scholarly journals In Vitro and In Vivo Studies of the Growth Inhibitory Effect of a Newly Synthesized Peptide, Obiopeptide-1, on Mice-Bearing Methylcholanthrene-Induced Murine Tumours.

1991 ◽  
Vol 53 (5) ◽  
pp. 823-831
Author(s):  
Haruhisa SAKURAI ◽  
Yasuhiro FUJII ◽  
Yoshiyuki MAKI ◽  
Ikuo IGARASHI ◽  
Yoshitaka OMATA ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Murine Tumours

scholarly journals NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Atsushi Takatori ◽  
Shamim Hossain ◽  
Atsushi Ogura ◽  
Jesmin Akter ◽  
Yohko Nakamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Inhibitory Effect ◽  
Tumor Cell Proliferation ◽  
Growth Inhibitory Effect ◽  
Extracellular Domains ◽  
Growth Inhibitory ◽  
Fniii Domain

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.

Abstract 1291: Tumor growth inhibitory effect in EIF4B silenced in vitro and in vivo lung cancer models

2012 ◽  
Author(s):  
Jung-Young Shin ◽  
Xiang-Hua Zhang ◽  
Jeong-Oh Kim ◽  
Ji-Eun Oh ◽  
Hiun Suk Chae ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Cancer Models

scholarly journals Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 189 ◽  
Author(s):  
Robert Hanes ◽  
Else Munthe ◽  
Iwona Grad ◽  
Jianhua Han ◽  
Ida Karlsen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Signaling Components ◽  
Fgfr Inhibition ◽  
Model Expression

Background: FGFR inhibition has been proposed as treatment for dedifferentiated liposarcoma (DDLPS) with amplified FRS2, but we previously only demonstrated transient cytostatic effects when treating FRS2-amplified DDLPS cells with NVP-BGJ398. Methods: Effects of the more potent FGFR inhibitor LY2874455 were investigated in three DDLPS cell lines by measuring effects on cell growth and apoptosis in vitro and also testing efficacy in vivo. Genome, transcriptome and protein analyses were performed to characterize the signaling components in the FGFR pathway. Results: LY2874455 induced a stronger, longer-lasting growth inhibitory effect and moderate level of apoptosis for two cell lines. The third cell line, did not respond to FGFR inhibition, suggesting that FRS2 amplification alone is not sufficient to predict response. Importantly, efficacy of LY2874455 was confirmed in vivo, using an independent FRS2-amplified DDLPS xenograft model. Expression of FRS2 was similar in the responding and non-responding cell lines and we could not find any major difference in downstream FGFR signaling. The only FGF expressed by unstimulated non-responding cells was the intracellular ligand FGF11, whereas the responding cell lines expressed extracellular ligand FGF2. Conclusion: Our study supports LY2874455 as a better therapy than NVP-BGJ398 for FRS2-amplified liposarcoma, and a clinical trial is warranted.

scholarly journals The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo

2008 ◽  
Vol 7 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Yan-rong Lu ◽  
Yu Yuan ◽  
Xiu-jie Wang ◽  
Ling-ling Wei ◽  
You-nan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Cells ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory

Inhibition of Impdh As an Effective Treatment for MLL-Fusion Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 750-750 ◽  
Author(s):  
Susumu Goyama ◽  
Shiori Shikata ◽  
Yasutaka Hayashi ◽  
Yuto Izawa ◽  
Janet Schibler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inhibitory Effect ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Guanine Nucleotide ◽  
Growth Inhibitory Effect ◽  
Nucleotide Biosynthesis ◽  
Growth Inhibitory

Abstract Uncontrolled cell proliferation is a hallmark of cancer and requires adequate nucleotide biosynthesis. Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme that catalyzes the conversion of IMP to XMP at the branch point of guanine nucleotide biosynthesis. Inhibition of IMPDH results in the depletion of guanine nucleotides, thereby suppressing the growth of cancers cells. Therefore, IMPDH inhibition constitutes a rational approach to treat cancers including acute myeloid leukemia (AML). We have developed an experimental system to model myeloid leukemogenesis using primary human cord blood (CB) cells. AML1-ETO is a leukemogenic fusion protein and promotes the self-renewal and long-term proliferation of CB cells in vitro. Another fusion protein MLL-AF9 immortalizes CB cells in vitro and produces human leukemia in immunodeficient mice. These engineered pre-leukemic and leukemic cells recapitulate many features of the clinical diseases and have been useful in testing potential anti-leukemic drugs. Using these human cell-based models, we assessed the effect of a specific IMPDH inhibitor, mycophenolic acid (MPA), on CB cells and those expressing AML1-ETO and MLL-AF9. MPA showed substantial growth-inhibitory effect against MLL-AF9-expressing CB cells, while it had only marginal effects on normal CB cells and AML1-ETO cells. Mechanistically, MPA treatment caused a cell cycle arrest at G0/G1-phase, triggered apoptosis, and induced upregulation of p53 and its downstream target genes including p21/CDKN1A in MLL-AF9 cells. The MPA-mediated changes in MLL-AF9 cells were almost fully reversed by the supplementation of guanosine, confirming that guanine nucleotide depletion underlies the effects of MPA. In contrast, knockdown of p53 or p21, or expression of a dominant-negative form of p53 (p53-DD), did not abrogate the growth-inhibitory effect of MPA on MLL-AF9 cells, indicating that MPA inhibits the leukemic growth largely through p53-independent mechanisms. To examine whether MPA has single-agent activity for MLL-fusion leukemia in vivo, we next established a mouse bone marrow transplant assay for MLL-AF9 leukemia. Bone marrow progenitors were transduced with MLL-AF9 and were transplanted into recipient mice. MLL-AF9-expressing bone marrow progenitors produced AML within 3 months. Leukemic cells were isolated from the spleens of moribund primary mice, and were transplanted into secondary recipient mice. These mice were treated either with injections of MPA (100 mg kg−1) every other day or with vehicle. MPA administration led to a delay in disease progression and significantly extended survival. We also tested the in vivo effect of another IMPDH inhibitor FF-10501-01 on MLL-AF9 leukemia. FF-10501-01 is a potent new competitive IMPDH inhibitor undergoing phase I clinical trials for patients with AML and high-risk myelodysplastic syndrome (MDS). As expected, FF-10501-01 also showed significant therapeutic value, providing survival benefit in a mouse MLL-AF9 leukemia model. Finally, we assessed the sensitivity of p53-deficient mouse MLL-AF9 leukemia cells to IMPDH inhibition. We generated p53-deficient leukemia cells by expressing MLL-AF9 into bone marrow progenitors derived from p53 knockout mice. Consistent with earlier results, the p53-deficient MLL-AF9 cells were still sensitive to MPA and FF-10501-01 both in vitro and in vivo, indicating that p53 activation is dispensable for the anti-leukemia effect of these IMPDH inhibitors. Taken together, these findings establish the inhibition of IMPDH as a promising therapy for MLL-fusion leukemia, including those with defective p53 signaling. Disclosures Goyama: Fuji Film: Research Funding. Iwamura:FUJIFILM Corporation: Employment. Saito:Fuji Film: Employment.

scholarly journals YM155 exerts a growth inhibitory effect on human osteosarcoma in vitro and in vivo

2015 ◽  
Vol 34 (2) ◽  
pp. 1074-1080 ◽  
Author(s):  
ZHUO ZHANG ◽  
LIANJUN MA ◽  
JINCHENG WANG
Keyword(s):  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Human Osteosarcoma ◽  
Growth Inhibitory

Growth-inhibitory effect of prostaglandin D2 on mouse glioma cells

1984 ◽  
Vol 61 (5) ◽  
pp. 912-917 ◽  
Author(s):  
Atsushi Keyaki ◽  
Hajime Handa ◽  
Junkoh Yamashita ◽  
Yasuhiko Tokuriki ◽  
Shin-Ichi Otsuka ◽  
...  
Keyword(s):  
Intraperitoneal Injection ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Prostaglandin D2 ◽  
Growth Inhibitory Effect ◽  
Content Type ◽  
Growth Inhibitory ◽  
Mouse Glioma

✓ The effects of prostaglandin D2 (PGD2) on the growth of mouse malignant glioma cells were studied in vitro and in vivo. The in vitro studies consisted of various concentrations of prostaglandins (PG's) being added to cultures of mouse glioma cells. At concentrations above 2.5 µg/ml, PGD2 strongly inhibited the proliferation of glioma cells, whereas PGE2 had no effect at the same value. Exposure to 5.0 µg/ml PGD2 for more than 2 hours resulted in inhibition of glioma cell proliferation. This growth-inhibitory effect of PGD2 was related to the inhibition of DNA synthesis of the cells. The in vivo studies were performed with a subcutaneously transplanted mouse glioma model. Injection of 0.5 mg/kg PGD2 into the tumor was more effective than the same concentration given by intraperitoneal injection. In mice with intracranially transplanted glioma, daily intraperitoneal injection of 0.5 mg/kg PGD2 had no significant effect on survival time.

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