Lung cancer is one of the most common causative cancers worldwide. Particularly, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC is a serious form of lung cancer that requires prompt diagnosis, and the 5-year survival rate for patients with this disease is only 24%. Gibbosic acid H (GaH), a natural lanostanoid obtained from the Ganoderma species (Ganodermataceae), has antiproliferative activities against colon and lung cancer cells. The aim of the present study was to evaluate the antiproliferative activity of GaH in NSCLC cells and to elucidate the underlying molecular mechanisms.GaH was found to induce G0/G1 cell cycle arrest and autophagy by activating adenosine monophosphate-activated protein kinase in A549 and H1299 cells. The induction of this cell cycle arrest was associated with the downregulation of cyclin E1 and CDK2.Additionally, the induction of autophagy by GaH was correlated with the upregulation of LC3B, beclin-1, and p53 expression. GaH also induced apoptosis by upregulating cleaved caspase-3 and Bax in the lung cancer cells. These findings suggest that GaH has a potential in the growth inhibition of human lung cancer cells.

Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G 2/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen ; Acetates ; Acetic Acid ; Anti-Inflammatory Agents, Non-Steroidal ; Cicatrix ; Classification ; Cyclooxygenase 2 Inhibitors ; Diethylpropion ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Hospitals, University ; Incidence ; Korea ; Phenotype ; Propionates ; Prospective Studies ; Retrospective Studies ; Salicylates ; Salicylic Acid ; Stevens-Johnson Syndrome

PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Epidemiologic Studies ; Hospitalization ; Humans ; Incidence ; Korea ; Length of Stay ; Mortality ; Referral and Consultation ; Risk Factors ; Stevens-Johnson Syndrome ; Thrombocytopenia ; Valproic Acid

BACKGROUND: 15,16-dihydrotanshinone I (DHTS) is a natural abietane diterpenoid that is mainly found in the roots of Salvia miltiorrhiza Bunge (Labiatae). DHTS exhibits a potential anti-proliferative effect in various human cancer cells. However, the mechanisms of action of DHTS as an anti-cancer agent have not been fully elucidated. Therefore, the present study investigated the anti-cancer effect of DHTS in terms of cell cycle regulation and the regulation of the AMP-activated protein kinase (AMPK)/Akt/mTOR signaling pathway in SK-HEP-1 human hepatocellular carcinoma cells. METHODS: The anti-proliferative effects of DHTS were evaluated by the sulforhodamine B assay in SK-HEP-1 cells. Cell cycle distribution was analyzed by flow cytometry. The elucidation of mechanisms of action such as the AMPK/AKT/mTOR and mitogen-activated protein kinase (MAPK) pathway was assessed by Western blot analysis. RESULTS: DHTS showed a significant anti-proliferative activity against SK-HEP-1 cells. DHTS induced cell cycle arrest in the G0/G1 phase, which was mediated by downregulation of cyclin D1, cyclin A, cyclin E, CDK4, CDK2, c-Myc and p-Rb expression and with increased expression of the CDK inhibitor p21. DHTS also activated the AMPK signaling. In addition, DHTS downregulated the Akt/mTOR and MAPK signaling pathways. CONCLUSIONS: Our results suggest that the anti-proliferative activity of DHTS might be associated with the induction of G0/G1 phase cell cycle arrest and regulation of AMPK/Akt/mTOR and MAPK signaling pathways in SK-HEP-1 cells.
AMP-Activated Protein Kinases ; Blotting, Western ; Carcinoma, Hepatocellular ; Cell Cycle Checkpoints ; Cell Cycle ; Cyclin A ; Cyclin D1 ; Cyclin E ; Cyclins ; Down-Regulation ; Flow Cytometry ; Humans ; Protein Kinases ; Salvia miltiorrhiza

BACKGROUND: The incidence of acute hepatitis A was reported to have increased recently. The purpose of this study was to investigate the epidemiological and clinical characteristics of cases of sporadic acute hepatitis A in Gwangju-Chonnnam area over the last 10 years. METHODS: The medical records of 73 cases with acute hepatitis A, which were diagnosed at the Chonnam National University Hospital from January 1996 to December 2005, were reviewed retrospectively for the epidemiological and clinical manifestations. RESULTS: Of the seventy three patients, there were forty males (54.8%). The mean age of the patients was 25 years and the peak incidence being in the 3rd decade (45.2%). The annual number of hepatitis A patients has increased. There were 16 patients (21.9%) from 1996 to 2000, and 57 patients (78.1%) from 2001 to 2005. There was no significant difference in the seasonal incidence (p=0.09). There were 7 cases (9.6%) in children less than 15 years of age and 66 adult cases (90.4%). Although the source of infection could not be identified in 40 patients (54.8%), it was found to be food in 31 patients (42.5%) and intimate contact in 2 patients (2.7%). Sixty five (89%) patients were hospitalized, and the average admission day was 14.5 days. All patients recovered without complications except for two patients who showed cholestatic hepatitis. CONCLUSIONS: The annual number of sporadic acute hepatitis A patients in Gwangju-Chonnam province has increased and most of patients were in their 3rd decade. Social concern for sporadic acute hepatitis A is needed in Gwangju-Chonnam area.
Adult ; Child ; Epidemiology ; Hepatitis A virus ; Hepatitis A* ; Hepatitis* ; Humans ; Incidence ; Jeollanam-do ; Male ; Medical Records ; Retrospective Studies ; Seasons

A primary thyroid lymphoma is rare among all types of thyroid malignancy. Usually, a thyroid lymphoma is associated with underlying chronic autoimmune thyroiditis. Recently, we experienced a primary thyroid mucosa-associated lymphoid tissue(MALT) lymphoma, with an incidental micropapillary thyroid carcinoma, but lacking evidence of autoimmune thyroiditis. A female patient visited our hospital for further evaluation of a rapidly enlarging, painless thyroid mass which had been stable for 8 years. Lymphocytic thyroiditis or a lymphoma was suspected from fine needle aspiration performed at another hospital. The thyroid function test and other routine laboratory tests were normal. The histopathological findings after a total thyroidectomy revealed a MALT lymphoma with a micropapillary thyroid carcinoma. There was no evidence of chronic autoimmune thyroiditis. This is, to the best of our knowledge, the first case report of a MALT lymphoma arising from the thyroid gland without evidence of chronic autoimmune thyroiditis in Korea
Biopsy, Fine-Needle ; Female ; Humans ; Korea ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroidectomy ; Thyroiditis, Autoimmune*

A primary thyroid lymphoma is rare among all types of thyroid malignancy. Usually, a thyroid lymphoma is associated with underlying chronic autoimmune thyroiditis. Recently, we experienced a primary thyroid mucosa-associated lymphoid tissue(MALT) lymphoma, with an incidental micropapillary thyroid carcinoma, but lacking evidence of autoimmune thyroiditis. A female patient visited our hospital for further evaluation of a rapidly enlarging, painless thyroid mass which had been stable for 8 years. Lymphocytic thyroiditis or a lymphoma was suspected from fine needle aspiration performed at another hospital. The thyroid function test and other routine laboratory tests were normal. The histopathological findings after a total thyroidectomy revealed a MALT lymphoma with a micropapillary thyroid carcinoma. There was no evidence of chronic autoimmune thyroiditis. This is, to the best of our knowledge, the first case report of a MALT lymphoma arising from the thyroid gland without evidence of chronic autoimmune thyroiditis in Korea
Biopsy, Fine-Needle ; Female ; Humans ; Korea ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroidectomy ; Thyroiditis, Autoimmune*

PURPOSE: Considering that nutritional state correlates to immunity, we performed this study to evaluate the correlation by assessing the numerical changes of the levels of serum albumin and lymphocyte subsets. MATERIALS AND METHODS: The study was performed on patients who were diagnosed as having gastric cancer and who underwent curative surgery from August 1998 to August 2004 in the Gyeongsang National University Hospital and whose peripheral blood lymphocyte subsets were tested prior to surgery. The study population was a total of 150 cases. RESULTS: The change in the lymphocyte subsets in relation to the change in the level of serum albumin in all patients with gastric cancer was determined, and was compared to disease stages. When patients were classified by using the level of serum albumin with 3.2 mg/dl as the cut-off point (low group: serum albumin <3.2 mg/dl, normal group = serum albumin >or=3.2 mg/dl), the number of peripheral blood lymphocytes, CD3+ cells, CD4+ cells, CD8+ cells, and CD16+56 cells were, significantly lower in the group with the level of serum albumin below 3.2 mg/dl (low group) than it was in the group with a serum albumin level above 3.2 mg/dl (normal group) (P<0.05). In stage I (n=59), CD16+56 cells were significantly lower in the low group. In stage II (n=29), the number of CD16+56 cells was lower and the ratio of CD4+/CD8+ was higher in the low group than in the normal group significantly. In stage IV (n=33), except for CD19+ cells, the number of all lymphocyte subsets was significantly lower and the ratio of CD4+/CD8+ was significantly higher in the low group. CONCLUSION: The group with a low level of serum albumin had a low absolute number of lymphocyte subsets. Based on this, we reconfirmed that the nutritional state is closely related with the immune state in patients with gastric cancer.
Humans ; Lymphocyte Subsets* ; Lymphocytes* ; Serum Albumin* ; Stomach Neoplasms*

PURPOSE: Considering that nutritional state correlates to immunity, we performed this study to evaluate the correlation by assessing the numerical changes of the levels of serum albumin and lymphocyte subsets. MATERIALS AND METHODS: The study was performed on patients who were diagnosed as having gastric cancer and who underwent curative surgery from August 1998 to August 2004 in the Gyeongsang National University Hospital and whose peripheral blood lymphocyte subsets were tested prior to surgery. The study population was a total of 150 cases. RESULTS: The change in the lymphocyte subsets in relation to the change in the level of serum albumin in all patients with gastric cancer was determined, and was compared to disease stages. When patients were classified by using the level of serum albumin with 3.2 mg/dl as the cut-off point (low group: serum albumin <3.2 mg/dl, normal group = serum albumin >or=3.2 mg/dl), the number of peripheral blood lymphocytes, CD3+ cells, CD4+ cells, CD8+ cells, and CD16+56 cells were, significantly lower in the group with the level of serum albumin below 3.2 mg/dl (low group) than it was in the group with a serum albumin level above 3.2 mg/dl (normal group) (P<0.05). In stage I (n=59), CD16+56 cells were significantly lower in the low group. In stage II (n=29), the number of CD16+56 cells was lower and the ratio of CD4+/CD8+ was higher in the low group than in the normal group significantly. In stage IV (n=33), except for CD19+ cells, the number of all lymphocyte subsets was significantly lower and the ratio of CD4+/CD8+ was significantly higher in the low group. CONCLUSION: The group with a low level of serum albumin had a low absolute number of lymphocyte subsets. Based on this, we reconfirmed that the nutritional state is closely related with the immune state in patients with gastric cancer.
Humans ; Lymphocyte Subsets* ; Lymphocytes* ; Serum Albumin* ; Stomach Neoplasms*