silicon and Carcinoma--Hepatocellular

The prevalence of hepatitis B virus (HBV) is a global healthcare threat, particularly chronic hepatitis B (CHB) that might lead to hepatocellular carcinoma (HCC) should not be neglected. Although many types of HBV diagnosis detection methods are available, some technical challenges, such as the high cost or lack of practical feasibility, need to be overcome. In this study, the polycrystalline silicon nanowire field-effect transistors (pSiNWFETs) were fabricated through commercial process technology and then chemically functionalized for sensing hepatitis B virus surface antigen (HBsAg) and hepatitis B virus X protein (HBx) at the femto-molar level. These two proteins have been suggested to be related to the HCC development, while the former is also the hallmark for HBV diagnosis, and the latter is an RNA-binding protein. Interestingly, these two proteins carried opposite net charges, which could serve as complementary candidates for evaluating the charge-based sensing mechanism in the pSiNWFET. The measurements on the threshold voltage shifts of pSiNWFETs showed a consistent correspondence to the polarity of the charges on the proteins studied. We believe that this report can pave the way towards developing an approachable tool for biomedical applications.

Topics: Carcinoma, Hepatocellular; Delivery of Health Care; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Liver Neoplasms; Nanowires; Silicon; Trans-Activators; Viral Regulatory and Accessory Proteins

Silicon nanopost array (NAPA) structures have been shown to be effective substrates for laser desorption/ionization-mass spectrometry (LDI-MS) and have been used to analyze a variety of samples including peptides, metabolites, drugs, explosives, and intact cells, as well as to image lipids and metabolites in tissue sections. However, no direct comparison has yet been conducted between NAPA-MS and the most commonly used LDI-MS technique, matrix-assisted laser desorption/ionization (MALDI)-MS. In this work, we compare the utility of NAPA-MS to that of MALDI-MS using two common matrices for the analysis of metabolites in cellular extracts and human urine. Considerable complementarity of molecular coverage was observed between the two techniques. Of 178 total metabolites assigned from cellular extracts, 68 were uniquely detected by NAPA-MS and 62 were uniquely detected by MALDI-MS. NAPA-MS was found to provide enhanced coverage of low-molecular weight compounds such as amino acids, whereas MALDI afforded better detection of larger, labile compounds including nucleotides. In the case of urine, a sample largely devoid of higher-mass labile compounds, 88 compounds were uniquely detected by NAPA-MS and 13 by MALDI-MS. NAPA-MS also favored more extensive alkali metal cation adduction relative to MALDI-MS, with the [M + 2Na/K - H]

Topics: Carcinoma, Hepatocellular; Hep G2 Cells; High-Throughput Screening Assays; Humans; Isotope Labeling; Lasers; Liver Neoplasms; Metabolome; Metabolomics; Nanostructures; Reproducibility of Results; Silicon; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The emergence of fluorescent nanomaterials with excellent performances has triggered the development of fluorescence analysis technique, which possesses several advantages in the research and clinical applications. However, current strategies for fluorescence immunoassay usually involve the routine fluorophore-labeled antibody and/or awkward signal generation procedure that may not be available in conventional enzyme-linked immunosorbent assay (ELISA) systems. Herein, we circumvent this problem by imparting an exquisite signal generation mechanism to commercially available alkaline phosphatase (ALP)-based ELISA platform and putting forward a conceptual fluorescent ELISA system based on an original ALP-enabled in situ synthesis of fluorescent nanomaterials. After adding target antigen, the presence of ALP labeled on antibody catalyzes the transformation of the substrate ascorbic acid 2-phosphate into ascorbic acid. Then the resultant ascorbic acid (i.e., ascorbate) interacts with amine-containing silane molecules (no fluorescence) to produce intense cyan fluorescent silicon nanoparticles. For the proof-of-concept, alpha-fetoprotein and human immunoglobulin G are chosen as the model antigen targets, and our proposed immunoassay (designated as the nanoparticles generation-based fluorescent ELISA) enables the detection with either fluorescence spectroscopy or naked-eye readout under the ultraviolet lamp. The convincing recognition mechanism and assay performance ensure fluorescent ELISA to quantitatively evaluate the alpha-fetoprotein level in serologic test and potentially apply in the clinic diagnosis of hepatocellular carcinoma.

Topics: Alkaline Phosphatase; alpha-Fetoproteins; Antigen-Antibody Reactions; Carcinoma, Hepatocellular; Enzyme-Linked Immunosorbent Assay; Fluorescence; Fluorescent Dyes; Humans; Immunoglobulin G; Liver Neoplasms; Molecular Structure; Nanoparticles; Silicon; Spectrometry, Fluorescence

Peptide nucleic acids (PNA) are a unique class of synthetic molecules that have a peptide backbone and can hybridize with nucleic acids. Here, a versatile method has been developed for the automated, in situ synthesis of PNA from a porous silicon (PSi) substrate for applications in gene therapy and biosensing. Nondestructive optical measurements were performed to monitor single base additions of PNA initiated from (3-aminopropyl)triethoxysilane attached to the surface of PSi films, and mass spectrometry was conducted to verify synthesis of the desired sequence. Comparison of in situ synthesis to postsynthesis surface conjugation of the full PNA molecules showed that surface mediated, in situ PNA synthesis increased loading 8-fold. For therapeutic proof-of-concept, controlled PNA release from PSi films was characterized in phosphate buffered saline, and PSi nanoparticles fabricated from PSi films containing in situ grown PNA complementary to micro-RNA (miR) 122 generated significant anti-miR activity in a Huh7 psiCHECK-miR122 cell line. The applicability of this platform for biosensing was also demonstrated using optical measurements that indicated selective hybridization of complementary DNA target molecules to PNA synthesized in situ on PSi films. These collective data confirm that we have established a novel PNA-PSi platform with broad utility in drug delivery and biosensing.

Topics: Biosensing Techniques; Carcinoma, Hepatocellular; DNA; Drug Delivery Systems; Humans; Liver Neoplasms; Mass Spectrometry; MicroRNAs; Nanoparticles; Nucleic Acid Hybridization; Peptide Nucleic Acids; Porosity; Propylamines; Silanes; Silicon; Tumor Cells, Cultured

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.

Topics: Animals; Carcinoma, Hepatocellular; Cosmic Radiation; Humans; Iron; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Liver Neoplasms, Experimental; Male; Mice, Inbred C3H; Radiation Injuries, Experimental; Silicon; Space Flight

The interactions of four novel silicon(IV) phthalocyanines (SiPc), namely SiPc[OC(3)H(5)(NMe(2))(2)](2) (1), SiPc[OC(3)H(5)(NMe(2))(2)](OMe) (2), {SiPc[OC(3)H(5)(NMe(3))(2)](2)}I(4) (3), and {SiPc[OC(3)H(5)(NMe(3))(2)](OMe)}I(2) (4) with human serum albumin (HSA), bovine serum albumin (BSA), and maleylated bovine serum albumin (mBSA) were studied by fluorescence spectroscopy. The fluorescence emission of the serum albumins was effectively quenched by these phthalocyanines mainly through a static quenching mechanism. The higher Stern-Volmer quenching constants for the unsymmetrically substituted phthalocyanines 2 and 4 suggested that they have a stronger interaction with these proteins than the symmetrically substituted analogues 1 and 3. A series of non-covalent BSA or mBSA conjugates of these phthalocyanines were also prepared and evaluated for their in vitro photodynamic activity against HepG2 human hepatocarcinoma cells. The bioconjugation could enhance the photocytotoxicity of 1 and 4 by up to eight folds, but the effects on 2 and 3 were negligible. The results could be partly explained by two counter-balancing effects, namely the enhanced uptake and increased aggregation tendency of phthalocyanine due to BSA conjugation. As shown by absorption spectroscopy, the tetracationic phthalocyanine 3 was significantly aggregated in the protein cavity and its photocytotoxicity remained the lowest among the four photosensitizers.

Topics: Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Indoles; Isoindoles; Liver Neoplasms; Photosensitizing Agents; Serum Albumin, Bovine; Silicon; Spectrometry, Fluorescence

32P BioSilicon is a new, implantable, radiological medical device that comprises particles of highly pure silicon encapsulating 32phosphorus (32P) for the treatment of unresectable solid tumors. Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32)P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study.. Cultured human carcinoma cells (HepG2 and 2119) were injected s.c. into the gluteal region of nude mice. When the implanted tumors were approximately 1 cm in diameter, 32P BioSilicon (0.5, 1.0, and 2.0 MBq) or formulant was injected into the tumors. Implanted tumor size was measured once a week for 10 weeks. At study termination, the tumor and surrounding normal tissue were collected and fixed in 10% formalin and processed for histopathologic analysis.. 32P BioSilicon produced a reduction in HepG2 tumor volume when compared with formulant control, and complete response was observed among tumors in the 1.0 and 2.0 MBq treatment groups after week 8. There was also significant reduction in 2119 tumor volume in all treated groups, with the complete response rate of 67% in the 2.0 MBq group.. 32P BioSilicon suppressed the growth of both human hepatocellular and pancreatic carcinoma xenografts implanted in nude mice and complete responses were also observed in tumors at higher radiation doses.

Topics: Animals; Brachytherapy; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Radiation; Humans; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms; Phosphorus Radioisotopes; Silicon; Treatment Outcome; Xenograft Model Antitumor Assays

It is essential to detect section planes during hepatectomy, notably for limited resections in cirrhotic patients. The authors describe a technical artifice, the use silicon-impregnated compresses, to help in the peroperative ultrasonographic detection of these section planes.

Topics: Carcinoma, Hepatocellular; Hepatectomy; Humans; Liver Cirrhosis; Liver Neoplasms; Silicon; Surgical Mesh; Ultrasonography

Topics: Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Fractionation; Chlorides; Chromatography; Electrophoresis; Escherichia coli; Gases; Hydrocarbons, Halogenated; Liver Neoplasms; Methods; Molecular Weight; Nucleosides; Nucleotides; Phosphoric Monoester Hydrolases; Quaternary Ammonium Compounds; Rats; Ribosomes; RNA; RNA, Bacterial; RNA, Neoplasm; RNA, Ribosomal; Silicon; Silicon Dioxide; Snakes; Solubility; Solvents; Spectrophotometry; Spleen; Ultracentrifugation; Ultraviolet Rays; Venoms