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Biomedical subjects

G Manenti

Publications and source records attributed to G Manenti.

At least 19 recordsLinked to original sources
PubMed2006

In vivo measurement of the apparent diffusion coefficient in normal and malignant prostatic tissue using thin-slice echo-planar imaging.

PURPOSE: Diffusion is a physical process based on the random movement of water molecules, known as Brownian movement. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that provides information on such biophysical properties of tissues as density, cell organisation and microstructure, which influence the diffusion of water molecules. The aim of this study was to evaluate the ability of MRI to obtain information on the diffusion of water molecules in normal and malignant prostate tissues. MATERIALS AND METHODS: Ten volunteers and 19 patients with prostate lesions diagnosed by transrectal ultrasound (TRUS) were enrolled in our study. Morphological imaging was obtained with T2-weighted turbo spin-echo (TSE) sequences with and without fat suppression [spectral presaturation with inversion recovery (SPIR)] and an axial dynamic T1-weighted SPIR fast-field echo (FFE) sequence during intravenous administration of contrast material. DWI was obtained with a high-spatial-resolution single-shot spin-echo echo planar imaging (EPI) inversion recovery (IR) sequence. The apparent diffusion coefficient (ADC) maps were analysed by positioning an 8-pixel region of interest (ROI) over different zones of the prostate, and the focal lesion when present. The tumour was confirmed by a TRUS-guided needle biopsy taken within 1 month of the MRI examination. RESULTS: The mean ADC value of the central zones (1,512.07+/-124.85x10(-3) mm2/s) was significantly lower than the mean ADC of the peripheral zones (1,984.11+/-226.23x10(-3) mm2/s) (p<0.01). The mean ADC value of tumours (958.97+/-168.98x10(-3) mm2/s) was significantly lower than the mean values of normal peripheral zones (p<0.01). CONCLUSIONS: Our preliminary results indicate that DWI is useful for characterising tissue in the different regions of the prostate gland and in distinguishing normal from cancerous tissues, given its ability to detect early changes in the structural organisation of prostate tissue.

Adult↗
PubMed2006

Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells.

The mouse parathyroid hormone-like hormone (Pthlh) gene encodes three allelic variants characterized by amino acid substitutions that are associated with susceptibility (Pthlh(Pro)) or resistance (Pthlh(Thr) and Pthlh(SerAspTyr)) to two-stage skin carcinogenesis and to modulation of cell migration in vitro in transfected human cancer cells. cDNA microarray hybridization analysis of 8473 transcript clones revealed a similar gene expression profile for the Pthlh(Thr) and Pthlh(SerAspTyr) alleles but a distinct pattern for the Pthlh(Pro) allele, suggesting an association between a specific gene expression profile and biological function of the Pthlh alleles. Some of the genes modulated by the Pthlh alleles, e.g., ANXA1, CCL2, FN1 and TFF3, play a role in cell migration and may represent candidate targets for this Pthlh function. Our study demonstrates the potential usefulness of gene expression profiling of genetic variants for the functional characterization of candidate cancer modifier genes.

Alleles↗
PubMed2006

Identification of RASSF8 as a candidate lung tumor suppressor gene.

The RASSF8 gene, which maps close to the KRAS2 gene, contains a RAS-associated domain and encodes a protein that is evolutionarily conserved from fish to humans. Analysis of the RASSF8 transcript revealed a complex expression pattern of 5'-UTR mRNA isoforms in normal lung and in lung adenocarcinomas (ADCAs), with no apparent differences. However, RASSF8 gene transcript levels were approximately seven-fold-lower in lung ADCAs as compared to normal lung tissue. Expression of RASSF8 protein by transfected lung cancer cells led to inhibition of anchorage-independent growth in soft agar in A549 cells and reduction of clonogenic activity in NCI-H520 cells. These results raise the possibility protein encoded by RASSF8 is a novel tumor suppressor for lung cancer.

5' Untranslated Regions↗
PubMed2006

Magnetic resonance imaging of the prostate with spectroscopic imaging using a surface coil. Initial clinical experience.

PURPOSE: The purpose of this study was to evaluate the diagnostic ability of proton magnetic resonance spectroscopic imaging (MRSI) in the detection and localisation of prostate cancer, prospectively compared with histopathologic findings. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) and MRSI were performed on 39 patients with prostate-specific antigen (PSA) levels greater than 4 ng/ml and suspicious findings at trans-rectal ultrasound (TRUS). All patients underwent a TRUS ten-core biopsy within 30 days according to a subdivision of the prostate into octants. All studies were interpreted by a dedicated radiologist who reported the areas of interest as normal, equivocal or suspicious on MRI. At MRSI, cancer was defined as possible if the ratio of choline plus creatine to citrate exceeded mean normal peripheral zone values by two standard deviations (SD) or as definite if that ratio exceeded the normal value by three SD. MRI and MRSI findings were spatially correlated with findings obtained from individual biopsy sites. RESULTS: MRI and MRSI alone had sensitivity, specificity, positive and negative predictive values and diagnostic accuracy in the detection of prostate cancer equal to 85%, 75%; 53%, 89%; 65%, 88%; 77%, 74%; and 69%, 79%, respectively. These values were 70%, 89%, 88%, 74% and 79% when MRI and MRSI were combined. Site-by-site analysis of MRI and MRSI findings and biopsy results yielded no significant correlation. CONCLUSIONS: The combination of MRSI and MRI provides a significantly higher specificity in the detection of tumours as compared with MRI alone and can be recommended as a problem-solving modality before biopsy in patients with high PSA levels and suspicious TRUS.

Adenocarcinoma↗
PubMed2005

MR spectroscopy of prostate cancer. Initial clinical experience.

Aim of the study was to evaluate the effectiveness of proton MR Spectroscopic (MRS) imaging in the detection and localization of prostate cancer, prospectively compared with histopathologic findings. Magnetic Resonance (MR) and MRS imaging were performed in 65 patients with high levels of prostate-specific antigen (PSA) and suspicious areas at the transrectal ultrasound (TRUS). At MR areas of interest were reported as normal, equivocal or suspicious. At MRS imaging, cancer was diagnosed as "possible" if the ratio of choline plus creatine to citrate exceeded 2 SDs above mean normal peripheral zone values or as "definite" if the ratio exceeded 3 SDs. All patients underwent a TRUS 10-core biopsy within 30 days of the imaging study. MR alone showed sensitivity, specificity, positive predictive values, negative predictive values and accuracy for detection of prostate cancer of 85%, 76%, 53%, 91% and 65%, respectively, whereas MRS alone showed 89%, 77%, 78%, 69% and 83%, respectively. These values were 71%, 90%, 89%, 74% and 80% when the prostate was evaluated combining MR and MRS. The addition of MRS to the MR imaging provides a higher specificity in tumour detection and can be recommended as a problem-solving modality for patients with elevated PSA levels and suspicious TRUS before biopsy.

Aged↗
PubMed2004

Diffusion-weighted MRI in the evaluation of renal lesions: preliminary results.

The purpose of this study was to evaluate the capability and the reliability of diffusion-weighted MRI in the evaluation of normal kidney and different renal lesions. 39 patients (10 normal volunteers and 29 patients with known renal lesions) underwent MRI of the kidneys by using a 1.5 T superconducting magnet. Axial fat suppressed turbo spin echo (TSE) T(2) and coronal fast field echo (FFE) T(1) or TSE T(1) weighted images were acquired for each patient. Diffusion-weighted (DW) images were obtained in the axial plane during breath-hold (17 s) with a spin-echo echo planar imaging (SE EPI) single shot sequence (repetition time (TR)=2883 ms, echo time (TE)=61 ms, flip angle=90 degrees ), with b value of 500 s mm(-2). 16 slices were produced with slice thickness of 7 mm and interslice gap of 1 mm. An apparent diffusion coefficient (ADC) map was obtained at each slice position. The ADC was measured in an approximately 1 cm region of interest (ROI) within the normal renal parenchyma, the detected renal lesions and the collecting system if dilated. ADC values in normal renal parenchyma ranged from 1.72 x 10(-3) mm(2) s(-1) to 2.65 x 10(-3) mm(2) s(-1), while ADC values in simple cysts (n=13) were higher (2.87 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1)). In hydronephrotic kidneys (n=6) the ADC values of renal pelvis ranged from 3.39 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1). In cases of pyonephrosis (n=3) ADC values of the renal pelvis were found to be lower than those of renal pelvis of hydronephrotic kidneys (0.77 x 10(-3) mm(2) s(-1) to 1.07 x 10(-3) mm(2) s(-1)). Solid benign and malignant renal tumours (n=7) showed ADC values ranging between 1.28 x 10(-3) mm(2) s(-1) and 1.83 x 10(-3) mm(2) s(-1). In conclusion diffusion-weighted MR imaging of the kidney seems to be a reliable way to differentiate normal renal parenchyma and different renal diseases. Clinical experience with this method is still preliminary and further studies are required.

Adult↗
PubMed2004

Diffusion-weighted MR imaging in the evaluation of renal tumours.

The aim of this study was to evaluate the capability and the reliability of diffusion-weighted MR imaging to differentiate benign from malignant renal lesions. Twenty healthy volunteers and 48 patients with known renal lesions underwent MR of the kidneys by using a 1.5 T superconductive magnet. Diffusion-weighted images (DWI) were obtained on the axial plane during breathhold (17 s) with a SE EPI single shot sequence using a b value of 500 s/mm2. One region of interest (ROI) (lesions < than 3 cm) or 3 ROI (lesions > than 3 cm) were placed within the lesion for the measurement of apparent diffusion coefficient (ADC). ADC map was obtained at each slice position. Mean ADC value in normal renal parenchyma was 2.2 +/- 0.20 x 10(-3) mm2/s, while ADC values in simple cysts (n = 20) were higher (mean ADC values 3.65 +/- 0.09 x 10(-3) mm2/s). Solid benign and malignant renal tumors (n = 19) showed a mean ADC value of 1.7 +/- 0.48 x 10(-3) mm2/sec. The comparison between ADC values in normal parenchyma group and tumour group were found to be statistically significant (p < 0.0001). ADC values of cystic renal cell carcinomas were higher than those of clear cell carcinomas (p < 0.001). In conclusion, DW MRI of the kidney seems to be a reliable means for differentiating normal renal parenchyma from different renal tumors.

Adenocarcinoma, Clear Cell↗
PubMed2003

Migraine-like disorder segregating with mtDNA 14484 Leber hereditary optic neuropathy mutation.

The authors report neurologic features in a large family harboring the mitochondrial DNA (mtDNA) mutation T14484C associated with Leber hereditary optic neuropathy (LHON). In the maternal line the mtDNA mutation was associated with optic neuropathy or migraine with aura or without aura and transient neurologic/visual disturbances. The segregation of familiar cases of migraine and LHON mutation broadens the clinical phenotype associated with a primary LHON mutation.

Adolescent↗
PubMed2001

Linkage disequilibrium pattern in the L-myc gene in Italian and Japanese non-small-cell lung-cancer patients.

Italian and Japanese non-small-cell lung-cancer patients were genotyped for an intragenic L-myc EcoRI restriction site polymorphism previously reported to be associated with lung-tumor prognosis in Asian populations but not in Caucasians. Screening of the L-myc sequence in Italian samples allowed identification of 2 additional 3'-UTR SNPs, located 2.3-3.0 kb from the EcoRI polymorphism, but no coding polymorphism was found. No significant association was found between any of the 3 SNPs and lung-tumor prognosis in Italian patients, consistent with the reported difference between Caucasian and Asian populations. Moreover, the newly discovered polymorphisms in the Italian group were not present in Japanese patients. Significant LD between EcoRI and the 2 other SNPs was detected in the Italian population, whereas no significant LD between the 2 3'-UTR markers was detected despite their close proximity (0.7 kb). Thus, the disparate conclusions about the role of L-myc polymorphism in tumor prognosis among different populations may rest in population-specific LD between the functional gene and the L-myc polymorphism.

Adenocarcinoma↗
PubMed2001

Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci.

Car-R and Car-S outbred mouse lines, phenotypically selected for resistance and susceptibility to skin carcinogenesis respectively, show significant linkage disequilibrium (LD) at genetic markers mapping on chromosomal regions where skin cancer modifier loci (Skts3, Skts1, and Psl1 on Chrs 5, 7, and 9 respectively) have been mapped in standard crosses. Analysis of these regions for genetic linkage with skin cancer phenotypes in 245 (Car-R x Car-S)F2 intercross mice, by using single nucleotide polymorphisms (SNPs), revealed significant linkage at a possible allelic form of the Skts1 locus, whose mapping region was shortened to a <5.5-cM interval near the Tyr locus. The Car-derived Skts1 locus was linked with papilloma multiplicity and latency by a recessive inheritance of the susceptibility allele. Putative loci on Chr 5 (Skts3) and 9 (Psl1) showed no significant linkage. These results point to the important role of the Stks1 locus in mouse skin tumorigenesis in independent crosses. The shortened Skts1 mapping region should facilitate the identification of candidate genes.

Animals↗
PubMed2001

A radiation hybrid transcript map of the mouse genome.

Expressed-sequence tag (EST) maps are an adjunct to sequence-based analytical methods of gene detection and localization for those species for which such data are available, and provide anchors for high-density homology and orthology mapping in species for which large-scale sequencing has yet to be done. Species for which radiation hybrid-based transcript maps have been established include human, rat, mouse, dog, cat and zebrafish. We have established a comprehensive first-generation-placement radiation hybrid map of the mouse consisting of 5,904 mapped markers (3,993 ESTs and 1,911 sequence-tagged sites (STSs)). The mapped ESTs, which often originate from small-EST clusters, are enriched for genes expressed during early mouse embryogenesis and are probably different from those localized in humans. We have confirmed by in situ hybridization that even singleton ESTs, which are usually not retained for mapping studies, may represent bona fide transcribed sequences. Our studies on mouse chromosomes 12 and 14 orthologous to human chromosome 14 show the power of our radiation hybrid map as a predictive tool for orthology mapping in humans.

Animals↗
PubMed2001

Laser thermal ablation in the treatment of small hepatocellular carcinoma: results in 74 patients.

PURPOSE: To evaluate the safety, local effectiveness, and long-term results of laser thermal ablation (LTA) in the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ninety-two biopsies proved small HCCs (range, 0.8-4.0 cm) in 74 patients who were treated percutaneously with LTA in an outpatient clinic. A laser at a power of 5.0 W was coupled with one to four fibers that were advanced through 21-gauge needle(s) for 6-12 minutes. All lesions were evaluated with computed tomography (CT) for changes in size and vascular pattern, recurrence rates, and cumulative survival rates. Patients were examined for complications. RESULTS: No major complications occurred in 117 LTA sessions, with an average of 1.3 sessions per tumor. At 3 months, CT scans showed a nonenhancing area (complete necrosis) in 89 (97%) of 92 lesions. During follow-up (range, 6-66 months; mean, 25.3 months), 84 tumors (91%) decreased in size. The local recurrence rates (range, 1-5 years) ranged from 1.6% to 6.0%. Recurrence rates (range, 12-60 months) in other liver segments ranged from 24% to 73%. Cancer-free survival rates (range, 1-4 years) ranged from 73% to 24%. Overall survival rates were 99%, 68%, and 15% at 1, 3, and 5 years, respectively. Twenty-one patients (28%) died. CONCLUSION: LTA is a safe and effective treatment for small HCC.

Aged↗
PubMed2000

A cancer modifier role for parathyroid hormone-related protein.

The parathyroid hormone-related protein (PTHrP) gene (Pthlh) maps in the distal region of mouse chromosome 6 that contains a quantitative trait locus associated with genetic predisposition to skin tumorigenesis. Here, we report a genetic polymorphism located in the osteostatin encoding region of the Pthlh gene and that produces Thr/ Pro PTHrP variants. PthlhThr and PthlhPro alleles were significantly linked with resistance and susceptibility to skin carcinogenesis in phenotypically selected Car-R and Car-S outbred mice. Transfection of human NCI-H520 squamous cell carcinoma cells with the PthlhPro allele resulted in cells growing in clusters, tending to pile up, and growing at a significantly faster rate in nude mice than non-transfected and PthlhThr-transfected cells. These results point to the role of the Pthlh gene as a cancer modifier gene in skin tumorigenesis.

Animals↗
PubMed2000

Population-based mapping of pulmonary adenoma susceptibility 1 locus.

Pulmonary adenoma susceptibility 1 (Pas1), the major locus affecting inherited predisposition to lung tumor development in mice, maps near the Kras2 gene. We previously reported a significant association between a KRAS2/RsaI polymorphism and the risk and prognosis of lung adenocarcinoma (ADCA) in the Italian population. In the present case-control study, we examined 269 lung ADCA patients, 121 squamous cell lung carcinoma patients, and 632 healthy individuals (general population controls) in the Japanese population with genetic markers spanning approximately 1200 kb in the KRAS2 region. Allele-specific oligonucleotide hybridization revealed the same KRAS2/RsaI polymorphism associated with risk and prognosis as in Italian lung ADCA patients; the polymorphism was significantly associated with clinical stage (P < 0.001) and survival rate (log rank = 0.0014), confirming the mapping of PAS1 and pointing to the role of this locus in human lung cancer.

Adenocarcinoma↗
PubMed2000

Predisposition to lung tumorigenesis.

Mouse inbred strains with inherited predisposition and resistance to lung cancer provide an essential tool for the dissection of the genetics of this complex disease. We have previously mapped a major locus (Pulmonary adenoma susceptibility 1, Pas1) affecting inherited predisposition to lung cancer in mice on chromosome 6, near Kras2. Appropriate crosses that include susceptible mice (Pas1(s)) provide a model system for identifying loci that can modify the lung cancer predisposition phenotype caused by Pas1. Using this approach we have mapped the Pulmonary adenoma resistance 1 (Par1) locus that behaves like a modifier locus of Pas1. More recently, we mapped additional lung tumor resistance loci (Par2, and Par4), and a locus specifically involved with lung tumor progression (Papg1). The mapping of Pas1 in mice stimulated us to test the possible association of genetic markers located in the homologous human region (12p12) with risk and prognosis of lung adenocarcinomas in man. In the Italian population, we carried out an association study by genotyping lung adenocarcinoma patients and healthy controls for genetic markers located in the putative region of interest. Homozygosity of the A2 allele at a Kras2/RsaI polymorphism, and allele 2 at a VNTR polymorphism in the PTHLH gene showed borderline statistically significant associations with lung cancer risk. Furthermore, the same alleles were significantly associated with tumor prognosis. Studies on association were then performed in the Japanese and in European populations. In the Japanese population, the KRAS2/RsaI marker was significantly associated with prognosis of lung adenocarcinoma, whereas the European study did not confirm this association. Our results may provide evidence for the existence of the human PAS1 locus, suggesting that the mouse model of inherited predisposition to lung tumorigenesis is predictive of a human genetic mechanism of susceptibility to lung cancer.

Adenocarcinoma↗
PubMed2000

Linkage disequilibrium and haplotype mapping of a skin cancer susceptibility locus in outbred mice.

Car-R (carcinogenesis-resistant) and Car-S (carcinogenesis-susceptible) outbred mice, obtained by phenotypic selection from an initial intercross of eight inbred strains, show a >100-fold difference in their susceptibility to two-stage skin tumorigenesis. We found that the lines carry a high degree of genetic polymorphism. with an average heterozygosity of 0.39. This polymorphism allowed the use of linkage disequilibrium (LD) and haplotype analysis for the mapping of a skin cancer modifier locus on Chr 7, in a short region of 6 cM, around the Tyr gene. Car-S mice inherited the susceptibility allele at this locus from the A/J, BALB/c, SJL/J, and SWR/J strains. Our results demonstrate the feasibility and usefulness of mapping disease genes by LD in phenotypically selected, genetically heterogeneous animals.

Animals↗
PubMed1999

Analysis of loss of heterozygosity in neoplastic nodules induced by diethylnitrosamine in the resistant BFF1 rat strain.

Loss of heterozygosity (LOH) at specific chromosomal regions is a frequent event in poorly differentiated human hepatocellular carcinomas (HCCs), but rare in mouse HCCs. This behavior could depend on interspecies differences in mechanisms of hepatocarcinogenesis or in developmental stage of lesions. To verify if LOH is involved in rat hepatocarcinogenesis, we studied LOH frequency in slowly growing neoplastic nodules induced by Solt-Farber model in diethylnitrosamine-initiated BFF1 rats. We analyzed, with microsatellites, markers at 67 rat loci dispersed over all chromosomes, corresponding to regions homologous to those lost in human HCCs or containing hepatocellular susceptibility (Hcs) or resistance (Hcr) loci in rat and mouse. In agreement with previous findings with mouse HCCs, but at variance with human HCCs, no detectable LOH was found at any locus in rats, suggesting rare LOH involvement in neoplastic nodules, with low tendency to progress to full malignancy, of BFF1 rats.

2-Acetylaminofluorene↗