Overexpression of fatty acid synthase (FASN), a key regulator the de novo synthesis acids, has been demonstrated in variety cancers and is associated with poor prognosis increased multidrug resistance. Inhibition FASN anti‐obesity drug orlistat shown to have significant anti‐tumourigenic effects many cancers, notably breast prostate. In our study, we investigated whether inhibition using an effective adjunctive treatment for ovarian that become platinum resistant cisplatin‐resistant tumour...

Non-invasive serial imaging is desirable to detect processes such as necrotic and apoptotic cell death in cancer patients undergoing treatment. This study investigated the use of diffusion-weighted (DW-) magnetic resonance (MRI) for induced by either a cytotoxic drug (irinotecan), or apoptosis-inducing agent birinapant, human tumour xenografts vivo. Nude mice bearing SW620 colon carcinoma were treated with vehicle, irinotecan (50 mg kg−1) birinapant (30 up 5 days. DW-MRI was performed prior...

Interleukin-15 (IL-15) is a cytokine that has been shown to expand CD8 T cell and natural killer (NK) populations, therefore potential for potentiating adoptive immune therapy cancer. Previously, IL-15 induce proliferation of memory cells through activation telomerase. Here, we investigated whether telomerase also activated during the mediated NK NKT-like (CD56+CD3+) cells. We examined extent each three signaling pathways known be stimulated by IL-2/IL-15 (JAK-STAT, PI3K-AKT Ras-RAF/MAPK)...

Prostate cancer is the second most commonly diagnosed in men with mortality rates, overtaking those for breast last 2 years UK. Despite advances prostate treatments, over 25% of do not survive 5 advanced disease. Due to success immunotherapies treating other cancers, this treatment modality has been investigated cancer, however, sole FDA approved immunotherapy so far (Provenge™) only extends life by a few months. Therefore, finding immunotherapeutic agents treat major interest. Our group...

Introduction Prostate cancer is one of the most commonly diagnosed malignancies in men with high mortality rates. Despite recent therapeutic advances, such as immunotherapies, survival patients advance disease remains significantly low. Blockade immune checkpoints has led to low response rates these probably due immunosuppressive microenvironment and mutation burden prostate tumors. Combination multiple immunotherapeutic regimes also been unsatisfactory augmented adverse effects. To activate...

Abstract The objective of this study was to evaluate the potential value ultrasound (US) shear wave elastography (SWE) in assessing relative change elastic modulus colorectal adenocarcinoma xenograft models vivo and investigate any correlation with histological analysis. We sought test whether non-invasive evaluation tissue stiffness is indicative pathological tumour changes can be used monitor therapeutic efficacy. US-SWE performed xenografts 15 NCr nude immunodeficient mice, which were...

Objectives To identify cytokines that can activate and expand NK cells in the presence of prostate cancer order to determine whether these agents may be useful future intra‐tumoural administration pre‐clinical clinical trials. Materials Methods Lymphocytes isolated from normal donor blood were set up co‐cultures with either or non‐cancerous cell lines, together each interleukin (IL)‐2, IL‐12, IL‐15, interferon (IFN)‐γ IL‐21 for a period 7 days. Then, expansion cells, NKT CD8 T was measured...

Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal tumour promoting effects have been attributed to NO, making its role cancer biology controversial unclear. To investigate the specific of tumour‐derived NO vascular development, C6 glioma cells were genetically modified include doxycycline regulated gene expression system that controls an antisense RNA inducible nitric synthase (iNOS)...

Photoacoustic imaging (PAI) provides information on haemoglobin levels and blood oxygenation (sO2). To facilitate assessment of the variability in sO2 tumours, for example response to therapies, baseline these parameters was evaluated subcutaneous head neck tumours mice, using a PAI system (MSOTinVision-256TF). Tumours anaesthetized animals (midazolam-fentanyl-medetomidine) were imaged 75 min, varying positions, repeatedly over 6 days. An increasing linear trend average tumoural observed,...

Background: The prostate cancer microenvironment is highly immunosuppressive; immune cells stimulated in the periphery by systemic immunotherapies will be rendered inactive once entering this environment. Immunotherapies for need to break tolerance. We have previously identified interleukin-15 (IL-15) as only cytokine tested that activates and expands presence of cells. In current study, we aimed identify a method boosting efficacy IL-15 cancer. Methods: engineered, conjugation myristoylated...

The coxsackie and adenovirus receptor (CAR) is a member of the junctional adhesion molecule (JAM) family receptors localised to epithelial cell tight adherens junctions. CAR has been shown be highly expressed in lung cancer where it proposed promote tumor growth regulate mesenchymal transition (EMT), however potential role metastasis remains poorly understood. To better understand this progression, we manipulated expression both epithelial-like mesenchymal-like cells. In cases,...

The fine structure of nuptial pad surface the anuran amphibians Bombina variegata , Pelophylax epeiroticus ridibundus and Rana dalmatina was examined by scanning electron microscopy. Nuptial pads are cutaneous secondary sexual characters males that appear during breeding season disappear afterwards following an annual cycle. In P. R. were observed on ventrolateral aspect first digit (the thumb) as darkish remarkably keratinized papillae. B. almost black very visible thumb, second third front...

The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with studies. Here the utility and sensitivity anatomical functional data/biomarkers acquired from transgenic mouse models neuroblastoma using a dedicated radiofrequency (RF) coil on 3T scanner was evaluated. Multiparametric mice bearing abdominal neuroblastomas performed at 3T, data cross-referenced that same 7T system. T2-weighted imaging, quantitation native longitudinal relaxation time (T1)...

Nitric oxide (NO) has been strongly implicated in glioma progression and angiogenesis. The endogenous inhibitors of NO synthesis, asymmetric dimethylarginine (ADMA) N-monomethyl-l-arginine (l-NMMA), are metabolized by dimethylaminohydrolase (DDAH), hence, DDAH is an intracellular factor that regulates NO. However, may also have NO-independent action. We aimed to investigate whether I any direct role tumour vascular development growth independent its NO-mediated effects, order establish the...

Interleukin-15 (IL-15) is a cytokine previously suggested as potential immunotherapy for cancer treatment. IL-15 can effectively reduce tumor growth in many preclinical models including prostate cancer. This due to its ability expand and activate immune cells, such CD8+ T cells natural killer cells. To increase the potency of IL-15, we have engineered protein variant that be modified localize retained tissues where it administered. However, production recombinant purity, correct refolding...

Abstract Photoacoustic imaging (PAI) provides information on haemoglobin levels and blood oxygenation (sO 2 ). To facilitate assessment of the variability in sO tumours, for example response to therapies, baseline these parameters was evaluated subcutaneous head neck tumours mice, using a PAI system (MSOT-inVision-256TF). Tumours anaesthetized animals (midazolam-fentanyl-medetomidine) were imaged 75 minutes; varying positions; repeatedly over 6 days. An increasing linear trend average...

Recently, an all-optical ultrasound imaging system was presented that capable of real-time, video-rate 2D pulse-echo imaging. This achieved through the use rapid scanning optics and a centimetre-scale optical generator, which allowed for synthesis 1D source arrays arbitrary geometry. Back-scattered recorded using highly sensitive fibre-optic detector. Here, modification to this is enabled array geometries. extension implementation 1.5D arrays, we demonstrated yield improved elevational...

Abstract Introduction & Objectives: Prostate cancer (PC) is the second most commonly diagnosed in men and eighth leading cause of cancer-related mortality world. The only successful immunotherapy for disease (ProvengeTM) extends life by a few months. Therefore finding immunotherapeutic agents treatment PC major interest. It has been previously shown our group that Interleukin-15 (IL-15), unlike other therapeutic cytokines such as IL-2 IL-12, can stimulate expansion activity CD8 NK cells...

Due to the difference between absorption spectra of reduced and oxygenated haemoglobin, spectroscopic photoacoustic imaging can be used determine, in vivo non-invasively, local blood oxygen saturation. Conventional methods achieve this by computing absolute concentrations which require models for, or computations of, fluence at depth. However, such estimates are potentially inaccurate expensive compute. In work, estimation is circumvented modelling spectra. Over wavelength ranges haemoglobin...

Abstract Background: The PI3K/AKT/mTOR pathway is known to regulate glucose metabolism, proliferation and apoptosis, hence the inhibition of mTOR expected have impact on these important mechanisms tumor growth survival. Studies cancer metabolism following reported date only been carried out allosteric inhibitors which selectively inhibit activity mTORC1. metabolic changes associated with dual mTORC1 2 inhibitions remain unknown. AZD2014 a mTORC1/2 inhibitor. aims this study are (i) examine...

Abstract Background: Effective tumour therapy requires induction of cell death. Non-invasive serial imaging is desirable to detect processes such as necrotic and apoptotic death in cancer patients undergoing treatment with conventional well new drugs within clinical trials. This study investigated the use diffusion-weighted magnetic resonance (DW-MRI) for induced human xenografts by either cytotoxic drug irinotecan, or mimetic second mitochondria-derived activator caspases (Smac) birinapant,...

Introduction & Objectives: Prostate cancer (PC) is the second most commonly diagnosed in men and eighth leading cause of cancer-related mortality world. The only successful immunotherapy for disease (ProvengeTM) extends life by a few months. Therefore finding immunotherapeutic agents treatment PC major interest. It has been previously shown our group that Interleukin-15 (IL-15), unlike other therapeutic cytokines such as IL-2 IL-12, can stimulate expansion activity CD8 NK cells vitro when...

Abstract The immunosuppressive prostate cancer microenvironment renders most infiltrating effector immune cells anergic or regulatory. Immunotherapeutic agents localized to the can break this tolerance, leading greater efficacy and less toxicity than systemically administered drugs. We have previously shown that cytotopic modification of interleukin-15 (cyto-IL-15) activate NK CD8+ T-cells in presence cells. In present study, we used cyto-IL-15 two immuno-checkpoint blocking antibodies...