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Biomedical subjects

A Bogni

Publications and source records attributed to A Bogni.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide approach to identify risk factors for therapy-related myeloid leukemia.

Using a target gene approach, only a few host genetic risk factors for treatment-related myeloid leukemia (t-ML) have been defined. Gene expression microarrays allow for a more genome-wide approach to assess possible genetic risk factors for t-ML. We assessed gene expression profiles (n=12 625 probe sets) in diagnostic acute lymphoblastic leukemic cells from 228 children treated on protocols that included leukemogenic agents such as etoposide, 13 of whom developed t-ML. Expression of 68 probes, corresponding to 63 genes, was significantly related to risk of t-ML. Hierarchical clustering of these probe sets clustered patients into three groups with 94, 122 and 12 patients, respectively; 12 of the 13 patients who went on to develop t-ML were overrepresented in the latter group (P<0.0001). A permutation test indicated a low likelihood that these probe sets and clusters were obtained by chance (P<0.001). Distinguishing genes included transcription-related oncogenes (v-Myb, Pax-5), cyclins (CCNG1, CCNG2 and CCND1) and histone HIST1H4C. Common transcription factor recognition elements among similarly up- or downregulated genes included several involved in hematopoietic differentiation or leukemogenesis (Maz, PU.1, ARNT). This approach has identified several genes whose expression distinguishes patients at risk of t-ML, and suggests targets for assessing germline predisposition to leukemogenesis.

Child↗
PubMed2001

A simple loop method for the automated preparation of (11C)raclopride from (11C)methyl triflate.

A simple automated preparation of [11C]raclopride by reaction of [11C]methyl triflate with demethylraclopride triflate is described. The conventional bubbling of [11C]methyl triflate into the precursor solution was compared with two alternative methods which used a commercially available C18 cartridge (on-column method) or an empty PTFE tube (loop method) as support for the precursor solution. The influence of several solvents was assessed for all three methods. The on-column method showed excellent trapping efficiencies of [11C]methyl triflate but gave the lowest radiochemical yields. The loop method proved to be a simplified alternative to the bubbling method, giving comparable radiochemical yields with less precursor and offering an easy way to transfer the reaction mixture into an HPLC column. By the simple-loop method [11C]raclopride could be prepared in over 40% radiochemical yields (decay-corrected and based on [11C]methyl triflate).

Carbon Radioisotopes↗
PubMed2000

A new, convenient method for the preparation of 4-[18F]fluorobenzyl halides.

A convenient method suitable for automated preparation of 4-[18F]fluorobenzyl halides from no-carrier-added [18F]fluoride has been developed. 4-[18F]Fluorobenzaldehyde, synthesized from [18F]fluoride by aromatic nucleophilic substitution on 4-trimethylammoniumbenzaldehyde triflate, was first retained on a C18 cartridge and there efficiently reduced to 4-[18F]fluorobenzyl alcohol simply by flowing an aqueous solution of NaBH4. The conversion of 4-[18F]fluorobenzyl alcohol to 4-[18F]fluorobenzyl halide was investigated using PBr3, PI3, P2I4, Ph3PBr2 and Ph3PI2 in CH2Cl2. 4-[18F]Fluorobenzyl halides were purified by passing through a disposable silica cartridge. The conversion rapidly proceeded in radiochemical yields of nearly 90% at 40 degrees C with P2I4 and almost quantitatively at room temperature with Ph3PBr2. With this last reagent 4-[18F]fluorobenzyl bromide was obtained in overall radiochemical yields of 50-60% within 30 min from EOB.

Journal Article↗
PubMed1998

Association between [18F]fluorodeoxyglucose uptake and postoperative histopathology, hormone receptor status, thymidine labelling index and p53 in primary breast cancer: a preliminary observation.

To investigate the possible role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in the prognostic evaluation of primary breast cancer, we studied 86 patients with T1-3 (TNM classification) breast tumours before surgery and compared the tumour FDG uptake, calculated as a standardized uptake value (SUV), with postoperative histopathological findings, steroid hormone receptor status of the tumour, thymidine labelling index (LI) and tissular expression of p53. SUV was significantly higher in infiltrating ductal carcinomas (n = 68; median SUV = 5.6) than in lobular ones (n = 18; median SUV = 3.8), and in grade 3 carcinomas (n = 26; median SUV = 6.2) than in grade 1-2 ones (n = 60; median SUV = 4.9). Moreover, SUV was significantly higher in carcinomas with high levels of p53 (n = 12; median SUV = 9.5) than in those with low levels (n = 48; median SUV = 4.25). By contrast, there was no significant correlation between SUV and the steroid hormone receptor status or LI of tumours. Our data demonstrate that FDG uptake, expressed as SUV, is associated with certain prognostic factors in breast cancer, such as histopathological grading and p53 expression, which can be assessed only by means of postoperative in vitro examinations. Hence, the information provided by FDG-PET is to some extent related to relevant information on tumour biology. The clinical value of these data will have to be confirmed by analysis of the independence of SUV from other prognostic factors by means of a multivariate analysis performed on a larger series of patients with adequate follow-up. If SUV is confirmed as an independent variable, FDG-PET could assume an important role in the determination of appropriate therapeutic strategies for primary breast cancer.

Adult↗
PubMed1998

Prospective evaluation of fluorine-18-FDG PET in presurgical staging of the axilla in breast cancer.

METHODS: The presurgical, noninvasive staging of axillary nodes for metastases was prospectively investigated in 68 patients who were diagnosed with primary breast cancer using PET with 18F-fluorodeoxyglucose (FDG). Four patients had bilateral nodules; therefore, the total number of evaluable cases was 72. Visual analyses of attenuation-corrected PET images and standardized uptake values (SUVs) of FDG uptake in carcinomas were compared with histopathological surgical findings. The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and receiver operating characteristics analyses. RESULTS: PET correctly classified 64 of the 72 cases; four false-positive and four false-negative PET results were found. The overall sensitivity, specificity and accuracy of PET for axillary metastases were 85%, 91% and 89%, respectively. With respect to the clinical axillary stage of the patients (TNM, or tumor-node-metastasis, classification), we obtained the following results: N0 patients, sensitivity = 70%, specificity = 92%, accuracy = 86%; N1a patients, sensitivity = 85.5%, specificity = 100%, accuracy = 95%; and N1b-2 patients, sensitivity = 100%, specificity = 67%, accuracy = 87%. The median SUV in carcinomas with axillary metastases (4.6) was significantly higher than that in carcinomas without metastases (2.9), but there was a great SUV overlap between the two groups (interquartile ranges = 2.7-7.2 and 1.9-4.5, respectively). Analysis of the receiver operating characteristics curve showed that a high sensitivity of SUV in predicting axillary metastases was associated with a very low specificity and vice versa. With the best SUV cutoff value of 2.9, the sensitivity and specificity were 74% and 56%, respectively. CONCLUSION: PET showed good overall diagnostic accuracy in the detection of axillary metastases (86%). The very high accuracy (95%) in N1a patients is of particular importance. False-negative PET findings, however, can be encountered. SUVs of breast carcinoma cannot predict the spread of the disease to the axilla, even if higher values are often associated with axillary metastases. Any decision on the use of PET in the presurgical staging of breast cancer should be incorporated into a more general debate on axillary management. In selected patients with a very low probability of axillary metastases (T1a), in whom axillary surgery can already be avoided according to data from follow-up studies, 18F-FDG PET could be proposed as a noninvasive imaging modality to improve the diagnosis of axillary relapses.

Axilla↗
PubMed1997

Comparison of three different methods for radiolabelling human activated T lymphocytes.

One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.

Cell Death↗
PubMed1997

Radiation dose to technicians per nuclear medicine procedure: comparison between technetium-99m, gallium-67, and iodine-131 radiotracers and fluorine-18 fluorodeoxyglucose.

The aim of this study was to determine the non-extremity gamma dose received by a technician while performing an ordinary nuclear medicine procedure or a static (i.e. without blood sampling) fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) study. The dose per patient was measured by means of a commercial electronic pocket Geiger Mueller dosimeter, worn in the upper left pocket of the overalls. This was previously tested by exposure to known point sources of technetium-99m, gallium-67, iodine-131 and fluorine-18 in the air. A further test was performed with 99mTc, 131I and 18F sources inserted in a water phantom to simulate the condition of high scattering degradation of the primary radiation due to the patient's tissues. Subsequently, the dose was measured by two technicians for a total of 314 clinical cases, covering the most common nuclear medicine procedures, including 44 static, two-level FDG PET studies with repositioning of the patient on the couch between the transmission and the emission scan and seven whole-body PET studies. The dose read by the dosimeter was corrected for environmental background and for detector efficiency measured with sources in the air. For a limited subset of cases, the time spent close to patients was also measured. Doses were then estimated by a crude non-absorbing point source approximation and by using experimental dose rates. A comparison between experimental and estimated doses, as well as with previously published data, completed the work. For most of the conventional procedures, the measured dose per procedure proved to be within the range 0.2-0.4 microSv, except for equilibrium angiocardioscintigraphy (1.0+/-0.5 microSv) and 99mTc-sestamibi single-photon emission tomography (1. 7+/-1.0 microSv). Comparison with data published in the last 20 years shows that our values are generally lower. The current more favourable working conditions are a result of technological improvements (for instance two-head gamma cameras capable of whole-body studies), and safer shielding and distance from patients. Two-level PET gave 11.5+/-4.4 microSv and whole-body PET 5.9+/-1.2 microSv. In a subset of patients these values could be subdivided into the separate contributions from each phase of the procedure. They were: 0.11+/-0.04 microSv for daily quality assurance, 2.9+/-3.0 microSv for two transmission scans, 0.3+/-0.1 microSv for syringe preparation, 2.8+/-1.8 microSv for injection and escorting the patient to the waiting room, 1.7+/-1.5 microSv for a whole-body emission scan, 7.7+/-5.2 microSv for two emission scans, and 0.8+/-0. 2 microSv for patient departure. The higher value from PET by comparison with conventional procedures is attributable to the higher specific gamma constant of 18F, as well as the longer time required for accurate positioning.

Fluorine Radioisotopes↗
PubMed1992

CA 15.3 determination in patients with breast cancer: clinical utility for the detection of distant metastases.

In 81 healthy women, 26 pregnant women, 25 patients with fibrocystic disease and 144 breast cancer patients, the overall diagnostic sensitivity and specificity of the CA 15.3 test was 27 and 97%, respectively. The positive and negative predictive values were 93 and 43%. In 150 node-negative patients taking part in a chemoprevention trial CA 15.3 was assayed at baseline and every 4 months for a median follow-up of 24 months (range 4-48). In these patients, 5 had local recurrences, 1 had a regional recurrence, 9 had distant metastases and 3 developed cancer in the contralateral breast. Among the patients with recurrences, those with distant metastases showed the highest ratio of CA 15.3 increase (8/9); in local and regional recurrences, this ratio was lower (2/6). The patients with contralateral breast cancer had no significant increase in CA 15.3. Patients in whom metastases were detected showed an increase in CA 15.3 4-48 months before clinical or instrumental detection of the metastases.

Adult↗
PubMedDate not supplied

The use of genetically engineered cells for assessing CYP2D6-related polymorphic effects.

As an example of advanced testing in the field of metabolism in an industrial environment, the introduction of some novel approaches, including the use of genetically engineered cell lines for assessing CYP 2D6-related polymorphic effects is illustrated. In this paper, it is demonstrated that novel in vitro test systems can be developed by using these genetically engineered cell lines for evaluating the potential risks associated with proprietary drugs (especially if their metabolism depends to a high extent on CYP 2D6). Moreover, it is demonstrated that, by the use of these in vitro methods, issues such as polymorphism, for which no animal models are available, can be assessed in such a way that predictions can be made on adverse effects which, up to now, could only be detected during clinical trials. Through the use of these new biotechnological in vitro metabolism models, clinically relevant data can be obtained for a scientifically-based human risk assessment, and animal use can be reduced.

Animal Testing Alternatives↗
PubMedDate not supplied

Structure, function and gene expression of epithelial mucins.

In this review the main characteristics, i.e., structure, function and gene expression, of the different mucins are discussed. Mucin-type molecules consist of a core protein moiety (apomucin) where a number of carbohydrate chains are attached to serines and threonines by glycosidic bonds. O-linked carbohydrates form up to 80% of the molecule and the length of the glucidic side chains varies from one to more than 20 residues. At least eight mucin-like genes have been isolated so far, and the main characteristic is the presence of a central domain composed of a variable number of "tandem repeats". The sequence homology of the central domain among the different members of the mucin-type family is limited, indicating that this internal domain is unique for each mucin. Thanks to the integrated results of genetic, immunological and biochemical studies, it is now possible to identify eight apomucin genes, namely MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7. MUC1 is the best characterized mucin and it is expressed on the apical surface of most polarized epithelial cells. The MUC1 gene has been cloned and sequenced. The MUC2 gene encodes a typical secretory gel-forming mucin which represents the predominant form in human intestinal and colon tissues. Another intestinal mucin is MUC3. The MUC4, MUC5AC and MUC5B genes have been isolated from a bronchial tissue cDNA library. The MUC4 and MUC5AC genes are mainly expressed in the respiratory tract, in gastric and reproductive mucosa, while MUC5B is highly detectable only in the bronchial glands. The MUC6 gene is expressed by gastric tissue and, recently, MUC7 has been cloned and sequenced using a salivary cDNA library.

Amino Acid Sequence↗
PubMedDate not supplied

The influence of blood glucose levels on [18F]fluorodeoxyglucose (FDG) uptake in cancer: a PET study in liver metastases from colorectal carcinomas.

AIMS AND BACKGROUND: To study the influence of blood glucose levels on the clinical reliability of positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) in the detection of liver metastases from colorectal carcinomas and in the analysis of tumor uptake of FDG. METHODS: After having given their informed consent, 8 patients with 20 liver metastases (mean size, 31.5 mm; range, 10-75 mm) detected by means of CT were submitted to a first FDG-PET examination under fasting conditions and, 2 days later, to a second FDG-PET examination performed after i.v. infusion of a glucose solution (4 mg/kg/min for 2 hrs). The results of the two studies were compared in each patient, considering both the localization of the metastases and the FDG uptake in the lesions. A non-kinetic method was used, calculating the Standardized Uptake Value (SUV). RESULTS: All 20 metastases were clearly visible on FDG-PET under fasting conditions. Moreover, in 2 patients FDG-PET detected a number of unknown liver metastases. The blood glucose levels after glucose infusion were significantly higher than the levels under fasting conditions, 158 +/- 13.8 mg/100 ml (mean +/- sd) and 92.4 +/- 10.2, respectively (P < 0.001), and the quality of the FDG-PET images showed a marked deterioration. FDG-PET was unable to detect 6 of the 20 lesions and another 10 lesions were localized less clearly. Moreover, 80% of the unknown liver metastases were not detected after glucose loading. The SUVs of metastases decreased from 9.4 +/- 5.7 (mean +/- sd) under fasting conditions to 4.3 +/- 8.3 after glucose loading (P < 0.001). CONCLUSIONS: FDG-PET studies may be particularly unreliable under conditions of high levels of blood glucose. Therefore, patients entering FDG-PET studies should fast, and blood glucose concentration needs to be taken into account when evaluating FDG uptakes in follow-up studies.

Adult↗
PubMedDate not supplied

The role of serum carcinoembryonic antigen (CEA) in the management of patients with colorectal carcinoma: the experience of the Istituto Tumori of Milan.

CEA determination has attained an important role in the clinical management of patients with tumors of the colorectal tract. In this paper the experience of the Istituto Tumori of Milan is reviewed and the results are discussed. Three hundred and thirty-six patients were followed after curative resection of colorectal carcinoma. The follow-up period was 15 years, from January 1975 to December 1990 (global follow-up 1358 years). In the course of follow-up 136 patients developed recurrent disease. The number of CEA determinations for each patient ranged from 1 to 37 (mean 8, total 3330). CEA levels of presurgical patients were related to the clinical stage. Among patients who developed recurrences 61% showed an increase in CEA serum levels. In 200 patients with a negative follow-up we observed only 15 cases of false-positive results.

Adult↗