scholarly journals Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model

2021 ◽  
Vol 22 (14) ◽  
pp. 7512
Author(s):  
Eui-Baek Byun ◽  
Ha-Yeon Song ◽  
Woo Sik Kim ◽  
Jeong Moo Han ◽  
Ho Seong Seo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Cell Damage ◽  
B Cell Lymphoma ◽  
In Vivo Studies ◽  
Raw264.7 Cells ◽  
Parp Cleavage ◽  
Bodyweight Loss ◽  
Chemotherapeutic Drugs ◽  
Cudrania Tricuspidata

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.

scholarly journals Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein

2021 ◽  
Vol 51 ◽  
pp. 151682
Author(s):  
Gerard J. Nuovo ◽  
Cynthia Magro ◽  
Toni Shaffer ◽  
Hamdy Awad ◽  
David Suster ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mouse Model ◽  
Cell Damage ◽  
Spike Protein ◽  
Endothelial Cell Damage

778 Preclinical study using a glutamatergic signaling and immune-checkpoint inhibitors in a spontaneous melanoma prone mouse model

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A828-A828
Author(s):  
Kevinn Eddy ◽  
Christina Marinaro ◽  
Maryam Rasheed ◽  
Joseph Campagnolo ◽  
Xiaoxuan Zhong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Checkpoint ◽  
Metabotropic Glutamate Receptor ◽  
Checkpoint Inhibitors ◽  
Ectopic Expression ◽  
Tumor Burden ◽  
In Vivo Studies ◽  
Combination Group ◽  
Glutamatergic Signaling ◽  
Melanoma Patients

BackgroundMuch progress has been made in understanding melanoma pathogenesis within the last few years through targeted therapies and immunotherapies. However, resistance to small molecule inhibitors remains an obstacle. Immunotherapies such as checkpoint inhibitors against PD-1/PD-L1 lead to durable responses but only in a subset of melanoma patients. Mouse models reflecting human cancers provide invaluable tools towards the translation of basic science discoveries to clinical therapies, but many of these in vivo studies are short-term and do not accurately mimic patient circumstances. Our lab has a melanoma-prone transgenic mouse model which is driven by ectopic expression of a normal neuronal receptor, metabotropic glutamate receptor 1 (GRM1). This mouse model recapitulates melanoma development and progression frequently associated with melanoma patients, where aberrant GRM1 expression is detected. We have shown that in >90% of late-stage melanoma patients, there is atypical GRM1 mediated signaling and expression.MethodsIn this study, we are using these mice, TGS, to determine the long-term, 18-week, therapeutic consequences of troriluzole, a prodrug for riluzole, which is an inhibitor of glutamatergic signaling plus anti-PD-1, an immune-checkpoint inhibitor. Tumor burden is monitored every 6 weeks for 18 weeks using a small imaging system, IVIS and tumor burden is quantified using ImageJ software. Blood, lymphoid, and tumor samples were collected at several time points during the study for molecular, and immune analyses.ResultsPreliminary results suggest a gender-biased treatment response and that the combination of troriluzole and anti-PD-1 is more efficacious than either agent alone. In males, a 43.9% reduction in tumor burden was observed while in females there was a 29.6% increase in tumor burden in the combination group compared to vehicle. In concordance, after the removal of the treatment modality, the male mice in the combinatorial group survived 42 days longer compared to vehicle controls with sustained tumor reduction by 68.3%. In female mice no significant advantage in survival or reduction in tumor burden was noted.ConclusionsN/A

scholarly journals The Neuroinflammatory Role of Pericytes in Epilepsy

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 759
Author(s):  
Gaku Yamanaka ◽  
Fuyuko Takata ◽  
Yasufumi Kataoka ◽  
Kanako Kanou ◽  
Shinichiro Morichi ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Current Knowledge ◽  
Morphological Changes ◽  
Cell Damage ◽  
Neurovascular Unit ◽  
Experimental Studies ◽  
Intractable Epilepsy ◽  
In Vivo Studies

Pericytes are a component of the blood–brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1β, TNFα, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1β, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders.

scholarly journals Characterization of Lung Cancer by Amide Proton Transfer (APT) Imaging: An In-Vivo Study in an Orthotopic Mouse Model

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77019 ◽  
Author(s):  
Osamu Togao ◽  
Chase W. Kessinger ◽  
Gang Huang ◽  
Todd C. Soesbe ◽  
Koji Sagiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Proton Transfer ◽  
In Vivo Study ◽  
Amide Proton ◽  
Orthotopic Mouse Model ◽  
Amide Proton Transfer ◽  
Apt Imaging

A first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3015-3015
Author(s):  
Anthony W. Tolcher ◽  
Benedito A. Carneiro ◽  
Afshin Dowlati ◽  
Albiruni Ryan Abdul Razak ◽  
Young Kwang Chae ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Solid Tumors ◽  
Cell Lung Cancer ◽  
Dose Escalation ◽  
Lymphocyte Count ◽  
B Cell Lymphoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

3015 Background: Mirzotamab clezutoclax (ABBV-155) is a first-in-class antibody drug conjugate comprised of a BCL-XL (B-cell lymphoma - extra long) inhibitor, solubilizing linker, and a monoclonal anti-B7H3 antibody. Methods: Patients (pts) with relapsed and/or refractory (R/R) solid tumors were administered mirzotamab clezutoclax with or without paclitaxel. Dose escalation of mirzotamab clezutoclax was guided by Bayesian continual reassessment. Primary outcomes were to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Secondary outcomes: safety, pharmacokinetics, and overall response rate per RECIST v1.1. Results: As of November 6, 2020, 31 pts received mirzotamab clezutoclax monotherapy (monoTx) and 28 pts received combination therapy with paclitaxel (comboTx). Overall demographics: median age 62 years (range 25–79); 61% female; 86% white; 24% ECOG 0, 76% ECOG 1; 51% had > 3 prior systemic therapies. The median duration of mirzotamab clezutoclax exposure was 3 cycles (range 1–14) for monoTx and 5 cycles (range 1–14) for comboTx. There were no dose limiting toxicities (DLT) reported with monoTx. In comboTx, 2 pts experienced a DLT: Grade 4 neutrophil count decreased and Grade 3 lymphocyte count decreased considered related to paclitaxel. 97% of all pts had adverse events (AEs). The most common AEs (in ≥20% of pts) overall were fatigue (39%), nausea (25%), diarrhea and arthralgia (22% each), vomiting and hypokalemia (20% each). AEs in ≥5 pts related to mirzotamab cleuzutoclax were fatigue (27%), diarrhea (12%), and nausea (9%). Related Grade 3/4 AEs overall (in > 1 patient) included anemia, lymphocyte count decreased, fatigue, and diarrhea (3% each). One patient on monoTx experienced a fatal cardiac arrest. No fatal AEs occurred on comboTx. Responses were observed with comboTx as shown in the Table. Conclusions: Mirzotamab clezutoclax as monotherapy and with paclitaxel demonstrates a tolerable safety profile (MTD not reached) with anti-tumor activity in R/R solid tumors. Further investigation in prospectively-selected B7H3 positive tumors as monoTx in pts with R/R small cell lung cancer and with paclitaxel in pts with R/R breast cancer and docetaxel in pts with R/R non-small cell lung cancer in the dose expansion phase is ongoing. Clinical trial information: NCT03595059. [Table: see text]

Protective effect of triterpenes against diabetes-induced β-cell damage: An overview of in vitro and in vivo studies

2018 ◽  
Vol 137 ◽  
pp. 179-192 ◽  
Author(s):  
Sihle E. Mabhida ◽  
Phiwayinkosi V. Dludla ◽  
Rabia Johnson ◽  
Musawenkosi Ndlovu ◽  
Johan Louw ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cell Damage ◽  
In Vivo Studies ◽  
Β Cell

Limitations of studying keloid scars using the nude athymic mouse model

2002 ◽  
Vol 10 (2) ◽  
pp. 56-61 ◽  
Author(s):  
Mp Hillmer ◽  
S Salama ◽  
Sm Macleod
Keyword(s):  
Mouse Model ◽  
Scar Tissue ◽  
In Vivo Studies ◽  
Athymic Mice ◽  
Athymic Mouse ◽  
Tissue Samples ◽  
Keloid Scars ◽  
Central Calcification ◽  
Sample Identity

Keloid scars are benign fibroproliferative growths that respond poorly to treatment. This study sought to determine the efficacy of three different glucocorticoids (triamcinolone, methylprednisolone and dexamethasone) in altering human keloid scar tissue implanted in athymic mice. Keloid tissue obtained from three patients (one man and two women) who sought cosmetic removal of their scars was implanted into athymic mice for a duration of 15 or 30 days. The keloid tissue was examined histopathologically and evaluated by a dermatopathologist who was blinded to sample identity and who was using predetermined qualitative scoring criteria. The appearance of central calcification, granulation tissue, foreign body granulomatous reaction and acute inflammatory reaction complicated the comparison of the keloid tissue samples. However, on the basis of observations reported in the present paper, it appears that triamcinolone should remain the treatment of choice for keloid scars. The athymic mouse model that is used for studying keloid scars is the best available approach to in vivo studies; however, limitations identified in this study confound the interpretation of experimental data. Ideally, promising and novel therapies should be investigated clinically.

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