Incremental yield of dysplasia detection in Barrett's esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol.

BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) is a new wide-field advanced imaging technology for Barrett's esophagus (BE). No data exist on incremental yield of dysplasia detection. Our aim is to report the incremental yield of dysplasia detection in BE using VLE. METHODS: This is a retrospective study from a prospectively maintained database from 2011 to 2017 comparing the dysplasia yield of 4 different surveillance strategies in an academic BE tertiary care referral center. The groups were (1) random biopsies (RB), (2) Seattle protocol random biopsies (SP), (3) VLE without laser marking (VLE), and (4) VLE with laser marking (VLEL). RESULTS: A total of 448 consecutive patients (79 RB, 95 SP, 168 VLE, and 106 VLEL) met the inclusion criteria. After adjusting for visible lesions, the total dysplasia yield was 5.7%, 19.6%, 24.8%, and 33.7%, respectively. When compared with just the SP group, the VLEL group had statistically higher rates of overall dysplasia yield (19.6% vs 33.7%, P = .03; odds ratio, 2.1, P = .03). Both the VLEL and VLE groups had statistically significant differences in neoplasia (high-grade dysplasia and intramucosal cancer) detection compared with the SP group (14% vs 1%, P = .001 and 11% vs 1%, P = .003). CONCLUSION: A surveillance strategy involving VLEL led to a statistically significant higher yield of dysplasia and neoplasia detection compared with a standard random biopsy protocol. These results support the use of VLEL for surveillance in BE in academic centers.

Defining Physician-Nurse Efforts toward Collaboration as Perceived by Medical Students.

Collaboration between physicians and nurses is essential to healthcare delivery and is associated with high-quality patient care, greater patient satisfaction, and better health outcomes. Hence, it is imperative that doctors and nurses have a particular set of interprofessional collaboration skills. This descriptive cross-sectional study assessed how medical students in the pre-clinical and clinical years perceived attitudes toward collaboration between physicians and nurses in a hospital setting. The Jefferson Scale of Attitude toward Physician-nurse Collaboration (JSAPNC) was reverse-translated into Arabic for the current study. The results showed a total JSAPNC mean score of 46.55, lower than other medical students in other universities. In general, the results of the study showed no significant difference in the total JSAPNC score among medical students when analyzed according to age, clinical exposure, and year level, except in the two factors of JSAPNC: shared education and teamwork (p = 0.038) and caring as opposed to curing (p = 0.043). The findings of this study suggest the necessity of integrating interprofessional education (IPE) across the medical school curriculum because, as future physicians, medical students would be well equipped to treat their patients in partnership with their nursing colleagues.

Comparing serum levels of cardiac biomarkers in cancer patients receiving chemotherapy and subjects with chronic periodontitis.

BACKGROUND: Chronic periodontitis (CP) is a chronic inflammation associated with elevations of several inflammatory and cardiac markers. Studies implicated CP as one of the etiologies in coronary heart disease (CHD). Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil (5FU). The most severe cardiac complications are heart failure, arrhythmia and coronary heart disease (CHD). In this study, we compared the level of inflammatory factors and cardiac markers between chronic periodontitis patients and cancer patients receiving chemotherapy. METHODS: 108 blood samples of periodontally healthy subjects were obtained on random from Hong Kong Red Cross, and these represented the controlled population. Forty-four patients diagnosed with chronic periodontitis were recruited from the West China Hospital of Stomatology, Sichuan University. They have received scaling and root planning with mean pocket depths of 6.05 mm. Thirty breast cancer patients diagnosed with invasive ductal carcinoma from UNIMED Medical Institute, Hong Kong gave consent to participate in this study. They received 4 cycles of 500mg/m2 5-fluorouracil, 75 mg/m2 epirubicin and 500mg/m2 cyclophosphamide at a 3-week interval between each cycle. Peripheral venous blood from each group was taken for measurement of blood cells, inflammatory marker (P-selectin, high sensitvity C-reactive protein) and cardiac markers (troponin T; troponin I; N-terminal pro brain natriuretic peptide (Nt-proBNP) and Lactate dehydrogenase (LDH). RESULTS: The lymphocyte count was higher (p < 0.05) in periodontitis patients than the other two groups, and more neutrophils (p < 0.05) were seen in cancer patients receiving chemotherapy. The two test groups demonstrated higher levels (p < 0.01) of inflammatory and cardiac markers than the control group. CONCLUSIONS: The elevated cardiac markers found in periodontitis patients suggested that they may carry potential risks in developing cardiac lesions. Troponin T, troponin I, pro-BNP, LDH and high sensitvity C-reactive protein may be used as markers to monitor cardiac lesions in chronic inflammatory patients.

Gene polymorphism and protein of human pro- and anti-inflammatory cytokines in Chinese healthy subjects and chronic periodontitis patients.

BACKGROUND: Periodontal disease is thought to arise from the interaction of various factors, including the susceptibility of the host, the presence of pathogenic organisms, and the absence of beneficial species. The genetic factors may play a significant role in the risk of periodontal diseases. Cytokines initiate, mediate and control immune and inflammatory responses. The aim of this study is to compare genotypes and soluble protein of pro and anti-inflammatory cytokines (IL-1α, IL-1ß, IL-6, IFN-γ, IL-10, TNF-α and IL-4) in subjects with or free of chronic periodontitis. METHODS: A total of 1,290 Chinese subjects were recruited to this clinical trial: 850 periodontally healthy controls and 440 periodontal patients. All subjects were free of systemic diseases. Oral examinations were performed, and the following parameters were recorded for each subject: supragingival/subgingival calculus, gingival recession, bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), gingival recession and tooth mobility. The peripheral blood samples were collected for genetic and enzyme linked immunosorbent assay (ELISA) analysis. Restriction enzymes were used for digestion of amplified fragments of IL-1α, IL-1ß, IL-6, IFN-γ, IL-10, TNF-α and IL-4. RESULTS: The protein expressions of patient and control samples for IL-1α, IL-1ß, IL-6, TNF-α, IFN-γ, IL-10, and IL-4 measured by ELISA confirmed a statistically significant difference (p < 0.001). The digestion of fragments of various genes showed that the pro-inflammatory cytokines IL-1α and TNF-α, and the anti-inflammatory cytokines IL-4 and IL-10 demonstrated a correlation with chronic inflammation in patients (X2: p < 0.001). The remaining genes investigated in patients and healthy subjects (IL-1ß, IL-6, IFN-γ and IL-10) did not show any significant difference. CONCLUSIONS: The cytokine gene polymorphisms may be used as a marker for periodontitis susceptibility, clinical behaviour and severity. This detection offers early diagnosis and induction of prophylaxis to other family members against disease progression.

Clinical application of human ß-defensin and CD14 gene polymorphism in evaluating the status of chronic inflammation.

BACKGROUND: Periodontitis is a common disease that affects the periodontal tissue supporting the teeth. This disease is attributed to multiple risk factors, including diabetes, cigarette smoking, alcohol, pathogenic microorganisms, genetics and others. Human beta-defensin-1 (hBD-1) is a cationic antimicrobial peptide with cysteine-rich ß-sheets and broad-spectrum antimicrobial activity. CD14 is a protein involved in the detection of bacterial lipopolysaccharide (LPS) and has also been associated with periodontitis. This study investigates the single nucleotide polymorphic (SNP) region, -1654(V38I), of the human beta-defensin-1 (hBD-1) gene as well as the -159 region of the CD14 gene in subjects with chronic periodontitis. METHODS: Blood samples from periodontally healthy subjects and periodontitis patients were obtained. DNA was extracted from the blood and was used to perform restriction digest at the polymorphic G1654A site of DEFB1 with the enzyme HincII. The polymorphic site 159TT of CD14 was digested with the enzyme AvaII. Enzyme-linked immunosorbent assay (ELISA) was performed on soluble samples to determine the protein expressions. RESULTS: The control and patient groups expressed 35% and 38% 1654 A/A genotype of DEFB1, respectively. The A allele frequency of the control group was 40%, while the patient blood group was 54%. The mean hBD-1 protein levels of the control and patient samples were 102.83 pg/mL and 252.09 pg/mL, respectively. The genotype distribution of CD14 in healthy subjects was 16% for C/C, 26% for T/T and 58% for C/T. The genotype frequencies of CD14 in periodontitis patients were 10% for C/C, 43% for T/T and 47% for C/T. The CD14 protein expression determined by ELISA showed a mean protein level of the control samples at 76.28ng/mL and the patient blood samples at 179.27ng/mL with a p value of 0.001.Our study demonstrated that patients suffering from chronic periodontitis present more commonly with the 1654A/A genotype on the DEFB1 gene and the 159T/T genotype on the CD14 gene. CONCLUSIONS: This study purely investigated the association between periodontitis and one polymorphic site on both DEFB1 and CD14 gene, with the purpose of expanding knowledge for the future development in diagnostic markers or therapeutic interventions to combat this disease.

Application of a nanotechnology antimicrobial spray to prevent lower urinary tract infection: a multicenter urology trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance.In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multi-center clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray. METHODS: Siliconized latex urinary catheters were cut into fragments and sterilized by autoclaving. The sterilized sample fragments were randomly divided into the therapy and control group, whereby they were sprayed with JUC and distilled water respectively and dried before use.The experimental standard strains of Escherichia coli (E. coli) were isolated from the urine samples of patients. At 16 hours and 7 days of incubation, the samples were extracted for confocal laser scanning microscopy.A total of 1,150 patients were accrued in the clinical study. Patients were randomized according to the order of surgical treatment. The odd array of patients was assigned as the therapy group (JUC), and the even array of patients was assigned as the control group (normal saline). RESULTS: After 16 hours of culture, bacterial biofilm formed on the surface of sample fragments from the control group. In the therapy group, no bacterial biofilm formation was observed on the sample fragments. No significant increase in bacterial colony count was observed in the therapy group after 7 days of incubation.On the 7th day of catheterization, urine samples were collected for bacterial culture before extubation. Significant difference was observed in the incidence of bacteriuria between the therapy group and control group (4.52% vs. 13.04%, p < 0.001). CONCLUSIONS: In this study, the effectiveness of JUC in preventing CAUTI in a hospital setting was demonstrated in both in vitro and clinical studies.

Association of matrix metalloproteinase (MMP)-1, 3, 9, interleukin (IL)-2, 8 and cyclooxygenase (COX)-2 gene polymorphisms with chronic periodontitis in a Chinese population.

Chronic periodontitis (CPs) could result in damage of periodontal tissues, loss of teeth and impose troublesome hindrance to restore teeth satisfyingly as well. Functional gene polymorphisms of matrix metalloproteinases, cytokines and cyclooxygenase-2 have been found to play important roles in periodontitis. This study was to investigate the association between MMP-1-1067, MMP-3-1171, MMP-9-1562, IL-2-330, IL-8-251, COX-2-765 polymorphisms, and the susceptibility to CP in a Chinese population. A total of 122 patients with CP were evaluated for MMP-1, MMP-3, MMP-9, IL-2, IL-8 and COX-2 genetic polymorphisms and were compared with 532 healthy control subjects using PCR-RFLP analysis. Clinical periodontal parameters were recorded. Serum levels of MMP-1, MMP-3, MMP-9, IL-2, IL-8 and COX-2 were measured by ELISA. The data were analyzed by chi-square, logistic regression and Mann-Whitney-U-tests and t test. There were significant differences between CP patients and healthy subjects in the genotype distribution and allele frequency of MMP-3-1171, MMP-9-1562, IL-2-330, IL-8-251 and COX-2-765 genetic polymorphisms. Significant difference between patients and controls were also observed for MMP-1-1067 genotype frequency, but not for allele frequency. Differences between rare allele carriage rates of CP and healthy groups regarding all the genetic polymorphisms in our study were significant (p<0.05). Serum levels of all the cytokines were higher in the CP patients compared to healthy subjects. These data show that MMP-1-1067, MMP-3-1171, MMP-9-1562 and IL-8-251 polymorphisms are associated with susceptibility to CP. MMP-1-1067 2G, MMP-3-1171 6A, MMP-9-1562 T and IL-8-251 A allele are associated with decreased susceptibility to CP in Chinese population.

Epigenetic change in E-cadherin and COX-2 to predict chronic periodontitis.

BACKGROUND: DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2) in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis. METHODS: Total DNA was extracted from the blood samples of 108 systemically healthy non-periodontitis subjects, and the gingival tissues and blood samples of 110 chronic periodontitis patient as well as neoplastic tissues of 106 breast cancer patients. Methylation-specific PCR for E-Cadherin and COX-2 was performed on these samples and the PCR products were analyzed on 2% agarose gel. RESULTS: Hypermethylation of E-Cadherin and COX-2 was observed in 38% and 35% of the breast cancer samples, respectively. In chronic periodontitis patients the detection rate was 25% and 19% respectively, and none was found in the systemically healthy non-periodontitis control subjects. The hypermethylation status was shown to be correlated among the three groups with statistical significance (p < 0.0001). The methylation of CpG islands in E-Cadherin and COX-2 genes in periodontitis patients occurs more frequently in periodontitis patients than in the control subjects, but occurs less frequently than in the breast cancer patients. CONCLUSIONS: This set of data shows that the epigenetic change in E-Cadherin and Cyclooxygenase-2 is associated with chronic periodontitis. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to the effects of cancer. Chronic periodontitis to some extent might be associated with DNA hypermethylation which is related to cancer risk factors.

Adjunctive Yield of Wide-Area Transepithelial Sampling for Dysplasia Detection After Advanced Imaging and Random Biopsies in Barrett's Esophagus.

INTRODUCTION: Little is known about the additive yield of wide-area transepithelial sampling with computer-assisted three-dimensional analysis (WATS-3D) after a thorough examination with advanced imaging. The aim was to evaluate the adjunctive yield of WATS-3D after advanced imaging. METHODS: This is an observational cohort study from January 2017 to December 2018 for consecutive patients who underwent an examination that consists of high-definition white light endoscopy (HDWLE), narrow-band imaging (NBI), volumetric laser endomicroscopy (VLE), and Seattle protocol (SP) biopsies (collectively termed HDWLE-NBI-VLE-SP examination). Raised lesions were removed by endoscopic resection. Areas suspicious for dysplasia on NBI and VLE were biopsied. This was followed by random biopsies and WATS-3D brush biopsies. RESULTS: One hundred thirty-eight cases were included in this study. Thirty-five cases (25% of the total) were identified as some degree of dysplasia on the HDWLE-NBI-VLE-SP examination. Adjunctive use of WATS-3D yielded an additional 12 new cases of dysplasia (9 with crypt dysplasia and 3 with low-grade dysplasia [LGD]), for added yield of 34.3% (=12/35, 95% confidence interval 14.6%-62.2%). When restricting the analysis to LGD and higher, 21 dysplastic cases (15% of the total cases) were identified by HDWLE-NBI-VLE-SP, while WATS-3D found 4 additional new cases (3 with LGD and 1 with high-grade dysplasia) for an added yield of 19% (=4/21, 95% confidence interval 0.6%-45.7%). DISCUSSION: The addition of WATS-3D to an already thorough examination with HDWLE-NBI-VLE-SP may increase the yield of dysplasia detection.

Propofol for sedation during colonoscopy.

BACKGROUND: Propofol is increasingly used for sedation during colonoscopy, with many recent reports of randomized controlled trials (RCTs) and large non-randomized case series. OBJECTIVES: The primary objective was to identify, analyze and summarize RCTs comparing the relative effectiveness, patient acceptance and safety of propofol for colonoscopy, to traditional sedatives (narcotics and/or benzodiazepines).The secondary objective was to synthesize the studies comparing propofol administration by anesthesiologists to that by non-anesthesiologists for sedation during colonoscopy. SEARCH STRATEGY: We searched Medline, Cancerlit, EMBASE, CINAHL, LILACS, Biological Abstracts, Web of Science and the Cochrane Controlled Trials Registry database between January 1980 and June 2007; and conference proceeding abstracts for DDW, EUGW and ACG between 1990 and June 2007. There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials comparing use of propofol and traditional agents or administration of propofol by anesthesiologists to that by non-anesthesiologists for sedation during colonoscopy. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data. The data were pooled using the Cochrane Collaborations' methodology and statistical software RevMan 4.2.10. MAIN RESULTS: Twenty studies met the inclusion criteria for the primary objective. Most studies included only healthy out-patients. Recovery and discharge times were shorter with use of propofol. There was higher patient satisfaction with use of propofol (OR for dissatisfaction 0.35, 95% CI 0.23, 0.53). There was no difference in procedure time, cecal intubation rate or complications. There was no difference in pain control with non- patient controlled sedation (PCS) use of propofol as compared to the traditional agents (OR 0.90; 95% CI 0.58, 1.39). Although there was higher patient satisfaction (OR for dissatisfaction 0.42, 95% CI 0.20, 0.89), the pain control was inferior with use of PCS use of propofol as compared to the use of traditional agents (OR 3.09; 95% CI 2.15, 4.46).There was only one study comparing administration of propofol by anesthesiologists to that by non-anesthesiologists for sedation during colonoscopy, with no difference in procedure time or patient satisfaction. AUTHORS' CONCLUSIONS: Propofol for sedation during colonoscopy for generally healthy individuals can lead to faster recovery and discharge times, increased patient satisfaction without an increase in side-effects. More studies with standardized end-points are needed to compare propofol administration by anesthesiologists to that by non-anesthesiologists.

Fructus schisandrae (Wuweizi)-containing compound inhibits secretion of HBsAg and HBeAg in hepatocellular carcinoma cell line.

Chronic hepatitis B is probably the major cause of cirrhosis and hepatocellular carcinoma. The detection of the hepatitis B virus surface antigen (HBsAg) and HBV core protein, the e antigen (HBeAg), indicates infection with the hepatitis B virus and replication activity, respectively. Fructus schisandrae containing compound (KY88) may affect the elimination of HBV, strengthen the immune system, as well as stimulate liver cell regeneration. The present study was conducted to demonstrate the ability of KY88 in inhibiting hepatocellular carcinoma cell proliferation and secretions of HBsAg and HBeAg. The hepatocellular carcinoma cell line HB-8064 was treated by KY88 followed by the measurement of cell proliferation rate and secretions of HBsAg and HBeAg on days 1, 3, 5, and 7. A semi-quantitative RT-PCR method was used to quantify the expression of the mRNA. Seventy Sprague-Dawley rats were fed for 28days with purified KY88 for a toxicity test. The expression of surface and e antigens was lower when the cells were treated for a longer time with KY88 or when the doses were higher. One-way ANOVA analysis confirmed the mRNA content of HBsAg to be significantly less than control. The body weight did not show a significant difference compared to the control group. Fructus schisandrae-containing compound (KY88) was potentially effective in suppressing the proliferation of hepatocellular carcinoma cells. The decreased secretion and gene expression of HBsAg and HBeAg might restrict the growth of tumour masses.

Clinical markers of Crohn's disease severity and their association with opiate use.

BACKGROUND: The safety of opiate use for patients with Crohn's disease (CD) has long been a concern. The recent Crohn's therapy, resource, evaluation, and assessment tool (TREAT) registry update has added to these concerns by demonstrating an association of opiate use with an increased risk of infection and death in CD. While the association is clear, the relationship of opiates to these negative outcomes is not. It is unknown whether opiates are a contributing factor to these negative outcomes or if their use is merely a marker of more severe disease. We hypothesized that opiate use is not harmful in CD but is a marker of disease severity and would be associated with commonly accepted clinical markers of severe CD such as early age at CD onset, disease duration, small intestinal involvement, a history of fistula or stricture, and lower quality of life (QOL) scores. METHODS: Data on CD history including pain medication usage were obtained from an interviewer directed survey of patients admitted to two tertiary care hospitals over a 2-year period. CD as the primary admitting diagnosis was not required. Active opiate use was defined by usage within the past month prior to admission. RESULTS: A total of 133 patients were approached to participate, of whom 108 consented to the survey, and 51 were active opiate users. Opiate using CD patients were more commonly smokers (22% vs. 3.45%, P < 0.010), had fistulas (40% vs. 22.4%, P < 0.048) and had a poorer quality of life score by short form inflammatory bowel disease questionnaire (mean 3.80 vs. 4.34, P < 0.036) than non-opiate users. No difference was found between opiate users and non-users for age of diagnosis, disease duration, or a history of strictures. CONCLUSIONS: The study findings demonstrate that opiate use in CD is associated with markers of disease severity including fistulas, smoking, and lower QOL scores. The findings suggest that opiates may not be directly harmful to patients with CD, but may merely be another marker of disease severity. However, given opiates unproven benefits for long term CD pain control and risk of dependence, caution should still be exercised in their use.

Production of matrix metalloproteinases in specific subpopulations of human-patient breast cancer invading in three dimensional culture system.

This article aims at investigating the effect of production of matrix metalloproteinases (MMP) in human breast cancer tissues by means of three dimensional culture system. Thirty-nine tumour samples were taken from breast cancer patients. The tumour blocks were cultured on sponge gel using the three dimensional culture system. Breast cancer cells began shedding into the culture medium after 24 hours of culture. The cells were stained with trypan blue dye to assess viability on days 2, 4, 6 and 8. The culture medium was collected at these time points and tested for matrix metalloproteinases (MMP) 1,2,3 and 9 activities. There was a progressive increase in migration of cancer cells into the gel and culture medium from day 2 to day 8 and the interval difference was statistically significant (F ratio=4.06; p=0.008). The levels of all the MMPs tested were also significantly raised (P<0.05 for all the MMPs tested). When the levels of MMPs were correlated with the metabolic activities in the gel, medium and tumour block, cells in block show no correlation whereas cells in gel correlated significantly with MMP-1 and MMP-3. Cancer cells in the culture medium correlated with MMP-9. In conclusion, there is a progressive migration of cancer cells outside the tumour block. The migration into the gel and culture medium is associated with progressive and differential production of MMPs. It is likely that the three dimensional culture model assists in the selection of different subpopulations of cancer cells with different invasion properties as exemplified by the differential production of MMP.

The inhibitory effect of a herbal formula comprising ginseng and carthamus tinctorius on breast cancer.

A compound (Zhu-xiang) from herbal extracts containing ginseng and carthamus tinctorius was used to treat the MDA-MB-231 breast cancer cell and normal human mammary gland cell lines. The inhibition of cell proliferation by Zhu-xiang, epirubicin, 5-fluorouracil and cyclophosphamide was determined by WST-1 assays. The apoptotic effect was studied by flow cytometry analysis of DNA strand breaks and ApopTag Peroxidase In Situ Apoptosis kit by the TUNEL assay. The proliferation index as well as cell cycle progression were also evaluated by flow cytometry using Ki-67 and propidium iodide respectively as markers. The Zhu-xiang showed significantly inhibition in cell proliferation and the inhibition was dose dependent. The inhibitory effect of Zhu-xiang was significantly greater than commonly used cytotoxic drugs. The inhibitory effect is a result of the induction of apoptosis, which is concentration- and time-dependent. DNA histograms indicate that the compound causes accumulation of cells mainly in the S phase. The viability of cells in breast solid tumours was measured by ATP bioluminescence assay to determine the drug-induced cytotoxicity of Zhu-xiang. The three different concentrations of Zhu-xiang all exhibited the ability to inhibit proliferation in solid tumour. Zhu-xiang could be a useful anti-cancer compound against breast cancer.

A rat cell line derived from DMBA-induced mammary carcinoma.

A new cell line, designated UHKBR-01, was successfully established from a 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumour. DMBA was administered orally at a dose of 4 mg/ml per rat on the first day of the experiment and thereafter at weekly intervals of same dosage, until the rats have reached a weight of around 150-200 g. The tumours grew rapidly after the injection, and were transplanted into nude mice one the harvest size (2.5 x 2 x 1 mm(3)) was reached, it was transplanted onto nude mice. We have developed a cell line from a portion of the DMBA-induced carcinoma of the nude mice. The UHKBR-01 cell exhibited a slow increase in growth rate during the time of culture and was highly tumourigenic in nude mice. The cells have been grown in culture for over 40 passages. Characterization of the cell line was performed. This included morphology by light and transmission electron microscopy, karyotype, growth rate, tumour antigen expression and xenograft implantation into nude mice. These cells exhibit ultrastructural and immunohistochemical features of epithelial cells of mammary origin. The above analyses also demonstrated that UHKBR-01 cells were oestrogen- and progesterone-receptor positive, in likeness to other established breast cancer cell lines such as MDA-MB-231 and MCF-7. The cell line grows as monolayers of oval-shaped cells with large folded nuclei accompanied by a rich supply of mitochondria. This report describes the first in vitro cell line from transplantable DMBA-induced mammary carcinoma of nude mice, which presents unique characteristics that may prove to be a good experimental model for investigating breast cancer biology.

Arimidex inhibition on proliferation of human breast solid tumors measured by ATP bioluminescence.

To determine the degree of Arimidex (Anastrozole) inhibition on proliferation of human breast solid tumors in vitro by ATP bioluminescence assay. Breast cancer solid tumors with different hormone receptors and grading were collected from 38 Chinese women with invasive breast cancers. Tumors were treated with three concentrations of Arimidex (1.5 mM, 15 mM and 150 mM). ATP bioluminescence assay was used to measure the metabolic rate in order to determine the degree of inhibition of Arimidex on the breast cancer tumors by comparing to the untreated tumors. 15 mM Arimidex shows greatest inhibitory effect on the proliferation of solid tumors with ER-postive/PR-positive. It can also inhibit the growth of metastatic tumors and tumors with HER-2/neu expression. It shows greater inhibitory effect in lower grading of tumors then higher. Arimidex may effectively inhibit the growth of breast tumors in in vitro system by inhibiting aromatase and block estrogen dependent tumor growth.

Radix bupleuri containing compound (KY88 liver-livo) induces apoptosis and production of interleukin-4 and tumor necrosis factor-alpha in liver cancer cells in vitro.

Hepatocellular carcinoma is an important health problem in Asia. A blend of herbal extracts containing radix bupleuri (KY88) was tested for its effects on liver cancer cells. A hepatocellular carcinoma cell line (HB8064) was cultured with methanol extract of KY88. We were able to produce a dose-dependent inhibition of cancer cell proliferation. At IC50 and IC100, KY88 induces a DNA ladder pattern, indicating the presence of apoptosis. We also checked the changes of the levels of interleukin (IL)-2, -4 and -6, interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha by ELISA kits. After 24 hours of culture, there was activation of IL-2 and -4 and TNF-alpha. However, significant changes were observed only for IL-4 and TNF-alpha. Therefore, we concluded that KY88 is able to induce apoptosis, which may be regulated through changes in IL-4 and TNF-alpha.

Angiotensin II induces mitochondrial dysfunction and promotes apoptosis via JNK signalling pathway in primary mouse calvaria osteoblast.

OBJECTIVES: This present study was designed to investigate the effects of Angiotensin II on mitochondrial functions, ROS generation and c-jun N-terminal kinases (JNK) signalling pathway-mediated cell apoptosis in mouse calvaria osteoblasts. METHODS: Calvaria osteoblast were isolated and cultured. The cells were separated into two groups-control and treated groups-where the latter was stimulated with angiotensin II (Ang II). Mitochondrial reactive oxygen species (ROS) and superoxide production were measured. Intracellular ATP levels were also detected. The cell proliferation rate was determined for the two groups. Protein production such as Anti-Bax, Bcl-2, COX IV and activation of c-jun N-terminal kinases signal (JNK) pathway was measured by enzyme-linked immunosorbent assay (ELISA) methods and Western blotting in this study. RESULTS: Ang II treated cells showed significantly higher levels of superoxide production compared to the control group (p<0.05). Conversely, Ang II induced inhibitory effects on mitochondrial respiratory enzyme complexes, cause membrane potential dissipation, ATP loss and promote ROS generation, cell apoptosis in cultured osteoblasts. In addition, JNK phosphorylations were involved in activating the mitochondria-dependent apoptotic pathway following Ang II stimulation, as pre-treatment of JNK-specific inhibitor SP600125 could rescue osteoblast cells from apoptosis by enhancing the anti-apoptotic protein Bcl-2 expressions, suppressing the translocation of Bax from cytosol into mitochondria, blocking cytochrome C release and caspase-3 activation. CONCLUSIONS: Ang II stimulates osteoblast apoptosis via suppression of the mitochondrial respiratory enzymes, membrane potential and cellular ATP productions. Clinical application with Ang II-stimulated osteoblast could be used for modelling or bone resorption in the oral region.

Case report: postradiation chondrosarcoma with a short latency period of 6 months.

We describe a case of postradiation chondrosarcoma after basal cell carcinoma treatment. At the time he presented, the patient was a 35-year-old man who had received radiotherapy at a dose of 70 Gy for 8 weeks. Six months after radiation treatment, a rapidly growing mass at the upper right alveolar ridge of the gums, where radiation had been given, was diagnosed as chondrosarcoma. Generally, chondrosarcoma occurs after a latency period of several years following radiation. However, there are a few relevant reports indicating that maxillofacial chondrosarcoma can develop after radiotherapy for basal cell carcinoma, with a short latency of 6 months. We hypothesize that the dosage and treatment time of radiation may have played a role in the opening/closing of the Hh-signaling pathway in the case of this patient.