鸦胆子油乳抑制肺癌NCI-H460细胞的增殖及其机制

目的:探讨鸦胆子油乳在体外对人大细胞肺癌NCI-H460细胞的抑制作用及其机制。方法:以不同质量浓度鸦胆子油乳(2.5、5.0、10、20、40、80μg/ml)处理NCI-H460细胞,24、48、72h后收集细胞,MTT法检测鸦胆子油乳对NCI-H460细胞增殖的抑制作用;吉姆萨染色后光学显微镜下观察NCI-H460细胞形态学改变;流式细胞仪测定NCI-H460细胞凋亡率;caspase-3酶活性试剂盒检测NCI-H460细胞caspase-3酶活性。结果:鸦胆子油乳可剂量和时间依赖性抑制NCI-H460细胞的增殖,80μg/ml鸦胆子油乳作用72h时的抑制率达(91.07±1.60)%。鸦胆子油乳作用后,NCI-H460细胞呈现典型凋亡形态学改变;流式细胞术检测结果显示,10、20和40μg/ml鸦胆子油乳作用48h后,NCI-H460细胞凋亡率分别为(45.23±4.30)%、(54.14±3.09)%和(61.57±7.28)%(P<0.01)。鸦胆子油乳可剂量依赖性上调NCI-H460细胞caspase-3酶活性,40μg/ml鸦胆子油乳时caspase-3酶活性为(1.07±0.07)μmol/μg,是对照组的4.97倍(P<0.01)。结论:鸦胆子油乳可能通过活化caspase-3诱导NCI-H460细胞凋亡,抑制NCI-H460细胞增殖。     

Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years

The carcinogenicity of 1,4-dioxane was examined by giving groups of 50 F344/DuCrj rats and 50 Crj:BDF₁ mice of each sex 1,4-dioxane in the drinking-water for 2 years. The concentrations of 1,4-dioxane were 0 (control), 200, 1000 and 5000 ppm (wt./wt.) for rats and 0, 500, 2000 and 8000 ppm for mice. The highest dose levels did not exceed the maximum tolerated dose. In the rat, there was significant induction of nasal squamous cell carcinomas in females and hepatocellular adenomas and carcinomas in males and females, peritoneal mesotheliomas in males, and mammary gland adenomas in females. In the mouse, there was significant induction of hepatocellular tumors in males and females. Two nasal tumors occurring in the 8000 ppm-dosed groups were spontaneously rare and, thus, were attributed to 1,4-dioxane exposure. The present studies provided clear evidence of carcinogenicity in rats and mice. Lifetime cancer risk of humans exposed to 1,4-dioxane through drinking-water was quantitatively estimated with a non-threshold approach by application of a linearized multistage model to dose–carcinogenic response relationships, in addition to a threshold approach for estimation of the tolerable daily intake using no-observed- or lowest-observed-adverse-effect levels of the carcinogenic responses and uncertainty factors.     

Data mining of NCI's anticancer screening database reveals mitochondrial complex I inhibitors cytotoxic to leukemia cell lines

Mitochondria are principal mediators of apoptosis and thus can be considered molecular targets for new chemotherapeutic agents in the treatment of cancer. Inhibitors of mitochondrial complex I of the electron transport chain have been shown to induce apoptosis and exhibit antitumor activity. In an effort to find novel complex I inhibitors which exhibited anticancer activity in the NCI's tumor cell line screen, we examined organized tumor cytotoxicity screening data available as SOM (self-organized maps) (http://www.spheroid.ncifcrf.gov) at the developmental therapeutics program (DTP) of the National Cancer Institute (NCI). Our analysis focused on an SOM cluster comprised of compounds which included a number of known mitochondrial complex I (NADH:CoQ oxidoreductase) inhibitors. From these clusters 10 compounds whose mechanism of action was unknown were tested for inhibition of complex I activity in bovine heart sub-mitochondrial particles (SMP) resulting in the discovery that 5 of the 10 compounds demonstrated significant inhibition with IC50's in the nM range for three of the five. Examination of screening profiles of the five inhibitors toward the NCI's tumor cell lines revealed that they were cytotoxic to the leukemia subpanel (particularly K562 cells). Oxygen consumption experiments with permeabilized K562 cells revealed that the five most active compounds inhibited complex I activity in these cells in the same rank order and similar potency as determined with bovine heart SMP. Our findings thus fortify the appeal of mitochondrial complex I as a possible anticancer molecular target and provide a data mining strategy for selecting candidate inhibitors for further testing.     

Effectiveness of chemotherapy counselling on self-esteem and psychological affects among cancer patients in Malaysia: Randomized controlled trial

Objectives

The aim of this study was to implement and evaluate the outcomes of chemotherapy counselling based on the “Managing Patients on Chemotherapy” module on self-esteem and psychological affect (anxiety, depression) of cancer patients by pharmacists in ten selected government hospitals in Peninsular Malaysia.

Identification of potent anticancer activity in Ximenia americana aqueous extracts used by African traditional medicine

The antineoplastic activity of a plant powder used in African traditional medicine for treating cancer was investigated by analyzing the activity of various extracts in vitro. The most active, aqueous extract was subsequently subjected to a detailed investigation in a panel of 17 tumor cell lines, showing an average IC50 of 49 mg raw powder/ml medium. The sensitivity of the cell lines varied by two orders of magnitude, from 1.7 mg/ml in MCF7 breast cancer cells to 170 mg/ml in AR230 chronic-myeloid leukemia cells. Immortalized, non-tumorigenic cell lines showed a marginal sensitivity. In addition, kinetic and recovery experiments performed in MCF7 and U87-MG cells and a comparison with the antineoplastic activity of miltefosine, gemcitabine, and cisplatinum in MCF7, U87-MG, HEp2, and SAOS2 cells revealed no obvious similarity between the sensitivity profiles of the extract and the three standard agents, suggesting a different mechanism of cytotoxicity. The in vivo antitumor activity was determined in the CC531 colorectal cancer rat model. Significant anticancer activity was found following administration of equitoxic doses of 100 (perorally) and 5 (intraperitoneally) mg raw powder/kg, indicating a 95% reduced activity following intestinal absorption. By sequencing the mitochondrial gene for the large subunit of the ribulose bis-phosphate carboxylase (rbcL) in DNA from the plant material, the source plant was identified as Ximenia americana. A physicochemical characterization showed that the active antineoplastic component(s) of the plant material are proteins with galactose affinity. Moreover, by mass spectrometry, one of these proteins was shown to contain a stretch of 11 amino acids identical to a tryptic peptide from the ribosome-inactivating protein ricin.     

Weight indicators and nutrient intake in children and adolescents do not vary by sugar content in ready-to-eat cereal: results from National Health and Nutrition Examination Survey 2001-2006

Few studies have explored the relationship between sugar content in cereal and health outcome among children and adolescents. This study was designed to investigate the associations between ready-to-eat cereals, categorized by sugar content, with weight indicators and nutrient intake profiles. Data collected from 6- to 18-year-old US children and adolescents (N = 9660) in the National Health and Nutrition Examination Survey 2001-06 were used to analyze cereal consumption. Body mass index (BMI), BMI-for-age, waist-to-height ratio, percent overweight or obese, mean day-1 intake, and usual daily intake of macronutrients and micronutrients were the dependent variables; day-1 cereal intake, categorized by tertiles of sugar content, was the main independent variable. Weighted regression with adjustment for the survey design was used to model the dependent variables as a function of day-1 cereal intake, adjusting for age group, sex, race/ethnicity, total day-1 intake of energy, calcium and sugar, the Healthy Eating Index-2005 total score, and household income. For all tertiles of sugar classifications of cereal, children who consumed cereal had significantly lower BMI compared with children who consumed no cereal (P's < .05). Similarly, when compared with children who consumed no cereal, those who ate cereal consumed significantly less fat and cholesterol and significantly more carbohydrates, sugar, whole grains, vitamin A, thiamin, riboflavin, niacin, vitamin B₆, folic acid, vitamin B₁₂, vitamin C, calcium, magnesium, iron, and zinc. Lower weight and positive nutrient profiles were associated with cereal consumption regardless of sugar content.     

One hundred percent orange juice consumption is associated with better diet quality, improved nutrient adequacy, and no increased risk for overweight/obesity in children

The purpose of this study was to examine the association of 100% orange juice (OJ) consumption by children 2 to 18 years of age (n = 7250) participating in the 2003 to 2006 National Health and Nutrition Examination Survey with intakes of select nutrients, MyPyramid food groups, diet quality—measured by the Healthy Eating Index-2005, weight status, and associated risk factors. The National Cancer Institute method was used to estimate the usual intake of 100% OJ consumption, selected nutrients, and MyPyramid food groups. Percentages of the population below the Estimated Average Requirement were determined. Covariate adjusted logistic regression was used to determine if consumers had a lower odds ratio of being overweight or obese. Usual per capita intake of 100% OJ was 1.7 oz/d. Among consumers, the usual intake of 100% OJ for children (n = 2183; 26.2% of population) was 10.2 oz/d. Consumers had higher (P < .05) energy intakes than nonconsumers (9148 ± 113 vs 8625 ± 473 kJ). However, there were no differences in weight or body mass index in consumers and nonconsumers, and there was no significant difference in the risk of being overweight or obese between consumers and nonconsumers (odds ratio, 0.86; 95% confidence interval, 0.70-1.05). Compared with nonconsumers, consumers had a higher (P < .01) percentage (% ± SE) of the population meeting the Estimated Average Requirement for vitamin A (19.6 ± 2.0 vs 30.2 ± 1.4), vitamin C (0.0 ± 0.0 vs 29.2 ± 1.2), folate (1.3 ± 0.3 vs 5.1 ± 0.6), and magnesium (25.5 ± 2.0 vs 39.0 ± 11). The Healthy Eating Index-2005 was significantly (P < .01) higher in consumers (52.4 ± 0.4 vs 48.5 ± 0.3). Consumers also had higher intakes of total fruit, fruit juice, and whole fruit. Moderate consumption of 100% OJ should be encouraged in children as a component of a healthy diet.     

NCI Summer Curriculum in Cancer Control and Prevention – A Practice Changing Course for Oncologists from Limited Resource Country Like India

Cancer has become an important public health issue in India. Oncologists in India spends most of their time indiagnosis and treatment of cancer patients. There is a large disparity geographically as far as cancer treatment facilitiesare concerned. Cancer control and cancer prevention is not a point of concern for most of the practicing oncologist.Although things are changing in India, but orientation, passion and dedication towards cancer prevention is still missing.There is no program on basic principles and practice of cancer control and prevention in India which addresses theessence of cancer control and prevention. Center for Global Health of National Cancer Institute, USA initiated summercurriculum is an excellent academic program to teach health care professionals working in cancer care in different partsof world. This covers all aspect of cancer care i.e. cancer education, epidemiology, screening, diagnosis, treatmentand the before world palliative care with dedicated session on upcoming molecular prevention in cancer. This givesan unique opportunity for learning and can be practice changing curriculum for many of the attendees who want topursue a career in cancer control and prevention a before practice.