Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoaR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Background/Aims: We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females. Methods: The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated. After a median follow-up of 11.4 years, 43,473 (0.74%) participants were defined as “newly diagnosed lung cancer”. Results: After adjusting for all variables at baseline, the variables older age, lower body mass index (BMI), less exercise, frequent alcohol drinking, meat-based diet, rural residence, and previous history of cancer were associated with a higher incidence of lung cancer. Low BMI (< 18.5 kg/m2: hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.27 to 1.40) was a significant independent risk factor; as BMI decreased, HR increased. Negative associations between BMI and lung-cancer development were also observed after controlling for age (p for trend < 0.001). Drinking alcohol one to two times a week (HR, 1.25; 95% CI, 1.21 to 1.28) and eating a meat-based diet (HR, 1.08; 95% CI, 1.01 to 1.15) were associated with lung-cancer incidence. Conclusions Modifiable baseline characteristics, such as BMI, exercise, alcohol consumption, and diet, are risk factors for lung-cancer development among never- smoking females. Thus, lifestyle modifications may help prevent lung cancer.

BACKGROUNDHippophae rhamnoides L. (HL) exerts antioxidant activities against various oxidative stress conditions. In this study, we investigated effects of extract from HL leaves (HLE) on cell proliferation and neuroblast differentiation in the subgranular zone (SGZ) of the dentate gyrus (DG) of aged gerbils.

METHODSAged gerbils (24 months) were divided into vehicle (saline)-treated- and HLE-treated-groups. The vehicle and HLE were orally administered with 200 mg/kg once a day for 20 days before sacrifice. Cell proliferation and neuroblast differentiation were examined in the DG using Ki67 and doublecortin (DCX), respectively. We also observed changes in immunoreactivities of superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2), brain-derived neurotrophic factor (BDNF), and phospho-glycogen synthase kinase-3-beta (p-GSK-3β) to examine their relation with neurogenesis using immunohistochemistry.

RESULTSThe administration of HLE significantly increased the number of Ki67-positive cells and DCX-positive neuroblasts with well-developed processes in the SGZ of the DG of the HLE-treated-group. In addition, immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in granule and polymorphic cells of the DG in the HLE-treated-group compared with those in the vehicle-treated-group.

CONCLUSIONSHLE treatment significantly increased cell proliferation and neuroblast differentiation, showing that immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in the DG. These indicate that increased neuroblast differentiation neurogenesis may be closely related to upregulation of SOD1, SOD2, BDNF, and p-GSK-3β in aged gerbils.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Dentate Gyrus ; drug effects ; metabolism ; Gerbillinae ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Hippophae ; drug effects ; metabolism ; Immunohistochemistry ; Intrinsic Factor ; metabolism ; Male ; Neurogenesis ; drug effects ; Superoxide Dismutase ; metabolism ; Superoxide Dismutase-1

We report a rare case of thyroid metastasis from early gastric cancer with lymph node metastasis in a 63-yr old woman. She was diagnosed with metastatic adenocarcinoma one and a half years after distal subtotal gastrectomy, by fine needle aspiration (FNA) using thyroid sonography. Thyroid metastasis from gastric cancer is extremely rare, and this case is particular in that it is the first report of thyroid metastasis from early gastric cancer.
*Adenocarcinoma/pathology/secondary ; Biopsy, Fine-Needle ; Fatal Outcome ; Female ; Humans ; Lymphatic Metastasis/*pathology ; Middle Aged ; Stomach Neoplasms/*pathology ; Thyroid Neoplasms/pathology/*secondary

Late stent thrombosis is one of the most serious complications associated with morbidity and mortality after coronary drug-eluting stent implantation, and is mainly caused by the withdrawal of antiplatelet agents. We report our experience of late stent thrombosis simultaneously involving three different coronary arteries in a young male patient who was treated with three drug-eluting stents two years ago. The patient stopped taking antiplatelet agents for several days. The patient did not recover from cardiogenic shock, even after repeated ballooning with thrombus aspiration, intra-aortic balloon pumping, and temporary pacing during cardiopulmonary resuscitation.
Blood Platelets ; Cardiopulmonary Resuscitation ; Coronary Vessels ; Drug-Eluting Stents ; Humans ; Intra-Aortic Balloon Pumping ; Male ; Platelet Aggregation Inhibitors ; Shock, Cardiogenic ; Stents ; Thrombosis

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002 and revised in 2006. The aim of this study was to compare the KMAP-BP 2006 with other recently published treatment guidelines for bipolar disorder. We conducted a systematic review of the six most recently published guidelines and treatment algorithms for bipolar disorder to compare the similarities and differences between these guidelines and the KMAPBP 2006. Most treatment guidelines had similarities in their treatment options. The guidelines generally advocated atypical antipsychotics as first-line treatment in the manic phase and lamotrigine in the depressive phase. While lithium and divalproex were commonly used as mood stabilizers in the manic phase, divalproex was recommended in mixed or dysphoric mania. Mood stabilizers or atypical antipsychotics were selected as first-line treatment in maintenance. Some guidelines were more concerned about special clinical situations such as pregnancy, obesity, metabolic syndrome, and elderly patients, which were not described in the KMAP-BP 2006. Our findings suggest that the medication strategies for bipolar disorder are based on data from recent studies and clinical experiences. Useful information and a rationale for making sequential treatment decisions can be provided by critically reviewing the treatment guidelines. The treatment algorithms and guidelines are not substitutes for clinical judgment, but can serve as critical references to complement individual clinical assessments.
Aged ; Antipsychotic Agents ; Bipolar Disorder ; Complement System Proteins ; Humans ; Judgment ; Lithium ; Obesity ; Pregnancy ; Triazines ; Valproic Acid

OBJECTIVE: Bipolar depression has a disabling course and its treatment represents a major challenge. Recently, a randomized, controlled trial of quetiapine monotherapy in patients with bipolar depression showed significant reductions in depressive symptomatology. The purpose of this study was to evaluate the efficacy of quetiapine in bipolar depression in the clinical setting. METHODS: This study was a multi-center, prospective, open-label, observational, 8-week evaluation of the efficacy of quetiapine in patients with bipolar depression. Patients with a DSM-IV-TR diagnosis of bipolar depression (bipolar I disorder, most recent episode depressed and bipolar II disorder, most recent episode depressed) were included and treated with quetiapine. The dose of quetiapine was flexible and concomitant mediations were permitted, by clinical judgment. Clinical improvements were rated with the Clinical Global Impression-Bipolar version (CGI-BP) and Montgomery-Asberg Depression Rating Scale (MADRS) at baseline, week 4, and week 8. RESULTS: A total of 1,193 patients were recruited and 46 (3.9%) patients were dropped from the study. The mean initial dose of quetiapine was 192.3+/-181.9 mg/day and the mean doses at weeks 4 and 8 were 315.2+/-229.7 mg/day and 337.1+/-229.9 mg/day, respectively. CGI-BP and MADRS were significantly improved at weeks 4 and 8, compared with baseline. In addition, improvements at week 8 were greater than at week 4. Subjectively, about 75% of the patients reported therapeutic compliance above 75% at weeks 4 and 8. Seven (0.6%) and four (0.3%) patients showed manic/hypomanic episodes at weeks 4 and 8, respectively. CONCLUSION: This study suggests that quetiapine improves depressive symptoms in bipolar depression, with minimal incidence of manic switching. We suggest that quetiapine could be an effective and safe option in treating bipolar depression.
Bipolar Disorder ; Compliance ; Depression ; Dibenzothiazepines ; Humans ; Incidence ; Judgment ; Prospective Studies ; Quetiapine Fumarate

OBJECTIVE: Although mood stabilizer monotherapy is the recommended initial therapy for bipolar disorder, the use of atypical antipsychotics in bipolar patients is increasing recently. Moreover, the medical literature is demonstrating that the combination of atypical antipsychotics and mood stabilizers is a more effective therapy. The goal of this study was to assess the efficacy of risperidone in patients with acute manic and mixed state of bipolar disorder. METHODS: This study was a 4-week, open-label, combination, prospective investigation using risperidone in combination with mood stabilizers. In total, 114 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed episode, were recruited. Risperidone was given in combination with mood stabilizers in doses according to clinical response and tolerability. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAMD), the Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and the Clinical Global Impressions Scale-Bipolar (CGI-BP). The Simpson-Angus Rating Scale (SARS) was applied to assess extrapyramidal symptoms. RESULTS: The combination of risperidone with mood stabilizers produced highly significant improvements (p<0.001) on the YMRS, HAMD, BPRS, GAS, and CGI-BP at both 1 week and 4 weekweeks. Analysis of the YMRS, BPRS, GAS, and CGI-BP scores revealed significant improvement in both the manic and mixed group. The HAMD score was decreased only in the mixed group. Body weight was increased significantly after 1 week. Risperidone was well tolerated, and adverse events were mostly mild, with the most frequent extrapyramidal symptoms and sedation. CONCLUSION: Our findings suggest that the combination of risperidone with mood stabilizers was an effective and safe treatment for acute manic symptoms and coexisting depressive symptoms of bipolar disorder. Randomized, double-blind, placebo or active controlled studies are needed.
Antipsychotic Agents ; Bipolar Disorder* ; Body Weight ; Brief Psychiatric Rating Scale ; Depression ; Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Prospective Studies* ; Risperidone*

OBJECTIVE: The development of treatment guidelines has emerged as an important element so as to standardize treatment and to provide clinicians with algorithms. From the previous publication of Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP): rapid cycling in 2002, we revised that in 2006. METHODS: The questionnaire to survey the expert opinion of medication for rapid cycling was completed by the review committee consisting of 53 experienced Korean psychiatrists. It is composed of 7 questions, and each question includes various options. We classified the expert opinion to 3 categories based on the lowest category in which the confidence interval fell (6.5 < or = for first-line and 3.5< or = for second-line treatment). RESULTS: Generally, 'treatment of choice' for rapid cycling was not demonstrated. The first-line treatment is the combination of a mood stabilizer and an atypical antipsychotic. Combination of two mood stabilizers was preferred as next strategy. Divalproex and lithium were the first-line choice as mood stabilizer. Compared to the surveys in 2002, the preference for lamotrigine and atypical antipsychotics has increased while that of carbamazepine and antidepressant has decreased. CONCLUSION: With the result of the survey, the discussion in executive committee, and the evidences from clinical studies, we have revised KMAP-BP for rapid cycling.
Advisory Committees ; Antipsychotic Agents ; Bipolar Disorder* ; Carbamazepine ; Expert Testimony ; Lithium ; Psychiatry ; Publications ; Surveys and Questionnaires ; Valproic Acid

OBJECTIVE: In 2002, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP 2002) was published to make clinical guidelines to understand and treat bipolar disorder, but due to recent reports of various studies and application of new drugs, the revision of treatment algorithm was inevitable. Therefore, we revised the KMAP-BP 2002 focused on the treatment strategies of bipolar depression. METHOD: The methods of this survey were similar to those of the KMAP-BP 2002. The review committee consisted of 70 experienced psychiatrists. Among the total 37 questions, 15 questions for bipolar depression were evaluated. We classified the expert opinions to 3 categories according to its confidence interval; first, second, and third line. Results: Compared to the previous algorithm, combination of mood stabilizers (MS) or atypical antipsychotics (AAP) and antidepressants is generally more recommended than antidepressant monotherapy for bipolar depression. Lithium and divalproex are the first-line treatment choices as well as MS. The preference for lamotrigine is increased, while that for carbamazepine is decreased. Olanzapine and quetiapine are preferred as the first-line AAP. Most antidepressants are not recommended as the first-line drug. The strategy for breakthrough of depression is changed into adding an antidepressant and/or AAP after combination of 2 MS. CONCLUSION: These results suggest that treatment of bipolar depression should be different from that of unipolar depression. The advanced new algorithm is considered to be useful and practical in the treatment of bipolar depression.
Advisory Committees ; Antidepressive Agents ; Antipsychotic Agents ; Bipolar Disorder* ; Carbamazepine ; Depression ; Depressive Disorder ; Expert Testimony ; Lithium ; Psychiatry ; Valproic Acid ; Quetiapine Fumarate