Prognostic Predictions for Patients with Glioblastoma after Standard Treatment: Application of Contrast Leakage Information from DSC-MRI within Nonenhancing FLAIR High-Signal-Intensity Lesions.

BACKGROUND AND PURPOSE: Attempts have been made to quantify the microvascular leakiness of glioblastomas and use it as an imaging biomarker to predict the prognosis of the tumor. The purpose of our study was to evaluate whether the extraction fraction value from DSC-MR imaging within nonenhancing FLAIR hyperintense lesions was a better prognostic imaging biomarker than dynamic contrast-enhanced MR imaging parameters for patients with glioblastoma. MATERIALS AND METHODS: A total of 102 patients with glioblastoma who received a preoperative dynamic contrast-enhanced MR imaging and DSC-MR imaging were included in this retrospective study. Patients were classified into the progression (n = 87) or nonprogression (n = 15) groups at 24 months after surgery. We extracted the means and 95th percentile values for the contrast leakage information parameters from both modalities within the nonenhancing FLAIR high-signal-intensity lesions. RESULTS: The extraction fraction 95th percentile value was higher in the progression-free survival group of >24 months than at ≤24 months. The median progression-free survival of the group with an extraction fraction 95th percentile value of >13.32 was 17 months, whereas that of the group of ≤13.32 was 12 months. In addition, it was an independent predictor variable for progression-free survival in the patients regardless of their ages and genetic information. CONCLUSIONS: The extraction fraction 95th percentile value was the only independent parameter for prognostic prediction in patients with glioblastoma among the contrast leakage information, which has no statistically significant correlations with the DCE-MR imaging parameters.

Correction: The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion.

The original version of this article contained an error in the published figures Fig 2 and Fig 3f, where the information was inadvertently duplicated. This error does not alter the conclusions of the paper. The corrected figures are published in this correction notice. The authors sincerely apologize for this error.

Correction: RCP induces Slug expression and cancer cell invasion by stabilizing ß1 integrin.

Following the publication of this article the authors noted that images were inadvertently duplicated in Fig. 1b. The corrected Fig. 1 can be found in the associated Correction. The conclusions of this paper are not affected. The authors sincerely apologize for this error. This error has not been corrected in the HTML or PDF of the original Article.

Predicting hypertension among Korean cancer survivors: A nationwide population-based study.

Hypertension is the most common comorbidity among cancer survivors, although there is no model for predicting hypertension in this population. Therefore, we developed a model for predicting hypertension using data from 6,480 Korean cancer survivors who were ≥20 years old. The odds ratios (ORs) for hypertension were calculated using stepwise logistic regression analyses, and a nomogram was generated to predict hypertension. Hypertension was independently associated with an age of ≥65 years (OR: 3.058), male gender (OR: 1.195), obesity (OR: 1.998), prehypertension (OR: 2.06), dyslipidaemia (OR: 2.011) and diabetes mellitus (OR: 2.297). Each variable in the nomogram was assigned a specific number of points, and the total score (range: 0-400) was used to obtain a value for predicting hypertension. The estimated prevalence of hypertension increased when the total nomogram score exceeded the sixth decile (total points: 128; p for trend <.001). Therefore, among Korean cancer survivors, hypertension was significantly associated with an age of >65 years, male gender, obesity, and having various comorbidities (e.g., prehypertension, dyslipidaemia and diabetes mellitus). Furthermore, our nomogram could predict the incidence of hypertension, and the sixth decile of the total nomogram score predicted an increased risk of hypertension.

RCP induces Slug expression and cancer cell invasion by stabilizing ß1 integrin.

Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. In the present study, we demonstrate that RCP stabilizes ß1 integrin leading to increased ß1 integrin levels and activation of a signaling cascade culminating in Slug induction, epithelial-to-mesenchymal transition and increased invasion. Ectopic expression of RCP induced Slug expression. Silencing ß1 integrin efficiently inhibited RCP-induced Slug expression and subsequent cancer cell invasion. Conversely, ectopic expression of ß1 integrin was sufficient to induce Slug expression. Pharmacological inhibition of integrin linked kinase (ILK), EGFR and NF-κB, as well as transfection of a dominant-negative mutant of Ras (RasN17), significantly inhibited RCP-induced Slug expression and cancer cell invasion. Strikingly, ectopic expression of RCP was sufficient to enhance metastasis of ovarian cancer cells to the lung. Collectively, we demonstrate a mechanism by which RCP promotes cancer cell aggressiveness through sequential ß1 integrin stabilization, activation of an ILK/EGFR/Ras/NF-κB signaling cascade and subsequent Slug expression.

Combined effect of individual and neighborhood socioeconomic status on mortality in patients with newly diagnosed dyslipidemia: A nationwide Korean cohort study from 2002 to 2013.

BACKGROUND AND AIM: The study aims to determine whether dyslipidemia patients living in less affluent neighborhood are at a higher risk of mortality compared to those living in more affluent neighborhoods. METHODS AND RESULTS: A population-based cohort study was conducted using a stratified representative sampling from the National Health Insurance claim data from 2002 to 2013. The target subjects comprise patients newly diagnosed with dyslipidemia receiving medication. We performed a survival analysis using the Cox proportional hazard model. Of 11,946 patients with dyslipidemia, 1053 (8.8%) subjects died during the follow-up period. Of the dyslipidemia patients earning a middle-class income, the adjusted HR in less affluent neighborhoods was higher than that in the more affluent neighborhoods compared to the reference category of high individual SES in more affluent neighborhoods (less affluent; hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.35-1.99 vs. more affluent; HR = 1.48, 95% CI: 1.20-1.81, respectively). We obtained consistent results in patients with lower income, wherein the adjusted HR in less affluent neighborhoods was higher than that in more affluent neighborhoods (less affluent; HR = 1.52, 95% CI: 1.16-1.97 vs. more affluent; HR = 1.41, 95% CI: 1.04-1.92, respectively). CONCLUSION: Living in a less affluent neighborhood contributes to higher mortality among dyslipidemia patients. The individual- and neighborhood-level variables cumulatively affect individuals such that the most at-risk individuals include those having both individual- and neighborhood-level risk factors. These findings raise important clinical and public health concerns and indicate that neighborhood SES approaches should be essentially considered in health-care policies similar to individual SES.

Relationship between socioeconomic and lifestyle factors and cataracts in Koreans: the Korea National Health and Nutrition Examination Survey 2008-2011.

PURPOSE: Cataracts are the leading cause of visual impairment and blindness, and therefore early identification and modification of the risk factors for cataracts are meaningful. This study aimed to investigate the relationship between socioeconomic status (SES) and lifestyle factors, and age-related cataracts in South Korea. METHODS: This cross-sectional study was based on data collected in the 2008-2011 Korea National Health and Nutrition Examination Survey. A total of 15 866 subjects, aged ≥40 years, were included. SES was defined using household income and education level. Sociodemographic, lifestyle, and other associated factors were assessed by health interviews and examinations. Cataracts were diagnosed via slit-lamp examination using the Lens Opacities Classification System III. RESULTS: The prevalence of any cataract was 38.9% in men and 42.3% in women (P<0.001). In women, the risk of cataracts increased with decreases in household income (P-value for trend=0.016 and 0.041 in any, and cortical cataract, respectively) and education level (P-value for trend=0.009, 0.027, and 0.016 in any, nuclear, and cortical cataract, respectively) after adjusting for confounding factors. Current smoking was correlated with nuclear cataracts in men (OR 1.21; 95% CI: 1.00, 1.46 in age-adjusted analysis) and cataract surgery in women (OR 2.25; 95% CI: 1.00, 5.04 in multivariate-adjusted analysis). CONCLUSIONS: Socioeconomic disparities in cataract prevalence were observed in women; current smoking increased the risk of nuclear cataracts in men and surgery in women. Public health interventions focusing on gender differences are warranted to prevent and treat cataracts.

hTERT mediates norepinephrine-induced Slug expression and ovarian cancer aggressiveness.

Stress hormones have been implicated in both tumor initiation and progression. Human telomerase reverse transcriptase (hTERT) is overexpressed in cancer cells and associated with malignant tumor progression and poor outcome. We thus sought to determine whether the stress hormone norepinephrine (NE) could induce hTERT expression and subsequently ovarian cancer progression. Unexpectedly, NE induced hTERT transcript and protein expression, and subsequently ovarian cancer cell invasion. Pharmacologic inhibition of ß2-adrenergic receptor 2 and protein kinase A, as well as silencing of hypoxia-inducible factor-1α and c-Myc expression, profoundly attenuated NE-induced hTERT expression. Strikingly, stimulation of the cells with NE or ectopic expression of hTERT induced expression of Slug, ovarian cancer cell epithelial-mesenchymal transition (EMT) and invasion. Silencing of hTERT expression abrogated NE-induced ovarian cancer cell invasion, EMT and Slug expression. In addition, silencing of Slug expression significantly inhibited NE- and hTERT-induced ovarian cancer cell EMT and invasion. Moreover, continuous exposure to NE was sufficient to enhance in vivo hTERT expression and metastasis of ovarian cancer cells to the lung. Finally, we provide evidence that hTERT links Src to Slug expression in NE-induced ovarian cancer EMT and metastasis. We thus demonstrate a novel role of hTERT in stress hormone-induced ovarian cancer aggressiveness through inducing Slug, providing novel biomarkers and potential therapeutic targets for ovarian cancer.

An empirical model for gas phase acidity and basicity estimation.

Gas phase acidity and basicity estimation models have been developed for acidic and basic functional groups of amino acid side-chains and also for a number of small organic molecules. The acidic functional groups include aliphatic and aromatic alcohol, and aliphatic and aromatic carboxylic acid, and the basic functional groups include aliphatic, aromatic and hetero-aromatic amines, and also pyridino-, pyrazolo- and imidazolo-groupings. The models are described in terms of a linear combination of descriptors that highly influence reactivity at the reaction centres of the functional groups. In order to describe the chemical environments of the deprotonating and protonating sites, atomic descriptors such as the effective atomic electronegativity and effective atomic polarizability of the atoms in the reaction field and the electrostatic potentials at the reaction sites have been introduced. The coefficient of determination (r(2)) of each model is above 0.8, apart from the imidazole model. The models are readily applicable, ranging from simple organic molecules to proteins.

In vivo and in vitro analysis of low level light therapy: a useful therapeutic approach for sensitive skin.

Sensitive skin is a relatively common dermatologic condition and no optimal treatments have been established so far. Low-level laser/light therapy (LLLT) has been used for its biostimulative effect in various clinical settings. The purpose of this study was to investigate whether low-level laser/light therapy can improve sensitive skin clinically and to evaluate the effects of LLLT on skin in vitro. Twenty-eight patients complaining of sensitive skin were treated with low-level polarized light, and clinical results were evaluated using subjective and objective method. To investigate possible working mechanism of LLLT on skin, cultured human keratinocytes pretreated with nontoxic concentration of sodium lauryl sulfate (SLS) were used. Cytokines released from irritated keratinocytes after LLLT were analyzed. All patients showed subjective and objective improvement after treatment. No adverse effects were reported. The average number of LLLT sessions required to achieve clinical improvement was 9.9, and cumulative dose of LLLT was 71.3 J/cm(2) on the average. Erythema index decreased significantly after LLLT treatment (p = 0.017). In vitro assay showed that LLLT significantly reduced the release of VEGF from SLS-pretreated keratinocytes (p = 0.021). Our results suggest that LLLT could be a useful and safe treatment modality for sensitive skin, and modification of inflammatory cytokines released from irritated keratinocytes may be considered as one of plausible mechanisms in sensitive skin treated with LLLT.

Eating rate is associated with cardiometabolic risk factors in Korean adults.

BACKGROUND AND AIM: Eating slowly is a crucial concept in behavioural nutrition and is recommended for weight management as it is believed to have an important effect on satiety control. This study aimed to determine whether or not eating rate is associated with cardiometabolic risk factors. METHODS AND RESULTS: This was a cross-sectional study involving 8775 Korean adults, who visited the Center for Health Promotion of Korea University Anam Hospital in Seoul, Korea. In male study participants, weight and body mass index (BMI) were found to depend on eating rate after adjusting for age, alcohol consumption, smoking, exercise and total energy intake. When adjusted for age, alcohol consumption, smoking, exercise and BMI, differences were found between the eating rate groups with respect to high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values, white blood cell (WBC) count and total energy intake. Female participants were found to be different from males in that diastolic blood pressure and low-density lipoprotein (LDL)- and HDL-cholesterol values were significantly different between each eating rate group, while ALT and ALP values, WBC count and total energy intake were not. Compared with the slow eating rate group (>15 min), the fastest eating rate group (<5 min) had significantly increased odds ratios for cardiometabolic risk factors such as high glucose and low HDL-cholesterol levels in males, even after adjusting for BMI. CONCLUSION: Fast eating rates are associated with obesity and other cardiometabolic risk factors, particularly in men. Thus, eating slowly is recommended for weight reduction and to decrease cardiovascular risk factors.

Superiority of conventional intensity-modulated radiotherapy over helical tomotherapy in locally advanced non-small cell lung cancer. A comparative plan analysis.

PURPOSE: To compare helical tomotherapy (HT) and conventional intensity-modulated radiotherapy (IMRT) using a variety of dosimetric and radiobiologic indexes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: A total of 20 patients with LA-NSCLC were enrolled. IMRT plans with 4-6 coplanar beams and HT plans were generated for each patient. Dose distributions and dosimetric indexes for the tumors and critical structures were computed for both plans and compared. RESULTS: Both modalities created highly conformal plans. They did not differ in the volumes of lung exposed to > 20 Gy of radiation. The average mean lung dose, volume receiving ≥ 30 Gy, and volume receiving ≥ 10 Gy in HT planning were 18.3 Gy, 18.5%, and 57.1%, respectively, compared to 19.4 Gy, 25.4%, and 48.9%, respectively, with IMRT (p = 0.004, p < 0.001, and p < 0.001). The differences between HT and IMRT in lung volume receiving ≥ 10-20 Gy increased significantly as the planning target volume (PTV) increased. For 6 patients who had PTV greater than 700 cm(3), IMRT was superior to HT for 5 patients in terms of lung volume receiving ≥ 5-20 Gy. The integral dose to the entire thorax in HT plans was significantly higher than in IMRT plans. CONCLUSION: HT gave significantly better control of mean lung dose and volume receiving ≥ 30-40 Gy, whereas IMRT provided better control of the lung volume receiving ≥ 5-15 Gy and the integral dose to entire thorax. In most patients with PTV greater than 700 cm(3), IMRT was superior to HT in terms of lung volume receiving ≥ 5-20 Gy. It is therefore advised that caution should be exercised when planning LA-NSCLC using HT.

Daily skin care habits and the risk of skin eruptions and symptoms in cancer patients.

BACKGROUND: Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer patients have rarely been studied. PATIENTS AND METHODS: We conducted a survey of daily skin care habits and the presence of skin problems in 866 cancer patients. RESULTS: Hot water bath>1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total results, including that hot water bath>1 h significantly increased the risk of definite eruptions (OR 3.41). CONCLUSIONS: Being a cross-sectional study, our study could not prove causality. However, at the present stage of knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to prevent skin problems in cancer patients.

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion.

Lysophosphatidic acid (LPA) is a biolipid that has diverse biological activities implicated in ovarian cancer initiation and progression. Previous studies have shown the critical role of the Rho/Rho-associated kinase (ROCK) pathway in LPA-induced ovarian cancer progression. However, detailed underlying mechanism by which the Rho/ROCK pathway induces ovarian cancer cell invasion is still incompletely understood. In the present study, we observed that the Rho/ROCK pathway is implicated in the production of proteolytic enzymes, leading to LPA-induced ovarian cancer cell invasion. LPA induced matrix metalloproteinase (MMP)-9 expression in CAOV-3 and PA-1 cells and urokinase-type plasminogen activator (uPA) expression in SKOV-3 cells. LPA-induced proteolytic enzyme expression was required for the invasion of ovarian cancer cells expressing corresponding enzymes. Pretreatment of cells with a pharmacological inhibitor of Rho/ROCK (Y-27632) or overexpression of a dominant-negative mutant of Rho (Rho N19) profoundly inhibited LPA-induced proteolytic enzyme expression as well as the invasive potential of ovarian cancer cells. In addition, transfection with dominant-negative Ras (Ras N17) significantly inhibited LPA-induced Rho activation as well as MMP-9 and uPA expression. Consistently, Y-27632 reduced LPA-induced nuclear factor (NF)-κB activation that is critical for proteolytic enzyme expression and cellular invasion. Collectively, we demonstrate a mechanism by which LPA promotes ovarian cancer progression through coordinate activation of a Ras/Rho/ROCK/NF-κB signaling pathway and the proteolytic enzyme secretion, providing novel biomarkers and promising therapeutic targets for ovarian cancer cell progression.

A study on the prognostic value of clinical and surgical features of dermatofibrosarcoma protuberans in Korean patients.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell tumour with locally aggressive characteristics. Only few studies on the epidemiology of DFSP in Asians have been reported. OBJECTIVES: : The purpose of the study was to evaluate the epidemiological and clinical characteristics of DFSP in Korean patients and determine the prognostic factors that affect disease-free survival. METHODS: We conducted a retrospective review of patients diagnosed with primary or recurrent DFSP between 2000 and 2009 at three Seoul National University Hospitals. Patient, tumour and treatment factors were analysed for local recurrence-free survival. RESULTS: We analysed data for 65 patients, of whom 36 (55.4%) were female. The mean age at disease onset was 34.4 years with 50% aged between 20 and 40 years. Involved sites were most often on the trunk (66.1%). Among the 65 patients, 60 patients underwent wide excision; seven patients (10.8%) experienced local recurrence during 3.6 years of follow-up. The recurrence-free survival was significantly related to the microscopic resection margins (P = 0.005), clinical presentation (P = 0.002) and frequency of recurrence (P = 0.014) in the univariate analysis. There were three cases with metastasis, two of whom died because of progression of the disease despite continuous chemotherapy with imatinib mesylate. CONCLUSIONS: We report the epidemiologic and clinical characteristics of DFSP in Korea. Patients with recurrent disease at presentation and frequent recurrence have a high risk of recurrence and metastasis, and therefore close observation is needed in these patients.

Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis.

BACKGROUND: Seborrhoeic keratoses (SKs) are very common benign epidermal lesions without malignant potential. Ultraviolet radiation, old age and viruses are well-known risk factors for disease development. However, the pathomechanisms of SK are not fully understood. OBJECTIVES: To detect and characterize the genes that are involved in the pathogenesis of SK. METHODS: We performed a gene expression study using paired lesional and nonlesional skin samples from patients with SK. RESULTS: We identified and validated 19 differentially expressed genes in SK. Of these 19 genes, we focused on p63 transcription factor, which plays a pivotal role in epidermal development by regulating its transcriptional programme. We found by immunofluorescence that the expression of ΔNp63α, the most abundantly expressed p63 isoform, was significantly increased in SK as compared with normal skin. Moreover, siRNA-mediated knockdown of ΔNp63 led to the downregulation of 11 genes, including a member of the tensin family TNS4. Chromatin immunoprecipitation assay revealed that TNS4 was a target gene of p63. CONCLUSIONS: We identified upregulated genes in SK using genome-wide cDNA microarray and elucidated the functional contribution of p63 to the disease transcriptome by gene-silencing assay. Taken together, these data may provide a novel insight into the molecular basis of these benign skin lesions.

CT and MRI of fibrous dysplasia of the spine.

OBJECTIVES: The purpose of this study was to present the CT and MRI findings of patients with fibrous dysplasia (FD) of the spine. METHODS: Among the patients with pathologically proven skeletal FD, 12 (8 males and 4 females; mean age, 43 years) who were evaluated with either spine CT or MRI were included. The number and location of the involved vertebral segments, the presence of lytic lesions, ground-glass opacity (GGO), an expansile nature, cortical disruption, a sclerotic rim, a decrease in body height and contour deformity were examined on CT scans (n=12), while signal intensity, enhancement patterns and the presence of a dark signal rim on the lesion were examined using MRI (n=9). RESULTS: Nine patients had polyostotic FD, including one with an isolated spinal localisation, while three had monostotic FD. An expansile nature (n=3) and osteolytic lesions with GGO (n=3) were seen. On CT images, GGO was noted in all patients. An expansile nature (n=11) and presence of lytic lesions (n=11) were noted. A decrease in body height (n=9) and sclerotic rim formation (n=9) were indicated. Contour deformities were visible in six patients. The MRI findings were non-specific. Dark signal rims were visible on MRI in seven patients. CONCLUSION: Typical imaging findings of extraspinal FD were noted on spine CT scans. These characteristic CT imaging findings of spinal FD may be helpful in differentiating FD from other common spine diseases.

Volumetric response evaluation after intensity modulated radiotherapy in patients with supratentorial gliomas.

Radiotherapy is frequently indicated to treat cerebral gliomas. Accurate response evaluation after radiotherapy is essential to determine the efficacy of treatment. We retrospectively analyzed the volumetric tumor response after simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in patients with gliomas. Thirty-five patients (Grade II, 7 patients; Grade III, 12; and Grade IV, 16) were treated with SIB-IMRT with a median total dose of 55.9 Gy/26 fractions for Grade II and 60 Gy/25 fractions for Grade III-IV tumors. Tumor responses were evaluated for enhancing volume on post-gadolinium T1-weighted images (Vgd) and hyper-intensity volume on T2-weighted FLAIR images (V(fl)) on serial MRIs. With the median follow-up of 24.0 months, overall response rates (RRs) were 57% for V(gd) and 51% for V(fl). Tumor grade was predictive of response favoring the lower grade in Vfl with RRs of 86% for Grade II, 75% for Grade III, and 19% for Grade IV tumors (p = 0.004). Time to 50% or greater volume reduction (T50) in Vgd was 8 months for grade III. The T50 in V(fl) was approximately 24 months both for Grade II and III tumors. Majority of Grade IV tumors continued to progress and never reached the T50 in Vgd or Vfl. Responders survived longer than non-responders for V(gd) and V(fl). Volume response after radiotherapy was dependent upon tumor grade and time. LGGs are very responsive to radiotherapy with the RRs of 86% in V(fl). The response of Vfl is more protracted compared to V(gd). Further investigation is needed to determine the clinical significance of volumetric response evaluation.