Hyun Yul Kim

Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide) Copolymer for Tumor Targeting

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.

Redox-Responsive nanophotosensitizer composed of chlorin e6-conjugated dextran for photodynamic treatment of colon cancer cells

We synthesized dextran-chlorin e6 conjugates having disulfide linkage for specific targeting of colonic region and cancer cells. Reductive end group of dextran was treated with sodium borocyanohydride and conjugated with cystamine. Cystamine end group was conjugated with carboxylic acid of chlorin e6 (DEX6ss). DEX6ss conjugates were formed as spherical nanoparticles with small sizes less than 100 nm. Chlorin e6 (Ce6) was specifically released from DEX6ss nanoparticles in the presence of dextranase or glutathione (GSH), indicating that DEX6ss nanoparticles have responsiveness against dextranase and redox-environment. In darktoxicity test using normal cells and cancer cells, Ce6 and DEX6ss nanoparticles were practically nontoxic. Intracellular delivery of DEX6ss nanoparticles was significantly improved compared to Ce6 itself. DEX6ss nanoparticles achieved significantly higher ROS production and phototoxicity against HCT116 colon cancer cells than Ce6 itself. Furthermore, DEX6ss nanoparticles showed enhanced tumor targeting efficiency and longer retention in the tumor tissues at in vivo animal study with HCT116 tumor-bearing mice. Furthermore, DEX6ss nanoparticles have responsiveness against colonic enzyme, dextranase, indicating that they have potential of colon-specific delivery and dextranase-specific drug delivery capacity. We fabricated colon-specific and tumor-targetable nanophotosensitizer using DEX6ss conjugates. They showed improved cellular uptake ratio, phototoxicity, and colon-specificity. We suggest that DEX6ss nanoparticles can be considered as a promising candidate for PDT of colon cancer.

Enhanced Photosensing and Photodynamic Treatment of Colon Cancer Cells Using Methoxy Poly(ethylene glycol)-Conjugated Chlorin e6

Nanophotosensitizer composed of methoxy poly(ethylene glycol) (MePEG) and chlorin e6 (Ce6) (abbreviated as Pe6) was synthesized for efficient delivery of Ce6 to the colon cancer cells. Pe6 nanophotosensitizer has small diameter less than 100 nm with spherical shape and core-shell structure. They were activated in aqueous solution while Ce6 was quenched due to its poor aqueous solubility. They showed no intrinsic cytotoxicity against normal cells and colon cancer cells. Pe6 nanophotosensitizers showed enhanced cellular uptake, phototoxicity, and reactive oxygen species (ROS) generation at in vitro cell culture experiment. Furthermore, they showed improved tumor tissue penetration and accumulation in vivo animal studies. We suggested Pe6 nanophotosensitizers as an ideal candidate for PDT of colon cancer.

The efficacy of elongated axillary incision on extended latissimus dorsi flap for immediate breast reconstruction

Background In performing extended latissimus dorsi (ELD) flap procedures, a skin paddle design on the bra line helps reduce visible scarring. This improves the patient’s satisfaction with the outcome. However, such a design leads to a longer operation time and increased fatigue of the surgeon due to the narrow operative field. In this study, the authors propose a method that elongates the axillary incision line posteriorly by 1.5 cm from the lateral border of the latissimus dorsi muscle. We examined whether this method could shorten the operation time and compared the incidence of complications between patients who underwent this novel procedure and patients who underwent the traditional procedure. Methods In this study of patients who underwent ELD flap procedures for immediate breast reconstruction, 89 underwent surgery with the elongated axillary incision and 45 underwent surgery without the elongated incision. The total operation time and complications were retrospectively examined based on the patients’ medical records, and we examined whether there was any statistically significant difference in the total operation time. Results In the experimental group with the elongated axillary incision, the operation time ranged from 125 to 255 minutes (median, 175 minutes). In contrast, in the control group without the elongated axillary incision, the operation time ranged from 142 and 340 minutes (median, 205 minutes). The operation time was statistically significantly different between the two groups, and no significant complications were observed in the experimental group. Conclusions Elongation of the axillary incision alone may shorten the operation time of the ELD flap procedure without causing additional complications.

Patterns of malignant non-mass enhancement on 3-T breast MRI help predict invasiveness: using the BI-RADS lexicon fifth edition

Background Non-mass enhancements (NME) with invasive components account for 10–42% of total malignant NMEs. The factors associated with invasiveness on magnetic resonance imaging (MRI) could be useful for clinical assessment and treatment. Purpose To evaluate the clinical significances of the distributions and internal enhancement patterns (IEP) of malignant NMEs on 3-T breast MRI. Material and Methods A total of 448 consecutive women with newly diagnosed breast cancer that had undergone preoperative MRI and surgery between February 2013 and March 2016 were identified. After exclusions, 72 malignant NMEs without a mass in 72 women (mean age = 51.5 years) were included. Two readers independently assessed distributions and IEPs of NME, according to the Breast Imaging Reporting and Data System lexicon fifth edition. Collected data included the presence of invasion and histopathologic factors. Results A clustered ring IEP was significantly associated with invasive cancer (75.0%, P = 0.001, Reader1; 72.9%, P < 0.001, Reader 2), absence of necrosis (79.0%, P < 0.001; 72.1%, P < 0.001, respectively), and high Ki-67 expression (74.2%, P = 0.048; 74.2%, P = 0.003, respectively). A clumped IEP was related to ductal carcinoma in situ (33.3%, P = 0.025; 50.0%, P = 0.001, respectively), absence of lymph node metastasis (24.1%, P = 0.029; 31.5%, P = 0.030, respectively), and presence of necrosis (34.5%, P = 0.003; 44.8%, P = 0.001, respectively). Conclusion The presence of a clustered ring IEP in patients with breast cancer was found to be significantly associated with invasive breast cancer and high Ki-67 expression.

Is Beta-Blocker Use Beneficial in Breast Cancer? A Meta-Analysis

Objective: Preclinical studies have proved that beta-blocking agents inhibit several pathways for breast cancer progression and metastasis. We aimed to evaluate the association between beta-blocker use and prognosis of breast cancer. Methods: A systematic search for studies from MEDLINE and EMBASE (inception to March 2014) was performed using the keywords “breast cancer” and “beta-blocker.” In 2 groups of breast cancer patients (beta-blocker users and non-beta-blocker users), overall deaths (ODs), cancer-specific deaths (CSDs), and recurrences were compared. Results: Six studies including 18,118 patients were eligible for this analysis. Two studies with 3,139 patients were included in the analysis of ODs. The random-effects model showed no significant difference in ODs between beta-blocker users and non-beta-blocker users (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.50-1.52, p = 0.49). Four studies with 13,782 patients were included in the measurement of CSDs. The difference in CSDs between beta-blocker users and non-beta-blocker users was not significant using the fixed-effect model (OR 0.93, 95% CI 0.82-1.06, p = 0.29). Three studies with 3,923 patients were included in the calculation of recurrences. Overall, beta-blockers did not affect the incidence of recurrence (OR 0.70, 95% CI 0.25-1.95, p = 0.49). Conclusion: Beta-blockers were not beneficial regarding ODs, CSDs, or recurrences. Further studies are needed to evaluate the associations between the effects of beta-blockers and subtypes of breast cancer.

Stereotactic vacuum-assisted breast biopsy under lateral decubitus position

Purpose Stereotactic vacuum-assisted breast biopsy (VAB) has been established as a standard method for histological diagnosis of microcalcification or nonpalpable breast lesions on mammography. Generally, the procedure has been done under the prone position or upright sitting position. We herein attempt to evaluate clinical utility of Stereotactic VAB under lateral decubitus position. Methods One hundred six women (mean age, 51.2 years) with mammographically detected microcalcification underwent lateral decubitus positioning VAB using the 8G probe. In all cases, we obtained mammography specimens for identification of microcalcification and postprocedure mammography. We reviewed mean procedure time, pieces of specimen, pathology and follow-up mammography. Results The procedure took approximately 20 minutes (range, 15-24 minutes). Average number of obtained specimens was 8.5 pieces (range, 6-12 pieces). Microcalcifications were confirmed in both specimen mammography and microscopic slides. Of 106 cases, 10 cases were diagnosed as ductal carcinoma in situ. Additional surgical management was performed. Atypical ductal hyperplasias were found in 8 cases, and fibrocystic changes in 88 cases. Conclusion Stereotactic VAB using the 8G probe under lateral decubitus position does not need a dedicated table, and is easier to maintain the position. Also, this procedure is accurate and safe. Thus, stereotactic VAB using the 8G probe under lateral decubitus position will be a useful method for diagnosis of microcalcification or nonpalpable breast lesions on mammography.