Therapeutics Commons^™

Tumor Targeting With Peptide-Drug Conjugates: Showcasing Key Progress And Hurdles, Keykavous Parang, Thuy Do, Clare Dinh, Dorna Davanidavari, Max Foroughi, Troy Khong, Mahsa Moazen, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss …

The Mycancergene Study: A Hybrid Type 1 Effectiveness-Implementation Randomized Study Comparing A Patient-Centered Digital Genetic Health Portal To Usual Care After Receipt Of Cancer Genetic Testing, Daniel Chavez-Yenter, Dominique Fetzer, Brian Egleston, Susan Domchek, Linda Fleisher, Lynne Wagner, Kuang-Yi Wen, Kelsey Karpink, Lauren Gutstein, Shelby Posen, Enida Selmani, Briana Mcleod, Arravinth Anantharajah, Sarah Brown, Cara Cacioppo, Jacqueline Cappadocia, Jessica Ebrahimzadeh, Dana Falcone, Sarah Howe, Claire Langer, Beth Mccarthy-Wood, Michelle Weinberg, Angela Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: Genetic testing has become more complex with the transition from single gene testing to multi-gene panels and whole-exome sequencing. The adoption of more complex genetic testing and the promise of precision medicine has created a critical and urgent need for longitudinal clinical follow-up with patients who undergo cancer genetic testing given the residual uncertainty. There is an increasing need for multidisciplinary translational research that focuses on how to advance precision medicine discoveries into clinical practice and to capitalize on connectivity (e.g. digital health) interventions in ways that optimize cancer risk reducing behaviors in real-world clinical populations.

METHODS: The overall …

Investigating Pinch-1 In Glioblastoma Multiforme: A Potential Adjuvant Therapy Target To Improve Treatment Outcomes, Saikrishna Gaddam, Dianne Langford

Rowan-Virtua Research Day

Gliomas account for approximately 80% of all brain cancers and 30% of central nervous system tumors. Glioblastoma multiforme (GBM), the most common, is unfortunately, the most aggressive glioma cancer type. Despite treatment efforts such as surgery, radiation, and chemotherapy, nearly all low-grade astrocytoma progress to GBM without complete surgical resection. Achieving full surgical removal is typically impossible, leading to an almost 100% recurrence rate of GBM after 9 months with a median survival of approximately 15 months. This poor prognosis is due to its high invasiveness and resistance to therapy. Therefore, improved therapeutic approaches are needed to reduce recurrence and …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Editorial: Adverse And Toxic Effects Of Childhood Cancer Treatments, Volume Ii, Antonio Ruggiero, Roderick Skinner, Pinki Prasad

School of Medicine Faculty Publications

No abstract provided.

Resection And Reconstruction Of Ewing Sarcoma Of The Cuboid Utilizing Vascularized Fibular Autograft: A Case Report, Brandon Cunha, Alexandre Arkader

Rowan-Virtua Research Day

Ewing Sarcoma (EWS) rarely presents in the bones of the foot, and particularly in the cuboid, making it an exceedingly rare occurrence. We present the case of a 7-year-old female diagnosed with EWS of the right cuboid, detailing the management and outcomes of this rare presentation. The patient, now almost 5 years post-initial local control, exhibits restored foot function, a normalized gait, and no evidence of disease recurrence. This case underscores the potential for preserving lower extremity function and improving postoperative quality of life in rare presentations of EWS through innovative reconstruction strategies.

Physical Medicine & Rehabilitation Referrals In Cancer Patients, Bhumik Patel, Venkateswar Venkataraman, Deanna Janora, Jack Goldberg

Rowan-Virtua Research Day

Physical Medicine and Rehabilitation (PM&R) can address functional limitations in various conditions, including cancer. Cancer rehabilitation aims to address functional impairments resulting from both the disease itself and its treatments, striving to optimize physical, social, psychological, and vocational functioning. Existing literature indicates that PM&R services significantly benefit cancer patients by improving their overall quality of life. Studies have found that optimal utilization of PM&R services can increase the Functional Independence Measure (FIM) in cancer patients. Current National Comprehensive Cancer Network and American Cancer Society guidelines emphasize the importance of incorporating PM&R services into oncology care to enhance the function and …

Neoadjuvant Versus Adjuvant Therapy For Stage Iiib-Iiid Melanoma, Bhumik Patel, Sangnya Upadhyaya

Rowan-Virtua Research Day

The treatment landscape for advanced stage melanoma is rapidly evolving due to advancements in our understanding of melanoma biology and the emergence of novel therapies. This necessitates a comprehensive review to guide clinicians in adopting evidence based and patient centric approaches to treat stage IIIB-IIID melanoma. A literature review was conducted to synthesize current information on the most optimal treatment available. Data available from different clinical trials found that neoadjuvant therapy was a more effective treatment compared to adjuvant therapies alone. Furthermore, neoadjuvant therapy with combination therapy was more efficacious in producing a complete pathological response compared to monotherapy. A …

Nebulization Based Inhalation Nanomedicine For Lung Cancer Treatments, Rahul Tiwari, Meghana Kolli, Neeraj Chauhan, Eswara Naga Hanuma, Vivek Kashyap, Subhash Chauhan, Murali Yallapu

Research Symposium

Background: Lung cancer is reported to have a high incidence rate and first leading cause of cancer-related morbidity and mortality across the world including in the United States. Noninvasive nebulized inhalation is a promising delivery strategy for lung, which can enhance the targeting efficiency and detention time interval of nanoparticles in the lung tissue, thus elevating the therapeutic index of therapeutic agent(s) at lower dosages. The aim of this study is to develop inhalable nanoparticles (INPs) for effective delivery of therapeutic agents in lung cancer cell lines and ex vivo models.

Methods: The inhalation nanoparticles (INPs) were prepared by solvent …

Sprtn Metalloprotease As A Target To Sensitize Cancer Cells To Crosslinking Chemotherapy, Cole J. Turner

Honors Theses

Bifunctional alkylating agents have demonstrated high clinical utility as a chemotherapeutic strategy against cancer. These compounds have been well-characterized for their capacity to exert cytotoxicity via interstrand DNA crosslinking. However, the same electrophilic chemistry can also form DNA-protein crosslinks (DPCs) whose contributions to these drugs’ antitumor effects have been less well-defined. Recently, the metalloprotease SPRTN has been implicated as a predominant mediator of DPC repair in mammalian cells. Previous work has demonstrated that SPRTN deficiency increases the sensitivity of cancer cells to DPC-inducing agents such as formaldehyde and cisplatin, but these findings have yet to be translated more broadly across …

Indwelling Pleural Catheterization Maximizes Functionality And Quality Of Life In Management Of Recurrent Malignant Pleural Effusions, Avinash Ramkissoon

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: The TIME2 randomized controlled trial. J Am Med Assoc. 2012;307(22):2383-2389. https://doi.org/10.1001/jama.2012.5535

for the management of recurrent malignant pleural effusions in a patient with metastatic renal cell carcinoma.

Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi

Electrical & Computer Engineering Faculty Publications

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

A Global Review On Short Peptides: Frontiers And Perspectives, Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha Alkhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth

Pharmacy Faculty Articles and Research

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. …

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …

Fluorescent Probe Development For Fructose Specific Transporters In Cancer, Joseph Fedie

Dissertations, Master's Theses and Master's Reports

Carbohydrate transporters or GLUTs of the major facilitator superfamily (MFS) are responsible for transporting sugars into the cell and have been of research interest for decades. Disruptions, mutations, and over-activations of GLUTs have been linked to a number of major diseases including cancer, obesity, and diabetes. Differentiating between transporters is incredibly difficult due to highly conserved structures, and so specific targeting between transporters has proven a complex challenge. GLUTs are highly flexible in their conformations however exactly what will and will not pass through the transporter is ambiguous at best, and many attempt to target these transporters have failed.

In …

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8⁺ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …

Selective Action Of Aqueous Maté Extract On Human Breast Cancer, Catherine Nguyen, Kenisha Nisbett, Vanessa Halvorsen, Calvin He, Amina Sadik

College of Osteopathic Medicine (TUN) Publications and Research

Ilex paraguariensis, Yerba Maté, is a subtropical plant native to South America, where it is consumed several times daily as a tea made with roasted leaves. Several studies have been conducted to elucidate the beneficial effects of this plant. A recent study has shown that saponins isolated from Yerba Maté extract induce apoptosis in human colon cancer cells, while another study indicated that the consumption of Maté tea causes higher incidence of esophageal cancer. Our study looked into the effects Yerba Maté extract have on human breast cancer cells and non-cancer cells from the same tissue. The findings show …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

Active Immunotherapy And Adoptive Cell Transfer As An Effective Cancer Treatment, Philip Jay Cynamon

The Science Journal of the Lander College of Arts and Sciences

There are many ways to fight cancer using the body’s own immune system. Some methods include the administration of vaccines while others involve stimulatory factors injected near tumors. One promising method is enlisting the help of T cells. To fight cancer effectively, T cells must be able to recognize cancerous antigens and the environment in which these T cells reside must be conducive to their function, survival, and proliferation. This paper discusses a method of providing such an environment called adoptive cell transfer, as well as the elements that effect this protocol and the ways in which the environment can …

Transposon Based Gene Therapy As A Treatment For Cancer, Jacob Stauber

The Science Journal of the Lander College of Arts and Sciences

Gene therapy is the use of genes to treat or prevent diseases. Diseases such as cancer, which are difficult to treat using conventional methods, can be treated using gene therapy. The transport of the therapeutic transgene can be accomplished using viral or non-viral methods. However, widespread use of viral vectors is limited due to its high cost of manufacture and safety concern. Non-viral vectors are limited in their effectiveness. The use of transposons such as the Sleeping Beauty transposon system can effectively deliver the transgene with less concern than viral vectors. This review discusses the various vectors and treatment strategies …

Are Oncolytic Viruses A Cure For Cancer? A Look At Reovirus, Adenovirus, And Hsv-1 In Cancer Treatment, Yehuda Rosenberg

The Science Journal of the Lander College of Arts and Sciences

This paper aims to evaluate the option of utilizing Oncolytic Viruses as a viable treatment in fighting cancer. However, due to the broad nature of the subject, a more limited purview is necessary. With that in mind, the focus will be on a few of the more researched ones: Reovirus, Adenovirus, and HSV-1. In each case, we will examine what makes each of these potential options. This will include an examination of each one's tumor-specificity. Cancer and viral physiology will be discussed as necessary to examine the distinct protein expressions in tumor cells, so that the virus's method of battling …

Chitosan/Ellagic Acid Composite Materials For Local Cancer Therapy, Sung Woo Kim

Theses and Dissertations (ETD)

Current advances in the drug delivery have improved the therapeutic efficacy of the drug and minimized risks of side effects associated with toxicity of the drug. Implantable polymeric delivery system has gained increasing attentions for controlled drug release and localized treatments. In comparison to conventional chemotherapy, polymeric delivery systems are implantable at a local targeted site and biodegradable after a sufficient therapeutic span. The objectives of this project were to fabricate and characterize an implantable polymeric vehicle for a local chemotherapy and investigate its biological properties against cancer cells including human WM115 melanoma, human U87 glioblastoma, and rat C6 glioma …

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs …