scholarly journals Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhi-Ran Yang ◽  
Zhi-Gao Chen ◽  
Xue-Mei Du ◽  
Yan Li
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Peritoneal Mesothelioma ◽  
Primary Cell ◽  
Malignant Peritoneal Mesothelioma ◽  
Primary Cell Lines ◽  
Proliferation And Metastasis ◽  
Pdx Models

ObjectiveMalignant peritoneal mesothelioma (MPM) is a rare malignancy with few effective molecular therapies. In this study, we evaluated the anti-tumor activity and safety of apatinib, a vascular endothelial growth factor receptor 2 inhibitor, in MPM in vitro and in vivo.MethodsWe established several patient-derived xenograft (PDX) models and primary cell lines of MPM. The cell lines were used to study the effects of apatinib on proliferation, cell cycle, migration, and apoptosis by CCK8, flow cytometry, wound-healing, Transwell, DAPI staining, and caspase-3 assays, respectively. For in vivo study, apatinib was delivered by gastric gavage into PDX models, and then efficacy and toxicity were determined by experimental peritoneal cancer index (ePCI) score and pathological examinations.ResultsOur results showed that apatinib significantly inhibited the proliferation and migration of MPM cells in vitro and induced cell cycle arrest. Studies on PDX models concurred that apatinib effectively suppressed subphrenic and liver invasions of nude mice. Moreover, histopathological analysis found that lymphocyte infiltration, coagulation necrosis and eosinophilic cell fragments were detected in tumor tissues after apatinib treatment. Apatinib showed no obvious effects on body mass of models and did not affect function of important organs, except for occasional focal lymphoid infiltration of liver (16.7%) and cardiac muscle (16.7%).ConclusionsWe successfully established MPM PDX models and primary cell lines, and confirmed that apatinib effectively inhibited proliferation and metastasis of MPM in vitro and in vivo study.

scholarly journals Establishment and Histopathological Study of Patient-derived Xenograft Models and Primary Cell Lines of Epithelioid Malignant Peritoneal Mesothelioma

2020 ◽  
Author(s):  
Zhi-Ran Yang ◽  
Zhi-Gao Chen ◽  
Zhong-He Ji ◽  
Yu-Lin Lin ◽  
Jue Zhang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Peritoneal Mesothelioma ◽  
Primary Cell ◽  
Histopathological Study ◽  
Malignant Peritoneal Mesothelioma ◽  
Pathological Characteristics ◽  
Patient Derived Xenograft ◽  
Primary Cell Lines ◽  
Mutant Genes ◽  
Pdx Models

Abstract Background: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with few effective therapies. This study established patient-derived xenograft (PDX) models and primary cell lines to provide a study platform for MPM in vitro and in vivo, and conducted histopathological analysis.Methods: Human MPM surgical specimen was collected to establish PDX models and primary cell lines. Experimental peritoneal cancer index (ePCI) score was used to evaluate gross pathology, and histopathological study was conducted by hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining. Pathological characteristics of the established primary MPM cell lines were analyzed by Swiss-Gimsa and immunofluorescence (IF) staining. The whole-exome sequencing (WES) was performed to identify the mutant genes between models and the patient.Results: MPM PDX models and primary cell lines were successfully established, replicated the pathological features of the patient. ePCI score of the female and male nude mice were 8.80 ± 1.75 and 9.20 ± 1.81 (P = 0.6219), respectively. The HE staining showed that the tumor was epithelioid mesothelioma and invaded multiple organs. IHC staining showed that Calretinin, Cytokeratin 5/6, WT-1 and Ki-67 were all positive. The Swiss-Gimsa and IF staining of primary cell lines were also consistent with the pathological characteristics of mesothelioma. The WES showed that 21 mutant genes were shared between models and the patient, and the genes related to tumorigenesis and development including BAP1, NF2, MTBP, NECTIN2, CDC23, LRPPRC, TRIM25, and DHRS2.Conclusions: PDX models and primary cell lines of MPM were successfully established with the epithelioid mesothelioma identity confirmed by histopathological evidence. Moreover, our study has also illustrated the shared genomic profile between models and the patient, then potentially provided new targets for MPM treatment.

scholarly journals In vitro and in vivo effect of human lactoferrin on glioblastoma growth

2015 ◽  
Vol 123 (4) ◽  
pp. 1026-1035 ◽  
Author(s):  
Antonietta Arcella ◽  
Maria Antonietta Oliva ◽  
Sabrina Staffieri ◽  
Silvia Aalberti ◽  
Giovanni Grillea ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Nude Mice ◽  
Tumor Size ◽  
Primary Cell ◽  
Continuous Cell Line ◽  
Human Lactoferrin ◽  
Primary Cell Lines

OBJECT Human lactoferrin (HLF) is a natural protein with antitumor activity. The aim of this study was to investigate the effects of HLF alone and in combination with temozolomide (TMZ), a conventional chemotherapeutic, on human glioblastoma (GBM) cells. METHODS The authors cultured fresh human primary cell lines NMD and FN and the continuous cell line U87MG to evaluate proliferation in the presence of HLF alone at different doses (1, 10, and 100 mg/ml, and 1 mg/ml) and in combination with TMZ. In in vivo experiments they assessed tumor size reduction in CD1 nude mice carrying an orthotopic GBM xenograft and orally treated with HLF. RESULTS Lactoferrin causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line. This inhibition seemed to be modulated by the downregulation of cyclin D1 and D4. Western blot and fluorescence-activated cell sorting analysis showed inhibition of the cell cycle in G0/G1 and G2 phases. When administered in nude mice, HLF (60 mg/kg/day) decreased tumor size about 30%, as shown in both histological analyses and high-field brain MRI. Administration of HLF with TMZ enhanced the effect of chemotherapy both in vitro and in vivo. CONCLUSIONS This study demonstrated that HLF can inhibit GBM cell growth, suggesting that this nontoxic substance may have a role in potentiating the effect of current TMZ treatment of GBM.

Carbon Nanotubes In Vitro and In Vivo Biological Effects

2010 ◽  
Vol 76 ◽  
pp. 229-234
Author(s):  
Stefano Bellucci
Keyword(s):  
Carbon Nanotubes ◽  
Cell Lines ◽  
Biological Effects ◽  
Human Lymphocytes ◽  
Primary Cell ◽  
Laboratory Rats ◽  
Primary Cell Lines

I review some recent results obtained by my group at INFN, in collaboration with Collegues at CNR-IREA, Napoli, Italy about the cytotoxicity of buckypaper in human lymphocytes, as well as with Collegues at “La Sapienza” Rome University about the effect of buckypaper on cancer and primary cell lines in vitro and in vivo on laboratory rats

scholarly journals Analysis of a transgenic mouse containing simian virus 40 and v-myc sequences.

1985 ◽  
Vol 5 (4) ◽  
pp. 642-648 ◽  
Author(s):  
J A Small ◽  
D G Blair ◽  
S D Showalter ◽  
G A Scangos
Keyword(s):  
Cell Lines ◽  
Choroid Plexus Papilloma ◽  
Simian Virus 40 ◽  
Soft Agar ◽  
Simian Virus ◽  
T Antigen ◽  
Primary Cell ◽  
Tissue Samples ◽  
Primary Cell Lines

Two plasmids, one containing the simian virus 40 (SV40) genome and the mouse metallothionein I gene and one containing the v-myc gene of avian myelocytomatosis virus MC29, were coinjected into mouse embryos. Of the 13 surviving mice, one, designated M13, contained both myc and SV40 sequences. This mouse developed a cranial bulge identified as a choroid plexus papilloma at 13 weeks and was subsequently sacrificed; tissue samples were taken for further analysis. Primary cell lines derived from these tissues contained both myc and SV40 DNA. No v-myc mRNA could be detected, although SV40 mRNA was present in all of the cell lines tested. T antigen also was expressed in all of the cell lines analyzed. These data suggest that SV40 expression was involved in the abnormalities of mouse M13 and was responsible for the transformed phenotype of the primary cell lines. Primary cell lines from this mouse were atypical in that the population rapidly became progressively more transformed with time in culture based on the following criteria: morphology, growth rate, and the ability to grow in soft agar and in serum-free medium. The data also suggest that factors present in the mouse regulated the ability of SV40 to oncogenically transform most cells and that in vitro culture of cells allowed them to escape those factors.

In vitro effects of erythromycin and florfenicol on primary cell lines of Unio crassus and Cyprinus carpio

2021 ◽  
Author(s):  
Pınar Arslan ◽  
Begum Yurdakok-Dikmen ◽  
Saniye Cevher Ozeren ◽  
Ozgur Kuzukiran ◽  
Ayhan Filazi
Keyword(s):  
Cell Lines ◽  
Cyprinus Carpio ◽  
Primary Cell ◽  
Primary Cell Lines ◽  
In Vitro Effects

scholarly journals Tanshinone IIA Inhibits Osteosarcoma Growth through a Src Kinase-Dependent Mechanism

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Chao Hu ◽  
Xiaobin Zhu ◽  
Taogen Zhang ◽  
Zhouming Deng ◽  
Yuanlong Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Src Kinase ◽  
Akt Signaling ◽  
Cellular Level ◽  
Tanshinone Iia

Introduction. Osteosarcoma is a malignant tumor associated with high mortality rates due to the toxic side effects of current therapeutic methods. Tanshinone IIA can inhibit cell proliferation and promote apoptosis in vitro, but the exact mechanism is still unknown. The aims of this study are to explore the antiosteosarcoma effect of tanshinone IIA via Src kinase and demonstrate the mechanism of this effect. Materials and Methods. Osteosarcoma MG-63 and U2-OS cell lines were stable transfections with Src-shRNA. Then, the antiosteosarcoma effect of tanshinone IIA was tested in vitro. The protein expression levels of Src, p-Src, p-ERK1/2, and p-AKt were detected by Western blot and RT-PCR. CCK-8 assay and BrdU immunofluorescence assay were used to detect cell proliferation. Transwell assay, cell scratch assay, and flow cytometry were used to detect cell invasion, migration, and cell cycle. Tumor-bearing nude mice with osteosarcoma were constructed. The effect of tanshinone IIA was detected by tumor HE staining, tumor inhibition rate, incidence of lung metastasis, and X-ray. Results. The oncogene role of Src kinase in osteosarcoma is reflected in promoting cell proliferation, invasion, and migration and in inhibiting apoptosis. However, Src has different effects on cell proliferation, apoptosis, and cell cycle regulation among cell lines. At a cellular level, the antiosteosarcoma effect of tanshinone IIA is mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. At the animal level, tanshinone IIA played a role in resisting osteosarcoma formation by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. Conclusion. Tanshinone IIA plays an antiosteosarcoma role in vitro and in vivo and inhibits the progression of osteosarcoma mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.

scholarly journals Menadione reduces CDC25B expression and promotes tumor shrinkage in gastric cancer

2020 ◽  
Vol 13 ◽  
pp. 175628481989543
Author(s):  
Amanda Braga Bona ◽  
Danielle Queiroz Calcagno ◽  
Helem Ferreira Ribeiro ◽  
José Augusto Pereira Carneiro Muniz ◽  
Giovanny Rebouças Pinto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Specific Inhibitor ◽  
Gastric Carcinogenesis ◽  
In Vivo Experiments ◽  
Cycle Arrest

Background: Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and poor prognosis. MYC oncogene overexpression is a key event in gastric carcinogenesis and it is known that its protein positively regulates CDC25B expression which, in turn, plays an essential role in the cell division cycle progression. Menadione is a synthetic form of vitamin K that acts as a specific inhibitor of the CDC25 family of phosphatases. Methods: To better understand the menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by N-Methyl-N-nitrosourea. We tested CDC25B expression by western blot and RT-qPCR. In-vitro assays include proliferation, migration, invasion and flow cytometry to analyze cell cycle arrest. In in-vivo experiments, in addition to the expression analyses, we followed the preneoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology and immunohistochemistry. Results: Our tests demonstrated menadione reducing CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in gastric cancer cell lines. Moreover, our in-vivo experiments demonstrated menadione inhibiting tumor development and progression. Conclusions: We suggest this compound may be an important ally of chemotherapeutics in the treatment of gastric cancer. In addition, CDC25B has proven to be an effective target for investigation and development of new therapeutic strategies for this malignancy.

scholarly journals Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

2015 ◽  
Vol 16 (12) ◽  
pp. 9936-9948 ◽  
Author(s):  
Mustafa El-Khatib ◽  
Carolin Tepe ◽  
Brigitte Senger ◽  
Maxine Dibué-Adjei ◽  
Markus Riemenschneider ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cell Lines ◽  
Aminolevulinic Acid ◽  
In Vitro Study ◽  
Vitro Study ◽  
Primary Cell ◽  
Human Meningioma ◽  
Primary Cell Lines

scholarly journals Anticancer Activity of Cynomorium coccineum

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 354 ◽  
Author(s):  
Mouna Sdiri ◽  
Xiangmin Li ◽  
William Du ◽  
Safia El-Bok ◽  
Yi-Zhen Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression

The extensive applications of Cynomorium species and their rich bioactive secondary metabolites have inspired many pharmacological investigations. Previous research has been conducted to examine the biological activities and numerous interesting pharmaceutical activities have been reported. However, the antitumor activities of these species are unclear. To understand the potential anticancer activity, we screened Cynomorium coccineum and Cynomorium songaricum using three different extracts of each species. In this study, the selected extracts were evaluated for their ability to decrease survival rates of five different cancer cell lines. We compared the cytotoxicity of the three different extracts to the anticancer drug vinblastine and one of the most well-known medicinal mushrooms Amaurederma rude. We found that the water and alcohol extracts of C. coccineum at the very low concentrations possessed very high capacity in decreasing the cancer cells viability with a potential inhibition of tumorigenesis. Based on these primitive data, we subsequently tested the ethanol and the water extracts of C. coccineum, respectively in in vitro and in vivo assays. Cell cycle progression and induction of programmed cell death were investigated at both biological and molecular levels to understand the mechanism of the antitumor inhibitory action of the C. coccineum. The in vitro experiments showed that the treated cancer cells formed fewer and smaller colonies than the untreated cells. Cell cycle progression was inhibited, and the ethanol extract of C. coccineum at a low concentration induced accumulation of cells in the G1 phase. We also found that the C. coccineum’s extracts suppressed viability of two murine cancer cell lines. In the in vivo experiments, we injected mice with murine cancer cell line B16, followed by peritoneal injection of the water extract. The treatment prolonged mouse survival significantly. The tumors grew at a slower rate than the control. Down-regulation of c-myc expression appeared to be associated with these effects. Further investigation showed that treatment with C. coccineum induced the overexpression of the tumor suppressor Foxo3 and other molecules involved in inducing autophagy. These results showed that the C. coccineum extract exerts its antiproliferative activity through the induction of cell death pathway. Thus, the Cynomorium plants appear to be a promising source of new antineoplastic compounds.

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