silicon and Pancreatic-Neoplasms

Drug-resistant capacity in a small population of tumor-initiating cancer stem cells (tiCSCs) can be due to aberrant epigenetic changes. However, currently available conventional detection methods are inappropriate and cannot be applied to investigate the scarce population (tiCSCs). In addition, selective inhibitor drugs are shown to reverse epigenetic changes; however, each cancer type is discrete. Hence, it is essential to probe the resultant changes in tiCSCs even after therapy. Therefore, we have developed a multimode nanoplatform to investigate tiCSCs, detect epigenetic changes, and subsequently explore their transformation signals following drug therapy. We performed this by developing a surface-enhanced Raman scattering (SERS)-active nanoplatform integrated with n-dopant using an ultrafast laser ionization technique. The dopant functionalization enhances Raman scattering ability and permits label-free analysis of biomarkers in tiCSCs with the resolution down to the cellular level. Here, we investigated epigenetic biomarkers of tiCSCs in pancreatic and lung cancers. An extended study using inhibitor drugs demonstrates an unexpected increase of tiCSCs from lung cancer; this difference can be attributed to transformation changes in lung tiCSC. Thus, our work brings new insight into the differentiation abilities of CSCs upon epigenetic reversal, emphasizing unique perceptions in cancer treatment.

Topics: Biomarkers, Tumor; Cell Cycle Checkpoints; Cell Line, Tumor; Decitabine; Epigenesis, Genetic; Humans; Hydroxamic Acids; Lasers; Lung Neoplasms; Nanostructures; Neoplastic Stem Cells; Pancreatic Neoplasms; Phosphorus; Silicon; Spectrum Analysis, Raman

Novel functions and involvement of circFARSA have not been reported in pancreatic cancer; in addition, its inhibitor screening has not yet been conducted. The purpose of this study was to (1) verify circFARSA as a novel anti-cancer target for pancreatic cancer and (2) to prepare a novel anti-pancreatic cancer agent targeting circFARSA. In this study, we designed and synthesized a small interfering RNA (siRNA, named siRNA-circFARSA), which specifically inhibits circFARSA expression. Using liposomes and porous silicon nanoparticles (pSiNPs) as siRNA delivery system, we prepared liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA and investigated their anti-cancer mechanism by quantitative real-time PCR and western blotting. Cell proliferation curves and transwell migration assays were performed to investigate the effect of siRNAs proliferation and migration capabilities of cancer cells. Patient-derived tumor xenograft mouse models were used to investigate the anti-cancer effects in vivo. The data showed that both liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA (Si: 0.7 µg/mL) significantly inhibited the proliferation and migration of pancreatic cancer cells in vitro. However, the biological safety and in vivo anti-cancer effects of pSiNP-PEI-siRNA-circFARSA (Si: 22.4 µg/mL) were higher than those of liposome-siRNA-circFARSA. The results showed that siRNA-circFARSA could inhibit the expression of circFARSA and then BCL-2 protein expression, thereby leading to pancreatic cancer cell apoptosis after transportation into pancreatic cancer cells. Therefore, this study provides tools for pancreatic cancer treatment in the future, as it (1) verified circFARSA as a novel target for pancreatic cancer treatment, and (2) prepared a novel anti-pancreatic cancer agent (pSiNP-PEI-siRNA-circFARSA).

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Silencing; Humans; Liposomes; Male; Mice; Mice, Nude; Nanoparticles; Pancreatic Neoplasms; RNA, Circular; RNA, Small Interfering; Silicon; Xenograft Model Antitumor Assays

Efficient and precise circulating tumor cells' (CTCs) capture and release with minimal effect on cell viability for CTCs' analysis are general requirements of CTCs' detection device in clinical application. However, these two essential factors are difficult to be achieved simultaneously.. In order to reach the aforementioned goal, we integrated multiple strategies and technologies of staggered herringbone structure, nanowires' substrate, peptides, enzymatic release, specific cell staining, and gene sequencing into microfluidic device and the sandwich structure peptide-silicon nanowires' substrate was termed as Pe-SiNWS.. The Pe-SiNWS demonstrated excellent capture efficiency (95.6%) and high release efficiency (92.6%). The good purity (28.5%) and cell viability (93.5%) of CTCs could be obtained through specific capture and biological release by using Pe-SiNWS. The good purity of CTCs facilitated precise and quick biological analysis, and five types of KRAS mutation were detected in 16 pancreatic cancer patients but not in healthy donors.. The results proved that the effective capture, minor damage release, and precise analysis of CTCs could be realized simultaneously by our novel strategy. The successful clinical application indicated that our work was anticipated to open up new opportunities for the design of CTC microfluidic device.

Topics: Case-Control Studies; Cell Separation; Humans; Lab-On-A-Chip Devices; Mutation; Nanowires; Neoplastic Cells, Circulating; Pancreatic Neoplasms; Peptide Fragments; Proto-Oncogene Proteins p21(ras); Silicon

Dimethyl sulfoxide porous silicon (DMSO-PSi) colloid in which DMSO was used as a surfactant suitable for inhibiting the agglomeration of PSi nanoparticles was prepared for use in cancer photothermotherapy. The photothermal effect of the DMSO-PSi colloid was found to be high enough to destroy cancer cells (T = ∼52 °C). The mean particle size of the PSi nanoparticles in the DMSO-PSi colloid was 67 nm, which is low enough to flow through blood vessels without causing a blockage. The DMSO-PSi colloid in combination with an NIR laser resulted in a cell viability of 5.70%, which is a sufficiently high cytotoxic effect.

Topics: Cell Line, Tumor; Cell Survival; Colloids; Dimethyl Sulfoxide; Humans; Hyperthermia, Induced; Lasers, Semiconductor; Low-Level Light Therapy; Nanoparticles; Pancreatic Neoplasms; Particle Size; Porosity; Silicon

Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we report the next generation of eDAR, where we designed and optimized a new hydrodynamic switching scheme for the active sorting step in eDAR, which provided fast cell sorting with an improved reproducibility and stability. The microfluidic chip was also simplified by incorporating a functional area for subsequent purification using microslits fabricated by standard lithography method. Using the reported second generation of eDAR, we were able to analyze 1 mL of whole-blood samples in 12.5 min, with a 95% recovery and a zero false positive rate (n = 15).

Topics: Cell Line, Tumor; Cell Separation; Humans; Hydrodynamics; Microfluidic Analytical Techniques; Neoplasm Metastasis; Neoplastic Cells, Circulating; Pancreatic Neoplasms; Silicon

Pancreatic cancer is a highly fatal disease characterized by a dominant stroma formation. Exploring new biological targets, specifically those overexpressed in stroma cells, holds significant potential for the design of specific nanocarriers to attain homing of therapeutic and imaging agents to the tumor. In clinical specimens of pancreatic cancer, we found increased expression of CD59 in tumor associated endothelial cells as well as infiltrating cells in the stroma as compared to uninvolved pancreas. We explored this dual targeting effect using orthotopic human pancreatic cancer in nude mice. By immunofluorescence analysis, we confirmed the increased expression of Ly6C, mouse homolog of CD59, in tumor associated endothelial cells as well as in macrophages within the stroma. We decorated the surface of porous silicon nanocarriers with Ly6C antibody. Targeted nanocarriers injected intravenously accumulated to tumor associated endothelial cells within 15min. At 4h after administration, 9.8±2.3% of injected dose/g tumor of the Ly6C targeting nanocarriers accumulated in the pancreatic tumors as opposed to 0.5±1.8% with non-targeted nanocarriers. These results suggest that Ly6C (or CD59) can serve as a novel dual target to deliver therapeutic agents to the stroma of pancreatic tumors.

Topics: Animals; Antigens, Ly; Antineoplastic Agents; Apoptosis; CD59 Antigens; Cell Line, Tumor; Cell Proliferation; Drug Delivery Systems; Endothelial Cells; Female; Humans; Macrophages; Male; Mice; Mice, Nude; Nanostructures; Pancreatic Neoplasms; Silicon

Conventional quantum dots have great potential in cancer-related imaging and diagnostic applications; however, these applications are limited by concerns about the inherent toxicity of their core materials (e.g., cadmium, lead). Virtually all imaging applications require conjugation of the imaging agent to a biologically active molecule to achieve selective uptake or binding. Here, we report a study of biocompatible silicon quantum dots covalently attached to biomolecules including lysine, folate, antimesothelin, and transferrin. The particles possess desirable physical properties, surface chemistry, and optical properties. Folate- and antimesothelin-conjugated silicon quantum dots show selective uptake into Panc-1 cells. This study contributes to the preclinical evaluation of silicon quantum dots and further demonstrates their potential as an imaging agent for cancer applications.

Topics: Cell Line, Tumor; Coated Materials, Biocompatible; Folic Acid; Humans; Luminescence; Lysine; Materials Testing; Molecular Imaging; Molecular Structure; Pancreatic Neoplasms; Particle Size; Quantum Dots; Silicon; Stereoisomerism; Surface Properties; Transferrin

The synthesis, radiolabeling, and initial evaluation of new silicon-fluoride acceptor (SiFA) derivatized octreotate derivatives is reported. So far, the main drawback of the SiFA technology for the synthesis of PET-radiotracers is the high lipophilicity of the resulting radiopharmaceutical. Consequently, we synthesized new SiFA-octreotate analogues derivatized with Fmoc-NH-PEG-COOH, Fmoc-Asn(Ac₃AcNH-β-Glc)-OH, and SiFA-aldehyde (SIFA-A). The substances could be labeled in high yields (38 ± 4%) and specific activities between 29 and 56 GBq/μmol in short synthesis times of less than 30 min (e.o.b.). The in vitro evaluation of the synthesized conjugates displayed a sst2 receptor affinity (IC₅₀ = 3.3 ± 0.3 nM) comparable to that of somatostatin-28. As a measure of lipophilicity of the conjugates, the log P(ow) was determined and found to be 0.96 for SiFA-Asn(AcNH-β-Glc)-PEG-Tyr³-octreotate and 1.23 for SiFA-Asn(AcNH-β-Glc)-Tyr³-octreotate, which is considerably lower than for SiFA-Tyr³-octreotate (log P(ow) = 1.59). The initial in vivo evaluation of [¹⁸F]SiFA-Asn(AcNH-β-Glc)-PEG-Tyr³-octreotate revealed a significant uptake of radiotracer in the tumor tissue of AR42J tumor-bearing nude mice of 7.7% ID/g tissue weight. These results show that the high lipophilicity of the SiFA moiety can be compensated by applying hydrophilic moieties. Using this approach, a tumor-affine SiFA-containing peptide could successfully be used for receptor imaging for the first time in this proof of concept study.

Topics: Animals; Carbohydrates; Cell Line, Tumor; Diagnostic Imaging; Drug Stability; Fluorides; Fluorine Radioisotopes; Humans; Hydrophobic and Hydrophilic Interactions; Isotope Labeling; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms; Polyethylene Glycols; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Somatostatin; Silicon; Somatostatin-28; Tissue Distribution

Luminescent silicon quantum dots (Si QDs) have great potential for use in biological imaging and diagnostic applications. To exploit this potential, they must remain luminescent and stably dispersed in water and biological fluids over a wide range of pH and salt concentration. There have been many challenges in creating such stable water-dispersible Si QDs, including instability of photoluminescence due their fast oxidation in aqueous environments and the difficulty of attaching hydrophilic molecules to Si QD surfaces. In this paper, we report the preparation of highly stable aqueous suspensions of Si QDs using phospholipid micelles, in which the optical properties of Si nanocrystals are retained. These luminescent micelle-encapsulated Si QDs were used as luminescent labels for pancreatic cancer cells. This paves the way for silicon quantum dots to be a valuable optical probe in biomedical diagnostics.

Topics: Biocompatible Materials; Cell Line, Tumor; Contrast Media; Humans; Image Enhancement; Luminescent Measurements; Pancreatic Neoplasms; Quantum Dots; Silicon

To investigate the use of metal oxide silicon field effect transistors (MOSFETs) as in vivo dosimetry detectors during electron beams at high dose-per-pulse intraoperative radiotherapy.. The MOSFET system response in terms of reproducibility, energy, dose rate and temperature dependence, dose-linearity from 1 to 25 Gy, angular response, and dose perturbation was analyzed in the 6-9-MeV electron beam energy range produced by an intraoperative radiotherapy-dedicated mobile accelerator. We compared these with the 6- and 9-MeV electron beams produced by a conventional accelerator. MOSFETs were also used in clinical dosimetry.. In experimental conditions, the overall uncertainty of the MOSFET response was within 3.5% (+/-SD). The investigated electron energies and the dose rate did not significantly influence the MOSFET calibration factors. The dose perturbation was negligible. In vivo dosimetry results were in accordance with the predicted values within +/-5%. A discordance occurred either for an incorrect position of the dosimeter on the patient or when a great difference existed between the clinical and calibration setup, particularly when performing exit dose measurements.. Metal oxide silicon field effect transistors are suitable for in vivo dosimetry during intraoperative radiotherapy because their overall uncertainty is comparable to the accuracy required in target dose delivery.

Topics: Breast Neoplasms; Calibration; Equipment Design; Female; Humans; Pancreatic Neoplasms; Particle Accelerators; Radiometry; Radiotherapy Dosage; Silicon; Transistors, Electronic

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

Epidemiologic studies have reported associations between gastrointestinal cancer mortality and exposure to cutting fluids and abrasives in metal machining and precision grinding operations. Two previous studies found excess stomach cancer among workers exposed to water-based cutting fluids in bearing plants. This study reports similar findings in a third and larger population. Cause of death and work histories were determined for 1,766 bearing plant workers who died between Jan 1, 1950 and June 30, 1982. Mortality odds ratios (SMOR) and proportional mortality ratios (PMR) revealed significant excesses of gastrointestinal malignancies. The proportional mortality excess for stomach cancer among white men was greatest among those with more than 10 years' exposure in the major grinding group (PMR = 13/3.8 = 3.39; P less than .001). The SMOR by logistic regression for stomach cancer among white men was 2.3 (P = .02) for 25 years' grinding experience. For cancer of the pancreas among white men, there were significant associations with both machining and grinding jobs in straight oil (SMOR = 9.9 and 3.2, respectively, for 25 years duration). These findings could not be explained by confounding due to the ethnic background of the decedents. This study confirms previous evidence that grinding operations using water-based cutting fluids increase the risk for stomach cancer and provides moderate evidence that exposures to straight oil-cutting fluids increase the risk for cancer of the pancreas. There were indications, meriting further investigation, that non-malignant liver disease is associated with cutting fluid exposures and that lung cancer is associated with oil smoke from operations such as forging or heat treating.

Topics: Aluminum; Aluminum Oxide; Carbon; Carbon Compounds, Inorganic; Chemical and Drug Induced Liver Injury; Connecticut; Female; Humans; Industrial Oils; Liver Diseases; Lung Neoplasms; Male; Metallurgy; Occupational Diseases; Pancreatic Neoplasms; Silicon; Silicon Compounds; Smoke; Stomach Neoplasms