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2013

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Articles 1 - 30 of 127

Full-Text Articles in Cancer Biology

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman Dec 2013

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Open Dartmouth: Faculty Open Access Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.


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 ...


Higher-Order Unfolding Of Satellite Heterochromatin Is A Consistent And Early Event In Cell Senescence, Eric C. Swanson, Benjamin J. Manning, Hong Zhang, Jeanne B. Lawrence Dec 2013

Higher-Order Unfolding Of Satellite Heterochromatin Is A Consistent And Early Event In Cell Senescence, Eric C. Swanson, Benjamin J. Manning, Hong Zhang, Jeanne B. Lawrence

Lawrence Lab Publications

Epigenetic changes to chromatin are thought to be essential to cell senescence, which is key to tumorigenesis and aging. Although many studies focus on heterochromatin gain, this work demonstrates large-scale unraveling of peri/centromeric satellites, which occurs in all models of human and mouse senescence examined. This was not seen in cancer cells, except in a benign senescent tumor in vivo. Senescence-associated distension of satellites (SADS) occurs earlier and more consistently than heterochromatin foci formation, and SADS is not exclusive to either the p16 or p21 pathways. Because Hutchinson Guilford progeria syndrome patient cells do not form excess heterochromatin, the ...


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 ...


Optimization Of Reconstituted High Density Lipoprotein Nanoparticles As A Delivery System For Neuroblastoma, Cheryl L. Hinze Dec 2013

Optimization Of Reconstituted High Density Lipoprotein Nanoparticles As A Delivery System For Neuroblastoma, Cheryl L. Hinze

Theses and Dissertations

Despite many advances in cancer therapy over the last few decades, cancer remains one of the most common causes of death in not only the United States, but around the world. Two of the major problems cancer patients face today are the horrific side effects associated with chemotherapy, and the development of drug resistance. Both of these become even bigger problems when they are applied to children. Neuroblastoma is one of the most common forms of pediatric cancer. High risk Neuroblastoma patients are commonly faced with intensive multi-modal therapies in attempt to overcome a very aggressive disease. Due to the ...


Protein Kinase C-Eta Signalling In Breast Cancer, Deepanwita Pal Dec 2013

Protein Kinase C-Eta Signalling In Breast Cancer, Deepanwita Pal

Theses and Dissertations

Pal, Deepanwita, Protein kinase C-eta signaling in breast cancer. Doctor of Philosophy (Biochemistry and Molecular Biology), November, 2013, 117 pp, 14 illustrations, 260 References Protein kinase C-eta (PKCη) is a novel member of the PKC family that is important for several cellular processes. PKCη is overexpressed in breast cancer and has been associated with chemotherapeutic resistance. PKCη is the only phorbol ester-sensitive PKC isozyme that resists downregulation upon prolonged treatment with tumorpromoting phorbol esters suggesting its unique regulation. The purpose of this dissertation is to elucidate the mechanism of PKCη regulation and its functional relevance in breast cancer. We have ...


Astrocyte Elevated Gene-1, A Novel Modulator Of Astrocyte Function: Implications For Neuroaids, Aging And Glioblastoma, Neha Vartak Dec 2013

Astrocyte Elevated Gene-1, A Novel Modulator Of Astrocyte Function: Implications For Neuroaids, Aging And Glioblastoma, Neha Vartak

Theses and Dissertations

Vartak-Sharma, Neha N., Astrocyte elevated gene-1, a novel modulator of astrocyte function: Implications for NeuroAIDS, aging and glioblastoma. Doctor of Philosophy (Biomedical Sciences), Nov, 2013, 180 pp., 1 table, 40 illustrations, 336 bibliographies. Recent attempts to analyze human immunodeficiency virus (HIV)-1-induced gene expression changes in astrocyte identified a multifunctional oncogene, astrocyte elevated gene-1 (AEG-1), as an HIV-1 and tumor necrosis factor-inducible transcript. Subsequently, due to its homology to mouse breast cancer metastasis protein, metadherin, AEG-1 was largely implicated in carcinogenesis of diverse cancer types. However, the role of AEG-1 in astrocytes, the original cell type in which AEG-1 ...


Smokeless Tobacco Use: A Risk Factor For Hyperhomocysteinemia In A Pakistani Population, Mohammad Perwaiz Iqbal, Mohsin Yakub Dec 2013

Smokeless Tobacco Use: A Risk Factor For Hyperhomocysteinemia In A Pakistani Population, Mohammad Perwaiz Iqbal, Mohsin Yakub

Department of Biological & Biomedical Sciences

Background

Smokeless tobacco (ST) use is highly prevalent in the South Asian populations. While there have been a number of reports on association of ST consumption with cancer, very few studies have been conducted to investigate its relationship with cardiovascular disease. Hyperhomocysteinemia is a well-recognized risk factor for cardiovascular disease; however, its association with ST use has never been investigated. The objective of this study was to evaluate the relationship of ST use with hyperhomocysteinemia in an urban Pakistani population.

Methodology/Principal Findings

In a cross-sectional study for assessment of risks of hyperhomocysteinemia, 872 healthy adults (355 males and 517 ...


Involvement Of S6 Kinase In Breast Cancer, Savitha Sridharan Dec 2013

Involvement Of S6 Kinase In Breast Cancer, Savitha Sridharan

Theses and Dissertations

Sridharan, S., Involvement of S6 Kinase in Breast Cancer. Doctor of Philosophy (Cancer Biology), November 2013, 129pp, 19 illustrations, 215 references. The 40S ribosomal protein S6 Kinase (S6K) is activated downstream of the mammalian target of rapamycin (mTOR)and is believed to play and important role in protein translation. In mammalian cells S6K is represented by two highly homologous proteins, S6K1 and S6K2. Both homologs have been shown to be amplicfied and over expressed in breast cancer cells and tissues. While the regulation and functions of S6K1 have been addressed, little is known about those of S6K2 . Hence we sought ...


Role Of Nk Cell Receptors In Acute Lymphoblastic Leukemia In Children, Charisse Tan Dec 2013

Role Of Nk Cell Receptors In Acute Lymphoblastic Leukemia In Children, Charisse Tan

Theses and Dissertations

Tan, Charisse S., Role of NK Cell Receptors in Acute Lymphoblastic Leukemia in Children. Master of Science (Biomedical Sciences), May, 2013, 94 pp., 6 tables, 57 illustrations, bibliography, 35 titles. Due to the many medical advances in recent years, treatment of acute lymphoblastic leukemia (ALL) has improved tremendously. It has been estimated that about 80% of children that are diagnosed with this disease will likely go into remission. However, there is still a need for a more specific, less invasive treatment that lessens any toxic side effects of current cancer treatments and at the same time, lowers the risk of ...


Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff Dec 2013

Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff

UT GSBS Dissertations and Theses (Open Access)

Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been ...


Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel Dec 2013

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

UT GSBS Dissertations and Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of 93 ...


C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein Dec 2013

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

UT GSBS Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy ...


New Insights Into The Roles Of Human Dna Damage Checkpoint Protein Atr In The Regulation Of Nucleotide Excision Repair And Dna Damage-Induced Cell Death, Zhengke Li Dec 2013

New Insights Into The Roles Of Human Dna Damage Checkpoint Protein Atr In The Regulation Of Nucleotide Excision Repair And Dna Damage-Induced Cell Death, Zhengke Li

Electronic Theses and Dissertations

Integrity of the human genome is frequently threatened by endogenous and exogenous DNA damaging reagents that may lead to genome instability and cancer. Cells have evolved multiple mechanisms to repair DNA damage or to eliminate the damaged cells beyond repair and to prevent diverse diseases. Among these are ataxia telangiectasia and Rad3-related (ATR)-mediated DNA damage checkpoint and nucleotide excision repair (NER) that are the major pathways by which cells handle ultraviolet C (UV-C)- or other exogenous genotoxin-induced bulky DNA damage. However, it is unclear how these 2 pathways may be coordinated. In this study we show that ATR physically ...


Investigating Potential Bioactive Compounds From Rhodococcus And Their Effects On Mcf7 Breast Cancer Cells, Megan N. Crabtree Dec 2013

Investigating Potential Bioactive Compounds From Rhodococcus And Their Effects On Mcf7 Breast Cancer Cells, Megan N. Crabtree

Electronic Theses and Dissertations

Many drugs used in the treatment of various cancers are derived from or influenced by compounds from nature. The soil bacterium Rhodococcus is of interest because of its identified secondary metabolic pathways and the production of novel natural antibiotics from several strains. In this study, a solid agar extraction method was used to collect compounds from strains of Rhodococcus. These bacterial compound extracts were then tested using a MTT assay in order to evaluate their effectiveness in augmenting MCF7 breast cancer cell death. The results of two way ANOVA analyses revealed 18 compound extracts from 15 strains of Rhodococcus that ...


Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli Venkata Govri Chandra Sekhar, Anil Kumar, Amir Nasrolahi Shirazi, Keykavous Parang Dec 2013

Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli Venkata Govri Chandra Sekhar, Anil Kumar, Amir Nasrolahi Shirazi, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized (1H NMR, 13C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemiacells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10mol) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines. Cancer is a leading cause of death worldwide. It is a group of diseases characterized ...


Protective Effects Of Sphingomyelin Against Uv Photodamage In Human Keratinocytes, Kathleen De Guzman Dec 2013

Protective Effects Of Sphingomyelin Against Uv Photodamage In Human Keratinocytes, Kathleen De Guzman

Master's Theses and Project Reports

Ultraviolet (UV) radiation has been demonstrated in numerous studies to be a major risk factor for non-melanoma skin cancer development. Despite the emergence of current UV-preventative strategies, such as sunscreens and skin-protective clothing, the incidence of non-melanoma skin cancer has continued to rise. This has encouraged investigations on alternative methods for UV prevention. In particular, bovine milk sphingomyelin has been studied for its potential in protecting human skin against UV photodamage. While the previous studies have suggested that sphingomyelin exhibits UV-protective properties in a human skin equivalent model, the exact mechanisms behind sphingomyelin’s photoprotective effects are yet unknown.

This ...


Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo Nov 2013

Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo

Electronic Thesis and Dissertation Repository

Transforming growth factor-beta 1 (TGF-β1) modulates regeneration after injury through induction of fibroblast proliferation, migration, and differentiation into myofibroblasts. Induction of myofibroblast differentiation by TGF-β1 requires expression of integrin-linked kinase (ILK). I now show that ILK interacts with TGF-β receptor type II (TβRII) in primary dermal fibroblasts. Further, colocalization of ILK and TβRII can be observed at the cell membrane and in intracellular vesicles. The association of TβRII and ILK does not require TGF-β1 stimulation, kinase activity of TGF-β1 receptor type I or TβRII, and it does not involve interactions between ILK and focal adhesion-associated proteins. When this interaction is ...


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 ...


Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari Oct 2013

Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari

Open Dartmouth: Faculty Open Access Scholarship

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using ...


Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs Oct 2013

Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs

The Summer Undergraduate Research Fellowship (SURF) Symposium

The Set1 complex, a histone methyltransferase complex found in S. cerevisiae (budding yeast), is the only histone methyltransferase responsible for catalyzing methylation of histone H3 at Lysine 4. It possesses homologues in other species, humans included. While yeast only have the Set1 complex, the human homologues of the yeast Set1 complex include mixed-lineage leukemia family (MLL1-4), Set1 A, Set1 B, among others. MLL1-4 has been shown to play a role in transcription, cell type specification, and the development of leukemia. One application of characterizing the role of a protein is that the information gained can provide insight into the function ...


Oncogenic Ras Directs Silencing Of Tumor Suppressor Genes Through Ordered Recruitment Of Transcriptional Repressors, Narendra Wajapeyee, Sunil K. Malonia, Rajendra Kumar Palakurthy, Michael R. Green Oct 2013

Oncogenic Ras Directs Silencing Of Tumor Suppressor Genes Through Ordered Recruitment Of Transcriptional Repressors, Narendra Wajapeyee, Sunil K. Malonia, Rajendra Kumar Palakurthy, Michael R. Green

University of Massachusetts Medical School Faculty Publications

We previously identified 28 cofactors through which a RAS oncoprotein directs transcriptional silencing of Fas and other tumor suppressor genes (TSGs). Here we performed RNAi-based epistasis experiments and found that RAS-directed silencing occurs through a highly ordered pathway that is initiated by binding of ZFP354B, a sequence-specific DNA-binding protein, and culminates in recruitment of the DNA methyltransferase DNMT1. RNAi and pharmacological inhibition experiments reveal that silencing requires continuous function of RAS and its cofactors and can be rapidly reversed, which may have therapeutic implications for reactivation of silenced TSGs in RAS-positive cancers.


Endogenous Human Mdm2-C Is Highly Expressed In Human Cancers And Functions As A P53-Independent Growth Activator, Danielle R. Okoro, Nicoleta Arva, Chong Gao, Alla Polotskaia, Cindy Puente, Melissa Rosso, Jill Bargonetti Oct 2013

Endogenous Human Mdm2-C Is Highly Expressed In Human Cancers And Functions As A P53-Independent Growth Activator, Danielle R. Okoro, Nicoleta Arva, Chong Gao, Alla Polotskaia, Cindy Puente, Melissa Rosso, Jill Bargonetti

Publications and Research

Human cancers over-expressing mdm2, through a T to G variation at a single nucleotide polymorphism at position 309 (mdm2 SNP309), have functionally inactivated p53 that is not effectively degraded. They also have high expression of the alternatively spliced transcript, mdm2-C. Alternatively spliced mdm2 transcripts are expressed in many forms of human cancer and when they are exogenously expressed they transform human cells. However no study to date has detected endogenous MDM2 protein isoforms. Studies with exogenous expression of splice variants have been carried out with mdm2-A and mdm2-B, but the mdm2-C isoform has remained virtually unexplored. We addressed the cellular ...


Directed Cell Migration In Multi-Cue Environments, Laura Lara Rodriguez, Ian C. Schneider Oct 2013

Directed Cell Migration In Multi-Cue Environments, Laura Lara Rodriguez, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell migration plays a critical role in development, angiogenesis, immune response, wound healing and cancer metastasis. During these processes, cells are often directed to migrate towards targets by sensing aligned fibers or gradients in concentration, mechanical properties or electric field. Often times, cells must integrate migrational information from several of these different cues. While the cell migration behavior, signal transduction and cytoskeleton dynamics elicited by individual directional cues has been largely determined, responses to multiple directional cues are much less understood. However, initial work has pointed to several interesting behaviors in multi-cue environments, including competition and cooperation between cues to ...


Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio Oct 2013

Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio

Cancer Biology Publications and Presentations

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains ...


Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar Oct 2013

Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 mu M after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 mu M ...


A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang Sep 2013

A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang

GSBS Dissertations and Theses

Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether ...


Cancer-Testis Gene Expression Is Associated With The Methylenetetrahydrofolate Reductase 677 C>T Polymorphism In Non-Small Cell Lung Carcinoma, Kerem M. Senses, Mithat Gonen, Ahmet Rasim Barutcu, Zeynep Kalaylioglu, Murat Isbilen, Ozlen Konu, Yao T. Chen, Nasser K. Altorki, Ali O. Gure Sep 2013

Cancer-Testis Gene Expression Is Associated With The Methylenetetrahydrofolate Reductase 677 C>T Polymorphism In Non-Small Cell Lung Carcinoma, Kerem M. Senses, Mithat Gonen, Ahmet Rasim Barutcu, Zeynep Kalaylioglu, Murat Isbilen, Ozlen Konu, Yao T. Chen, Nasser K. Altorki, Ali O. Gure

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels ...


Sonic Hedgehog Mediates The Proliferation And Recruitment Of Transformed Mesenchymal Stem Cells To The Stomach, Jessica M. Donnelly, Ambreesh Chawla, Jeanmarie Houghton, Yana Zavros Sep 2013

Sonic Hedgehog Mediates The Proliferation And Recruitment Of Transformed Mesenchymal Stem Cells To The Stomach, Jessica M. Donnelly, Ambreesh Chawla, Jeanmarie Houghton, Yana Zavros

University of Massachusetts Medical School Faculty Publications

Studies using Helicobacter-infected mice show that bone marrow-derived mesenchymal stem cells (MSCs) can repopulate the gastric epithelium and promote gastric cancer progression. Within the tumor microenvironment of the stomach, pro-inflammatory cytokine interferon-gamma (IFNgamma) and Sonic hedgehog (Shh) are elevated. IFNgamma is implicated in tumor proliferation via activation of the Shh signaling pathway in various tissues but whether a similar mechanism exists in the stomach is unknown. We tested the hypothesis that IFNgamma drives MSC proliferation and recruitment, a response mediated by Shh signaling. The current study uses transplantation of an in vitro transformed mesenchymal stem cell line (stMSC(vect)), that ...