The role of angiotensin-(1-7) on acquired platinum resistance-induced angiogenesis in non-small cell lung cancer in vitro and in vivo.

Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis.

Targeting CD133 reverses drug-resistance via the AKT/NF-κB/MDR1 pathway in colorectal cancer.

Background: Recent studies have shown that multidrug resistance may be induced by the high stemness of cancer cells. Following prolonged chemotherapy, MDR protein 1 (MDR1) and CD133 increase in CRC, but the relationship between them is unclear.

Methods: The relationship between MDR and CSC properties in CRC was determined via CCK-8 assay, apoptosis assay, DOX uptake and retention, immunohistochemistry, immunofluorescence and flow cytometry.

Bufalin reverses multidrug resistance by regulating stemness through the CD133/nuclear factor-κB/MDR1 pathway in colorectal cancer.

Recent studies have shown that MDR could be induced by the high stemness of cancer cells. In a previous study, we found bufalin could reverse MDR and inhibit cancer cell stemness in colorectal cancer, but the relationship between them was unclear. Here we identified overexpressing CD133 increases levels of Akt/nuclear factor-κB signaling mediators and MDR1, while increasing cell chemoresistance.

Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy.

Photodynamic therapy (PDT), a regulatory approved cancer treatment, is reported to be capable of causing immunogenic apoptosis. The current data reveal PDT can cause the dysregulation of "eat me" and "don't eat me" signal by generating reactive oxygen species (ROS) -mediated endoplasmic reticulum (ER) stress. This dysregulation probably contribute to the increased uptake of PDT-killed Lewis lung carcinoma (LLC) cells by homologous dendritic cells (DCs), accompanied by phenotypic maturation (CD80(high), CD86(high), and CD40(high)) and functional stimulation (NO(high), IL-10(absent)) of dendritic cells as well as subsequent T-cell responses.

Photodynamic therapy-mediated cancer vaccination enhances stem-like phenotype and immune escape, which can be blocked by thrombospondin-1 signaling through CD47 receptor protein.

Like most of the strategies for cancer immunotherapy, photodynamic therapy-mediated vaccination has shown poor clinical outcomes in application. The aim of this study is to offer a glimpse at the mechanisms that are responsible for the failure based on cancer immuno-editing theory and to search for a positive solution. In this study we found that tumor cells were able to adapt themselves to the immune pressure exerted by vaccination.

An investigation of antitumor efficiency of novel sustained and targeted 5-fluorouracil nanoparticles.

Traditional chemotherapeutic drugs remain the major treatment for advanced colorectal cancer. However, due to the lack of tumor specificity these drug also destroy healthy tissue and organs, which has been the main reason for treatment failure and mortality. Folate-based drug delivery systems for improving nanoparticle endocytosis have been used to address these problems.

A collagen-based multicellular tumor spheroid model for evaluation of the efficiency of nanoparticle drug delivery.

Targeted drug delivery systems, especially those that use nanoparticles, have been the focus of research into cancer therapy during the last decade, to improve the bioavailability and delivery of anticancer drugs to specific tumor sites, thereby reducing the toxicity and side effects to normal tissues. However, the positive antitumor effects of these nanocarriers observed in conventional monolayer cultures frequently fail in vivo, due to the lack of physical and biological barriers resembling those seen in the actual body. Therefore, the collagen-based 3-D multicellular culture system, to screen new nanocarriers for drug delivery and to obtain more adequate and better prediction of therapeutic outcomes in preclinical experiments, was developed.

Discovery of novel 1,5-benzodiazepine-2,4-dione derivatives as potential anticancer agents.

A series of novel 1,5-benzodiazepine-2,4-dione derivatives with C-6 amide substituents were designed and synthesized using three-component reactions. The preliminary assays showed that most of them displayed moderate to good antitumor activities against human lung carcinoma (A549), human breast epithelial carcinoma (MCF-7), human colon carcinoma (HCT116), human cervical carcinoma (Hela) and Lewis lung carcinoma (2LL). Exhilaratingly, the activity level of 6m rivaled that of 5-Fluorouracil (5-Fu) against MCF-7 cell lines, which might be used as novel lead scaffold for potential anticancer development.

Astragaloside IV inhibits progression of lung cancer by mediating immune function of Tregs and CTLs by interfering with IDO.

Purpose: Tumor cells have developed multiple mechanisms to escape immune recognition mediated by T cells. Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme inducing immune tolerance, is involved in tumor escape from host immune systems in mice. Astragaloside IV (AS-IV), an extract from a commonly used Chinese medicinal plant Astragalus membranaceus, has been shown to be capable of restoring the impaired T-cell functions in cancer patients.

Post-transcriptional regulation of the tumor suppressor miR-139-5p and a network of miR-139-5p-mediated mRNA interactions in colorectal cancer.

MicroRNAs play key roles in many biological processes, and are frequently dysregulated in tumor cells. However, there are few studies on how microRNAs are dysregulated. miR-139-5p, an important tumor suppressor, is often underexpressed in gastrointestinal cancer cells.

Preparation of polysaccharide derivates chitosan-graft-poly(ɛ-caprolactone) amphiphilic copolymer micelles for 5-fluorouracil drug delivery.

Biodegradable graft copolymer, chitosan-graft-poly(ɛ-caprolactone) (CS-g-PCL) was synthesized via ring opening polymerization and characterized by (1)H NMR and FTIR spectroscopy. Then graft copolymers were self-assembled into micelles as drug delivery system. To evaluate drug-polymer compatibility, the Flory-Huggins interaction parameter between 5-fluorouraci (5-Fu) and hydrophobic segment was calculated.

Overcoming multidrug resistance in 2D and 3D culture models by controlled drug chitosan-graft poly(caprolactone)-based nanoparticles.

The principal limitations of chemotherapy are dose-limiting systemic toxicity and the development of multidrug-resistant phenotypes. The aim of this study was to investigate the efficiency of a new sustained drug delivery system based on chitosan and ε-caprolactone to overcome multidrug resistance in monolayer and drug resistance associated with the three-dimensional (3D) tumor microenvironment in our established 3D models. The 5-fluorouracil (5-FU)-loaded nanoparticles (NPs) were characterized by transmission electron microscope and dynamic light scattering, and its released property was determined at different pH values.

Hypericin-based Photodynamic Therapy Induces a Tumor-Specific Immune Response and an Effective DC-based cancer Immunotherapy.

In our study, we find that photodynamic therapy (PDT), which generates reactive oxygen species (ROS) -mediated endoplasmic reticulum (ER) stress to inflict trauma in the targeted lesion, can break the balance between membrane damage-associated molecular patterns (DAMPs) and integrin-associated protein (CD47). The imbalance undermines the ability of lewis lung carcinoma (LLC) cells to escape immune attack by increasing the uptake of hypericin-mediated PDT(hyp-PDT) killed lewis lung carcinoma (LLC) cells by homologous dendritic cells (DCs), accompanied by phenotypic maturation (CD80, CD86, and CD40) and functional stimulation (NO, IL-10) of dendritic cells as well as subsequent T-cell response. Besides, C57BL/6 mice vaccinated with dendritic cells (DCs) pulsed with PDT-treated LLCs (PDT-DCs) or PDT-treated LLCs alone (PDT-LLCs) show potent immunity against LLC tumor.

Development of rapid and highly sensitive HSPA1A promoter-driven luciferase reporter system for assessing oxidative stress associated with low-dose photodynamic therapy.

Photodynamic therapy (PDT) is a regulatory-approved modality for treating a variety of malignant tumors. It induces tumor tissue damage via photosensitizer-mediated oxidative cytotoxicity. The heat shock protein 70 (HSP70-1) is a stress protein encoded by the HSPA1A gene and is significantly induced by oxidative stress associated with PDT.