Peripheral T-lymphocyte subsets in patients treated with Rituximab-Chlorambucil combination therapy for indolent NHL.
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Antibodies, Monoclonal↗
Biomedical subjects
F Bertolini
Publications and source records attributed to F Bertolini.
The prevalence and clinical implications of c-kit expression in plasma cell myeloma.
AIM: To evaluate the clinical implications of c-kit (CD117) expression in plasma cell myeloma (PCM). METHODS AND RESULTS: We first evaluated the reliability of immunohistochemistry in assessing c-kit expression by comparing the results with those obtained by flow cytometry and gene expression arrays in 22 PCM and in 10 PCM cell lines. Immunohistochemical results showed a perfect concordance with those of flow cytometry; likewise, immunohistochemical and gene expression data were also concordant in all but one PCM and cell lines analysed. Then, we investigated the clinical implications of c-kit immunoreactivity in bone marrow biopsies of 85 PCM patients with a mean follow-up of 41 months. C-kit immunoreactivity was detected in 24 (28.2%) of the 85 cases and it was significantly associated with a high microvessel density, but not with traditional clinicopathological characteristics or with survival. CONCLUSIONS: Our findings suggest that immunohistochemistry is a reliable indicator of c-kit gene expression and reinforce the notion that approximately one-third of PCM express high levels of c-kit. The lack of association with traditional clinicopathological parameters and patient survival suggests that c-kit expression may not be an adjunct in predicting the clinical course of the disease.
Adult↗
Systemic effects of surgery: quantitative analysis of circulating basic fibroblast growth factor (bFGF), Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) in patients with breast cancer who underwent limited or extended surgery.
BACKGROUND: To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta). PATIENTS AND METHODS: We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D(-1)), at the end of surgical tumor removal (D0), and on 1st (D(+1)), 2nd (D(+2)) and 5th (D(+5)) day after surgery. Serum VEGF, bFGF and TGF-beta levels were measured by the enzyme immunoassay method. RESULTS: On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D(+5)) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-beta at 24-48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery. CONCLUSIONS: Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.
Aged↗
Endothelial precursors and mature endothelial cells are increased in the peripheral blood of myelodysplastic syndromes.
Increased angiogenesis has been demonstrated to be a significant prognostic factor in many solid tumors. In the oncohematological setting, it has been associated with myelodysplastic syndromes (MDS), chronic myeloid leukemia, acute lymphoid, and myeloid leukemias. Recently, increased circulating endothelial cells (CECs) have been associated with breast cancer and non-Hodgkin lymphoma (NHL). Based on these premises we analysed total and activated CECs, and endothelial precursors (CEPs) in 50 MDS patients and 20 healthy donors. CECs and CEPs were quantified by flow cytometry. CEC levels were compared with bone marrow (BM) microvessel density (MVD). In addition, some angiogenic factors, namely vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble VEGF-Receptor2 (VEGFR2), were tested in the sera from 25 MDS patients. Total, activated CECs and CEPs were significantly increased in MDS when compared to control group (p<0.0001); whereas in the MDS cases no association was found with French--American--British (FAB), International Prognostic Scoring System (IPSS) subtypes or survival. Patients with higher CECs also showed higher MVD. Among the cytokines analysed, sVEGFR2 was significantly higher in the lower IPSS risk classes, while the levels of bFGF directly correlated with total and activated CECs. Taken together these data strengthen the hypothesis of a possible role of angiogenesis in MDS pathogenesis.
Adult↗
PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract.
AIMS: To investigate the value of platelet-derived growth factor receptors (PDGFRs) by immunohistochemistry in discriminating KIT-negative gastrointestinal stromal tumours (GISTs) from other soft-tissue neoplasms of the digestive tract. METHODS AND RESULTS: One-hundred and sixty-seven primary gastrointestinal mesenchymal tumours (125 GISTs, 15 intra-abdominal desmoids, 12 leiomyomas, eight leiomyosarcomas, three schwannomas, two solitary fibrous tumours, and one case each of inflammatory pseudotumour and fibroid polyp) were reclassified based on morphology and on the immunohistochemical panel recommended by the National Institutes of Health consensus on GIST. All cases were then tested with antibodies specific for PDGFR alpha and beta. Of 125 GISTs, 117 were KIT-positive (93.6%) and eight KIT-negative (6.4%). All the KIT-positive GISTs were negative for both PDGFRs, while all the eight KIT-negative GISTs expressed PDGFR-alpha, with two of them also coexpressing PDGFR-beta. Among the 42 non-GIST tumours, only a small percentage (26.6%) of desmoids immunostained for PDGFR-alpha, two of them coexpressing PDGFR-beta. CONCLUSIONS: Immunostaining with PDGFR-alpha is a helpful marker in discriminating between KIT-negative GISTs and other gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for PDFGR-alpha, while none of the other gastrointestinal mesenchymal tumours analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These preliminary data demonstrate the suitability of commercially available antibodies to detect immunohistochemically the mutually exclusive expression of KIT and PDGFR-alpha previously reported in GISTs by molecular biological techniques. Since PDGFR exists in the form of a homodimer (alphaalpha, betabeta) or heterodimer (alphabeta) and two of the KIT-negative GISTs coexpressed both PDGFR isoforms, further investigations are required to elucidate the role of PDGFR-beta in GISTs.
Adult↗
The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour.
The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.
Adult↗
Idarubicin containing regimen in multiple myeloma: preliminary results of a pilot study using a modified "TANDEM" transplant program.
Tandem autologous transplant actually represents a challenge in multiple myeloma treatment, but the best conditioning regimen is still under investigation. With the aim of evaluating the feasibility of a modified tandem transplant strategy, we treated 10 multiple myeloma patients after conventional first line chemotherapy with a two step conditioning regimen consisting of high-dose melphalan (200 mg/m2) followed by high-dose melphalan (180 mg/m2) together with indarubicin (15 mg/sqm2 c.i. x 3 days) both with peripheral stem cell support. At first transplant, the median age wasyears, performance status was good and disease status was CR in 2 patients and PR in the rest. At the end of the first transplant, 70% of patients achieved CR and only mild toxicity was observed. After the second transplant further improvement of the response rate was obtained with 90% CR. However, we observed three toxic early infection-related deaths from CMV and legionella pneumonia at day + 17, +26, +54 after transplantation. Although this schedule seems to be effective in terms of response rate, the 30% TRM imposes an anthracycline dose-reduction with careful patient selection. This approach could reduce the toxic effects and maintain the efficacy of therapy at the same time.
Aged↗
Oromandibular reconstruction with simultaneous free flaps: experience on 10 cases.
Composite defects resulting from surgery for advanced oral cancer represent a difficult reconstructive problem and, in some cases, tissutal defects are extensive requiring multiple free flaps. Personal experience is reported with double free-flap technique in the reconstruction of large complex defects in 10 patients treated for T4 oral squamous-cell carcinoma. Fibula osteo-cutaneous free flap was used in association with forearm free flap in 5 cases, fibula osseous-forearm in 3 cases, fibula osseous-rectus abdominis in 1 case, iliac crest-forearm in 1 case. Forearm free flap was used for intra-oral reconstruction in all cases. Total flap survival is 100% and all patients regained adequate oral diet. At the time of evaluation (February 2001), 40% of patients are alive and mean survival rate is 36 months. In conclusion, simultaneous free flap reconstruction, in massive oro-mandibular defects, represents in some selected patients, a good choice to achieve satisfactory aesthetic and functional results.
Adult↗
Synovial cell sarcoma of the neck. Case report and review of the literature.
Synovial sarcoma is an uncommon neoplasm accounting between 8 and 10% of all soft tissue malignancies. Involvement of the head and neck region is rare. So far, fewer than 100 cases have been reported in the literature and only a few originated in the soft palate, tongue, larynx, hypopharynx, and cervical oesophagus. We report the case of a synovial sarcoma of the parapharyngeal space in a 72-year-old female, and experience in the behaviour and surgical treatment of this neoplasm is described. The patient has remained disease free for 28 months, with regular follow-up. Based upon this case and the others reported in the literature, synovial sarcoma does not have a good overall prognosis, and on account of its rarity and unpredictable biologic behaviour, surgical excision, and regular clinical and radiographic follow-up for at least 3 years are strongly recommended.
Aged↗
Short- and long-term safety of the 2 x 10(6) CD34+ cells/kg threshold for hematopoietic reconstitution after high-dose chemotherapy and peripheral blood progenitor cell support.
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Antigens, CD34↗
Clinical relevance of microvessel density in laryngeal squamous cell carcinomas.
The clinical implications of microvessel density (MVD) in head and neck tumors have not been fully elucidated. We investigated the clinicopathologic correlates and prognostic relevance of MVD in a series of 122 consecutive patients with surgically treated laryngeal squamous cell carcinoma followed-up for a mean of 79 months. MVD was evaluated after CD34 immunostaining in 3 250x microscopic fields representative of the "hot spot" area, and expressed as the mean value of the vessel counts per millimeter squared. The overall median value of the intratumoral vessel count was 69.5/mm(2). In the 20 cases we analyzed, MVD increased significantly from normal to dysplastic mucosa and infiltrating carcinoma (p = 0.0001). Nineteen carcinomas (15.6%) had MVD values that were equal to or lower than the highest MVD value (52.7/mm(2)) observed in normal mucosa samples (in which the median MVD count was 34.5/mm(2), range 16.6-52.7/mm(2), mean 35.1 +/- 11.5/mm(2)) and were therefore considered poorly vascularized. Periodic acid-Schiff (PAS) staining revealed intratumoral PAS-positive connective tissue septa in 13 cases (10.7%). The patients with poorly vascularized tumors showed a tendency toward a better prognosis, but the anatomical site, tumor extension and clinical stage were the only variables significantly associated with disease-free and overall survival.
Adult↗
Resting and activated endothelial cells are increased in the peripheral blood of cancer patients.
Circulating endothelial cells (CECs) were enumerated in 20 healthy controls and 76 newly diagnosed cancer patients by means of 4-color flow cytometry. In breast cancer (n = 46) and lymphoma (n = 30) patients, both resting and activated CECs were increased by 5-fold (P <.0008 vs control). CECs significantly correlated with plasma levels of vascular cell adhesion molecule-1 and vascular endothelial growth factor. Resting and activated CECs were similar to healthy controls in 7 lymphoma patients achieving complete remission after chemotherapy, and activated CECs were found to decrease in 13 breast cancer patients evaluated before and 24 hours after quadrantectomy. (Blood. 2001;97:3658-3661)
Breast Neoplasms↗
Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma.
Circulating endothelial cells (CECs) were evaluated by flow cytometry in immunodeficient mice bearing human lymphoma. A trend toward higher CEC values was observed on days 7 and 14 after transplant, and differences versus controls were highly significant on day 21 (P = 0.0061). A strong correlation was found between CEC and tumor volume (r, 0.942; P = 0.004) and between CEC and tumor-generated VEGF (r, 0.669; P = 0.02). In mice given cyclophosphamide, most of the circulating apoptotic cells were hematopoietic and not endothelial. Conversely, in mice given endostatin, all of the increase in apoptotic cells was in the endothelial cell compartment. CEC evaluation is promising as a noninvasive, surrogate angiogenesis marker.
Angiogenesis Inhibitors↗
Mosaic tumour blood vessels and high-dose chemotherapy for breast cancer.
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Antineoplastic Agents↗
Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers.
BACKGROUND: Thalidomide, as a single agent, has been recently found to induce a clinical response in one third of refractory or relapsed myeloma patients. Although it has been reported that thalidomide significantly inhibits angiogenesis. it is still unclear whether its clinical effect is mediated, at least in part, by its anti-angiogenic properties. PATIENTS AND METHODS: We evaluated thalidomide as a single agent in myeloma, myelodysplastic syndromes (MDS) and histiocytosis, i.e. hematological diseases characterized by increased angiogenesis, and measured prospectively a number of surrogate angiogenesis markers. RESULTS: Clinical responses were observed in 7 of 17 myeloma and 2 of 5 MDS patients. The histiocytosis patient had a partial response. At the time of the best clinical response, plasma levels of angiogenic growth factors, vascular endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF), were significantly decreased, and flow cytometry indicated a decrease of activated endothelial cells in the bone marrow of responding MDS patients. CONCLUSIONS: These observations confirm thalidomide efficacy in myeloma, suggest a possible use in MDS and histiocytosis and may contribute to the prediction of clinical response and to understanding the mechanism of thalidomide's action.
Aged↗
Osteosarcoma of the mandibular condyle: case report.
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Adult↗
Myoepithelioma of the palate: a case report.
Myoepithelioma is a rare malignant neoplasm, representing about the 1% of all the salivary gland's tumors. It mainly affects women, particularly in the 7th and 8th decade of life. A case of myoepithelioma of the palate in a 70-year-old woman is described. The tumor was completely excised two years ago. Nowadays, there are no signs of local recurrence and/or distant metastasis. The discrepancy between the histological diagnosis of low-grade malignancy and the clinical aggressive behavior of the tumor is discussed.
Aged↗
Hemimandibular hyperplasia treated by early high condylectomy: a case report.
A case of hemimandibular hyperplasia in a young patient treated 12 years ago is presented. Clinical and radiographic findings were consistent with a diagnosis of right hemimandibular hyperplasia. An early high condylectomy was performed. In our opinion, the esthetic and functional results after this long-term follow-up are fairly satisfactory. We present a brief review of the literature to make a differentiation between condylar hyperplasia and hemimandibular hyperplasia and to stress the importance of early condylectomy to correct this disease.
Child↗