scholarly journals Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Preliminary Patient Results

2002 ◽  
Vol 1 (3) ◽  
pp. 153535002002021
Author(s):  
Joanne M. Wells ◽  
David A. Mankoff ◽  
Janet F. Eary ◽  
Alexander M. Spence ◽  
Mark Muzi ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Kinetic Analysis ◽  
Cellular Proliferation ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Normal Brain ◽  
Arterial Blood ◽  
Pet Tracer ◽  
Wide Range ◽  
Thymidine Transport

2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. Kinetic analysis of dynamic TdR images was performed to estimate the rate of thymidine transport ( K1t) and thymidine flux ( KTdR) into brain tumors and normal brain. These estimates were compared to MRI and pathologic results. Methods: Twenty patients underwent sequential [11C]CO2 (major TdR metabolite) and TdR PET studies with arterial blood sampling and metabolite analysis. The data were fitted using the five-compartment model described in the companion article. Results: Comparison of model estimates with clinical and pathologic data shows that K1t is higher for MRI contrast enhancing tumors ( p > .001), and KTdR increases with tumor grade ( p > .02). On average, TdR retention was lower after treatment in high-grade tumors. The model was able to distinguish between increased thymidine transport due to blood–brain barrier breakdown and increased tracer retention associated with tumor cell proliferation. Conclusion: Initial analysis of model estimates of thymidine retention and transport show good agreement with the clinical and pathological features of a wide range of brain tumors. Ongoing studies will evaluate its role in measuring response to treatment and predicting outcome.

scholarly journals Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis

2002 ◽  
Vol 1 (3) ◽  
pp. 153535002002021
Author(s):  
Joanne M. Wells ◽  
David A. Mankoff ◽  
Mark Muzi ◽  
Finbarr O'Sullivan ◽  
Janet F. Eary ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Cellular Proliferation ◽  
Compartment Model ◽  
Response To Therapy ◽  
Model Parameters ◽  
Normal Brain ◽  
Identifiability Analysis ◽  
Pet Tracer ◽  
Thymidine Transport

2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors. Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estimate the model parameters, and conducted simulations to determine whether it can distinguish between thymidine transport and retention. Results: Sensitivity and identifiability analysis suggested that the non-CO2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K1t and KTdR could be estimated accurately ( r = .97 and .98 for estimated vs. true parameters) with standard errors < 15%. The model was able to separate increased transport from increased retention associated with tumor proliferation. Conclusion: Our model adequately describes normal brain and brain tumor kinetics for thymidine and its metabolites, and it can provide an estimate of the rate of cellular proliferation in brain tumors.

scholarly journals Maximizing the use of batch production of 18F-FDOPA for imaging of brain tumors to increase availability of hybrid PET/MR imaging in clinical setting

2020 ◽  
Author(s):  
M S Aboian ◽  
R Barajas ◽  
J Shatalov ◽  
V Ravanfar ◽  
E Bahroos ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Amino Acid ◽  
Brain Tumors ◽  
Pet Imaging ◽  
Critical Role ◽  
Normal Brain ◽  
Mri Imaging ◽  
Pet Tracer ◽  
Amino Acid Pet ◽  
The Cost

Abstract Background Amino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of post-radiation changes, but is not commonly used in clinical practice due to high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET. Methods Seventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3-5 patients. The first group of consecutively imaged patients contained three patients, followed by two groups of 5 patients, and last group of 4 patients. Results For each of the patients, standard of care gadolinium enhanced MRI and dynamic PET imaging with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28,321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout. Conclusion Amino acid PET tracers have been shown to play a critical role in characterization of brain tumors but their adaptation to clinical practice has been limited due to high cost of PET. Scheduling patient imaging to maximally utilize the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology.

scholarly journals Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ajaz A. Bhat ◽  
Sabah Nisar ◽  
Selma Maacha ◽  
Tatiana Correa Carneiro-Lobo ◽  
Sabah Akhtar ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Growth Factors ◽  
Intracellular Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Distant Metastases ◽  
Cell Types ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Mesenchymal Transition ◽  
Wide Range

AbstractEsophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases among patients with advanced disease account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, and growth factors, which play a significant role in supporting the growth and aggressive behavior of cancer cells. The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. The molecular changes in the TME are used as biological markers for diagnosis, prognosis, and response to treatment in patients. This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development. In addition, it discusses the wide range of changes and intracellular signaling pathways that occur in the TME. Overall, this is a relatively unexplored field that could provide crucial insights into tumor immunology and encourage the effective application of modulatory cytokine-chemokine therapy to EC.

scholarly journals Movement Disorders in Oncology: From Clinical Features to Biomarkers

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 26
Author(s):  
Luca Marsili ◽  
Alberto Vogrig ◽  
Carlo Colosimo
Keyword(s):  
Brain Tumors ◽  
Movement Disorders ◽  
Clinical Laboratory ◽  
Checkpoint Inhibitors ◽  
Diagnostic Testing ◽  
Response To Treatment ◽  
Immune Checkpoints ◽  
Laboratory Findings ◽  
Antineuronal Antibodies ◽  
Wide Range

Background: the study of movement disorders associated with oncological diseases and anticancer treatments highlights the wide range of differential diagnoses that need to be considered. In this context, the role of immune-mediated conditions is increasingly recognized and relevant, as they represent treatable disorders. Methods: we reappraise the phenomenology, pathophysiology, diagnostic testing, and treatment of movement disorders observed in the context of brain tumors, paraneoplastic conditions, and cancer immunotherapy, such as immune-checkpoint inhibitors (ICIs). Results: movement disorders secondary to brain tumors are rare and may manifest with both hyper-/hypokinetic conditions. Paraneoplastic movement disorders are caused by antineuronal antibodies targeting intracellular or neuronal surface antigens, with variable prognosis and response to treatment. ICIs promote antitumor response by the inhibition of the immune checkpoints. They are effective treatments for several malignancies, but they may cause movement disorders through an unchecked immune response. Conclusions: movement disorders due to focal neoplastic brain lesions are rare but should not be missed. Paraneoplastic movement disorders are even rarer, and their clinical-laboratory findings require focused expertise. In addition to their desired effects in cancer treatment, ICIs can induce specific neurological adverse events, sometimes manifesting with movement disorders, which often require a case-by-case, multidisciplinary, approach.

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

Radiotherapy for Brain Tumors: Current Practice and Future Directions

2020 ◽  
Vol 16 (3) ◽  
pp. 182-195
Author(s):  
Sarah Baker ◽  
Natalie Logie ◽  
Kim Paulson ◽  
Adele Duimering ◽  
Albert Murtha
Keyword(s):  
Brain Tumors ◽  
Treatment Strategies ◽  
Brain Parenchyma ◽  
Benign Tumors ◽  
Tumor Control ◽  
Normal Brain ◽  
Neurocognitive Deficits ◽  
Close Proximity ◽  
Recent Developments ◽  
High Level

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

scholarly journals LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Leptomeningeal Metastasis ◽  
Breast Cancer Cell Lines ◽  
Normal Brain ◽  
Breast Cancers

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

Development and Validation of a New Scoring Tool to Evaluate the Clinical Evolution of Adult Patients with Nonsegmental Vitiligo

Dermatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
María Luisa Peralta-Pedrero ◽  
Denisse Herrera-Bringas ◽  
Karla Samantha Torres-González ◽  
Martha Alejandra Morales-Sánchez ◽  
Fermín Jurado Santa-Cruz ◽  
...  
Keyword(s):  
Body Surface ◽  
Task Force ◽  
Intraclass Correlation ◽  
The Body ◽  
Response To Treatment ◽  
Similar Response ◽  
Clinical Evolution ◽  
Wide Range ◽  
Patient Reported ◽  
Extreme Groups

<b><i>Background:</i></b> Vitiligo has an unpredictable course and a variable response to treatment. Furthermore, the improvement of some vitiligo lesions cannot be considered a guarantee of a similar response to the other lesions. Instruments for patient-reported outcome measures (PROM) can be an alternative to measure complex constructions such as clinical evolution. <b><i>Objective:</i></b> The aim of this study was to validate a PROM that allows to measure the clinical evolution of patients with nonsegmental vitiligo in a simple but standardized way that serves to gather information for a better understanding of the disease. <b><i>Methods:</i></b> The instrument was created through expert consensus and patient participation. For the validation study, a prospective cohort design was performed. The body surface area affected was measured with the Vitiligo Extension Score (VES), the extension, the stage, and the spread by the evaluation of the Vitiligo European Task Force assessment (VETFa). Reliability was determined with test-retest, construct validity through hypothesis testing, discriminative capacity with extreme groups, and response capacity by comparing initial and final measurements. <b><i>Results:</i></b> Eighteen semi-structured interviews and 7 cognitive interviews were conducted, and 4 dermatologists were consulted. The instrument Clinical Evolution-Vitiligo (CV-6) was answered by 119 patients with a minimum of primary schooling. A wide range was observed in the affected body surface; incident and prevalent cases were included. The average time to answer the CV-6 was 3.08 ± 0.58 min. In the test-retest (<i>n</i> = 53), an intraclass correlation coefficient was obtained: 0.896 (95% CI 0.82–0.94; <i>p</i> &#x3c; 0.001). In extreme groups, the mean score was 2 (2–3) and 5 (4–6); <i>p</i> &#x3c; 0.001. The initial CV-6 score was different from the final one and the change was verified with VES and VETFa (<i>p</i> &#x3c; 0.05, <i>n</i> = 92). <b><i>Conclusions:</i></b> The CV-6 instrument allows patient collaboration, it is simple and brief, and it makes it easier for the doctor to focus attention on injuries that present changes at the time of medical consultation.

scholarly journals IMMU-45. CUSTOMIZED LIPID NANOPARTICLES DELIVER NUCLEIC ACIDS TO IMMUNE CELLS IN BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii114-ii114
Author(s):  
Adam Grippin ◽  
Brandon Wummer ◽  
Hector Mendez-Gomez ◽  
Tyler Wildes ◽  
Kyle Dyson ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Nucleic Acids ◽  
Immune Cells ◽  
White Blood Cells ◽  
Lipid Nanoparticles ◽  
Intracranial Tumor ◽  
Innate Immune ◽  
Checkpoint Blockade ◽  
Normal Brain ◽  
Innate Immune Cells

Abstract BACKGROUND Brain tumors are notoriously difficult to treat in part due to their isolation behind the blood brain barrier and their power to suppress antitumor immune responses. We have previously reported cationic liposome formulations capable of delivering immune modulatory nucleic acids to immune cells in various peripheral organs, but there is currently no reliable method to deliver nucleic acids into brain tumors without direct injection into the tumor site. OBJECTIVE Here, we report the development of a customized lipid nanoparticle to deliver immune modulatory nucleic acids to immune cells in brain tumors. APPROACH Cationic liposomes composed of varying lipid combinations were evaluated for their ability to deliver functional mRNA and siRNA to innate immune cells in vitro and in intracranial tumor models. Nucleic acids were labelled with Cy3 to monitor particle distribution in vivo. RESULTS Lipids composed of DOTAP and cholesterol selectively delivered mRNA and siRNA to intracranial GL261 and KR158b tumors. Interestingly, these particles selectively delivered these nucleic acids to CD45+ white blood cells with minimal delivery to CD45- tumor cells or normal brain tissue. Encapsulation of siRNA blocking programmed death ligand 1 (PDL1) significantly reduced PDL1 expression on innate immune cells in brain tumors, with the greatest effects on tumor-associated macrophages. Co-administration of systemic checkpoint blockade with intravenous administration of these lipid nanoparticles bearing PDL1 siRNA enabled systemic and intratumoral checkpoint blockade, leading to 37% long term survivorship in an otherwise fatal intracranial tumor model. CONCLUSIONS Our customized lipid nanoparticles enable potent intratumoral immune modulation via delivery of nucleic acids to immune cells in brain tumors.

scholarly journals Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System

2021 ◽  
Vol 11 (6) ◽  
pp. 475
Author(s):  
Joaquín Dopazo ◽  
Douglas Maya-Miles ◽  
Federico García ◽  
Nicola Lorusso ◽  
Miguel Ángel Calleja ◽  
...  
Keyword(s):  
Public Health ◽  
Health Care ◽  
Clinical Practice ◽  
Personalized Medicine ◽  
Local Level ◽  
Individual Variability ◽  
Response To Therapy ◽  
Control Measures ◽  
Response To Treatment ◽  
Specific Patient

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems.

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