Heparan sulfate targeting strategy for enhancing liposomal drug accumulation and facilitating deep distribution in tumors.

Heparan sulfate targeting strategy for enhancing liposomal drug accumulation and facilitating deep distribution in tumors. Drug Deliv. 2020 Dec;27(1):542-555 Authors: Kuo PH, Teng YH, Cin AL, Han W, Huang PW, Wang LH, Chou YT, Yang JL, Tseng YL, Kao M, Chang MD Abstract Nanoparticles (NPs), such as liposomes, effectively evade the severe toxicity of unexpected accumulation and passively shuttle drugs into tumor tissues by enhanced permeability and retention. In the case of non-small cell lung cancer and pancreatic ductal adenocarcinoma, cancer-associated fibroblasts promote the aggregation of a gel-like extracellular matrix that forms a physical barrier in the desmoplastic stroma of the tumor. These stroma are composed of protein networks and glycosaminoglycans (GAGs) that greatly compromise tumor-penetrating performance, leading to insufficient extravasation and tissue penetration of NPs. Moreover, the presence of heparan sulfate (HS) and related proteoglycans on the cell surface and tumor extracellular matrix may serve as molecular targets for NP-mediated drug delivery. Here, a GAG-binding peptide (GBP) with high affinity for HS and high cell-penetrating activity was used to develop an HS-targeting delivery system. Specifically, liposomal doxorubicin (L-DOX) was modified by post-insertion with the GBP. We show that the in vitro uptake of L-DOX in A549 lung adenocarcinoma cells increased by GBP modification. Cellular uptake of GBP-modified L-DOX (L-...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research

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Conditions:   Pancreatic Ductal Adenocarcinoma;   Non-small Cell Lung Cancer;   Squamous Cell Carcinoma of Head and Neck Interventions:   Biological: Durvalumab;   Biological: Oleclumab Sponsors:   University Health Network, Toronto;   AstraZeneca Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
CONCLUSION: Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors. PMID: 31969095 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
AbstractBackgroundTumor Treating Fields (TTFields) are a non-invasive, antimitotic therapy delivered to the tumor via transducer arrays applied to the skin at tumor site. The only TTFields-related adverse event (AE) reported in clinical trials was localized dermatitis beneath the arrays. The safety of TTFields has also been investigated in glioblastoma, non-small-cell lung cancer (NSCLC), mesothelioma, pancreatic and ovarian cancer. This meta-analysis reported AEs in clinical studies with TTFields torso delivery.Methods192 patients from 4 pilot studies were included in the analysis: EF-15 (n  = 41, advanced N...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Abstract Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Conclusions: The combination of ibrutinib 560 mg daily and durvalumab 10 mg/kg every 2 weeks had an acceptable safety profile. The antitumor activity of the ibrutinib-durvalumab combination was limited in our study population.Oncology
Source: Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: The combination of ibrutinib 560 mg daily and durvalumab 10 mg/kg every 2 weeks had an acceptable safety profile. The antitumor activity of the ibrutinib-durvalumab combination was limited in our study population. PMID: 31230047 [PubMed - as supplied by publisher]
Source: Oncology - Category: Cancer & Oncology Authors: Tags: Oncology Source Type: research
Abstract The adrenal gland is a common site for metastasis from non-small-cell lung cancer (NSCLC). Adrenal metastases are usually solitary, asymptomatic and diagnosed incidentally during staging of patients with lung adenocarcinoma. Huge but sole adrenal gland metastasis with rapid growth and local invasion is extremely rare and those occurring in the setting of NSCLC have not been reported previously. Herein we describe a 66 year old male patient with NSCLC who had huge but sole adrenal gland metastasis with rapid growth and local invasion and extension into stomach, pancreas and left kidney. Interestingly there...
Source: Tuberkuloz ve Toraks - Category: Respiratory Medicine Authors: Tags: Tuberk Toraks Source Type: research
Cancers, Vol. 11, Pages 765: α11β1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration Cancers doi: 10.3390/cancers11060765 Authors: Zeltz Alam Liu Erusappan Hoschuetzky Molven Parajuli Cukierman Costea Lu Gullberg Integrin α11β1 is a collagen receptor that has been reported to be overexpressed in the stroma of non-small cell lung cancer (NSCLC) and of head and neck squamous cell carcinoma (HNSCC). In the current study, we further analyzed integrin α11 expression in 1...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we reported the case of a patient with non-small cell metastatic lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. It achieved a progression-free survival and a28-months overall survival (OS) for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapy treatmentsshowed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms w...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Case Report Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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