Targeted drug delivery of capecitabine to mice xenograft gastric cancer by PAMAM dendrimer nanocarrier

2019 ◽  
Vol 1 (1) ◽  
pp. 28-52
Author(s):  
Sharareh Jafari ◽  
Fatemeh Nabavizadeh ◽  
Jalal Vahedian ◽  
Mehdi Shafie Ardestani ◽  
Hedayat Samandari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Delivery ◽  
Side Effects ◽  
Xenograft Model ◽  
Therapeutic Index ◽  
Pamam Dendrimer ◽  
Cancer Tissue ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Drug Induced

Aims: In this study, we used an animal xenograft model of gastric cancer induction to investigate the therapeutic effects of capecitabine polyamidoamine (PAMAM) dendrimer complex against cancer, and its potential side effects. Methods and Materials: Human gastric cancer tissue was obtained from patients with gastric carcinoma and transplanted into mice. Anticancer drug capecitabine was loaded into PAMAM dendrimer nano-carrier and injected into the animals. All animals received cyclosporine before the surgery. Results: Capecitabine-dendrimer complex reduced the size of the axillary implanted tumor, the levels of AST and ALP, and the drug-induced adverse effects on other body organs. Furthermore, it increased apoptotic and necrotic responses in the grafted tumor, RBC, WBC, and platelet counts in comparison to free capecitabine. Conclusions: In the gastric cancer setting, PAMAM dendrimer drug delivery method effectively improved therapeutic index and outcomes, and reduced undesirable side-effects of the capecitabine. Keywords: Gastric cancer, Xenograft, Capecitabine, Cyclosporine, Poly amidoamine dendrimer (PAMAM), Mice.

Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 1084-1098
Author(s):  
Fengqian Chen ◽  
Yunzhen Shi ◽  
Jinming Zhang ◽  
Qi Liu
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Drug Delivery Systems ◽  
Therapeutic Index ◽  
Delivery Systems ◽  
Epigenetic Therapy ◽  
Cancer Therapies ◽  
Therapeutic Benefits ◽  
High Therapeutic Index

This review summarizes the epigenetic mechanisms of deoxyribonucleic acid (DNA) methylation, histone modifications in cancer and the epigenetic modifications in cancer therapy. Due to their undesired side effects, the use of epigenetic drugs as chemo-drugs in cancer therapies is limited. The drug delivery system opens a door for minimizing these side effects and achieving greater therapeutic benefits. The limitations of current epigenetic therapies in clinical cancer treatment and the advantages of using drug delivery systems for epigenetic agents are also discussed. Combining drug delivery systems with epigenetic therapy is a promising approach to reaching a high therapeutic index and minimizing the side effects.

scholarly journals Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 302 ◽  
Author(s):  
Xin Zhang ◽  
Yao Qin ◽  
Zhaohai Pan ◽  
Minjing Li ◽  
Xiaona Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
G1 Phase ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Expression Levels ◽  
Cycle Arrest

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

scholarly journals Doxorubicin Embedded into Nanofibrillated Bacterial Cellulose (NFBC) Produces a Promising Therapeutic Outcome for Peritoneally Metastatic Gastric Cancer in Mice Models via Intraperitoneal Direct Injection

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1697
Author(s):  
Hidenori Ando ◽  
Takashi Mochizuki ◽  
Amr S. Abu Lila ◽  
Shunsuke Akagi ◽  
Kenji Tajima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Delivery ◽  
Tumor Growth ◽  
Bacterial Cellulose ◽  
Anticancer Agents ◽  
Intraperitoneal Administration ◽  
In Vitro Release ◽  
Xenograft Model ◽  
Tumor Growth Inhibition

Natural materials such as bacterial cellulose are gaining interest for their use as drug-delivery vehicles. Herein, the utility of nanofibrillated bacterial cellulose (NFBC), which is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) in a medium supplemented with carboxymethylcellulose (CMC) that is referred to as CM-NFBC, is described. Recently, we demonstrated that intraperitoneal administration of paclitaxel (PTX)-containing CM-NFBC efficiently suppressed tumor growth in a peritoneally disseminated cancer xenograft model. In this study, to confirm the applicability of NFBC in cancer therapy, a chemotherapeutic agent, doxorubicin (DXR), embedded into CM-NFBC, was examined for its efficiency to treat a peritoneally disseminated gastric cancer via intraperitoneal administration. DXR was efficiently embedded into CM-NFBC (DXR/CM-NFBC). In an in vitro release experiment, 79.5% of DXR was released linearly into the peritoneal wash fluid over a period of 24 h. In the peritoneally disseminated gastric cancer xenograft model, intraperitoneal administration of DXR/CM-NFBC induced superior tumor growth inhibition (TGI = 85.5%) by day 35 post-tumor inoculation, compared to free DXR (TGI = 62.4%). In addition, compared with free DXR, the severe side effects that cause body weight loss were lessened via treatment with DXR/CM-NFBC. These results support the feasibility of CM-NFBC as a drug-delivery vehicle for various anticancer agents. This approach may lead to improved therapeutic outcomes for the treatment of intraperitoneally disseminated cancers.

scholarly journals Establishment of a Human Gastric Cancer Xenograft Model in Immunocompetent Mice Using the Microcarrier-6

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yanzhen Bi ◽  
Quanyi Wang ◽  
Yonghong Yang ◽  
Quanquan Wang ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Animal Model ◽  
Gastric Carcinoma ◽  
Malignant Tumors ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Tumor Xenograft ◽  
Gastric Neoplasms ◽  
Human Gastric Cancer ◽  
Immunocompetent Mice

Gastric cancer is among the most common malignant tumors of the digestive tract. Establishing a robust and reliable animal model is the foundation for studying the pathogenesis of cancer. The present study established a mouse model of gastric carcinoma by inoculating immunocompetent mice with MKN45 cells using microcarrier. Sixty male C57BL/6 mice were randomly divided into three groups: a 2D group, an empty carrier group, and a 3D group, according to the coculture system of MKN45 and the microcarrier. The mouse models were established by hypodermic injection. Time to develop tumor, rate of tumor formation, and pathological features were observed in each group. In the 3D group, the tumorigenesis time was short, while the rate of tumor formation was high (75%). There was no detectable tumor formation in either the 2D or the empty carrier group. Both H&E and immunohistochemical staining of the tumor xenograft showed characteristic evidence of human gastric neoplasms. The present study successfully established a human gastric carcinoma model in immunocompetent mice, which provides a novel and valuable animal model for the cancer research and development of anticancer drugs.

scholarly journals Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells

2013 ◽  
Vol 42 (5) ◽  
pp. 2988-2998 ◽  
Author(s):  
Xiaoli Tang ◽  
Dong Zheng ◽  
Ping Hu ◽  
Zongyue Zeng ◽  
Ming Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Cell Functions

Abstract Glycogen synthase kinase 3 beta (GSK3β) is a critical protein kinase that phosphorylates numerous proteins in cells and thereby impacts multiple pathways including the β-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of noncoding small RNAs of ∼22 nucleotides in length. Both GSK3β and miR play myriad roles in cell functions including stem cell development, apoptosis, embryogenesis and tumorigenesis. Here we show that GSK3β inhibits the expression of miR-96, miR-182 and miR-183 through the β-Catenin/TCF/LEF-1 pathway. Knockout of GSK3β in mouse embryonic fibroblast cells increases expression of miR-96, miR-182 and miR-183, coinciding with increases in the protein level and nuclear translocation of β-Catenin. In addition, overexpression of β-Catenin enhances the expression of miR-96, miR-182 and miR-183 in human gastric cancer AGS cells. GSK3β protein levels are decreased in human gastric cancer tissue compared with surrounding normal gastric tissue, coinciding with increases of β-Catenin protein, miR-96, miR-182, miR-183 and primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183-96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and migration of AGS cells. Knockdown of GSK3β with siRNA increases the proliferation of AGS cells. Mechanistically, we show that β-Catenin/TCF/LEF-1 binds to the promoter of miR-183-96-182 cluster gene and thereby activates the transcription of the cluster. In summary, our findings identify a novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

scholarly journals NSAIDs and PPIs - review of new reports

2021 ◽  
Vol 11 (9) ◽  
pp. 462-472
Author(s):  
Jakub Klas ◽  
Natalia Kluz ◽  
Klaudia Piwowar
Keyword(s):  
Side Effects ◽  
Enzyme Inhibitors ◽  
Supportive Therapy ◽  
Kidney Injury ◽  
Complementary Therapy ◽  
Cardiovascular Complications ◽  
Therapeutic Effects ◽  
Drug Induced ◽  
Hydrogen Atpase ◽  
Meta Analyses

The aim of this study is to systematise knowledge on non-steroidal anti-inflammatory drugs (NSAIDs) - cyclooxygenase (COX) enzyme inhibitors and proton pump inhibitors (PPIs) inhibiting potassium hydrogen ATPase. A review of recent reports on possible side effects and new therapeutic options will be presented. Results: Over the last few years, reports of PPI side effects have been published: drug-induced thrombocytopenia, severe hypomagnesemia, hyponatremia or rhabdomyolysis. In the case of NSAIDs, ancillary therapeutic effects in the supportive therapy of multiple myeloma or in the reduction of adenoma formation in the colon stand out, but also cases of acute kidney injury in children. On the basis of meta-analyses, attempts were made to demonstrate the effect of individual NSAIDs on the occurrence of cardiovascular complications, stroke or myocardial infarction Conclusions: Despite the fact that the indicated preparations were admitted to the list of drugs several decades ago, still their pharmacological potential (on the example of NSAIDs, which can be successfully used even in complementary therapy) has not been fully exploited. The aforementioned reports on side effects must not be forgotten. It is possible that the examples presented in the review will raise awareness in order to use these drugs with greater respect, in accordance with the recommendations in the leaflet.

scholarly journals Establishment and characterization of a new gastric cancer cell line, XGC-1

2020 ◽  
Author(s):  
Jigui Peng ◽  
Hao Xu ◽  
Jianchun Cai
Keyword(s):  
Gastric Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Nude Mice ◽  
Colony Formation ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Cancer Tissue ◽  
Human Gastric Cancer

Abstract Background To establish a primary human gastric cancer cell line. Methods Fresh gastric cancer tissue samples were separated into a cell suspension, and DMEM/F12 medium containing 10% foetal bovine serum was used for primary culture and subculture. The morphology of the cells was observed under a light microscope, and the cell growth curve was plotted. A soft agar colony formation assay was used to detect the colony formation ability of the cell line. Immunohistochemical methods were used to detect cytokeratin, vimentin and Ki-67, the chromosome G banding method was used to analyse the karyotype of the cells, and the tumourigenic ability of the cells was detected by subcutaneous inoculation of BALB/C nude mice. Results We established a gastric cancer cell line from a 68-year-old male patient. This gastric cancer cell line was named XGC-1 and had a doubling time of approximately 48 h. The cell line displayed strong colony formation ability and tumourigenicity in BALB/C nude mice and had complicated chromosomal abnormalities. When nutrients were insufficient, the cells shed and floated in the medium, but adherent growth was observed in nutrient-rich conditions. Conclusions The XGC-1 cell line will be useful for future studies of gastric cancer development, progression, metastasis and therapy.

Sign in / Sign up

Export Citation Format

Share Document