Comparison Of Antitumor Activity Research Articles

Comparison of anti-tumor activities and underlying mechanisms of glucuronomannan oligosaccharides and its sulfated derivatives on the hepatocarcinoma Huh7.5 cells

Hepatocellular carcinoma (HCC) is an aggressive tumor triggered by various factors such as virus infection and alcohol abuse. Glucuronomannan polysaccharide (Gx) is a subtype of fucoidans that possesses many bioactivities, but its anti-tumor activities in HCC have not been reported. In this paper, the anti-tumor effects of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) on hepatocarcinoma Huh7.5 cells were investigated. The anti-proliferation, anti-metastasis activities, and underlying mechanism of Gx and GxSy on Huh7.5 cells were analyzed and compared by MTT, wound healing, transwell, and western blotting assays, respectively. Results showed that the best anti-proliferation effects were G4S1 and G4S2 among 13 drugs, which were 38.67% and 30.14%, respectively. The cell migration rates were significantly inhibited by G2S1, G4S2, G6S2, and unsulfated Gn. In addition, cell invasion effects treated with G4S1, G4S2, and G6S1 decreased to 48.62%, 36.26%, and 42.86%, respectively. Furthermore, sulfated G4 regulated the expression of (p-) FAK and MAPK pathway, and sulfated G6 down-regulated the MAPK signaling pathway while activating the PI3K/AKT pathway. On the contrary, sulfated G2 and unsulfated Gx had no inhibited effects on the FAK-mTOR pathway. These results indicated that sulfated Gx derivatives have better anti-tumor activities than unsulfated Gx in cell proliferation and metastasis process in vitro, and those properties depend on the sulfation group levels. Moreover, degrees of polymerization of Gx also played a vital role in mechanisms and bioactivities. This finding shows the structure-activity relationship for developing and applying the marine oligosaccharide candidates.

Abstract 4759: Antitumor activity of eribulin after fulvestrant plus palbociclib treatments in the HR(+) human breast PDx model

Abstract Fulvestrant (FLV) and Palbociclib (Palb), which have an effect on degradation of estrogen receptor (ER) and inhibition of cyclin dependent kinases 4 and 6 (CDK4/6), respectively are used for treatments to postmenopausal breast cancer patients. However, there is not a clinical rationale to define a standard treatment regimen against breast cancer patients who are resistant to endocrine therapy plus Palb. Eribulin is a fully synthetic analog of the marine sponge natural product halichondrin B. Its clinical formulation is currently approved for advanced breast cancer (BC) and advanced liposarcoma in numerous countries. We examined the antitumor activity of eribulin after endocrine therapy (combination of FLV and Palb) compared with that of Capecitabine (Cape) in the luminal type breast cancer PDx model (OD-BRE-0438). OD-BRE-0438 is a patient derived xenograft (PDx) model developed from patient with luminal B breast cancer. Gene expression analysis by RNA-Seq showed that OD-BRE-0438 highly expressed ER and PR, but not ERBB2. OD-BRE-0438 tumor bearing mice were treated for 2 weeks of FLV (5mg/ head, Q7Dx2, sc) and Palb (10mg/kg, Q1Dx14, po), and treated mice were randomly divided using tumor volume around 350 mm3 as an index (day1). After that, mice were treated with eribulin (0.5 or 1 mg/kg, which are 1/4 MTD or 1/2 MTD in this model, Q7Dx2, iv) or Cape (125 or 250 mg/kg, which are 1/2 MTD or MTD in this model, Q1Dx14, po for 2 weeks). We measured tumor volume of each mouse after treatments (day 15) and analyzed the ratio of tumor volume at day 15 divided by that at day 1 (RTV: relative tumor volume). Treatments of FLV and Palb nearly completely inhibited in vivo growth of OD-BRE-0438 tumors, but didn’t cause tumor shrinkage. After two weeks of combination treatment with endocrine therapy, we started treatments with either eribulin or Cape, and compared the antitumor activity. Both drug showed strong antitumor activity with tumor shrinkage. In comparison of antitumor activity with either eribulin or Cape, that of eribulin was significantly greater than Cape. [eribulin 0.5mg/kg (RTV=0.42) vs Cape 125mg/kg (RTV=0.62, p=0.0068), eribulin 1.0mg/kg (RTV=0.32) vs Cape 250mg/kg (RTV=0.59, p=0.0008)]. Further investigation for mechanism of action of eribulin to show clear antitumor activity after treatments of FLV and Palb in the luminal type breast cancer PDx model are warranted. Citation Format: Makoto Asano, Takayuki Nakagawa, Taro Semba, Akira Yokoi, Junji Matsui, Yasuhiro Funahashi. Antitumor activity of eribulin after fulvestrant plus palbociclib treatments in the HR(+) human breast PDx model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4759.

Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells.

Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity.

Comparison of Antitumor Activity of Some Benzothiophene and Thienothiophene Carboxanilides and Quinolones in 2D and 3D Cell Culture System

Comparison of Antitumor Activity of Some Benzothiophene and Thienothiophene Carboxanilides and Quinolones in 2D and 3D Cell Culture System

Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-a]quinoline derivatives tested in 2D and 3D cell culture systems

Due to a poor clinical predictive power of 2D cell cultures, standard tool for in vitro assays in drug discovery process, there is increasing interest in developing 3D in vitro cell cultures, biologically relevant assay feasible for the development of robust preclinical anti-cancer drug screening platforms. Herein, we tested amidino-substituted benzimidazoles and benzimidazo[1,2-a]quinolines as a small platform for comparison of antitumor activity in 2D and 3D cell culture systems and correlation with structure–activity relationship. 3D cell culture method was applied on a human cancer breast (SK-BR-3, MDA-MB-231, T-47D) and pancreatic cancer cells (MIA PaCa-2, PANC-1). Results obtained in 2D and 3D models were highly comparable, but in some cases we have observed significant disagreement indicating that some prominent compounds can be discarded in early phase of researching because of compounds with false positive result. To confirm which of cell culture systems is more accurate, in vivo profiling is needed.

Comparison of antitumor activities in tumor xenograft treatment

To compare treatment effects with antitumor therapies, we proposed an intuitive approach to compare the antitumor effects of two different antitumor treatments by investigating tumor volumes which were measured in a given period of time. The approach is, in essence, a comparison of two unknown functions. The implementation of the approach is simple and straightforward. The approach is applied to analyze a real xenograft study of a new antitumor agent, irofulven, combined with irinotecan.

778A comparison of antitumor activities of three N-substituted benzamides: Sensamide, neu-sensamide and 3-chloroprocainamide

778A comparison of antitumor activities of three N-substituted benzamides: Sensamide, neu-sensamide and 3-chloroprocainamide

制癌性白金錯体のヒト肺癌細胞に対する抗腫よう効果に関する研究 １．制癌性白金錯体のヒト肺癌細胞に対するｉｎ ｖｉｔｒｏにおける殺細胞効果の比較

制癌性白金錯体のヒト肺癌細胞に対する抗腫よう効果に関する研究 １．制癌性白金錯体のヒト肺癌細胞に対するｉｎ ｖｉｔｒｏにおける殺細胞効果の比較

Intraperitoneal cisplatin: Comparison of antitumor activity and toxicity as a function of solvent saline concentration

The use of increasing concentrations of NaCl in the solvent during administration of cisplatin is known to decrease nephrotoxicity, but its effect on antitumor activity is less certain. A murine tumor model employing the subrenal capsule assay was used to test the toxicity and antitumor activity of intraperitoneal cisplatin at different doses of the drug using varying concentrations of NaCl in the vehicle of administration. Toxicity (measured by LD 50, weight loss, and nephrotoxicity) was significantly lower in mice treated with cisplatin prepared in 4.5% NaCl as compared to cisplatin prepared in distilled water (DW) or 0.9% NaCl. Administraton of 4.5% NaCl subcutaneously along with intraperitoneal cisplatin prepared in DW failed to decrease toxicity. Despite lower toxicity, no decrease in antitumor activity could be demonstrated based on increasing concentrations of NaCl in the solvent during intraperitoneal therapy.

A simple method for predicting modes of actions of antitumor agents.

Modes of actions of antitumor agents can be predicted by comparison of antitumor activities against L1210 cells in the presence and absence of some nucleosides. 1) Deoxyribonucleic acid (DNA) inhibitors were mainly antagonized by thymidine. 2) Both DNA and ribonucleic acid (RNA) inhibitors were mainly antagonized by adenosine and uridine. 3) Uridine antagonized the activities of an RNA inhibitor. 4) None of these nucleosides tested antagonized the antitumor activities of an inhibitor of protein synthesis. 5) A mitotic inhibitor was weakly antagonized by thymidine, adenosine and uridine. This method is useful for approximating the modes of actions of antitumor agents without using radioactive precursors.

Systemic mitomycin C versus cisplatin: comparison of antitumor activity in primary murine bladder cancer

The FANFT-induced bladder cancer murine model was used to evaluate the effect of DDP and MMC on the incidence and size of subsequent tumors. MMC was at least equally effective as DDP in inhibiting tumor growth in this model. There was no apparent synergistic effect when the two agents were combined although toxicity was increased. Further clinical trials with systemic MMC for locally advanced or metastatic urothelial transitional cell carcinoma appear to be indicated.