Liver Cancer Chemotherapy Research Articles

Co-delivery of vinorelbine and rutin by lipid polymer nanoparticles for enhanced liver cancer chemotherapy

The purpose of this study was to develop a lipid polymer hybrid nanoparticle (LPNs) for the codelivery of Vinorelbine (VBL) and Rutin (RUT) for the treatment of hepatic carcinoma. The VBL loaded LPNs (VBL-LPNs), and VBL and RUT loaded LPNs (VBL-RUT-LPNs) were prepared using PLGA (polymer) and dynasan 114 (lipid) by probe sonication and high pressure homogenization method. The VBL-LPNs and VBL-RUT-LPNs exhibited a particle size (260±5.40 and 298±3.51 nm), PDI (0.312±0.03 and 0.286±0.03), ZP (-18.8±2.60 and -19.8±2.70 mV), EE (73.7±1.52 and 77.9±2.19%) and LC (2.3±0.49 and 2.5±0.73%), respectively. In-vitro release studies exhibited a sustained release patter for 48 hours, with korsmayer peppas kinetics model. No significatnt changes in VBL-LPNs and VBL-RUT-LPNs was confirmed by stability studies. As compared to free VBL and VBL-LPNs, we observed increased cytotoxicity and lowered inhibitory concentration IC50 in HepG2 cells treated with VBL-RUT-LPNs, indicating the synergistic effects of VBL and RUT. The VBL-RUT-LPNs also upregulated caspase 3 and downregulated Bcl-2, indicating a successful apoptosis. When combined, VBL and RUT are delivered concurrently by VBL-RUT-LPNs, which may offer a promising treatment for hepatic carcinoma.

A Triterpene-Based bioactive drug delivery system for combined chemotherapy of liver cancer

Carrier materials always account for the majority particularly in nanosized formulations, which are administrated along with the active ingredient part might result in metabolism related toxicity. The usage of bioactive excipients could not only reduce the sided effect but also provide additional therapeutic effects. In the present study, a triterpene based micellar drug delivery system was developed using a bioactive solanesol derivative. Solanesylamine was prepared firstly followed by conjugating with poly (ethylene glycol) using maleic acid amide linkage. The amphiphilic drug carrier PEGylated (2-propyl-3-methylmaleic acid)-block-solanesol amine (mPEG-CDM-NH-SOL) could be formed into micelles and loaded with doxorubicin (DOX) inside. The micelles were about 112 nm in size and the drug loading content was about 5.97 wt%. An acid triggered drug release behavior was obviously observed for the DOX loaded pH-sensitive micelle mPEG-CDM-NH-SOL-DOX. While not for DOX-loaded micelles without pH-sensitivity (mPEG-NHS-NH-SOL). CCK8 assay showed that the micelles of PEGylated solanesylamines exhibited certain inhibitory effect on tumor cells at high concentration and the pH sensitive ones seemed more toxic. In vivo studies showed that the pH sensitive mPEG-CDM-NH-SOL-DOX had a superior anti-tumor effect, indicating its great potential in cancer treatment.

Prospective Exploratory Phase I Clinical Trial Assessing the Safety of Preoperative Marking for Small Liver Tumors.

Background Small tumors in liver cirrhosis are difficult to distinguish using intraoperative ultrasonography. In addition, preoperative chemotherapy for metastatic liver cancer may diminish tumor size, thus making tumors difficult to identify intraoperatively. To address such difficulties, we devised a method to mark liver tumors preoperatively to facilitate intraoperative identification. This study aimed to investigate the safety of a preoperative liver tumor marking method. Methodology This exploratory prospective clinical trial included patients with liver tumors measuring ≤20 mm requiring resection. Preoperative marking was performed by placing a coil for embolization of blood vessels near the tumor using either the transcatheter or percutaneous approach. The tumor was identified and resected by intraoperative ultrasonography based on the marker. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028608). Results Overall, 19 patients (9 with primary liver cancer and 10 with metastatic tumors) were recruited. The transcatheter and percutaneous methods were used in 13 and 6 patients, respectively. Marking was not possible in two patients in the transcatheter group because the catheter could not be guided to the vicinity of the tumor. There were no marking-related complications. Hepatectomy was performed in all but one patient who was not fit for hepatectomy owing to the development of a metastatic liver tumor. The markers were adequately identified during hepatectomy. Additionally, there were no difficulties in the surgical procedure or postoperative complications. Conclusions Preoperative marking with embolization coils can be performed safely for intraoperative identification of liver nodules.

Potentiating sorafenib efficacy against hepatocellular carcinoma via a carrier-free nanomedicine of artesunate prodrug

Sorafenib is a first-line drug for liver cancer treatment, but its clinical efficacy is still limited by drawbacks such as drug tolerance, toxic effects, and low bioavailability. Therefore, it is urgent to find efficient ways to synergize sorafenib with other agents and increase its bioavailability in order to enhance its clinical efficacy. Herein, we report the successful development of a carrier-free nanoplatform of an artesunate prodrug to potentiate the efficacy of sorafenib against hepatocellular carcinoma. The artesunate prodrug was synthesized by conjugating artesunate and linoleic acid through a thioketone (TK) bond. This prodrug can self-assemble in an aqueous solution via a one-step precipitation method. Furthermore, the inclusion of sorafenib during the self-assembly process results in a carrier-free artesunate/sorafenib mixed nanomedicine (SA@NPs) with a uniform and stable particle size. In addition, SA@NPs possess ROS-responsive drug-releasing ability by breaking up thioketone bonds under high H2O2 levels in tumors. The synergistic anticancer effects of SA@NPs have been demonstrated both in vivo and in vitro. SA@NPs can achieve significantly enhanced synergetic ferroptosis of tumor cells and show potentiated sorafenib efficacy against hepatocellular carcinoma. Moreover, SA@NPs have a tumor inhibition rate of 84.2%, which is 1.63-, 4.22-, and 1.29-fold higher than that in the experimental groups treated with free sorafenib, artesunate, and the simplified combined medication of sorafenib/artesunate, respectively. Overall, this work presents a significant advancement in the clinical chemotherapy of liver cancer and may pave the way for promising developments in the compatibility and clinical combination application of traditional Chinese medicine.

Core-shell cisplatin/SiO2 nanocapsules combined with PTC-209 overcome chemotherapy–Acquired and intrinsic resistance in hepatocellular carcinoma

The primary cause of cisplatin resistance in liver cancer is reduced intracellular drug accumulation and altered DNA repair/apoptosis signaling. Existing strategies to reverse cisplatin resistance have limited efficacy, as they target individual factors. This study proposes a drug delivery system consisting of a cisplatin core, a silica shell with a tetra-sulfide bond, and a PEG-coated surface (Core/shell-PGCN). The system is designed to consume glutathione (GSH) and reduce cisplatin excretion from cells, thereby overcoming acquired cisplatin resistance. In addition, Core/shell-PGCN incorporates PTC-209 (Core/shell-PGCN@PTC-209), a Bmi1 inhibitor that suppresses liver cancer stem cells (CSC), to mitigate DNA repair/apoptosis signaling and reverse intrinsic cisplatin resistance. In vivo and in vitro results demonstrate that Core/shell-PGCN@PTC-209 can comprehensively regulate GSH and CSC, reverse intrinsic and acquired cisplatin resistance, and enhance the efficacy of cisplatin in treating liver cancer. This "inner cultivation, outer action" approach may offer a new strategy for reversing cisplatin resistance in liver cancer. Statement of significanceCisplatin resistance is widely observed in liver cancer (HCC) chemotherapy, with two mechanisms identified: acquired and intrinsic. Most strategies aimed at overcoming cisplatin resistance focus on a single perspective. This study introduces a core-shell drug delivery system (DDS) combined with HCC stem cell inhibitors, which can effectively address cisplatin resistance in HCC by targeting both acquisition and internality. Specifically, the core-shell drug delivery system can impede cisplatin efflux by neutralizing the acquired resistance factor (GSH), thus overcoming acquired resistance. Additionally, HCC stem cell inhibitors can reverse intrinsic resistance by inhibiting HCC stem cells. Therefore, this study contributes to the application of DDS in combating drug resistance in HCC and enhances its potential for clinical implementation.

Self-Assembly of a Linear-Dendritic Polymer Containing Cisplatin and Norcantharidin into Raspberry-like Multimicelle Clusters for the Efficient Chemotherapy of Liver Cancer.

Combination chemotherapy has been proved to be an effective strategy in the clinic, and nanoformulations have drawn much attention in the field of drug delivery. However, conventional nanocarriers suffer from shortcomings such as inefficient coloading and undesired molar ratios of the combined drugs, preleakage of cargos during systemic circulation, and lack of cancer-selective drug release. To achieve tumor-specific codelivery of cisplatin (CDDP) and norcantharidin (NCTD) for synergistic treatment of liver cancer, a novel linear-dendritic polymer, termed as G1(PPDC)x, was designed and synthesized, where a prodrug consisting of cisplatin (CDDP) and norcantharidin (NCTD) was conjugated to PEG2000 via ester bonds to fabricate linear polymer-drug conjugates, and the conjugates were subsequently grafted to the terminal hydroxyls of a dendritic polycarbonate core. Benefiting from the hydrogen bond interactions, G1(PPDC)x could spontaneously self-assemble into a unique type of raspberry-like multimicelle clusters in solution (G1(PPDC)x-PMs). G1(PPDC)x-PMs possessed an optimal synergistic ratio of CDDP and NCTD, without obvious premature release or disassembly in biological environments. Intriguingly, upon extravasation into the interstitial tumor tissues, G1(PPDC)x-PMs (132 nm in diameter) could disassemble and reassemble into smaller micelles (40 nm in diameter) in response to the mildly acidic tumor microenvironment, which would enhance the deep tumor penetration and cellular accumulation of drugs. In vivo delivery of G1(PPDC)x-PMs led to a significantly prolonged blood circulation half-life, which is beneficial to achieve sufficient tumor accumulation through the enhanced permeability and retention (EPR) effect. G1(PPDC)x-PMs displayed the best antitumor activity in H22 tumor-bearing mice with a tumor inhibition rate of 78.87%. Meanwhile, G1(PPDC)x-PMs alleviated both myelosuppression toxicities of CDDP and vascular irritation of NCTD. Our results demonstrated that G1(PPDC)x-PMs could serve as an effective drug delivery system for codelivery of CDDP and NCTD to treat liver cancer efficiently.

Chia Seeds Oil Suppresses the Resistance of Hepatocellular Carcinoma Cells to Liposomal-doxorubicin and Upregulates the Tumor Suppressor miRNAs.

Chia seed is an oil seed with multiple biological activities. Doxorubicin is effective chemotherapy for liver cancer. Resistance and adverse effects are doxorubicin limitations. This study aimed to investigate the effect of chia seeds oil (CSO) on the resistance of HepG2 cells to liposomal-doxorubicin (DOX). The objective were investigated through measuring cytotoxicity, doxorubicin-metabolizing enzyme Cytochrome P450 3A4 (CYP-3A4), multidrug resistance-associated protein (MRP1), and the expression of multiple tumor suppressor microRNAs. The findings indicated that low concentration of CSO increased HepG2 cells' sensitivity to DOX, as concluded from its higher cytotoxicity. DOX-induced mRNAs of CYP-3A4 and MRP1 and their protein levels. CSO inhibited both in DOX-treated cells. CSO-induced tumor suppressor miRNAs. Doxorubicin inhibited miR-122 and let-7/b/e expression, while it led to overexpression of let- 7a. CSO/DOX upregulated let-7/b/e, miR-34a, and miR-122 (which inhibits MRP1) and downregulated let-7a, which may lead to increased apoptosis. CSO effectively re-sensitized HepG2 cells to liposomal-doxorubicin via inhibiting MRP1 and CYP-3A4, which may increase in vivo doxorubicin bioavailability and decrease its therapeutic dose to diminish its adverse effects.

Advances In the Study of Hypoxia Inducible Factors and Prognosis of Hepatocellular Carcinoma Development

Hypoxia-inducible factors (HIF) plays a major role in the regulation of hypoxia. It occurs not only under normal physiological conditions but also under pathological conditions such as some inflammatory reactions and tumor diseases. Studies have shown that the mechanisms of hepatocarcinogenesis include cellular molecules signaling pathways and gene levels in which Hypoxia-inducible factors play an important role. At present, surgical resection liver transplantation and chemotherapy are still the main treatment methods in the clinical treatment of patients with liver cancer but conventional chemotherapy drugs have toxic side effects on human body and the prognosis is poor. HIF is not only involved in reducing the efficacy of radiotherapy chemotherapy and targeted therapy but also closely related to angiogenesis and immune escape. In this article, we will focus on the Hypoxia-inducible factors of liver cancer and discuss its relationship with the development and prognosis of liver cancer and provide new ideas for the precise treatment of malignant liver tumors.

Hyaluronidase-trigger nanocarriers for targeted delivery of anti-liver cancer compound.

Chemotherapy is recognized as one of the significant treatment methods for liver cancer. The compound celastrol (CSL) could effectively inhibit the proliferation, migration, and invasion of liver cancer cells, which is regarded as a promising candidate to become a mainstream anti-liver cancer drug. However, the application of CSL in liver cancer chemotherapy is limited due to its systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and lack of tumor targeting. Meanwhile, in order to comply with the current concept of precision medicine, precisely targeted delivery of the anti-liver compound CSL was desired. This paper takes into account that liver cancer cells were equipped with hyaluronic acid (HA) receptors (CD44) on their surface and overexpressed. Hyaluronidase (HAase) capable of degrading HA, HAase-responsive nanocarriers (NCs), named HA/(MI)7-β-CD NCs, were prepared based on the electrostatic interaction between HA and imidazole moieties modified β-cyclodextrin (MI)7-β-CD. HA/(MI)7-β-CD NCs showed disassembly properties under HAase stimuli, which was utilized to trap, deliver, and the controllable release of the anti-liver cancer compound CSL. Furthermore, cytotoxicity assay experiments revealed that CSL-trapped HA/(MI)7-β-CD NCs not only reduced cytotoxicity for normal cells but also effectively inhibited the survival for five tumor cells, and even the apoptotic effect of CSL-trapped NCs with a concentration of 5 μg mL-1 on tumor cells (SMMC-7721) was consistent with free CSL. Cell uptake experiments demonstrated HA/(MI)7-β-CD NCs possessed the capability of targeted drug delivery to cancerous cells. HA/(MI)7-β-CD NCs exhibited site-specific and controllable release performance, which is anticipated to proceed further in precision-targeted drug delivery systems.

Combination of chloroquine diphosphate and salidroside induces human liver cell apoptosis via regulation of mitochondrial dysfunction and autophagy.

Hepatocellular carcinoma (HCC) is the leading cause of cancer‑associated death in the world. Chemotherapy remains the primary treatment method for HCC. Despite advances in chemotherapy and modalities, recurrence and resistance limit therapeutic success. Salidroside (Sal), a bioactive component extracted from the rhizome of Rhodiolarosea L, exhibits a spectrum of biological activities including antitumor effects. In the present study, it was demonstrated that Sal could induce apoptosis and autophagy of 97H cells by using CCK‑8 assay, transmission electron microscopy (TEM), Hoechst33342 staining, MDC staining, western blotting. Pretreatment with Sal enhanced apoptosis and autophagy via upregulation of expression levels of Bax, Caspase‑3, Caspase‑9, light chain (LC)3‑II and Beclin‑1 proteins and downregulation of expression levels of Bcl‑2, LC3‑I and p62 protein in 97H cells. Furthermore, Sal was demonstrated to inhibit activation of the PI3K/Akt/mTOR signaling pathway and, when combined with autophagy inhibitor chloroquine diphosphate (CQ), increased phosphorylation of PI3K, Akt and mTOR proteins. The combined treatment with Sal and CQ not only decreased Sal‑induced autophagy, but also accelerated Sal‑induced apoptosis. Therefore, Sal‑induced autophagy might serve a role as a defense mechanism in human liver cancer cells and its inhibition may be a promising strategy for the adjuvant chemotherapy of liver cancer.

The role of tumor microenvironment reprogramming in primary liver cancer chemotherapy resistance.

Primary liver cancer (PLC), including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), and other rare tumours, is the second leading cause of cancer-related mortality. It has been a major contributor to the cancer burden worldwide. Of all primary liver cancer, HCC is the most common type. Over the past few decades, chemotherapy, immunotherapy and other therapies have been identified as applicable to the treatment of HCC. However, evidence suggests that chemotherapy resistance is associated with higher mortality rates in liver cancer. The tumour microenvironment (TME), which includes molecular, cellular, extracellular matrix(ECM), and vascular signalling pathways, is a complex ecosystem. It is now increasingly recognized that the tumour microenvironment plays a pivotal role in PLC prognosis, progression and treatment response. Cancer cells reprogram the tumour microenvironment to develop resistance to chemotherapy drugs distinct from normal differentiated tissues. Chemotherapy resistance mechanisms are reshaped during TME reprogramming. For this reason, TME reprogramming can provide a powerful tool to understand better both cancer-fate processes and regenerative, with the potential to develop a new treatment. This review discusses the recent progress of tumour drug resistance, particularly tumour microenvironment reprogramming in tumour chemotherapy resistance, and focuses on its potential application prospects.

FRONTIERS IN EARLY DETECTION OF HEPATOCELLULAR CARCINOMA

It is the most common cancer in the world, and in the United States it is the fifth most common. It is common for liver cancer patients to be diagnosed at an advanced stage, which has a negative impact on their prognosis. Hepatocellular carcinomas (HCCs) account for more than 90% of all liver cancer cases, and chemotherapy and immunotherapy are the most effective treatments. Patients with liver cancer need new therapeutic choices. It's possible that natural chemicals and/or nanotechnology can improve patient outcomes while minimizing negative effects. Improved treatment options can lead to better outcomes. This study concludes by highlighting a few of the challenges people with liver cancer face, as well as some promising new treatments.

ASIC1α up-regulates MMP-2/9 expression to enhance mobility and proliferation of liver cancer cells via the PI3K/AKT/mTOR pathway

A major challenge in the treatment of liver cancer is that a large proportion of patients fail to achieve long-term disease control, with death from liver cancer cell migration and invasion. Acid-sensitive ion channel 1α (ASIC1α) is involved in the migration, invasion, and proliferation of liver cancer cells. Therefore, we explored the mechanism of ASIC1α-mediated liver cancer cell migration and invasion. We determined the levels of ASIC1α by western blotting and immunofluorescence in HepG2 and SK-Hep1 cells cultured in various acidic conditions. In addition, wound healing assay, transwell invasion assay, and MTT assay were conducted to assess the migration, invasion, and proliferation abilities of liver cancer cells. Western blotting was conducted to determine the levels of MMP2, MMP9, ASIC1α, p-PI3Kp85, t-PI3Kp85, p-AKT(Ser473), t-AKT, p-mTOR (Ser2448), t-mTOR. We first found that the levels of ASIC1α in the HepG2 and SK-Hep1 cells in acidic conditions (pH 6.5) were significantly increased. Inhibition and knockdown of ASIC1α down-regulated MMP-2/9 expression and inhibited the migration, invasion, and proliferation of HepG2 and SK-Hep1 cells; overexpression of ASIC1α had the opposite effect. We further demonstrated that ASIC1α up-regulates MMP-2/9 via activation of the PI3K/AKT/mTOR pathway, thereby promoting migration, invasion, and proliferation of liver cancer cells. Overexpression of MMP-2/9 and activation of AKT reversed these effects on liver cancer cells caused by inhibition of ASIC1α. We conclude that ASIC1α can regulate migration, invasion, and proliferation of liver cancer cells through the MMP-2/9/PI3K/AKT/mTOR pathway. These observations may provide a new reference for liver cancer chemotherapy.

Drug Transport via Nanocarrier for Liver Cancer Treatment

<p>The requirement of having multiple nanocarriers (NCs) and active agents for improved therapy, imaging, and controlled release of medications efficiently in one platform has made the creation of therapeutics and theragnostic nanodrug delivery systems a difficult task for present researchers. Multiple drug resistance (MDR), a high clearance rate, severe side effects, undesirable drug distribution to the specific site of liver cancer, and a low concentration of medication that reaches liver cancer cells are just a few of the drawbacks of traditional liver cancer chemotherapy. As a result, new techniques and NCs must be developed to transport the medication molecules targeted to the malignant hepatocytes in an acceptable number and duration inside the therapeutic window. Because of the great efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimal adverse effects, therapeutics and theragnostic systems have benefits over conventional chemotherapy. These NCs have a high drug accumulation rate in tumours while causing minimal toxicity in healthy tissues. This study focuses on current research on NC-based therapies and theragnostic drug delivery systems, omitting nanotechnology's negative consequences in the field of drug delivery systems. Clinical advancements of theragnostic NCs for liver cancer, on the other hand, are not covered in this article. Only the most current breakthroughs in NC-based drug delivery systems for liver cancer therapy and diagnosis are discussed in this study. This review will not go over the detrimental effects of individual NCs in the medication delivery system.</p>

Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher ‘effective’ doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

Hyper-branched multifunctional carbon nanotubes carrier for targeted liver cancer therapy

The systemic toxicity of anticancer drugs regularly restricts the use of conventional chemotherapy to treat cancer. In this study, the limitations overcome by profitably fabricating a multifunctional nanocarrier system to carry the anticancer drug into the specific location of the cancer cells. The polyethylene glycol (PEG) was functionalized in the carboxylated multiwalled carbon nanotubes (MWCNT-COOH) through an esterification reaction (MWCNT-PEG). The targeting ligand of folic acid (FA) was covalently bonded with hyperbranched poly-L-lysine (HBPLL) using adipic acid (AA) as a cross-linking agent. Doxorubicin (DOX), an anticancer drug, was effectively loaded on MWCNT-PEG-AA-HBPLL-FA carrier loading, and in-vitro drug release was investigated by UV–Vis spectrophotometer. The chemical functionalization, morphological properties, crystalline nature, surface charge, and thermal stability of the synthesized materials were studied by FT-IR, FE-SEM, HR-TEM, DLS, and TGA techniques. In-vitro cytotoxicity and anticancer properties of DOX-loaded nanocarrier were studied in human liver cancer (HepG2) cells and human embryonic kidney (HEK293) cells. The activities of caspases (caspase −3, −8 & −9) were analyzed using luminometry. The intrinsic apoptosis pathway proteins (Bcl-2 & BAX) were determined by western blot and RT-PCR analysis. The synthesized DOX-loaded nanocarriers exhibited increased cytotoxicity and apoptosis in liver HepG2 cells. The results suggest that the DOX-loaded nanocarrier possesses strong anticancer properties and could be an applicable and potential drug carrier for liver cancer chemotherapy.

The first experience of partial spleen embolization for the correction of thrombocytopenia in patients with liver cirrhosis

Aim. To assess the efficacy and safety of interventional endovascular partial spleen embolization for the correction of thrombocytopenia in patients with liver cirrhosis.Material and methods. From September 2019 to March 2020, 5 partial spleen embolizations were performed at the surgical clinic of the Botkin Hospital. The indication was the impossibility of conducting courses of regional chemotherapy for primary liver cancer in 2 patients with cirrhosis, portal hypertension, hypersplenism, thrombocytopenia, in 3 patients – the impossibility of conducting adequate antiviral therapy with cirrhosis as a result of chronic viral hepatitis C. The platelet count was < 25 thousand/μl (19.34 ± 1.34 thousand/μl) in all patients at the time of the procedure. The median spleen volume was 1967.54 ± 476.13 (1324.34–2163.54) cm3 . We used Progreat® Terumo 2.8 Fr microcatheter 130 cm for catheterization branches of the splenic artery. Endovascular embolization was performed with microspheres 600 ± 75 nm – 2 ml before occlusion. Computed tomography scan of abdominal cavity with intravenous contrast enhancement and laboratory test of platelet levels were performed. Follow up of patients was carried out at 1, 3 and 6 months after this intervention.Results. The postoperative period in all patients was uncomplicated. Postembolization syndrome (pain, hyperthermia) developed in the early postoperative period in all patients on the next day after the procedure. Computed tomography scan of the abdominal cavity revealed areas of an irregular shape of low density that did not accumulate a contrast agent. The duration of hospitalization was 7.63 ± 3.32 (5–11) days. There were not in-hospital and 30-day mortality in our study.Conclusion. The first experience of endovascular partial spleen embolization showed its safety and efficacy in the correction of thrombocytopenia in patients with liver cirrhosis.

Long-circulating doxorubicin and schizandrin A liposome with drug-resistant liver cancer activity: preparation, characterization, and pharmacokinetic

The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (–31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t 1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 μmol/L and 1.38 μmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR.

CK2α causes stemness and chemotherapy resistance in liver cancer through the Hedgehog signaling pathway

BackgroundLiver cancer is one of the major causes of cancer-related deaths globally. Cancer cell stemness and chemotherapy resistance contribute to the high mortality. Although evidence indicates that the alpha subunit of protein kinase 2 (CK2α) is involved in several human cancers, its function in liver cancer remains unknown. In the present study, we aimed to elucidate the role of CK2α in liver cancer. MethodsWe examined the role of CK2α regulation in stemness and chemotherapy resistance capacity of liver cancer cells. MTT assays, tumor sphere formation assays, RT-PCR, flow cytometry, Western blotting assay, clonogenicity assay, matrigel invasion assay and bioinformatics were conducted in this study. ResultsCK2α expression in the liver cancer tissues was notably upregulated compared with that in the corresponding non-tumorous tissues. The overexpression of CK2α promoted tumor sphere formation, increased the percentage of CD133(+) and side population cells, caused the resistance of liver cancer cells to 5-FU treatment, increased the expression levels of NANOG, OCT4, SOX2, Gli1 and Ptch1, and enhanced the ability of CD133(+) cell clone formation and invasion. Consistently, the downregulation of CK2α had the opposite effects. CK2α silencing inhibited the Hedgehog pathway by reducing the expression of Gli1 and Ptch1. Mechanistically, CK2α regulation on liver cancer cell stemness and chemotherapy resistance was found to be involved in the Hedgehog signaling pathway. ConclusionsOur study may bring some new insights into the occurrence of liver cancer. Furthermore, these findings suggest that targeting CK2α may be a novel therapeutic strategy for patients with liver cancer.

Comparison of radiation doses between hepatic artery infusion chemotherapy and transarterial chemoembolization for liver cancer

ObjectiveTo analyze the radiation dose received by patients during hepatic artery infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE) procedures and the related influencing factors. MethodsData of 162 cases in the HAIC group and 230 cases in the TACE group were collected. The included covariates were Age (<45/45–59/≥60 years), BMI levels (underweight/normal weight/obesity), focus Dye of tumor (present/absent), lesion size (<5cm/≥5cm), superselection (present/absent), hepatic vascular variation (present/absent). The endpoints were postoperative dose-area product (DAP), exposure time and Air kerma (AK). ResultsOf all included patients, the HAIC group patients were younger than those in the TACE group (P ​= ​0.028). The proportion of patients with large lesions in the HAIC group was higher than the TACE group (45.7% vs. 33.9%, P ​= ​0.019). The proportion of patients who had superselection was lower in the HAIC group as compared to the TACE group (61.7% vs. 82.2%, P ​< ​0.001). Generally, the HAIC group has lower DAP, exposure time and AK by 36.3% (P ​< ​0.001), 38.2% (P ​< ​0.001), and 41.3% (P ​< ​0.001) than the TACE group, respectively. Linear regression analysis showed the procedure method (HAIC/TACE, P ​< ​0.001), type of DSA machine (Pheno/FD20, P ​< ​0.001), BMI levels (P ​< ​0.001), age (P ​= ​0.021), lesion size (<5cm/≥5 ​cm, P ​= ​0.031) significantly correlated with low DAP. In the HAIC group, the type of DSA machine and BMI correlated with the radiation dose, while in the TACE group, the type of DSA machine, BMI, and lesion size correlated with the radiation dose. ConclusionCompared with TACE, HAIC enables doctors and patients to receive lower radiation doses. Obese patients in both HAIC and TACE groups increase the radiation exposure in interventional doctors and patients, but large lesions only affect the radiation dose in the TACE procedure.