PMCID string | Title string | Sentences string |
|---|---|---|
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | While restricted to specialized cell types in normal human tissues, polyploidy has been associated with almost all solid and liquid cancers . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Interestingly, chemotherapy, the standard treatment for Diffuse Large B-Cell Lymphoma (DLBCL) has been observed to increase ploidy over time, a known mechanism for drug resistance [, , , , ]. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | These polyploid cells can avoid apoptosis and/or escape cell death though cellular senescence . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | However, post-chemotherapy polyploid cells have been shown to re-enter the cell cycle, resulting in relapsed disease . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Chemotherapy induced polyploidy (CIP) is a mechanism of inherited drug resistance. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Additionally, proliferating CIP cancer cells can produce progeny with increased ploidy or aneuploid genomes that drive aggressive disease . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | CIP can arise in a variety of ways, including cell cycle slippage, an unconventional cell cycle where DNA replication is uncoupled from mitosis . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | These cancer cells post-mitosis will begin replicate their DNA during the synthesis (S) phase and then transition to a gap (G2) phase, thereby skipping G1 entirely . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Alternatively, cells can undergo mitotic slippage by entering mitosis, arresting, reentering G1 phase without attempting or completing cytokinesis (endomitosis) . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | CIP cells may double their genome or, conversely, produce daughter cells with smaller aneuploid genomes due to the increased risk of chromosomal instability (CIN) and chromosome loss during mitosis . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | A myriad of aberrant conditions can contribute to CIN, including the presence of multiple centrosomes, defects in proper kinetochore–microtubule attachment, spindle assembly checkpoint (SAC) dysfunction, defects in chromosome cohesion, nuclear envelope reformation, and cytokinesis [, , , ]. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The Aurora Kinase (AK) family of mitotic enzymes has been identified as a major proponent of suppressing chromosome mis-segregation . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Of interest these c-MYC-regulated mitotic serine/threonine kinases, AK-A and AK-B, induce tetraploidy/polyploidy in DLBCL when disrupted . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | AK-A is associated with centrosome duplication and mitotic spindle formation, while AK-B (chromosome passenger protein) localizes to the prometaphase kinetochores and the spindle midzone of anaphase cells . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | In many tumor types, inhibitors of AK-A and/or AK-B lead to polyploidy, latter due to cytokinesis failure . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | AK-A inhibition mediated polyploid tumor cells appear resistant to a range of chemotherapies, which presents new challenges in use of these agents in the clinic . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Working in tandem with AK-A, the microtubule associated TPX2 (Targeting protein for Xklp2) protein plays vital role in spindle formation [, , ]. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Pre-metaphase, TPX2 assists with the nucleation of microtubules required for the mitotic spindle . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | During metaphase, TPX2 localizes and allosterically activates AK-A. The allosteric binding of TPX2, induces a conformational change that not only activates AK-A, but also prevents deactivation through phosphatase activity . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | TPX2 is also a substrate of AK-A. AK-A activated TPX2 has been shown to play a role in the maintenance of mitotic spindle length during mitosis . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Two potential strategies to cull CIP DLBCL cells are to promote mitotic catastrophe in proliferating polyploid cells, and/or disrupt polyploid cell formation, thus maintaining sensitivity to standard of care chemotherapy . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Hence the importance to establish the interrelationships of CIP cells and quiescence, senescence, and cell cycle dysregulation. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Thus, deciphering the mechanistic kinetics and dynamics of polyploidization, cell cycle dysregulation, and depolyploidization are key to identifying and designing novel therapeutic strategies to disrupt drug resistant CIP cells. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | We surmise that CIP cells acquire novel inheritable genetic changes to generate drug resistance progeny (2n+) via depolyploidation post-therapy. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Extensive analysis of the DNA content of two Myc-Bcl2 DLBCL cell lines demonstrated that alisertib therapy dramatically promotes polyploidization, as previously reported by others in DLBCL . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | By conducting cell cycle analysis using fluorescent reporter, we can start to explain this phenotype and address it using a TPX2 site inhibitor Here we describe the use of Aurkin A, an AK-A TPX2 site inhibitor, which prevents TPX2-AK-A interaction. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Combination of Aurkin A plus alisertib disrupts alisertib induced polyploidy in a dose-dependent manner with associated increased apoptosis. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Using the fluorescence ubiquitination-based cell cycle indicator (FUCCI) system we demonstrate by live cell imaging DLBCL cells treated with alisertib accumulate in S-G2 phase . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Importantly, a sub-population does not synchronize in S, but rather undergoes multiple division cycles via endomitosis compared to control. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Similarly, this endomitotic DNA replication was not observed with Aurkin A (TPX2/AK-A inhibitor) or alisertib plus Aurkin A combination DLBCL cells. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Thus, total AK-A inhibition was able to limit cell cycle slippage and is synthetic lethal to CIP cells. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 (DSMZ; ACC 633) and VAL (DSMZ; ACC 586)) cells were grown in RPMI-1640 media supplemented with 10% Fetal Bovine Serum. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | HeLa (ATCC; CCL-2), MDA MB-231 (ATCC; HTB-26), U-2 OS (ATCC; HTB-96), Granta-519 (DSMZ; ACC 342), and MIA PaCa-2 (ATCC; CRL-1420) cells were grown in DMEM supplemented with 10% Fetal Bovine Serum. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | All cells have been authenticated and are mycoplasma negative. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were grown in a 5% CO2 incubator at 37°C. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | All drug treatments were administered in a final volume of 1% DMSO. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Drug treatments for flow cytometry and immunostaining were performed over a period of five days, with a readministration of the corresponding drug and fresh media at day three. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells treated for five days with 1uM alisertib or DMSO, were fixed onto microscope slides using 5% paraformaldehyde solution, and treated with a nuclear extraction buffer (10mM PIPES,100mM NaCl, 300mM sucrose, 3mM MgCl2,1mM EGTA, 0.5% tritionx-100) to remove the cell membrane and cytoplasm. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were then blocked for one hour using 4% Bovine Serum Albumin solution. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | After blocking slides were washed three times with TBS-T and then stained with DAPI and rabbit CENP-B (Cell signaling Technology). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were washed, counterstained with anti-rabbit FITC conjugated antibody. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Imaging was performed using a confocal microscope at 40x magnification. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Drug treated U2932 and VAL, cells were fixed for 24-hours at 4°C in a 70% methanol solution. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were stained for one hour using a propidium iodide solution (100 mg/mL RNase, 150 mg/mL propidium iodide, and 5 mM EDTA-pH 8.0) and analyzed via flow cytometry for 100,000 events. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Results were quantified and plotted using FlowJo. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells were drug treated over a period of five days washed with fresh media and allowed to grow for an additional four days without drug. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | On days five and nine cells were collected and stained with PI and FITC Annexin V apoptosis kit (Biolegend). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were analyzed via flow cytometry for 100,000 events within an hour of initial staining and cell populations were quantified in FlowJo. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 and VAL cells were then assessed for cell proliferation via CellTiter 96 AQueous One Solution Cell Proliferation Assay (Promega, G5421). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | 96-well plates were seeded with 10,000 cells per well in 100uL aliquots of colorless RPM 1640 media with 10% FBS. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Drugs were added to each well with a 1% final volume of DMSO. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Each condition was tested in four replicates. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Plates were incubated in a 5% CO2 incubator at 37°C for four days. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | 20µL of via CellTiter 96 AQueous One Solution Reagent was added to each well and was incubated for an additional four hours. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The absorbance of each plate was recorded via an absorbance plate reader at 490nm. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cell proliferation assay results were graphed using GraphPad prism, and the IC50, IC75, and IC90 of alisertib with and without 100µM Aurkin A was identified. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Using the Loewe additivity method, the combination index was calculated to determine if the addition of 100µM Aurkin A was synergistic at each inhibitory concentration . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | An isobologram of the combination indexes was created using GraphPad Prism. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were established like previously described . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Briefly, plasmids containing the fluorescent markers Geminin-clover (green) and cdt1-mKO (red), were used to transfect 293FT cells and generate lentiviral particles. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Lentiviruses were used to infect U2932 cells and generate stable cell lines upon Zeocin selection. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The FUCCI U2932 cell line was then FACS sorted for the total population of dual green and red (yellow) fluorescence. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were then allowed to recover and grow for one week and then were subjected to a second FACS sorting, in which the top 10% of green cells were sorted and expanded. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This homogenous population of FUCCI cells was synchronized using a double thymidine block . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | After block release cells were drug treated and live imaging was performed using an Incucyte (Essen) imaging system. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Images were taken every 30 minutes and used for quantification and analysis. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Quantification of total green and red fluorescence (A.U) was plotted over time in GraphPad. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | A representative example of images was used for figures (as detailed in figure legends) while full time courses are shown as supplemental movies. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | SCID mice (Jackson laboratory) were injected with 1 × 10 VAL cells in sterile saline subcutaneously in the left flank. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were pair matched based on tumor volume three weeks post injection and grouped into an alisertib 20mg/kg, Aurkin A 30mg/kg, Alisertib 20mg/kg + Aurkin A 30mg/kg combination, and vehicle control (DMSO volume match), each containing six mice. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Two mice in the Aurkin A and one mouse in the Alisertib treatment groups did not exhibit tumor growth post cell injection and were excluded. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were given the corresponding treatment once a day for five days a week. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | After two weeks, treatment was then withheld for a week, followed by another five-day-a-week treatment cycle. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Paired T tests were used to evaluate the tumor volume differences between the groups. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The tumors were then dissected and formalin-fixed paraffin-embedded. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Slides were stained with hematoxylin and eosin by the Tissue Acquisition and Cellular/Molecular Analysis core facility at the University of Arizona. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | All procedures were completed in accordance with the University of Arizona Institutional Animal Care and Use Committee (IACUC) protocol 07-029. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mouse tumor slides were scanned at 20x magnification by The University of Texas Health Science Center at Houston Histology Core Facility. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Tumor slides were analyzed using the QuPath Bioimaging Analysis software (V0.4.3). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Deconvoluted H&E scanned slides were first evaluated for cell detection using the image optical density sum. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were then classified as polyploid or normalploid based nucleus to cell area ratio. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cell ploidy classification was repeated in three random areas of each slide for at least 10,000 cells per field. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Results were graphed via GraphPad Prism. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | To determine the effectiveness of inhibition of TPX2 binding to AK-A to prevent polyploidy, the effectiveness of alisertib to induce polyploidy was first established. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells (Myc/Bcl2 double expresser, DLBCL) were treated with alisertib at increasing concentrations from 1nM to 1M for five days. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | These cells were harvested, stained using a 10% PI solution, and analyzed via flow cytometry for DNA content to establish cellular ploidy. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Flow cytometry showed an increased level of 4n and 8n aneuploid cells with increasing alisertib concentration (Fig. 1a and Sup Fig. 1). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The highest-level polyploidy after five days of alisertib treatment was observed at 1µM, with 4n and 8n aneuploid cells making up 40% and 25% of the cell population respectively (Fig. 1b).Fig. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | 1Alisertib induced polyploidization in Diffuse Large B Cell Lymphoma. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells treated with DMSO, 50nM, 100nM, 500nM, or 1000nM alisertib for five days were fixed in 70% methanol solution, stained with PI, and analyzed via flow cytometry (A, B). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells were treated with DMSO (C) or 1µM Alisertib (D). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were treated stained with CENP-B and DAPI and imaged at 40x magnification via confocal microscopy. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Fig 1 Alisertib induced polyploidization in Diffuse Large B Cell Lymphoma. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells treated with DMSO, 50nM, 100nM, 500nM, or 1000nM alisertib for five days were fixed in 70% methanol solution, stained with PI, and analyzed via flow cytometry (A, B). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | U2932 cells were treated with DMSO (C) or 1µM Alisertib (D). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were treated stained with CENP-B and DAPI and imaged at 40x magnification via confocal microscopy. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | To further investigate ploidy changes in alisertib treated U2932 cells, immunofluorescent (IF) confocal microscopy was utilized. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells treated for five-day with either 1mM alisertib or vehicle (DMSO) were collected and stained with both a CENP-B antibody and the nuclear stain DAPI. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | CENP-B, a highly conserved centromere protein, is commonly used to help with chromosome observations and numeration. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Microscopy showed a drastic increase in nucleus size between treatment and control, as 1µM alisertib treated nuclei were more than five times larger than DMSO (Fig. 1c and d). |
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