PURPOSE: In order to understand in vivo radiation damage modifying effect of bFGF on jejunal mucosa, bone marrow and the effect of bFGF on the growth of transplanted mouse sarcoma 180 tumor in mice. MATERIALS AND METHODS: Mice were treated with 6 microgram of bFGF at 24 hours and 4 hours before exposing to 600 cGy, 800 cGy and 1,000 cGy total body irradiation (TBI), and then exposed to 3,000 cGy local radiation therapy on the tumor bearing thigh. Survival and tumor growth curve were plotted in radiation alone group and combined group of bFGF and irradiation (RT). Histologic examination was performed in another experimental group. Experimental groups consisted of normal control, tumor control, RT (radiation therapy) alone, 6 microgram bFGF alone, combined group of 3 microgram bFGF and irradiation (RT), combined group of 6 microgram bFGF and irradiation (RT). Histologic examination was performed with H-E staining in marrow, jejunal mucosa, lung and sarcoma 180 bearing tumor. Radiation induced apoptosis was determined in each group with the DNA terminal transferase nick-end labeling method (ApopTag S7100-kit, Intergen Co.) RESULTS: The results were as follows 1) 6 microgram bFGF given before TBI significantly improved the survival of lethally irradiated mice. bFGF would protect against lethal bone marrow syndrome. 2) 6 microgram bFGF treated group showed a significant higher crypt depth and microvilli length than RT alone group (p<0.05). 3) The bone marrow of bFGF treated group showed less hypocellularity than radiation alone group on day 7 and 14 after TBI (p<0.05), and this protective effect was more evident in 6 microgram bFGF treated group than that of 3 microgram bFGF treated group. 4) bFGF protected against early radiation induced apoptosis in intestinal crypt cell but might have had no antiapoptotic effect in bone marrow stem cell and pulmonary endothelial cells. 5) There was no significant differences in tumor growth rate between tumor control and bFGF alone groups (p>0.05). 6) There were no significant differences in histopathologic findings of lung and mouse sarcoma 180 tumor between radiation alone group and bFGF treated group. CONCLUSIONS: Our results suggest that bFGF protects small bowel and bone marrow from acute radiation damage without promoting the inoculated tumor growth in C3H mice. Improved recovery of early responding normal tissue and reduced number of radiation induced apoptosis may be possible mechanism of radioprotective effect of bFGF.
Animals ; Apoptosis ; Bone Marrow ; DNA ; Endothelial Cells ; Fibroblast Growth Factor 2* ; Lung ; Mice ; Mice, Inbred C3H* ; Microvilli ; Mucous Membrane ; Sarcoma 180 ; Stem Cells ; Thigh ; Transferases ; Whole-Body Irradiation

It is known that dehydroepiandrosterone (DHEA) shows a dual effect, prooxidant or antioxidant, depending on the dosage or physiological status of animals. The purpose of this study was to determine the effects of DHEA administration at low dose on lipid peroxidation, protein carbonylation and fatty acid composition in liver. Sprague Dawley male rats were fed either corn oil diet containing 15% corn oil or fish oil diet containing 2% corn oil + 13% sardine oil, with or without 0.2% DHEA for 9 weeks. Atherogenic index and hepatic triglyceride and cholesterol levels were significantly reduced by DHEA administration in rats fed with fish oil diet. Hepatic lipid peroxide product (TBARS) and protein carbonyl levels were significantly higher in rats fed with fish oil diet than in rats fed with corn oil diet. However, DHEA administration significantly reduced the hepatic thiobarbituric acid-reactive substance (TBARS) and conjugated diene levels in rats fed with fish oil diet. Contents of C16 : 0, C16 : 1, C20 : 5 and C22 : 6 in hepatic microsome were higher in rats fed with fish oil diet than in rats fed with corn oil diet, and contents of C18 : 2 and C20 : 4 were lower than in rats fed with corn oil diet. DHEA administration significantly increased C16 : 0 and C18 : 3 contents and reduced C18 : 2 content in rats fed with corn oil diet, while it increased C16 : 0 and C18 : 1 and reduced C20 : 5 and C22 : 6 in rats fed with fish oil diet. On overall, DHEA administration increased saturated fatty acid (SFA) and reduced polyunsaturated fatty acid (PUFA) in hepatic microsome, thereby PUFA/SFA ratio was significantly (p < 0.0001) reduced without the change of n-3/n-6 ratio. Taken together, low dose of DHEA administration lowered PUFA/SFA ratio in hepatic microsomal membranes and also showed antioxidative effect especially in fish oil-induced highly oxidative stress condition through blocking increases of C20 : 5 and C22 : 6 contents.
Animals ; Cholesterol ; Corn Oil ; Dehydroepiandrosterone* ; Diet ; Humans ; Lipid Peroxidation ; Liver* ; Male ; Membranes ; Microsomes ; Microsomes, Liver* ; Oxidative Stress ; Protein Carbonylation ; Rats* ; Triglycerides

It is reported that a fermented soybean food, Doenjang, has strong antimutagenic and cytotoxic effect on cancer cells. This study investigated the effect of Chungkookjang, another traditional popular Korean soybean fermented food, on growth of cancer cells: HL-60, SNU-638 and MCF-7, and also its in vivo antitumorigenic effect in DMBA-induced mammary tumor rat model. For the in vitro study, Chungkookjang and steamed soybeans were extracted with ethanol and sequentially fractioned with 5 kinds of solvents differing in grades of polarity such as hexane, dichloromethane, ethylacetate, butanol and water. Almost all Chungkookjang extracts significantly inhibited the growth of HL-60 (human leukemic cancer cell), SNU-638 (human gastric cancer cell) and MCF-7 (human breast cancer cell) when compared to steamed soybean extracts. Butanol fraction of Chungkookjang extract especially showed a remarkable inhibitory effect in all the three kinds of cancer cells. To induce a mammary gland tumor, DMBA (50 mg/BW) was administered to 50 day-old female rats and followed by Chungkookjang or steamed soybean supplemented diets. Freezedried Chungkookjang powder (20% of diet in wet weight) was added to AIN-93G based diet for the Chungkookjang group of rats. Likewise, steamed soybean powder containing equal protein content to that of Chungkookjang powder was supplemented to soybean group of rats. At 13 weeks later, the mammary tumor incidence, average tumor number and tumor weight a rat were lower in Chungkookjang group compared to the control or soybean group. In conclusion, Chungkookjang showed a strong inhibitory effect on cancer cell growth in vitro, as well as a more preventive effect against chemically induced mammary tumorigenesis in vivo, while steamed soybeans did not. Therefore, these results suggest that Chungkookjang acquire its anticancer activity through the fermentation process.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Breast Neoplasms ; Carcinogenesis ; Diet ; Ethanol ; Female ; Fermentation ; Humans* ; Incidence ; Mammary Glands, Human ; Methylene Chloride ; Models, Animal ; Rats* ; Solvents ; Soybeans* ; Steam ; Stomach Neoplasms ; Tumor Burden ; Water

PURPOSE: Granulocyte-colony stimulating factor (G-CSF) has been widely used to treat neutropenia caused by chemotherapy or radiotherapy. The efficacy of recombinant human hematopoietic growth factors in improving oral mucositis after chemotherapy or radiotherapy has been recently demonstrated in some clinical studies. This study was designed to determine whether G-CSF can modify the radiation injury of the intestinal mucosa in mice. MATERIALS AND METHODS: One hundred and five BALB/c mice weighing 20 grams were divided into nine subgroups including G-CSF alone group (I : 10 microgram/kg or II : 100 microgram/kg), radiation alone group (7.5 or 12 Gy on the whole body), combination group with G-CSF and radiation (G-CSF I or II plus 7.5 Gy, G-CSF I or II plus 12 Gy), and control group. Radiation was administered with a 6 MV linear accelerator (Mevatron Siemens) with a dose rate of 3 Gy/min on day 0. G-CSF was injected subcutaneously for 3 days, once a day, from day -2 to day 0. Each group was sacrificed on the day 1, day 3, and day 7. The mucosal changes of jejunum were evaluated microscopically by crypt count per circumference, villi length, and histologic damage grading. RESULTS: In both G-CSF I and II groups, crypt counts, villi length, and histologic damage scores were not significantly different from those of the control one (p>0.05). The 7.5 Gy and 12 Gy radiation alone groups showed significantly lower crypt counts and higher histologic damage scores compared with those of control one (p<0.05). The groups exposed to 7.5 Gy radiation plus G-CSF I or II showed significantly higher crypt counts and lower histologic damage scores on the day 3, and lower histologic damage scores on the day 7 compared with those of the 7.5 Gy radiation alone one (p<0.05). The 12 Gy radiation plus G-CSF I or II group did not show significant difference in crypt counts and histologic damage scores compared with those of the 12 Gy radiation alone one (p>0,05). Most of the mice in 12 Gy radiation with or without G-CSF group showed intestinal death within 5 days. CONCLUSION: These results suggest that G-CSF may protect the jejunal mucosa from the acute radiation damage following within the tolerable ranges of whole body irradiation in mice.
Animals ; Drug Therapy ; Granulocyte Colony-Stimulating Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; Intestinal Mucosa ; Jejunum ; Mice* ; Mucous Membrane* ; Neutropenia ; Particle Accelerators ; Radiation Dosage ; Radiation Injuries ; Radiotherapy ; Stomatitis ; Whole-Body Irradiation

The previous extensive in vitro studies on the antioxidative activities of a number of Korean grains, vegetables, seaweeds and mushrooms, and the various combinations of these food source exhibited a wide range of antioxidative activities, and four food mixtures composed of 5 kinds of foods (5A, 5B, 5C and 5D) were designed from 16 selective foods showing high antioxidant effect, in vitro, to find the good combinations for the meal planning. Mixture 5B or 5C contained very high levels of total flavonoid and polyphenol, and ethanol extract from 5A, 5B or 5C showed very strong inhibitory effects against in vitro Fe2+-induced lipid peroxidation and ethanol extract from 5B or 5C showed remarkable DPPH radical scavenging effect and lipid peroxide-protein conjugation inhibition effect. And in vivo study was also carried out with two mixtures (5B, 5C). Powders (P5B, P5C) or ethanol extracts (E5B, E5C) of these mixtures were supplemented to Sprague-Dawley rats fed on high fat (15%)-high cholesterol (1%) semipurified diet for 5 weeks. The total antioxidant power in serum was significantly higher in P5B, P5C, E5B and E5C groups than in high fat control group, and ascorbate-Fe2+-induced TBARS was significantly lowered by E5B supplementation in rat liver. In liver tissue, Cu, Zn-SOD activity was significantly higher in P5B and E5B groups than in high fat control group, while catalase or GSH-peroxidase (GPx) activity was not changed by any supplementations. In kidney, Cu, Zn- SOD activity was significantly higher in P5B group than in high fat control group, while GPx activity was not changed by any supplementations. Taken together, mixture 5B and 5C showed very strong antioxidative effects both in vitro and in vivo. Therefore, the ingredient Korean foods of 5B and 5C could be recommended to take a lot together for prevention from age-related chronic diseases.
Agaricales ; Animals ; Antioxidants ; Catalase ; Cholesterol* ; Chronic Disease ; Diet* ; Edible Grain ; Ethanol ; Kidney ; Lipid Peroxidation ; Liver ; Meals ; Plants* ; Powders ; Rats* ; Rats, Sprague-Dawley ; Thiobarbituric Acid Reactive Substances ; Vegetables

The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or with 8% freeze-dried red beet leaf (RBL group) for 4 weeks. In RBL mice, lipid peroxidation determined as 2-thiobarbituric acid-reactive substances (TBARS value) was significantly reduced in the plasma and selected organs (liver, heart, and kidney). Levels of antioxidants (glutathione and beta-carotene) and the activities of antioxidant enzyme (glutathione peroxidase) in plasma and liver were considerably increased, suggesting that antioxidant defenses were improved by RBL diet. Comet parameters such as tail DNA (%), tail extent moment, olive tail moment and tail length were significantly reduced by 25.1%, 49.4%, 35.4%, and 23.7%, respectively, in plasma lymphocyte DNA of RBL mice compared with control mice, and indicated the increased resistance of lymphocyte DNA to oxidative damage. In addition, the RBL diet controlled body weight together with a significant reduction of fat pad (retroperitoneal, epididymal, inguinal fat, and total fat). Therefore, the present study suggested that the supplementation of 8% red beet leaf in high fat high cholesterol diet could prevent lipid peroxidation and improve antioxidant defense system in the plasma and tissue of C57BL/6J mice.
Acclimatization ; Adipose Tissue ; Animals ; Antioxidants ; Beta vulgaris ; Body Weight ; Cholesterol ; Diet ; DNA ; Heart ; Lipid Peroxidation ; Liver ; Lymphocytes ; Mice ; Olea ; Plasma

BACKGROUND: Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. METHODS: We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. RESULTS: Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. CONCLUSION: Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.
Adrenocorticotropic Hormone* ; Cushing Syndrome* ; Dehydroepiandrosterone Sulfate ; Dexamethasone ; Diagnosis, Differential ; Diagnostic Tests, Routine ; Humans ; Hydrocortisone ; Pituitary ACTH Hypersecretion* ; Plasma* ; Retrospective Studies ; Sensitivity and Specificity

PURPOSE: This retrospective study was performed to evaluate the effect of postoperative adjuvant radiation therapy of breast cancer on survival, failure patterns and to identify unfavorable prognostic factors. MATERIALS AND METHODS: Seventy-seven patients were analysed retrospectively. Median follow up period was 72 months. According to AJCC system, fifty-eight patients (75%) were advanced than Stage IIb. Among 77 patients, 66 patients (86%) received mastectomy and axillary LN dissection and the other 11 patients (14%) received partial mastectomy and axillary LN dissection. Postoperative radiation therapy with 6 MV X-ray was given to the chest wall and regional lymphatics with total dose of 50 to 55 Gy. Fifty-five patients (71%) received CMF or CAF chemotherapy prior to or after radiation therapy. RESULTS: The 5 year and 10 year survival rate were 64.4% and 51.3%, respectively and 5 year and 10 year disease free survival rate were 57.6% and 47.5%, respectively. Median survival duration was 91 months. Of the 77 patients, 59 patients were evaluable for pattern of failure. Of these, eighteen patients (31%) failed. Initial failure pattern was as follow: 7 (12%) at locoregional, 3 (5%) in distant metastasis, 8 (14%) with locoregional and distant metastasis. But the pattern of final failure at the time of last follow up was contrasted. Distanf failure was the predominant pattern of failure with 29% of patients. Overall survival and disease free survival was significantly influenced by 6 factors with univariated analysis (p<0.05): AJC Stage, T stage, N Stage, number of involved axilliary LN, SCL LN mets, failure pattern. By multivariate analysis the survival difference continued to be significant in 3 factors : T stage, number of involved axillary LN, failure pattern. CONCLUSION: These data demonstrate high locoregional control and survival rate using the combination of surgery and radiotherapy for the patients with locally advanced breast cancer. But predominant failure pattern was distant dissemination. Therefore more effective systemic therapy is needed to improve overall survival.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Mastectomy ; Mastectomy, Segmental ; Multivariate Analysis ; Neoplasm Metastasis ; Radiotherapy ; Retrospective Studies ; Survival Rate ; Thoracic Wall

PURPOSE: This study was designed to evaluate the prognostic factors, survival rate and local recurrence rate of the patients with rectal cancer who received postoperative radiation therapy. METHODS & MATERIALS: Seventy patients with rectal cancer received postoperative radiation therapy after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medial College between May 1984 and April 1993. Of the seventy patients, sixty-four evaluable patients were analysed retrospectively. There were 34 men and 28 women. Age at diagnosis ranged from 23 to 74 years. The distribution of stage according to the modified Astler-Coller (MAC) system was as follow: 12 in B2+3, 2 in C1, and 50 in C2+3. Postoperative adjuvant therapy included pelvic radiotherapy in all cases and chemotherapy in addition in 55 cases. A total dose of 45 to 60 Gy (median dose: 55.8Gy) was delivered in a period of 5 to 6 weeks and the follow-up period ranged from 26 to 133 months with a median of 55 months. RESULTS: Overall two-year and five-year actuarial survival rate were 70.3% and 51.4%, 90.9% and 90.9% in stage B2+3, and 68.2% and 53.6% in stage C. Local failure occurred in 13 (20.3%) of the 64 patients and distant failure rate was 18.8% (12/64). Severe late complication was small bowel obstruction in 4 patients and surgery was required in 3 patients (5%). The significant prognostic factors were stage (p=0.0019) and histologic differentiation (p=0.0046). CONCLUSION: This study suggested a potential adjuvant role for radiation. However, the possible reduction in local failure rates in this study compared with historic control groups must be verified in randomized trial.
Diagnosis ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Radiation Oncology ; Radiotherapy ; Rectal Neoplasms* ; Recurrence ; Retrospective Studies ; Survival Rate

PURPOSE: To differentiate multiple myeloma from metastasis involving the spine at MR imaging. MATERIALS AND METHODS: Twenty-five patients with multiple myeloma and 37 with vertebral metastasis were included in this study. MR images were retrospectively analyzed with regard to infiltration and enhancement patterns, signal intensity, the involvement of three consecutive vertebrae, the number of lesions within one vertebra, and paraspinal and epidural masses. Using a 1.5-T imager, we obtained sagittal and axial, unen-hanced and enhanced T1-weighted images, and fast spin-echo images. For statistical analysis, Fisher's exact test was used. RESULTS: All cases of multiple myeloma and metastasis showed low signal intensity on T1-weighted images, and there were no significant differences in signal intensities or enhancement patterns. Infiltration and enhancement patterns were classified as focal (52% in multiple myeloma vs 68% in metastasis, p> 0.05), diffuse (32% vs 32%, p > 0.05) or salt and pepper (16% vs 0%, p < 0.05) pattern. Differentiation between multiple myeloma and metastasis was based on two criteria: the involvement of three consecutive vertebrae (80% vs 43%, p < 0.01), and the presence of more than five lesions within one vertebra (59% vs 8%, p < 0.05). On fast spin-echo T2-weighted images, signal intensity was as follows: hyperintensity (12% vs 32%, p > 0.05), isoin-tensity (36% vs 3%, p < 0.05), and hypointensity (52% vs 65%, p > 0.05). Paraspinal and epidural masses played little part. CONCLUSION: The salt and pepper infiltration pattern, the presence of more than five lesions within one vertebra, and the involvement of more than three consecutive vertebrae were useful MR findings for differentiation between multiple myeloma and metastasis involving the spine. In most cases, however, it is difficult to distinguish between the two conditions.
Humans ; Magnetic Resonance Imaging ; Multiple Myeloma* ; Neoplasm Metastasis* ; Retrospective Studies ; Spine*