants and a registered nurse conducted all measurements. The trained research assistant and registered nurse measured WC, weight, and height. Study participants completed all questionnaires in a separate room where a research assistant could ans...
PMC10218157
2.4. Data Analysis
Because this is a pilot study aimed at testing the feasibility, acceptance, and preliminary efficacy, a power analysis was not conducted. Since this pilot RCT has a limited sample size, analyses were intended to be exploratory, and we set α = 0.05 (two-sided). Descriptive statistics (means and standard deviations, or m...
PMC10218157
3. Results
PMC10218157
3.1. Sample Characteristics
A total of 102 women (52 in the SCOPE intervention and 50 in the control group) participated in this study (see
PMC10218157
3.2. Effect of the Intervention
Results from the mixed-model analysis found that at the 3-month follow-up, compared to baseline, participants in the SCOPE program compared to control significantly reduced WC (At 6 months, compared to baseline, women in the SCOPE group compared to control significantly reduced WC (
PMC10218157
3.3. Feasibility and Satisfaction of the SCOPE Modules
A total of 85% of participants completed 6 months of follow-up. The main reasons for missing the follow-up assessment include lack of time and inability to come to the site for assessment. The average number of modules viewed was 8.5 out of 12 modules. Most participants in the SCOPE intervention program (93%) indicated...
PMC10218157
4. Discussion
obesity, abdominal obesity, breast cancer
OBESITY, SDH, BREAST CANCER
As breast cancer is a significant health issue, and obesity increases the risk for breast cancer, especially for women with children, we developed a smartphone-based intervention using a popular communication app tailored to Chinese mothers. Our intervention aimed at reducing obesity, increasing knowledge and attitude,...
PMC10218157
5. Conclusions
obesity, breast cancer
OBESITY, BREAST CANCER
This pilot study demonstrates a promising way to prevent obesity and breast cancer. The SCOPE intervention delivered via a communication app is feasible and may positively reduce women’s risk for obesity and improve breast cancer knowledge and attitude. This intervention has great potential to promote the health and we...
PMC10218157
Author Contributions
Conceptualization, J.-L.C. and J.G.; methodology, J.-L.C.; software, T.J.H. and C.-X.L.; validation, J.-L.C., J.G. and T.J.H.; formal analysis, T.J.H., J.-L.C. and C.-X.L.; investigation, Q.Z., Y.J., P.M., H.Z. and Q.H.; resources, P.M., H.Z. and Q.H.; data curation, C.-X.L., Q.Z., Y.J. and Q.H.; writing—original draft...
PMC10218157
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee on Human Research of the University of California San Francisco (IRB 18-27025).
PMC10218157
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC10218157
Data Availability Statement
The data presented in this study are available on request from the corresponding author. The data are not publicly available due to them containing personal information.
PMC10218157
Conflicts of Interest
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
PMC10218157
References
RECRUITMENT
Sample session in WeChat. Patient recruitment flow chart.Demographics.Baseline data.Comparisons between control and SCOPE experimental groups.Mixed model and effect size of the intervention.
PMC10218157
Visual Abstract
breast cancer
METASTATIC DISEASE, BREAST CANCER
Published online Jul. 13, 2023. Imaging using the human epidermal growth factor receptor 2 (HER2)–binding tracer Up to 20% of breast cancer cases have human epidermal growth factor receptor 2 (HER2) overexpression with or without HER2 oncogene amplification (Currently, treatment failure is relatively common, and cure r...
PMC10478820
MATERIALS AND METHODS
PMC10478820
Patient Population
tumor, PBC, neutropenia
TUMOR, HER2-POSITIVE BREAST CANCER, PBC, NEUTROPENIA, MALIGNANCIES, CONGESTIVE HEART FAILURE, CONCOMITANT DISEASE, HER2-NEGATIVE BREAST CANCER
The current study was a planned interim analysis of a phase II study embedded within a larger academically driven prospective open-label phase II and phase III diagnostic trial, approved by the Swedish Medical Products Agency (EudraCT 2017-002115-34; diarienummer, 5.1-2018-30296; Women with newly diagnosed stage II or ...
PMC10478820
Production of [
The ABY-025 peptide was provided by Affibody AB. Production of [
PMC10478820
[
All scans were performed using a Discovery MI PET/CT scanner (GE Healthcare), and scans included a section from the skull apex to mid thigh. [The first 10 patients were closely monitored by electrocardiograms and clinical examinations during their stay at the PET center. All patients received a phone call after 24 h fr...
PMC10478820
[
[
PMC10478820
PET Measurements
Images obtained from both [
PMC10478820
Biopsies
Lesions were selected for study biopsies on the basis of uptake on both PET scans and accessibility at a multidisciplinary trial conference the day after the last baseline PET scan. The biopsied lesions were carefully located and manually defined on [
PMC10478820
HER2-Targeted Treatment
multiple recurrent disease
RECURRENT DISEASE
Patients planned for neoadjuvant treatment and patients with first-time recurrent disease received trastuzumab, pertuzumab, and chemotherapy according to guidelines, whereas patients with multiple recurrent disease received trastuzumab emtansine.
PMC10478820
Statistical Analysis
PET metrics were reported as mean ± SD unless otherwise stated. Receiver operating characteristic curve analysis was used to investigate the predictive value of the variables and to define a cutoff for [
PMC10478820
RESULTS
PMC10478820
Patient Characteristics
RECRUITMENT, BREAST CANCER
Patient characteristics and descriptive data are shown in Patient Characteristics and Descriptive DataBased on immunohistochemistry and ISH results.Qualitative data are number and percentage; continuous data are median and range.Anatomic Distribution and [Number of biopsied lesions is in parentheses, 1 per patient. SUV...
PMC10478820
Tumor Lesions
We measured tracer uptake in up to 5 of the largest lesions per patient, including the biopsied lesion. Anatomic distribution of measured lesions is shown in [
PMC10478820
[
In total, 12 patients showed a mismatch between PET and HER2 status, using SUV
PMC10478820
Clinical and Metabolic Response
therapy-naïve, PBC, breast cancer
DISEASE, PBC, BREAST CANCER
Thirty-two patients had either partial or complete metabolic response after receiving 2 cycles of treatment. Clinically, 22 patients had complete response, 11 had partial response, 2 had stable disease, and 5 had progressive disease. Global Δ-TLG was significantly associated with the clinical response ([Receiver operat...
PMC10478820
DISCUSSION
coronavirus disease 2019
CORONAVIRUS DISEASE 2019
The potential of [The results showed that immunohistochemistry staining did not always reflect the biologic availability of the receptors; a HER2-positive biopsy sample with low [We found an inverse association between the number of previous treatments and the metabolic response to current treatment. The more treatment...
PMC10478820
CONCLUSION
BREAST CANCER
Immunohistochemistry staining and ISH are currently the gold standards to determine HER2 status in breast cancer. However, limitations in the metastatic setting still hinder accurate biopsy-based evaluation of heterogeneous HER2 expression. Hence, the advantage of noninvasive techniques such as [
PMC10478820
DISCLOSURE
Breast Cancer, Cancer
BREAST CANCER, CANCER
This work was partially supported by grants from the Swedish Breast Cancer Association, Swedish Cancer Foundation (19 0507 Pj), Roche AB Sweden, and the Percy Falk Foundation. Fredrik Frejd and Joachim Feldwisch are employees and own shares in Affibody AB. Jens Sörensen received clinical advisor remunerations from Affi...
PMC10478820
REFERENCES
PMC10478820
Subject terms
AML, cancers, myelofibrosis
CANCERS, ACUTE MYELOID LEUKEMIA, AML, MYELOFIBROSIS, MUTANT, MYELODYSPLASTIC SYNDROMES
Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transc...
PMC10824665
Main
blood cancer, AML
BLOOD CANCER, DISEASE, AML, LEUKEMIA STEM CELL
AML is an aggressive and lethal blood cancer with a 5-year overall survival rate of less than 45% for patients younger than 60 years of age and less than 10% for older patients, predominantly due to disease relapse after chemotherapy or targeted treatments. AML has been extensively classified based on biological featur...
PMC10824665
Results
PMC10824665
Generation of a comprehensive AML PDX resource
AML, thrombocytopenia, anemia, splenomegaly, AML PDX
DISEASE, THROMBOCYTOPENIA, AML, ANEMIA
To generate a representative AML PDX inventory, primary bone marrow or blood samples from 50 patients were tested for engraftment and development of AML in NOD/SCID/IL2gR−/−/hIL3,CSF2,KITLG (NSGS). The overall success rate for primary engraftment in NSGS was 70%, defined by bone marrow, spleen or peripheral blood donor...
PMC10824665
A phase II-like preclinical trial of imetelstat in AML PDX
AML
AML
To test the preclinical efficacy of imetelstat in AML, the characterized 30 individual samples from patients with AML were each transplanted into 12 NSGS recipients (
PMC10824665
A CRISPR/Cas9 screen to identify key effectors of imetelstat
AML
To investigate the mechanism of action of imetelstat in AML in an unbiased manner, we applied the Brunello guide RNA (gRNA) library
PMC10824665
Lipophagy precedes imetelstat-induced ferroptosis
AML
By integrating transcriptomics and functional genetics, we aimed to investigate the mechanism by which imetelstat induces ferroptosis. We performed an overlay of the in vivo AML PDX RNA-seq datasets from imetelstat and vehicle-treated mice with the Brunello library CRISPR/Cas9 knockout screen data (cutoff criteria of R...
PMC10824665
Oxidative stress signatures distinguish sustained responders
AML, hematological malignancies
DISEASE, AML, HEMATOLOGICAL MALIGNANCIES
We next aimed to identify biomarkers of imetelstat response and resistance. Improved survival in imetelstat-treated AML PDXs correlated with significantly reduced engraftment and disease burden; however, there were clear differences in the magnitude and duration of individual responses (Extended Data Fig. We next aimed...
PMC10824665
Oxidative stress induction sensitizes AML PDX to imetelstat
OXIDATIVE STRESS
The finding that responses to imetelstat are associated with baseline molecular signatures annotated as oxidative stress and that the mechanism of action of imetelstat features ROS-mediated ferroptosis led to the hypothesis that oxidative stress induction can sensitize to imetelstat therapy.Standard induction chemother...
PMC10824665
Discussion
AML, death, hematological myeloid malignancies, myelofibrosis
ESSENTIAL THROMBOCYTHEMIA, OXIDATIVE STRESS, AML, MYELOFIBROSIS
Imetelstat is a first-in class telomerase inhibitor with clinical efficacies in hematological myeloid malignancies, including essential thrombocythemia, myelofibrosis and lower-risk myelodysplastic syndromesFerroptosis is a recently discovered type of non-apoptotic regulatory cell death that relies on the balance of th...
PMC10824665
Methods
Our research complies with all relevant ethical regulations, including QIMR Berghofer human research ethics committee protocol P1382 (HREC/14/QRBW/278) and QIMR Berghofer animal research ethics committee protocol A11605M. Animals were monitored daily and immediately killed based on the scoring criteria detailed below.
PMC10824665
Mouse monitoring
weight loss, hunching, paralysis
Animals were monitored daily and always immediately killed as soon as a cumulative clinical score of 3 or above was reached, based on weight loss (score 1, >10–20%; and score 2, >20% or >15% if maintained for >72 h), posture (score 1, hunching noted only at rest; and score 2, severe hunching), activity (score 1, mild t...
PMC10824665
Mouse models
All mouse experiments were approved by the institutional (QIMR Berghofer) ethics committee protocol A11605M. NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjz/SzJ), NSGS (NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg[CMV-IL3,CSF2,KITLG]1Eav/MloySzJ) and NRGS (NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl Tg[CMV-IL3,CSF2,KITLG]1Eav/J) were imported from Jackson Lab...
PMC10824665
Xenograft transplantation experiments
AML
AML
AML samples were obtained from patients, after informed consent in accordance with the Declaration of Helsinki. Ficoll density gradient was used to recover viable mononuclear cells. Viably frozen AML cells were thawed and CD3-depleted with biotinylated anti-human CD3 (SK7) and biotin-binder Dynabeads (Invitrogen) and s...
PMC10824665
Oligonucleotide sequences of imetelstat and mismatch controls
Imetelstat (GRN163L): 5′ R-TAGGGTTAGACAA-NH2 3′.Mismatch 1 (GRN140833): 5′ R-TAGGTGTAAGCAA-NH2 3′.Mismatch 2 (GRN142865): 5′ R-TAGGGATTCAGAA-NH2 3′.
PMC10824665
Drug treatment studies
NSG, NSGS or NRGS mice were treated with 15 mg kg
PMC10824665
Blood analysis
BLOOD
Blood was collected into EDTA-coated tubes and analyzed on a Hemavet 950 (Drew Scientific). PB smears were stained with Wright-Giemsa according to the manufacturer’s protocol (BioScientific).
PMC10824665
Histology
Tissues were fixed in 10% neutral buffered formalin, embedded in paraffin and stained with hematoxylin and eosin. Images of histological slides were obtained on a ScanScope FL (Aperio).
PMC10824665
Flow cytometry analysis of AML PDX and cord blood transplants
AML
LYSIS, AML
For monitoring AML engraftment, 25–50 μl of PB were stained after red cell lysis (BD Pharm Lyse, BD Biosciences) with anti-human CD45-AF647 (H130) and anti-mouse CD45.1-PE (A20). For AML phenotyping, cell populations were purified from bone marrow (both femurs and tibiae) or SPL and after red blood cell lysis stained w...
PMC10824665
Terminal restriction fragment analysis
TRFs were obtained from genomic DNA by complete digestion with the restriction enzymes HinfI and RsaI. TRFs were separated by pulsed-field gel electrophoresis. Gels were dried, denatured and subjected to in-gel hybridization with a γ-[32P]-ATP-labeled (CCCTAA)4 oligonucleotide probe. Gels were washed and the telomeric ...
PMC10824665
Telomere length qPCR
BLOOD
Samples were purified using the DNeasy Blood and Tissue kit (QIAGEN). DNA isolation was performed as described previously
PMC10824665
Cell lines
The
PMC10824665
Cell culture and in vitro cell growth analysis
AML
AML
AML cell lines were cultured in RPMI with 10% fetal calf serum, 2 mM glutamine and 200 U ml
PMC10824665
Imaging flow cytometry
Lipophagy was detected by assessing colocalization of C12-BODIPY and LAMP1 using a previously published method with modifications
PMC10824665
Flow cytometry analysis of AML cell lines
Before staining, 2 × 10Flow cytometry analysis of lipid peroxidation was performed using C11-BODIPY 581/591 (Sapphire Bioscience) according to a previously published protocol
PMC10824665
Western blotting
LYSED, SECONDARY, LYSIS
Cells were lysed on ice using m-PER lysis buffer (Thermo Fisher Scientific) supplemented with a protease and phosphatase inhibitor (Cell Signaling, 5872) and protein was quantified using Pierce BCA protein assay kit (Thermo Fisher Scientific). In total, 20–50 μg of protein extract was electrophoresed on a 4–15% SDS gra...
PMC10824665
Confocal microscopy
FLUOR, COLD
Cytospins were fixed and permeabilized with methanol:acetone (prechilled) at a ratio of 1:1 for 10 min at room temperature, then washed twice with cold PBS and once with room temperature PBS (5 min each). Cytospins were then incubated with 1% BSA–PBS at room temperature for 1 h, washed three times in PBS for 5 min each...
PMC10824665
CRISPR/Cas9 editing
The Brunello genome-wide gRNA library contains 76,441 gRNAs targeting 19,114 genes and was obtained from Addgene (cat. 73178)
PMC10824665
Mutational sequencing
cancer
CANCER, HEMATOLOGICAL MALIGNANCIES
Genomic alterations were profiled using the HemePACT assay (integrated mutation profiling of actionable cancer targets related to hematological malignancies)
PMC10824665
RNA sequencing
RNA was isolated from a maximum of 0.5 × 10
PMC10824665
Lipidomics
Targeted lipidomics was performed on a 1290 Infinity II UHPLC coupled to a 6470 QQQ mass spectrometer via AJS ESI source (Agilent) in positive ionization mode, using a scheduled multiple reaction monitoring (MRM) method
PMC10824665
Statistical analyses
Unless otherwise stated, statistical analyses were carried out using GraphPad Prism v.9.4.0. Microsoft Excel for Mac v.16.75.2 was used to re-calculate those
PMC10824665
Statistics and reproducibility
Study design was based on sample sizes that proved to be adequate in previous experiments using similar approaches and thus no statistical methods were used to predetermine sample sizes for this study
PMC10824665