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Biomedical subjects

V Russo

Publications and source records attributed to V Russo.

At least 73 records · Page 4Linked to original sources

Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy.

Gastric cancers are rarely diagnosed before the age of 40 years and the incidence reaches a peak during the 7th decade in the general population. A molecular mechanism of early tumor onset may be determined by comparing microsatellite instability (MSI), indicative of error-prone mismatch repair, and loss of heterozygosity (LOH) between gastric cancers in patients < or = 40 years of age and those of older ages. Three to 5 chromosomal loci, where MSI and/or LOH are commonly found in gastric cancers in the general population, were examined in formalin-fixed, paraffin-embedded samples from 102 patients < or = 40 years of age using a polymerase chain reaction-based non-radioactive screening method. MSI and/or LOH at a minimum of 1 locus were detected in 11/102 patients. The frequency of MSI and/or LOH at the D11S904 locus was significantly higher than that at the D2S119, D2S123, D5S409 and IFNA regions. No preferential genetic changes at the D11S904 locus were observed in elderly patients. Among several clinicopathological variables, a statistically significant association with MSI and/or LOH was observed only for tumors located at the cardia, compared with tumors at the antrum and the corpus. Our findings suggest that a unique mechanism may be involved in increasing the susceptibility of the D11S904 locus for either MSI or LOH, especially for cardia tumors in young patients. Early onset of gastric cancers in patients < or = 40 years of age is associated with genetic changes at preferential chromosomal loci, including D11S904.

Adolescent↗

Patients younger than 40 years with gastric carcinoma: Helicobacter pylori genotype and associated gastritis phenotype.

BACKGROUND: In the general population, Helicobacter pylori (H. pylori), particularly the cagA positive strain, has been associated with intestinal-type gastric carcinoma. Gastric carcinomas are rarely observed in patients age < or = 40 years. Host-related factors have been thought to be more important than environmental agents in these early-onset cancers. The aim of this study was to ascertain the possible role of H. pylori infection and that of cagA positive strains in the development of gastric carcinoma in these young patients. METHODS: In this case-control study, 105 gastric carcinoma patients (male-to-female ratio = 1.1; mean age, 34.4 years; range, 16-40 years) and an equal number of controls (matched for gender and age) were retrospectively selected from the same geographic area. The phenotypes of gastritis and H. pylori were histologically assessed, and the presence of the ureC gene, which is indicative of H. pylori infection, and the cagA genotype were determined by polymerase chain reaction. Gastric carcinoma risk was calculated by both univariate and multivariate statistical methods, taking into account the cancer phenotype, the gastritis phenotype detected in both patients and controls, and the H. pylori genotype. RESULTS: For 74 diffuse and 31 intestinal gastric carcinomas, multivariate logistic regression analysis produced results consistent with those of univariate statistical tests, showing a significant association between gastric carcinoma and both H. pylori infection (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.52-5.11) and cagA positive status (OR = 2.94; 95% CI = 1.56-5.52). CONCLUSIONS: In young Italian patients with gastric carcinoma, the significant association with cagA positive H. pylori infection suggests that the bacterium has an etiologic role in both diffuse-type and intestinal-type gastric carcinoma.

Adenocarcinoma↗

Analysis of expressed sequence tags of porcine skeletal muscle.

Porcine skeletal muscle genes play a major role in determining muscle growth and meat quality. Therefore, to progress towards a better understanding of the genetic factors influencing these traits, the first step is to characterize the genes expressed in skeletal muscle tissue in pig. To this aim, we constructed a porcine biceps femoris muscle cDNA library and sequenced 111 randomly isolated clones. By FASTA analysis, we identified 72 unique clones: 47 showed homology to previously identified genes in human or other mammals, 20 matched uncharacterized expressed sequence tags (ESTs), two showed no significant matches to sequences already present in DNA databases, and three other clones containing only repetitive elements were excluded from further analysis. Mitochondrial genes (16.2%), myosin heavy chain genes (9%) and the actin alpha skeletal muscle gene (9%) were the most abundant transcripts. Among the 47 identified genes several muscle-specific or predominant sequences expressed in skeletal muscle were found. The sequences of the clones matching uncharacterized human, mouse or porcine ESTs were tested by GRAIL in order to identify putative coding regions. The results of our analysis allowed the establishment of a first list of genes expressed in porcine skeletal muscle.

Amino Acid Sequence↗

Identification of a promiscuous T-cell epitope encoded by multiple members of the MAGE family.

One of the major limitations of tumor-specific vaccination is the generation of antigen-loss variants that are able to escape the immune response elicited by a monoantigenic peptide epitope. Here, we report the identification of a new HLA-B*3701-restricted epitope shared by four different members of the MAGE family. Peripheral blood lymphocytes isolated from a melanoma patient were stimulated in vitro with the autologous HLA-negative melanoma line transfected with autologous HLA B*3701 molecule. This protocol led to the induction of tumor-specific, B*3701-restricted CTLs specific for a peptide epitope encoded by codons 127-136 of the gene MAGE-1. The same epitope is also encoded by the homologous region of three other members of the MAGE family, MAGE-2, -3, and -6. Consistent with the notion that the peptide encoded by MAGE-1 codons 127-136 is, indeed, processed from the proteins encoded by all four MAGE family members, the CTLs were able to specifically recognize Cos-7 cells cotransfected with HLA-B*3701 and any of these MAGE genes. Moreover, the CTLs also recognized a MAGE-6-positive melanoma line transfected with the B*3701 molecule. These findings allow the inclusion of a new set of tumor patients into clinical cancer vaccination trials. Furthermore, they suggest that some promiscuous peptide epitopes shared by different members of the MAGE family might be less prone to escape the immune response by generation of MAGE antigen loss variants.

Antigens, Neoplasm↗

Major histocompatibility complex class I restricted cytotoxic T cells specific for natural melanoma peptides recognize unidentified shared melanoma antigen(s).

CTLs were generated in vitro from two healthy donors and one melanoma patient by stimulation of CD8+ T cells with autologous dendritic cells pulsed with natural melanoma peptides (NMPs), obtained by acid treatment of HLA-matched melanoma cells. CTLs showed MHC class I-restricted melanoma-specific cytolytic activity. Importantly, CTLs from the patient, induced with NMPs obtained from an allogeneic HLA-A-matched melanoma, killed the autologous tumor. COS-7 cells cotransfected with the cDNA of 13 melanoma antigens and the HLA-A1-restricting allele did not induce cytokines release from NMP-specific CTLs, suggesting that they recognize unidentified shared melanoma antigens and that they may be valuable for identification of new tumor antigens. These results strongly support the use of autologous and/or allogeneic NMP-pulsed dendritic cells as cancer vaccines in patients whose neoplasms do not express or have lost expression of known tumor antigens.

Alleles↗

Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1.

Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease-free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE-3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced.

Adult↗

Toxic adenoma and papillary thyroid carcinoma in a patient with Graves' disease.

A case of a very rare association of toxic adenoma and papillary carcinoma with Graves' disease is presented. A 34-year-old woman developed Graves' disease with mild ophthalmopathy. An ultrasound revealed diffuse thyroid enlargement with a hypoechoic pattern and a hypoechoic nodule with regular edges of 1.6 cm in diameter at the lower pole of the left lobe. A thyroid 131I scintiscan showed a diffuse and homogeneous 131I distribution. The 131I uptake (RAIU) was elevated. One year later, while still on a low dose of methimazole, the patient had a recurrence of hyperthyroidism following an iodine load from a contrast agent. A further thyroid ultrasound confirmed the previously described pattern but showed a new hypoechoic nodule of 1.1 cm with irregular edges in the left lobe. A thyroid 131I scintiscan this time demonstrated a hyperactive area localised in the larger nodule and a lower diffuse uptake of the remaining tissue. Because of the worsening of the symptoms of hyperthyroidism, the patient had a left lobectomy. On histological examination, the larger nodule was well encapsulated and showed the characteristics of a hyperfunctioning follicular adenoma. The smaller nodule was a typically unencapsulated papillary carcinoma. Several other microfoci of papillary carcinoma were also found in the adjacent tissue. Completion of thyroidectomy was therefore performed, followed by 131I ablative therapy and thyroxine suppressive treatment. This observation suggests that the chronic abnormal stimulation of the thyroid gland by the thyroid-stimulating antibody (TSAb) may facilitate the neoplastic transformation of the thyrocytes in individuals with a critical genetic background.

Adenoma↗

Mapping of the Na+, K(+)-ATPase subunit alpha 2 (ATP1A2) and muscle phosphofructokinase (PFKM) genes in pig by somatic cell hybrid analysis.

Two expressed sequence tags were isolated from a porcine skeletal muscle cDNA library and identified as the putative partial cDNAs of the porcine Na+, K(+)-ATPase subunit alpha 2 (ATP1A2) and muscle phosphofructokinase (PFKM) genes after sequencing and homology search. Results of analysis of a pig-rodent somatic cell hybrid panel by PCR allowed the assignments of ATP1A2 to porcine chromosome (chr) 4 and of PFKM to porcine chr 5. These assignments support previously observed conservation of syntenic relationships between human chr 1 and porcine chr 4 and between human chr 12 and porcine chr 5.

Animals↗

High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: implications for protocol design of therapeutic antigen-specific vaccination strategies.

Human melanoma cells express several antigens which are recognized by autologous and specific CTL clones in association with HLA-class-I molecules. Many of these antigens represent suitable targets for tumor immunotherapy, since their expression in human melanoma cells is common and highly specific. In order to achieve real clinical success with therapeutic vaccination strategies, one important requirement is the expression of the target antigen by all the tumor lesions of a patient. We have studied this issue by assessing, through an RT-PCR approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic lesions (82%), the homogeneity in the pattern of gene expression within the cluster was complete. Heterogeneity within the same cluster was observed in only 3 out of 17 clusters (18%) and represented only minor features. Our data reveal that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic lesions express the same pattern of antigen-coding genes. These observations have 2 main clinical implications: (i) the antigenic characterization of one single and easily accessible lesion allows identification of optimal targets for an active antigen-specific immunotherapy treatment; (ii) almost all the metastatic lesions are expected to be hit by the immune response eventually induced against the tumor antigen. Moreover, these data suggest that active specific immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in high-risk AJCC-stage-III-melanoma patients.

Antigens, Neoplasm↗

Isolation and mapping of two porcine skeletal muscle myosin heavy chain isoforms.

The present paper describes the isolation and linkage mapping of two isoforms of skeletal muscle myosin heavy chain in pig. Two partial cDNAs (pAZMY4 and pAZMY7), coding for the porcine myosin heavy chain-2B and -beta respectively, have been isolated from a pig skeletal muscle cDNA library. Four RFLPs were detected with the putative porcine skeletal myosin heavy chain-2B probe (pAZMY4) and one RFLP was identified with the putative myosin heavy chain-beta probe (pAZMY7). Two myosin heavy chain loci were mapped by linkage analysis performed with the five RFLPs against the PiGMaP linkage consortium ResPig database: the MYH1 locus, which identifies the fast skeletal muscle myosin heavy chain gene cluster, was located at the end of the map of porcine chromosome 12, while the MYH7 locus, which identifies the myosin heavy chain-alpha/-beta gene cluster, was assigned to the long arm of porcine chromosome 7.

Animals↗

The porcine proteasome subunit A4 (PSMA4) gene: isolation of a partial cDNA, linkage and physical mapping.

A partial cDNA clone encoding the porcine proteasome subunit A4 (PSMA4 or proteasome subunit C9) has been isolated from a porcine muscle cDNA library and sequenced. A biallelic TaqI RFLP was identified in Large White, Landrace and Duroc breeds. Moreover, the 3'-untranslated region of the gene showed a triallelic SSCP. By linkage analysis the PSMA4 locus was assigned to pig chromosome 7 and by radioactive in situ hybridization this locus was mapped to the region 7q13-q14.

3' Untranslated Regions↗

[Evaluation of the filtering bleb using ultrasound biomicroscopy].

BACKGROUND: Sometimes in glaucomatous patients treated with trabeculectomy there is not a correlation between bleb shape and intraocular pressure. So we studied the functional anatomy of the filtering bleb by a ultrasound biomicroscope, using high frequency (50 Mhz) probe, which provides high resolution images of filtering blebs. MATERIALS AND METHODS: A total of 46 filtering blebs of 46 patients after trabeculectomy were analyzed by ultrasound biomicroscopy (50 Mhz). Dimensions, shapes and structure of blebs were evaluated in 2 groups of patients. RESULTS: It was possible to obtain longitudinal or transverse images of filtering blebs, to measure the height, to evaluate the reflectivity inside and to follow the route under the scleral flap. Blebs with lower reflectivity and a visible route under the scleral flap had a lower intraocular pressure while the height was not important for a good intraocular pressure. CONCLUSIONS: So ultrasound biomicroscopy can be a useful method to study filtering blebs and also to explain the mechanisms of filtering structures in patients who underwent trabeculectomy.

Aged↗

The role of the insulin-like growth factor system in the developing brain.

Insulin-like growth factors (IGFs) play a central role in brain growth and development, with IGF-1, its receptors and binding proteins (IGFBPs) being highly expressed, particularly in the olfactory bulb (OB), representing a local paracrine system. A potential role of IGFBPs in transporting and targeting IGFs to their receptors is supported by the finding that abundant IGFBP-2 is associated with cell surface proteoglycans. An OB organ culture system expressing IGF-1 and IGFBPs represents an in vitro injury model. Although IGF-1 is potently antiapoptotic for neurons and oligodendrocytes, marked gliosis and IGFBP-3 expression are seen, similar to in vivo injury responses, where intraventricular injection of IGF-1 postinjury enhances neuronal survival by blocking apoptosis. In contrast, des (1-3) IGF-1, which has low affinity for IGFBPs, is ineffective, supporting a transport or receptor targeting role for local IGFBPs. We conclude that the IGF system plays a crucial cell survival and growth role in the developing and injured brain and that IGFs have significant therapeutic potential.

Animals↗

Corneal oedemas: diagnosis and surgical planning with ultrasound biomicroscopy.

We used the Humphrey Ultrasound Biomicroscope (UBM System 840 by Zeiss-Humprey Instruments, San Leandro, Calif. USA) to study various corneal oedemas and leucomas. This UBM system, using a high-resolution probe of 50 Mhz, has an axial and lateral resolution of about 50 micrometer. We analysed 36 eyes divided into two groups, 27 (group A) affected by corneal oedema caused by traumatic-mechanic or phlogistic-toxic lesions, 9 (group B) affected by postsurgery oedema. Thanks to its high-resolution power, we could study their pathogenesis and their clinical evolution and so arrange a suitable therapy and perform an accurate follow-up of these pathologies.

Burns, Chemical↗