In vivo tumor-suppressing and anti-angiogenic activities of a recombinant anti-CD3ε nanobody in breast cancer mice model

Aim: Achievements in cancer immunotherapy require augmentation of a host's anti-tumor immune response for anti-cancer modality. Materials & methods: Different concentrations of recombinant anti-CD3 nanobody were administered at predetermined time intervals during a 24-day treatment period and then expression of angiogenic biomarkers including VEGFR2, MMP9 and CD31, as well as tumor cell proliferation marker ki67, was determined in tumor sections by immunohistochemistry. Furthermore, expression of cytokines was examined in peripheral blood of mice. Results: Based on our results, administration of nanobody could reduce biomarker expression in tumor sections. Tumor growth was also delayed and survival rate was increased in response to nanobody treatment. Moreover, expression of pro-inflammatory cytokines was reduced. Conclusion: In conclusion, we demonstrated that administration of nanobody could effectively suppress angiogenesis as well as tumor growth.

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Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model

Endocrine Related Cancer ◽

10.1530/erc-18-0121 ◽

2018 ◽

Vol 25 (6) ◽

pp. 677-686 ◽

Cited By ~ 4

Author(s):

Shani Avniel-Polak ◽

Gil Leibowitz ◽

Victoria Doviner ◽

David J Gross ◽

Simona Grozinsky-Glasberg

Keyword(s):

Mouse Model ◽

Tumor Growth ◽

Mtor Inhibitors ◽

Degradation Pathway ◽

Neuroendocrine Neoplasms ◽

Histopathological Analysis ◽

Anti Cancer ◽

Subcutaneous Xenograft ◽

Rheumatic Drug

Patients with neuroendocrine neoplasms (NENs) often require systemic treatment, which is frequently limited by the emergence of drug resistance. mTOR inhibitors (mTORi), such as RAD001 (everolimus), have been shown to inhibit neoplasm progression. mTORi stimulates autophagy, a degradation pathway that might promote the survival of neoplasm cells that are exposed to anti-cancer therapy. Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppresses autophagy. Based on our previous results, we hypothesized that CQ may enhance the anti-tumorigenic effects of mTORi by inhibiting autophagy and we aimed to examine the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We established a NEN subcutaneous xenograft mouse model and evaluated the effect of the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. CQ alone and in combination with RAD001 significantly decreased neoplasm volume. Histopathological analysis revealed that the combination of CQ and RAD001 markedly inhibited mTOR activity and neoplasm cell growth, along with accumulation of autophagosomes and increased apoptosis. In conclusion, CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on neoplasm progression in patients with NENs, mainly in those treated with mTORi, are warranted.

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The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach

Scientific Reports ◽

10.1038/s41598-020-62293-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Diana Spiegelberg ◽

Andris Abramenkovs ◽

Anja Charlotte Lundgren Mortensen ◽

Sara Lundsten ◽

Marika Nestor ◽

...

Keyword(s):

Tumor Growth ◽

External Beam Radiotherapy ◽

Heat Shock Protein 90 ◽

Hsp90 Inhibitor ◽

Control Group ◽

A431 Cells ◽

Anti Cancer ◽

Client Proteins

AbstractOncogenic client-proteins of the chaperone Heat shock protein 90 (HSP90) insure unlimited tumor growth and are involved in resistance to chemo- and radiotherapy. The HSP90 inhibitor Onalespib initiates the degradation of oncoproteins, and might also act as a radiosensitizer. The aim of this study was therefore to evaluate the efficacy of Onalespib in combination with external beam radiotherapy in an in vitro and in vivo approach. Onalespib downregulated client proteins, lead to increased apoptosis and caused DNA-double-strands. Monotherapy and combination with radiotherapy reduced colony formation, proliferation and migration assessed in radiosensitive HCT116 and radioresistant A431 cells. In vivo, a minimal treatment regimen for 3 consecutive days of Onalespib (3 × 10 mg/kg) doubled survival, whereas Onalespib with radiotherapy (3 × 2 Gy) caused a substantial delay in tumor growth and prolonged the survival by a factor of 3 compared to the HCT116 xenografted control group. Our results demonstrate that Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy, most prominent in the radiosensitive cell models. We speculate that the depletion and downregulation of client proteins involved in signalling, migration and DNA repair mechanisms is the cause. Thus, individually, or in combination with radiotherapy Onalespib inhibits tumor growth and has the potential to improve radiotherapy outcomes, prolonging the overall survival of cancer patients.

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Chemo-enzymatic Synthesis of Ester-Linked Docetaxel-Glycoside Conjugate and its Drug Delivery System Using Hybrid-Bio-Nanocapsules Targeted With Trastuzumab and Cetuximab

Natural Product Communications ◽

10.1177/1934578x19858803 ◽

2019 ◽

Vol 14 (6) ◽

pp. 1934578X1985880

Author(s):

Yuya Fujitaka ◽

Hiroki Hamada ◽

Hatsuyuki Hamada ◽

Noriyoshi Masuoka ◽

Kei Shimoda ◽

...

Keyword(s):

Drug Delivery ◽

Tumor Growth ◽

Drug Delivery System ◽

Delivery System ◽

Enzymatic Synthesis ◽

Effective Suppression ◽

Anti Cancer ◽

Cancer Activity

Synthesis of ester-linked glucoside conjugate of docetaxel, 7-propionyldocetaxel 3''- O-α-D-glucopyranoside, was carried out by chemo-enzymatic procedures. The EE and LE values for hybrid-bio-nanocapsules of 7-propionyldocetaxel 3''- O-α-D-glucopyranoside were much improved rather than those of docetaxel. The hybrid-bio-nanocapsules targeted with trastuzumab and cetuximab, which contained 7-propionyldocetaxel 3''- O-α-D-glucopyranoside, showed high in vivo anti-cancer activity, ie, effective suppression of tumor growth, respectively.

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Abstract 5555: Honokiol inhibits tumor growth in a xenograft melanoma mice model and activates the apoptotic signaling pathway in vivo.

10.1158/1538-7445.am2013-5555 ◽

2013 ◽

Author(s):

Ruth F. Guillermo ◽

Sreevidya Santha ◽

Jonathan Stevens ◽

Emily Coughlin ◽

Pious Patel ◽

...

Keyword(s):

Tumor Growth ◽

Signaling Pathway ◽

Mice Model ◽

Apoptotic Signaling

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Inhibition of Tumor Growth and Immunomodulatory Effects of Flavonoids and Scutebarbatines ofScutellaria barbataD. Don in Lewis-Bearing C57BL/6 Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/630760 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Tao Gong ◽

Chun-Fei Wang ◽

Jia-Rui Yuan ◽

Yu Li ◽

Jun-Fei Gu ◽

...

Keyword(s):

Immune Responses ◽

Tumor Growth ◽

Tumor Volume ◽

Chinese Herb ◽

Mice Model ◽

Immunomodulatory Effects ◽

Therapeutic Measure ◽

Inhibition Of Tumor Growth

Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition ofScutellaria barbataD. Don (SB), an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effectsin vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of44.41±5.44%,33.56±4.85%, and27.57±4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-β1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γlevels. Our results demonstrated that SB could inhibit tumor growthin vivothrough regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer.

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Rosiglitazone impairs proliferation of human adrenocortical cancer: preclinical study in a xenograft mouse model

Endocrine Related Cancer ◽

10.1677/erc-09-0170 ◽

2010 ◽

Vol 17 (1) ◽

pp. 169-177 ◽

Cited By ~ 24

Author(s):

Michaela Luconi ◽

Monica Mangoni ◽

Stefania Gelmini ◽

Giada Poli ◽

Gabriella Nesi ◽

...

Keyword(s):

Tumor Growth ◽

Day Treatment ◽

Xenograft Model ◽

Preclinical Study ◽

Histological Evaluation ◽

Control Group ◽

Adrenocortical Cancer ◽

Ki 67

Adrenocortical carcinoma (ACC) is a rare aggressive tumor with a poor prognosis. The lack of a specific and effective medical treatment is due to the poor knowledge of the mechanisms underlying tumor growth. Research on potential drugs able to specifically interfere with tumor proliferation is essential to develop more efficacious therapies. We evaluated for the first time the in vivo effect of rosiglitazone (RGZ), an anti-diabetic drug with in vitro anti-tumor properties, on ACC proliferation in a xenograft model obtained by s.c. injection of human ACC H295R cells in athymic mice. When the tumor size reached 5 mm, animals were allocated to 5 mg/kg RGZ- or water-treated groups. Tumor volume was measured twice a week. A significant reduction of tumor growth in RGZ versus control (control) group was observed and was already maximal following 17 day treatment (1−T/C=75.4% (43.7–93.8%)). After 31 days of treatment, mice were killed and tumor analyzed. Tumor histological evaluation revealed characteristics of invasiveness, richness in small vessels and mitotic figures in control group, while RGZ group tumors presented non infiltrating borders, few vessels, and many apoptotic bodies. Tumor immunohistochemistry showed that Ki-67 was reduced in RGZ versus control group. Quantitative real-time RT-PCR demonstrated a significant reduction in the expression of angiogenic (VEGF), vascular (CD31), proliferation (BMI-1), and anti-apoptotic (Bcl-2) genes in RGZ versus control group tumors. The same inhibitory effects were confirmed in in vitro RGZ-treated H295R. Our findings support and expand the role of RGZ in controlling ACC proliferation and angiogenesis in vivo and in vitro.

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Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53

Cancers ◽

10.3390/cancers11020168 ◽

2019 ◽

Vol 11 (2) ◽

pp. 168 ◽

Cited By ~ 4

Author(s):

Yi-Ting Lin ◽

Shu-Man Liang ◽

Ya-Ju Wu ◽

Yi-Ju Wu ◽

Yi-Jhu Lu ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Tumor Growth ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Epithelial Mesenchymal Transition ◽

Endothelial Cell Proliferation ◽

Mice Model ◽

Mesenchymal Transition

Focal adhesion kinase (FAK) plays an important role in vascular development, including the regulation of endothelial cell (EC) adhesion, migration, proliferation, and survival. 3’-deoxyadenosine (cordycepin) is known to suppress FAK expression, cell migration, and the epithelial–mesenchymal transition in hepatocellular carcinoma (HCC). However, whether cordycepin affects FAK expression and cellular functions in ECs and the specific molecular mechanism remain unclear. In this study, we found that cordycepin suppressed FAK expression and the phosphorylation of FAK (p-FAK) at Tyr397 in ECs. Cordycepin inhibited the proliferation, wound healing, transwell migration, and tube formation of ECs. Confocal microscopy revealed that cordycepin significantly reduced FAK expression and decreased focal adhesion number of ECs. The suppressed expression of FAK was accompanied by induced p53 and p21 expression in ECs. Finally, we demonstrated that cordycepin suppressed angiogenesis in an in vivo angiogenesis assay and reduced HCC tumor growth in a xenograft nude mice model. Our study indicated that cordycepin could attenuate cell proliferation and migration and may result in the impairment of the angiogenesis process and tumor growth via downregulation of FAK and induction of p53 and p21 in ECs. Therefore, cordycepin may be used as a potential adjuvant for cancer therapy.

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BG-4 from Bitter Gourd (Momordica charantia) Differentially Affects Inflammation In Vitro and In Vivo

Antioxidants ◽

10.3390/antiox8060175 ◽

2019 ◽

Vol 8 (6) ◽

pp. 175 ◽

Cited By ~ 1

Author(s):

Andrea Nieto-Veloza ◽

Zhihong Wang ◽

Qixin Zhong ◽

Hari B. Krishnan ◽

Vermont P. Dia

Keyword(s):

Intraperitoneal Administration ◽

Bitter Gourd ◽

Myeloperoxidase Activity ◽

Local Effects ◽

Anti Cancer ◽

Mouse Macrophages ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

BG-4 isolated from bitter gourd has been reported for anti-cancer properties. The objective was to evaluate the anti-inflammatory properties of BG-4 in vitro and in vivo. Comparative study of the anti-inflammatory properties of BG-4 in vitro and in vivo was conducted on lipopolysaccharide (LPS)-activated mouse macrophages, and on dextran sodium sulfate (DSS)-induced colitis in mice. BG-4 reduced the production of pro-inflammatory markers in LPS-activated macrophages. On the other hand, intraperitoneal administration of BG-4 in DSS-induced colitis led to colon shortening, elevated neutrophils infiltration and myeloperoxidase activity, presence of blood in the stool, and loss of body weight, with differential systemic and local effects on pro-inflammatory cytokines in vivo. The results demonstrated that BG-4 differentially affected inflammation in vitro and in vivo.

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