silicon and Breast-Neoplasms

Dear Editor, Silicone is a hydrophobic polymer containing silicon. Silicon is an essential compound of soft tissue proteoglycans. Reports about morphea and other autoimmune connective tissue disorders in association with silicone implants have stimulated the discussion of a possible link between the two, such as immunological cross-reactivity of silicone and connective tissue components (1). A number of case reports suggested a possible link to adjuvant autoimmune syndrome (2), morphea of the breast (3-5), and systemic scleroderma (6-8), among others. One study measured tissue silicon levels in women with silicone breast implants with and without symptoms or signs and compared these data with women who had either a saline breast implant or no augmentation at all. The authors detected higher levels of silicon in capsular tissue of patients with silicone implants, independent of the presence of any symptoms or signs (9,10). The conclusion was that there is no evidence of an association between silicone implants and autoimmune connective tissue disorders. Three other clinical trials investigating the role of silicone implants and induction of autoimmune connective tissue disorders also failed to find an association between the two (11-13). We report the case of a 32-year-old female patient who developed morphea of the breasts after silicone implants for augmentation after risk-reducing mastectomy for Cowden syndrome. She presented with pronounced capsule fibrosis of the implants. With a delay of several years, an ill-defined slightly hyperpigmented area developed on the breasts and ventral chest (Figure 1). The lesion was analyzed by dermoscopy (Figure 2), which found mild erythema, reduced vessels, and white areas (ill-defined dull white globules, fibrotic beams). A skin biopsy was taken. Histopathological analysis showed a normal epidermal layer, minor papillary edema, and some vascular ectasias in the papillary dermis and upper corium (Figure 3). There was mild perivascular inflammatory infiltrate of the deep dermal vascular plexus, composed of lymphocytes and monocytes with some plasma cells (Figure 4). Elastic fibers seemed unaffected (Figure 5). The diagnosis of an early morphea of the edematous-inflammatory stage was established. Treatment with topical corticosteroids and UVB-311 nm irradiation was recommended. Morphea of the breasts is an uncommon disorder. It may occur after radiotherapy of breast cancer, after silicone augmentation, or without any

Topics: Adult; Autoimmune Diseases; Breast Neoplasms; Female; Fibrosis; Humans; Mastectomy; Scleroderma, Localized; Silicon; Silicones

Breast cancer (BC) is known to be a highly heterogeneous disease that is clinically subdivided into four primary molecular subtypes, each having distinct morphology and clinical implications. These subtypes are principally defined by hormone receptors and other proteins involved (or not involved) in BC development. BC therapeutic vaccines [including peptide-based vaccines, protein-based vaccines, nucleic acid-based vaccines (DNA/RNA vaccines), bacterial/viral-based vaccines, and different immune cell-based vaccines] have emerged as an appealing class of cancer immunotherapeutics when used alone or combined with other immunotherapies. Employing the immune system to eliminate BC cells is a novel therapeutic modality. The benefit of active immunotherapies is that they develop protection against neoplastic tissue and readjust the immune system to an anti-tumor monitoring state. Such immunovaccines have not yet shown effectiveness for BC treatment in clinical trials. In recent years, nanomedicines have opened new windows to increase the effectiveness of vaccinations to treat BC. In this context, some nanoplatforms have been designed to efficiently deliver molecular, cellular, or subcellular vaccines to BC cells, increasing the efficacy and persistence of anti-tumor immunity while minimizing undesirable side effects. Immunostimulatory nano-adjuvants, liposomal-based vaccines, polymeric vaccines, virus-like particles, lipid/calcium/phosphate nanoparticles, chitosan-derived nanostructures, porous silicon microparticles, and selenium nanoparticles are among the newly designed nanostructures that have been used to facilitate antigen internalization and presentation by antigen-presenting cells, increase antigen stability, enhance vaccine antigenicity and remedial effectivity, promote antigen escape from the endosome, improve cytotoxic T lymphocyte responses, and produce humoral immune responses in BC cells. Here, we summarized the existing subtypes of BC and shed light on immunomodulatory and nano-therapeutic strategies for BC vaccination. Finally, we reviewed ongoing clinical trials on BC vaccination and highlighted near-term opportunities for moving forward.

Topics: Adjuvants, Immunologic; Breast Neoplasms; Calcium; Cancer Vaccines; Chitosan; Female; Hormones; Humans; Lipids; Peptides; Phosphates; Selenium; Silicon; Vaccines; Vaccines, DNA; Vaccines, Subunit

In 2006, the group of Dr C.M. Lieber pioneered the field of nanowire sensors by fabricating devices for the ultra-sensitive label-free detection of biological macromolecules. Since then, nanowire sensors have demonstrated their ability to detect cancer-associated analytes in peripheral blood, tumor tissue, and the exhaled breath of cancer patients. These innovative developments have marked a new era with unprecedented detection performance, capable of addressing crucial needs such as cancer diagnosis and monitoring disease progression and patient response to therapy. The ability of nanowire sensors to identify molecular features of patient tumor represents a first step toward precision medicine, and their integration into portable devices has the potential to revolutionize cancer diagnosis and patient monitoring.

Topics: Antigens, Neoplasm; Biosensing Techniques; Breast Neoplasms; Female; Humans; Molecular Diagnostic Techniques; Nanowires; Silicon

Approximately 500,000 cosmetic breast operations will be done in 2006. The majority of these are for cosmetic reasons and include breast augmentations, mastopexies, and breast reductions. Augmentations are most commonly performed using saline implants in strictly cosmetic situations and occasionally silicon implants in select cases. Complications are unusual, breast feeding is usually possible and mammographic cancer detection is accurate provided that specific mammographic views are obtained. Most cosmetic breast surgery is not covered by insurance with the exception of breast reduction.

Topics: Breast; Breast Implantation; Breast Implants; Breast Neoplasms; Esthetics; Female; Humans; Mammaplasty; Quality of Life; Silicon; Sodium Chloride

Twenty patients with early breast cancer were treated with external irradiation, delivered with two tangential beams (6 MV X-rays) using a half-beam block (HBB) and 3-D compensating filters. All patients were immobilized with individualized cellulose acetate casts. Patient dosimetry was performed using p-type silicon detectors. Midline doses were calculated by combined entrance and exit dose measurements. The mean ratio of the measured and the prescribed doses was 96.6 +/- 3.8% at the reference point, 96.8 +/- 4.3% at off-axis points on the central plane and 96.8 +/- 7.6% at off-plane points.

Topics: Breast Neoplasms; Calibration; Dose-Response Relationship, Radiation; Female; Humans; Immobilization; Quality Assurance, Health Care; Radiotherapy Dosage; Radiotherapy, Computer-Assisted; Radiotherapy, High-Energy; Silicon

Currently, traditional cancer treatment strategies are greatly challenged by the existence of cancer stem cells (CSCs), which are root cause of chemotherapy resistance. Differentiation therapy presents a novel therapeutic strategy for CSC-targeted therapy. However, there are very few studies on the induction of CSCs differentiation so far. Silicon nanowire array (SiNWA) with many unique properties is considered to be an excellent material for various applications ranging from biotechnology to biomedical applications. In this study, we report the SiNWA differentiates MCF-7-derived breast CSCs (BCSCs) into non-CSCs by modulating the morphology of cells. In vitro, the differentiated BCSCs lose the stemness properties and thus become sensitive to chemotherapeutic drugs, eventually leading to the death of BCSCs. Therefore, this work suggests a potential approach for overcoming chemotherapeutic resistance.

Topics: Breast Neoplasms; Cell Differentiation; Cell Line, Tumor; Female; Humans; Nanowires; Neoplastic Stem Cells; Silicon

Currently, the treatment strategy for bone metastasis is mainly to inhibit the growth of tumor cells and the activity of osteoclasts, while ignoring the influence of the tumor stromal microenvironment (TSM) on the progression of bone metastasis. Herein, a dual-target liquid metal (LM)-based drug delivery system (DDS) with favorable photothermal performance is designed to spatially program the delivery of multiple therapeutic agents to enhance the treatment of bone metastasis through TSM remodeling. Briefly, mesoporous silicon-coated LM is integrated into zeolitic imidazolate framework-8 (ZIF-8) with both bone-seeking and tumor-targeting capacities. Curcumin (Cur), a tumor microenvironment modulator, is encapsulated into ZIF-8, and doxorubicin (DOX) is enclosed inside mesoporous silicon. Specific accumulation of the LM-based DDS in bone metastases first relieves the tumor stroma by releasing Cur in response to the acidic tumor microenvironment and then releases DOX deep into the tumor under near-infrared light irradiation. The combined strategy of the LM-based DDS and mild photothermal therapy has been shown to effectively restrain cross-talk between osteoclasts and tumor cells by inhibiting the secretion of transforming growth factor-β, degrading extracellular matrix components, and increasing infiltration of CD4

Topics: Bone Neoplasms; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Doxorubicin; Female; Humans; Hyperthermia, Induced; Metal Nanoparticles; Nanoparticles; Phototherapy; Photothermal Therapy; Silicon; Tumor Microenvironment

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Topics: Biosensing Techniques; Breast Neoplasms; Female; Humans; Metal Nanoparticles; Silicon; Silver; Spectrum Analysis, Raman

Breast cancer (BC) is the most common malignant tumors and the leading cause of cancer deaths among women. The early diagnosis and treatment of BC are effective measures that can increase survival rates and reduce mortality. Carbohydrate antigens 15-3 (CA15-3) and carcinoma embryonic antigens (CEA) have been regarded as the most two valuable tumor markers of BC. The combined detection of CA15-3 and CEA could improve the sensitivity and accuracy of early diagnosis for BC.. The multi-channel double-gate silicon nanowire field effect transistor (SiNW-FET) biosensors were fabricated by using the top-down semiconductor manufacturing technology. By surface modification of the different SiNW surfaces with monoclonal CA15-3 and CEA antibodies separately, the prepared SiNW-FET was processed into biosensor for dual-channel detection of CA15-3 and CEA.. The prepared SiNW-FET biosensors were proved to have high sensitivity and specificity for the dual-channel detection of CA15-3 and CEA, and the detection limit is as low as 0.1U/mL CA15-3 and 0.01 ng/mL CEA. Moreover, the SiNW-FET biosensors were able to detect CA15-3 and CEA in serum by connecting a miniature hemodialyzer.. The present study reported a SiNW-FET biosensor for dual-channel detection of breast cancer biomarkers CA15-3 and CEA in serum, which has potential clinical application value for the early diagnosis and curative effect observation of BC.

Topics: Biomarkers, Tumor; Biosensing Techniques; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Early Detection of Cancer; Female; Humans; Mucin-1; Nanowires; Renal Dialysis; Silicon

Topics: Algorithms; Breast Neoplasms; Data Interpretation, Statistical; Female; Gold; Humans; Models, Biological; Multivariate Analysis; Nanoparticles; Reproducibility of Results; Silicon; Spectrum Analysis, Raman; Uterine Cervical Neoplasms

Electrochemical devices for transdermal monitoring of key biomarkers are the potential next frontier of wearable technologies for point-of-care disease diagnosis, including Cancer in which Cancer is the leading cause of death worldwide with estimated 10 million deaths in 2018 according to the World Health Organization and breast cancer is one of the five most common causes of cancer death with over two million cases recorded in 2018. Early diagnosis and prognosis based on monitoring of breast cancer biomarkers is of high importance. In this work, high-density gold coated silicon microneedle arrays (Au-Si-MNA) were simultaneously used as biomarker extraction platform and electrochemical transducer, enabling the selective immunocapture of epidermal growth factor receptor 2 (ErbB2), a key breast cancer biomarker, and its subsequent quantification. The analytical performance of the device was tested in artificial interstitial fluid exhibiting a linear response over a wide concentration range from 10 to 250 ng/mL, with a detection limit of 4.8 ng/mL below the biomarker levels expected in breast cancer patients. As a proof of concept, the immunosensor demonstrated its ability to successfully extract ErbB2 from a phantom gel mimicking the epidermis and dermis layers, and subsequently quantify it showing a linear range from 50 to 250 ng/mL and a detection limit of 25 ng/mL. The uniqueness of this sensing platform combining direct transdermal biomarker extraction and quantification opens up new avenues towards the development of high performing wearable point-of-care devices.

Topics: Biomarkers, Tumor; Biosensing Techniques; Breast Neoplasms; Electrochemical Techniques; Female; Gold; Humans; Immunoassay; Limit of Detection; Metal Nanoparticles; Silicon

The development of drug delivery systems based on external stimuli-responsive nanocarriers is important to overcome multidrug resistance in breast cancer cells. Herein, iron oxide/gold (Fe3O4/Au) nanoparticles were first fabricated via a simple hydrothermal reaction, and subsequently loaded into porous silicon nanoparticles (PSiNPs) via electrostatic interactions to construct PSiNPs@(Fe3O4/Au) nanocomposites. The as-prepared PSiNPs@(Fe3O4/Au) nanocomposites exhibited excellent super-paramagnetism, photothermal effect, and T2-weight magnetic resonance imaging capability. In particular, with the help of a magnetic field, the cellular uptake of PSiNPs@(Fe3O4/Au) nanocomposites was significantly enhanced in drug-resistant breast cancer cells. Moreover, PSiNPs@(Fe3O4/Au) nanocomposites as carriers showed a high loading and NIR light-triggered release of anticancer drugs. Based on the synergistic effect of magnetic field-enhanced cellular uptake and NIR light-triggered intracellular release, the amount of anticancer drug carried by PSiNPs@(Fe3O4/Au) nanocarriers into the nuclei of drug-resistant breast cancer cells sharply increased, accompanied by improved chemo-photothermal therapeutic efficacy. Finally, PSiNPs@(Fe3O4/Au) nanocomposites under the combined conditions of magnetic field attraction and NIR light irradiation also showed improved anticancer drug penetration and accumulation in three-dimensional multicellular spheroids composed of drug-resistant breast cancer cells, leading to a better growth inhibition effect. Overall, the fabricated PSiNPs@(Fe3O4/Au) nanocomposites demonstrated great potential for the therapy of multidrug-resistant breast cancer in future.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cell Proliferation; Cell Survival; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Ferric Compounds; Gold; Humans; Infrared Rays; Magnetic Fields; Materials Testing; MCF-7 Cells; Nanoparticles; Particle Size; Phototherapy; Porosity; Silicon; Static Electricity; Surface Properties; Tumor Cells, Cultured

In advanced breast cancer (BCa) patients, not the primary tumor, but the development of distant metastases, which occur mainly in the organ bone, and their adverse health effects are responsible for high mortality. Targeted delivery of already known drugs which displayed potency, but rather unfavorable pharmacokinetic properties, might be a promising approach to overcome the current limitations of metastatic BCa therapy. Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific. Here, CPT was loaded into porous silicon nanoparticles (pSiNP) displaying the epidermal growth factor receptor (EGFR)-targeting antibody (Ab) cetuximab to generate a soluble and targeted nanoscale delivery vehicle for cancer treatment. After confirming the cytotoxic effect of targeted CPT-loaded pSiNP in vitro on MDA-MB-231BO cells, nanoparticles were studied in a humanized BCa bone metastasis mouse model. Humanized tissue-engineered bone constructs (hTEBCs) provided a humanized microenvironment for BCa bone metastases in female NOD-scid IL2Rg

Topics: Animals; Breast Neoplasms; Camptothecin; Cell Line, Tumor; Female; Humans; Mice; Mice, Inbred NOD; Nanoparticles; Silicon; Tumor Microenvironment

Targeting is vital for precise positioning and efficient therapy, and integrated platforms for diagnosis and therapy have attracted more and more attention. Herein, we established dual-template molecularly imprinted polymer (MIP) coated fluorescent silicon nanoparticles (Si NPs) by using the linear peptide of the extracellular region of human epidermal growth factor receptor-2 (HER2) and adopting doxorubicin (DOX) as templates for targeted imaging and targeted therapy. Benefiting from the epitope imprinting approach, the imprinted sites generated by peptides on the MIP surface can be employed for recognizing the corresponding protein, which allowed the MIP to specifically and actively target HER2-positive breast cancer cells. Because of its ability to identify breast cancer cells, the MIP was applied for targeted fluorescence imaging by taking advantage of the excellent fluorescence properties of Si NPs, and the DOX-loaded MIP (MIP@DOX) can act as a therapeutic probe to effectively target and kill breast cancer cells. In fluorescence images, the targeting of the MIP promoted more uptake of the nanoparticles by cells than the non-imprinted polymer (NIP), so HER2-positive breast cancer cells incubated with the MIP exhibited stronger fluorescence, and there was no significant difference in fluorescence when HER2-negative cells and normal cells were respectively hatched with the MIP and NIP. Importantly, the cell viability was evaluated to demonstrate targeted accumulation and therapy of MIP@DOX for breast cancer cells. The nanoplatform for diagnosis and therapy combined the high sensitivity of fluorescence with the high selectivity of the molecular imprinting technique, which holds vital potential in targeted imaging and targeted therapy in vitro.

Topics: Breast Neoplasms; Cell Line, Tumor; Coated Materials, Biocompatible; Doxorubicin; Drug Delivery Systems; Epitopes; Female; Human Umbilical Vein Endothelial Cells; Humans; Nanoparticles; Optical Imaging; Receptor, ErbB-2; Silicon

Nanocarriers with both targeting ability and stable loading of drugs can more effectively deliver drugs to precise tumor sites for therapeutic effects. Accordingly, we have rationally designed fluorescent molecularly imprinted polymer nanoparticles (FMIPs), which use N-terminal epitope of P32 membrane protein as the primary template and doxorubicin (DOX) as the secondary template. The DOX imprinted cavity can stably carry the drug and the epitope-imprinted cavity allows FMIPs to actively recognize the P32-positive 4T1 cancer cells. The targeted therapeutic effect of DOX-loaded FMIPs (FMIPs@DOX) is investigated in vitro and in vivo. The FMIPs@DOX only causes apoptosis in 4T1 cancer cells compared to C8161 cells (expressing low level of P32). In addition, highly effective inhibition of 4T1 malignant breast tumors using FMIPs@DOX is achieved in the model of tumor-bearing mice. Importantly, the antitumor effect achieved by intravenous injection of FMIPs@DOX is almost identical to that by intratumoral injection. Furthermore, the FMIPs can serve as a targeted fluorescence imaging agent due to the high specificity of the epitope-imprinted cavity and the stable fluorescence of the embedded silicon nanoparticles. These results demonstrate the effectiveness of the FMIPs for active targeted drug delivery and imaging. Furthermore, the FMIPs provide a direction for drug-loaded nanocarrier.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Carriers; Epitopes; Female; Fluorescent Dyes; Humans; Membrane Proteins; Mice; Microscopy, Confocal; Molecular Imprinting; Nanoparticles; Optical Imaging; Silicon; Tissue Distribution; Xenograft Model Antitumor Assays

In this manuscript, we demonstrate that the in situ growth of fluorescent silicon (Si) nanomaterials is stimulated when organosilicane molecules interact with different green teas, producing multifunctional Si nanomaterials with controllable zero- (e.g., nanoparticles), two- (e.g., nanosheets), and three- (e.g., nanospheres) dimensional nanostructures. Such green tea-originated Si nanomaterials (GTSN) exhibit strong fluorescence (quantum yield: ∼19-30%) coupled with ultrahigh photostability, as well as intrinsic anti-cancer activity with high specificity (e.g., the GTSN can accurately kill various cancer cells, rather than normal cells). Taking advantage of these unique merits, we further performed systematic in vitro and in vivo experiments to interrogate the mechanism of the green tea- and GTSN-related cancer prevention. Typically, we found that the GTSN entered the cell nuclei and induced cell apoptosis/death of cancer cells. The prepared GTSN were observed in vivo to accumulate in the tumour tissues after 14-d post-injection, leading to an efficient inhibition of tumour growth. Our results open new avenues for designing novel multifunctional and side-effect-free Si nanomaterials with controllable structures.

Topics: Animals; Antineoplastic Agents; Apoptosis; Biocompatible Materials; Breast Neoplasms; Cell Proliferation; Female; Fluorescence; Humans; In Vitro Techniques; Mice; Mice, Inbred BALB C; Mice, Nude; Nanostructures; Silicon; Tea; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Topics: Biosensing Techniques; Breast Neoplasms; Electronics; Equipment Design; Female; Gallium; Humans; Indium; Mammography; Radiographic Image Enhancement; Selenium; Silicon; Systems Analysis; Zinc Oxide

The rapid growth of point-of-care tests demands for biosensors with high sensitivity and small size. This paper demonstrates an optofluidic metasurface that combines silicon-on-insulator (SOI) nanophotonics and nanofluidics to realize a high-performance, lateral flow-through biosensor. The metasurface is made of a periodic array of silicon nanoposts on an SOI substrate, and functionalized with specific receptor molecules. Bonding of a polydimethylsiloxane slab directly onto the surface results in an ultracompact biosensor, where analyte solutions are restricted to flow only in the space between the nanoposts. No flow exists above the nanoposts. This sensor design overcomes the issue with diffusion-limited detection of many other biosensors. The lateral flow-through feature, in conjunction with high-Q resonance modes associated with optical bound states of the metasurface, offers an improved sensitivity to subtle molecule-bonding induced changes in refractive index. The device exhibits a resonance mode around 1550 nm wavelength and provides an index sensitivity of 720 nm/RIU. Biosensing is conducted to detect the epidermal growth factor receptor 2 (ErbB2), a protein biomarker for early-stage breast cancer screening, by monitoring resonance wavelength shifts in response to specific analyte-ligand binding events at the metasurface. The limit of detection of the device is 0.7 ng mL

Topics: Antibodies, Immobilized; Biomarkers, Tumor; Biosensing Techniques; Breast Neoplasms; Equipment Design; Female; Humans; Receptor, ErbB-2; Refractometry; Silicon

Topics: Air Pollution, Indoor; Animals; Asthma; Biofuels; Biomarkers, Tumor; Breast Neoplasms; Copper; Coronavirus Infections; Crops, Agricultural; Feces; Female; Gene Editing; Gold; Graphite; Helminthiasis; Hong Kong; Humans; Influenza A Virus, H5N1 Subtype; Korea; Lighting; Malaysia; MicroRNAs; Severe Acute Respiratory Syndrome; Silicon; Singapore; Speech Recognition Software; Taiwan; Video Recording

Vertically ordered arrays of silicon nanoneedles (Si NNs), due to their nanoscale dimension and low cytotoxicity, could enable minimally invasive nanoinjection of biomolecules into living biological systems such as cells and tissues. Although production of these Si NNs on a bulk Si wafer has been achieved through standard nanofabrication technology, there exists a large mismatch at the interface between the rigid, flat, and opaque Si wafer and soft, curvilinear, and optically transparent biological systems. Here, we report a unique methodology that is capable of constructing vertically ordered Si NNs on a thin layer of elastomer patch to flexibly and transparently interface with biological systems. The resulting outcome provides important capabilities to form a mechanically elastic interface between Si NNs and biological systems, and simultaneously enables direct imaging of their real-time interactions under the transparent condition. We demonstrate its utility in intracellular, intradermal, and intramuscular nanoinjection of biomolecules into various kinds of biological cells and tissues at their length scales.

Topics: Animals; Breast Neoplasms; Cells, Cultured; Elastomers; Female; Fibroblasts; Humans; Injections, Intradermal; Mice; Mice, Nude; Nanotechnology; Nanowires; Ovarian Neoplasms; Porosity; Silicon

Active matrix flat-panel imagers, which typically incorporate a pixelated array with one a-Si:H thin-film transistor (TFT) per pixel, have become ubiquitous by virtue of many advantages, including large monolithic construction, radiation tolerance, and high DQE. However, at low exposures such as those encountered in fluoroscopy, digital breast tomosynthesis and breast computed tomography, DQE is degraded due to the modest average signal generated per interacting x-ray relative to electronic additive noise levels of ~1000 e, or greater. A promising strategy for overcoming this limitation is to introduce an amplifier into each pixel, referred to as the active pixel (AP) concept. Such circuits provide in-pixel amplification prior to readout as well as facilitate correlated multiple sampling, enhancing signal-to-noise and restoring DQE at low exposures. In this study, a methodology for theoretically investigating the signal and noise performance of imaging array designs is introduced and applied to the case of AP circuits based on low-temperature polycrystalline silicon (poly-Si), a semiconductor suited to manufacture of large area, radiation tolerant arrays.. Computer simulations employing an analog circuit simulator and performed in the temporal domain were used to investigate signal characteristics and major sources of electronic additive noise for various pixel amplifier designs. The noise sources include photodiode shot noise and resistor thermal noise, as well as TFT thermal and flicker noise. TFT signal behavior and flicker noise were parameterized from fits to measurements performed on individual poly-Si test TFTs. The performance of three single-stage and three two-stage pixel amplifier designs were investigated under conditions relevant to fluoroscopy. The study assumes a 20 × 20 cm. The total noise results were found to exhibit a strong dependence on circuit design and operating conditions, with TFT flicker noise generally found to be the dominant noise contributor. For the single-stage designs, significantly increasing the size of the source-follower TFT substantially reduced flicker noise - with the lowest total noise found to be ~574 e [rms]. For the two-stage designs, in addition to tuning TFT sizes and introducing a low-pass filter, replacing a p-type TFT with a resistor (under the assumption in the study that resistors make no flicker noise contribution) resulted in significant noise reduction - with the lowest total noise found to be ~336 e [rms].. A methodology based on circuit simulations which facilitates comprehensive explorations of signal and noise characteristics has been developed and applied to the case of poly-Si AP arrays. The encouraging results suggest that the electronic additive noise of such devices can be substantially reduced through judicious circuit design, signal amplification, and multiple sampling. This methodology could be extended to explore the noise performance of arrays employing other pixel circuitry such as that for photon counting as well as other semiconductor materials such as a-Si:H and a-IGZO.

Topics: Breast Neoplasms; Equipment Design; Female; Fluoroscopy; Humans; Mammography; Silicon; X-Rays

One of the most challenging obstacles in nanoparticle's surface modification is to achieve the concept that one ligand can accomplish multiple purposes. Upon such consideration, 3-aminopropoxy-linked quercetin (AmQu), a derivative of a natural flavonoid inspired by the structure of dopamine, is designed and subsequently used to modify the surface of thermally hydrocarbonized porous silicon (PSi) nanoparticles. This nanosystem inherits several advanced properties in a single carrier, including promoted anticancer efficiency, multiple drug resistance (MDR) reversing, stimuli-responsive drug release, drug release monitoring, and enhanced particle-cell interactions. The anticancer drug doxorubicin (DOX) is efficiently loaded into this nanosystem and released in a pH-dependent manner. AmQu also effectively quenches the fluorescence of the loaded DOX, thereby allowing the use of the nanosystem for monitoring the intracellular drug release. Furthermore, a synergistic effect with the presence of AmQu is observed in both normal MCF-7 and DOX-resistant MCF-7 breast cancer cells. Due to the similar structure as dopamine, AmQu may facilitate both the interaction and internalization of PSi into the cells. Overall, this PSi-based platform exhibits remarkable superiority in both multifunctionality and anticancer efficiency, making this nanovector a promising system for anti-MDR cancer treatment.

Topics: Breast Neoplasms; Doxorubicin; Drug Carriers; Drug Resistance, Neoplasm; Female; Humans; MCF-7 Cells; Nanoparticles; Porosity; Quercetin; Silicon

Nanomaterials have proven to possess great potential in biomaterials research. Recently, they have suggested considerable promise in cancer diagnosis and therapy. Among others, silicon (Si) nanomaterials have been extensively employed for various biomedical applications; however, the utilization of Si for cancer therapy has been limited to nanoparticles, and its potential as anticancer substrates has not been fully explored. Noble nanoparticles have also received considerable attention owing to unique anticancer properties to improve the efficiency of biomaterials for numerous biological applications. Nevertheless, immobilization and control over delivery of the nanoparticles have been challenge. Here, we develop hybrid nanoplatforms to efficiently hamper breast cancer cell adhesion and proliferation. Platforms are synthesized by femtosecond laser processing of Si into multiphase nanostructures, followed by sputter-coating with gold (Au)/gold-palladium (Au-Pd) nanoparticles. The performance of the developed platforms was then examined by exploring the response of normal fibroblast and metastatic breast cancer cells. Our results from the quantitative and qualitative analyses show a dramatic decrease in the number of breast cancer cells on the hybrid platform compared to untreated substrates. Whereas, fibroblast cells form stable adhesion with stretched and elongated cytoskeleton and actin filaments. The hybrid platforms perform as dual-acting cytophobic/cytostatic stages where Si nanostructures depress breast cancer cell adhesion while immobilized Au/Au-Pd nanoparticles are gradually released to affect any surviving cell on the nanostructures. The nanoparticles are believed to be taken up by breast cancer cells via endocytosis, which subsequently alter the cell nucleus and may cause cell death. The findings suggest that the density of nanostructures and concentration of coated nanoparticles play critical roles on cytophobic/cytostatic properties of the platforms on human breast cancer cells while having no or even cytophilic effects on fibroblast cells. Because of the remarkable contrary responses of normal and cancer cells to the proposed platform, we envision that it will provide novel applications in cancer research.

Topics: Biocompatible Materials; Breast Neoplasms; Cell Proliferation; Gold; Humans; Nanoparticles; Nanostructures; Silicon

Electrochemical approaches have played crucial roles in bio sensing because of their Potential in achieving sensitive, specific and low-cost detection of biomolecules and other bio evidences. Engineering the electrochemical sensing interface with nanomaterials tends to new generations of label-free biosensors with improved performances in terms of sensitive area and response signals. Here we applied Silicon Nanowire (SiNW) array electrodes (in an integrated architecture of working, counter and reference electrodes) grown by low pressure chemical vapor deposition (LPCVD) system with VLS procedure to electrochemically diagnose the presence of breast cancer cells as well as their response to anticancer drugs. Mebendazole (MBZ), has been used as antitubulin drug. It perturbs the anodic/cathodic response of the cell covered biosensor by releasing Cytochrome C in cytoplasm. Reduction of cytochrome C would change the ionic state of the cells monitored by SiNW biosensor. By applying well direct bioelectrical contacts with cancer cells, SiNWs can detect minor signal transduction and bio recognition events, resulting in precise biosensing. Our device detected the trace of MBZ drugs (with the concentration of 2nM) on electrochemical activity MCF-7 cells. Also, experimented biological analysis such as confocal and Flowcytometry assays confirmed the electrochemical results.

Topics: Biosensing Techniques; Breast; Breast Neoplasms; Cytochromes c; Drug Screening Assays, Antitumor; Electrochemical Techniques; Female; Humans; MCF-7 Cells; Mebendazole; Nanowires; Silicon; Tubulin Modulators

One of the most interested molecular research in the field of cancer detection is the mechanism of drug effect on cancer cells. Translating molecular evidence into electrochemical profiles would open new opportunities in cancer research. In this manner, applying nanostructures with anomalous physical and chemical properties as well as biocompatibility would be a suitable choice for the cell based electrochemical sensing. Silicon based nanostructure are the most interested nanomaterials used in electrochemical biosensors because of their compatibility with electronic fabrication process and well engineering in size and electrical properties. Here we apply silicon nanograss (SiNG) probing electrodes produced by reactive ion etching (RIE) on silicon wafer to electrochemically diagnose the effect of anticancer drugs on breast tumor cells. Paclitaxel (PTX) and mebendazole (MBZ) drugs have been used as polymerizing and depolymerizing agents of microtubules. PTX would perturb the anodic/cathodic responses of the cell-covered biosensor by binding phosphate groups to deformed proteins due to extracellular signal-regulated kinase (ERK(1/2)) pathway. MBZ induces accumulation of Cytochrome C in cytoplasm. Reduction of the mentioned agents in cytosol would change the ionic state of the cells monitored by silicon nanograss working electrodes (SiNGWEs). By extending the contacts with cancer cells, SiNGWEs can detect minor signal transduction and bio recognition events, resulting in precise biosensing. Effects of MBZ and PTX drugs, (with the concentrations of 2 nM and 0.1 nM, respectively) on electrochemical activity of MCF-7 cells are successfully recorded which are corroborated by confocal and flow cytometry assays.

Topics: Breast Neoplasms; Electrodes; Female; Humans; MCF-7 Cells; Mebendazole; Nanotechnology; Paclitaxel; Silicon; Tubulin

Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers (PMCs) to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator (SOI) substrate, which significantly reduces the fabrication costs. The PMCs are 260 μm long, 35 μm wide and 2 μm thick with resistivity of order 1.316×10(-3) Ω cm obtained by using boron diffusion technique. For indenting the tissue, we utilized 8 μm thick cylindrical SU-8 tip. The PMC was calibrated against a known AFM probe. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores. Furthermore, field emission scanning electron microscopy (FE-SEM) of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues, further investigation is necessary to perform automated mechano-phenotyping (classification) of breast cancer: from onset to disease progression.

Topics: Biosensing Techniques; Breast; Breast Neoplasms; Female; Humans; Micro-Electrical-Mechanical Systems; Microscopy, Electron, Scanning; Silicon

Research on specific drug responses of circulating tumor cells (CTCs) provides very important information for treatment of cancer patients at a patient-specific level. For this reason, platforms for high capture efficiency of CTCs are essential for clinical evaluation of patient-specific drug responses of CTCs. Recently, nanostructure based platforms have been developed with a high capture efficiency of more than 93% due to high-affinity binding and the 3D nanotopographic features of the nanostructure substrate. In this study, the breast carcinoma cell-line (BT20) cells with an ultra-low abundance range were captured by streptavidin (STR)-functionalized silicon nanowire (SiNW) platforms for evaluation of capture efficiency. A capture efficiency of more than 90% was achieved. Specific drug responses of BT20 cells captured on STR-SiNW platforms were analyzed using tamoxifen or docetaxel as a function of incubation time and dose, and compared with a 96-well plate platform. The drug responses of CTCs on STR-SiNW platforms were more sensitive than a 96-well plate platform. In addition, CTCs were successfully captured and evaluated their size distribution from the blood of breast cancer patients using fluorescence imaging. In conclusion, we suggest that the SiNW platform is adaptable for clinical use in evaluation of CTCs and drug response tests.

Topics: Biosensing Techniques; Breast Neoplasms; Docetaxel; Female; Humans; MCF-7 Cells; Microfluidic Analytical Techniques; Nanowires; Neoplastic Cells, Circulating; Silicon; Streptavidin; Taxoids

Biophysical studies on individual cells can help to establish the relationship between mechanics and biological function. In the case of cancer, mechanical properties of cells have been linked to metastatic activity and disease progression and can be crucial for understanding cellular physiology and metabolism. In this study, we report measurements of the stiffness of breast cancer cells using a novel silicon MEMS resonant sensor and validated the results with atomic force microscopy (AFM). We measured the mass and stiffness of individual benign (MCF-10A), non-invasive malignant (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells using the silicon resonant MEMS sensors. The sensor extracts the average stiffness value of the whole cell and allows comparison of stiffness of different cell types. We found differences between the cell lines in both elasticity and viscosity, and confirmed our observations through independent measurements with atomic force microscopy (AFM). Coupled with measurements over time, this approach could lead to a multimodal investigation of both growth and physical properties of single cells. The mechanical property sensitivity and resolution of these pedestal sensors were investigated to understand the significance of the frequency shift during operation. The lowest achievable spring constant and damping constant resolutions have a range of 0.06 to 17.10 mN m(-1) and 1.63 to 1.96 nN s m(-1), respectively, measured across the range of physiological cell mechanical properties.

Topics: Breast Neoplasms; Cells, Cultured; Female; Humans; MCF-7 Cells; Micro-Electrical-Mechanical Systems; Microscopy, Atomic Force; Silicon

Over the past decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability, and drug-release kinetics. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated with heptakis(6-amino-6-deoxy)-β-cyclodextrin (HABCD) to show the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi-HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs. UnTHCPSi-HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and also sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi-HABCD NPs efficiently inhibited cell proliferation of the breast cancer cells.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclodextrins; Drug Delivery Systems; Drug Liberation; Female; Flow Cytometry; Humans; Kidney; Liver; Nanoparticles; Niacinamide; Particle Size; Phenylurea Compounds; Porosity; Rats; Silicon; Sorafenib; Spectroscopy, Fourier Transform Infrared

A highly sensitive detection of breast cancer marker, carbohydrate antigen 15-3 (CA 15-3) by carbon nanotube (CNT) based immuno-polymerase chain reaction was reported. The study was aimed to develop a precise and sensitive method to diagnose breast cancer and its recurrence. The hydrofluoric acid (HF) treated silicon wafer layered with bundled CNT was used as the substrate. The surface was treated with HNO3/H2SO4 to graft carboxyl groups on the tips of CNT. Subsequently, polyoxyethylene bis-amine was grafted to conjugate anti human CA 15-3 antibodies. Water contact angle measurement, scanning electron microscope, Fourier transform infrared spectrometer, Raman spectrometer and sodium dodecyl sulfate polyacrylamide gel electrophoresis were employed to confirm the surface modification. The captured antibodies on the CNT were used to capture the target antigen CA 15-3 and the biotinylated secondary antibodies were subsequently bound with the target antigen. A bi-functional streptavidin was used to link biotinylated DNA to the biotinylated detection antibodies. The biotinylated target DNA was amplified by PCR, and then analyzed by agarose gel electrophoresis. The lower limit of detection of CA 15-3 by the proposed immuno-PCR system was 0.001 U/mL, which is extremely sensitive than the other bioanalytical techniques.

Topics: Antibodies, Immobilized; Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Immunoassay; Microscopy, Electron, Scanning; Mucin-1; Nanotubes, Carbon; Polymerase Chain Reaction; Silicon; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman

Nanoporous silicon particles (pSi), with a pore size in the range of 20-60 nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30 nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both in vitro and in vivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.

Topics: Biocompatible Materials; Breast Neoplasms; Cell Line, Tumor; Female; Gene Silencing; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nanoparticles; Polyamines; Polyelectrolytes; RNA, Small Interfering; Silicon

Cell-derived membrane vesicles that are released in biofluids, like blood or saliva, are emerging as potential non-invasive biomarkers for diseases, such as cancer. Techniques capable of measuring the size and concentration of membrane vesicles directly in biofluids are urgently needed. Fluorescence single particle tracking microscopy has the potential of doing exactly that by labelling the membrane vesicles with a fluorescent label and analysing their Brownian motion in the biofluid. However, an unbound dye in the biofluid can cause high background intensity that strongly biases the fluorescence single particle tracking size and concentration measurements. While such background intensity can be avoided with light sheet illumination, current set-ups require specialty sample holders that are not compatible with high-throughput diagnostics. Here, a microfluidic chip with integrated light sheet illumination is reported, and accurate fluorescence single particle tracking size and concentration measurements of membrane vesicles in cell culture medium and in interstitial fluid collected from primary human breast tumours are demonstrated.

Topics: Artifacts; Biomarkers; Biosensing Techniques; Breast Neoplasms; Cell Line, Tumor; Equipment Design; Fluorescent Dyes; Green Fluorescent Proteins; Humans; Light; Materials Testing; Microfluidic Analytical Techniques; Microfluidics; Motion; Particle Size; Scattering, Radiation; Silicon

The culturing of cancer cells on micropatterned substrates can provide insight into the factors of the extracellular environment that enable the control of cell growth. We report here a novel non-UV-based technique to quickly micropattern a poly-(ethylene) glycol diacrylate (PEGDA)-based hydrogel on top of modified glass substrates, which were then used to control the growth patterns of breast cancer cells. Previously, the fabrication of micropatterned substrates required relatively complicated steps, which made it impractical for researchers to rapidly and systematically investigate the effects of different cell growth patterns. The technique presented herein operates on the principle of optically-induced electrokinetics (OEKs) and uses computer-generated projection light patterns to dynamically pattern the hydrogel on a hydrogenated amorphous silicon (a-Si:H) thin-film, atop an indium tin oxide (ITO) glass substrate. This technique allows us to pattern lines, circles, pentagons, and more complex shapes in the hydrogel with line widths below 3 μm and thicknesses of up to 6 μm within 8 s by simply controlling the projected illumination pattern and applying an appropriate AC voltage between the two ITO glass substrates. After separating the glass substrates to expose the patterned hydrogel, we experimentally demonstrate that MCF-7 breast cancer cells will adhere to the bare a-Si:H surface, but not to the hydrogel patterned in various geometric shapes and sizes. Theoretical analysis and finite-element model simulations reveal that the dominant OEK forces in our technique are the dielectrophoresis (DEP) force and the electro-osmosis force, which enhance the photo-initiated cross-linking reaction in the hydrogel. Our preliminary cultures of breast cancer cells demonstrate that this reported technique could be applied to effectively confine the growth of cancer cells on a-Si:H surfaces and affect individual cell geometry during their growth.

Topics: Breast Neoplasms; Cell Culture Techniques; Cell Line, Tumor; Female; Humans; Hydrogels; Polyethylene Glycols; Silicon; Ultraviolet Rays

Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur.. In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2)) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion.. Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

Topics: Animals; Blood Vessels; Breast Neoplasms; E-Selectin; Endothelial Cells; Erythrocytes; Female; Humans; Hyperthermia, Induced; Liposomes; MCF-7 Cells; Mice; Mice, Nude; Microscopy; Neoplasm Transplantation; Perfusion; Silicon

Effective treatment of cancer metastasis to the bone relies on bone marrow drug accumulation. The surface proteins in the bone marrow vascular endothelium provide docking sites for targeted drug delivery. We have developed a thioaptamer that specifically binds to E-selectin that is overexpressed in the vasculature of tumor and inflammatory tissues. In this study, we tested targeted delivery of therapeutic siRNA loaded in the E-selectin thioaptamer-conjugated multistage vector (ESTA-MSV) drug carrier to bone marrow for the treatment of breast cancer bone metastasis. We evaluated tumor type- and tumor growth stage-dependent targeting in mice bearing metastatic breast cancer in the bone, and carried out studies to identify factors that determine targeting efficiency. In a subsequent study, we delivered siRNA to knock down expression of the human STAT3 gene in murine xenograft models of human MDA-MB-231 breast tumor, and assessed therapeutic efficacy. Our studies revealed that the CD31(+)E-selectin(+) population accounted for 20.8%, 26.4% and 29.9% of total endothelial cells respectively inside the femur of mice bearing early, middle and late stage metastatic MDA-MB-231 tumors. In comparison, the double positive cells remained at a basal level in mice with early stage MCF-7 tumors, and jumped to 23.9% and 28.2% when tumor growth progressed to middle and late stages. Accumulation of ESTA-MSV inside the bone marrow correlated with the E-selectin expression pattern. There was up to 5-fold enrichment of the targeted MSV in the bone marrow of mice bearing early or late stage MDA-MB-231 tumors and of mice with late stage, but not early stage, MCF-7 tumors. Targeted delivery of STAT3 siRNA in ESTA-MSV resulted in knockdown of STAT3 expression in 48.7% of cancer cells inside the bone marrow. Weekly systemic administration of ESTA-MSV/STAT3 siRNA significantly extended survival of mice with MDA-MB-231 bone metastasis. In conclusion, targeting the overexpressed E-selectin provides an effective approach for tissue-specific drug delivery to the bone marrow. Tumor growth in the bone can be effectively inhibited by blockage of the STAT3 signaling.

Topics: Animals; Aptamers, Nucleotide; Bone Marrow; Bone Neoplasms; Breast Neoplasms; Cell Line, Tumor; Drug Carriers; E-Selectin; Endothelial Cells; Endothelium; Female; Femur; Humans; MCF-7 Cells; Mice; Mice, Nude; RNA, Small Interfering; Silicon; STAT3 Transcription Factor

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.

Topics: Antimetabolites, Antineoplastic; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Delayed-Action Preparations; Endosomes; Female; Humans; Ions; Maleates; MCF-7 Cells; Methotrexate; Nanoparticles; Polyethyleneimine; Polyethylenes; Polymers; Porosity; Silicon; Surface Properties

Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA(+)) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA(+) nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA(+) relies on the capability of the conjugated HA(+) to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA(+)-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.

Topics: Antineoplastic Agents; Biogenic Amines; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Diffusion; Drug Compounding; Humans; Hyaluronic Acid; Materials Testing; Nanocapsules; Nanoconjugates; Nanopores; Particle Size; Porosity; Silicon; Treatment Outcome

The development of DNA detection techniques on large-area plasmonics-active platforms is critical for many medical applications such as high-throughput screening, medical diagnosis and systems biology research. Here, we report for the first time a unique "molecular sentinel-on-chip" (MSC) technology for surface-enhanced Raman scattering (SERS)-based DNA detection. This unique approach allows label-free detection of DNA molecules on chips developed on a wafer scale using large area nanofabrication methodologies. To develop plasmonics-active biosensing platforms in a repeatable and reproducible manner, we employed a combination of deep UV lithography, atomic layer deposition, and metal deposition to fabricate triangular-shaped nanowire (TSNW) arrays having controlled sub-10 nm gap nanostructures over an entire 6 inch wafer. The detection of a DNA sequence of the Ki-67 gene, a critical breast cancer biomarker, on the TSNW substrate illustrates the usefulness and potential of the MSC technology as a novel SERS-based DNA detection method.

Topics: Biomarkers; Biosensing Techniques; Breast Neoplasms; DNA; Female; Humans; Ki-67 Antigen; Nanowires; Oligonucleotide Array Sequence Analysis; Oligonucleotide Probes; Silicon; Spectrum Analysis, Raman

Non-toxic porous silicon nanoparticles carry porphyrin covalently attached to their surface inside breast cancer cells for a more efficient photodynamic effect.

Topics: Anions; Breast Neoplasms; Female; Humans; MCF-7 Cells; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Porosity; Porphyrins; Silicon

Silicon nanoparticles (SiNPs) hold prominent interest in various aspects of biomedical applications. For this purpose, surface functionalization of the NPs is essential to stabilize them, target them to specific disease area, and allow them to selectively bind to the cells or the bio-molecules present on the surface of the cells. However, no such functionalization has been explored with Si nanoparticles. Carbohydrates play a critical role in cell recognition. Here, we report the first synthesis of silicon nanoparticles functionalized with carbohydrates. In this study, stable and brightly luminescent d-Mannose (Man) capped SiNPs have been synthesized from amine terminated SiNPs and d-mannopyranoside acid. The surface functionalization is confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and energy dispersive X-ray spectroscopy (EDX) studies. The mean diameter of the crystal core is 5.5 nm, as measured by transmission electron microscopy (TEM), while the hydrodynamic diameter obtained by dynamic light scattering (DLS) is 16 nm. The quantum yield (QY) of photoluminescence emission is found to be 11.5%, and the nanoparticles exhibit an exceptional stability over two weeks. The Man-capped SiNPs may prove to be valuable tools for further investigating glycobiological, biomedical, and material science fields. Experiments are carried out using Concanavalin A (ConA) as a target protein in order to prove the hypothesis. When Man functionalized SiNPs are treated with ConA, cross-linked aggregates are formed, as shown in TEM images as well as monitored by photoluminescence spectroscopy (PL). Man functionalized SiNPs can target cancerous cells. Visualization imaging of SiNPs in MCF-7 human breast cancer cells shows the fluorescence is distributed throughout the cytoplasm of these cells.

Topics: Breast Neoplasms; Cell Line, Tumor; Concanavalin A; Cytoplasm; Female; Humans; Light; Magnetic Resonance Spectroscopy; Mannose; Materials Testing; MCF-7 Cells; Microscopy, Electron, Transmission; Nanoparticles; Nanotechnology; Scattering, Radiation; Silicon; Spectrometry, X-Ray Emission; Spectroscopy, Fourier Transform Infrared; Surface Properties

A new paradigm for an effective delivery of therapeutics into cancer cells is presented. Degradable porous silicon carriers, which are tailored to carry and release a model anti-cancer drug, are biolistically bombarded into in-vitro cancerous targets. We demonstrate the ability to launch these highly porous microparticles by a pneumatic capillary gene gun, which is conventionally used to deliver cargos by heavy metal carriers. By optimizing the gun parameters e.g., the accelerating gas pressure, we have successfully delivered the porous carriers, to reach deep targets and to cross a skin barrier in a highly spatial resolution. Our study reveals significant cytotoxicity towards the target human breast carcinoma cells following the delivery of drug-loaded carriers, while administrating empty particles results in no effect on cell viability. The unique combination of biolistics with the temporal control of payload release from porous carriers presents a powerful and non-conventional platform for designing new therapeutic strategies.

Topics: Antineoplastic Agents; Biolistics; Breast Neoplasms; Cell Line, Tumor; Delayed-Action Preparations; Drug Carriers; Humans; Mitoxantrone; Porosity; Silicon

In this study, we have used newly developed Silicon nanowire (SiNW) arrays to evaluate their feasibility for the quantification of different markers of interests. We have quantified four different markers of PSA, EGF, IL-6, and VDBP. Each marker showed measurements in the range of 0.184∼17.79 ng/mL (PSA), 10 pg/mL∼10 ng/mL (EGF), 10 pg/mL∼50 ng/mL (IL-6), and 10 pg∼5 ng/mL (VDBP), respectively. For the experiment, we collected 10 different serum samples, 5 prostate cancer patients and 5 breast cancer patients, and measured and compared the resulting signal from the SiNW FET to serum sample from normal patients. As a result, we observed a meaningful pattern of markers associated with each type of cancer. In addition, we have measured the response signal of SiNWs conjugated with Epithelial cell adhesion molecules (EpCAM) markers against tumor cells as they interacted with those markers.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Cell Adhesion Molecules; Epithelial Cell Adhesion Molecule; Female; Humans; Immunoassay; Male; Nanowires; Phase Transition; Plastics; Prostatic Neoplasms; Silicon

Gene silencing agents such as small interfering RNA (siRNA) and microRNA offer the promise to modulate expression of almost every gene for the treatment of human diseases including cancer. However, lack of vehicles for effective systemic delivery to the disease organs has greatly limited their in vivo applications. In this study, we developed a high capacity polycation-functionalized nanoporous silicon (PCPS) platform comprised of nanoporous silicon microparticles functionalized with arginine-polyethyleneimine inside the nanopores for effective delivery of gene silencing agents. Incubation of MDA-MB-231 human breast cancer cells with PCPS loaded with STAT3 siRNA (PCPS/STAT3) or GRP78 siRNA (PCPS/GRP78) resulted in 91 and 83% reduction of STAT3 and GRP78 gene expression in vitro. Treatment of cells with a microRNA-18a mimic in PCPS (PCPS/miR-18) knocked down 90% expression of the microRNA-18a target gene ATM. Systemic delivery of PCPS/STAT3 siRNA in murine model of MDA-MB-231 breast cancer enriched particles in tumor tissues and reduced STAT3 expression in cancer cells, causing significant reduction of cancer stem cells in the residual tumor tissue. At the therapeutic dosage, PCPS/STAT3 siRNA did not trigger acute immune response in FVB mice, including changes in serum cytokines, chemokines, and colony-stimulating factors. In addition, weekly dosing of PCPS/STAT3 siRNA for four weeks did not cause signs of subacute toxicity based on changes in body weight, hematology, blood chemistry, and major organ histology. Collectively, the results suggest that we have developed a safe vehicle for effective delivery of gene silencing agents.

Topics: Animals; Arginine; Breast Neoplasms; Cell Line, Tumor; Endoplasmic Reticulum Chaperone BiP; Female; Gene Expression Profiling; Gene Silencing; Heat-Shock Proteins; Humans; Kinetics; Mammary Neoplasms, Experimental; Mice; MicroRNAs; Microscopy, Electron, Scanning; Nanomedicine; Nanoparticles; Polyethyleneimine; RNA, Small Interfering; Silicon; STAT3 Transcription Factor

Silicon-containing combretastatin analogs were designed, synthesized and evaluated for stability and biological activities. Among them, compound 31 exhibited strong tubulin polymerization-inhibitory activity and very potent tumor cell growth-inhibitory activity (IC50=0.007 μM) in MCF-7 cell proliferation assay. This compound also potently inhibited [(3)H]colchicine binding (90.7% inhibition at 3 μM). These activities were comparable to those of combretastatin A-4 (CA-4) (1). In addition, compound 31 was physico-chemically more stable than 1. These results suggest that a silicon linker can act as a bioisoster of a cis carbon-carbon double bond.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Colchicine; Drug Design; Female; Humans; Silicon; Stilbenes; Tubulin; Tubulin Modulators

Nanostructured porous silicon (PSi) thin films, fabricated by the electrochemical anodization of single crystalline Si wafers, are studied as delivery systems for the anticancer drug mitoxantrone dihydrochloride (MTX). The surface chemistry of the PSi carriers was tailored by surface alkylation using thermal hydrosilylation of 1-dodecene and undecylenic acid, followed by physical adsorption or covalent attachment of MTX to the Si scaffold. The nanostructure and the physiochemical properties of the different carriers were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, nitrogen adsorption-desorption and contact angle measurements, demonstrating that surface alkylation results in a pronounced effect on the hydrophobicity/hydrophilicity of the scaffolds and a volumetric gain in pore wall, which in turn results in a decrease in pore diameter (>23%) and available porous volume (>40%). The effect of these key parameters on MTX loading efficacy, release profile, Si scaffold erosion kinetics and in vitro cytotoxicity on human breast carcinoma (MDA-MB-231) cells was studied and compared to the behavior of neat PSi carriers. We show that the chemically modified PSi carriers exhibit sustained release for several days to weeks with minimal to no burst effect, while for the native PSi MTX release was completed within 5h with a substantial burst release of ~40%. Moreover, our in vitro cytotoxicity experiments have clearly demonstrated that the MTX released from all PSi carriers maintained its cytotoxic effect towards MDA-MB-231 cells, in comparison to the low toxicity of the PSi carriers.

Topics: Absorption; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Diffusion; Humans; Materials Testing; Mitoxantrone; Nanocapsules; Porosity; Silicon; Treatment Outcome

Nanobiosensors based on silicon nanowire field effect transistors offer advantages of low cost, label-free detection, and potential for massive parallelization. As a result, these sensors have often been suggested as an attractive option for applications in point-of-care (POC) medical diagnostics. Unfortunately, a number of performance issues, such as gate leakage and current instability due to fluid contact, have prevented widespread adoption of the technology for routine use. High-k dielectrics, such as hafnium oxide (HfO(2)), have the known ability to address these challenges by passivating the exposed surfaces against destabilizing concerns of ion transport. With these fundamental stability issues addressed, a promising target for POC diagnostics and SiNWFETs has been small oligonucleotides, more specifically, microRNA (miRNA). MicroRNAs are small RNA oligonucleotides which bind to mRNAs, causing translational repression of proteins, gene silencing, and expressions are typically altered in several forms of cancer. In this paper, we describe a process for fabricating stable HfO(2) dielectric-based silicon nanowires for biosensing applications. Here we demonstrate sensing of single-stranded DNA analogues to their microRNA cousins using miR-10b and miR-21 as templates, both known to be upregulated in breast cancer. We characterize the effect of surface functionalization on device performance using the miR-10b DNA analogue as the target sequence and different molecular weight poly-l-lysine as the functionalization layer. By optimizing the surface functionalization and fabrication protocol, we were able to achieve <100 fM detection levels of the miR-10b DNA analogue, with a theoretical limit of detection of 1 fM. Moreover, the noncomplementary DNA target strand, based on miR-21, showed very little response, indicating a highly sensitive and highly selective biosensing platform.

Topics: Base Sequence; Biosensing Techniques; Breast Neoplasms; Electrochemical Techniques; Female; Hafnium; Humans; Limit of Detection; MicroRNAs; Nanotechnology; Nanowires; Nucleic Acids; Oxides; Point-of-Care Systems; Silicon; Transistors, Electronic

A 59-year-old woman was referred for a diagnostic video thoracoscopy under general anesthesia. At the end of the procedure, the patient presented with subcutaneous emphysema and cyanosis, abdominal distension, and bradycardia. A rigid bronchoscopy showed a longitudinal laceration in the pars membranacea of the trachea. A tracheal silicon stent was positioned on an emergency basis. She was intubated, positioning the tracheal tube cuff distal of the stent under bronchoscopic vision. A computed tomographic scan performed immediately after the procedure showed left pneumothorax, pneumoperitoneum, pneumopericardium, and diffuse subcutaneous emphysema. The subsequent course of the patient was uneventful. The patient was discharged home on postoperative day 4. After 1 year, the stent was removed with the evidence of complete trachel healing.

Topics: Breast Neoplasms; Bronchoscopy; Cyanosis; Female; Follow-Up Studies; Humans; Iatrogenic Disease; Intubation, Intratracheal; Lacerations; Lung Neoplasms; Middle Aged; Pneumoperitoneum; Pneumothorax; Risk Assessment; Silicon; Stents; Subcutaneous Emphysema; Thoracoscopy; Tomography, X-Ray Computed; Trachea; Treatment Outcome

The large number of estrogen receptor (ER) binding sites of various sequence patterns requires a sensitive detection to differentiate between subtle differences in ER-DNA binding affinities. A self-assembled monolayer (SAM)-assisted silicon nanowire (SiNW) biosensor for specific and highly sensitive detection of protein-DNA interactions, remarkably in nuclear extracts prepared from breast cancer cells, is presented. As a typical model, estrogen receptor element (ERE, dsDNA) and estrogen receptor alpha (ERα, protein) binding was adopted in the work. The SiNW surface was coated with a vinyl-terminated SAM, and the termination of the surface was changed to carboxylic acid via oxidation. DNA modified with amine group was subsequently immobilized on the SiNW surface. Protein-DNA binding was finally investigated by the functionalized SiNW biosensor. X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were employed to characterize the stepwise functionalization of the SAM and DNA on bare silicon surface, and to visualize protein-DNA binding on the SiNW surface, respectively. We observed that ERα had high sequence specificity to the SiNW biosensor which was functionalized with three different EREs including wild-type, mutant and scrambled DNA sequences. We also demonstrate that the specific DNA-functionalized SiNW biosensor was capable of detecting ERα as low as 10 fM. Impressively, the developed SiNW biosensor was able to detect ERα-DNA interactions in nuclear extracts from breast cancer cells. The SAM-assisted SiNW biosensor, as a label-free and highly sensitive tool, shows a potential in studying protein-DNA interactions.

Topics: Biosensing Techniques; Breast Neoplasms; Cell Line, Tumor; Cell Nucleolus; DNA; Female; Humans; Microscopy, Atomic Force; Nanowires; Photoelectron Spectroscopy; Protein Binding; Proteins; Sensitivity and Specificity; Silicon

Topics: Breast Neoplasms; Complex Mixtures; Equipment Design; Female; Humans; Male; Microfluidics; Molecular Imaging; Nanostructures; Neoplastic Cells, Circulating; Prostatic Neoplasms; Silicon; Surface Properties

The depth of two-photon fluorescence imaging in turbid media can be significantly enhanced by the use of the here described fluorescence detection method that allows to efficiently collect scattered fluorescence photons from a wide area of the turbid sample. By using this detector we were able to perform imaging of turbid samples, simulating brain tissue, at depths up to 3 mm, where the two-photon induced fluorescence signal is too weak to be detected by means used in conventional two-photon microscopy.

Topics: Agar; Brain; Breast Neoplasms; Cell Line, Tumor; Computer Simulation; Diagnostic Imaging; Female; Gelatin; Humans; Microscopy, Fluorescence, Multiphoton; Microspheres; Models, Biological; Nephelometry and Turbidimetry; Scattering, Radiation; Silicon

Luminescent silicon nanocrystals (ncSi) are showing great promise as photoluminescent tags for biological fluorescence imaging, with size-dependent emission that can be tuned into the near-infrared biological window and reported lack of toxicity. Here, colloidally stable ncSi with NIR photoluminescence are synthesized from (HSiO1.5)n sol-gel glasses and are used in biological fluorescence imaging. Modifications to the thermal processing conditions of (HSiO1.5)n sol-gel glasses, the development of new ncSi oxide liberation chemistry, and an appropriate alkyl surface passivation scheme lead to the formation of colloidally stable ncSi with photoluminescence centered at 955 nm. Water solubility and biocompatibility are achieved through encapsulation of the hydrophobic alkyl-capped ncSi within PEG-terminated solid lipid nanoparticles. Their applicability to biological imaging is demonstrated with the in-vitro fluorescence labelling of human breast tumor cells.

Topics: Breast Neoplasms; Cell Line, Tumor; Colloids; Female; Humans; Luminescence; Microscopy, Electron, Transmission; Nanoparticles; Optical Imaging; Quantum Dots; Silicon; Spectroscopy, Near-Infrared

We developed istotropically etched silicon chip micro-arrays for co-culture of metastatic human breast cancer (MDA-MB-231) and non-tumorigenic human breast (MCF10A) cells. The micro-arrays were fabricated using a single-mask, single-etch step process. Each chip contained a 16×16 array of cavities 140 μm wide by 60 μm deep separated by planar silicon surfaces. Cells occupied 97-100% of the etched cavities. The cavities were enriched three-fold in MDA-MB-231 cells relative to the seeding ratio of, MDA-MB-231(1): MCF10A(10) cells. Micro co-cultures comprised of both MCF10A and MDA-MB-231 cells formed in 26% of cavities and contained 2-10 cells per cavity. Heterotropic cell interactions were seen in co-culture, and sites of these interactions were enriched with vinculin spikes. A selective morphological response to the histone deacetylase inhibitor (HDI), SAHA (suberoylanilide hydroxamic acid), occurred in MDA-MB-231 cells which was quantified by significant increases in cell length and cell area on flat surfaces and in the number of stretched cells inside the etched cavities. The morphology of MCF10A cells was unaltered in response to SAHA. Real time imaging showed the formation of highly dynamic and randomly orienting cytoplasmic extensions in MDA-MB-231 cells 1h after adding SAHA; this is the first report of a rapid, morphological response in breast tumor cells to a histone deacetylase inhibitor. The findings demonstrate the utility of etched silicon micro-arrays for the propagation of human breast cell co-cultures and the application of HDI as a potential marker to distinguish metastatic breast cancer cells in a background of normal breast cell types.

Topics: Antineoplastic Agents; Breast; Breast Neoplasms; Cell Line; Cell Line, Tumor; Coculture Techniques; Equipment Design; Female; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Silicon; Tissue Array Analysis; Vorinostat

Studying the cytoskeletal organization as cells interact in their local microenvironment is interest of biological science, tissue engineering and cancer diagnosis applications. Herein, we describe the behavior of cell lines obtained from metastatic breast tumor pleural effusions (MDA-MB-231), normal fibrocystic mammary epithelium (MCF10A), and HS68 normal fibroblasts inside three dimensional (3-D) isotropic silicon microstructures fabricated by a single-mask, single-isotropic-etch process. We report differences in adhesion, mechanism of force balance within the cytoskeleton, and deformability among these cell types inside the 3-D microenvironment. HS68 fibroblasts typically stretched and formed vinculin-rich focal adhesions at anchor sites inside the etched cavities. In contrast, MCF10A and MDA-MB-231 cells adopted the curved surfaces of isotropic microstructures and exhibited more diffuse vinculin cytoplasmic staining in addition to vinculin localized in focal adhesions. The measurement of cells elasticity using atomic force microscopy (AFM) indentation revealed that HS68 cells are significantly stiffer (p < 0.0001) than MCF10A and MDA-MB-231 cells. Upon microtubule disruption with nocodazole, fibroblasts no longer stretched, but adhesion of MCF10A and MDA-MB-231 within the etched features remained unaltered. Our findings are consistent with tensegrity theory. The 3-D microstructures have the potential to probe cytoskeletal-based differences between healthy and diseased cells that can provide biomarkers for diagnostics purposes.

Topics: Breast Neoplasms; Cell Culture Techniques; Cell Line; Cytoskeleton; Elastic Modulus; Equipment Design; Female; Fibroblasts; Humans; Microscopy, Atomic Force; Nocodazole; Silicon; Tubulin Modulators

Gold nanoparticle (GN) embedded silicon nanowire (SiNW) configuration was proposed as a new biosensor for label-free DNA detection to enhance the sensitivity. The electric current flow between two terminals, a source and a drain electrode, were measured to sense the immobilization of probe oligonucleotides and their hybridization with target oligonucleotides. The complementary target oligonucleotide, breast cancer DNA with 1 pM, was sensed. In addition, its sensing mechanism and limit of detection (LOD) enhancement was investigated through simulation. The results support that the LOD can be improved by reducing the SiNW doping concentration. This emerging architecture combined nanostructure of spherical GN and SiNW has high potential as a label-free biosensor due to its facile fabrication process, high thermal stability, immobilization efficiency with a thiol-group in a self-assembled monolayer (SAM), and improved sensitivity.

Topics: Base Sequence; Biosensing Techniques; Breast Neoplasms; DNA; DNA Probes; DNA, Neoplasm; Electrochemical Techniques; Female; Gold; Humans; Metal Nanoparticles; Microscopy, Electron, Scanning; Nanowires; Silicon

Topics: Aged; Breast Neoplasms; Female; Humans; Lung Neoplasms; Lymphadenitis; Mediastinal Diseases; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Silicon

To investigate the structure and composition of ground orthodontic adhesive particulates produced under simulated clinical conditions and assess their estrogenic action in vitro.. A chemically cured and a light-cured adhesive were included in the study. Specimens were prepared by simulating bonding procedures, covering the bracket base surface with cellulose films to detach the full set material. The adhesives prepared under this method were grounded in glass chambers with an 8-fluted tungsten carbide on a high-speed handpiece; a new bur and different chamber was used for each adhesive sample and grindings were performed on different days to avoid contamination of the room. The adhesive particulates produced were subjected to FT-IR spectroscopy for the molecular characterization of particles; scanning electron microscopy for the morphologic condition and structure; and X-ray microanalysis for the elemental composition of the particles. Amounts of the ground adhesives were immersed in saline for 1 month at 37 degrees C. Eluents from solution of the two adhesives were added to media of an estrogen-responsive cell line derived from human breast adenocarcinoma (MCF-7), to assess the estrogenicity. Positive (estradiol and bisphenol-A) and negative (saline) controls were used; all assays were repeated four times and the results were averaged. Estrogenicity data were analyzed with one-way ANOVA and the Tukey test at the .05 level of significance.. The study of the composition of particles revealed compounds related to monomers with no major differences noted. Significant structural alterations were observed between the materials studied, with the chemically cured adhesive having larger particles. The ground samples contained Si, Na and Al apparently deriving from fillers, whereas large Ba fillers were identified only in the chemically cured group, whereas no distinct molecular variation was noted between the set material and its corresponding particulate form. Both chemically cured and light-cured adhesives exhibited an estrogenic action through induction of the proliferation rate of MCF-7 cells (160% and 128%, respectively, compared to control).. Apart from the potentially hazardous action of adhesive particulate aerosol produced by grinding, composite resin particulates may act as endocrinological disruptors.

Topics: Adenocarcinoma; Aluminum; Barium; Benzhydryl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Dental Debonding; Dental High-Speed Equipment; Electron Probe Microanalysis; Endocrine Disruptors; Estradiol; Estrogens, Non-Steroidal; Female; Humans; Materials Testing; Microscopy, Electron, Scanning; Orthodontic Appliances; Phenols; Resin Cements; Silicon; Sodium; Sodium Chloride; Spectroscopy, Fourier Transform Infrared; Temperature; Time Factors

The paper reports the development of three dimensional (3-D) silicon microstructures and the utilization of these microenvironments for discriminating between normal fibroblast (HS68) and breast cancer cells (MDA-MB-231). These devices consist of arrays of microchambers connected with channels and were fabricated using a single-mask, single-isotropic-etch process. The behavior and response of normal fibroblast and breast cancer cells, two key cell types in human breast tumor microenvironments, were explored in terms of adhesion and growth in these artificial 3-D microenvironments having curved sidewalls. Breast cancer cells formed stable adhesions with the curved sidewalls however fibroblasts stretched and elongated their cytoskeleton and actin filaments inside the microchambers. Statistical analysis revealed that fibroblast cells grew on both flat silicon surfaces and inside the microchambers regardless of microchamber depth. However, the localization of breast cancer cells in these same substrates was dependent on the microchamber depth. After 72 h in culture, the ratio of the number of breast cancer cells on flat surfaces compared to breast cancer cells inside the microchambers was significantly decreased within the deeper microchambers; for microchambers having depths 88 mum less than 5% of the breast cancer cells grew on the flat surfaces. This behavior was sustained for 120 h, the longest time point examined. The results suggest that certain 3-D silicon microstructures have potential application as a tool to detect breast cancer cells and also as a platform for separating normal fibroblasts from breast cancer cells for cancer diagnosis applications.

Topics: Biocompatible Materials; Breast Neoplasms; Cell Culture Techniques; Cell Line; Computer-Aided Design; Equipment Design; Equipment Failure Analysis; Fibroblasts; Humans; Materials Testing; Membranes, Artificial; Reproducibility of Results; Sensitivity and Specificity; Silicon; Surface Properties; Tissue Engineering

In this paper we studied differential adhesion of normal human fibroblast cells and human breast cancer cells to three dimensional (3-D) isotropic silicon microstructures and investigated whether cell cytoskeleton in healthy and diseased state results in differential adhesion. The 3-D silicon microstructures were formed by a single-mask single-isotropic-etch process. The interaction of these two cell lines with the presented microstructures was studied under static cell culture conditions. The results show that there is not a significant elongation of both cell types attached inside etched microstructures compared to flat surfaces. With respect to adhesion, the cancer cells adopt the curved shape of 3-D microenvironments while fibroblasts stretch to avoid the curved sidewalls. Treatment of fibroblast cells with cytochalasin D changed their adhesion, spreading and morphology and caused them act similar to cancer cells inside the 3-D microstructures. Statistical analysis confirmed that there is a significant alteration (P < 0.001) in fibroblast cell morphology and adhesion property after adding cytochalasin D. Adding cytochalasin D to cancer cells made these cells more rounded while there was not a significant alteration in their adhesion properties. The distinct geometry-dependent cell-surface interactions of fibroblasts and breast cancer cells are attributed to their different cytoskeletal structure; fibroblasts have an organized cytoskeletal structure and less deformable while cancer cells deform easily due to their impaired cytoskeleton. These 3-D silicon microstructures can be used as a tool to investigate cellular activities in a 3-D architecture and compare cytoskeletal properties of various cell lines.

Topics: Actins; Biomechanical Phenomena; Breast Neoplasms; Cell Adhesion; Cell Culture Techniques; Cell Line; Cell Line, Tumor; Cell Shape; Cytochalasin D; Cytoskeleton; Female; Fibroblasts; Humans; Microscopy, Electron, Scanning; Microtechnology; Miniaturization; Silicon; Substrate Specificity; Time Factors

Quantification of the heterogeneity of tumor cell populations is of interest for many diagnostic and therapeutic applications, including determining the cancerous stage of tumors. We attempted to differentiate human breast cancer cell lines from different pathologic stages and compare that with a normal human breast tissue cell line by characterizing the impedance properties of each cell line.. A microelectrical impedance spectroscopy system has been developed that can trap a single cell into an analysis cavity and measure the electrical impedance of the captured cell over a frequency range from 100 Hz to 3.0 MHz. Normal human breast tissue cell line MCF-10A, early-stage breast cancer cell line MCF-7, invasive human breast cancer cell line MDA-MB-231, and metastasized human breast cancer cell line MDA-MB-435 were used.. The whole-cell impedance signatures show a clear difference between each cell line in both magnitude and phase of the electrical impedance. The membrane capacitance calculated from the impedance data was 1.94 +/- 0.14, 1.86 +/- 0.11, 1.63 +/- 0.17, and 1.57 +/- 0.12 muF/cm(2) at 100 kHz for MCF-10A, MCF-7, MDA-MB-231, and MDA-MB-435, respectively. The calculated resistance for each cancer cell line at 100 kHz was 24.8 +/- 1.05, 24.8 +/- 0.93, 24.9 +/- 1.12, and 26.2 +/- 1.07 MOhm, respectively. The decrease in capacitances of the cancer cell lines compared with that of the normal cell line MCF-10A was 4.1%, 16.0%, and 19.1%, respectively, at 100 kHz.. These findings suggest that microelectrical impedance spectroscopy might find application as a method for quantifying progression of cancer cells without the need for tagging or modifying the sampled cells.

Topics: Breast Neoplasms; Cell Line, Tumor; Disease Progression; Electric Impedance; Electrodes; Electrophysiology; Equipment Design; Humans; Medical Oncology; Microcomputers; Silicon; Spectrum Analysis

We describe a compact diffuse optical tomography system specifically designed for breast imaging. The system consists of 64 silicon photodiode detectors, 64 excitation points, and 10 diode lasers in the near-infrared region, allowing multispectral, three-dimensional optical imaging of breast tissue. We also detail the system performance and optimization through a calibration procedure. The system is evaluated using tissue-like phantom experiments and an in vivo clinic experiment. Quantitative two-dimensional (2D) and three-dimensional (3D) images of absorption and reduced scattering coefficients are obtained from these experiments. The ten-wavelength spectra of the extracted reduced scattering coefficient enable quantitative morphological images to be reconstructed with this system. From the in vivo clinic experiment, functional images including deoxyhemoglobin, oxyhemoglobin, and water concentration are recovered and tumors are detected with correct size and position compared with the mammography.

Topics: Algorithms; Breast; Breast Neoplasms; Calibration; Hemoglobins; Humans; Image Enhancement; Mammography; Optics and Photonics; Oxyhemoglobins; Phantoms, Imaging; Silicon; Tomography, Optical; Water

Electrochemical monitoring of cellular signal transduction under three-dimensional (3-D) cell culture conditions has been demonstrated by combining cell-based microarrays with a secreted alkaline phosphatase (SEAP) reporter system. The cells were genetically engineered to produce SEAP under the control of nuclear factor kappaB (NFkappaB) enhancer elements, and they were embedded with a small volume of a collagen gel matrix on a pyramidal-shaped silicon microstructure. Cellular SEAP expression triggered by NFkappaB activation was assessed by two types of electrochemical systems. First, SEAP expression of a 3-D cell array on a chip was continuously monitored in situ for 2 days by scanning electrochemical microscopy (SECM). Since the SECM-based assay enables the evaluation of cellular respiratory activity, simultaneous measurements of cellular viability and signal transduction were possible. Further, we have developed an electrode-integrated cell culture device for parallel evaluation of cellular SEAP expression. The detector electrode was integrated around the silicon microhole. Two kinds of cells were immobilized on the array of microholes on the same chip for comparative characterization of their SEAP activity. This electrochemical microdevice can be applied to evaluate the SEAP expression activity in multiple cellular microarrays by a high-throughput method.

Topics: Alkaline Phosphatase; Biosensing Techniques; Breast Neoplasms; Cell Communication; Cell Culture Techniques; Cell Survival; Cells, Cultured; Electrochemistry; Electrodes; Female; Genes, Reporter; Genetic Engineering; Humans; Microscopy; NF-kappa B; Signal Transduction; Silicon; Time Factors

A novel three-dimensional cell culture system was constructed with an array of cell panels (4 x 5) in a silicon chip, together with multi-channel drug containers. Human breast cancer (MCF-7) cells were embedded in a collagen-gel matrix and entrapped in a pyramidal-shaped silicon hole. Each cell panel can be isolated by a channel composed of a microfluid part and a reservoir. A cell panel was exposed to 200 mm KCN for 2 days to demonstrate that each cell panel could be independently evaluated under various stimulation conditions. Based on the cellular respiration activity, the proliferation behavior was continuously monitored on the silicon-based cell array for 5 days using scanning electrochemical microscopy (SECM). The cells entrapped in the device (3-D culture) proliferated normally, and the proliferation rate was lower than that of cells grown in a monolayer cell culture (2-D culture). The effects of three anticancer drugs measured simultaneously on the cell chip were in good agreement with those obtained by a conventional colorimetric assay. Our results suggest that the silicon-based device for 3D culture is appropriate for a chemosensitivity assay involving multi-chemical stimulation.

Topics: Antineoplastic Agents; Biosensing Techniques; Breast Neoplasms; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Screening Assays, Antitumor; Electrochemistry; Equipment Design; Equipment Failure Analysis; Humans; Microfluidic Analytical Techniques; Microscopy, Scanning Probe; 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

A system for in vivo breast imaging with monochromatic x-rays has been designed and built at the synchrotron radiation facility Elettra in Trieste (Italy) and will be operational in 2004. The system design involves the possibility of performing both planar mammography and breast tomography. In the present work, the first results obtained with a test set-up for breast tomography are shown and discussed. Tomographic images of in vitro breasts were acquired using monochromatic x-ray beams in the energy range 20-28 keV and a linear array silicon pixel detector. Tomograms were reconstructed using standard filtered backprojection algorithms; the effect of different filters was evaluated. The attenuation coefficients of fibroglandular and adipose tissue were measured, and a quantitative comparison of images acquired at different energies was performed by calculating the differential signal-to-noise ratio of fibroglandular details in adipose tissue. All images required a dose comparable to the dose delivered in clinical, conventional mammography and showed a high resolution of the breast structures without the overlapping effects that limit the visibility of the structures in 2D mammography. A quantitative evaluation of the images proves that the image quality at a given dose increases in the considered energy range and for the considered breast sizes.

Topics: Adipose Tissue; Breast; Breast Neoplasms; Connective Tissue; Humans; Image Enhancement; Italy; Mammography; Radiation; Radiation Dosage; Silicon; Synchrotrons; Tomography, X-Ray Computed

Breast paraffinomas and siliconomas are granulomas caused by tissue reaction to paraffin oil and silicone injection after mammoplasty. These granulomas usually present as multiple hard masses that mimic breast cancer. Mammography and sonography have only a limited role in differentiating these masses. Magnetic resonance (MR) imaging findings of these granulomas have rarely been reported. This study evaluated the MR imaging manifestations of these granulomas.. MR imaging, mammography, and sonography were used to examine 58 breasts in 29 women with breast lumps who had undergone mammoplasty with injections of paraffin oil (n = 8) or liquid silicone (n = 50). The protocol included T1-weighted images (T1WI), fat-suppressed (FS) T2WI, post-contrast FS three-dimensional fast dynamic sequences, and FS T1WI.. Deep structures of the 58 breasts could not be clearly evaluated by sonography or mammography. Two types of MR imaging characteristics were identified: type I lesions were hypointense on T2WI and type II lesions had mixed hypointense and hyperintense components on T2WI. Both showed intermediate intensity on T1WI and revealed no enhancement on post-contrast dynamic sequences and FS T1WI. Type II lesions were seen only in siliconomas. Mastectomy was performed on seven breasts and paraffinomas or siliconomas were confirmed by pathology. When correlating MR images with pathology, hypointense lesions on T2WI in both type I and II lesions were foreign body granulomas with fibrosis and calcification. Hyperintense lesions on T2WI in type II were liquid silicone. A case of infiltrating ductal carcinoma was found in one breast in which MR imaging was successful in identifying the strongly enhanced solitary tumor from a background of type I lesions of paraffinomas preoperatively. Of the 51 breasts that did not receive surgery, no breast cancers were detected clinically or by follow-up imaging after a median of 27 months (19-54 mo).. Breast paraffinomas and siliconomas after mammoplasty have specific MR findings that are distinct from those of breast cancers. MR imaging is superior to sonography and mammography in the evaluation of breast paraffinomas and siliconomas.

Topics: Adult; Aged; Breast Neoplasms; Diagnosis, Differential; Female; Granuloma, Foreign-Body; Humans; Magnetic Resonance Imaging; Mammaplasty; Middle Aged; Paraffin; Silicon

We assessed the cosmetic and psychological effects of prosthetic intramammary breast reconstruction on women undergoing complete local excision for breast cancer.. Twenty-two women (mean age 54) underwent insertion of a Nagor silicone prosthesis into the breast cavity immediately following complete local excision. Following surgery, patients were assessed (range: 6 weeks to 1 year) by a postal questionnaire and independent photographs.. Eighteen out of twenty-two (81.8%) women completed and returned the questionnaire, and 14 out of 22 (63.6%) women were photographed. Thirteen out of eighteen (72.2%) women were either satisfied or very satisfied with the prosthesis, and 10 had experienced no problems since surgery. From the group of patients who were either satisfied or very satisfied, the total photograph assessment score was 135 out of a possible maximum score of 165. Five patients (27.8%) were very dissatisfied and requested removal of the prosthesis.. When performing a complete local excision for carcinoma of the breast, insertion of an intracavity prosthesis should be considered when this would significantly improve the cosmetic outcome.

Topics: Breast Implantation; Breast Implants; Breast Neoplasms; Female; Humans; Mastectomy; Middle Aged; Silicon; Surveys and Questionnaires; Treatment Outcome

As a part of multimodality therapy, many patients with tumors of the trunk receive radiation therapy. The major morbidity of this therapy is often secondary to incidental radiation damage to tissues adjacent to treatment areas.. We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field.. Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues.. We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites.

Topics: Abdominal Muscles; Adult; Breast Neoplasms; Cystadenocarcinoma, Mucinous; Female; Humans; Middle Aged; Neoplasms, Radiation-Induced; Ovarian Neoplasms; Prostheses and Implants; Radiation Injuries; Radiotherapy, Adjuvant; Sarcoma; Silicon; Sodium Chloride; Soft Tissue Neoplasms; Surgical Mesh; Viscera

Topics: Adult; Breast Neoplasms; Electron Probe Microanalysis; Female; Humans; Injections; Mammaplasty; Prostheses and Implants; Silicon; Silicones

Topics: Adult; Breast Neoplasms; Case-Control Studies; Confounding Factors, Epidemiologic; Female; Humans; Mammaplasty; Middle Aged; Prostheses and Implants; Silicon; Silicones

Every year in the German Federal Republic there are 15000 new cases of carcinoma of the breast in woman. In those cases in which metastases in the lymph nodes have not appeared, the rate of recovery is so high that a rehabilitation is worth careful consideration in each case. Methods of operation have been worked out over years of experimentation, with results that are now so good that not only breast-like forms, but genuine female breasts are created. With the reconstruction possibilities, the quality of the patients' survival time is improved.

Topics: Breast Neoplasms; Female; Humans; Mastectomy; Nipples; Prostheses and Implants; Silicon; Surgery, Plastic

Topics: Breast Diseases; Breast Neoplasms; Carcinoma; Female; Humans; Mastectomy; Mastitis; Pregnancy; Prostheses and Implants; Silicon; Surgery, Plastic

Topics: Animals; Breast; Breast Neoplasms; Carcinogens; Face; Granuloma; Haplorhini; Humans; Injections; Pathology; Plastics; Research; Silicon; Silicon Compounds; Skin Neoplasms; Surgery, Plastic; Toxicology