orthotropic cancer model

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+ /IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+ /IL-22R1+ myeloid cells...

BACKGROUND: Two main problems examining the mechanism of cancer progression in the tissues using the computational models are lack of enough knowledge on the effective factors for such events in vivo environments and lack of specific parameters in the available computational models to simulate such complicated reactions. METHODS: In this study, it was tried to simulate the progression of cancerous lesions in the bone tissues by an independent parameter from the anatomical and physiological characteristics of the tissues, so to degrade the orthotropic mechanical properties of the bone tissues, a virtual temperature was determined to be used by a well-known framework for simulation of damages in the composite materials...

Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A...

BACKGROUND: Numerous attempts have been devoted to designing anti-angiogenic agents as a strategy to slow tumor growth and progression. Clinical applications of conventional anti-angiogenic agents face some challenges, e.g., off-target effects for TKIs and also low solid tumor penetration for mAbs. Furthermore, although anti-angiogenic therapy provides a normalization window for better chemo-RT response, in long-term treatments, tumor hypoxia as a result of total removal of VEGF-A by mAbs from the TME or complete blockade of TK receptors induces over-activation of compensatory angiogenic pathways, causing escape...

BACKGROUND/AIM: In this study, we used an orthotropic breast cancer model combined with ketamine addiction and next-generation sequencing (NGS) to comprehensively investigate molecular alterations in ketamine-mediated metastasis. Ketamine is widely used in anesthesia and drug abuse. Our previous study revealed that ketamine promotes the growth of breast cancer cells; however, the detailed molecular mechanism remains unknown. MATERIALS AND METHODS: An orthotropic breast cancer model was established by injecting EO771 breast cancer cells into the mammary fat pad of mice intraperitoneally administered ketamine (30 mg/kg, daily) for 68 days...

INTRODUCTION: The emergence of resistance to the highly successful BCL2-directed therapy is a major unmet need in acute myeloid leukemia (AML), an aggressive malignancy with poor survival rates. Towards identifying therapeutic options for AML patients who progress on BCL2-directed therapy, we studied a clinical-stage CDK7 inhibitor XL102, which is being evaluated in solid tumors (NCT04726332). MATERIALS AND METHODS: To determine the anti-proliferative effects of XL102, we performed experiments including time-resolved fluorescence resonance energy transfer, target occupancy, cell cycle and apoptosis-based assays...

Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose transporter activity - a widely-used surrogate for metabolism, we evaluate hemodynamics of 2-DG-MP by fitting the dynamic MSOT signal of 2-DG-800 into two-compartment models including the extended Tofts model (ETM) and reference region model (RRM)...

Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked...

Pancreatic cancer is known for its tumor microenvironment (TME), which is rich in stromal and immune cells supporting cancer growth and therapy resistance. In particular, tumor-associated macrophages (TAMs) are known for their angiogenesis- and metastasis-promoting properties, which lead to the failure of conventional therapies for pancreatic cancer. Hence, treatment options targeting TAMs are needed. The C-C chemokine receptor type 4 (CCR4) is critical for immune cell recruitment into the TME, and in this paper we explore the effects of its genetic or immunotherapeutic blockade in pancreatic-cancer-bearing mice...

Metastasis, a complex process, is responsible for most deaths in patients with cancer. Clinically relevant research models are indispensable to advancing our understanding of metastatic mechanisms and developing new treatments. We here describe detailed protocols to establish mouse models for melanoma metastasis using the single-cell imaging system and orthotropic footpad injection. The single-cell imaging system permits the tracking and quantification of early metastatic cell survival, while the orthotropic footpad transplantation mimics aspects of the complex metastatic process...

Inositol hexaphosphate (IP6), a widely found natural bioactive substance in grains, effectively inhibits the progression of colorectal cancer (CRC) when used in combination with inositol (INS). We previously showed that supplementation of IP6 and INS upregulated the claudin 7 gene in orthotropic CRC xenografts in mice. The aim of this study was to elucidate the role of claudin7 in the inhibition of CRC metastasis by IP6 and INS, and explore the underlying mechanisms. We found that IP6, INS and their combination inhibited the epithelial-mesenchymal transition (EMT) of colon cancer cell lines (SW480 and SW620), as indicated by upregulation of claudin 7 and E-cadherin, and downregulation of N-cadherin...

BACKGROUND & AIMS: Transforming growth factor-β (TGFβ) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating cluster of differentiation 8 (CD8) T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFβ inhibition has shown limited efficacy against pancreatic cancer in mice or humans. METHODS: We evaluated the TGFβ-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models...

OBJECTIVE: Liver cancer is a deadly malignancy associated with high mortality and morbidity. Less than 20% of patients with advanced liver cancer respond to a single anti-PD-1 treatment. The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade (ICB). However, the underlying mechanism remains largely unknown. METHODS: We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and Kras G12D into the genome in liver cells from conditional Trp53 null/null mice (pTMK/Trp53-/- )...

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane...

Proteins involved in immune checkpoint pathways, such as CTLA4, PD1, and PD-L1, have become important targets for cancer immunotherapy; however, development of small molecule drugs targeting these pathways has proven difficult due to the nature of their protein-protein interfaces. Here, using a hierarchy of computational techniques, we design a cyclic peptide that binds CTLA4 and follow this with experimental verification of binding and biological activity, using bio-layer interferometry, cell culture, and a mouse tumor model...

Lung cancer with the highest mortality poses a great threat to human health. Ferroptosis therapy has recently been raised as a promising strategy for lung cancer treatment by boosting the reactive species (ROS) production and lipid peroxidation (LPO) accumulation intracellularly. However, the insufficient intracellular ROS level and the unsatisfactory drug accumulation in lung cancer lesions hamper the efficacy of ferroptosis therapy. Here, an inhalable biomineralized liposome LDM co-loaded with dihydroartemisinin (DHA) and pH-responsive calcium phosphate (CaP) was constructed as a ferroptosis nanoinducer for achieving Ca2+ -burst-centered endoplasmic reticulum (ER) stress enhanced lung cancer ferroptosis therapy...

OBJECTIVE: Intercellular communication within pancreatic ductal adenocarcinoma (PDAC) dramatically contributes to metastatic processes. The underlying mechanisms are poorly understood, resulting in a lack of targeted therapy to counteract stromal-induced cancer cell aggressiveness. Here, we investigated whether ion channels, which remain understudied in cancer biology, contribute to intercellular communication in PDAC. DESIGN: We evaluated the effects of conditioned media from patient-derived cancer-associated fibroblasts (CAFs) on electrical features of pancreatic cancer cells (PCC)...

BACKGROUND: Photodynamic therapy (PDT) using an 808 nm laser irradiation with indocyanine green (ICG) has shown tumoricidal effects in a hepatocellular (HCC) orthotopic xenograft model. Recently, combining PDT with concurrent chemotherapy has shown synergistic outcomes and a better therapeutic effect for cancer treatment. In the present study, we utilized a combination of chemotherapy drugs and PDT using ICG in vitro and in vivo in a patient-derived orthotopic xenograft (PDoX) model...

BACKGROUND: Heat shock protein 27 (HSP27) is overexpressed during pulmonary fibrosis (PF) and exacerbates PF; however, the upregulation of HSP27 during PF and the therapeutic strategy of HSP27 inhibition is not well elucidated. METHODS: We have developed a mouse model simulating clinical stereotactic body radiotherapy (SBRT) with focal irradiation and validated the induction of RIPF. HSP25 (murine form of HSP27) transgenic (TG) and LLC1-derived orthotropic lung tumor models were also used...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a five-year survival rate of around 10 %. CXCR4 and STAT3 display crucial effects on proliferation, metastasis, angiogenesis, and formation of immunosuppressive microenvironment in pancreatic tumors. Here, we have tested the hypothesis that conjugation of α-tocopherol (TOC) to a polycation (PAMD), synthesized from CXCR4-antagonist AMD3100, will improve delivery of therapeutic siRNA to silence STAT3 in PDAC tumors. PAMD-TOC/siSTAT3 nanoparticles showed superior anti-cancer and anti-migration performance compared to the parent PAMD/siSTAT3 nanoparticles in both murine and human PDAC cell lines...