A theoretical study of the response of vascular tumours to different types of chemotherapy

In this paper we formulate and explore a mathematical model to study continuous infusion of a vascular tumour with isolated and combined blood-borne chemotherapies. The mathematical model comprises a system of nonlinear partial differential equations that describe the evolution of the healthy (host) cells, the tumour cells and the tumour vasculature, coupled with distribution of a generic angiogenic stimulant (TAF) and blood-borne oxygen. A novel aspect of our model is the presence of blood-borne chemotherapeutic drugs which target different aspects of tumour growth (cf. proliferating cells, the angiogenic stimulant or the tumour vasculature). We run exhaustive numerical simulations in order to compare vascular tumour growth before and following therapy. Our results suggest that continuous exposure to anti-proliferative drug will result in the vascular tumour being cleared, becoming growth-arrested or growing at a reduced rate, the outcome depending on the drug’s potency and its rate of uptake. When the angiogenic stimulant or the tumour vasculature are targeted by the therapy, tumour elimination can not occur: at best vascular growth is retarded and the tumour reverts to an avascular form. Application of a combined treatment that destroys the vasculature and the TAF, yields results that resemble those achieved following successful treatment with anti-TAF or anti-vascular therapy. In contrast, combining anti-proliferative therapy with anti-TAF or antivascular therapy can eliminate the vascular tumour. In conclusion, our results suggest that tumour growth and the time of tumour clearance are highly sensitive to the specific combinations of anti-proliferative, anti-TAF and anti-vascular drugs

Not what you expected: Implementing design thinking as a leadership practice

Changing user needs have created new opportunities for libraries, requiring evolving leadership practices that support innovation and rapid change. Design thinking can provide leaders with a concrete process to move toward action. The authors – one an executive administrator at a large, multi-branch public library, the other an academic librarian who leads a small team – share how design thinking has positively influenced their leadership practices. The benefits of implementing this flexible process have included improved user experience, more creative solutions, wise investments, staff empowerment, increased transparency and trust, and employee learning and development. Both leaders experienced these benefits even though they are in different positions on their hierarchical organization charts. The authors propose that implementing design thinking as a leadership practice has a place in the evolving role of libraries and can shift organizational cultures to become more user-centered and embrace innovation. In addition to these benefits, the chapter discusses specific project examples, challenges, and tips for library leaders to successfully implement the process. Design thinking is translatable across library types and throughout private industry. Discussing design thinking as a leadership practice can benefit the profession and communities by giving leaders a common language to use when learning from and sharing with each other in conversations about innovation

Are Metastases from Metastases Clinical Relevant? Computer Modelling of Cancer Spread in a Case of Hepatocellular Carcinoma

Background: Metastasis formation remains an enigmatic process and one of the main questions recently asked is whether metastases are able to generate further metastases. Different models have been proposed to answer this question; however, their clinical significance remains unclear. Therefore a computer model was developed that permits comparison of the different models quantitatively with clinical data and that additionally predicts the outcome of treatment interventions. Methods: The computer model is based on discrete events simulation approach. On the basis of a case from an untreated patient with hepatocellular carcinoma and its multiple metastases in the liver, it was evaluated whether metastases are able to metastasise and in particular if late disseminated tumour cells are still capable to form metastases. Additionally, the resection of the primary tumour was simulated. The simulation results were compared with clinical data. Results: The simulation results reveal that the number of metastases varies significantly between scenarios where metastases metastasise and scenarios where they do not. In contrast, the total tumour mass is nearly unaffected by the two different modes of metastasis formation. Furthermore, the results provide evidence that metastasis formation is an early event and that late disseminated tumour cells are still capable of forming metastases. Simulations also allow estimating how the resection of the primary tumour delays the patient’s death. Conclusion: The simulation results indicate that for this particular case of a hepatocellular carcinoma late metastases, i.e.

The influence of P-glycoprotein expression and its inhibitors on the distribution of doxorubicin in breast tumors

Abstract Background Anti-cancer drugs access solid tumors via blood vessels, and must penetrate tumor tissue to reach all cancer cells. Previous studies have demonstrated steep gradients of decreasing doxorubicin fluorescence with increasing distance from blood vessels, such that many tumor cells are not exposed to drug. Studies using multilayered cell cultures show that increased P-glycoprotein (PgP) is associated with better penetration of doxorubicin, while PgP inhibitors decrease drug penetration in tumor tissue. Here we evaluate the effect of PgP expression on doxorubicin distribution in vivo. Methods Mice bearing tumor sublines with either high or low expression of PgP were treated with doxorubicin, with or without pre-treatment with the PgP inhibitors verapamil or PSC 833. The distribution of doxorubicin in relation to tumor blood vessels was quantified using immunofluorescence. Results Our results indicate greater uptake of doxorubicin by cells near blood vessels in wild type as compared to PgP-overexpressing tumors, and pre-treatment with verapamil or PSC 833 increased uptake in PgP-overexpressing tumors. However, there were steeper gradients of decreasing doxorubicin fluorescence in wild-type tumors compared to PgP overexpressing tumors, and treatment of PgP overexpressing tumors with PgP inhibitors led to steeper gradients and greater heterogeneity in the distribution of doxorubicin. Conclusion PgP inhibitors increase uptake of doxorubicin in cells close to blood vessels, have little effect on drug uptake into cells at intermediate distances, and might have a paradoxical effect to decrease doxorubicin uptake into distal cells. This effect probably contributes to the limited success of PgP inhibitors in clinical trials

Antimicrobial activity and chemical composition of the essential oil from Campanula glomerata L. subsp. hispida (Witasek) Hayek

The volatile components of the essential oil from Campanula glomerata L. subsp. hispida (Witasek) Hayek was analyzed by GC and GCMS. Forty-eight compounds representing 89.0 % of the total oil were characterized and the main constituents of this specie were found to be hexadecanoic acid (24.51 %), docosane (15.9 %), isocitronellene (12.6 %), heneicosane (4.6 %), hexahydrofarnesyl acetone (3.2 %), ?-tricosene (1.6 %), octadecanol (1.4 %), caryophyllene oxide (1.3 %), ?-funebrene (1.2 %), ?-thujaplicinol (1.1 %), pentadecanoic acid (1.1 %), tricosane (1.1 %), (2E,4E)-decadienal (1.0 %), (E)-?-damascenone (1.0 %) and (E)-caryophyllene (1.0 %). The antimicrobial activity of the isolated essential oil of the plant was also investigated and it showed moderate antimicrobial and antifungal activities against Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, Mycobacterium smegmatis, Candida albicans and Saccharomyces cerevisiae

Microwave assisted essential oil analysis and antimicrobial activity of M. alpestris subsp. alpestris

The present work describes the chemical composition and antimicrobial activity of the essential oil of Myosotis alpestris F.W. Schmidt subsp. alpestris (Boraginaceae). The essential oil was obtained from all parts of the plant by microwave distillation and analyzed by GCFID and GC-MS. Forty-seven components representing 88.2 % of the total oil were characterized and the main components of this species were found to be n-nonanal (11.8 %), decanal (10.8 %), n-octanal (10.7 %), hexahydrofanesyl acetone (6.6 %), o-cymene (3.9 %), tetradecanal (3.7 %), eicosanol (2.2 %) and E-?-farnesene (2.0 %). The isolated essential oils of M. alpestris subsp. alpestris was tested for antimicrobial activity against the bacteria Escherichia coli, Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Listeria monocytogenes, Bacillus cereus, Mycobacterium smegmatis and the fungus Candida albicans and Saccharomyces cerevisiae at maximum essential oil concentration in hexane of 1000 ?g/mL and they showed only antibacterial activity against fungus bacteria