Reversion of p-glycoprotein-mediated multidrug resistance in human leukemic cell line by diallyl trisulfide.

Multidrug resistance (MDR) is the major obstacle in chemotherapy, which involves multiple signaling pathways. Diallyl trisulfide (DATS) is the main sulfuric compound in garlic. In the present study, we aimed to explore whether DATS could overcome P-glycoprotein-(P-gp-)mediated MDR in K562/A02 cells, and to investigate whether NF-κB suppression is involved in DATS-induced reversal of MDR. MTT assay revealed that cotreatment with DATS increased the response of K562/A02 cells to adriamycin (the resistance reversal fold was 3.79) without toxic side effects. DATS could enhance the intracellular concentration of adriamycin by inhibiting the function and expression of P-gp, as shown by flow cytometry, RT-PCR, and western blot. In addition, DATS resulted in more K562/A02 cell apoptosis, accompanied by increased expression of caspase-3. The expression of NF-κB/p65 (downregulation) was significantly linked to the drug-resistance mechanism of DATS, whereas the expression of IκBα was not affected by DATS. Our findings demonstrated that DATS can serve as a novel, nontoxic modulator of MDR, and can reverse the MDR of K562/A02 cells in vitro by increasing intracellular adriamycin concentration and inducing apoptosis. More importantly, we proved for the first time that the suppression of NF-κB possibly involves the molecular mechanism in the course of reversion by DATS.

Association of genetic polymorphisms of aldehyde dehydrogenase-2 with esophageal squamous cell dysplasia.

AIM: To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and esophageal squamous cell dysplasia (ESCD). METHODS: All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination; biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology. Based on the examinations, the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group. ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls. The odds ratio (OR) and 95% confidence intervals (95% CI) were calculated by binary logistic regression models. RESULTS: The distribution of ALDH2 genotypes showed significant differences between the two groups. The adjustment factors were gender and age in the logistic regression models. Compared with 2*2/2*2 genotype, 2*1/2*1 genotype was found to be a risk factor for ESCD, and the OR (95% CI) was 4.50 (2.21-9.19). There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer. CONCLUSION: The ALDH2 polymorphism is significantly associated with ESCD.

The association between serum levels of oxLDL-lgG and oxLDL-lgM autoantibody with adult acute myeloblastic leukaemia.

AIM: To evaluate the relationship between serum antibodies against ox-LDL levels and adult acute myeloblastic leukemia (AML). METHODS: Forty three patients with AML and 52 normal controls were enrolled in this study in the Department of Hematology, Tumor Center of Qilu Hospital of Shandong University from Feb. 2008 to Mar.2009. Serum lgG and lgM antibodies versus the oxLDL levels were evaluated by ELISA method. Data was analyzed by covariance and binary Logistic regression. RESULTS: Serum mean levels of oxLDL-lgG in patients (38.92 +/- 21.1259 ug/ml) were significantly lower than in control subjects (78.88 +/- 9.3705 ug/ml); Meanwhile, Serum mean levels of oxLDL-lgM in patients (20.53 +/- 10.2990 IU/L) were significantly higher than in control subjects (10.29 +/- 10.5771 IU/L). Binary logistic regression showed the odds ratios of association of oxLD-lgG and oxLD-lgM with adult AML were 0.72(95%CI: 0.55-0.94) and 1.11(95%CI: 1.01-1.21) respectively after adjusted for potential confounders. CONCLUSION: In the preliminary investigation we found a descensive oxLDL- lgG and an elevated oxLDL-lgM serum levels for the adult AML. Future studies need to confirm the hypothesis whether they related to the development and progression of adult AML.

[Time trends on the prevalence of cancer during 1970-2005 in Shandong province].

OBJECTIVE: To analyze time trend of cancer during 1970-2005 in Shandong province so as to develop strategies for control and prevention of cancer at the community level. METHODS: Data was from 4 retrospective surveys regarding all causes of death during 1970-1974, 1985-1989, 1990-1992 and 2004-2005, in Shandong province. Other than one set of data collected in 1985-1989 by Shandong province itself, the other 3 set of data were from the national surveys, in which the survey-point sampling of choice was based on data of 1970-1974 for assessing its representativeness. The observing indices would include standardized mortality and mortality. A join-point regression model was used to analyze the changing rate of tumor. RESULTS: The mortality rate of the entire tumor increased 143.15 percent in 2005 than in 1970. The changing slope of standardized rate of all tumors in the regression model showed that the inter-annual growth rate were 0.54 and 1.24 percent from 1970 to 1984 and from 1985 to 1992. The rate of increase since 1992 had been 0.18 percent. During 2004-2005, the main malignant cancers were lung, stomach, liver, esophageal, colorectal, leukemia, breast and cervical cancer, in order. Lung cancer rose from the 4th ranking to the first while cervical cancer dropped from the fifth ranking to the 8th place. Esophageal cancer and cervical cancer were decreased annually while gastric cancer was increased in the early days but decreased later on. The rest of the cancers were on the rise year by year. Rates of lung and breast cancers were higher while gastric and esophageal cancers were lower seen in the urban than in rural areas. CONCLUSION: In Shandong province, a marked increase was seen in the mortality rate of tumors in the past 35 years. Evidence showed that the spectrum of death among main malignant tumors had changed which might provide a scientific basis for the development of a community-based prevention and control program on cancer.

[The distribution of the pre-cancerous condition and pathological changes of esophageal cancer of the community residents in high-incidence area].

OBJECTIVE: To observe the distribution of the pre-cancerous condition and pathological changes of esophageal cancer of the community residents in high-incidence area, and to provide etiological evidences for secondary prevention. METHODS: An iodine-staining endoscope census was conducted in 9536 residents with high-risk factors at Feicheng, a high esophageal cancer incidence community in Shandong province. Of which, 1507 pathologic biopsies were performed and chi2 test administrated. RESULTS: There was no statistical significance found in biopsy pathologic diagnosis between females and males among 1507 samples. The mild and medium atypical hyperplasia was taken as pre-cancerous condition and severe atypical hyperplasia was taken as pre-cancerous lesion. Taking all the population attending census as denominator, the detection rate of the precancerous state and precancerous lesion were 6.98% (294/4214) and 1.23% (52/4214) for the males, and 3.68% (196/5322) and 0.47% (25/5322) for the females, respectively. A statistical significance was observed when comparing males with females (chi2 were 52.349 and 15.267, respectively, P < 0.05). Analyzed by age group, severe atypical hyperplasia pathological changes were mainly distributed in the age group of 50- and 65-. The constituent ratio between 45 - and 50 - was the highest for CIS. Early carcinoma was mainly distributed in five age groups from 45- to 65-. It showed that high incidence town had a high detection rate of cancer and pathological changes of esophageal cancer in the analysis of urban and rural distribution. CONCLUSION: The distribution of the pre-cancerous state and pathological changes of esophageal cancer of the residents should have provided a scientific basis for the primary and secondary prevention.

[The risk factors related to esophageal squamous cell cancer in Feicheng county, China].

OBJECTIVE: To investigate the risk factors related to the esophageal squamous cell cancer in Feicheng county in Shandong province. METHODS: A case-control study was carried out in Feicheng county. There were two parts consisted in the cases. 253 cases, aged from 40 to 69 years old, were recruited from the screened endoscopic survey program from January 2004 to December 2006. The other part of cases was recruited from the people's Hospital of Feicheng city. 8159 subjects whose had normal endoscope test result were recruited as the control group. Besides cardiograph and ventral ultrasound examination the screening program also included an endoscope test during which mucosal stain with 1.2% iodine solution. The biopsies were taken from the screen and underwent pathologic evaluation by two pathologists; A self-administrative questionnaire survey was conducted in all the subjects to collect information about smoking, alcohol consumption and dietary. The binary Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (95% CI). The study protocol was approved by the local ethics committee and the study was conducted with the informed consents of all the study subjects. RESULTS: There were 235 esophageal cancers cases (70 identified in screening program, 183 were hospitalized patients) and 8159 controls in the case-control study. Three potential confounders were detected after univariate analysis. After adjusted the three confounders, age, sex and education, we found, smoking, alcohol drinking were the top ranked risk factors for esophageal cancer. When combing smoking and alcohol drinking, the or was 2.73 (95% CI: 1.54 - 4.82) for male, and the proportional attribute relative risk was 51.47%. We also observed that more dietary cellulose and vitamin C intake have protective effects. CONCLUSION: Smoking and alcohol drinking could increase the risk of esophageal cancer, and taking more dietary cellulose and vitamin C might decrease the risk.

Role of serum angiopoietin-2 level in screening for esophageal squamous cell cancer and its precursors.

BACKGROUND: Angiopoietin-2 (Ang-2) is one of the critical regulators of tumor angiogenesis. Studies have shown a significant correlation of Ang-2 expression to tumor invasion and metastasis in various human cancers, but little is known about the serum Ang-2 (sAng-2) levels in esophageal squamous cell cancer (ESCC) and its precursors. In this study, we aimed to investigate its role in screening for ESCC and its precursors. METHODS: We carried out a free endoscopic screening in Feicheng City, a high ESCC incidence area in Shandong Province of China. Serum samples were collected as follows: 91 from normal subjects, 44 from patients with esophagitis, 85 from patients with hyperplasia, and 13 from patients with early ESCC. In addition, 28 serum samples were obtained from patients with invasive ESCC undergoing surgery in People's Hospital of Feicheng City. All the subjects of the five groups were diagnosed by histopathology. The sAng-2 levels were tested and compared, and the diagnostic power in early or/and invasive ESCC was calculated in terms of sensitivity and other parameters. RESULTS: The sAng-2 levels were (22.0 +/- 5.5), (21.3 +/- 3.2), (20.5 +/- 3.3), (24.0+/- 5.0), and (29.8 +/- 5.0) U/ml in normal, esophagitis, hyperplasia, early ESCC, and invasive ESCC groups respectively. It was significantly higher in early ESCC than inhyperplasia group (P = 0.009). The invasive ESCC group showed the highest Ang-2 level among all groups (all P = 0.000). The sensitivities of sAng-2 to early and invasive ESCC were 23.1% and 78.6% respectively. CONCLUSION: sAng-2 level is related to carcinogenesis and progression of ESCC, but it can not be used to screen for early ESCC.