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Giancarlo Pruneri

Publications and source records attributed to Giancarlo Pruneri.

53 records · Page 3Linked to original sources
PubMed2003

Cyclin D3 immunoreactivity in gastrointestinal stromal tumors is independent of cyclin D3 gene amplification and is associated with nuclear p27 accumulation.

An abnormal expression of cyclin D3, a key regulator of the cell cycle, has been documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 6p21, may be deregulated in human tumors as a result of the t(6;14)(p21.1;q32.3) translocation or gene amplification. In the current study, we for the first time investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) the prevalence of cyclin D3 abnormalities in gastrointestinal stromal tumors (GISTs), comparing the results with traditional pathological characteristics, p27 immunoreactivity (IR), and Ki-67 labeling index (LI). All the tumors showed nuclear cyclin D3 IR, with a percentage of immunostained neoplastic cells ranging from 10 to 95% (mean, 67.3 +/- 22.9%). In 4 (40%) of the 10 cases analyzed by FISH, cyclin D3 extrasignals were detected. Cohybridization with probes specific for the centromeric region and the long arm of chromosome 6 indicated trisomy in one case, whereas in the remaining three cases the pattern was highly suggestive for the occurrence of an isochromosome 6p. There was no association between the cyclin D3 gene copy number and IR for the encoded protein. Cyclin D3 IR was positively associated with p27 IR (P =.004) but not with Ki-67 LI or tumor malignant potential. On the contrary, p27 IR was inversely associated with Ki-67 LI (P =.004) and was more prevalent in tumors of low or intermediate malignant potential, though at a borderline level of statistical significance (P =.066) only. These data suggest that cyclin D3 expression in GISTs is independent of gene amplification and that this protein may be involved in the pathogenesis of GISTs by counteracting the inhibitory activities of p27.

Adult↗
PubMed2003

Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors.

PURPOSE: We investigated the effect of endostatin on differentiation, mobilization, and clonogenic potential of circulating endothelial cell (EC) progenitors, and whether the effect of endostatin was improved by continuous infusion (CI) versus bolus administration. EXPERIMENTAL DESIGN: Four-color flow cytometry and clonogenic EC cultures were used to study EC progenitors in tumor-free mice, tumor-bearing immunodeficient mice, and immunodeficient mice xenotransplanted with human bone marrow (BM) cells. RESULTS: Endostatin significantly reduced the number of circulating EC progenitors in tumor-free BALB/c mice. The effect of endostatin on EC progenitors was enhanced significantly in mice treated with CI drug treatment. When immunodeficient mice xenotransplanted with human BM cells were treated with CI of endostatin we observed a significant decrease in the engraftment and differentiation of human BM-derived EC progenitors. Numbers of circulating EC progenitors increased 7-fold in immunodeficient mice bearing human lymphoma. In this preclinical model, treatment with CI of endostatin inhibited host murine EC progenitor mobilization and human tumor growth. Furthermore, the clonogenic potential of EC progenitors was impaired severely. CONCLUSIONS: Endostatin is a potent inhibitor of the mobilization and clonogenic potential of human and murine EC progenitors, and its preclinical activity is increased significantly in CI compared with bolus administration. These observations might be useful in the design of future clinical trials.

Animals↗
PubMed2003

Stroma cells: a novel target of herceptin activity.

PURPOSE: Stroma cells play a relevant role in tumor development and progression. We investigated the activity of herceptin (HER), a humanized monoclonal antibody widely used for the treatment of HER2-overexpressing epithelial cancer, toward stroma cell lines L87/4 and L88/5. EXPERIMENTAL DESIGN: We studied the antiproliferative potential of HER and role of human serum in HER activity. We also investigated the ability of HER to alter ancillary functions of L87/4 and L88/5, such as support to long-term hematopoiesis, growth factor production, breast cancer cell adhesion, and proliferation. RESULTS: Flow cytometry showed that HER2 membrane expression in L87/4 and L88/5 stroma cells was intermediate between the expression in HER2-negative/dim MCF-7 breast cancer cells and HER2-bright SK-BC3 breast cancer cells. HER2 gene amplification was not detected by fluorescence in situ hybridization in either stromal cell lines. HER significantly inhibited L87/4 and L88/5 proliferation. Mean ID(50)s were found to be 2000 and 1700 micro g/ml for L87/4 and L88/5, respectively, after 3-day exposure and 800 micro g/ml for both cell lines after 9-day exposure. The presence of 10% human serum in the culture increased HER inhibitory activity. IC(50) of stroma cells was found to be intermediate between HER2-bright breast cancer cells (SK-BC3) and HER2-negative/dim breast cancer cells (MCF-7). The drug did not significantly affect the ability of stroma cells to support long-term hematopoiesis in the cobblestone area forming cell assay. In contrast, in coculture assay, MCF7 cells demonstrated a worse adhesion and growth capability on HER-treated stroma layers when compared with untreated stroma. Moreover, HER significantly reduced vascular endothelial growth factor production by L88/5 cells. CONCLUSIONS: Our data support the novel finding that HER may have a relevant activity against stroma cells.

Antibodies, Monoclonal↗
PubMed2002

Follicular dendritic cell sarcoma of the breast.

Extranodal follicular dendritic cell sarcoma (FDCS) is an extremely uncommon tumor with only a single case arising in the breast having been reported. We describe the clinico-pathological features of an additional FDCS of the lower outer quadrant of the right breast in a 40-year-old woman. The tumor showed three patterns of growth, i.e., diffuse, myxoid and fascicular. The neoplastic cells were large, polygonal, with a slightly eosinophilic cytoplasm and oval or convoluted nuclei. They were intermingled with small lymphocytes, plasma cells and a few bizarre multinucleated giant cells. In the fascicular areas, the cells were spindled, while in the myxoid areas they showed a dendritic-like appearance, with long cytoplasmic processes. Mitoses were numerous and often atypical. The neoplastic cells were intensely immunoreactive for CD21, S-100 protein and epithelial membrane antigen, and focally for CD35, CD68 and cytokeratins. Polymerase chain reaction analysis did not reveal any Epstein Barr virus genome in the neoplastic tissue. Electron microscopy highlighted numerous interdigitating cytoplasmic processes with intercellular junctions of the serrated, immature desmosomal or undifferentiated types. The post-surgical course of the patient was uneventful and she is currently free of disease 19 months after surgery.

Adult↗
PubMed2002

CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin's lymphoma.

The chemokine stromal cell-derived factor-1 (CXCL12/SDF-1) and its monogamous receptor CXCR4 are involved in trafficking of B cells and hematopoietic progenitors. CXCR4 expression was found in the large majority of non-Hodgkin's lymphoma (NHL) cell lines and primary cells, and CXCR4 neutralization by monoclonal antibodies had profound in vitro effects on NHL cells including inhibition of transendothelial/stromal migration, enhanced apoptosis, decreased proliferation, and inhibition of pseudopodia formation. In a nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mouse model of human high-grade NHL, CXCR4 neutralization had an impressive efficacy. In a first tumor-challenge trial, CXCR4 neutralization of Namalwa cells injected i.p. delayed tumor growth and reduced tumor weight. In a second tumor-challenge trial, NOD/SCID mice received Namalwa cells i.v. All of the controls died of neoplasia within day 36, whereas 83% of mice injected with cells incubated with anti-CXCR4 were still alive and disease-free >150 days after transplant. The crucial role of CXCR4 in tumor cell extravasation was confirmed by the finding that CXCR4 neutralization before i.v. injection of Namalwa cells in NOD/SCID mice increased the number of cancer cells circulating 24 h after injection. In additional preclinical trials, the therapeutic effect of anti-CXCR4 antibodies was evaluated in mice bearing Namalwa cells injected 3 days before. Tumor growth was abrogated in the majority of treated mice and significantly delayed in the remaining group. Taken together, these data support clinical studies on CXCR4 neutralization in NHL patients by monoclonal antibodies or CXCR4 antagonists.

Animals↗
PubMed2002

Sentinel lymph node biopsy performed with local anesthesia in patients with early-stage breast carcinoma.

HYPOTHESIS: Sentinel lymph node (SN) biopsy performed with local anesthesia has a positive effect on patients' quality of life and on treatment management for early-stage breast carcinoma. This method represents an interesting development in breast-conserving surgery. DESIGN: We performed SN biopsy with local anesthesia in selected patients to test the feasibility of the technique and its impact on our organization and on patients' quality of life. PATIENTS AND METHODS: From September 2000 to December 2001, we studied 115 patients with a palpable breast tumor (maximum diameter, 2.5 cm). The axilla was clinically negative for metastasis in all cases. RESULTS: Forty-eight patients (41.7%) had SNs that were positive for metastasis. In 20 cases (17.4%), the SN was macrometastatic and in 28 cases (24.3%), it was micrometastatic (diameter <2 mm). The SN was negative for metastasis in 66 cases (57.4%). In 1 case, the histologic examination revealed the presence of a non-Hodgkin B-cell lymphoma. The complete axillary dissection performed in the subgroup of patients with macrometastatic SNs showed that in 9 cases (45%), the SN was the only positive node. In another 9 cases (45%), patients had fewer than 4 positive axillary lymph nodes; more than 4 axillary nodes were metastatic in 2 cases (10%). Among the 28 patients with SN micrometastasis, 21 received complete axillary dissection: 15 patients (53.6%) had no other metastasis to the axillary nodes and 6 patients (21.4%) had cancer cells in other axillary nodes. In case of micrometastasis, we suggested that patients enter the International Breast Cancer Study Group 2301 trial (15 of them accepted and signed the informed consent), which compared completion of axillary dissection with no further surgical treatment of the axilla. Based on randomization, 7 patients (25%) in the group with micrometastasis to the SN received no axillary dissection. Patients' tolerance to this kind of treatment was excellent. CONCLUSION: Our experience indicates that SN biopsy performed with local anesthesia can be a suitable alternative to standard intraoperative evaluation with general anesthesia in patients with unifocal, early-stage breast carcinoma.

Anesthesia, Local↗
PubMed2002

p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas?

The p63 protein, a member of the p53 family of nuclear transcription factors, is characterized by different capabilities of transactivating reporter genes, inducing apoptosis, and functioning as dominant-negative agent. This study evaluated the prevalence and prognostic implications of p63 immunoreactivity in 221 patients with stage I non-small cell lung carcinoma (NSCLC) and in 57 patients with stage I-IV neuroendocrine tumours (NET). The results were correlated with the tumour proliferative fraction, the accumulation of p53 protein, and with patient survival. p63 immunoreactivity was seen in 109/118 squamous cell carcinomas, 15/95 adenocarcinomas, 2/2 adenosquamous carcinomas, 4/6 large cell carcinomas, 9/20 poorly differentiated NET, and 1/37 typical and atypical carcinoids (p < 0.001). Furthermore, the prevalence of p63-immunoreactive cells increased progressively from pre-neoplastic and pre-invasive lesions to invasive squamous cell carcinomas. In these latter tumours, but not in adenocarcinomas, p63 immunoreactivity correlated directly with the tumour proliferative fraction (p = 0.028), and inversely with the tumour grade (p = 0.004). No relationship was found with p53 protein immunoreactivity or the other clinico-pathological variables examined. Although p63 is likely to be involved in the development of pulmonary squamous cell carcinoma, it does not carry any prognostic implication for NSCLC patients.

Adenocarcinoma↗
PubMed2002

In vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue.

OBJECTIVE: We studied the in vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue collected from adults with head and neck cancer. MATERIALS AND METHODS: Adherent muscle cells were cultured in F12 medium with 10% fetal bovine serum and transplanted into immunodeficient mice. RESULTS: On day 12 we obtained a median of 500,000 adherent cells per gram muscle sample. Thy-1, endoglin, HER2/neu, and P1H12 were expressed in the majority of cells. CD34, VEGFR2, c-kit, VCAM-1, and CXCR4 were expressed in 0.5-1.5%, 1-5%, 1-15%, 9-15%, and 30% of cells, respectively. Immunodeficient mice transplanted with fresh muscle cells or less than 500,000 cultured cells showed little or no human engraftment. In mice transplanted with more than 500,000 cultured cells, up to 14% human CD45(+) hematopoietic cells (including myeloid and lymphoid subsets) were detected by flow cytometry. Engraftment was confirmed by polymerase chain reaction, Southern blotting, and DNA sequencing. Liver, muscle, and spleen evaluated for human DNA were positive in the majority of mice showing hematopoietic engraftment in the bone marrow. In vivo hematopoietic engraftment potential was maintained in cultured CD45(-) muscle cells transduced with the green fluorescence protein gene. CONCLUSIONS: Human stem cells residing in muscle tissue can generate multilineage hematopoiesis in immunodeficient mice. Surprisingly, this hematopoietic potential increased in cultured versus fresh cells from muscle tissue.

Adult↗
PubMed2002

Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients.

We evaluated microvessel density (MVD) in bone marrow biopsies (BM) from multiple myeloma (MM) patients after staining with anti-CD34 and anti-CD105 antibodies (mAbs). The anti-CD105 mAb was significantly more sensitive than the anti-CD34 mAb in visualizing blood vessels both in controls and MM samples. MVD was significantly higher in MM than in controls with both anti-CD34 and anti-CD105 mAbs. Patients with low CD34+ MVD survived longer than patients with higher MVD (P = 0.01), whereas there was no difference in survival between patients with low and high CD105+ MVD. Multivariate analysis confirmed the independent significant association between CD34+ MVD and survival (P = 0.001).

Adult↗
PubMed2002

p63 in laryngeal squamous cell carcinoma: evidence for a role of TA-p63 down-regulation in tumorigenesis and lack of prognostic implications of p63 immunoreactivity.

p63 is a p53-related gene that encodes for multiple mRNA transcripts with (TA-p63) or without (DeltaN-p63) transactivating properties on p53-responsive genes. We evaluated for the first time the prevalence and clinical implications of p63 immunoreactivity (IR) and mRNA expression in laryngeal squamous cell carcinomas (LSCCs). Moreover, we also assessed the relationships between p63 expression and p53 gene status. p63 IR was detectable in the basal cell layers of non-neoplastic epithelium and in the whole thickness of dysplastic epithelium. All the 150 LSCCs analyzed were immunoreactive for p63, with 28 (18.7%) cases showing p63 IR in </=50% of neoplastic cells. DeltaN-p63 mRNA transcripts were detected in all the 23 tumors analyzed, whereas TA-p63 mRNA transcripts were absent in 5 (21.7%) cases. p53 gene mutations were found in 24 (29.2%) of the 82 cases analyzed and p53 IR was found in 58 (53.7%) of the 108 cases analyzed; neither was associated with p63 IR. No significant association was found between p63 IR and patients' survival. Interestingly, down-regulation of TA-p63 mRNA levels was more prevalent in patients with T3-T4 tumors and advanced clinical stage. Although the risk of death for cancer was higher in these patients (40% versus 16.6%), this difference did not reach statistical significance. Our results suggest that abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis irrespective of p53 gene status and that TA-p63 mRNA down-regulation, but not p63 IR, may be clinically relevant in patients with LSCC.

Adult↗
PubMed2002

Lack of Bcl10 gene mutations in laryngeal squamous cell carcinoma.

The Bcl10 gene encodes a protein probably involved in some apoptotic regulatory pathways. Bcl10 mutations lead to the translation of truncated proteins that show gain-of-function transforming activity; it has been suggested that Bcl10 may represent a major target gene for inactivation in many human cancers. To define the frequency of Bcl10 mutations in laryngeal squamous cell carcinoma and their possible association with tumour progression, we investigated a large panel of tumours representative of all grades and stages of malignancy. To detect pathogenic mutations in exons 1, 2 and 3 of the Bcl10 gene, we performed a silver-staining polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis followed by direct DNA sequencing. We revealed the presence of SSCP variants in 18 out of 91 laryngeal tumours. Direct DNA sequencing showed previously described polymorphisms but no pathogenic mutations. We have strong evidence that the Bcl10 gene is not involved in laryngeal carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Sentinel Node Biopsy Interpretation: The Milan Experience.

From March 1996 to December 1999 we performed 1,266 sentinel node biopsies (SNBs) in patients with small breast cancers. The technique is to inject technetium 99m-labeled albumin particles close to the tumor, locate the sentinel node (SN) scintigraphically, and use a handheld gamma-detecting probe to guide its removal via a small incision during breast surgery. Our experience was divided into three phases. In the first phase, complete axillary dissection was performed to assess the accuracy of SNB in predicting axillary status. We also assessed safety, perfected tracer injection technique, determined optimal particle size and radioactivity levels, optimized lymphoscintigraphic scanning, and perfected the surgical technique. The SN was identified and removed in 98.7% of cases. Comparison with complete axillary dissection showed that the SN predicted axillary status in 96.8% of cases. However, use of an intraoperative frozen section method predicted axillary status in only 86.5% of cases. In the second phase we developed a new method for intraoperative histologic analysis. Extensive sampling (up to 60 sections/SN) and an experienced pathologist proved more important than use of antikeratin immunostaining in identifying tumor cells, and the new method has the accuracy of a definitive histologic examination. The third phase, a randomized trial, closed at the end of 1999. Trial objectives were to confirm that the SN predicts axillary status, to determine the number of axillary relapses, and to assess overall and disease-free survival. Patients were randomized in the operating room to complete axillary dissection or SNB. If the SN was positive, complete axillary dissection was performed; if the SN was negative, no further axillary treatment was given. We expect the trial to confirm our clinical experience that SNB is a safe and accurate procedure for staging patients with early breast cancer and a clinically negative axilla.

Journal Article↗
PubMedDate not supplied

Report on a case of breast sarcoma metastatic to the axillary lymph nodes.

Breast sarcoma is a rare entity that accounts for less than 1% of all breast malignancies; it may spread by direct invasion and/or through the blood. Axillary lymph node involvement is extremely rare and usually associated with advanced-stage disease. In the surgical treatment of this neoplasm, complete axillary lymphadenectomy is important for the local clearance of the clinically involved lymph nodes. We report a case of a 65-year-old woman affected by follicular dendritic cell sarcoma of the left breast. Six months after breast surgery she developed an axillary metastasis from the same disease.

Aged↗
PubMedDate not supplied

Report on a case of pure cribriform carcinoma of the breast with internal mammary node metastasis: description of the case and review of the literature.

AIMS AND BACKGROUND: Pure ductal invasive carcinoma of the breast is more frequently associated with lymphatic invasion, lymph node involvement and high malignant histological grade than combined forms of breast carcinoma. Internal mammary node metastases are not frequently detected when the axillary nodes are negative. PATIENTS AND METHODS: We report our experience of a case of pure cribriform carcinoma, associated with an intraductal cribriform component, in which the sentinel axillary nodes were negative, while nodal and perinodal metastasis was detected in one internal mammary lymph node. CONCLUSIONS: Data from the literature show that positive internal mammary nodes are an unusual finding when the axillary sentinel node is negative, especially in cases of cancer with a relatively good prognosis, such as cribriform cases.

Adenocarcinoma↗
PubMedDate not supplied

Surgical treatment of advanced colorectal cancer in the elderly.

The aim of the study was to compare the short and long-term outcomes of older and younger colorectal cancer patients with advanced disease resected with a curative intent. Six hundred and ninety-two patients were analysed. Four hundred and seventy-nine patients were younger than 70 years (Group 1), and 213 were 70 years of age or above (Group 2). The overall perioperative mortality rate in the younger group was 0.8% (n = 7), as against 1.4% (n = 3) in the elderly group (p = NS). The morbidity rates were 35% and 42%, respectively (p = NS). At univariate analysis, the elderly patients had a worse overall survival compared to the younger group, when only patients undergoing postoperative chemo-radiotherapy were considered (54% vs 67% overall survival at 5 years; p = 0.03). Using logistic regression analysis, tumour stage (p < 0.0001) and radicality of surgery (p < 0.0001) correlated significantly with overall survival rates in the elderly. Colorectal surgery for malignancy can be performed safely in the elderly with acceptable morbidity and mortality rates and long-term survival.

Age Factors↗