Lung adenocarcinoma (LUAD), which comprises over 50% of all cases of non-small-cell lung cancer, has a poor prognosis and requires novel therapeutic approaches. The sonic Hedgehog (Shh) pathway, which plays a crucial role in differentiation, proliferation, and survival of cancer cells, is likely to be activated in LUADs, suggesting the Shh pathway as a potential therapeutic target for LUAD treatment. In this study, we reported that vismodegib, an inhibitor of the Shh pathway, only elicited minor antitumor efficacy in A549 and NCI-H1975 LUAD cells as well as in the xenograft tumors, with overexpressed GLI2 and increased autophagic activity.
View Article and Find Full Text PDFEpidermal growth factor receptor (EGFR)-targeted cancer therapy requires an accurate estimation of EGFR expression in tumors to identify responsive patients, monitor therapeutic effect, and estimate prognosis. The EGFR molecular imaging is an optimal method for evaluating EGFR expression in vivo accurately and noninvasively. In this review, we discuss the recent advances in EGFR-targeted molecular imaging in cancer, with a special focus on the development of imaging agents, including epidermal growth factor (EGF) ligand, monoclonal antibodies, antibody fragments, Affibody, and small molecules.
View Article and Find Full Text PDFImmunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) due to the presence of an immunosuppressive tumor-associated stroma. Here, we demonstrate an effective modulation of that stroma by irreversible electroporation (IRE), a local ablation technique that has received regulatory approval in the United States. IRE induces immunogenic cell death, activates dendritic cells, and alleviates stroma-induced immunosuppression without depleting tumor-restraining collagen.
View Article and Find Full Text PDFAim: To demonstrate the feasibility of intratracheal administration in orthotopic lung cancer model with F MRI.
Materials & Methods: αβ-integrin targeting ability of the perfluorocarbon (PFC) nanoparticles was tested. Orthotopic lung cancer model was established in rabbits under computed tomography guidance.
Connexins are a family of gap junction proteins widely distributed in human organs and tissues. Gap junctions are organized systems of intercellular protein channels that allow the exchange of ions, chemical signals, and energy substrates between two adjacent cells. Connexin43 (Cx43) is the most abundant isoform of connexins in the heart which play an important role in myocardium disease.
View Article and Find Full Text PDFElevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of the c-Met signaling pathway contributes to tumorigenesis and cancer progression and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for NSCLC, and methods for noninvasive in vivo assessment of c-Met expression would improve NSCLC treatment and diagnosis.
View Article and Find Full Text PDFJ Magn Reson Imaging
December 2018
Background: Folate receptors (FRs) hold great potential as important diagnostic and prognostic biological marker for cancer.
Purpose: To assess the targeted capability of the FR-targeted perfluorocarbon (PFC) nanoparticles and to assess in vivo the relationship between FR expression and tumor proliferation with fluorine-19 ( F) MR molecular imaging.
Study Type: Prospective animal cancer model.
Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) mutation status over time challenge the design of effective EGFR tyrosine kinase inhibitor (TKI) treatment strategies for non-small cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for comprehensive tumor EGFR profiling in real time, particularly in lung cancer precision medicine trials. We report a positron emission tomography (PET) tracer, -(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (F-MPG), with high specificity to activating EGFR mutant kinase.
View Article and Find Full Text PDFPiwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines.
View Article and Find Full Text PDFEighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications.
View Article and Find Full Text PDFHypoxia is a common feature of solid tumors that is closely associated with radiotherapy and chemotherapy resistance, metastasis and tumors prognosis. Thus, it is important to assess hypoxia in tumors for estimating prognosis and selecting appropriate treatment procedures. F-Fluoromisonidazole positron emission tomography (F-FMISO PET) has been widely used to visualize tumor hypoxia in a comprehensive and noninvasive way, both in the clinical and preclinical settings.
View Article and Find Full Text PDFThe important role of insulin-like growth factor 1 receptor (IGF-1R) in malignant tumors has been well established. Increased IGF-1R activity promotes cancer cell proliferation, migration, and invasion and is associated with tumor metastasis, treatment resistance, poor prognosis, and shortened survival in patients with cancer. However, while IGF-1R has become a promising target for cancer therapy, IGF-1R-targeted therapy is ineffective in unselected patients.
View Article and Find Full Text PDFUsing X-ray as the irradiation source, a photodynamic therapy process can be initiated from under deep tissues. This technology, referred to as X-ray induced PDT, or X-PDT, holds great potential to treat tumors at internal organs. To this end, one question is how to navigate the treatment to tumors with accuracy with external irradiation.
View Article and Find Full Text PDFTo prepare and evaluate a new radiotracer F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging.
View Article and Find Full Text PDFTyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point mutation). However, despite their great success in the clinic, a significant number of patients do not respond to EGFR-TKIs, such as those carrying the L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status before EGFR-TKIs therapy is essential to ensure its efficacy.
View Article and Find Full Text PDFBackground: Mesenchymal-epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis. c-MET-targeted therapies have been tested in preclinical models and patients, with significant benefits for cancer treatment. In recent years, many studies have shown that the expression level and activation status of c-MET are closely correlated to c-MET-targeted therapy response and clinical prognosis, thus highlighting the importance of evaluating the c-MET status during and prior to targeted therapy.
View Article and Find Full Text PDFDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI.
View Article and Find Full Text PDF18F-fluorodeoxyglucose (18F-FDG) positron emission tomography has become an important tool for detection, staging and management of many types of cancer. Oncology application of 18F-FDG bases on the knowledge that increase in glucose demand and utilization is a fundamental features of cancer. Pasteur effect, Warburg effect and reverse Warburg effect have been used to explain glucose metabolism in cancer.
View Article and Find Full Text PDFRecent reports suggest promises on using oncolytic Newcastle disease viruses (NDV) to treat different cancers, while the effects of a NDV-D90 strain on gastric cancer remain unknown. Here we showed that NDV-D90 induced gastric cancer cell apoptosis in a dose-dependent manner in 3 gastric cancer cell lines BGC-823, SGC-7901 and MKN-28. Pronounced reduction in cell invasion was detected in NDV-D90-treated BGC-823 and SGC-7901 cells, but not in MKN-28 cells.
View Article and Find Full Text PDFLemur tyrosine kinase-3 (LMTK3) is a member of the serine/threonine tyrosine kinase family, which is thought to be involved in tumor progression and prognosis. The purpose of the present study was to determine the diagnostic significance and therapeutic targets in thyroid cancer. ELISA assay was used to detect the protein expression of serum LMTK3.
View Article and Find Full Text PDFRecent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death.
View Article and Find Full Text PDFObjectives: The aim of this study was to investigate the predictive value of the numbers of metabolically positive lymph nodes (MPLN) detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced gastric cancer (LAGC).
Methods: We retrospectively analyzed the records of 50 patients with LAGC (stage T2-T4) who had undergone pre-operative PET/CT examination and laparotomy (total gastrectomy, n = 11; subtotal gastrectomy, n = 13; distal gastrectomy, n = 22; and bypass with gastrojejunstomy, n = 4). The numbers of MPLN were determined by combining visual observations with semi-quantitative measurements of the maximized standardized uptake value (SUVmax).
Bioorg Med Chem Lett
December 2016
EGFR (epidermal growth factor receptor) targeted therapy has shown great success in clinical comparing with chemotherapy in EGFR mutation NSCLCs. Such as, gefitinib, first generation EGFR TKI, has obviously prolonged the FPS (progression free survival) of the subgroup of patients, but to those who did not get a certain mutation in EGFR kinase domain, the outcome is poor. In view of this situation, scientists have synthesized many radiotracers for selecting the right people by PET/CT imaging to NSCLC TKI therapy.
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