Browsing by Subject "Cancer treatment"
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Item Open Access Cardiovascular comorbidities and survival of lung cancer patients: Medicare data based analysis.(Lung Cancer, 2017-06-05) Kravchenko, Julia; Berry, Mark; Arbeev, Konstantin; Lyerly, H Kim; Yashin, Anatoly; Akushevich, IgorOBJECTIVES: To evaluate the role of cardiovascular disease (CVD) comorbidity in survival of patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The impact of seven CVDs (at the time of NSCLC diagnosis and during subsequent follow-up) on overall survival was studied for NSCLC patients aged 65+ years using the Surveillance, Epidemiology, and End Results data linked to the U.S. Medicare data, cancer stage- and treatment-specific. Cox regression was applied to evaluate death hazard ratios of CVDs in univariable and multivariable analyses (controlling by age, TNM statuses, and 78 non-CVD comorbidities) and to investigate the effects of 128 different combinations of CVDs on patients' survival. RESULTS: Overall, 95,167 patients with stage I (n=29,836, 31.4%), II (n=5133, 5.4%), IIIA (n=11,884, 12.5%), IIIB (n=18,020, 18.9%), and IV (n=30,294, 31.8%) NSCLC were selected. Most CVDs increased the risk of death for stages I-IIIB patients, but did not significantly impact survival of stage IV patients. The worse survival of patients was associated with comorbid heart failure, myocardial infarction, and cardiac arrhythmias that occurred during a period of follow-up: HRs up to 1.85 (p<0.001), 1.96 (p<0.05), and 1.67 (p<0.001), respectively, varying by stage and treatment. The presence of hyperlipidemia at baseline (HR down to 0.71, p<0.05) was associated with better prognosis. Having multiple co-existing CVDs significantly increased mortality for all treatments, especially for stages I and II patients treated with surgery (HRs up to 2.89, p<0.05) and stages I-IIIB patients treated with chemotherapy (HRs up to 2.59, p<0.001) and chemotherapy and radiotherapy (HRs up to 2.20, p<0.001). CONCLUSION: CVDs impact the survival of NSCLC patients, particularly when multiple co-existing CVDs are present; the impacts vary by stage and treatment. This data should be considered in improving cancer treatment selection process for such potentially challenging patients as the elderly NSCLC patients with CVD comorbidities.Item Open Access Multifunctional Gold Nanostars for Cancer Theranostics(2016) Liu, YangThe prevalence of cancer has increasingly become a significant threat to human health and as such, there exists a strong need for developing novel methods for early detection and effective therapy. Nanotheranostics, a combination of diagnostic and therapeutic functions into a single nanoplatform, has great potential to be used for cancer management by allowing detection, real-time tracking, image-guided therapy and therapeutic response monitoring. Gold nanostars (GNS) with tip-enhanced plasmonics have become one of the most promising platforms for cancer nanotheranostics. This work is aimed at addressing the challenges of sensitive cancer detection, metastasis treatment and recurrence prevention by combining state-of-the-art nanotechnology, molecular imaging and immunotherapy. A multifunctional GNS nanoprobe is developed with capabilities ranging from non-invasive, multi-modality cancer detection using positron emission tomography (PET), magnetic resonance imaging (MRI) and X-ray computed tomography (CT), to intraoperative tumor margin delineation with surface enhanced Raman spectroscopy (SERS) and high-resolution nanoprobe tracking with two-photon photoluminescence (TPL), as well as cancer treatment with photoimmunotherapy. The GNS nanoprobe with PET scans is particularly exceptional in detecting brain malignancies as small as 0.5 mm. To the best of our knowledge, the developed GNS nanoprobe for PET imaging provides the most sensitive means of brain tumor detection reported so far. In addition, the GNS nanoprobe exhibits superior performance as photon-to-heat transducer and can be used for specific photothermal therapy (PTT). More importantly, GNS-mediated PTT combined with checkpoint inhibitor immunotherapy has been found to trigger a memorized immunoresponse to treat cancer metastasis and prevent recurrence in mouse model studies. Furthermore, a 6-month in vivo toxicity study including body weight monitoring, blood chemistry test and histopathology examination demonstrate GNS nanoparticles’ biocompatibility. Therefore, the multifunctional GNS nanoprobe exhibits superior cancer detection and treatment capabilities and has great promise for future clinical translation in cancer management.
Item Embargo RNA Aptamers that Internalize into Cancer Cells for Drug Delivery(2023) Song, XiruiThere has been a long history of humans fighting against cancer. Conventional treatments including surgery, radiation therapy, and chemotherapy remain the mainstream approaches, but an increasing understanding of tumor formation and advances in technology have revealed a new approach to cancer treatment: personalized medicine. Personalized medicine considers tumor heterogeneity and tailors treatments to individual patients based on their genetic information and their tumors. Targeted therapy, for example, could precisely attack specific types of cells that express targeted proteins. In recent years, a subclass of targeted therapy, antibody-drug conjugates (ADC), has received vast clinical attention due to their ability to deliver highly toxic drugs to cancer cells and effectively kill them while sparing healthy cells. Intrigued by the working philosophy of ADCs while acknowledging their limitations, a group of scientists, including our lab, proposed the use of aptamers to create a new class of targeted therapeutics. Aptamers are RNA or DNA ligands that do not require humanization and pose minimal immunogenic risks to patients. Previously, our group reported an RNA aptamer, named E3, which was selected to target prostate cancer cells and demonstrated the ability to effectively eliminate cancer cells when conjugated with drugs. Here, I observe that E3 can also target a broad range of other cancer types, leading me to investigate its molecular target. The following study shows that the E3 aptamer targets human transferrin receptor 1 (hTfR) to enter the cancer cells, consistent with the upregulated expression of hTfR in most cancer types. However, I encountered challenges in the next-step laboratory development of E3 since it did not exhibit cross-reactivity in murine cells. Therefore, I demonstrated that E3 also targets canine cancer cells, which highlights the potential to test E3 in canine models. To further develop a TfR targeting aptamer that can work in both mouse models and against human cancer, I performed a new selection for an aptamer using 2’OMe A, C, U, and 2’OH G modified RNA library that can recognize both human and murine TfR with better resistance for nuclease degradation. Additionally, a non-transferrin (Tf) competing TfR-aptamer is also identified in the study with more nuclease resistance. The results of this study offer several potential weapons used for treating cancers. E3 aptamer targeting hTfR works well in human cancer xenograft mouse models but encounters challenges for characterizations in vivo. Therefore, I select and report a panel of TfR-targeting aptamers that can be used for mouse study or clinical development. Through this study, I aim to contribute to the advancement of targeted delivery and improve drug efficacy in cancer patients.