242 results on '"Andrew Z. Wang"'
Search Results
2. Supplementary Figures 1-2, Supplementary Tables 1-2 from Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture
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Seungpyo Hong, Andrew Z. Wang, Bhishamjit S. Chera, Joel E. Tepper, Tian Zhang, Ronald C. Chen, Colette Shen, Seth M. Miller, Kevin A. Tam, Kyle Wang, Michael J. Poellmann, Sin-Jung Park, Joseph M. Caster, Michael J. Eblan, and Ja Hye Myung
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Table S1. Clinical and demographic characteristics of recruited cancer patients; Table S2. Demographic characteristics of recruited healthy donors; Figure S1. Reproducibility confirmation of CapioCyte-D by testing duplicated blood samples from three cancer patients (A-C) using separately prepared capture surfaces (slides 1 and 2); Figure S2. A comparison of the captured epithelial cell number from two healthy donor groups with different age ranges (under 35 years vs. above 50 years).
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- 2023
3. Data from Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis
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Andrew Z. Wang, Leaf Huang, Paul A. Dayton, Juan D. Rojas, Liantao Li, Amanda Graboski, Jiajie Zhang, Ellie McCabe, Amber S. Moody, Jie Wang, Nikhila Sultanpuram, Mengying Hu, Mostafa Yazdimamaghani, and Hossein Sendi
- Abstract
Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA.Significance:Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.
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- 2023
4. Supplementary Figure S1 from CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α
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Andrew Z. Wang, Scott Eliasof, Joel E. Tepper, Edward G. Garmey, Lata Jayaraman, Pauline Wu, Christian G. Peters, Kyle C. Roche, Joseph M. Caster, Henry P. Foote, Minh Nguyen, and Xi Tian
- Abstract
There is a linear relationship between the number of HT-29-Luc2 cells and the luminescence intensity.
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- 2023
5. Data from CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α
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Andrew Z. Wang, Scott Eliasof, Joel E. Tepper, Edward G. Garmey, Lata Jayaraman, Pauline Wu, Christian G. Peters, Kyle C. Roche, Joseph M. Caster, Henry P. Foote, Minh Nguyen, and Xi Tian
- Abstract
Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle–drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared with standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demonstrated that the addition of CRLX101 to standard chemoradiotherapy significantly increased therapeutic efficacy by inhibiting DNA repair and HIF1α pathway activation in tumor cells. Notably, CRLX101 was more effective than oxaliplatin at enhancing the efficacy of chemoradiotherapy, with CRLX101 and 5-fluorouracil producing the highest therapeutic efficacy. Gastrointestinal toxicity was also significantly lower for CRLX101 compared with CPT when combined with radiotherapy. Our results offer a preclinical proof of concept for CRLX101 as a modality to improve the outcome of neoadjuvant chemoradiotherapy for rectal cancer treatment, in support of ongoing clinical evaluation of this agent (LCC1315 NCT02010567). Cancer Res; 77(1); 112–22. ©2016 AACR.
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- 2023
6. Supplementary Figure S2 from CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α
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Andrew Z. Wang, Scott Eliasof, Joel E. Tepper, Edward G. Garmey, Lata Jayaraman, Pauline Wu, Christian G. Peters, Kyle C. Roche, Joseph M. Caster, Henry P. Foote, Minh Nguyen, and Xi Tian
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Evaluation of skin toxicity following drug with radiation (XRT) treatment. (A) Representative images and (B) quantification of skin toxicities observed in animals 49 days following treatment with PBS (Control), CPT, or CRLX101 with radiation.
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- 2023
7. In Vivo Bioengineering of Beta Cells with Immune Checkpoint Ligand as a Treatment for Early-Onset Type 1 Diabetes Mellitus
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Andrew Z. Wang, Kin Man Au, and Roland Tisch
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Autoimmune disease ,Type 1 diabetes ,endocrine system diseases ,business.industry ,Insulin ,medicine.medical_treatment ,General Engineering ,nutritional and metabolic diseases ,General Physics and Astronomy ,medicine.disease ,Ligand (biochemistry) ,Immune checkpoint ,immune system diseases ,In vivo ,medicine ,Cancer research ,General Materials Science ,Beta (finance) ,business ,human activities ,Pretargeting - Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by autoreactive T cells targeting the insulin-producing beta (β) cells. Despite advances in insulin therapy, T1DM still leads to high...
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- 2021
8. Predicting patient-specific response to adaptive therapy in metastatic castration-resistant prostate cancer using prostate-specific antigen dynamics
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Andrew Z. Wang, Robert E. Butler, Jingsong Zhang, Tian Zhang, Heiko Enderling, Robert A. Gatenby, and Renee Brady-Nicholls
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Male ,Patient-Specific Modeling ,Oncology ,Cancer Research ,medicine.medical_specialty ,Abiraterone Acetate ,Antineoplastic Agents ,Pilot Projects ,Castration resistant ,Predictive ,Prostate cancer ,chemistry.chemical_compound ,Antigen ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Treatment resistance ,RC254-282 ,Original Research ,Mathematical ,Adaptive therapy ,business.industry ,Modeling ,Abiraterone acetate ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Models, Theoretical ,Prostate-Specific Antigen ,Patient specific ,medicine.disease ,Prostatic Neoplasms, Castration-Resistant ,Prostate-specific antigen ,Treatment Outcome ,chemistry ,Neoplastic Stem Cells ,Metastatic ,Stem cell ,business - Abstract
Abiraterone acetate (AA) has been proven effective for metastatic castration-resistant prostate cancer (mCRPC), and it has been proposed that adaptive AA may reduce toxicity and prolong time to progression, when compared to continuous AA. We developed a simple quantitative model of prostate-specific antigen (PSA) dynamics to evaluate prostate cancer (PCa) stem cell enrichment as a plausible driver of AA treatment resistance. The model incorporated PCa stem cells, non-stem PCa cells and PSA dynamics during adaptive therapy. A leave-one-out analysis was used to calibrate and validate the model against longitudinal PSA data from 16 mCRPC patients receiving adaptive AA in a pilot clinical study. Early PSA treatment response dynamics were used to predict patient response to subsequent treatment. We extended the model to incorporate metastatic burden and also investigated the survival benefit of adding concurrent chemotherapy for patients predicted to become resistant. Model simulations demonstrated PCa stem cell self-renewal as a plausible driver of resistance to adaptive therapy. Evolutionary dynamics from individual treatment cycles combined with metastatic burden measurements predicted patient response with 81% accuracy (specificity=92%, sensitivity=50%). In those patients predicted to progress, simulations of the addition of concurrent chemotherapy suggest a benefit between 1% and 11% reduction in probability of progression when compared to adaptive AA alone. This study developed the first mCRPC patient-specific mathematical model to use early PSA treatment response dynamics to predict subsequent responses to adaptive AA, demonstrating the putative value of integrating mathematical modeling into clinical decision making.
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- 2021
9. Preliminary Evaluation of PTV Margins for Online Adaptive Radiation Therapy of the Prostatic Fossa
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Howard E. Morgan, Kai Wang, Yulong Yan, Neil Desai, Raquibul Hannan, Eric Chambers, Bin Cai, Mu-Han Lin, David J. Sher, Jing Wang, Andrew Z. Wang, Steve Jiang, Robert Timmerman, Chunjoo 'Justin' Park, and Aurelie Garant
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Oncology ,Radiology, Nuclear Medicine and imaging - Abstract
In modern trials, traditional planning target volume (PTV) margins for postoperative prostate radiation therapy have been large (7-10 mm) to account for both daily changes in patient positioning and target deformation. With daily adaptive radiation therapy, these interfractional changes could be minimized, potentially reducing the margins required for treatment and improving adjacent normal-tissue dosimetry.A single-center retrospective study was conducted from March 2021 to November 2021. Patients receiving conventionally fractionated postoperative radiation therapy (PORT) for prostate cancer with pretreatment and posttreatment cone beam computed tomography (CBCT) imaging (pre-CBCT and post-CBCT, respectively) were included (248 paired images). Pretreatment and posttreatment clinical target volumes (pre-CTVs and post-CTVs) were contoured by a single observer on all CBCTs and verified by a second observer. Motion was calculated from pre-CTV to that of the post-CTV, and predicted margins were calculated with van Herk's formula. Adequate coverage of the proposed planning target volume (PTV) margin expansions (pre-PTV) were verified by determining overlap with post-CTV. In a smaller cohort (25 paired images), dosimetric changes with the proposed online adaptive margins were compared with conventional plans in the Ethos emulator environment.The estimated margins predicted to achieve ≥95% CTV coverage for 90% of the population were 1.6 mm, 2.0 mm, and 2.2 mm (x-, y-, and z -xes, respectively), with 95% of the absolute region of interest displacement being within 1.9 mm, 2.8 mm, and 2.1 mm. After symmetrically expanding all pre-CTVs by 3 mm, the percentage of paired images achieving ≥95% CTV coverage was 97.1%. When comparing adaptive plans (3-mm margins) with scheduled plans (7-mm margins), rectum dosimetry significantly improved, with an average relative reduction in V40Gy[cc] of 59.2% and V65Gy[cc] of 79.5% (where V40Gy and V65Gy are defined as the volumes receiving 40 Gy and 65 Gy or higher dose, respectively).Online daily adaptive radiation therapy could significantly decrease PTV margins for prostatic PORT and improve rectal dosimetry, with a symmetrical expansion of 3 mm achieving excellent coverage in this cohort. These results need to be validated in a larger prospective cohort.
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- 2022
10. The Role of Immune Cells in Therapeutic Angiogenesis: Concepts in Tissue Engineering
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Zoleikha Azari, Sarah Gorgani, Seyede Atefe Hosseini, Andrew Z. Wang, Hae-Won Kim, and Saeid Kargozar
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Biomaterials ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering - Published
- 2023
11. Circulating tumor cell abundance in head and neck squamous cell carcinoma decreases with successful chemoradiation and cetuximab treatment
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Michael J. Poellmann, Jiyoon Bu, DaWon Kim, Mari Iida, Heejoo Hong, Andrew Z. Wang, Deric L. Wheeler, Randall J. Kimple, and Seungpyo Hong
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Cancer Research ,Oncology - Published
- 2023
12. Nanotechnology and machine learning enable circulating tumor cells as a reliable biomarker for radiotherapy responses of gastrointestinal cancer patients
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Michael J. Poellmann, Jiyoon Bu, Stanley Liu, Andrew Z. Wang, Steven N. Seyedin, Chandrikha Chandrasekharan, Heejoo Hong, YoungSoo Kim, Joseph M. Caster, and Seungpyo Hong
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Electrochemistry ,Biomedical Engineering ,Biophysics ,General Medicine ,Biotechnology - Published
- 2023
13. Radiosensitivity of Breast Cancer Cells Is Dependent on the Organ Microenvironment
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Genyan Guo, Ryan T. Morse, Jie Wang, Xuan Chen, Jiajie Zhang, and Andrew Z. Wang
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Cancer Research ,Oncology - Abstract
BackgroundDistant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer “metastases” in liver and lung organ-specific tissues.MethodsLiver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells.ResultsThe response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death.ConclusionsThe therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.
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- 2022
14. COVID-19 vaccines for patients with cancer: benefits likely outweigh risks
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Joyce K. Hwang, Andrew Z. Wang, Zihai Li, and Tian Zhang
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0301 basic medicine ,Patients with cancer and COVID-19 ,Cancer Research ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,COVID-19 vaccines ,Antineoplastic Agents ,Review ,Malignancy ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Pandemic ,Animals ,Humans ,Medicine ,Intensive care medicine ,Adverse effect ,Pandemics ,Molecular Biology ,business.industry ,COVID-19 and cancer ,lcsh:RC633-647.5 ,Vaccination ,Cancer ,COVID-19 ,Hematology ,Immunotherapy ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Clinical trial ,SARS-CoV-2 virus vaccines ,Cancer therapies ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
Less than a year since the start of the COVID-19 pandemic, ten vaccines against SARS-CoV-2 have been approved for at least limited use, with over sixty others in clinical trials. This swift achievement has generated excitement and arrives at a time of great need, as the number of COVID-19 cases worldwide continues to rapidly increase. Two vaccines are currently approved for full use, both built on mRNA and lipid nanotechnology platforms, a success story of mRNA technology 20 years in the making. For patients with cancer, questions arise around the safety and efficacy of these vaccines in the setting of immune alterations engendered by their malignancy and/or therapies. We summarize the current data on leading COVID-19 vaccine candidates and vaccination of patients undergoing immunomodulatory cancer treatments. Most current cancer therapeutics should not prevent the generation of protective immunity. We call for more research in this area and recommend that the majority of patients with cancer receive COVID vaccinations when possible.
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- 2021
15. The Radiobiology of Radiopharmaceuticals
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Zachary S. Morris, Susan J. Knox, and Andrew Z. Wang
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Cancer Research ,medicine.medical_specialty ,Radiobiology ,medicine.medical_treatment ,Targeted radionuclide therapy ,External beam radiation ,Planning target volume ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,Dosimetry ,Linear Energy Transfer ,Radiology, Nuclear Medicine and imaging ,Medical physics ,External beam radiotherapy ,Radiometry ,business.industry ,Oncology ,Treatment delivery ,030220 oncology & carcinogenesis ,Radiopharmaceuticals ,business ,Dose rate - Abstract
Radiopharmaceutical therapy or targeted radionuclide therapy (TRT) is a well-established class of cancer therapeutics that includes a growing number of FDA-approved drugs and a promising pipeline of experimental therapeutics. Radiobiology is fundamental to a mechanistic understanding of the therapeutic capacity of these agents and their potential toxicities. However, the field of radiobiology has historically focused on external beam radiation. Critical differences exist between TRT and external beam radiotherapy with respect to dosimetry, dose rate, linear energy transfer, duration of treatment delivery, fractionation, range, and target volume. These distinctions simultaneously make it difficult to extrapolate from the radiobiology of external beam radiation to that of TRT and pose considerable challenges for preclinical and clinical studies investigating TRT. Here, we discuss these challenges and explore the current understanding of the radiobiology of radiopharmaceuticals.
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- 2021
16. Enhancing Combined Immunotherapy and Radiotherapy through Nanomedicine
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Yu Mi, Nicole M. Knape, Andrew Z. Wang, and C. Tilden Hagan
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medicine.medical_specialty ,medicine.medical_treatment ,Biomedical Engineering ,Pharmaceutical Science ,Bioengineering ,02 engineering and technology ,01 natural sciences ,Neoplasms ,medicine ,Animals ,Humans ,Combined Modality Therapy ,Medical physics ,Pharmacology ,010405 organic chemistry ,Chemistry ,Extramural ,Organic Chemistry ,Cancer ,Neoplasms therapy ,Immunotherapy ,021001 nanoscience & nanotechnology ,medicine.disease ,0104 chemical sciences ,Cancer treatment ,Radiation therapy ,Nanomedicine ,0210 nano-technology ,Biotechnology - Abstract
[Image: see text] Radiotherapy and immunotherapy are two key treatments for cancer. There is growing evidence that they are also synergistic, and combination treatments are being studied extensively in the clinical setting. In addition, there is emerging evidence that nanotechnology-enabled therapeutics can potentiate both radiotherapy and immunotherapy, in turn improving both treatments. This is an exciting new area of interdisciplinary science and has significant potential for major clinical impact. Some of the approaches in this area have already reached the clinical stage. In this review, we will discuss recent advances in the interface between radiotherapy, immunotherapy, and nanomedicine. We plan to review the many approaches to combine these three fields for cancer treatment.
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- 2020
17. 3D Printed Drug-Loaded Implantable Devices for Intraoperative Treatment of Cancer
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C. Tilden Hagan, Cameron Bloomquist, Samuel Warner, Nicole M. Knape, Isaiah Kim, Hayley Foley, Kyle T. Wagner, Sue Mecham, Joseph DeSimone, and Andrew Z. Wang
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Mice ,Drug Delivery Systems ,Paclitaxel ,Pharmaceutical Preparations ,Neoplasms ,Printing, Three-Dimensional ,Pharmaceutical Science ,Animals ,Article - Abstract
Surgery is an important treatment for cancer; however, local recurrence following macroscopically-complete resection is common and a significant cause of morbidity and mortality. Systemic chemotherapy is often employed as an adjuvant therapy to prevent recurrence of residual disease, but has limited efficacy due to poor penetration and dose-limiting off-target toxicities. Selective delivery of chemotherapeutics to the surgical bed may eliminate residual tumor cells while avoiding systemic toxicity. While this is challenging for traditional drug delivery technologies, we utilized advances in 3D printing and drug delivery science to engineer a drug-loaded arrowhead array device (AAD) to overcome these challenges. We demonstrated that such a device can be designed, fabricated, and implanted intraoperatively and provide extended release of chemotherapeutics directly to the resection area. Using paclitaxel and cisplatin as model drugs and murine models of cancer, we showed AADs significantly decreased local recurrence post-surgery and improved survival. We further demonstrated the potential for fabricating personalized AADs for intraoperative application in the clinical setting.
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- 2022
18. Continuous liquid interface production of 3D printed drug-loaded spacers to improve prostate cancer brachytherapy treatment
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C. Tilden Hagan, Cameron Bloomquist, Isaiah Kim, Nicole M. Knape, James D. Byrne, Litao Tu, Kyle Wagner, Sue Mecham, Joseph DeSimone, and Andrew Z. Wang
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Male ,Brachytherapy ,Biomedical Engineering ,Prostate ,Prostatic Neoplasms ,General Medicine ,Docetaxel ,Biochemistry ,Dexamethasone ,Biomaterials ,Mice ,Pharmaceutical Preparations ,Printing, Three-Dimensional ,Animals ,Humans ,Molecular Biology ,Biotechnology - Abstract
Brachytherapy, which is the placement of radioactive seeds directly into tissue such as the prostate, is an important curative treatment for prostate cancer. By delivering a high dose of radiation from within the prostate gland, brachytherapy is an effective method of killing prostate cancer cells while limiting radiation dose to normal tissue. The main shortcomings of this treatment are: less efficacy against high grade tumor cells, acute urinary retention, and sub-acute urinary frequency and urgency. One strategy to improve brachytherapy is to incorporate therapeutics into brachytherapy. Drugs, such as docetaxel, can improve therapeutic efficacy, and dexamethasone is known to decrease urinary side effects. However, both therapeutics have high systemic side effects. To overcome this challenge, we hypothesized that we can incorporate therapeutics into the inert polymer spacers that are used to correctly space brachytherapy seeds during brachytherapy to enable local drug delivery. To accomplish this, we engineered 3D printed drug-loaded brachytherapy spacers using continuous liquid interface production (CLIP) with different surface patterns to control drug release. These devices have the same physical size as existing spacers, allowing them to easily replace commercial spacers. We examined these drug-loaded spacers using docetaxel and dexamethasone as model drugs in a murine model of prostate cancer. We found that drug-loaded spacers led to higher therapeutic efficacy for brachytherapy, and there was no discernable systemic toxicity from the drug-loaded spacers. STATEMENT OF SIGNIFICANCE: There has been high interest in the application of 3D printing to engineer novel medical devices. However, such efforts have been limited by the lack of technologies that can fabricate devices suitable for real world medical applications. In this study, we demonstrate a unique application for 3D printing to enhance brachytherapy for cancer treatment. We engineered drug-loaded brachytherapy spacers that can be fabricated using Continuous Liquid Interface Production (CLIP) 3D printing, allowing tunable printing of drug-loaded devices, and implanted intraoperatively with brachytherapy seeds. In combined chemotherapy and brachytherapy we are able to achieve greater therapeutic efficacy through local drug delivery and without systemic toxicities. We believe our work will facilitate further investigation in medical applications of 3D printing.
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- 2022
19. Contributors
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Kristy M. Ainslie, Amal A. Al-Dossary, Khuloud T. Al-Jamal, Mansoor M. Amiji, Eric M. Bachelder, Baljevan Dhadwar, Shreya Basireddy, Surinder K. Batra, Wolfgang A. Beck, Elana Ben-Akiva, Brandon W. Carpenter, Flávia Castro, Guiyuan Chen, Vipin Dalal, Dan Peer, Peter Doran, Shailendra K. Gautam, Elizabeth G. Graham-Gurysh, Jordan J. Green, Ian Hay, Faith Hannah Nutter Howard, Di Huang, Alessandra Iscaro, Maneesh Jain, Johan Karlsson, Hiroshi Katoh, Dongyoon Kim, Ashish A. Kulkarni, Soonbum Kwon, Tianqun Lang, Jiahe Li, Jiawei Li, Yamin Li, Yaping Li, Zhaoji Liu, Xin Lu, Sandro Matosevic, Lara Milane, Yuanzeng Min, Munitta Muthana, Yu-Kyoung Oh, Smrithi Padmakumar, Neha Parayath, Sharif Rahmy, Anujan Ramesh, Bruno Sarmento, Myria Scott, Elisa Stephens, Lior Stotsky, Lanhong Su, Xin Sun, Dana Tarab, Stephany Y. Tzeng, Devika M. Varma, Benjamin G. Vincent, Adam A. Walters, Andrew Z. Wang, Yina Wu, Yuqianxun Wu, Qiaobing Xu, Yoon Yeo, Qi Yin, Hongzhe Yu, Yong Zhang, and Runqi Zhu
- Published
- 2022
20. Delivery strategies to overcome tumor immunotherapy resistance
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Andrew Z. Wang, Zhaoji Liu, Guiyuan Chen, Lanhong Su, and Yuanzeng Min
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Immunotherapy ,medicine.disease ,Immune checkpoint ,Blockade ,Clinical trial ,Cell therapy ,Radiation therapy ,Cancer immunotherapy ,Internal medicine ,medicine ,business - Abstract
Immunotherapy is a promising treatment for cancer nowadays, which induces a long-lasting response in contrast to chemotherapy and radiotherapy. The immunotherapies, mainly including immune checkpoint blockade therapy, adoptive cell therapy, and therapeutic cancer vaccines, have yielded remarkable clinical outcomes in cancer patients. However, most of the patients did not benefit from immunotherapy due to primary resistance and only a small part of initial responders developed acquired resistance that relapsed after a period of treatment. Improving the efficacy of immunotherapy is necessary to understand the mechanisms of immunotherapy resistance, namely primary resistance and acquire resistance, and then develop combination therapies through various delivery strategies to overcome immunotherapy resistance. In this chapter, we review different types of cancer immunotherapy, elaborate the predominant mechanisms of immunotherapy resistance and describe several delivery strategies at the proof-of-concept or clinical trial phase that can overcome tumor immunotherapy resistance.
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- 2022
21. Consolidative or palliative whole brain radiation for secondary CNS diffuse large B-Cell lymphoma
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Kyle Wang, Raghuveer Ranganathan, Andrew Z. Wang, Tyler Walburn, Anne W. Beaven, Natalie S Grover, Colette J. Shen, and Christopher Dittus
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Oncology ,Cancer Research ,medicine.medical_specialty ,Central Nervous System Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Partial response ,Internal medicine ,medicine ,Humans ,Brain Neoplasms ,business.industry ,Brain ,Whole brain irradiation ,Hematology ,medicine.disease ,Lymphoma ,Treatment Outcome ,030220 oncology & carcinogenesis ,Palliative intent ,Lymphoma, Large B-Cell, Diffuse ,Cranial Irradiation ,Neoplasm Recurrence, Local ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
We analyzed 25 patients receiving whole brain radiation (WBRT) for secondary CNS lymphoma (SCNSL), grouped by consolidative intent (after complete/partial response, n = 13) vs. palliative intent (i...
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- 2020
22. Dosimetric correlations with urinary quality of life in patients receiving post-prostatectomy radiation therapy
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J Dooley, R. Basak, Panayiotis Mavroidis, Kevin A. Pearlstein, Xianming Tan, J.K. Sun, Ronald C. Chen, Srinivas Saripalli, and Andrew Z. Wang
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medicine.medical_specialty ,Receiver operating characteristic ,business.industry ,Urinary system ,medicine.medical_treatment ,Urology ,medicine.disease ,030218 nuclear medicine & medical imaging ,Radiation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Quality of life ,030220 oncology & carcinogenesis ,medicine ,Nocturia ,Dysuria ,medicine.symptom ,Radiation treatment planning ,business - Abstract
Acute urinary toxicity is well-documented in individuals receiving post-prostatectomy radiation. However, dosimetric correlations between bladder dose and acute urinary symptoms in the post-prostatectomy setting have not been well-studied. We examined the relationship between bladder dosimetry and acute changes in individual urinary symptoms among men receiving post-prostatectomy radiation therapy. Patient-reported urinary symptoms were prospectively collected for 90 consecutive prostate cancer patients receiving post-prostatectomy radiation using the validated quality of life instrument Prostate Cancer Symptom Indices. Data were collected prior to treatment and weekly during treatment. Individual symptom scores were examined and a change in severity of an individual symptom (from baseline) of ≥ 2 points was considered clinically significant. DVHs were generated for all the patients. Receiver operating characteristic curves were generated to evaluate the ability of different dose-volume metrics to identify patients who developed individual urinary symptoms during radiation treatment from those who did not. Logistic regression was used to examine the relationship between dose-volume parameters and worsening of individual urinary symptoms. Worsening of individual urinary symptoms during radiation treatment was reported by 7% (urinary flow) to 29% (urgency) of patients. The relative bladder volume receiving moderate doses of radiation was associated with urgency (AUC 0.67 for V30 Gy). Dose-volume parameters were not significantly associated with flow, frequency, nocturia, or dysuria. There is an acute worsening of urinary symptoms among men receiving modern post-prostatectomy radiation. Worsening of urgency is associated with bladder dosimetry while flow, frequency, nocturia, and dysuria are not. This data can be used during treatment planning to reduce acute urinary toxicity during post-prostatectomy radiation.
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- 2020
23. Confidence Boost in Dyadic Online Teamwork: An Individual-Focused Perspective
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Liye Fu, Andrew Z. Wang, and Cristian Danescu-Niculescu-Mizil
- Abstract
Individuals are often more confident in their solutions when working in teams than when working on their own. This confidence boost is observed even when it is not accompanied by a corresponding gain in performance, raising the question of what other factors might be responsible. We address this question by developing a large-scale experimental setting in the form of a two-player online game that allows us to track the confidence of individuals in naturally-occurring online collaborative tasks. This setting enables us to disentangle and compare the effects of different components of the collaborative process on the confidence of each team member. We show that confidence evaluations are subject to social influence: a low-confidence individual receives a confidence boost as a direct consequence of interacting with their teammate, and the extent of the increase depends more on the confidence, rather than on the competence, of the teammate. The resulting framework can enhance our understanding of confidence boost as an often overlooked byproduct of online teamwork and has implications for designing better online collaboration platforms to meet diverse collaborative objectives.
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- 2020
24. Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment
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Hyesun Hyun, Andrew Z. Wang, Bo Sun, and Liantao Li
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0301 basic medicine ,medicine.medical_treatment ,enzymes ,Review Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,immune cells ,Cancer immunotherapy ,Neoplasms ,medicine ,Tumor Microenvironment ,Humans ,Immunologic Factors ,Pharmacology (medical) ,Tumor stroma ,Pharmacology ,Tumor microenvironment ,cancer immunotherapy ,immunosuppression ,business.industry ,Immunosuppression ,General Medicine ,Immunotherapy ,nanomedicine ,cytokines ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Nanomedicine ,sense organs ,business ,METABOLIC FEATURES - Abstract
Cancer immunotherapy has received extensive attention due to its ability to activate the innate or adaptive immune systems of patients to combat tumors. Despite a few clinical successes, further endeavors are still needed to tackle unresolved issues, including limited response rates, development of resistance, and immune-related toxicities. Accumulating evidence has pinpointed the tumor microenvironment (TME) as one of the major obstacles in cancer immunotherapy due to its detrimental impacts on tumor-infiltrating immune cells. Nanomedicine has been battling with the TME in the past several decades, and the experience obtained could be exploited to improve current paradigms of immunotherapy. Here, we discuss the metabolic features of the TME and its influence on different types of immune cells. The recent progress in nanoenabled cancer immunotherapy has been summarized with a highlight on the modulation of immune cells, tumor stroma, cytokines and enzymes to reverse the immunosuppressive TME.
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- 2020
25. Nanotechnology in Radiation Oncology
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Bo Sun, Joseph M. Caster, Andrew Z. Wang, and C. Tilden Hagan
- Subjects
medicine.medical_treatment ,Nanotechnology ,Diagnostic tools ,Article ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Neoplasms ,Radiation oncology ,Biomarkers, Tumor ,medicine ,Humans ,Liquid biopsy ,business.industry ,Cancer ,Hematology ,Neoplastic Cells, Circulating ,medicine.disease ,Biomarker (cell) ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,Radiation Oncology ,Cancer biomarkers ,business ,030215 immunology - Abstract
Nanotechnology has made remarkable contributions to clinical oncology. Nanotherapeutics and diagnostic tools have distinctive characteristics which allow them superior abilities to deliver therapeutics and imaging agents for radiation oncology. Compared to solid biopsies and imaging, the analysis of circulating tumor cells (CTCs) offers a more rapid, real-time, and less invasive method to monitor the dynamic molecular profiles of tumors. The potential of CTCs to be translated as a novel cancer biomarker has been demonstrated in numerous clinical studies. This review will discuss clinical applications of nanomaterials in radiation oncology and the implication of CTCs in cancer detection and monitoring.
- Published
- 2019
26. Tissue engineered cancer metastases as cancer vaccine to improve cancer immunotherapy
- Author
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Nikhila Reddy Sultanpuram, Umer Ahmed, Jonathan Thomas Peters, Tian Zhang, and Andrew Z. Wang
- Subjects
Tissue Engineering ,Biomedical Engineering ,General Medicine ,Radiosurgery ,Biochemistry ,Cancer Vaccines ,Rats ,Biomaterials ,Mice ,Tumor Microenvironment ,Animals ,Immunotherapy ,Molecular Biology ,Melanoma ,Biotechnology - Abstract
Radiotherapy is often used to improve cancer immunotherapy outcomes. While there are both pre-clinical and clinical data supporting this approach, there are also significant challenges. One key challenge is that not all patients have tumors that can be easily treated with radiotherapy due to potential normal tissue toxicity and prior treatment. In addition, it is difficult to control the tumor microenvironment to promote the immune response after radiosurgery. To overcome these challenges, we hypothesize that we can engineer cancer metastasis and utilize irradiated engineered tumor cells as a personalized cancer vaccine to improve cancer immunotherapy. Herein, we report the development of engineered lung metastasis using decellularized rat lung tissue. Using the B16F10 melanoma tumor model, we showed that radiotherapy-treated engineered metastases are highly effective in improving cancer immunotherapy responses and more effective than in vivo metastasis. Our work has demonstrated the potential of applying tissue engineering to cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Combination of radiation and immunotherapy are an effective way to treat metastasis. Despite their success, long term response still remains low. Tumor microenvironment evading the immune response, normal tissue toxicity to radiation and inaccessibility to radiosurgery are some of the limitations. To overcome these challenges, in this paper we present with data supporting the use of high dose radiation treated ex vivo engineered B16F10 metastasis model using decellularized lung scaffolds. These engineered metastases closely mimic the in vivo tumors and when given into tumor bearing mice along with check point inhibitors are highly effective in improving the cancer immunotherapy response.
- Published
- 2021
27. Bimodal liquid biopsy for cancer immunotherapy based on peptide engineering and nanoscale analysis
- Author
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Jiyoon Bu, Woo-jin Jeong, Roya Jafari, Luke J. Kubiatowicz, Ashita Nair, Michael J. Poellmann, Rachel S. Hong, Elizabeth W. Liu, Randall H. Owen, Piper A. Rawding, Caroline M. Hopkins, DaWon Kim, Daniel J. George, Andrew J. Armstrong, Petr Král, Andrew Z. Wang, Justine Bruce, Tian Zhang, Randall J. Kimple, and Seungpyo Hong
- Subjects
Lung Neoplasms ,Liquid Biopsy ,Biomedical Engineering ,Biophysics ,Biosensing Techniques ,General Medicine ,B7-H1 Antigen ,Carcinoma, Non-Small-Cell Lung ,Biomarkers, Tumor ,Electrochemistry ,Humans ,Immunotherapy ,Peptides ,Biotechnology - Abstract
Despite its high potential, PD-L1 expressed by tumors has not been successfully utilized as a biomarker for estimating treatment responses to immunotherapy. Circulating tumor cells (CTCs) and tumor-derived exosomes that express PD-L1 can potentially be used as biomarkers; however, currently available assays lack clinically significant sensitivity and specificity. Here, a novel peptide-based capture surface is developed to effectively isolate PD-L1-expressing CTCs and exosomes from human blood. For the effective targeting of PD-L1, this study integrates peptide engineering strategies to enhance the binding strength and specificity of a β-hairpin peptide derived from PD-1 (pPD-1). Specifically, this study examines the effect of poly(ethylene glycol) spacers, the secondary peptide structure, and modification of peptide sequences (e.g., removal of biologically redundant amino acid residues) on capture efficiency. The optimized pPD-1 configuration captures PD-L1-expressing tumor cells and tumor-derived exosomes with 1.5-fold (p = 0.016) and 1.2-fold (p = 0.037) higher efficiencies, respectively, than their whole antibody counterpart (aPD-L1). This enhanced efficiency is translated into more clinically significant detection of CTCs (1.9-fold increase; p = 0.035) and exosomes (1.5-fold increase; p = 0.047) from patients' baseline samples, demonstrating stronger correlation with patients' treatment responses. Additionally, we confirmed that the clinical accuracy of our system can be further improved by co-analyzing the two biomarkers (bimodal CTC/exosome analysis). These data demonstrate that pPD-1-based capture is a promising approach for capturing PD-L1-expressing CTCs and exosomes, which can be used as a reliable biomarker for cancer immunotherapy.
- Published
- 2022
28. Prognostic and Predictive Clinical and Biological Factors in HPV Malignancies
- Author
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Ashley A. Weiner, Gaorav P. Gupta, Shivani Sud, Colette J. Shen, and Andrew Z. Wang
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Uterine Cervical Neoplasms ,Disease ,Alphapapillomavirus ,medicine.disease_cause ,Biological Factors ,Internal medicine ,medicine ,Anal cancer ,Humans ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Human papillomavirus ,Papillomaviridae ,Tumor biology ,business.industry ,Papillomavirus Infections ,medicine.disease ,Anus Neoplasms ,Prognosis ,Vaccination ,Oropharyngeal Neoplasms ,Molecular targets ,Female ,Carcinogenesis ,business - Abstract
Human papillomavirus (HPV) causes the majority of oropharyngeal, cervical, and anal cancers, among others. These HPV-associated cancers cause substantial morbidity and mortality despite ongoing vaccination efforts. Aside from the earliest stage tumors, chemoradiation is used to treat most HPV-associated cancers across disease sites. Response rates are variable, and opportunities to improve oncologic control and reduce toxicity remain. HPV malignancies share multiple commonalities in oncogenesis and tumor biology that may inform personalized methods of screening, diagnosis, treatment and surveillance. In this review we discuss the current literature and identify promising molecular targets, prognostic and predictive clinical factors and biomarkers in HPV-associated oropharyngeal, cervical and anal cancer.
- Published
- 2021
29. Asymmetrical Multi-task Attention U-Net for the Segmentation of Prostate Bed in CT Image
- Author
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Shuai Wang, Trevor J. Royce, Xuanang Xu, Andrew Z. Wang, Chunfeng Lian, Ronald C. Chen, Jun Lian, and Dinggang Shen
- Subjects
business.industry ,Computer science ,Deep learning ,Multi-task learning ,Article ,030218 nuclear medicine & medical imaging ,Task (project management) ,03 medical and health sciences ,0302 clinical medicine ,Discriminative model ,Prostate Bed ,030220 oncology & carcinogenesis ,Segmentation ,Computer vision ,Artificial intelligence ,business - Abstract
Segmentation of the prostate bed, the residual tissue after the removal of the prostate gland, is an essential prerequisite for post-prostatectomy radiotherapy but also a challenging task due to its non-contrast boundaries and highly variable shapes relying on neighboring organs. In this work, we propose a novel deep learning-based method to automatically segment this “invisible target”. As the main idea of our design, we expect to get reference from the surrounding normal structures (bladder&rectum) and take advantage of this information to facilitate the prostate bed segmentation. To achieve this goal, we first use a U-Net as the backbone network to perform the bladder&rectum segmentation, which serves as a low-level task that can provide references to the high-level task of the prostate bed segmentation. Based on the backbone network, we build a novel attention network with a series of cascaded attention modules to further extract discriminative features for the high-level prostate bed segmentation task. Since the attention network has one-sided dependency on the backbone network, simulating the clinical workflow to use normal structures to guide the segmentation of radiotherapy target, we name the final composition model asymmetrical multi-task attention U-Net. Extensive experiments on a clinical dataset consisting of 186 CT images demonstrate the effectiveness of this new design and the superior performance of the model in comparison to the conventional atlas-based methods for prostate bed segmentation. The source code is publicly available at https://github.com/superxuang/amta-net.
- Published
- 2021
30. Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer
- Author
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Autumn J. McRee, Courtney Bui, Jeremiah C. Boles, Hanna K. Sanoff, Bert H. O'Neil, William Blackstock, Michael S. Lee, Dominic H. Moon, Joel E. Tepper, Dominic T. Moore, Cheryl Ann Carlson, Andrew Z. Wang, and Somasundaram Subramaniam
- Subjects
Adult ,Male ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Biomedical Engineering ,Locally advanced ,Urology ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,Article ,Cohort Studies ,Capecitabine ,03 medical and health sciences ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,General Materials Science ,Dosing ,Aged ,Neoplasm Staging ,030304 developmental biology ,Aged, 80 and over ,Cyclodextrins ,0303 health sciences ,Rectal Neoplasms ,business.industry ,Middle Aged ,021001 nanoscience & nanotechnology ,medicine.disease ,Neoadjuvant Therapy ,Radiation therapy ,CRLX101 ,Toxicity ,Nanoparticles ,Molecular Medicine ,Camptothecin ,Female ,0210 nano-technology ,business ,medicine.drug - Abstract
CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.
- Published
- 2019
31. Optimizing Advances in Nanoparticle Delivery for Cancer Immunotherapy
- Author
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Andrew Z. Wang, Kelly Henderson, C.M. Callaghan, Joseph M. Caster, Bo Sun, and Steven N. Seyedin
- Subjects
T-Lymphocytes ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Pharmaceutical Science ,02 engineering and technology ,03 medical and health sciences ,Drug Delivery Systems ,Immune system ,Cancer immunotherapy ,Neoplasms ,medicine ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,Tumor microenvironment ,business.industry ,Melanoma ,Cancer ,Immunotherapy ,021001 nanoscience & nanotechnology ,medicine.disease ,Drug delivery ,Cancer research ,Nanoparticles ,0210 nano-technology ,business - Abstract
Cancer immunotherapy is one of the fastest growing and most promising fields in clinical oncology. T-cell checkpoint inhibitors are revolutionizing the management of advanced cancers including non-small cell lung cancer and melanoma. Unfortunately, many common cancers are not responsive to these drugs and resistance remains problematic. A growing number of novel cancer immunotherapies have been discovered but their clinical translation has been limited by shortcomings of conventional drug delivery. Immune signaling is tightly-regulated and often requires simultaneous or near-simultaneous activation of multiple signals in specific subpopulations of immune cells. Nucleic acid therapies, which require intact intracellular delivery, are among the most promising approaches to modulate the tumor microenvironment to a pro-immunogenic phenotype. Advanced nanomedicines can be precisely engineered to overcome many of these limitations and appear well-poised to enable the clinical translation of promising cancer immunotherapies.
- Published
- 2019
32. Co-delivery of paclitaxel and cisplatin in poly(2-oxazoline) polymeric micelles: Implications for drug loading, release, pharmacokinetics and outcome of ovarian and breast cancer treatments
- Author
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Rainer Jordan, Alexander V. Kabanov, Andrew Z. Wang, Yuanzeng Min, James J. Beaudoin, Herdis Bludau, Natasha Vinod, Xiaomeng Wan, Marina Sokolsky, and Naoki Makita
- Subjects
Drug ,Paclitaxel ,media_common.quotation_subject ,Biophysics ,Mice, Nude ,Antineoplastic Agents ,Breast Neoplasms ,Bioengineering ,02 engineering and technology ,Micelle ,Article ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmacokinetics ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Oxazoles ,Micelles ,030304 developmental biology ,media_common ,Ovarian Neoplasms ,Cisplatin ,Drug Carriers ,0303 health sciences ,Chemistry ,Cancer ,Combination chemotherapy ,Prodrug ,021001 nanoscience & nanotechnology ,medicine.disease ,Drug Liberation ,Mechanics of Materials ,Ceramics and Composites ,Cancer research ,Female ,0210 nano-technology ,medicine.drug - Abstract
Concurrent delivery of multiple drugs using nanoformulations can improve outcomes of cancer treatments. Here we demonstrate that this approach can be used to improve the paclitaxel (PTX) and alkylated cisplatin prodrug combination therapy of ovarian and breast cancer. The drugs are co-loaded in the polymeric micelle system based on amphiphilic block copolymer poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline-block-2-methyl-2-oxazoline) (P(MeOx-b-BuOx-b -MeOx). A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50 wt.% drug in a stable micellar solution is demonstrated. The drugs co-loading in the micelles result in a slowed-down release to serum, improved pharmacokinetics and increased tumor distribution for both drugs. A superior anti-tumor activity of co-loaded PTX/CP drug micelles compared to single drug micelles or their mixture was demonstrated in cisplatin-resistant human ovarian carcinoma A2780/CisR xenograft tumor and multidrug resistant breast cancer LCC-6-MDR orthotopic tumor models. The improved tumor delivery of co-loaded drugs was related to decreased drug release rates as confirmed by simulation for micelle, serum and tumor compartments in a three-compartmental model. Overall, the results provide support for the use of PTX and cisplatin co-loaded micelles as a strategy for improved chemotherapy of ovarian and breast cancer and potential for the clinical translation.
- Published
- 2019
33. Leptin ameliorates the immunity, but not reproduction, trade-off with endurance in lizards
- Author
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Jerry F. Husak, Andrew Z. Wang, and Matthew B. Lovern
- Subjects
Leptin ,Male ,030110 physiology ,0106 biological sciences ,0301 basic medicine ,Physiology ,Ecoimmunology ,media_common.quotation_subject ,Calorie restriction ,Zoology ,Biology ,Trade-off ,010603 evolutionary biology ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Endocrinology ,Immune system ,Endurance training ,Animals ,Testosterone ,Phytohemagglutinins ,Ecology, Evolution, Behavior and Systematics ,media_common ,Reproductive function ,Reproduction ,Lizards ,Female ,Animal Science and Zoology ,Corticosterone ,Energy Intake ,Spleen - Abstract
Life-history trade-offs result from allocation of limited energetic resources to particular traits at the expense of others. When resources are scarce, some traits will take priority over others in the degree of their expression. For example, the current reproduction may be sacrificed to enhance survival. Although intuitive from an evolutionary perspective, such priorities must be based on proximate mechanisms that respond to the current conditions. The hormone leptin serves as a signal of energy availability in vertebrates, and has been proposed as a mediator of energy allocation between reproduction and traits that enhance survival, such as the immune system. However, since leptin affects reproduction and immunity in a similar way, it remains unclear which takes priority when energy availability is low. Green anole lizards (Anolis carolinensis) with increased activity, via exercise training, have a marked decrease in immune function as well as reproduction, especially when calories are restricted. We hypothesized that endurance training and calorie restriction would lower immune and reproductive function due to energy limitation, and supplemental leptin would 'rescue' either immune function or reproduction (or both) due to the hormonal signal that energetic resources are available. We found that supplementary leptin rescued immune function in calorie-restricted, trained lizards, but reproduction was not rescued in males or females. This suggests that immune function and reproduction have different sensitivities to leptin in both sexes, or that reproduction is more energy limited and takes low priority even when the signal of energy availability is present.
- Published
- 2019
34. Cardiovascular Preventive Care and Coordination of Care in Prostate Cancer Survivors: A Multi-Institutional Prospective Study
- Author
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Jordan A. Holmes, Sean P. Collins, Timothy N. Showalter, Ronald C. Chen, Mohit Kasibhatla, Brittany D. Barbosa, Andrew Z. Wang, Zahra Mahbooba, Leroy G. Hoffman, Michael A. Papagikos, Kristy Alligood, L. Stravers, and Roger F. Anderson
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Disease ,030218 nuclear medicine & medical imaging ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Cancer Survivors ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Aged ,Preventive healthcare ,Aged, 80 and over ,Radiation ,business.industry ,Medical record ,Prostatic Neoplasms ,Cancer ,Androgen Antagonists ,Middle Aged ,medicine.disease ,Clinical trial ,Oncology ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Emergency medicine ,Preventive Medicine ,business - Abstract
Purpose Prostate cancer survivors who receive androgen deprivation therapy (ADT) are at increased risk of cardiovascular disease. They require coordinated care between cancer specialists and primary care physicians to monitor for cancer control and manage cardiovascular risk factors. Methods and Materials We prospectively enrolled 103 men receiving ADT with radiation therapy (RT) from 7 institutions to assess cardiovascular risk factors and survivorship care. Medical records, fasting laboratory test values, and patient-reported outcomes using a validated instrument were assessed at baseline (pretreatment) and 1 year post-RT. Results Cardiovascular disease (39%) and risk factors (diabetes, 22%; hypertension, 63%; hyperlipidemia, 31%) were prevalent at baseline. During the first year after RT completion, 63% received cardiovascular monitoring concordant with American Heart Association guidelines. Fasting laboratory test values at 1 year showed 24% with inadequately controlled blood sugar and 22% elevated cholesterol. Patient perceptions about care coordination were relatively low. At 1 year, 57% reported that their primary care physicians “always know about the care I receive at other places,” 67% reported that their cancer physician “communicated with other providers I see,” and 65% reported that the cancer care physician “knows the results of my visits with other doctors.” Conclusions Patients with prostate cancer who receive ADT and RT are a vulnerable population with prevalent baseline cardiovascular disease and risk factors and suboptimal survivorship care specifically related to coordinated care and cardiovascular monitoring. Clinical trials examining ways to improve the care and outcomes of these survivors are needed.
- Published
- 2019
35. Prospective Characterization of Circulating Tumor Cell Kinetics in Patients With Oligometastatic Disease Receiving Definitive Radiation Therapy
- Author
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Andrew Z. Wang, Dana L. Casey, Xianming Tan, O. Roberts, J. Bu, Shivani Sud, Seungpyo Hong, Rebecca L. Green, Michael J. Poellmann, J. Hall, and Sin-jung Park
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.medical_treatment ,Cancer ,Disease ,Immunotherapy ,medicine.disease ,Malignancy ,Circulating tumor cell ,Internal medicine ,medicine ,Biomarker (medicine) ,Radiology, Nuclear Medicine and imaging ,Hormone therapy ,Prospective cohort study ,business - Abstract
Purpose/Objective(s) To characterize circulating tumor cell (CTC) kinetics in response to definitive radiation therapy (RT) among patients with oligometastatic cancer and identify a profile of CTC kinetics associated with subsequent disease progression. Materials/Methods Patients with oligometastatic disease, defined as any solid malignancy with ≤ 5 sites of metastatic disease, limited to 3 anatomic organ systems undergoing definitive RT to all known metastatic sites were enrolled on a prospective study. Blood specimens were collected at baseline, during RT and at routine follow up visits up to 24 months after completion of RT. Patients received additional lines of therapy per standard of care. CTCs were captured and quantified using a nanotechnology-based assay functionalized with aEpCAM, aHER-2, and aEGFR to facilitate biomimetic cell rolling and dendrimer-mediated multivalent binding. Results A total of 43 patients were enrolled with a median follow-up of 14.3 months corresponding to 255 CTC measurements. The median number of oligometastatic lesions at the time of RT was 1 per patient (range 1-5). Thirty-four patients (79%) received stereotactic body radiation therapy, and 24 patients (56%) went on to receive systemic therapy while on study (cytotoxic chemotherapy, hormone therapy, immunotherapy or targeted kinase inhibitors). All patients with available baseline specimens had detectable CTCs prior to RT, median 28 CTCs/ml (range 0.17-1085). In the post RT setting, CTC counts declined over a 100-day period, median 15 CTCs/ml ( 15/ml at a given time point was significantly associated with clinical disease progression within the subsequent 6 months (OR 3.31, P = 0.007). An increase in CTCs to > 15/ml preceded radiographic or biochemical progression in 8 of 31 (26%) of patients who progressed. Conclusion Our data suggests CTCs may serve as a biomarker for disease control in oligometastatic disease and may predict future disease progression prior to standard of care assessments for patients receiving diverse therapies.
- Published
- 2021
36. Abstract 296: Antigen-independent delivery of 4-1BB agonist to the tumor microenvironment improves immune response while reducing hepatotoxicity
- Author
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Hyesun Hyun, Bo Sun, Stephanie A. Montgomery, Teresa Griffin, Juanzhu Yan, Albert Wielgus, Yue Wang, Tian Zhang, Jianjun Cheng, and Andrew Z. Wang
- Subjects
Cancer Research ,Oncology - Abstract
Background: Clinical progress of α4-1BB has been impeded by hepatotoxicity. Current research is focused on improving targeted delivery of α4-1BB to the tumor using tumor-specific markers. However, targeted delivery of 4-1BB agonists to tumors faces challenges due to a lack of tumor biomarkers and effector T cells within tumors. To overcome these challenges, we developed antigen-independent targeting approach based on unnatural sugar-mediated metabolic glycoengineering and bio-orthogonal click chemistry to deliver α4-1BB to tumors. We utilized nanoparticles that can deliver a sugar analogue containing click-chemistry moiety to the tumor microenvironment. Method: The Ac4ManNAz was loaded in mPEG-PLGA nanoparticles (MazNP), and the loading efficiency was determined by HPLC. DBCO-functionalized α4-1BB (DBCO-α4-1BB) was synthesized via amine-NHS coupling reaction. The tumor inhibition efficiency was assessed on mice bearing different tumor models. Mice were either inoculated subcutaneously on the left flank (75,000 B16F10 cells) or injected on the left fourth mammary fat pad (100,000 4T1 cells). Mice were given MazNPs (IV) on day 5, 6, 10, and 11, and DBCO-α4-1BB (IV) and αPD-1 (IP) on day 8 and 13. T lymphocytes were analyzed by fluorescent IF staining. Serum liver enzyme was examined to evaluate hepatotoxicity of treatments. Liver pathology was assessed by H&E and CD8+ IHC staining. Results: The αPD1 plus DBCO-α4-1BB with MazNPs showed a 36.4% cure rate, compared to 0% of αPD1 plus DBCO-α4-1BB or αPD1 plus DBCO-α4-1BB with free Ac4ManNAz in B16F10 melanoma model. We then re-challenged the cured mice with 200,000 B16F10 cells and 50% of cured mice survived without any further treatment. In 4T1 breast cancer model, the survival data analyzed using the log-rank test showed that the median survival of αPD1 plus DBCO-α4-1BB with MazNP was increased by 71%, compared to the PBS, and 26% αPD1 plus α4-1BB or αPD1 plus DBCO-α4-1BB with free Ac4ManNAz. We showed that the involvement of NK and CD8+ T cells in the antitumor efficacy of αPD1 plus DBCO-α4-1BB with MazNP. Notably, a massive CD8+ T cell infiltration in the liver was observed in both αPD1 plus α4-1BB (29.8 ± 18.2%) and αPD1 plus DBCO-α4-1BB with Ac4ManNAz (22.1 ± 10.9), significantly higher than PBS control (0.9 ± 0.6%), while the percentage of CD8+ T cells in the MazNP treatment (5.4 ± 5.8%) was five times lower. Hepatotoxicity was further confirmed by serum liver enzyme analysis that ALT and AST levels were substantially elevated by αPD1 plus α4-1BB or αPD1 plus DBCO-α4-1BB with free Ac4ManNAz, as compared to PBS control group, while the MazNP-treated mice had normal serum ALT and AST levels except for one. Conclusion: Our findings demonstrated that antigen-independent targeted delivery of α4-1BB can improve anti-tumor immune responses while reducing hepatotoxicity. Citation Format: Hyesun Hyun, Bo Sun, Stephanie A. Montgomery, Teresa Griffin, Juanzhu Yan, Albert Wielgus, Yue Wang, Tian Zhang, Jianjun Cheng, Andrew Z. Wang. Antigen-independent delivery of 4-1BB agonist to the tumor microenvironment improves immune response while reducing hepatotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 296.
- Published
- 2022
37. High-Performance Concurrent Chemo-Immuno-Radiotherapy for the Treatment of Hematologic Cancer through Selective High-Affinity Ligand Antibody Mimic-Functionalized Doxorubicin-Encapsulated Nanoparticles
- Author
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Andrew Z. Wang, Rod Balhorn, Kin Man Au, Monique Cosman Balhorn, and Steven I. Park
- Subjects
010405 organic chemistry ,Chemistry ,General Chemical Engineering ,Cell ,technology, industry, and agriculture ,Cancer ,General Chemistry ,010402 general chemistry ,medicine.disease ,01 natural sciences ,0104 chemical sciences ,3. Good health ,Cell killing ,medicine.anatomical_structure ,In vivo ,Cancer cell ,medicine ,Cancer research ,Cytotoxic T cell ,Immunogenic cell death ,Doxorubicin ,QD1-999 ,Research Article ,medicine.drug - Abstract
Non-Hodgkin lymphoma is one of the most common types of cancer. Relapsed and refractory diseases are still common and remain significant challenges as the majority of these patients eventually succumb to the disease. Herein, we report a translatable concurrent chemo-immuno-radiotherapy (CIRT) strategy that utilizes fully synthetic antibody mimic Selective High-Affinity Ligand (SHAL)-functionalized doxorubicin-encapsulated nanoparticles (Dox NPs) for the treatment of human leukocyte antigen-D related (HLA-DR) antigen-overexpressed tumors. We demonstrated that our tailor-made antibody mimic-functionalized NPs bound selectively to different HLA-DR-overexpressed human lymphoma cells, cross-linked the cell surface HLA-DR, and triggered the internalization of NPs. In addition to the direct cytotoxic effect by Dox, the internalized NPs then released the encapsulated Dox and upregulated the HLA-DR expression of the surviving cells, which further augmented immunogenic cell death (ICD). The released Dox not only promotes ICD but also sensitizes the cancer cells to irradiation by inducing cell cycle arrest and preventing the repair of DNA damage. In vivo biodistribution and toxicity studies confirm that the targeted NPs enhanced tumor uptake and reduced systemic toxicities of Dox. Our comprehensive in vivo anticancer efficacy studies using lymphoma xenograft tumor models show that the antibody-mimic functional NPs effectively inhibit tumor growth and sensitize the cancer cells for concurrent CIRT treatment without incurring significant side effects. With an appropriate treatment schedule, the SHAL-functionalized Dox NPs enhanced the cell killing efficiency of radiotherapy by more than 100% and eradicated more than 80% of the lymphoma tumors., Antibody mimic Selective High-Affinity Ligand-functionalized doxorubicin-encapsulated nanoparticles have been engineered for concurrent chemo-immuno-radiotherapy of hematological cancer.
- Published
- 2018
38. Underascertainment of Clinically Meaningful Symptoms During Prostate Cancer Radiation Therapy-Does This Vary by Patient Characteristics?
- Author
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Brandon S. Wacaser, Sarah S. Tatko, Xianming Tan, Brandon C. Gerringer, Trevor J. Royce, Shivani Sud, Ronald C. Chen, and Andrew Z. Wang
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Logistic regression ,Radiation Dosage ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Prostate ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Patient Reported Outcome Measures ,Aged ,Radiation ,business.industry ,Prostatic Neoplasms ,Common Terminology Criteria for Adverse Events ,Radiotherapy Dosage ,Odds ratio ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Confidence interval ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Hormone therapy ,Radiotherapy, Intensity-Modulated ,business - Abstract
Purpose It is well known that physicians underascertain chemotherapy-related toxicity compared with patient self-report. However, symptom underascertainment in radiation therapy and characterization of patient groups at increased risk for underascertainment have not been examined. Methods and Materials As part of routine clinical care, 7 urinary and gastrointestinal symptoms were prospectively collected with both patient-report outcomes (PROs) using the validated Prostate Cancer Symptom Indices and physician-graded symptoms using Common Terminology Criteria for Adverse Events (CTCAE) for 544 consecutive patients from 2010 to 2018 who received intensity modulated radiation therapy to the prostate or prostate bed. Data from weekly treatment visits and the first posttreatment follow-up were analyzed. Underascertainment was defined as an occurrence when a clinically meaningful symptom was indicated on PROs but not physician CTCAE assessment. Univariate and multivariable logistic regression examined characteristics associated with underascertainment. Results Overall, 85.3% of patients had underascertainment of at least 1 symptom. Per PRO, 16.9% of assessments reported clinically meaningful symptoms, in contrast to only 3.4% per CTCAE, representing an approximate 5-fold difference. Multivariable analysis showed underascertainment was more common in patients who were unmarried (odds ratio [OR] 1.28; 95% confidence interval [CI], 1.18-1.38), lived in rural regions (OR 1.10; 95% CI, 1.01-1.21), incarcerated (OR 1.58; 95% CI, 1.36-1.84), retired/unemployed (OR 1.29; 95% CI, 1.18-1.40), received prostate gland (vs prostate bed) treatment (OR 1.43; 95% CI, 1.31-1.58), and received concurrent hormone therapy (OR 1.16; 95% CI, 1.04-1.29). Patients age >70 years were less likely to have underascertainment compared with those age Conclusions This is the first study to show underascertainment of clinically meaningful symptoms in radiation therapy patients in routine clinical care and further to demonstrate that certain patient groups are especially vulnerable to underascertainment. These results highlight the importance of incorporating PROs in the clinical care of radiation therapy patients. If PROs are not routinely used, vulnerable patient groups may need additional attention during cancer treatment to ensure accurate toxicity assessment and management.
- Published
- 2020
39. Immune Checkpoint Ligand Bioengineered Schwann Cells as Antigen‐Specific Therapy for Experimental Autoimmune Encephalomyelitis (Adv. Mater. 5/2022)
- Author
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Kin Man Au, Roland Tisch, and Andrew Z. Wang
- Subjects
Mechanics of Materials ,Mechanical Engineering ,General Materials Science - Published
- 2022
40. Quality-of-life Benefits and Harms from Prostate Radiotherapy in Patients with Low-burden Metastatic Prostate Cancer
- Author
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Andrew Z. Wang, Ronald C. Chen, and Trevor J. Royce
- Subjects
Oncology ,Male ,medicine.medical_specialty ,business.industry ,Urology ,MEDLINE ,Prostatic Neoplasms ,Androgen Antagonists ,medicine.disease ,Prostate cancer ,Quality of life ,Internal medicine ,Androgens ,Quality of Life ,Medicine ,Prostate radiotherapy ,Humans ,In patient ,Patient Reported Outcome Measures ,Prospective Studies ,business - Published
- 2020
41. Asymmetric multi-task attention network for prostate bed segmentation in computed tomography images
- Author
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Andrew Z. Wang, Chunfeng Lian, Jun Lian, Trevor J. Royce, Ronald C. Chen, Tong Zhu, Dinggang Shen, Pew Thian Yap, Shuai Wang, and Xuanang Xu
- Subjects
Male ,Organs at Risk ,Source code ,Computer science ,media_common.quotation_subject ,Health Informatics ,Residual ,Article ,Task (project management) ,Discriminative model ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Segmentation ,media_common ,Backbone network ,Radiological and Ultrasound Technology ,business.industry ,Deep learning ,Prostate ,Rectum ,Pattern recognition ,Computer Graphics and Computer-Aided Design ,Workflow ,Computer Vision and Pattern Recognition ,Artificial intelligence ,business ,Tomography, X-Ray Computed - Abstract
Post-prostatectomy radiotherapy requires accurate annotation of the prostate bed (PB), i.e., the residual tissue after the operative removal of the prostate gland, to minimize side effects on surrounding organs-at-risk (OARs). However, PB segmentation in computed tomography (CT) images is a challenging task, even for experienced physicians. This is because PB is almost a "virtual" target with non-contrast boundaries and highly variable shapes depending on neighboring OARs. In this work, we propose an asymmetric multi-task attention network (AMTA-Net) for the concurrent segmentation of PB and surrounding OARs. Our AMTA-Net mimics experts in delineating the non-contrast PB by explicitly leveraging its critical dependency on the neighboring OARs (i.e., the bladder and rectum), which are relatively easy to distinguish in CT images. Specifically, we first adopt a U-Net as the backbone network for the low-level (or prerequisite) task of the OAR segmentation. Then, we build an attention sub-network upon the backbone U-Net with a series of cascaded attention modules, which can hierarchically transfer the OAR features and adaptively learn discriminative representations for the high-level (or primary) task of the PB segmentation. We comprehensively evaluate the proposed AMTA-Net on a clinical dataset composed of 186 CT images. According to the experimental results, our AMTA-Net significantly outperforms current clinical state-of-the-arts (i.e., atlas-based segmentation methods), indicating the value of our method in reducing time and labor in the clinical workflow. Our AMTA-Net also presents better performance than the technical state-of-the-arts (i.e., the deep learning-based segmentation methods), especially for the most indistinguishable and clinically critical part of the PB boundaries. Source code is released at https://github.com/superxuang/amta-net.
- Published
- 2020
42. Feasibility and Delivery of Patient-Reported Outcomes in Clinical Practice Among Racially Diverse Bladder and Prostate Cancer Patients
- Author
-
Sean McCabe, Cleo A. Samuel, Mattias Jonsson, Andrew Z. Wang, Hung-Jui Tan, Eric Wallen, Ethan Basch, Ronald C. Chen, Angela B. Smith, Raj S. Pruthi, Bryce B. Reeve, Arlene E. Chung, Antonia V. Bennett, Allison M. Deal, Matthew E. Nielsen, Zahra Mahbooba, and Dana Mueller
- Subjects
Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Black People ,Disease ,Article ,White People ,Cystectomy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Patient Reported Outcome Measures ,Depression (differential diagnoses) ,Aged ,Bladder cancer ,business.industry ,Prostatectomy ,Cancer ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,Oncology ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Anxiety ,Feasibility Studies ,Female ,medicine.symptom ,business - Abstract
Objective: To assess the feasibility of enrollment and collecting PRO data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time. Subjects/Patients and Methods: We recruited 76 patients (n=29 Black and n=47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy. Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at three time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time. Results: 63% of study participants completed all PRO measures at all three time points. Black patients were more likely to select IVR as their survey mode (40% vs 13%, p
- Published
- 2020
43. Endurance and sprint training affect immune function differently in green anole lizards (
- Author
-
Andrew Z, Wang and Jerry F, Husak
- Subjects
Sheep ,Physical Conditioning, Animal ,Reproduction ,Immunity ,Animals ,Nutritional Status ,Lizards - Abstract
Limited resources must be partitioned among traits that enhance fitness. Although survival-related traits often trade off with reproduction, survival-related traits themselves may trade off with each other under energy limitations. Whole-organism performance and the immune system both enhance survival, yet are costly, but it is unclear how the two might trade off with each other under energy-limited conditions. Resources can be allocated to very different types of performance (e.g. aerobic endurance versus anaerobic sprinting), just as they can be allocated to different components of the immune system (e.g. innate versus acquired) to maximize survival. We forced allocation to different performance traits in green anole lizards (
- Published
- 2020
44. Surface engineering for efficient capture of circulating tumor cells in renal cell carcinoma: From nanoscale analysis to clinical application
- Author
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Andrew Z. Wang, Ashita Nair, Jiyoon Bu, Daniel J. George, Tian Zhang, Woo Jin Jeong, Andrew J. Armstrong, Luke J. Kubiatowicz, Marco Reyes-Martinez, Seungpyo Hong, and Michael J. Poellmann
- Subjects
Dendrimers ,Surface Properties ,Receptor expression ,Cell ,Biomedical Engineering ,Biophysics ,02 engineering and technology ,Biosensing Techniques ,Cell Separation ,01 natural sciences ,chemistry.chemical_compound ,Circulating tumor cell ,Cell Line, Tumor ,Electrochemistry ,medicine ,Humans ,Epidermal growth factor receptor ,Receptor ,Carcinoma, Renal Cell ,biology ,010401 analytical chemistry ,Epithelial cell adhesion molecule ,General Medicine ,Equipment Design ,021001 nanoscience & nanotechnology ,Neoplastic Cells, Circulating ,Kidney Neoplasms ,0104 chemical sciences ,medicine.anatomical_structure ,chemistry ,Tumor progression ,Cancer cell ,Cancer research ,biology.protein ,Nanoparticles ,0210 nano-technology ,Antibodies, Immobilized ,Biotechnology - Abstract
Sensitive detection of circulating tumor cells (CTCs) from patients' peripheral blood facilitates on-demand monitoring of tumor progression. However, clinically significant capture of renal cell carcinoma CTCs (RCC-CTCs) remains elusive due to their heterogenous surface receptor expression. Herein, a novel capture platform is developed to detect RCC-CTCs through integration of dendrimer-mediated multivalent binding, a mixture of antibodies, and biomimetic cell rolling. The nanoscale binding kinetics measured using atomic force microscopy reveal that dendrimer-coated surfaces exhibit an order of magnitude enhancement in off-rate kinetics compared to surface without dendrimers, which translated into cell capture improvements by ~60%. Selectin-induced cell rolling facilitates surface recruitment of cancer cells, further improving cancer cell capture by up to 1.7-fold. Lastly, an antibody cocktail targeting four RCC-CTC surface receptors, which included epithelial cell adhesion molecule (EpCAM), carbonic anhydrase IX (CA9), epidermal growth factor receptor (EGFR), and hepatocyte growth factor receptor (c-Met), improves the capture of RCC cells by up to 80%. The optimal surface configuration outperforms the conventional assay solely relying on EpCAM, as demonstrated by detecting significantly more CTCs in patients’ samples (9.8 ± 5.1 vs. 1.8 ± 2.0 CTCs mL-1). These results demonstrate that the newly engineered capture platform effectively detects RCC-CTCs for their potential use as tumor biomarkers.
- Published
- 2020
45. Endurance and sprint training affect immune function differently in green anole lizards (Anolis carolinensis)
- Author
-
Andrew Z. Wang and Jerry F. Husak
- Subjects
030110 physiology ,0106 biological sciences ,0301 basic medicine ,biology ,Physiology ,Ecoimmunology ,Zoology ,biochemical phenomena, metabolism, and nutrition ,Aquatic Science ,Trade-off ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Anolis ,03 medical and health sciences ,Immune system ,Immunity ,Insect Science ,Humoral immunity ,Aerobic exercise ,Animal Science and Zoology ,Molecular Biology ,Anaerobic exercise ,Ecology, Evolution, Behavior and Systematics - Abstract
Limited resources must be partitioned among traits that enhance fitness. Although survival-related traits often trade off with reproduction, survival-related traits themselves may trade off with each other under energy limitations. Whole-organism performance and the immune system both enhance survival, yet are costly, but it is unclear how the two might trade off with each other under energy-limited conditions. Resources can be allocated to very different types of performance (e.g. aerobic endurance versus anaerobic sprinting), just as they can be allocated to different components of the immune system (e.g. innate versus acquired) to maximize survival. We forced allocation to different performance traits in green anole lizards (Anolis carolinensis) using specialized exercise training, to determine how different components of the immune system would be impacted by shifts in energy use. We measured immunocompetence in endurance-trained, sprint-trained and untrained control lizards by evaluating swelling response to phytohemagglutinin (cell-mediated immunity), antibody response to sheep red blood cells (acquired humoral immunity) and wound healing (integrated immunity). Endurance-trained lizards had reduced cell-mediated immunity, whereas sprint-trained lizards had reduced rates of wound healing. The acquired immune response was not affected by either type of training. Because each immune measure responded differently to the different types of training, our results do not support the hypothesis that simple energy limitation determines overall investment in immunity. Instead, different components of the immune system appear to be affected in ways specific to how energy is invested in performance.
- Published
- 2020
46. 9. Nanomedicines: Diagnostic and Therapeutic Applications in Radiation Oncology
- Author
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Tian Zhang, Andrew Z. Wang, Joseph M. Caster, Nichole J. Newman, and Artish N. Patel
- Subjects
medicine.medical_specialty ,business.industry ,Radiation oncology ,medicine ,Medical physics ,business - Published
- 2019
47. Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models
- Author
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Xi Tian, Kyle C. Roche, Kin Man Au, Andrew Z. Wang, Feifei Yang, Yu Mi, Yuangzeng Min, Kyle Wagner, C. Tilden Hagan, Hayley Foley, Zachary L. Rodgers, Yusra Medik, and Maofan Zhang
- Subjects
Combination therapy ,Polyesters ,medicine.medical_treatment ,Biophysics ,Antineoplastic Agents ,Bioengineering ,02 engineering and technology ,Article ,Polyethylene Glycols ,Biomaterials ,Wortmannin ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Platinum resistance ,Animals ,Humans ,Medicine ,Ovarian Neoplasms ,Cisplatin ,Drug Carriers ,Chemotherapy ,business.industry ,Drug Synergism ,Chemoradiotherapy ,021001 nanoscience & nanotechnology ,medicine.disease ,Xenograft Model Antitumor Assays ,Regimen ,chemistry ,Mechanics of Materials ,030220 oncology & carcinogenesis ,Ceramics and Composites ,Cancer research ,Nanoparticles ,Female ,0210 nano-technology ,business ,Ovarian cancer ,medicine.drug - Abstract
Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic.
- Published
- 2018
48. Pretargeted delivery of PI3K/mTOR small-molecule inhibitor-loaded nanoparticles for treatment of non-Hodgkin's lymphoma
- Author
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Andrew Z. Wang, Steven I. Park, and Kin Man Au
- Subjects
medicine.medical_treatment ,Drug Compounding ,Targeted therapy ,Immunophenotyping ,03 medical and health sciences ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Antigen ,In vivo ,immune system diseases ,hemic and lymphatic diseases ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Tissue Distribution ,Health and Medicine ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Research Articles ,030304 developmental biology ,CD20 ,0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Lymphoma, Non-Hodgkin ,TOR Serine-Threonine Kinases ,Imidazoles ,SciAdv r-articles ,HLA-DR Antigens ,medicine.disease ,Antigens, CD20 ,Xenograft Model Antitumor Assays ,3. Good health ,Lymphoma ,Non-Hodgkin's lymphoma ,Disease Models, Animal ,Treatment Outcome ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Quinolines ,Nanoparticles ,Drug carrier ,Research Article - Abstract
Dual pretargeting with anti-CD20 and anti–HLA-DR allows effective therapeutic delivery of a BEZ235 nanoformulation to NHL cells., Overactivation of the PI3K/mTOR signaling has been identified in non-Hodgkin’s lymphoma. BEZ235 is an effective dual PI3K/mTOR inhibitor, but it was withdrawn from early-phase clinical trials owing to poor solubility and on-target/off-tumor toxicity. Here, we developed a nanoparticle (NP)–based pretargeted system for the therapeutic delivery of BEZ235 to CD20- and HLA-DR–expressing lymphoma cells for targeted therapy. The pretargeted system is composed of dibenzocyclooctyne-functionalized anti-CD20 and anti-Lym1 antibodies as the tumor-targeting components and azide-functionalized BEZ235-encapsulated NPs as the effector drug carrier. Using lymphoma cell lines with different CD20 and HLA-DR antigen densities as examples, we demonstrate that the dual antibody pretargeted strategy effectively raises the number of NPs retained on the target tumor cells and improves the in vitro and in vivo antitumor activity of BEZ235 through the inhibition of the PI3K/mTOR pathway. Our data demonstrate that the NP-based pretargeted system improves the therapeutic window of small-molecule kinase inhibitor.
- Published
- 2019
49. Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells (CTCs)
- Author
-
Sin jung Park, Seungpyo Hong, Ja Hye Myung, and Andrew Z. Wang
- Subjects
0301 basic medicine ,Pharmaceutical Science ,Nanotechnology ,Tumor cells ,Cell Separation ,Article ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Biomimetic Materials ,Neoplasms ,Biomarkers, Tumor ,Humans ,Medicine ,Personalized therapy ,Liquid biopsy ,business.industry ,Cancer ,Neoplastic Cells, Circulating ,medicine.disease ,Nanostructures ,Solid tissue ,030104 developmental biology ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Multivalent binding ,business - Abstract
Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity. Among many approaches that are currently under development, this review paper focuses on a unique, promising approach that takes advantages of naturally occurring processes achievable through application of nanotechnology to realize significant improvement in sensitivity and specificity of CTC capture. We provide an overview of successful outcome of this biomimetic CTC capture system in detection of tumor cells from in vitro, in vivo, and clinical pilot studies. We also emphasize the clinical impact of CTCs as biomarkers in cancer diagnosis and predictive prognosis, which provides a cost-effective, minimally invasive method that potentially replaces or supplements existing methods such as imaging technologies and solid tissue biopsy. In addition, their potential prognostic values as treatment guidelines and that ultimately help to realize personalized therapy are discussed.
- Published
- 2018
50. Bespoke Pretargeted Nanoradioimmunotherapy for the Treatment of Non-Hodgkin Lymphoma
- Author
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Ashutosh Tripathy, Andrew Z. Wang, Seungpyo Hong, Steven I. Park, Kyle Wagner, Carolina Lin, and Kin Man Au
- Subjects
0301 basic medicine ,Dendrimers ,Immunoconjugates ,General Physics and Astronomy ,Article ,Mice ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Tissue Distribution ,Yttrium Radioisotopes ,General Materials Science ,Pretargeted Radioimmunotherapy ,Pretargeting ,biology ,Effector ,business.industry ,Lymphoma, Non-Hodgkin ,Immunogenicity ,General Engineering ,Antibodies, Monoclonal ,Radioimmunotherapy ,Antigens, CD20 ,medicine.disease ,Lymphoma ,Clinical trial ,Nanomedicine ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Radiopharmaceuticals ,Antibody ,business ,Ligation - Abstract
Non-Hodgkin lymphoma (NHL) is one of the most common types of hematologic malignancies. Pretargeted radioimmunotherapy (PRIT), the sequential administration of a bispecific antibody-based primary tumor-targeting component followed by a radionucleotide-labeled treatment effector, has been developed to improve the treatment efficacy and to reduce the side effects of conventional RIT. Despite the preclinical success of PRIT, clinical trials revealed that the immunogenicity of the bispecific antibody as well as the presence of competing endogenous effector molecules often compromised the treatment. One strategy to improve PRIT is to utilize bio-orthogonal ligation reactions to minimize immunogenicity and improve targeting. Herein, we report a translatable pretargeted nanoradioimmunotherapy strategy for the treatment of NHL. This pretargeting system is composed of a dibenzylcyclooctyne (DBCO)-functionalized anti-CD20 antibody (α-CD20) tumor-targeting component and an azide- and yttrium-90-((90)Y) dual-functionalized dendrimer. The physicochemical properties of both pretargeting components have been extensively studied. We demonstrated that an optimized dual-functionalized dendrimer can undergo rapid strain-promoted azide–alkyne cycloaddition with the DBCO-functionalized α-CD20 at the physiological conditions. The treatment effector in our pretargeting system can not only selectively deliver radionucleotides to the target tumor cells but also increase the complement-dependent cytotoxicity of α-CD20 and thus enhance the antitumor effects, as justified by comprehensive in vitro and in vivo studies in mouse NHL xenograft and disseminated models.
- Published
- 2018
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