A pulmonary mucinous cystadenocarcinoma is an extremely rare tumor that is considered to be a cystic variant of mucin-producing lung adenocarcinoma. We present a case of pulmonary mucinous cystadenocarcinoma in a 54-year-old woman. Chest CT scans showed a 4.3-cm-sized, lobulated, well-defined, and homogeneous mass in the right middle lobe with peripheral stippled calcifications that demonstrated low-attenuation with no enhancement after contrast administration; 18F-fluorodeoxyglucose (FDG) PET/CT demonstrated mild heterogeneous FDG uptake. The mass was diagnosed as adenocarcinoma with mucin production by transbronchial lung biopsy. Right middle lobectomy was performed, and the pathologic examination disclosed a pulmonary mucinous cystadenocarcinoma.
doi:10.3348/kjr.2013.14.2.384
PMCID: PMC3590356
PMID: 23483761
Pulmonary mucinous cystadenocarcinoma; Lung cancer; CT; PET/CT
Protein lysine acetylation networks can regulate central processes such as carbon metabolism and gene expression in bacteria. In Escherichia coli, cyclic-AMP (cAMP) regulates protein lysine acetyltransferase (PAT) activity at the transcriptional level, but in Mycobacterium tuberculosis, fusion of a cyclic-nucleotide binding domain to a Gcn5-like PAT domain enables direct cAMP control of protein acetylation. Here we describe the allosteric activation mechanism of M. tuberculosis PAT. The crystal structures of the auto-inhibited and cAMP-activated PAT reveal that cAMP binds to a cryptic site in the regulatory domain over 32 Å from the catalytic site. An extensive conformational rearrangement relieves auto-inhibition by a substrate-mimicking lid that covers the protein-substrate binding surface. A steric double latch couples the domains by harnessing a classic, cAMP-mediated, conformational switch. The structures suggest general features that enable the evolution of long-range communication between linked domains.
doi:10.1038/nsmb.2318
PMCID: PMC3414669
PMID: 22773105
evolution of allosteric regulation; Rv0998; domain coupling; conformational change; Ringer
Abstract
Cynanchum wilfordii is used in traditional Chinese medicine with almost all parts of this plant considered beneficial for various vascular diseases. This study was performed to evaluate the effect of an ethanol extract of C. wilfordii (ECW) on vascular dysfunction in apolipoprotein E (apoE)−/− mice fed with high fat/cholesterol diets (HFCDs). The apoE−/− mice were fed HFCD consisting of 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg ECW. Chronic ECW treatment significantly lessened the level of low-density lipoprotein (P<.05) and elevated that of high-density lipoprotein-cholesterol (P<.01). Chronic ECW treatment normalized the HFCD-induced increase in systolic blood pressure, maintained smooth and soft intimal endothelial layers, and decreased intima-media thickness in aortic sections of HFCD-fed apoE−/− mice. ECW significantly restored the diet-induced decrease in vasorelaxation response to acetylcholine; however, the response to sodium nitroprusside did not change. ECW clearly restored the HFCD-induced reduction in endothelial nitric oxide synthase expression levels in aortic tissue, leading to decreased vascular inflammation through an inhibition of cellular adhesion molecules such as E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1 as well as endothelin-1 (ET-1) expression. In conclusion, ECW ameliorates endothelial dysfunction via improvement of the nitric oxide/cyclic GMP signaling pathway in a diet/genetic model of hyperlipidemia. ECW also substantially inhibited the development of atherosclerosis, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation, suggesting a vascular protective role for this herb in the treatment and prevention of atherosclerotic vascular disease.
doi:10.1089/jmf.2010.1222
PMCID: PMC3264958
PMID: 22082065
Cynanchum wilfordii; hyperlipidemia; hypertension; vascular inflammation; vasorelaxation
Lee, Jong Cheol | Lee, Ho Yong | Moon, Chang Hoon | Lee, Seung Ju | Lee, Won Hyeok | Cha, Hee Jeong | Park, Sungchan | Lee, Young Han | Park, Hyun Jin | Song, Ho-Taek | Min, Young Joo
The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numerous signal transduction pathways and resulting in a vast range of cellular effects. Among these mechanisms of action, ATO has been shown to cause acute vascular shutdown and massive tumor necrosis in a murine solid tumor model like vascular disrupting agent (VDA). However, relatively little is understood about this VDA-like property and its potential utility in developing clinical regimens. We focused on this VDA-like action of ATO. On the basis of the endothelial cell cytotoxicity assay and tubulin polymerization assay, we observed that higher concentrations and longer treatment with ATO reduced the level of α- and β-tubulin and inhibited the polymerization of tubulin. The antitumor action and quantitative tumor perfusion studies were carried out with locally advanced murine CT26 colon carcinoma grown in female BALB/c mice. A single injection of ATO intraperitoneally displayed central necrosis of the tumor tissue by 24 hours. T1-weighted dynamic contrast-enhanced magnetic resonance image revealed a significant decrease in tumor enhancement in the ATO-treated group. Similar to other VDAs, ATO treatment alone did not delay the progression of tumor growth; however, ATO treatment after injection of other cytotoxic agent (irinotecan) showed significant additive antitumor effect compared to control and irinotecan alone therapy. In summary, our data demonstrated that ATO acts as a VDA by means of microtubule depolymerization. It exhibits significant vascular shutdown activity in CT26 allograft model and enhances antitumor activity when used in combination with another cytotoxic chemotherapeutic agent.
PMCID: PMC3573657
PMID: 23418620
Moon, Chang Hoon | Lee, Seung Ju | Lee, Ho Yong | Lee, Jong Cheol | Cha, HeeJeong | Cho, Wha Ja | Park, Jeong Woo | Park, Hyun Jin | Seo, Jin | Lee, Young Han | Song, Ho-Taek | Min, Young Joo | Lebedeva, Irina V.
KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant Kep value representing capillary permeability was significantly decreased (p<0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shut-down activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors.
doi:10.1371/journal.pone.0053900
PMCID: PMC3543270
PMID: 23326531
Woo, Seung Hoon | Kim, Jin Pyeong | Park, Jung Je | Shim, Hyun Seok | Lee, Sang Ha | Lee, Ho Joong | Won, Seong Jun | Son, Hee Young | Kim, Rock Bum | Son, Young-Ik
Purpose
The aim of this study was to compare a negative pressure drain with a natural drain in order to determine whether a negative pressure drainage tube causes an increase in the drainage volume.
Materials and Methods
Sixty-two patients who underwent total thyroidectomy for papillary thyroid carcinoma (PTC) were enrolled in the study between March 2010 and August 2010 at Gyeongsang National University Hospital. The patients were prospectively and randomly assigned to two groups, a negative pressure drainage group (n=32) and natural drainage group (n=30). Every 3 hours, the volume of drainage was checked in the two groups until the tube was removed.
Results
The amount of drainage during the first 24 hours postoperatively was 41.68±3.93 mL in the negative drain group and 25.3±2.68 mL in the natural drain group (p<0.001). After 24 additional hours, the negative drain group was 35.19±4.26 mL and natural drain groups 21.53±2.90 mL (p<0.001). However, the drainage at postoperative day 3 was not statistically different between the two groups. In addition, the vocal cord palsy and temporary and permanent hypocalcemia were not different between the two groups.
Conclusion
These results indicate that a negative pressure drain may increase the amount of drainage during the first 24-48 hours postoperatively. Therefore, it is not necessary to place a closed suction drain when only a total thyroidectomy is done.
doi:10.3349/ymj.2013.54.1.204
PMCID: PMC3521271
PMID: 23225820
Total thyroidectomy; drainage; papillary thyroid carcinoma
Cho, Yong Won | Hong, Seung Bong | Kim, Do Hyung | Lee, Ho Won | Joo, Eun Yeon | Kim, Jee Hyun | Shin, Won Chul | Park, Kee Hyung | Han, Sun Jung | Lee, Hyang Woon
Background and Purpose
Dopamine agonists are first-line drugs for treating the symptoms of restless legs syndrome (RLS). However, few studies have investigated the effect of dopamine agonists on the quality of life (QoL) in RLS patients. We conducted a study to determine whether ropinirole exerts positive effects on the QoL in RLS patients and to analyze the underlying factors.
Methods
Primary RLS patients from eight medical centers were recruited in the study. They were evaluated in the baseline phase using various questionnaires including the Korean versions of the International Restless Legs Scale (K-IRLS), RLS QoL questionnaire (K-RLSQoL), and the Short Form 36 Health Survey (SF-36). After taking ropinirole for 8 weeks the same questionnaires were again completed as a re-evaluation. We analyzed the statistical difference using a paired t-test, a Pearson's correlation, and a stepwise multiple regression in order to identify the factors associated with the QoL change.
Results
A total of 107 subjects, including 65 (60.7%) females, completed this study. They were aged 51.68±14.80 years (mean±SD) and had a symptom duration of 8.8±9.0 months. After treatment with ropinirole, there were significant improvements on the K-RLSQoL, SF-36, and K-IRLS. The Pearson's correlation analysis showed that the improvement of QoL in RLS patients was significantly correlated with the severity of RLS (r=0.236, p<0.014) at baseline.
Conclusions
The results from this study suggest that treatment with ropinirole can improve the QoL in RLS patients. The improvement in the QoL is more related with the improvement of RLS symptoms.
doi:10.3988/jcn.2013.9.1.51
PMCID: PMC3543910
PMID: 23346161
restless legs syndrome; dopamine agonists; quality of life; sleep
Lee, Ho Sup | Kim, Yang Soo | Kim, Kihyun | Kim, Jin Seok | Kim, Hyo Jung | Min, Chang-Ki | Suh, Cheolwon | Eom, Hyeon-Seok | Yoon, Sung-Soo | Lee, Jae Hoon | Kim, Min Kyong | Kim, Sung-Hyun | Bae, Sung Hwa | Mun, Yeung-Chul | Jo, Deog Yeon | Chung, Joo-Seop
Novel agents to treat multiple myeloma (MM) have increased complete respone (CR) rates compared with conventional chemotherapy, and the quality of the response to treatment has been correlated with survival. The purpose of our study was to show how of early response to bortezomib combined chemotherapy influences survival in patients with newly diagnosed MM who are ineligible for stem cell transplantation. We assessed patient responses to at least four cycles of bortezomib using the International Myeloma Working Group response criteria. The endpoints were comparisons of progression free survival (PFS) and overall survival (OS) between early good response group (A group) and poor response group (B group). We retrospectively analyzed data from 129 patients registered by the Korean Multiple Myeloma Working Party, a nationwide registration of MM patients. The 3 yr PFS for the A and B groups was 55.6% and 18.4%, respectively (P < 0.001). The 3 yr OS for the A and B groups was 65.3% and 52.9%, respectively (P = 0.078). The early response to at least four cycle of bortezomib before next chemotherapy may help predict PFS in patients with MM who are ineligible stem cell transplantation.
doi:10.3346/jkms.2013.28.1.80
PMCID: PMC3546109
PMID: 23341716
Early Response; Multiple Myeloma; Bortezomib; Survival
Postherpetic neuralgia (PHN) is a debilitating complication of herpes zoster, especially in elderly and comorbid patients. Unfortunately, the currently available treatments have shown limited efficacy and some adverse events that are poorly tolerated in elderly patients. Scrambler Therapy, proposed as an alternative treatment for chronic neuropathic pain recently, is a noninvasive approach to relieve pain by changing pain perception at the brain level. Here, we report our clinical experiences on the effect of Scrambler Therapy for three patients with PHN refractory to conventional treatment.
doi:10.3344/kjp.2013.26.1.98
PMCID: PMC3546221
PMID: 23342218
chronic neuropathic pain; noninvasive approach; postherpetic neuralgia; Scrambler Therapy
Recent reports have shown limited anticancer therapeutic efficacy of insulin-like growth factor receptor (IGF-1R)-targeted monoclonal antibodies (mAbs), but the resistance mechanisms have not been completely identified. Because cooperation between epidermal growth factor receptor (EGFR) and IGF-IR could cause resistance to inhibitors of individual RTKs, we investigated the involvement of EGFR signaling in resistance to IGF-1R mAb and the underlying mechanisms of action. Most head and neck squamous cell carcinoma (HNSCC) tissues had co-expression of total and phosphorylated IGF-1R and EGFR at high levels compared to paired adjacent normal tissues. Treatment with cixutumumab (IMC-A12), a fully humanized IgG1 mAb, induced activation of Akt and mammalian target of rapamycin (mTOR), resulting in de novo synthesis of EGFR, Akt1, and survivin proteins and activation of the EGFR pathway in cixutumumab-resistant HNSCC and non-small cell lung cancer (NSCLC) cells. Targeting mTOR and EGFR pathways by treatment with rapamycin and cetuximab (an anti-EGFR mAb), respectively, prevented cixutumumab-induced expression of EGFR, Akt, and survivin and induced synergistic antitumor effects in vitro and in vivo. These data show that resistance to IGF-1R inhibition by mAbs is associated with Akt/mTOR-directed enhanced synthesis of EGFR, Akt1, and survivin. Our findings suggest that Akt/mTOR might be effective targets to overcome the resistance to IGF-1R mAbs in HNSCC and NSCLC.
doi:10.1158/1535-7163.MCT-11-0235
PMCID: PMC3237768
PMID: 21980128
EGFR; IGF-IR; head and neck squamous cell carcinoma; survivin; cixutumumab
Meningioma's account for around 15% of all primary brain tumors with some 10% of meningiomas arising in the posterior fossa. In rare cases, a meningioma can form around the endolymphatic sac. When formed in the posterior fossa, meningioma tumors can produce vague, non-specific vertiginous symptoms. Research has observed that a subset of these lesions could produce symptoms indistinguishable from those of Meniere's disease. Therefore, we described the clinical features of a case of posterior petrous meningioma with recurrent vertigo as well as the substantial resolution of symptoms after tumor removal via transmastoid approach.
doi:10.3342/ceo.2012.5.4.234
PMCID: PMC3506776
PMID: 23205230
Meningioma; Endolymphatic hydrops; Transmastoid
Cerebral hemorrhage is one of the most common causes of dysphagia. In many cases, dysphagia gets better once the acute phase has passed. Structural lesions such as thyromegaly, cervical hyperostosis, congenital web, Zenker's diverticulum, neoplasm, radiation fibrosis, and retropharyngeal abscess must be considered as other causes of dysphagia as well. Retropharyngeal abscess seldom occur in adults and if it does so, a search for a prior dental procedure, trauma, head and neck infection is needed. The symptoms may include neck pain, dysphagia, sore throat, and in rare cases, dyspnea accompanied by stridor. We present a case and discuss a patient who had dysphagia and neck pain after a cerebral hemorrhage. Testing revealed a retropharyngeal abscess. The symptoms were successfully treated after the administration of antibiotics.
doi:10.5535/arm.2012.36.6.861
PMCID: PMC3546191
PMID: 23342321
Retropharyngeal abscess; Dysphagia; Neck pain
Neuroendocrine carcinomas from an unknown primary site are uncommon. The authors report on a case of neuroendocrine carcinoma in a perigastric lymph node (LN) with no primary site. A 52-year-old male patient with early gastric adenocarcinoma underwent treatment by endoscopic submucosal dissection, and, six months later, findings on a computed tomographic scan of the abdomen revealed a LN enlargement measuring 2.0 cm in the perigastric region. The patient underwent subtotal gastrectomy and regional LN dissection under a suggestive preoperative diagnosis of gastric adenocarcinoma with LN metastasis. However, microscopically, no residual tumor was found in the stomach, and the perigastric LN showed poorly differentiated neuroendocrine carcinoma (PDNEC). After an extensive workup, no primary site was identified. The patient also received four cycles of etoposide and cisplatin. Despite its extremely rare incidence, this case suggests that PDNEC of an unknown primary site is limited to a single site, and that resection should be considered in combination with chemotherapy.
doi:10.4143/crt.2012.44.4.271
PMCID: PMC3546275
PMID: 23341792
Lymph nodes; Neuroendocrine carcinoma; Unknown primary neoplasms
Edema is a symptom that results from the abnormal accumulation of fluid in the body. The cause of edema is related to the level of aquaporin (AQP)2 protein expression, which regulates the reabsorption of water in the kidney. Edema is caused by overexpression of the AQP2 protein when the concentration of Na+ in the blood increases. The rhizome of Atractylodes macrocephala has been used in traditional oriental medicine as a diuretic drug; however, the mechanism responsible for the diuretic effect of the aqueous extract from A. macrocephala rhizomes (AAMs) has not yet been identified. We examined the effect of the AAM on the regulation of water channels in the mouse inner medullary collecting duct (mIMCD)-3 cells under hypertonic stress. Pretreatment of AAM attenuates a hypertonicity-induced increase in AQP2 expression as well as the trafficking of AQP2 to the apical plasma membrane. Tonicity-responsive enhancer binding protein (TonEBP) is a transcription factor known to play a central role in cellular homeostasis by regulating the expression of some proteins, including AQP2. Western immunoblot analysis demonstrated that the protein and mRNA expression levels of TonEBP also decrease after AAM treatment. These results suggest that the AAM has a diuretic effect by suppressing water reabsorption via the downregulation of the TonEBP-AQP2 signaling pathway.
doi:10.1155/2012/650809
PMCID: PMC3522508
PMID: 23258995
Objective
To evaluate tumor responses in patients treated with anti-angiogenic agents for non-small cell lung cancer (NSCLC) by assessing intratumoral changes using a dual-energy CT (DECT) (based on Choi's criteria) and to compare it to traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Materials and Methods
Ten NSCLC patients treated with bevacizumab underwent DECT. Tumor responses to anti-angiogenic therapy were assessed and compared with the baseline CT results using both RECIST (size changes only) and Choi's criteria (reflecting net tumor enhancement). Kappa statistics was used to evaluate agreements between tumor responses assessed by RECIST and Choi's criteria.
Results
The weighted κ value for the comparison of tumor responses between the RECIST and Choi's criteria was 0.72. Of 31 target lesions (21 solid nodules, 8 lymph nodes, and two ground-glass opacity nodules [GGNs]), five lesions (16%) showed discordant responses between RECIST and Choi's criteria. Iodine-enhanced images allowed for a distinction between tumor enhancement and hemorrhagic response (detected in 14% [4 of 29, excluding GGNs] of target lesions on virtual nonenhanced images).
Conclusion
DECT may serve as a useful tool for response evaluation after anti-angiogenic treatment in NSCLC patients by providing information on the net enhancement of target lesions without obtaining non-enhanced images.
doi:10.3348/kjr.2012.13.6.702
PMCID: PMC3484290
PMID: 23118568
Targeted therapy; Tumor response assessment; Response criteria; Guideline; Non-small cell lung cancer; Dual energy CT
A 67-year-old woman presented with memory impairment and behavioral changes. Brain MRI indicated hepatic encephalopathy. Abdominal CT scans revealed an intrahepatic portosystemic venous shunt that consisted of two shunt tracts to the aneurysmal sac that communicated directly with the right hepatic vein. The large tract was successfully occluded by embolization using the newly available AMPLATZERTM Vascular Plug II and the small tract was occluded by using coils. The patient's symptoms disappeared after shunt closure and she remained free of recurrence at the 3-month follow-up evaluation.
doi:10.3348/kjr.2012.13.6.827
PMCID: PMC3484308
PMID: 23118586
Hepatic encephalopathy; Portosystemic shunt; Surgical; Embolization; Therapeutic
Background
Proton pump is an integral membrane protein that is ubiquitous ATP binding cassette (ABC) involved in many transport processes in all living organisms, among which a specialized form of pump, so called p-type proton pump, exists in the parietal cells of stomach. Though proton pump inhibitors (PPIs) are frequently prescribed to prevent nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage, the acid suppressive actions do not suffice to explain.
Methods
In order to document the effects of pantoprazole, one of PPIs, on the NSAIDs-induced gastric damage, in vitro and in vivo studies were performed. Immunocytochemistry, Western blot analysis, electrophoretic mobility shift assay and RT-PCR were conducted to evaluate the induction of heme oxygenase-1 (HO-1) through Nrf2 activation in normal gastric mucosal RGM-1 cells or in vivo stomach tissues from rats treated with indomethacin and/or pantoprazole.
Results
Pantoprazole activated Nrf2 through inactivation of Keap1, after which the expression of HO-1 was significantly increased in a dose-dependent manner in RGM-1 cells. Increased ARE-DNA binding activity was observed maximally at 1 h with 300 μM of pantoprazole. The expression of HO-1 induced by pantoprazole was significantly associated with the increased in vitro tube formation (P < 0.05) and angiogenic factors including VEGF, bFGF, and HIF-1α. Indomethacin markedly increased the expressions of TNF-α, IL-1ß, IL-8, NOX-1, ICAM-1 and VCAM, whereas pantoprazole significantly decreased the expressions of indomethacin-induced these inflammatory mediators in accord with pantoprazole-induced HO-1 (P < 0.05) as documented with HO-1 inhibitor. In vivo model of indomethacin-induced gastric damage could validate in vitro-drawn results that pantoprazole remarkably protected against indomethacin-induced gastric damage, in which zinc protoporphyrin (5 mg/kg, ip) significantly abolished the protective efficacy of pantoprazole.
Conclusion
These results demonstrate that Nrf2-mediated HO-1 induction of PPIs afforded a significant protective effect against NSAIDs-induced gastric damage beyond acid suppressive actions.
doi:10.1186/1471-230X-12-143
PMCID: PMC3548718
PMID: 23066659
Heme oxygenase-1; Proton pump inhibitor; NSAIDs-induced gastropathy; Nrf2
Olanzapine (OLZ) is used to treat bipolar disorder, but its therapeutic mechanism of action is not clear. Arachidonic acid (AA, 20:4n-6) plays a critical role in brain signaling and an upregulated AA metabolic cascade was reported in postmortem brains from bipolar disorder patients. Here we tested whether, similar to the action of the mood stabilizers lithium, carbamazepine and valproate, chronic OLZ treatment would reduce AA turnover in rat brain. We administered OLZ (6 mg/kg/day) or vehicle i.p. to male rats once daily for 21 days. A washout group received 21 days of OLZ followed by vehicle on day 22. Two hours after the last injection, [1-14C]AA (170 µCi/kg) was infused intravenously for 5 min, and timed arterial blood samples were taken. After the rat was euthanized at 5 min, its brain was microwaved, removed and analyzed. Chronic OLZ decreased plasma unesterified AA concentration, AA incorporation rates and AA turnover in brain phospholipids. These effects were absent after washout. Consistent with reduced AA turnover, OLZ decreased brain cyclooxygenase activity and the brain concentration of the proinflammatory AA-derived metabolite, prostaglandin E2. In view of upregulated brain AA metabolic markers in bipolar disorder, the abilities of OLZ and the mood stabilizers to commonly decrease prostaglandin E2 and AA turnover in rat brain phospholipids, albeit by different mechanisms, may be related to their efficacy against the disease.
doi:10.1111/j.1471-4159.2011.07410.x
PMCID: PMC3188676
PMID: 21812779
bipolar disorder; antipsychotic; washout; phospholipid; cyclooxygenase; prostaglandin E2
Background
Ezrin, a member of the ezrin-radixin-moesin family, is implicated in tumor progression, metastatic dissemination, and adverse outcomes, in several cancer types. In this study, we explored the clinicopathological significance of ezrin expression in non-small cell lung carcinomas (NSCLCs).
Methods
Immunohistochemical analysis of tissue microarray with 112 surgically resected NSCLC specimens, was performed to examine the ezrin expression. We also correlated ezrin expression with other clinicopathological features and prognosis.
Results
The ezrin-positive group revealed significantly higher correlation with pleural invasion (p=0.016) and pathologic stage (p=0.050). Univariate survival analysis showed that ezrin-positive group had a significantly shorter cancer-specific survival than ezrin-negative group (p=0.016). Meanwhile, female (p=0.030), no pleural invasion (p=0.023), no lymphatic invasion (p=0.026), and early pathologic stage (p=0.008) significantly correlated with longer survival. Multivariate survival analysis showed that variables such as ezrin positivity (p=0.032), female (p=0.035), and early pathologic stage (p=0.001) were independent prognostic factors for NSCLC.
Conclusions
Ezrin might be a molecular marker to predict poor prognosis of NSCLC.
doi:10.4132/KoreanJPathol.2012.46.5.470
PMCID: PMC3490123
PMID: 23136574
Carcinoma, non-small cell lung; Ezrin; Prognosis
Purpose
Even though aural fullness is ubiquitous among patients presenting to otolaryngology clinics, the association between aural fullness and disease development has not yet been clearly determined.
Materials and Methods
Our study was performed on outpatients from June 2006 to February 2010 whose major complaint was "ear fullness", "aural fullness", or "ear pressure". We assessed their demographic and clinical characteristics, including sex, associated diseases, symptoms, otoscopic findings, audiology test results, and final diagnoses.
Results
Among 432 patients, 165 (38.2%) were males and 267 (61.8%) were females, with mean ages of 42±19 years and 47±17 years, respectively. Tinnitus, hearing disturbance, autophony (p<0.01) as well as nasal obstruction and sore throat (p<0.05) showed a statistically significant correlation with aural fullness. Among patients who complained of hearing fullness, tests and measures such as impedance audiometry, speech reception threshold, and pure tone audiometry generated statistically significant results (p<0.05). Ear fullness was most frequently diagnosed as Eustachian tube dysfunction (28.9%), followed by otitis media with effusion (13.4%) and chronic otitis media (7.2%). However, 13.4% of patients could not be definitively diagnosed.
Conclusion
Among patients complaining of ear fullness, Eustachian tube dysfunction, otitis media with effusion, chronic otitis media were most commonly observed. Performance of otoscopy, nasal endoscopy, the Valsalva maneuver, and additional audiological tests is necessary to exclude other diseases.
doi:10.3349/ymj.2012.53.5.985
PMCID: PMC3423854
PMID: 22869482
Aural fullness; tinnitus; hearing; audiologic test; nasopharyngeal cancer
Shin, Hong Won | Yoon, Hyuck Jun | Choi, Sang Woong | Bae, Han Jun | Sohn, Ji Hyun | Lee, Ho Myung | Cho, Hyun Ok | Cho, Yun Kyeong | Park, Hyoung Seob | Kim, Hyungseop | Nam, Chang Wook | Hur, Seung Ho | Kim, Yoon Nyun | Kim, Kwon Bae
Heparin is an essential drug in the treatment of acute coronary syndrome and it is used during percutaneous coronary intervention (PCI). Heparin-induced thrombocytopenia (HIT), albeit a serious complication of heparin therapy characterized by thrombocytopenia and high risk for venous and arterial thrombosis, has rarely been previously reported during PCI. We report a case of an acute stent thrombosis due to an unusual cause, HIT during primary PCI, in a patient with acute myocardial infarction.
doi:10.4070/kcj.2012.42.9.646
PMCID: PMC3467452
PMID: 23091513
Heparin; Thrombocytopenia; Thrombosis; Myocardial infarction
Koom, Woong Sub | Ahn, Seung Do | Song, Si Yeol | Lee, Chang Geol | Moon, Sung Ho | Chie, Eui Kyu | Jang, Hong Seok | Oh, Young-Taek | Lee, Ho Sun | Keum, Ki Chang
Purpose
The purpose of this prospective multi-institutional study was to evaluate the nutritional status of patients undergoing radiotherapy (RT) for treatment of head and neck, lung, or gastrointestinal cancer.
Materials and Methods
A total of 1,000 patients were enrolled in this study at seven different hospitals in Seoul, Korea between October 2009 and May 2010. The nutritional status of patients after receiving 3 weeks of RT was evaluated using subjective global assessment (SGA). The nutritional status of each patient was rated as well nourished (A), moderately malnourished (B), or severely malnourished (C).
Results
The mean age of patients in this study was 59.4 ± 11.9 years, and the male to female ratio was 7:3. According to the SGA results, 60.8%, 34.5%, and 4.7% of patients were classified as A, B, or C, respectively. The following criteria were significantly associated with malnutrition (SGA B or C; p < 0.001): loss of subcutaneous fat or muscle wasting (odds ratio [OR], 11.473); increased metabolic demand/stress (OR, 8.688); ankle, sacral edema, or ascites (OR, 3.234); and weight loss ≥5% (OR, 2.299).
Conclusion
SGA was applied successfully to assess the nutritional status of most patients. The prevalence of malnutrition in a radiation oncology department was 39.2%. The results of this study serve as a basis for implementation of nutrition intervention to patients being treated at radiation oncology departments.
doi:10.3857/roj.2012.30.3.132
PMCID: PMC3496847
PMID: 23170292
Malnutrition; Nutrition assessment; Subjective global assessment; Radiotherapy
Background
Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD).
Method
EAL-I (100 mg·kg−1/day), EAL-II (200 mg·kg−1/day), and fluvastatin (3 mg·kg−1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks.
Results
Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model.
Conclusion
The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.
doi:10.1186/1472-6882-12-116
PMCID: PMC3517347
PMID: 22866890
Arctium lappa; Hyperlipidemia; Hypertension; Vasorelaxation; Inflammation
Background
Recently, identification of fungi have been supplemented by molecular tools, such as ribosomal internal transcribed spacer (ITS) sequence analysis. According to these tools, morphological Exophiala species was newly introduced or redefined.
Objective
This study was designed to investigate the phylogenetics based on ribosomal ITS sequence analysis from clinical Exophiala species isolated in Korea.
Methods
The strains of Exophiala species were 4 clinical isolates of phaeohyphomycosis agents kept in the department of dermatology, Dongguk University Medical Center(DUMC), Gyeongju, Korea. The DNAs of total 5 strains of Exophiala species were extracted by bead-beating method. Polymerase chain reaction of ITS region using the primer pairs ITS1-ITS4, was done and phylogenetic tree contributed from sequences of ITS region from 5 Korean isolates including E. dermatitidis CBS 109154 and comparative related strains deposited in GenBank.
Results
The strains of Exophiala species were 3 strains of E. dermatitidis, 1 strain of E. jeanselmei and 1 strain of Exophiala new species. Among the 3 subtypes (type A, B, C) of E. jeanselmei, E. jeanselmei DUMC 9901 belonged to type B. Of the 2 main types of E. dermatitidis (type A, B) and 3 subtypes of E. dermatitidis type A (A0, A1 and A2), two strains (E. dermatitidis CBS 709.95, E. dermatitidis CBS 109154) belonged to A0 subtypes, 1 strain (E. dermatitidis DUMC 9902) A1 subtype, respectively.
Conclusion
Phylogenetic analysis of ITS region sequence provided useful information not only for new species identification but for the subtyping and origin of Exophiala species.
doi:10.5021/ad.2012.24.3.287
PMCID: PMC3412237
PMID: 22879712
Exophiala; Phylogeny; Ribosomal internal transcribed spacer
Background
Skin acts as the first line of defense against any foreign materials outside of our body. In inflammatory skin disease, the pathogenesis is due to an immune reaction in the keratinocytes, immune cells and soluble mediators. Balneotherapy is widely used for the treatment of inflammatory skin disease, but the mechanisms are only partly understood by immune regulation. Balneotherapy in dermatologic disease can affect the secretion of pro-inflammatory cytokines, IL-1α and tumor necrosis factor from keratinocytes, and possibly affect the T cell differentiation.
Objective
In this study, we evaluated the effect of spa spring water from Yong-gung oncheon on the cells, and investigated the skin immune reaction.
Methods
We investigated the immunomodulatory or anti-inflammatory effect of thermal spring water on the expression of pro-inflammatory cytokines in the HaCaT cells under Toll-like receptor (TLR) stimulation, as well as the effect on the differentiation of CD4+ T cells under spring water.
Results
The treatment of spa spring water from Yong-gung oncheon decreased the expression of proinflammatory cytokines under TLR stimulation to the HaCaT cells and antigen presenting cells. In addition, spa spring water attenuated the differentiation process of subsets of CD4+ T cells, i.e., Th1, Th2 and Th17 cells. All these immune parameters can be used to evaluate the efficacy of spa spring water in Korea, in terms of the immune modulatory effect.
Conclusion
Spa spring water treatment suppressed the inflammatory cytokines production and also modulated the differentiation of CD4+ T cells into Th1, Th2, and Th17 cells, but not the Tregs cells.
doi:10.5021/ad.2012.24.3.324
PMCID: PMC3412242
PMID: 22879717
Balneotherapy; CD4+ T cells; Cytokines; HaCaT cells; Skin inflammation