RESUMO
Response to anticancer agents is often restricted to subsets of patients. The recognition of factors underlying this heterogeneity and the identification of biomarkers associated with response to drugs would greatly improve the efficacy of drug treatment. Platforms that can comprehensively map drug response in high-throughput ex vivo provide a unique tool to identify associated biomarkers and provide hypotheses for mechanisms underlying variable response. Such screens can be performed on cell lines and short-term cultures of primary cells to take advantage of the respective models' strength, which include, e.g., the ability to silence genes in cell lines and the "indefinite" supply of primary cells where clonal selection can be avoided. Cohorts of such samples represent the natural diversity of cancers, including rarer mutations and combinatorial patterns of mutations.We here summarize a simple and scalable method for the measurement of viability after drug exposure based on ATP measurements as a surrogate for viability, which we use to measure and understand drug response in cell lines and primary cells.
Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Biomarcadores Farmacológicos/análise , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Triagem em Larga Escala/economia , Ensaios de Triagem em Larga Escala/métodos , Humanos , Células Tumorais CultivadasRESUMO
Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Microfluídica/métodos , Neoplasias/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Feminino , Ensaios de Triagem em Larga Escala/economia , Ensaios de Triagem em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/métodos , Humanos , Camundongos , Microfluídica/economia , Microfluídica/instrumentação , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão/métodosRESUMO
Hollow fiber cell fishing (HFCF) based on hepatoma HepG-2 cells, human renal tubular ACHN cells or human cervical carcinoma HeLa cells, coupled with high-performance liquid chromatography (HPLC), was developed and employed to research the major active components in Zi-Cao-Cheng-Qi decoction both in vitro and in vivo. The research showed that the active components, such as hesperidin, magnolol, honokiol, shikonin, emodin and ß,ß'-dimethylacrylshikonin were screened out by HFCF based on the cancer cells in vitro, furthermore they can be absorbed into blood and reach in the target organ, and some of the active components can be fished by the cells and maintain effective concentrations. Before application of HFCF with HPLC, cell growth state, cell survival rate, positive effect on screening results binding between active centers on the fiber and target components, repeatability of retention times and relative peak areas of the target analytes were analysed and investigated. In short, HFCF with HPLC is a simple, inexpensive, effective, and reliable method that can be used in researching active components from traditional Chinese medicine (TCM) and its formula both in vitro and in vivo, elucidating preliminarily the TCM characteristics of multiple components and multiple targets, laying a foundation for expounding the antitumor efficacy material basis in TCM.
Assuntos
Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Medicamentos de Ervas Chinesas/farmacologia , Administração Oral , Animais , Antineoplásicos/química , Técnicas de Cultura de Células/economia , Técnicas de Cultura de Células/métodos , Cromatografia Líquida de Alta Pressão/economia , Cromatografia Líquida de Alta Pressão/métodos , Ensaios de Seleção de Medicamentos Antitumorais/economia , Medicamentos de Ervas Chinesas/química , Células HeLa , Células Hep G2 , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Ratos , Ratos Sprague-DawleyRESUMO
Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening.
Assuntos
Antineoplásicos/farmacologia , Técnicas Biossensoriais/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Apoptose/efeitos dos fármacos , Técnicas Biossensoriais/economia , Técnicas Biossensoriais/instrumentação , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Desenho de Equipamento , Humanos , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de TempoRESUMO
A novel hollow fiber cell fishing with high performance liquid chromatography (HFCF-HPLC) was extended and used to screen flavonoid and anthraquinone active compound groups simultaneously from traditional Chinese medicines (TCMs). In this study, three cells (MCF-7, SGC7901, and MADB-106) were seeded on the inner wall of the hollow fiber employed to screen bioactive components from TCM water decoction. The variables influencing HFCFHPLC, such as cell seeding time, screening stirring rate and time, and active compound concentration, were investigated and optimized. The surface property of the hollow fiber seeded with cells, the cell survival rate under different conditions, the nonspecific binding between active centers in the fiber and the target compounds, and the repeatability and recovery of HFCF-HPLC were analyzed and validated. Certain structures of the compounds fished by HFCF-HPLC were identified after comparing the retention times of the reference substances. To verify preliminarily the binding site between the bioactive components and cells, we separated the cell membrane and cell organelle from live MCF-7 cells. We then employed the cell membrane, cell organelle, and the whole cells to screen simultaneously the active compounds. The cell fishing factor of the active compound was calculated and discussed as the index of cell-drug binding ability in HFCFHPLC. Tamoxifen as a positive control and indomethacin as a negative control were screened by HFCF-HPLC to verify the method. The results indicate that HFCF-HPLC is an effective and reliable method for the screening and analysis of bioactive components. Moreover, this method can be applied to predict bioactive candidates in TCMs.
Assuntos
Antineoplásicos/farmacologia , Cromatografia Líquida de Alta Pressão/instrumentação , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Medicamentos de Ervas Chinesas/farmacologia , Ensaios de Triagem em Larga Escala/instrumentação , Animais , Cromatografia Líquida de Alta Pressão/economia , Ensaios de Seleção de Medicamentos Antitumorais/economia , Desenho de Equipamento , Ensaios de Triagem em Larga Escala/economia , Humanos , Células MCF-7 , Neoplasias/tratamento farmacológico , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Drug screening is an essential and widely used technique for drug discovery in various biomedical fields notably in oncology. Here we describe a functional screening assay based on the bioluminescence detection of a secreted luciferase for monitoring cell viability of cancer cells in a high-throughput format. This assay allows the screening of large libraries comprising thousands of compounds and the identification of potential anticancer molecules in a rapid, facile, and cost-effective manner.
Assuntos
Ensaios de Seleção de Medicamentos Antitumorais/métodos , Medições Luminescentes , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Análise Custo-Benefício , Ensaios de Seleção de Medicamentos Antitumorais/economia , Vetores Genéticos/genética , Humanos , Lentivirus/genética , Luciferases/genética , Luciferases/metabolismo , TransfecçãoRESUMO
Structure-based modeling combined with rational drug design, and high throughput screening approaches offer significant potential for identifying and developing lead compounds with therapeutic potential. The present review focuses on these two approaches using explicit examples based on specific derivatives of Gossypol generated through rational design and applications of a cancer-specificpromoter derived from Progression Elevated Gene-3. The Gossypol derivative Sabutoclax (BI-97C1) displays potent anti-tumor activity against a diverse spectrum of human tumors. The model of the docked structure of Gossypol bound to Bcl-XL provided a virtual structure-activity-relationship where appropriate modifications were predicted on a rational basis. These structure-based studies led to the isolation of Sabutoclax, an optically pure isomer of Apogossypol displaying superior efficacy and reduced toxicity. These studies illustrate the power of combining structure-based modeling with rational design to predict appropriate derivatives of lead compounds to be empirically tested and evaluated for bioactivity. Another approach to cancer drug discovery utilizes a cancer-specific promoter as readouts of the transformed state. The promoter region of Progression Elevated Gene-3 is such a promoter with cancer-specific activity. The specificity of this promoter has been exploited as a means of constructing cancer terminator viruses that selectively kill cancer cells and as a systemic imaging modality that specifically visualizes in vivo cancer growth with no background from normal tissues. Screening of small molecule inhibitors that suppress the Progression Elevated Gene-3-promoter may provide relevant lead compounds for cancer therapy that can be combined with further structure-based approaches leading to the development of novel compounds for cancer therapy.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Gossipol/análogos & derivados , Gossipol/farmacologia , Neoplasias/tratamento farmacológico , Animais , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Triagem em Larga Escala , Humanos , Neoplasias/genética , Regiões Promotoras Genéticas/efeitos dos fármacosRESUMO
Small molecules with potent biological effects on the fate of normal and cancer-derived stem cells represent both useful research tools and new drug leads for regenerative medicine and oncology. Long-term expansion of mouse and human neural stem cells is possible using adherent monolayer culture. These cultures represent a useful cellular resource to carry out image-based high content screening of small chemical libraries. Improvements in automated microscopy, desktop computational power, and freely available image processing tools, now means that such chemical screens are realistic to undertake in individual academic laboratories. Here we outline a cost effective and versatile time lapse imaging strategy suitable for chemical screening. Protocols are described for the handling and screening of human fetal Neural Stem (NS) cell lines and their malignant counterparts, Glioblastoma-derived neural stem cells (GNS). We focus on identification of cytostatic and cytotoxic "hits" and discuss future possibilities and challenges for extending this approach to assay lineage commitment and differentiation.
Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Glioma/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Técnicas de Cultura de Células , Linhagem Celular , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/economia , Glioma/patologia , Ensaios de Triagem em Larga Escala/economia , Ensaios de Triagem em Larga Escala/métodos , Humanos , Camundongos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neurais/citologiaRESUMO
AIM: The insulin-like growth factor-1 receptor (IGF1R) is over-expressed in a wide variety of tumors and contributes to tumor cell proliferation, metastasis and drug resistance. The aim of this study was to establish a sensitive screening platform to identify novel IGF1R inhibitors. METHODS: The catalytic domain of IGF1R was expressed using the Bac-to-Bac baculovirus expression system. The screening platform for IGF1R inhibitors was established based on ELISA. The binding profile of IGF1R with the inhibitors was predicted with molecular docking and then subjected to the surface plasmon resonance (SPR) approach. The growth inhibition of cancer cells by the inhibitors was assessed with MTT assay. Apoptosis was analyzed using flow cytometry and Western blotting. RESULTS: A naturally occurring small molecule compound hematoxylin was identified as the most potent inhibitor (IC50 value=1.8±0.1 µmol/L) within a library of more than 200 compounds tested. Molecular simulation predicted the possible binding mode of hematoxylin with IGF1R. An SPR assay further confirmed that hematoxylin bound directly to IGF1R with high binding affinity (Kd=4.2 × 10â»6 mol/L). In HL-60 cancer cells, hematoxylin inactivated the phosphorylation of IGF1R and downstream signaling and therefore suppressed cell proliferation. Mechanistic studies revealed that hematoxylin induced apoptosis in HL-60 cells via both extrinsic and intrinsic pathways. CONCLUSION: A simple, sensitive ELISA-based screening platform for identifying IGF1R inhibitors was established. Hematoxylin was identified as a promising IGF1R inhibitor with effective antitumor activity that deserves further investigation.
Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Hematoxilina/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo , Animais , Cátions Bivalentes/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Clonagem Molecular , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaio de Imunoadsorção Enzimática/economia , Células HL-60 , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Estrutura Terciária de Proteína , Receptor IGF Tipo 1/química , Receptor IGF Tipo 1/genética , Sensibilidade e EspecificidadeRESUMO
Medulloblastoma is an aggressive childhood cerebellar tumor. We recently reported a mouse model with conditional deletion of Patched1 gene that recapitulates many characteristics of the human medulloblastoma. Qualitative symptoms observed in the mouse model include irregular stride length, impaired cranial nerve function and decreased motor coordination and performance. In our current study, several quantitative behavioral assays including a mouse rotarod, a forced air challenge, a screen inversion test, a horizontal wire test, and stride length analysis were evaluated to determine the most sensitive and cost-effective functional assay for impaired neuromotor behavior associated with disease progression. Magnetic resonance imaging (MRI) was used to confirm and monitor tumor growth and as an anatomical biomarker for therapeutic response. Wild type mice or medulloblastoma-prone, conditional Patched1 knockout mice were observed by behavioral assays and MRI from postnatal weeks 3-6. Bortezomib treatment was administered during this period and therapeutic response was assessed using cerebellar volumes at the end of treatment. Of the behavioral tests assessed in this study, stride length analysis was best able to detect differences between tumor-prone mice and wild type mice as early as postnatal day 37 (P=0.003). Significant differences between stride lengths of bortezomib treated and control tumor-bearing mice could be detected as early as postnatal day 42 (P=0.020). Cerebellar volumes measured by MRI at the end of treatment validated the therapeutic effects seen by behavioral tests (P=0.03). These findings suggest that stride length analysis may serve as one of the more sensitive and cost-effective method for assessing new therapeutic compounds in this and other preclinical model of brain tumors.
Assuntos
Antineoplásicos/uso terapêutico , Ataxia/etiologia , Ácidos Borônicos/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Desempenho Psicomotor , Pirazinas/uso terapêutico , Receptores de Superfície Celular/deficiência , Animais , Bortezomib , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Transtornos Neurológicos da Marcha/etiologia , Coxeadura Animal/etiologia , Imageamento por Ressonância Magnética , Meduloblastoma/patologia , Meduloblastoma/fisiopatologia , Camundongos , Camundongos Knockout , Receptores Patched , Receptor Patched-1 , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/fisiologiaAssuntos
Produtos Biológicos/uso terapêutico , Descoberta de Drogas , Biologia Marinha , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Ensaios Clínicos Fase II como Assunto , Conservação dos Recursos Naturais/legislação & jurisprudência , Dioxóis/isolamento & purificação , Dioxóis/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Tetra-Hidroisoquinolinas/isolamento & purificação , Tetra-Hidroisoquinolinas/uso terapêutico , TrabectedinaRESUMO
The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development.
Assuntos
Antineoplásicos/economia , Antineoplásicos/farmacologia , Interpretação Estatística de Dados , Ensaios de Seleção de Medicamentos Antitumorais/economia , Drogas em Investigação/economia , Determinação de Ponto Final , Projetos de Pesquisa , Roedores , Animais , Disponibilidade Biológica , Dacarbazina/análogos & derivados , Dacarbazina/economia , Dacarbazina/farmacologia , Aprovação de Drogas , Desenho de Fármacos , Humanos , Estimativa de Kaplan-Meier , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/economia , Veículos Farmacêuticos , Distribuição Aleatória , Ratos , Projetos de Pesquisa/normas , Tamanho da Amostra , Tamoxifeno/economia , Tamoxifeno/farmacologia , Temozolomida , Topotecan/economia , Topotecan/farmacologia , Transplante Heterólogo , Estados UnidosRESUMO
BACKGROUND: An electronic radio frequency (RF) microchip, the microtransponder (MTP), has been developed as a platform for assays in the fields of genomics and proteomics. Upon activation by light, each MTP provides a unique RF identification (ID) signal that matches a chip to the specific biological material attached to it. The MTP is powered by a photocell and has an antenna that transmits the signal. The aim of the present study was to explore utility of MTPs as a platform for cell growth in cytotoxicity assays. METHODS: The MCF-7, MCF-116, A549, or T-24 cells growing on MTPs placed in petri dishes or slide chambers were cultured untreated or exposed to antitumor drugs topotecan, mitoxantrone, or onconase for up to 4 days. Their attachment to- and growth on- MTPs was assessed by fluorescence microscopy and laser scanning cytometry (LSC) and compared with growth on the dish surface in the MTP neighborhood. The MTPs were fixed in ethanol, stained with propidium iodide (PI), and interrogated in flow in the instrument capable to rapidly (up to 103 MTPs/s) identify their ID signal and measure fluorescence. RESULTS: The cells plated on MTPs exhibited similar attachment properties to those plated in culture dishes. When measured by LSC, they had similar mitotic activity, growth rate, and cell cycle distributions as the cells adhering to the culture dish in the neighborhood of MTPs. The fluorescence intensity of MTPs provided information about the cell number per MTP, which made it possible to assess cell growth rate and monitor the cytostatic/cytotoxic effects of the tested drugs. CONCLUSIONS: The MTP-based system holds promise for the multiplexed cell assays in which numerous different cell lines can be screened for their growth rate or sensitivity while exposed to particular agents in the same vessel. Other advantages of the system are the rapidity of the screening and a very large number of ID codes. Because many cell lines/types can be assayed in a single dish, the system also offers cost savings on tissue culture reagents.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Eletrônica/instrumentação , Dispositivos Lab-On-A-Chip , Citometria de Varredura a Laser/instrumentação , Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Carcinoma de Células de Transição/patologia , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Controle de Custos , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Eletrônica/métodos , Humanos , Citometria de Varredura a Laser/métodos , Neoplasias Pulmonares/patologia , Procedimentos Analíticos em Microchip/métodos , Microscopia de Fluorescência , Mitoxantrona/farmacologia , Ondas de Rádio , Ribonucleases/farmacologia , Topotecan/farmacologiaRESUMO
Although the in vivo hollow fibre assay (HFA) as utilised by the National Cancer Institute is a highly effective screening tool, it has not been adopted en masse in the cancer pharmacology field. However, in laboratories which have adopted it, the effectiveness of HFA has also been confirmed. If immunocompetent mice could be used with the HFA, thereby reducing the cost of the assay, accessibility would increase and reductions in the cost of selecting appropriate agents for early clinical trials would result. It was demonstrated here that there was no difference in terms of cell growth and response to chemotherapy for cancer cells in hollow fibres in immunocompetent compared with immunodeficient mice. The HFA can thus be performed in these less expensive and more easily available mice with the implication of considerable savings to the preclinical cancer pharmacology community.
Assuntos
Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Doxorrubicina/farmacologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Paclitaxel/farmacologiaAssuntos
Antineoplásicos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais/economia , Feminino , Previsões , Humanos , Masculino , National Institutes of Health (U.S.) , Neoplasias/epidemiologia , Estados UnidosAssuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Medicare/normas , Animais , Antineoplásicos/uso terapêutico , Análise Custo-Benefício , Ensaios de Seleção de Medicamentos Antitumorais/economia , Guias como Assunto , Humanos , Técnicas In Vitro , Medicare/economia , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Sensibilidade e Especificidade , Células Tumorais Cultivadas/efeitos dos fármacos , Estados UnidosRESUMO
Determining which chemotherapy treatment to administer to a patient with cancer is challenging because each patient's cancer is unique. Hundreds of different forms of cancer exist, and tumors of the same type or classification can have very different responses to the same, often standard, treatment. A scientifically-based analysis of how the chemotherapy options for an individual patient may affect that patient's specific tumor could benefit both the clinician and the patient. Chemosensitivity testing can provide this information. A Chemosensitivity assay is a laboratory test that is performed by isolating the cancer cells from a tumor specimen, exposing the cells to the desired chemotherapy agents, and evaluating the effectiveness of those agents. The results provide patient-specific tumor information.
Assuntos
Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais/economia , Ensaios de Seleção de Medicamentos Antitumorais/normas , Humanos , Enfermagem Oncológica , Análise de SobrevidaRESUMO
The differential staining cytotoxicity (DiSC) assay involves in vitro drug panel testing against patient tumor cells to identify optimal therapy. This observational study investigated whether DiSC assay guided treatment could improve outcome in patients with chronic lymphocytic leukemia. A cohort of 178 patients were categorized either as sensitive to drugs in vitro and receiving a sensitive drug in vivo, sensitive in vitro but not treated with a sensitive drug, or having disease resistant to all drugs tested in vitro. Response and survival for these patient categories were compared using multivariate regression techniques. Patients receiving a sensitive drug, compared with those who though having sensitivity did not, had a higher remission rate (odds ratio, 6.5; 95% CI, 2.91-14.53) and reduced death rate (hazard ratio, 0.29; 95% CI, 0.16-0.53). Having adjusted for all known confounding factors, the results suggest that in vitro drug sensitivity is an important independent prognostic variable to include in future trials, and that the DiSC assay may be a cost-effective use of health resources: the estimated incremental cost-effectiveness was 1,470 Pounds per life-year gained. A randomized controlled trial is required to confirm the benefit and estimate reliably the potential impact of assay-guided choice of therapy.