Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumour in humans and has a very poor prognosis. The existing treatments have had limited success in increasing overall survival. Thus, identifying and understanding the key molecule(s) responsible for the malignant phenotype of GBM will yield new potential therapeutic targets. The treatment of brain tumours faces unique challenges, including the presence of the blood brain barrier (BBB), which limits the concentration of drugs that can reach the site of the tumour. Nevertheless, several promising treatments have been shown to cross the BBB and have shown promising pre-clinical results. This review will outline the status of several of these promising targeted therapies.

Extracellular vesicles (EVs) are produced and secreted from most cells of the body and can be recovered in biological fluids. Although there has been extensive characterisation of the protein and nucleic acid component of EVs, their lipidome has received little attention and may represent a unique and untapped source of biomarkers for prostate cancer diagnosis and prognosis. EVs were isolated from non-tumourigenic (RWPE1), tumourigenic (NB26) and metastatic (PC-3) prostate cell lines. Lipids were extracted and subsequently used for targeted lipidomics analysis for the quantitation of molecular lipid species. A total of 187 molecular lipid species were quantitatively identified in EV samples showing differential abundance between RWPE1, NB26 and PC-3 EV samples. Fatty acids, glycerolipids and prenol lipids were more highly abundant in EVs from non-tumourigenic cells, whereas sterol lipids, sphingolipids and glycerophospholipids were more highly abundant in EVs from tumourigenic or metastatic cells. This study identified differences in the molecular lipid species of prostate cell-derived EVs, increasing our understanding of the changes that occur to the EV lipidome during prostate cancer progression. These differences highlight the importance of characterising the EV lipidome, which may lead to improved diagnostic and prognostic biomarkers for prostate cancer.

Chlamydia trachomatisis a pathogen of the genital tract and ocular epithelium. Infection is established by the binding of the metabolically inert elementary body (EB) to epithelial cells. These are taken up by endocytosis into a membrane-bound vesicle termed an inclusion. The inclusion avoids fusion with host lysosomes, and the EBs differentiate into the metabolically active reticulate body (RB), which replicates by binary fission within the protected environment of the inclusion. During the extracellular EB stage of theC. trachomatislife cycle, antibody present in genital tract or ocular secretions can inhibit infection both in vivo and in tissue culture. The RB, residing within the intracellular inclusion, is not accessible to antibody, and resolution of infection at this stage requires a cell-mediated immune response mediated by gamma interferon-secreting Th1 cells. Thus, an ideal vaccine to protect againstC. trachomatisgenital tract infection should induce both antibody (immunoglobulin A [IgA] and IgG) responses in mucosal secretions to prevent infection by chlamydial EB and a strong Th1 response to limit ascending infection to the uterus and fallopian tubes. In the present study we show that transcutaneous immunization with major outer membrane protein (MOMP) in combination with both cholera toxin and CpG oligodeoxynucleotides elicits MOMP-specific IgG and IgA in vaginal and uterine lavage fluid, MOMP-specific IgG in serum, and gamma interferon-secreting T cells in reproductive tract-draining caudal and lumbar lymph nodes. This immunization protocol resulted in enhanced clearance ofC. muridarum(C. trachomatis, mouse pneumonitis strain) following intravaginal challenge of BALB/c mice.

Many studies have implicated Ca2+ and calmodulin (CaM) as regulators of the cell cycle. Ca2+/CaM-stimulated proteins, including the family of multifunctional Ca2+/CaM-stimulated protein kinases (CaMK), have also been identified as mediators of cell cycle progression. CaMKII is the best-characterized member of this family, and is regulated by multi-site phosphorylation and targeting. Using pharmacological inhibitors that were believed to be specific for CaMKII, CaMKII has been implicated in every phase of the cell cycle. However, these ‘specific’ inhibitors also produce effects on other CaMKs. These additional effects are usually ignored, and the effects of the inhibitors are normally attributed to CaMKII without further investigation. Using new specific molecular techniques, it has become clear that CaMKI is an important regulator of G1, whereas CaMKII is essential for regulating G2/M and the metaphase-anaphase transition. If the mechanisms controlling these events can be fully elucidated, new targets for...

Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases widely expressed in many tissues that is capable of mediating diverse functional responses depending on its cellular and molecular microenvironment. This review briefly summarises current knowledge on the structure and regulation of CaMKII and focuses on how the molecular environment, and interaction with binding partner proteins, can produce different populations of CaMKII in different cells, or in different subcellular locations within the same cell, and how these different populations of CaMKII can produce diverse functional responses to activation following an increase in intracellular calcium concentration. This review also explores the possibility that identifying and characterising the molecular interactions responsible for the molecular targeting of CaMKII in different cells in vivo, and identifying the sites on CaMKII and/or the binding proteins through which these interactions occur, could lead to the development of highly selective inhibitors of specific CaMKII-mediated functional responses in specific cells that would not affect CaMKII-mediated responses in other cells. This may result in the development of new pharmacological agents with therapeutic potential for many clinical conditions.

The importance of Ca²⁺ signalling in key events of cancer cell function and tumour progression, such as proliferation, migration, invasion and survival, has recently begun to be appreciated. Many cellular Ca²⁺-stimulated signalling cascades utilise the intermediate, calmodulin (CaM). The Ca²⁺/CaM complex binds and activates a variety of enzymes, including members of the multifunctional Ca²⁺/calmodulin-stimulated protein kinase (CaMK) family. These enzymes control a broad range of cancer-related functions in a multitude of tumour types. Herein, we explore the cancer-related functions of these kinases and discuss their potential as targets for therapeutic intervention.