During the race for ASG president, Lavender says, her friend's opponent had more money and used it to make professional yard signs. In addition to the walk, there will be drawings, games, entertainment and retail booths. To continue their mission today, Shah says the RF must "directly confront climate change." Basal ECAR values from the Seahorse XF glycolysis stress test are depicted, and means SEM are shown (ttest,n=5-6 measurements). ); and the Translational Research Institute (TRI) and grant KL2 TR003108 through the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (T.C.A.). [20][21] She and two of her children, John and Editha, are buried in Graceland Cemetery in Chicago. This is further substantiated by our GEP results showing that AKT inhibition resulted in the FOXO-dependent decreased expression of metabolic genes and gene sets. In 1912, they hired prominent architect Charles A. Platt to build a mansion on their large country estate, located directly on Lake Michigan in Lake Forest, Illinois, which they named Villa Turicum, and which had extensive architecturally landscaped gardens. For the LE TCA and LE OXPHOS high groups (n= 178 and n= 170, respectively), the 5.5-year survival rate was 57% vs for the LE TCA and LE OXPHOS low groups, it was 71% (n= 598 and n= 606, respectively) (Figure5A). She would continue her practice after her return to America, attracting many socialite patients from around the United States. She knew something was wrong, so she planned to drive to Texarkana to see a doctor her family knew. Texarkana is actually two cities -- one in Texas and one in Arkansas -- divided by the Texas-Arkansas state line. Interestingly, the spare respiratory capacity and the maximum respiration increased in the majority of the HMCLs (5 out of 6) (Figure1D). Established in 1913, the foundation used the Rockefeller family wealth to ostensibly promote "public health" by funding mass vaccination campaigns and the founding of public health authorities around the world. In September 2012, Lavender was on her way home to Little Rock from the 2012 Democratic National Convention in Charlotte, N.C., when she began feeling ill. She had coordinated travel plans for Biden and his family and had stayed up all night making sure everyone made flights back home. It's sad to know how brainwashed breast cancer awareness is about chemotherapy, radiation, and surgery. Correspondence: Jeroen E.J. "She is literally living proof that screening saves lives. We raise nearly all of our money through private individual donations, which helps to . CI, confidence interval; B2M, beta2-microglobulin; Hb, hemoglobin; HR, hazard ratio; ISS, International Staging System; LDH, lactate dehydrogenase. ); grants or awards from the US Department of Defense, National Cancer Institute (R01 CA236814) (DoD; CA180190), the Myeloma Crowd Research Initiative award, and the Riney Family Multiple Myeloma Research Program Fund (F.Z. Edith Rockefeller McCormick (August 31, 1872 August 25, 1932) was an American socialite, daughter of Standard Oil co-founder John D. Rockefeller. Upon graduation from high school, Lavender headed to the University of Arkansas at Fayetteville where she studied advertising and public relations. In agreement, the phosphorylation of FOXO1 (Thr24) and FOXO3 (Thr32), which mark their inactivation, followed a similar pattern (Figure1F). To test this, the effects of the hexokinase inhibitor 2-deoxy-D-glucose (2-DG) on the survival of BCLs were determined. Most well-known for his career in big oil and the petroleum sector, Rockefeller, at the time of his death, was estimated to be worth 300 to 400 billion dollars making him the "richest man in modern history." Like many people though of the time, his influence on medicine has had detrimental long-term negative effects on society as a whole. Whereas in patients with smoldering MM, only the LE OXPHOS gene set was significantly enriched (supplemental Figure4A-C). On Saturday, Betsy Lavender will lead a team in the "Be a Part of the Cure Walk" hosted by the University of Arkansas for Medical Sciences' Winthrop P. Rockefeller Cancer Institute in Little Rock. NONE OF FAMILY ON SHIP $50,000 Fee Reported for Psychoanalyst Who Will See Herto Chicago Home", "MRS. H. F. M'CORMICK OBTAINS DIVORCE IN FIFTY MINUTES; John D. Rockefeller's Daughter Gains Decree for Desertion, Which Husband Admits. ROCKEFELLER JR. GREETS DYING SISTER; Mrs. Edith McCormick Has Relapse in the Night, but Soon Rallies", "MRS. McCORMICK'S ESTATE; Once Estimated at $40,000,000 -- Great Losses Since Crash of 1929", Edith Rockefeller McCormick Trust records, https://en.wikipedia.org/w/index.php?title=Edith_Rockefeller_McCormick&oldid=1152097548, John Rockefeller McCormick (18971901), who died young from. She attributes her good outcome to the doctors, especially her surgeon, Dr. Jason Mizell, and her oncologist, Dr. Sam Makhoul (now at CARTI), nurses and other staff who helped in her recovery. [12], Edith and Harold were divorced in December 1921. "The Rockefeller Women." At Christmas, she and her family, which included a younger sister and brother, would carol throughout the neighborhood. by However, when glucose is present, glycolysis remains the major source of ATP production for HMCLs, as is evident from their limited glycolytic reserve. He was also a "big, big" Razorback fan, she says, a passion she shares with him. Metabolic alterations are important cancer-associated features that allow cancer cell transformation and survival under stress conditions. Moreover, our results suggest that AKT signaling sustains OXPHOS independently of its effects on glycolysis because AKT inhibition still decreased mitochondrial respiration when pyruvate was present as the sole carbon source, thereby obviating the need for pyruvate provided by glycolysis. This indicates that in HMCLs and BLCLs, the glycolytic function is at its maximum and suggests that MM and BL are particularly reliant on glycolysis for proliferation and survival and have limited capacity to utilize glycolysis in response to increased energetic demands. Longtime friends are not surprised at Lavender's dedication to colorectal cancer awareness and prevention. Similarly, the normalized spare respiratory capacity of HMCLs was similar to that of other BCLs, demonstrating that HMCLs and BCLs do not differ with regard to mitochondrial adaptability.27 However, both HMCLs and Burkitt lymphoma cell lines (BLCLs) showed very limited normalized glycolytic reserve (Figure1A). In 2016, Lavender caught the attention of Katie Couric, the former co-anchor of NBC's Today Show, who led a national colorectal cancer awareness campaign in the late 1990s after her husband, Jay Monahan, died from the disease at age 42. "My mission is to promote timely screenings," she says. She and her husband Harold Fowler McCormick were prominent in Chicago society, supporting many causes, including the citys first opera company. Her father, on the other hand, was more serious and disciplined as he worked hard at his law practice. The full-text version of this article contains a data supplement. After recovering, she moved back to Fayetteville, where she had always hoped to return, and began focusing on fundraising projects. To explore whether these findings also apply to patients with MM, a large GEP dataset comprising 542 patients with MM was partitioned into 2 groups representing either high (n= 387) or low (n= 155) FOXO activity, based on the expression of the shared FOXOrepressed gene set.18 GSEA showed that patients with MM with low FOXO activity were significantly enriched (FDR <0.25) for glycolysis, TCA cycle, and OXPHOS-associated gene sets in comparison with those with high FOXO activity. Interestingly, our findings could be extended to patients with MM and have important prognostic implications. This suggests that AKT is the pivotal kinase that crucially regulates both glycolysis and mitochondrial respiration in MM. It was shown previously that AKT has a direct effect on metabolism by phosphorylating several metabolic enzymes, such as HK2,47 ACLY,48 and phosphofructokinase.49 Although this may also occur in MM cells, our results suggest that this is not the major mode of action by which AKT regulates the metabolic features of MM cells. Undaunted, her team countered by putting attention-grabbing balloons on her friend's homemade signs. Nov. 5, 2018. Despite the known role of AKT in modulating cellular metabolism, little is known about the downstream factors of AKT that control the metabolic adaptability of MM cells. Lavender would spend 14 years at Alltel, moving up to a position where she worked on the development of Alltel's national wireless footprint with a partnership that put Alltel stores in Walmart stores across the nation. They would go to the beach, to the Smoky Mountains, to Disney World, Cape Canaveral and more. All univariate P values were reported regardless of significance. This experiment further indicated that glutamine can be used by HMCLs to fuel OXPHOS, which requires AKT activity. Of note, galactose is oxidized to pyruvate, yielding all glycolysis intermediates, thus indicating that it is unlikely that cell death is caused by the lack of glycolysis-derived metabolites required for anabolic processes.30. WASHINGTON A top official of the American Cancer Society has resigned in part because of concern over some of the organization's fund-raising partnerships. However, our results suggest that acetyl-CoA is not limiting for OXPHOS in MM cells because an increased acetyl-CoA formation caused by DCA treatment did not boost basal mitochondrial respiration. To determine the functional metabolic features of HMCLs in comparison with other mature malignant B-cell lines (BCLs), normal activated human peripheral blood mononuclear cells (PBMNCs), and activated purified B cells, glycolysis and mitochondrial stress tests were performed. P-values were determined with Wald 2 test in Cox regression analysis. After that successful event, Lavender was offered a full-time campaign job, working with the media. She was born in Fayetteville in 1970 while her father, Bill Lavender, was finishing law school at the University of Arkansas. Datasets from the HMCLs LME-1, MM1.S, and XG-3 were combined for GSEA. OCR decreased upon AKT inhibition in the presence of pyruvate as the sole carbon source, indicating that AKT directly regulates mitochondrial respiration. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The gene set enrichment analysis (GSEA) software (http://www.broad.mit.edu/gsea)26 and the Molecular Signature Database were used for GSEAs and leading edge (LE) analyses. American Cancer Society - 1913 . The GraphPad Prism software package was used for statistical analyses (GraphPad Software, La Jolla, CA). Timon A. Bloedjes, Guus de Wilde, Gerarda H. Khan, Timothy C. Ashby, John D. Shaughnessy, Fenghuang Zhan, Riekelt H. Houtkooper, Richard J. Bende, Carel J. M. van Noesel, Marcel Spaargaren, Jeroen E. J. Guikema; AKT supports the metabolic fitness of multiple myeloma cells byrestricting FOXO activity. After arriving at her parents' home, she felt worse and went to the local hospital where she found out she had colorectal cancer. New York: St. Martin's Press, 1995. We demonstrate that active FOXO diminished glycolysis and mitochondrial respiration in MM cell lines, and that the expression of glycolysis- and TCA cyclerelated genes in patients with MM negatively correlates with the transcriptional activity of FOXO. (C) Basal respiration and spare respiratory capacity in HMCLs and MMPCs (n= 2 patients) treated with 2.5 M MK2206 (blue bars) or untreated(red bars) for 20 hours. Gene expression profile (GEP) dataset E-TABM-113822 was obtained from the ArrayExpress archive, and datasets GSE6477,23 GSE2658,24,25 and GSE12094118 were obtained from the NCBI Gene Expression Omnibus database. His father, William Avery . Nevertheless, the glycolytic reserve of the primary MM cells was limited and similar to that observed in the HMCLs. Contribution: T.A.B., G.d.W., and J.E.J.G. April 30, 2023 at 7:30 a.m. Betsy Lavender at the Winthrop Rockefeller Cancer Institute at UAMS. (B) Half maximal effective concentrations (EC50) of 2-DG for cell death in HMCLs and BCLs after 3 days of treatment. Univariate and multivariate Cox regression analysis of OS in the TT2 and TT3 cohort of patients with MM. Margaret Higgins Sanger (born Margaret Louise Higgins; September 14, 1879 - September 6, 1966), also known as Margaret Sanger Slee, was an American birth control activist, sex educator, writer, and nurse.Sanger popularized the term "birth control", opened the first birth control clinic in the United States, and established organizations that evolved into the Planned Parenthood Federation of . After radiation, chemotherapy and surgery at UAMS, Lavender spent time recuperating in Texarkana at her family home. As expected, ECAR decreased upon DCA treatment, confirming reduced lactate production, whereas basal respiration was generally not increased in HMCLs. Within days of Harold's remarriage, Edith announced plans to marry Edward Krenn, a 28 year old Austrian architect. Means SEM of OCR values are depicted (n= 5 measurements for each clone) and Seahorse XF injections are shown: oligomycin (=A), FCCP (=B), rotenone and antimycin A (=C). From this we conclude that AKT-mediated negative regulation of FOXO licenses the expression of glycolysis- and TCA-associated genes in MM but not in premalignant plasma cell disorders, most likely reflecting higher energetic demands due to the increased proliferation of MM cells. (A) Seahorse XF real-time metabolic profiling of HMCLs (red symbols) and BCLs (blue, green, yellow, and light blue symbols), CpG-activated PBMNCs and purified human peripheral blood B cells (pink symbols). "I had no reason to believe I was sick," she says. She was on student council and attended Girls' State and the Governor's School, a summer program then held at Hendrix College. -actin served as a loading control. "I remembered that I loved everything at UAMS then," she says. "It was a wonderful experience being on the 'Hill,'" she says. "My mother was a stay-at-home mom, but she was always involved in things," Lavender says, adding that her mother was "always the fun mom." "It's not just awareness for the patient to do their screenings," she says. Furthermore, we demonstrated that AKT signaling is of crucial importance for glycolysis and mitochondrial respiration in MM cells. Moreover, we show that the FOXO-dependent repression of metabolic genes predicts superior overall survival (OS) in a large cohort of patients with MM. AKT regulates glycolysis and OXPHOS in a FOXO-dependent fashion in MM cells. By establishing the China Medical Board in 1914 and purchasing the Union Medical College from the London Missionary Society in 1915, the Foundation took its first steps toward that goal. The oxidation of galactose to pyruvate by glycolysis yields no netATP, forcing cells to rely on mitochondrial respiration for ATPgeneration, which is characterized by an increased OCR (Figure1D).30,31 Galactose caused a significant decrease in the ECAR/OCR ratio in all HMCLs tested, indicating that HMCLs can switch to OXPHOS when forced to do so (Figure1E). Established in 1913, the foundation used the Rockefeller family wealth to ostensibly promote "public health" by funding mass vaccination campaigns and the founding of public health authorities around the world. When evidence began to emerge that petroleum based medicine was causing cancer, Rockefeller founded the American Cancer Society, through which he suppressed that information. Her mother would play piano and they would all sing. MM cells are characterized by the high expression of lactate dehydrogenase,35-37 which catalyzes the conversion of pyruvate into lactate instead of into acetyl-CoA. To investigate the effects of FOXO activation on the expression of genes involved in metabolism, gene expression data obtained from FOXO1- (LME-1) or FOXO3- (MM1.S and XG-3) deficient clones treated with MK2206 were investigated. Edith began support of the Art Institute in 1909 as a charter member and supported it with monetary contributions and loans from her extensive personal art collection. She remained prominent after her divorce from McCormick and helped sponsor and organize several "Women's World Fairs" celebrating female achievement in the 1920s. 01 May 2023 02:14:13 . By the turn on the 20th century, he controlled 90% of all oil refineries in the U.S. through his oil company, Standard Oil, which was later on broken up to become Chevron, Exxon, Mobil etc. Multiple myeloma (MM) is a malignancy characterized by the clonal expansion of plasma cells in the bone marrow. The plan fell through for undisclosed reasons in December 1922. (F) Immunoblot analysis of total and phosphorylated (Ser473) AKT, total and phosphorylated (Thr24) FOXO1, and total and phosphorylated (Thr32) FOXO3 in the HMCLs LME-1, LP-1, and XG-1 cells cultured for 20 hours with or without 25 mM DCA or in a galactose-containing, glucose-free medium. 1 Cancer cells are characterized by metabolic alterations, which are driven by oncogenes. and G.d.W performed the experiments and analyses; R.J.B. The effects of AKT inhibition on the OCRs were similar in MCL-1 overexpressing MM cells and the control cells, indicating that survival and mitochondrial respiration are independently regulated by AKT (supplemental Figure2H). This was the pivotal moment when the AMA was no longer about the medicine and the physicians, it became America's most profitable LOBBY group. [11] She returned to America in 1921 after an eightyear stay. [8] After extended analysis and intense study, Edith became a Jungian analyst, with a full-time practice of more than fifty patients. From hectic politics to the unexpected peril of colorectal cancer, Lavender just laces up her shoes and deals with whatever life throws at her. Furthermore, we provide evidence that AKT sustains glycolysis and OXPHOS in MM by restricting FOXO. Similar effects of DCA treatment were observed in other cancer types, such as non-small cell lung cancer cells38 and breast cancer cells.39 Our results indicate that the reliance of MM cells on glycolysis for proliferation and survival is not related to an intrinsic inability to perform OXPHOS because MM cells are able to switch to OXPHOS when cultured in the presence of galactose instead of glucose. (E) OCR/ECAR ratios of HMCLs cultured for 4 days in a glucose-containing medium or in a galactose-containing, glucose-free medium. Replacing glucose with galactose resulted in a significant increase in cell death in several HMCLs (LME-1, XG-3, and RPMI-8226), suggesting that these cell lines are unable to generate sufficient ATP from OXPHOS, thus indicating defective mitochondrial respiration and limited metabolic adaptability. In the summers, she says, they went swimming, set up Kool-Aid stands and played wiffleball. Mean values for basal glycolysis andnormalized glycolytic reserve (percentage of basal glycolysis) based on ECAR and mean values for basal respiration and normalized spare respiratory capacity(percentage of basal respiration) based on OCR are depicted (one-way ANOVA with Bonferroni multiple comparisons test; HMCLs vs BCLs, n= 5 measurements. Protein expression of the glycolysis rate-limiting enzyme HK2 was decreased upon MK2206 treatment, whereas the effects on pyruvate kinase M2 (PKM2) were modest (Figure2A). ", Copyright 2023, Northwest Arkansas Newspapers LLC. Oftentimes, younger patients don't get timely diagnoses because doctors don't think they are old enough to have colorectal cancer, she says. "Having that many people there, it was just incredible.". | Expression of FOXO-repressed metabolic genes predicts poor survival in patients with MM. She also studied astrology and reincarnation. Most recently, Lavender has been involved with the "Be a Part of the Cure Walk" hosted by the UAMS Winthrop P. Rockefeller Cancer Institute. HR (diamond symbols) and 95% CI (lines) are indicated. We developed a strategy to covalently tether drug fragments adjacent to allosteric sites in GPCRs to enhance . The American Society for the Control of Cancer (the forerunner of the American Cancer Society) was established with the aid of John D. Rockefeller, and the first X-ray machine was put into use. Although novel treatment strategies have improved the prognosis and outcome of MM, most patients eventually relapse and become refractory to further treatment. A local paper noted, of the first fair, that "One feature of the exhibit will be a collection of newspaper and magazine clippings, from various countries during the last 200 years emphasizing the storm of protest which greeted every suggestion for a freer social status for women. These effects appear to be cell/tissue contextspecific because several studies report the opposite, showing that FOXO expression is actually required for glucose metabolism and the TCA cycle in neural and intestinal stem cells.50,51 In agreement with our data, it was shown that FOXO3a antagonized MYC and repressed genes involved in the mitochondrial respiration in colon cancer cells52 and in glycolysis in melanoma cells.53. (A) Univariate analysis of subgroups (n= 776 patients; alternative numbers of patients indicated in case values/data were missing) for OS. The authors thank Berend Hooibrink (flow cytometry core facility, Amsterdam University Medical Centers) for excellent flow cytometry assistance. [1] Edith helped fund the juvenile probation program of Chicago's pioneering Juvenile Court system when it was revealed that, although legislation set up the system, there was no provision to fund the probation officers. "[16] She followed up in Time magazine by stating "My interest in reincarnation is of many years' standing. "It was a fabulous environment that day," Lavender says, noting that more than 1,000 people participated in 2022. To further investigate the role of AKT signaling in the metabolic features of MM cells, HMCLs were treated with the allosteric AKT inhibitor MK2206. Nonetheless, DCA increased the maximum respiration rate in MM cells, indicating an increased influx of pyruvate into the mitochondria and improved usage of mitochondrial respiration. We have previously shown that AKT regulates the stability of the antiapoptotic Myeloid-cell leukemia 1 (MCL-1) protein, which is essential for the survival of MM cells.18 Consequently, HMCLs overexpressing MCL-1 were resistant to AKT inhibitorinduced cell death.18 However, MCL-1 overexpression did not prevent reduced glycolysis induced by MK2206 treatment, indicating that the effects of AKT inhibition on glycolysis were not related to the induction of apoptosis (supplemental Figure2C). FOXO-dependent repression of metabolic genes is associated with favorable prognosis in MM. Search for other works by this author on: Metabolic signature identifies novel targets for drug resistance in multiple myeloma, Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib, On respiratory impairment in cancer cells, An HK2 antisense oligonucleotide induces synthetic lethality in HK1-HK2+ multiple myeloma, Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells, Metabolic heterogeneity in human lung tumors, The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type, Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin, Bortezomib resistance in multiple myeloma is associated with increased serine synthesis, Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells, The AKT kinase is activated in multiple myeloma tumor cells, Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma, The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses, PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells, Loss of PTEN expression leading to high Akt activation in human multiple myelomas, AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma, Is Akt the Warburg kinase?-Akt-energy metabolism interactions and oncogenesis, The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism, Analysis of PTEN deletions and mutations in multiple myeloma, Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3, Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling, Prognostic value of cyclin D2 mRNA expression in newly diagnosed multiple myeloma treated with high-dose chemotherapy and tandem autologous stem cell transplantations, Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Mitochondrial spare respiratory capacity: Mechanisms, regulation, and significance in non-transformed and cancer cells, Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation, Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells, Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants, Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells, The role of FOXO in the regulation of metabolism, Avalidated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1, TP53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3, Metabolic effects of recurrent genetic aberrations in multiple myeloma, Lactate dehydrogenase production and release in a newly established human myeloma cell line, Lactate, a putative survival factor for myeloma cells, is incorporated by myeloma cells through monocarboxylate transporters 1, Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer, Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines, Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited, Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements, Characterization of MYC translocations in multiple myeloma cell lines, Regulation of cancer cell metabolism: oncogenic MYC in the drivers seat, Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1, Myc-induced proliferation and transformation require Akt-mediated phosphorylation of FoxO proteins, Akt stimulates aerobic glycolysis in cancer cells, Hexokinase-II positively regulates glucose starvation induced autophagy through TORC1 inhibition, The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes, Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis, FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells, Mitochondria define intestinal stem cell differentiation downstream of a FOXO/notch axis, FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression, FOXO3a-SIRT6 axis suppresses aerobic glycolysis in melanoma, Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration, 2023 by The American Society of Hematology.

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did rockefeller found the american cancer society