In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells

Following removal of the primary breast tumour by conservative surgery, patients may still have additional malignant foci scattered throughout the breast. Radiation treatments are not designed to eliminate all these residual cancer cells. Rather, the radiation dose is calculated to optimise long-term results with minimal complications. In a tumour, cancer cells are surrounded by a basement membrane, which plays an important role in the regulation of gene expression. Using an invasion chamber, we have shown that irradiation before cell plating of a reconstituted basement membrane (Matrigel; Becton Dickinson, Bedford, MA, USA) increased the invasiveness of the breast cancer cells MDA-MB-231. This radiation enhancement of invasion was associated with the upregulation of the pro-invasive gene matrix metalloproteinase (MMP)-2. The expression of membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP), which are required to activate the MMP-2, were also increased. Confirming the role of MMP-2 and MT1-MMP, radiation enhancement of cancer cell invasion was prevented by an MMP-2 inhibitor and an anti-MT1-MMP antibody. This study also demonstrated that radiation can potentially enhance the invasion ability by inducing the release of pro-invasive factors stored in the Matrigel. Conversely, no enhancement of invasiveness was observed with the low metastatic cell line MCF-7. This lack of invasiveness correlated with the absence of the MMP-2 activator MT1-MMP in the MCF-7 cells. Radiotherapy is an efficient modality to treat breast cancer which could be further improved by inhibiting the pro-invasive gene upregulated by radiation

A preliminary pharmacokinetic study of liposomal leuprolide dry powder inhaler: A technical note

The developed liposomal DPI of LEU (LLEUn-DPI) demonstrated approximately 50% bioavailability compared with SC route. The studies justify the role of the pulmonary route as a promising alternative to the presently available SC route. The components of liposomal vesicles may be suitably changed to achieve higher bioavailability. Pulmonary delivery of LEU is expected to help in improving patient compliance, self-administration and avoiding the complications related to injection procedure. The developed LEU-DPI may be employed for both male and female contraception and treatment of prostate cancer in men and early puberty in children. In women it may be used for ovarian, endometrial, pancreas, and breast cancer; endometriosis; Uterine Leiomyoma; and anemia due to uterine fibroid tumors. However, the role of LEU-DPI in clinical practice can only be justified only after in vivo studies on 2 species of animals followed by extensive clinical trials

Rural health workers and their work environment: the role of inter-personal factors on job satisfaction of nurses in rural Papua New Guinea

Background: Job satisfaction is an important focal attitude towards work. Understanding factors that relate to job satisfaction allows interventions to be developed to enhance work performance. Most research on job satisfaction among nurses has been conducted in acute care settings in industrialized countries. Factors that relate to rural nurses are different. This study examined inter-personal, intra-personal and extra-personal factors that influence job satisfaction among rural primary care nurses in a Low and Middle Income country (LMIC), Papua New Guinea. Methods. Data was collected using self administered questionnaire from rural nurses attending a training program from 15 of the 20 provinces. Results of a total of 344 nurses were available for analysis. A measure of overall job satisfaction and measures for facets of job satisfaction was developed in the study based on literature and a qualitative study. Multi-variate analysis was used to test prediction models. Results: There was significant difference in the level of job satisfaction by age and years in the profession. Higher levels of overall job satisfaction and intrinsic satisfaction were seen in nurses employed by Church facilities compared to government facilities (