Translational Medical Research Commons^™

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Nirnoy Dan, Poornima Devi Shaji, Swathi Holla, Murali M. Yallapu, Sheema Khan

Research Colloquium

Introduction: Although, surgical resection and chemotherapy are the gold standard for treating Pancreatic Ductal Adenocarcinoma (PDAC), low patient survival rate remains the problem. The activating point mutation of the KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRASG12D regulates cell proliferation, differentiation, apoptosis. Recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both pancreatic cancer and stromal cells, which modulate tumor microenvironment and metastasis. Additionally, genetic deletion of gal1 inhibits metastasis and improves survival in KRAS mouse model of PDAC (1). Therefore, our objective is …

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Poornima Devi Shaji, Swathi Holla, Nirnoy Dan, Shabnam Malik, Murali M. Yallapu, Meena Jaggi, Stephen W. Behrman, Subhash C. Chauhan, Sheema Khan

Research Colloquium

Introduction: In pancreatic ductal adenocarcinoma (PDAC), low patient survival rate remains a problem. The activating point mutation of KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRAS^G12D regulates cell proliferation, differentiation, apoptosis; recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both PDAC and stromal cells, which modulate tumor microenvironment and metastasis. Therefore, we have developed a novel combination therapy for PDAC by targeting mutated KRAS^G12D and Gal-1 to target both proliferation and metastasis in PDAC. This includes the delivery of KRAS^{G12D …}

Smoking And Drinking Activates Nf-Κb /Il-6 Axis To Promote Inflammation During Cervical Carcinogenesis, Vivek Kumar Kashyap, Prashanth Kb Nagesh, Ajay K. Singh, Andrew Massey, Godwin P. Darkwah, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

Research Symposium

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated the molecular mechanisms involved in the interplay of smoking and/or drinking with HPV infectivity and defined a systematic therapeutic approach for their attenuation in cervical cancer.

Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in cell proliferation, clonogenicity, biophysical properties, cell migration, and invasion. Expression of HPV16 E6/E7, NF-κB, cytokines, cell cycle, and …

An Ngqd Based Diagnostic Tool For Pancreatic Cancer, Ryan Ketan Ajgaonkar, Bong Lee, Alina Valimukhametova, Anton Naumov, Giridhar Akkaraju

Research Symposium

Background: Pancreatic cancer remains difficult to detect at early stages which contributes to a poor five-yearsurvival rate. Therefore, early detection approaches based on novel technologies should be explored to address this critical health issue. Nanomaterials have recently emerged as frontrunners for diagnostic applications due to their small size in the 1-100 nm range, which facilitates one-on-one interactions with a variety of biomolecules like oligonucleotides and makes them suitable for a plethora of detection and delivery applications. In this work, the presence of specific pancreatic cancer miRNA (pre-miR-132) is detected utilizing the fluorescence properties of highly biocompatible nitrogen-doped graphene quantum dots …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee

Theses & Dissertations

Pancreatic Cancer (PC) is a lethal disease claiming approximately 45000 lives in the US in 2018, and it establishes an elaborate immunosuppressive tumor microenvironment that aids in disease pathogenesis. Immunotherapy has emerged as a strategy to target tumor cells by reprogramming patient’s immune system. Challenges present in PC immunotherapy are: i) identifying a tumor-associated antigen that could be targeted, ii) identifying adjuvants that could efficiently deliver antigens, iii) eliciting robust anti-tumor responses and iv) overcoming peripheral tolerance and immunosuppression elicited by the tumor.

Firstly, we detected circulating autoantibodies to MUC4 present in PC patients and observed that IgM autoantibodies to …

Developing Hyperpolarized Silicon Particles For In Vivo Mri Targeting Of Ovarian Cancer, Nicholas Whiting, Jingzhe Hu, Niki M. Zacharias, Ganesh L. R. Lokesh, David E. Volk, David G. Menter, Rajesha Rupaimoole, Rebecca Previs, Anil K. Sood, Pratip Bhattacharya

Nicholas Whiting

Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations Of Conps’ Pharmacokinetics, Efficacy, And Mechanisms Of Action, Philip R. Mcdonagh Iii

Theses and Dissertations

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH₂), dextran T10-polyethylene …

Interrogating Metabolism In Brain Cancer, Travis Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth Gammon, Frederick F. Lang, Amy B. Heimberger, Pratip Bhattacharya

Nicholas Whiting

Prostate Cancer Microparticles As A Next Generation Screening Tool For Prostate Cancer, Khurram M. Siddiqui

Electronic Thesis and Dissertation Repository

Currently available screening tests for prostate cancer (PCa) are neither very sensitive nor specific. Microparticles (MP) are submicron tumor cell fragments released by PCa cells into the circulation and offer a possible means of sampling the tumor. We evaluated the utility of a MP blood test using nanoscale flow cytometry to distinguish patients with PCa from patients with benign prostatic hyperplasia (BPH). We used monoclonal antibodies against prostate specific membrane antigen, gastrin releasing peptide receptor and ghrelin peptide ligand.

We found higher but statistically insignificant, PSMA and Ghrelin dual +ve MP counts in the BPH group. Our results show that …