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Articles 1 - 17 of 17
Full-Text Articles in Oncology
Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum
Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th1 enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th1 microenvironment.
Methods
We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] …
Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni
Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni
Wayne State University Associated BioMed Central Scholarship
Abstract
Introduction
The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis.
Methods
Murine prostate epithelial cells from PTEN+/+, PTEN +/− , and PTEN−/− (prostate …
Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad
Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.
Results
GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression …
Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar
Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.
Methods
Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …
Network Insights On Oxaliplatin Anti-Cancer Mechanisms, Osama M. Alian, Asfar S. Azmi, Ramzi M. Mohammad
Network Insights On Oxaliplatin Anti-Cancer Mechanisms, Osama M. Alian, Asfar S. Azmi, Ramzi M. Mohammad
Wayne State University Associated BioMed Central Scholarship
Abstract
Oxaliplatin has been a crucial component of combination therapies since admission into the clinic causing modest gains in survival across multiple malignancies. However, oxaliplatin functions in a non-targeted manner, posing a difficulty in ascertaining precise efficacy mechanisms. While previously thought to only affect DNA repair mechanisms, Platinum-protein adducts (Pt-Protein) far outnumber Pt-DNA adducts leaving a big part of oxaliplatin function unknown. Through preliminary network modeling of high throughput data, this article critically reviews the efficacy of oxaliplatin as well as proposes a better model for enhanced efficacy based on a network approach. In our study, not only oxaliplatin’s function …
Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar
Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar
Wayne State University Associated BioMed Central Scholarship
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several important biological processes through regulation of genes post-transcriptionally. Carcinogenesis is one of the key biological processes where miRNAs play important role in the regulation of genes. The miRNAs elicit their effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNA, depending on the degree of complementary base pairing. To-date more than 1,000 miRNAs are postulated to exist, although the field is moving rapidly. Currently, miRNAs are becoming the center of interest in a …
Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang
Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.
Methods
We established the MCF10A-ERLIN2 …
An Mdm2 Antagonist (Mi-319) Restores P53 Functions And Increases The Life Span Of Orally Treated Follicular Lymphoma Bearing Animals, Ramzi M. Mohammad, Jack Wu, Asfar S. Azmi, Amro Aboukameel, Angela Sosin, Sherwin Wu, Dajun Yang, Shaomeng Wang, Ayad M. Al-Katib
An Mdm2 Antagonist (Mi-319) Restores P53 Functions And Increases The Life Span Of Orally Treated Follicular Lymphoma Bearing Animals, Ramzi M. Mohammad, Jack Wu, Asfar S. Azmi, Amro Aboukameel, Angela Sosin, Sherwin Wu, Dajun Yang, Shaomeng Wang, Ayad M. Al-Katib
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
MI-319 is a synthetic small molecule designed to target the MDM2-P53 interaction. It is closely related to MDM2 antagonists MI-219 and Nutlin-3 in terms of the expected working mechanisms. The purpose of this study was to evaluate anti-lymphoma activity of MI-319 in WSU-FSCCL, a B-cell follicular lymphoma line. For comparison purpose, MI-319, MI-219 and Nutlin-3 were assessed side by side against FSCCL and three other B-cell hematological tumor cell lines in growth inhibition and gene expression profiling experiments.
Results
MI-319 was shown to bind to MDM2 protein with an affinity slightly higher than that of MI-219 and Nutlin-3. …
Gene Expression Profiles In Primary Pancreatic Tumors And Metastatic Lesions Of Ela-C-Myc Transgenic Mice, Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J. Liao
Gene Expression Profiles In Primary Pancreatic Tumors And Metastatic Lesions Of Ela-C-Myc Transgenic Mice, Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J. Liao
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials.
Results
Data indicate that genes …
Inhibition Of Proteasome Activity By The Dietary Flavonoid Apigenin Is Associated With Growth Inhibition In Cultured Breast Cancer Cells And Xenografts, Di Chen, Kristin R. Landis-Piwowar, Marina S. Chen, Q Ping Dou
Inhibition Of Proteasome Activity By The Dietary Flavonoid Apigenin Is Associated With Growth Inhibition In Cultured Breast Cancer Cells And Xenografts, Di Chen, Kristin R. Landis-Piwowar, Marina S. Chen, Q Ping Dou
Wayne State University Associated BioMed Central Scholarship
Abstract
Introduction
Proteasome inhibition is an attractive approach to anticancer therapy and may have relevancy in breast cancer treatment. Natural products, such as dietary flavonoids, have been suggested as natural proteasome inhibitors with potential use for cancer prevention and therapeutics. We previously reported that apigenin, a flavonoid widely distributed in many fruits and vegetables, can inhibit proteasome activity and can induce apoptosis in cultured leukemia Jurkat T cells. Whether apigenin has proteasome-inhibitory activity in the highly metastatic human breast MDA-MB-231 cells and xenografts, however, is unknown.
Methods
MDA-MB-231 breast cancer cell cultures and xenografts were treated with apigenin, followed by …
Paradoxical Antiproliferative Effect By A Murine Mammary Tumor-Derived Epithelial Cell Line, Esteban N. Gurzov, Sanaa M. Nabha, Hamilto Yamamoto, Hong Meng, O Graciela Scharovsky, R Daniel Bonfil
Paradoxical Antiproliferative Effect By A Murine Mammary Tumor-Derived Epithelial Cell Line, Esteban N. Gurzov, Sanaa M. Nabha, Hamilto Yamamoto, Hong Meng, O Graciela Scharovsky, R Daniel Bonfil
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells.
Methods
Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas …
Progression Of Renal Cell Carcinoma Is Inhibited By Genistein And Radiation In An Orthotopic Model, Gilda G. Hillman, Yu Wang, Mingxin Che, Julian J. Raffoul, Mark Yudelev, Omer Kucuk, Fazlul H. Sarkar
Progression Of Renal Cell Carcinoma Is Inhibited By Genistein And Radiation In An Orthotopic Model, Gilda G. Hillman, Yu Wang, Mingxin Che, Julian J. Raffoul, Mark Yudelev, Omer Kucuk, Fazlul H. Sarkar
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory.
Methods
The KCI-18 RCC cell line was generated …
Genistein Inhibits Radiation-Induced Activation Of Nf-Κb In Prostate Cancer Cells Promoting Apoptosis And G2/M Cell Cycle Arrest, Julian J. Raffoul, Yu Wang, Omer Kucuk, Jeffrey D. Forman, Fazlul H. Sarkar, Gilda G. Hillman
Genistein Inhibits Radiation-Induced Activation Of Nf-Κb In Prostate Cancer Cells Promoting Apoptosis And G2/M Cell Cycle Arrest, Julian J. Raffoul, Yu Wang, Omer Kucuk, Jeffrey D. Forman, Fazlul H. Sarkar, Gilda G. Hillman
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
New cancer therapeutic strategies must be investigated that enhance prostate cancer treatment while minimizing associated toxicities. We have previously shown that genistein, the major isoflavone found in soy, enhanced prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated the cellular and molecular interaction between genistein and radiation using PC-3 human prostate cancer cells.
Methods
Tumor cell survival and progression was determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-κB, and western blot analysis of cyclin B1, p21WAF1/Cip1, and cleaved PARP protein.
Results
Genistein combined with radiation caused greater inhibition in PC-3 …
Increased Therapeutic Potential Of An Experimental Anti-Mitotic Inhibitor Sb715992 By Genistein In Pc-3 Human Prostate Cancer Cell Line, David A. Davis, Sarah H. Sarkar, Maha Hussain, Yiwei Li, Fazlul H. Sarkar
Increased Therapeutic Potential Of An Experimental Anti-Mitotic Inhibitor Sb715992 By Genistein In Pc-3 Human Prostate Cancer Cell Line, David A. Davis, Sarah H. Sarkar, Maha Hussain, Yiwei Li, Fazlul H. Sarkar
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer …
Gene Expression Profiling Revealed Novel Mechanism Of Action Of Taxotere And Furtulon In Prostate Cancer Cells, Yiwei Li, Maha Hussain, Sarah H. Sarkar, James Eliason, Ran Li, Fazlul H. Sarkar
Gene Expression Profiling Revealed Novel Mechanism Of Action Of Taxotere And Furtulon In Prostate Cancer Cells, Yiwei Li, Maha Hussain, Sarah H. Sarkar, James Eliason, Ran Li, Fazlul H. Sarkar
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer.
Methods
The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot …
Clioquinol And Pyrrolidine Dithiocarbamate Complex With Copper To Form Proteasome Inhibitors And Apoptosis Inducers In Human Breast Cancer Cells, Kenyon G. Daniel, Di Chen, Shirley Orlu, Qiuzhi Cui, Fred R. Miller, Q Ping Dou
Clioquinol And Pyrrolidine Dithiocarbamate Complex With Copper To Form Proteasome Inhibitors And Apoptosis Inducers In Human Breast Cancer Cells, Kenyon G. Daniel, Di Chen, Shirley Orlu, Qiuzhi Cui, Fred R. Miller, Q Ping Dou
Wayne State University Associated BioMed Central Scholarship
Abstract
Introduction
A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome …
Imaging Genome Abnormalities In Cancer Research, Henry Hq Heng, Joshua B. Stevens, Guo Liu, Steven W. Bremer, Christine J. Ye
Imaging Genome Abnormalities In Cancer Research, Henry Hq Heng, Joshua B. Stevens, Guo Liu, Steven W. Bremer, Christine J. Ye
Wayne State University Associated BioMed Central Scholarship
Abstract
Increasing attention is focusing on chromosomal and genome structure in cancer research due to the fact that genomic instability plays a principal role in cancer initiation, progression and response to chemotherapeutic agents. The integrity of the genome (including structural, behavioral and functional aspects) of normal and cancer cells can be monitored with direct visualization by using a variety of cutting edge molecular cytogenetic technologies that are now available in the field of cancer research. Examples are presented in this review by grouping these methodologies into four categories visualizing different yet closely related major levels of genome structures. An integrated …