Bone-targeting radiopharmaceuticals for the treatment of bone-metastatic castration-resistant prostate cancer: exploring the implications of new data.

Background: Clinical features of patients with castration-resistant prostate cancer (CRPC) are characterized by a high incidence of bone metastases, which are associated with impairment of quality of life, pain, skeletal-related events (SREs), and a negative impact on prognosis. Advances in the understanding of cancer cell-bone stroma interactions and molecular mechanisms have recently permitted the development of new agents.

Purpose: We review the merits, applications, and limitations of emerging data sets on bone-metastatic CRPC with a focus on radium-223, an α-emitting radiopharmaceutical, and its use in therapy for this disease.

Role of proteasome inhibition in sensitized transplant candidates.

Objective: To review this efficacy and safety of bortezomib, a proteasome inhibitor, in the setting of the sensitized transplant candidate.

Data Sources: The data used in this review were from articles published (PubMed) between 2000 to 2010. Additionally abstracts from medical meetings related to transplant were also used.

Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection.

Background: Rapid and complete elimination of donor-specific anti-human leukocyte antigen antibodies (DSA) during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. Proteasome inhibitor-based therapy has been shown to effectively treat refractory AMR, but its use as a primary therapy for AMR has not been presented. Our initial experience with proteasome inhibition as a first-line therapy for AMR is presented.

Proteasome inhibition for antibody-mediated rejection.

Purpose Of Review: The purpose of this review is to describe the biochemistry and physiology of proteasome inhibition and to discuss recent studies with proteasome inhibitor therapy in organ transplantation.

Recent Findings: Traditional antihumoral therapies do not deplete plasma cells, the source of antibody production. Proteasome inhibition depletes both transformed and nontransformed plasma cells in animal models and human transplant recipients.

De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population.

Background: Transplant recipients are at increased risk of malignancy; however, the influence of transplantation on cancer outcomes has not been rigorously defined. The purpose of this study was to examine the influence of transplantation on the outcomes of individual cancers.

Methods: De novo nonsmall cell lung cancer, colon cancer, breast cancer, prostate cancer, bladder cancer, renal cell cancer (RCC), and malignant melanoma data in 635 adult (>18 years of age) transplant recipients (from the Israel Penn International Transplant Tumor Registry) were compared with data from 1,282,984 adults in the general population (from the Surveillance, Epidemiology, and End Results database).

Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection.

Background: Current antihumoral therapies in transplantation and autoimmune disease do not target the mature antibody-producing plasma cell. Bortezomib is a first in class proteosomal inhibitor, that is Food and Drug Administration approved, for the treatment of plasma cell-derived tumors that is multiple myeloma. We report the first clinical experience with plasma cell-targeted therapy (bortezomib) as an antirejection strategy.

Immunomodulatory effects of human recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF): evidence of antitumour activity.

Human recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) is traditionally used as supportive care for patients undergoing cytotoxic chemotherapy or haematopoietic cell progenitor mobilisation. Emerging evidence suggests rhuGM-CSF, through activity on monocytes and dendritic cells, acts as a potent modulator of immune responses and has the ability to recruit inflammatory cells and cytokines to local and systemic sites of infection. The immunomodulatory effects of rhuGM-CSF suggest the potential to enhance innate and acquired immune responses against tumour-related antigens.