bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells
Authors: Koo Chuay-Yeng , Giacomini Caterina , Reyes-Corral Marta , Olmos Yolanda , Tavares Ignatius A. , Marson Charles M. , Linardopoulos Spiros , Tutt Andrew N. , Morris Jonathan D.H.
Published: April 2023

Abstract
Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11 to 15 nmol/L, is ATP-competitive, and targets these kinases selectively. TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growth. In contrast, nontumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death, and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes, and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome-amplified cancer cells preferentially, while sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells, and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur. Mol Cancer Ther; 16(11); 2410–21. ©2017 AACR.
Data from Acquired Resistance to the Hsp90 Inhibitor, Ganetespib, in KRAS-Mutant NSCLC Is Mediated via Reactivation of the ERK–p90RSK–mTOR Signaling Network
Authors: Chatterjee Suman , Huang Eric H.-B. , Christie Ian , Kurland Brenda F. , Burns Timothy F.
Published: April 2023

Abstract
Approximately 25% of non–small cell lung cancer (NSCLC) patients have KRAS mutations, and no effective therapeutic strategy exists for these patients. The use of Hsp90 inhibitors in KRAS-mutant NSCLC appeared to be a promising approach, as these inhibitors target many KRAS downstream effectors; however, limited clinical efficacy has been observed due to resistance. Here, we examined the mechanism(s) of acquired resistance to the Hsp90 inhibitor, ganetespib, and identified novel and rationally devised Hsp90 inhibitor combinations, which may prevent and overcome resistance to Hsp90 inhibitors. We derived KRAS-mutant NSCLC ganetespib-resistant cell lines to identify the resistance mechanism(s) and identified hyperactivation of RAF/MEK/ERK/RSK and PI3K/AKT/mTOR pathways as key resistance mechanisms. Furthermore, we found that ganetespib-resistant cells are “addicted” to these pathways, as ganetespib resistance leads to synthetic lethality to a dual PI3K/mTOR, a PI3K, or an ERK inhibitor. Interestingly, the levels and activity of a key activator of the mTOR pathway and an ERK downstream target, p90 ribosomal S6 kinase (RSK), were also increased in the ganetespib-resistant cells. Genetic or pharmacologic inhibition of p90RSK in ganetespib-resistant cells restored sensitivity to ganetespib, whereas p90RSK overexpression induced ganetespib resistance in naïve cells, validating p90RSK as a mediator of resistance and a novel therapeutic target. Our studies offer a way forward for Hsp90 inhibitors through the rational design of Hsp90 inhibitor combinations that may prevent and/or overcome resistance to Hsp90 inhibitors, providing an effective therapeutic strategy for KRAS-mutant NSCLC. Mol Cancer Ther; 16(5); 793–804. ©2017 AACR.
Data from Preclinical Activity of Abemaciclib Alone or in Combination with Antimitotic and Targeted Therapies in Breast Cancer
Authors: O'Brien Neil , Conklin Dylan , Beckmann Richard , Luo Tong , Chau Kevin , Thomas Josh , Mc Nulty Ann , Marchal Christophe , Kalous Ondrej , von Euw Erika , Hurvitz Sara , Mockbee Colleen , Slamon Dennis J.
Published: April 2023

Abstract
The cyclinD:CDK4/6:Rb axis is dysregulated in a variety of human cancers. Targeting this pathway has proven to be a successful therapeutic approach in ER+ breast cancer. In this study, in vitro and in vivo preclinical breast cancer models were used to investigate the expanded use of the CDK4/6 inhibitor, abemaciclib. Using a panel of 44 breast cancer cell lines, differential sensitivity to abemaciclib was observed and was seen predominately in the luminal ER+/HER2− and ER+/HER2+ subtypes. However, a subset of triple-negative breast cancer (TNBC) cell lines with intact Rb signaling were also found to be responsive. Equivalent levels of tumor growth inhibition were observed in ER+/HER2−, ER+/HER2+ as well as biomarker selected TNBC xenografts in response to abemaciclib. In addition, abemaciclib combined with hormonal blockade and/or HER2-targeted therapy induced significantly improved antitumor activity. CDK4/6 inhibition with abemaciclib combined with antimitotic agents, both in vitro and in vivo, did not antagonize the effect of either agent. Finally, we identified a set of Rb/E2F-regulated genes that consistently track with growth inhibitory response and constitute potential pharmacodynamic biomarkers of response to abemaciclib. Taken together, these data represent a comprehensive analysis of the preclinical activity of abemaciclib, used alone or in combination, in human breast cancer models. The subtypes most likely to respond to abemaciclib-based therapies can be identified by measurement of a specific set of biomarkers associated with increased dependency on cyclinD:CDK4/6:Rb signaling. These data support the clinical development of abemaciclib as monotherapy or as a combination partner in selected ER+/HER2−, HER2+/ER+, and TNBCs. Mol Cancer Ther; 17(5); 897–907. ©2018 AACR.
Data from Dimethyl Fumarate Controls the NRF2/DJ-1 Axis in Cancer Cells: Therapeutic Applications
Authors: Saidu Nathaniel Edward Bennett , Noé Gaëlle , Cerles Olivier , Cabel Luc , Kavian-Tessler Niloufar , Chouzenoux Sandrine , Bahuaud Mathilde , Chéreau Christiane , Nicco Carole , Leroy Karen , Borghese Bruno , Goldwasser François , Batteux Frédéric , Alexandre Jérôme
Published: April 2023

Abstract
The transcription factor NRF2 (NFE2L2), regulates important antioxidant and cytoprotective genes. It enhances cancer cell proliferation and promotes chemoresistance in several cancers. Dimethyl fumarate (DMF) is known to promote NRF2 activity in noncancer models. We combined in vitro and in vivo methods to examine the effect of DMF on cancer cell death and the activation of the NRF2 antioxidant pathway. We demonstrated that at lower concentrations (<25 μmol/L), DMF has a cytoprotective role through activation of the NRF2 antioxidant pathway. At higher concentrations, however (>25 μmol/L), DMF caused oxidative stress and subsequently cytotoxicity in several cancer cell lines. High DMF concentration decreases nuclear translocation of NRF2 and production of its downstream targets. The pro-oxidative and cytotoxic effects of high concentration of DMF were abrogated by overexpression of NRF2 in OVCAR3 cells, suggesting that DMF cytotoxicity is dependent of NRF2 depletion. High concentrations of DMF decreased the expression of DJ-1, a NRF2 protein stabilizer. Using DJ-1 siRNA and expression vector, we observed that the expression level of DJ-1 controls NRF2 activation, antioxidant defenses, and cell death in OVCAR3 cells. Finally, antitumoral effect of daily DMF (20 mg/kg) was also observed in vivo in two mice models of colon cancer. Taken together, these findings implicate the effect of DJ-1 on NRF2 in cancer development and identify DMF as a dose-dependent modulator of both NRF2 and DJ-1, which may be useful in exploiting the therapeutic potential of these endogenous antioxidants. Mol Cancer Ther; 16(3); 529–39. ©2017 AACR.
Data from Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling
Authors: Nakai Sho , Tamiya Hironari , Imura Yoshinori , Nakai Takaaki , Yasuda Naohiro , Wakamatsu Toru , Tanaka Takaaki , Outani Hidetatsu , Takenaka Satoshi , Hamada Kenichiro , Myoui Akira , Araki Nobuhito , Ueda Takafumi , Yoshikawa Hideki , Naka Norifumi
Published: April 2023

Abstract
Clear cell sarcoma (CCS) is a rare but chemotherapy-resistant and often fatal high-grade soft-tissue sarcoma (STS) characterized by melanocytic differentiation under control of microphthalmia-associated transcription factor (MITF). Eribulin mesilate (eribulin) is a mechanistically unique microtubule inhibitor commonly used for STS treatment, particularly liposarcoma and leiomyosarcoma. In this study, we examined the antitumor efficacy of eribulin on four human CCS cell lines and two mouse xenograft models. Eribulin inhibited CCS cell proliferation by inducing cell-cycle arrest and apoptosis, shrunk CCS xenograft tumors, and increased tumor vessel density. Eribulin induced MITF protein upregulation and stimulated tumor cell melanocytic differentiation through ERK1/2 inactivation (a MITF negative regulator) in vitro and in vivo. Moreover, tumor reoxygenation, probably caused by eribulin-induced vascular remodeling, attenuated cell growth and inhibited ERK1/2 activity, thereby upregulating MITF expression and promoting melanocytic differentiation. Finally, downregulation of MITF protein levels modestly debilitated the antiproliferative effect of eribulin on CCS cells. Taken together, eribulin suppresses CCS through inhibition of cell proliferation and promotion of tumor differentiation by acting both directly on tumor cells and indirectly through tumor reoxygenation.
Data from The Exportin-1 Inhibitor Selinexor Exerts Superior Antitumor Activity when Combined with T-Cell Checkpoint Inhibitors
Authors: Farren Matthew R. , Hennessey Rebecca C. , Shakya Reena , Elnaggar Omar , Young Gregory , Kendra Kari , Landesman Yosef , Elloul Sivan , Crochiere Marsha , Klebanov Boris , Kashyap Trinayan , Burd Christin E. , Lesinski Gregory B.
Published: April 2023

Abstract
Selinexor, a selective inhibitor of nuclear export (SINE) compound targeting exportin-1, has previously been shown to inhibit melanoma cell growth in vivo. We hypothesized that combining selinexor with antibodies that block or disrupt T-cell checkpoint molecule signaling would exert superior antimelanoma activity. In vitro, selinexor increased PDCD1 and CTLA4 gene expression in leukocytes and induced CD274 gene expression in human melanoma cell lines. Mice bearing syngeneic B16F10 melanoma tumors demonstrated a significant reduction in tumor growth rate in response to the combination of selinexor and anti-PD-1 or anti-PD-L1 antibodies (P < 0.05). Similar results were obtained in B16F10-bearing mice treated with selinexor combined with anti-CTLA4 antibody. Immunophenotypic analysis of splenocytes by flow cytometry revealed that selinexor alone or in combination with anti-PD-L1 antibody significantly increased the frequency of both natural killer cells (P ≤ 0.050) and CD4+ T cells with a Th1 phenotype (P ≤ 0.050). Further experiments indicated that the antitumor effect of selinexor in combination with anti-PD-1 therapy persisted under an alternative dosing schedule but was lost when selinexor was administered daily. These data indicate that the efficacy of selinexor against melanoma may be enhanced by disrupting immune checkpoint activity. Mol Cancer Ther; 16(3); 417–27. ©2017 AACR.

See related article by Tyler et al., p. 428.
Data from Sentinel Lymph Node–Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model
Authors: Tanaka Yuya , Araki Koji , Tanaka Shingo , Miyagawa Yoshihiro , Suzuki Hiroshi , Kamide Daisuke , Tomifuji Masayuki , Uno Kosuke , Kimura Eiko , Yamashita Taku , Ueda Yasuji , Shiotani Akihiro
Published: April 2023

Abstract
In clinical N0 (cN0) cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)–targeted therapy using the urokinase-type plasminogen activator (uPA)-dependent oncolytic Sendai virus “BioKnife.” The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its antitumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue squamous cell carcinoma cells, in the tongue of the nude mice, and after 2 weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imaging system. We also examined its antitumor effects and mechanisms through serial section analysis of lymph nodes. GFP reporter expression was clearly visible in the lymph nodes of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and lymph nodes in the virus groups compared with that in the control group (P < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant antitumor effect against LNM compared with the control groups (P < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in cN0 patients with HNSCC.
Data from Targeting the Mevalonate Pathway Suppresses VHL-Deficient CC-RCC through an HIF-Dependent Mechanism
Authors: Thompson Jordan M. , Alvarez Alejandro , Singha Monika K. , Pavesic Matthew W. , Nguyen Quy H. , Nelson Luke J. , Fruman David A. , Razorenova Olga V.
Published: April 2023

Abstract
Clear cell renal cell carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advanced stages. The objective of this study was to investigate HMG-CoA reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel–Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins. Inhibition of mevalonate synthesis by statins causes a profound cytostatic effect at nanomolar concentrations and becomes cytotoxic at low micromolar concentrations in VHL-deficient CC-RCC. The synthetic lethal effect can be fully rescued by both mevalonate and geranylgeranylpyrophosphate, but not by squalene, indicating that the effect is due to disruption of small GTPase isoprenylation and not the inhibition of cholesterol synthesis. Inhibition of Rho and Rho kinase (ROCK) signaling contributes to the synthetic lethality effect, and overactivation of hypoxia-inducible factor signaling resulting from VHL loss is required. Finally, statin treatment is able to inhibit both tumor initiation and progression of subcutaneous 786-OT1-based CC-RCC tumors in mice. Thus, statins represent potential therapeutics for the treatment of VHL-deficient CC-RCC. Mol Cancer Ther; 17(8); 1781–92. ©2018 AACR.
Data from EZH2 Inhibition by Tazemetostat Results in Altered Dependency on B-cell Activation Signaling in DLBCL
Authors: Brach Dorothy , Johnston-Blackwell Danielle , Drew Allison , Lingaraj Trupti , Motwani Vinny , Warholic Natalie M. , Feldman Igor , Plescia Christopher , Smith Jesse J. , Copeland Robert A. , Keilhack Heike , Chan-Penebre Elayne , Knutson Sarah K. , Ribich Scott A. , Raimondi Alejandra , Thomenius Michael J.
Published: April 2023

Abstract
The EZH2 small-molecule inhibitor tazemetostat (EPZ-6438) is currently being evaluated in phase II clinical trials for the treatment of non-Hodgkin lymphoma (NHL). We have previously shown that EZH2 inhibitors display an antiproliferative effect in multiple preclinical models of NHL, and that models bearing gain-of-function mutations in EZH2 were consistently more sensitive to EZH2 inhibition than lymphomas with wild-type (WT) EZH2. Here, we demonstrate that cell lines bearing EZH2 mutations show a cytotoxic response, while cell lines with WT-EZH2 show a cytostatic response and only tumor growth inhibition without regression in a xenograft model. Previous work has demonstrated that cotreatment with tazemetostat and glucocorticoid receptor agonists lead to a synergistic antiproliferative effect in both mutant and wild-type backgrounds, which may provide clues to the mechanism of action of EZH2 inhibition in WT-EZH2 models. Multiple agents that inhibit the B-cell receptor pathway (e.g., ibrutinib) were found to have synergistic benefit when combined with tazemetostat in both mutant and WT-EZH2 backgrounds of diffuse large B-cell lymphomas (DLBCL). The relationship between B-cell activation and EZH2 inhibition is consistent with the proposed role of EZH2 in B-cell maturation. To further support this, we observe that cell lines treated with tazemetostat show an increase in the B-cell maturation regulator, PRDM1/BLIMP1, and gene signatures corresponding to more advanced stages of maturation. These findings suggest that EZH2 inhibition in both mutant and wild-type backgrounds leads to increased B-cell maturation and a greater dependence on B-cell activation signaling. Mol Cancer Ther; 16(11); 2586–97. ©2017 AACR.
Data from Expression Levels of Therapeutic Targets as Indicators of Sensitivity to Targeted Therapeutics
Authors: Roy Riti , Winteringham Louise N. , Lassmann Timo , Forrest Alistair R.R.
Published: April 2023

Abstract
Cancer precision medicine aims to predict the drug likely to yield the best response for a patient. Genomic sequencing of tumors is currently being used to better inform treatment options; however, this approach has had a limited clinical impact due to the paucity of actionable mutations. An alternative to mutation status is the use of gene expression signatures to predict response. Using data from two large-scale studies, The Genomics of Drug Sensitivity of Cancer (GDSC) and The Cancer Therapeutics Response Portal (CTRP), we investigated the relationship between the sensitivity of hundreds of cell lines to hundreds of drugs, and the relative expression levels of the targets these drugs are directed against. For approximately one third of the drugs considered (73/222 in GDSC and 131/360 in CTRP), sensitivity was significantly correlated with the expression of at least one of the known targets. Surprisingly, for 8% of the annotated targets, there was a significant anticorrelation between target expression and sensitivity. For several cases, this corresponded to drugs targeting multiple genes in the same family, with the expression of one target significantly correlated with sensitivity and another significantly anticorrelated suggesting a possible role in resistance. Furthermore, we identified nontarget genes that are significantly correlated or anticorrelated with drug sensitivity, and find literature linking several to sensitization and resistance. Our analyses provide novel and important insights into both potential mechanisms of resistance and relative efficacy of drugs against the same target.
Data from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer
Authors: Naidoo Kalnisha , Wai Patty T. , Maguire Sarah L. , Daley Frances , Haider Syed , Kriplani Divya , Campbell James , Mirza Hasan , Grigoriadis Anita , Tutt Andrew , Moseley Paul M. , Abdel-Fatah Tarek M.A. , Chan Stephen Y.T. , Madhusudan Srinivasan , Rhaka Emad A. , Ellis Ian O. , Lord Christopher J. , Yuan Yinyin , Green Andrew R. , Natrajan Rachael
Published: April 2023

Abstract
Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. We therefore aimed to assess the frequency and distribution of CDK12 protein expression by IHC in independent cohorts of breast cancer and correlate this with outcome and genomic status. We found that 21% of primary unselected breast cancers were CDK12 high, and 10.5% were absent, by IHC. CDK12 positivity correlated with HER2 positivity but was not an independent predictor of breast cancer–specific survival taking HER2 status into account; however, absent CDK12 protein expression significantly correlated with a triple-negative phenotype. Interestingly, CDK12 protein absence was associated with reduced expression of a number of DDR proteins including ATR, Ku70/Ku80, PARP1, DNA-PK, and γH2AX, suggesting a novel mechanism of CDK12-associated DDR dysregulation in breast cancer. Our data suggest that diagnostic IHC quantification of CDK12 in breast cancer is feasible, with CDK12 absence possibly signifying defective DDR function. This may have important therapeutic implications, particularly for triple-negative breast cancers. Mol Cancer Ther; 17(1); 306–15. ©2017 AACR.
Abstract 49: Comparison of subcutaneous and orthotopic tumor growth in syngeneic mouse models of ovarian and renal cancer
Authors: Suominen Mari I. , Zdrojewska Justyna , Konkol Yvonne , Fagerlund Katja M. , Ristola Mervi , Rissanen Jukka P.
Published: April 2023

Oncology drug development has markedly lower success rate (3.4%) than other indications (20.9%) as reported by Wong, Siah and Lo in 2019. Animal models are often pointed at as the culprits for failure in clinical trials. While better animal models for cancer are needed and constantly developed, the incentive of drug developers to use those might not be clear, because the regulatory authorities do not require it. Subcutaneous tumors have earned their place in drug development but adding more sophisticated models to the testing panel before entering the clinical phase should improve the success rate. We present here the properties of subcutaneous and orthotopic tumor growth in two syngeneic models. HM-1 murine ovarian cancer cells were inoculated subcutaneously (s.c.) and intraperitoneally (representing the stage of intraperitoneal carcinomatosis) and murine renal adenocarcinoma Renca cells s.c. and orthotopically within the renal capsule. Body weight and tumor growth were followed, and mice were sacrificed according to humane endpoint criteria. To compare tumor growth in s.c. sites and within the abdomen, the tumor weight at sacrifice was divided by the number of days since the inoculation. In the HM-1 model, the mice with intraperitoneal tumor were sacrificed due to build-up of ascites on average six days earlier that the mice with s.c. tumor. In s.c. HM-1 tumor-bearing mice, the reason for sacrifice was tumor ulceration. In the Renca model, the s.c. and intrabursal models were approximately the same length. There was a striking difference in the tumor growth rate (mg/day) in s.c. versus abdominal sites in both models. The growth was 4-5 times faster in the abdominal sites than subcutaneously, highlighting the effect of tumor specific microenvironment. It is easy to understand that having promising results might be easier in a slower growing model. However, since both ovarian and renal cancer show very different growth kinetics within the abdominal cavity, testing drug candidates aimed for those indications in orthotopic models before accessing the clinical trials could give a more relevant evaluation of the potency of the drug candidates.

Citation Format: Mari I. Suominen, Justyna Zdrojewska, Yvonne Konkol, Katja M. Fagerlund, Mervi Ristola, Jukka P. Rissanen. Comparison of subcutaneous and orthotopic tumor growth in syngeneic mouse models of ovarian and renal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 49.
Abstract 563: Preclinical development of YL202, a novel HER3-targeting antibody-drug conjugate (ADC) with novel DNA topoisomerase I inhibitor for treatment of solid tumors
Authors: Xu Jian , Zong Qing , Zhu Liang , Liu Qigang , Stann Sasha , Cai Jiaqiang
Published: April 2023

HER3, a member of the HER family, is over-expressed in cancer cells and further elevated after HER2/EGFR/endocrine targeting treatment. YL202 is a novel HER3-targeting antibody-drug conjugate (ADC) structurally composed of a human anti-HER3 antibody, protease-cleavable linker, and a novel topoisomerase I inhibitor. This ADC was prepared using MediLink’s TMALIN platform, a proprietary tumor microenvironment activable linker-payload platform, which achieved a high drug-to-antibody ratio through homogeneously conjugated and favorable hydrophilic linker-payload.

In preclinical studies, YL202 exhibited strong reactivity, highly internalization and potent cytotoxicity toward tumor cells. YL202 also demonstrated significant dose-dependent antitumor activity in cell line- and patient-derived xenograft (CDX and PDX) mouse models representing several cancer types and could induce complete tumor regressions with no observable toxicity. YL202 showed stable PK profile with overlapping ADC and TAb curves in a 28-day cynomolgus monkey study. GLP toxicity studies using cynomolgus monkeys showed that YL202 is well tolerated with calculated therapeutic index (TI, HNSTD/MED) of ~100 for repeat dosing. No lung or platelet toxicity findings were observed at doses up to the maximum tolerated dose (MTD).

Based on these preclinical results, it demonstrates that YL202’s advanced ADC design results in an increased therapeutic margin, and YL201 could be further developed in HER3 positive cancer patients.

Citation Format: Jian Xu, Qing Zong, Liang Zhu, Qigang Liu, Sasha Stann, Jiaqiang Cai. Preclinical development of YL202, a novel HER3-targeting antibody-drug conjugate (ADC) with novel DNA topoisomerase I inhibitor for treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 563.
Abstract 5883: Computational analysis of immune synapses in melanoma tumor microenvironment
Authors: Liu Zichao , Wang Victor G. , Martinek Jan , Foroughi pour Ali , Zhou Jie , Palucka Karolina , Chuang Jeffrey H.
Published: April 2023

High-resolution multiplexed tissue imaging such as imaging mass cytometry (IMC) has enabled quantitative cell characterization with preserved tissue architecture. However, the subcellular resolution information has not been fully leveraged yet, as most analyses have focused on cellular or compartment level features. Here, we have developed a robust computational approach integrating cellular spatial and molecular features in multiplexed images to quantify immune synapses. Our approach enables computational detection of subcellular enrichment of T cell co-receptors at immune synapses, which are key regulators of T cell functions in the tumor microenvironment (TME). We quantified immune synapse strength between T cells and various antigen-presenting cells in tumor regions in one melanoma whole tissue immunofluorescence dataset and two independent melanoma IMC datasets covering 99 patients. We observed that sub-localizations of immune synapse-related molecules are highly correlated, e.g. CD3 with CD8. These co-localizations are cell type-specific, with differential behaviors in CD4+ or CD8+ T subtypes. Intra-tumoral T-cell-myeloid synapses are associated with improved T cell proliferation (p = 2.8E-4). In addition, we also observed that cytotoxic T cell - melanoma synapses in immune rich regions are stronger in immune checkpoint inhibition therapy responders than in non-responding patients (p = 0.013). Our approach enables computational resolution of spatial inter-cellular interactions within the TME, is applicable across imaging modalities, and facilities assessment of biological and clinical significance.

Citation Format: Zichao Liu, Victor G. Wang, Jan Martinek, Ali Foroughi pour, Jie Zhou, Karolina Palucka, Jeffrey H. Chuang. Computational analysis of immune synapses in melanoma tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5883.
Supplementary Fig. 6 from Transcription Factor Interactions Mediate EGF-Dependent COX-2 Expression
Authors: Xu Kaiming , Shu Hui-Kuo G.
Published: April 2023

Supplementary Fig. 6 - PDF file 30K, P2.6 reporter construct display EGF-induced activity
Supplementary Fig. 3 from Transcription Factor Interactions Mediate EGF-Dependent COX-2 Expression
Authors: Xu Kaiming , Shu Hui-Kuo G.
Published: April 2023

Supplementary Fig. 3 - PDF file 87K, Src kinase is upstream of the p38-MAPK/PKC-delta signaling cascade
Supplementary Figure 3 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells
Authors: Ladam Franck , Damour Isabelle , Dumont Patrick , Kherrouche Zoulika , de Launoit Yvan , Tulasne David , Chotteau-Lelievre Anne
Published: April 2023

PDF file - 42K, Relative luciferase activity measured for the human cyclin d2 promoter. Alignment of the 55 bp Mouse, Rat and Human proximal cyclin d2 promoter region.
Supplementary Figures from TDP1 and PARP1 Deficiency Are Cytotoxic to Rhabdomyosarcoma Cells
Authors: Fam Hok Khim , Walton Cheryl , Mitra Sheetal A. , Chowdhury Miraj , Osborne Nichola , Choi Kunho , Sun Guobin , Wong Patrick C.W. , O'Sullivan Maureen J. , Turashvili Gulisa , Aparicio Samuel , Triche Timothy J. , Bond Mason , Pallen Catherine J. , Boerkoel Cornelius F.
Published: April 2023

Supplementary Figures - PDF file 381K, S1. Specificity of the Tdp1 antiserum. S2. Tdp1 expression in pediatric solid tumors. S3. Generation of transient and constitutive TDP1 knockdown by treatment with siRNA and shRNA and assay for sensitivity of Tdp1-deficient MEFs to DNA breaks. S4. Detection of Tdp1 cleavage activity in cell lysates by kinetic determination of Tdp1 cleavage activity in nuclear lysates using a real-time fluorophorequencher coupled DNA substrate. S5. Effect of cellular growth rate vs. Tdp1 expression on sensitivity to CPT treatment. S6. Analysis of PARP-1 and PARP-2 expression levels in RMS and normal myoblasts. S7. PARP-1 inhibitor treatment sensitizes RMS cell lines to CPT. S8. RMS cells develop resistance to PARP-1 inhibitors posttreatment with TDP1 shRNA
Supplementary Table 1 from Oncogenic MUC1-C Promotes Tamoxifen Resistance in Human Breast Cancer
Authors: Kharbanda Akriti , Rajabi Hasan , Jin Caining , Raina Deepak , Kufe Donald
Published: April 2023

PDF file - 19K, Supplemental Table S1. Primers used for qRT-PCR of Rab31.
Supplementary Figure 3 from Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid
Authors: Junco Jacob J. , Mancha Anna , Malik Gunjan , Wei Sung-Jen , Kim Dae Joon , Liang Huiyun , Slaga Thomas J.
Published: April 2023

PDF file - 1694K, Figure S3: UA and RES synergistically induced mixed apoptotic/necrotic death of Ca3/7 cells.
Supplementary Table 2 from Tumor Suppressor Functions of miR-133a in Colorectal Cancer
Authors: Dong Yujuan , Zhao Junhong , Wu Chung-Wah , Zhang Lijing , Liu Xiaodong , Kang Wei , Leung Wing-Wah , Zhang Ning , Chan Francis K.L. , Sung Joseph J.Y. , Ng Simon S.M. , Yu Jun
Published: April 2023

PDF file - 45K, Characteristics of the CRC patients for miRNA validation.
Supplementary Table 1 from Tumor Suppressor Functions of miR-133a in Colorectal Cancer
Authors: Dong Yujuan , Zhao Junhong , Wu Chung-Wah , Zhang Lijing , Liu Xiaodong , Kang Wei , Leung Wing-Wah , Zhang Ning , Chan Francis K.L. , Sung Joseph J.Y. , Ng Simon S.M. , Yu Jun
Published: April 2023

PDF file - 48K, Characteristics of the CRC patients for miRNA array.
Supplementary Figure 1 from Tumor Suppressor Functions of miR-133a in Colorectal Cancer
Authors: Dong Yujuan , Zhao Junhong , Wu Chung-Wah , Zhang Lijing , Liu Xiaodong , Kang Wei , Leung Wing-Wah , Zhang Ning , Chan Francis K.L. , Sung Joseph J.Y. , Ng Simon S.M. , Yu Jun
Published: April 2023

PDF file - 207K, miR-133a exerted inhibitory effects on p53 mutant cell lines DLD1 and HT29.
Supplementary Figure 5 from Autophagy-Dependent Metabolic Reprogramming Sensitizes TSC2-Deficient Cells to the Antimetabolite 6-Aminonicotinamide
Authors: Parkhitko Andrey A. , Priolo Carmen , Coloff Jonathan L. , Yun Jihye , Wu Julia J. , Mizumura Kenji , Xu Wenping , Malinowska Izabela A. , Yu Jane , Kwiatkowski David J. , Locasale Jason W. , Asara John M. , Choi Augustine M.K. , Finkel Toren , Henske Elizabeth P.
Published: April 2023

PDF file - 204K, mTORC1 signaling upon chloroquine/6-AN treatment and effect of mTORC1 inhibition on the proliferation of Tsc2-/- cells treated with the dual drug combination.
Supplementary Figure 4 from Autophagy-Dependent Metabolic Reprogramming Sensitizes TSC2-Deficient Cells to the Antimetabolite 6-Aminonicotinamide
Authors: Parkhitko Andrey A. , Priolo Carmen , Coloff Jonathan L. , Yun Jihye , Wu Julia J. , Mizumura Kenji , Xu Wenping , Malinowska Izabela A. , Yu Jane , Kwiatkowski David J. , Locasale Jason W. , Asara John M. , Choi Augustine M.K. , Finkel Toren , Henske Elizabeth P.
Published: April 2023

PDF file - 35K, Chloroquine treatment induces ROS production.
Supplementary Figure 1 from Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells
Authors: Guo Xingjun , Wang Min , Jiang Jianxin , Xie Chengchen , Peng Feng , Li Xu , Tian Rui , Qin Renyi
Published: April 2023

PDF file - 11375K, A. Sorting of lentivirally transduced cell cultures to highest purity based on GFP expression. B. Western blot analysis of Tiam1 protein expression. C. Real-time RT-PCR analysis of Tiam1 mRNA expression. D. Rac1 activity determined by G-LISA assays. E. Western blotting for β-catenin in the cytoplasm and nucleus of panc-1 cells after transfection with si-rac1 or si-β-catenin or stimulation with NSC23766. F. CCK-8 analysis of cell proliferation after transfection with si-rac1 or si-β-catenin or treatment with NSC23766. G. EDU analysis of cell proliferation after transfection with si-rac1 or si-β-catenin or treatment with NSC23766.
Supplementary Figures 1 - 6 from Nuclear Expression of β-Catenin Promotes RB Stability and Resistance to TNF-Induced Apoptosis in Colon Cancer Cells
Authors: Han Jinbo , Soletti Rossana C. , Sadarangani Anil , Sridevi Priya , Ramirez Michael E. , Eckmann Lars , Borges Helena L. , Wang Jean Y.J.
Published: April 2023

PDF file - 2529K, S1 Similar levels of TUNEL-positive cells were observed in the splenic tissue sections from Rb+/+ and RbMI/MI mice at 24 hr after PBS (Veh) or TNF-α i.p. injection. Scale bar: 50 μm. **p<0.01, error bars: SD. S2 Characterization of colonic tumors induced by AOM/DSS in Rb+/+ and RbMI/MI mice. S3 β-catenin exon-3 sequencing, E-cadherin staining, TNF-induced IκB degradation and RB cleavage in colon cancer cells. S4 RB knockdown enhanced TNF/CHX induced apoptosis in HCT116 cells. S5 Effects of GSK-3β inhibitor AR on HCT116 cells S6 Co-immunoprecipiation of RB and β-catenin and in vitro Caspase Cleavage of RB
Supplementary Table from Integrin α3β1 Can Function to Promote Spontaneous Metastasis and Lung Colonization of Invasive Breast Carcinoma
Authors: Zhou Bo , Gibson-Corley Katherine N. , Herndon Mary E. , Sun Yihan , Gustafson-Wagner Elisabeth , Teoh-Fitzgerald Melissa , Domann Frederick E. , Henry Michael D. , Stipp Christopher S.
Published: April 2023

PDF file, 38K, Flow cytometry of integrin expression in 4T1 carcinoma cells.
Supplementary Figures from Integrin α3β1 Can Function to Promote Spontaneous Metastasis and Lung Colonization of Invasive Breast Carcinoma
Authors: Zhou Bo , Gibson-Corley Katherine N. , Herndon Mary E. , Sun Yihan , Gustafson-Wagner Elisabeth , Teoh-Fitzgerald Melissa , Domann Frederick E. , Henry Michael D. , Stipp Christopher S.
Published: April 2023

PDF file, 707K, S1. Comparison of alpha3beta1 and alpha6beta4 integrin expression in 4T1 cell lines. S2. BLI of spontaneous and experimental metastasis (color) S3. Certain large primary mammary fat pad tumors exhibited substantial centralized zones of necrosis. S4. Silencing alpha3 integrin leads to fewer pulmonary metastases following mammary fat pad injection. S5. RNAi-mediated silencing of RhoC has no impact on 4T1 cell metastatic colonization. S6. Cox-2, matrix metalloproteinase, VEGF, and transendothelial migration assays. S7. MDA-MB-231 breast cancer cells do not secrete laminin-332 or laminin-511 or depend on alpha3 integrin in short term proliferation assays.
Supplementary Figures 1 - 6 from miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression
Authors: Bousquet Marina , Zhuang Guoqing , Meng Cong , Ying Wei , Cheruku Patali S. , Shie Andrew T. , Wang Stephanie , Ge Guangtao , Wong Piu , Wang Gang , Safe Stephen , Zhou Beiyan
Published: April 2023

PDF file - 146K, Figure S1. Analysis of microRNA profiles in various MLL-associated leukemias. Figure S2. Analysis of MLL-AF9 expression cells transformed from bone marrow stem/progenitors. Figure S3. Phenotypic analysis of leukemia from mice transplanted with MLL-AF9 cells. Figure S4. Quantitative PCR analysis of miR-150 expression in various cell types. Figure S5. Wild type and mutated binding sites of miR-150 in Myb luciferase constructs. Figure S6. Wild type and mutated binding sites of miR-150 in CBL and Egr2 luciferase constructs.
Supplementary Figures 1 - 5, Table 1 from miR-106a Represses the Rb Tumor Suppressor p130 to Regulate Cellular Proliferation and Differentiation in High-Grade Serous Ovarian Carcinoma
Authors: Liu Zhaojian , Gersbach Elizabeth , Zhang Xiyu , Xu Xiaofei , Dong Ruifen , Lee Peng , Liu Jinsong , Kong Beihua , Shao Changshun , Wei Jian-Jun
Published: April 2023

PDF file - 1114K, S1. RT-PCR analysis illustrates the stable miR-106a expression in two benign (FTE187, T29) and malignant (SKOV3, HEY) cell lines.1 supplementary table S2. Growth curve of SKOV3 cell line with (red square) and without (blue diamonds) miR-106a overexpression in different doses of paclitaxel (A) and cisplatin (B)treatment in vitro. S3. Immunohistochemical stain of CD133 in four xenografts of SKOV3 tumor cells with (left panel) and without (right panel) miR-106a overexpression. S4. The side-population, major population of normal (T29) and malignant (HEY) cell lines with (top) and without (bottom) miR-106a overexpression were analyzed by flow cytometer. S5. Hematoxylin and eosin stained slides illustrate four xenografts of SKOV3 tumor masses without (left panel) and with (right panel) miR-106a overexpression. Supplementary Table 1 The published data show upregulation of miR-106a and its family members in ovarian cancer.
Supplementary Figure 1 from NEDD9 Depletion Leads to MMP14 Inactivation by TIMP2 and Prevents Invasion and Metastasis
Authors: McLaughlin Sarah L. , Ice Ryan J. , Rajulapati Anuradha , Kozyulina Polina Y. , Livengood Ryan H. , Kozyreva Varvara K. , Loskutov Yuriy V. , Culp Mark V. , Weed Scott A. , Ivanov Alexey V. , Pugacheva Elena N.
Published: April 2023

PDF file - 1345K, Supplementary Fig. 1 (A). Statistical analysis of NEDD9 expression based on intensity and number of positively stained cells in Fig.1(A) visually determined by two pathologists according to the scoring procedure described in Material and Methods section. (B). Immunofluorescent (IF) staining of ZR-75-1 cells with Rhodamine-Phalloidin (red) and cortactin (green), FITC-gelatin (pseudo colored white). (C). Immuofluorescent analysis of structural components of invadopodia: Arp3 (green), N-WASP (green), cortactin (red), DNA (blue), FITC-gelatin (white) in MDA231- MB-231-shCon, -shNEDD9 (N4) cells.
Supplementary Materials, Figures 1 - 6 from Inhibition of NF-κB Signaling Ablates the Invasive Phenotype of Glioblastoma
Authors: Westhoff Mike-Andrew , Zhou Shaoxia , Nonnenmacher Lisa , Karpel-Massler Georg , Jennewein Claudia , Schneider Matthias , Halatsch Marc-Eric , Carragher Neil O. , Baumann Bernd , Krause Alexander , Simmet Thomas , Bachem Max G. , Wirtz Christian R. , Debatin Klaus-Michael
Published: April 2023

PDF file - 1858K, S1. Further characterization of NF-kappaB signaling in U87MG GBM cells. S2. The role of NF-kappaB signaling in T98G is similar to that in U87MG GBM cells. S3. Influence of NF-kappaB signaling in U87MG GBM cells on different cellular aspects. S4. The effect of Disulfiram on U87MG cells. S5. Protein expression/phosphorylation: IkappaBalpha-Superrepressor vs. Disulfiram. S6. Further characterization of primary tumor-initiating GBM cells.
Supplementary Figure 2 from PHD4 Stimulates Tumor Angiogenesis in Osteosarcoma Cells via TGF-α
Authors: Klotzsche-von Ameln Anne , Prade Ina , Grosser Marianne , Kettelhake Antje , Rezaei Maryam , Chavakis Triantafyllos , Flamme Ingo , Wielockx Ben , Breier Georg
Published: April 2023

PDF file - 40K, S2. Overexpression of PHD4 in LM8 osteosarcomas has no effect on the relative endothelial area.
Supplementary Figure Legends from Epithelial-Specific Deletion of 11β-HSD2 Hinders Apcmin/+ Mouse Tumorigenesis
Authors: Jiang Li , Yang Shilin , Yin Huiyong , Fan Xiaofeng , Wang Suwan , Yao Bing , Pozzi Ambra , Chen Xiaoping , Harris Raymond C. , Zhang Ming-Zhi
Published: April 2023

PDF - 72KB, Legends for Supplementary Figures 1-5.
Supplementary Table 3 from The Impact of miRNA-Based Molecular Diagnostics and Treatment of NRF2-Stabilized Tumors
Authors: Yamamoto Shinsuke , Inoue Jun , Kawano Tatsuyuki , Kozaki Ken-ichi , Omura Ken , Inazawa Johji
Published: April 2023

XLSX file - 79K, TaqMan MicroRNA Assays ID and target sequence of analyzed miRNAs.
Supplementary Figure 5 from Activation of the NF-κB Pathway by the STAT3 Inhibitor JSI-124 in Human Glioblastoma Cells
Authors: McFarland Braden C. , Gray G. Kenneth , Nozell Susan E. , Hong Suk W. , Benveniste Etty N.
Published: April 2023

PDF file - 75K, Inhibition of NF-κB does not prevent JSI-124 induced apoptosis.
Supplementary Figure 3 from Activation of the NF-κB Pathway by the STAT3 Inhibitor JSI-124 in Human Glioblastoma Cells
Authors: McFarland Braden C. , Gray G. Kenneth , Nozell Susan E. , Hong Suk W. , Benveniste Etty N.
Published: April 2023

PDF file - 102K, JSI-124 induces the mRNA expression of inflammatory genes in human xenograft GBM cells and murine primary astrocytes.
Supplementary Figures 3 - 4 from Hematopoietic Expression of Oncogenic BRAF Promotes Aberrant Growth of Monocyte-Lineage Cells Resistant to PLX4720
Authors: Kamata Tamihiro , Dankort David , Kang Jing , Giblett Susan , Pritchard Catrin A. , McMahon Martin , Leavitt Andrew D.
Published: April 2023

PDF file - 95K, S3. Purity and morphology of the sorted bone marrow populations. S4. Morphology of the colonies developed in the presence of lowdose IL-3.
Supplementary Figure 1 from Hematopoietic Expression of Oncogenic BRAF Promotes Aberrant Growth of Monocyte-Lineage Cells Resistant to PLX4720
Authors: Kamata Tamihiro , Dankort David , Kang Jing , Giblett Susan , Pritchard Catrin A. , McMahon Martin , Leavitt Andrew D.
Published: April 2023

PDF file - 247K, Histological analysis of spleen and liver in primary mice.
Supplementary Table 1 from EGFR Inhibition Induces Proinflammatory Cytokines via NOX4 in HNSCC
Authors: Fletcher Elise V.M. , Love-Homan Laurie , Sobhakumari Arya , Feddersen Charlotte R. , Koch Adam T. , Goel Apollina , Simons Andrean L.
Published: April 2023

PDF file - 77K
Supplementary Figures 1 through 3 from Spontaneous Reversion of the Angiogenic Phenotype to a Nonangiogenic and Dormant State in Human Tumors
Authors: Rogers Michael S. , Novak Katherine , Zurakowski David , Cryan Lorna M. , Blois Anna , Lifshits Eugene , Bø Trond H. , Oyan Anne M. , Bender Elise R. , Lampa Michael , Kang Soo-Young , Naxerova Kamila , Kalland Karl-Henning , Straume Oddbjorn , Akslen Lars A. , Watnick Randolph S. , Folkman Judah , Naumov George N.
Published: April 2023

PDF - 254K, Supplemental Figure 1: In vivo proliferation of angiogenic and non-angiogenic cell clones. Supplemental Figure 2: Chromosomal locations of genes with relative overexpression in either angiogenic or revertant clones. Supplemental Figure 3: Canonical pathways overrepresented in angiogenic and revertant clones.
Figure S2 from Hypoxia Selectively Enhances Integrin α5β1 Receptor Expression in Breast Cancer to Promote Metastasis
Authors: Ju Julia A. , Godet Inês , Ye I Chae , Byun Jungmin , Jayatilaka Hasini , Lee Sun Joo , Xiang Lisha , Samanta Debangshu , Lee Meng Horng , Wu Pei-Hsun , Wirtz Denis , Semenza Gregg L. , Gilkes Daniele M.
Published: April 2023

MCF-7 cells require HIF-1 and HIF-2 for cell surface expression of ITGA5.
Supplementary Table 2 from Differential Expression of Stress and Immune Response Pathway Transcripts and miRNAs in Normal Human Endothelial Cells Subjected to Fractionated or Single-Dose Radiation
Authors: Palayoor Sanjeewani T. , John-Aryankalayil Molykutty , Makinde Adeola Y. , Falduto Michael T. , Magnuson Scott R. , Coleman C. Norman
Published: April 2023

PDF - 56K, Microarray data depicting gene expression fold changes respective to control group in genes from stress response category following SD and MF radiation exposure at 6h and 24h.
Supplemental Figure 3: from β-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation
Authors: Kallifatidis Georgios , Munoz Daniel , Singh Rajendra Kumar , Salazar Nicole , Hoy James J. , Lokeshwar Bal L.
Published: April 2023

C4-2B cells were seeded in 8 well chamber slides in antibiotic-free media (30,000 cells per well). Twenty-four hours later, cells were transfected with ARR2-eGFP plasmid using Lipofectamine 2000. After overnight incubation, culture medium was replaced with low serum media (1% FBS). Twenty-four hours later, cells were washed with PBS-Tween and fixed with PFA, 4%.
Supplementary Figure 2 from PI3K and Bcl-2 Inhibition Primes Glioblastoma Cells to Apoptosis through Downregulation of Mcl-1 and Phospho-BAD
Authors: Pareja Fresia , Macleod David , Shu Chang , Crary John F. , Canoll Peter D. , Ross Alonzo H. , Siegelin Markus D.
Published: April 2023

PDF file - 72K, S2. A) U87 or LN229 cells were treated with increasing concentration of ABT-263 for 16 h. Subsequently, cells were harvested, stained with Annexin V/Propidium iodide and subjected to flow cytometry. Provided are the percentages of viable cells under the indicated treatment conditions. 2 way ANOVA was performed and three stars "***" indicates a p value of less than 0.001. ABT10/ABT40 - 10/40 μM ABT-263.
Supplemental Figure Legends from MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling
Authors: McNew Kelsey L. , Whipple William J. , Mehta Anita K. , Grant Trevor J. , Ray Leah , Kenny Connor , Singh Anurag
Published: April 2023

Supplemental Figure Legends
Supplemental Figure 8 from Tumor Suppressor Activity of Selenbp1, a Direct Nkx2-1 Target, in Lung Adenocarcinoma
Authors: Caswell Deborah R. , Chuang Chen-Hua , Ma Rosanna K. , Winters Ian P. , Snyder Eric L. , Winslow Monte M.
Published: April 2023

Selenbp1 cutting efficiency and expression.
Figure S2 from MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling
Authors: McNew Kelsey L. , Whipple William J. , Mehta Anita K. , Grant Trevor J. , Ray Leah , Kenny Connor , Singh Anurag
Published: April 2023

KRAS and MEK and TAK1 dependent effects on cell cycle progression and apoptosis in colon cancer cell lines.