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1.  Germline Variants of Prostate Cancer in Japanese Families 
PLoS ONE  2016;11(10):e0164233.
Prostate cancer (PC) is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family). We also found shared variants of BRCA2, HOXB13, and TRRAP from 59 additional small PC families (two patients per family). We identified two deleterious HOXB13 variants (F127C and G132E). Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4, and TCF3). The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.
PMCID: PMC5049788  PMID: 27701467
2.  Heme stabilization of α-Synuclein oligomers during amyloid fibril formation 
Biochemistry  2015;54(30):4599-4610.
Alpha-Synuclein (αSyn), which forms amyloid fibrils, is linked to the neuronal pathology of Parkinson’s disease, as it is the major fibrillar component of Lewy bodies, the inclusions that are characteristic of the disease. Oligomeric structures, common to many neurodegenerative disease-related proteins, may in fact be the primary toxic species, while the amyloid fibrils exist as either a less toxic dead-end species, or even as a beneficial mechanism to clear damaged proteins. In order to alter the progression of the aggregation and gain insights into the pre-fibrillar structures, the effect of heme on αSyn oligomerization was determined by several different techniques including native (non-denaturing) polyacrylamide gel electrophoresis, thioflavin T fluorescence, transmission electron microscopy, atomic force microscopy, circular dichroism and membrane permeation using a calcein release assay. During aggregation, heme is able to bind the αSyn in a specific fashion, stabilizing distinct oligomeric conformations and promoting the formation of αSyn into annular structures, thereby delaying and/or inhibiting the fibrillation process. These results indicate that heme may play a regulatory role in the progression of Parkinson’s disease; in addition, they provide insights of how the aggregation process may be altered, which may be applicable to the understanding of many neurodegenerative diseases.
PMCID: PMC4526360  PMID: 26161848
Alpha-Synuclein; Parkinson’s disease; oligomer; heme; inhibitor
3.  Molecular Self-Assembly Strategy for Generating Catalytic Hybrid Polypeptides 
PLoS ONE  2016;11(4):e0153700.
Recently, catalytic peptides were introduced that mimicked protease activities and showed promising selectivity of products even in organic solvents where protease cannot perform well. However, their catalytic efficiency was extremely low compared to natural enzyme counterparts presumably due to the lack of stable tertiary fold. We hypothesized that assembling these peptides along with simple hydrophobic pockets, mimicking enzyme active sites, could enhance the catalytic activity. Here we fused the sequence of catalytic peptide CP4, capable of protease and esterase-like activities, into a short amyloidogenic peptide fragment of Aβ. When the fused CP4-Aβ construct assembled into antiparallel β-sheets and amyloid fibrils, a 4.0-fold increase in the hydrolysis rate of p-nitrophenyl acetate (p-NPA) compared to neat CP4 peptide was observed. The enhanced catalytic activity of CP4-Aβ assembly could be explained both by pre-organization of a catalytically competent Ser-His-acid triad and hydrophobic stabilization of a bound substrate between the triad and p-NPA, indicating that a design strategy for self-assembled peptides is important to accomplish the desired functionality.
PMCID: PMC4846159  PMID: 27116246
4.  Adaptive bill morphology for enhanced tool manipulation in New Caledonian crows 
Scientific Reports  2016;6:22776.
Early increased sophistication of human tools is thought to be underpinned by adaptive morphology for efficient tool manipulation. Such adaptive specialisation is unknown in nonhuman primates but may have evolved in the New Caledonian crow, which has sophisticated tool manufacture. The straightness of its bill, for example, may be adaptive for enhanced visually-directed use of tools. Here, we examine in detail the shape and internal structure of the New Caledonian crow’s bill using Principal Components Analysis and Computed Tomography within a comparative framework. We found that the bill has a combination of interrelated shape and structural features unique within Corvus, and possibly birds generally. The upper mandible is relatively deep and short with a straight cutting edge, and the lower mandible is strengthened and upturned. These novel combined attributes would be functional for (i) counteracting the unique loading patterns acting on the bill when manipulating tools, (ii) a strong precision grip to hold tools securely, and (iii) enhanced visually-guided tool use. Our findings indicate that the New Caledonian crow’s innovative bill has been adapted for tool manipulation to at least some degree. Early increased sophistication of tools may require the co-evolution of morphology that provides improved manipulatory skills.
PMCID: PMC4783770  PMID: 26955788
5.  Peptide Assembly-Driven Metal-Organic Framework (MOF) Motors for Micro Electric Generator 
Peptide-MOF motors, whose motions are driven by anisotropic surface gradients created via peptide self-assembly around nanopores of MOFs, can rotate microscopic rotors and magnet fast enough to generate electric power of 0.1 µW. To make the peptide-MOF generator recyclable, a new MOF is applied as a host motor engine, which has a more rigid framework with higher H2O affinity so that peptide release occurs more efficiently via guest exchange without the destruction of MOF.
PMCID: PMC4289433  PMID: 25418936
peptide assembly; metal-organic frameworks (MOFs); chemical motors; power generator
6.  Hot Spot Mutation in TP53 (R248Q) Causes Oncogenic Gain-of-Function Phenotypes in a Breast Cancer Cell Line Derived from an African American patient 
African American (AA) breast cancer patients often have triple negative breast cancer (TNBC) that contains mutations in the TP53 gene. The point mutations at amino acid residues R273 and R248 both result in oncogenic gain-of-function (GOF) phenotypes. Expression of mutant p53 (mtp53) R273H associates with increased cell elasticity, survival under serum deprivation conditions, and increased Poly (ADP ribose) polymerase 1 (PARP1) on the chromatin in the AA-derived TNBC breast cancer cell line MDA-MB-468. We hypothesized that GOF mtp53 R248Q expression could stimulate a similar phenotype in the AA-derived TNBC cell line HCC70. To test this hypothesis we depleted the R248Q protein in the HCC70 cell line using shRNA-mediated knockdown. Using impedance-based real-time analysis we correlated the expression of mtp53 R248Q with increased cell deformability. We also documented that depletion of mtp53 R248Q increased PARP1 in the cytoplasm and decreased PARP1 on the chromatin. We conclude that in the AA-derived TNBC HCC70 cells mtp53 R248Q expression results in a causative tumor associated phenotype. This study supports using the biological markers of high expression of mtp53 R273H or R248Q as additional diagnostics for TNBC resistant subtypes often found in the AA community. Each mtp53 protein must be considered separately and this work adds R248Q to the increasing list of p53 mutations that can be used for diagnostics and drug targeting. Here we report that when R248Q mtp53 proteins are expressed in TNBC, then targeting the gain-of-function pathways may improve treatment efficacy.
PMCID: PMC4730413  PMID: 26703669
TNBC; African American; p53; impedance; deformability
7.  Reciprocal effects of capsaicin and menthol on thermosensation through regulated activities of TRPV1 and TRPM8 
Transient receptor potential vanilloid 1 (TRPV1) is activated by elevated temperature (>42 °C), and it has been reported that cold temperature decreases capsaicin-induced TRPV1 activity. In contrast, transient receptor potential melastatin 8 (TRPM8) is activated by low temperatures and menthol, and heat stimulation suppresses menthol-evoked TRPM8 currents. These findings suggest that the effects of specific agents on TRPV1 and TRPM8 channels are intricately interrelated. We examined the effects of menthol on human (h)TRPV1 and of capsaicin on hTRPM8. hTRPV1 currents activated by heat and capsaicin were inhibited by menthol, whereas hTRPM8 currents activated by cold and menthol were similarly inhibited by capsaicin. An in vivo sensory irritation test showed that menthol conferred an analgesic effect on the sensory irritation evoked by a capsaicin analogue. These results indicate that in our study the agonists of TRPV1 and TRPM8 interacted with both of these channels and suggest that the anti-nociceptive effects of menthol can be partially explained by this phenomenon.
Electronic supplementary material
The online version of this article (doi:10.1007/s12576-015-0427-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4752590  PMID: 26645885
Menthol; Capsaicin; TRPV1; TRPM8; Analgesic
9.  Clinical endocrinological evaluation of the gonadal axis (testosterone, LH and FSH) in prostate cancer patients switched from a GnRH antagonist to a LHRH agonist 
To investigate the levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prostate-specific antigen (PSA) in prostate cancer patients before and after the switch from degarelix to leuprolide treatments.
We enrolled 40 treatment-naïve prostate cancer patients who were treated initially with degarelix and were later switched to leuprolide. The subjects were divided into three groups depending on when they were switched to leuprolide: the 3-month group (3m; switched after 84 days, n=10), the 2-month group (2m; 56 days, n=10), and the 1-month group (1m; 28 days, n=20). Patient symptoms and hormone levels were measured after switching therapy. The castration level was defined as a serum testosterone level ≤50 ng/dl.
Thirty-nine subjects (97.5%) achieved castration levels of testosterone (11±5.8 ng/dl) 2 weeks after degarelix was first administered, and the characteristics of these patients were investigated. Testosterone levels increased and exceeded the castration level in one subject each of the 3m (142 ng/dl), 2m (72 ng/dl), and 1m groups (63 ng/dl). All subjects achieved the castration level by day 5. In contrast to testosterone levels, the LH and FSH surge on day 2 was significantly higher in the 1m group than in the other groups. The clinical symptoms were not exacerbated before or after switching in any patients.
A testosterone surge was observed in 8.3 % of the study patients; however, it was very short-lived and mild. LH and FSH levels were significantly higher 1 month after administration compared with 2 or 3 months after degarelix administration.
PMCID: PMC4490683  PMID: 26146562
Prostate cancer; GnRH-antagonist; LHRH-agonist; Testosterone
10.  Immunostimulatory Lipid Nanoparticles from Herbal Medicine 
Chemical biology & drug design  2014;83(4):493-497.
Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of these lipids could vary substantially from experiment to experiment. Further analysis of this reproducibility issue led to the discovery of solvent-dependent nanoparticle formation by these lipids. While larger nanoparticles (approximately 100 nm) of these lipids showed modest macrophage-stimulatory activity, smaller nanoparticles (<10 nm) of the same lipids exhibited substantially higher potency. Thus, the study revealed an unexpected link between nanoparticle formation and macrophage-stimulatory activity of plant lipids. Although nanoparticles have been extensively studied in the context of vehicles for drug delivery, our finding indicates that drugs themselves can form nanoassemblies, and their biological properties may be altered by the way they assemble.
PMCID: PMC4078915  PMID: 24495243
atomic force microscopy; dynamic light scattering; Juzen-taiho-to; macrophages; macrophages; nanoparticles; β-sitosteryl β-D-glucoside
11.  A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer 
Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase. We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC).
We conducted a phase 1 study in men with progressive and chemotherapy-naïve CRPC. Patients received orteronel orally at doses of 200–400 mg twice daily (BID) with or without oral prednisolone (5 mg BID). Dose-limiting toxicity (DLT) was assessed during Cycle 1 (28 days). Patients could continue study treatment until any of criteria for treatment discontinuation were met. Gonadotropin-releasing hormone therapy was continued in patients without prior orchidectomy.
Fifteen patients were enrolled and administered at least one dose of orteronel. No DLTs were reported during Cycle 1 in this study. Adverse events (AEs) were reported in all 15 patients. Most common AEs (>30 %) were hyperlipasemia (47 %), hyperamylasemia (40 %), and constipation (33 %). Acute pancreatitis (Grades 2 and 3) and pancreatitis (Grade 1) were complicated in three patients during the study. Dose-dependent increase in plasma orteronel concentrations was indicated over the 200–400 mg BID dose range. Prednisolone coadministered did not alter PK of orteronel. Serum testosterone was rapidly suppressed below the lower limit of quantification across all doses. Of 15 subjects, 13 achieved at least a 50 % reduction from baseline in prostate-specific antigen.
Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients. The present results support further evaluation of orteronel with or without prednisolone.
PMCID: PMC4305367  PMID: 25537627
Orteronel; Castration-resistant prostate cancer; 17,20-Lyase inhibitor; Phase 1
12.  Negative differential resistance in ZnO coated peptide nanotube 
We investigate the room temperature electronic transport properties of a zinc oxide (ZnO) coated peptide nanotube contacted with Au electrodes. Current–voltage (I–V ) characteristics show asymmetric negative differential resistance (NDR) behavior along with current rectification. The NDR phenomenon is observed in both negative and positive voltage sweep scans, and found to be dependent on the scan rate and humidity. Our results suggest that the NDR is due to protonic conduction arising from water molecule redox reaction on the surface of ZnO coated peptide nanotubes rather than the conventional resonant tunneling mechanism.
PMCID: PMC4240313  PMID: 25419052
13.  Rational strategy for shaped nanomaterial synthesis in reverse micelle reactors 
Nature communications  2014;5:3870.
The shape-controlled synthesis of nanoparticles was established in single-phase solutions by controlling growth directions of crystalline facets on seed nanocrystals kinetically; however, it was difficult to rationally predict and design nanoparticle shapes. Here we introduce a methodology to fabricate nanoparticles in smaller sizes by evolving shapes thermodynamically. This strategy enables a more rational approach to fabricate shaped nanoparticles by etching specific positions of atoms on facets of seed nanocrystals in reverse micelle reactors where the surface energy gradient induces desorption of atoms on specific locations on the seed surfaces. From seeds of 12 nm palladium nanocubes, the shape is evolved to concave nanocubes and finally hollow nanocages in the size ~10 nm by etching the center of {200} facets. The high surface area-to-volume ratio and the exposure of a large number of palladium atoms on ledge and kink sites of hollow nanocages are advantageous to enhance catalytic activity and recyclability.
PMCID: PMC4112590  PMID: 24828960
14.  Suppression of Microbial Metabolic Pathways Inhibits the Generation of the Human Body Odor Component Diacetyl by Staphylococcus spp 
PLoS ONE  2014;9(11):e111833.
Diacetyl (2,3-butanedione) is a key contributor to unpleasant odors emanating from the axillae, feet, and head regions. To investigate the mechanism of diacetyl generation on human skin, resident skin bacteria were tested for the ability to produce diacetyl via metabolism of the main organic acids contained in human sweat. l-Lactate metabolism by Staphylococcus aureus and Staphylococcus epidermidis produced the highest amounts of diacetyl, as measured by high-performance liquid chromatography. Glycyrrhiza glabra root extract (GGR) and α-tocopheryl-l-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), a phosphate diester of α-tocopherol and ascorbic acid, effectively inhibited diacetyl formation without bactericidal effects. Moreover, a metabolic flux analysis revealed that GGR and EPC-K1 suppressed diacetyl formation by inhibiting extracellular bacterial conversion of l-lactate to pyruvate or by altering intracellular metabolic flow into the citrate cycle, respectively, highlighting fundamentally distinct mechanisms by GGR and EPC-K1 to suppress diacetyl formation. These results provide new insight into diacetyl metabolism by human skin bacteria and identify a regulatory mechanism of diacetyl formation that can facilitate the development of effective deodorant agents.
PMCID: PMC4229079  PMID: 25390046
15.  Impedimetric Detection of Mutant p53 Biomarker-Driven Metastatic Breast Cancers under Hyposmotic Pressure 
PLoS ONE  2014;9(6):e99351.
In cancer cells, the oncogenic mutant p53 (mtp53) protein is present at high levels and gain-of-function (GOF) activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have higher cellular elasticity as compared to normal cells assessed by monitoring the degree of deformation under hyposmotic pressure. To make fast detection in large scale, the impedance measurement was applied to monitor the swelling ratio of cells with time. The results showed that knockdown of mtp53 leads to decrease in cell swelling. In addition, by means of two types of impedimetric detection systems we consistently detected enhancement of impedance signal in mtp53-expressing breast cancer cells. Based on this observation we hypothesize that highly expressed mtp53 in metastatic mutant breast cancers can promote tumor progression by making cells more deformable and easier to spread out through extracellular matrix. The identification via the electric measurement can be accomplished within 10 minutes. All results in this report suggest that electric probing for the extent of the mtp53 expression of breast cancer cells may serve as a meaningful fingerprint for the cancer diagnostics, and this outcome will also have an important clinical implication for the development of mtp53-based targeting for tumor detection and treatment.
PMCID: PMC4060997  PMID: 24937470
16.  New Autonomous Motors of Metal-Organic Framework (MOF) Powered by Reorganization of Self-Assembled Peptides at interfaces 
Nature materials  2012;11(12):1081-1085.
There have developed a variety of microsystems that harness energy and convert it to mechanical motion. Here we developed new autonomous biochemical motors by integrating metal-organic framework (MOF) and self-assembling peptides. MOF is applied as an energy-storing cell that assembles peptides inside nanoscale pores of the coordination framework. The robust assembling nature of peptides enables reconfiguring their assemblies at the water-MOF interface, which is converted to fuel energy. Re-organization of hydrophobic peptides could create the large surface tension gradient around the MOF and it efficiently powers the translation motion of MOF. As a comparison, the velocity of normalized by volume for the DPA-MOF particle is faster and the kinetic energy per the unit mass of fuel is more than twice as large as the one for previous gel motor systems. This demonstration opens the new application of MOF and reconfigurable molecular self-assembly and it may evolve into the smart autonomous motor that mimic bacteria to swim and harvest target chemicals by integrating recognition units.
PMCID: PMC3505225  PMID: 23104155
17.  Assemblies of Functional Peptides and Their Applications in Building Blocks for Biosensors 
Advanced functional materials  2011;21(6):1018-1026.
We highlight our recent applications of functional peptide nanotubes, self-assembled from short peptides with recognition elements, as building blocks to develop sensors. Peptide nanotubes with high aspect ratios are excellent building blocks for directed assembly into device configurations, and their combining structures with the nanometric diameters and the micrometric lengths enables to bridge the nano-world and the micro-world.
PMCID: PMC3584348  PMID: 23459763
peptide nanotube; biosensor; self-assembly; pathogens; heavy metals; bionanotechnology; electrochemistry
18.  Biomimetic Fabrication of Genetically-Engineered Collagen Peptide-Assembled Freestanding Films Reinforced by Quantum Dot Joints 
Soft matter  2012;8(26):6871-6875.
Genetically-engineered collagen peptides were assembled into freestanding films when QDs are co-assembled as joints between collagen domains. These peptide based films show excellent mechanical properties with Young’s modulus of ~20 GPa, much larger than most of multi-composite polymer films and previously reported freestanding nanoparticle-assembled sheets, and it is even close to the bone tissue in nature. These films show little permanent deformation under small indentation while the mechanical hysteresis becomes remarkable when the load approaches near and beyond the rupture point, which is also characteristic to the bone tissue.
PMCID: PMC3439209  PMID: 22982983
19.  Simple method for preventing inguinal hernias after radical retropubic prostatectomy 
Prostate International  2013;1(2):76-80.
Inguinal hernias often occur after radical retropubic prostatectomy (RRP). We present a novel and simple technique for preventing inguinal hernias after RRP, which any surgeon can complete within a few minutes.
A total of 230 Japanese prostate cancer patients underwent RRP between January 2007 and September 2011. From July 2009, 115 patients underwent inguinal hernia prevention procedures at the same time as RRP. In this procedure, we released approximately 5 cm of the bilateral vas deferens and spermatic vessels from the peritoneum. In cases in which the processus vaginalis had spread into the abdomen, we ligated it close to the peritoneal cavity and then transected it. The remaining 115 patients who underwent RRP but did not undergo the hernia prevention procedure were used as the control group. The incidence rate of postoperative inguinal hernia was compared between the 2 groups.
Inguinal hernias developed during the postoperative follow-up period in 18 of the 115 control patients (15.7%) (median duration, 50 months). The hernia-free survival rate of this group was 89.6% and 84.1% at 1 and 2 postoperative years, respectively. In contrast, only 1 of the 115 patients (0.87%) who underwent the hernia prevention procedure developed an inguinal hernia during the follow-up period (median duration, 27 months). The hernia-free survival rate of this group was 100% at both 1 and 2 postoperative years (P<0.0001).
We developed a simple method for preventing post-RRP inguinal hernias. The procedure is easy to perform and produces excellent outcomes.
PMCID: PMC3814116  PMID: 24223406
Inguinal hernia; Control and prevention; Prostate neoplasms; Prostatectomy
20.  Chlormadinone acetate is effective for hot flush during androgen deprivation therapy 
Prostate International  2013;1(3):113-116.
To investigate the clinical efficacy of low-dose chlormadinone acetate (CMA) in prostate cancer patients who suffer from hot flushes that is a major side effect of androgen deprivation therapy.
Our study included 32 prostate cancer patients who had severe hot flush after undergoing hormone therapy for more than 3 months. The average age of the patients was 72.5 years. In the beginning, patients received CMA at 100 mg orally per day. We defined the hot flush as disappeared, improved, or not improved. In patients with disappeared or improved symptoms, we decreased CMA dose to 50 mg per day, and after we reevaluated the effect, we decreased CMA dose to 25 mg per day. When hot flush appeared again at 25 mg per day, we returned the dose of CMA to 50 mg per day. In cases with no change for more than two months, we canceled the treatment of CMA.
Hot flush disappeared in 17 patients, improved in 10 patients, and did not improve in 5 patients (reduction in 84% of hot flush patients). The median time to hot flush reduction was 1.16 months. The effect of CMA was maintained at 25 mg per day in 19 patients and at 50 mg per day in 8 patients. No patients had prostate-specific antigen failure in the treatment of CMA.
When hot flush appears during treatment with luteinizing hormone-releasing hormone agonist for prostate cancer, it seems that CMA can improve it immediately in most patients.
PMCID: PMC3814123  PMID: 24223412
Hormonal antineoplastic agents; Chlormadinone acetate; Hot flashes; Prostate neoplasms
21.  Androgen receptor coactivator p120 subtype β is highly expressed in prostate cancer 
Prostate International  2013;1(1):10-15.
The β form of p120 is reported to be a strong coactivator of the androgen receptor. We investigated the gene expression profiles of the α and β forms of p120 in prostate cancer cell lines, benign prostatic hyperplasia (BPH), nontreated prostate cancer (NTPC), and prostate cancer after androgen deprivation therapy (PCA-ADT).
We obtained 154 prostate needle biopsy specimens (81 in BPH, 51 in NTPC, and 22 in PCA-ADT). Levels of p120α and β expression were determined by multiplex real-time polymerase chain reaction.
Prostate cancer cell lines, LNCaP, PC-3, DU-145, and LNCaP-LA, which is a derivative of LNCaP under androgen deprivation, expressed both p120α and p120β. p120α expression levels were significantly higher than those of p120β in all cell lines examined. In human prostate tissues, p120α expression was significantly higher than that of p120β in BPH and NTPC. p120α expression in BPH was significantly higher than in other groups. In contrast, p120β expression was significantly higher in NTPC and PCA-ADT than in BPH. Expression of the two forms of p120 was not correlated with age, prostate-specific antigen, or Gleason score.
The expression profiles of p120α and p120β significantly differ in cancerous and benign prostatic tissues.
PMCID: PMC3821517  PMID: 24223396
Androgen receptor; Nuclear coactivator; Prostatic neoplasms
22.  Catalytic Peptides for Inorganic Nanocrystal Synthesis Discovered by New Combinatorial Phage Display Approach 
PMCID: PMC3517003  PMID: 21928455
catalytic peptides; biomineralization; phage display; nanocrystals; ZnO; bionanotechnology
23.  Comparison of Electrical Properties of Viruses Studied by AC Capacitance Scanning Probe Microscopy 
Capacitances of five types of viruses, adenovirus type 5 (AV 5) herpes simplex virus type 1 (HSV1), simian virus 40 (SV40), vaccinia (MVA), and cowpea mosaic virus (CPMV) were compared by AC capacitance scanning probe microscopy. This technique, using a Pt-coated AFM tip as an electrode to probe capacitance of materials between the tip and a bottom electrode, has been applied to study surface structures of semiconductors and polymers with nanometer spacial resolution, however biological samples at the nanoscale have not been explored by this technique yet. Because most biological cells are poor conductors, this approach to probe electric properties of cells by capacitance is logical. This scanning probe technique (SPM) showed that all of these viruses have distinguishable and characteristic capacitances, respectively. Series of control experiments were carried out using mutant viruses in order to validate the origin of the characteristic capacitance responses for different viruses. A mutation on the capsid in HSV1 virus with green fluorescence proteins (GFP) increased capacitance from 9×10−6 F/cm2 to 1×10−5 F/cm2 at the frequency of 104 Hz. HSV2 virus decreased capacitance when its envelope and glycoproteins were chemically extracted. These control experiments indicate that dielectric properties of capsid proteins and envelope glycoproteins significantly influence overall dielectric constants of viruses. Because those capsid proteins and glycoproteins are characteristic to the virus strain, this technique could be applied to detect and identify viruses at the single viron level using their distinct capacitance spectra as fingerprints without labeling.
PMCID: PMC3474603  PMID: 18092777
AC impedance; Bionanotechnology; Capacitance; Virus; Sensor; Label-free detection
25.  Label-free cancer cell detection with impedimetric transducers 
Analytical chemistry  2009;81(24):10167-10171.
While cancer is still an implacable disease, many cancers can be cured if they are diagnosed in an early stage. Recently, it was reported that the transformation from normal cells to cancer cells can change their mechanoelastic properties to become softer and more deformable. If some cancer cells are more deformable, then a progressive increase of the volume of softer cancer cells should be induced as an abrupt change in osmolarity is applied. Based on this hypothesis, we developed a sensor that can electronically monitor the volume increase of cancer cells under hyposmotic pressure. By this methodology, K:Molv NIH 3T3 cells, 786-O human kidney carcinoma cells, and MPSC-1 ovarian cancer cells were successfully detected within 30 minutes using on the order of 10 cells. These cancer cells could be detected with the same sensitivity even in the presence of a vast excess of the respective non-cancerous cells (NIH 3T3 cells, Human Embryonic Kidney (HEK) 293 cells, ovarian surface epithelial (OSE) cells). Since the proposed impedimetric sensor could be useful for detecting cancer cells fast and reliably, it could be further implemented in the screening of large populations of tissue samples and the detection of circulating tumor cells for point-of-care applications.
PMCID: PMC2797081  PMID: 19911810

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