Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK)

An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15. In the second cycle, patients received cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without bevacizumab. The complete remission rates in the 2 arms were not different (65%). Event-free survival at 12 months was 33% for the standard arm versus 30% for the bevacizumab arm; at 24 months, it was 22% and 16%, respectively (P = .42). The frequencies of severe adverse events (SAEs) were higher in the bevacizumab arm (n = 63) compared with the control arm (n = 28; P = .043), but the percentages of death or life-threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). The results of the present study show that the addition of bevacizumab to standard chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR904 in The Nederlands Trial Register (www.trialregister.nl).

Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group

To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements.

Functionalisation of PLLA nanofiber scaffolds using a possible cooperative effect between collagen type I and BMP-2: impact on colonization and bone formation in vivo

The reconstruction of large bone defects after injury or tumor resection often requires the use of bone substitution. Artificial scaffolds based on synthetic biomaterials can overcome disadvantages of autologous bone grafts, like limited availability and donor side morbidity. Among them, scaffolds based on nanofibers offer great advantages. They mimic the extracellular matrix, can be used as a carrier for growth factors and allow the differentiation of human mesenchymal stem cells. Differentiation is triggered by a series of signaling processes, including integrin and bone morphogenetic protein (BMP), which act in a cooperative manner. The aim of this study was to analyze whether these processes can be remodeled in artificial poly-(l)-lactide acid (PLLA) based nanofiber scaffolds in vivo. Electrospun matrices composed of PLLA-collagen type I or BMP-2 incorporated PLLA-collagen type I were implanted in calvarial critical size defects in rats. Cranial CT-scans were taken 4, 8 and 12 weeks after implantation. Specimens obtained after euthanasia were processed for histology and immunostainings on osteocalcin, BMP-2 and Smad5. After implantation the scaffolds were inhomogeneously colonized and cells were only present in wrinkle- or channel-like structures. Ossification was detected only in focal areas of the scaffold. This was independent of whether BMP-2 was incorporated in the scaffold. However, cells that migrated into the scaffold showed an increased ratio of osteocalcin and Smad5 positive cells compared to empty defects. Furthermore, in case of BMP-2 incorporated PLLA-collagen type I scaffolds, 4 weeks after implantation approximately 40 % of the cells stained positive for BMP-2 indicating an autocrine process of the ingrown cells. These findings indicate that a cooperative effect between BMP-2 and collagen type I can be transferred to PLLA nanofibers and furthermore, that this effect is active in vivo. However, this had no effect on bone formation. The reason for this seems to be an unbalanced colonization of the scaffolds with cells, due to insufficient pore size.

Cooperative and Noncooperative Assembly of Oligopyrenotides Resolved by Atomic Force Microscopy

The supramolecular assembly of amphiphilic oligopyrenotide building blocks (covalently linked heptapyrene, Py7) is studied by atomic force microscopy (AFM) in combination with optical spectroscopy. The assembly process is triggered in a controlled manner by increasing the ionic strength of the aqueous oligomer solution. Cooperative noncovalent interactions between individual oligomeric units lead to the formation of DNA-like supramolecular polymers. We also show that the terminal attachment of a single cytidine nucleotide to the heptapyrenotide (Py7-C) changes the association process from a cooperative (nucleation−elongation) to a noncooperative (isodesmic) regime, suggesting a structure misfit between the cytidine and the pyrene units. We also demonstrate that AFM enables the identification and characterization of minute concentrations of the supramolecular products, which was not accessible by conventional optical spectroscopy.

Challenges of the Cooperative Movement In Addressing Issues of Human Security In the Context of a Neoliberal World: the Case of Argentina

The response of some Argentine workers to the 2001 crisis of neoliberalism gave rise to a movement of worker-recovered enterprises (empresas recuperadas por sus trabajadores or ERTs). The ERTs have emerged as former employees took over the control of generally fraudulently bankrupt factories and enterprises. The analysis of the ERT movement within the neoliberal global capitalist order will draw from William Robinson’s (2004) neo-Gramscian concept of hegemony. The theoretical framework of neo-Gramscian hegemony will be used in exposing the contradictions of capitalism on the global, national, organizational and individual scales and the effects they have on the ERT movement. The ERT movement has demonstrated strong level of resilience, despite the numerous economic, social, political and cultural challenges and limitations it faces as a consequence of the implementation of neoliberalism globally. ERTs have shown that through non-violent protests, democratic principles of management and social inclusion, it is possible to start constructing an alternative social order that is based on the cooperative principles of “honesty, openness, social responsibility and caring for others” (ICA 2007) as opposed to secrecy, exclusiveness, individualism and self-interestedness. In order to meet this “utopian” vision, it is essential to push the limits of the possible within the current social order and broaden the alliance to include the organized members of the working class, such as the members of trade unions, and the unorganized, such as the unemployed and underemployed. Though marginal in number and size, the members of ERTs have given rise to a model that is worth exploring in other countries and regions burdened by the contradictory workings of capitalism. Today, ERTs serve as living proofs that workers too are capable of successfully running businesses, not capitalists alone.

The Dual Ownership Structure: a Model to Connect the Cooperative Model With Financial Markets

In business literature, the conflicts among workers, shareholders and the management have been studied mostly in the frame of stakeholder theory. The stakeholder theory recognizes this issue as an agency problem, and tries to solve the problem by establishing a contractual relationship between the agent and principals. However, as Marcoux pointed out, the appropriateness of the contract as a medium to reduce the agency problem should be questioned. As an alternative, the cooperative model minimizes the agency costs by integrating the concept of workers, owners and management. Mondragon Corporation is a successful example of the cooperative model which grew into the sixth largest corporation in Spain. However, the cooperative model has long been ignored in discussions of corporate governance, mainly because the success of the cooperative model is extremely difficult to duplicate in reality. This thesis hopes to revitalize the scholarly examination of cooperatives by developing a new model that overcomes the fundamental problem in the cooperative model: the limited access to capital markets. By dividing the ownership interest into financial and control interest, the dual ownership structure allows cooperatives to issue stock in the capital market by making a financial product out of financial interest.