ERK Inhibition Increases RANKL-Induced Osteoclast Differentiation in RAW 264.7 Cells by Stimulating AMPK Activation and RANK Expression and Inhibiting Anti-Osteoclastogenic Factor Expression.

Bone absorption is necessary for the maintenance of bone homeostasis. An osteoclast (OC) is a monocyte-macrophage lineage cell that absorbs bone tissue. Extracellular signal-regulated kinases (ERKs) are known to play important roles in regulating OC growth and differentiation. In this study, we examined specific downstream signal pathways affected by ERK inhibition during OC differentiation. Our results showed that the ERK inhibitors PD98059 and U0126 increased receptor activator of NF-κB ligand (RANKL)-induced OC differentiation in RAW 264.7 cells, implying a negative role in OC differentiation. This is supported by the effect of ERK2-specific small interfering RNA on increasing OC differentiation. In contrast to our findings regarding the RAW 264.7 cells, the ERK inhibitors attenuated the differentiation of bone marrow-derived cells into OCs. The ERK inhibitors significantly increased the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) but not the activation of p38 MAPK, Lyn, and mTOR. In addition, while the ERK inhibition increased the expression of the RANKL receptor RANK, it decreased the expression of negative mediators of OC differentiation, such as interferon regulatory factor-8, B-cell lymphoma 6, and interferon-γ. These dichotomous effects of ERK inhibition suggest that while ERKs may play positive roles in bone marrow-derived cells, ERKs may also play negative regulatory roles in RAW 264.7 cells. These data provide important information for drug development utilizing ERK inhibitors in OC-related disease treatment.

Diffusion Tensor Tractography Studies on Recovery Mechanisms of Aphasia in Stroke Patients: A Narrative Mini-Review.

Aphasia is a common and serious clinical feature of stroke. Various neural tracts are known to be involved in language processing. Diffusion tensor tractography (DTT) appears to be an appropriate imaging technique for the elucidation of the recovery mechanisms of aphasia in the language-related neural tracts in stroke patients. In this article, twelve previous DTT-based studies on the recovery mechanisms of aphasia in stroke were reviewed. We classified the twelve studies into the following three categories according to the recovery mechanisms: recovery via the neural tracts in the dominant hemisphere (eight studies), via transcallosal fibers (two studies), and via the neural tracts in the non-dominant hemisphere (two studies). Although there are various neural tracts for language processing, eight of the ten studies focused only on the role of the arcuate fasciculus (AF) in the recovery process. Consequently, it appears from the studies that only one recovery mechanism of aphasia via the restoration of the integrity of the injured AF in the dominant hemisphere was clearly demonstrated. However, because various neural tracts are involved in language processing, there could be other mechanisms that have not yet been elucidated. Therefore, further original studies involving a larger number of patients with aphasia in stroke should be encouraged forthwith. Further studies involving various lesion locations and severity levels of injuries to the language-related neural tracts are also necessary because the recovery mechanisms of aphasia in stroke could be dependent on these factors.

Relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex in hypoxic-ischemic brain injury: a pilot study.

This pilot study investigated the relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex (mPFC SNC) in patients with hypoxic-ischemic brain injury (HI-BI), using diffusion tensor tractography (DTT). Twenty-three patients with HI-BI were recruited into the study based on predefined inclusion criteria. Their consciousness levels were evaluated using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R). Using DTT, the mPFC SNC was reconstructed for each patient. The average of the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and voxel number (VN) for the mPFC SNC in both hemispheres were determined. The GCS score showed moderate positive correlations with the FA value and VN of the mPFC SNC [(FA) r = 0.439; (VN) r = 0.466; P < 0.05], and a strong negative correlation with ADC value ( r = -0.531; P < 0.05). The CRS-R score had a strong positive and negative correlation with the FA and ADC values of the mPFC SNC, respectively, [(FA) r = 0.540; (ADC) r = -0.614; P < 0.05] and a moderate positive correlation with the VN of the mPFC SNC ( r = 0.488; P < 0.05). We found that the severity of the injury to the mPFC SNC was closely related to the consciousness level. Our results suggest that the mPFC SNC appears to be a neural correlate for the control of consciousness in patients with HI-BI. Based on these results, we believe that the mPFC could be a target area for noninvasive neurostimulation therapies for patients with impaired consciousness following HI-BI.

Differences in the thalamocortical tract of the ascending reticular activating system in disorders of consciousness after hypoxic-ischemic brain injury: A pilot study.

This study purposed to investigate differences in the thalamocortical tract of the ascending reticular activating system between vegetative state (VS) and minimally conscious state (MCS) patients with hypoxic-ischemic brain injury (HI-BI). Fourteen patients with disorders of consciousness following HI-BI (VS group: 7 patients, MCS group: 7 patients) and 12 normal subjects were recruited. The 5 parts of reconstructed thalamocortical tract were prefrontal cortex (PFC), premotor cortex, primary motor cortex (M1), primary somatosensory cortex (S1), and posterior parietal cortex (PPC). The fractional anisotropy (FA) value and tract volume (TV) in each part of the thalamocortical tract were estimated. The FA values and TV of all parts of the thalamocortical tract in the VS group and the FA values of all parts and TV of PFC, premotor cortex, and PPC parts in the MCS group were lower than the control group (P < .05). In addition, the FA values of PFC and PPC parts were significantly lower in the VS group than the MCS group (P < .05). The results of our pilot study indicate that PFC and PPC parts of the thalamocortical tract are important areas to assess for differentiation of VS and MCS after HI-BI.

Incidence and characteristics of physical disabilities in patients with postconcussion syndromefollowing mTBI.

This study aimed to examine the incidence and characteristics of physical disabilities in patients with postconcussion syndrome (PCS) after a mild traumatic brain injury (mTBI). Of 203 patients diagnosed with PCS after mTBI, 10 patients with definite physical disabilities (worse than moderate disability on the Glasgow outcome scale [GOS], <4 points and inability to walk independently on the Functional Ambulation Category [FAC], <3 points) were enrolled. Ten of the 203 patients included in the analysis based on prespecified inclusion criteria were further evaluated. Seven patients had moderate disability on the GOS, whereas the remaining 3 showed severe disability. On the Modified Barthel Index, 5 patients were moderately dependent, and 2 patients were severely dependent. By the Motricity Index, 9 patients showed mild quadriparesis, and 1 had mild hemiparesis. All 10 patients could grasp-release their fingers as per the Modified Brunnstrom Classification. By contrast, 7 patients required verbal supervision for independent gait by the FAC, and the remaining 3 patients needed intermittent support from 1 person for independent gait. Approximately 5% of patients with PCS after mTBI had a definite physical disability, and most of these patients showed mild quadriparesis. These results suggest that a definite physical disability can occur in patients with PCS after mTBI.

Evaluation of Structural Neural Connectivity Between the Primary Auditory Cortex and Cognition-Related Brain Areas Using Diffusion Tensor Tractography in 43 Normal Adults.

BACKGROUND Little is known about the structural neural connectivity between the primary auditory cortex and cognition-related brain areas in the human brain. This study aimed to evaluate the structural neural connectivity between the primary auditory cortex and cognition-related brain areas in normal subjects, using diffusion tensor tractography (DTT). MATERIAL AND METHODS Forty-three healthy subjects with no prior history of audiological, neurological, physical, or psychiatric illnesses were recruited for this study. Diffusion tensor imaging data analysis was performed using the Oxford Centre for Functional Magnetic Resonance Imaging of Brain (FMRIB) Software Library. In each subject, a region of interest was set on the primary auditory cortex, including the subcortical white matter. We assessed the neural connectivity between the primary auditory cortex and cognition-related brain areas (the dorsolateral prefrontal cortex [DLPFC]; ventrolateral prefrontal cortex [VLPFC]; orbitofrontal cortex [OFC]; hippocampus; parahippocampal cortex; amygdala, anterior and posterior cingulate gyrus; and fornix). RESULTS According to the results of DTT, the primary auditory cortex showed neural connectivity (over 50%) with the following areas: the threshold of 1 streamline - the VLPFC (94.2%), OFC (84.9%), fornix (80.2%), hippocampus (76.7%), parahippocampal cortex(74.4%) and DLPFC (58.1%); the threshold of 5 streamlines - the VLPFC (88.4%), OFC (81.4%), fornix (66.3%), hippocampus (55.8%), and parahippocampal cortex (53.5%); and the threshold of 15 streamlines - the VLPFC (82.6%), OFC (74.4%), and fornix (53.5%). CONCLUSIONS In normal human subjects, DTT showed that the primary auditory cortex had a high degree of neural connectivity with the prefrontal cortex, fornix, hippocampus, and parahippocampal cortex, which are brain areas associated with cognition and memory.

Use of a Brain Navigator to Identify the Precentral Knob of the Precentral Gyrus in Normal Subjects.

BACKGROUND [color=black]The precentral knob of the precentral gyrus is the original site for hand somatotopy in the corticospinal tract, and it is considered an important target for neuromodulation. However, little is known about the anatomical location of the precentral knob for easy clinical use. This study aimed to describe the use of an optical tracking brain navigator to identify the anatomical location of the precentral knob in the precentral gyrus in normal subjects. [/color] MATERIAL AND METHODS [color=black]Twenty healthy right-handed subjects were enrolled for this study. The locations of target and surface points in each subject were determined using a brain navigator. The target and surface points were defined as the precentral knob and the area of the scalp in the vertical direction from the target point, respectively. Then, by placing a marked 1-cm grid on each subject's head, the horizontal and vertical distances from the midline central (Cz) were measured using the point marker.[/color] RESULTS [color=black]The average distance from Cz to the location of the precentral knob in the horizontal direction was 30.75 mm in the right hemisphere, 31.25 mm in the left hemisphere, and 31.00 mm in both hemispheres. The average distance from Cz to the location of the precentral knob in the vertical direction was -12.75 mm in the right hemisphere, -14.50 mm in the left hemisphere, and -13.62 mm in both hemispheres. [/color] CONCLUSIONS [color=black]This study showed that the anatomical location of the precentral knob in normal subjects could be identified using a brain navigator and this method may be used clinically for patients requiring neuromodulation.[/color].

Relation Between the Corticospinal Tract State and Activities of Daily Living in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: We investigated the relation between the ipsilesional corticospinal tract (CST) state and activity of daily living independence in patients with chronic intracerebral hemorrhage. METHODS: Fifty-six consecutive patients with unilateral intracerebral hemorrhage and 38 healthy control subjects were recruited for this study. The Motricity index and the modified Barthel index were used to evaluate motor function of the affected extremities and activity of daily living independence, respectively. The diffusion tensor imaging parameter values for fractional anisotropy (FA) and voxel number (VN) of the CST were determined. Ratios of the ipsilesional to the contralesional CST measures were calculated and are presented as the CST-ratio (FA value and VN). RESULTS: The FA value and VN of the ipsilesional CST and the CST-ratio in the patient group were lower than those of the control group (P<0.05). There was a strong positive correlation between the Motricity index score of the affected extremities and the modified Barthel index score (P<0.05), while the FA value and VN of the ipsilesional CST and the CST-ratio showed moderate and strong positive correlations with the Motricity index and modified Barthel index scores, respectively (P<0.05). In addition, the VN of the ipsilesional CST showed excellent utility as a classifier, whereas the FA value of the ipsilesional CST and the FA value and VN of the CST-ratio showed good classifier utility (P<0.05). CONCLUSIONS: We demonstrated that impairment of activity of daily living independency was closely related to the injury severity of the ipsilesional CST in patients with chronic intracerebral hemorrhage. In addition, the injury severity of the ipsilesional CST can be used to classify the degree of activity of daily living independency. Registration: URL: http://www.e-irb.com/index.jsp; Unique identifier: 2021-03-014.

Taurine Protects against Postischemic Brain Injury via the Antioxidant Activity of Taurine Chloramine.

Taurine is ubiquitously distributed in mammalian tissues and is highly concentrated in the heart, brain, and leukocytes. Taurine exerts neuroprotective effects in various central nervous system diseases and can suppress infarct formation in stroke. Taurine reacts with myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) to produce taurine chloramine (Tau-Cl). We investigated the neuroprotective effects of taurine using a rat middle cerebral artery occlusion (MCAO) model and BV2 microglial cells. Although intranasal administration of taurine (0.5 mg/kg) had no protective effects, the same dose of Tau-Cl significantly reduced infarct volume and ameliorated neurological deficits and promoted motor function, indicating a robust neuroprotective effect of Tau-Cl. There was neutrophil infiltration in the post-MCAO brains, and the MPO produced by infiltrating neutrophils might be involved in the taurine to Tau-Cl conversion. Tau-Cl significantly increased the levels of antioxidant enzymes glutamate-cysteine ligase, heme oxygenase-1, NADPH:quinone oxidoreductase 1, and peroxiredoxin-1 in BV2 cells, whereas taurine slightly increased some of them. Antioxidant enzyme levels were increased in the post-MCAO brains, and Tau-Cl further increased the level of MCAO-induced antioxidant enzymes. These results suggest that the neutrophils infiltrate the area of ischemic injury area, where taurine is converted to Tau-Cl, thus protecting from brain injury by scavenging toxic HOCl and increasing antioxidant enzyme expression.

Changes in the prefronto-thalamic tract following cranioplasty: Case reports.

RATIONALE: The prefrontothalamic tract (PTT) injury is associated with various neuropsychological impairments including cognitive impairment. We report on three women with hemorrhagic stroke who showed changes in the PTT following cranioplasty (C/P) using diffusion tensor tractography (DTT) images. PATIENT CONCERNS: The 3 women with hemorrhagic stroke showed reductions of cognitive impairment following C/P. Mini-Mental State Examination scores (MMSE) were increased by 7-, 8-, and 5-point in patient 1, 2, and 3, respectively, after C/P compared with the patients' pre-C/P MMSE scores. DIAGNOSIS: Three patients were diagnosed with spontaneous intracerebral hemorrhage. Three patients underwent C/P using auto-bone at 7 (patient 1 and 3) and 13 (patient 2) weeks after onset. INTERVENTIONS: Diffusion tensor imaging data were acquired within 3 days before and 21 days after C/P. OUTCOMES: The pre-C/P DTT results showed non-reconstruction of the dorsolateral prefrontal cortex (DLPFC; patient 2 and 3) on the contralateral operation (contra-OP) side and orbitofrontal cortex (OFC; patient 3) on both sides, but those were reconstructed on post-C/P DTT. Except for the contra-OP side OFC of patient 2, all fractional anisotropy values decreased on post-C/P DTT compared with pre-C/P DTT. The mean diffusivity values of the VLPFC and OFC were higher on post-C/P DTT except for the contra-OP side VLPFC of patient 1 and contra-OP side OFC of patient 2. The voxel numbers also increased except for the contra-OP side VLPFC of patient 1. LESSONS: We demonstrated structural changes in the PTT along with concomitant reductions of cognitive impairments following C/P in 3 women with hemorrhagic stroke using DTT. The DTT changes suggest that C/P can affect the state of the PTT on both the OP and contra-OP sides. However, the limitation that DTT analysis may underestimate or overestimate fiber tract status due to regions of fiber complexity and crossing fiber should be considered.

Degeneration of core neural tracts for emotional regulation in a patient with traumatic brain injury: A case report.

RATIONALE: Several brain structures, including the orbital prefrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, amygdala, and anterior cingulate cortex, are considered key structures in the neural circuitry underlying emotion regulation. We report on a patient showing behavior changes and degeneration of core neural tracts for emotional regulation following traumatic brain injury (TBI). PATIENT CONCERNS: A 51-year-old male patient suffered an in-car accident. The patient lost consciousness for approximately 30 days, and his Glasgow Coma Scale score was 3. He underwent stereotactic drainage for traumatic intraventricular and intracerebral hemorrhages. At approximately 6.5-year after onset, he began to show disinhibition behaviors such as shouting with anger, which worsened over time. At approximately 8-year after onset, he showed severe depression signs and disinhibition, including violence. DIAGNOSES: The patient who showed delayed-onset behavioral changes (disinhibition and depression). INTERVENTIONS: Diffusion tensor imaging data were acquired at 3 months and 8 years after TBI onset. OUTCOMES: The patient showed degeneration of core neural tracts for emotional regulation that was associated with delayed behavioral changes following TBI. On both 3-month and 8-year diffusion tensor tractographies (DTTs), the right dorsolateral prefronto-thalamic tract, ventrolateral prefronto-thalamic tract, orbital prefronto-thalamic tract, uncinate fasciculus, and both cinguli were reconstructed whereas other neural tracts were not reconstructed. Compared with the 3-month DTT, all reconstructed neural tracts on the 8-year DTT were narrow, except for the left cingulum, which showed new transcallosal fibers between both anterior cingula. The fractional anisotropy and tract volume of all reconstructed neural tracts were lower on the 8-year DTT than the 3-month DTT, except for the tract volume of left cingulum. LESSONS: The evaluation of dorsolateral, ventrolateral, and orbital prefronto-thalamic tract, uncinate fasciculus, and cingulum using follow-up DTTs is useful when a patient with TBI shows delayed-onset behavioral problems.

Diffusion Tensor Imaging Studies on Recovery of Injured Optic Radiation: A Minireview.

The optic radiation (OR) is a visual neural fiber pathway for the transfer of visual information from the lateral geniculate body of the thalamus to the primary visual cortex. To demonstrate the recovery of an OR injury, quantification and visualization of changes to the injured OR are necessary. Diffusion tensor imaging (DTI) allows determination of the state of an OR by assessing the obtained DTI parameters. In particular, diffusion tensor tractography (DTT), which is derived from DTI data, allows three-dimensional visualization of the OR. Thus, recovery of an injured OR can be demonstrated by examining changes in DTI parameters and/or configuration on follow-up DTI scans or via DTT of the injured OR. Herein, we review nine DTI-based studies that demonstrated recovery of OR injuries. The results reported in these studies suggest that an OR injury has a potential for recovery. Moreover, the results of these studies can form a basis for elucidating the recovery mechanisms of injured OR. These studies have suggested two recovery mechanisms for OR injury: recovery via the original OR pathway or via the transcallosal fibers of the corpus callosum. However, only nine studies on this topic have been conducted to date and six of those nine studies were case reports. Therefore, further studies involving larger numbers of subjects and reporting precise evaluations of changes in OR injury during recovery are warranted.

Motor recovery of hemiparetic leg by improvement of limb-kinetic apraxia in a chronic patient with traumatic brain injury: A case report.

RATIONALE: Limb-kinetic apraxia (LKA), a kind of apraxia, means the inability to perform precise and voluntary movements of extremities resulting from injury of the premotor cortex (PMC) or the corticofugal tract (CFT) from the PMC. Diagnosis of LKA is made by observation of movements without specific assessment tools. PATIENT CONCERNS: A 44-year-old male underwent conservative management for traumatic intracerebral hemorrhage in the left basal ganglia and subarachnoid hemorrhage due to a pedestrian-car crash. When he was admitted to the rehabilitation department of a university hospital after 41 months after onset, he presented with right hemiparesis (Medical Research Council (MRC): shoulder abductor; 3, elbow flexor; 3, finger extensor; 0, hip flexor; 2- [range: 30°], knee extensor; 1 and ankle dorsiflexor; 3-). In addition, he exhibited slow, clumsy, and mutilated movements when performing movements of his right ankle. DIAGNOSES: The patient was diagnosed as traumatic brain injury (TBI). INTERVENTIONS: Clinical assessments and DTI were performed at 41 and 44 months after onset. During three months, rehabilitative therapy was performed including dopaminergic drugs (pramipexole 2.5 mg, ropinirole 2.5 mg, and amantadine 300 mg, and carbidopa/levodopa 75 mg/750 mg). OUTCOMES: The right leg weakness slowly recovered during 3 months, until 44 months after the initial injury (MRC: shoulder abductor, 3; elbow flexor, 3; finger extensor, 0; hip flexor, 3; knee extensor, 3; and ankle dorsiflexor, 3+). The fiber number of the right corticospinal tract (CST) was decreased on 44-month diffusion tensor tractography (DTT) (1319) compared with 41-month DTT (1470) and the left CST was not reconstructed on both DTTs. The fiber number of both CRTs were decreased on 44-month DTT (right: 1547, left: 698) than 41-month DTT (right: 3161, left: 1222). LESSONS: A chronic patient with TBI showed motor recovery of the hemiparetic leg by improvement of LKA after rehabilitation. This results have important implications for neurorehabilitation.

Diagnosis of the Trigeminal Nerve Injury in a Patient with Pontine Hemorrhage.

Herein, we present a patient who was diagnosed with trigeminal nerve injury following a pontine hemorrhage. A 38-year-old male was diagnosed with a left pontine hemorrhage and underwent conservative management at the neurosurgery department of a university hospital. After hemorrhage onset, he felt facial pain on the right side. After seven years, he visited the rehabilitation department of another hospital for evaluation of his right facial pain. He complained of somatosensory impairment and facial pain (tingling and cold sensation) on the right side as well as difficulty chewing and gait disturbance. On neurological examination, decreased touch sensation (approximately 30%) was observed on the right side of the face, in the oral cavity, and on the tongue (anterior two-thirds) as well as weakness of the right-sided masseter muscles. He also exhibitedallodynia without dysesthesia on the right side of the face. Diffusion tensor tractography showed the right trigeminal nerve to be discontinued at the anterior margin of the pons (arrow) compared to the state of the left trigeminal nerve.

What Do Korean Women Know and Want to Know about Thyroid Cancer? A Qualitative Study.

BACKGROUND: Despite increasing debate about overdiagnosis and overtreatment of thyroid cancer in Korea, information to guide decisions on whether or not to undergo screening for and treatment of abnormal lesions of the thyroid is lacking. Moreover, studies have yet to outline what lay people know and want to know about thyroid cancer. The primary aim of this study was to explore general awareness of thyroid cancer among Korean women, their sources of information, and their satisfaction with the information they are provided. The secondary aim was to investigate information needs about thyroid cancer. MATERIALS AND METHODS: A qualitative study using focus group interviews was conducted. Twenty-nine women were divided into four groups: (1) participants who had never undergone thyroid ultrasound screening; (2) those who had undergone screening, (3) those who continued to undergo regular check-ups with ultrasonography for benign nodules of the thyroid; and (4) participants who had undergone surgery for thyroid cancer. RESULTS: A widespread lack of awareness of information on thyroid cancer was noted among participants in groups 1 and 2 who were not well aware of thyroid cancer and generally recognized it as a'good cancer'. Surprisingly, instead of doctors and medical personnel, most participants reported obtaining information from acquaintances and media outlets. Moreover, most participants described dissatisfaction with their experience with screening and a lack of explanation on treatment and test results from medical personnel. CONCLUSIONS: Women in Korea seek reliable information on thyroid cancer that could help them to better understand the disease and make informed decisions regarding screening and treatment. More effort is needed from medical personnel to communicate the implications of thyroid cancer, screening results, and treatments thereof to lay people.

A qualitative study of women's views on overdiagnosis and screening for thyroid cancer in Korea.

BACKGROUND: The incidence of thyroid cancer in Korea has increased by about 25 % every year for the past 10 years. This increase is largely due to a rising incidence in papillary thyroid cancer, which is associated with an overdiagnosis of small tumors that may never become clinically significant. This study was conducted to explore Korean women's understanding of overdiagnosis and to investigate changes in screening intention in response to overdiagnosis information. METHODS: Focus group interviews were conducted among women of ages 30-69 years, who are commonly targeted in Korea for cancer screening. Women were divided into four groups according to thyroid cancer screening history and history of thyroid disease. Of 51 women who were contacted, 29 (57 %) participated in the interviews. RESULTS: Prior awareness of thyroid cancer overdiagnosis was minimal. When informed about the risks of overdiagnosis, the participants were often surprised. Overcoming initial malcontent, many women remained skeptic about overdiagnosis and trusted in the advice of their physicians. Meanwhile, some of the study participants found explanations of overdiagnosis difficult to understand. Further, hearing about the risks of overdiagnosis had limited impact on the participants' attitudes and intentions to undergo thyroid cancer screening, as many women expressed willingness to undergoing continued screening in the future. CONCLUSION: A large majority of Korean women eligible for and had undergone thyroid cancer screening were unaware of the potential for overdiagnosis. Nevertheless, overdiagnosis information generally had little impact on their beliefs about thyroid cancer screening and their intentions to undergo future screening. Further research is needed to determine whether these findings could be generalized to the wider Korean population.

Aptamer-conjugated gold nanorod for photothermal ablation of epidermal growth factor receptor-overexpressed epithelial cancer.

Biomarker-specific photothermal nanoparticles that can efficiently sense markers that are overexpressed in distinguished adenocarcinomas have attracted much interest in an aspect of efficacy increase of cancer treatment. We demonstrated a promising prospect of a smart photothermal therapy agent employing anti-epidermal growth factor receptor aptamer (AptEGFR)-conjugated polyethylene glycol (PEG) layted gold nanorods (AptEGFR-PGNRs). The cetyltrimethylammonium bromide bilayer on GNRs was replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve as a biocompatible stabilizer and but also to conjugate AptEGFR. Subsequently, to direct photothermal therapy agent toward epithelial cancer cells, the carboxylated PEGylated GNRs (PGNRs) were further functionalized with AptEGFR using carbodiimide chemistry. Then, to assess the potential as biomarker-specific photothermal therapy agent of synthesized AptEGFR-PGNRs, the optical properties, biocompatibility, colloidal stability, binding affinity, and epicellial cancer cell killing efficacy in vitro/in vivo under near-infrared laser irradiation were investigated. As a result, AptEGFR-PGNRs exhibit excellent tumor targeting ability and feasibility of effective photothermal ablation cancer therapy.

A biodegradable polymersome containing Bcl-xL siRNA and doxorubicin as a dual delivery vehicle for a synergistic anticancer effect.

Combined cancer treatment via co-delivery of siRNAs and an anticancer drug can be a promising strategy due to the synergistic effect of simultaneously minimizing gene/drug administration. In this study, Bcl-xL siRNA and doxorubicin (DOX) are encapsulated into designed methoxy-poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-b-PLA) block copolymer polymersomes (PSomes). A study of the cytotoxicity of Bcl-xL siRNA and DOX co-encapsulated PSomes (CPSomes) shows more inhibited proliferation of MKN-45 and MKN-28 human gastric cancer cell lines than only gene- and drug-loaded ones. Consequently, these results demonstrate that co-delivery of genes and drugs using PSomes results in a synergistic efficacy and indicates the potential of PSomes as efficient nanocarriers for combined cancer therapy.