Jin-Suck Suh

Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex

We investigated the synergism between shRNAs against Bcl-xL and doxorubicin (DOX) using aptamer-conjugated polyplexes (APs) in combination cancer therapy. Synergistic and selective cancer cell death was achieved by AP-mediated co-delivery of very small amounts of DOX and Bcl-xL-specific shRNA, which simultaneously activated an intrinsic apoptotic pathway. A branched polyethyleneimine (PEI) was grafted to polyethylene glycol (PEI-PEG) to serve as a vehicle for shRNA delivery, and its surface was further conjugated with an anti-PSMA aptamer (APT) for the selective delivery of APs to prostate cancer cells that express prostate-specific membrane antigens (PSMA) on their cell surface. The APs were finally obtained after intercalation of DOX to form shRNA/PEI-PEG-APT/DOX conjugates. Cell viability assays and FACS analysis of GFP expression against PC3 (PSMA deficient) and LNCaP (PSMA overexpressed) cells demonstrated that the synthesized APs inhibited the growth of PSMA-abundant prostate cancer cells with strong cell selectivity. Consequently, IC(50) values of APs loaded with both DOX and shRNA were approximately 17-fold less than those for the simple mixture of shRNA plus drug (shRNA/Lipofectamine + DOX). These results suggest that AP-mediated co-delivery of an anti-cancer drug and shRNA against Bcl-xL may widen the therapeutic window and allow for the selective destruction of cancer cells.

Antibody conjugated magnetic PLGA nanoparticles for diagnosis and treatment of breast cancer

DOX–magnetic PLGA nanoparticles conjugated with well-tailored antibodies were synthesized for the detection and therapy of breast cancer. Magnetic nanocrystals embedded in polymeric nanoparticles did not inhibit the nanoparticle formulation or drug release kinetics. The multimodal nanoparticles demonstrated remarkable cancer cell affinity and ultrasensitivity via magnetic resonance imaging. Furthermore, the loaded anticancer drugs were released and sustained for three weeks.

Nanoparticle-enabled terahertz imaging for cancer diagnosis.

This paper demonstrates the principle of the nanoparticle-contrast-agent-enabled terahertz imaging (CATHI) technique, which yields a dramatic sensitivity of the differential signal from cancer cells with nanoparticles. The terahertz (THz) reflection signal increased beam by 20% in the cancer cells with nanoparticles of gold nano-rods (GNRs) upon their irradiation with a infrared (IR) laser, due to the temperature rise of water in cancer cells by surface plasma ploritons. In the differential mode, the THz signal from the cancer cells with GNRs was 30 times higher than that from the cancer cells without GNRs. As the high sensitivity is achieved by the surface plasmon resonance through IR laser irradiation, the resolution of the CATHI technique can be as good as a few microns and THz endoscopy becomes more feasible.

Chronic Tibiofibular Syndesmosis Injury: The Diagnostic Efficiency of Magnetic Resonance Imaging and Comparative Analysis of Operative Treatment

Background: The purpose of this study was to determine the sensitivity and specificity of MRI in chronic syndesmosis injury by comparing the arthroscopic findings with MRI findings and to suggest therapeutic guidelines of syndesmotic fixation. Methods: Between January, 2003, and January, 2004, 20 patients were diagnosed with chronic syndesmosis injury according to syndesmosis widening (>2 mm) on arthroscopic examination. The average age of the patients was 32 years. The minimum followup was 22 (22 to 30) months. MRI was obtained in all patients. For evaluating the therapeutic role of syndesmotic fixation, we separated the patients into two groups (with and without transfixation) and compared preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and patient satisfaction. Results: The sensitivity, specificity, and accuracy of MRI were 90.0%, 94.8%, and 93.4%, respectively. In group I with syndesmotic fixation, the AOFAS ankle-hindfoot scale improved from 52 to 87, and in group II without syndesmotic fixation the score improved from 63 to 90 at last followup, which showed no statistically significant difference (p = 0.6453). Also, patient satisfaction showed no difference between the two groups. Conclusions: MRI showed high sensitivity, specificity, and accuracy under the criteria we proposed, and we recommend it as the main diagnostic tool for diagnosing a chronic syndesmosis injury. These findings might suggest that pain is mainly caused by hypertrophy and impingement of the soft tissue in the distal tibiofibular joint. Arthroscopic debridement alone can be recommended if the distal tibiofibular chronic syndesmosis injury is not combined with medial ankle instability and lateral displacement of the talus.

Targetable Gold Nanorods for Epithelial Cancer Therapy Guided by Near-IR Absorption Imaging

Well-designed nanoparticle-mediated, image-guided cancer therapy has attracted interest for increasing the efficacy of cancer treatment. A new class of smart theragnostic nanoprobes employing cetuximab (CET)-conjugated polyethylene glycol (PEG)ylated gold nanorods (CET-PGNRs) is presented; these nanoprobes target epithelial cancer cells using near-infrared light. The cetyltrimethylammonium bromide bilayer on GNRs is replaced with heterobifunctional PEG (COOH-PEG-SH) to serve as a biocompatible stabilizer and to increase specificity. The carboxylated GNRs are further functionalized with CET using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry. To assess the potential of such GNRs, their optical properties, biocompatibility, colloidal stability, in vitro/in vivo binding affinities for cancer cells, absorption imaging, and photothermal therapy effects are investigated. CET-PGNRs exhibit excellent tumor targeting ability and strong potential for simultaneous absorption imaging and photothermal ablation of epithelial cancer cells.

Magnetic resonance imaging for the diagnosis of tuberculous spondylitis

Objectives The purposes of this study were to evaluate the nature of the paraspinal soft tissue mass and the location of the lesion involved using magnetic resonance imaging and to correlate these observations with surgical findings. Summary of Background Data In the past, tuberculous spondylitis was diagnosed by plain radiography and since the 1970s, computed tomography has been a useful method for assessing tuberculous spondylitis. In contrast to most imaging methods, MRI has the advantages of improved contrast resolution for bone and soft tissues and versatility of direct imaging in multiple planes. Methods Medical records and magnetic resonance imaging studies of 22 patients with bacteriologically and/or histologiacally proved tuberculous spondylitis were reviewed. In each patient, the numbers of verterae involved were evaluated as well as which columns of vertebrae were affected and the signal intensities of lesions. In addition, and attempt was made to determine if granulation tissue differed from the abscess based on magnetic resonance imaging appearance and to compare the outcome with surgical findings. Results The average number of vertebrae involved per patient was 2.8 and T8 and T9 were the vertebrae most frequently affected. The destruction of vertebrae and discs was easily identified in both sagittal and axial planes. The peripheral margins were exclusively enhanced in all cases. Of particular interest, the posterior aspect of the vertebral body was predominantly involved. Mostly the involvement of both anterior and middle columns was noted. With the aid of intravenous, administration of magnetic resonance contrast agents, magnetic resonance imaging was highly accurate in distinguishing the granulation tissue from the cold abscess. Conclusions Magnetic resonance imaging demonstrated excellent images of bone destruction and soft tissue mass, and provided information in multiple planes, thereby delineating the extent of involvement in tuberculous spandylitis. Magnetic resonance imaging is most helpful in planning a surgical approach to tuberculous spondylitis.

Alveolar soft part sarcoma: MR and angiographic findings

Abstract Objective. To present the MR and angiographic findings of alveolar soft part sarcoma (ASPS). Design and patients. MR examinations (12 tumors of 10 patients) of ASPS performed at multiple hospitals were retrospectively reviewed. The tumors were found in the thigh (n=4), lower leg (n=4), femur (n=2, local metastasis), scalp (n=1) and arm (n=1). The MR signal characteristics including signal intensity, homogeneity and signal void of lesions and bony invasion including direct invasion or local metastasis were evaluated. Angiographic findings (n=4) and post-embolotherapy follow-up MR imaging (n=2) findings were also assessed. Results. Local bony metastasis was found in two cases. Seven tumors showed heterogeneous high signal intensity on T1- and T2-weighted images with good enhancement. One tumor had a very high signal on T1-weighted images. Eight tumors (67%) showed numerous signal voids in or near the tumors. All four angiographic studies showed numerous enlarged vessels, arteriovenous shunts and delayed washout. Two cases mimicked arteriovenous malformations on angiographic studies but MR images demonstrated solid soft tissue components as well as tortuous vessels. Conclusions. High signal on T1-weighted image and numerous signal voids are highly suggestive of ASPS, although they are not universal as has been suggested and arteriovenous malformation should be included in the differential diagnosis. Local bony metastases in ASPS were seen in two cases and should be carefully investigated.

Consecutive Targetable Smart Nanoprobe for Molecular Recognition of Cytoplasmic microRNA in Metastatic Breast Cancer

We report smart nanoprobe, hyaluronic acid (HA)-based nanocontainers containing miR-34a beacons (bHNCs), for the intracellular recognition of miR-34a levels in metastatic breast cancer cells, which is distinct from the imaging of biomarkers such of cell membrane receptors such as HER2. In this study, we demonstrate that a nanoscale vesicle that couples a targeting endocytic route, CD44, and a molecular imaging probe enables the efficient detection of specific miRNAs. Furthermore, bHNCs showed no cytotoxicity and high stability due to the anchored HA molecules on the surface of nanocontainers, and enables the targeted delivery of beacons via CD44 receptor-mediated endocytosis. In vitro and in vivo optical imaging using bHNCs also allow the measurement of miR-34a expression levels due to the selective recognition of the beacons released from the internalized bHNCs. We believe that the technique described herein can be further developed as a cancer diagnostic as well as a miRNA-based therapy of metastatic cancer.

Chondroblastoma: MR Characteristics with Pathologic Correlation:

PURPOSE The purpose of this study was to describe the MR findings of chondroblastoma with pathologic correlation. METHOD In 22 patients with pathologically proven chondroblastoma, MR signal characteristics were correlated with pathological findings. RESULTS On T2-weighted images, 12 (55%) lesions were hyperintense with hypointense areas in 9 lesions, whereas 10 (45%) were hypointense. Therefore, 19 of 22 (86%) lesions with pathologic correlation had hypointense areas entirely (n = 10) or partly (n = 9) on T2-weighted images. On gadolinium-enhanced images, 13 (59%) lesions showed lobular enhancement and 9 (41%) showed marginal and septal enhancement. Low signal intensity on T2-weighted MR images was most strongly associated with an abundance of immature chondroid matrix, hypercellularity of the chondroblasts, calcifications, and hemosiderin on histology. CONCLUSION Chondroblastoma was found to show hypointense portions on T2-weighted images. Signal intensity on T1- and T2-weighted MR images in chondroblastoma was dependent on the amounts of histopathological components.

Tumor volume change as a predictor of chemotherapeutic response in osteosarcoma

The change in osteosarcoma tumor volume after preoperative adjuvant chemotherapy and its relationship to the histopathologic response was investigated using various reproducible volumetric methods. Tumor volume was measured before and after chemotherapy in 41 patients with osteosarcoma using an ellipsoid formula in plain radiography and magnetic resonance imaging and three-dimensional magnetic resonance imaging measurement. Based on intraobserver and interobserver variability for the volumetric measurements of each method, three-dimensional magnetic resonance imaging measurement was the most reproducible. In three-dimensional magnetic resonance measurements, the correlation of the histopathologic response with absolute and relative total tumor volume changes and extraosseous volume change were significant. The good responder group showed a greater reduction in tumor volume after chemotherapy, although there was no significant difference in pretreatment tumor volume between the good and poor responder groups. The group with a decreased or stable tumor volume represented a good histopathologic response with a sensitivity of 85%, specificity of 76%, and positive predictive value of 88%. The change in tumor volume of osteosarcoma measured by three-dimensional magnetic resonance imaging could predict histopathologic response after three cycles of neoadjuvant chemotherapy.