Browsing by Author "Ranjan, Amalendu P."
Now showing 1 - 12 of 12
- Results Per Page
- Sort Options
Item A Quality Improvement Initiative: Evaluating the Impact of Standardized Data Tracking Tools in the Radiation Oncology Clinical Research Office at the University of Texas Southwestern Medical Center(2022-05) Acevedo, Katalina V.; Mathew, Stephen O.; Ranjan, Amalendu P.Developing preventative measures through intentional planning and oversight of clinical trials has the potential to increase efficiency and quality of trial processes and data. This practicum report details a Quality Improvement (QI) initiative evaluating implementation and impact of a standardized data-tracking software on clinical research data compliance in the Radiation Oncology Clinical Research Office at UT Southwestern Medical Center (UTSW). The standardized data tracker evaluated in this study was built through Quickbase, a cloud-based, low-code application development platform specializing in project management and operations optimization. This project evaluated data sets from two active radiation oncology clinical trials using repeated cross-sectional methods to compare rates of data non-compliance and trends in the types of non-compliance exhibited at baseline, one-month, and three-month post data-tracker implementation. Trends in non-compliance were reviewed and preventative measures backed by recommendations from the literature were proposed to facilitate future QI initiatives within the department. The Chi-Squared (X2) Test for Independence was used to determine whether there was a statistical difference in rates of data non-compliance across the three timepoints within studies and overall followed by post-hoc tests consisting of pairwise comparisons with Bonferroni corrections. Overall, statistical analysis revealed a significant difference in rates on non- compliance across timepoints, suggesting that implementation of the standardized Quickbase data-tracking management tool does significantly decrease rates of non-compliance. Descriptive statistics were performed to characterize the trends in non-compliance within each study across timepoints. This quality improvement project was the first of its kind to formally examine data management trends and practices within the Radiation Oncology Clinical Research Office at UT Southwestern Medical Center. The results provide positive feedback regarding the implementation of a standardized Quickbase data-tracking management tool and characterization of non-compliant data illuminated pressure points in data management workflow that can inform future QI initiatives in shifting data management from its current reactive state to a more proactive data-driven approach. Future work should evaluate the proposed preventative measurements to provide further insight into best practices that can support continuous improvement initiatives within the department.Item Bioengineered Nanoparticles for Targeted Cancer Therapy(2018-05) Gdowski, Andrew S.; Vishwanatha, Jamboor K.; Ranjan, Amalendu P.; Cistola, David P.; Olivencia-Yurvati, Albert H.Despite improved overall survival in cancer patients over the past 50 years, limited advances have been made in treating patients with metastatic cancers. Multiple types of cancers demonstrate the unique ability to specifically metastasize to the bone. Among these, prostate cancer exhibits increased capacity to create bone specific lesions with high frequency. Once bone localization takes place, treatment regimens are limited and overall survival is poor. These bone metastases often cause debilitating and life threatening problems including: uncontrollable pain, hypercalcemia, broken bones, spinal cord compression, and the inability to perform activities of daily living. The overarching goal of this thesis was to develop novel bone targeted nanoparticle therapies. The first generation of nanoparticles we engineered and tested were designed to target the hydroxyapatite structure of the bone particularly in areas of high bone turnover with subsequent therapeutic release at the site of the tumor. Notably, this nanoparticle formulation was efficacious in decreasing prostate cancer bone metastatic tumors, improving bone structure, and reducing pain in a mouse model. The next generation of nanoparticles were developed to simultaneously target the bone endothelium and tumor cells using a programmable bioinspired approach with guidance from genomic information of prostate cancer patients. This novel bioinspired nanoparticle demonstrated enhanced ability to self-recognize cancer cells as well as improved bone homing and retention in our in vivo evaluation. Finally, we addressed the challenge of nanoparticle manufacturing scale up from lab size quantities to large scale batches using a microfluidic process. It is our sincere hope that concepts and publications derived from this thesis will help guide future efforts for targeted therapy and improve the lives of patients with cancer.Item Cabazitaxel-Loaded Nanoparticles Reduce the Invasiveness in Metastatic Prostate Cancer Cells: Beyond the Classical Taxane Function(MDPI, 2023-02-26) Lampe, Jana B.; Desai, Priyanka P.; Tripathi, Amit K.; Sabnis, Nirupama A.; Chen, Zhe; Ranjan, Amalendu P.; Vishwanatha, Jamboor K.Bone-metastatic prostate cancer symbolizes the beginning of the later stages of the disease. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. We hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuated the EMT marker, Vimentin, and led to an increased E-cadherin expression. These changes impart epithelial characteristics and inhibit invasive properties in cancer progression. Consequently, progression to distant sites is also mitigated. We observed the reduction of phosphorylated Src at tyrosine 416, along with increased expression of phosphorylated cofilin at serine 3. These changes could affect migration and invasion pathways in cancer cells. Both increased p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for metastatic prostate cancer by inhibiting EMT, invasion, and migration, in prostate cancer cells.Item Comparative Patient Outcome Analysis Between Two Radiation Therapies for Head and Neck Cancers(2023-05) Stein, Maggie J.; Ranjan, Amalendu P.; Basha, Riyaz; Neufeld, Sarah; Desai, KajalItem Development and In Vitro Characterization of Gemcitabine Loaded Nanoparticles for Pancreatic Cancer Therapy(2021-05) Pham, Jennifer H.; Ranjan, Amalendu P.; Fudala, Rafal; Mathew, Stephen O.Pancreatic Ductal Adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths worldwide and the most common type of pancreatic malignancy (90%). With a poor five-year survival rate of only 5-8%, complete surgical resection remains the only curative treatment. However, most patients are diagnosed at a later stage where chemotherapy and radiotherapy are the only options. Gemcitabine is the FDA-approved treatment for PDAC, but the current therapy leads to more severe side effects due to the instability of gemcitabine in the blood stream and its poor membrane permeability. Nanoparticles are effective in cancer therapy because they allow modifications that make for a more effective delivery method and also reduces the toxicity to normal tissue. In this proposed study, we aim to formulate, optimize and evaluate the in vitro effectiveness of gemcitabine loaded nanoparticles in a PDAC cell line in order to improve the effectiveness of current chemotherapy treatments for pancreatic ductal adenocarcinoma. We found out of the three types of nanoplatforms used for encapsulating gemcitabine (GEM-NPs): polymeric, liposomal and lipid polymer hybrid, the liposomal nanoparticles were the most effective in the encapsulation of gemcitabine according to the physicochemical properties, such as average particle size, zeta potential, drug loading and encapsulation efficiency. In vitro functional evaluation of liposomal formulation was done in a PDAC cell line (PANC-1). This study suggests that the use of liposomal nanoparticles is the most beneficial in the encapsulation and delivery of gemcitabine.Item Development of methylene blue-loaded nanoparticles for glioblastoma treatment(2015-03) Castañeda-Gill, Jessica M.; Ranjan, Amalendu P.; Yang, Shaohua; Vishwanatha, Jamboor K.Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults over 45, resulting in an average survival of 15 months post-diagnosis and treatment. While recent research has provided essential information to aid diagnosis and treatment, GBM is known to cause relapse following traditional combinatorial regimens, necessitating the development of more effective and less toxic therapies. Methylene blue (MB), a dye with noted medicinal applications, has received recent consideration as a potential neurotherapeutic due to its ability to infiltrate the blood-brain barrier (BBB) and improve cellular processes within distinct brain cell compartments and types; however, one drawback is an increased administration to produce desired therapeutic effects, leading to excessive brain deposition and potential neurotoxicity. A method commonly used to enhance drug delivery while reducing unwanted side effects is via encapsulation in nanoparticles (NPs) composed of the biodegradable/biocompatible co-polymer, poly(lactic-co-glycolic) acid (PLGA). Based on our previous studies, we are developing a MB-loaded PLGA NP capable of permeating the BBB to treat GBM, to test our hypothesis that MB encapsulation into PLGA NPs will enhance accumulation in cancerous brain regions, resulting in reduced tumor size and prolonged survival. In this study, we formulated and characterized MB-loaded PLGA NPs, with a 3:1 molar ratio of sodium oleate to methylene blue at 5mg, based on particle size, drug loading, encapsulation efficiency, and release kinetics. Currently, we are establishing their in vitro effects in two different commercially-available GBM cell lines, according to their responses to commonly-used chemotherapeutics. Following loading of 5mg MB and their comparison to blank NPs, we obtained NP preparations in the range of 120-145nm, with encapsulation efficiencies from 25-40% and drug loading between 1-2%. Additionally, we have found that 50% of the MB initially added is released at 24 hours, and stays constant up to two weeks, demonstrating sustained drug release. In conclusion, based on studies that have demonstrated in vitro effects with MB at a minimum of 1μM (~0.3mg) and 150nm particles, our formulation should elicit comparable, if not better, results when treating GBM.Item Intensity of Usual Care Therapeutic Interventions in Inpatient Rehabilitation - A Pilot Study(2019-12) Di Pasquale, Jake A.; Millar, J. Cameron; Ranjan, Amalendu P.Minimal evidence exists describing key dosing parameters of interventions used during the subacute phase of recovery after neurological injury. This prospective cohort study aims to assess cardiorespiratory strain resulting from novel and conventional therapeutic interventions. Gait training provided relatively more moderate to vigorous exercise, reaching the associated %HRR 25% and 42% of the time in patients post spinal cord injury (SCI) and stroke, respectively. Specifically, EksoGT overground robotic gait training appears more effective, evoking targeted %HRR for 48% and 52% of sessions. Rate of Perceived Exertion (RPE) was moderately correlated with very light intensity in patients with SCI but ultimately ineffective at gauging %HRR. EksoGT can administer moderate to vigorous intensity exercise to patients with severe disabilities. Inpatient rehabilitation is inherently variable in method and population but can provide minimally sufficient exercise intensity. Further research into the dose-response relationship and accurate estimation of intensity are needed.Item Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers(MDPI, 2016-03-29) Enciso, Alan E.; Neun, Barry; Rodriguez, Jamie; Ranjan, Amalendu P.; Dobrovolskaia, Marina A.; Simanek, Eric E.Triazine and PAMAM dendrimers of similar size and number of cationic surface groups were compared for their ability to promote platelet aggregation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in surface groups 16-256. PAMAM dendrimers selected for comparison included G3 (7 kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). The treatment of human platelet-rich plasma (PRP) with low generation triazine dendrimers (0.01-1 microM) did not show any significant effect in human platelet aggregation in vitro; however, the treatment of PRP with larger generations promotes an effective aggregation. These results are in agreement with studies performed with PAMAM dendrimers, where large generations promote aggregation. Triazine dendrimers promote aggregation less aggressively than PAMAM dendrimers, a factor attributed to differences in cationic charge or the formation of supramolecular assemblies of dendrimers.Item Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses(MDPI, 2023-02-26) Donkor, Michael; Choe, Jamie Y.; Reid, Danielle; Quinn, Byron; Pulse, Mark; Ranjan, Amalendu P.; Chaudhary, Pankaj; Jones, Harlan P.Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses. The nasal nano-vaccine-induced T-cell-mediated antitumor mucosal immune response was shown to increase tumor-specific production of IFN-gamma and granzyme B by lung-derived CD8(+) T cells. These findings demonstrate that our engineered nasal nano-vaccine has the potential to be used as a prophylactic approach prior to the seeding of tumors in the lungs, and thereby prevent overt lung metastases from existing extra pulmonary tumors.Item Proof-of-concept studies with a computationally designed M(pro) inhibitor as a synergistic combination regimen alternative to Paxlovid(National Academy of Sciences, 2024-04-15) Papini, Christina; Ullah, Ifan; Ranjan, Amalendu P.; Zhang, Shuo; Wu, Qihao; Spasov, Krasimir A.; Zhang, Chunhui; Mothes, Walther; Crawford, Jason M.; Lindenbach, Brett D.; Uchil, Pradeep D.; Kumar, Priti; Jorgensen, William L.; Anderson, Karen S.As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (M(pro)) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 muM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 M(pro). In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.Item Retrospective Analysis of Phase 4 Clinical Trial to Evaluate the Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension(2021-05) Lombard, Diandra; Mathew, Stephen O.; Alam, Sami Bin; Ranjan, Amalendu P.One of the biggest challenges patients with rare diseases face is the availability of safe and effective treatment options. Patients with symptomatic neurogenic orthostatic hypotension have a very limited number of pharmacological treatment options available, none of which are approved by the FDA for long term use. This study reviewed preliminary data from a single site in a nationwide clinical trial testing the long-term effectiveness of Droxidopa in patients with symptomatic neurogenic orthostatic hypotension. Long-term effectiveness was measured using two different patient reported surveys completed at various time points in the study. This data was analyzed using a linear regression as well as other descriptive statistics like mean, median, mode and range to assess the effectiveness of Droxidopa over time.Item Targeted Delivery of [alpha]-Mangostin to Prostate Cancer Cells Utilizing Reconstituted High-Density Lipoprotein Nanoparticles(2022-08) Kapic, Ammar; Berg, Rance E.; Basha, Riyaz; Ranjan, Amalendu P.