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  1. Article ; Online: Pretherapy Ferumoxytol-enhanced MRI to Predict Response to Liposomal Irinotecan in Metastatic Breast Cancer.

    Ravi, Harshan / Arias-Lorza, Andres M / Costello, James R / Han, Hyo Sook / Jeong, Daniel K / Klinz, Stephan G / Sachdev, Jasgit C / Korn, Ronald L / Raghunand, Natarajan

    Radiology. Imaging cancer

    2023  Volume 5, Issue 2, Page(s) e220022

    Abstract: Purpose To investigate ferumoxytol (FMX)-enhanced MRI as a pretreatment predictor of response to liposomal irinotecan (nal-IRI) for thoracoabdominal and brain metastases in women with metastatic breast cancer (mBC). Materials and Methods In this phase 1 ... ...

    Abstract Purpose To investigate ferumoxytol (FMX)-enhanced MRI as a pretreatment predictor of response to liposomal irinotecan (nal-IRI) for thoracoabdominal and brain metastases in women with metastatic breast cancer (mBC). Materials and Methods In this phase 1 expansion trial (ClinicalTrials.gov identifier, NCT01770353; 27 participants), 49 thoracoabdominal (19 participants; mean age, 48 years ± 11 [SD]) and 19 brain (seven participants; mean age, 54 years ± 8) metastases were analyzed on MR images acquired before, 1-4 hours after, and 16-24 hours after FMX administration. In thoracoabdominal metastases, tumor transverse relaxation rate (R*
    MeSH term(s) Female ; Humans ; Middle Aged ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/drug therapy ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Ferrosoferric Oxide ; Irinotecan/therapeutic use ; Magnetic Resonance Imaging/methods
    Chemical Substances Ferrosoferric Oxide (XM0M87F357) ; Irinotecan (7673326042)
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2638-616X
    ISSN (online) 2638-616X
    DOI 10.1148/rycan.220022
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  2. Article ; Online: Identification of sarcomatoid differentiation in renal cell carcinoma by machine learning on multiparametric MRI.

    Mazin, Asim / Hawkins, Samuel H / Stringfield, Olya / Dhillon, Jasreman / Manley, Brandon J / Jeong, Daniel K / Raghunand, Natarajan

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3785

    Abstract: Sarcomatoid differentiation in RCC (sRCC) is associated with a poor prognosis, necessitating more aggressive management than RCC without sarcomatoid components (nsRCC). Since suspected renal cell carcinoma (RCC) tumors are not routinely biopsied for ... ...

    Abstract Sarcomatoid differentiation in RCC (sRCC) is associated with a poor prognosis, necessitating more aggressive management than RCC without sarcomatoid components (nsRCC). Since suspected renal cell carcinoma (RCC) tumors are not routinely biopsied for histologic evaluation, there is a clinical need for a non-invasive method to detect sarcomatoid differentiation pre-operatively. We utilized unsupervised self-organizing map (SOM) and supervised Learning Vector Quantizer (LVQ) machine learning to classify RCC tumors on T2-weighted, non-contrast T1-weighted fat-saturated, contrast-enhanced arterial-phase T1-weighted fat-saturated, and contrast-enhanced venous-phase T1-weighted fat-saturated MRI images. The SOM was trained on 8 nsRCC and 8 sRCC tumors, and used to compute Activation Maps for each training, validation (3 nsRCC and 3 sRCC), and test (5 nsRCC and 5 sRCC) tumor. The LVQ classifier was trained and optimized on Activation Maps from the 22 training and validation cohort tumors, and tested on Activation Maps of the 10 unseen test tumors. In this preliminary study, the SOM-LVQ model achieved a hold-out testing accuracy of 70% in the task of identifying sarcomatoid differentiation in RCC on standard multiparameter MRI (mpMRI) images. We have demonstrated a combined SOM-LVQ machine learning approach that is suitable for analysis of limited mpMRI datasets for the task of differential diagnosis.
    MeSH term(s) Algorithms ; Carcinoma, Renal Cell/diagnosis ; Carcinoma, Renal Cell/diagnostic imaging ; Carcinoma, Renal Cell/pathology ; Cell Differentiation/genetics ; Diagnosis, Differential ; Female ; Humans ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/diagnostic imaging ; Kidney Neoplasms/pathology ; Machine Learning ; Male ; Multiparametric Magnetic Resonance Imaging
    Language English
    Publishing date 2021-02-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-83271-4
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  3. Article ; Online: Novel clinical and radiomic predictors of rapid disease progression phenotypes among lung cancer patients treated with immunotherapy: An early report.

    Tunali, Ilke / Gray, Jhanelle E / Qi, Jin / Abdalah, Mahmoud / Jeong, Daniel K / Guvenis, Albert / Gillies, Robert J / Schabath, Matthew B

    Lung cancer (Amsterdam, Netherlands)

    2019  Volume 129, Page(s) 75–79

    Abstract: Objectives: Immune-checkpoint blockades have exhibited durable responses and improved long-term survival in a subset of advanced non-small cell lung cancer (NSCLC) patients. However, highly predictive markers of positive and negative responses to ... ...

    Abstract Objectives: Immune-checkpoint blockades have exhibited durable responses and improved long-term survival in a subset of advanced non-small cell lung cancer (NSCLC) patients. However, highly predictive markers of positive and negative responses to immunotherapy are a significant unmet clinical need. The objective of this study was to identify clinical and computational image-based predictors of rapid disease progression phenotypes in NSCLC patients treated with immune-checkpoint blockades.
    Materials and methods: Using time-to-progression (TTP) and/or tumor growth rates, rapid disease progression phenotypes were developed including hyperprogressive disease. The pre-treatment baseline predictors that were used to identify these phenotypes included patient demographics, clinical data, driver mutations, hematology data, and computational image-based features (radiomics) that were extracted from pre-treatment computed tomography scans. Synthetic Minority Oversampling Technique (SMOTE) was used to subsample minority groups to eliminate classification bias. Patient-level probabilities were calculated from the final clinical-radiomic models to subgroup patients by progression-free survival (PFS).
    Results: Among 228 NSCLC patients treated with single agent or double agent immunotherapy, we identified parsimonious clinical-radiomic models with modest to high ability to predict rapid disease progression phenotypes with area under the receiver-operator characteristics ranging from 0.804 to 0.865. Patients who had TTP < 2 months or hyperprogressive disease were classified with 73.41% and 82.28% accuracy after SMOTE subsampling, respectively. When the patient subgroups based on patient-level probabilities were analyzed for survival outcomes, patients with higher probability scores had significantly worse PFS.
    Conclusions: The models found in this study have potential important translational implications to identify highly vulnerable NSCLC patients treated with immunotherapy that experience rapid disease progression and poor survival outcomes.
    MeSH term(s) Aged ; Biomarkers, Pharmacological ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/therapy ; Computational Biology ; Diagnostic Imaging ; Disease Progression ; Female ; Humans ; Immunotherapy/methods ; Lung/diagnostic imaging ; Lung Neoplasms/diagnosis ; Lung Neoplasms/therapy ; Male ; Phenotype ; Prognosis ; Tomography, X-Ray Computed/methods
    Chemical Substances Biomarkers, Pharmacological
    Language English
    Publishing date 2019-01-23
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2019.01.010
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  4. Article ; Online: Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia.

    Nanjappa, Sowmya / Jeong, Daniel K / Muddaraju, Manjunath / Jeong, Katherine / Hill, Ebone D / Greene, John N

    Cancer control : journal of the Moffitt Cancer Center

    2016  Volume 23, Issue 3, Page(s) 272–277

    Abstract: Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying ...

    Abstract Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed.
    MeSH term(s) Aged ; Female ; Hemorrhage/etiology ; Hemorrhage/therapy ; Humans ; Leukemia, Myeloid, Acute/complications ; Leukemia, Myeloid, Acute/drug therapy ; Lung Diseases/etiology ; Male ; Middle Aged
    Language English
    Publishing date 2016-07
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 1328503-8
    ISSN 1526-2359 ; 1073-2748
    ISSN (online) 1526-2359
    ISSN 1073-2748
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    Zs.A 4467: Show issues Location:
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  5. Article ; Online: A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms.

    Park, Margaret A / Zaw, Thinzar / Yoder, Sean J / Gomez, Maria / Genilo-Delgado, Maria / Basinski, Toni / Katende, Esther / Dam, Aamir / Mok, Shaffer R S / Monteiro, Alvaro / Mohammadi, Amir / Jeong, Daniel K / Jiang, Kun / Centeno, Barbara A / Hodul, Pamela / Malafa, Mokenge / Fleming, Jason / Chen, Dung-Tsa / Mo, Qianxing /
    Teer, Jamie K / Permuth, Jennifer B

    G3 (Bethesda, Md.)

    2022  Volume 13, Issue 2

    Abstract: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or ... ...

    Abstract Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.
    MeSH term(s) Humans ; Pancreatic Intraductal Neoplasms/genetics ; Pancreatic Intraductal Neoplasms/pathology ; Pilot Projects ; Retrospective Studies ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Mutation ; Neoplasms, Cystic, Mucinous, and Serous
    Language English
    Publishing date 2022-12-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkac314
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  6. Article: A Mathematical Model to Estimate Chemotherapy Concentration at the Tumor-Site and Predict Therapy Response in Colorectal Cancer Patients with Liver Metastases.

    Anaya, Daniel A / Dogra, Prashant / Wang, Zhihui / Haider, Mintallah / Ehab, Jasmina / Jeong, Daniel K / Ghayouri, Masoumeh / Lauwers, Gregory Y / Thomas, Kerry / Kim, Richard / Butner, Joseph D / Nizzero, Sara / Ramírez, Javier Ruiz / Plodinec, Marija / Sidman, Richard L / Cavenee, Webster K / Pasqualini, Renata / Arap, Wadih / Fleming, Jason B /
    Cristini, Vittorio

    Cancers

    2021  Volume 13, Issue 3

    Abstract: Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid ... ...

    Abstract Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid tumors. In this proof-of-concept study, we evaluated chemotherapy concentration at the tumor-site and its association with therapy response by applying a mathematical model. By using pre-treatment imaging, clinical and biologic variables, and chemotherapy regimen to inform the model, we estimated tumor-site chemotherapy concentration in patients with colorectal cancer liver metastases, who received treatment prior to surgical hepatic resection with curative-intent. The differential response to therapy in resected specimens, measured with the gold-standard Tumor Regression Grade (TRG; from 1, complete response to 5, no response) was examined, relative to the model predicted systemic and tumor-site chemotherapy concentrations. We found that the average calculated plasma concentration of the cytotoxic drug was essentially equivalent across patients exhibiting different TRGs, while the estimated tumor-site chemotherapeutic concentration (eTSCC) showed a quadratic decline from TRG = 1 to TRG = 5 (
    Language English
    Publishing date 2021-01-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13030444
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  7. Article ; Online: Nonfluorodeoxyglucose-Avid Persistent Splenomegaly at Time of Transplantation Delays Neutrophil and Platelets Engraftment without Affecting Survival in Patients with Lymphomas Undergoing Allogeneic Hematopoietic Cell Transplantation.

    Khimani, Farhad / Jeong, Daniel K / Miladinovic, Branko / Nishihori, Taiga / Ayala, Ernesto / Locke, Frederick / Mishra, Asmita / Chavez, Julio / Shah, Bijal / Gage, Kenneth / Kharfan-Dabaja, Mohamed A

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2016  Volume 22, Issue 12, Page(s) 2201–2207

    Abstract: It is unclear if persistent splenomegaly in the presence of a negative positron emission tomography (PET) scan before allogeneic hematopoietic cell transplantation (HCT) influences post-transplantation outcomes in patients with lymphoma. We ... ...

    Abstract It is unclear if persistent splenomegaly in the presence of a negative positron emission tomography (PET) scan before allogeneic hematopoietic cell transplantation (HCT) influences post-transplantation outcomes in patients with lymphoma. We retrospectively reviewed records of 152 patients who underwent allogeneic HCT for various lymphomas. Centralized review of pretransplantation computed tomography (CT) and PET images was performed. Spleen volume (SV) was measured using the freehand volume segmentation tool in AW Workstation software (General Electric, Waukesha, WI). Splenic index (SI) was calculated as a product of width, thickness, and length of the spleen. Normal SV was defined as SV < 314.5 cm
    Language English
    Publishing date 2016-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2016.09.014
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    Zs.MO 462: Show issues

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