Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.
Journal of Physiology & Pathology in Korean Medicine
/
v.20
no.2
/
pp.460-466
/
2006
We wondered whether the mechanisms of antiplatelet aggregation of DJS-WE were through multiple pathways. Danggijakyak-san(DJS) consisting of 6 herbes of Paeoniae Radix, Poria Cocos, Angelicae Sinensis Radix, Cnidii Rhizoma, Atractylodis Macrocephalae Rhizoma and Alismatis Rhizoma, is a crude mixture of a commonly used Korean herbal medicine. The water extract (DJS-WE) of DJS has been known to have an anti-platelet aggregation activity. We have reported that DJS-WE inhibited ADP-induced aggregation as well as arachidonic acid-induced aggregation of human platelet. Clinical studies on the cardiovascular effects of DJS-WE have been done in Korea. The DJS has been used as a remedy for gastrointestinal disorders (abdominal pain, dysentery), headache, amenorrhea, and postpartum hemorrhage. It has also been claimed to have a remarkable central stimulant effect, a transient hypertensive effect, and positive inotropic and chronotropic effects. In this paper, we evaluated the possible mechanisms of the antiplatelet activity of DJS-WE using human platelets. On the other hand, the role of DJS-ethanol extract on the inhibition of platelet aggregation and hemolytic effect have not yet been investigated in detail. We also used the method of activated partial thromboplastin times (APTT) for the first time to study the inhibition on platelet aggregation activity of DJS-ethanol extract. The effect of DJS-WE on hemolysis was also investigated. DJS-WE showed a high hemolysis ability on human blood.
The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.
Purpose: The aim of this study is to determine the involvement of the upper gastrointestinal system (GIS) in patients diagnosed with Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) and to compare their differences. Methods: This study included patients aged between 2 and 18 years who underwent colonoscopy and esophagogastroduodenoscopy (EGD) for the first time due to the prediagnosis of IBD. In EGD, samples were taken from duodenum, antrum, corpus, and esophagus; and gastritis, duodenitis, and esophagitis were identified through histopathologic examination. The data gathered the ends of the research were compared between IBD with non-IBD groups and between CD-UC with non-IBD groups, and the presence of significant differences between groups were determined. Results: In our study, 16 patients were diagnosed with CD, 13 with UC, 3 with undeterminate colitis, and 13 with non-IBD. In the histopathological examination of the groups, GIS involvement was found in 94.1% of patients diagnosed with IBD and in 38.5% of non-IBD patients. Moreover, the difference was found to be statistically significant (p=0.032). No significant difference was found between the CD and UC groups. Gastritis was mostly observed in 93.8% of CD-diagnosed patients, 76.8% of UC-diagnosed patients, 81.2% of IBD-diagnosed patients, and 38.5% of non-IBD-diagnosed patients. On the other hand, significant differences were found between CD and non-IBD groups (p=0.03), UC and non-IBD groups (p=0.047), and IBD and non-IBD groups (p=0.03). Conclusion: The results of the study show that gastritis was highly observed in UC- and CD-diagnosed patients than in non-IBD-diagnosed patients.
Endoscopic diagnosis and medical management from K43 and C45 patients, whose sex, occupation, character and life patterns are quite different each other, were discussed. The K43 was patient with erosive gastritis, which may caused by maldietary habits and life stresses. Although the effective drugs such as H2-receptor antagonists with atacids, H+/K+-pump inhibitors, prokinetics, colloidal bismuth, and sucralfates, were administrated for long time, symptomatic relief of abdominal pain was not improved. The tests of clinical phathology and abdominal sonogram were normal, visceral hypersensitivity was appeared from barostat test of stomach. However C45 had taken headache during every day life, and endoscopically confirmed as a gastric·duodenal ulcer patiant, which may caused by chronic use of NSAIDs. The her ulceric symptoms were suppressed from active stage to healing stage by using combination therapy for H. pylori with traditional antipeptic ulcer drugs, where as amitriptyline was administrated to the K43 but not effective. Nonulcer dyspepsia and irritable bowel syndrome is pooly defined, and affect about 15% of the population annually in U. S. A. but don't seek medical care. Author would like to point out that statistics for visceral pains are absent in Korea.
This study aims to provide information about the acute poisoning patients transferred by 119 ambulance service for nurses and emergency medical technicians. The data is based on 119 ambulance services patients charts of Seocho area in Seoul. The results were as follows: 1. Total number of emergency patients all over the country has been nearly fourtimes in 1995 compared to 1991. Total number of emergency patients were 322.051 in 1994. 2. About $35\%$ of total E.R. patients were transferred by 119 ambulance services in Seoul in the last 5years. Acute drug intoxication patients occupied $2-3\%$ of E.R. patients in Seoul. 3. About $4\%$ of E.R. patients in Seoul were transferred by 119 E.R. services of Seocho area in Seoul in 1995. Among them $2.4\%$ patients were drug intoxication patients. 4. Data were collected from available patients of 119 ambulance services from Jan. 1993 to Dec. 1995 in Seocho area. Total poisoning patients were 184. - The female/male ratio was 69.7:30.4 and most of patients$(69.7\%)$ were in the age of 20th and 30th. - The busy time of calling 119 ambulance service was from 6P.M. to midnight$(37.5\%)$ - It took within 10 minutes for patients$(62.8\%)$ from notification to arrival in hospital. - Regarding poisoning substances. hypnotics $(22.8\%)$, tranquilizer$(14.7\%)$, agricultural agents$(6.0\%)$ rodenticide$(27\%)$ and others $(10.3\%)$ were in order and unknown were $43.5\%$. - Most of the patients or protector $(72.8\%)$ chose hospitals. Among them $(87.3\%)$ were general hospital. - The most predominant symptoms were coma$(22.3\%)$. dizziness$(6.5\%)$ and then allergy. vomiting. gastrointestinal cramps etc. - Airway management and oxygen administration together was the main medical control of prehospital emergency medical services$(33.7\%)$. It is proposed that first, a systematic survey of drug intoxication patients must be conducted to give an appropriate prehospital emergency care for the emergency medical technician and second, a wide and regular public education to improve understanding of first aids should be undertaken.
Background: Survival rates after resection of advanced gastric cancer are extremely poor. An increasing number of patients with gastric carcinomas (GC) are therefore being treated with preoperative chemotherapy. We evaluated 36 month survival rate of GC patients that were treated by adding a neoadjuvant chemoradiotherapy before gastrostomy.Materials and Methods: Patients with stage II or III gastric adenocarcinomas were enrolled. The patients divided into two groups: (A) Neoadjuvant group that received concurrent chemoradiation before surgery (4500cGy of radiation at 180cGy per day plus chemotherapy with cisplatin and 5-fluorouracil, in the first and the end four days of radiotherapy). Resection was attempted 5 to 6 weeks after end of chemoradiotherapy. (B) Adjuvant group that received concurrent chemo-radiation after surgical resection. Results: Two (16.7%) patients out of 12 patients treated with neoadjuvant chemo-radiotherapy and 5 (38.5%) out of 13 in the surgery group survived after 36 months. These rates were not significantly different with per protocol and intention-to-treat analysis. The median survival time of patients in group A and B were 13.4 and 21.6 months, respectively, again not significantly different. Survival was significantly greater in patients with well differentiated adenocarcinoma in group B than in group A (p<0.004). Conclusions: According to this study we suggest surgery then chemoradiotherapy for patients with well differentiated gastric adenocarcinoma rather than other approaches. Additional studies with greater sample size and accurate matching relying on cancer molecular behavior are recommended.
Background: The efficacy of concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer is well established. We aimed to investigate the long-term efficacy of definitive concurrent chemoradiotherapy for cervical cancer in the University of Malaya Medical Centre. Materials and Methods: A cohort of 60 patients with FIGO stage IB2-IVA cervical cancer who were treated with definitive concurrent chemoradiotherapy with cisplatin followed by intracavitary brachytherapy or external beam radiotherapy (EBRT) boost between November 2001 and May 2008 were analysed. Patients were initially treated with weekly intravenous cisplatin ($40mg/m^2$) concurrent with daily EBRT to pelvis of 45-50Gy followed by low dose rate brachytherapy or EBRT boost to tumour. Local control rate, progression free survival, overall survival and treatment related toxicities graded by the RTOG criteria were evaluated. Results: The mean age was 56. At the median follow-up of 72 months, the estimated 5-year progression-free survival (PFS) (median PFS 39 months) and the 5-year overall survival (OS) (median OS 51 months) were 48% and 50% respectively. The 5-year local control rate was 67.3%. Grade 3-4 late gastrointestinal and genitourinary toxicity occurred in 9.3% of patients. Conclusions: The 5-year PFS and the 5-year OS in this cohort were lower than in other institutions. More advanced stage at presentation, longer overall treatment time (OTT) of more than fifty-six days and lower total dose to point A were the potential factors contributing to a lower survival.
Background: To evaluate treatment outcomes of patients with stage I-III endometrial cancer treated with postoperative radiation. Materials and Methods: A retrospective review of 166 endometrial cancer patients, undergoing surgery and postoperative radiotherapy at Siriraj Hospital from 2005-2008 was performed. Pathology was reviewed. Results of treatment were reported with 5-year loco-regional recurrence free survival (LRRFS), 5-year overall survival (OS), patterns of failure and toxicity, and according to stage and risk groups. Results: Median follow up time was 62.8 months. Pathological changes were found in 36.3% of the patients after central reviews, leading to 19% changes in risk groups. Most of the patients (83.7%) received pelvic radiation (PRT) and vaginal brachytherapy (VBT). Five-year LRRFS and OS of all patients were 94.9% and 85.5%, respectively. There was no recurrence or death in low and low-intermediate risk groups. For the high-intermediate risk group, 5-year LRRFS and OS were 96.2% and 90.8%, respectively, and for the high risk group 90.5% and 71%. Late grade 3 and 5 gastrointestinal toxicity was found in 3% and 1.2% of patients, respectively. All of them received PRT 5,000 cGy in 25 fractions. Conclusions: Low and intermediate risk patients had good results with surgery and adjuvant radiation therapy. For high risk patients, postoperative radiation therapy alone appeared to be inadequate as the most common pattern of failure was distant metastasis.
Background: The value of 5-aminolevulinic acid (ALA) in fluorescence detection of peritoneal metastases and the underlying mechanisms were evaluated in patients with peritoneal surface malignancies. Materials and Methods: Oral 5-ALA was administered at a concentration of 20 mg/kg body weight with 50 ml of water 2 hours prior to surgery (n=115). The diagnostic value of 5-ALA based fluorescence production was evaluated following white light inspection during prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Then, peptide transporter PEPT1 (ALA influx transporter) and ATP-binding cassette transporter ABCG2 (porphyrin efflux transporter) gene expression was determined with quantitative real time (qRT)-PCR and pathological diagnoses confirmed for all tissue samples. Results: The 5-ALA based photodynamic detection rate was 17% for appendiceal mucinous neoplasms, 54% for colorectal cancers, 33% for gastric cancers, 67% for diffuse malign peritoneal mesotheliomas, and 89% for epithelial ovarian cancer of peritoneal metastases. 5-ALA was detected in all cases of peritoneal metastases originating from cholangiocarcinomas whereas it was not able to detect any in granulosa cell and gastrointestinal stromal tumor cases. Furthermore, PEPT1 was overexpressed whereas ABCG2 expression was downregulated in tumors detected with fluorescence. Conclusions: 5-ALA provided 100% specificity and high sensitivity to detect peritoneal metastases in subgroups of patients with peritoneal surface mailgnancies. ALA influx transporter PEPT1 and porphyrin efflux transporter ABCG2 genes are important in tumor specific 5-ALA induced fluorescence in vivo. Further studies should clarify diagnostic utility of 5-ALA in peritoneal surface malignancies.
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