Mechanism Underlying Curcumin-induced Apoptosis and Cell Cycle Arrest on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

Several studies have shown that curcumin, which is derived from the rhizomes of turmeric, possesses antimicrobial, antioxidant and anti-inflammatory properties. The antitumor properties of curcumin have also now been demonstrated more recently in different cancers. This study was undertaken to investigate the modulation of cell cycle-related proteins and the mechanisms underlying apoptosis induction by curcumin in the SCC25 human tongue squamous cell carcinoma cell line. Curcumin treatment of the SCC25 cells resulted in a time- and dose-dependent reduction in cell viability and cell growth, and onset of apoptotic cell death. The curcumin-treated SCC25 cells showed several types of apoptotic manifestations, such as nuclear condensation, DNA fragmentation, reduced MMP and proteasome activity, and a decreased DNA content. In addition, the treated SCC25 cells showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40/CAD into the nuclei, a significant shift in the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-7, caspase-6, caspase-3, PARP, lamin A/C, and DFF45/ICAD. Furthermore, curcumin exposure resulted in a downregulation of G1 cell cycle-related proteins and upregulation of p27KIP1. Taken together, our findings demonstrate that curcumin strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via proteasomal, mitochondrial, and caspase cascades in SCC25 cells.

The Inhibition of Oxidative Stress by Chios Gum Mastic is Associated with Autophagy

Chios Gum Mastic (CGM) is a natural resin extracted from the leaves of Pistacia lentiscus, a plant endemic to the Greek island of Chios. It has been used by traditional healers, and it has antibacterial, antifungal properties, and therapeutic benefits for the skin. The CGM reduces the formation of dental plaque and bacterial growth in oral saliva, and recent studies have demonstrated the role of antioxidant activity of CGM. Although CGM has been widely investigated, its protective effect against oxidative-damage to keratinocytes, as well as the relationship between CGM and autophagy, has not been investigated. The aim of this study was to assess the protective effect of CGM against H2O2-induced oxidative stress and to evaluate the autophagic features induced by CGM in human keratinocytes. The pretreatment with CGM significantly reduced apoptosis in H2O2-exposed HaCaT cells. It promoted the degradation of caspase-3, caspase-8, and caspase-9; and it induced the formation of the processed PARP. The treatment with CGM caused an increase in vesicle formation compared to control group. The level of p62 was reduced and the conversion of LC3-I to LC3-II was increased in CGM treated HaCaT cells. Also, the treatment with CGM increased cleavage of ATG5-ATG12 complex. In summary, CGM helps the cells to survive under stressful conditions by preventing apoptosis and enhancing autophagy. Besides, the present investigation provides evidence to support the antioxidant potential of CGM in vitro and opens up a new horizon for future experiments.

A case of plexiform neurofibroma involving the mediastinum and abdomen in a patient with neurofibromatosis / 대한내과학회지

Plexiform neurofibroma is a benign proliferation that arises from the peripheral nerves and represents one of the diagnostic features of neurofibromatosis type I (NF-1). They are commonly found in the gastrointestinal tract, and intrathoracic neurofibroma is relatively uncommon. Ultimately, this tumor grows along the length of any single nerve and may involve multiple fascicles or branches of major nerves. Here, we report a case of multiple-site plexiform neurofibromas in a 40-year-old man previously diagnosed with NF-1. Although he had no perceptible symptoms, contrast-enhanced CT revealed massive diffuse neurofibromas that involved the mediastinum, periportal region, retroperitoneal space, and the mesentery. Histopathological studies of the neck, skin, and intra-abdominal soft tissue showed loose spindle cells and collagen bundles. The microscopic appearance was typical of a plexiform-type neurofibroma. It was decided that we would observe the patient without surgical management, because the neurofibromas were asymptomatic.

A Case of Primary Extragastrointestinal Stromal Tumor Presenting as Peritoneal Dissemination / 대한소화기학회지

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, but also occurs at a lower frequency in extra-gastrointestinal regions such as omentum, mesentery, retroperitoneum and undefined abdominal sites. This tumor is called extragastrointestinal stromal tumor (EGIST). EGIST is mostly diagnosed as a cystic mass, but rarely occurs as a disseminated abdominal tumor. We experienced a 70-year-old man with primary EGIST presenting as peritoneal dissemination. Abdominal CT showed diffuse peritoneal thickening with a large amount of ascites, but no definite mass lesion. Laparoscopic biopsy was performed and histologic findings showed tumor composed of epithelioid cells. In the results of immunohistochemical stains, the tumor showed positive reactivity with CD117 (c-kit), CD34, vimentin and actin, but negative reactivity with desmin and S-100 protein. On account of unresectability and histologic parameters of malignant behavior, he was started on imatinib.

Hereditary Hemolytic Anemia in Korea: a Retrospective Study from 1997 to 2006

BACKGROUND: The aim of this study was to investigate the prevalence, clinical and laboratory findings of hereditary hemolytic anemia (HHA) in Korea from 1997 to 2006 and to develop the appropriate diagnostic approach for HHA. METHODS: By the use of questionnaires, information on the clinical and laboratory findings ofHHA diagnosed from 1997 to 2006 in Korea was collected and analyzed retrospectively. A total of 431 cases were enrolled in this study from 46 departments of 35 hospitals. RESULTS: The overall frequency of HHA did not change through the 10-year period for pediatrics but did show an increasing tendency for internal medicine. The overall male to female sex ratio did not show sex predominance (1.17:1), but a significant male predominance with a ratio of 1.49:1 was seen for pediatrics while a significant female predominance with a ratio of 1:1.97 was seen forinternal medicine. Of the total cases, 74.2% (282/431) were diagnosed before the age of 15 years. The etiologies of HHA were classified as red cell membrane defects, hemoglobinopathies, red cell enzyme deficiencies and unknown causes. There were 382 cases (88.6%) of red cell membrane defects with 376 cases (87.2%) of hereditary spherocytosis and 6 cases (1.4%) of hereditary elliptocytosis, 20 cases (4.6%) of hemoglobinopathies with 18 cases (4.2%) of beta-thalassemia, a case (0.2%) of alpha-thalassemia and a case (0.2%) of Hemoglobin Madrid, 7 cases (1.6%) of red cell enzyme deficiencies with 5 cases (1.2%) of glucose-6- phosphate dehydrogenase (G-6-PD) deficiency, a case (0.2%) of pyruvate kinase (PK) deficiency and a case (0.2%) of enolase deficiency, and 22 cases (5.1%) of unknown causes. The most common chief complaint in pediatric patients was pallor and that in adult patients was jaundice. In the red cell membrane defect group of patients, the level of hemoglobin was significantly higher than in adult patients. The mean corpuscular volume, mean corpuscular hemoglobin, corrected reticulocyte count, total and indirect bilirubin level and lactate dehydrogenase levels in the hemoglobinopathy group of patients were significantly lower than the values in the red cell membrane defect group of patients. The mean concentration of G-6-PD was 0.8+/-0.7U/1012RBC in the G-6-PD deficient patients, PK was 1.7U/1010 RBC in the PK deficient patient, and the level of enolase was 0.04U/g of Hb in the enolase deficient patient. CONCLUSION: The most prevalent cause of HHA in Korea during 1997 to 2006 was hereditary spherocytosis, but HHA by other causes such as hemoglobinopathy and red cell enzyme deficiency gradually increased with the development of molecular diagnostic methods and increasing general interest. However, the etiologies of HHA need to be pursued further in 5.1% of the patients. An systematic standard diagnostic approach is needed in a nationwide prospective study for correct diagnoses and appropriate management of HHA.

Eugenol Induces a Reactive Oxygen Species-mediated Apoptosis in HL-60 Human Promyelocytic Leukemia Cells

BACKGROUND: Eugenol is a major component of the essential oil isolated from Eugenia caryophyllata (Myrtaceae), and has been widely used as a traditional medicine. In this study, the effects of eugenol on the cytotoxicity, induction of apoptosis and putative pathways of its actions were investigated in human promyelocytic leukemia cells (HL-60). METHODS: After applying eugenol to cultured HL-60, the changes in the mitochondrial membrane potential of the cells were monitored after double staining with propidium iodide and rhodamine 123, with 2', 7'-dicholorofluorescin diacetate was used to measure of levels of reactive oxygen species (ROS) RESULTS: Eugenol was shown to be a potent inducer of apoptosis; transducing the apoptotic signal via ROS generation; thereby, inducing mitochondrial permeability transition (MPT) and cytochrome c release to the cytosol. The production of ROS, mitochondrial alteration and subsequent apoptotic cell death in eugenol-treated cells were blocked by the antioxidant, N-acetylcystein (NAC). CONCLUSION: Taken together, the present study has demonstrated that eugenol induces ROS-mediated mitochondrial permeability transition and resultant cytochrome c release.

A Skeletal Traction on the Radiolucent Table in Closed Intramedullary nailing of Femoral Fracture

PURPOSE: To evaluate the clinical results of femoral shaft fracture treated by Intramedullary (IM) nailing through skeletal traction compared with manual traction on a radiolucent table. MATERIALS AND METHODS: Thirty cases with femoral shaft fracture treated with closed IM nailing from January 2000 to June 2002 were divided into two groups; fifteen fractures reduced by manual traction (Group A) and fifteen fractures reduced by skeletal traction (Group B) on a radiolucent table. The number of people participated in the operations, operation and radiation exposure time, and post-operative complications were evaluated. RESULTS: The number of people participated in the operations was five in Group A and four in Group B. The average operation time was 116 minutes and 82 minutes (p<0.001). The radiation exposure time was 2.8 minutes and 1.2 minutes (p<0.001). However, there was no significant difference in the post-operative complications such as shortening or lengthening of bone between two groups. CONCLUSION: There was no significant difference in the operative outcome between two groups. However, skeletal traction has positive effects of reducing the operation time, radiation exposure time, and number of people participating in the operations. Also, regarding the consistent traction power, skeletal traction is the better treatment modality in maintaining the alignment and length of femoral bone than manual traction.

The Comparative Study Of Cancer Incidence Between Urban And Rural Area In Gangneung: Gastric Cancer, Hepatoma And Lung Cancer / 대한내과학회지

BACKGROUND: Since most of epidemiologic studies of cancer disease in Korea are on the basis of data from large hospitals in metropolitan area, they neither represent the separate district, nor reflect the characters of rural area. We aimed to help prevent cancer and present control strategies in good accordance with regional features by evaluating the epidemiologic characters of cancers and performing a comparative study between urban and rural area. METHODS: We retrospectively reviewed the medical records of newly diagnosed cancer patients from January 1997 to December 2000 in Gangneung Asan Hospital, who resided in Gangneung city on diagnosis and investigated their pathologic results, radiologic findings, risk factors, stages, treatment modalities, etc. On the basis of them, we estimated incidence rates including crude rates and age standardized rates and compaed the differences between urban and rural area. RESULTS: The numbers of newly diagnosed cancer patients during this period were 367 in gastric cancer, 186 in hepatoma and 177 in lung cancer. The age standardized annual incidence rates of gastric cancer were estimated to be 49.7/17.8 (M/F) in urban area and 52.7/25.9 (M/F) in rural area per 100,000 persons. In hepatoma, the rates were 28.4/6.3 in urban and 36.3/6.5 in rural area and in the case of lung cancer, 23.5/6. 1 in urban and 32.0/7.4 in rural area. As a consequence, the age standardized annual incidence rates of rural area were higher than those of urban area in all the three cancers and the diffences were statistically significant except female hepatoma and lung cancer. However, risk factor survey among cancer patients revealed only difference in the amount of alcohol consumption associated with hepatoma, between urban and rural area. CONCLUSION: In rural area, the age standardized incidence rates were significantly higher than those of urban area in Gangneung city except female hepatoma and lung cancer. Moreover, in rural area, cancers were detected as more advanced state. Hence, preventive measures fit for these features were required urgently. In addition, more investigations about risk factors were needed to discover the cause of difference, including environmental and host factors which were not covered in this study.

Culture of Rabbit Chondrocytes Using Chitosan Bead / 대한정형외과연구학회지

PURPOSE: To confirm the adhesion and matrix formation of chondrocytes which were cultured on chitosan beads and to elucidate the difference between the porous chitosan beads and non-porous chitsan beads as scaffold for chondrocytes. MATERIALS AND METHODS: Chondrocytes isolated from rabbit articular cartilage were cultured in vitro on porous and non-porous chitosan bead for 2 weeks. Histochemical (H&E stain, Toluidin blue stain) and scanning electromicroscopic approaches were used to compare the differences between two groups. RESULTS: In both groups, adhesion and proliferation of chondrocytes were observed on scanning electron microscopy. which were more active in the porous chitosan bead group. On histochemical staining with toluidine blue, the porous chitosan bead group showed stronger metachromasia than that of the non-porous chitosan bead. CONCLUSION: It is concluded that both chitosan beads could work as an effective scaffold for culturing chondrocytes, and that porous chitosan bead may be a better scaffold than non-porous chitosan bead because of cavities in former bead.

Combination Chemotherapy with Vinorelbine and Ifosfamide in Patients with Advanced Non-Small Cell Lung Cancer / 대한암학회지

PURPOSE: We conducted a phase II study of vinorelbine and ifosfamide combination chemotherapy in patients with advanced or recurrent non-small cell lung cancer (NSCLC) to evaluate response rate, response duration, and toxicities of this regimen. MATERIALS AND METHODS: From June 1998 to March 2000, twenty seven patients with advanced or recurrent non- small cell lung cancer (stage IIIB and IV) who had no prior systemic chemotherapy were enrolled in this study. All patients were treated with vinorelbine and ifosfamide combination chemotherapy (vinorelbine 25 mg/m2 i.v. days 1 & 8, and ifosfamide 2 g/m2 i.v. days 1~3 with Mesna 1600 mg/m2). Each cycle was repeated every 21 days. RESULTS: All twenty seven patients were eligible and assessable. Age ranged from 41 to 72 (median 57 years). 14 patients were male and 13 were female. Overall response rate was 33.3%. One complete response (3.7%) and 8 partial responses (29.6%) were observed. Stable disease was 15 (55.6%) and progressive disease was 3 (11.1%). Overall median survival duration was 7.8 months. The median progression-free and response durations were 6.6 months and 3.5 months respectively. World Health Organization grade 3 to 4 neutropenia occurred in 6.5%. Nonhematologic toxicities including nausea/vomiting, nephropathy and hepatopathy were generally grade 1 or 2. CONCLUSION: The combination chemotherapy with vinorelbine and ifosfamide in the patients with advanced or recurrent non-small cell lung cancer can be considered as an effective and safe treatment.

Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells

Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.

Clinical Outcome of the Chromosomal Abnormalities in Adult Acute Lymphoblastic Leukemia (Preliminary Data) / 대한혈액학회지

BACKGROUND: Adult acute lymphoblastic leukemia (ALL) is a hematologic malignant disease characterized by an uncontrolled proliferation of immature lymphocytes and their progenitors. Because specific chromosomal abnormalities are associated with ALL, cytogenetic studies can help classifying the disease, providing the clues of disease, progression and being used to monitor remission after chemotherapy. So, we have performed cytogenetic studies to identify the incidence of chromosomal abnormalities and their prognostic significance in patients with ALL. METHODS: From August 1996 to July 1999, we evaluated chromosomal abnormalities in 25 patients with acute lymphoblastic leukemia by high resolution banding technique. Among them, 22 patients were treated with vincristine, prednisone, daunorubicin, L-asparagenase (VPDL) to induce complete remission. We divided patients who had hyperdiploidy, normal karyotype into good risk group (A), and t(9;22), undetermined prognostic karyotype group into poor risk group (B). RESULTS: The incidence of chromosomal ab-normalities was 50% (11/22). The median follow up duration of 22 evaluable patients was 11.1 months. The complete remission (CR) rate was 82% (18/22). The CR rate in group A and B were 100% (14/14), 50% (4/8) respectively (P=0.01). The median remission duration was 30.1 months. The median remission duration of group B was 7.3 months, and that of group A was 30.1 months (P=0.0188). Overall median survival duration was 13.7 months, and the median survival duration in A and B group was 32.5 months and 3.5 months respectively (P= 0.0261). CONCLUSION: The incidence of chromosomal abnormalities in patients with acute lymphoblastic leukemia were relatively high and chromosomal abnormalities were one of useful prognostic factors in remission duration and survival duration. Tailored therapy according to chromosomal abnormalities is desired for more effective results.

A Case of Multiple Myeloma with Biclonal Gammopathy / 대한내과학회지

Multiple myeloma is a disease originated from plasma cell line. A single protein is generally produced by myeloma cells, but a few cases of biclonal gammopathy are reported. We experienced a case of multiple myeloma, a 53-year-old woman, with IgG and IgA biclonal gammopathy. She has maintained in complete remission after 6 cycles of combination chemotherapy with cyclophosph- amide, vincristine, adriamycin, and prednisolone.

Unilateral Absence of Lung Perfusion Caused by Non-thromboembolic Compression in Bronchogenic Carcinoma / 대한내과학회지

Perfusion scintigraphy has proved to be an essential part for the diagnosis of pulmonary thromboembolism. The wedge shaped perfusion defect extending to lung base is a highly probable finding of pulmonary embolism. Occasionally, great perfusion defects could be presented as a false positive finding under the circumstance of nonthromboembolic origin, such as neoplastic compression or invasion of pulmonary artery. We report an unusual case of massive perfusion defect resulting from pulmonary arterial compression by bronchogenic carcinoma. A 71-year-old man visited our hospital because of productive cough and was diagnosed as bronchogenic carcinoma. The perfusion scintigraphy showed unilateral total defect of lung, not accompanied by any clinical evidence of thromboembolism. A contrast enhanced computed tomogram showed heterogeneous mass shadow in left hilum, abutting to the descending aorta and compressing left main pulmonary artery. These findings suggested a nonembolic mechanism of perfusion defects which were produced by the neoplastic compression of pulmonary artery.

A Case of Bronchial Mucoepidermoid Carcinoma / 결핵

Mucoepidermoid carcinoma developed in tracheobronchjal tree is one of rare lung tumor. It is histologically divided into low grade malignancy of relatively benign course versus high grade malignancy of fatal course. In low grade malignancy, it can be curative with a surgical resection. We experienced a case of mucoepidermoid carcinoma in a 28-year-old woman who complained sudden dyspnea and presented right total lung collapse on chest roentgenogram. It was diagnesed as a low grade mucoepidermoid carcinoma and removed by the surgical excision.

A Study of Effect on Pulmonary Function of Pleural Effusion in Tuberculous pleurisy patients / 결핵

BACKGROUND: Pleural effusion is a common disease in clinical practice but its effect on pulmonary function and altered pulmonary mechanics after removal of effusion are not still largely understood. Previous studies have shown that there is little or a relatively small improvement in pulmonary function and arterial blood oxygenation after therapeutic thoracentesis. The present study was designed to assess the effect on pulmonary function of pleural effusion and to test whether there was a significant improvement in pulmonary function and arterial oxygenation after thoracentesis and to observe long term effect after thoracentesis. METHOD: We examined flow-volume curve, body box and arterial blood gas analysis according to severity of effusion, present symptom, and symptom duration. Then, we measured changes of pulmonary function after thoracentesis and observed longterm effect after thoracentesis. RESULT: 1) Pleural effusion cause restrictive pulmonary insufficiency. Not only functional impairment of small airway but also large airway is provoked. 2) MMFR, FEV1, Raw, PO2 are earlier improved than FVC and TLC after thoracentesis and patients without complication have mild restrictive pulmonary insufficiency after longterm observation 3) FVC, FEV1, & TLC are similarly restricted as severity of pleural effusion and PO2 is relatively decreased. 4) Cases with symptom duration 1 week or less and cases with dyspnea have more severe pulmonary insufficiency than others. 5) The flow volume curves show a relatively greater improvement in flow rates at large lung volumes than small airway. 6) Significant relationship is shown between first thoracentesis amount and changes of FEV1, FVC, TLC. CONCUSION: Pleural effusion cause restrictive pulmonary insufficiency and not only functional impairment of small airway impairment but also large airway is provoked. Then, Pulmonary function is progressively improved after thoracentesis and remained mild restrictive pulmonary insufficiency after recovery

Bacterial Contamination of The Wetting Solution in Cases of Soft Contact Lens

Soft contact lenses have become a popular modality for the cosmetic correction of refractive errors. Recent reports of bacterial corneal ulcer in cosmetic soft contact lens wearers prompted the evaluation of the possible sources of bacterial contamination which are wetting saline solution, soft contact lens case, concurrent conjunctivitis, lens surface abnormalities, inadequate temperature and duration of disinfection, poor hygiene in contact lens handling and aging of the lens. Of these factors, the authors considered that the wetting solution and cases of contact lens were most important sources. The extensive bacteriologic study and sensitivity test to antibiotics were done with 200 soft contact lens cases containing; wetting saline solution in 100 patients. The study showed that 149 cases containing wetting saline solution(74.5%) were contaminated with bacteria which serve as a possible source of corneal ulcers. Form 149 contaminated cases of soft contact lens, a total of 231 isolates were cultured. Of these 231 isolates, 32 isolates(13.9%) showed gram positive bacteria; 199 isolates(86.1%) gram negative bacteria. Major organisms were Enterobacter species(21.2%), Serratia marcescens(19.9%), pseudomonas species(17.7%), Adnetobacter calco var. antitrat(10.4%) and Bacillus subtilis(10.0%). Therofore, it should be emphasized that adequate and meticulous home disinfection of contact lens cases and wetting solution is done for prevention of bacterial contamination of soft contact lens.

Allergic Contact Dermatitis and Conjuntivitis due to Pontocaine

A patient with corneoscleral dermoid was suspected of having allergic contact dermatitis and conjuntivitisdue to Pontocaine. She was tested with standard European patch test including other suspected medicaments used in the preparation of eye drops. The patient showed + + positive patch test reaction to pontocaine, caine mixture and benzocaine under 2 day and 4 day patch test reading. The importance of routine patch test in ophthalmic patients whenever contact conjuntivitis is suspected is stressed.

A Case Report of Human Thelaziasis in Korea

Thelazia callipaeda was first described by Railliet and Henry in 1910. The first human case was reported by Stuckey in 1917, who extracted four worms in the eye of a coolie in Peiping. In Korea, seven cases of human thelaziasis have been already reported and all of the worms were identified to be thelazia callipaeda. The present paper is to report the 8th human infested case of Thelazia callipaeda in Korea. The patient was 25 years old virgin who had lived in Seoul since birth. She experienced lacrimation and moving foreign body sensation of the left eye, and extracted 1 living worm from the left eye by herself on one day prior to examination. Microscopic measurements of an extracted worm are as follows; A worm(male) is 13.0 mm B worm(male) is 13.1 mm and C worm(female) is 19.0 mm in length. It was confirmed as Thelazia callipaeda Railliet et Henry 1910.