Fabrication and evaluation of bilateral Helmholtz radiofrequency coil for thermo-stable breast image with reduced artifacts.

PURPOSE: The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer. MATERIALS AND METHODS: For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided with nonmagnetic components. Element values were optimized with an electromagnetic field simulation. Images were acquired on a GE 600 PET-computed tomography (CT) and GE 3.0 T MR system. For this study, we used the T1-weighted image (volunteer; repetition time (TR), 694 ms; echo time (TE), 9.6 ms) and T2-weighted image (phantom; TR, 8742 ms; TE, 104 ms) with the fast spin-echo sequence. RESULTS: The results of measuring image factors with the proposed radiofrequency (RF) coil and standard conventional RF coil were as follows: signal-to-noise ratio (breast; 207.7 vs. 175.2), percent image uniformity (phantom; 89.22%-91.27% vs. 94.63%-94.77%), and Hounsfield units (phantom; -4.51 vs. 2.38). CONCLUSIONS: Our study focused on the feasibility of proposed two-channel Helmholtz loops (by minimizing metallic components and soldering) for PET-MR imaging and found the comparable image quality to the standard conventional coil. We believe our work will help significantly to improve image quality with the development of a less metallic breast MR coil.

Comprehensive Immuno-Molecular Profiles for Liposarcoma: Roles of Programmed Death Ligand 1, Microsatellite Instability, and PIK3CA.

BACKGROUND: Developing personalized strategies for cancer has shown good efficacies. METHODS: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. RESULTS: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). CONCLUSIONS: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

Labeling-free detection of ECD-HER2 protein using aptamer-based nano-plasmonic sensor.

A gold nanoparticle-based localized surface plasmon resonance substrate has been developed as nano-sensors for various bio-applications. However, reproducible and robust sensing substrates anchored gold nanoparticles has not yet been explored. In this study, dopamine-coated gold nanorods (DGNRs) were prepared and immobilized onto the micro-grooving PDMS substrates (mgPDMS). Subsequently, HER2-specific aptamers were conjugated with DGNR/mgPDMS for ECD-HER2 detection. By screening of the optimal concentration of DGNR and aptamers, the effective HER2-specific aptasensor was built up. In particular, the real-time binding assay for the evaluation of limit-of-detection (<5 ng ml-1) was conducted. Furthermore, the binding kinetics for ECD-HER2 was investigated under the biological fluid using a rat serum. Our HER2-specific aptasensor demonstrated the effective sensitivity and selectivity for ECD-HER2.

Differences in the Efficacies of Pazopanib and Gemcitabine/Docetaxel as Second-Line Treatments for Metastatic Soft Tissue Sarcoma.

BACKGROUND: We retrospectively investigated the treatment outcomes of second-line treatment with pazopanib or gemcitabine/docetaxel in patients with advanced soft tissue sarcoma (STS). METHODS: Ninety-one patients who were treated with pazopanib or gemcitabine/docetaxel for advanced STS between 1995 and 2015 were analyzed. RESULTS: Forty-six and 45 patients received pazopanib and gemcitabine/docetaxel, respectively. The median progression-free survival for the group treated with pazopanib was 4.5 months compared with 3.0 months for the gemcitabine/docetaxel group (p = 0.593). The median overall survival for the group treated with pazopanib was 12.6 months compared with 14.2 months for the gemcitabine/docetaxel group (p = 0.362). The overall response rates (ORRs) were 6.5 and 26.7% in the pazopanib and gemcitabine/docetaxel groups, respectively. The following parameters had ORRs favoring gemcitabine/docetaxel: age ≥50 years (31.6 vs. 2.9%, p = 0.006), histologic grade 1-2 (40.9 vs. 0%, p = 0.001), and poor first-line treatment response (23.3 vs. 3.0%, p = 0.022). Gemcitabine/docetaxel was associated with better ORRs for the following histologic subtypes: leiomyosarcoma (p = 0.624), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (p = 0.055), and angiosarcoma (p = 0.182). However, the ORR of synovial sarcoma favored pazopanib (p = 0.99). CONCLUSIONS: The efficacies of pazopanib and gemcitabine/docetaxel as second-line treatments after doxorubicin or ifosfamide failure differed among clinical and histologic subgroups and appeared to facilitate a more personalized treatment approach for advanced STS.

Double-inversion recovery with synthetic magnetic resonance: a pilot study for assessing synovitis of the knee joint compared to contrast-enhanced magnetic resonance imaging.

OBJECTIVES: To investigate the agreement between double-inversion recovery (DIR) with synthetic magnetic resonance imaging (MRI) and T1-weighted contrast-enhanced (CE)-MRI for the assessment of knee synovitis. METHODS: T1-weighted CE-MRI and synthetic MRI of 30 patients were compared. Synthetic DIR image reconstruction was performed with two inversion times (280-330 ms and 2800-2900 ms). Subjective image quality, visibility of synovium, detection of synovitis, and total synovitis score in the knee joint were evaluated on both MR images. The relative signal intensity (SI) and relative contrast of synovium, joint effusion, and bone marrow for two imaging were assessed. Differences in data between two imaging were assessed by using Wilcoxon's signed-rank test and chi-square test/Fisher's exact test. Interobserver agreement was expressed as weighted kappa value. Accuracy of synthetic DIR image was calculated by using CE-MRI as reference standard. RESULTS: T1-weighted CE-MRI yielded better image quality than synthetic DIR imaging (p < 0.001). Interobserver agreements for detecting synovitis diagnosis/sum of the synovitis score were moderate to almost perfect (κ = 0.58/0.44, synthetic DIR; κ = 0.83/0.65, T1-weighted CE-MRI). There were no statistical differences in visibility of synovium (p = 0.058-0.190), detection of synovitis (p < 0.001), and relative SI of structures between two imaging (p = 0.086-0.360). Synovium-to-effusion contrast was higher in synthetic DIR (p = 0.003) and synovium-to-bone marrow contrast was higher in CE-MRI (p < 0.001). CONCLUSION: Synthetic DIR imaging showed a moderate degree of interobserver agreement and good accuracy for detecting synovitis. Though it has limitations, it may play a role in imaging of degenerative joint disease or larger cohort scientific studies where gadolinium application is not feasible. KEY POINTS: • Synthetic double-inversion recovery (DIR) imaging avoids the use of contrast agent. • There was no significant difference between T1-weighted CE-MRI and synthetic DIR imaging in evaluating presence of synovitis in knee joint. • Synthetic DIR imaging showed moderate degree of interobserver agreement and good accuracy for detecting synovitis compared to CE-MRI, and it may facilitate evaluation of some regions of peripatellar synovitis.

Microsphere-Based Nanoindentation for the Monitoring of Cellular Cortical Stiffness Regulated by MT1-MMP.

Biophysical properties are intimately connected to metastatic functions and aggressiveness in cancers. Especially, cellular stiffness is regarded as a biomarker for the understanding of metastatic potential and drug sensitivity. Here, protease-mediated changes of cortical stiffness are identified due to the deformation of cytoskeleton alignment at a cortex. For the past few decades, membrane type 1-matrix metalloproteinase (MT1-MMP) has been well known as a kernel protease enriched in podosomes during metastasis for extracellular matrix degradation. However, the biophysical significance of MT1-MMP expressing cancer cells is still unknown. Therefore, the nanomechanics of cancer cells is analyzed by a nanoindentation using a microsphere-attached cantilever of atomic force microscopy (AFM). In conclusion, the results suggest that MT1-MMP has contributed as a key regulator in cytoskeletal deformation related with cancer metastasis. Particularly, the AFM-based nanoindentation system for the monitoring of cortical nanomechanics will be crucial to understand molecular networks in cancers.

Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma.

BACKGROUND: Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification by H3K27me3. In the present study, we characterized the PRC expression pattern and its clinical implication in sarcoma. METHODS: Using immunohistochemistry, we analyzed PRC expression in 105 sarcoma patients with 5 subtypes: synovial sarcoma (n = 18), rhabdomyosarcoma (n = 28), Ewing sarcoma (n = 15), osteosarcoma (n = 30), and others (n = 14). RESULTS: The median age at diagnosis in the patient cohort was 26.8 years (range: 1-78 years) and the male-to-female ratio was 1:4. Initial disease presentation was locoregional disease in 83% of patients and initial metastatic disease in the remaining 17%. PRC expression was not significantly different according to histologic subtype (P = 0.400). Overall survival (OS) was significantly poor for SUZ12 high (P = 0.001), EED1 high (P = 0.279), and H3K27me3 high (P = 0.009). Ultimately, patients with PRC2high had significantly inferior OS than the no expression group (P = 0.009). In the Cox proportional hazard model adjusted for stage, histologic grade, surgery, margin and initial metastasis, SUZ12 expression (P = 0.020, HR 29.069, 95% CI 1.690-500.007), H3K27me3 (P = 0.010, HR 3.743, 95% CI 1.370-10.228) expression was significantly associated with shorter OS. CONCLUSION: We detected PRC expression in various sarcomas and demonstrated its independent negative prognostic role, suggesting the PRC axis as promising therapeutic target for treating sarcoma.

Optimization of T2-weighted imaging for shoulder magnetic resonance arthrography by synthetic magnetic resonance imaging.

Background Synthetic magnetic resonance imaging (MRI) allows reformatting of various synthetic images by adjustment of scanning parameters such as repetition time (TR) and echo time (TE). Optimized MR images can be reformatted from T1, T2, and proton density (PD) values to achieve maximum tissue contrast between joint fluid and adjacent soft tissue. Purpose To demonstrate the method for optimization of TR and TE by synthetic MRI and to validate the optimized images by comparison with conventional shoulder MR arthrography (MRA) images. Material and Methods Thirty-seven shoulder MRA images acquired by synthetic MRI were retrospectively evaluated for PD, T1, and T2 values at the joint fluid and glenoid labrum. Differences in signal intensity between the fluid and labrum were observed between TR of 500-6000 ms and TE of 80-300 ms in T2-weighted (T2W) images. Conventional T2W and synthetic images were analyzed for diagnostic agreement of supraspinatus tendon abnormalities (kappa statistics) and image quality scores (one-way analysis of variance with post-hoc analysis). Results Optimized mean values of TR and TE were 2724.7 ± 1634.7 and 80.1 ± 0.4, respectively. Diagnostic agreement for supraspinatus tendon abnormalities between conventional and synthetic MR images was excellent (κ = 0.882). The mean image quality score of the joint space in optimized synthetic images was significantly higher compared with those in conventional and synthetic images (2.861 ± 0.351 vs. 2.556 ± 0.607 vs. 2.750 ± 0.439; P < 0.05). Conclusion Synthetic MRI with optimized TR and TE for shoulder MRA enables optimization of soft-tissue contrast.

Response evaluation of giant-cell tumor of bone treated by denosumab: Histogram and texture analysis of CT images.

BACKGROUND: This study aimed to compare computed tomography (CT) features, including tumor size and textural and histogram measurements, of giant-cell tumors of bone (GCTBs) before and after denosumab treatment and determine their applicability in monitoring GCTB response to denosumab treatment. METHODS: This retrospective study included eight patients (male, 3; female, 5; mean age, 33.4 years) diagnosed with GCTB, who had received treatment by denosumab and had undergone pre- and post-treatment non-contrast CT between January 2010 and December 2016. This study was approved by the institutional review board. Pre- and post-treatment size, histogram, and textural parameters of GCTBs were compared by the Wilcoxon signed-rank test. Pathological findings of five patients who underwent surgery after denosumab treatment were evaluated for assessment of treatment response. RESULTS: Relative to the baseline values, the tumor size had decreased, while the mean attenuation, standard deviation, entropy (all, P = 0.017), and skewness (P = 0.036) of the GCTBs had significantly increased post-treatment. Although the difference was statistically insignificant, the tumors also exhibited increased kurtosis, contrast, and inverse difference moment (P = 0.123, 0.327, and 0.575, respectively) post-treatment. Histologic findings revealed new bone formation and complete depletion or decrease in the number of osteoclast-like giant cells. CONCLUSION: The histogram and textural parameters of GCTBs changed significantly after denosumab treatment. Knowledge of the tendency towards increased mean attenuation and heterogeneity but increased local homogeneity in post-treatment CT histogram and textural features of GCTBs might aid in treatment planning and tumor response evaluation during denosumab treatment.

Location of residual viable tumor cells after neoadjuvant chemotherapy: A new concept with high prognostic performance in osteosarcoma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to establish a new concept for evaluating responses to neoadjuvant chemotherapy in osteosarcoma. METHODS: A total of 56 high-grade extremity osteosarcoma patients were retrospectively reviewed. A new conceptual method was derived from locations of residual viable tumor cells (LRVTC) after chemotherapy, whether extracompartmental or intracompartmental, rather than quantitative measurements of necrosis rates of tumor cells. RESULTS: LRVTC after chemotherapy was independently associated with overall survival ([OS]hazard ratio [HR] = 6.502, P = 0.008) after adjustment for Huvos grade (HR = 3.694, P = 0.045), alkaline phosphatase ([ALP] HR = 2.140, P = 0.226), size (HR = 0.318, P = 0.133), joint extension (HR = 2.309, P = 0.162), and metastasis at diagnosis (HR = 8.228, P = 0.009). LRVTC was also independently associated with metastasis (HR = 5.096, P = 0.002) after adjustment for Huvos grade (HR = 2.261, P = 0.101), ALP (HR = 2.558, P = 0.053), size (HR = 1.280, P = 0.641), and joint extension (HR = 1.800, P = 0.254). AUC values of LRVTC for OS and metastasis were superior to those of Huvos grade: AUCs for OS (LRVTC: 0.757, Confidence Interval [CI] = 0.618 to 0.865 vs Huvos grade: 0.590, [CI] = 0.445 to 0.725; AUC = 0.167, P = 0.086) and metastasis (LRVTC: 0.769, CI = 0.631 to 0.874 vs Huvos grade: 0.606, [CI] = 0.461 to 0.739; AUC = 0.163, P = 0.046). CONCLUSIONS: LRVTC after chemotherapy may be useful as a new method with high performance for evaluating chemo-responses in osteosarcoma.

Lateral Cortical Thickening and Bone Heterogeneity of the Subtrochanteric Femur Measured With Quantitative CT as Indicators for Early Detection of Atypical Femoral Fractures in Long-Term Bisphosphonate Users.

OBJECTIVE: The objective of our study was to compare subtrochanteric femur bone mineral density (BMD) and bone quality of long-term bisphosphonate (BP) users who sustained an atypical femoral fracture (AFF) with BP users who did not sustain a femoral fracture and BP-naïve patients with no history of femoral fracture using quantitative CT (QCT). MATERIALS AND METHODS: Fourteen female BP users with an AFF (mean age, 72.6 years; mean duration of BP use, 6.2 years; mean body mass index, 21.9) who had undergone QCT before fracture events were sex-, age-, BP use duration-, and body mass index-matched to 14 BP users who did not sustain a fracture and 14 BP-naïve patients. The lateral cortical thickness index (CTI) and the mean BMD (BMDmean) and SD of the BMD (BMDSD) within the lateral cortex and within the entire cross-sectional area of the subtrochanteric femur were measured on axial QCT. Femoral neck-shaft angles were measured on the QCT scout image. Parameters were analyzed using the Kruskal-Wallis test. RESULTS: Lateral CTIs were greater in the BP users with an AFF (median, 0.28) than in the BP users without a femoral fracture (median, 0.21) (p = 0.038) and the BP-naïve group (median, 0.21) (p = 0.009). The lateral cortex BMDSD was significantly higher in the BP users with an AFF (median, 59.59 mg/cm3) than the BP users without a femoral fracture (median, 39.27 mg/cm3; p = 0.049) and the BP-naïve group (median, 31.02 mg/cm3; p = 0.037). There was no significant difference among groups in lateral cortex BMDmean, BMDmean and BMDSD of the entire cross-sectional area, and femoral neck-shaft angle. CONCLUSION: Long-term BP users with a subsequent AFF had a thicker lateral cortex and higher lateral cortex BMDSD at the subtrochanteric area before the fracture on QCT than BP users who did not sustain a femoral fracture and BP-naïve patients.

Articular cartilage grading of the knee: diagnostic performance of fat-suppressed 3D volume isotropic turbo spin-echo acquisition (VISTA) compared with 3D T1 high-resolution isovolumetric examination (THRIVE).

Background Conventionally, two-dimensional (2D) fast spin-echo (FSE) sequences have been widely used for clinical cartilage imaging as well as gradient (GRE) sequences. Recently, three-dimensional (3D) volumetric magnetic resonance imaging (MRI) has been introduced with one 3D volumetric scan, and this is replacing slice-by-slice 2D MR scans. Purpose To evaluate the image quality and diagnostic performance of two 3D sequences for abnormalities of knee cartilage: fat-suppressed (FS) FSE-based 3D volume isotropic turbo spin-echo acquisition (VISTA) and GRE-based 3D T1 high-resolution isovolumetric examination (THRIVE). Material and Methods The institutional review board approved the protocol of this retrospective review. This study enrolled 40 patients (41 knees) with arthroscopically confirmed abnormalities of cartilage. All patients underwent isovoxel 3D-VISTA and 3D-THRIVE MR sequences on 3T MRI. We assessed the cartilage grade on the two 3D sequences using arthroscopy as a gold standard. Inter-observer agreement for each technique was evaluated with the intraclass correlation coefficient (ICC). Differences in the area under the curve (AUC) were compared between the 3D-THRIVE and 3D-VISTA. Results Although inter-observer agreement for both sequences was excellent, the inter-observer agreement for 3D-VISTA was higher than for 3D-THRIVE for cartilage grading in all regions of the knee. There was no significant difference in the diagnostic performance ( P > 0.05) between the two sequences for detecting cartilage grade. Conclusion FSE-based 3D-VISTA images had good diagnostic performance that was comparable to GRE-based 3D-THRIVE images in the evaluation of knee cartilage, and can be used in routine knee MR protocols for the evaluation of cartilage.

Magnetic resonance arthrography results that indicate surgical treatment for partial articular-sided supraspinatus tendon avulsion: a retrospective study in a tertiary center.

Background Specific findings on magnetic resonance arthrography (MRA) that indicate the need for surgery in patients with partial articular-sided supraspinatus tendon avulsion (PASTA) are not well understood. Purpose To determine which MRA findings are characteristic of patients who undergo surgery for PASTA. Material and Methods From July 2011 to February 2014, MRA findings for patients treated for PASTA were retrospectively reviewed. The patients were divided into two groups: conservative treatment and surgical repair. MRA findings were compared between the groups. The following MRA results were assessed: length grade, width grade, co-existing superior labrum anterior posterior (SLAP) lesions, degenerative changes in the glenohumeral joint, presence of subacromial-subdeltoid bursitis, acromion type, presence of adhesive capsulitis, and tears of the subscapularis or infraspinatus tendon within the rotator cuff. Logistic regression analyses were conducted to identify which MRA findings were significantly associated with surgical treatment. Results Forty-five surgically treated patients and 203 conservatively treated ones were evaluated. The MRA findings showed significant differences between the groups with respect to length grade, width grade, degenerative changes in glenohumeral joint, bursitis, and co-existing rotator cuff tears ( P < 0.05). Multivariate logistic regression showed correlations between surgical repair and both grade 3 length tears (odds ratio, 30.8) and co-existing tears of the subscapularis or infraspinatus tendon (odds ratio, 2.9). Conclusion Surgical treatment is commonly performed in PASTA patients whose lesion lengths are grade 3 or who have co-existing tears in the subscapularis or infraspinatus tendon. Radiologists should pay attention to these MRA signs when evaluating PASTA patients.

Value of the Strain Ratio on Ultrasonic Elastography for Differentiation of Benign and Malignant Soft Tissue Tumors.

OBJECTIVES: The purpose of this study was to evaluate whether the strain ratio provides additional value to conventional visual elasticity scores in the differentiation of benign and malignant soft tissue tumors by ultrasonic elastography. METHODS: The Institutional Review Board approved the protocol of this retrospective review. Seventy-three patients who underwent elastography and had a soft tissue mass pathologically confirmed by ultrasound-guided core biopsy or surgical excision were enrolled from April 2012 through October 2014. On elastography, elasticity scores were determined with a 5-point visual scale, and the strain ratio to adjacent soft tissue at the same depth was calculated. Tumors were divided into benign and malignant groups according to the pathologic diagnoses. Elasticity scores and strain ratios were compared between benign and malignant groups, and diagnostic performance was evaluated by receiver operating characteristic curves. RESULTS: Of the 73 patients, 40 had benign tumors, and 33 had malignant tumors. Strain ratios (P = .003) and elasticity scores (P = .048) were significantly different between pathologic results. The areas under the receiver operating characteristic curves were 0.700 (95% confidence interval, 0.581-0.802) for the strain ratio and 0.623 (95% confidence interval, 0.515-0.746) for elastography. CONCLUSIONS: The strain ratios of malignant soft tissue tumors were lower than those of benign tumors and showed better diagnostic performance than did elasticity scores. The strain ratio can be used as a diagnostic indicator to predict the malignant potential of soft tissue tumors.

Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma.

BACKGROUND: The PD-1/PD-L1 axis plays a paramount role in the immune escape of tumor cells by negative regulation of T-cell functions. The aim of the present study was to characterize the PD-L1 expression pattern and its clinical implication in soft-tissue sarcomas (STS). METHODS: We analyzed PD-L1 expression in 82 STS patients with 5 subtypes: rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma, epithelioid sarcoma, and mesenchymal chondrosarcoma. RESULTS: The median age at diagnosis was 26 (range: 1-78) and the male to female ratio was 1.6. The majority (80 %) of patients showed locoregional disease rather than metastatic disease at diagnosis. Thirty-five cases (43 %) showed PD-L1 expression and the proportion of PD-L1 expression was significantly different according to histologic subtypes (P = 0.004); highest in epithelioid sarcoma (100 %, 7/7), followed by synovial sarcoma (53 %, 10/19), rhabdomyosarcoma (38 %, 12/32), and Ewing sarcoma (33 %, 6/18), while it was not expressed in mesenchymal chondrosarcoma (0 %, 0/6). STS patients with PD-L1 expression had worse overall survival compared with those without PD-L1 expression (5-year survival rate: 48 % vs. 68 %, P = 0.015). The Cox proportional hazard model adjusted for histologic subtype, initial metastasis, and PD-L1 expression showed that PD-L1 expression was significantly associated with shorter overall survival (P = 0.037, HR 2.57, 95 % CI 1.060-6.231). CONCLUSION: We have confirmed PD-L1 expression in various STS of young population and demonstrated its independent negative prognostic role, thereby suggesting the PD-1/PD-L1 axis as a potential therapeutic target for the treatment of young STS patients.

Biomarker-specific conjugated nanopolyplexes for the active coloring of stem-like cancer cells.

Stem-like cancer cells possess intrinsic features and their CD44 regulate redox balance in cancer cells to survive under stress conditions. Thus, we have fabricated biomarker-specific conjugated polyplexes using CD44-targetable hyaluronic acid and redox-sensible polyaniline based on a nanoemulsion method. For the most sensitive recognition of the cellular redox at a single nanoparticle scale, a nano-scattering spectrum imaging analyzer system was introduced. The conjugated polyplexes showed a specific targeting ability toward CD44-expressing cancer cells as well as a dramatic change in its color, which depended on the redox potential in the light-scattered images. Therefore, these polyaniline-based conjugated polyplexes as well as analytical processes that include light-scattering imaging and measurements of scattering spectra, clearly establish a systematic method for the detection and monitoring of cancer microenvironments.

Femto-molar detection of cancer marker-protein based on immuno-nanoplasmonics at single-nanoparticle scale.

We describe an in vitro biomarker sensor based on immuno-silver nanomarbles (iSNMs) and the nanoscattering spectrum imaging analysis system using localized surface plasmon resonance (LSPR). In particular, highly monodisperse SNMs with large figures of merit are prepared, and the sensing substrates are also fabricated using the nanoparticle adsorption method. The high sensitivity of the LSPR sensor based on an SNM is confirmed using various solvents that have different refractive indexes. For the sensitive and specific detection of epithelial cell adhesion molecules (EpCAMs) expressed on cancer cells, the surface of the SNM is conjugated with an anti-EpCAM aptamer, and molecular sensing for the EpCAM expression level is carried out using whole cell lysates from various cancer cell lines. Collectively, we have developed a biomarker-detectable LSPR sensor based on iSNMs, which allows for the sensitive and effective detection of EpCAMs at both the single-cell and femto-molar level.

Photothermal ablation of cancer cells using self-doped polyaniline nanoparticles.

Water-stable confined self-doping polyaniline nanocomplexes are successfully fabricated by nano-assembly using lauric acid both as a stabilizer and as a localized dopant. In particular, the colloidal stability of the polyaniline nanocomplexes in neutral pH and the photothermal potential by near-infrared light irradiation are characterized. We demonstrate that confined self-doping polyaniline nanocomplexes as a photothermal nanoagent are preserved in the doped state even at a neutral pH. Finally, confined self-doping polyaniline nanocomplexes aided by lauric acid are successfully applied for the photothermal ablation of cancer cells.

Effects for Sequential Treatment of siAkt and Paclitaxel on Gastric Cancer Cell Lines.

Real-time screening of cellular response on the drugs could provide valuable insights for the early detection of therapeutic efficiency and the evaluation of disease progression. Cancer cells have the ability to vary widely in response to stress in a manner to adjust the signaling pathway to promote the survival or having a resistance to stimulation. Cell-based label-free technologies using electronic impedance sensor have strategies for constructing the signature profiles of each cells. To achieve exquisite sensitivity to substantially change of live-cell response have an important role that predict the potential of therapeutic effects. In this study, we use an impedance-based real-time cell analysis system to investigate dynamic phenotypes of cells described as a cellular index value. We show that gastric cancer cells generated characteristic kinetic patterns that corresponded to the treatment order of therapeutics. The kinetic feature of the cells offers insightful information that cannot be acquired from a conventional single end-point assay. Furthermore, we employ a 'sequential treatment strategy' to increase cytotoxic effects with minimizing the use of chemotherapeutics. Specifically, treatment of paclitaxel (PTX) after down-regulating Akt gene expression using RNAi reduces the cell proliferation and increases apoptosis. We propose that the sequential treatment may exhibit more effective approach rather than traditional combination therapy. Moreover, the dynamic monitoring of cell-drug interaction enables us to obtain a better understanding of the temporal effects in vitro.

Molecular Imaging of CD44-Overexpressing Gastric Cancer in Mice Using T2 MR Imaging.

Novel diagnostic techniques have been developed in many research area using targetable contrast agents with magnetic resonance imaging (MRI) for cancer diagnosis. For cancer diagnosis, the use of MRI with biocompatible targeting moieties and manganese ferrite nanoparticles (MFNPs) is preferred. Thus, we synthesized MFNPs using a thermal decomposition method which enables sensitive T2 or T2 Turbo Spin Echo (TSE) MRI and coated them with hyaluronic acid (HA). The high targeting ability of HA-MFNPs was observed at MKN-45 cells (gastric cancer cell line) which high-expressing CD44 in contrast with MKN-28 cells which low-expressing CD44. We also prepared the gastric cancer mice model using MKN-45 cells which has the stem-like property was implanted into BALB/c nude mice. And then HA-MFNPs of the T2 contrast enhancement effects and targeting ability were investigated by in vivo MR imaging. As a result of these studies, we conclude that HA coated MFNPs can be effectively used as a novel probes for visualizing gastric cancer stem cells.