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Supplementation Of H1n1pdm09 Split Vaccine With Heterologous Tandem Repeat M2e5x Virus-Like Particles Confers Improved Cross-Protection In Ferrets, Nedzad Music, Adrian J. Reber, Min-Chul Kim, Ian A. York, Sang-Moo Kang Dec 2015

Supplementation Of H1n1pdm09 Split Vaccine With Heterologous Tandem Repeat M2e5x Virus-Like Particles Confers Improved Cross-Protection In Ferrets, Nedzad Music, Adrian J. Reber, Min-Chul Kim, Ian A. York, Sang-Moo Kang

Biology Faculty Publications

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus- like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine (“Split”) alone, influenza split vaccine supplemented with M2e5x VLP (“Split+M2e5x”), M2e5x VLP alone (“M2e5x”), …


Monoaminergic Tone Supports Conductance Correlations And Stabilizes Activity Features In Pattern Generating Neurons Of The Lobster, Panulirus Interruptus, Wulf-Dieter C. Krenz, Anna R. Parker, Edmund William Rodgers, Deborah J. Baro Oct 2015

Monoaminergic Tone Supports Conductance Correlations And Stabilizes Activity Features In Pattern Generating Neurons Of The Lobster, Panulirus Interruptus, Wulf-Dieter C. Krenz, Anna R. Parker, Edmund William Rodgers, Deborah J. Baro

Biology Faculty Publications

Experimental and computational studies demonstrate that different sets of intrinsic and synaptic conductances can give rise to equivalent activity patterns. This is because the balance of conductances, not their absolute values, defines a given activity feature. Activity-dependent feedback mechanisms maintain neuronal conductance correlations and their corresponding activity features. This study demonstrates that tonic nM concentrations of monoamines enable slow, activity-dependent processes that can maintain a correlation between the transient potassium current (IA ) and the hyperpolarization activated current (Ih ) over the long-term (i.e., regulatory change persists for hours after removal of modulator). Tonic 5 nM DA acted through an …


Alum Adjuvant Enhances Protection Against Respiratory Syncytial Virus But Exacerbates Pulmonary Inflammation By Modulating Multiple Innate And Adaptive Immune Cells, Ki-Hye Kim, Young-Tae Lee, Hye Suk Hwang, Young-Man Kwon, Yu-Jin Jung, Youri Lee, Jong Seok Lee, Yu-Na Lee, Soojin Park, Sang-Moon Kang Oct 2015

Alum Adjuvant Enhances Protection Against Respiratory Syncytial Virus But Exacerbates Pulmonary Inflammation By Modulating Multiple Innate And Adaptive Immune Cells, Ki-Hye Kim, Young-Tae Lee, Hye Suk Hwang, Young-Man Kwon, Yu-Jin Jung, Youri Lee, Jong Seok Lee, Yu-Na Lee, Soojin Park, Sang-Moon Kang

Biology Faculty Publications

Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FIRSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+ TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV …


Mechanisms Of Cross-Protection By Influenza Virus M2-Based Vaccines, Yu-Na Lee, Min-Chul Kim, Young-Tae Lee, Yu-Jin Kim, Sang-Moo Kang Sep 2015

Mechanisms Of Cross-Protection By Influenza Virus M2-Based Vaccines, Yu-Na Lee, Min-Chul Kim, Young-Tae Lee, Yu-Jin Kim, Sang-Moo Kang

Biology Faculty Publications

Current influenza virus vaccines are based on strain-specific surface glycoprotein hemagglutinin (HA) antigens and effective only when the predicted vaccine strains and circulating viruses are well-matched. The current strategy of influenza vaccination does not prevent the pandemic outbreaks and protection efficacy is reduced or ineffective if mutant strains emerge. It is of high priority to develop effective vaccines and vaccination strategies conferring a broad range of cross protection. The extracellular domain of M2 (M2e) is highly conserved among human influenza A viruses and has been utilized to develop new vaccines inducing cross protection against different subtypes of influenza A virus. …


Cross Protection Against Influenza A Virus By Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins, Yu-Na Lee, Min-Chul Kim, Young-Tae Lee, Hye Suk Hwang, Jongsang Lee, Cheol Kim, Sang-Moon Kang Sep 2015

Cross Protection Against Influenza A Virus By Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins, Yu-Na Lee, Min-Chul Kim, Young-Tae Lee, Hye Suk Hwang, Jongsang Lee, Cheol Kim, Sang-Moon Kang

Biology Faculty Publications

The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, …


Effect Of Osmotic Pressure On The Stability Of Whole Inactivated Influenza Vaccine For Coating On Microneedles, Hyo-Jick Choi, Jae-Min Song, Brian J. Bondy, Richard W. Compans, Sang-Moon Kang, Mark R. Prausnitz Jul 2015

Effect Of Osmotic Pressure On The Stability Of Whole Inactivated Influenza Vaccine For Coating On Microneedles, Hyo-Jick Choi, Jae-Min Song, Brian J. Bondy, Richard W. Compans, Sang-Moon Kang, Mark R. Prausnitz

Biology Faculty Publications

Enveloped virus vaccines can be damaged by high osmotic strength solutions, such as those used to protect the vaccine antigen during drying, which contain high concentrations of sugars. We therefore studied shrinkage and activity loss of whole inactivated influenza virus in hyperosmotic solutions and used those findings to improve vaccine coating of microneedle patches for influenza vaccination. Using stopped-flow light scattering analysis, we found that the virus underwent an initial shrinkage on the order of 10% by volume within 5 s upon exposure to a hyperosmotic stress difference of 217 milliosmolarity. During this shrinkage, the virus envelope had very low …


Lkb1 In Transmembrane Receptor Signaling, Imoh S. Okon, Ming-Hui Zou Jul 2015

Lkb1 In Transmembrane Receptor Signaling, Imoh S. Okon, Ming-Hui Zou

Biology Faculty Publications

No abstract provided.


Respiratory Syncytial Virus-Like Nanoparticle Vaccination Induces Long-Term Protection Without Pulmonary Disease By Modulating Cytokines And T-Cells Partially Through Alveolar Macrophages, Young-Tae Lee, Eun-Ju Ko, Hye Suk Hwang, Jong Seok Lee, Ki-Hye Kim, Young-Man Kwon, Sang-Moo Kang Jul 2015

Respiratory Syncytial Virus-Like Nanoparticle Vaccination Induces Long-Term Protection Without Pulmonary Disease By Modulating Cytokines And T-Cells Partially Through Alveolar Macrophages, Young-Tae Lee, Eun-Ju Ko, Hye Suk Hwang, Jong Seok Lee, Ki-Hye Kim, Young-Man Kwon, Sang-Moo Kang

Biology Faculty Publications

The mechanisms of protection against respiratory syncytial virus (RSV) are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs) in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL)-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon …


The Paramyxovirus Polymerase Complex As A Target For Next-Generation Anti-Paramyxovirus Therapeutics, Robert Cox, Richard K. Plemper May 2015

The Paramyxovirus Polymerase Complex As A Target For Next-Generation Anti-Paramyxovirus Therapeutics, Robert Cox, Richard K. Plemper

Biology Faculty Publications

The paramyxovirus family includes major human and animal pathogens, including measles virus, mumps virus, and human respiratory syncytial virus (RSV), as well as the emerging zoonotic Hendra and Nipah viruses. In the U.S., RSV is the leading cause of infant hospitalizations due to viral infectious disease. Despite their clinical significance, effective drugs for the improved management of paramyxovirus disease are lacking. The development of novel anti-paramyxovirus therapeutics is therefore urgently needed. Paramyxoviruses contain RNA genomes of negative polarity, necessitating a virus-encoded RNA-dependent RNA polymerase (RdRp) complex for replication and transcription. Since an equivalent enzymatic activity is absent in host cells, …


Analysis Of Activation Of The Nf-Κb Pathway By Shfv Infection, Ashley Aisabor Apr 2015

Analysis Of Activation Of The Nf-Κb Pathway By Shfv Infection, Ashley Aisabor

Georgia State Undergraduate Research Conference

No abstract provided.


Complex Eukaryotic Protein Expression Using A Prokaryotic Chassis (Escherichia Coli), Derrica Burke, Julia Dave, Jasmine Padalla, Tre Landry Apr 2015

Complex Eukaryotic Protein Expression Using A Prokaryotic Chassis (Escherichia Coli), Derrica Burke, Julia Dave, Jasmine Padalla, Tre Landry

Georgia State Undergraduate Research Conference

No abstract provided.


Characterization Of Potent Fusion Inhibitors Of Influenza Virus, Michael Rowse, Shihong Qiu, Jun Tsao, Tongmei Xian, Sarah Khawaja, Yohei Yamauchi, Zhen Yang, Guoxin Wang, Ming Luo Mar 2015

Characterization Of Potent Fusion Inhibitors Of Influenza Virus, Michael Rowse, Shihong Qiu, Jun Tsao, Tongmei Xian, Sarah Khawaja, Yohei Yamauchi, Zhen Yang, Guoxin Wang, Ming Luo

Biology Faculty Publications

New inhibitors of influenza viruses are needed to combat the potential emergence of novel human influenza viruses. We have identified a class of small molecules that inhibit replication of influenza virus at picomolar concentrations in plaque reduction assays. The compound also inhibits replication of vesicular stomatitis virus. Time of addition and dilution experiments with influenza virus indicated that an early time point of infection was blocked and that inhibitor 136 tightly bound to virions. Using fluorescently labeled influenza virus, inhibition of viral fusion to cellular membranes by blocked lipid mixing was established as the mechanism of action for this class …


Rampant Centrosome Amplification Underlies More Aggressive Disease Course Of Triple Negative Breast Cancers, Vaishali Pannu, Karuna Mittal, Guilherme Cantuaria, Michelle D. Reid, Xiaoxian Li, Shashikiran Donthamsetty, Michelle Mcbride, Sergey Klimov, Remus Osan, Meenakshi V. Gupta, Padmashree C.G. Rida, Ritu Aneja Mar 2015

Rampant Centrosome Amplification Underlies More Aggressive Disease Course Of Triple Negative Breast Cancers, Vaishali Pannu, Karuna Mittal, Guilherme Cantuaria, Michelle D. Reid, Xiaoxian Li, Shashikiran Donthamsetty, Michelle Mcbride, Sergey Klimov, Remus Osan, Meenakshi V. Gupta, Padmashree C.G. Rida, Ritu Aneja

Biology Faculty Publications

Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non- TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC …


Enhanced Immune Responses By Skin Vaccination With Influenza Subunit Vaccine In Young Hosts, Dimitrois G. Koutsonanos, E. Stein Esser, Sean R. Mcmaster, Priya Kalluri, Jeong-Woo Lee, Mark R. Prausnitz, Ioanna Skountzou, Timothy L. Denning, Jacob E. Kohlmeier, Richard W. Compans Mar 2015

Enhanced Immune Responses By Skin Vaccination With Influenza Subunit Vaccine In Young Hosts, Dimitrois G. Koutsonanos, E. Stein Esser, Sean R. Mcmaster, Priya Kalluri, Jeong-Woo Lee, Mark R. Prausnitz, Ioanna Skountzou, Timothy L. Denning, Jacob E. Kohlmeier, Richard W. Compans

Biology Faculty Publications

Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could ben- efit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of …


Neonatal Infection With Species C Adenoviruses Confirmed In Viable Cord Blood Lymphocytes, David A. Ornelles, Linda R. Gooding, Charlie Garnett-Benson Mar 2015

Neonatal Infection With Species C Adenoviruses Confirmed In Viable Cord Blood Lymphocytes, David A. Ornelles, Linda R. Gooding, Charlie Garnett-Benson

Biology Faculty Publications

Credible but conflicting reports address the frequency of prenatal infection by species C adenovirus. This question is important because these viruses persist in lymphoid cells and suppress double-stranded DNA-break repair. Consequently, prenatal adenovirus infections may generate the aberrant clones of lymphocytes that precede development of childhood acute lymphoblastic leukemia (ALL). The present study was designed to overcome technical limitations of prior work by processing cord blood lymphocytes within a day of collection, and by analyzing sufficient numbers of lymphocytes to detect adenovirus-containing cells at the lower limits determined by our previous studies of tonsil lymphocytes. By this approach, adenoviral DNA …


Microrna-223 Delivered By Platelet-Derived Microvesicles Promotes Lung Cancer Cell Invasion Via Targeting Tumor Suppressor Epb41l3, Hongwei Liang, Xin Yan, Yi Pan, Yongsheng Wang, Nan Wang, Limin Li, Yuan Liu, Xi Chen, Chen-Yu Zhang, Hongwei Gu, Ke Zen Mar 2015

Microrna-223 Delivered By Platelet-Derived Microvesicles Promotes Lung Cancer Cell Invasion Via Targeting Tumor Suppressor Epb41l3, Hongwei Liang, Xin Yan, Yi Pan, Yongsheng Wang, Nan Wang, Limin Li, Yuan Liu, Xi Chen, Chen-Yu Zhang, Hongwei Gu, Ke Zen

Biology Faculty Publications

Background: Patients with hematogenous metastatic lung cancer displayed significantly increased platelet count and aggregation compared to lung cancer patients without hematogenous metastasis. The mechanism underlying the correlation between the lung cancer hematogenous metastasis and platelet activation remains unknown. Results: In the present study, we explored the role of microRNA-223 (miR-223) derived from platelets in modulating lung cancer cell invasion. Our results demonstrated that platelets from NSCLC patients contain higher level of miR-223 than that from healthy subjects. The concentration of miR-223 in the platelet-secreted microvesicles (P-MVs) from NSCLC patients was also increased compared to that from healthy subjects. Incubation of …


Systems Biology From Virus To Humans, Youri Lee, Yu-Jin Kim, Yu-Jin Jung, Young-Man Kwon, Seung Il Kim, Sang-Moo Kang Feb 2015

Systems Biology From Virus To Humans, Youri Lee, Yu-Jin Kim, Yu-Jin Jung, Young-Man Kwon, Seung Il Kim, Sang-Moo Kang

Biology Faculty Publications

Natural infection and then recovery are considered to be the most effective means for hosts to build protective immunity. Thus, mimicking natural infection of pathogens, many live attenuated vaccines such as influenza virus, and yellow fever vaccine 17D were developed and have been successfully used to induce protective immunity. However, humans fail to generate long-term protective immunity to some pathogens after natural infection such as influenza virus, respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV) even if they survive initial infections. Many vaccines are suboptimal since much mortality is still occurring, which is exampled by influenza and tuberculosis. It …


Ginseng Protects Against Respiratory Syncytial Virus By Modulating Multiple Immune Cells And Inhibiting Viral Replication, Jong Seok Lee, Yu-Na Lee, Young-Tae Lee, Hye Suk Hwang, Ki-Hye Kim, Eun-Ju Ko, Min-Chul Kim, Sang-Moo Kang Feb 2015

Ginseng Protects Against Respiratory Syncytial Virus By Modulating Multiple Immune Cells And Inhibiting Viral Replication, Jong Seok Lee, Yu-Na Lee, Young-Tae Lee, Hye Suk Hwang, Ki-Hye Kim, Eun-Ju Ko, Min-Chul Kim, Sang-Moo Kang

Biology Faculty Publications

Ginseng has been used in humans for thousands of years but its effects on viral infection have not been well understood. We investigated the effects of red ginseng extract (RGE) on respiratory syncytial virus (RSV) infection using in vitro cell culture and in vivo mouse models. RGE partially protected human epithelial (HEp2) cells from RSV-induced cell death and viral replication. In addition, RGE significantly inhibited the production of RSV-induced pro-inflammatory cytokine (TNF-α) in murine dendritic and macrophage-like cells. More importantly, RGE intranasal pre-treatment prevented loss of mouse body weight after RSV infection. RGE treatment improved lung viral clearance and enhanced …


Hset Overexpression Fuels Tumor Progression Via Centrosome Clustering-Independent Mechanisms In Breast Cancer Patients, Vaishali Pannu, Padmashree C.G. Rida, Angela Ogden, Ravi C. Turaga, Shashikiran Donthamsetty, Nathan Bowen, Katie Rudd, Meenakshi V. Gupta, Michelle D. Reid, Guilherme Cantuaria, Claire E. Walczak, Ritu Aneja Feb 2015

Hset Overexpression Fuels Tumor Progression Via Centrosome Clustering-Independent Mechanisms In Breast Cancer Patients, Vaishali Pannu, Padmashree C.G. Rida, Angela Ogden, Ravi C. Turaga, Shashikiran Donthamsetty, Nathan Bowen, Katie Rudd, Meenakshi V. Gupta, Michelle D. Reid, Guilherme Cantuaria, Claire E. Walczak, Ritu Aneja

Biology Faculty Publications

Human breast tumors harbor supernumerary centrosomes in almost 80% of tumor cells. Although amplified centrosomes compromise cell viability via multipolar spindles resulting in death-inducing aneuploidy, cancer cells tend to cluster extra centrosomes during mitosis. As a result cancer cells display bipolar spindle phenotypes to maintain a tolerable level of aneuploidy, an edge to their survival. HSET/KifC1, a kinesin-like minus-end directed microtubule motor has recently found fame as a crucial centrosome clustering molecule. Here we show that HSET promotes tumor progression via mechanisms independent of centrosome clustering. We found that HSET is overexpressed in breast carcinomas wherein nuclear HSET accumulation correlated …


Tonic 5nm Da Stabilizes Neuronal Output By Enabling Bidirectional Activity-Dependent Regulation Of The Hyperpolarization Activated Current Via Pka And Calcineurin, Wulf-Dieter C. Krenz, Edmund William Rodgers, Deborah J. Baro Jan 2015

Tonic 5nm Da Stabilizes Neuronal Output By Enabling Bidirectional Activity-Dependent Regulation Of The Hyperpolarization Activated Current Via Pka And Calcineurin, Wulf-Dieter C. Krenz, Edmund William Rodgers, Deborah J. Baro

Biology Faculty Publications

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activitydependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated …


Detecting Conserved Protein Complexes Using A Dividing-And-Matching Algorithm And Unequally Lenient Criteria For Network Comparison, Yi Pan, Wei Peng, Jianxin Wang, Fangxiang Wu Jan 2015

Detecting Conserved Protein Complexes Using A Dividing-And-Matching Algorithm And Unequally Lenient Criteria For Network Comparison, Yi Pan, Wei Peng, Jianxin Wang, Fangxiang Wu

Biology Faculty Publications

The increase of protein–protein interaction (PPI) data of different species makes it possible to identify common subnetworks (conserved protein complexes) across species via local alignment of their PPI networks, which benefits us to study biological evolution. Local alignment algorithms compare PPI network of different species at both protein sequence and network structure levels. For computational and biological reasons, it is hard to find common subnetworks with strict similar topology from two input PPI networks. Consequently some methods introduce less strict criteria for topological similarity. However those methods fail to consider the differences of the two input networks and adopt equally …


Interaction Between Leucine And Phosphodiesterase 5 Inhibition In Modulating Insulin Sensitivity And Lipid Metabolism, Lizhi Fu, Fenfen Li, Antje Bruckbauer, Qiang Cao, Xin Cui, Rui Wu, Hang Shi, Bingzhong Xue, Michael B. Zemel Jan 2015

Interaction Between Leucine And Phosphodiesterase 5 Inhibition In Modulating Insulin Sensitivity And Lipid Metabolism, Lizhi Fu, Fenfen Li, Antje Bruckbauer, Qiang Cao, Xin Cui, Rui Wu, Hang Shi, Bingzhong Xue, Michael B. Zemel

Biology Faculty Publications

Purpose: Leucine activates SIRT1/AMP-activated protein kinase (AMPK) signaling and markedly potentiates the effects of other sirtuin and AMPK activators on insulin signaling and lipid metabolism. Phosphodiesterase 5 inhibition increases nitric oxide–cGMP signaling, which in turn exhibits a positive feedback loop with both SIRT1 and AMPK, thus amplifying peroxisome proliferator-activated receptor γ co-activator α (PGC1α)-mediated effects. Methods: We evaluated potential synergy between leucine and PDE5i on insulin sensitivity and lipid metabolism in vitro and in diet-induced obese (DIO) mice. Results: Leucine (0.5 mM) exhibited significant synergy with subtherapeutic doses (0.1–10 nM) of PDE5-inhibitors (sildenafil and icariin) on fat oxidation, nitric oxide …


Combination Treatment With Sublethal Ionizing Radiation And The Proteasome Inhibitor, Bortezomib, Enhances Death-Receptor Mediated Apoptosis And Anti-Tumor Immune Attack, Ercan Cacan Cacan, Alexander M. Spring, Anita Kumari, Susanna F. Greer, Charlie Garnett-Benson Jan 2015

Combination Treatment With Sublethal Ionizing Radiation And The Proteasome Inhibitor, Bortezomib, Enhances Death-Receptor Mediated Apoptosis And Anti-Tumor Immune Attack, Ercan Cacan Cacan, Alexander M. Spring, Anita Kumari, Susanna F. Greer, Charlie Garnett-Benson

Biology Faculty Publications

Sub-lethal doses of radiation can modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. Proteasome inhibitors demonstrate broad anti-tumor activity in clinical and pre-clinical cancer models. Here, we use a combination treatment of proteasome inhibition and irradiation to further induce immunomodulation of tumor cells that could enhance tumor-specific immune responses. We investigate the effects of the 26S proteasome inhibitor, bortezomib, alone or in combination with radiotherapy, on the expression of immunogenic genes in normal colon and colorectal cancer cell lines. We examined cells for changes in the expression of several death receptors (DR4, DR5 and Fas) commonly …