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Biomedical subjects

E E Kim

Publications and source records attributed to E E Kim.

At least 55 records · Page 3Linked to original sources

Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer.

UNLABELLED: We retrospectively investigated the value of PET with fluorine-18 fluorodeoxyglucose (FDG) for preoperative chemotherapy response in patients with locally advanced breast cancer. METHODS: FDG-PET studies were performed on 16 consecutive patients. All patients had PET studies before chemotherapy, 13 patients between the end of the first cycle and at the midpoint of chemotherapy, and 14 patients before surgery. Visual diagnoses and the standardized uptake values (SUV) of PET scans were compared with pathology findings at surgery and with the results of mammography, ultrasonography (US) or both, which were performed before chemotherapy and before local surgery for residual disease. Each patient's clinical course was monitored for up to 3 yr. RESULTS: Sensitivity for detection of pathologically proven primary lesions was 100%, 62.5% and 87.5% with FDG-PET, mammography and US, respectively; and sensitivity for detection of initial nodal involvement was 77%, 70% and 87.5%, respectively. Sensitivity for detection of residual primary tumor was 75%, 71.4% and 87.5%, respectively; and sensitivity for detection of residual nodal involvement was 41.6%, 71.4% and 66.6%, respectively. The mean SUV value of primary lesions was 9.4 (range 2.0-20.7, n = 16), with only two lesions showing an SUV below 3. Clinical improvement of primary lesions was seen in all patients; improvement with smaller size and less FDG uptake was visible as early as the second study in 11 patients (69%). Mean SUV values obtained at the second and third studies decreased significantly from those obtained in the first study. In four patients, the disease recurred after breast surgery with high SUV values. The mammograms and sonograms obtained before surgery showed a decrease in the diameter of 6 and 12 primary lesions of the 13 and 14 patients examined, respectively. CONCLUSION: FDG-PET is valuable for monitoring the effects of preoperative chemotherapy in patients with locally advanced breast cancer with better sensitivity for primary tumor and better specificity for nodal metastasis in comparison with ultrasonography.

Adult↗

[Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase].

Two recombinant bacteriophage lambda clones encoding a 27.8-kb fragment of the human phosphodiesterase beta-subunit gene were isolated from a human genomic library. The nucleotide sequences of 19 exons (from the 4th to 22nd), 18 introns, and the 3'-flanking region were determined. The analysis of the nucleotide sequence of the phosphodiesterase beta-subunit gene revealed four Alu repeats and four minisatellite regions.

3',5'-Cyclic-GMP Phosphodiesterases↗

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors.

UNLABELLED: Two commonly used tumor-seeking agents for PET are 2-deoxy-2-18F-fluoro-D-glucose (FDG) and L-methyl-11C-methionine (Met). This study compared FDG and Met in detecting residual or recurrent malignant tumors in the same patients. METHODS: Thirty-four lesions in 24 patients with clinically suspected recurrent or residual tumors were studied with PET using Met as well as FDG. FDG scans were conducted 1 hr after the completion of PET with Met. The color-coded superimposed images of standardized uptake values (SUVs) and transmission data were produced, and the peak SUVs in the lesions were then evaluated. Lesions above 2.5 SUV were interpreted as positive results for active tumor. RESULTS: The sensitivity of FDG-PET and Met-PET were 64.5% (20/31 lesions) and 61.3% (19/31 lesions), respectively. The mean SUV of FDG in residual or recurrent malignant tumors (n = 31) was significantly higher than that of Met but there was a significant correlation (r = 0.788, p < 0.01) between FDG and Met SUVs in all lesions (n = 34). CONCLUSION: PET using FDG and Met appear equally effective in detecting residual or recurrent malignant tumors although FDG uptakes were slightly higher than Met uptakes. Both showed a limited diagnostic sensitivity for small (< 1.5 cm) tumors.

Adult↗

Comparison of fluorine-18-FDG PET and technetium-99m-MIBI SPECT in evaluation of musculoskeletal sarcomas.

UNLABELLED: We compared the diagnostic accuracy of [18F]FDG PET and 99mTc-MIBI SPECT in musculoskeletal sarcomas. METHODS: Forty-eight patients with clinically suspected recurrent or residual musculoskeletal sarcomas were examined with both FDG-PET and MIBI-SPECT within 2 wk of each study (one follow-up study in nine patients and we follow-up studies in one patient). Imaging findings were visually inspected with grading scales in conjunction with CT and/or MRI, and count-density ratios of lesion-to-contralateral area and standard uptake values (SUVs) of FDG and MIBI in lesions were also generated. The results were correlated with histologic findings (in 51 studies) and/or long-term follow-up evaluations. RESULTS: The diagnostic sensitivities and specificities were 98% and 90% using FDG, and 81.6% and 80% using MIBI, respectively, with statistical significance in the sensitivity. The tumors were demonstrated better in FDG studies, which produced higher visual grades (2.1 versus 1.6), and the tumors showed increasing SUVs with time (from 6.3 to 7.3). Four of nine patients with positive FDG but negative MIBI scans failed to respond to multidrug therapy. CONCLUSION: FDG-PET and MIBI-SPECT are useful in differentiating active sarcomas from post-treatment changes and in evaluating therapeutic response. MIBI-SPECT and FDG-PET findings should be interpreted in con junction with CT and/or MRI. FDG-PET shows statistically significant higher sensitivity than MIBI-SPECT. A positive FDG but negative MIBI scan might suggest a multidrug resistance.

Adult↗

Phase II study of docetaxel in patients with epithelial ovarian carcinoma refractory to platinum.

We analyzed the efficacy and toxicity of docetaxel in patients with ovarian cancer who failed previous chemotherapy with platinum. Fifty-five patients with measurable ovarian cancer were entered in this Phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of 100 mg/m2 docetaxel given i.v. every 3 weeks. Because of hypersensitivity reactions, premedication with steroids and antihistamine was initiated during the study. Twenty-two (40%) patients responded (there were 3 complete responders and 19 partial responders). Twenty-one (38%) patients had stable disease. The median survival was 10 months. The main toxicity was neutropenia (98% of patients), with 13 episodes of neutropenic fever. Cumulative fluid retention was the main reason for dose modification and required a combination of diuretics and steroids for palliation. Other side effects were alopecia (100%); anemia (87%); dermatitis (67%); gastrointestinal disorders (53%); stomatitis (49%); neurotoxicity (45%); excessive lacrimation (33%); and hypersensitivity reactions (11%), which in one case were life threatening (loss of consciousness, fluid resuscitation). Docetaxel as a single agent proved to be active in heavily pretreated ovarian cancer patients but is associated with significant side effects. Objective toxicity consisted mainly of neutropenia and fluid retention. Neutropenia was dose limiting and required therapy with granulocyte colony-stimulating factor. Fluid retention was improved but not eliminated by diuretics and corticosteroids. Additional studies of docetaxel in ovarian carcinoma are indicated to define the activity in relation to paclitaxel and in platinum combination therapy.

Adult↗

X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex.

The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 A resolution, providing a description of how FK506 functions at the atomic level. In the structure, the FKBP12-FK506 binary complex does not contact the phosphatase active site on calcineurin A that is more than 10 A removed. Instead, FKBP12-FK506 is so positioned that it can inhibit the dephosphorylation of its macromolecular substrates by physically hindering their approach to the active site. The ternary complex described here represents the three-dimensional structure of a Ser/Thr protein phosphatase and provides a structural basis for understanding calcineurin inhibition by FKBP12-FK506.

Amino Acid Sequence↗

Radioimmunoscintigraphy in the differential diagnosis of hepatic mass lesion.

A patient with suspected recurrent cancer of the colon underwent a variety of imaging procedures for the differential diagnosis of a hepatic mass lesion. Computed tomography (CT) showed a low-density lesion in the left hepatic lobe, and the initial CT-guided biopsy of the liver mass was reported to demonstrate a benign lesion. Ultrasonography (US) showed a hypoechoic lesion, and technetium-99m red blood cell (RBC) scan failed to suggest a hemangioma. However, radioimmunoscintigraphy (RIS) using 99mTc- labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody clearly demonstrated increase uptake of antibody in the liver lesion. Scheduled hepatic angiography was canceled and subsequent exploratory laparotomy confirmed liver metastasis. RIS appears most helpful in the diagnosis of hepatic metastasis in patients with colorectal cancer and a rising CEA level. CT, US, and 99mTc-RBC studies for the investigation of hepatic masses are briefly discussed.

Adenocarcinoma↗

Positron emission tomography in the detection of residual laryngeal carcinoma.

Positron emission tomography measures the metabolic activity of tissue. Because metabolism rates are higher in tumors than in normal tissue, positron emission tomography can be used to identify abnormal tissue. Positron emission tomography has proved useful in detecting residual or recurrent tumor in the brain and gastrointestinal tract after definitive treatment. We selectively used positron emission tomography in a preliminary trial to examine patients with laryngeal cancer who had previously been treated with organ-preservation therapy with radiation therapy alone or in combination with induction chemotherapy. These patients are often difficult to examine both clinically and radiographically because of posttreatment edema and fibrosis. From 1991 to 1993 patients at our institution who were treated with either radiation therapy or a combination of induction chemotherapy and radiotherapy for laryngeal carcinoma were evaluated after treatment. If clinical examination was suspicious for residual tumor or recurrence, a computed tomography or magnetic resonance imaging scan was obtained. In 10 patients neither clinical examination nor conventional imaging could absolutely rule out residual/recurrent carcinoma. In these patients positron emission tomography with 2-fluoro-2-deoxy-D-glucose was used to detect disease. The results from positron emission tomography were compared with the results from subsequent biopsy (five patients) or clinical follow-up. Positron emission tomography had a sensitivity of 67% and a specificity of 57%. The positive predictive value of positron emission tomography was 67%. The negative predictive value of positron emission tomography was 80%.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗

In-111 DTPA Ommayagrams in leptomeningeal carcinomatosis.

Radionuclide Ommayagrams in 25 patients with leptomeningeal carcinomatosis were performed after injection of 0.5 mCl of In-111 DTPA into Ommaya shunt reservoirs to evaluate cerebrospinal fluid-shunt communication, detect the blockage of the cerebrospinal fluid pathway, evaluate the cerebrospinal fluid flow pattern, and predict the distribution of the chemotherapeutics. All results were correlated with MRI evaluations of the brain and spine, as well as clinical findings. Radionuclide Ommayagrams were found to be 73% sensitive and 100% specific in the evaluation of cerebrospinal fluid space disease. MRI of the spine and head was found to be 100% sensitive, but 86% specific for obstructive cerebrospinal fluid space disease.

Adolescent↗

Comparison of nuclear bone and gallium scans in the therapeutic evaluation of bone lymphoma.

The objective of this study was to compare Tc-99m MDP bone and Ga-67 scans for the therapeutic response to bone lymphoma in 40 patients. The authors retrospectively compared 40 Tc-99m MDP bone scans and 20 Ga-67 scans before therapy, 29 bone scans and 13 Ga-67 scans during the therapy, and 33 bone scans and 15 Ga-67 scans after therapy. Tc-99m MDP and Ga-67 whole body scans were obtained within 2 weeks of each study and were graded visually (grades 1-4) in which grade 3 means similar count density to that of normal iliac alar activity on bone scans and normal liver activity on Ga-67 scans, respectively. The findings of lesion improvement during and after therapy were found in 66.0% (19 of 29) and 72.7% (24 of 33) with Tc-99m MDP bone scans, 84.6% (11 of 13) and 86.7% (13 of 15) with Ga-67 scans, respectively. The mean grades of Tc-99m MDP uptake were 3.06 before, 2.34 during, and 1.75 after therapy. The mean grades of Ga-67 uptake were 3.22 before, 1.42 during, and 1.30 after therapy. Ga-67 scans appear to be more reliable than Tc-99m MDP bone scans in evaluating the therapeutic response of bone lymphoma.

Adult↗

Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia.

PURPOSE: To develop a hydrophilic ligand to image tumor hypoxia at positron emission tomography (PET). MATERIALS AND METHODS: Biodistribution of fluorine-18-labeled fluoroerythronitroimidazole (FETNIM) and F-18-labeled fluoromisonidazole (FMISO) was determined at PET and autoradiography in three mammary-tumor-bearing rats. The partition coefficient of FETNIM, FMISO, and misonidazole was determined. RESULTS: Biodistribution of F-18-labeled FETNIM at 1, 2, and 4 hours showed tumor-to-blood ratios of 2.29 +/- 0.599, 2.41 +/- 0.567 and 8.02 +/- 2.420, respectively, and tumor-to-muscle ratios of 0.66 +/- 0.267, 2.11 +/- 0.347, and 5.92 +/- 2.240, respectively. The tumor-to-blood count density ratio with F-18-labeled FETNIM at 4 hours after injection was significantly higher than with F-18-labeled FMISO. Autoradiographs indicated that both agents could help differentiate hypoxic versus necrotic region in the tumor. CONCLUSION: F-18-labeled FETNIM can help detect tumor hypoxia and is easier to prepare, less costly, and more hydrophilic than F-18-labeled FMISO.

Animals↗

Detecting recurrent or residual lung cancer with FDG-PET.

UNLABELLED: We investigated the diagnostic accuracy of FDG-PET in the detection of recurrent lung cancer. METHODS: Thirty-nine lesions in 38 patients with clinically suspected recurrent or residual lung cancer were studied with PET. All PET images were visually interpreted in conjunction with thoracic CT or MRI. Semiquantitative analysis using standardized uptake values (SUVs) was also performed in 25 lesions. FDG-PET diagnoses were correlated with pathological diagnoses and clinical outcome. RESULTS: The sensitivity and specificity of FDG-PET for detecting recurrent tumors were 100% (26/26) and 61.5% (8/13), respectively. The difference in mean SUV between recurrent tumors and noncancerous lesions was statistically significant [11.2 +/- 5.7 (n = 16) vs. 3.5 +/- 1.8 (n = 9), p < 0.0001]. False-positive results showed relatively lower SUVs than true-positives and also demonstrated increased uptake in a curvilinear rather than nodular shape. CONCLUSION: FDG-PET is useful for detecting recurrent lung cancer after treatment. False-positive diagnoses might be reduced by analysis of uptake shape and serial changes in SUV, but further study is needed.

Adult↗

Primary breast lymphoma detected with SPECT using gallium-67-citrate.

Breast involvement by malignant lymphoma either as a primary site or as a secondary site from lymphoma elsewhere is rare. Primary breast lymphoma (PBL) accounts for only a small percentage of total malignant lymphoma involving the breast. The incidence of PBL varies from 0.004% to 0.5%. We present a case of PBL which was well demonstrated on total-body imaging as well as SPECT using 67Ga-citrate.

Breast Neoplasms↗

Structure and mechanism of interleukin-1 beta converting enzyme.

Interleukin-1 beta converting enzyme (ICE) processes an inactive precursor to the proinflammatory cytokine, interleukin-1 beta, and may regulate programmed cell death in neuronal cells. The high-resolution structure of human ICE in complex with an inhibitor has been determined by X-ray diffraction. The structure confirms the relationship between human ICE and cell-death proteins in other organisms. The active site spans both the 10 and 20K subunits, which associate to form a tetramer, suggesting a mechanism for ICE autoactivation.

Amino Acid Sequence↗

Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer.

Our laboratory has previously reported on the derivation of LNCaP cell sublines from LNCaP tumors maintained in castrated and intact athymic male mice. These LNCaP sublines differ from the parental line in tumorigenicity and androgen dependence. This paper demonstrates that one of these sublines acquired metastatic potential. When inoculated either s.c. or orthotopically, the C4-2 subline metastasized to the lymph node and bone with an incidence of 11-50%. Interestingly, the incidence of osseous metastasis was higher in castrated than in intact male hosts. We evaluated the chromosomal, immunohistochemical, and biochemical characteristics of the LNCaP sublines derived from C4-2 tumors that metastasized to the lymph node and bone. Cytogenetic analysis showed that all sublines were human and shared common marker chromosomes with the parental LNCaP cells. This experimental human prostate cancer model may permit, for the first time, the study of the molecular mechanisms underlying human prostate cancer metastasis.

Animals↗