Vascular Endothelial Growth Factor Receptor 1 Targeting Fusion Polypeptides with Stimuli-Responsiveness for Anti-angiogenesis.

Genetically engineered fusion polypeptides have been investigated to introduce unique bio-functionality and improve some therapeutic activity for anti-angiogenesis. We report herein that stimuli-responsive, vascular endothelial growth factor receptor 1 (VEGFR1) targeting fusion polypeptides composed of a VEGFR1 (fms-like tyrosine kinase-1 (Flt1)) antagonist, an anti-Flt1 peptide, and a thermally responsive elastin-based polypeptide (EBP) were rationally designed at the genetic level, biosynthesized, and purified by inverse transition cycling to develop potential anti-angiogenic fusion polypeptides to treat neovascular diseases. A series of hydrophilic EBPs with different block lengths were fused with an anti-Flt1 peptide, forming anti-Flt1-EBPs, and the effect of EBP block length on their physicochemical properties was examined.

Thrombopoietin receptor agonist antibody for treating chemotherapy-induced thrombocytopenia.

Background: Thrombocytopenia is a common complication in cancer patients undergoing chemotherapy. Chemotherapy-induced thrombocytopenia (CIT) leads to dose reduction and treatment delays, lowering chemotherapy efficacy and survival rate. Thus, rapid recovery and continuous maintenance of platelet count during chemotherapy cycles are crucial in patients with CIT.

Impact of Obesity on the IL-6 Immune Marker and Th17 Immune Cells in C57BL/6 Mice Models with Imiquimod-Induced Psoriasis.

Obese psoriatic patients experience higher disease severity and exhibit poorer treatment responses and clinical outcomes. It has been proposed that proinflammatory cytokines produced by adipose tissue exacerbate psoriasis; however, the role of obesity in psoriasis remains unclear. This study aimed to elucidate the role of obesity in the pathogenesis of psoriasis, focusing on immunological changes.

Efficacy of Polydeoxyribonucleotide in Promoting the Healing of Diabetic Wounds in a Murine Model of Streptozotocin-Induced Diabetes: A Pilot Experiment.

We assessed the efficacy of polydeoxyribonucleotide (PDRN) in accelerating the healing of diabetic wounds in a murine model of streptozotocin (STZ)-induced diabetes. After the creation of diabetic wounds, the mice of the PDRN SC, PDRN IP and PBS groups received a subcutaneous, an intra-peritoneal injection of PDRN and a subcutaneous injection of PBS, respectively. After euthanasia, time-dependent changes in the wound diameter and histologic scores were measured and vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and collagen types I and III were assessed for their expression levels.

Promoter Methylation of Cancer Stem Cell Surface Markers as an Epigenetic Biomarker for Prognosis of Oral Squamous Cell Carcinoma.

Growing evidence suggests that genetic and epigenetic factors, including environmental factors, contribute to the development of oral squamous cell carcinoma (OSCC). Here, we investigated the transcriptional silencing of the CD24, CD44, CD133, and CD147 genes, which are well-known cancer stem cell surface markers in various cancer types, including OSCC. We first examined the correlation between the transcriptional expression level and reactivation by 5-aza-2′-deoxycytidine (5-aza-dC) and the promoter methylation levels of the four genes in several OSCC cell lines.

Role of the JAK/STAT pathway in a streptozotocin-induced diabetic retinopathy mouse model.

Purpose: The Janus tyrosine kinase and signal transducers and activators of transcription (JAK/STAT) pathway is involved in vascular endothelial growth factor (VEGF) expression, but the role of this pathway in diabetic retinopathy (DR) remains unclear. We investigated the role of the JAK/STAT pathway on DR and VEGF expression using a streptozotocin (STZ)-induced DR mouse model.

Methods: Cultured ARPE-19 cells were exposed to high-glucose conditions and treated with JAK/STAT inhibitors (JAK inhibitor I [JAKiI], tofacitinib, STAT3 inhibitor [STAT3i]) for 48 h.

Benzyl Isothiocyanate Attenuates Inflammasome Activation in LPS-Stimulated THP-1 Cells and Exerts Regulation through the MAPKs/NF-κB Pathway.

Inflammasomes are a group of intracellular multiprotein platforms that play important roles in immune systems. Benzyl isothiocyanate (BITC) is a constituent of cruciferous plants and has been confirmed to exhibit various biological activities. The modulatory effects of BITC on inflammasome-mediated interleukin (IL)-1β expression and its regulatory mechanisms in () LPS/ATP-stimulated THP-1 cells was investigated.

Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge.

Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer that is treated with anti-HER2/neu monoclonal antibody (mAb) is not free from late recurrences. Addition of anti-4-1BB mAb to anti-HER2/neu mAb has been demonstrated to strengthen the cytotoxic antitumor response. Our study expands on this by revealing the influence of anti-4-1BB mAb addition on the immune memory of anti-HER2/neu mAb.

Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.

Myeloid cell leukemia sequence 1 (MCL‑1), an anti‑apoptotic B‑cell lymphoma 2 (BCL‑2) family molecule frequently amplified in various human cancer cells, is known to be critical for cancer cell survival. MCL‑1 has been recognized as a target molecule for cancer treatment. While various agents have emerged as potential MCL‑1 blockers, the present study presented acriflavine (ACF) as a novel MCL‑1 inhibitor in triple‑negative breast cancer (TNBC).

Enlightening the Immune Mechanism of the Abscopal Effect in a Murine HCC Model and Overcoming the Late Resistance With Anti-PD-L1.

Purpose: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study.

Methods And Materials: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody.

Induces Immunogenic Cell Death and Enhances Antitumor Immunogenic Response in Breast Cancer.

has been widely used as a traditional medicine in East Asia. Its effects against breast cancer have been reported previously. However, whether -induced breast cancer cell death is immunogenic remains unelucidated.

Genome-Wide Analysis of the DNA Methylation Profile Identifies the Fragile Histidine Triad () Gene as a New Promising Biomarker of Crohn's Disease.

Inflammatory bowel disease is known to be associated with a genetic predisposition involving multiple genes; however, there is growing evidence that abnormal interactions with environmental factors, particularly epigenetic factors, can also significantly contribute to the development of inflammatory bowel disease (IBD). Although many genome-wide association studies have been performed to identify the genetic changes underlying the pathogenesis of Crohn's disease, the role of epigenetic alterations based on molecular complications arising from Crohn's disease (CD) is poorly understood. We employed an unbiased approach to define DNA methylation alterations in colonoscopy samples from patients with CD using the HumanMethylation450K BeadChip platform.

Extracellular Acidosis Promotes Metastatic Potency via Decrease of the Circadian Clock Gene in Breast Cancer.

Circadian oscillation is an essential process that influences many physiological and biological mechanisms and a decrease of circadian genes is associated with many diseases such as cancer. Despite many efforts to identify the detailed mechanism for decreasing circadian genes and recovering reduced circadian genes in cancer, it is still largely unknown. We found that BMAL1 was reduced in tumor hypoxia-induced acidosis, and recovered by selectively targeting acidic pH in breast cancer cell lines.

Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells.

Arsenic compounds (AsO and AsO) have demonstrated anticancer effects in various malignancies. In this study, the cytotoxicity of arsenic compounds on ovarian cancer cell lines and the anticancer activity of the combination of arsenic compounds and cisplatin IN chemoresistant ovarian cancer cells were investigated. We investigated the cytotoxicity of AsO and AsO and their combinations with cisplatin in the paclitaxel-sensitive ovarian cancer cell lines SKOV3ip1 and HeyA8 and paclitaxel-resistant ovarian cancer cell lines SKOV3TRip2 and HeyA8-MDR.

Type I pig collagen enhances the efficacy of PEDF 34-mer peptide in a mouse model of laser-induced choroidal neovascularization.

Background: Pigment epithelium-derived factor (PEDF)-derived 34-mer peptide (PEDF34, Asp-Asn) has anti-angiogenic activity but has limitations in clinical application because of an inverted bell-shaped dose-effect relationship and a short half-life. In this study, we attempted to mitigate these problems by mixing PEDF34 with type I collagen.

Methods: The anti-angiogenic activity of the PEDF34/atelocollagen mixture was evaluated by HUVEC tube formation assay and in a laser-induced choroidal neovascular (CNV) mouse model.

Effect of anthracycline and taxane on the expression of programmed cell death ligand-1 and galectin-9 in triple-negative breast cancer.

This study identified chemotherapeutic agents that up-regulate programmed cell death ligand-1 (PD-L1) and galectin-9 (Gal-9) in breast cancer cells. Immunohistochemical (IHC) staining was used to evaluate changes in PD-L1 and Gal-9 expression in the tumor tissue of triple-negative breast cancer (TNBC) patients who received anthracycline- and taxane-based neoadjuvant chemotherapy. To determine whether PD-L1 and Gal-9 expression changes were attributable directly to chemotherapeutics, MDA-MB-231 cells and HS578T cells were treated with different concentrations of anthracycline and taxane.

A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice.

Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of class I PI3K isoforms (pan-PI3K inhibitors). The present study investigated the therapeutic effect and potential for stimulating anti-tumor immunity of combined therapy with an anti-HER2/neu antibody and pan-PI3K inhibitor (GDC-0941) or a PI3K p110α isoform-selective inhibitor (A66) in mouse models of breast cancer.

ALDH1 and tumor infiltrating lymphocytes as predictors for neoadjuvant chemotherapy response in breast cancer.

Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC.

Inhibition of acute lethal pulmonary inflammation by the IDO-AhR pathway.

The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4 T cells transiently induced expression of indoleamine 2,3-dioxygenase (IDO) in lung parenchyma in an IFN-γ-dependent manner early after allogeneic hematopoietic stem cell transplantation (HSCT). Abrogation of host IDO expression by deletion of the IDO gene or the IFN-γ gene in donor T cells or by FK506 treatment resulted in acute lethal pulmonary inflammation known as idiopathic pneumonia syndrome (IPS).

Fucoxanthin inhibits profibrotic protein expression in vitro and attenuates bleomycin-induced lung fibrosis in vivo.

Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs).

Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation.

Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood.

NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels.

A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger.

Pre-stimulation of CD81 expression by resting B cells increases proliferation following EBV infection, but the overexpression of CD81 induces the apoptosis of EBV-transformed B cells.

Hepatitis C virus (HCV) E2 protein binds to CD81, which is a component of the B cell co-stimulatory complex. The E2-CD81 interaction leads to B cell proliferation, protein tyrosine phosphorylation and to the hypermutation of immunoglobulin genes. Epidemiological studies have reported a high prevalence of B cell non-Hodgkin lymphoma (NHL) in HCV-positive patients, suggesting a potential association between HCV and Epstein-Barr virus (EBV) in the genesis of B lymphocyte proliferative disorders.

Effect of upregulated TLR2 expression from G-CSF-mobilized donor grafts on acute graft-versus-host disease.

Our previous study demonstrated that G-CSF treatment increased the expression of TLR2 in donor grafts; this contributed to rapid engraftment after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. In the current study, we investigated the effects of upregulated TLR2 expression in G-CSF-mobilized donor grafts on acute graft-versus-host disease (GVHD). We found that TLR2 was highly expressed on myeloid cell populations but not T and B cells from the spleens of G-CSF-treated donor mice.

Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model.

Experimental autoimmune uveoretinitis (EAU) is an autoimmune disease that models human uveitis. Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, possesses anti-inflammatory and immunomodulatory properties. CAPE demonstrates therapeutic potential in several animal disease models through its ability to inhibit NF-κB activity.