Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer.

Purpose: Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and blocks its ability to dimerize with other HER receptors. Pertuzumab represents a new class of targeted therapeutics known as HER dimerization inhibitors. A clinical study was conducted to investigate safety and pharmacokinetics of pertuzumab and to perform a preliminary assessment of HER dimerization inhibition as a treatment strategy.

Role of Smac in human leukaemic cell apoptosis and proliferation.

Smac (or DIABLO) is a recently identified, novel proapoptotic molecule, which is released from mitochondria into the cytosol during apoptosis. Smac functions by eliminating the caspase-inhibitory properties of the inhibitors of apoptosis proteins (IAP), particularly XIAP. In this study, we stably transfected both full-length (FL) and mature (MT) Smac genes into the K562 and CEM leukaemic cell lines.

Role of DNA methylation in the suppression of Apaf-1 protein in human leukaemia.

Apaf-1 protein deficiency occurs in human leukaemic blasts and confers resistance to cytochrome-c-dependent apoptosis. Demethylation treatment with 5-aza-2'-deoxycytidine (5aza2dc) increased the sensitivity of the K562 leukaemic cell line to UV light-induced apoptosis in association with increased Apaf-1 protein levels. There was no correlation between Apaf-1 protein expression and Apaf-1 mRNA levels after the demethylation treatment.

Liposomal encapsulation diminishes daunorubicin-induced generation of reactive oxygen species, depletion of ATP and necrotic cell death in human leukaemic cells.

In this study, we tested the mechanisms of daunorubicin (DNR)- and the liposomal encapsulated daunorubicin (DaunoXome or DNX)-induced killing in three human leukaemic cell lines, K562, K/Bax and CEM. DNX showed less cytotoxicity in leukaemic cells than conventional DNR. The intracellular accumulation of DNX was 10 times less than conventional DNR during exposure to drugs for up to 5 h.

Malignancy: Granulocyte Colony Stimulating Factor Increases the Efficacy of Conventional Amphotericin in the Treatment of Presumed Deep-Seated Fungal Infection in Neutropenic Patients following Intensive Chemotherapy or Bone Marrow Transplantation for Haematological Malignancies.

A prospective, comparative study of empiric amphotericin B with, or without, granulocyte colony stimulating factor was carried out to assess whether the addition of granulocyte colony stimulating factor to empiric amphotericin B improves the clinical response in neutropenic patients with suspected or proven fungal infection. Fifty nine neutropenic adults with haematological malignancy and antibiotic-refractory fever or clinical evidence of deep-seated fungal infection were studied. Patients received intravenous colloidal amphotericin B (1 milligram per kilogram body weight) with or without subcutaneous granulocyte colony stimulating factor (three to five micrograms per kilogram body weight).