Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006 . The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer

Honokiol Induces Calpain-Mediated Glucose-Regulated Protein-94 Cleavage and Apoptosis in Human Gastric Cancer Cells and Reduces Tumor Growth

Background. Honokiol, a small molecular weight natural product, has been shown to possess potent anti-neoplastic and anti-angiogenic properties. Its molecular mechanisms and the ability of anti-gastric cancer remain unknown. It has been shown that the anti-apoptotic function of the glucose-regulated proteins (GRPs) predicts that their induction in neoplastic cells can lead to cancer progression and drug resistance. We explored the effects of honokiol on the regulation of GRPs and apoptosis in human gastric cancer cells and tumor growth. Methodology and Principal Findings. Treatment of various human gastric cancer cells with honokiol led to the induction of GRP94 cleavage, but did not affect GRP78. Silencing of GRP94 by small interfering RNA (siRNA) could induce cell apoptosis. Treatment of cells with honokiol or chemotherapeutics agent etoposide enhanced the increase in apoptosis and GRP94 degradation. The calpain activity and calpain-II (m-calpain) protein (but not calpain-I (mu-calpain)) level could also be increased by honokiol. Honokiol-induced GRP94 down-regulation and apoptosis in gastric cancer cells could be reversed by siRNA targeting calpain-II and calpain inhibitors. Furthermore, the results of immunofluorescence staining and immunoprecipitation revealed a specific interaction of GRP94 with calpain-II in cells following honokiol treatment. We next observed that tumor GRP94 over-expression and tumor growth in BALB/c nude mice, which were inoculated with human gastric cancer cells MKN45, are markedly decreased by honokiol treatment. Conclusions and Significance. These results provide the first evidence that honokiol-induced calpain-II-mediated GRP94 cleavage causes human gastric cancer cell apoptosis. We further suggest that honokiol may be a possible therapeutic agent to improve clinical outcome of gastric cancer

Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan.</p> <p>Methods</p> <p>We developed a Markov model to compare the health and economic outcomes of vaccinating preadolescent girls (at the age of 12 years) for the prevention of cervical cancer with current practice, including cervical cytological screening. Data were synthesized from published papers or reports, and whenever possible, those specific to Taiwan were used. Sensitivity analyses were performed to account for important uncertainties and different vaccination scenarios.</p> <p>Results</p> <p>Under the assumption that the HPV vaccine could provide lifelong protection, the massive vaccination among preadolescent girls in Taiwan would lead to reduction in 73.3% of the total incident cervical cancer cases and would result in a life expectancy gain of 4.9 days or 8.7 quality-adjusted life days at a cost of US$324 as compared to the current practice. The incremental cost-effectiveness ratio (ICER) was US$23,939 per life year gained or US$13,674 per quality-adjusted life year (QALY) gained given the discount rate of 3$30,000 per QALY under most conditions, even when vaccine efficacy was suboptimal or when vaccine-induced immunity required booster shots every 13 years.</p> <p>Conclusions</p> <p>Although gains in life expectancy may be modest at the individual level, the results indicate that prophylactic HPV vaccination of preadolescent girls in Taiwan would result in substantial population benefits with a favorable cost-effectiveness ratio. Nevertheless, we should not overlook the urgency to improve the compliance rate of cervical screening, particularly for older individuals.</p

In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography

Development of hypoxia-targeted therapies has stimulated the search for clinically applicable noninvasive markers of tumour hypoxia. Here, we describe the validation of [18F]fluoroetanidazole ([18F]FETA) as a tumour hypoxia marker by positron emission tomography (PET). Cellular transport and retention of [18F]FETA were determined in vitro under air vs nitrogen. Biodistribution and metabolism of the radiotracer were determined in mice bearing MCF-7, RIF-1, EMT6, HT1080/26.6, and HT1080/1-3C xenografts. Dynamic PET imaging was performed on a dedicated small animal scanner. [18F]FETA, with an octanol–water partition coefficient of 0.16±0.01, was selectively retained by RIF-1 cells under hypoxia compared to air (3.4- to 4.3-fold at 60–120 min). The radiotracer was stable in the plasma and distributed well to all the tissues studied. The 60-min tumour/muscle ratios positively correlated with the percentage of pO2 values <5 mmHg (r=0.805, P=0.027) and carbogen breathing decreased [18F]FETA-derived radioactivity levels (P=0.028). In contrast, nitroreductase activity did not influence accumulation. Tumours were sufficiently visualised by PET imaging within 30–60 min. Higher fractional retention of [18F]FETA in HT1080/1-3C vs HT1080/26.6 tumours determined by dynamic PET imaging (P=0.05) reflected higher percentage of pO2 values <1 mmHg (P=0.023), lower vessel density (P=0.026), and higher radiobiological hypoxic fraction (P=0.008) of the HT1080/1-3C tumours. In conclusion, [18F]FETA shows hypoxia-dependent tumour retention and is, thus, a promising PET marker that warrants clinical evaluation

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Evidence for cervical cancer mortality with screening program in Taiwan, 1981–2010: age-period-cohort model

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is the most common cancer experienced by women worldwide; however, screening techniques are very effective for reducing the risk of death. The national cervical cancer screening program was implemented in Taiwan in 1995. The objective of this study was to examine and provide evidence of the cervical cancer mortality trends for the periods before and after the screening program was implemented.</p> <p>Methods</p> <p>Data from 1981 to 2010 of the causes of death registered were obtained from the Department of Health, Taiwan. Age-standardized mortality rates, age-specific rates, and age-period-cohort models that employed the sequential method were used to assess temporal changes that occurred between 1981 and 2010, with 1995 used as the separating year.</p> <p>Results</p> <p>The results showed that for both time periods of 1981 to 1995 and 1996 to 2010, age and period had significant effects, whereas the birth cohort effects were insignificant. For patients between 80 and 84 years of age, the mortality rate for 1981 to 1995 and 1996 to 2010 was 48.34 and 68.08. The cervical cancer mortality rate for 1996 to 2010 was 1.0 for patients between 75 and 79 years of age and 1.4 for patients between 80 and 84 years of age compared to that for 1981 to 1995. Regarding the period effect, the mortality trend decreased 2-fold from 1996 to 2010.</p> <p>Conclusions</p> <p>The results of this study indicate a decline in cervical cancer mortality trends after the screening program involving Papanicolaou tests was implemented in 1995. However, the positive effects of the screening program were not observed in elderly women because of treatment delays during the initial implementation of the screening program.</p