Drug Discovery
Follow
Find
211 views | +0 today
 
Scooped by CYTOO
onto Drug Discovery
Scoop.it!

UM Team Performs 100th Stem Cell Transplant « Florida Biotechnology News

Krishna Komanduri, M.D., the director of the Adult Stem Cell Transplant Program, and his multidisciplinary team at Sylvester Comprehensive Cancer Center performed their 100th stem cell transplant on October 26 — a historic milestone that underscores the cancer center’s growing prominence.

 

more...
No comment yet.
Your new post is loading...
Your new post is loading...
Scooped by CYTOO
Scoop.it!

Silicate Fiber-based 3D Cell Culture System for Anticancer Drug Screening

Silicate Fiber-based 3D Cell Culture System for Anticancer Drug Screening | Drug Discovery | Scoop.it

Background: Three-dimensional (3D) in vitro cultures can recapitulate the physiological in vivo microenvironment. 3D Modeling techniques have been investigated and applied in anticancer drug screening. Materials and Methods: A silicate fiber scaffold was used for 3D cell cultures, and used to model the efficacy of anticancer drugs, such as mytomicin C and doxorubicin. Results: A unique 3D structure was observed in 13 human tumor cell lines on scaffold, and these cells exhibited higher drug resistance than cells in two-dimensional (2D) cultures. Furthermore, the production of lactate and expression of the nuclear factor-kappa B (NF-κB)-regulated genes B cell lymphoma-2 (BCL2), cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) were higher in 3D cultures than in 2D cultures. Conclusion: These findings suggest that a 3D model using a silicate fiber scaffold can mimic features of cancer, and is also a suitable model for the evaluation of anticancer drugs in vitro.

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Stopping cancer in its tracks

Stopping cancer in its tracks | Drug Discovery | Scoop.it

Cell division works flawlessly most of the time. However, in some cases, the division into two daughter cells can malfunction, which can be a factor in the cause and spread of cancer. Dr. Yanchang Wang, an associate professor in the College of Medicine’s Department of Biomedical Sciences, believes that through his research over the next four years, he may, in his own words, be able to “introduce an entirely new cancer treatment process.”

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

High-Throughput Screening (HTS) of Anticancer Drug Efficacy on a Micropillar/Microwell Chip Platform

High-Throughput Screening (HTS) of Anticancer Drug Efficacy on a Micropillar/Microwell Chip Platform | Drug Discovery | Scoop.it

Contemporary cancer therapy refers to treatment based on genetic abnormalities found in patient’s tumor. However, this approach is faced with numerous challenges, including tumor heterogeneity and molecular evolution, insufficient tumor samples available along with genetic information linking to clinical outcomes, lack of therapeutic drugs containing pharmacogenomic information, and technical limitations of rapid drug efficacy tests with insufficient quantities of primary cancer cells from patients. To address these problems and improve clinical outcomes of current personalized gene-targeted cancer therapy, we have developed a micropillar/microwell chip platform, which is ideally suited for encapsulating primary cancer cells in nanoscale spots of hydrogels on the chip, generating efficacy data with various drugs, eventually allowing to compare the in vitro data obtained from the chip with clinical data as well as gene expression data. As a proof of concept in this study, we have encapsulated a U251 brain cancer cell line and three primary brain cancer cells from patients (448T, 464T, and 775T) in 30 nL droplets of alginate, and then tested the therapeutic efficacy of 24 anticancer drugs by measuring their dose responses. As a result, the IC50 values of 24 anticancer drugs obtained from the brain cancer cells clearly showed patient cell-specific efficacy, some of which were well correlated with their oncogene over-expression (c-Met and FGFR1) as well as in vivo previous results of mouse xenograft model with the three primary brain cancer cells.

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Rapid lead compounds discovery through high-throughput screening

Rapid lead compounds discovery through high-throughput screening | Drug Discovery | Scoop.it

High-Throughput Screening (HTS) is an approach to drug discovery that has gained widespread popularity over the past few years and expanded its applications for the pharmaceutical and biotechnology companies, university research laboratories et al. The technology includes screening of large chemical libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis. Since its first advent in the early to mid 1990s, the field of HTS has seen not only a continuous change in technology and processes, but has gone through various adaptations to suit industry needs which have given an edge to drug discovery. HTS has now evolved into a mature discipline that is a crucial for the end to end manufacturing of drugs, namely from the raw material that is the chemical to the actual drug formation.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis | Drug Discovery | Scoop.it

There is a growing demand for in vitro assays for toxicity screening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Aging Tumor Cells May Treat Cancer

Aging Tumor Cells May Treat Cancer | Drug Discovery | Scoop.it

Scientists at the Univ. of Massachusetts Medical School have shown that diffuse large B-cell lymphoma (DLBCL) may be susceptible to treatment by re-activating the normal aging program in tumor cells so they can no longer divide. The study, published in Nature Communications, details a novel, tumor-suppressive role for the Smurf2 protein — which typically plays an "enforcer" role in cellular aging, also called senescence — in a subset of DLBCL. Identification of this novel function for Smurf2 provides a new therapeutic target for treating this cancer.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

New Cancer Therapy Target Prevents Cell Division

New Cancer Therapy Target Prevents Cell Division | Drug Discovery | Scoop.it

Cell division is an essential process for the development of an organism. This process, however, can cause tumor growth when it stops working properly. Tumor cells accumulate alterations in their genetic material, and this makes them divide in an uncontrolled fashion, thus encouraging growth of the tumor. Over the past few years, knowledge of the regulation of this process has led to the discovery of new therapeutic strategies based on blocking cell division or mitosis

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Validation of an Algorithm to Quantify Changes in Actin Cytoskeletal Organization

The actin cytoskeleton plays an important role in most, if not all, processes necessary for cell survival. Given the fundamental role that the actin cytoskeleton plays in the progression of cancer, it is an ideal target for chemotherapy. Although it is possible to image the actin cytoskeleton in a high-throughput manner, there is currently no validated method to quantify changes in the cytoskeleton in the same capacity, which makes research into its organization and the development of anticytoskeletal drugs difficult. We have validated the use of a linear feature detection algorithm, allowing us to measure changes in actin filament organization. Its ability to quantify changes associated with cytoskeletal disruption will make it a valuable tool in the development of compounds that target the cytoskeleton in cancer. Our results show that this algorithm can quantify cytoskeletal changes in a cell-based system after addition of both well-established and novel anticytoskeletal agents using either fluorescence microscopy or a high-content imaging approach. This novel method gives us the potential to screen compounds in a high-throughput manner for cancer and other diseases in which the cytoskeleton plays a key role.

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Chemists find new way to put the brakes on cancer

While great strides have been achieved in cancer treatment, scientists are looking for the new targets and next generation of therapeutics to stop this second leading cause of death nationwide. A new platform for drug discovery has been developed through a collaborative effort linking chemists at NYU and pharmacologists at USC.

In a study appearing in Proceedings of the National Academy of Sciences, the research groups of Paramjit Arora, a professor in NYU's Department of Chemistry, and Bogdan Olenyuk from the USC School of Pharmacy have developed a synthetic molecule, "protein domain mimetic," which targets the interaction between two proteins, called transcription factor-coactivator complex at the point where intracellular signaling cascade converges resulting in an up-regulation of genes that promote tumor progression.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Disabling Protein Cripples Cancer Cells

Disabling Protein Cripples Cancer Cells | Drug Discovery | Scoop.it

WASHINGTON — Scientists have successfully crippled aggressive cancer cells by disabling a single protein known as an ether lipid, part of a family of fatty molecules that includes cholesterol. Researchers hope to develop drugs that can be used alongside chemotherapy to treat some malignant cancers.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Protein that delays cell division in bacteria may lead to the identification of new antibiotics

Scientists at Washington University have worked out how two bacterial strains delay cell division when food is abundant, an understanding that might be used to design drugs that stop division entirely

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

New High-Tech Laser Method Allows DNA to Be Inserted 'Gently' Into Living Cells

New High-Tech Laser Method Allows DNA to Be Inserted 'Gently' Into Living Cells | Drug Discovery | Scoop.it

The applications of gene therapy and genetic engineering are broad: everything from pet fish that glow red to increased crop yields worldwide to cures for many of the diseases that plague humankind. But realizing them always starts with solving the same basic scientific question -- how to "transfect" a cell by inserting foreign DNA into it. Many methods already exist for doing this, but they tend to be clumsy and destructive, not allowing researchers to precisely control how and when they insert the DNA or requiring them to burn through large numbers of cells before they can get it into one.

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

High Content Screening as High Quality Assay for Biological Evaluation of Photosensitizers In Vitro

High Content Screening as High Quality Assay for Biological Evaluation of Photosensitizers In Vitro | Drug Discovery | Scoop.it

A novel single step assay approach to screen a library of photdynamic therapy (PDT) compounds was developed. Utilizing high content analysis (HCA) technologies several robust cellular parameters were identified, which can be used to determine the phototoxic effects of porphyrin compounds which have been developed as potential anticancer agents directed against esophageal carcinoma. To demonstrate the proof of principle of this approach a small detailed study on five porphyrin based compounds was performed utilizing two relevant esophageal cancer cell lines (OE21 and SKGT-4). The measurable outputs from these early studies were then evaluated by performing a pilot screen using a set of 22 compounds. These data were evaluated and validated by performing comparative studies using a traditional colorimetric assay (MTT). The studies demonstrated that the HCS assay offers significant advantages over and above the currently used methods (directly related to the intracellular presence of the compounds by analysis of their integrated intensity and area within the cells). A high correlation was found between the high content screening (HCS) and MTT data. However, the HCS approach provides additional information that allows a better understanding of the behavior of these compounds when interacting at the cellular level. This is the first step towards an automated high-throughput screening of photosensitizer drug candidates and the beginnings of an integrated and comprehensive quantitative structure action relationship (QSAR) study for photosensitizer libraries.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Manipulation of protein could help stop spread of cancer cells

Manipulation of protein could help stop spread of cancer cells | Drug Discovery | Scoop.it

Understanding how and why cancer cells move away from their original location is important to find ways to stop the spread of the disease. New findings, published in the Nature journal Oncogene, reveal how a protein, called 'PRH', is normally able to prevent cells from unnecessary migration. It is likely that this protein is less effective in cancer cells allowing the cells to venture away.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Accelerating drug discovery via organs-on-chips

Accelerating drug discovery via organs-on-chips | Drug Discovery | Scoop.it

Considerable advances have been made in the development of micro-physiological systems that seek to faithfully replicate the complexity and functionality of animal and human physiology in research laboratories. Sometimes referred to as “organs-on-chips”, these systems provide key insights into physiological or pathological processes associated with health maintenance and disease control, and serve as powerful platforms for new drug development and toxicity screening. In this Focus article, we review the state-of-the-art designs and examples for developing multiple “organs-on-chips”, and discuss the potential of this emerging technology to enhance our understanding of human physiology, and to transform and accelerate the drug discovery and preclinical testing process. This Focus article highlights some of the recent technological advances in this field, along with the challenges that must be addressed for these technologies to fully realize their potential.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

New Way to Kill Chemo-Resistant Cancer Cells

New Way to Kill Chemo-Resistant Cancer Cells | Drug Discovery | Scoop.it

Cisplatin is a chemotherapy drug given to more than half of all cancer patients. The drug kills cells very effectively by damaging nuclear DNA, but if tumors become resistant to cisplatin they often grow back.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

High-throughput chip for drug screening in 3D | Chemistry World

High-throughput chip for drug screening in 3D | Chemistry World | Drug Discovery | Scoop.it
Growing cells in three dimensions could help weed out ineffective drug candidates at an earlier stage
more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Identification of novel small molecule inhibitors of centrosome clustering in cancer cells

Most normal cells have two centrosomes that form bipolar spindles during mitosis, while cancer cells often contain more than two, or “supernumerary” centrosomes. Such cancer cells achieve bipolar division by clustering their centrosomes into two functional poles, and inhibiting this process then leads to cancer-specific cell death. A major problem with clinically used anti-mitotic drugs, such as paclitaxel, is their toxicity in normal cells. To discover new compounds with greater specificity for cancer cells, we established a high-content screen for agents that block centrosome clustering in BT-549 cells, a breast cancer cell line that harbors supernumerary centrosomes. Using this screen, we identified 14 compounds that inhibit centrosome clustering and induce mitotic arrest. Some of these compounds were structurally similar, suggesting a common structural motif important for preventing centrosome clustering. We next compared the effects of these compounds on the growth of several breast and other cancer cell lines, an immortalized normal human mammary epithelial cell line, and progenitor-enriched primary normal human mammary epithelial cells. From these comparisons, we found some compounds that kill breast cancer cells, but not their normal epithelial counterparts, suggesting their potential for targeted therapy. One of these compounds, N2-(3-pyridylmethyl)-5-nitro-2-furamide (Centrosome Clustering Chemical Inhibitor-01, CCCI-01), that showed the greatest differential response in this screen was confirmed to have selective effects on cancer as compared to normal breast progenitors using more precise apoptosis induction and clonogenic growth endpoints. The concentration of CCCI-01 that killed cancer cells in the clonogenic assay spared normal human bone marrow hematopoietic progenitors in the colony-forming cell assay, indicating a potential therapeutic window for CCCI-01, whose selectivity might be further improved by optimizing the compound. Immunofluorescence analysis showed that treatment with CCCI-01 lead to multipolar spindles in BT-549, while maintaining bipolar spindles in the normal primary human mammary epithelial cells. Since centrosome clustering is a complex process involving multiple pathways, the 14 compounds identified in this study provide a potentially novel means to developing non-cross-resistant anti-cancer drugs that block centrosome clustering.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Neurological Disorders Could Be Treated With Cell-Culture Transplants

Neurological Disorders Could Be Treated With Cell-Culture Transplants | Drug Discovery | Scoop.it
A new study has shown that small brain biopsies could be used to grow large numbers of cells for brain transplants, opening up new treatment options for neurological disorders.
more...
No comment yet.
Scooped by CYTOO
Scoop.it!

USC scientists ID protein that regulates cellular trafficking, potential for anti-cancer therapy

USC scientists ID protein that regulates cellular trafficking, potential for anti-cancer therapy | Drug Discovery | Scoop.it

Molecular microbiologists at the University of Southern California (USC) have uncovered intricate regulatory mechanisms within the cell that could lead to novel therapeutics for the treatment of cancer and other diseases. Their findings, which have long-standing significance in the basic understanding of cell biology, appear in the journal Nature Cell Biology.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Discovery of cell division 'master controller' may improve understanding and treatment of cancer

Discovery of cell division 'master controller' may improve understanding and treatment of cancer | Drug Discovery | Scoop.it

Hanover, NH – In a study to be published in the journal Nature, two Dartmouth researchers have found that the protein cyclin A plays an important but previously unknown role in the cell division process, acting as a master controller to ensure the faithful segregation of chromosomes during cell division.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Exendin-4 induces cell adhesion and differentiation and counteracts the invasive potential of human neuroblastoma cells.

Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening

Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal population involved in the higher cognitive functions of the human and are particularly affected by psychiatric diseases with developmental manifestations such as schizophrenia and autism. Differentiation protocols of human pluripotent stem cells (PSC) into cortical neurons have been achieved, opening the way to in vitro modeling of neuropsychiatric diseases. However, these protocols commonly result in the asynchronous production of neurons typical for the different layers of the cortex within an extended period of culture, thus precluding the analysis of specific subtypes of neurons in a standardized manner. Addressing this issue, we have successfully captured a stable population of self-renewing late cortical progenitors (LCPs) that synchronously and massively differentiate into glutamatergic cortical neurons of the upper layers. The short time course of differentiation into neurons of these progenitors has made them amenable to high-throughput assays. This has allowed us to analyze the capability of LCPs at differentiating into post mitotic neurons as well as extending and branching neurites in response to a collection of selected bioactive molecules. LCPs and cortical neurons of the upper layers were successfully produced from patient-derived-induced PSC, indicating that this system enables functional studies of individual-specific cortical neurons ex vivo for disease modeling and therapeutic purposes.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

American researchers have shed a light on how colon cancer occurs

American researchers have shed a light on how colon cancer occurs | Drug Discovery | Scoop.it

There’s a very fine balance between normal cell division and the start of cancer – where cell division gets out of control, leading to tumour formation. There’s a network of genes which keep the cell division process under control and understanding how these work is giving researchers new leads on how to treat cancer.

 

 

more...
No comment yet.
Scooped by CYTOO
Scoop.it!

A systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening

A systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening | Drug Discovery | Scoop.it

A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. A critical contribution of the NIH Chemical Genomics center (NCGC) to the Tox21 program is the implementation of a quantitative high throughput screening (qHTS) approach, using cell- and biochemical-based assays to generate toxicological profiles for thousands of environmental compounds. Here, we evaluated the effect of chemical compounds on mitochondrial membrane potential in HepG2 cells by screening a library of 1,408 compounds provided by the National Toxicology Program (NTP) in a qHTS platform. Compounds were screened over 14 concentrations, and results showed that 91 and 88 compounds disrupted mitochondrial membrane potential after treatment for one or five h, respectively. Seventy-six compounds active at both time points were clustered by structural similarity, producing 11 clusters and 23 singletons. Thirty-eight compounds covering most of the active chemical space were more extensively evaluated. Thirty-six of the 38 compounds were confirmed to disrupt mitochondrial membrane potential using a fluorescence plate reader and 35 were confirmed using a high content imaging approach. Among the 38 compounds, 4 and 6 induced LDH release, a measure of cytotoxicity, at 1 or 5 h, respectively. Compounds were further assessed for mechanism of action (MOA) by measuring changes in oxygen consumption rate, which enabled identification of 20 compounds as uncouplers. This comprehensive approach allows for evaluation of thousands of environmental chemicals for mitochondrial toxicity and identification of possible MOAs.

more...
No comment yet.