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The Rational Design, Synthesis, Characterization, And Biological Evaluation Of Cancer-Targeting Immunostimulatory Peptide-Protein Conjugates And Tripeptides, Keith Smith 2018 Seton Hall University

The Rational Design, Synthesis, Characterization, And Biological Evaluation Of Cancer-Targeting Immunostimulatory Peptide-Protein Conjugates And Tripeptides, Keith Smith

Seton Hall University Dissertations and Theses (ETDs)

With the advent of cancer immunotherapy and the rise in applications of synthetic biologics, there has been a steady decline in the incidence of cancer. Despite this trend, there is an anticipated 1.7 million new cancer cases with an estimated 610,000 deaths expected by the end of 2018.2 Therefore, the call for continued efforts in creating more effective treatment options are still in high demand. In this thesis, the rational design of a semi-synthetic cancer-targeting immunostimulatory peptide-protein bioconjugate—using N-succinimidyl carbamate chemistry is described. This bio-orthogonal chemistry approach was used to conjugate the synthetic Pep42, cancer-targeting peptide ...


“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi 2018 Chapman University

“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on ...


Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari 2018 Chapman University

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected ...


Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang 2018 Chapman University

Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant ...


Two Phase Model To Study The Correlation Between Brain Tumor Growth Rate And The Formation Of Peritumoral Edema, Inmaculada Sorribes, Helen Byrne, Nicholas Moore, Harsh Jain 2018 Florida State University

Two Phase Model To Study The Correlation Between Brain Tumor Growth Rate And The Formation Of Peritumoral Edema, Inmaculada Sorribes, Helen Byrne, Nicholas Moore, Harsh Jain

Biology and Medicine Through Mathematics Conference

No abstract provided.


Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann 2018 University of Massachusetts Medical School

Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann

Open Access Articles

BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.

METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material ...


Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio 2018 University of Massachusetts Medical School

Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio

Open Access Articles

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with many aggressive cancers and implicated in the function of breast cancer stem cells (CSCs). The mechanisms involved, however, are poorly understood. We observed that IMP3 facilitates the activation of TAZ, a transcriptional co-activator of Hippo signaling that is necessary for the function of breast CSCs. The mechanism by which IMP3 activates TAZ involves both mRNA stability and transcriptional regulation. IMP3 stabilizes the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitates ...


Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio 2018 University of Massachusetts Medical School

Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio

University of Massachusetts Medical School Faculty Publications

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with many aggressive cancers and implicated in the function of breast cancer stem cells (CSCs). The mechanisms involved, however, are poorly understood. We observed that IMP3 facilitates the activation of TAZ, a transcriptional co-activator of Hippo signaling that is necessary for the function of breast CSCs. The mechanism by which IMP3 activates TAZ involves both mRNA stability and transcriptional regulation. IMP3 stabilizes the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitates ...


Mechanisms Of Age-Related Prostate Growth And Tumorigenesis, Deon O'Bryant 2018 Atlanta University Center

Mechanisms Of Age-Related Prostate Growth And Tumorigenesis, Deon O'Bryant

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

Prostate cancer is the most commonly diagnosed malignancy among men, but few genetic factors that drive prostate cancer initiation have been identified. The WD repeat domain 77 (Wdr77) protein is essential for cellular proliferation when it localizes in the cytoplasm of epithelial cells at the early stage of prostate development. In the adult prostate, it is transported into the nucleus and functions as a co-regulator of the androgen receptor to promote cellular differentiation and prostate function. This developmental process is reversed during prostate tumorigenesis i.e., Wdr77 is translocated from the nucleus into the cytoplasm to drive proliferation of prostate ...


Inhibition Of Aryl Hydrocarbon Receptor (Ahr) Activity Decreases Abcg2 Expression And Activity, Stanley J. Williams 2018 Atlanta University Center

Inhibition Of Aryl Hydrocarbon Receptor (Ahr) Activity Decreases Abcg2 Expression And Activity, Stanley J. Williams

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

The androgen receptor’s (AR) resurgence following treatment leads to castration resistant prostate cancer (CRPC). Studies show that the aryl hydrocarbon receptor (AhR) regulates AR signaling, is constitutively active, and enhances AR signaling in CRPC. AhR has ligands with carcinogenic properties and interacts with phytochemicals with anti-tumorigenic properties. Curcumin inhibits AhR activity and multidrug transporter ABCG2 activity, which mediates substrates out of the cell. Elevated ABCG2 expression causes resistance to anticancer drugs. AhR transcriptionally activates ABCG2 and our hypothesis is that inhibition of AhR activity by curcumin will decrease ABCG2 expression and activity in CRPC cells. C4-2 cells were treated ...


Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah 2018 Atlanta University Center

Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah

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

Transforming growth factor -β (TGF-β) plays an important role in the progression of prostate cancer. It acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. The PI3-kinase pathway has been shown to play integral roles in many cellular processes including cell proliferation, survival, and cell migration in many cell types. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. In this present study, we investigated possible roles of ...


Systematic Pan-Cancer Analysis Of Somatic Allele Frequency, Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A. Crandall, Nathan Edwards, Anelia Horvath 2018 George Washington University

Systematic Pan-Cancer Analysis Of Somatic Allele Frequency, Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A. Crandall, Nathan Edwards, Anelia Horvath

Open Access Articles

Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in ...


Pi3k/Akt Signaling Activates Hsf1 To Preserve Proteostasis And Sustain Growth, Zijian Tang 2018 The University of Maine

Pi3k/Akt Signaling Activates Hsf1 To Preserve Proteostasis And Sustain Growth, Zijian Tang

Electronic Theses and Dissertations

Signaling through oncogenic PI3K/AKT kinase pathway is crucial to cell and organ growth. Phosphorylation by AKT has long been perceived as a key factor to enhance protein biosynthesis that enables cell growth and survival. Here, we report that HSF1, the master regulator of the proteotoxic stress response (PSR), is a new AKT substrate. Beyond mobilizing the PSR under heat shock, the AKT-mediated HSF1 activation supports robust growth. In a mouse model of human megalencephaly, expression of a constitutively active PI3KCAsuffices to drive brain overgrowth, and strikingly, it also provokes proteomic chaos including protein aggregation and amyloidogenesis. Deletion of ...


Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla 2018 University of Nebraska at Omaha

Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla

Theses/Capstones/Creative Projects

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, and 95% of these cases are caused by PDAC (pancreatic ductal adenocarcinoma). Ketone bodies have previously been shown to decrease cell proliferation and cancer-induced cachexia. The molecular mechanism of ketone body-mediated growth inhibition of pancreatic cancer cells is not well understood. Research conducted thus far has not explored which molecular pathways are affected by ketone body treatment in pancreatic cancer cells. In the current study, the effect of the ketone body sodium hydroxybutyrate on the JAK-STAT and mTOR pathways and cell migration was explored. A decrease ...


Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence 2018 University of Tennessee, Knoxville

Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence

University of Tennessee Honors Thesis Projects

No abstract provided.


Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin 2018 University of Connecticut

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates ...


Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford 2018 Boise State University

Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford

Biology Faculty Publications and Presentations

DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions ...


Periostin Antisense Oligonucleotide Suppresses Bleomycin-Induced Formation Of A Lung Premetastatic Niche For Melanoma, Takashi Semba, Eiji Sugihara, Nagisa Kamoshita, Sayaka Ueno, Keitaro Fukuda, Masafumi Yoshino, Kazumasa Takao, Kazunori Yoshikawa, Kenji Izuhara, Yoshimi Arima, Makoto Suzuki, Hideyuki Saya 2018 Keio University

Periostin Antisense Oligonucleotide Suppresses Bleomycin-Induced Formation Of A Lung Premetastatic Niche For Melanoma, Takashi Semba, Eiji Sugihara, Nagisa Kamoshita, Sayaka Ueno, Keitaro Fukuda, Masafumi Yoshino, Kazumasa Takao, Kazunori Yoshikawa, Kenji Izuhara, Yoshimi Arima, Makoto Suzuki, Hideyuki Saya

Open Access Articles

Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin-induced lung fibrosis, and that ...


Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro 2018 University of Rhode Island

Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro

Senior Honors Projects

In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other ...


Preleukemia And Leukemia-Initiating Cell Activity In Inv(16) Acute Myeloid Leukemia, John A. Pulikkan, Lucio H. Castilla 2018 University of Massachusetts Medical School

Preleukemia And Leukemia-Initiating Cell Activity In Inv(16) Acute Myeloid Leukemia, John A. Pulikkan, Lucio H. Castilla

Open Access Articles

Acute myeloid leukemia (AML) is a collection of hematologic malignancies with specific driver mutations that direct the pathology of the disease. The understanding of the origin and function of these mutations at early stages of transformation is critical to understand the etiology of the disease and for the design of effective therapies. The chromosome inversion inv(16) is thought to arise as a founding mutation in a hematopoietic stem cell (HSC) to produce preleukemic HSCs (preL-HSCs) with myeloid bias and differentiation block, and predisposed to AML. Studies in mice and human AML cells have established that inv(16) AML follows ...


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