Purpose: Ras association domain family 4 (RASSF4) is a putative tumor suppressor that is frequently inactivated in multiple human cancers. However, its candidacy as a suppressor in gastric tumorigenesis remains undefined. To understand the role for RASSF4 in gastric tumorigenesis, we investigated its expression status in cancer cell lines and tissues and regulatory role in tumor growth. Materials and Methods: RASSF4 expression was analyzed in 13 cancer cell lines and 20 carcinoma tissues using polymerase chain reaction and immunoblot assays. RASSF4 effect on cell proliferation and apoptosis was examined by flow cytometry, colony formation, and [3H]thymidine incorporation assays and its regulation of p53 was determined using cycloheximide chase, promoter reporter, and immunoprecipitation assays. Mouse xenograft assay was performed to verify RASSF4 effect on tumor growth and therapeutic response. Results: RASSF4 expression is epigenetically inactivated in eight of 13 (61.5%) cancer cell lines and 15 of 20 (75%) primary carcinomas. RASSF4 suppresses cell proliferation by inducing a G2/M cell cycle arrest and enhances apoptotic response to therapeutic drugs. RASSF4 is induced in response to genotoxic agents to facilitate stress-induced apoptosis in a highly p53-dependent fashion. Mechanistically, RASSF4 stabilizes p53 through Chk2 activation and its apoptotic function is profoundly impaired by depletion of either p53 or Chk2. RASSF4 attenuates xenograft tumor growth and enhances tumor response to 5-fluorouracil. Clinically, RASSF4 expression correlates strongly with the overall survival of gastric cancer patients. Conclusion RASSF4 suppresses gastric tumor growth through the activation of the Chk2-p53 axis, illuminating the mechanistic consequence of its inactivation in gastric tumorigenesis.

PURPOSE: In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the effect of the paraquat ban on the epidemiology and mortality of herbicide-induced poisoning. MATERIALS AND METHODS: This retrospective study analyzed patients treated for herbicide poisoning at 17 emergency departments in South Korea between January 2010 and December 2014. The overall and paraquat mortality rates were compared pre- and post-ban. Factors associated with herbicide mortality were evaluated using logistic analysis. To determine if there were any changes in the mortality rates before and after the paraquat sales ban and the time point of any such significant changes in mortality, R software, version 3.0.3 (package, bcp) was used to perform a Bayesian change point analysis. RESULTS: We enrolled 2257 patients treated for herbicide poisoning (paraquat=46.8%). The overall and paraquat poisoning mortality rates were 40.6% and 73.0%, respectively. The decreased paraquat poisoning mortality rate (before, 75% vs. after, 67%, p=0.014) might be associated with increased intentionality. The multivariable logistic analysis revealed the paraquat ban as an independent predictor that decreased herbicide poisoning mortality (p=0.035). There were two major change points in herbicide mortality rates, approximately 3 months after the initial paraquat ban and 1 year after complete sales ban. CONCLUSION: This study suggests that the paraquat ban decreased intentional herbicide ingestion and contributed to lowering herbicide poisoning-associated mortality. The change point analysis suggests a certain timeframe was required for the manifestation of regulatory measures outcomes.
Commerce ; Eating ; Emergency Service, Hospital ; Epidemiology ; Herbicides ; Humans ; Intention ; Korea ; Mortality* ; Paraquat* ; Poisoning ; Retrospective Studies

BACKGROUND: Since the treatment guidelines for atopic dermatitis (AD) were issued by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been further advances in the systemic treatment of AD. OBJECTIVE: We aimed to establish updated evidence- and experience-based systemic treatment guidelines for Korean AD. METHODS: We compiled a database of references from relevant systematic reviews and guidelines regarding the systemic management of AD, including antihistamines, antimicrobials, systemic immunomodulators, allergen-specific immunotherapy, phototherapy, adjunctive treatment, and complementary and alternative medicines. Evidence for each statement was graded and classified based on the strength of the recommendation. Thirty-nine council members of KADA participated in the three rounds of votes and expert consensus recommendations were established. RESULTS: The use of antihistamines is recommended to relieve pruritus and to prevent exacerbation due to scratching in AD patients. Infection should be controlled as needed and long-term medication should be avoided. For moderate to severe AD patients, concomitant active treatments with systemic immunomodulators are indicated. Cyclosporine is the first choice among systemic immunomodulators and others should be considered as second-line alternatives. Allergen-specific immunotherapy could be effective in AD patients with aeroallergen hypersensitivity. Phototherapy can be useful for moderate to severe AD patients and narrow-band ultraviolet B is the most effective option. Complementary and alternative medicines cannot be recommended for treating AD. CONCLUSION: We expect these recommendations to be a reference guide for physicians and AD patients in choosing the appropriate treatment to improve quality of life and decrease unnecessary social medical costs.
Consensus* ; Cyclosporine ; Dermatitis ; Dermatitis, Atopic* ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunologic Factors ; Immunotherapy ; Korea* ; Phototherapy ; Pruritus ; Quality of Life

BACKGROUND: Since the treatment guidelines for atopic dermatitis (AD) were released by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been several advances in AD management. OBJECTIVE: We aimed to establish updated evidence- and experience-based treatment guidelines for Korean AD. METHODS: We collected a database of references from relevant systematic AD reviews and guidelines regarding general AD management such as bathing and skin care, avoidance of exacerbating factors, education and psychosocial support, and the use of moisturizers and topical anti-inflammatory and antipruritic drugs. Evidence for each statement was graded and the strength of the recommendation for each statement classified. Thirty-nine KADA council members participated in three rounds of voting to establish an expert consensus of recommendations. RESULTS: Basic AD treatment includes proper bathing and skin care, avoidance of exacerbating factors, proper education and psychosocial support, and use of moisturizers. The regular use of moisturizer has a steroid-sparing effect and reduces relapse episodes. The short- and long-term use of topical corticosteroids and calcineurin inhibitors improves AD symptoms and should be encouraged to use in an active and proactive treatment. Wet-wrap therapy can be used for rapid recovery of acute exacerbation. Topical antipruritic drugs cannot be recommended for the treatment of AD. CONCLUSION: This report provides up-to-date evidence- and experience-based treatment guidelines for AD regarding general management and topical treatment. In addition, the average agreement scores obtained by a panel of experts based on the Korean healthcare system and patient adherence are presented.
Adrenal Cortex Hormones ; Antipruritics ; Baths ; Calcineurin ; Consensus* ; Delivery of Health Care ; Dermatitis, Atopic* ; Education ; Korea* ; Patient Compliance ; Politics ; Recurrence ; Skin Care

BACKGROUND: Since the treatment guidelines for atopic dermatitis (AD) were issued by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been further advances in the systemic treatment of AD. OBJECTIVE: We aimed to establish updated evidence- and experience-based systemic treatment guidelines for Korean AD. METHODS: We compiled a database of references from relevant systematic reviews and guidelines regarding the systemic management of AD, including antihistamines, antimicrobials, systemic immunomodulators, allergen-specific immunotherapy, phototherapy, adjunctive treatment, and complementary and alternative medicines. Evidence for each statement was graded and classified based on the strength of the recommendation. Thirty-nine council members of KADA participated in the three rounds of votes and expert consensus recommendations were established. RESULTS: The use of antihistamines is recommended to relieve pruritus and to prevent exacerbation due to scratching in AD patients. Infection should be controlled as needed and long-term medication should be avoided. For moderate to severe AD patients, concomitant active treatments with systemic immunomodulators are indicated. Cyclosporine is the first choice among systemic immunomodulators and others should be considered as second-line alternatives. Allergen-specific immunotherapy could be effective in AD patients with aeroallergen hypersensitivity. Phototherapy can be useful for moderate to severe AD patients and narrow-band ultraviolet B is the most effective option. Complementary and alternative medicines cannot be recommended for treating AD. CONCLUSION: We expect these recommendations to be a reference guide for physicians and AD patients in choosing the appropriate treatment to improve quality of life and decrease unnecessary social medical costs.
Consensus* ; Cyclosporine ; Dermatitis ; Dermatitis, Atopic* ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunologic Factors ; Immunotherapy ; Korea* ; Phototherapy ; Pruritus ; Quality of Life

BACKGROUND: Since the treatment guidelines for atopic dermatitis (AD) were released by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been several advances in AD management. OBJECTIVE: We aimed to establish updated evidence- and experience-based treatment guidelines for Korean AD. METHODS: We collected a database of references from relevant systematic AD reviews and guidelines regarding general AD management such as bathing and skin care, avoidance of exacerbating factors, education and psychosocial support, and the use of moisturizers and topical anti-inflammatory and antipruritic drugs. Evidence for each statement was graded and the strength of the recommendation for each statement classified. Thirty-nine KADA council members participated in three rounds of voting to establish an expert consensus of recommendations. RESULTS: Basic AD treatment includes proper bathing and skin care, avoidance of exacerbating factors, proper education and psychosocial support, and use of moisturizers. The regular use of moisturizer has a steroid-sparing effect and reduces relapse episodes. The short- and long-term use of topical corticosteroids and calcineurin inhibitors improves AD symptoms and should be encouraged to use in an active and proactive treatment. Wet-wrap therapy can be used for rapid recovery of acute exacerbation. Topical antipruritic drugs cannot be recommended for the treatment of AD. CONCLUSION: This report provides up-to-date evidence- and experience-based treatment guidelines for AD regarding general management and topical treatment. In addition, the average agreement scores obtained by a panel of experts based on the Korean healthcare system and patient adherence are presented.
Adrenal Cortex Hormones ; Antipruritics ; Baths ; Calcineurin ; Consensus* ; Delivery of Health Care ; Dermatitis, Atopic* ; Education ; Korea* ; Patient Compliance ; Politics ; Recurrence ; Skin Care

We report the case of a 48-year-old man with schwannoma involving the orbit. Computerized tomography and magnetic resonance imaging revealed a 2X3X2cm-sized well-enhanced round lesion which mildly compressed the optic nerve. The patient underwent fronto-orbitotemporal craniotomy, with successful total removal of the tumor. To our knowledge, this is the first report of schwannoma involving the orbit : a review of the literature is also included.
Craniotomy ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neurilemmoma* ; Optic Nerve ; Orbit*

Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency. Adrenal crisis in isolated ACTH deficiency is less common compared to primary adrenal insufficiency, but isolated ACTH deficiency is an important cause of hypoglycemia. Recently we experienced a 41-year-old man admitted because of mental confusion. On admission, plasma glucose and sodium concentration were 1.7, 132 mmol/L, respectively. Basal plasma ACTH and cortisol levels were low and other pituitary hormone showed normal response to combined pituitary stimulation test except growth hormone. Plasma ACTH concentration remained low even after intravenous injection of ovine corticotropin releasing factor. It suggest that the defect of ACTH secretion was apparently due to intrinsic pituitary rather than hypothalamic disease. The sellar CT showed the fossa to be filled by cerebrospinal fluid. After treatment with glucocorticoid, he had no further evidence of hypoglycemia and hyponatremia. In conclusion, we report a case of isolated ACTH deficiency with empty sella.
Addison Disease ; Adrenocorticotropic Hormone ; Adult ; Blood Glucose ; Cerebrospinal Fluid ; Corticotropin-Releasing Hormone ; Growth Hormone ; Humans ; Hydrocortisone ; Hypoglycemia ; Hyponatremia ; Hypothalamic Diseases ; Injections, Intravenous ; Plasma ; Sodium