Evolution of blood–brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 11(8), P. 2306 - 2325

Published: Dec. 31, 2020

Blood-brain barrier (BBB) strictly controls matter exchange between blood and brain, severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy diseases. However, during the onset progression diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting delivery strategies designed based evolutions related applications various diseases including Alzheimer's disease, Parkinson's epilepsy, stroke, traumatic injury tumor. The advances optimization small molecules for crossing non-systemic administration routes (e.g., intranasal treatment) bypassing are not included review.

Language: Английский

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Steps in metastasis: an updated review

Medical Oncology, Journal Year: 2021, Volume and Issue: 38(1)

Published: Jan. 1, 2021

Language: Английский

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Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition

Cancer Discovery, Journal Year: 2020, Volume and Issue: 10(9), P. 1352 - 1373

Published: June 22, 2020

A hallmark of metastasis is the adaptation tumor cells to new environments. Metabolic constraints imposed by serine and glycine-limited brain environment restrict metastatic growth. How metastases overcome these growth-prohibitive conditions poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes rate-limiting step glucose-derived synthesis, a major determinant in multiple human cancer types preclinical models. Enhanced synthesis proved important for nucleotide production cell proliferation highly aggressive cells. In vivo, genetic suppression pharmacologic inhibition PHGDH attenuated metastasis, but not extracranial growth, improved overall survival mice. These results reveal extracellular amino acid availability determines pathway dependence, suggest inhibitors may be useful treatment metastasis. SIGNIFICANCE: Using proteomics, metabolomics, models, nutrient-limited potentiates susceptibility inhibition. findings underscore importance studying metabolism physiologically relevant contexts, provide rationale using treat metastasis.This article highlighted This Issue feature, p. 1241.

Language: Английский

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A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy

Annals of Oncology, Journal Year: 2020, Volume and Issue: 31(10), P. 1397 - 1404

Published: July 5, 2020

•Osimertinib 160 mg exhibited promising ORR and survival benefit in EGFR T790M-positive NSCLC patients with CNS metastasis.•As it caused only grade 1–2 adverse events, osimertinib also showed a tolerable safety profile.•It is suitable for BM or LM after TKI treatment those treated T790M-targeting agents radiotherapy. BackgroundUp to 40% of non-small-cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) mutations tyrosine kinase inhibitors (TKIs) present disease progression the central nervous system (CNS), either as brain metastases (BM) leptomeningeal (LM). Osimertinib (80 mg), third-generation, irreversible, oral TKI, has shown efficacy active metastases. However, unclear.Patients methodsThis prospective, single-arm, two cohort study evaluated who progressed on prior (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) overall (OS) 5 months) cohort.ResultsThe median follow-up duration was 10.1 months 9.6 cohorts, respectively. In cohort, intracranial control 55.0% 77.5%, progression-free (PFS) 7.6 [95% confidence interval (CI) 5.0–16.6]; OS 16.9 CI 7.9–not reached (NR)]. 92.5% complete 12.5%. 13.3 (95% 9.1–NR); PFS 8.0 7.2–NR). Subgroup analyses based previous exposure agents, including 80 other third-generation TKIs, no difference both (n 18, P 0.39) 17, 0.85) cohorts. Previous radiotherapy favored (hazard ratio 0.42, 0.04). most common events decreased appetite, diarrhea, skin rash; however, 1–2.ConclusionThus, demonstrated profile metastasis TKIs. Up unclear. This cohort. 1–2. Thus,

Language: Английский

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Cellular architecture of human brain metastases

Cell, Journal Year: 2022, Volume and Issue: 185(4), P. 729 - 745.e20

Published: Jan. 20, 2022

Language: Английский

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Anticancer peptides prediction with deep representation learning features

Briefings in Bioinformatics, Journal Year: 2021, Volume and Issue: 22(5)

Published: Jan. 6, 2021

Abstract Anticancer peptides constitute one of the most promising therapeutic agents for combating common human cancers. Using wet experiments to verify whether a peptide displays anticancer characteristics is time-consuming and costly. Hence, in this study, we proposed computational method named identify via deep representation learning features (iACP-DRLF) using light gradient boosting machine algorithm features. Two kinds sequence embedding technologies were used, namely soft symmetric alignment unified (UniRep) embedding, both which involved neural network models based on long short-term memory networks their derived networks. The results showed that use greatly improved capability discriminate from other peptides. Also, UMAP (uniform manifold approximation projection dimension reduction) SHAP (shapley additive explanations) analysis proved UniRep have an advantage over identification. python script pretrained could be downloaded https://github.com/zhibinlv/iACP-DRLF or http://public.aibiochem.net/iACP-DRLF/.

Language: Английский

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Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 23, 2022

Tumor-associated macrophages have emerged as crucial factors for metastases. Microglia are indispensable components of the brain microenvironment and play vital roles in metastasis (BM). However, underlying mechanism how activated microglia promote non-small cell lung cancer (NSCLC) remains elusive. Here, we purified lines with brain-metastatic tropism employed a co-culture system to reveal their communication microglia. By single-cell RNA-sequencing transcriptome difference analysis, identified IL6 key regulator cells (A549-F3) induce anti-inflammatory via JAK2/STAT3 signaling, which turn promoted colonization process metastatic A549-F3 cells. In our clinical samples, patients higher levels serum showed propensity metastasis. Additionally, TCGA (The Cancer Genome Atlas) data revealed that NSCLC lower level had longer overall survival time compared those IL6. Overall, indicate targeting IL6/JAK2/STAT3 signaling may be promising new approach inhibiting patients.

Language: Английский

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Nanomedicine for brain cancer

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 182, P. 114115 - 114115

Published: Jan. 22, 2022

Language: Английский

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Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions

Neuro-Oncology, Journal Year: 2022, Volume and Issue: 24(10), P. 1613 - 1646

Published: May 3, 2022

Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain than cancer-related entities of similar incidence. Advances oncologic care have heightened the importance intracranial management. Here, this consensus review supported by Society for Neuro-Oncology (SNO), we landscape particular attention to management approaches and ongoing efforts potential shape future paradigms care. Each coauthor carried an area expertise within field initially composed, edited, or reviewed their specific subsection interest. After each was accordingly written, multiple drafts manuscript were circulated entire list authors group discussion feedback. The hope that these guidelines will accelerate progress understanding metastases, highlight key areas need further exploration lead dedicated trials other research investigations designed advance field.

Language: Английский

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Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis

Nature Cancer, Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 30, 2022

Abstract The AURORA US Metastasis Project was established with the goal to identify molecular features associated metastasis. We assayed 55 females metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome low-pass whole-genome sequencing global methylation microarrays. Expression subtype changes were observed in ~30% of samples coincident clonality shifts, especially involving HER2. Downregulation estrogen receptor (ER)-mediated cell–cell adhesion genes through mechanisms metastases. Microenvironment differences varied according tumor subtype; ER + /luminal had lower fibroblast endothelial content, while triple-negative cancer/basal metastases showed a decrease B T cells. In 17% metastases, hypermethylation and/or focal deletions identified near HLA-A reduced expression immune cell infiltrates, brain liver These findings could have implications for treating individuals immune- HER2-targeting therapies.

Language: Английский

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