scholarly journals Intraperitoneal Administration of Synthetic MicroRNA-214 Exhibits Tumor Suppression in an Intraperitoneal Dissemination Mouse Model of Canine Hemangiosarcoma

2021 ◽  
Author(s):  
Ryutaro Yoshikawa ◽  
Atsushi Maeda ◽  
Yoshihito Ueno ◽  
Hiroki Sakai ◽  
Shintaro Kimura ◽  
...  
Keyword(s):  
Mouse Model ◽  
Caspase 3 ◽  
Systemic Treatment ◽  
Chemotherapeutic Agent ◽  
Intraperitoneal Administration ◽  
Median Number ◽  
Antitumor Effects ◽  
Ki 67 ◽  
Novel Mirna ◽  
Nuclease Resistance

Abstract Canine hemangiosarcoma (HSA) has extremely poor prognosis, making it necessary to develop new systemic treatment methods. MicroRNA-214 (miR-214) is one of many microRNAs (miRNA) that can induce apoptosis in HSA cell lines. Synthetic miR-214 (miR-214/5AE), which showed higher cytotoxicity and greater nuclease resistance than mature miR-214, has been developed for clinical application. In this study, we evaluated the effects of miR-214/5AE on stage 2 HSA in a mouse model. Mice intraperitoneally administered with miR-214/5AE (5AE group) had significantly fewer intraperitoneal dissemination tumor foci (median number: 80 vs. 233; p < 0.05) and lighter median foci weight (0.26 g vs. 0.74 g; p < 0.05). There was an increase in p53 and cleaved caspase-3 expression in the 5AE group. The mice in this group also had a significantly lower proportion of Ki-67-positive cells than those in the non-specific miR group. Notably, there were no significant side effects observed. These results indicate that intraperitoneal administration of miR-214/5AE exhibits antitumor effects in the intraperitoneal dissemination mouse model of HSA by inducing apoptosis and suppressing cell proliferation. We strongly believe that miR-214/5AE could be a novel miRNA-based chemotherapeutic agent capable of improving the prognosis of HSA.

ROLE OF THE STROMAL CELLULAR COMPONENT IN COMPENSATORY PROCESSES IN DIFFUSE LIVER DAMAGE

2018 ◽  
pp. 32-37 ◽  
Author(s):  
Z. A. Shafigullina ◽  
S. Yu. Medvedeva ◽  
I. G. Danilova
Keyword(s):  
Toxic Hepatitis ◽  
Intraperitoneal Administration ◽  
Sharp Decrease ◽  
Cellular Component ◽  
Ki 67 ◽  
Sinusoidal Cells ◽  
Toxic Damage ◽  
Stromal Component ◽  
Regeneration Processes

The aim of the study was to assess the role of the cellular component of the stroma in liver regeneration after its toxic damage. The experimental model of toxic hepatitis caused by intraperitoneal administration of tetrachloromethane (CCl4) showed that regeneration processes in the liver on the 3rd day are manifested in an increase in binuclear hepatocytes, Ki-67 + cells and hepatocytes dividing by mitosis. The reaction of the stromal component is expressed in an increase in the number of CD45 +, mast and sinusoidal cells (SC). On the 7th day of the development of toxic hepatitis the hepatocyte alteration increases, that is accompanied by a sharp decrease in the mitotic index and the number of Ki-67 + cells. In the stromal component there is a decrease in the number of sinusoidal cells, CD45 + and a significant increase in mast cells with a high secretion granule content.

scholarly journals Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3407 ◽  
Author(s):  
Paola Imbriani ◽  
Annalisa Tassone ◽  
Maria Meringolo ◽  
Giulia Ponterio ◽  
Graziella Madeo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Synaptic Function ◽  
Adult Brain ◽  
Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

scholarly journals Long Term Real-World Outcomes of Trifluridine/Tipiracil in Metastatic Colorectal Cancer—A Single UK Centre Experience

2021 ◽  
Vol 28 (3) ◽  
pp. 2260-2269
Author(s):  
Daniel Tong ◽  
Lei Wang ◽  
Jeewaka Mendis ◽  
Sharadah Essapen
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Median Number ◽  
Current Data ◽  
Real World Data

In the UK, Trifluridine-tipiracil (Lonsurf) is used to treat metastatic colorectal cancer in the third-line setting, after prior exposure to fluoropyrimidine-based regimes. Current data on the real-world use of Lonsurf lack long-term follow-up data. A retrospective evaluation of patients receiving Lonsurf at our Cancer Centre in 2016–2017 was performed, all with a minimum of two-year follow-up. Fifty-six patients were included in the review. The median number of cycles of Lonsurf administered was 3. Median follow-up was 6.0 months, with all patients deceased at the time of analysis. Median progression-free survival (PFS) was 3.2 months, and overall survival (OS) was 5.8 months. The median interval from Lonsurf discontinuation to death was two months, but seven patients received further systemic treatment and median OS gained was 12 months. Lonsurf offered a slightly better PFS but inferior OS to that of the RECOURSE trial, with PFS similar to real-world data previously presented. Interestingly, 12.5% had a PFS > 9 months, and this cohort had primarily left-sided and RAS wild-type disease. A subset received further systemic treatment on Lonsurf discontinuation with good additional OS benefit. Lonsurf may alter the course of disease for a subset of patients, and further treatment on progression can be considered in carefully selected patients.

scholarly journals Antitumor Effects of Systemically Delivered Adenovirus Harboring Trans-Splicing Ribozyme in Intrahepatic Colon Cancer Mouse Model

2008 ◽  
Vol 14 (1) ◽  
pp. 281-290 ◽  
Author(s):  
J.-S. Jeong ◽  
S.-W. Lee ◽  
S.-H. Hong ◽  
Y.-J. Lee ◽  
H.-I. Jung ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mouse Model ◽  
Antitumor Effects ◽  
Trans Splicing

Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model

2018 ◽  
Vol 107 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Jerena Manoharan ◽  
Volker Fendrich ◽  
Pietro Di Fazio ◽  
Carmen Bollmann ◽  
Silvia Roth ◽  
...  
Keyword(s):  
Mouse Model ◽  
Somatostatin Analogues ◽  
Control Group ◽  
Histopathological Analysis ◽  
Ki 67 ◽  
Chemopreventive Agents ◽  
Knockout Mouse Model ◽  
Angiotensin I Converting Enzyme ◽  
Significant Difference

Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g., with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+/T) knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n = 25) compared to controls (n = 25) were evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 18 months. After each study period, mice were sacrificed and the resected pancreata were evaluated by histopathological analysis, immunostaining, and real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a pNEN size reduction of 80% (167,518 vs. 838,876 µm2, p < 0.001) and 79% (174,758 vs. 838,876 µm2, p < 0.001) compared to controls. Furthermore, aspirin and enalapril treatment resulted in a significant reduction of the number of pNENs by 33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 revealed a higher positive expression in pNEN of treated Men1(+/T) mice. Immunostaining of VEGF in pNEN detected a downregulation of its expression in treated Men1(+/T) mice compared to the control group. REL A transcript was significantly downregulated in 18-months treated enalapril Men1(+/T) mice, but not in aspirin-treated Men1(+/T) mice. There was no significant difference in the Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents that aid in the progression of pNENs.

scholarly journals Time-serial Assessment of Drug Combination Interventions in a Mouse Model of Colorectal Carcinogenesis Using Optical Coherence Tomography

2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21216 ◽  
Author(s):  
Susan LeGendre-McGhee ◽  
Photini S. Rice ◽  
R. Andrew Wall ◽  
Kyle J. Sprute ◽  
Ramireddy Bommireddy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Rate ◽  
Optical Coherence Tomography ◽  
Mouse Model ◽  
Tumor Burden ◽  
Colorectal Carcinogenesis ◽  
Optical Coherence ◽  
Ki 67 ◽  
Tumor Number ◽  
Cox 2

Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX)-2, β-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups ( P < 0.0001), but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency ( P = 0.04). In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models.

scholarly journals Combination of oncolytic adenovirus and luteolin exerts synergistic antitumor effects in colorectal cancer cells and a mouse model

2017 ◽  
Vol 16 (6) ◽  
pp. 9375-9382 ◽  
Author(s):  
Boduan Xiao ◽  
Yun Qin ◽  
Chang Ying ◽  
Buyun Ma ◽  
Binrong Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Oncolytic Adenovirus ◽  
Antitumor Effects ◽  
Colorectal Cancer Cells

scholarly journals Evaluation of the antitumor effects of PP242 in a colon cancer xenograft mouse model using comprehensive metabolomics and lipidomics

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Md Mamunur Rashid ◽  
Hyunbeom Lee ◽  
Byung Hwa Jung
Keyword(s):  
Colon Cancer ◽  
Mouse Model ◽  
High Performance ◽  
Tca Cycle ◽  
Treated Group ◽  
Metabolic Changes ◽  
Antitumor Effects ◽  
Xenograft Mouse Model ◽  
Metabolic Mechanism ◽  
Comprehensive Metabolomics

Abstract PP242, an inhibitor of mechanistic target of rapamycin (mTOR), displays potent anticancer effects against various cancer types. However, the underlying metabolic mechanism associated with the PP242 effects is not clearly understood. In this study, comprehensive metabolomics and lipidomics investigations were performed using ultra-high-performance chromatography-Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS) in plasma and tumor tissue to reveal the metabolic mechanism of PP242 in an LS174T cell-induced colon cancer xenograft mouse model. After 3 weeks of PP242 treatment, a reduction in tumor size and weight was observed without any critical toxicities. According to results, metabolic changes due to the effects of PP242 were not significant in plasma. In contrast, metabolic changes in tumor tissues were very significant in the PP242-treated group compared to the xenograft control (XC) group, and revealed that energy and lipid metabolism were mainly altered by PP242 treatment like other cancer inhibitors. Additionally, in this study, it was discovered that not only TCA cycle but also fatty acid β-oxidation (β-FAO) for energy metabolism was inhibited and clear reduction in glycerophospholipid was observed. This study reveals new insights into the underlying anticancer mechanism of the dual mTOR inhibitor PP242, and could help further to facilitate the understanding of PP242 effects in the clinical application.

scholarly journals Musa balbisiana and Musa paradisiaca Starches Increase SCFA and Caspase-3 as well as Decrease β-glucuronidase and MDA of Mouse Model for Colon Cancer

2021 ◽  
Vol 13 (1) ◽  
pp. 91-6
Author(s):  
Diana Nur Afifah ◽  
Fauzia Purnamasari ◽  
Luthfiatul Khusna ◽  
Noviasti Rahma Utami ◽  
Aida Fitri Nazillah ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mouse Model ◽  
Resistant Starch ◽  
Caspase 3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Musa Balbisiana ◽  
Chromatography Analysis ◽  
Musa Paradisiaca ◽  
Gas Chromatography Analysis ◽  
Low Glycemic Index

BACKGROUND: Administration of resistant starch (RS) influences the diversity and the composition of microbiota as well as inhibits the growth of cancer cell. Banana as a potential source of RS has been reported. Although Musa paradisiaca has been reported to induce apoptosis in colon cancer cells, Musa balbisiana, which has low glycemic index and suitable for particular patients, has not been investigated yet.METHODS: Starches of M. balbisiana and M. paradisiaca were prepared and mixed with other components to make 3 types of mouse pellets. Mouse model for colon cancer was prepared and fed with different types of mouse pellets. Blood was collected and processed for measuring β-glucuronidase and malondialdehyde (MDA) with Enzyme-linked Immunosorbent Assay (ELISA) method. Resected ceca were incised to collect the inner part for short-chain fatty acid (SCFA) measurement with gas chromatography analysis. Resected colas were fixed and processed for immunohistochemistry to detect Caspase-3.RESULTS: Colon-cancer-mice fed with the M. balbisiana and M. paradisiaca starches-contained pellets had significant higher concentrations of total SCFA (p=0.003), acetic acid (p=0.000), propionic acid (p=0.000) and butyric acid (p=0.000); lower concentration of β-glucuronidase (p<0.001); higher Caspase-3 score (p=0.040); and lower MDA concentration (p<0.001) than colon-cancer-mice fed with standard pellet (control).CONCLUSION: M. balbisiana and M. paradisiaca starches could be suggested as potential anti-colon cancer RS. Further research should be carried out to disclose the starches mechanisms in colon cancer cell.KEYWORDS: Musa balbisiana, Musa paradisiaca, colon cancer, resistant starch, Caspase-3, SCFA, β-glucuronidase, malondialdehyde

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