Objective: Assess the contribution of early tumor growth dynamics modeling to predict clinical outcomes in non-small cell lung cancer patients receiving immunotherapy, alongside standard RECIST 1.1 criteria.
Methods: Our retrospective studies used data from 861 patients with advanced NSCLC enrolled in three randomized Phase III trials evaluating immunotherapy plus chemotherapy were analyzed. Tumor size measurements up to two follow-up time points were used to fit a novel Gompertz model and estimate growth rate (GR) and kinetic parameters representing depth of response (A), speed of response (B), and long-term modulation (M). Correlations between these early tumor growth parameters and clinical outcomes such as progression-free survival (PFS) and time to response (TTR) were assessed. Descriptive and discriminative analyses were performed to delineate tumor growth dynamics across various response profiles based on RECIST 1.1 criteria.
Results: The novel Gompertz model accurately described early tumor growth kinetics in 861 non-small cell lung cancer patients treated with immunotherapy. Lower growth rate (GR) and model parameter M were associated with longer progression-free survival (PFS) (HR=0.897 and 7.47x10^-7, respectively). Higher GR and parameter A correlated with shorter time to response (HR=0.575 and 0.696, respectively). Responders had significantly lower A (p=1.51e-53) and higher GR (p=0.4e-12) than non-responders. Non-durable stable disease patients had higher GR (p=0.0001) and parameter B (p=0.0002) compared to late responders. Early tumor growth parameters showed potential for predicting long-term outcomes and treatment response patterns.
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http://dx.doi.org/10.3389/fimmu.2024.1470555 | DOI Listing |
Nanomedicine (Lond)
January 2025
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Aim: To develop pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL) of CD40a to enhance anti-tumor activity in pancreatic cancer while reducing systemic toxicity.
Materials And Methods: A small library of nanoliposomes (NL) with various lipid compositions were synthesized to prepare pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL). Physical and functional characterization of pHTANL-CD40a was performed via dynamic light scattering (DLS), Transmission Electron Microscopy (TEM), confocal microscopy, and flow cytometry.
Kaohsiung J Med Sci
January 2025
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
SET domain bifurcated histone lysine methyltransferase 1 (SETDB1/ESET), a pivotal H3K9 methyltransferase, has been extensively studied since its discovery over two decades ago. SETDB1 plays critical roles in immune regulation, including B cell maturation, T-cell activity modulation, and endogenous retrovirus (ERV) silencing. While essential for normal immune cell function, SETDB1 overexpression in cancer cells disrupts immune responses by suppressing tumor immunogenicity and facilitating immune evasion.
View Article and Find Full Text PDFPharm Dev Technol
January 2025
Department of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China.
In this paper, the pH-sensitive targeting functional material NGR-poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (NGR-PEtOz-CHMC, NPC) modified quercetin (QUE) liposomes (NPC-QUE-L) was constructed. The structure of NPC was confirmed by infrared spectroscopy (IR) and nuclear magnetic resonance hydrogen spectrum (H-NMR). Pharmacokinetic results showed that the accumulation of QUE in plasma of the NPC-QUE-L group was 1.
View Article and Find Full Text PDFNMR Biomed
February 2025
Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Cellular metabolism is inextricably linked to transmembrane levels of proton (H), sodium (Na), and potassium (K) ions. Although reduced sodium-potassium pump (Na-K ATPase) activity in tumors directly disturbs transmembrane Na and K levels, this dysfunction is a result of upregulated aerobic glycolysis generating excessive cytosolic H (and lactate) which are extruded to acidify the interstitial space. These oncogene-directed metabolic changes, affecting intracellular Na and H, can be further exacerbated by upregulation of ion exchangers/transporters.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of CM, No. 19, Renmin Road, Jinshui District, Zhengzhou City, Henan Province, China.
This study systematically explores the oncogenic role of the long non-coding RNA (lncRNA) LINC00115 in endometrial cancer (EC) and reveals its unique mechanism in promoting proliferation, invasion, and metastasis via the JAK/STAT signaling pathway. LINC00115 is significantly upregulated in EC tissues and closely associated with advanced TNM staging and lymph node metastasis. Functional assays showed that knockdown of LINC00115 suppressed EC cell proliferation, invasion, and metastasis, while overexpression enhanced these malignant behaviors.
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