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1.
Clin Obes ; : e12660, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602005

RESUMO

To harmonise computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) body composition measurements allowing easy conversion in longitudinal assessments and across cohorts to assess cardiometabolic risk and disease. Retrospective cross-sectional observational study from 1996 to 2008 included participants in the Pennington Center Longitudinal Study (PCLS) (N = 1967; 571 African American/1396 White). Anthropometrics, whole-body DXA and abdominal CT images were obtained. Multi-layer segmentation techniques (Analyze; Rochester, MN) quantified visceral adipose tissue (VAT). Clinical biomarkers were obtained from routine blood samples. Linear models were used to predict CT-VAT from DXA-VAT and examine the effects of traditional biomarkers on cross-sectional-VAT. Predicted CT-VAT was highly associated with measured CT-VAT using ordinary least square linear regression analysis and random forest models (R2 = 0.84; 0.94, respectively, p < .0001). Model stratification effects showed low variability between races and sexes. Overall, associations between measured CT-VAT and DXA-predicted CT-VAT were good (R2 > 0.7) or excellent (R2 > 0.8) and improved for all stratification groups except African American men using random forest models. The clinical effects on measured CT-VAT and DXA-VAT showed no significant clinical difference in the measured adipose tissue areas (mean difference = 0.22 cm2). Random forest modelling seamlessly predicts CT-VAT from measured DXA-VAT to a degree of accuracy that falls within the bounds of universally accepted standard error.

2.
Transl Med UniSa ; 25(1): 16-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143509

RESUMO

Introduction: Ineffective anticancer therapy can result in unnecessary toxicity and the development of resistant clones. Many types of solid tumors, including head and neck squamous cell carcinoma, have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. Materials and methods: Selectively enriched CSCs from primary cancer cell cultures can be used in a chemosensitivity assay for a functional test (ChemoID) that uses patients' live tumor cells to indicate which chemotherapy agent (or "combinations") will kill not only the bulk of tumor cells but also the CSCs that are known to cause cancer to recur. This study aimed to show the potential of testing the sensitivity of CSCs enriched from oral cancer patients' biopsies to conventional chemotherapies. A case series of eleven patients affected by advanced oral squamous cell carcinoma (OSCC) have been included in this study. We compared the results of the CSC assay among all the patients and found that there was variability in the chemotherapy response predicted by the assay. Results: Variability in chemotherapy response was found by the CSC assay in advanced OSCC patients suggesting more precise and personalized therapies to the Oncologist. Conclusions: Variability in chemosensitivity for OSCC warrants the need to investigate further the use of the assay in larger cohorts to gain a broader understanding of the utility of the clinical test.

3.
Circ Cardiovasc Imaging ; 16(9): e015145, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37655462

RESUMO

BACKGROUND: Current clinical guidelines recommend a coronary artery calcium (CAC) score of 100 Agatston Units or demographic-specific 75th percentile as high-risk thresholds for guiding atherosclerotic cardiovascular disease preventive therapy. Meanwhile, low CAC can help derisk individuals who may safely defer statin therapy. However, limited data from the early 2000s, including just 208 older Black individuals, inform CAC percentiles for adults aged 75 to 85 years, and none have been established in adults aged ≥85 years. This study aims to characterize the distribution of CAC and establish demographic-specific CAC percentiles in the population aged ≥75 years. METHODS: We assessed 2886 participants aged ≥75 years without clinical coronary heart disease from the ARIC study (Atherosclerosis Risk in Communities) visit 7 (2018-2019; n=2217) and the MESA (Multi-Ethnic Study of Atherosclerosis) visit 5 (2010-2011; n=669). Prevalence of any CAC >0 and sex- and race-specific CAC percentiles across age were estimated nonparametrically with locally weighted regression models and pooled residual ranking. RESULTS: The median age was 80 (interquartile interval, 77-83) years, and 60% were female. The prevalence of zero CAC was lowest in White males (4%), followed by Black males (13%), White females (14%), and highest in Black females (18%). Regardless of sex and race, most participants had CAC>100 (62.5%). CAC scores increased with age, with CAC identified in ≈95% of participants aged ≥90 years across sex-race subgroups. The 75th percentile corresponded to higher CAC scores for Black older adults (n=741), especially females, than currently used thresholds. CONCLUSIONS: In community-dwelling adults aged ≥75 years free of clinical coronary heart disease, the prevalence of zero CAC was 11%, and CAC >100 as a threshold for high ASCVD risk would categorize most of this older population as high risk. Demographic-specific CAC percentiles from this study are a valuable tool for interpreting CAC in the population aged ≥75 years.


Assuntos
Aterosclerose , Cálcio , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Vasos Coronários/diagnóstico por imagem , População Negra , Demografia
4.
J Surg Res ; 292: 190-196, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37633248

RESUMO

INTRODUCTION: Anatomic distribution of adipose tissue has demonstrated variable associations with hypercoagulability. Utilizing a retrospective analysis of a previously enrolled prospective cohort, we assessed computed tomography (CT) scan-based anthropometric and volumetric measures of adiposity as predictors of postinjury hypercoagulability. METHODS: Segmentation analysis of arrival CT scans in significantly injured patients at a single level-I trauma center enrolled from December 2017 to August 2021 were analyzed for anthropometric indices of waist circumference (WC) and sagittal abdominal diameter (SAD), and volumetric parameters of visceral adipose tissue, superficial/deep subcutaneous adipose tissue, psoas/paravertebral muscle volume, and abdominal wall muscle volume. Associations with thromboelastography (TEG) were explored. RESULTS: Data from 91 patients showed strong correlations between body mass index and standard anthropometric measures of WC and SAD (P < 0.001); calculated volumes of subcutaneous adipose tissue and visceral adipose tissue (P < 0.001); and ratios of subcutaneous adipose:psoas muscle (SP ratio) and visceral adipose:psoas muscle ratio (both with P < 0.001, respectively). Correlation between TEG maximal amplitude (MA) and body mass index and SAD were not significant, with only weak correlation between TEG-MA and WC (r = 0.238, P = 0.041). Moderate but significant correlations existed between SP ratio and TEG-MA (r = 0.340, P = 0.005), but not visceral adipose:psoas muscle ratio (r = 0.159, P = 0.198). The relationship between TEG-MA and SP ratio remained significant when adjusted for injury severity score and lactate level (b = 0.302, P = 0.001). CONCLUSIONS: SP ratio is more strongly correlated with TEG-MA than standard obesity measures, and independently predicts increasing clot strength/stability after injury. Coagulation-relevant measures of sarcopenic obesity can be measured on CT scan, and may be used to optimize thromboprophylaxis strategies for obese injured patients.


Assuntos
Trombofilia , Tromboembolia Venosa , Humanos , Adiposidade , Estudos Retrospectivos , Estudos Prospectivos , Anticoagulantes , Obesidade/complicações , Índice de Massa Corporal , Gordura Intra-Abdominal/diagnóstico por imagem
5.
Neurooncol Adv ; 5(1): vdad055, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37287692

RESUMO

Background: Glioblastoma (GBM) is a lethal disease. At least in part, the recurrence of GBM is caused by cancer stem cells (CSCs), which are resistant to chemotherapy. Personalized anticancer therapy against CSCs can improve treatment outcomes. We present a prospective cohort study of 40 real-world unmethylated Methyl-guanine-methyl-transferase-promoter GBM patients treated utilizing a CSC chemotherapeutics assay-guided report (ChemoID). Methods: Eligible patients who underwent surgical resection for recurrent GBM were included in the study. Most effective chemotherapy treatments were chosen based on the ChemoID assay report from a panel of FDA-approved chemotherapies. A retrospective chart review was conducted to determine OS, progression-free survival, and the cost of healthcare costs. The median age of our patient cohort was 53 years (24-76). Results: Patients treated prospectively with high-response ChemoID-directed therapy, had a median overall survival (OS) of 22.4 months (12.0-38.4) with a log-rank P = .011, compared to patients who could be treated with low-response drugs who had instead an OS of 12.5 months (3.0-27.4 months). Patients with recurrent poor-prognosis GBM treated with high-response therapy had a 63% probability to survive at 12 months, compared to 27% of patients who were treated with low-response CSC drugs. We also found that patients treated with high-response drugs on average had an incremental cost-effectiveness ratio (ICER) of $48,893 per life-year saved compared to $53,109 of patients who were treated with low-response CSC drugs. Conclusions: The results presented here suggest that the ChemoID Assay can be used to individualize chemotherapy choices to improve poor-prognosis recurrent GBM patient survival and to decrease the healthcare cost that impacts these patients.

7.
Cell Rep Med ; 4(5): 101025, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37137304

RESUMO

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Resultado do Tratamento , Células-Tronco Neoplásicas
8.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982548

RESUMO

Currently, the response to cancer treatments is highly variable, and severe side effects and toxicity are experienced by patients receiving high doses of chemotherapy, such as those diagnosed with triple-negative breast cancer. The main goal of researchers and clinicians is to develop new effective treatments that will be able to specifically target and kill tumor cells by employing the minimum doses of drugs exerting a therapeutic effect. Despite the development of new formulations that overall can increase the drugs' pharmacokinetics, and that are specifically designed to bind overexpressed molecules on cancer cells and achieve active targeting of the tumor, the desired clinical outcome has not been reached yet. In this review, we will discuss the current classification and standard of care for breast cancer, the application of nanomedicine, and ultrasound-responsive biocompatible carriers (micro/nanobubbles, liposomes, micelles, polymeric nanoparticles, and nanodroplets/nanoemulsions) employed in preclinical studies to target and enhance the delivery of drugs and genes to breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Portadores de Fármacos , Micelas , Lipossomos/uso terapêutico , Sistemas de Liberação de Medicamentos
9.
Biomedicines ; 10(6)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35740462

RESUMO

Immunotherapy has been extensively explored in recent years with encouraging results in selected types of cancer. Such success aroused interest in the expansion of such indications, requiring a deep understanding of the complex role of the immune system in carcinogenesis. The definition of hot vs. cold tumors and the role of the tumor microenvironment enlightened the once obscure understanding of low response rates of solid tumors to immune check point inhibitors. Although the major scope found in the literature focuses on the T cell modulation, the innate immune system is also a promising oncolytic tool. The unveiling of the tumor immunosuppressive pathways, lead to the development of combined targeted therapies in an attempt to increase immune infiltration capability. Oncolytic viruses have been explored in different scenarios, in combination with various chemotherapeutic drugs and, more recently, with immune check point inhibitors. Moreover, oncolytic viruses may be engineered to express tumor specific pro-inflammatory cytokines, antibodies, and antigens to enhance immunologic response or block immunosuppressive mechanisms. Development of preclinical models capable to replicate the human immunologic response is one of the major challenges faced by these studies. A thorough understanding of immunotherapy and oncolytic viruses' mechanics is paramount to develop reliable preclinical models with higher chances of successful clinical therapy application. Thus, in this article, we review current concepts in cancer immunotherapy including the inherent and synthetic mechanisms of immunologic enhancement utilizing oncolytic viruses, immune targeting, and available preclinical animal models, their advantages, and limitations.

10.
J Craniofac Surg ; 33(3): e245-e247, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34406154

RESUMO

ABSTRACT: Mandibular fractures are the third most prevalent maxillofacial traumatic events. Surgical approaches to the condyle are a debated topic. This study describes a mini-invasive technique for condylar fracture reduction. The patient of this study suffered multiple traumatic injuries including a carotid artery dissecting aneurysm, which contraindicated the standard open reduction and internal fixation technique. The novel minimally invasive technique involves intraoral access and fracture fragment realignment using a periosteal elevator, a molar occlusal splint, and intermaxillary fixation after intraoperative radiologic imaging confirmation of condyle reposition.The approach avoids skin incisions and tissue dissection, with good aesthetic outcomes and facial nerve preservation. This technique proved to be safe and simple to be less demanding for the patient, with a shorter recovery time than experienced with other techniques.The results suggest this technique is a good option for the surgical treatment of condylar neck fractures showing favorable rim morphology with primary stability after reduction.


Assuntos
Côndilo Mandibular , Fraturas Mandibulares , Estética Dentária , Fixação Interna de Fraturas/métodos , Humanos , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/lesões , Côndilo Mandibular/cirurgia , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Redução Aberta , Resultado do Tratamento
11.
Int J Mol Sci ; 22(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768922

RESUMO

Gene therapy has continuously evolved throughout the years since its first proposal to develop more specific and effective transfection, capable of treating a myriad of health conditions. Viral vectors are some of the most common and most efficient vehicles for gene transfer. However, the safe and effective delivery of gene therapy remains a major obstacle. Ultrasound contrast agents in the form of microbubbles have provided a unique solution to fulfill the need to shield the vectors from the host immune system and the need for site specific targeted therapy. Since the discovery of the biophysical and biological effects of microbubble sonification, multiple developments have been made to enhance its applicability in targeted drug delivery. The concurrent development of viral vectors and recent research on dual vector strategies have shown promising results. This review will explore the mechanisms and recent advancements in the knowledge of ultrasound-mediated microbubbles in targeting gene and drug therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Microbolhas/uso terapêutico , Neoplasias/tratamento farmacológico , Ultrassonografia/métodos , Técnicas de Transferência de Genes , Vetores Genéticos/farmacologia , Humanos , Resultado do Tratamento
12.
Artigo em Inglês | MEDLINE | ID: mdl-34796266

RESUMO

BACKGROUND: Disease recurrence and progression of ovarian cancer is a common event, which is accompanied by the development of platinum-resistant or refractory disease. The presence of chemo-resistant Cancer Stem Cells (CSCs) contribute to tumor propagation, maintenance, and treatment resistance of this difficult to treat disease. We have developed ChemoID, a cytotoxic synergy assay against CSCs that identifies the most effective chemotherapy treatment from a panel of FDA-approved chemotherapies using fresh cancer biopsies. PATIENTS AND METHODS: Ascites or interventional radiology biopsies were collected under physician order from 78 consecutive patients affected by 3rd relapsed ovarian cancer. Test results from the assay were used when possible to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, if needed. A chart analysis and review of CT and PET scans were performed to determine patients' outcomes for tumor response, Progression-Free Survival (PFS), and Overall Survival (OS). RESULTS: We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs drug response assay had an improvement in their median PFS and OS when compared to historical median PFS and OS and/or when compared to patients who could not receive high cell kill chemotherapies (PFS low cell kill 3.5 months vs. high cell kill 12.0 months; OS low cell kill 6.0 months vs. high cell kill 15.0 months). CONCLUSION: This data indicates that the drug cytotoxicity assay aimed at targeting CSCs may be a useful tool for optimizing treatment selection when first-line therapy fails, and when there are multiple clinically-acceptable and -equivalent treatments available.

13.
Radiol Case Rep ; 16(8): 2274-2279, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34194590

RESUMO

Immunoglobulin G4-related aortitis (IgG4-RA) is histologically characterized by the infiltration of IgG4 positive plasma cells and fibrosis in systemic organs and the elevation of serum IgG4 levels. The cardiovascular system is commonly involved with various possible presentations such as aortitis, arteritis, periaortitis, periarteritis, and inflammatory aneurysm. We present a case of a 48-year-old male without known previous medical history, admitted for further workup of long-standing chest pain and shortness of breath with suspected aortic dissection on initial assessment. Investigation with computed tomography angiography (CTA) and magnetic resonance angiography (MRA) indicated severe thoracic and abdominal aortoarteritis associated with an ascending thoracic aortic aneurysm, which was confirmed to be IgG4-RA on histopathologic analysis. Thoracic and abdominal IgG4-RA clinical and radiological presentation may simulate other causes of acute aortic syndrome such as aortic dissection, atherosclerotic aneurysm and inflammatory conditions. Accurate recognition of IgG4-RA diagnostic imaging features are essential for early diagnosis and treatment surveillance.

14.
Dent J (Basel) ; 9(5)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946237

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) frequently affects patients after treatments with bisphosphonates or denosumab, especially with high doses in patients with bone osteoporosis, neoplastic metastases, or possibly anti-angiogenic treatment for cancer. The aim of this article was to show a new treatment planning for stage 2 and stage 3 MRONJ using platelet-rich fibrin (PRF) at the surgical field to enhance healing in association with a new epi-mucosal fixation technique to prevent or treat mandibular fracture. Two cases were treated by epi-mucosa fixation and autologous PRF use for prevention of mandibular fracture risks related to necrotic bone resection or a narrow fracture reduction. Both cases were successfully treated by this new technique of epi-mucosa fixation combined with autologous PRF and achieved good results and good quality of life. Ability to wear prosthesis with good mastication in the absence of side effect such as infection, plate and screw mobilization, pain, and other disabilities or extension of necrosis was reported. After surgical removal of necrotic bone, no infection was detected without any extension of the necrosis.

15.
Radiol Case Rep ; 16(3): 538-542, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33384752

RESUMO

A left ventricle pseudoaneurysm (LV PSA) is defined as a free wall rupture of the left ventricle contained by the adjacent pericardial tissue. This rare complication is most commonly encountered following myocardial infarction, trauma, or infection. Surgery is typically warranted to avoid progression to spontaneous rupture, which may potentially lead to cardiac tamponade and death. Cardiac magnetic resonance imaging is the modality of choice to characterize left ventricle morphology and function. Accurate distinction between a pseudoaneurysm and a true aneurysm is crucial, since management and prognosis are significantly different between these 2 entities. We present a case of a 63-year-old male heart transplant recipient, admitted for suspicion of acute cellular rejection, with an unexpected finding of a LV PSA.

16.
Transl Oncol ; 13(12): 100860, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32862103

RESUMO

INTRODUCTION: Disease recurrence and progression of ovarian cancer is common with the development of platinum-resistant or refractory disease. This is due in large part to the presence of chemo-resistant cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. We developed a CSCs drug cytotoxicity assay (ChemoID) to identify the most effective chemotherapy treatment from a panel of FDA approved chemotherapies. METHODS: Ascites and pleural fluid samples were collected under physician order from 45 consecutive patients affected by 3rd-5th relapsed ovarian cancer. Test results from the assay were used to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, as needed. A retrospective chart review of CT and PET scans was used to determine patients' outcomes for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). RESULTS: We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs drug response assay had an improvement in the median PFS corresponding to 5.4 months (3rd relapse), 3.6 months (4th relapse), and 3.9 months (5th relapse) when compared to historical data. Additionally, we observed that ovarian cancer patients identified as non-responders by the CSC drug response assay had 30 times the hazard of death compared to those women that were identified as responders with respective median survivals of 6 months vs. 13 months. We also found that ChemoID treated patients on average had an incremental cost-effectiveness ratio (ICER) between -$18,421 and $7,241 per life-year saved (LYS). CONCLUSIONS: This study demonstrated improved PFS and OS for recurrent ovarian cancer patients treated with assay-guided chemotherapies while decreasing the cost of treatment.

17.
Transl Oncol ; 13(4): 100755, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32197147

RESUMO

BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21-63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0-10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. IMPORTANCE OF THE STUDY: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp's protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient's derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1-10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies.

18.
J Transl Med ; 17(1): 19, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635014

RESUMO

BACKGROUND: Gene transfer to malignant sites using human adenoviruses (hAds) has been limited because of their immunogenic nature and host specificity. Murine cells often lack some of the receptors needed for hAds attachment, thus murine cells are generally non-permissive for human adenoviral infection and replication, which limits translational studies. METHODS: We have developed a gene transfer method that uses a combination of lipid-encapsulated perfluorocarbon microbubbles and ultrasound to protect and deliver hAds to a target tissue, bypassing the requirement of specific receptors. RESULTS: In an in vitro model, we showed that murine TRAMP-C2 and human DU145 prostate cancer cells display a comparable expression pattern of receptors involved in hAds adhesion and internalization. We also demonstrated that murine and human cells showed a dose-dependent increase in the percentage of cells transduced by hAd-GFP (green fluorescent protein) after 24 h and that GFP transgene was efficiently expressed at 48 and 72 h post-transduction. To assess if our image-guided delivery system could effectively protect the hAds from the immune system in vivo, we injected healthy immunocompetent mice (C57BL/6) or mice bearing a syngeneic prostate tumor (TRAMP-C2) with hAd-GFP/MB complexes. Notably, we did not observe activation of innate (TNF-α and IL-6 cytokines), or adaptive immune response (neutralizing antibodies, INF-γ+ CD8+ T cells). CONCLUSIONS: This study brings us a step closer to demonstrating the feasibility of murine cancer models to investigate the clinical translation of image guided site-specific adenoviral gene therapy mediated by ultrasound-targeted microbubble destruction.


Assuntos
Imunidade Adaptativa , Adenovírus Humanos/fisiologia , Imunidade Inata , Imunocompetência , Microbolhas , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Animais , Linhagem Celular Tumoral , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imunidade Humoral , Mediadores da Inflamação/sangue , Integrinas/metabolismo , Interferon gama/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neoplasias da Próstata/sangue
19.
Cureus ; 10(10): e3426, 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30542636

RESUMO

Purpose The definition of radiotherapy target volume is a critical step in treatment planning for all tumor sites. Conventional magnetic resonance imaging (MRI) pulse sequences are used for the definition of the gross target volume (GTV) and the contouring of glioblastoma multiforme (GBM) and meningioma. We propose the use of multiparametric MRI combined with radiomic features to improve the texture-based differentiation of tumor from edema for GTV definition and to differentiate vasogenic from tumor cell infiltration edema. Methods Twenty-five patients with brain tumor and peritumoral edema (PTE) were assessed. Of the enrolled patients, 17 (63 ± 10 years old, six female and 11 male patients) were diagnosed with GBM and eight (64 ± 14 years old, five female and three male patients) with meningioma. A 3 Tesla (3T) MRI scanner was used to scan patients using a 3D multi-echo Gradient Echo (GRE) sequence. After the acquisition process, two experienced neuroradiologists independently used an in-house semiautomatic algorithm to conduct a segmentation of two regions of interest (ROI; edema and tumor) in all patients using functional MRI sequences, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced MRI (DCE-MRI), as well as anatomical MRI sequences-T1-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR). Radiomic (computer-extracted texture) features were extracted from all ROIs through different approaches, including first-, second-, and higher-order statistics, both with and without normalization, leading to the calculation of around 300 different texture parameters for each ROI. Based on the extracted parameters, a least absolute shrinkage and selection operator (LASSO) analysis was used to isolate the parameters that best differentiated edema from tumors while irrelevant parameters were discarded. Results and conclusions The parameters chosen by LASSO were used to perform statistical analyses which allowed identification of the variables with the best discriminant ability in all scenarios. Receiver operating characteristic results showcase both the best single discriminator and the discriminant capacity of the model using all variables selected by LASSO. Excellent results were obtained for patients with GBM with all MRI sequences, with and without normalization; a T1-weighted sequence postcontrast (T1W+C) with normalization offered the best tumor classification (area under the curve, AUC > 0.97). For patients with meningioma, a good model of tumor classification was obtained through the T1-weighted sequence (T1W) without normalization (AUC > 0.71). However, there was no agreement between the results of both radiologists for some MRI sequences analyzed for patients with GBM and meningioma. In conclusion, a small subset of radiomic features showed an excellent ability to distinguish edema from tumor tissue through its most discriminating features.

20.
Cureus ; 10(6): e2895, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-30175001

RESUMO

Transarterial radioembolization using yttrium-90 microspheres is an established and effective treatment for liver malignancies. Determining response to this treatment is difficult due to the radical changes that occur in tissue as a response to radiation. Though accurate assessment of treatment response is paramount for proper patient disposition, there is currently no standardized assessment protocol. Current methods of assessment often consider changes in size, necrosis, vascularity, fluorodeoxyglucose-positron emission tomography FDG-PET metabolic activity, and diffusion using diffusion-weighted magnetic resonance imaging (DWI). Current methods of assessment require a lag time of one to two months post-treatment to determine treatment effectiveness. This delay is a hindrance to obtaining better patient outcomes, giving rise to a need to identify markers for faster determination of treatment efficacy.

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