Basic medical education is important for developing the competencies of medical doctors, and it includes basic biomedical sciences, preventive medicine, medical ethics, and clinical science. This study aimed to reveal the current status of the Korean Medical Licensing Examination (KMLE) regarding its evaluation of competencies in basic biomedical sciences. The basic science-related questions were screened and selected from the test forms of the KMLE (2016–2018) by personnel conducting basic biomedical science education, and the selected questions were evaluated with three independent groups of undergraduate students at Chonnam National University Medical School in terms of the learning outcomes of basic medical education. The study scope includes the proportion of basic medicine-related questions, which consist of basic medicine questions and basic medicine-related clinical medicine questions, and its annual change, discipline distribution, and associated learning outcomes. The average proportions of basic biomedical sciences, preventive medicine and medical law, and clinical sciences were 2.3%, 5.8%, and 91.9% of all questions, respectively. The proportion of basic medicine-related questions, except those on preventive medicine and medical law, was 22.0% of the total, and questions on pharmacology and microbiology accounted for 83.0% of the basic medicine-related questions. The proportion of sub-enabling learning outcomes linked with basic medicine-related questions comprised 14.0% of the total outcomes for basic biomedical sciences and 30.4% for preventive medicine and medical law. It is concluded that the KMLE questions may not sufficiently cover the essential competencies of basic medical education for medical doctors, and the KMLE may need to be improved with regard to competencies in basic biomedical sciences.

Physicians play a central role in the fields of medical service, research, and industry, so it is imperative to produce well-qualified doctors. Medicine is composed of science and arts, both necessary for its practice, and thus, the education outcomes in basic medical education in a medical school include basic biomedical sciences, social sciences and clinical sciences. Adequate science competencies create a deeper and better understanding of scientific knowledge, concepts, and methods fundamental to clinical science, and contribute to the scientific, technological, and clinical developments. The science competencies are primarily obtained by studying basic medicine in basic medical education, which has been criticized for failing to do so sufficiently in Korea. The failure is attributed to insufficient education time, teachers, and budgets, but the most critical factor is the lack of awareness regarding the importance of the science competencies of the physicians. Such ignorance also affects the Korean Medical Licensing Examination (KMLE). The KMLE tests competency in clinical sciences, preventive medicine, and medical laws, but not in basic biomedical sciences, which might result in insufficient science competency of the physicians and a decrease in the overall quality of the medical health service. Tests must be urgently introduced in KMLE on the competencies of basic biomedical sciences to improve the science competency of the physicians. The representative organizations of the medical society should take vigorous actions for the introduction of the basic medicine examination in KMLE.
Budgets ; Education ; Education, Medical ; Fibrinogen ; Health Services ; Jurisprudence ; Korea ; Licensure ; Preventive Medicine ; Schools, Medical ; Social Sciences ; Societies, Medical

Physicians play a central role in the fields of medical service, research, and industry, so it is imperative to produce well-qualified doctors. Medicine is composed of science and arts, both necessary for its practice, and thus, the education outcomes in basic medical education in a medical school include basic biomedical sciences, social sciences and clinical sciences. Adequate science competencies create a deeper and better understanding of scientific knowledge, concepts, and methods fundamental to clinical science, and contribute to the scientific, technological, and clinical developments. The science competencies are primarily obtained by studying basic medicine in basic medical education, which has been criticized for failing to do so sufficiently in Korea. The failure is attributed to insufficient education time, teachers, and budgets, but the most critical factor is the lack of awareness regarding the importance of the science competencies of the physicians. Such ignorance also affects the Korean Medical Licensing Examination (KMLE). The KMLE tests competency in clinical sciences, preventive medicine, and medical laws, but not in basic biomedical sciences, which might result in insufficient science competency of the physicians and a decrease in the overall quality of the medical health service. Tests must be urgently introduced in KMLE on the competencies of basic biomedical sciences to improve the science competency of the physicians. The representative organizations of the medical society should take vigorous actions for the introduction of the basic medicine examination in KMLE.

Physicians play a central role in the fields of medical service, research, and industry, so it is imperative to produce well-qualified doctors. Medicine is composed of science and arts, both necessary for its practice, and thus, the education outcomes in basic medical education in a medical school include basic biomedical sciences, social sciences and clinical sciences. Adequate science competencies create a deeper and better understanding of scientific knowledge, concepts, and methods fundamental to clinical science, and contribute to the scientific, technological, and clinical developments. The science competencies are primarily obtained by studying basic medicine in basic medical education, which has been criticized for failing to do so sufficiently in Korea. The failure is attributed to insufficient education time, teachers, and budgets, but the most critical factor is the lack of awareness regarding the importance of the science competencies of the physicians. Such ignorance also affects the Korean Medical Licensing Examination (KMLE). The KMLE tests competency in clinical sciences, preventive medicine, and medical laws, but not in basic biomedical sciences, which might result in insufficient science competency of the physicians and a decrease in the overall quality of the medical health service. Tests must be urgently introduced in KMLE on the competencies of basic biomedical sciences to improve the science competency of the physicians. The representative organizations of the medical society should take vigorous actions for the introduction of the basic medicine examination in KMLE.

Background: Cyclic AMP (cAMP) signaling is activated by various hormones and neurotransmitters and regulates numerous physiological phenomena, including energy metabolism, gene expression, and proliferation. cAMP signaling plays a role in the repair of DNA damage, but its specific function is inconsistent in the literature. The present study aimed to investigate the mechanism of the different roles of cAMP signaling in DNA repair by analyzing the cell-type differences in the modulation of DNA repair by cAMP signaling following γ-ray irradiation. Methods: cAMP signaling was activated in human malignant melanoma cells (SK-MEL-2 and SK-MEL-28), human uterine cervical cancer cells (HeLa and SiHa) and human non-small cell lung cancer cells (H1299 and A549) by expressing a constitutively active mutant of the long-form stimulatory α subunit of GTP-binding protein or by treating with isoproterenol and prostaglandin E2 before γ-ray irradiation. DNA damage was quantitated by western blot analysis of γ-H2AX, and non-homologous end joining (NHEJ) was assessed by fluorescent reporter plasmid repair assay and immunofluorescence of microscopic foci of XRCC4 and DNA-ligase IV. Results: cAMP signaling modulated DNA damage, apoptosis and the NHEJ repair following γ-ray irradiation differently depending upon the cell type. cAMP signaling regulated the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at Ser2056 and Thr2609 in cell-type-specific manners following γ-ray irradiation, an activity that was mediated by protein kinase A. Conclusion cAMP signaling modulates the NHEJ repair of γ-ray-induced DNA damage in melanoma cells, uterine cervical cancer cells and lung cancer cells in a cell-typespecific manner, and the modulation is likely mediated by protein kinase A-dependent phosphorylation of DNA-PKcs. This study suggests that cell- and tissue-specific modulation of DNA damage repair by cAMP signaling may contribute to improve the therapeutic efficiency of radiation therapy.

This study was performed to investigate the signaling pathway that mediates cyclic AMP (cAMP)-induced inhibition of histone deacetylase 8 (HDAC8) degradation, and the effect and underlying mechanisms of the resulting increase in HDAC8 expression on cisplatin-induced apoptosis in lung cancer cells. cAMP signaling increased HDAC8 expression via a protein kinase A (PKA)-independent pathway in H1299 non-small cell lung cancer cells. However, treatment with a selective activator of an exchange protein that was activated by cAMP (Epac) increased HDAC8 expression, and Epac2 inhibition abolished the isoproterenol (ISO)-induced increase in HDAC8 expression. ISO and the Epac activator activated Rap1, and Rap1A activation increased HDAC8 expression; moreover, inhibition of Rap1A with a dominant negative Rap1A or by shRNA-mediated knockdown abolished the ISO-induced increase in HDAC8 expression. Activation of cAMP signaling and Rap1A decreased the activating phosphorylation of Akt. Akt inhibition with a pharmacological inhibitor or expression of a dominant negative Akt inhibited the MKK4/JNK pathway and increased HDAC8 expression. The Akt inhibitor-induced increase in HDAC8 expression was abolished by pretreatment with proteasomal or lysosomal inhibitors. The ISO treatment increased cisplatin-induced apoptosis, which was abolished by HDAC8 knockdown. Exogenous HDAC8 expression increased cisplatin-induced apoptosis and decreased TIPRL expression, and the knockdown of TIPRL increased the apoptosis of cisplatin-treated cells. The ISO treatment decreased cisplatin-induced transcription of the TIPRL gene in a HDAC8-dependent manner. In conclusion, the Epac–Rap1–Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells.
Apoptosis ; Carcinoma, Non-Small-Cell Lung ; Cyclic AMP ; Cyclic AMP-Dependent Protein Kinases ; Histone Deacetylases* ; Histones* ; Isoproterenol ; Lung Neoplasms* ; Lung* ; Phosphorylation

Stress conditions are correlated with tumor growth, progression and metastasis. We hypothesized that stress signals might affect tumor progression via epigenetic control of gene expression and investigated the effects of stress signals on the expression levels of histone deacetylases (HDACs) and the underlying mechanisms of these effects in lung cancer cells. Treatment with isoproterenol (ISO), an analog of the stress signal epinephrine, increased the expression of HDAC6 protein and mRNA in H1299 lung cancer cells. ISO caused the deacetylation of α-tubulin and stimulated cell migration in an HDAC6-dependent manner. HDAC6 expression was increased by treatment with selective activators of cAMP-dependent protein kinase (PKA) or exchange protein activated by cAMP (Epac). ISO activated Rap1 via Epac, and constitutively active Rap1A increased the HDAC6 level; however, the knockdown of Rap1A decreased the 8-(4-cholorophenylthio)-2′-O-methyl-cAMP-induced increase in HDAC6 expression. Both PKA and Rap1A decreased c-Raf activation to inhibit extracellular signal-regulated kinase (ERK) signaling. Inhibition of ERK caused an increase in HDAC6 expression, and constitutively active MEK1 decreased the ISO-induced HDAC6 expression. We concluded that ISO increases HDAC6 expression via a PKA/Epac/ERK-dependent pathway that stimulates the migration of lung cancer cells. This study suggests that stress signals can stimulate the migration of cancer cells by inducing HDAC6 expression in lung cancer cells.
Cell Movement* ; Cyclic AMP-Dependent Protein Kinases ; Epigenomics ; Epinephrine ; Gene Expression ; Histone Deacetylases* ; Histones* ; Humans* ; Isoproterenol* ; Lung Neoplasms* ; Lung* ; Neoplasm Metastasis ; Phosphotransferases ; RNA, Messenger

Stimulatory heterotrimeric GTP-binding proteins (Gs protein) stimulate cAMP generation in response to various signals, and modulate various cellular phenomena such as proliferation and apoptosis. This study aimed to investigate the effect of Gs proteins on gamma ray-induced apoptosis of lung cancer cells and its molecular mechanism, as an attempt to develop a new strategy to improve the therapeutic efficacy of gamma radiation. Expression of constitutively active mutant of the alpha subunit of Gs (GalphasQL) augmented gamma ray-induced apoptosis via mitochondrial dependent pathway when assessed by clonogenic assay, FACS analysis of PI stained cells, and western blot analysis of the cytoplasmic translocation of cytochrome C and the cleavage of caspase-3 and ploy(ADP-ribose) polymerase (PARP) in H1299 human lung cancer cells. GalphasQL up-regulated the Bak expression at the levels of protein and mRNA. Treatment with inhibitors of PKA (H89), SP600125 (JNK inhibitor), and a CRE-decoy blocked GalphasQL-stimulated Bak reporter luciferase activity. Expression of GalphasQL increased basal and gamma ray-induced luciferase activity of cAMP response element binding protein (CREB) and AP-1, and the binding of CREB and AP-1 to Bak promoter. Furthermore, prostaglandin E2, a Galphas activating signal, was found to augment gamma ray-induced apoptosis, which was abolished by treatment with a prostanoid receptor antagonist. These results indicate that Galphas augments gamma ray-induced apoptosis by up-regulation of Bak expression via CREB and AP-1 in H1299 lung cancer cells, suggesting that the efficacy of radiotherapy of lung cancer may be improved by modulating Gs signaling pathway.
Apoptosis/*radiation effects ; Cell Line, Tumor ; Cyclic AMP Response Element-Binding Protein/metabolism ; GTP-Binding Protein alpha Subunits, Gs/*metabolism ; *Gamma Rays ; Heterotrimeric GTP-Binding Proteins/metabolism ; Humans ; Lung/*cytology/physiology/radiation effects ; Lung Neoplasms ; Transcription Factor AP-1/metabolism ; *Up-Regulation ; bcl-2 Homologous Antagonist-Killer Protein/*metabolism

OBJECTIVE: The interaction between MK-801, a model of psychosis and KCl-induced depolarization or electroconvulsive shock (ECS), a therapeutic model of electroconvulsive therapy (ECT), was investigated in SH-SY5Y cells and the rat frontal cortex. METHODS: SH-SY5Y cells were pretreated with 1 microM MK-801 for 15 min, followed by cotreatment with 100 mM KCl for 5 min. MK-801 was reintroduced after the KCl was washed out, and the samples were incubated before harvesting. For the experiments in rats, male Sprague-Dawley rats were treated with MK-801 followed by ECS. Immunoblot analyses of glycogen synthase kinase 3beta (GSK3beta) (Ser9), AKT (Ser473) and extracellular legulated kinase (ERK)1/2 in SH-SY5Y cells and the rat frontal cortex were performed. RESULTS: KCl-induced neuronal depolarization resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), followed by increased phosphorylation of the enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KCl inhibited the initial dephosphorylation of AKT and GSK3beta produced by KCl-induced neuronal depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), whereas cotreatment with MK-801 inhibited the initial dephosphorylation of AKT (Ser473) and GSK3beta (Ser9) produced by ECS in the rat frontal cortex. No significant interaction was observed between MK-801 and KCl in the dephosphorylation of ERK1/2. CONCLUSION: These results suggest that an antagonistic interplay between MK-801 and neuronal depolarization by KCl or ECS is involved the regulation of AKT (Ser473) and GSK3beta (Ser9) phosphorylation.
Animals ; Dizocilpine Maleate* ; Electroconvulsive Therapy ; Electroshock ; Glycogen Synthase Kinases ; Humans ; Male ; Neurons* ; Phosphorylation ; Phosphotransferases ; Psychotic Disorders ; Rats* ; Rats, Sprague-Dawley

Repeated electroconvulsive seizure (ECS), a model for electroconvulsive therapy (ECT), exerts neuroprotective and proliferative effects in the brain. This trophic action of ECS requires inhibition of apoptotic activity, in addition to activation of survival signals. c-Myc plays an important role in apoptosis of neurons, in cooperation with the Bcl-2 family proteins, and its activity and stability are regulated by phosphorylation and ubiquitination. We examined c-Myc and related proteins responsible for apoptosis after repeated ECS. In the rat frontal cortex, repeated ECS for 10 days reduced the total amount of c-Myc, while increasing phosphorylation of c-Myc at Thr58, which reportedly induces degradation of c-Myc. As expected, ubiquitination of both phosphorylated and total c-Myc increased after 10 days ECS, suggesting that ECS may reduce c-Myc protein level via ubiquitination-proteasomal degradation. Bcl-2 family proteins, caspase, and poly(ADP-ribose) polymerase (PARP) were investigated to determine the consequence of down-regulating c-Myc. Protein levels of Bcl-2, Bcl-X(L), Bax, and Bad showed no change, and cleavage of caspase-3 and PARP were not induced. However, phosphorylation of Bad at Ser-155 and binding of Bad to 14-3-3 increased without binding to Bcl-X(L) after repeated ECS, implying that repeated ECS sequesters apoptotic Bad and frees pro-survival Bcl-X(L). Taken together, c-Myc down-regulation via ubiquitination-proteasomal degradation and Bad inactivation by binding to 14-3-3 may be anti-apoptotic mechanisms elicited by repeated ECS in the rat frontal cortex. This finding further supports the trophic effect of ECS blocking apoptosis as a possible therapeutic effect of ECT.
14-3-3 Proteins/metabolism ; Animals ; Down-Regulation ; Electroconvulsive Therapy/*adverse effects ; Frontal Lobe/*metabolism ; Male ; Models, Biological ; Neurons/metabolism ; Periodicity ; Phosphorylation ; Protein Binding ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-myc/*metabolism ; Rats ; Rats, Sprague-Dawley ; Seizures/etiology/*metabolism ; Tumor Cells, Cultured ; Ubiquitination ; bcl-Associated Death Protein/antagonists & inhibitors/*metabolism