Over several decades, a hierarchical cancer stem cell (CSC) model has been established in development of solid cancers, including hepatocellular carcinoma(HCC). In terms of this concept, HCCs originate from liver CSCs. Clinically HCCs show a wide range of manifestations from slow growth to very aggressive metastasis. One of the reasons may be that liver CSCs originate from different cells. This review describes the basic concept of CSCs and the cellular origin of liver CSCs.
Carcinoma, Hepatocellular ; Liver ; Liver Neoplasms* ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Stem Cells*

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor alpha (TNFalpha) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNFalpha production in vitro and in vivo, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNFalpha mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP-activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNFalpha production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The in vivo effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNFalpha mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNFalpha production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNFalpha production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNFalpha production by cilostazol.
Aminoimidazole Carboxamide ; AMP-Activated Protein Kinases ; Animals ; Binge Drinking ; Ethanol ; Hepatitis, Alcoholic ; Liver ; Liver Diseases, Alcoholic ; Liver Failure ; Macrophages ; Mice ; Pentoxifylline ; Reactive Oxygen Species ; Ribonucleotides ; RNA, Messenger ; Tetrazoles ; Tumor Necrosis Factor-alpha

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.
Antiviral Agents ; Apoptosis ; Carcinoma, Hepatocellular ; Cytokines ; Diet ; Drug Therapy ; Dyslipidemias ; Fibrosis ; Hepatitis B ; Humans ; Insulin Resistance ; Korea ; Liver Cirrhosis ; Liver Diseases ; Liver Transplantation ; Non-alcoholic Fatty Liver Disease ; Obesity ; United States ; Weight Loss

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

BACKGROUND: The North Korean defectors are suffering from multiple psychologic and physical health problems. However, because of their emotional maladaptation, noncooperation and suspiciousness and distrust toward others, it is difficult for South Korean doctors to build effective therapeutic relationships with them. Therefore, we made efforts to clarify the characteristics of North Korean defectors in symptom expressions and illness behaviors which would help South Korean doctors to gain rapport. METHODS: We performed qualitative study with focus group interview. Three focus groups were composed of 14 North Korean defectors and group interviews were performed twice for each group. The contents of each interview were analyzed and conclusions were drawn by extracting and arranging significant findings. RESULTS: The North Korean defectors showed psychologic symptoms such as anxiety, depression and various somatic symptoms. Among them, 'Laeng-Dol ('cold mass) and 'Jeog' mean subjective mass-feeling, such as globus sensation. And 'Tag-Gi-Byeong ('chicken heart disease')' means recurrent chest pain. These expressions reflect their anxious, depressive, and somatizing tendency. Among illness concept, 'Laeng-Byeong' ('cold related disease') means that they consider the cold weather to be the cause of various somatic symptoms. Characteristic illness behaviors include continuous complaining of recurrent symptoms, distrusting medical staffs and institutions, self-diagnosis, self- prescription, and reliance upon folk remedies. These illness behaviors were precipitated by the current breakdown of health-care system and economic crisis of the North Korea. CONCLUSION: South Korean doctors should be able to understand these characteristics of the North Korean defectors in order to build effective therapeutic relationship with them.
Anxiety ; Chest Pain ; Democratic People's Republic of Korea ; Depression ; Focus Groups ; Heart ; Humans ; Illness Behavior* ; Interviews as Topic ; Medical Staff ; Medicine, Traditional ; Prescriptions ; Sensation ; Weather

BACKGROUND: The North Korean defectors are suffering from multiple psychologic and physical health problems. However, because of their emotional maladaptation, noncooperation and suspiciousness and distrust toward others, it is difficult for South Korean doctors to build effective therapeutic relationships with them. Therefore, we made efforts to clarify the characteristics of North Korean defectors in symptom expressions and illness behaviors which would help South Korean doctors to gain rapport. METHODS: We performed qualitative study with focus group interview. Three focus groups were composed of 14 North Korean defectors and group interviews were performed twice for each group. The contents of each interview were analyzed and conclusions were drawn by extracting and arranging significant findings. RESULTS: The North Korean defectors showed psychologic symptoms such as anxiety, depression and various somatic symptoms. Among them, 'Laeng-Dol ('cold mass) and 'Jeog' mean subjective mass-feeling, such as globus sensation. And 'Tag-Gi-Byeong ('chicken heart disease')' means recurrent chest pain. These expressions reflect their anxious, depressive, and somatizing tendency. Among illness concept, 'Laeng-Byeong' ('cold related disease') means that they consider the cold weather to be the cause of various somatic symptoms. Characteristic illness behaviors include continuous complaining of recurrent symptoms, distrusting medical staffs and institutions, self-diagnosis, self- prescription, and reliance upon folk remedies. These illness behaviors were precipitated by the current breakdown of health-care system and economic crisis of the North Korea. CONCLUSION: South Korean doctors should be able to understand these characteristics of the North Korean defectors in order to build effective therapeutic relationship with them.
Anxiety ; Chest Pain ; Democratic People's Republic of Korea ; Depression ; Focus Groups ; Heart ; Humans ; Illness Behavior* ; Interviews as Topic ; Medical Staff ; Medicine, Traditional ; Prescriptions ; Sensation ; Weather

Gallbladder (GB) cancer is relatively rare and has a poor prognosis, with a median survival time of less than 3 months. It is resistant to chemotherapy. Therefore, the role of systemic chemotherapy is limited. However, administering the anticancer agent directly into the hepatic artery can result in a higher drug concentration in the cancer tissue. In this paper, we report a case of advanced GB cancer treated with hepatic arterial infusion chemotherapy (HAIC) using the port system. The patient received six cycles of HAIC with 5-fluorouracil (750 mg/m²) and cisplatin (25 mg/m²); each cycle lasted for 4 days every month. The tumor showed objective response during HAIC, and the patient survived for 15 months from the first therapy. HAIC using the port system might be a promising therapeutic modality for treating locally advanced GB cancer.
Cisplatin ; Drug Therapy ; Fluorouracil ; Gallbladder Neoplasms ; Gallbladder ; Hepatic Artery ; Humans ; Prognosis

Gallbladder (GB) cancer is relatively rare and has a poor prognosis, with a median survival time of less than 3 months. It is resistant to chemotherapy. Therefore, the role of systemic chemotherapy is limited. However, administering the anticancer agent directly into the hepatic artery can result in a higher drug concentration in the cancer tissue. In this paper, we report a case of advanced GB cancer treated with hepatic arterial infusion chemotherapy (HAIC) using the port system. The patient received six cycles of HAIC with 5-fluorouracil (750 mg/m²) and cisplatin (25 mg/m²); each cycle lasted for 4 days every month. The tumor showed objective response during HAIC, and the patient survived for 15 months from the first therapy. HAIC using the port system might be a promising therapeutic modality for treating locally advanced GB cancer.

BACKGROUND: We attempted to study functional and structural changes in the hearts of volleyball players and cardiac effects of a short-term intensive training as disclosed by electrocardiograms(ECG's) and echocardiograms(UCG's). METHODS: In 12 volleyball players of a university team with the mean age and career of 19.9 and 9.2 years, respectively, comparisons of ECG's and UCG's M-mode & Doppler, were made before and after an intensive training of 8 weeks duration. The players have been trained 2-3 hours daily almost year around for many years, and the intensive and comprehensive training given for the current study was 3 hours daily, which included strenuous interval training of 20-30 minutes. The training was divided into two successive sessions. For the first session, the players ran 4km daily as a part of the training for 2 weeks. The second session included repetition of runnging at their maximal speed with short intermissions of stationary running for 6 weekes. RESULTS: The major findings in ECG's were sinus bradycardia(25.0%) and high voltage(33.3%), and those in M-mode UCG's were left ventricular(LV) hypertrophy, LV dilatation or left atrial dilatation being seen in all cases, alone or in combinations. After the training however, there were no significant changes in the incidences of these abnormal findings in ECG's & UCG's, and also in the mean of various echocardiographic parameters reflecting cardiac functions. The E and A waves in Doppler UCG's also showed no changes. The slight but significant changes after the training were limited to the increases in the mean of the sum of S wave in V1 & R wave in V5, and left atrial dimensions. CONCLUSION: In volleyball players who have been regularly trained for many years, the major findings in ECG's were sinus bradycardia and high voltage. Those in UCG's were LV hypertrophy. LV dilatation or left atrial dilation being seen in all cases, alone or in combinations. Nonetheless, after the intensive training of 8 weeks duration, the incidences of these abnormal findings in ECG's and UCG's remained essentially similar, and slight but significant changes were limited to the increases in the sum of S wave in V1 & R wave in V5, and left atrial internal dimensions. These facts suggest that in the regularly trained volleyball players, a short-term intensive training induces only limited cardiac changes as disclosed by ECG's and UCG's.
Bradycardia ; Dilatation ; Echocardiography ; Electrocardiography* ; Heart ; Hypertrophy ; Incidence ; Running ; Volleyball*

BACKGROUND: Assessment of left ventricular function with conventional 2-dimensional echocardiography (2D echo) remains largely qualitative and subjective because the manual tracing of endocardial borders is laborious and tedious. An automatic border detection (ABD) echo has been recently developed that permits real-time measurements of chamber areas and cardiac function. METHODS: To determine usefulness of ABD echo, left ventricular cross-sectional areas were automatically measured from the parasternal short-axis image in 25 cases including 9 cardiac patients, and compared with those by off-line analysis of the conventional 2D echo image. RESULTS: In on-line ABD analysis, short axis end-diastolic area averaged 13.1+/-2.2cm2, end-systolic area 5.3+/-1.3cm2 and fractional area change 59.4+/-9.0% and off-line manual analysis yielded corresponding values of 14.7+/-2.5cm2, 6.2+/-1.3cm2, and 57.1+/-7.1%. The end-diastolic and end-systolic areas by both methods were significantly different, respectively. Left ventricular end-diastolic and end-systolic area and fractional area change obtained from ABD echo correlated significantly with those of off-line measurements(r=0.897, p<0.001 ; r=0.505, p<0.01 ; r=0.427, p<0.05). CONCLUSION: Thus, these facts suggest that ABD echo is useful for on-line continuous measurement of chamber areas and cardiac function.
Axis, Cervical Vertebra ; Echocardiography* ; Humans ; Ventricular Function, Left