Effect of Thrombin-Containing Local Hemostatics on Postoperative Spinal Epidural Hematoma in Biportal Endoscopic Spinal Surgery

Methods@#Patients with and without TCLH were assigned to groups A and B, respectively. POSEH between the two groups was compared morphometrically and symptomatically. The risk factors for symptomatic and morphometric POSEH in BESS were identified. @*Results@#The morphometric POSEH was greater in group B, and the difference was significant (p =0.019). The incidence of symptomatic POSEH was lower in group A with 4.6% (5/109) than in group B with 9.5% (9/95); however, the rate was not significantly different (p =0.136). The morphometric POSEH was classified into two small (hG1 and hG2) and large (hG3 and hG4) and were compared between groups A and B, and the difference was significant (p =0.02). In the multivariable logistic regression, nonuse of TCLH (p =0.004) and preoperative diagnosis of stenosis (p =0.016) were variables found to be significant risk factors of morphometric POSEH. @*Conclusions@#Severe compression of the thecal sac by POSEH is more common in patients without TCLH. The risk of hematoma formation was higher when bilateral decompression was needed and the cut bone surface was more exposed.

Comparison of Corneal Epithelial Wound Healing between Topical RCI001, Solcoseryl, and Polydeoxyribonucleotide in the Murine Ocular Alkali Burn Model

Purpose@#To compare the corneal epithelial wound healing effects of RCI001, Solcoseryl, and polydeoxyribonucleotide (PDRN) in a rat alkali burn model. @*Methods@#In 40 male Sprague-Dawley rats, we induced alkali burn using filter paper soaked in 0.2N sodium hydroxide. The rats were then treated with topical 0.5% RCI001, 1.0% RCI001, Solcoseryl, or PDRN twice a day for 2 weeks. Corneal epithelial integrity and epithelial healing rate were measured at day 0, 3, 5, 7, 10, and 14. Histologic and immunohistochemistry findings were also assessed. @*Results@#Both the 0.5% and 1.0% RCI001 groups showed significantly more epithelial healing compared to the control group at day 5, 7, 10, and 14 (each p < 0.05). No statistical difference was found between the 0.5% and 1.0% RCI001 groups. Neither the Solcoseryl nor the PDRN groups showed a significant difference from the control. RCI001 treatment resulted in significantly reduced stromal edema, and a trend towards less inflammatory cell infiltration. @*Conclusions@#Topical application of RCI001 showed enhanced corneal epithelial wound healing in the murine corneal alkali burn model, presumably by suppressing inflammation. Meanwhile, Solcoseryl and PDRN did not show sufficient therapeutic effects compared to RCI001.

The Influence of Systolic Blood Pressure at the Time of Extubation on the Development of Postoperative Spinal Epidural Hematoma

Background@#The most common cause of neurological complications after a biportal endoscopic spine surgery (BESS) is postoperative spinal epidural hematomas (POSEH). The objective of this study was to determine the influence of systolic blood pressure at extubation (e-SBP) on POSEH. @*Methods@#A total of 352 patients who underwent single-level decompression surgery including laminectomy and/or discectomy with BESS under the diagnosis of spinal stenosis and herniated nucleus pulposus between August 1, 2018, and June 30, 2021, were reviewed retrospectively. The patients were divided into two, a POSEH group and a normal group without POSEH (no neurological complication). The e-SBP, demographic factors, and the preoperative and intraoperative factors suspected to influence the POSEH were analyzed. The e-SBP was converted to a categorical variable by the threshold level that was decided by maximum area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Antiplatelet drugs (APDs) were taken in 21 patients (6.0%), discontinued in 24 patients (6.8%), and not taken in 307 patients (87.2%). Tranexamic acid (TXA) was used in 292 patients (83.0%) in the perioperative period. @*Results@#Of the 352 patients, 18 patients (5.1%) underwent revision surgery for the removal of POSEH. The POSEH and normal groups were homogenous in age, sex, diagnosis, operation segments, operation time, and lab findings that were related to blood clotting, whereas there were differences in e-SBP (163.7 ± 15.7 mmHg in POSEH group and 154.1 ± 18.3 mmHg in normal group), APD (4 takers, 2 stoppers, 12 non-takers in POSEH group and 16 takers, 22 stoppers, 296 non-takers in normal group), and TXA (12 use, 6 not use in POSEH group and 280 use, 54 not use in normal group) in single variable analysis. The highest AUC in the ROC curve analysis was 0.652 for 170 mmHg e-SBP (p < 0.05). There were 94 patients in the high e-SBP group (≥ 170 mmHg) and 258 patients in the low e-SBP group. In multivariable logistic regression analysis, only high e-SBP was a significant risk factor for POSEH (p = 0.013; odds ratio, 3.434). @*Conclusions@#High e-SBP (≥ 170 mmHg) can influence the development of POSEH in biportal endoscopic spine surgery.

Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice / 神经科学通报·英文版

Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.

Oncologic Outcomes after Laparoscopic and Open Distal Gastrectomy for Advanced Gastric Cancer: Propensity Score Matching Analysis

PURPOSE: This study aimed to compare the oncologic and short-term outcomes of laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for advanced gastric cancer (AGC). MATERIALS AND METHODS: From July 2006 to November 2016, 384 patients underwent distal gastrectomy for AGC. Data on short- and long-term outcomes were prospectively collected and reviewed. Propensity score matching was applied at a ratio of 1:1 to compare the LDG and ODG groups. RESULTS: The operative times were longer for the LDG group than for the ODG group. However, the time to resumption of diet and the length of hospital stay were shorter in the LDG group than in the ODG group (4.7 vs. 5.6 days, P=0.049 and 9.6 vs. 11.5 days, P=0.035, respectively). The extent of lymph node dissection in the LDG group was more limited than in the ODG group (P=0.002), although there was no difference in the number of retrieved lymph nodes between the 2 groups. The 3-year overall survival rates were 98% and 86.9% (P=0.018), and the 3-year recurrence-free survival rates were 86.3% and 75.3% (P=0.259), respectively, in the LDG and ODG groups. CONCLUSIONS: LDG is safe and feasible for AGC, with earlier recovery after surgery and long-term oncologic outcomes comparable to those of ODG.

The Effects of Sagittal Spino-Pelvic Alignment on the Clinical Symptoms of Thoracolumbar Kyphosis in Osteoporotic Patients

OBJECTIVES@#The purpose of this study was to assess the effect of sagittal spino-pelvic alignment on the clinical symptoms of thoracolumbar kyphosis (TLK; T10-L2 Cobb's angle >20°) in osteoporotic patients.SUMMARY OF LITERATURE REVIEW: Few studies have investigated the clinical symptoms and radiological features of TLK caused by degenerative changes. There is also controversy over whether clinical symptoms will deteriorate in patients with TLK or which treatment should be chosen according to the degree of TLK.@*MATERIALS AND METHODS@#From May 2005 to May 2016, we reviewed 75 patients who were diagnosed with TLK (T10-L2 Cobb's angle >20°) and osteoporosis. Patients were excluded from the study if they had neurological symptoms, underlying spinal disorders, or unstable vertebral fractures. Fifty patients with TLK due to an osteoporotic vertebral compression fracture (group F) and 25 patients with senile TLK (group S) were assessed by clinical symptoms and radiological parameters. Thoracolumbar kyphosis angle and sagittal vertical axis (SVA) were also analyzed. Clinical symptoms were assessed using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI).@*RESULTS@#There were no significant differences in clinical symptoms (VAS, ODI) and radiological parameters between groups F and S, or according to the degree of TLK(20°–30°, 30°–40°, >40°). Clinical symptoms were significantly more severe in patients with sagittal imbalance (SVA >5 cm) than in those with sagittal balance.@*CONCLUSIONS@#Sagittal imbalance is a more important factor affecting clinical symptoms than the cause or the degree of TLK. Therefore, sagittal imbalance should be considered in the management of TLK in osteoporotic patients.

The Effects of Sagittal Spino-Pelvic Alignment on the Clinical Symptoms of Thoracolumbar Kyphosis in Osteoporotic Patients

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of this study was to assess the effect of sagittal spino-pelvic alignment on the clinical symptoms of thoracolumbar kyphosis (TLK; T10-L2 Cobb's angle >20°) in osteoporotic patients. SUMMARY OF LITERATURE REVIEW: Few studies have investigated the clinical symptoms and radiological features of TLK caused by degenerative changes. There is also controversy over whether clinical symptoms will deteriorate in patients with TLK or which treatment should be chosen according to the degree of TLK. MATERIALS AND METHODS: From May 2005 to May 2016, we reviewed 75 patients who were diagnosed with TLK (T10-L2 Cobb's angle >20°) and osteoporosis. Patients were excluded from the study if they had neurological symptoms, underlying spinal disorders, or unstable vertebral fractures. Fifty patients with TLK due to an osteoporotic vertebral compression fracture (group F) and 25 patients with senile TLK (group S) were assessed by clinical symptoms and radiological parameters. Thoracolumbar kyphosis angle and sagittal vertical axis (SVA) were also analyzed. Clinical symptoms were assessed using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). RESULTS: There were no significant differences in clinical symptoms (VAS, ODI) and radiological parameters between groups F and S, or according to the degree of TLK(20°–30°, 30°–40°, >40°). Clinical symptoms were significantly more severe in patients with sagittal imbalance (SVA >5 cm) than in those with sagittal balance. CONCLUSIONS: Sagittal imbalance is a more important factor affecting clinical symptoms than the cause or the degree of TLK. Therefore, sagittal imbalance should be considered in the management of TLK in osteoporotic patients.

Epidemiological investigation on the outbreak of foodborne and waterborne disease due to Norovirus with delayed notification / 農村醫學 地域保健

OBJECTIVES: There was an outbreak of foodborne and waterborne disease among high school students at Okcheon in June, 2018. First attack occurred June 5(th) but seven days later it was notified. The purpose of this investigation was to evaluate the pathogen of outbreak and cause of delayed notification. METHODS: First, we did a questionnaire survey for 61 cases and 122 controls to find what symptoms they had and whether they ate foods or drank water from June 2(nd) to June 12(th). Second, we investigated the environment of cafeteria and drinking water. Third, we examined specimen of cases and environment to identify bacteria or virus. RESULTS: Attack rate of this outbreak was 7.8%. Drinking water was strongly suspected as a source of infection in questionnaire survey but we could not find the exact time of exposure. Norovirus was identified in specimen of cases (2 students), drinking water (at main building and dormitory) and cafeteria (knife, dishtowel, hand of chef) CONCLUSIONS: We decided norovirus as the pathogen of this outbreak based on the clinical features of cases with diarrhea vomiting, abdominal pain and recovery within 2 or 3 days after onset, outbreak due to drinking water and microbiologic examination, And the cause of delayed notification might be the non-existence of the nurse teacher at that time and the lack of understanding of teachers on immediate notification under the outbreak. To prevent the delayed notification, notification system about outbreak of foodborne and waterborne disease in school is needed to be improved.

Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel / 神经科学通报·英文版

Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1.7 (~18%). To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel (0.1-1 μmol/L) for 24 h. Paclitaxel increased the Nav1.7 but not Nav1.8 expression and also increased the transient Na currents and action potential firing frequency in small-diameter (<50 μm) hDRG neurons. Thus, the hDRG provides a translational model in which to study "human pain in a dish" and test new pain therapeutics.

Multicenter Planning Comparison of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis (KROG 16-17)

BACKGROUND/AIMS: To evaluate the technical feasibility of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) with the major portal vein tumor thrombosis (PVTT). METHODS: Ten institutions affiliated with the Korean Stereotactic Radiosurgery Group were provided the contours of four cases: the first case was the first branch PVTT with sufficient normal liver volume (NLV), the second was the first branch PVTT with insufficient NLV, the third was the main trunk PVTT at confluence level, and the fourth was the main trunk PVTT with entire length. The institutions were asked to make SBRT plans according to their current treatment protocols and to complete facility questionnaires. RESULTS: Based on institutional protocols, SBRT was feasible in nine institutions for the first case (32–60 Gy in 3–5 fractions), in eight institutions for the second case (32–50 Gy in 3–5 fractions), in seven institutions for the third case (35–60 Gy in 3–5 fractions), and in four institutions for the fourth case (35–42 Gy in 4–5 fractions). The other institutions recommended hypo- or conventional fractionation due to insufficient NLV or gastrointestinal organ proximity. With analysis of the SBRT dose to the central hepatobiliary tract, the major PVTT could theoretically be associated with a high risk of hepatobiliary toxicity. CONCLUSIONS: Although SBRT is a technically feasible option for HCC with the major PVTT, there was a variability among the participating institutions. Therefore, further studies will be necessary to standardize the practice of SBRT for the major PVTT.

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies / 神经科学通报·英文版

The voltage-gated Na channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.

Natural History of Lumbar Degenerative Kyphosis with Conservative Treatment

STUDY DESIGN: Retrospective study. OBJECTIVES: To evaluate the natural history of conservatively treated lumbar degenerative kyphosis (LDK). SUMMARY OF LITERATURE REVIEW: The correlations between the clinical and radiologic parameters of general adult spinal deformity (ASD) are widely known. However, in LDK, dynamic sagittal imbalance is present during ambulation, meaning that its pathogenesis and natural history are different and not widely recognized compared to those of other forms of ASD, resulting in many controversies regarding treatment. To elucidate the natural history of LDK, we analyzed the clinical and radiologic outcomes of patients, comparing their first and final follow-up visits, and evaluated correlations among clinical and radiologic parameters. MATERIALS AND METHODS: From June 2006 to January 2014, 31 patients diagnosed with LDK who underwent conservative treatment were studied. The mean age of the patients was 72.5 years, and the mean follow-up period was 59.2 months. Clinical and radiologic evaluations were conducted on the first and final follow-up visits. Clinical evaluations were done using a visual analog scale and the Oswestry disability index, and radiologic evaluations were performed using spinal and pelvic parameters over a follow-up period of at least 24 months. RESULTS: Patients who were diagnosed with LDK and underwent conservative treatment showed no significant differences in their clinical outcomes between the first and final follow-up. Some radiologic parameters significantly progressed. There were no significant differences between clinical and radiologic parameters at the initial and final follow-up visits. CONCLUSIONS: During the follow-up period of patients diagnosed with LDK, some radiologic parameters progressed. However, the progress of LDK and the clinical symptoms reported by the patients did not significantly change. Decisions regarding the treatment of LDK should not be made according to radiologic parameters showing the degree of deformity, but by carefully determining the patients' clinical symptoms and disability level.

The role of surgical clips in the evaluation of interfractional uncertainty for treatment of hepatobiliary and pancreatic cancer with postoperative radiotherapy

PURPOSE: To evaluate the utility of implanted surgical clips for detecting interfractional errors in the treatment of hepatobiliary and pancreatic cancer with postoperative radiotherapy (PORT). METHODS AND MATERIALS: Twenty patients had been treated with PORT for locally advanced hepatobiliary or pancreatic cancer, from November 2014 to April 2016. Patients underwent computed tomography simulation and were treated in expiratory breathing phase. During treatment, orthogonal kilovoltage (kV) imaging was taken twice a week, and isocenter shifts were made to match bony anatomy. The difference in position of clips between kV images and digitally reconstructed radiographs was determined. Clips were consist of 3 proximal clips (clip_p, ≤2 cm) and 3 distal clips (clip_d, >2 cm), which were classified according to distance from treatment center. The interfractional displacements of clips were measured in the superior-inferior (SI), anterior-posterior (AP), and right-left (RL) directions. RESULTS: The translocation of clip was well correlated with diaphragm movement in 90.4% (190/210) of all images. The clip position errors greater than 5 mm were observed in 26.0% in SI, 1.8% in AP, and 5.4% in RL directions, respectively. Moreover, the clip position errors greater than 10 mm were observed in 1.9% in SI, 0.2% in AP, and 0.2% in RL directions, despite respiratory control. CONCLUSION: Quantitative analysis of surgical clip displacement reflect respiratory motion, setup errors and postoperative change of intraabdominal organ position. Furthermore, position of clips is distinguished easily in verification images. The identification of the surgical clip position may lead to a significant improvement in the accuracy of upper abdominal radiation therapy.

Surgical Outcomes of Schwannoma Occurring at Major Peripheral Nerves of Extremity: A Single Institution Analysis / 대한정형외과학회잡지

PURPOSE: We analyzed the surgical result of schwannoma occurring in the major peripheral nerves of the extremity and factors that influence these surgical results. MATERIALS AND METHODS: Fifty-one patients, who were followed for more than 1 year, were included. The mean age was 51 years. There were 23 male cases and 28 female cases. There were 27 cases of schwannoma in the upper extremity and 24 cases in the lower extremity. The involved nerves were classified. The maximal diameter of excised tumors was measured. Clinical and neurological symptoms were analyzed at preoperative, postoperative, and final follow-up. Risk factors of neurological complications were also analyzed. RESULTS: The mean follow-up period was 20 months. The average maximal diameter of tumors was 2.9 cm. The most affected nerve in the upper extremity was the ulnar nerve in 10 cases, and tibial nerve in the lower extremity in 10 cases. The most prevalent preoperative symptom was Tinel in 38 cases. Clinical symptoms were improved in more than 90% of patients following the surgery. There were 13 cases with preoperative sensory deficits. Symptom improvement after surgery was observed in 9 cases; and symptoms persisted in 4 cases following surgery. At the final follow-up, sensory deficits disappeared in 2 cases and persisted in 2 cases. There were 2 cases of preoperative motor deficits. There was improvement in 1 case following the surgery and persisted in 1 case until the final follow-up. There was a statistical significance between maximal diameter of schwannoma and postoperative neurological deficits (p<0.05). CONCLUSION: Schwannoma at the major peripheral nerves of the extremity can be excised with acceptable risk for neurological deficits. Meticulous dissection is required to avoid injuries of the involved nerves.

Effect of Coenzyme Q10 on Radiation Nephropathy in Rats

The kidney is one of the most radiosensitive organs in the abdominal cavity and is the dose-limiting structure in cancer patients receiving abdominal or total body irradiation. In the present study, the effect of coenzyme Q10 (CoQ10) on radiation nephropathy was evaluated in rats. A total of 72 rats were equally randomized into 4 groups: Control, CoQ10, irradiation with 10 Gy (RT) + placebo, or RT + CoQ10. The 2 RT groups received single 10 Gy of abdominal irradiation. The 2 CoQ10 groups were supplemented daily with 1 mL of soybean oil containing 10 mg/kg of CoQ10. The RT + placebo and control groups received same dose of soybean oil. After 24 weeks, laboratory and histopathologic findings were compared. The 2 RT groups showed significant increases in blood urea nitrogen (BUN) and creatinine levels and significant pathologic changes such as glomerulosclerosis and tubulointerstitial fibrosis. CoQ10 supplementation resulted in significant reductions of BUN and creatinine levels compared with the RT + placebo group (P < 0.001 and P = 0.038, respectively). CoQ10 treatment significantly attenuated glomerular and tubular changes of irradiated kidney in semiquantitative analysis (P < 0.001 for both). Administration of CoQ10 can alleviate the radiation-induced nephropathy.

Antioxidant Effect of Eugenol in Human Periodontal Ligament Fibroblasts / 체질인류학회지

Periodontal disease (PD) is the most common osteolytic disease of alveolar bone, oral infection seen in humans worldwide. PD is a common, chronic immunoinflammatory disease initiated by a complex subgingival bacterial and results in the inflammatory destruction of periodontal tissues, including the alveolar bone periodontal ligament, and gingivae. The effects of eugenol on periodontal ligament fibroblasts (PDLF) cell under oxidative injury have not been fully studied. Despite many studies in regard to the antioxidant effect of eugenol, the protective effect of eugenol against oxidative damage to PDLF cell, as well as the relationship between eugenol and apoptosis, has not been investigated so far. The aim of this study was to assess the protective effect of eugenol against H2O2-induced oxidative stress in PDLF cell. Cell lines were separately grown as monolayers at 5% CO2 and 37degrees C humidified atmosphere using appropriate media supplemented with 10% fetal bovine serum, 2 mM glutamine and 100 microg/mL penicillin-streptomycin. DMEM/F12 was used as the culture medium for periodontal ligament fibroblast cells. The viability of the PDLF cells which induced by the different concentrations of H2O2 (control, 50, 100, 200, 400 microM) for 24 h was detected by MTT assay. Cell viability was significantly reduced in a H2O2-concentration dose-dependent manner. The mitochondria-dependent pathway of apoptosis is regulated by Bcl-xl family, such as the anti-apoptotic protein Bcl-xl, pro-apoptotic protein Bak. With H2O2 injury, the protein level of Bak was up-regulated while the protein level of Bcl-xl was down-regulated. In group treated H2O2 and eugenol, the ratio was reduced and the expression of Bak decreased at the same time, indicating that eugenol can attenuate apoptosis through mitochondrial related pathway in PDLF cells. Therefore, although the findings of this study are limited to an in vitro interpretation, we suggest that eugenol preconditioning may have a beneficial effect in the recovery of periodontal ligament from oxidative stress.

Mechanism Underlying Shikonin-induced Apoptosis and Cell Cycle Arrest on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

Shikonin, a major ingredient in the traditional Chinese herb Lithospermumerythrorhizon, exhibits multiple biological functions including antimicrobial, anti-inflammatory, and antitumor effects. It has recently been reported that shikonin displays antitumor properties in many cancers. This study was aimed to investigate whether shikonin could inhibit oral squamous carcinoma cell (OSCC) growth via mechanisms of apoptosis and cell cycle arrest. The effects of shikonin on the viability and growth of OSCC cell line, SCC25 cells were assessed by MTT assay and clonogenic assays, respectively. Hoechst staining and DNA electrophoresis indicated that the shikonin-treated SCC25 cells were undergoing apoptosis. Western blotting, immunocytochemistry, confocal microscopy, flow cytometry, MMP activity, and proteasome activity also supported the finding that shikonin induces apoptosis. Shikonin treatment of SCC25 cells resulted in a time- and dose-dependent decrease in cell viability, inhibition of cell growth, and increase in apoptotic cell death. The treated SCC25 cells showed several lines of apoptotic manifestation as follows: nuclear condensation; DNA fragmentation; reduced MMP and proteasome activity; decrease in DNA contents; release of cytochrome c into cytosol; translocation of AIF and DFF40 (CAD) onto the nuclei; a significant shift in Bax/Bcl-2 ratio; and activation of caspase-9, -7, -6, and -3, as well as PARP, lamin A/C, and DFF45 (ICAD). Shikonin treatment also resulted in down-regulation of the G1 cell cycle-related proteins and up-regulation of p27(KIP1). Taken together, our present findings demonstrate that shikonin strongly inhibits cell proliferation by modulating the expression of the G1 cell cycle-related proteins, and that it induces apoptosis via the proteasome, mitochondria, and caspase cascades in SCC25 cells.

Autophagy Inhibition Promotes Quercetin Induced Apoptosis in MG-63 Human Osteosarcoma cells

Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.

The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa

BACKGROUND/AIMS: The aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage. METHODS: The enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (-) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a 13C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay. RESULTS: BSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups. CONCLUSIONS: BSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.

Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer

PURPOSE: To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the alpha/beta value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy10 (median, 55 Gy10). Nineteen lesions were treated with concurrent chemotherapy (CCRT). RESULTS: With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV 48 Gy10 were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. CONCLUSION: The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.