boron and Liver-Neoplasms

An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

Topics: Boron; Boron Compounds; Boron Neutron Capture Therapy; Fructose; Humans; Isotopes; Liver; Liver Neoplasms; Molecular Imaging; Radiopharmaceuticals

As part of the studies on Boron Neutron Capture Therapy at the University of Mainz, Germany, a clinical trial has been started in which, four patients suffering from liver metastases of colorectal carcinoma have been enrolled. Specimens of blood and healthy tissue samples taken from the patients were measured at the PGAA facilities at the HFR in Petten, The Netherlands, and at the FRM II in Munich, Germany. From the measured boron concentrations, pharmacokinetic curves and blood-to-tissue concentration ratios were produced.

Topics: Boron; Colorectal Neoplasms; Humans; Liver Neoplasms

Ex-situ BNCT for multifocal unresectable liver metastases employing whole or partial autograft techniques requires knowledge of boron concentrations in healthy liver and metastases following perfusion and immersion in Wisconsin solution (W), the procedure employed for organ preservation during ex-situ irradiation. Measurements of boron concentration in blood, liver and metastases following an intravenous infusion of BPA-F in five colorectal liver metastases patients scheduled for surgery were performed. Tissue samples were evaluated for boron content pre and post perfusion and immersion in W. Complementary histological studies were performed. The data showed a dose-dependent BPA uptake in liver, a boron concentration ratio liver/blood close to 1 and a wide spread in the metastases/liver concentration ratios in the range 0.8-3.6, partially attributable to histological variations between samples. Based on the boron concentrations and dose considerations (liver < or =15 Gy-Eq and tumor> or =40 Gy-Eq) at the RA-3 thermal neutron facility (mean flux of about (6+/-1) x 10(9) n cm(-2)s(-1)), ex-situ treatment of liver metastases at RA-3 would be feasible.

Topics: Adenocarcinoma; Aged; Argentina; Boron; Boron Compounds; Boron Neutron Capture Therapy; Colorectal Neoplasms; Female; Humans; In Vitro Techniques; Infusions, Intravenous; Isotopes; Liver; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Phenylalanine; Radiation-Sensitizing Agents; Tissue Distribution; Transplantation, Autologous

Ferroptosis is a form of regulated cell death (RCD) characterized by intracellular iron ion accumulation and reactive oxygen species (ROS)-induced lipid peroxidation. Ferroptosis in cancer and ferroptosis-related anticancer drugs have recently gained interest in the field of cancer treatment. Boron is an essential trace element playing an important role in several biological processes. Recent studies have described contrasting effects of boric acid (BA) in cancer cells, ranging from protective/mitogenic to damaging/antiproliferative. Interestingly, boron has been shown to interfere with critical factors involved in ferroptosis-intracellular glutathione and lipid peroxidation in the first place. Thus, the present study was aimed to verify the ability of boron to modulate the ferroptotic process in HepG2 cells, a model of hepatocellular carcinoma. Our results indicate that-when used at high, pharmacological concentrations-BA can increase intracellular ROS, glutathione, and TBARS levels, and enhance ferroptosis induced by RSL3 and erastin. Also, high BA concentrations can directly induce ferroptosis, and such BA-induced ferroptosis can add to the cytotoxic effects of anticancer drugs sorafenib, doxorubicin and cisplatin. These observations suggest that BA could be exploited as a chemo-sensitizer agent in order to overcome cancer drug resistance in selected conditions. However, the possibility of reaching suitably high concentrations of BA in the tumor microenvironment will need to be further investigated.

Topics: Antineoplastic Agents; Boron; Cell Death; Ferroptosis; Glutathione; Humans; Lipid Peroxidation; Liver Neoplasms; Reactive Oxygen Species; Tumor Microenvironment

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes.

Topics: Boranes; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Liver Neoplasms; Oligosaccharides

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Poor prognosis of HCC patients is a major issue, thus, better treatment options for patients are required. Curcumin (Cur), hydrophobic polyphenol of the plant turmeric, shows anti-proliferative, apoptotic, and anti-oxidative properties. Boron is a trace element which is essential part of human nutrition. Sodium pentaborate pentahydrate (NaB), a boron derivative, is an effective agent against cancer. In the current study, we performed in vitro experiments and transcriptome analysis to determine the response of NaB, Cur, piperine (Pip) and their combination in two different HCC cell lines, HepG2 and Hep3B. NaB and Cur induced cytotoxicity in a dose and time dependent manner in HepG2 and Hep3B, whereas Pip showed no significant toxic effect. Synergistic effect of combined treatment with NaB, Cur and Pip on HCC cells was observed on cytotoxicity, apoptosis and cell cycle assay. Following in vitro studies, we performed RNA-seq transcriptome analysis on NaB, Cur and Pip and their combination on HepG2 and Hep3B cells. Transcriptome analysis reveals combined treatment of NaB, Cur and Pip induces anti-cancer activity in both of HCC cells.

Topics: Boron; Carcinoma, Hepatocellular; Cell Line; Curcumin; Humans; Liver Neoplasms

The possible anti-cancer properties of boron, a trace element for humans, have been demonstrated in various experimental and epidemiological studies, although the effects of boron on liver cancer are unclear. In the present study we evaluate the effects of boric acid on the cell lines of hepatocellular carcinoma (HCC) of the liver, as the leading form of liver cancer, for which a poorly-differentiated HCC cell line (Mahlavu cell line) was used.. The anti-cancer effect of boric acid was investigated with a cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques. Also, the effect of boric acid on the AKT signaling pathway was determined through a western blot analysis.. Boric acid was found to reduce cell viability in a dose- and time-dependent manner, and decreased survival, colony formation ability, migration capability and HCC cell tumor spheroid growth in HCC cell lines, while also inducing apoptosis, autophagy and morphological alteration. Furthermore, boric acid inhibited AKT phosphorylation, and anticancer biological responses in HCC cells were observed only in cells in which AKT phosphorylation was suppressed by boric acid.. Our results suggest that boric acid might be a promising therapeutic candidate in hepatocellular carcinoma via the inhibition of AKT signaling pathway.

Topics: Apoptosis; Boric Acids; Boron; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Humans; Liver Neoplasms; Proto-Oncogene Proteins c-akt; Signal Transduction

Reactive oxygen species (ROS) regulate various cellular signaling pathways and play an important role in the occurrence and development of hepatocellular carcinoma (HCC). Excessive accumulation of ROS can promote HCC. Trace element boron has a wide range of biological effects, including anti-oxidation, anti-tumor, immune regulation and so on.. In this study, we investigated the anticancer effects of Sodium tetraborate decahydrate (NaB) in improving oxidative stress and regulating apoptosis in mouse HCC. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN) 25 mg/kg once at the age of 2 weeks and 100 mg/kg again at the age of 6 weeks in healthy C3H/HeN male mice. At 8 weeks of age, different concentrations of NaB were given intragastric treatment once a day for 20 weeks. Oxidative stress markers, antioxidant status and liver enzyme analysis were detected to evaluate the effectiveness of NaB in inhibiting cancer induction. The anticancer properties of NaB were confirmed by observing the liver index and morphology, and analyzing the expression of apoptotic genes and proteins. Our results showed that boron significantly reduced the production of ROS, and down-regulated the expression of the anti-apoptotic protein Bcl2 and up-regulated the expression of the pro-apoptotic proteins P53, Bax, and caspase 3.. Boron has great potential to reduce the effects of oxidative stress, which may help it inhibit the progression of HCC.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Boron; Carcinoma, Hepatocellular; Caspase 3; Diethylnitrosamine; Liver Neoplasms; Male; Mice; Mice, Inbred C3H; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Trace Elements; Tumor Suppressor Protein p53

Boron has an important potential for facilitating biological activity and for use in pharmaceutical drug design. Boron glycine monoester (BGM) and boron glycine diester (BGD) compounds containing boron atoms were synthesized and investigated their cytotoxic, oxidative stress, and antimicrobial activities on the HepG2 cancer cell line. The cytotoxic activity of newly synthesized boron compounds on hepatocellular carcinoma was determined by the MTT method for 48 h. Antioxidant (CAT, GSH), lipid peroxidation (MDA), and enzyme activity (ACP, ALP) analyses were determined by spectrophotometric methods in HepG2 cells. Antimicrobial activity was determined by the disk diffusion method. After 48 h of BGM and BGD application to HepG2 cells, we found the IC

Topics: Antioxidants; Boron; Boron Compounds; Carcinoma, Hepatocellular; Glycine; Humans; Liver Neoplasms

Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a. We prepared the. Biodistribution results have revealed that. Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the

Topics: Animals; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Disease Models, Animal; Emulsions; Liver Neoplasms; Papaver; Plant Oils; Rabbits; Seeds; Tissue Distribution

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model.. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses.. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded.. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

Topics: Animals; Boric Acids; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Disease Models, Animal; Liver; Liver Neoplasms; Male; Rats; Rats, Sprague-Dawley; Tissue Distribution

Hepatocellular carcinoma (HCC) is a common malignancy and the main cause of mortality in patients with chronic liver diseases. This study reports the inhibitory effect of boron on HCC induced in rats by administering thioacetamide (TAA) (0.03%) in drinking water for 400days. Boron (4mg/kg body weight) was administered orally after induction of carcinoma. Treatment was continued for 122days, and cell proliferation, histology and biochemistry of treated and control group of rats were studied. Proliferating cell nuclear antigen (PCNA), and [(3)H]-thymidine incorporation, which increased in rats exposed to carcinogen, significantly decreased after boron treatment. PCNA index decreased from 80 in HCC rats to 32 after boron treatment. In the control group, it was 20. Boron caused a dose-dependent decrease in carcinogen-induced [(3)H]-thymidine uptake by the rat hepatocyte. It could partially reverse the activity of selected biochemical indicators of hepatic damage, oxidative stress, selenium and serum retinol, which are depleted in liver cancer, and improved overall health of animal. The study implicates the elevated levels of mammalian molybdenum Fe-S containing flavin hydroxylases, which increase the free radical production and oxidative stress, consequently causing increased hepatic cell proliferation in HCC, and reports boron to ameliorate these changes in liver cancer.

Topics: Animals; Boron; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation; Female; Liver Neoplasms; Molybdenum; Oxidative Stress; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Treatment Outcome

Hepatocellular carcinoma remains widely prevalent in tropical Africa and south-east Asia. At present, there are no effective treatments for hepatoma and its prognosis is extremely poor unless the tumor was diagnosed in an early stage and resected before metastasis. Therefore, boron neutron capture therapy (BNCT) may provide an alternative therapy for treatment of hepatocellular carcinoma. In this study, the intracellular concentrations of L-boronophenylalanine (BPA), sodium borocaptate (BSH) and boric acid (BA) were examined in human hepatoma HepG2 and liver Clone 9 cell cultures. With the use of 25 microgB/mL media of BPA, BSH and BA, the intracellular uptake of boron in HepG2 and Clone 9 cells was compared. The suitability of BPA, BSH and BA were further evaluated on the basis of organ-specific boron distribution in normal rat tissues. BPA, BSH and BA were administered via intraperitoneal injection into rats with corresponding boron concentrations of 7, 25, and 25mg/kg body weight, respectively. The accumulation rates of BPA, BSH and BA in HepG2 cells were higher than that of Clone 9 cells. Boron concentration in BPA, BSH and BA treated HepG2 cells were 1.8, 1.5, and 1.6-fold of Clone 9 cells at 4h, respectively. In both HepG2 and Clone 9 cells, although the concentration of boron in BPA-treated cells exceeded that in BA-treated ones, however, cells treated with BPA had similar surviving fraction as those treated with BA after neutron irradiation. The accumulation ratios of boron in liver, pancreas and kidney to boron in blood were 0.83, 4.16 and 2.47, respectively, in BPA treated rats, and 0.75, 0.35 and 2.89, respectively, in BSH treated rats at 3h after treatment. However, boron does not appear to accumulate specifically in soft tissues in BA treated rats. For in situ BNCT of hepatoma, normal organs with high boron concentration and adjacent to liver may be damaged in neutron irradiation. BPA showed high retention in pancreas and may not be a good drug for BNCT of hepatoma. BSH had higher retention in liver but low level in pancreas and spleen appears to be a better candidate BNCT drug for hepatoma. These preliminary results provide useful information on future application of BNCT for hepatoma.

Topics: Animals; Boric Acids; Borohydrides; Boron; Boron Compounds; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Clone Cells; Hepatocytes; Humans; Liver Neoplasms; Phenylalanine; Radiation-Sensitizing Agents; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds; Tissue Distribution

For the application of the BNCT for the excorporal treatment of organs at the TRIGA Mainz, the basic characteristics of the radiation field in the thermal column as beam geometry, neutron and gamma ray energies, angular distributions, neutron flux, as well as absorbed gamma and neutron doses must be determined in a reproducible way. To determine the mixed irradiation field thermoluminescence detectors (TLD) made of CaF(2):Tm with a newly developed energy-compensation filter system and LiF:Mg,Ti materials with different (6)Li concentrations and different thicknesses as well as thin gold foils were used.

Topics: Boron; Boron Neutron Capture Therapy; Energy Transfer; Fast Neutrons; Fluorides; Gamma Rays; Germany; Humans; In Vitro Techniques; Isotopes; Lithium Compounds; Liver Neoplasms; Liver Transplantation; Nuclear Reactors; Phantoms, Imaging; Radiation-Sensitizing Agents; Radiotherapy Planning, Computer-Assisted; Thermoluminescent Dosimetry; Transplantation, Autologous

A Monte Carlo calculation was carried out for boron neutron capture therapy (BNCT) of extra corporal liver phantom. The present paper describes the basis for a subsequent clinical application of the prompt gamma spectroscopy set-up aimed at in vivo monitoring of boron distribution. MCNP code was used first to validate the homogeneity in thermal neutron field in the liver phantom and simulate the gamma ray detection system (collimator and detector) in the treatment room. The gamma ray of 478 keV emitted by boron in small specific region can be detected and a mathematical formalism was used for the tomography image reconstruction.

Topics: Boron; Boron Neutron Capture Therapy; Fast Neutrons; Humans; Image Processing, Computer-Assisted; In Vitro Techniques; Liver Neoplasms; Models, Statistical; Monte Carlo Method; Netherlands; Phantoms, Imaging; Spectrometry, Gamma

The purpose of this study was to evaluate boron distribution for a safe and effective BNCT (Boron Neutron Capture Therapy) of liver metastases. Samples both from healthy and tumour liver parenchyma were analysed, after i.v. boron administration, by: alpha particles counting under neutron irradiation; morphological analysis by standard haematoxylin-eosin staining; neutron autoradiography. Our method was unaffected by the cytological heterogeneity inside tumour nodules; it demonstrated selective boron distribution in tumour tissue and predicted estimated mean therapeutic doses in tumour and safety doses in healthy tissue. The time interval for efficient BNCT was 2 to 4 hours after i.v. boron administration.

Topics: Animals; Boron; Boron Neutron Capture Therapy; Colorectal Neoplasms; Liver Neoplasms; Male; Rats; Tissue Distribution