PREFACE

No abstract available.

Brief Introduction of Panax ginseng C.A. Meyer

For many many thousand years, mankind has been using various plants as nutrient, beverage, cosmetics, dye and medicine to maintain health and to improve quality of life. In Aisa, particularly, Panax ginseng C.A. Meyer is considered to be the most precious plant among herbs, and ginseng has been in the spotlight worldwide. Even in the Western world, where there are greatly advanced research facilities and highly qualified man-power available, and are regarded to be capable of conquering any hard-to-cure ailments, many peoples has recently been reported to use herbal medicine, particularly ginseng. In the present compilation of papers, many scientists contributed papers pertaining to "Chemopreventive effects of ginseng". In order to facilitate the readers understand easier and better, I catalogued this collection as follows: The spiritual nature of ginseng in the Far East, the history of ginseng, nomenclature and geographical distribution of ginseng, and type of ginseng products.

Anticarcinogenic Effect of Panax ginseng C.A. Meyer and Identification of Active Compounds

The failure to improve the five-year survival rate of cancer patients, from one in three in the 1960s to one in two in the 1970s, stimulated awareness of the importance of primary prevention of cancer. Korean investigators carried out extensive long-term anticarcinogenicity experiments with 2000 newborn mice to investigate whether Panax ginseng C.A. Meyer inhibited carcinogenesis induced by several chemical carcinogens in 1978. There was a 22% decrease (p<0.05) in the incidence of urethane induced lung adenoma by the combined use of red ginseng extract. In the group sacrificed at 56 weeks after the treatment with aflatoxin B1, the incidence of hepatoma significantly decreased to 75% by the addition of red ginseng extract (p<0.05). The result showed that natural products can provide hope for human cancer prevention. By the newly established '9 week medium-term anticarcinogenicity test model of lung tumors in mice' (Yun's model), we confirmed significant anticarcinogenic effects of powders and extracts of the 6- yr-old dried fresh ginseng, 5- and 6-yr old white ginsengs, and 4-, 5-, and 6-yr old red ginseng. We also demonstrated that the anticarcinogencity of ginseng was more prominent in aged or heat treated extracts of ginseng and red ginseng made by steaming. To investigate the active components for cancer prevention, several fractions of 6-yr old fresh ginseng and red ginseng, four semi-synthetic ginsenoside Rh1, Rh2, Rg3 and Rg5, major saponin components in red ginseng, were prepared. Among the ginsenosides, Rg3 and Rg5 showed statistically significant reduction of lung tumor incidence and Rh2 had a tendency of decreasing the incidence. Ginsenoside Rg3, Rg5 and Rh2 were found to be active anticarcinogenic compounds. Rg3, Rg5 and Rh2 are active components in red ginseng, and they prevent cancer either singularly or synergistically.

Epidemiological Study on Cancer Prevention by Ginseng: Are All Kinds of Cancers Preventable by Ginseng?

In the light of experimental results, two case-control studies and one cohort study in a population of ginseng cultivation area were conducted to confirm whether ginseng has any anticarcinogenic effect on human cancers. All participants were interviewed using a standardised questionnaire to obtain the information on demographics, cigarette smoking, alcohol consumption and ginseng intake. In 905 pairs case-control study, 62% had a history of ginseng intake compared to 75% of the controls, a statistically significant difference (p<0.01). The odds ratio (OR) for cancer in relation to ginseng intake was 0.56. In extended case-control study with 1987 pairs, the ORs for cancer were 0.37 in fresh ginseng extract users, 0.57 in white ginseng extract users, 0.30 in white ginseng extract users, 0.30 in white ginseng powder users, and 0.20 in red ginseng users. Those who took fresh ginseng slices, fresh ginseng juice, and white ginseng tea, however, did not show decrease in the risk. Overall, the risk decreased as the frequency and duration of ginseng intake increased. With respect to the site of cancer, the ORs for cancers of the lip, oral cavity, pharynx, esophagus, stomach, colorectum, liver, pancreas, larynx, lung and ovary were significantly reduced by ginseng intake. Smokers with ginseng intake showed lower ORs for cancers of lung, lip, oral cavity and pharynx and liver than those without ginseng intake. In 5 yr follow- up cohort study conducted in the ginseng cultivation area, Kangwha-eup, ginseng intakers had significantly lower risk than non-intakers. As for the type of ginseng, cancer risk significantly decreased among intakers of fresh ginseng extract, alone or together with other ginseng preparations. Among 24 red ginseng intakers, no cancer death occurred during the follow-up period. The risk for stomach and lung cancers was significantly reduced by ginseng intake, showing a statistically significant dose-response relationship in each follow-up year. In conclusion, Panax ginseng C.A. Meyer has been established as non-organ specific cancer preventive, having dose response relationship. These results warrant that ginseng extracts and its synthetic derivatives should be examined for their preventive effect on various types of human cancers.

The Cancer-preventive Potential of Panax ginseng: A Review of Human and Experimental Evidence / 예방의학회지

OBJECTIVE: We have reviewed the potential cancer preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in oriental countries. DATA IDENTIFICATION AND STUDY SELECTION: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-2000) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were also considered. RESULTS: Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

A Phase 2 Trial of Verapamil for Reversal of Drug Resistance in Refractory Non - Hodgkin's Lymphoma / 대한암학회지

PURPOSE: Drug resistance is one of the major obstacles to treatment of cancer. Multidrug resistance (MDR) caused by overexpression of p-glycoprotein (Pgp) in cancer cell membrane is a well-known mechanism of drug resistance in in vitro system and was reported to be a significant mechanism of resistance in non-Hodgkins lymphoma (NHL). Verapamil, a calcium channel blocker, is proven in vitro to overcome the MDR caused by Pgp. We performed a phase II trial of verapamil in patients with NHL refractory to EPOCH regimen (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) to overcome the MDR caused by Pgp. MATERIALS AND METHODS: Verapamil was administered via intravenous route from 1 hour before to 12 hour after the 96-hour infusion of etoposide, doxorubicin, and vincristine which were known to be substrates of Pgp in EPOCH regimen. The dose of verapamil was 0.15 mg/Kg in bolus and 0.2 mg/Kg/hr in infusion at the beginning and escalated by 0.05 mg/Kg/hr every 24 hours if there was no dose-limiting toxicities such as 2nd or 3rd degree AV block, hypotension, or congestive heart failure. Plasma verapamil concentrations were measured every 24 hour by gas chromatography. Mdrl expression level in tumor tissues was measured by RT-PCR. RESULTS: From Feb. to Nov. 1994, 14 patients were treated with this protocoL However, poor tolerability and no response in these patients led to early closure of the study at this 1st stage of patient accrual according to Gehans method. Among 14 patients, 12 experienced 2nd or 3rd degree AV block and/or hypotension and required temporary cessation of infusion and reduction of verapamil dose. However, there was no congestive heart failure or treatment-related death. The peak concentrations of verapamil were 0.29-1.94 pM (mean 0.93 pM) and mean concentrations during the 4-day infusion were 0.22-1.21 pM (mean 0.6 pM). Mdrl expression levels measured in 6 patients were 0.99-14.43 U (median 4.39). CONCLUSION: These results suggest that verapamil in this dose and schedule was neither tolerable nor effective for the reversal of drug resistance in NHL patients.

Transarterial Chemoembolization ( TACE ) for Hepatocellular carcinoma: Comparison of Adriamycin alone vs . Cisplatin alone vs . Adriamycin + Cisplatin / 대한암학회지

PURPOSE: Although transarterial chemoembolization (TACE) has been widely used for the treatment of unresectable hepatocellular carcinoma, it has not been determined yet which chemotherapeutic agents were best for TACE. To determine the best chemotherapeutic regimen for TACE, we performed a prospective randomized study comparing 3 chemo- therapeutic regimen (adriamycin alone vs. cisplatin alone vs. adriamycin + cisplatin). MATERIALS AND METHODS: The patients with unresectable hepatocellular carcinoma were eligible for this study and were randomly assigned to three treatment groups (A: adriamycin 30 mg/m(2), B: cisplatin 60 mg/m(2), C: adriamycin 30 mg/m(2) + cisplatin 60 mg/m(2)). The TACE were performed by administering the mixture of lipiodol and the assigned chemotherapeutic drugs through the hepatic artery, followed by embolization with gelfoam powder. The treatment was planned to be repeated every 4 weeks. RESULTS: After 40 patients (14 in group A, 16 in group B, 10 in group C) entered, the study was stopped prematurely because of serious treatment-related complications including 15% of local complications, 18% of hepatic encephalopathy, and 8% of deaths. Because TACE could result in necrosis without reduction of mass size, the response could not be evaluated by the change of mass size, but by the change of serum alpha-fetoprotein level. Of 25 patients who had elevated serum alpha-fetoprotein and were assessable for response, there were one complete response (CR) and 5 partial responses (PR) out of 10 in group A, 5 PRs out of 10 in group B, and 2 PRs out of 5 in group C. There was no difference in response rates among the 3 treatment groups (p > 0.05). The response rate in patients treated with gelform embolization was higher than patients without embolization (63% (12/19) vs 19% (1/6): p<0.05). The median survival (OS) was 23 weeks for all 40 patients, 15 weeks for group A, 42 weeks for group B and 24 weeks for group C. The difference of OS between group A and B was statistically significant (p=0.02). However, the OS was not associated with any prognostic factors including treatment group in multivariate analysis. CONCLUSION: Although cisplatin seemed to be more effective in TACE than adriamycin, no firm conclusion could be drawn from this prematurely ended study. However, we could conclude that the TACE with gelform powder is so toxic that it could not be given safely to the patients with unresectable hepatocellular carcinoma

A Phase 2 Trial of PEF ( Cispatin , Etoposide , 5-Fluorouracil ) Chemotherapy for Metastatic Stomach Cancer / 대한암학회지

PURPOSE: To determine the activity and toxicities of PEF (Cisplatin, Etoposide, 5-Fluorouracil) chemotherapy for stomach cancer. MATERIALS AND METHODS: Patients with previously untreated metastatic stomach cancer were treated with PEF regimen which consisted of cisplatin (20 mg/m2 i.v. days 1~5), etoposide (100 mg/m2 i.v. days 1, 3, 5), and 5-fluorouracil (5-FU)(800 mg/m2 i.v. infusion for 12 hours days 1~5). Chemotherapy was repeated every 3 weeks until disease progressed or toxicities were intolerable. RESULTS: Between May 1989 and July 1990, 40 patients were enrolled in this protocol. Twelve patients were lost to follow up after one cycle of chemotherapy and inevaluable. After 2~8 cycles (median 3) of chemotherapy, 20 out of 28 evaluable patients showed objective responses without any complete response, making the response rate 71% (95% confidence interval: 54~89%). The responses lasted from 4+ to 39 weeks (median: 38 weeks). The overall survival of total evaluable patients was 4+ ~50+ weeks (median 38 weeks). Among total 109 cycles of chemotherapy, cycles were delayed or doses were reduced in 48 cycles (44%) because of leukopenia (in 61 cycles: 56%) and/or thrombocytopenia (in 14 cycles: 13%). However, there was no treatment-related death. Nausea/vomiting and alopecia were experienced in most of patients. The stomatitis was experienced in 7 patients (25%) but completely reversible. In contrast, the peripheral neuropathy which developed in 4 patients (14%) after 5 cycles of chemotherapy was not reversible. CONCLUSION: The PEF regimen was active and tolerable in stomach cancer.

A Phase 2 Trial of EPOCH (Etoposide, Vincristine, Doxorubicin, Cyclophophamide and Prednisolone) Chemotherapy for Previously Treated Non - Hodgkin's Lymphoma / 대한암학회지

PURPOSE: As a new strategy to modulate drug resistance in the treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL), continuos infusion of drugs has been incorporated into the chemotherapy. We conducted a phase II study to determine the activity and safety of EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisolone) chemotherapy, in which the natursl products are administered as a continuous infusion, for previously treated NHL's of intermediate grade. MATERIALS AND METHODS: EPOCH chemotherapy (etoposide 50 mg/m2/day 24 hour- continuous infusion, days 1~4, vincristine 0.4 mg/m2/day 24 hour-continuous infusion, days 1~4, doxorubicin 10 mg/m2/day 24 hour-continuous infusion, days 1~4, cyclophosphamide 750 mg/m2 i.v., day 5, prednisolone 60 mg/m2/day p.o. days 1-5) was given to eligible patients every 3 weeks and we assessed response and toxicity of the regimen. RESULTS: Between June 1993 and December 1995, total 56 patients entered this trial and 49 were evaluable. The complete response rate was 41%(95% C.I.: 27-55%). After follow up of 9~50(median 38) months, progression free survival was 0~39+(median 7) months and the overall survival was 1~44+(median 14) months. The prognostic factor analyses showed that B symtoms and serum LDH level before treatment and response to previous treatment affected complete response rate, and patients' performance status and response to previous treatment affected progression free survival and overall survival. Toxicities of EPOCH regimen were leukopenia, stomatitis, nausea/vomiting and neurotoxicity, but they were tolerable. There was 1 case of treatment-related death due to sepsis. CONDUSION: EPOCH chemotherapy was safe and effective for the patients with relapsed NHL. However, the results of patients with NHL refractory to previous treatment were so poor that more intensive, novel treatment would be needed for this category of patients.

Preventive effect of ginseng intake against various human cancers: a case-control study on 1,987 pairs / 한국역학회지

No abstract available.

Uranyl Nitrate Induced Polyuric Acute Tubular Necrosis in Rats

We investigated the pathobiological course of uranyl nitrate (UN) induced polyuric acute tubular necrosis (ATN) in male Sprague Dawley rats. UN (5mg/kg 15mg/kg and 3Omg/kg) in 5% NaHCO3 induced weight loss, polydipsia, and polyuria 24 hrs after injection when compared to the controls which were treated with 5% NaHCO3 only. Twenty four hours following the injection of UN, serum creatinine and blood urea nitrogen levels had increased. These changes continued for at least 72 hours, although the concentration of uranium had decreased. Light microscopic studies conducted 24 hours after injection, revealed partial degeneration and necrosis of the proximal tubules and many casts m the distal convoluted tubules. These changes progressed for 72 hours. Despite this tubular damage, the glomeruli were relatively intact. 5 days after injection, the epithelial cells lining the proximal tubules displayed regenerative activities; these findings were more prominent after 10 days. Through electron microscopic examination, we observed the destruction of mitochondria in the proximal tubular cells, a possible cause of polyuria. Ten days post injection regenerative activities in the proximal tubular cells showed that the maturation of intracellular organelles followed the proliferation of the premature cells.

High Activities of Protein Kinases C and M in Fresh Human Stomach and Breast Tumors

The activities of Ca+2-PL dependent protein Kinase (PKC) and independent protein kinase(RKM) were measured in human stomach and breast tumors and in the respective counterparts of normal tissue. Expression of c-fos and c-myc of the tissues were also measured. RNAs of c-fos and c-myc were unexpectedly high in the tissue from normal stomach and breast as well as in all cancer tissue. On the other hand, cytosolic and particulate PKC activities were higher in the tumors as compared to those of normal controls. Notably, some cases exhibited. altered activities of PKC i.e. increased RKM activities as high as RKC, which might be related to the autocrine control of growth in the tumor mass.