Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts.

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM is often diagnosed late, at a point where limited treatment options are available, but early intervention could improve the chances of successful treatment for MPM patients. Biomarkers to detect MPM in at-risk individuals are needed to implement early diagnosis technologies.

Dysregulation of Stress-Induced Translational Control by in Host Cells.

contributes to the chronic oral disease periodontitis, triggering the activation of host inflammatory responses, inducing cellular stresses such as oxidation. During stress, host cells can activate the Integrated Stress Response (ISR), a pathway which determines cellular fate, by either downregulating protein synthesis and initiating a stress-response gene expression program, or by initiating programmed cell death. Recent studies have implicated the ISR within both host antimicrobial defenses and the pathomechanism of certain microbes.

The effect of apigenin and chemotherapy combination treatments on apoptosis-related genes and proteins in acute leukaemia cell lines.

Apigenin is a dietary polyphenol found abundantly in fruit and vegetables, which sensitizes leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and alkylating agents (e.

Comparison of Osteosarcoma Aggregated Tumour Models with Human Tissue by Multimodal Mass Spectrometry Imaging.

Osteosarcoma (OS) is the most common primary bone malignancy and largely effects adolescents and young adults, with 60% of patients under the age of 25. There are multiple cell models of OS described in vitro that express the specific genetic alterations of the sarcoma. In the work reported here, multiple mass spectrometry imaging (MSI) modalities were employed to characterise two aggregated cellular models of OS models formed using the MG63 and SAOS-2 cell lines.

Bacterial Manipulation of the Integrated Stress Response: A New Perspective on Infection.

Host immune activation forms a vital line of defence against bacterial pathogenicity. However, just as hosts have evolved immune responses, bacteria have developed means to escape, hijack and subvert these responses to promote survival. In recent years, a highly conserved group of signalling cascades within the host, collectively termed the integrated stress response (ISR), have become increasingly implicated in immune activation during bacterial infection.

Role of MALDI-MSI in combination with 3D tissue models for early stage efficacy and safety testing of drugs and toxicants.

: Three-dimensional (3D) cell cultures have become increasingly important materials to investigate biological processes and drug efficacy and toxicity. The ability of 3D cultures to mimic the physiology of primary tissues and organs in the human body enables further insight into cellular behavior and is hence highly desirable in early-stage drug development. Analyzing the spatial distribution of drug compounds and endogenous molecules provides an insight into the efficacy of a drug whilst simultaneously giving information on biological responses.

The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment.

Programmed death-ligand 1 (PD-L1) is an immune checkpoint inhibitor that binds to its receptor PD-1 expressed by T cells and other immune cells to regulate immune responses; ultimately preventing exacerbated activation and autoimmunity. Many tumors exploit this mechanism by overexpressing PD-L1 which often correlates with poor prognosis. Some tumors have also recently been shown to express PD-1.

Characterization of an Aggregated Three-Dimensional Cell Culture Model by Multimodal Mass Spectrometry Imaging.

Mass spectrometry imaging (MSI) is an established analytical tool capable of defining and understanding complex tissues by determining the spatial distribution of biological molecules. Three-dimensional (3D) cell culture models mimic the pathophysiological environment of tumors and are rapidly emerging as a valuable research tool. Here, multimodal MSI techniques were employed to characterize a novel aggregated 3D lung adenocarcinoma model, developed by the group to mimic the tissue.

Mass spectrometry imaging of endogenous metabolites in response to doxorubicin in a novel 3D osteosarcoma cell culture model.

Three-dimensional (3D) cell culture is a rapidly emerging field, which mimics some of the physiological conditions of human tissues. In cancer biology, it is considered a useful tool in predicting in vivo chemotherapy responses, compared with conventional two-dimensional (2D) cell culture. We have developed a novel 3D cell culture model of osteosarcoma composed of aggregated proliferative tumour spheroids, which shows regions of tumour heterogeneity formed by aggregated spheroids of polyclonal tumour cells.

Polyphenols enhance the activity of alkylating agents in leukaemia cell lines.

Polyphenols have been shown to sensitize solid tumours to alkylating agents such as cisplatin, and induce apoptosis and/or cell-cycle arrest. Here, we assess the effects of five polyphenols alone and in combination with three alkylating agents: cisplatin, cyclophosphamide and chlorambucil in lymphoid and myeloid leukaemia cells lines, and non-tumour control cells. In lymphoid leukaemia cell lines there was a synergistic reduction in ATP and glutathione levels, an induction of cell cycle arrest, DNA damage and apoptosis when quercetin, apigenin, emodin and rhein were combined with cisplatin and cyclophosphamide; and when apigenin and rhein were combined with chlorambucil.

Dietary polyphenols influence antimetabolite agents: methotrexate, 6-mercaptopurine and 5-fluorouracil in leukemia cell lines.

Polyphenols have been previously shown to sensitize leukemia cell lines to topoisomerase inhibitors. Here, we assess the effects of five polyphenols when used alone and in combination with antimetabolites: methotrexate, 6-mercaptopurine and 5-fluorouracil; in lymphoid and myeloid leukemia cells lines, and non-tumor control cells. The effects of combined treatments were investigated on ATP and glutathione levels, cell-cycle progression, DNA damage and apoptosis.

Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics.

Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed "cancer stem cells" (CSCs).

Methods: Expression of postulated stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in UM cell lines and primary UM short-term cultures (STCs) established from tumor samples.

Biological and structural studies of phosphonium 'masked thiolate' compounds.

The ability of phosphonium cations to act as intracellular transport vectors is well-established. Phosphonioalkylthiosulfate zwitterions, and ω-thioacetylalkylphosphonium salts, which act as 'masked thiolate' ligands, are useful precursors for the formation of phosphonium-functionalised gold nanoparticles, enabling the nanoparticles to be transported into cells for diagnostic and therapeutic purposes. In this study we have completed cytotoxicity studies of ω-thioacetylpropylphosphonium salts derived from triphenylphosphine and tri(4-fluorophenyl)phosphine, which show that the compounds are only toxic towards PC3 prostate cancer cells at high concentrations and at prolonged incubation periods and display IC values of 67 μM and 252 μM respectively, significantly higher than those of other phosphonium salts.

MALDI-MSI for the analysis of a 3D tissue-engineered psoriatic skin model.

MALDI-MS Imaging is a novel label-free technique that can be used to visualize the changes in multiple mass responses following treatment. Following treatment with proinflammatory cytokine interleukin-22 (IL-22), the epidermal differentiation of Labskin, a living skin equivalent (LSE), successfully modeled psoriasis in vitro. Masson's trichrome staining enabled visualization and quantification of epidermal differentiation between the untreated and IL-22 treated psoriatic LSEs.

Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines.

Background: Mortality rates for leukemia are high despite considerable improvements in treatment. Since polyphenols exert pro-apoptotic effects in solid tumors, our study investigated the effects of polyphenols in haematological malignancies. The effect of eight polyphenols (quercetin, chrysin, apigenin, emodin, aloe-emodin, rhein, cis-stilbene and trans-stilbene) were studied on cell proliferation, cell cycle and apoptosis in four lymphoid and four myeloid leukemic cells lines, together with normal haematopoietic control cells.

Anti-angiogenic properties of ADAMTS-4 in vitro.

Angiogenesis is an indispensable mechanism in development and in many pathologies, including cancer, synovitis and aberrant wound healing. Many angiogenic stimulators and inhibitors have been investigated, and some have progressed to the clinic. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a group of multifunctional proteinases.

What hope for the future? GNAQ and uveal melanoma.

Uveal melanomas (UM) are aggressive ocular tumours that spread to the liver. They are characterised by alterations of chromosome 3 and 8, which are highly predictive of a poor prognosis. Unfortunately, being able to identify those patients with aggressive disease has not, as yet, translated into improved survival.

Use of macrophages to target therapeutic adenovirus to human prostate tumors.

New therapies are required to target hypoxic areas of tumors as these sites are highly resistant to conventional cancer therapies. Monocytes continuously extravasate from the bloodstream into tumors where they differentiate into macrophages and accumulate in hypoxic areas, thereby opening up the possibility of using these cells as vehicles to deliver gene therapy to these otherwise inaccessible sites. We describe a new cell-based method that selectively targets an oncolytic adenovirus to hypoxic areas of prostate tumors.

Analysis of modulated gene expression in a model of Interferon-gamma-induced persistence of Chlamydia trachomatis in HEp-2 cells.

Background: Chlamydia trachomatis is an important pathogen, being the commonest sexually transmitted bacterial disease in the Western world and is also implicated in a number of acute and chronic diseases. Persistent infections of C. trachomatis are particularly associated with chronic infections, which although eliciting an immune response, result in tissue damage leading to complications such as pelvic inflammatory disease.

In vitro propagation and characterization of neoplastic stem/progenitor-like cells from human prostate cancer tissue.

Background: According to the cancer stem cell hypothesis, tumor growth is sustained by a subpopulation of cancer stem/progenitor-like cells. Self-renewal and high clonogenic potential are characteristics shared by normal stem and neoplastic stem/progenitor-like cells. We investigated whether human prostate cancer specimens contain cells with these properties.

Real-time polymerase chain reaction shows that density centrifugation does not always remove Chlamydia trachomatis from human semen.

Objective: To evaluate the efficiency of sperm washing procedures to remove Chlamydia trachomatis from semen both in clinical samples and experimental inoculations.

Design: Laboratory-based study.

Setting: Research laboratory in a university hospital.

Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors.

Tubulin-binding vascular-disrupting agents (VDA) are currently in clinical trials for cancer therapy but the factors that influence tumor susceptibility to these agents are poorly understood. We evaluated the consequences of modifying tumor vascular morphology and function on vascular and therapeutic response to combretastatin-A4 3-O-phosphate (CA-4-P), which was chosen as a model VDA. Mouse fibrosarcoma cell lines that are capable of expressing all vascular endothelial growth factor (VEGF) isoforms (control) or only single isoforms of VEGF (VEGF120, VEGF164, or VEGF188) were developed under endogenous VEGF promoter control.