Abplatin(IV) Inhibited Tumor Growth On A Patient Derived Cancer Model of Hepatocellular Carcinoma And Its Comparative Multi-Omics Study With Cisplatin

Abstract Background: Cisplatin is the most common antitumor alkylating agent of platinum(II) (Pt(II)) in clinic, however it had many side effects. It is necessary to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics was frequently used to help one understand the mechanism of a certain therapy at the molecular level. Little was known about the mechanism of Pt(IV) drugs, which may be benifical for clinical translation. Methods: We developed a Pt(IV) drug of cisplatin with two hydrophobic aliphatic chains and further encapsulated it with a drug carrier human serum albumin (HSA) to prepare Abplatin(IV). Transcriptomics, metabolomics and lipidomics were performed to clarify the mechanism of Pt(IV) drugs. T-test assay and fold change were used to find the differential substances.Results: We had further shown Abplatin(IV) had better tumor-targeting performance and greater tumor inhibtion rate than cisplatin. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and caused the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) mainly disturbed more significant purine metabolism pathway than cisplatin.Conclusions: This research highlighted the development of Abplatin(IV) and the use of multi-omics to help one understand the mechanism of action of prodrugs and their DDS, which was the key to the clinical translation of them.

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Synthesis, Characterization of Nano-β-Tricalcium Phosphate and the Inhibition on Hepatocellular Carcinoma Cells

Journal of Nanomaterials ◽

10.1155/2018/7083416 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Langlang Liu ◽

Yanzeng Wu ◽

Chao Xu ◽

Suchun Yu ◽

Xiaopei Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Particle Size ◽

Cell Viability ◽

Tricalcium Phosphate ◽

Hepg2 Cells ◽

Drug Carrier ◽

Average Particle Size ◽

Crystal Habit ◽

Average Particle ◽

Dependent Manner

It is difficult to synthesize nano-β-tricalcium phosphate (nano-β-TCP) owing to special crystal habit. The aim of this work was to synthesize nano-β-TCP using ethanol-water system and characterize it by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Malvern laser particle size analyzer, and transmission electron microscope (TEM). In addition, the inhibitory effect of nano-β-TCP on human hepatocellular carcinoma (HepG2) cells was also investigated using MTT assay, lactate dehydrogenase (LDH) leakage test, and 4′-6-diamidino-2-phenylindole (DAPI) staining. The results showed that negatively charged rod-like nano-β-TCP with about 55 nm in diameter and 120 nm in length was synthesized, and the average particle size of nano-β-TCP was 72.7 nm. The cell viability revealed that nano-β-TCP caused reduced cell viability of HepG2 cells in a time- and dose-dependent manner. These findings presented here may provide valuable reference data to guide the design of nano-β-TCP-based anticancer drug carrier and therapeutic systems in the future.

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Traditional Herbal Medicine: A Review of Potential of Inhibitory Hepatocellular Carcinoma in Basic Research and Clinical Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/268963 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Zhidong Wang ◽

Jun Li ◽

Yuanyuan Ji ◽

Peng An ◽

Shu Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Herbal Medicine ◽

Herbal Remedy ◽

Low Cost ◽

Basic Research ◽

Traditional Herbal Medicine ◽

Aggressive Cancer ◽

Low Toxicity ◽

Arterial Chemoembolization

Although significantly develops in hepatocellular carcinoma (HCC), features of HCC remain an aggressive cancer with a dismal outcome. Traditional Chinese medicine (TCM), specifically Chinese herbal medicine (CHM), is one of the most popular complementary and alternative medicine modalities worldwide. The use of heat-clearing and detoxicating (Chinese namedqingre jiedu) CHM has attracted great attention as an alternative antitumor including HCC considering its low toxicity and high activity. Together these reports indicate that CHM is a promising anti-HCC herbal remedy in basic research. For patients with advanced HCC, CHM including formula and single combined with transcatheter arterial chemoembolization or chemotherapy is able to decrease tumor growth and the side effect of toxicity and improve overall survival, quality of life, and immune function. Due to its abundance, low cost, and safety in consumption, CHM remains a species with tremendous potential for further investigation in HCC.

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Mitochondria-targeting fluorescent molecules for high efficiency cancer growth inhibition and imaging

Chemical Science ◽

10.1039/c9sc01410a ◽

2019 ◽

Vol 10 (34) ◽

pp. 7946-7951 ◽

Cited By ~ 10

Author(s):

Hao Chen ◽

Jing Wang ◽

Xin Feng ◽

Mark Zhu ◽

Simon Hoffmann ◽

...

Keyword(s):

Growth Inhibition ◽

High Efficiency ◽

Clinical Translation ◽

Cancer Growth ◽

Lipophilic Cations ◽

Anti Cancer ◽

Low Toxicity ◽

Fluorescent Molecules ◽

Mitochondria Targeting

5BMF is a new fluorescent mitochondria-accumulating delocalized lipophilic cations [DLC] that boasts significantly increased anti-cancer effects and low toxicity in comparison to previous DLCs, addressing current hurdles in DLC clinical translation.

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Balloon-Occluded Trans-Arterial Chemoembolization Technique with Alternate Infusion of Cisplatin and Gelatin Slurry for Small Hepatocellular Carcinoma Nodules Adjacent to the Glisson Sheath

BioMed Research International ◽

10.1155/2019/8350926 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Toshiyuki Irie ◽

Nobuyuki Takahashi ◽

Toshiro Kamoshida

Keyword(s):

Hepatocellular Carcinoma ◽

Contrast Medium ◽

Drug Carrier ◽

Objective Response ◽

Small Hepatocellular Carcinoma ◽

Small Tumor ◽

Study Results ◽

Significant Difference ◽

Tace Group ◽

Arterial Chemoembolization

Objective. It is difficult to control small hepatocellular carcinoma (HCC) nodules adjacent to the Glisson sheath (GS) by trans-arterial chemoembolization (TACE) probably due to multiple small tumor feeders directly branching from the trunk artery. The purpose of this study was to conduct a retrospective evaluation of a new TACE technique called the repeated alternate infusion of cisplatin solution and gelatin slurry distal to balloon occlusion (RAIB-TACE), for the treatment of small HCC nodules adjacent to GS. Materials and Methods. Small nodules less than 4 cm attached to proximal portion of the subsegmental to lobar level portal branch were retrospectively selected. Between January 2011 and April 2014, 29 nodules in 29 patients were treated by super-selective lipiodol TACE/balloon-occluded TACE (B-TACE) (Lip-TACE group). Since April 2014, treatment protocols for small nodules adjacent to GS were changed, and 14 nodules in 12 patients were treated by RAIB-TACE (RAIB-TACE group). In RAIB-TACE group, alternate infusion of cisplatin solution and sparse gelatin slurry (mixture of 80 mg of gelatin fragments and 20 mL of contrast medium) were repeated until arterial flow was ceased. In Lip-TACE group, lipiodol was used as drug carrier and dense gelatin slurry (mixture of 80 mg of gelatin fragments and 2 mL of contrast medium) as embolization material. Dynamic CT/MRI was obtained 1-3 months after TACE, and response of each nodule was evaluated basing on modified RECIST criteria. Results. In RAIB-TACE group, all 14 nodules (100%) were diagnosed as CR or PR. In Lip-TACE group, 18 of 29 (62.1%) were diagnosed as CR or PR. There was a statistically significant difference in objective response ratio between the groups (p=0.008, Fisher’s test). Biloma (n=1) and benign stricture of the right hepatic duct (n=1) were seen in RAIB-TACE group. The biloma shrunk without treatment and the patient had no symptom, but the patient with biliary stricture repeated cholangitis and was treated by administration of antibiotics. Conclusion. The study results show that RAIB-TACE is more effective than lipiodol TACE/B-TACE for small hepatocellular carcinoma adjacent to GS. We speculate that one of the reasons to explain why Lip-TACE is inferior to RAIB-TACE is that viscous lipiodol or dense gelatin slurry could not flow into small tumor feeders effectively.

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One Step Closer to Clinical Translation: Enhanced Tumor Targeting of [99mTc]Tc-DB4 and [111In]In-SG4 in Mice Treated with Entresto

Pharmaceutics ◽

10.3390/pharmaceutics12121145 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1145

Author(s):

Panagiotis Kanellopoulos ◽

Aikaterini Kaloudi ◽

Maritina Rouchota ◽

George Loudos ◽

Marion de Jong ◽

...

Keyword(s):

Tumor Targeting ◽

Metabolic Stability ◽

Clinical Translation ◽

Tumor Uptake ◽

Gastrin Releasing Peptide ◽

Cognate Receptor ◽

One Step ◽

The Stability ◽

The Impact

Background: Peptide radioligands may serve as radionuclide carriers to tumor sites overexpressing their cognate receptor for diagnostic or therapeutic purposes. Treatment of mice with the neprilysin (NEP)-inhibitor phosphoramidon was previously shown to improve the metabolic stability and tumor uptake of biodegradable radiopeptides. Aiming to clinical translation of this methodology, we herein investigated the impact of the approved pill Entresto, releasing the potent NEP-inhibitor LBQ657 in vivo, on the stability and tumor uptake of two radiopeptides. Methods: The metabolic stability of [99mTc]Tc-DB4 (DB4, N4-Pro-Gln-Arg-Tyr-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Nle-NH2) and [111In]In-SG4 (SG4, DOTA-DGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2) was tested in LBQ657/Entresto-treated mice vs. untreated controls. The uptake in gastrin-releasing peptide receptor (GRPR)-, or cholecystokinin subtype 2 receptor (CCK2R)-positive tumors respectively, was compared between LBQ657/Entresto-treated mice and untreated controls. Results: LBQ657/Entresto treatment induced marked stabilization of [99mTc] Tc-DB4 and [111In]In-SG4 in peripheral mice blood, resulting in equally enhanced tumor uptake at 4 h post-injection. Accordingly, the [99mTc]Tc-DB4 uptake of 7.13 ± 1.76%IA/g in PC-3 tumors increased to 16.17 ± 0.71/17.50 ± 3.70%IA/g (LBQ657/Entresto) and the [111In]In-SG4 uptake of 3.07 ± 0.87%IA/g in A431-CCK2R(+) tumors to 8.11 ± 1.45/9.61 ± 1.70%IA/g. Findings were visualized by SPECT/CT. Conclusions: This study has shown the efficacy of Entresto to notably improve the profile of [99mTc]Tc-DB4 and [111In]In-SG4 in mice, paving the way for clinical translation of this approach.

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HBV Induced HCC: Major Risk Factors from Genetic to Molecular Level

BioMed Research International ◽

10.1155/2013/810461 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 28

Author(s):

Ambreen Ayub ◽

Usman Ali Ashfaq ◽

Asma Haque

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Molecular Level ◽

Asian Countries ◽

Dna Virus ◽

Polygenic Risk ◽

B Virus ◽

Transactivator Protein

Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative.

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