Kuk Hui Son

Carbon nanotubes as cancer therapeutic carriers and mediators

Carbon nanotubes (CNTs) have received increasing attention in biomedical fields because of their unique structures and properties, including high aspect ratios, large surface areas, rich surface chemical functionalities, and size stability on the nanoscale. Particularly, they are attractive as carriers and mediators for cancer therapy. Through appropriate functionalization, CNTs have been used as nanocarriers for anticancer drugs including doxorubicin, camptothecin, carboplatin, cisplatin, paclitaxel, Pt(II), and Pt(IV), and genes including plasmid DNA, small-interfering RNA, oligonucleotides, and RNA/DNA aptamers. CNTs can also deliver proteins and immunotherapy components. Using combinations of light energy, they have also been applied as mediators for photothermal therapy and photodynamic therapy to directly destroy cancer cells without severely damaging normal tissue. If limitations such as a long-term cytotoxicity in the body, lack of size uniformity during the synthetic process, loading deviations for drug–CNT complexes, and release controllability at the target point are overcome, CNTs will become one of the strongest tools that are available for various other biomedical fields as well as for cancer therapy.

Surgical Planning by 3D Printing for Primary Cardiac Schwannoma Resection

We report herein a case of benign cardiac schwannoma in the interatrial septum. A 42-year-old woman was transferred from a clinic because of cardiomegaly as determined by chest X-ray. A transthoracic echocardiography and chest computed tomography examination revealed a huge mass in the pericardium compressing the right atrium, superior vena cava (SVC), left atrium, and superior pulmonary vein. To confirm that the tumor originated from either heart or mediastinum, cine magnetic resonance imaging was performed, but the result was not conclusive. To facilitate surgical planning, we used 3D printing. Using a printed heart model, we decided that tumor resection under cardiopulmonary bypass (CPB) through sternotomy would be technically feasible. At surgery, a huge tumor in the interatrial septum was confirmed. By incision on the atrial roof between the aorta and SVC, tumor enucleation was performed successfully under CPB. Pathology revealed benign schwannoma. The patient was discharged without complication. 3D printing of the heart and tumor was found to be helpful when deciding optimal surgical approach.

The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation

Background Extracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation. Methods Mongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was performed before and at 1, 2, and 3 hours after ECC commencement. To eliminate bias induced by hematocrit and plasma, all blood samples were adjusted to a hematocrit of 45% using baseline plasma. Blood viscoelasticity, plasma viscosity, hematocrit, arterial blood gas analysis, central venous O2 saturation, and lactate were measured. Results The blood viscosity and aggregation index decreased abruptly 1 hour after ECC and then remained low during ECC in both groups, but blood elasticity did not change during ECC. Blood viscosity, blood elasticity, plasma viscosity, and the aggregation index were not significantly different in the groups at any time. Hematocrit decreased abruptly 1 hour after ECC in both groups due to dilution by the priming solution used. Conclusion After ECC, blood viscoelasticity and RBC aggregation were not different in the pulsatile and nonpulsatile groups in the adult dog model. Furthermore, pulsatile flow did not have a more harmful effect on blood viscoelasticity or RBC aggregation than nonpulsatile flow.

Development of simple and sensitive hydrogel based colorimetric sensor array for the real-time quantification of gaseous ammonia

A real-time colorimetric sensor array (CSA) offers the advantages of diversity and accuracy for the quantification of multiple analytes; however, traditional sensors require a complex fabrication process. Therefore, to take full advantage of this sensing platform, we have developed a simple CSA system composed of a polymer, a reducing agent, and different pH indicators. Distinctive color response patterns were classified by extracting the hidden information, (i.e., red, green, and blue (RGB) values) from the indicators. This triple-channel sensing platform is further applied for statistical analysis, to quantify different concentrations of ammonia and other analytes. The sensor array showed a limit of detection of 0.3ppm, which is well below the diagnostic criteria for ammonia concentration in the breath of healthy individuals and of patients with end-stage renal disease. As this sensor would be able to quantify gaseous ammonia in the breath, it is relevant to the point-of-care diagnosis of patients with renal diseases.

Bronchial Artery Aneurysm Presenting as Hematemesis and Mediastinal Hemorrhage

Hematemesis is a rare manifestation of a ruptured bronchial artery aneurysm (BAA) in the mediastinum. It is difficult to diagnose a ruptured BAA presenting as hematemesis, because it can be confused with other diseases, such as Boerhaave’s syndrome, variceal disease, or a perforated ulcer. In this report, we describe a case of BAA resulting in hematemesis and mediastinal hemorrhage.

Simulated Microgravity Effects on Nonsmall Cell Lung Cancer Cell Proliferation and Migration

BACKGROUND Despite improvements in medical technology, lung cancer metastasis remains a global health problem. The effects of microgravity on cell morphology, structure, functions, and their mechanisms have been widely studied; however, the biological effects of simulated microgravity on the interaction between cells and its eventual influence on the characteristics of cancer cells are yet to be discovered. We examined the effects of simulated microgravity on the metastatic ability of different lung cancer cells using a random positioning machine. METHODS Human lung cancer cell lines of adenocarcinoma (A549) and squamous cell carcinoma (H1703) were cultured in a 3D clinostat system which was continuously rotated at 5 rpm for 36 h. The experimental and control group were cultured under identical conditions with the exception of clinorotation. RESULTS Simulated microgravity had different effects on each lung cancer cell line. In A549 cells, the proliferation rate of the clinostat group (2.267 ± 0.010) after exposure to microgravity did not differ from that of the control group (2.271 ± 0.020). However, in H1703 cells, the proliferation rates of the clinostat group (0.534 ± 0.021) was lower than that of the control group (1.082 ± 0.021). The migratory ability of both A549 [remnant cell-free area: 33% (clinostat) vs. 78% (control)] and H1703 cells [40% (clinostat) vs. 68% (control)] were increased after exposure to microgravity. The results of the molecular changes in biomarkers after exposure to microgravity are preliminary. DISCUSSION Simulated microgravity had different effects on the proliferation and migration of different lung cancer cell lines.Chung JH, Ahn CB, Son KH, Yi E, Son HS, Kim H-S, Lee SH. Simulated microgravity effects on nonsmall cell lung cancer cell proliferation and migration. Aerosp Med Hum Perform. 2017; 88(2):82-89.

Could Difference of Smoking Rate Between Men and Women Affect the Risk Difference of Acute Kidney Injury According to Sex

David and coworkers [1] have recently reported a large series of N0M0 non-small cell lung cancer (NSCLC) with visceral pleural invasion (VPI). They concluded that VPI was not associated with survival for tumors smaller than 5 cm, but showed negative effects on disease-free survival for tumors larger than 5 cm. This conclusion prompted us to raise an interesting question: does the varied effect of VPI on survival with different tumor sizes associate with VPI classification? Patients with VPI can be further classified into two groups, PL1 and PL2, representing patients without and with visceral pleural surface invasion (VPSI). VPSI as an independent factor for poor prognosis and recurrence in NSCLC has been reported [2, 3]. Large tumor size was related to more frequent occurrence of VPSI [2]. Therefore, the correlation of VPI and poor prognosis for large tumors but not small tumors may be related to more frequent occurrence of VPSI in large tumors. The poor prognostic effect of VPSI may be explained by the rapidity with which lung cancer cells in a subpleural location invade the pleura and disseminate throughout the pleural cavity. Once these cells exfoliate into the pleural cavity, preformed stomas that connect subpleural lymphatics with the pleural space could account for the systemic dissemination. Concerning the standard definitions and evaluations of VPSI we previously reported [2], we would like to share with readers more detailed descriptions for processing the specimens with VPSI. Despite careful inspection and sampling of the retracted pleural surface with all for section of the retracted areas, serial microsections for definite diagnosis are recommended to avoid the probably missing microscopic foci of VPSI. Immunohistochemical studies of thyroid transcription factor-1 protein and calretinin instead of elastic stain are necessary for differential diagnosis in those questionable cases associated with pleural hemorrhage and scanty floating tumor cells beyond the disrupted mesothelium. The accuracy of pathologic diagnosis should be emphasized because it may influence the patient’s postoperative treatment and outcome.

Two Phase Modulation of NH4+ Entry and Cl−/HCO3- Exchanger in Submandibular Glands Cells by Dexmedetomidine

Dexmedetomidine (Dex), a highly selective α2-adrenoceptor agonist, attenuates inflammatory responses induced by lipopolysaccharide (LPS) and induces sedative and analgesic effects. Administration of Dex also reduces salivary secretion in human subjects and inhibits osmotic water permeability in rat cortical collecting ducts. However, little is known about the mechanisms underlying the effects of Dex on salivary glands fluid secretion. We demonstrated the α2-adrenoceptor expression in the basolateral membrane of mouse submandibular glands (SMG). To investigate fluid secretion upon treatment with Dex, we studied the effects of Dex on the activity of Na+-K+-2Cl− cotransporter1 (NKCC1) and Cl−/HCO3- exchange (CBE), and on downstream pro-inflammatory cytokine expression in isolated primary mouse SMG cells. Dex acutely increased CBE activity and NKCC1-mediated and independent NH4+ entry in SMG duct cells, and enhanced ductal fluid secretion in a sealed duct system. Dex showed differential effects on cholinergic/adrenergic stimulations and inflammatory mediators, histamine, and LPS, stimulations-induced Ca2+ in mouse SMG cells. Both, histamine- and LPS-induced intracellular Ca2+ increases were inhibited by Dex, whereas carbachol-stimulated Ca2+ signals were not. Long-lasting (2 h) treatment with Dex reduced CBE activity in SMG and in human submandibular glands (HSG) cells. Moreover, when isolated SMG cells were stimulated with Dex for 2 h, phosphodiesterase 4D (PDE4D) expression was enhanced. These results confirm the anti-inflammatory properties of Dex on LPS-mediated signaling. Further, Dex also inhibited mRNA expression of interleukin-6 and NADPH oxidase 4. The present study also showed that α2-adrenoceptor activation by Dex reduces salivary glands fluid secretion by increasing PDE4D expression, and subsequently reducing the concentration of cAMP. These findings reveal an interaction between the α2-adrenoceptor and PDE4D, which should be considered when using α2-adrenoceptor agonists as sedative or analgesics.

Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly.

Tissue regeneration in the pores of poly(lactide-co-glycolide)-impregnated wall of expanded polytetrafluoroethylene (ePTFE) hybrid grafts

Understanding of relationship between pore properties and tissue regeneration of expanded polytetrafluoroethylene (ePTFE) is important in design of vascular tissue engineering. Tissue regeneration into a micron scale pore of the ePTFE wall was investigated by employing techniques of superficial surface modification of ePTFE, fabrication of the hybrid scaffold composed of biodegradable poly (lactide-co-glycolide) (PLGA) and ePTFE, and seeding of vascular cells on its lumen surface. The ePTFE was in advance transformed into a hybrid scaffold by sequential four steps of treatments such as chemical modification of ePTFE surfaces, impregnation of biodegradable PLGA polymer into its wall pores, and coatings of both PLGA polymer on the ePTFE lumen surface and collagens on the PLGA-coated lumen surface. The hybrid scaffold was in advance in vitro tissue-cultured with vascular smooth muscle for 12 weeks and stem cells for another 2 weeks on its collagen-coated lumen surface, thus obtaining an in vitro tissue-cultured scaffold. This in vitro tissue-cultured hybrid scaffold was implanted in a carotid artery of mongrel dog for 4 weeks. The morphologies of the hybrid grafts explanted from the artery were analyzed by light microscopy, scanning electron microscopy and transmission electron microscopy (TEM), focusing on tissue regeneration in the modified pores of ePTFE wall. They demonstrated migration of smooth muscle cells into the PLGA-impregnated/surface-modified pores of ePTFE wall along biodegradation of impregnated PLGA polymer, leading to tissue regeneration in its surface-modified pores. TEM results of the patent hybrid grafts showed both cell organelles and extracellular matrix of the regenerated media tissues in the pore channels of ePTFE wall with 20–30 μm inter-nodal distances.