The challenge of evaluating annual mammography screening for young women with a family history of breast cancer

It has been recommended that women aged 40-49 years with a significant family history of breast cancer should be offered annual mammography screening (http://www.nice.org.uk). An observational study known as FH01 (http://www.screeningservices.org/btw/fh01/index.asp) is evaluating this policy in a cohort of 6000 women at moderately increased risk of breast cancer due to family history. The main aims are to assess the likely impact on breast cancer mortality and cost-effectiveness. Measuring these outcomes is challenging in an environment where a randomized trial is not feasible and there is no natural comparison group. In this paper, we present some approaches to estimating effectiveness and the planned analyses. These involve comparison of disease stage and likely consequent breast cancer mortality in the cohort offered screening with that estimated in the absence of screening. The estimation uses observed outcomes in external populations and estimated outcomes for the hypothetical situation where screening had not taken place.     

Non-invasive measurement of liver fibrosis: application of the FibroScan in hepatology

The liver biopsy is still regarded as the gold standard for the assessment of liver disease. However, there is a growing demand for non-invasive assessment of liver fibrosis, which is the most important prognostic factor in chronic liver disease, in particular in viral hepatitis. Transient elastography is a novel, non-invasive and rapid bedside method for assessing liver fibrosis by measuring liver stiffness. Some recent extensive studies, mainly from France, have demonstrated that measurement with the FibroScan is a good alternative for the liver biopsy. The amount of fibrosis can be quantified very easily and reliably. In this review, we describe the technique and discuss the available studies in order to establish applicability and to provide points for discussion.     

Consequences of Noncompliance for Therapy Efficacy and Emergence of Resistance in Murine Tuberculosis Caused by the Beijing Genotype of Mycobacterium tuberculosis

Despite great effort by health organizations worldwide in fighting tuberculosis (TB), morbidity and mortality are not declining as expected. One of the reasons is related to the evolutionary development of Mycobacterium tuberculosis, in particular the Beijing genotype strains. In a previous study, we showed the association between the Beijing genotype and an increased mutation frequency for rifampin resistance. In this study, we use a Beijing genotype strain and an East-African/Indian genotype strain to investigate with our mouse TB model whether the higher mutation frequency observed in a Beijing genotype strain is associated with treatment failure particularly during noncompliance therapy. Both genotype strains showed high virulence in comparison to that of M. tuberculosis strain H37Rv, resulting in a highly progressive infection with a rapid lethal outcome in untreated mice. Compliance treatment was effective without relapse of TB irrespective of the infecting strain, showing similar decreases in the mycobacterial load in infected organs and similar histopathological changes. Noncompliance treatment, simulated by a reduced duration and dosing frequency, resulted in a relapse of infection. Relapse rates were correlated with the level of noncompliance and were identical for Beijing infection and East African/Indian infection. However, only in Beijing-infected mice, isoniazid-resistant mutants were selected at the highest level of noncompliance. This is in line with the substantial selection of isoniazid-resistant mutants in vitro in a wide isoniazid concentration window observed for the Beijing strain and not for the EAI strain. These results suggest that genotype diversity of M. tuberculosis may be involved in emergence of resistance and indicates that genotype-tailor-made treatment should be investigated.     

Serum Markers and Intestinal Mucosal Injury in Chronic Gastrointestinal Ischemia

Background  

Diagnosing chronic gastrointestinal ischemia (CGI) is a challenging problem in clinical practice. Serum markers for CGI would be of great diagnostic value as a non-invasive test method.     

单克隆抗体—表阿霉素免疫偶合物的制备和体外活性

用双功能试剂己二酰肼制备腙键连接的聚谷氨酸—表阿霉素,通过控制交联条件,所得产物克服了大分子自身交联的缺点,交联率较高。聚谷氨酸的载药量与分子量呈正比,平均每8～11个谷氨酸单体连接1分子表阿霉素。分子量为14300的聚谷氨酸做载体其载药量为1:11,与单抗交联所得的偶合物McAb:PGA:PAR为1:2:22。偶合物较好地保留了抗体活性,体外细胞毒性较游离药物略有下降,但表现出单抗介导的靶细胞选择性杀伤作用。本研究用腙键交联法成功地制备了药/抗比高且体外有效的免疫偶合物,为进一步制备细胞靶向的肿瘤化疗制剂奠定了基础。     

Role of Resveratrol as Radiosensitizer by Targeting Cancer Stem Cells in Radioresistant Prostate Cancer Cells (PC-3)

Aim of Work: Here, we examined the role of resveratrol as a radiosensitizer by targeting cancer stem cells in radioresistant prostate cancer cells (PC-3) using stem cell markers CD44, CD49b and CD29, SOX2, OCT4, CXCR4, DCLK1 and EMT markers such as VIM and E-cadherin. Material and Methods: This study was an in vitro study involving PC-3 cell line which was dividing into four groups. Group I (CO): Control group composed of cells grown in the same medium without treatment with ionizing radiation or resveratrol. Group II (IR): Cells were treated with ionizing radiation alone. Group III (RV): Cells were treated with resveratrol alone. Group VI (IR&RV): The cells were treated with ionizing radiation and resveratrol in combination. The viability of cells was assessed by MTT assay. Genes of interest were measured by RT-PCR and the radiosensitizing efficacy of RV on proliferating cancer cells was determined by clonogenic assay. Results: Ionizing radiation significantly reduced PC-3 viability, lowered stem cell markers and affected epithelial to mesenchymal transition (EMT) genes expression at all doses (2, 4, 6 and 8 Gray). Resveratrol significantly decreased PC-3 viability and lowered stem cell markers and EMT genes expression at concentrations 35, 70 and 140 µM. Combining resveratrol treatment with ionizing radiation leads to significant reduction in cell viability and stem cell markers genes which was noticed with increasing the radiation dose when compared to ionizing radiation alone treated group. Conclusion: Resveratrol has a radiosensitizing effect, that ability is triggered by reducing the expression of cancer stem cell markers and affecting EMT markers. Resveratrol showed to be a good candidate for further studies as anticancer drug in the treatment of human prostate cancer.     

Facial nerve function in carcinoma of the parotid gland

AimTo analyse, for patients with carcinoma of the parotid gland, the prognostic value for treatment outcome of the function of the facial nerve (NVII), and determining facial nerve dysfunction after treatment.Methods and materialsIn a retrospective study of the Dutch head and Neck cooperative group (NWHHT), data of 324 patients with parotid carcinoma were analysed. The function of N VII before treatment was intact in 77%, partially and completely impaired in 14% and 7%, respectively. Eighty-eight percent of the patients were treated surgically, and 77% of them were treated by a combination of postoperative radiotherapy. In 21% NVII was sacrificed, a reconstruction was performed in one of three.ResultsIndependent risk factors for N VII dysfunction before treatment were tumour localisation, positive neck nodes at presentation, pain, increasing age, and perineural invasion. Regional, not local, control was significantly impaired for complete facial paralysis. N VII dysfunction was an independent factor for disease free survival, and was 69%, 37% and 13% for normal, partially and completely impaired function, respectively. After treatment 22% of the patients experienced a partial paralysis, and 13% of the patients experienced a complete parlysis of N VII.ConclusionFor patients with parotid carcinoma, facial nerve function before treatment is a strong prognostic factor for disease free survival.