The In Vitro Development of a Metabolomic Test for Response to Antineoplastic Drugs

Background: Only a fraction of patients benefit from any given chemotherapeutic. An assay that enables early identification of individuals who are/are not benefiting from a drug would be useful. We postulate that a response to systemic therapy is associated with characteristic changes in extracellular metabolites. Methods: Multiple tumor cell lines were exposed to a variety of chemotherapeutics. Supernatants collected at baseline and at 72 hours were analyzed by gas chromatography-mass spectrometry to identify metabolomic changes. An MTT assay was used to quantify growth inhibition. Results: We identified 23 candidate metabolites that change with response to therapy, independent of cell and drug type. This model had a sensitivity and specificity of 0.714 and 0.813 respectively in an ROC analysis. Conclusions: The candidate metabolites identified will be assessed in clinical samples from patients treated with systemic therapy. Identification of response-related changes in the circulating metabolome may represent a novel means of detecting response to chemotherapy

A Strategy for Early Detection of Response to Chemotherapy Drugs Based on Treatment-related Changes in the Metabolome

We describe a biomarker-based approach to delivering chemotherapy that entails monitoring treatment changes in the circulating metabolome that reflect efficacy. In-vitro, multiple tumor cell lines were exposed to numerous chemotherapeutics. Supernatants were collected at baseline and 72 hours post treatment. MTT assays were used to quantify growth inhibition. Clinical samples were derived from a phase II clinical trial of second-line axitinib in patients with advanced hepatocellular carcinoma. Sera were collected at baseline and 2-4 weeks after treatment initiation. Response to therapy was estimated by CT scan at 8 weeks. Samples were analyzed by gas chromatography-mass spectrometry to identify metabolomic changes associated with response. In vitro, we found drug-specific and generalizable patterns of change in the extracellular metabolome accompany growth inhibition. A cell death signature was also identified. This approach was also applied to clinical samples. While the in vitro signatures were detectable in vivo, a more robust signal was identified clinically that appeared within 4 weeks of administering drug that distinguished individuals with a treatment response. These changes were extinguished as tumor growth resumed. Serial monitoring of the metabolome during chemotherapy is a means to follow treatment efficacy and emergence of resistance, informing the oncologist whether to modify treatment

An overview of graphene materials: properties, applications and toxicity on aquatic environments

Due to unique chemical and physical properties, nanomaterials from the Graphene family are being increasingly introduced in all fields of science. The specific roles they can occupy within different applications are attracting increased attention by several industrial sectors. These carbon nanoparticles are released into the environment especially accumulating in aquatic systems. Since the discovery of graphene, a number of research actives are being conducted to find out the toxic potential of the Graphene family materials to different organism's models. Although their toxicity effects are well described for biomedical applications, few data were produced with the specific aim of assessing the toxic effects of these carbon nanomaterials in the aquatic environment. The purpose of this review is to compile up-to-date information on properties, applications and characterization methods of graphene family materials in aquatic environments and identified biological toxic impacts of these NMs, with special focus on graphene oxide based on the most recent literature.publishe