We previously showed that elevated TYMS exhibits oncogenic properties and promotes tumorigenesis after a long latency, suggesting cooperation with sequential somatic mutations. Here we report the ...cooperation of ectopic expression of human TYMS with loss of Ink4a/Arf, one of the most commonly mutated somatic events in human cancer. Using an hTS/Ink4a/Arf
genetically engineered mouse model we showed that deregulated TYMS expression in Ink4a/Arf null background accelerates tumorigenesis and metastasis. In addition, tumors from TYMS-expressing mice were associated with a phenotype of genomic instability including enhanced double strand DNA damage, aneuploidy and loss of G1/S checkpoint. Downregulation of TYMS in vitro decreased cell proliferation and sensitized tumor cells to antimetabolite chemotherapy. In addition, depletion of TYMS in vivo by TYMS shRNA reduced tumor incidence, delayed tumor progression and prolonged survival in hTS/Ink4a/Arf
mice. Our data shows that activation of TYMS in Ink4a/Arf null background enhances uncontrolled cell proliferation and tumor growth, supporting the development of new agents and strategies targeting TYMS to delay tumorigenesis and prolong survival.
Placental metastasis of maternal neoplasms is well documented in solid tumors, unlike hematologic neoplasms. We reviewed placental findings from deliveries complicated by maternal hematologic ...neoplasms exploring the prevalence and patterns of placental transmission and insufficiency. In the 8-yr study period, 11 cases were analyzed. Acute myeloid leukemia was the most common diagnosis (4/11, 36%). Seven cases (63%) showed no evidence of placental spread of neoplasm, while four cases (36%) showed placental spread, restricted to the maternal compartment. Maternal vascular malperfusion was documented in 8/11 (72%) cases. Neonatal follow up was available in 10 cases, all children were alive and well.
•Maternal hematologic neoplasms can involve the placenta.•Involvement was typically restricted to the intervillous space (maternal compartment).•Maternal vascular malperfusion was the common pattern of placental pathology.
•We report a case of a brain abscess caused by Nocardia farcinica.•The patient had completed chemotherapy for diffuse large B cell lymphoma 2 months before infection.•Initial imaging was unable to ...differentiate infection vs disease recurrence.•Biopsy and diagnosis were delayed by the patient's comorbidities and goals of care.•Clinical suspicion for Nocardia merits expeditious diagnostic evaluation.
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical ...imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
To describe longitudinal health service utilization and expenditures for homeless family members before and after entering an emergency shelter.
We linked Massachusetts emergency housing assistance ...data with Medicaid claims between July 2008 and June 2015, constructing episodes of health care 12 months before and 12 months after families entered a shelter. We modeled emergency department visits, hospital admissions, and expenditures over the 24-month period separately for children and adults.
Emergency department visits, hospital admissions, and expenditures rose steadily before shelter entry and declined gradually afterward, ending, in most cases, near the starting point. Infants, pregnant women, and individuals with depression, anxiety, or substance use disorder had significantly higher rates of all outcomes. Many children's emergency department visits were potentially preventable.
Increased service utilization and expenditures begin months before families become homeless and are potentially preventable with early intervention. Infants are at greater risk. Public Health Implications. Early identification and intervention to prevent homeless episodes, focusing on family members with behavioral health disorders, who are pregnant, or who have young children, may save money and improve family health.
Objectives
To compare the diagnostic performance of
18
FFDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients.
...Material and methods
A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body
18
FFDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar
χ
2
test was performed to compare sensitivity and specificity between the modalities.
Results
Forty-one bone metastases were present in 7/154 patients (4.5%). Both
18
FFDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (
p
< 0.01, difference 43.9%) and bone scintigraphy (
p
< 0.01, difference 63.4%).
Conclusion
18
FFDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases.
Key Points
•
18
FFDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer.
•
Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients.
As atherosclerotic plaque ruptures are the primary cause of ischaemic events, their preventive identification by imaging remains a clinical challenge. Matrix metalloproteinases (MMP) are involved in ...plaque progression and destabilisation and are therefore promising targets to characterize rupture-prone unstable plaques. This study aims at evaluating MMP imaging to discriminate unstable from stable plaque phenotypes.
ApoE deficient mice (ApoE-/-) on a high cholesterol diet underwent implantation of a tapered cuff around the right common carotid artery (CCA) inducing a highly inflamed atherosclerotic plaque upstream (US) and a more stable plaque phenotype downstream (DS) of the cuff. 8 weeks after surgery, the MMP inhibitor-based photoprobe Cy5.5-AF443 was administered i.v. 3h prior to in situ and ex vivo fluorescence reflectance imaging of the CCAs. Thereafter, CCAs were analysed regarding plaque size, presence of macrophages, and MMP-2 and MMP-9 concentrations by immunohistochemistry and ELISA.
We found a significantly higher uptake of Cy5.5-AF443 in US as compared to DS plaques in situ (1.29 vs. 1.06 plaque-to-background ratio; p<0.001), which was confirmed by ex vivo measurements. Immunohistochemistry revealed a higher presence of macrophages, MMP-2 and MMP-9 in US compared to DS plaques. Accordingly, MMP-2 concentrations were significantly higher in US plaques (47.2±7.6 vs. 29.6±4.6 ng/mg; p<0.05).
In the ApoE-/- cuff model MMP-2 and MMP-9 activities are significantly higher in upstream low shear stress-induced unstable atherosclerotic plaques as compared to downstream more stable plaque phenotypes. MMP inhibitor-based fluorescence molecular imaging allows visualization of these differences in shear stress-induced atherosclerosis.
The patient was a 62-year-old Caucasian man with blood smear and flow cytometry concerning for acute promyelocytic leukemia with FISH ultimately confirming PML-RARA translocation. He had a 30-year ...history of employment at a nuclear power plant. He presented with diffuse intravascular coagulation, hyperleukocytosis, and quickly developed acute respiratory distress syndrome. On day four of ATRA + Hydrea, a bronchoalveolar lavage was performed and was non-bloody. On microscopic fluid review, abnormal immature cells with bilobed nuclear contours were identified, similar in morphology to those seen on the diagnostic blood smear review, amidst background alveolar-type macrophages. Subsequent flow cytometric analysis showed these cells to be abnormal promyelocytes; however, they differed from the blood flow cytometry study performed prior to initiation of ATRA by showing maturational immunophenotypic changes. While the leukemic promyelocytes on bronchoalveolar lavage were morphologically immature, these immunophenotypic changes somewhat recapitulated those seen in normal granulocyte maturation and were thus suggestive of so-called differentiation syndrome. Unfortunately, the patient passed away during induction chemotherapy due to complications from diffuse intravascular coagulation and differentiation syndrome. Important pathobiological information can be gathered from fluid review and concomitant flow cytometric analysis.
Passive monitoring techniques have been used for peak temperature measurements during irradiation tests by exploiting the melting point of well-characterized materials. Recent efforts to expand the ...capabilities of such peak temperature detection instrumentation include the development and testing of additively manufactured (AM) melt wires. In an effort to demonstrate and benchmark the performance and reliability of AM melt wires, we conducted a study to compare prototypical standard melt wires to an AM melt wire capsule, composed of printed aluminum, zinc, and tin melt wires. The lowest melting-point material used was Sn, with a melting point of approximately 230 °C, Zn melts at approximately 420 °C, and the high melting-point material was aluminum, with an approximate melting point of 660 °C. Through differential scanning calorimetry and furnace testing we show that the performance of our AM melt wire capsule was consistent with that of the standard melt-wire capsule, highlighting a path towards miniaturized peak-temperature sensors for in-pile sensor applications.
PDF
