A phase I open-label dose-escalation study of intravenous BI 2536 together with pemetrexed in previously treated patients with non-small-cell lung cancer.

Introduction: BI 2536 is a potent, highly selective inhibitor of polo-like kinase (Plk) 1. This open-label, phase I study investigated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics (PK) of BI 2536 IV in combination with standard-dose pemetrexed in previously treated advanced or metastatic non-small-cell lung cancer.

Patients And Methods: A standard 3 + 3 design was used.

Phase I open-label study of continuous treatment with BIBF 1120, a triple angiokinase inhibitor, and pemetrexed in pretreated non-small cell lung cancer patients.

Introduction: BIBF 1120 (planned brand name Vargatef) is a novel, oral, triple angiokinase inhibitor targeting three receptor classes involved in blood vessel formation. The objectives of this phase I, open-label dose-escalation study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of BIBF 1120 with pemetrexed in patients with recurrent advanced-stage non-small cell lung carcinoma.

Patients And Methods: Patients harboring a tumor of any non-small cell lung carcinoma histology, previously treated with one first-line platinum-based chemotherapy regimen, received a BIBF 1120 starting dose of 100 mg bid (days 2-21) with pemetrexed 500 mg/m2 (day 1) over a 21-day cycle.

Mesenchymal stem cells and adipogenesis in hemangioma involution.

Hemangioma is a benign tumor of infancy whose hallmark is rapid growth during the first year of life followed by slow regression during early childhood. The proliferating phase is characterized by abundant immature endothelial cells, the involuting phase by prominent endothelial-lined vascular channels and endothelial apoptosis, and the involuted phase by few remaining capillary-like vessels surrounded by loose fibrofatty tissue. Nothing is known about the mechanisms that contribute to the adipogenesis during this spontaneous regression.

Cell-based cancer gene therapy: breaking tolerance or inducing autoimmunity?

This review examines the mechanisms involved in anti-tumor immunity and how peptides present in many tumor types (tumor-associated antigens) are recognized by T cells from tumor-bearing cancer patients. Tumor-associated antigens are derived from proteins that are also expressed in normal cells. It is predicted that immune responses to such peptides will be compromised by self-tolerance or that stimulation of effective immune responses will be accompanied by autoimmunity.

Bone marrow-derived dendritic cell vaccination of dogs with naturally occurring melanoma by using human gp100 antigen.

Canine malignant melanoma (CMM) is a common and aggressive form of cancer in dogs. Established therapeutic approaches such as surgery, chemotherapy, and radiation therapy (RT) have not proven curative. As a coadjuvant of RT and to enhance the antimelanoma immune response, we characterized dendritic cells (DCs) from the bone marrow (BM) of dogs with CMM, ex vivo, for use in therapeutic vaccines.

Therapeutic effect of angiostatin gene transfer in a murine model of endometriosis.

Endometriosis, the growth of ectopic endometrial tissue, is a chronic recurrent disease affecting 10% of the female population causing dyspareunia, pelvic pain, dysmenorrhea, and infertility. Suppression of ovarian activity is the cornerstone of medical therapy with limited benefit and severe adverse effects. Angiogenesis plays a major role in the development of endometriosis suggesting that anti-angiogenic therapy would offer a new therapeutic approach.

Antiangiogenic and antifibrotic gene therapy in a chronic infusion model of peritoneal dialysis in rats.

To identify the relative importance of peritoneal fibrosis and angiogenesis in peritoneal membrane dysfunction, adenoviral mediated gene transfer of angiostatin, a recognized angiogenesis inhibitor, and decorin, a transforming growth factor-beta-inhibiting proteoglycan, were used in a daily infusion model of peritoneal dialysis. A peritoneal catheter and subcutaneous port were inserted in rats. Five and fourteen d after insertion, adenovirus-expressing angiostatin, decorin, or AdDL70, a null control virus, were administered.