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Journal articles on the topic '4AC 1 CELL TINE'

Author: Grafiati

Published: 11 September 2023

Last updated: 31 July 2025

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1

Sakao, Kozue, Hanako Saruwatari, Shohei Minami, and De-Xing Hou. "Hydroxyl Group Acetylation of Quercetin Enhances Intracellular Absorption and Persistence to Upregulate Anticancer Activity in HepG2 Cells." International Journal of Molecular Sciences 24, no. 23 (2023): 16652. http://dx.doi.org/10.3390/ijms242316652.

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Quercetin, a flavonoid compound widely distributed in many plants, is known to have potent antitumor effects on several cancer cells. Our previous study revealed that the acetylation of quercetin enhanced its antitumor effect. However, the mechanisms remain unknown. This study aimed to elucidate the bioavailability of acylated quercetin in the HepG2 cell model based on its antitumor effect. The positions of quercetin 3,7,3′,4′-OH were acetylated as 3,7,3′,4′-O-tetraacetylquercetin (4Ac-Q). The inhibitory effect of 4Ac-Q on HepG2 cell proliferation was assessed by measuring cell viability. The

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2

Roth, Z., and P. J. Hansen. "324SPHINGOSINE-1-PHOSPHATE PROTECTS CULTURED BOVINE OOCYTES FROM PHYSIOLOGICALLY RELEVANT THERMAL STRESS." Reproduction, Fertility and Development 16, no. 2 (2004): 282. http://dx.doi.org/10.1071/rdv16n1ab324.

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Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that can block the sphingomyelin cell-death pathway by suppressing ceramide-induced apoptosis. The present study was performed to test whether S1P protects oocytes from heat shock during in vitro maturation. Cumulus-oocyte complexes obtained by slicing follicles were placed in maturation medium with or without 50nM S1P and cultured at 38.5°C (CON) or 41°C (41C) for the first 12h of maturation. Incubation during the last 10h of maturation (22-h total maturation time), fertilization, and embryonic development were performed at 38.5°C and

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Mohankumar, Kumaravel, Gus Wright, Subhashree Kumaravel, et al. "Abstract 236: Nuclear receptor 4A1 ligands target T-cell exhaustion in colorectal cancer." Cancer Research 82, no. 12_Supplement (2022): 236. http://dx.doi.org/10.1158/1538-7445.am2022-236.

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Abstract Colorectal cancer (CRC) is a highly complex disease with multiple risk factors. The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in several cancers and is a negative prognostic factor for cancer patient survival. Previous reports indicate a potential role for overexpression of NR4A1 in T-cell exhaustion and in this study, we aim to investigate the antitumorigenic activity of two bis-indole derived ligands (DIMs) that act as receptor antagonists. Immune competent C57BL/6 mice and mouse MC-38 colon cancer cells were used and tumor Infiltrating Lymphocytes (TILs) were isolated fr

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Mohankumar, Kumaravel, Gus Wright, Subhashree Kumaravel, et al. "732 A novel nuclear receptor 4A1 (NR4A1) antagonists attenuates T-cell exhaustion in colorectal cancer." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A761—A762. http://dx.doi.org/10.1136/jitc-2021-sitc2021.732.

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BackgroundColorectal cancer (CRC) is a highly complex disease with multiple risk factors and both genetic and environmental components contribute to disease incidence.1 2 Cancer immunotherapy using immune-checkpoint blockades represents a major advance in treatment strategy.3 4 The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in lung, colon, liver and breast cancers and in Rhabdomyosarcoma and is a negative prognostic factor for cancer patient survival.5–8 Previous studies in breast cancer cells showed that PD-L1 was regulated by NR4A1 which activates transcription factor Sp1 bound to

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D'Angelo, Sandra P., Steven Attia, Jean-Yves Blay, et al. "Identification of response stratification factors from pooled efficacy analyses of afamitresgene autoleucel (“Afami-cel” [Formerly ADP-A2M4]) in metastatic synovial sarcoma and myxoid/round cell liposarcoma phase 1 and phase 2 trials." Journal of Clinical Oncology 40, no. 16_suppl (2022): 11562. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.11562.

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11562 Background: Afami-cel is an autologous, HLA-A*02-restricted, specific peptide enhanced affinity receptor, T-cell therapy engineered to target MAGE-A4+ solid tumors. The pivotal, 2-cohort, single-arm, Phase 2, SPEARHEAD-1 trial (NCT04044768) with afami-cel met its primary endpoint based on Cohort 1 data. As of September 1, 2021, in 47 patients (pts) with metastatic synovial sarcoma (SyS) or myxoid/round cell liposarcoma (MRCLS), the overall response rate (ORR) per independent review was 34% with encouraging durability (Van Tine, et al. Paper 30: CTOS 2021; Virtual). To identify potential

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D'Angelo, Sandra P., Steven Attia, Jean-Yves Blay, et al. "Identification of response stratification factors from pooled efficacy analyses of afamitresgene autoleucel (“Afami-cel” [Formerly ADP-A2M4]) in metastatic synovial sarcoma and myxoid/round cell liposarcoma phase 1 and phase 2 trials." Journal of Clinical Oncology 40, no. 16_suppl (2022): 11562. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.11562.

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11562 Background: Afami-cel is an autologous, HLA-A*02-restricted, specific peptide enhanced affinity receptor, T-cell therapy engineered to target MAGE-A4+ solid tumors. The pivotal, 2-cohort, single-arm, Phase 2, SPEARHEAD-1 trial (NCT04044768) with afami-cel met its primary endpoint based on Cohort 1 data. As of September 1, 2021, in 47 patients (pts) with metastatic synovial sarcoma (SyS) or myxoid/round cell liposarcoma (MRCLS), the overall response rate (ORR) per independent review was 34% with encouraging durability (Van Tine, et al. Paper 30: CTOS 2021; Virtual). To identify potential

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7

Lunt, Colin, Sandra P. D’Angelo, Albiruni Ryan Abdul Razak, et al. "Abstract A038: Enrollment of pediatric and adolescent patients with MAGE-A4+ advanced synovial sarcoma into cohort 2 of SPEARHEAD-1: a phase 2 trial of afamitresgene autoleucel (“afami-cel” [formerly ADP-A2M4])." Clinical Cancer Research 28, no. 18_Supplement (2022): A038. http://dx.doi.org/10.1158/1557-3265.sarcomas22-a038.

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Abstract Background: Afami-cel is an autologous, specific peptide enhanced affinity receptor T-cell therapy genetically engineered to target MAGE-A4+ solid tumors in HLA-A*02+ patients. SPEARHEAD-1 (NCT04044768) is a Phase 2, two-cohort, single-arm, open-label trial evaluating afami-cel in patients with advanced/metastatic synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) and is the largest trial in metastatic synovial sarcoma to date. Preliminary data from Cohort 1 in 47 heavily pre-treated patients aged 16–75 years from 22 centers in North America and Europe, showed an overall respon

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Labonte, Melissa Janae, Pierre Oliver Bohanes, Dongyun Yang та ін. "Novel colon cancer tumor suppressor gene, β-defensin 1, to predict recurrence in patients with stage II and III colon cancer." Journal of Clinical Oncology 30, № 15_suppl (2012): 3622. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3622.

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3622 Background: Human β-defensin 1 (hBD-1) encoded by the DEFB1 gene is an antimicrobial peptide involved in the innate immune response and is expressed in epithelial cells, including the colon. hBD-1 has been shown to have tumor suppressor functions in urothelial cancer models. We tested whether 4 germline single nucleotide polymorphisms (SNPs) in DEFB1 could predict time to tumor recurrence (TTR) in stage II and III colon cancer (CC) patients. We then sought to demonstrate if hBD-1 has tumor suppressor functions in CC models. Methods: A total of 234 patients, 105 stage II and 129 stage III,

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Welsh, James, Danxia Ke, Nahum Puebla Osorio, et al. "376 Radiation sub-study to characterize safety and tolerability of low-dose radiation in combination with afami-cel in patients with advanced cancers (NCT03132922)." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A407. http://dx.doi.org/10.1136/jitc-2021-sitc2021.376.

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BackgroundAutologous cell therapies with an engineered T-cell receptor targeting MAGE-A4 have shown responses in patients with synovial sarcoma1 with additional responses in myxoid/round cell liposarcoma (MRCLS), head and neck, lung, esophagogastric junction, and melanoma cancers.2 3 Low-dose radiation may control tumor growth locally and modulate stroma of solid tumors,4 potentially facilitating T-cell infiltration into tumors and antitumor activity.MethodsSub-study designed to assess safety, tolerability, and efficacy in up to 10 patients with low-dose radiation in combination with lymphodep

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Giles, David, Timothy Woodiwiss, Rowland Han, et al. "SURG-48. LASER INTERSTITIAL THERMAL THERAPY REMODELS THE TUMOR IMMUNE LANDSCAPE IN A MOUSE GLIOMA MODEL." Neuro-Oncology 26, Supplement_8 (2024): viii284—viii285. http://dx.doi.org/10.1093/neuonc/noae165.1127.

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Abstract BACKGROUND Laser interstitial thermal therapy (LITT), a minimally invasive surgical technique for tumor ablation, is increasingly being used to treat primary and recurrent glioma. While the primary goal of using LITT has been to destroy tumor tissue, little is known about the impact of LITT on the overall immune response. To investigate changes in the tumor immune landscape, we utilized a mouse model of LITT and applied it to a poorly immunogenic mouse model of glioma. METHODS SB28 glioma cells were implanted in the right frontal lobe of C57BL/6 mice, and on day 7, an optical fiber is

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Huang, Qian, Jingying Xu, Yanyan Ge, Yue Shi, Fei Wang та Mingli Zhu. "NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling". Open Life Sciences 17, № 1 (2022): 447–54. http://dx.doi.org/10.1515/biol-2022-0047.

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Abstract This study aimed to examine whether nuclear receptor 4a1 (NR4A1) is involved in inhibiting hepatic stellate cell (HSC) activation and liver fibrosis through the epithelial–mesenchymal transition (EMT). HSC-T6 cells were divided into the control group, the acetaldehyde (200 μM, an EMT activator) group, and the NR4A1 activation group (Cytosporone B; 1 μM). The expression levels of the epithelial marker E-cadherin, the mesenchymal markers fibronectin (FN), vimentin, smooth muscle alpha-actin (α-SMA), and fibroblast-specific protein 1 (FSP-1), and the components of the transforming growth

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Kim, Hanjun, Sewoon Kim, Yonghee Song, Wantae Kim, Qi-Long Ying, and Eek-hoon Jho. "Dual Function of Wnt Signaling during Neuronal Differentiation of Mouse Embryonic Stem Cells." Stem Cells International 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/459301.

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Activation of Wnt signaling enhances self-renewal of mouse embryonic and neural stem/progenitor cells. In contrast, undifferentiated ES cells show a very low level of endogenous Wnt signaling, and ectopic activation of Wnt signaling has been shown to block neuronal differentiation. Therefore, it remains unclear whether or not endogenous Wnt/β-catenin signaling is necessary for self-renewal or neuronal differentiation of ES cells. To investigate this, we examined the expression profiles of Wnt signaling components. Expression levels of Wnts known to induceβ-catenin were very low in undifferenti

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Bianchi, Paola, Klaus Schwarz, Elisa Fermo, et al. "Molecular Analysis of the SEC23B Gene In Patients Affected by Congenital Dyserythropoietic Anemia Type II (CDAII)." Blood 116, no. 21 (2010): 4227. http://dx.doi.org/10.1182/blood.v116.21.4227.4227.

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Abstract Abstract 4227 CDAII, the most frequent type of congenital dyserythropoietic anemia, is an autosomal recessive disease characterized by ineffective erythropoiesis, peripheral hemolysis, erythroblast morphological abnormalities and hypoglycosylation of some RBC membrane proteins. Last year we and others identified SEC23B as the gene responsible for CDAII (Schwarz et al, 2009, Bianchi et al, 2009). SEC23B is a member of the SEC23/SEC24 family, a component of COPII coat protein complex which is involved in protein trafficking through membrane vesicles from the endoplasmic reticulum to the

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Zanozina, E. A., A. D. Zikiryakhodzhaev, L. V. Bolotina, et al. "Treatment outcomes of stage IIA–IIB breast cancer patients of hormone-positive HER2-negative subtype after neoadjuvant polychemotherapy depending on Ki-67 levels." P.A. Herzen Journal of Oncology 14, no. 2 (2025): 13. https://doi.org/10.17116/onkolog20251402113.

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Objective. To evaluate clinical and pathological responses to neoadjuvant polychemotherapy (NACT) in patients with stage IIA-IIB breast cancer of hormone-positive HER2-negative subtype depending on the level of tumor cell proliferation index (Ki-67), and to analyze the volume of surgical intervention. Material and methods. We analyzed the results of treatment of 100 patients who received NACT according to the 4AC+12P/4T regimen at the first stage of complex treatment followed by surgical treatment in the Department of Oncology and Reconstructive and Plastic Surgery of Breast and Skin of the P.

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Chen, Youhao, Haoming Wang, Nan Li, et al. "A Novel Approach Combined with MIPO Technique for the Treatment of Type C Pilon Fractures." Oxidative Medicine and Cellular Longevity 2022 (June 14, 2022): 1–10. http://dx.doi.org/10.1155/2022/7427255.

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Objective. Type C fracture is a complete intra-articular fracture, and the mainstay of treatment remains open reduction and internal fixation. The purpose of the study is to observe the clinical effect of an anterior ankle C approach (ankle-C) combined with minimal invasive plate osteosystems (MIPO) for tibial pilon fractures (AO/OTA 43C, combined with fibula fractures). Methods. A retrospective comparative analysis was performed on the clinical data of 33 patients with C-type pilon fractures (combined fibula fractures) admitted to our department from July 2018 to July 2021, including 12 cases

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D'Angelo, Sandra P., Brian Andrew Van Tine, Steven Attia, et al. "SPEARHEAD-1: A phase 2 trial of afamitresgene autoleucel (Formerly ADP-A2M4) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma." Journal of Clinical Oncology 39, no. 15_suppl (2021): 11504. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.11504.

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11504 Background: This phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety, and tolerability of afamitresgene autoleucel in 45 patients (pts) with advanced/metastatic synovial sarcoma or Myxoid/Round Cell Liposarcoma (MRCLS). Methods: Eligible pts are HLA-A*02 positive with MAGE-A4-expressing tumors. Pts undergo leukapheresis for collection of autologous T-cells for processing and manufacture into afamitresgene autoleucel cells. Pts were treated with afamitresgene autoleucel doses between 1–10 × 109 transduced T-cells after receiving lymphodepletin

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McAlpine, Cheryl, Martin Isabelle, Robyn Broad, et al. "Abstract 892: Afamitresgene autoleucel (afami-cel; formerly ADP-A2M4) demonstrates durable clinical responses by inducing broad immune engagement with anti-tumor activity." Cancer Research 83, no. 7_Supplement (2023): 892. http://dx.doi.org/10.1158/1538-7445.am2023-892.

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Abstract Afami-cel is a mixed CD4+ CD8+ autologous T-cell therapy engineered to target the cancer testis antigen melanoma-associated antigen A4 in HLA-A*02-positive patients with advanced/metastatic synovial sarcoma or myxoid/round cell liposarcoma (MRCLS). Pooled data from the Phase 1 (NCT03132922) and Phase 2 (SPEARHEAD-1, NCT04044768) trials of afami-cel showed an acceptable benefit to risk profile with an overall response rate of 36.2% and a median duration of response of 52.0 weeks.1 To support the continued investigation of potential mechanisms of durable anti-tumor activity, we previous

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Rowland, Emma, Jordan Walter, Anna Jermakowicz, Robert Suter, Rebecca Riggins, and Nagi Ayad. "Abstract 1747: Targeting metabolic and epigenetic programs to re-sensitize glioblastoma to chemotherapy." Cancer Research 83, no. 7_Supplement (2023): 1747. http://dx.doi.org/10.1158/1538-7445.am2023-1747.

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Abstract Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase

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Ramadoss, Jayanth, and Ronald R. Magness. "Multiplexed digital quantification of binge-like alcohol-mediated alterations in maternal uterine angiogenic mRNA transcriptome." Physiological Genomics 44, no. 11 (2012): 622–28. http://dx.doi.org/10.1152/physiolgenomics.00009.2012.

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Genomic studies on fetal alcohol spectrum disorders (FASD) have utilized either genome-wide microarrays/bioinformatics or targeted real-time PCR (RT-PCR). We utilized herein for the first time a novel digital approach with high throughput as well as the capability to focus on one physiological system. The aim of the present study was to investigate alcohol-induced alterations in uterine angiogenesis-related mRNA abundance using digital mRNA technology. Four biological and three technical replicates of uterine arterial endothelial cells from third-trimester ewes were fluorescence-activated cell

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Alareeqi, Ola A. A., Yaser H. A. Obady, Mansoor Q. Al-Khulaidi, and Khalid Al-Mureish. "SOME STUDIES ON RED BLOOD CELLS MORPHOLOGY OF HEALTHY AND DIABETIC PATIENTS IN TAIZ, YEMEN." Electronic Journal of University of Aden for Basic and Applied Sciences 2, no. 3 (2021): 109–23. http://dx.doi.org/10.47372/ejua-ba.2021.3.105.

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The aim of this study was to: 1- Identify and quantify the prevalence of RBC abnormalities in healthy and diabetic subjects. 2- Provide supporting evidence about the relation between RBC storage duration at 4oC and alterations to RBC morphology (compare with the morphology at the time of collection). 3- The obtain information about how the number of normal cells in different times of storage declines as a function of the storage period. 4- Estimate the prevalence of red cell morphological changes in diabetic patients. One hundred and ninety-six slides of 49 healthy and 49 diabetic patien

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Andreasen, Tine G., Trine Strandgaard, Line Raaby, Jørgen Bjerggaard Jensen, and Lars Dyrskjøt. "Abstract 6479: High expression of the exhaustion markers PD-1 and PD-L1 in non-muscle invasive bladder cancer is associated with poor outcome following Bacillus Calmette-Guérin immunotherapy." Cancer Research 85, no. 8_Supplement_1 (2025): 6479. https://doi.org/10.1158/1538-7445.am2025-6479.

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Abstract Introduction: The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) includes intravesical instillations of Bacillus Calmette-Guérin (BCG). Despite completing BCG therapy, up to 40 % of patients experience disease recurrence within five years. T cell exhaustion has been associated with poor outcome following treatment with BCG. In this study, we investigated whether T cell exhaustion, characterized by protein expression of PD-1 and PD-L1 in paired samples obtained before and after BCG treatment could provide further insight into BCG response and help predic

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Ligon, John, Woonyoung Choi, Gady Cojocaru, et al. "506 The tumor immune microenvironment of metastatic osteosarcoma is marked by lymphocyte exclusion and impacts patient progression-free survival." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A541—A542. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0506.

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BackgroundPatients with relapsed metastatic osteosarcoma have no effective treatments available to them,1 and immunotherapy thus far has not succeeded in improving outcomes.2–5 We aim to understand the immune architecture of the tumor microenvironment (TME) of osteosarcoma, with the goal of harnessing the immune system as a major therapeutic strategy for the treatment of patients with osteosarcoma.Methods66 osteosarcoma tissue specimens were stained and analyzed by immunohistochemistry. Tumor-infiltrating lymphocytes (TILs) from 25 specimens were profiled by functional multiparameter flow cyto

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Mardilovich, Katerina, Lilli Wang, Rachel Kenneil, et al. "95 Inhibition of AKT signaling during expansion of TCR-engineered T-cells from patient leukocyte material generates SPEAR T-cells with enhanced functional potential in vitro." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A106. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0095.

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BackgroundT-cells attributes for adoptive cell therapy of patients with advanced cancer can be optimized during ex vivo expansion culture. Autologous TCR-engineered T-cells targeting the MAGE-A4 antigen with Specific Peptide Enhanced Affinity Receptors (SPEAR T-cells) have shown promise in the clinic.1 The highly variable leukocyte material obtained from individual patients during apheresis can present a manufacturing challenge for autologous T-cell therapies. The degree of ex vivo expansion and the functional attributes of the expanded T-cell product impact therapeutic efficacy and can be sub

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Colenbier, Robin, Tine Logghe, Gaëlle Boulet, Johannes Bogers, and Jean-Pierre Timmermans. "Abstract A017: Comprehensive evaluation of the therapeutic effects of whole-body hyperthermia for pancreatic ductal adenocarcinoma (PDAC) and the potential synergy with standard-of-care chemotherapeutics." Cancer Research 84, no. 17_Supplement_2 (2024): A017. http://dx.doi.org/10.1158/1538-7445.pancreatic24-a017.

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Abstract Whole-body hyperthermia (WBHT) is a promising therapeutic approach that leverages elevated temperatures to enhance cancer treatment efficacy. By inducing controlled hyperthermia in the range of 39-42.5°C, cellular processes are disrupted and cancer cells can be sensitized to standard-of-care chemotherapies. However, the precise cellular and molecular mechanisms by which WBHT exerts its effects are not fully understood. Elucidating these mechanisms is particularly crucial for optimizing treatment protocols and improving outcomes in aggressive malignancies such as pancreatic ductal aden

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Chen, Yongping, Haotian Yang, Tianyuan Yang, et al. "Protective Effects of Low-Dose Alcohol against Acute Stress-Induced Renal Injury in Rats: Involvement of CYP4A/20-HETE and LTB4/BLT1 Pathways." Oxidative Medicine and Cellular Longevity 2021 (October 13, 2021): 1–14. http://dx.doi.org/10.1155/2021/4475968.

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Low-dose alcohol possesses multiple bioactivities. Accordingly, we investigated the protective effect and related molecular mechanism of low-dose alcohol against acute stress- (AS-) induced renal injury. Herein, exhaustive swimming for 15 min combined with restraint stress for 3 h was performed to establish a rat acute stress model, which was verified by an open field test. Evaluation of renal function (blood creatinine and urea nitrogen), urine test (urine leukocyte esterase and urine occult blood), renal histopathology, oxidative stress, inflammation, and apoptosis was performed. The key ind

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Ferry-Galow, Katherine V., Kristin K. Fino, Geraldine O'Sullivan Coyne, et al. "Abstract CT263: Atezolizumab clinical trial biopsies reveal varied immune landscapes in clear cell sarcoma and chondrosarcoma." Cancer Research 84, no. 7_Supplement (2024): CT263. http://dx.doi.org/10.1158/1538-7445.am2024-ct263.

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Abstract Introduction: Clear cell sarcoma (CCS) constitutes &lt;1% of sarcomas and frequently presents in adolescents and young adults. Chondrosarcoma is one of the most common bone malignancies in adults, occurring as conventional chondrosarcoma (CS) or the more-aggressive dedifferentiated chondrosarcoma (dCS). There is no standard of care therapy approved for these malignancies. The activity of immune checkpoint inhibition (ICI) in alveolar soft part sarcoma, together with case reports of ICI activity in these other sarcoma subtypes, prompted us to conduct a phase 2 clinical trial of ate

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Carneiro, Benedito A., Maria Diab, Brian A. Van Tine, et al. "Abstract CT116: First-in-human study of AZD8853, an anti-growth and differentiation factor 15 (GDF15) antibody, in patients (pts) with advanced/metastatic solid tumors." Cancer Research 83, no. 8_Supplement (2023): CT116. http://dx.doi.org/10.1158/1538-7445.am2023-ct116.

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Abstract Background: The cytokine GDF15 is overexpressed in solid malignant tumors such as colorectal, lung and urothelial cancer, where it modulates T cells, dendritic cells (DCs) and myeloid-derived cells, driving the tumor microenvironment toward an immunosuppressive, tumor-promoting state. AZD8853 is a humanized immunoglobulin G1 monoclonal antibody that binds to, and neutralizes, GDF15. Anti-GDF15 treatment increased T cell proliferation and DC activation, leading to an antitumor immune response in preclinical studies of anti-PD-L1 resistant models. In vitro and in vivo preclinical data s

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Strandgaard, Trine, Tine Ginnerup Andreasen, Tessa Jane Divita, et al. "Abstract 769: Spatial proteomics and transcriptomics reveal an altered immune cell landscape in bladder cancer patients unresponsive to BCG treatment." Cancer Research 85, no. 8_Supplement_1 (2025): 769. https://doi.org/10.1158/1538-7445.am2025-769.

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Abstract Introduction: Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are recommended treatment with Bacillus Calmette-Guérin (BCG). The therapeutic effect of BCG is highly dependent on the host immune system and the tumor microenvironment (TME). The cellular composition and the functional status of the TME have been shown to play crucial roles for treatment efficacy. However, much is still unknown regarding the cellular interactions and mechanisms of BCG. Using spatial proteomics and transcriptomics we investigated the immune cell landscape in a cohort of BCG treated patie

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Holowiecki, Jerzy, Sebastian Giebel, Malgorzata Krawczyk-Kulis, et al. "Lower Relapse Incidence after Non-Cryopreserved Autologous Bone Marrow Transplantation Compared to Peripheral Blood Stem Cell Transplantation for High-Risk Hodgkin’s Lymphoma." Blood 104, no. 11 (2004): 912. http://dx.doi.org/10.1182/blood.v104.11.912.912.

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Abstract In a number of studies on Hodgkin’s lymphoma (HL), autologous transplantation of peripheral blood hematopoietic stem cells (autoPBSCT) was proved to result in faster hematopoietic recovery compared to bone marrow transplantation (autoBMT), however, no difference regarding long-term outcome has been demonstrated so far. In Katowice transplant centre we developed a new method of autoBMT with bone morrow not-cryopreserved but stored for 3 days in 40C and reinfused 24 hours after completion of CBV conditioning. In this study we analyzed outcome of 40 HL patients treated with this method i

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Van Tine, Brian A. "Abstract IA022: Arginine, serine, xCT and ME, the therapeutic metabolism of different sarcomas." Clinical Cancer Research 28, no. 18_Supplement (2022): IA022. http://dx.doi.org/10.1158/1557-3265.sarcomas22-ia022.

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Abstract The absolute diversity of the biology of the sarcomas makes therapeutic development challenging. As most of tumor metabolism is composed of transporters and enzymes, finding metabolic dependencies should allow for small molecule targeting. Due to the rapid metabolic evolution that tumors undergo in response to the targeting of any one metabolic pathway, a deep understanding of sarcoma metabolism is needed. First, the most common metabolic adaptation that sarcomas undergo is loss of expression of argininosuccinate synthetase 1 (ASS1), which is silenced in ~90% of cases by methylation.

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Tourneau, Christophe Le, Luca Mazzarella, Bastien Cabarrou, et al. "Abstract 6413: Biomarkers of response and progression to Pembrolizumab and Vorinostat combination in late-stage squamous cell carcinoma patients of different locations included in the PEVOsq basket trial." Cancer Research 84, no. 6_Supplement (2024): 6413. http://dx.doi.org/10.1158/1538-7445.am2024-6413.

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Abstract Background: Epigenetic modulation plays a major role in escaping tumor immunosurveillance. PEVOsq (NCT04357873) was an open-label, non-randomized, multi-center, basket phase II trial evaluating the efficacy of pembrolizumab (P) and the vorinostat (V) HDAC inhibitor in 112 patients (pts) with recurrent and/or metastatic squamous cell carcinoma (SCC) of the cervix, head and neck, anus, vulva/vagina, penis, and lung. Results showed an objective response rate (ORR) of 25%, the highest being in anal (31%) and cervical (39%) (ASCO #397612). We report here early biomarkers of response and pr

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Mita, Monica, Alain Mita, Miguel Villalona-Calero, et al. "Abstract PO4-18-07: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in triple negative breast cancer and transcriptionally addicted relapsed or refractory solid tumors." Cancer Research 84, no. 9_Supplement (2024): PO4–18–07—PO4–18–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-po4-18-07.

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Abstract Background: MYC deregulation is a hallmark of triple negative breast cancer (TNBC) and is associated with aggressive tumors and poor clinical outcomes. Although MYC remains undrugged, targeting of its cofactors has emerged as an attractive strategy to inhibit MYC oncogenic activity. Cyclin-dependent kinase 9 (CDK9) is a critical regulator of oncogenic MYC expression and an important MYC cofactor. KB-0742 is an oral CDK9 inhibitor that demonstrates promising preclinical activity against TNBC. In a real-world cohort, TNBCs have higher MYC expression and higher rates of MYC genomic ampli

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Andreasen, Tine G., Trine Strandgaard, Jørgen B. Jensen, and Lars Dyrskjøt. "Abstract B008: High expression of the exhaustion markers PD1 and PD-L1 in non-muscle invasive bladder cancer is associated with poor outcome following Bacillus Calmette-Guérin immunotherapy." Clinical Cancer Research 30, no. 10_Supplement (2024): B008. http://dx.doi.org/10.1158/1557-3265.bladder24-b008.

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Abstract Introduction: The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is intravesical instillations of Bacillus Calmette-Guérin (BCG). However, 40 % experience recurrence within 5 years despite completing BCG treatment. T cell exhaustion has been associated with poor outcome following treatment with BCG. Here we investigated if T cell exhaustion, characterized by protein expression of PD1 and PD-L1 measured in paired samples obtained before and after BCG treatment could further explain BCG response and help predict outcome in patients with NMIBC. Methods: We

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Leonard, Alexis, Aylin Bonifacino, Venina Marcela Dominical, et al. "Bone Marrow Characterization in Sickle Cell Disease: Inflammation and Stress Erythropoiesis Lead to Suboptimal CD34 Recovery Compared to Normal Volunteer Bone Marrow." Blood 130, Suppl_1 (2017): 966. http://dx.doi.org/10.1182/blood.v130.suppl_1.966.966.

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Abstract Introduction Gene therapy for sickle cell disease (SCD) requires modification of a high number of long term engrafting hematopoietic stem cells (LT-HSCs) sufficient to sustain production of the gene of interest at levels capable of overcoming the pathogenic HbSS phenotype. Unlike β-Thalassemia, the inflammatory bone marrow (BM) environment and stress erythropoiesis associated with SCD may have significant impacts on HSC quality and yield necessary for disease amelioration. Important work to optimize gene therapy through improvement in gene transfer efficiency, editing strategies, or t

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Spigel, David R., Eugene Ahn, Herbert L. Duvivier, et al. "Abstract CT152: Phase I study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing advanced solid tumors." Cancer Research 82, no. 12_Supplement (2022): CT152. http://dx.doi.org/10.1158/1538-7445.am2022-ct152.

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Abstract This is the first-in-human study of MT-6402, a unique, first-in-class potent PD-L1-targeted engineered toxin body (ETB) capable of direct killing of PD-L1 expressing cells via rapid PD-L1-mediated internalization of a fused Shiga-like toxin A subunit (SLTA) resulting in permanent ribosomal inactivation. MT-6402 also delivers an HLA-A*02 restricted pp65 cytomegalovirus (CMV) antigen into PD-L1 expressing tumor cells leading to MHC-I presentation to existing CMV-specific cytotoxic T cells (antigen seeding). MT-6402 functions by targeting tumor and inhibitory immune cells directly and al

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Strandgaard, Trine, Iver Nordentoft, Karin Birkenkamp-Demtröder, et al. "Abstract 3340: Bladder field cancerization impacts tumor development and T-cell exhaustion, and is reflected in urinary tumor DNA." Cancer Research 83, no. 7_Supplement (2023): 3340. http://dx.doi.org/10.1158/1538-7445.am2023-3340.

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Abstract Introduction: Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are treated with Bacillus Calmette-Guérin (BCG), which targets altered normal-appearing urothelium (field cancerization). Field cancerization may affect treatment response and outcome. High urinary tumor DNA (utDNA) levels in patients with NMIBC have been associated with worse clinical outcomes, and utDNA may be used for real-time assessment of residual disease. The prognostic and predictive values of field cancerization and utDNA need further investigation. Materials and methods: We analyzed samples proc

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Roy, Nil, Tine Wyseure, I.-Chung Lo, et al. "Abstract PR011: Discovery of VVD-065, a first-in-class allosteric molecular glue of the Keap1-Cul3 E3-ligase complex for the treatment of NRF2-activated cancers." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): PR011. http://dx.doi.org/10.1158/1535-7163.targ-23-pr011.

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Abstract Somatic gain of function mutations in nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor or loss of function mutations in Kelch-like ECH Associated Protein 1 (KEAP1) E3 ligase, which regulates NRF2 protein levels, are frequently identified in many solid cancers such as non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), and head and neck squamous cell carcinoma (HNSCC). These genomic alterations drive the activation of cytoprotective NRF2 transcriptional programs. In addition to mutational activation, NRF2 pathway activation has been doc

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Calero, Miguel Villalona, Mark Agulnik, Monica Mita, et al. "Abstract CT158: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory and transcriptionally addicted solid tumors." Cancer Research 84, no. 7_Supplement (2024): CT158. http://dx.doi.org/10.1158/1538-7445.am2024-ct158.

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Abstract Background MYC transcriptional deregulation is a hallmark of cancer and is associated with poor clinical outcomes. MYC deregulated solid tumors including non-small cell (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), and ovarian cancer are known for their aggressiveness and frequent relapse. Analysis of a real-world solid tumor cohort including NSCLC (n= 20,470), SCLC (n=1,517), TNBC (n=2,576) and ovarian cancer (n=1,667) demonstrated MYC family overexpression and/or genomic amplification in 47% to 87% of patients. Although MYC remains difficult to drug,

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Loya, Matthew, Tine Casneuf, Helene Bon, et al. "Abstract 2990: Single-slide FFPE proteomic profiling enables therapeutic target quantification and molecular subtyping in non-Hodgkin’s lymphoma and bone marrow tumor biopsies." Cancer Research 85, no. 8_Supplement_1 (2025): 2990. https://doi.org/10.1158/1538-7445.am2025-2990.

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Abstract Molecular profiling of formalin-fixed paraffin-embedded (FFPE) tumors in clinical research is performed with low-plex immunohistochemistry or genome-wide transcriptomics. The application of unbiased, highly multiplexed proteomics to FFPE is limited by sample input requirements, assay throughput and complex bioinformatics. Here we report a proteomic method amenable to low-input FFPE profiling which complements transcriptomics. We applied Biognosys’ mass-spectrometry platform (TrueDiscovery, DIA-MS) to samples encountered in routine histopathology laboratories (e.g. B-cell malignancies

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Villalona-Calero, Miguel, Monica Mita, Alain Mita, et al. "Abstract B112: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in relapsed, refractory ovarian cancer and transcriptionally addicted relapsed or refractory solid tumors." Cancer Research 84, no. 5_Supplement_2 (2024): B112. http://dx.doi.org/10.1158/1538-7445.ovarian23-b112.

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Abstract Ovarian cancer is responsible for more female cancer deaths than any other female reproductive malignancy. MYC deregulation is a hallmark of ovarian cancer and is associated with poor clinical outcome. In a real-world cohort (n=1,667), the MYC family of genes is overexpressed and/or genomically amplified in up to 87% of ovarian cancer. Although MYC remains undrugged, targeting of its cofactors has emerged as an attractive strategy to inhibit MYC oncogenic activity. Cyclin-dependent kinase 9 (CDK9) is a critical regulator of oncogenic MYC expression and activity. KB-0742 is an orally b

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Cranmer, Lee D., Andrew J. Wagner, Vinod Ravi, et al. "Abstract LB288: Biomarker analysis from AMPECT correlating response to nab-sirolimus with TSC1 and TSC2 inactivating alterations." Cancer Research 83, no. 8_Supplement (2023): LB288. http://dx.doi.org/10.1158/1538-7445.am2023-lb288.

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Abstract nab-Sirolimus is an mTOR inhibitor (mTORi) approved in the US for the treatment of adult patients with locally advanced, unresectable, or metastatic malignant perivascular epithelioid cell tumor (PEComa) based on clinical efficacy and safety data from the phase 2, multicenter, open-label AMPECT trial (NCT02494570). TSC1 and TSC2 are tumor suppressor genes and key upstream regulators of mTOR complex 1 (mTORC1); inactivating alterations (loss-of-function mutations or deletions) in these genes lead to mTORC1 hyperactivation, which may contribute to tumor formation. Phosphorylation of S6

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Okera, Meena, Brian A. Van Tine, Joleen M. Hubbard, et al. "Abstract OT2-11-01: A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results." Cancer Research 83, no. 5_Supplement (2023): OT2–11–01—OT2–11–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-ot2-11-01.

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Abstract MT-5111 is a 55kD engineered toxin body targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 works by internalizing, self-routing through intracellular compartments to the cytosol, and inducing potent cell-kill via the enzymatic and permanent inactivation of ribosomes. This is a phase 1 study in adults with advanced HER2+ solid tumors. MT-5111 is dosed weekly IV over 30 min in every 21-day cycle until disease progression, unacceptable toxicity, death, or wit

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Van Tine, Brian A., Monica Mita, Minal A. Barve, et al. "Abstract P2-13-45: Interim results of a phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+tumors." Cancer Research 82, no. 4_Supplement (2022): P2–13–45—P2–13–45. http://dx.doi.org/10.1158/1538-7445.sabcs21-p2-13-45.

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Abstract Background: Engineered toxin bodies (ETBs) are composed of a de-immunized Shiga-like Toxin A subunit genetically fused to an antibody-like binding domain. ETBs can force receptor internalization, induce potent cell-kill via enzymatic and permanent inactivation of ribosomes, and may not be subject to resistance mechanisms of other therapeutics. MT-5111 is a 55 kD ETB targeting HER2 in solid tumors that binds to an epitope distinct from trastuzumab and pertuzumab, offering potential combination strategies with other HER2-targeting agents. MT-5111 may demonstrate efficacy in patients (pt

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Kannan, Meganathan, Firdos Ahmad, Birendra K. Yadav, Rajive Kumar, Jawed Fareed, and Renu Saxena. "Glanzmann’s Thrombasthenia Patients with No Mutations in Both the ITGA2B and ITGB3 Genes as Identified by Conformation Sensitive Gel Electrophoresis (CSGE)." Blood 112, no. 11 (2008): 1236. http://dx.doi.org/10.1182/blood.v112.11.1236.1236.

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Abstract Glanzmann’s Thrombasthenia (GT) is an autosomal recessive inherited platelet function disorder that is due to defect platelet aggregation in response to multiple physiologic agonists. The defect may be because of mutations in the genes encoding either ITGA2B or ITGB3 that result in qualitative or quantitative abnormalities of the platelet receptor aIIbb3. A total of 45 unrelated GT patients were analyzed for mutations in all the exons of ITGA2B and ITGB3 genes by a mutation screening technique, Conformation Sensitive Gel Electrophoresis (CSGE). Mutation was identified in 36 out of 45

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Nakamaki, Tsuyoshi, Kunihiko Fukuchi, Takashi Maeda, et al. "Constitutive Cyclin A1 Expression Impairs Retinoic Acid-Induced Growth Arrest and Differentiation of Myeloid Leukemia Cells." Blood 116, no. 21 (2010): 2894. http://dx.doi.org/10.1182/blood.v116.21.2894.2894.

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Abstract Abstract 2894 Acute promyelocytic leukemia (APL) differentiation syndrome (DS) in all-trans retinoic acid (ATRA) therapy is often associated with increase of leukocyte count (hyperleukocytosis). It suggests deregulated cell proliferation of ATRA-induced APL cells is possibly involved in the development of DS. The molecular mechanism(s) of hyperleukocytosis are unknown. We previously found increased expression of cyclin A1 mRNA were associated with both increase of initial leukocyte count and development of DS in the therapy with ATRA in APL. To clarify role(s) of cyclin A1 in the prol

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Man, Jennifer, Bruno Fang, Alexander Philipovskiy, et al. "Abstract P4-08-20: Trial in progress: A first-in-human phase 1a/b, dose-escalation/expansion study of BG-68501/ETX-197 (CDK2 inhibitor) as monotherapy or in combination with fulvestrant for patients with HR+/HER2- breast cancer and other advanced solid tumors." Clinical Cancer Research 31, no. 12_Supplement (2025): P4–08–20—P4–08–20. https://doi.org/10.1158/1557-3265.sabcs24-p4-08-20.

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Abstract Background: Cyclin-dependent kinase (CDK) 2 can regulate the cell cycle through the interaction with cyclin E or cyclin A during the G1/S and S/G2 transitions, respectively. Elevated CDK2 activity is a key resistance mechanism to CDK4/6 inhibition in HR+/HER2− breast cancer (BC). Other genomic alterations, eg, loss of RB1, can cause resistance in additional solid tumors, including high-grade serous ovarian cancer, gastric cancer, small cell lung cancer (SCLC), and endometrial cancers. CCNE1 amplification or cyclin E overexpression may confer sensitivity to CDK2 inhibition. BG-68501/ET

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Van Tine, Brian A., Eugene Ahn, Rebecca A. Redman, et al. "Abstract CT191: First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim data." Cancer Research 84, no. 7_Supplement (2024): CT191. http://dx.doi.org/10.1158/1538-7445.am2024-ct191.

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Abstract MT-6402 is a PD-L1-targeted ETB capable of directly killing PD-L1 expressing cells by internalization of a de-immunized Shiga-like toxin A subunit (SLTA), resulting in ribosomal destruction. Targeting PD-L1 expressing tumor cells may directly drive tumor regression, whereas targeting PD-L1 expressing immune cells may release immunosuppression and drive tumor immune recognition. MT-6402 also delivers an HLA-A*02 restricted cytomegalovirus (CMV) class I antigen into PD-L1 expressing cells (antigen seeding) that can be recognized by existing CMV-specific cytotoxic T cells. A first-in-hum

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Cui, Bing, Liguang Chen, Laura Z. Rassenti, et al. "High-Level Expression of ROR1 Associates with Early Disease Progression in Patients with Chronic Lymphocytic Leukemia." Blood 126, no. 23 (2015): 1713. http://dx.doi.org/10.1182/blood.v126.23.1713.1713.

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Abstract ROR1 is a type-1 tyrosine kinase-like orphan-receptor that ordinarily is expressed during embryogenesis, but that also is found on leukemia cells of patients (pts) with chronic lymphocytic leukemia (CLL). In prior studies we found ROR1 served as a receptor for Wnt5a, which could promote survival/growth of CLL cells. We found Wnt5a in the plasma is significantly higher in pts with CLL (3.2±1.6 ng/ml (mean ±S.D.), N = 36) than in healthy adults (0.14±0.16 ng/ml, N=14, p<0.01) and also may be elaborated by accessory cells in the CLL microenvironment. On the other hand, reducing expres

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Chaturvedi, Shalini, Anke Weispfenning, David Bauer, et al. "Abstract CT082: Next-generation sequencing (NGS) and cytokine assessment from a phase III study of copanlisib in combination with rituximab in patients with indolent non-Hodgkin lymphoma (iNHL) - associations with survival endpoints." Cancer Research 83, no. 8_Supplement (2023): CT082. http://dx.doi.org/10.1158/1538-7445.am2023-ct082.

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Abstract Introduction: The PI3K inhibitor copanlisib (C) plus the anti-CD20 antibody rituximab (R) was superior to R plus placebo (P) in patients (pts) with relapsed iNHL (Matasar et al. Lancet Oncol 2021). We previously reported that C+R improved median progression-free survival (PFS) in the iNHL, follicular lymphoma (FL), and non-FL groups, with a statistically significant improvement in the PTEN-positive population (Shalini et al., AACR 2022). Here we conducted NGS analysis from pts treated with either C+R or P+R for possible impact on PFS outcomes. We also determined if there was an associ

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Van Tine, Brian Andrew, Christopher T. Chen, Victor Moreno, et al. "Abstract CT059: Phase 1b trial Mipasetamab Uzoptirine (ADCT-601-102) dose escalation in patients with advanced bone and soft tissue sarcomas." Cancer Research 84, no. 7_Supplement (2024): CT059. http://dx.doi.org/10.1158/1538-7445.am2024-ct059.

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Abstract Background: AXL is a cell surface receptor tyrosine kinase widely expressed in solid tumors (ST), including sarcomas. ADCT-601 (Mipasetamab uzoptirine; Mipa) is an antibody-drug conjugate comprising a humanized anti-AXL antibody conjugated via a cleavable linker to SG3199 (pyrrolobenzodiazepine dimer cytotoxin). Mipa demonstrated antitumor activity in pre-clinical mice models of sarcoma, adrenocortical carcinoma and pancreatic cancer, and clinical activity in ST patients (pts) in its first-in-human trial. Here, we report initial clinical data in pts with advanced bone and soft tissue

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