PubMed Health⌕ Search

Biomedical subjects

F Bertoni

Publications and source records attributed to F Bertoni.

At least 73 records · Page 4Linked to original sources
PubMed1999

Allelic expression of p73 in human ovarian cancers.

BACKGROUND: The p73 gene is structurally related to the tumor suppressor gene p53. The role of p73 in tumor development is still unclear and no data on ovarian cancer are so far available. For this reason we have analyzed, in a panel of ovarian cancers, the allelic distribution and expression of p73. PATIENTS AND METHODS: Fifty-one samples from ovarian cancers and five human ovarian cancer cell lines growing in culture were analyzed. Allelic origin was analyzed by PCR after digestion with the restriction enzyme Sty I. Heterozygous, informative cases were selected for studies aimed at evaluating allelic expression of p73. RESULTS: We found an allelic distribution similar to that previously reported. LOH was found in two patients with ovarian cancer. In one case in which normal ovarian tissue was available biallelic expression of p73 was found. CONCLUSION: In comparisons of ovarian cancers and borderline tumors, no differences in allelic distribution and/or expression were found, suggesting that p73 does not play an important role in the pathogenesis and development of ovarian cancer.

Alleles↗
PubMed1999

Microsatellite instability in gastric MALT lymphomas and other associated neoplasms.

BACKGROUND: Microsatellite instability (MSI), caused by a reduced efficacy of the DNA mismatch repair (MMR) machinery, represents a type of genomic instability frequently detected in HNPCC spectrum cancers and in a subset of sporadic carcinomas. The involvement of MSI in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has never been conclusively investigated. In this study, we tested the presence of MSI in tumor samples of patients harboring both MALT lymphomas and other types of malignancies. MATERIALS AND METHODS: We examined 10 microsatellite loci (D3S11, D3S1261, D3S1265, D6S262, D6S193, BAT-26, BAT-25, D17S250, APC, D2S123) out of a total of 34 primary tumors from 14 patients with MALT lymphomas and one or more additional neoplasms. The patients' MSI results were also tested for an association with a positive family history of cancer. RESULTS: MSI, defined by the presence of microsatellite alterations in more than 40% of the examined loci, was scored negative in all tumors studied, and pedigree analysis failed to identify any condition of familial cancer among the patients examined. CONCLUSIONS: The present study suggests that defects in DNA mismatch repair do not contribute significantly to the molecular pathogenesis of MALT lymphomas and associated neoplasms.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1999

Analysis of SAS gene and CDK4 and MDM2 proteins in low-grade osteosarcoma.

The region q13-15 of chromosome 12 contains SAS, CDK4, and MDM2 genes that are rearranged or amplified in a variety of human sarcomas. This study evaluated SAS gene amplification, and MDM2 and CDK4 protein expression in 20 tumor samples of central low-grade osteosarcoma (16 primary, 3 recurrences, 1 lung metastasis). SAS amplification was analyzed by quantitative polymerase chain reaction (PCR), while from the same paraffin-embedded samples, MDM2 and CDK4 protein expression was evaluated by immunohistochemistry. MDM2 and CDK4 proteins were found strongly expressed in 35% and 65%, respectively, of the samples. SAS was found amplified in 15% of the samples. These findings indicate that these genes may be involved in tumorigenesis and progression of low-grade osteosarcoma.

Adolescent↗
PubMed1999

Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Actuarial Analysis↗
PubMed1999

Diagnosis and tumor response in osteosarcoma and Ewing's sarcoma, according to treatment protocols SSG II, SSG VIII, ISG/SSG I, SSG IV and SSG IX.

114 patients with osteosarcoma in the extremities had been reported to the SSG II trial, 132 to the SSG VIII trial and, until October 1998, 99 to the ISG/SSG I trial. The SSG IV trial included 53 patients and the SSG IX trial 104 patients until October 1998. In the SSG II trial, 19% were good responders (grades III and IV) as compared to 51% in the SSG VIII trial. On reevaluation was the response changed in one forth of the cases in both the SSG II and SSG VIII trials. In 9 and 10 cases (8%), respectively, the reevaluation resulted in a change from "good responder" to "bad responder". In the ISG/SSG I trial, the preliminary results showed a good response in 22% of the cases. In the SSG IV trial, 44% were good responders (grades III and IV), as compared to 54% in the SSG IX trial.

Antineoplastic Agents↗
PubMed1999

Molecular genetics of extranodal marginal zone (MALT-type) B-cell lymphoma.

Mucosa-associated lymphoid tissue lymphoma is now classified as extranodal marginal zone B-cell lymphoma. We reviewed the current literature on the biological and genetic mechanisms that lead to the development and progression of this unusual lymphoma. Particular attention was given to the clinical and biological significance of the immunoglobulin genes rearrangement, that has been proposed and widely used both diagnostically and as a tool to monitor the response to antibiotic treatment.

Amino Acid Sequence↗
PubMed1999

Primary mediastinal large B-cell lymphoma (PMLCL): the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) patients and bulky disease in 10 (37%). All patients were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year TTP and OS were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. In conclusion our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular lymphoma entity should be evaluated in prospective randomized trials.

Adult↗
PubMed1999

Immunoglobulin light chain kappa deletion rearrangement as a marker of clonality in mantle cell lymphoma.

Mantle cell lymphoma (MCL) express immunoglobulin light chain lambda (IgL-lambda) more frequently than other non-Hodgkin's lymphomas, and IgL-lambda producing B-cells usually delete one or both alleles of their IgL-kappa genes. This inactivation is mediated by a rearrangement between the kappa deletion element (kappa de) and the Recombinant Signal Sequence (RSS) in the region between the Joining genes and the Constant region, or the RSS at the 3'-site of a Variable (Vkappa) segment. This deletion appears as a feasible tool for detecting monoclonality and minimal residual disease by polymerase chain reaction (PCR). Among twelve MCL patients studied, ten presented IgL-lambda expression, and all but one among these revealed a monoclonal kappa de rearrangement by PCR analysis. Six of the nine cases showed a fusion between the kappa de and the intron RSS, whilst three with a Vkappa segment. Since MCL has the worst prognosis of all B-cell lymphomas and high-dose chemotherapy regimens have been proposed, PCR for the kappa de rearrangement might be a useful molecular tool to evaluate the ability of the different treatment modalities to eradicate the malignant clones.

Biomarkers↗
PubMed1999

Clonality assessment in blood of patients with mantle cell lymphoma.

The presence of circulating neoplastic cells at diagnosis was assessed in the blood of patients presenting with mantle cell lymphoma (MCL) to determine the feasibility of a diagnostic molecular assay. Blood samples from 16 patients with pathologically reviewed MCL were analysed for the t(11;14)(q13;q32) translocation by the polymerase chain reaction (PCR): 7 (44%) were found positive. The remaining cases were examined by PCR for the presence of circulating neoplastic B-cells by amplifying the third complementarity region (CDR3) of immunoglobulin heavy chain genes and the immunoglobulin light kappa chain deletion rearrangements. A further 7 (44%) patients showed the presence of clonal lymphoma cells, leaving only 2 (12%) of cases negative for circulating lymphomatous cells. This study suggests that there is a high incidence of lymphoma cells in the blood of patients presenting with MCL. PCR for these clonal cells may be diagnostically useful.

Clone Cells↗
PubMed1999

Relationship between P-glycoprotein expression and p53 status in high-grade osteosarcoma.

The transcription of MDR1 gene may be increased by mutation or loss of function of p53 gene. In this study, we investigated whether in osteosarcoma, the p53 status is correlated with overexpression of the MDR1 gene product P-glycoprotein. The relationship between P-glycoprotein expression and p53 status was analyzed by immunohistochemistry in 64 primary and 11 metastatic high-grade osteosarcomas. In the same series, we also assessed the nuclear accumulation of MDM2 protein, whose binding to p53 protein provides an alternative mechanism of p53 inactivation. No association was found between mutant-p53 and MDM2 nuclear accumulation either with P-glycoprotein expression or with clinical course. Only increased expression of P-glycoprotein in tumor cells was significantly associated with a poor outcome, further supporting the adverse prognostic value of this marker in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Myxoid synovial sarcoma: an underappreciated morphologic subset.

Focal myxoid change is a well-recognized feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare. We describe seven cases of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis, leading to confusion (principally with malignant peripheral nerve sheath tumor). The median age (20 yr) and tumor location (four lower extremity, two upper extremity, and one head and neck region) were similar to those found in typical synovial sarcoma. Histologically, five cases were monophasic spindle cell lesions with a lacy appearance in areas with a prominent Alcian blue-positive myxoid stroma. Each case had foci with more typical features of synovial sarcoma, including a fascicular growth pattern with a variably collagenized stroma, stromal mast cells, a hemangiopericytoma-like vascular pattern, and calcification. Two cases showed small foci of glandular (biphasic) differentiation. Immunohistochemically, all of the seven cases were positive for epithelial membrane antigen, four of six were positive for pan-keratin, three of six were positive for S-100, two of four were positive for CD99, and six of six were negative for desmin. Clinical follow-up in six cases ranged from 8 to 48 months (median, 21 mo). Local recurrence developed in three patients at 9, 20, and 24 months, respectively. In one of these three patients, lung metastases developed at 13 months, and the patient died of disseminated disease at 23 months. In another of the three patients, lung metastases developed at 27 months. Three patients had no evidence of disease at 8, 15, and 15 months. Our data are too limited to indicate any clinical differences between myxoid synovial sarcoma and conventional synovial sarcoma Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.

Adolescent↗
PubMed1999

CHK1 frameshift mutations in genetically unstable colorectal and endometrial cancers.

The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian cells. In its coding region it presents a sequence of nine consecutive adenines that are a potential site of mutations in tumors with microsatellite instability (MSI). We analyzed the presence of frameshift mutations in the CHK1 gene in human colon and endometrial cancer samples. In the same cancer samples genes known to be altered in these tumors (BAX, TGFBRII, and IGFIIR) were also analyzed. CHK1 frameshfit mutations were found in 1 out 10 colon cancers and 2 out of 7 endometrial cancers showing MSI. CHK1 alterations were associated with the presence of a high degree of MSI. No alterations were found in patients with tumors showing low frequency or lacking instability (microsatellite stable). The same was true for the other four genes analyzed. The insertion or deletion of one A in the poly A tract resulted in a truncated protein. Alterations of the CHK1 gene could represent an alternative way of cancer cells to escape from cell cycle control. Genes Chromosomes Cancer 26:176-180, 1999.

Biomarkers, Tumor↗
PubMed1999

Microsatellite instability and frameshift mutations in genes involved in cell cycle progression or apoptosis in ovarian cancer.

The loss of mismatch repair enzymes increases the mutation rate in microsatellites and coding regions of the genome and appears to be involved in drug resistance. The replication error (RER+) phenotype, associated with microsatellite instability, has been widely described for both familial and sporadic colon cancers and for gastric and endometrial tumors. For ovarian cancer, the incidence of RER+ cases among sporadic tumors is still uncertain. We analyzed epithelial ovarian tumors and ovarian carcinoma cell lines for microsatellite instability and for mutations in the coding regions of different genes, including the recently discovered human CHK-1 gene, which has an important role in controlling cell cycle progression and whose coding region contains a poly(A)9 tract. Microsatellite instability and frameshift mutations in coding regions of BAX, TGFbetaRII, IGFIIR, E2F-4, ICE, and CHK-1 genes were analyzed in ovarian cancer samples and cell lines by polymerase chain reaction (PCR). Approximately 26% of patients showed microsatellite instability in two or more loci. BAT-26 locus showed no alteration in primary tumors. We detected a BAX mutation in one tumor sample and a TGFbetaRII mutation in one cell line. Our findings confirm the presence of the RER+ phenotype in sporadic ovarian cancer. The low rate of mutation in genes previously reported to be altered in colon and gastric cancer suggests that other not yet identified genes might be altered and could play a role in tumor progression and response to treatment in RER+ ovarian tumors.

Adult↗
PubMed1998

A multifaceted study of human papillomavirus and prostate carcinoma.

BACKGROUND: The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS: The cases were comprised of 51 African-American (men at high risk for prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/ GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be 1 HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS: All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS: The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men.

Aged↗
PubMed1998

Prognostic relevance of C-myc gene expression in giant-cell tumor of bone.

Giant-cell tumor is a primary bone tumor, of uncertain origin, with the potential capacity to metastasize. To study the role of c-myc and c-fos oncogene overexpression in the tumorigenesis and metastatic spread of giant-cell tumors, 32 primary tumors were collected; of these, 19 remained disease-free and 13 metastasized to the lung. Samples of lung metastasis from these 13 patients were also available for study. The expression of c-myc and c-fos mRNA was studied by reverse transcription-polymerase chain reaction and by in situ hybridization. The expression of protein was studied by Western blot analysis and by immunohistochemistry. C-myc mRNA was overexpressed in 12 (38%) of the 32 primary tumors. Thirteen primary tumors metastasized to the lung; in nine (69%) of these, c-myc mRNA was overexpressed. The c-myc protein was overexpressed in seven (54%) of the 13 tumors that metastasized to the lung. C-fos was overexpressed in only one lung metastasis. A strong correlation between the overexpression of c-myc, and the occurrence of metastases was found: thus, c-myc seems a powerful prognosticator in giant-cell tumor. C-myc was overexpressed both in giant cells and in mononuclear cells, suggesting that both cell types are involved in the progression of this tumor.

Adolescent↗