silicon and Liver-Neoplasms

Topics: alpha-Fetoproteins; Biomarkers, Tumor; Biosensing Techniques; Carcinoembryonic Antigen; Humans; Liver Neoplasms; Nanowires; Silicon; Transistors, Electronic

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

We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Humans; Indoles; Isoindoles; Liver Neoplasms; Mice; Mice, Nude; Random Allocation; Rhodamines; Silicon; Xenograft Model Antitumor Assays

We demonstrate the synthesis of water-soluble allylamine-terminated Fe-doped Si (Si(xFe)) nanoparticles as bimodal agents for optical and magnetic imaging. The preparation involves the synthesis of a single-source iron-containing precursor, Na(4)Si(4) with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH(4)Br to produce hydrogen-terminated Si(xFe) nanoparticles. The hydrogen-capped nanoparticles are further terminated with allylamine via thermal hydrosilylation. Transmission electron microscopy indicates that the average particle diameter is ∼3.0 ± 1.0 nm. The Si(5Fe) nanoparticles show strong photoluminescence quantum yield in water (∼10%) with significant T(2) contrast (r(2)/r(1) value of 4.31). Electron paramagnetic resonance and Mössbauer spectroscopies indicate that iron in the nanoparticles is in the +3 oxidation state. Analysis of cytotoxicity using the resazurin assay on HepG2 liver cells indicates that the particles have minimal toxicity.

Topics: Cell Line, Tumor; Contrast Media; Echo-Planar Imaging; Humans; Iron; Liver Neoplasms; Microscopy, Fluorescence; Nanoparticles; Silicon

It is known that cellular behavior is affected by nano-patterned topography. For example, many cell types tend to align and extend along the direction of nano-grooves/ridges structures. In this study, we investigated the impact of nano-grooves/ridges on hepatocyte morphology and functions. HepG2/C3A (C3A) cells were cultured on nano-grooved silicon or polystyrene substrata with various widths (from 100 to 500 nm) and depths (from 100 to 380 nm). Nano-grooved substrates induced dramatic changes in C3A cell morphology. The cells formed spheroids on the flat substrates, while C3A cells spread and grew confluently with elongated and aligned morphology along the nano-grooves/ridges. Albumin synthesis was enhanced on the nano-grooved silicon substrates compared to the flat surface, and was decreased with increasing groove depths. Urea conversion on the shallow grooves (400 nm wide and 100 nm deep) remained at the same level of that on the flat surfaces, but was decreased on the deeper grooves. We found that the functions of hepatocytes were enhanced on the substrates with shallow grooves. The nano-grooved substrates may be applied as in vitro culture systems of hepatocytes for both diagnostic and therapeutic applications.

Topics: Albumins; Cell Line, Tumor; Cell Shape; Cytoskeleton; Fluorescent Antibody Technique; Hepatoblastoma; Humans; Liver Neoplasms; Nanostructures; Polystyrenes; Silicon; Surface Properties; Urea

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

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

To evaluate the possible health effects of occupational exposure to a nonasbestos mineral fiber, a cohort of 2,302 males employed for at least 1 month between 1940 and 1975 at an attapulgite (clay fiber) mining and milling facility was followed through 1975. A significant deficit of mortality (SMR = 43, 90% CI 23-76) from nonmalignant respiratory disease (NMRD) was observed for the cohort based on age-, calendar year-, and race-specific rates for U.S. males. A marked deficit of NMRD was seen regardless of presumed dust exposure level, induction-latency period, or duration employed. A statistically significant excess of mortality from lung cancer was observed among whites (SMR = 193, 90% CI 121-293), but a deficit occurred among nonwhites (SMR = 53, 90% CI 21-112). Lung cancer risk in either race was not altered substantially with presumed dust exposure level, induction-latency period, or duration employed with one exception-those employed for at least 5 years in high-exposure-level jobs.

Topics: Dust; Gastrointestinal Neoplasms; Humans; Liver Neoplasms; Lung Neoplasms; Magnesium; Magnesium Compounds; Male; Mining; Occupational Diseases; Retrospective Studies; Risk Factors; Silicon; Silicon Compounds

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