The combinational therapy of trastuzumab and cetuximab inhibits tumor growth in a patient-derived tumor xenograft model of gastric cancer

2015 ◽  
Vol 18 (5) ◽  
pp. 507-514 ◽  
Author(s):  
C. J. Wang ◽  
P. J. Tong ◽  
M. Y. Zhu
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Combinational Therapy

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 Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Chongyang Li ◽  
Chaowei Deng ◽  
Guangzhao Pan ◽  
Xue Wang ◽  
Kui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Xenograft Model ◽  
Resistant Cell ◽  
Tumor Xenograft ◽  
Gastric Cancer Cells ◽  
Bcl2 Family ◽  
Ubiquitin E3 Ligase ◽  
Underlying Mechanisms

Abstract Background Lycorine hydrochloride (LH), an alkaloid extracted from the bulb of the Lycoris radiata, is considered to have anti-viral, anti-malarial, and anti-tumorous effects. At present, the underlying mechanisms of LH in gastric cancer remain unclear. MCL1, an anti-apoptotic protein of BCL2 family, is closely related to drug resistance of tumor. Therefore, MCL1 is considered as a potential target for cancer treatment. Methods The effect of LH on gastric cancer was assessed in vitro (by MTT, BrdU, western blotting…) and in vivo (by immunohistochemistry). Results In this study, we showed that LH has an anti-tumorous effect by down-regulating MCL1 in gastric cancer. Besides, we unveiled that LH reduced the protein stability of MCL1 by up-regulating ubiquitin E3 ligase FBXW7, arrested cell cycle at S phase and triggered apoptosis of gastric cancer cells. Meanwhile, we also demonstrated that LH could induce apoptosis of the BCL2-drug-resistant-cell-lines. Moreover, PDX (Patient-Derived tumor xenograft) model experiment proved that LH combined with HA14–1 (inhibitor of BCL2), had a more significant therapeutic effect on gastric cancer. Conclusions The efficacy showed in our data suggests that lycorine hydrochloride is a promising anti-tumor compound for gastric cancer.

scholarly journals Review of: Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells

2008 ◽  
Vol 11 (2) ◽  
Author(s):  
Alison J. Butt
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Single Agent ◽  
Xenograft Model ◽  
Estrogen Receptor Α ◽  
Tumor Xenograft ◽  
Breast Cancers ◽  
Induced Apoptosis

Citation of original article:C. Lagadec, E. Adriaenssens, R. A. Toillon, V. Chopin, R. Romon, F. Van Coppenolle, H. Hondermarck, X. Le Bourhis. Oncogene advance online publication, 3 September 2007; doi:10.1038/sj.onc.1210749.Abstract of the original article:Tamoxifen (TAM), is widely used as a single agent in adjuvant treatment of breast cancer. Here, we investigated the effects of TAM in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in estrogen receptor-α (ER-α)-positive and -negative breast cancer cells. We showed that cotreatment with TAM and TRAIL synergistically induced apoptosis regardless of ER-α status. By contrast, cotreatment did not affect the viability of normal breast epithelial cells. Cotreatment with TAM and TRAIL in breast cancer cells decreased the levels of antiapoptotic proteins including FLIPs and Bcl-2, and enhanced the levels of proapoptotic proteins such as FADD, caspase 8, tBid, Bax and caspase 9. Furthermore, cotreatment-induced apoptosis was efficiently reduced by FADD- or Bid-siRNA, indicating the implication of both extrinsic and intrinsic pathways in synergistic apoptosis induction. Importantly, cotreatment totally arrested tumor growth in an ER-α-negative MDA-MB-231 tumor xenograft model. The abrogation of tumor growth correlated with enhanced apoptosis in tumor tissues. Our findings raise the possibility to use TAM in combination with TRAIL for breast cancers, regardless of ER-α status.

scholarly journals Lanreotide promotes apoptosis and is not radioprotective in GH3 cells

2009 ◽  
Vol 16 (3) ◽  
pp. 1045-1055 ◽  
Author(s):  
Shoucheng Ning ◽  
Susan J Knox ◽  
Griffith R Harsh ◽  
Michael D Culler ◽  
Laurence Katznelson
Keyword(s):  
Tumor Growth ◽  
Survival Curve ◽  
Somatostatin Analogs ◽  
Xenograft Model ◽  
Somatostatin Analog ◽  
Tumor Xenograft ◽  
Gh3 Cells ◽  
Growth Delay ◽  
Human Pituitary ◽  
The Impact

Somatostatin analogs are a mainstay of medical therapy in patients with GH producing human pituitary tumors, and it has been suggested that somatostatin analogs may be radioprotective. We utilized GH secreting rat GH3 cells to investigate whether a somatostatin analog may limit the effects of radiation on proliferation and apoptosis in vitro and on tumor growth in vivo. Treatment with lanreotide alone at doses of either 100 or 1000 nM for 48 h reduced clonogenic survival by 5–10%. Radiation alone produced a dose-dependent survival curve with a SF2 of 48–55%, and lanreotide had no effect on this curve. The addition of lanreotide resulted in a 23% increase in the proportion of apoptotic sub-G1 cells following irradiation (P<0.01). In a mouse GH3 tumor xenograft model, lanreotide 10 mg/kg moderately inhibited the growth of GH3 tumors, with a 4× tumor growth delay (TGD) time that ranged from 4.5 to 8.3 days. Fractionated local tumor radiation alone significantly inhibited tumor growth and produced a TGD of 35.1±5.7 days for 250 cGy fractions. The combination of lanreotide, either antecedent to or concurrent, with radiation of 250, 200 or 150 cGy/fraction for 5 days inhibited tumor growth and produced the TGD times that were similar to radiation alone (P>0.05). Pretreatment with lanreotide had the most significant radiosensitizing effect. These studies demonstrate that the somatostatin analog lanreotide is not radioprotective in GH3 cells, and further studies are necessary to determine the impact of lanreotide on apoptosis.

Prader–Willi region non-protein coding RNA 1 suppressed gastric cancer growth as a competing endogenous RNA of miR-425-5p

2018 ◽  
Vol 132 (9) ◽  
pp. 1003-1019 ◽  
Author(s):  
Zihao Chen ◽  
Hongping Ju ◽  
Shan Yu ◽  
Ting Zhao ◽  
Xiaojie Jing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Western Blot ◽  
Microarray Analysis ◽  
Tumor Xenograft ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Protein Coding ◽  
Qrt Pcr ◽  
Rip Assay

Gastric cancer (GC) is one of the major global health problems, especially in Asia. Nowadays, long non-coding RNA (lncRNA) has gained significant attention in the current research climate such as carcinogenesis. This research desires to explore the mechanism of Prader–Willi region non-protein coding RNA 1 (PWRN1) on regulating GC process. Differentially expressed lncRNAs in GC tissues were screened out through microarray analysis. The RNA and protein expression level were detected by quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation, apoptosis rate, metastasis abilities were respectively determined by cell counting kit 8 (CCK8), flow cytometry, wound healing, and transwell assay. The luciferase reporter system was used to verify the targetting relationships between PWRN1, miR-425-5p, and phosphatase and tensin homolog (PTEN). RNA-binding protein immunoprecipitation (RIP) assay was performed to prove whether PWRN1 acted as a competitive endogenous RNA (ceRNA) of miR-425-5p. Tumor xenograft model and immunohistochemistry (IHC) were developed to study the influence of PWRN1 on tumor growth in vivo. Microarray analysis determined that PWRN1 was differently expressed between GC tissues and adjacent tissues. qRT-PCR revealed PWRN1 low expression in GC tissues and cells. Up-regulated PWRN1 could reduce proliferation and metastasis and increase apoptosis in GC cells, while miR-425-5p had reverse effects. The RIP assay indicated that PWRN1 may target an oncogene, miR-425-5p. The tumor xenograft assay found that up-regulated PWRN1 suppressed the tumor growth. The bioinformatics analysis, luciferase assay, and Western blot indicated that PWRN1 affected PTEN/Akt/MDM2/p53 axis via suppressing miR-425-5p. Our findings suggested that PWRN1 functioned as a ceRNA targetting miR-425-5p and suppressed GC development via p53 signaling pathway.

scholarly journals Combination of Sodium Selenite and Doxorubicin Prodrug Ac-Phe-Lys-PABC-ADM Affects Gastric Cancer Cell Apoptosis in Xenografted Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Bo Wu ◽  
Jian Ge ◽  
Zixiong Zhang ◽  
Chuying Huang ◽  
Xiaodan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Sodium Selenite ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Mitochondrial Apoptosis ◽  
Gastric Cancer Cells ◽  
Apoptosis Pathway

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.

In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenografts of gastric cancer using multiphoton microscopy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22205-e22205
Author(s):  
Koji Tanaka ◽  
Tadanobu Shimura ◽  
Masato Okigami ◽  
Yuji Toiyama ◽  
Yuhki Morimoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Response ◽  
Fluorescent Protein ◽  
Multiphoton Microscopy ◽  
Xenograft Model ◽  
Metastatic Tumor ◽  
Tumor Xenograft ◽  
Tumor Vessels ◽  
Paclitaxel Treatment

e22205 Background: Peritoneal metastasis shows an extremely poor prognosis in patients with gastric cancer. Clinically, the tumor response to chemotherapeutics depends on anatomical location of metastasis. Metastatic tumor xenografts have been shown to be more resistant to chemotherapy than subcutaneous non-metastatic tumor xenografts in preclinical murine model. We have reported a method of in vivo optical pathology using multiphoton microscopy (MPM) in colorectal liver metastatic tumor xenograft model. Aim: We established a method of time-series in vivo optical pathology of peritoneal metastatic xenografts of gastric cancer using MPM. Then, we imaged and evaluated paclitaxel efficacy in the tumor microenvironment with regard to both tumor cell itself and intravascular change in tumor vessels. Methods: Red fluorescent protein (RFP) expressing human gastric cancer cell line (NUGC4) was inoculated into the peritoneal cavity of green fluorescent protein (GFP) expressing nude mice. Paclitaxel (10 mg/kg) was administered three times a week for more than three weeks. Intravital MPM was performed before and after paclitaxel treatment for the exteriorized peritoneal metastatic lesion in the same living mouse. Results: Four to six weeks later, RFP-NUGC4 cells formed macroscopic peritoneal metastases. Red-colored cancer cells and green-colored surrounding stroma with tumor vessels were clearly imaged at the cellular level (in vivooptical pathology). Their cross-sectional images were obtained from the tissue surface to the area of depth of 200 μm (z-stacks imaging). After paclitaxel treatment, tumor cell fragmentation, condensation, swelling and intracellular vacuoles were observed. Within the tumor vessels, platelet aggregation and platelet adhesion to endothelial cells were observed. Conclusions: In vivo optical pathology using MPM provides histopathological information about three-dimensional tissue microarchitecture without tissue shrinkage by fixation and tissue destruction by microtome-sectioning. Our method may become a powerful tool to evaluate the tumor response to new chemotherapeutics on ‘metastatic site’ in preclinical tumor xenograft model.

scholarly journals Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model

2021 ◽  
Vol 27 ◽  
Author(s):  
Sunyi Lee ◽  
Kyoung Mee Kim ◽  
Seung Yeon Lee ◽  
Joohee Jung
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Rna Sequencing ◽  
Xenograft Model ◽  
Diffuse Gastric Cancer ◽  
Diffuse Type ◽  
Female Mice ◽  
Exogenous Estrogen ◽  
Endogenous Estrogen ◽  
Diffuse Type Gastric Cancer

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.

scholarly journals Baicalin Promotes Mammary Gland Development via Steroid-Like Activities

2021 ◽  
Vol 9 ◽  
Author(s):  
Weizhen Chen ◽  
Wei Wei ◽  
Liya Yu ◽  
Xin Zhang ◽  
Fujing Huang ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Tumor Growth ◽  
Cell Line ◽  
Cancer Progression ◽  
Mammary Gland Development ◽  
Biological Activities ◽  
Xenograft Model ◽  
Mammary Development ◽  
Tumor Xenograft ◽  
Gland Development

Baicalin, the main flavonoid component extracted from Scutellaria roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found that baicalin administration significantly accelerates duct elongation at puberty, and promotes alveolar development and facilitates milk secretion during pregnancy. Furthermore, self-renewal of MaSCs was significantly promoted in the presence of baicalin. Moreover, in a tumor xenograft model, baicalin promoted tumor growth of the MDA-MB-231 cell line, but suppressed tumor growth of the ZR-751 cell line. Mechanistically, baicalin can induce expression of the protein C receptor, while inhibiting the expression of the estrogen receptor. Transcriptome analysis revealed that baicalin is involved in signaling pathways related to mammary gland development, immune response, and cell cycle control. Taken together, our results from comprehensive investigation of the biological activity of baicalin provide a theoretical basis for its rational clinical application.

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