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1.
J Nucl Med Technol ; 2022 May 24.
Article in English | MEDLINE | ID: mdl-35610040

ABSTRACT

Introduction: Hyperthyroidism is often managed with radioactive iodine therapy. The dose of 131Iadministered to the patient is determined based on the calculated size of the thyroid gland in gram and 24 hour iodine uptake. Ultrasonography is a validated modality for determination of thyroid volume. Though necessary for assessing degree of 123I uptake, nuclear scintigraphy also allows for the capability of estimating thyroid volume. Here we compare volume measurements calculated based on ultrasonography and nuclear scintigraphy in a cohort of hyperthyroid patients. Methods: This prospective study designed to evaluate 110 consecutive hyperthyroidism patients who were undergoing thyroid ultrasound and 123I scintigraphy. Scintigraphy was performed after oral administration of approximately 11 MBq 123Isodium, and uptakes at 2 and 24 hours were measured. At 24 hours, the patients underwent thyroid scan with a nuclear medicine camera with LEHR (low energy high resolution) collimator next to the patient's chin. Thyroid measurements were calculated via the formula for determining a prolate ellipsoid. The formula was modified for RAIU as it is a planar image. Volumes calculated with these two modalities were subsequently analyzed and compared by linear regression. All patients had undergone ultrasonography with an average three months from nuclear scan. All of our patient 131I dosages were based on the thyroid measurements obtained by thyroid scintigraphy. Results: We included 110 patients (95 females, 15 males) with age range 20-95 years and average age 56 +/- 17.4 years old. Diagnoses included 66 patients with nodular goiter, and 44 patients with Graves' Disease. There was a linear relationship between measurement of thyroid gland weight by two modalities which can be explained in the following formula: log US(g) = 0.841 + 0.649*log NM(g). Conclusion: We have validated that this method has helped obtain more accurate measurements of the thyroid gland by thyroid scintigraphy. Additionally, we have derived conversion factors that convert the estimated thyroid volume calculated from thyroid scintigraphy to the expected ultrasound value.

2.
Clin Nucl Med ; 47(3): e294-e295, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35025799

ABSTRACT

ABSTRACT: Thyroid hemiagenesis is a rare developmental anomaly. Patients with thyroid hemiagenesis have higher incidence of coexisting thyroid disorders in the remaining lobe. We present a rare case of a 21-year-old woman with subclinical hyperthyroidism incidentally found to have thyroid hemiagenesis on thyroid 123I-Na scan, which is confirmed on thyroid ultrasound. On scintigraphy, only the right lobe showed activity. Thyroid ultrasound demonstrated that the right lobe was normal without any nodule. The left lobe was not visualized. This patient's thyroid uptake and scan also revealed low uptake in the remaining right thyroid lobe in keeping with subacute thyroiditis.


Subject(s)
Thyroid Dysgenesis , Thyroiditis, Subacute , Adult , Female , Humans , Radionuclide Imaging , Thyroid Dysgenesis/diagnostic imaging , Thyroiditis, Subacute/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
3.
Clin Nucl Med ; 47(6): 555-556, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35085168

ABSTRACT

ABSTRACT: Acrometastasis is a rare clinical entity, estimated to represent less than 0.3% of all bone metastases. Here, we present a case of esophageal cancer that was treated with esophagectomy, chemotherapy, and radiation therapy and developed oligometastases of the foot after 8 years in remission. The patient developed pain and swelling in his left ankle and foot as the presenting symptom. He underwent radiography and MRI of the affected area, which revealed the lesion. A 99mTc-MDP whole-body bone scan did not reveal any other sites of metastasis.


Subject(s)
Bone Neoplasms , Esophageal Neoplasms , Bone Neoplasms/pathology , Esophageal Neoplasms/diagnostic imaging , Esophagectomy , Humans , Male , Technetium Tc 99m Medronate , Tomography, X-Ray Computed
4.
Clin Nucl Med ; 47(1): 79-80, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34284476

ABSTRACT

ABSTRACT: A 59-year-old woman with a history of papillary thyroid cancer status post total thyroidectomy and 131I ablation therapy presented with lower back pain and leg weakness. MRI of the lumbar spine revealed homogenously enhancing lesions at L1-L2 and L3-L4. Subsequent whole-body 123I-Na scan demonstrated significant 123I retention in the mid to distal esophagus, as well as diffuse uptake in basal segments of the lungs bilaterally. SPECT/CT of the lumbar vertebra was unremarkable. Although 123I-Na uptake often indicates metastatic recurrence, these findings were better explained by nonspecific radioiodine uptake secondary to systemic complications of the patient's underlying scleroderma.


Subject(s)
Lung Diseases, Interstitial , Thyroid Neoplasms , Female , Humans , Iodine Radioisotopes , Lung , Lung Diseases, Interstitial/diagnostic imaging , Middle Aged , Thyroid Neoplasms/complications , Thyroid Neoplasms/diagnostic imaging
5.
Immunity ; 50(1): 166-180.e7, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30650375

ABSTRACT

Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.


Subject(s)
Colorectal Neoplasms/immunology , Inflammation/metabolism , Interleukin-17/metabolism , Interleukin-1/metabolism , Neutrophils/immunology , Salmonella Infections, Animal/immunology , Salmonella/immunology , Animals , Carcinogenesis , Cells, Cultured , Humans , Interleukin-1/genetics , Interleukin-1/immunology , Interleukins/metabolism , Mice , Mice, Knockout , Neutrophils/ultrastructure , Organ Specificity , Receptors, Interleukin-1/genetics , Signal Transduction , Tumor Microenvironment , Interleukin-22
6.
Leukemia ; 33(1): 181-190, 2019 01.
Article in English | MEDLINE | ID: mdl-29884903

ABSTRACT

Juvenile myelomonocytic leukemia (JMML) is an uncommon myeloproliferative neoplasm driven by Ras pathway mutations and hyperactive Ras/MAPK signaling. Outcomes for many children with JMML remain dismal with current standard-of-care cytoreductive chemotherapy and hematopoietic stem cell transplantation. We used patient-derived induced pluripotent stem cells (iPSCs) to characterize the signaling profiles and potential therapeutic vulnerabilities of PTPN11-mutant and CBL-mutant JMML. We assessed whether MEK, JAK, and PI3K/mTOR kinase inhibitors (i) could inhibit myeloproliferation and aberrant signaling in iPSC-derived hematopoietic progenitors with PTPN11 E76K or CBL Y371H mutations. We detected constitutive Ras/MAPK and PI3K/mTOR signaling in PTPN11 and CBL iPSC-derived myeloid cells. Activated signaling and growth of PTPN11 iPSCs were preferentially inhibited in vitro by the MEKi PD0325901 and trametinib. Conversely, JAK/STAT signaling was selectively activated in CBL iPSCs and abrogated by the JAKi momelotinib and ruxolitinib. The PI3Kδi idelalisib and mTORi rapamycin inhibited signaling and myeloproliferation in both PTPN11 and CBL iPSCs. These findings demonstrate differential sensitivity of PTPN11 iPSCs to MEKi and of CBL iPSCs to JAKi, but similar sensitivity to PI3Ki and mTORi. Clinical investigation of mutation-specific kinase inhibitor therapies in children with JMML may be warranted.


Subject(s)
Induced Pluripotent Stem Cells/pathology , Leukemia, Myelomonocytic, Juvenile/pathology , Mutation , Neoplastic Stem Cells/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinases/chemistry , Protein Kinases/genetics , Child , Humans , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Leukemia, Myelomonocytic, Juvenile/drug therapy , Leukemia, Myelomonocytic, Juvenile/genetics , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Signal Transduction/drug effects , Tumor Cells, Cultured
7.
Science ; 361(6399): 285-290, 2018 07 20.
Article in English | MEDLINE | ID: mdl-30026227

ABSTRACT

Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of ß-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, we employed a protein kinase domain-focused CRISPR-Cas9-based genetic screen with a newly optimized single-guide RNA scaffold. The screen uncovered the heme-regulated inhibitor HRI (also known as EIF2AK1), an erythroid-specific kinase that controls protein translation, as an HbF repressor. HRI depletion markedly increased HbF production in a specific manner and reduced sickling in cultured erythroid cells. Diminished expression of the HbF repressor BCL11A accounted in large part for the effects of HRI depletion. Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies.


Subject(s)
Anemia, Sickle Cell/genetics , Carrier Proteins/genetics , Erythroid Cells/metabolism , Fetal Hemoglobin/genetics , Gene Expression Regulation , Nuclear Proteins/genetics , eIF-2 Kinase/genetics , Anemia, Sickle Cell/drug therapy , CRISPR-Cas Systems , Carrier Proteins/metabolism , Cell Line , Genetic Testing , Humans , Molecular Targeted Therapy , Nuclear Proteins/metabolism , RNA, Guide, Kinetoplastida , Repressor Proteins , eIF-2 Kinase/metabolism
8.
Carcinogenesis ; 38(1): 51-63, 2017 01.
Article in English | MEDLINE | ID: mdl-27797827

ABSTRACT

The tumor microenvironment offers multiple targets for cancer therapy, including pro-tumorigenic inflammation. Natural compounds represent an enormous source of new anti-inflammatory and anticancer agents. We previously showed that the styryl lactone goniothalamin (GTN) has promising antiproliferative and anti-inflammatory activities. Because inflammation is a major driver of colorectal cancer (CRC), we therefore evaluated the therapeutic and preventive potentials of GTN in colitis, colitis-associated cancer (CAC) and spontaneous CRC. First, in a simplistic model of inflammation in vitro, GTN was able to inhibit cytokine production in bone marrow-derived macrophages induced by lipopolysaccharide. Next, in dextran sulfate sodium (DSS) induced-colitis model, mice treated with GTN displayed restored tissue architecture, increased cell proliferation in the colonic crypts and reduced epithelial damage. Moreover, colon tissue from GTN-treated mice had significantly less expression of the inflammatory genes interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), S100A9, interleukin 23A (IL-23A), IL-22 and IL-17A In the azoxymethane/DSS model of CAC, GTN reduced tumor multiplicity, load and size. Additionally, GTN suppressed production of IL-6, IL-17 and TNF-α in tumor tissue, as well as abrogated stromal immune cell activation and nuclear translocation of NF-κB. Finally, in a tamoxifen inducible model of sporadic CRC, GTN-treated mice had significantly fewer tumors and decreased levels of IL-17A, IL-6, S100A9 and TNF-α protein within the tumors. These results suggest that GTN possesses anti-inflammatory and antitumor activities and represents a preventive and therapeutic agent modulating the inflammatory environment in the colon during colitis as well as CAC and CRC development.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cell Transformation, Neoplastic/drug effects , Colitis/complications , Colorectal Neoplasms/prevention & control , Inflammation Mediators/antagonists & inhibitors , Pyrones/pharmacology , Animals , Azoxymethane/toxicity , Biological Products/pharmacology , Carcinogens/toxicity , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Cells, Cultured , Colitis/chemically induced , Colorectal Neoplasms/etiology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/metabolism , Dextran Sulfate/toxicity , Inflammation/chemically induced , Inflammation/complications , Inflammation Mediators/metabolism , Macrophages/drug effects , Macrophages/metabolism , Macrophages/pathology , Mice , Mice, Inbred C57BL
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