Multi-drug Screening Research Articles

High Throughput Bioprinting Using Decellularized Adipose Tissue-Based Hydrogels for 3D Breast Cancer Modeling.

3D bioprinting allows rapid automated fabrication and can be applied for high throughput generation of biomimetic constructs for in vitro drug screening. Decellularized extracellular matrix (dECM) hydrogel is a popular biomaterial choice for tissue engineering and studying carcinogenesis as a tumor microenvironmental mimetic. This study proposes a method for high throughput bioprinting with decellularized adipose tissue (DAT) based hydrogels for 3D breast cancer modeling. A comparative analysis of decellularization protocol using detergent-based and detergent-free decellularization methods for caprine-origin adipose tissue is performed, and the efficacy of dECM hydrogel for 3D cancer modeling is assessed. Histological, biochemical, morphological, and biological characterization and analysis showcase the cytocompatibility of DAT hydrogel. The rheological property of DAT hydrogel and printing process optimization is assessed to select a bioprinting window to attain 3D breast cancer models. The bioprinted tissues are characterized for cellular viability and tumor cell-matrix interactions. Additionally, an approach for breast cancer modeling is shown by performing rapid high throughput bioprinting in a 96-well plate format, and in vitro drug screening using 5-fluorouracil is performed on 3D bioprinted microtumors. The results of this study suggest that high throughput bioprinting of cancer models can potentially have downstream clinical applications like multi-drug screening platforms and personalized disease models.

A fully 3D-printed versatile tumor-on-a-chip allows multi-drug screening and correlation with clinical outcomes for personalized medicine.

Optimal clinical outcomes in cancer treatments could be achieved through the development of reliable, precise ex vivo tumor models that function as drug screening platforms for patient-targeted therapies. Microfluidic tumor-on-chip technology is emerging as a preferred tool since it enables the complex set-ups and recapitulation of the physiologically relevant physical microenvironment of tumors. In order to overcome the common hindrances encountered while using this technology, a fully 3D-printed device was developed that sustains patient-derived multicellular spheroids long enough to conduct multiple drug screening tests. This tool is both cost effective and possesses four necessary characteristics of effective microfluidic devices: transparency, biocompatibility, versatility, and sample accessibility. Compelling correlations which demonstrate a clinical proof of concept were found after testing and comparing different chemotherapies on tumor spheroids, derived from ten patients, to their clinical outcomes. This platform offers a potential solution for personalized medicine by functioning as a predictive drug-performance tool.

Optimizing the Combination of Cytotoxic Drugs Along with Radiotherapy as Effective Treatment for Extranodal NK/T-Cell Lymphoma.

The optimal combination of cytotoxic drugs along with radiotherapy (RT) is unknown. We undertook multidrug screening process to identify the most efficacious cytotoxic drugs, and appraise the efficacy of various drug combinations. We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of nine drug classes and/or RT. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drugs. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/PLA-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens led to significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, P = 0.001), ASP/MTX-based (63.5%, P = 0.011), or ASP/NOS-based (63.2%, P<0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW. These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option, and provides a rationale and strategy for developing combination therapies.

ETMR-12. Novel cell models of CNS tumors with BCOR fusion or internal tandem duplication suggest FGFR and PDGFR as promising therapy targets

Central nervous system (CNS) tumors with BCOR internal tandem duplications (CNS-BCOR ITD) are aggressive malignancies recently included in the 2021 WHO Classification of CNS tumors. This entity is characterized by ITDs within the PUFD domain of BCOR, potentially interfering with protein-protein interactions and preventing non-canonical polycomb repressive complex 1.1 (ncPRC1.1) complex formation. Additionally, other BCOR alterations like frame shift mutations and gene fusions have been described. However, the underlying molecular mechanisms promoting tumor aggressiveness remain unknown. We established cell models from one patient harboring a BCOR frameshift mutation and another one with a concomitant BCORL1-fusion. Two additional models were derived from a patient with a CNS-BCOR ITD tumor. Multidrug screening uncovered high sensitivity against defined receptor tyrosine kinase (RTK) inhibitors (TKIs). In detail, ponatinib, nintedanib, and dovitinib reduced cell viability at half maximal inhibitory concentrations (IC50) in the low micro-molar range (<2.5 µM). Expression analyses of the respective TKI targets suggested fibroblast growth factor receptor 3 (FGFR3) and platelet derived growth factor receptor A (PDGFRA) as central players in this response. RTK inhibition resulted in strongly impaired downstream MAPK and Pi3K/AKT signaling. Vice versa, exposure to the RTK ligands bFGF and PDGFAA increased S6, Erk and Akt phosphorylation. Next, we treated two patients – one with a BCOR frame shift mutation/BCORL1-gene fusion and one with an ITD with nintedanib – within a multimodal treatment approach and achieving complete remission and disease stabilization, respectively. Ultimately, we analyzed respective RTK ligands in patient cerebral spinal fluid (CSF) and found FGF18 and PDGFA to correlate with tumor treatment response and progression. Summarizing, we uncover a central role of defined RTK signaling modules in the malignant phenotype of CNS-BCOR-ITD and tumors harboring BCOR alterations and elucidate their potential as therapeutic targets. Currently, we aim to dissect the interconnection between BCOR/BCORL1 alterations and RTK hyperactivation.

Sensitizing drug-resistant cancer cells from blood using microfluidic electroporator.

Direct assessment of patient samples holds unprecedented potential in the treatment of cancer. Circulating tumor cells (CTCs) in liquid biopsies are a rapidly evolving source of primary cells in the clinic and are ideal candidates for functional assays to uncover real-time tumor information in real-time. However, a lack of routines allowing direct and active interrogation of CTCs directly from liquid biopsy samples represents a bottleneck for the translational use of liquid biopsies in clinical settings. To address this, we present a workflow for using a microfluidic vortex-assisted electroporation system designed for the functional assessment of CTCs purified from blood. Validation of this approach was assessed through drug response assays on wild-type (HCC827 wt) and gefitinib-resistant (HCC827 GR6) non-small cell lung cancer (NSCLC) cells. HCC827 cells trapped within microscale vortices were electroporated to sequentially deliver drug agents into the cytosol. Electroporation conditions facilitating multi-agent delivery were characterized for both cell lines using an automatic single-cell image fluorescence intensity algorithm. HCC827 GR6 cells spiked into the blood to emulate drug-resistant CTCs were able to be collected with high purity, demonstrating the ability of the device to minimize background cell impact for downstream sensitive cell assays. Using our proposed workflow, drug agent combinations to restore gefitinib sensitivity reflected the anticipated cytotoxic response. Taken together, these results represent a microfluidics multi-drug screening panel workflow that can enable functional interrogation of patient CTCs in situ, thereby accelerating the clinical standardization of liquid biopsies.

Work schedule and substance abuse in vocational students.

Background: Drug abuse is one of the world’s most serious and rapidly rising problems, causing a wide variety of health issues with significant morbidity and mortality. This study aimed to explore the association between part-time work and substance abuse among vocational students.Design and methods: We conducted a cross-sectional analytical study that included all part-time working male students from five vocational male schools, and we used a standardized pretested questionnaire after obtaining written informed consent. A One- Step Multi-Drug Screen Test was used to assess the substances that were abusedResults: A total of 316 out of the 400 invited students participated in our study. Of the total screened subjects, 26.6 % were abusing substances. Twenty-five (36.2%) day working adolescents, nine (14.0%) night working adolescents, and forty (36.0%) day and night working adolescents were abusers.Tobacco was the most widely abused drug (68%) in the form of smoking, followed by cannabis (24%), marijuana (16.4%), alcohol (10%), and opioid (6.3%).Night workers had significantly lower rates of smoking, cannabis, Marijuana, alcohol, or opioids abuse, and Logistic regression was performed to ascertain the effects of the work schedule on the likelihood that participants have substance abuse; Night workers were 7.14 times less likely to have substance abuse than day workers, while day and night work did not differ from day work.Conclusions The prevalence of drug abuse in vocational students is considered high and a serious problem that damages the youth and the community. Significance for public health Throughout human history, substance abuse has been a challenging public health issue, particularly among adolescents. Work schedules, families, friends, and religious commitments all play a part in the abuse of vocational students. Part-time employment and substance abuse among vocational students are major issues. We advocate that the authorities and planners involved in the area work together to solve this issue.

Abstract 2643: Human and mouse reconstructed plate-based 3-dimensional culture assays that mimic the tumor microenvironment

Abstract In order to predict efficacy and toxicity of compounds advancing in the oncology drug discovery pipeline, and to minimize requirements for multiple animal studies, the development of in vitro assays that recapitulate in vivo conditions is increasingly important. While high throughput screening favors 2D assays, both for cost and relative speed in culturing and plating, they do not recapitulate the tumor architecture and the microenvironment that is more comparable to in vivo models. We now report this has been accomplished using zPREDICTA's organ-specific three-dimensional (3D) culture models which support long-term culture of carcinoma cells. Physiologic extracellular matrix (ECM) components are critical in maintaining the physical and spatial microenvironment as well as tumor phenotypes in reconstructed bone marrow (r-Bone) and mouse breast (r-mBreast) models. The r-Bone ECM allows for co-culture of tumor cells with mesenchymal stem cells, fibroblasts, lymphoid, myeloid, and CAR-T cells. The data here describes clear differences in the in vitro pharmacology of several standard of care agents in 2D, in adherent or suspension cultures, compared to the recapitulated 3D tumor microenvironment of the human hematopoietic compartment or the mouse breast ductal epithelium. For example, we find that cisplatin has a 10-30 fold higher IC50 in 4 different murine cell lines (MMTV-PyMT, 4T1, EMT6, and E0771) when cultured in the r-mBreast model than when those cells are adhered to the polystyrene in a 2D culture. Cytotoxicity assays such as CellTiter-Glo® can also be performed in a high throughput format in both 96 and 384-well 3D assay formats and we demonstrate equivalent bortezomib IC50 values in RPMI 8226 cell r-Bone cultures in both plate types. Additionally, cells can be isolated from the matrix after test agent exposure and analyzed by an appropriate downstream application, such as flow cytometry, where we show anti-CD19 CAR-T cell killing of CD19+ NALM6 cells in r-Bone cultures. These 3D models represent new early opportunities to screen test agents in a platform that is designed to more closely mimic in vivo tissue microenvironments and serve as a more relevant tool for multi drug screening and as a prerequisite to animal studies. Citation Format: Michael E. Steffey, Ying Qu, Andrew Karalewitz, Sumithra Urs, Julia Kirshner, Scott Wise. Human and mouse reconstructed plate-based 3-dimensional culture assays that mimic the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2643.

Cancer drug screening with an on-chip multi-drug dispenser in digital microfluidics.

Microfluidics has been the most promising platform for drug screening with a limited number of cells. However, convenient on-chip preparation of a wide range of drug concentrations remains a large challenge and has restricted wide acceptance of microfluidics in precision medicine. In this paper, we report a digital microfluidic system with an innovative control structure and chip design for on-chip drug dispensing to generate concentrations that span three to four orders of magnitude, enabling single drug or combinatorial multi-drug screening with simple electronic control. Specifically, we utilize droplet ejection from a drug drop sitting on a special electrode, named a drug dispenser, under high-voltage pulse actuation to deliver the desired amount of drugs to be picked up by a cell suspension drop driven by low-voltage sine wave actuation. Our proof-of-principle validation for this technique as a convenient single and multi-drug screening involved testing of the drug toxicity of two chemotherapeutics, cisplatin (Cis) and epirubicin (EP), towards MDA-MB-231 breast cancer cells and MCF-10A normal breast cells. The results are consistent with those screened based on traditional 96-well plates. These findings demonstrate the reliability of the drug screening system with an on-chip drug dispenser. This system with fewer cancer cells, less drug consumption, a small footprint, and high scalability with regard to concentration could pave the way for drug screening on biopsied primary tumor cells for precision medicine or any concentration-related research.

Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment.

To select the most efficient chemical to induce apoptosis in leukemia cells, a multidrug screen was applied on bone marrow mononuclear cells from chronic myeloid leukemia (CML) patients. Oprozomib (Cpd 21) was chosen for the subsequent experiments. The isobaric tags for relative and absolute quantitation (iTRAQ) was then performed to identify the responsible pathway relative to apoptosis and the results showed that endoplasmic reticulum (ER) chaperones were upregulated. Apoptosis was attributed to a joint effect of calcium leakage andPERK and IRE1α phosphorylation. The PERK branch was responsible for the first wave of cell death that occurred within 24 hours. The later wave of apoptosis was mediated by IRE1α, which transmit apoptotic signals through the ASK‐JNK‐BIM axis. Release of Ca2+ from ER into cytosol resulted in activation of calpain, which, in turn, cleaved caspase‐12. Our data also explained the selective killing effects of oprozomib on CML cells, which relied on proteasome activity. The present study demonstrated that prolonged inhibition of proteasome to trigger unfolded protein response could be an alternative strategy for treating CML in light of tyrosine kinase inhibitors resistance.

A 3D multi-drug screen reveals STAT3 signaling as the central regulator of neural invasion in pancreatic cancer.

A 3D multi-drug screen reveals STAT3 signaling as the central regulator of neural invasion in pancreatic cancer.

Novel Small Molecule Stimulants of Hematopoietic Stem Cells and Their Mode of Action

Agents that can improve the function and/or numbers of hematopoietic progenitor and stem cells (HSC) are of great importance for the treatment of bone marrow failures of different etiology. However, except for the hematopoietic growth factors, which lead to significant depletion HSC via simultaneous differentiation and some anabolic steroids, the list of capable agents that can improve the function or numbers of HSC is very short. However, such drugs would have a tremendous range of application from ex vivo expansion, to bone marrow regeneration in aplastic anemia (AA) post chemotherapy, HSC transplantation or to improve the function of normal HSC in aging.While performing a multidrug screen for the agents that could simultaneously decrease senescence and overcome proliferative block in pre-senescent cells, we have identified two compounds violuric acid (VA) and 1-naphthoquinone-2-monoxime (N2N1). Both compounds considerably extended the replicative life span (RLS) of normal cells. We applied these drugs to stromal/mesenchymal cells obtained from healthy bone marrows, primary human normal dermal fibroblasts, progeroid primary cells derived from the patients diagnosed with Werner or Bloom syndromes and small panel of cancer cell lines (SKM-1, K562, KG-1, THP-1). Both compounds, in dose dependent manner prolonged the RLS of replicatively pre-aged cells. On an average, 10-15 additional population doublings (PD) were achieved after addition of N2N1 at 1μM. VA treatment has added 8-10 extra population doublings. If compared with untreated controls that can propagate up to 45-50 PD, the treatment with VA or N2N1 adds from 16 to 30% increase in replicative life span. To compare, the effect of rapamycin (1nM) on human fibroblasts showed the RLS increase ranged from 5 to 10%. Treatment with both VA and N2N1 results in restoration of cell cycle progression, decreased activity of SAβG, down-regulation of p16, p21 and γH2A.X and, up-regulation of lamin B1 protein. Treatment with both compounds resulted in maintenance of normal telomere length.In term of HSC these agents in vivo increased the performance of HSC in competitive repopulation assay. Bone marrow cells were isolated from mice (CD45.1) treated with the vehicle or experimental drugs for three weeks. After that, they were mixed with the equal number of competitor bone marrow cells CD45.2 and injected into irradiated CD45.2 host animals. In three weeks, we observed a substantial domination of CD45.1 cells over CD45.2 in experimental groups, while control (vehicle) group exhibited equal representation of both genotypes. In vitro, treatment with VA or N2N1 contributed to prolonged availability of HSC in serial replating CFU assays in methylcellulose and long-term culture initiating cell (LTC-IC) assays. Addition of VA or N2N1 to the short-term cultures (7-14 days) of normal bone marrow cells in a medium containing a cocktail of growth factors (Il6, IL3, FLT3L, TPO, SCF) resulted in maintenance and growth of HSC or progenitors. Gated on lymphocyte sub-population, treated with N2N1 or VA samples revealed ~0.3%±0.02 or 0.2% ±0.02 of CD34+, CD45+ cells correspondingly, while control samples had 0.08% of these cells (the result of three independent experiments). Most importantly, we observed colonies formation, after application of these drugs to the bone marrow isolated from the patients diagnosed with severe AA. Further studies also indicated that these agents do not promote growth of leukemic cell.Analysis of mechanism of action showed that VA and N1N2 function as redox co-factors in oxidations of NAD(P)H. VA transfers electrons non-enzymaticly from NAD(P)H to oxidized glutathione or peroxides. N2N1 is a redox co-factor for the NAD(P)H dehydrogenase (quinone) 1 (NQO1) and together they move electrons from NAD(P)H to cytochrome c or CoQ10. As such, we presented here a comprehensive prove that pharmacologic manipulation of redox balance controlled by glutathione or NQO1 activity via redox catalysts can ameliorate the detrimental consequences of HSC loss during normal aging by interfering with direct ROS mediated signaling or attenuating collateral ROS mediated damages. [Display omitted] DisclosuresMaciejewski:Ra Pharmaceuticals, Inc: Consultancy; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Concomitant drug abuse of opioid dependent patients in maintenance treatment detected with a multi-target screening of oral fluid.

Numbers of drug-related deaths have been growing in Europe and the USA, especially those attributable to mixed drug consumption. Overdose deaths account for about one third up to one half of all illicit drug deaths worldwide. In most cases opioids are involved. Opioid maintenance treatment (OMT) is a well-established therapy option among people with opioid dependence. The aim of this study was to assess concomitant substance abuse in opioid-dependent patients under OMT in two centers in Munich, Germany. Oral fluid samples of opioid-dependent patients (n = 388) in OMT were randomly collected and analyzed by a multi-drug screening covering a wide range of psychotropic agents with UPLC-MS/MS techniques. Fifty-one percent of the patients had concomitant substance abuse of at least one non-prescribed substance, 32% were positive for substances that were not tested in routine urine diagnostics, especially pregabalin. Fifty-seven percent received take-home opioid medication, and 26% had contact with underage children. Among the take-home subgroup, a concomitant substance abuse of 43.5% was detected. Furthermore 52.5% of the patients with contact to underaged children exhibited concomitant substance abuse. Concomitant substance abuse is a serious issue among OMT patients. Screening for a broader range of substances than usually analyzed, reveals additional relevant abuse among OMT patients, including pregabalin-an anticonvulsant. Our study underscores the importance of monitoring a broad range of substances including others than usually screened in opioid-dependent patients in OMT. (Am J Addict 2018;XX:1-6).

DBT for co-morbid borderline personality disorder and substance use disorder without drug replacement in Egyptian outpatient settings: A non-randomized trial

BackgroundDialectical behavior therapy has demonstrated effectiveness for patients suffering from co-morbid borderline personality and substance use disorder. The current study tries to replicate results of previous studies in a mixed gender sample of Egyptian outpatients.AimThe aim of the current study was to examine the effectiveness of DBT without drug replacement relative to treatment as usual “TAU” in improving behavioral outcomes related to SUD and BPD, and improving emotional regulation.MethodsForty outpatients with co-morbid BPD and SUD in Alexandria and Cairo were assigned for one year either to comprehensive DBT program (20 patients), or TAU defined as ongoing outpatient psychotherapeutic treatment from referring center (20 patients). Patients were assessed at baseline and follow up assessment at 4, 8, 12 and 16 months was done using Arabic version of Difficulties in Emotion Regulation Scale (DERS), urine multidrug screen and time line follow-back method for assessment of alcohol and substance use history.ResultsFollowing one year of treatment, DBT group showed significantly lower doses of drugs used, DERS score, rates of hospital admission, ER visits, suicidal attempts and episodes of NSSI. Also, DBT patients showed markedly increased retention in treatment and longer duration of total alcohol abstinence and other drugs of abuse. Positive outcomes were maintained for four months post-treatment.ConclusionDBT demonstrated superior efficacy in comparison to TAU for treatment of Egyptian patients suffering from co-morbid borderline personality and substance use disorder across behavioral domains of SUD, BPD and reduction hospital admission, emergency room visits and DERS score.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Simultaneous label-free screening of G-quadruplex active ligands from natural medicine via a microfluidic chip electrophoresis-based energy transfer multi-biosensor strategy.

Rapid screening of active compounds plays a crucial role in the research and application of complex natural medicines. Herein, a new method of simultaneous label-free multi-drug screening based on a selective aptamer-carboxyfluorescein/graphene oxide energy transfer optical sensor combined with microfluidic chip electrophoretic separation is reported. In this study, seven traditional Chinese medicinal monomers were chosen as targets for the screening of G-quadruplex ligands. The screening results of the G-quadruplex active ligands, including daidzein, berberine hydrochloride, jatrorrhizine hydrochloride, and fangchinoline, and non-active ligands, including geniposide and oxymatrine, were consistent with those reported in literature. Moreover, one new potential G4DNA active drug, jujuboside A, was identified. Molecular simulation of the interaction between G4DNA and drugs was also carried out using HyperChem and AutoDock to verify the results of the experimental screening. It further demonstrated the reliability of our strategy. This novel separation and concentration based multi-sensing strategy provides a simple, rapid, and sensitive tool for simultaneous multi-drug screening, which is very meaningful for drug screening and bio-interaction analysis.

P2.06-043 3-Dimensional High Throughput Multi-Drug Screening Using Patient-Derived Tumor Cells (PDC) Established from Surgical Specimens of NSCLC: Topic: LAB, Other

To investigate the clinical applicability of the high throughput screening (HTS) using patient-derived tumor cells (PDC) which were established from patients with non-small cell lung cancer undergoing surgery. PDCs were isolated and cultured from surgical specimen from NSCLC at Samsung Medical Center. We performed the HTS for 24 drugs (23 targeted agents and 1 positive control drug) with a micropillar/microwell chip platform using PDCs. Scanned images of the live cells were obtained using an optical fluorescence. With 6 dosages per drug in 7 replicates, the dose response curves and corresponding IC50 values were calculated from the scanned images. From October 2015 to February 2016, 15 samples from patients with non-small cell lung cancer were collected. PDCs were successfully established in 12 (80%) patients, and nine of 12 cases were successfully cultured in 3-d suitable for 23-drug HTS platform. Three PDCs demonstrated a sensitivity to Neratinib (HER-2/EGFR inhibitor). These PDCs are currently being profiled to elucidate the underlying molecular mechanisms for neratinib sensitivity. Differential chemosensitivity were observed which suggests that this HTS platform based on 3D culture with micropillar/microwell chips and PDC model could potentially provide a preclinical tool for predicting the efficacy of targeted agents in lung cancer.

Theranostic barcoded nanoparticles for personalized cancer medicine.

Personalized medicine promises to revolutionize cancer therapy by matching the most effective treatment to the individual patient. Using a nanoparticle-based system, we predict the therapeutic potency of anticancer medicines in a personalized manner. We carry out the diagnostic stage through a multidrug screen performed inside the tumour, extracting drug activity information with single cell sensitivity. By using 100 nm liposomes, loaded with various cancer drugs and corresponding synthetic DNA barcodes, we find a correlation between the cell viability and the drug it was exposed to, according to the matching barcodes. Based on this screen, we devise a treatment protocol for mice bearing triple-negative breast-cancer tumours, and its results confirm the diagnostic prediction. We show that the use of nanotechnology in cancer care is effective for generating personalized treatment protocols.

False Positive Phencyclidine Results Caused by Venlafaxine

Back to table of contents Previous article Next article Letters to the EditorFull AccessFalse Positive Phencyclidine Results Caused by VenlafaxinePATRICIO MOLERO SANTOS M.D.PILAR LÓPEZ-GARCÍA M.D., Ph.D.JAVIER SCHLATTER NAVARRO M.D., Ph.D.ANTONIO SEVA FERNÁNDEZ M.D., Ph.D.BELÉN SÁDABA M.D., Ph.D.JORGE PLA VIDAL M.D., Ph.D.,PATRICIO MOLERO SANTOS M.D.Search for more papers by this authorPILAR LÓPEZ-GARCÍA M.D., Ph.D.Search for more papers by this authorJAVIER SCHLATTER NAVARRO M.D., Ph.D.Search for more papers by this authorANTONIO SEVA FERNÁNDEZ M.D., Ph.D.Search for more papers by this authorBELÉN SÁDABA M.D., Ph.D.Search for more papers by this authorJORGE PLA VIDAL M.D., Ph.D.Search for more papers by this author,Published Online:1 Feb 2007https://doi.org/10.1176/ajp.2007.164.2.349AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We report the case of an unexpected positive result on routine urine drug screening for phencyclidine in a patient who assured that she had never used such substance. Because similar results have recently been reported (1 , 2) and in order to avoid inappropriate suspicion by medical caregivers, we performed a blood test that confirmed the absence of phencyclidine and the interpretation of the former urine test as a false positive result. “Ms. A,” a 48-year-old patient with a 31-year history of recurrent depressive disorder, was admitted to the psychiatric hospitalization unit for an acute exacerbation of her mental disorder. She was receiving treatment with venlafaxine 225 mg/day, lamotrigine 100 mg/day, and lormetazepam 2 mg/day. During the prior month she experienced worsening of the depressive symptoms, concurrent with mood-incongruent psychotic symptoms that were not of a clearly depressive nature (thought broadcasting, paranoid and mystic delusions, delusions of control and influence, and grossly disorganized behavior). A routine drug screening by the qualitative immunoassay INSTANT-VIEW Multi-Drug Screen Urine Test (Alpha Laboratories) upon admission was positive for phencyclidine and negative for other drugs. The package insert for the test (3) shows cross-reactivity to methylphenidate, pheniramine, and tenocyclidine, but not for venlafaxine. Given the importance of knowing the origin of the psychotic symptoms, because she would meet DSM-IV criteria for schizoaffective disorder if a toxic etiology was excluded, we performed another urine test 2 weeks later that was also positive for phencyclidine. We then extracted, on the same day, blood and urine samples to check this result by means of a gas chromatography-mass spectrometry analysis. This technique revealed the absence of phencyclidine in blood and in urine (and confirmed that the two prior positive urine tests for phencyclidine were false positives) and confirmed the presence of venlafaxine in blood and of venlafaxine and norvenlafaxine in urine. The urine analysis by gas chromatography-mass spectrometry revealed only prescribed drugs and caffeine. The patient was hospitalized and compliance of the other prescribed drugs was adequate. The diagnosis was changed to schizoaffective disorder, and treatment with amisulpride 100 mg/day yielded a significant improvement of the psychotic symptoms. Pamplona, SpainThe authors report no competing interests.

False Positive Phencyclidine Results Caused by Venlafaxine

Back to table of contents Previous article Next article Letters to the EditorFull AccessFalse Positive Phencyclidine Results Caused by VenlafaxinePATRICIO MOLERO SANTOS M.D.PILAR LÓPEZ-GARCÍA M.D., Ph.D.JAVIER SCHLATTER NAVARRO M.D., Ph.D.ANTONIO SEVA FERNÁNDEZ M.D., Ph.D.BELÉN SÁDABA M.D., Ph.D.JORGE PLA VIDAL M.D., Ph.D.,PATRICIO MOLERO SANTOS M.D.Search for more papers by this authorPILAR LÓPEZ-GARCÍA M.D., Ph.D.Search for more papers by this authorJAVIER SCHLATTER NAVARRO M.D., Ph.D.Search for more papers by this authorANTONIO SEVA FERNÁNDEZ M.D., Ph.D.Search for more papers by this authorBELÉN SÁDABA M.D., Ph.D.Search for more papers by this authorJORGE PLA VIDAL M.D., Ph.D.Search for more papers by this author,Published Online:1 Feb 2007https://doi.org/10.1176/ajp.2007.164.2.349AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We report the case of an unexpected positive result on routine urine drug screening for phencyclidine in a patient who assured that she had never used such substance. Because similar results have recently been reported (1 , 2) and in order to avoid inappropriate suspicion by medical caregivers, we performed a blood test that confirmed the absence of phencyclidine and the interpretation of the former urine test as a false positive result. “Ms. A,” a 48-year-old patient with a 31-year history of recurrent depressive disorder, was admitted to the psychiatric hospitalization unit for an acute exacerbation of her mental disorder. She was receiving treatment with venlafaxine 225 mg/day, lamotrigine 100 mg/day, and lormetazepam 2 mg/day. During the prior month she experienced worsening of the depressive symptoms, concurrent with mood-incongruent psychotic symptoms that were not of a clearly depressive nature (thought broadcasting, paranoid and mystic delusions, delusions of control and influence, and grossly disorganized behavior). A routine drug screening by the qualitative immunoassay INSTANT-VIEW Multi-Drug Screen Urine Test (Alpha Laboratories) upon admission was positive for phencyclidine and negative for other drugs. The package insert for the test (3) shows cross-reactivity to methylphenidate, pheniramine, and tenocyclidine, but not for venlafaxine. Given the importance of knowing the origin of the psychotic symptoms, because she would meet DSM-IV criteria for schizoaffective disorder if a toxic etiology was excluded, we performed another urine test 2 weeks later that was also positive for phencyclidine. We then extracted, on the same day, blood and urine samples to check this result by means of a gas chromatography-mass spectrometry analysis. This technique revealed the absence of phencyclidine in blood and in urine (and confirmed that the two prior positive urine tests for phencyclidine were false positives) and confirmed the presence of venlafaxine in blood and of venlafaxine and norvenlafaxine in urine. The urine analysis by gas chromatography-mass spectrometry revealed only prescribed drugs and caffeine. The patient was hospitalized and compliance of the other prescribed drugs was adequate. The diagnosis was changed to schizoaffective disorder, and treatment with amisulpride 100 mg/day yielded a significant improvement of the psychotic symptoms. Pamplona, SpainThe authors report no competing interests.

Tests for Drugs of Abuse

Tests for Drugs of Abuse