Abstract 2535: PrevOnco® exhibits anti-tumor activity inin vitroandin vivohuman tumor models: Combination therapy (PrevOnco® / Doxorubicin) demonstrates a better efficacy profile with enhanced survival rate in a liver cancer model

Abstract Background Echinacoside (ECH) is the main active ingredient of Cistanches Herba, which is known to have therapeutic effects on metastatic tumors. However, the effects of ECH on liver cancer are still unclear. This study was to investigate the effects of ECH on the aggression of liver cancer cells. Methods Two types of liver cancer cells Huh7 and HepG2 were treated with different doses of ECH at different times and gradients. MTT and colony formation assays were used to determine the effects of ECH on the viability of Huh7 and HepG2 cells. Transwell assays and flow cytometry assays were used to detect the effects of ECH treatment on the invasion, migration, apoptosis and cell cycle of Huh7 and HepG2 cells. Western blot analysis was used to detect the effects of ECH on the expression levels of TGF-β1, smad3, smad7, apoptosis-related proteins (Caspase-3, Caspase-8), and Cyto C in liver cancer cells. The relationship between miR-503-3p and TGF-β1 was detected using bioinformatics analysis and Luciferase reporter assay. Results The results showed that ECH inhibited the proliferation, invasion and migration of Huh7 and HepG2 cells in a dose- and time-dependent manner. Moreover, we found that ECH caused Huh7 and HepG2 cell apoptosis by blocking cells in S phase. Furthermore, the expression of miR-503-3p was found to be reduced in liver tumor tissues, but ECH treatment increased the expression of miR-503-3p in Huh7 and HepG2 cells. In addition, we found that TGF-β1 was identified as a potential target of miR-503-3p. ECH promoted the activation of the TGF-β1/Smad signaling pathway and increased the expression levels of Bax/Bcl-2. Moreover, ECH could trigger the release of mitochondrial Cyto C, and cause the reaction Caspases grade. Conclusions This study demonstrates that ECH exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer, and provides a safe and effective anti-tumor agent for liver cancer.

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208 E7777 (denileukin diftitox) enhances anti-tumor activity and significantly extends survival benefit of anti-PD-1 in syngeneic solid tumor models

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0208 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A224-A225

Author(s):

Mary Woodall-Jappe ◽

A Raghav Chari ◽

Anil Namboodiripad ◽

Chandrasekhar Goda

Keyword(s):

Overall Survival ◽

Tumor Growth ◽

Solid Tumor ◽

Therapeutic Benefit ◽

Tumor Models ◽

Treg Depletion ◽

Immune Biomarkers ◽

Group 5 ◽

Tumor Measurements ◽

Anti Tumor Activity

BackgroundRegulatory T cell (Tregs) inhibit activity of anti-tumor T cells, and have been shown to limit checkpoint inhibitor effectiveness. Depletion of Tregs seems desirable during immunotherapy, but chronic Treg depletion with antibody therapies can lead to serious autoimmune adverse events. Compared to antibodies, the fusion protein E7777 (IL-2/diphtheria toxin) has a relatively short half-life in circulation, which allows for transient and selective Treg depletion. The potential therapeutic benefit of combining E7777 with anti-PD-1 was tested in syngeneic solid tumor models.MethodsCT26 colon and H22 liver cancer tumors were implanted subcutaneously in immunocompetent BALB/c mice. E7777 (2.5 mcg/mouse, i.v.) was given on a Q7Dx3 schedule. Anti-murine PD-1 was given (100 mcg/mouse, i.v.) Q4Dx5. Groups of 16 mice received each agent as monotherapy or in combinations. Sequencing of combination administration was also varied: Group 4 started treatment on the same day; Group 5 received E7777 2 days prior to start of anti-PD-1; Group 6 received anti-PD-1 first. Tumor growth was compared across all groups. In survival studies, mice were treated for 3 weeks and observed with twice weekly tumor measurements. In other experiments, tumors, tumor-draining lymph nodes, and spleens were examined by IHC and by flow cytometry of immune cells from dissociated tissues at defined points, for immune biomarkers.ResultsFigure 1 shows additive benefit from the E7777 + anti-PD-1 combinations over either monotherapy. Most importantly, figure 2 and table 1 show significantly enhanced overall survival from a 3 week course of combinations compared to either agent alone (p<0.005) or to vehicle controls (p<0.000001). There was no clear distinction among different sequencing regimens. Benefit correlated with enhanced CD8:Treg ratios in tumors.Abstract 208 Figure 1Tumor growth in s.c. syngeneic solid tumors. N=16/groupAbstract 208 Figure 2Overall survival in s.c. syngeneic models. N=16/groupAbstract 208 Table 1Calculated median survivalConclusionsDepletion of Tregs by E7777 significantly increased anti-tumor activity and durably extended overall survival compared to treatment with anti-PD-1 alone in syngeneic solid tumor models. Clinical studies of a combination of the two agents are planned.Ethics ApprovalAll studies were conducted at Crown Bio, and were approved by the Crown Bio IACUC.

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In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00310-19 ◽

2019 ◽

Vol 63 (10) ◽

Author(s):

Seong Eun Kim ◽

Hee Kyung Kim ◽

Su-Mi Choi ◽

Yohan Yu ◽

Uh Jin Kim ◽

...

Keyword(s):

Survival Rate ◽

Mortality Rate ◽

Combination Therapy ◽

Combination Treatment ◽

Vibrio Vulnificus ◽

Antibiotic Regimen ◽

Content Type ◽

Time Kill

ABSTRACT The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

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Anti-tumor activity of folate targeted biodegradable polymer–paclitaxel conjugate micelles on EMT-6 breast cancer model

Materials Science and Engineering C ◽

10.1016/j.msec.2015.04.012 ◽

2015 ◽

Vol 53 ◽

pp. 68-75 ◽

Cited By ~ 20

Author(s):

Di Wu ◽

Yonghui Zheng ◽

Xiuli Hu ◽

Zhimin Fan ◽

Xiabin Jing

Keyword(s):

Breast Cancer ◽

Biodegradable Polymer ◽

Cancer Model ◽

Breast Cancer Model ◽

Anti Tumor Activity

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Potent CYP17 inhibitors: improved syntheses, pharmacokinetics and anti-tumor activity in the LNCaP human prostate cancer model

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2004.07.006 ◽

2004 ◽

Vol 92 (3) ◽

pp. 155-165 ◽

Cited By ~ 15

Author(s):

Venkatesh D. Handratta ◽

Danijela Jelovac ◽

Brian J. Long ◽

Ritesh Kataria ◽

Ivo P. Nnane ◽

...

Keyword(s):

Prostate Cancer ◽

Human Prostate ◽

Human Prostate Cancer ◽

Cancer Model ◽

Anti Tumor Activity ◽

Prostate Cancer Model

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Reprogramming Tumor Associated Macrophage Phenotype by a Polysaccharide from Ilex asprella for Sarcoma Immunotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms19123816 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3816 ◽

Cited By ~ 4

Author(s):

Qiu Li ◽

Zhihui Hao ◽

Yeting Hong ◽

Wei He ◽

Wenwen Zhao

Keyword(s):

Survival Rate ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Signal Transducer ◽

Macrophage Phenotype ◽

Therapeutic Tool ◽

Acidic Polysaccharide ◽

Tumor Associated Macrophage ◽

Animal Survival ◽

Anti Tumor Activity

We report here the discovery of an acidic polysaccharide, namely IAPS-2, from the root of Ilex asprella, with anti-tumor activity via a repolarizing tumor associated macrophages (TAMs) phenotype. We obtained IAPS-2 polysaccharide from this herb based on acidity and found that IAPS-2 expressed the activity of promoting the secretion of anti-tumor cytokines in macrophages. Furthermore, we evaluated its anti-tumor effect on TAM cells, through the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT) signaling. In particular, in the tumor murine model, IAPS-2 demonstrated that it could significantly inhibit the growth of tumors via modulating the function of TAMs and increase the animal survival rate. In summary, IAPS-2, with a clearly illustrated chemical composition, potent anti-tumor activity, and a solid mechanism of action, may be developed into a valuable therapeutic tool for cancer immunotherapy.

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