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Stellaris Fish Workshop Gadph And Dapi Z-Series, George Mcnamara Dec 2013

Stellaris Fish Workshop Gadph And Dapi Z-Series, George Mcnamara

George McNamara

Stellaris FISH workshop GADPH and DAPI Z-series at MD Anderson Cancer Center, Houston, TX.

The zip file contains raw and GPU deconvolved image data from a workshop Biosearch Technologies conducted for MDACC researchers in December 2013. Image data was acquired on a Leica DMI6000 microscope with Lumencor SOLA light engine, DAPI and Cy5 filter cubes, Hamamatsu ORCA FLASH4.0 sCMOS camera (500 ms exposure time per plane for Quasar 670).

Pixel size 100 nm XY.

Z-step size 200 nm.

32 planes (power of 2 is optimal for GPU deconvolution). With 500 ms exposure time, the Quasar 670 GADPH FISH probes ...


A Functional Notch-Survivin Gene Signature In Basal Breast Cancer, Connie Wing-Ching Lee, Karl Simin, Qin Liu, Janet Plescia, Minakshi Guha, Ashraf Khan, Chung-Cheng Hsieh, Dario C. Altieri Dec 2013

A Functional Notch-Survivin Gene Signature In Basal Breast Cancer, Connie Wing-Ching Lee, Karl Simin, Qin Liu, Janet Plescia, Minakshi Guha, Ashraf Khan, Chung-Cheng Hsieh, Dario C. Altieri

Qin Liu

INTRODUCTION: Basal-type, or triple-negative, breast cancer (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression) is a high-risk disease for which no molecular therapies are currently available. We studied genetic signatures of basal breast cancer potentially suitable for therapeutic intervention. METHODS: We analyzed protein expression of the Notch-1 intracellular domain and survivin by immunohistochemistry in a series of basal breast cancer patients. A hierarchical clustering and overall survival analysis was carried out on a microarray mRNA database of 232 breast cancer patients. Fifteen published mRNA datasets containing estrogen receptor-negative or estrogen receptor-positive samples were subjected to meta-analysis ...


Statins Induce Apoptosis In Ovarian Cancer Cells Through Activation Of Jnk And Enhancement Of Bim Expression, Hongli Liu, Shu-Ling Liang, Sheetal Kumar, Crystal M. Weyman, Wendy Liu, Aimin Zhou Nov 2013

Statins Induce Apoptosis In Ovarian Cancer Cells Through Activation Of Jnk And Enhancement Of Bim Expression, Hongli Liu, Shu-Ling Liang, Sheetal Kumar, Crystal M. Weyman, Wendy Liu, Aimin Zhou

Crystal M. Weyman

Ovarian cancer is the leading cause of death among all gynecological malignancies in Western countries. Although therapy for ovarian cancer has been greatly improved in the past 20 years, the overall survival for patients with advanced ovarian cancer has not changed signiWcantly. The poor survival rates in patients with advanced ovarian cancer are due both to late diagnosis and to lack of eVective drugs for the majority of patients who have a relapse and develop resistance to current chemotherapy agents used for ovarian cancer. Thus, developing and discovering eVective novel drugs with diVerent molecular structures from conventional chemotherapy agents have ...


Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George Mcnamara Nov 2013

Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George Mcnamara

George McNamara

McNamara 20131101Fri Leica widefield microscope CUDA Deconvolution Stellaris FISH probe cultured cells dataset #1.zip

A text file in the zip archive has experiment details. I am posting this online so that researchers - whether academic or commercial - can evaluate the acquired data, the Bruce and Butte 2013 Optics Express ( http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-21-4-4766 ) deconvolution result (note: I may not have used optimal settings), and to compare these deconvolution results to other methods. If anyone generates alternative spatial deconvolution output, such as from: * SVI Huygens * Media Cy AutoQuant * Agard's ER-Decon (Arigovindan 2013 PNAS) * Vicidomini SGP ...


Fluorescence Microscopy Digital Deconvolution Comparison, George Mcnamara, Vinita Popat Aug 2013

Fluorescence Microscopy Digital Deconvolution Comparison, George Mcnamara, Vinita Popat

George McNamara

Presentation by Ms. Vinita Popat, Cornell University, 2013 summer student in Prof. Laurence J.N. Cooper lab, MD Anderson Cancer Center, Houston, TX. Project was evaluation of several deconvolution software for improving (or making worse!) fluorescence microscopy Z-series.


Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio Aug 2013

Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio

Arthur M. Mercurio

Summary: Autocrine VEGF signaling in tumor cells contributes to de-differentiation and function of tumor initiating/stem cells. NRP2 is the nexus of a signaling pathway that promotes de-differentiation and sustains tumor initiating/stem sells. Anti-NRP2 therapy is worth pursuing, especially for high-grade cancers. Therapeutic Abs are available. This presentation was part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.


Gli1 Regulates A Novel Neuropilin-2/Alpha6beta1 Integrin Based Autocrine Pathway That Contributes To Breast Cancer Initiation, Hira Lal Goel, Bryan M. Pursell, Cheng Chang, Leslie M. Shaw, Junhao Mao, Karl Simin, Prashant Kumar, Craig W. Vander Kooi, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Charlotte Kuperwasser, Arthur M. Mercurio Jul 2013

Gli1 Regulates A Novel Neuropilin-2/Alpha6beta1 Integrin Based Autocrine Pathway That Contributes To Breast Cancer Initiation, Hira Lal Goel, Bryan M. Pursell, Cheng Chang, Leslie M. Shaw, Junhao Mao, Karl Simin, Prashant Kumar, Craig W. Vander Kooi, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Charlotte Kuperwasser, Arthur M. Mercurio

Arthur M. Mercurio

The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin-2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the alpha6beta1 integrin, focal adhesion kinase-mediated activation of Ras/MEK signalling and consequent expression of the ...


Repression Of Mir-143 Mediates Cr (Vi)-Induced Tumor Angiogenesis Via Igf-Ir/Irs1/Erk/Il-8 Pathway., Jun He Jun 2013

Repression Of Mir-143 Mediates Cr (Vi)-Induced Tumor Angiogenesis Via Igf-Ir/Irs1/Erk/Il-8 Pathway., Jun He

Jun He

Hexavalent chromium [Cr (VI)] is a well-known human carcinogen associated with the increased risk of lung cancer. However, the mechanism underlying the Cr (VI)-induced carcinogenesis remains unclear due to the lack of suitable experimental models. In this study, we developed an in vitro model by transforming nontumorigenic human lung epithelial BEAS-2B cells through long-term exposure to Cr (VI). By utilizing this model, we found that miR-143 expression levels were dramatically repressed in Cr (VI)-transformed cells. The repression of miR-143 led to Cr (VI)-induced cell malignant transformation and angiogenesis via upregulation of insulin-like growth factor-1 receptor (IGF-IR) and ...


Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre May 2013

Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre

Alfred M Legendre DVM, MS, DACVIM

No abstract provided.


Molecular Imaging Of Cyclooxygenase-2 In Canine Transitional Cell Carcinomas In Vitro And In Vivo, Maria Cekanova, M Uddin, Joseph Bartges, Amanda Callens, Kusum Rathore, Alfred Legendre, L Wright, L Marnett Apr 2013

Molecular Imaging Of Cyclooxygenase-2 In Canine Transitional Cell Carcinomas In Vitro And In Vivo, Maria Cekanova, M Uddin, Joseph Bartges, Amanda Callens, Kusum Rathore, Alfred Legendre, L Wright, L Marnett

Maria Cekanova MS, RNDr, PhD

The enzyme COX-2 is induced at high levels in tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of fluorocoxib A by COX-2-expressing K9TCC xenograft tumors in vivo. Fluorocoxib A uptake by COX-2-expressing xenograft tumors was blocked by 70% (P < 0.005) when pretreated with the COX-2 selective inhibitor, celecoxib (10 mg/kg), 4 hours before intravenous administration of fluorocoxib A (1 mg/kg). Fluorocoxib A was taken up by COX-2-expressing tumors but not by COX-2-negative human UMUC-3 xenograft tumors. UMUC-3 xenograft tumors with no expression of COX-2 showed no uptake of fluorocoxib A. In addition, fluorocoxib A uptake was evaluated in five dogs diagnosed with TCC. Fluorocoxib A specifically detected COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that fluorocoxib A selectively bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary cancer cells in vitro and in heterogeneous cancers in vivo.


Flash4 Dark Reference Images, George Mcnamara Apr 2013

Flash4 Dark Reference Images, George Mcnamara

George McNamara

Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).

George McNamara, Ph.D.

Single Cells Analyst at L.J.N. Cooper Lab

University of Texas M.D. Anderson Cancer Center


Modulation Of Adipose Tissue Inflammation By Bioactive Food Compounds, N. Siriwardhana, N. Kalupahana, Maria Cekanova, M. Lemieux, B. Greer, N, Moustaid-Moussa Mar 2013

Modulation Of Adipose Tissue Inflammation By Bioactive Food Compounds, N. Siriwardhana, N. Kalupahana, Maria Cekanova, M. Lemieux, B. Greer, N, Moustaid-Moussa

Maria Cekanova MS, RNDr, PhD

Adipose tissue has an important endocrine function in the regulation of whole-body metabolism. Obesity leads to a chronic low-grade inflammation of the adipose tissue, which disrupts this endocrine function and results in metabolic derangements, such as type-2 diabetes. Dietary bioactive compounds, such as polyphenols and certain fatty acids, are known to suppress both systemic and adipose tissue inflammation and have the potential to improve these obesity-associated metabolic disorders. Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating ...


Video Codec Performance (Excel Spreadsheet), George Mcnamara Feb 2013

Video Codec Performance (Excel Spreadsheet), George Mcnamara

George McNamara

Video codec performance (Excel spreadsheet). Movie was made in 2005-2006 when I worked at City of Hope National Medical Center. VTLF refers to Video Timelapse Light Facility. Videos were outputted from MetaMorph as AVI files. Personally, I always recommend uncompressed video files fro scientific uses. I also encourage posting the original scientific data format (ex. .lsm, .zvi, .lif, .stk).


Brca1 Dna-Binding Activity Is Stimulated By Bard1, Amanda Simons, Andrew Horwitz, Lea Starita, Karen Griffin, R Williams, J.N. Glover, Jeffrey Parvin Feb 2013

Brca1 Dna-Binding Activity Is Stimulated By Bard1, Amanda Simons, Andrew Horwitz, Lea Starita, Karen Griffin, R Williams, J.N. Glover, Jeffrey Parvin

Amanda Simons

The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including transcription, ubiquitination, and DNA repair. Its tumor suppression activity is tightly linked to that of BARD1, a protein that heterodimerizes with BRCA1. It has been previously shown that BRCA1 binds to DNA, an interesting functional observation in light of the genetic data linking BRCA1 to DNA repair pathways. In this work, we reexamine the DNA-binding properties of BRCA1, comparing them with the DNA-binding properties of the BRCA1/BARD1 heterodimer. Because nuclear BRCA1 exists as a heterodimer with BARD1, it is likely that in vitro studies ...


Pubspectra Tattletales, George Mcnamara Feb 2013

Pubspectra Tattletales, George Mcnamara

George McNamara

Tattletales for Multiplex Fluorescent Reporters in Single Cells for Metabolomics

George McNamara

As of April 2013: L.J.N. Cooper & D.A. Lee Cellular Immunotherapy Lab, University of Texas M.D. Anderson Cancer Center, Houston, TX

Email: gtmcnamara@mdanderson.org, geomcnamara@earthlink.net

Tattletales is my concept for spatial multiplexing many fluorescent protein (FP) biosensors in the same live cell. For example, there are excellent FP biosensors to Ca++ ions, pH, glucose, ribose, glutamine, glutamate, ATP, redox, ROS, pyruvate, cAMP, cGMP, IP3, PI(3,4,5)P3, cell cycle indicators (Fucci2), PKA, PKC, photsphatases, caspase(s) [1, 2]. However, these are typically used one biosensor per experiment, due in part to flooding the cell with soluble biosensor. That is, conventionally, either a metabolite (glucose) reporter or a signal transduction (Ca++) reporter can be imaged. By flooding the cell with the reporter, signal to noise ratio is compromized by autofluorescence.

Tattletales takes advantage of spatial multiplexing to both increase the number of different reporters, and improve signal to noise ratio by localizing each biosensor to a small volume. I started with the observation by Robinett et al [3] who localized 512 GFP-nls-LacI to a 256 LacO array as a 200 nm diameter diffraction limited spot (nuclear background due to overexpression). Many thousands of DNA binding proteins, of known sequence specifities, exist (LacI, TetR, GalR, etc for cell line studies; ZF-FPs, TALE-FPs to STRs, telomere repeat binding factors-FPs, etc for primary cells) and can be fused (as cDNAs) to different fluorescent proteins and FP biosensors.

Many biosensors are available as affinity series [1, 4], now enabling extended dynamic range. I realized that spatial multiplexing of many DNA binding protein-reporters by localizing to different spots in the cell nucleus and distinguished by combinatorial addressing, where N address colors provide 2^N addresses (example, 3 colors is 2^3 = 8 combinations). Multiplexing ...


Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre Jan 2013

Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre

Maria Cekanova MS, RNDr, PhD

No abstract provided.


Neuropilin-2 Promotes Branching Morphogenesis In The Mouse Mammary Gland, Hira Lal Goel, Donggoo Bae, Bryan M. Pursell, Lindsey M. Gouvin, Shaolei Lu, Arthur M. Mercurio Jan 2013

Neuropilin-2 Promotes Branching Morphogenesis In The Mouse Mammary Gland, Hira Lal Goel, Donggoo Bae, Bryan M. Pursell, Lindsey M. Gouvin, Shaolei Lu, Arthur M. Mercurio

Arthur M. Mercurio

Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre ...


Microfabricated Nanotopological Surfaces For Study Of Adhesion-Dependent Cell Mechanosensitivity, Weiqiang Chen, Yubing Sun, Jianping Fu Jan 2013

Microfabricated Nanotopological Surfaces For Study Of Adhesion-Dependent Cell Mechanosensitivity, Weiqiang Chen, Yubing Sun, Jianping Fu

Weiqiang Chen

Cells exhibit high sensitivity and diverse responses to the intrinsic nanotopography of the extracellular matrix through their nanoscale cellular sensing machinery. A simple microfabrication method for precise control and spatial patterning of the local nanoroughness on glass surfaces by using photolithography and reactive ion etching is reported. It is demonstrated that local nanoroughness as a biophysical cue could regulate a diverse array of NIH/3T3 fi broblast behaviors, including cell morphology, adhesion, proliferation, migration, and cytoskeleton contractility. The capability to control and further predict cellular responses to nanoroughness might suggest novel methods for developing biomaterials mimicking nanotopographic structures in vivo ...


Complementary Genomic Screens Identify Serca As A Therapeutic Target In Notch1 Mutated Cancer, G. Roti, A. Carlton, Kn. Ross, Michele Markstein, K. Pajcini, A. H. Su, N. Perrimon, W. S. Pear, A. L. Kung, S. C. Blacklow, J. C. Aster, K. Stegmaier Jan 2013

Complementary Genomic Screens Identify Serca As A Therapeutic Target In Notch1 Mutated Cancer, G. Roti, A. Carlton, Kn. Ross, Michele Markstein, K. Pajcini, A. H. Su, N. Perrimon, W. S. Pear, A. L. Kung, S. C. Blacklow, J. C. Aster, K. Stegmaier

Michele Markstein

Notch1 is a rational therapeutic target in several human cancers, but as a transcriptional regulator, it poses a drug discovery challenge. To identify Notch1 modulators, we performed two cell-based, high-throughput screens for small-molecule inhibitors and cDNA enhancers of a NOTCH1 allele bearing a leukemia-associated mutation. Sarco/endoplasmic reticulum calcium ATPase (SERCA) channels emerged at the intersection of these complementary screens. SERCA inhibition preferentially impairs the maturation and activity of mutated Notch1 receptors and induces a G0/G1 arrest in NOTCH1-mutated human leukemia cells. A small-molecule SERCA inhibitor has on-target activity in two mouse models of human leukemia and interferes with ...


Modeling Colorectal Cancer As A 3-Dimensional Disease In A Dish: The Case For Drug Screening Using Organoids, Zebrafish, And Fruit Flies, Michele Markstein Jan 2013

Modeling Colorectal Cancer As A 3-Dimensional Disease In A Dish: The Case For Drug Screening Using Organoids, Zebrafish, And Fruit Flies, Michele Markstein

Michele Markstein

This review discusses recent shifts in the understanding of colorectal cancer as a stem cell based disease, based on findings that tie patient prognosis to the presence of cancer stem cells in colorectal tumors. Currently no drugs specifically target CSCs in colorectal tumors. However, recent advances in the culturing of colorectal stem cells using mammalian organoids, zebrafish, and Drosophila offer promising avenues for anti-CSC drug discovery.


Mesenchymal And Stem-Like Properties Targeted In Suppression Of Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Hwa-Chain Wang Dec 2012

Mesenchymal And Stem-Like Properties Targeted In Suppression Of Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Synergistic Induction Of Cancer Cell Death And Reduction Of Clonogenic Resistance By Cisplatin And Fk228, Shambhunath Choudhary, Shilpa Sood, Hwa-Chain Wang Dec 2012

Synergistic Induction Of Cancer Cell Death And Reduction Of Clonogenic Resistance By Cisplatin And Fk228, Shambhunath Choudhary, Shilpa Sood, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Rab5 Function In Breast Cancer Cells, Nicole Porther, M Alejandro Barbieri Dec 2012

Rab5 Function In Breast Cancer Cells, Nicole Porther, M Alejandro Barbieri

Nicole Porther

Metastasis is characterized pathologically by cell invasion, proliferation, migration and angiogenesis. Growth factors, which include epithelial growth factor (EGF), insulin growth factors I and II (IGFI and IGFII); have been associated with most if not all of the features of metastasis.  Our study has highlighted the possible role growth factors may have in mediating cancer metastasis via Rab GTPses.  We determined that the invasive and migratory properties of breast cancer cells were abrogated in cell lines that only expressed the inactive (GDP-bound) form of Rab 5 irrespective of growth factor stimulation. Breast cancer cell lines expressing the wild type and ...


Phenytoin Reduces 5-Ala Mediated Fluorescence In Glioblastoma Cells, Christopher Steele, Johnathan E. Lawrence, Richard A. Rovin, Robert J. Winn Dec 2012

Phenytoin Reduces 5-Ala Mediated Fluorescence In Glioblastoma Cells, Christopher Steele, Johnathan E. Lawrence, Richard A. Rovin, Robert J. Winn

Johnathan Lawrence

Glioblastoma multiforme (GBM) is a devastating form of cancer, and essentially all GBM tumors recur causing fatality. A new surgical technique, fluorescence-guided resection of GBM using 5-aminolevulinic acid (5-ala), improves the extent of resection and positively impacts the length and quality of patient survival. The fluorescence achieved in neoplastic tissue depends directly on the accumulation of porphyrins derived from the metabolism of the 5-ala prodrug within the cancer cell. However, 5-ala induced fluorescence has been reported to be inconsistent. In an effort to determine the cause of the inconsistent fluorescence, the authors investigated the effect of medications commonly prescribed to ...