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Biomedical subjects

F C Wong

Publications and source records attributed to F C Wong.

At least 19 recordsLinked to original sources

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Adolescent↗

Factors affecting uptake of cervical and breast cancer screening among perimenopausal women in Hong Kong.

OBJECTIVES: To identify factors affecting cervical and breast cancer screening attendance among women aged 44 to 55 years by comparing self-reported uptake of cervical smear and clinical breast examination between patients and a population sample. DESIGN AND SETTING: Telephone survey and audit of clinic records to confirm patients' self-report. PARTICIPANTS: Two thousand and sixty-seven women identified through random telephone dialling from the residence directory and 319 patients ever-registered at a family practice teaching clinic. MAIN OUTCOME MEASURES: Uptake of cervical smear and clinical breast examination. RESULTS: The proportion of women undergoing cervical smear tests and clinical breast examination in the previous 12 months were 35.4% and 22.6%, respectively, for randomly selected women, while the figures were 47.2% and 50.6%, respectively, for patients. Record audit confirmed high rates of screening for patients according to evidence-based protocols (85.1% had had a cervical smear within 3 years). For women in the random sample (mean age, 48.9 years; standard deviation, 3.3 years), those who were older, postmenopausal, not receiving hormone therapy, educated to primary level, and with no chronic diseases were least likely to have had screening. For clinic patients (mean age, 47.9 years; standard deviation, 2.8 years), lower education level was the only variable associated with no recent smears. CONCLUSIONS: Healthy perimenopausal and postmenopausal women in the community with lower educational level and not receiving hormone therapy were more likely to be underscreened. Attendance of 44- to 55-year-old women at a family medicine clinic that actively promotes preventive medicine was associated with high screening uptake.

Adult↗

The hetF gene product is essential to heterocyst differentiation and affects HetR function in the cyanobacterium Nostoc punctiforme.

A novel gene, hetF, was identified as essential for heterocyst development in the filamentous cyanobacterium Nostoc punctiforme strain ATCC 29133. In the absence of combined nitrogen, hetF mutants were unable to differentiate heterocysts, whereas extra copies of hetF in trans induced the formation of clusters of heterocysts. Sequences hybridizing to a hetF probe were detected only in heterocyst-forming cyanobacteria. The inactivation and multicopy effects of hetF were similar to those of hetR, which encodes a self-degrading serine protease thought to be a central regulator of heterocyst development. Increased transcription of hetR begins in developing cells 3 to 6 h after deprivation for combined nitrogen (N step-down), and the HetR protein specifically accumulates in heterocysts. In the hetF mutant, this increase in hetR transcription was delayed, and a hetR promoter::green fluorescent protein (GFP) transcriptional reporter indicated that increased transcription of hetR occurred in all cells rather than only in developing heterocysts. When a fully functional HetR-GFP fusion protein was expressed in the hetF mutant from a multicopy plasmid, HetR-GFP accumulated nonspecifically in all cells under nitrogen-replete conditions; when expressed in the wild type, HetR-GFP was observed only in heterocysts after N step-down. HetF therefore appears to cooperate with HetR in a positive regulatory pathway and may be required for the increased transcription of hetR and localization of the HetR protein in differentiating heterocysts.

Bacterial Proteins↗

Small cell carcinoma of the cervix complicated by pregnancy.

We report the results of treatment in a 26-year old patient with stage IB2 small cell carcinoma of the cervix complicated by pregnancy. A pathological complete remission was achieved following sandwich chemotherapy and radiotherapy. The patient remains in clinical remission 14 months after presentation.

Adult↗

Correlation between bone scan findings and collagenase activities in patients with breast cancer.

RATIONALE AND OBJECTIVES: This study correlates nuclear bone scan findings and measurements of type IV collagenases for the evaluation of bony metastasis in patients with proven breast cancer. METHODS: The authors retrospectively evaluated the final diagnosis of a bone scan and the results of an immunohistochemical staining for 92 kDa and 72 kDa type IV collagenases in, respectively, 30 and 30 patients with metastatic breast cancer, and, respectively, 27 and 26 patients with primary breast cancer. The immunohistochemical staining was performed with tissue specimens obtained from a primary or metastatic breast tumor lesion. The amounts of the enzyme were graded from 0 to 4 and scored by multiplication with the percentage of tumor cells. The confidence of bone scan interpretation also was scored from 1 to 5 with increasing probability. RESULTS: There was a significant difference in enzyme scores between patients with and without metastases. Patients with < 170 92 kDa (26 of 27), 72 kDa (26 of 26) type IV collagenase, showed no active bony, lung, or liver metastases. However, there were variable bone scan findings in patients with a > 200 enzyme score. CONCLUSIONS: Bone scan provides no additional benefit in breast cancer patients with a type IV collagenase score of < 170. A bone scan is necessary to confirm, localize, or followup bony metastases in patients with an enzyme score of > 200.

Bone Neoplasms↗

Isolated limb perfusion in the sarcoma-bearing rat: a novel preclinical gene delivery system.

Reliable site-specific delivery of genetic constructs remains a challenging component of gene-based therapy of solid tumors. Isolated limb perfusion (ILP) continues to be evaluated for treatment of locally advanced soft tissue sarcomas because this approach uniquely directs therapeutic agents into the tumor-bearing extremity without significant systemic leak. In light of these considerations, we tested the hypothesis that ILP could be used to deliver genes carried in viral vectors to the sarcoma-bearing rat extremity, resulting in demonstrable gene transfer into the tumor. ILP was performed in rats by cannulating the femoral artery and vein, isolating the hind limb from systemic circulation by tourniquet, and cycling perfusate for 15 min at a rate of 2.4 ml/min. Leakage into the systemic circulation was 7.5% of the total perfusate concentrated in the isolated limb, as determined by perfusion with technetium 99m-tagged RBCs. We used the ILP technique to perfuse rat hind limbs bearing syngeneic fibrosarcoma tumor nodules with the replication-defective adenovirus Ad5LacZ, which expresses the bacterial beta-galactosidase. 5-Bromo-4-chloro-3-indolyl-beta-D-galactoside staining of the perfused limb tissues confirmed gene transfer to the tumor and peritumoral tissue, demonstrating that the tumor was part of the perfusion circuit and that gene therapy delivered via this method was feasible. These results suggest that adaptation of this preclinical gene delivery model to administer genetic constructs aimed at controlling tumor growth may prove beneficial to patients with extremity sarcomas.

Adenoviruses, Human↗

Positron emission tomography using [18F]fluorotamoxifen to evaluate therapeutic responses in patients with breast cancer: preliminary study.

Positron emission tomography (PET) was used to assess the biodistribution and clinical usefulness of [18F]fluorotamoxifen (FTX) in 10 patients with estrogen-receptor(ER)-positive breast tumors. Ten patients with ER-positive breast cancer were prospectively studied, and the consecutive PET imagings (each takes 15 or 20 min) were obtained for 60 or 80 min after the injection of 88.8-392.2 MBq (2.4-10.6 mCi) of [18F]FTX. Twenty three suspected primary or metastatic lesions in 10 patients were evaluated and the tumor uptakes of [18F]FTX in nineteen tumor lesions were correlated to the response of tamoxifen therapy. Three lesions in three patients were considered to be truly negative for breast cancer on the bases of biopsy specimens and/or clinical course. Five (71.4%) of seven patients and 16 (80.0%) of 20 lesions were interpreted to be truly positive for breast cancer. The mean standardized uptake value (SUV) of the radiotracer in tumor was 3.0 on delayed images. There was no significant correlation between the standardized uptake values of [18F]FTX and the ER concentrations in primary lesions. Nineteen tumor lesions in six patients were evaluable to compare the [18F]FTX uptake with responses to tamoxifen therapy after the PET study. Three patients who had a good response to tamoxifen therapy showed positive lesions on PET images, whereas two of three patients who had a poor response showed negative lesions and one showed mixed results. There was no significant difference of [18F]FTX uptake in bone lesions between good and poor responders. However, when bone lesions were excluded, [18F]FTX uptakes in tumors with good responses were significantly higher than those with poor responses (mean and standard deviation of SUV: 2.46 +/- 0.62 vs 1.37 +/- 0.59, P < 0.05). PET imaging using [18F]FTX provides useful information in predicting the effect of tamoxifen therapy in patients with ER-positive breast cancer. Further study is warranted to confirm the clinical utility of PET using [18F]FTX in breast cancer patients.

Aged↗

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↗

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↗

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↗

Middle cerebral artery blood flow velocity in patients with cirrhosis.

BACKGROUND: Brain dysfunction is common in patients with advanced liver disease; it is often manifested as hepatic encephalopathy, but its cause is not clearly understood. METHODOLOGY: Intracranial blood flow velocity parameters, including peak systolic velocity, end diastolic velocity and mean velocity of both middle cerebral arteries were measured by transcranial Doppler ultrasonography in 37 patients with cirrhosis without encephalopathy (16 Child's A, 10 Child's B and 11 Child's C) and 12 normal controls. The cause was alcohol-related in 24 and non-alcohol-related in 13. RESULTS: No significant differences in any of the Doppler parameters were detected in Child's group A when compared with controls. However, a statistically significant decrease in middle cerebral artery blood flow velocity was evident when Child's B and C patients without clinically apparent encephalopathy were compared with controls irrespective of the cause. Our results demonstrate that intracranial blood flow is abnormal in patients with advanced liver disease without clinically apparent encephalopathy.

Analysis of Variance↗

Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia.

PURPOSE: To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS: We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted > or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of < or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (> or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS: One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (> or = 10% to a level < or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (> or = 15% to a level < or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION: In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.

Adolescent↗

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↗

Reversible neurotoxicity of interleukin-2 and tumor necrosis factor: correlation of SPECT with neuropsychological testing.

A 41-year-old man developed subacute neurotoxicity associated with interleukin-2 and tumor necrosis factor therapy for metastatic renal cell carcinoma. Cognitive deficits revealed on neuropsychological testing and frontal lobe perfusion deficits revealed on SPECT resolved after 1 month. Findings suggest possible neuroanatomic and physiologic substrates of cytokine neurotoxicity.

Adult↗