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Full-Text Articles in Cancer Biology

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association Sep 2019

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

MD Anderson Cancer Center Postdoctoral Association Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.


Role Of A 19s Proteasome Subunit- Psmd10(Gankyrin) In Neurogenesis Of Human Neuronal Progenitor Cells, Indrajit Sahu, Padma P. Nanaware, Minal Mane, Saim Wasi Mulla, Soumen Roy, Prasanna Venkatraman Aug 2019

Role Of A 19s Proteasome Subunit- Psmd10(Gankyrin) In Neurogenesis Of Human Neuronal Progenitor Cells, Indrajit Sahu, Padma P. Nanaware, Minal Mane, Saim Wasi Mulla, Soumen Roy, Prasanna Venkatraman

Open Access Articles

PSMD10(Gankyrin), a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10(Gankyrin) overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis ...


Modeling Of Cisplatin-Induced Signaling Dynamics In Triple-Negative Breast Cancer Cells Reveals Mediators Of Sensitivity, Anne Margriet Heijink, Marieke Everts, Megan E. Honeywell, Ryan Richards, Yannick P. Kok, Elisabeth G. E. De Vries, Michael J. Lee, Marcel A T M Van Vugt Aug 2019

Modeling Of Cisplatin-Induced Signaling Dynamics In Triple-Negative Breast Cancer Cells Reveals Mediators Of Sensitivity, Anne Margriet Heijink, Marieke Everts, Megan E. Honeywell, Ryan Richards, Yannick P. Kok, Elisabeth G. E. De Vries, Michael J. Lee, Marcel A T M Van Vugt

Open Access Articles

Triple-negative breast cancers (TNBCs) display great diversity in cisplatin sensitivity that cannot be explained solely by cancer-associated DNA repair defects. Differential activation of the DNA damage response (DDR) to cisplatin has been proposed to underlie the observed differential sensitivity, but it has not been investigated systematically. Systems-level analysis-using quantitative time-resolved signaling data and phenotypic responses, in combination with mathematical modeling-identifies that the activation status of cell-cycle checkpoints determines cisplatin sensitivity in TNBC cell lines. Specifically, inactivation of the cell-cycle checkpoint regulator MK2 or G3BP2 sensitizes cisplatin-resistant TNBC cell lines to cisplatin. Dynamic signaling data of five cell cycle-related signals predicts ...


Hsp90/Axl/Eif4e-Regulated Unfolded Protein Response As An Acquired Vulnerability In Drug-Resistant Kras-Mutant Lung Cancer, Haitang Yang, Shun-Qing Liang, Duo Xu, Zhang Yang, Thomas M. Marti, Yanyun Gao, Gregor J. Kocher, Heng Zhao, Ralph A. Schmid, Ren-Wang Peng Aug 2019

Hsp90/Axl/Eif4e-Regulated Unfolded Protein Response As An Acquired Vulnerability In Drug-Resistant Kras-Mutant Lung Cancer, Haitang Yang, Shun-Qing Liang, Duo Xu, Zhang Yang, Thomas M. Marti, Yanyun Gao, Gregor J. Kocher, Heng Zhao, Ralph A. Schmid, Ren-Wang Peng

Open Access Articles

Drug resistance and tumor heterogeneity are formidable challenges in cancer medicine, which is particularly relevant for KRAS-mutant cancers, the epitome of malignant tumors recalcitrant to targeted therapy efforts and first-line chemotherapy. In this study, we delineate that KRAS-mutant lung cancer cells resistant to pemetrexed (MTA) and anti-MEK drug trametinib acquire an exquisite dependency on endoplasmic reticulum (ER) stress signaling, rendering resistant cancer cells selectively susceptible to blockage of HSP90, the receptor tyrosine kinase AXL, the eukaryotic translation initiation factor 4E (eIF4E), and the unfolded protein response (UPR). Mechanistically, acquisition of drug resistance enables KRAS-mutant lung cancer cells to bypass canonical ...


Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito Aug 2019

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito

University of Massachusetts Medical School Faculty Publications

Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these ...


Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw Aug 2019

Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw

Open Access Articles

The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma ...


Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla Aug 2019

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

UT GSBS Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate ...


Multimodal Quantitative Imaging Of Brain Cancer In Cultured Cells, Xin Feng, Alona Muzikansky, Alonzo H. Ross, Michael R. Hamblin, Peter R. Jermain, Anna N. Yaroslavsky Jul 2019

Multimodal Quantitative Imaging Of Brain Cancer In Cultured Cells, Xin Feng, Alona Muzikansky, Alonzo H. Ross, Michael R. Hamblin, Peter R. Jermain, Anna N. Yaroslavsky

Open Access Articles

Fluorescence emission, polarization and subcellular localization of methylene blue (MB) were studied in four cancerous and two normal human brain cell lines. Fluorescence emission and polarization images were acquired and analyzed. The co-localization of MB with mitochondria, lysosomes and nuclei of the cells was evaluated. Glioblastoma cells exhibited significantly higher MB fluorescence polarization compared to normal astrocytes. Preferential accumulation of MB in mitochondria of glioblastoma cells may explain higher fluorescence polarization values in cancer cells as compared to normal. These findings may lead to the development of a quantitative method for the detection of brain cancer in single cells.


Inactivating Mutations And X-Ray Crystal Structure Of The Tumor Suppressor Opcml Reveal Cancer-Associated Functions, James R. Birtley, Zachary Maben, Grant C. Weaver, Mollie M. Jurewicz, Lawrence J. Stern, Chiara Recchi, Hani Gabra Jul 2019

Inactivating Mutations And X-Ray Crystal Structure Of The Tumor Suppressor Opcml Reveal Cancer-Associated Functions, James R. Birtley, Zachary Maben, Grant C. Weaver, Mollie M. Jurewicz, Lawrence J. Stern, Chiara Recchi, Hani Gabra

Open Access Articles

OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 A resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and ...


Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari Jul 2019

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a ...


F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra Jul 2019

F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra

Open Access Articles

Aberrant activation of beta-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/beta-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of the SCF (SKP1-Cullin1-F-box protein) complex, which targets the nuclear beta-catenin protein to facilitate proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of beta-catenin and promotes its lysine 48-linked polyubiquitination. In addition, it inhibits epithelial-to-mesenchymal transition (EMT) by attenuating the level of beta-catenin. Therefore, depletion ...


Gene Expression Signature Of Atypical Breast Hyperplasia And Regulation By Sfrp1, Kelly J. Gregory, Giovanna M. Crisi, Brooke A. Bentley, Grace Makari-Judson, Holly S. Mason, Jun Yu, Lihua Julie Zhu, Karl J. Simin, Jacob P. S. Johnson, Ashraf Khan, Sallie S. Schneider, D. Joseph Jerry Jun 2019

Gene Expression Signature Of Atypical Breast Hyperplasia And Regulation By Sfrp1, Kelly J. Gregory, Giovanna M. Crisi, Brooke A. Bentley, Grace Makari-Judson, Holly S. Mason, Jun Yu, Lihua Julie Zhu, Karl J. Simin, Jacob P. S. Johnson, Ashraf Khan, Sallie S. Schneider, D. Joseph Jerry

Open Access Articles

BACKGROUND: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERalpha+) and represent risk indicators and/or precursor lesions to low grade ERalpha+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation.

METHODS: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and ...


Pathognomonic And Epistatic Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Benjamin J. Chen, Michael R. Green Jun 2019

Pathognomonic And Epistatic Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Benjamin J. Chen, Michael R. Green

University of Massachusetts Medical School Faculty Publications

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level, but other less common subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 755 B-NHL tumors at high depth; primarily including DLBCL, MCL, follicular lymphoma ...


Somatic Molecular Analysis Augments Cytologic Evaluation Of Pancreatic Cyst Fluids As A Diagnostic Tool, Ali Sakhdari, Parnian Ahmadi Moghaddam, Chi Young Ok, Otto Walter, Keith Tomaszewicz, Mandi-Lee Caporelli, Xiuling Meng, Jennifer Lafemina, Giles F. Whalen, Edward Belkin, Jaroslav Zivny, Wahid Y. Wassef, Bruce A. Woda, Lloyd Hutchinson, Ediz F. Cosar Jun 2019

Somatic Molecular Analysis Augments Cytologic Evaluation Of Pancreatic Cyst Fluids As A Diagnostic Tool, Ali Sakhdari, Parnian Ahmadi Moghaddam, Chi Young Ok, Otto Walter, Keith Tomaszewicz, Mandi-Lee Caporelli, Xiuling Meng, Jennifer Lafemina, Giles F. Whalen, Edward Belkin, Jaroslav Zivny, Wahid Y. Wassef, Bruce A. Woda, Lloyd Hutchinson, Ediz F. Cosar

Open Access Articles

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens.

Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF ...


Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker Jun 2019

Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to ...


Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii May 2019

Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara May 2019

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Jnk(1/2) Represses Lkb(1)-Deficiency-Induced Lung Squamous Cell Carcinoma Progression, Jian Liu, Tianyuan Wang, Chad J. Creighton, San-Pin Wu, Madhumita Ray, Kyathanahalli S. Janardhan, Cynthia J. Willson, Sung-Nam Cho, Patricia D. Castro, Michael M. Ittmann, Jian-Liang Li, Roger J. Davis, Francesco J. Demayo May 2019

Jnk(1/2) Represses Lkb(1)-Deficiency-Induced Lung Squamous Cell Carcinoma Progression, Jian Liu, Tianyuan Wang, Chad J. Creighton, San-Pin Wu, Madhumita Ray, Kyathanahalli S. Janardhan, Cynthia J. Willson, Sung-Nam Cho, Patricia D. Castro, Michael M. Ittmann, Jian-Liang Li, Roger J. Davis, Francesco J. Demayo

Open Access Articles

Mechanisms of lung squamous cell carcinoma (LSCC) development are poorly understood. Here, we report that JNK1/2 activities attenuate Lkb1-deficiency-driven LSCC initiation and progression through repressing DeltaNp63 signaling. In vivo Lkb1 ablation alone is sufficient to induce LSCC development by reducing MKK7 levels and JNK1/2 activities, independent of the AMPKalpha and mTOR pathways. JNK1/2 activities is positively regulated by MKK7 during LSCC development. Pharmaceutically elevated JNK1/2 activities abates Lkb1 dependent LSCC formation while compound mutations of Jnk1/2 and Lkb1 further accelerate LSCC progression. JNK1/2 is inactivated in a substantial proportion of human LSCC and JNK1 ...


Circulating Micrornas Mir-331 And Mir-195 Differentiate Local Luminal A From Metastatic Breast Cancer, Peter Mcanena, Kahraman Tanriverdi, Catherine Curran, K. Gilligan, Jane E. Freedman, James A. L. Brown, Michael J. Kerin May 2019

Circulating Micrornas Mir-331 And Mir-195 Differentiate Local Luminal A From Metastatic Breast Cancer, Peter Mcanena, Kahraman Tanriverdi, Catherine Curran, K. Gilligan, Jane E. Freedman, James A. L. Brown, Michael J. Kerin

Open Access Articles

BACKGROUND: Breast cancer is the leading cause of cancer related death in women, with metastasis the principle cause of mortality. New non-invasive prognostic markers are needed for the early detection of metastasis, facilitating treatment decision optimisation. MicroRNA (miRNA) are small, non-coding RNAs regulating gene expression and involved in many cellular processes, including metastasis. As biomarkers, circulating miRNAs (in blood) hold great promise for informing diagnosis or monitoring treatment responses.

METHODS: Plasma extracted RNA from age matched local Luminal A (n = 4) or metastatic disease (n = 4) were profiled using Next Generation Sequencing. Selected differentially expressed miRNA were validated on a ...


Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu May 2019

Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu

Theses and Dissertations

Ipomoeassin F is a flagship congener of a resin glycoside family that inhibits growth of many tumor cell lines with only single-digital nanomolar IC50 values. However, biological and pharmacological mechanisms of ipomoeassin F have been undefined. To facilitate exploration of the biological and pharmacological properties, we performed sophisticate SAR (Structure–activity relationship) studies of ipomoeassin F to understand its pharmacophore and structure properties so that we can design favorable probes for further biological investigation. By applying appropriate deviates that possess fluorescent groups and similar bio-activity, the target protein was found to be localized in endoplasmic reticulum (ER). Through biotin affinity ...


Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd May 2019

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of ...


Acute Promyelocytic Leukemia: A Case Study Correlating Cytogenetic Abnormality With Prognosis, Alyssa Lamond, Theresa Tellier-Castellone May 2019

Acute Promyelocytic Leukemia: A Case Study Correlating Cytogenetic Abnormality With Prognosis, Alyssa Lamond, Theresa Tellier-Castellone

Senior Honors Projects

Advancements in medical technology today have positively impacted the diagnosis, treatment, and prognosis of cancers. Particularly acute promyelocytic leukemia (APL) has completely improved from having the poorest prognosis to one of the best. Acute promyelocytic leukemia is a malignant disease of hematopoietic tissue classified by WHO as leukemia with >20% blasts from the myeloid lineage, specifically promyelocytes. Determined in 1976, FAB classified AML subtypes M1-M7, with APL being M3. Specific characteristics classify the subtype of AML, with each resulting from a different genetic abnormality. The focus of APL diagnosis, treatment, and prognosis occurs around the known PML-RARα fusion gene. Flow ...


Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap May 2019

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb ...


Exploiting Unique Biological Features Of Leukemia Stem Cells For Therapeutic Benefit, Haojian Zhang, Shaoguang Li Apr 2019

Exploiting Unique Biological Features Of Leukemia Stem Cells For Therapeutic Benefit, Haojian Zhang, Shaoguang Li

Open Access Articles

Cancer stem cells play a critical role in disease initiation and insensitivity to chemotherapy in numerous hematologic malignancies and some solid tumors, and these stem cells need to be eradicated to achieve a cure. Key to successful targeting of cancer stem cells is to identify and functionally test critical target genes and to fully understand their associated molecular network in these stem cells. Human chronic myeloid leukemia (CML) is well accepted as one of the typical types of hematopoietic malignancies that are derived from leukemia stem cells (LSCs), serving as an excellent model disease for understanding the biology of LSCs ...


Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi Apr 2019

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient ...


Crispr-Sonic: Targeted Somatic Oncogene Knock-In Enables Rapid In Vivo Cancer Modeling, Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue Apr 2019

Crispr-Sonic: Targeted Somatic Oncogene Knock-In Enables Rapid In Vivo Cancer Modeling, Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue

RNA Therapeutics Institute Publications

CRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by CRISPR/Cas9 is well-established, generating gain-of-function alleles in somatic cancer models is still challenging because of the low efficiency of gene knock-in. Here we developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC), a method for rapid in vivo cancer modeling using homology-independent repair to integrate oncogenes at a targeted genomic locus. Using a dual guide RNA strategy, we integrated a plasmid donor in the 3'-UTR of mouse beta-actin, allowing co-expression of reporter genes or oncogenes from the beta-actin promoter. We showed that knock-in of oncogenic Ras and ...


Therapeutic Peptide Sequences And Gatekeepers Loaded With Mesoporous Silica Nanoparticles, Dursitu Hassen Apr 2019

Therapeutic Peptide Sequences And Gatekeepers Loaded With Mesoporous Silica Nanoparticles, Dursitu Hassen

Kansas State University Undergraduate Research Conference

The research community is developing and looking into new ways of effectively delivering anti-cancer treatment. According to National Cancer Institute over 1.5 million new cases of cancer are predicted in the United States, just alone in 2018. The major hurdles that have been identified by scientists are finding mechanisms that assist in decreasing the side effects of cancer treatment and to increase the effectiveness of the drug. In our lab, a highly toxic peptide sequence, SA-K6L9-AS is encapsulated in MSNs (mesoporous silica nanoparticles) and capped with a gatekeeper. The function of a gatekeeper is preventing ...


Establishment Of 3-D Human Colorectal Cancer Spheroids, India Barnett Apr 2019

Establishment Of 3-D Human Colorectal Cancer Spheroids, India Barnett

Kansas State University Undergraduate Research Conference

Three-Dimensional (3D) cell culture plays an important role in cancer biology by providing a life-like microenvironment as a model for drug discovery and treatment. Hydrogels, like many other 3D scaffolds, demonstrate a unique property as matrices for 3D cell culture. The goal of this project is to establish a 3D cell culture for colorectal cancer and apply this 3D model to drug testing. Colorectal cancer is one of the most common cancers in the United States with an early detection rate of 39%. Previously, 2D cell culture of human colorectal cancer cells, SW480, was used to determine the efficacy of ...


Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio Mar 2019

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine ...