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4. Interaction of M2 Macrophages with Hepatocellular Carcinoma Co-Culture System in the Presence of Doxorubicin-Loaded Nanoparticles

Author

Mahmoudian, Mohammad, primary, Namdar, Afshin, additional, Zakeri-Milani, Parvin, additional, Valizadeh, Hadi, additional, Elahi, Shokrollah, additional, Darwesh, Ahmed M., additional, Seubert, John M., additional, Siraki, Arno G., additional, Roa, Wilson H., additional, Chacra, Nadia B., additional, and Loebenberg, Raimar, additional

Published
2022
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6. A Novel Composite Biomarker Panel For Detection Of Early Stage Non-small Cell Lung Cancer

Author

Bédard, Eric L.R., Abraham, Aswin G., Joy, Anil A., Ghosh, Sunita, Wang, Xiaoyu, Lim, Andrew, Shao, Dongyu, Loebenberg, Raimar, Roa, Wilson H., Bédard, Eric L.R., Abraham, Aswin G., Joy, Anil A., Ghosh, Sunita, Wang, Xiaoyu, Lim, Andrew, Shao, Dongyu, Loebenberg, Raimar, and Roa, Wilson H.

Abstract

Purpose: To investigate a novel composite methodology of using targeted serum microRNAs (micro ribonucleic acid; miRNA) and urine metabolites for the accurate detection of early stage non-small cell lung cancer (NSCLC). Methods: Consecutively consenting NSCLC patients and matched control subjects were recruited to provide samples of serum for miRNA and/or urine for metabolite analyses. Serum miRNA levels were measured using quantitative real-time reverse-transcription with exogenous control, and the comparative delta cycle threshold (&#9651CT) method was used to calculate relative miRNA expression of two targeted miRNAs (miR-21 and miR-223). The concentrations of six targeted urinary metabolites in patients and healthy controls were measured using proton nuclear magnetic resonance (1H NMR) spectroscopy. A composite methodology of using the 35 accruals with both serum and urine biomarkers was then established with binary logistic regression, receiver operating characteristic (ROC) models with or without artificial intelligence (AI). Results: The ROC analysis of miRNA expression yielded a sensitivity of 96.4% and a specificity of 88.2% for the detection of early stage NSCLC, with area under the curve (AUC) = 0.91 (CI 95%: 0.80-1.0). Relative urinary concentrations of 4-methoxyphenylacetic acid (4MPLA) were significantly different between NSCLC and healthy control (p=0.008). The ROC analysis of 4MPLA yielded a sensitivity of 82.1% and a specificity of 88.2%, with AUC = 0.85. The composite process combining miRNA and metabolite expression demonstrated a sensitivity and specificity of nearly 100% and AUC=1. Conclusions: A highly specific, sensitive and non-invasive detection method for NSCLC was developed. Pending validation, this can potentially improve the early detection and, hence, the treatment and survival outcomes of patients.

Published
2021

12. Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation

Author

Wu, H Helena, primary, Wang, Benfan, additional, Armstrong, Stephen R, additional, Abuetabh, Yasser, additional, Leng, Sarah, additional, Roa, Wilson H Y, additional, Atfi, Azeddine, additional, Marchese, Adriano, additional, Wilson, Beverly, additional, Sergi, Consolato, additional, Flores, Elsa R, additional, Eisenstat, David D, additional, and Leng, Roger P, additional

Published
2021
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18. A Phase II Multi-institutional Clinical Trial Assessing Fractionated Simultaneous In-Field Boost Radiotherapy for Brain Oligometastases

Author

Rodrigues, George, primary, Yartsev, Slav, additional, Roberge, David, additional, MacRae, Robert, additional, Roa, Wilson H, additional, Panet-Raymond, Valérie, additional, Masucci, Giuseppina Laura, additional, Yaremko, Brian P, additional, D'Souza, David, additional, Palma, David, additional, Sexton, Tracy, additional, Yu, Edward, additional, Pantarotto, Jason, additional, Ahmad, Belal, additional, Fisher, Barbara, additional, Dar, A. Rashid, additional, Lambert, Carole, additional, Pond, Gregory, additional, Tay, Keng Yeow, additional, and Bauman, Glenn, additional

Published
2019
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22. Lead-In Phase to Randomized Trial of Motexafin Gadolinium and Whole-Brain Radiation for Patients With Brain Metastases: Centralized Assessment of Magnetic Resonance Imaging, Neurocognitive, and Neurologic End Points

Author

Mehta, Minesh P., Shapiro, William R., Glantz, Michael J., Patchell, Roy A., Weitzner, Michael A., Meyers, Christina A., Schultz, Christopher J., Roa, Wilson H., Leibenhaut, Mark, Ford, Judith, Curran, Walter, Phan, See, Smith, Jennifer A., Miller, Richard A., and Renschler, Markus F.

Published
2002

25. Dose-escalated Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy for Inoperable or Unresectable Non-Small Cell Lung Cancer

Author

Kim, Julian O., primary, Chu, Karen P., additional, Fairchild, Alysa, additional, Ghosh, Sunita, additional, Butts, Charles, additional, Chu, Quincy, additional, Gabos, Zsolt, additional, Joy, Anil A., additional, Nijjar, Tirath, additional, Robinson, Donald M., additional, Sangha, Randeep, additional, Scrimger, Rufus, additional, Smylie, Micheal, additional, Yee, Don, additional, and Roa, Wilson H., additional

Published
2017
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35. The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model

Author

Razzak, Rene, Zhou, Joe, Yang, XiaoHong, Pervez, Nadim, Bédard, Eric LR, Moore, Ronald B, Shaw, Andrew, Amanie, John, Roa, Wilson H, Razzak, Rene, Zhou, Joe, Yang, XiaoHong, Pervez, Nadim, Bédard, Eric LR, Moore, Ronald B, Shaw, Andrew, Amanie, John, and Roa, Wilson H

Abstract

Purpose: Gold nanoparticles (GNPs) have attracted significant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. The aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI). Methods: Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Toxicity of choline-GNPs was examined on DU-145 prostate cancer cells using an MTT assay. Using balb/c mice bearing flank DU-145 prostate tumors, choline-GNPs bio-distribution was measured using inductively coupled mass spectroscopy (ICP-MS). Blood, heart, lung, liver, spleen, brain, kidney and tumor gold content were examined at multiple time points over a 24-hour period after tail vein injection. Results: An MTT assay using DU-145 prostate cancer cells yielded a 95% cell viability 72 hours after choline-GNP administration. The tumor GNP area under the concentration-time curve during the first 4 hours (AUC0-4) was 2.2 µg/ml h, representing 13% of the circulating blood GNP concentration over the same time period. The maximum intra-tumor GNP concentration observed was 1.4% of the injected dose per gram of tumor tissue (%ID/g) one hour post injection. Conclusions: GNPs functionalized with choline demonstrates a viable future nanoparticle platform with increased intra-tumor uptake as compared to unconjugated GNPs. Decreased intra-hepatic accumulation appears to be the reason for the improved systemic bioavailability. The next logical translational investigation will incorporate external beam radiation with the observed maximum intra-tumor uptake.

Published
2013

36. Sputum MicroRNA Profiling: A Novel Approach for the Early Detection of Non-Small Cell Lung Cancer

Author

Roa, Wilson H., Kim, Julian O., Razzak, Rene, Du, Hongfei, Guo, Linghong, Singh, Ravinder, Gazala , Sayf, Ghosh, Sunita, Wong, Eric, Joy, Anil A., Xing, James Z., Bedard, Eric L., Roa, Wilson H., Kim, Julian O., Razzak, Rene, Du, Hongfei, Guo, Linghong, Singh, Ravinder, Gazala , Sayf, Ghosh, Sunita, Wong, Eric, Joy, Anil A., Xing, James Z., and Bedard, Eric L.

Abstract

Purpose: MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis thereby controlling vital biological processes, including cellular proliferation, differentiation and apoptosis. MiRNA profiling is an emerging tool for the potential early detection of a variety of malignancies. This study was conducyed to assess the feasibility and methodological robustness of quantifying sputum miRNAs, employing quantitative real-time polymerase chain reaction (RT-qPCR) and cluster analysis on an optimized miRNA profile as a novel approach for the early detection of non-small cell lung cancer (NSCLC). Methods: The relative expressions of 11 miRNAs in sputum (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, and let-7a) in addition to U6 were retrospectively assessed in four NSCLC-positive and four negative controls. Subsequently, a set of five miRNAs (miR-21, miR-143, miR-155, miR-210, miR-372) was selected because of degree of relatedness observed in the cluster analysis and tested in the same sputum sample set. The five optimized miRNAs accurately clustered these eight retrospective patients into NSCLC positive cases and negative controls. The five miRNA panel was then prospectively quantified in the sputum of 30 study patients (24 NSCLC cases and six negative controls) in a double-blind fashion to validate a five miRNA panel using hierarchical cluster analysis. Results: The optimized five miRNA panel detected NSCLC (83.3% sensitivity and 100% specificity) in 30 prospectively accrued study patients. Conclusion: Sputum miRNA profiling using cluster analysis is a promising approach for the early detection of non-small cell lung cancer. Further investigation using this approach is warranted.

Published
2012

38. Dosimetry Study of [I-131] and [I-125]-Meta-Iodobenzyl Guanidine in a Simulating Model for Neuroblastoma Metastasis

Author

Roa, Wilson H. Y., primary, Yaremko, Brian, additional, McEwan, Alexander, additional, Amanie, John, additional, Yee, Don, additional, Cho, John, additional, McQuarrie, Steve, additional, Riauka, Terence, additional, Sloboda, Ronald, additional, Wiebe, Leonard, additional, Loebenberg, Raimar, additional, and Janicki, Christian, additional

Published
2013
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41. Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non–Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

Author

Mehta, Minesh P., primary, Shapiro, William R., additional, Phan, See C., additional, Gervais, Radj, additional, Carrie, Christian, additional, Chabot, Pierre, additional, Patchell, Roy A., additional, Glantz, Michael J., additional, Recht, Lawrence, additional, Langer, Corey, additional, Sur, Ranjan K., additional, Roa, Wilson H., additional, Mahe, Marc A., additional, Fortin, Andre, additional, Nieder, Carsten, additional, Meyers, Christina A., additional, Smith, Jennifer A., additional, Miller, Richard A., additional, and Renschler, Markus F., additional

Published
2009
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44. Results of a phase I study to dose escalate using intensity modulated radiotherapy guided by combined PET/CT imaging with induction chemotherapy for patients with non-small cell lung cancer

Author

Holloway, Caroline L., primary, Robinson, Don, additional, Murray, Brad, additional, Amanie, John, additional, Butts, Charles, additional, Smylie, Michael, additional, Chu, Karen, additional, McEwan, A.J., additional, Halperin, Ross, additional, and Roa, Wilson H., additional

Published
2004
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47. Calcium/Calmodulin-dependent Protein Kinase II Regulation of c-FLIP Expression and Phosphorylation in Modulation of Fas-mediated Signaling in Malignant Glioma Cells.

Author

Bao Feng Yang, Chang Xiao, Roa, Wilson H., Krammer, Peter H., and Chunhai Hao

Subjects
*CALCIUM, *CALMODULIN, *PROTEIN kinases, *PHOSPHORYLATION
Abstract

Studies calcium/calmodulin-dependent protein kinase II regulation of c-FLIP expression and phosphorylation in modulation of Fas-mediated signaling in malignant glioma cells. Ability of Fas agonistic antibody CH-11 to induce apoptosis in sensitive glioma cells; Molecular mechanisms that control Fas-mediated signalin in glioma cells.

Published
2003
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48. Effect of radiation on cytokine and cytokine receptor messenger-RNA profiles in p53 wild and mutated human glioblastoma cell lines.

Author

Yee, Don, Hao, Chunhai, Cheung, Hannah C., Chen, Hua T., Dabbagh, Laith, Hanson, John, Coupland, Robert, Petruk, Kenneth C., Fulton, Dorcas, and Roa, Wilson H.

Subjects
*PHYSIOLOGICAL effects of radiation, *P53 antioncogene, *CYTOKINES, *IRRADIATION
Abstract

Conclusion: These results suggest that cobalt irradiation alone at clinically relevant doses does not significantly alter the cytokine and cytokine receptor profiles in human glioblastoma cell lines. [ABSTRACT FROM AUTHOR]

Published
2001

49. Fabrication and in vitro characterization of gadolinium-based nanoclusters for simultaneous drug delivery and radiation enhancement.

Author

Yoo SS, Guo L, Sun X, Shaw AR, Yuan Z, Löbenberg R, and Roa WH

Subjects
Doxorubicin, Drug Delivery Systems, Magnetic Resonance Imaging, Nanoparticles, Theranostic Nanomedicine, Gadolinium chemistry
Abstract

We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective wet-chemical method was utilized in the presence of manganese (Mn) ions and Dox to produce the Gd(OH)3:Mn·Dox nanocluster structure. The Gd(OH)3:Mn·Dox nanocluster was composed of Mn-doped Gd(OH)3 nanorods arranged in parallel with Dox as a linker molecule between the adjacent nanorods. No other studies have utilized Dox as both the linker and therapeutic molecule in a nanostructure to date. The Gd(OH)3 nanorod is reported to have no significant cellular or in vivo toxicity, which makes it an ideal base material for this biomedical application. The Gd(OH)3:Mn·Dox nanocluster exhibited paramagnetic behavior and was stable in a colloidal solution. The nanocluster also enabled high Dox loading capacity and specifically released Dox in a sustained and pH-dependent manner. The positively charged Gd(OH)3:Mn·Dox nanoclusters were readily internalized into MDA-MB-231 breast cancer cells via endocytosis, which resulted in intracellular release of Dox. The released Dox in cells was effective in conferring cytotoxicity and inhibiting proliferation of cancer cells. Furthermore, a synergistic anticancer effect could be observed with radiation treatment. Overall, the Gd(OH)3:Mn·Dox nanocluster drug delivery system described herein may have potential utility in clinics as a multifunctional theranostic nanoparticle with combined benefits in both diagnosis and therapy in the management of cancer.

Published
2016
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50. Non-small cell lung cancer detection using microRNA expression profiling of bronchoalveolar lavage fluid and sputum.

Author

Kim JO, Gazala S, Razzak R, Guo L, Ghosh S, Roa WH, and Bédard EL

Subjects
Aged, Aged, 80 and over, Biomarkers, Tumor isolation & purification, Bronchoalveolar Lavage Fluid, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung pathology, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, MicroRNAs isolation & purification, Middle Aged, Sputum metabolism, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, MicroRNAs genetics, Prognosis
Abstract

Aim: To assess if miRNA expression profiling of bronchoalveolar lavage (BAL) fluid and sputum could be used to detect early-stage non-small cell lung cancer (NSCLC)., Materials and Methods: Hierarchical cluster analysis was performed on the expression levels of 5 miRNAs (miR-21, miR-143, miR-155, miR-210, and miR-372) which were quantified using RNA reverse transcription and quantitative real-time polymerase chain reaction in sputum and BAL samples from NSCLC cases and cancer-free controls., Results: Cluster analysis of the miRNA expression levels in BAL samples from 21 NSCLC cases and sputum samples from 10 cancer-free controls yielded a diagnostic sensitivity of 85.7% and specificity of 100%. Cluster analysis of sputum samples from the same patients yielded a diagnostic sensitivity of 67.8% and specificity of 90%., Conclusion: miRNA expression profiling of sputum and BAL fluids represent a potential means to detect early-stage NSCLC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Published
2015

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