No abstract availble.
Anticarcinogenic Agents/*therapeutic use ; Aspirin/*therapeutic use ; Colonic Neoplasms/*prevention & control ; Humans

OBJECTIVE: To investigate the inhibitory effect of genistein on activation of hepatic stellate cells (HSCs) and the role of the autophagy pathway regulated by PPAR-γ in mediating this effect. METHODS: Cultured HSC-T6 cells were exposed to different concentrations of genistein for 48 h, and HSC activation was verified by detecting the expressions of -SMA and 1(I) collagen; autophagy activation in the cells was determined by detecting the expressions of LC3-II and p62 using Western blotting. The autophagy inhibitor 3-MA was used to confirm the role of autophagy in genistein-induced inhibition of HSC activation. A PPAR-γ inhibitor was used to explore the role of PPAR-γ in activating autophagy in the HSCs. RESULTS: Genistein at concentrations of 5 and 50 μmol/L significantly inhibited the expressions of -SMA and 1(I) collagen ( < 0.05), markedly upregulated the expressions of PPAR-γ and the autophagy-related protein LC3-II ( < 0.05) and significantly down-regulated the expression of the ubiqutin-binding protein p62 ( < 0.05) in HSC-T6 cells. The cells pretreated with 3-MA prior to genistein treatment showed significantly increased protein expressions of -SMA and 1(I) collagen compared with the cells treated with genistein only ( < 0.05). Treatment with the PPAR-γ inhibitor obviously lowered the expression of LC3-II and enhanced the expression p62 in genistein-treated HSC-T6 cells, suggesting the activation of the autophagy pathway. CONCLUSIONS PPAR-γ- regulated autophagy plays an important role in mediating genistein-induced inhibition of HSC activation .
Anticarcinogenic Agents ; pharmacology ; Autophagy ; Collagen Type I ; Genistein ; pharmacology ; Hepatic Stellate Cells ; Humans ; PPAR gamma ; physiology

Basal autophagy plays a critical role in maintaining cellular homeostasis and genomic integrity by degrading aged or malfunctioning organelles and damaged or misfolded proteins. However, autophagy also plays a complicated role in tumorigenesis and treatment responsiveness. It can be tumor-suppressing during the early stages of tumorigenesis (i.e., it is an anti-tumor mechanism), as reduced autophagy is found in tumor cells and may be associated with malignant transformation. In this case, induction of autophagy would seem to be beneficial for cancer prevention. In established tumors, however, autophagy can be tumor-promoting (i.e., it is a pro-tumor mechanism), and cancer cells can use enhanced autophagy to survive under metabolic and therapeutic stress. The pharmacological and/or genetic inhibition of autophagy was recently shown to sensitize cancer cells to the lethal effects of various cancer therapies, including chemotherapy, radiotherapy and targeted therapies, suggesting that suppression of the autophagic pathway may represent a valuable sensitizing strategy for cancer treatments. In contrast, excessive stimulation of autophagy may also provide a therapeutic strategy for treating resistant cancer cells having high apoptotic thresholds. In order for us to develop successful autophagy-modulating strategies against cancer, we need to better understand how the roles of autophagy differ depending on the tumor stage, cell type and/or genetic factors, and we need to determine how specific pathways of autophagy are activated or inhibited by the various anti-cancer therapies.
Anticarcinogenic Agents/therapeutic use ; Autophagy/*physiology ; Cell Transformation, Neoplastic/drug effects ; Humans ; Neoplasms/*drug therapy/metabolism/*pathology

This study was performed to evlauate the usefulness of red ginseng extract as an adjuvant therapeutic agent to improve immune function in immune compromizing gastrointestinal carcinoma patients. We treated 48 patients with two regimens after we undertook the curative resection for gastrointestinal carcinoma: 1) only chemotherapy and immunotherapy (control group), 2) chemotherapy and immunotherapy with 4500-5400mg red ginseng for 6 months (study group). For investigating the immunologic alternations alongside the numerical changes in peripheral blood lymphocyte and their subsets in the gastrointestinal carcinoma patients, lymphocyte surface markers were determined by monoclonal antibodies on the preoperative 1st day, and postoperative 5th day, 1 month, 3 month and 6 month in 28 controls and 20 red ginseng groups in gastrointestinal carcinoma patients which were recruited at Korea University Hospital from March, 1995 to December, 1995. The mean value for body weight was increased in the ginseng group than in the control group. There were no significant differences of serum hematocrit, hemoglobin, total protein and albumin in both groups. The total lymphocyte count was much more increased in the ginseng group than in the control group. The number of T cell, B cell, CD8, CD4, NK cell and activated T cell were increased in ginseng group more than in control group. The T cell was significantly increased on postoperative 5th day, 3 month and 6 month, and B cell on postoperative 6 month in ginseng group than in control group. The CD8 was significantly increased on postoperative 3 month and 6 month, CD4 on postoperative 5th day, and NK cell and activated T cell also on postoperative 6 month in ginseng group than in control group. In conclusion, red ginseng may be useful as a longterm adjuvant therapeutic agent for improving the immune function and anticarcinogenic effect after curative operation for immune compromizing gastrointestinal carcinoma patients.
Antibodies, Monoclonal ; Anticarcinogenic Agents ; Body Weight ; Drug Therapy ; Hematocrit ; Humans ; Immunotherapy ; Killer Cells, Natural ; Korea ; Lymphocyte Count ; Lymphocytes ; Panax*

AIMTo study the pharmacokinetics of genistein in Beagle dogs.

METHODSGenistein, suspended in 0.5% CMC-Na solution, was orally administered to Beagle dogs at the dose of 5.34 mg.kg-1. At various time intervals, 1.5 mL of blood was drawn from the vein of dogs in their front legs. At the same time, urine and feces were collected. After the collection, the feces were homogenized with physiological saline (to 1 g feces, 10 mL physiological saline were added). The genistein in plasma, urine and homogenized feces was extracted twice by vortexing with 2.0 mL mixture of methyl tert-butyl ether and pentane (8:2). The organic phase was transferred into tubes and evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol and 20 microL of the solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameter was calculated by 3P97 software.

RESULTSThe plasma concentration-time curve was fitted to a one-open-compartment model. The peak time was 0.29 h, and the elimination half-life was 0.52 h. After genistein was administered, 10.79% of genistein were excreted from urine and 21.55% from feces within 24 h. It was also found that 13.00% genistein were excreted from urine and 52.46% from feces within 60 h.

CONCLUSIONIt showed that the speed of absorption and elimination of genistein was high in Beagle dog, and genistein was mainly excreted in the form of parent compound in urine and feces.

Animals ; Anticarcinogenic Agents ; blood ; pharmacokinetics ; urine ; Area Under Curve ; Chromatography, High Pressure Liquid ; Dogs ; Feces ; chemistry ; Genistein ; blood ; pharmacokinetics ; urine

In the western world, prostate cancer is a most common malignant neoplasm in human males. In recent years, its incidence has been rising dramatically in China. Prevention of this disease would have a positive impact on the disease-related cost, morbidity, and mortality for a large portion of the population. Cancer chemoprevention is defined as the use of natural, synthetic or biologic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. This article reviews the progress in chemoprevention of prostate cancer.
Aged ; Aged, 80 and over ; Anticarcinogenic Agents ; therapeutic use ; Chemoprevention ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; prevention & control

The development of gastric cancer is a multi-factor process. In addition to genetic factors, environmental factors including smoking, low gastric acidity, excessive intake of salt or salty food and low consumption of fresh fruits and vegetables all contribute to the development of gastric cancer. Of particular interest, epidemiological and experimental studies have demonstrated that Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. Most studies using micronutrient supplementation have failed to demonstrate any preventive effect against the development of gastric cancer. The use of non-steroidal anti-inflammatory drugs has been consistently observed to protect against the development of gastric cancer. Recently, eradication of H. pylori infection by a chemopreventative approach is being studied in a number of trials. Studies using precancerous lesions as an end point of the treatment have produced conflicting and mostly negative results. Trials using cancer as an end point are being cautiously carried out in high-risk populations, and will provide the definitive answer to this important question. In the end, vaccination may be proven to be the optimal strategy in human for the management of H. pylori infection and prevention of gastric cancer.
Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Anticarcinogenic Agents ; therapeutic use ; Dietary Supplements ; Helicobacter Infections ; complications ; drug therapy ; prevention & control ; Humans ; Stomach Neoplasms ; etiology ; prevention & control ; Vaccination

Mangosteen (Garcinia mangostana Linn.) is a well-known tropical tree indigenous to Southeast Asia. Its fruit's pericarp abounds with a class of isoprenylated xanthones which are referred as mangostins. Numerous in vitro and in vivo studies have shown that mangostins and their derivatives possess diverse pharmacological activities, such as antibacterial, antifungal, antimalarial, anticarcinogenic, antiatherogenic activities as well as neuroprotective properties in Alzheimer's disease (AD). This review article provides a comprehensive review of the pharmacological activities of mangostins and their derivatives to reveal their promising utilities in the treatment of certain important diseases, mainly focusing on the discussions of the underlying molecular targets/pathways, modes of action, and relevant structure-activity relationships (SARs). Meanwhile, the pharmacokinetics (PK) profile and recent toxicological studies of mangostins are also described for further druggability exploration in the future.
Animals ; Anti-Infective Agents ; pharmacology ; Anticarcinogenic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antioxidants ; pharmacology ; Cardiovascular Agents ; pharmacology ; Fruit ; chemistry ; Garcinia mangostana ; chemistry ; Humans ; Neuroprotective Agents ; pharmacology ; Phytotherapy ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Xanthones ; pharmacology

Adult ; Anticarcinogenic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Disease Progression ; Female ; Humans ; Interdisciplinary Communication ; Neoplasm Staging ; Pregnancy ; Pregnancy Complications, Neoplastic ; drug therapy ; pathology ; Treatment Outcome

Anticarcinogenic Agents ; pharmacology ; therapeutic use ; Diterpenes, Abietane ; Humans ; Medical Oncology ; methods ; trends ; Medicine, Chinese Traditional ; methods ; trends ; Neoplasm Metastasis ; prevention & control ; Neoplasms ; drug therapy ; Phenanthrenes ; pharmacology ; therapeutic use