Albumin-based cancer therapeutics for intraperitoneal drug delivery : a review

Albumin is a remarkable carrier protein with multiple cellular receptor and ligand binding sites, which are able to bind and transport numerous endogenous and exogenous compounds. The development of albumin-bound drugs is gaining increased importance in the targeted delivery of cancer therapy. Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal metastasis (PM). PM is characterized by the presence of widespread metastatic tumor nodules on the peritoneum, mostly originating from gastro-intestinal or gynaecological cancers. Albumin as a carrier for chemotherapy holds considerable promise for IP delivery in patients with PM. Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of PM compared to standard chemotherapy formulations. Here, we review the evidence on albumin-bound chemotherapy with a focus on IP administration and its efficacy in PM

Ideologies implicated in IT innovation in government: a critical discourse analysis of Mexico’s international trade administration

We develop a perspective of IT innovation in the public sector as a process that involves three complementary areas of ideology and concomitant dispute: first, the widespread view of e-government as a transformative force that leads to major improvements of public sector functions for the benefit of society at large; second, ideologies concerning the substantive policies enacted by public sector organizations; and third, ideology regarding public sector modernization. Our research examines how the objectives of IT projects and their actual effects in government are influenced by such ideologies and contestations that surround them. We develop our theoretical contribution with a critical discourse analysis that traces the ideological underpinnings of two consecutive IT projects for the administration of international trade in Mexico. This analysis associates the objectives of the IT projects with the emergence and ensuing contestation in Mexican politics of two ideologies: the first ideology concerns free international trade as imperative for economic development; the second ideology concerns public sector modernization that sought to overcome historically formed dysfunctionalities of public administration bureaucracies by adopting management practices from the private sector. The analysis then identifies the effects of the ideologically shaped IT projects on two key values of public administration: efficiency and legality. The insights of this research on the role of ideology in IT innovation complement organizational perspectives of e-government; socio-cognitive perspectives that focus on ideas and meaning, such as technology frames and organizing visions; and perspectives that focus on politics in IT innovation

Investigating the Information Systems Heterarchy

This article assesses how one IS organization is changing in response to the increased globalization of software development and posits the emergence of a new form of multi-national enterprise (MNE)—the heterarchy. Data from two projects create new insights into the structures and behaviors of ISMNEs as they adapt to global systems development. The article identifies four primary dimensions of impact—cultural, economic, operational, and organizational—and suggests how such organizations are evolvin

Controlled production of atomic oxygen and nitrogen in a pulsed radio-frequency atmospheric-pressure plasma

International audienceRadio-frequency driven atmospheric pressure plasmas are efficient sources for the production of reactive species at ambient pressure and close to room temperature. Pulsing the radio-frequency power input provides additional control over species production and gas temperature. Here, we demonstrate the controlled production of highly reactive atomic oxygen and nitrogen in a pulsed radio-frequency ( ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn001.gif] 13.56 MHz) atmospheric-pressure plasma, operated with a small ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn002.gif] 0.1 % air-like admixture ( ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn003.gif] \rm N_2 / ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn004.gif] \rm O_2 at ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn005.gif] 4:1 ) through variations in the duty cycle. Absolute densities of atomic oxygen and nitrogen are determined through vacuum-ultraviolet absorption spectroscopy using the DESIRS beamline at the SOLEIL synchrotron coupled with a high resolution Fourier-transform spectrometer. The neutral-gas temperature is measured using nitrogen molecular optical emission spectroscopy. For a fixed applied-voltage amplitude (234?V), varying the pulse duty cycle from 10% to 100% at a fixed 10?kHz pulse frequency enables us to regulate the densities of atomic oxygen and nitrogen over the ranges of ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn006.gif] (0.18±0.03) ? ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn007.gif] (3.7±0.1)× 10^20 ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn008.gif] \rm m^-3 and ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn009.gif] (0.2±0.06) ? ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn010.gif] (4.4±0.8) × 10^19 ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn011.gif] \rm m^-3 , respectively. The corresponding 11?K increase in the neutral-gas temperature with increased duty cycle, up to a maximum of ##IMG## [http://ej.iop.org/images/0022-3727/50/45/455204/daa8da2ieqn012.gif] (314±4) K, is relatively small. This additional degree of control, achieved through regulation of the pulse duty cycle and time-averaged power, could be of particular interest for prospective biomedical applications

Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases

BACKGROUND: For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM) to induce neutropenia. Although high doses (350–450 mg/kg) are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg) is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. METHODS: Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 μL) were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus), meningoencephalitis (S. pneumoniae), and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis). RESULTS: The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm(3)). Profound neutropenia (≤10 neutrophils/mm(3)) was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. CONCLUSION: A CPM total dose of 250 mg/kg is sufficient to induce profound and sustained neutropenia (<10 neutrophils/mm(3)) at least during 3 days in outbred mice, is simpler than previously described methods, and allows successful induction of infection in a variety of experimental models

Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTXePC) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3Luc) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with Taxol®, sustained PTXePC therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTXePC implant system, which could potentially translate into successful clinical outcomes

Global value trees

The fragmentation of production across countries has become an important feature of the globalization in recent decades and is often conceptualized by the term “global value chains” (GVCs). When empirically investigating the GVCs, previous studies are mainly interested in knowing how global the GVCs are rather than how the GVCs look like. From a complex networks perspective, we use the World Input-Output Database (WIOD) to study the evolution of the global production system. We find that the industry-level GVCs are indeed not chain-like but are better characterized by the tree topology. Hence, we compute the global value trees (GVTs) for all the industries available in the WIOD. Moreover, we compute an industry importance measure based on the GVTs and compare it with other network centrality measures. Finally, we discuss some future applications of the GVTs

Comparative genomics of Cluster O mycobacteriophages

Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange