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Biomedical subjects

F Bertolini

Publications and source records attributed to F Bertolini.

At least 37 records · Page 2Linked to original sources
PubMed2000

Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma.

Both chemotherapy and chimeric anti-CD20 monoclonal antibodies are effective agents against B-cell non-Hodgkin lymphoma (NHL). However, patients achieving remission are at risk of relapse. To evaluate the effect of the antiangiogenic drug endostatin used alone and after the administration of cyclophosphamide (CTX) or the anti-CD20 antibody rituximab, we generated a new model of human NHL by transplanting Namalwa cells intraperitoneally into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. First, we determined the most effective treatment schedule for the drugs assessed. When administered alone, CTX (3 courses of 75 mg/kg of body weight given intraperitoneally), rituximab (3 courses of 25 mg/kg given intraperitoneally), and endostatin (5 courses of 50 microg given subcutaneously) delayed tumor growth, and CTX was the most effective in controlling bulky disease. When given after chemotherapy or immunotherapy, endostatin effectively induced tumor stabilization. When mice given CTX or rituximab on days 3, 5, and 7 after transplantation were randomly assigned to receive endostatin or phosphate-buffered saline on days 15 to 19, tumor growth was prevented in endostatin-treated mice as long as the drug was administered. Furthermore, administration of endostatin on days 25 to 29 after tumor regrowth still induced significant tumor regression, whereas CTX and rituximab were not effective. The specific antiangiogenic action of endostatin was confirmed by in vitro and in vivo studies indicating that the drug inhibited proliferation and induced apoptosis of endothelial (but not of NHL) cells. In conclusion, sequential administration of chemotherapy and endostatin seems promising for treating bulky NHL, and the less toxic sequential administration of rituximab and endostatin is promising for treating limited disease. (

Angiogenesis Inhibitors↗
PubMed2000

Human myeloid and lymphoid malignancies in the non-obese diabetic/severe combined immunodeficiency mouse model: frequency of apoptotic cells in solid tumors and efficiency and speed of engraftment correlate with vascular endothelial growth factor production.

Recent studies have suggested that non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice transplanted with human hematological malignancies show higher levels of engraftment compared with other strains. We used this model to compare xenotransplantability of human leukemia and lymphoma cell lines and to investigate angiogenesis in hematopoietic malignancies. Ten of 12 evaluated cell lines were able to engraft NOD/SCID mice within 120 days. A strong correlation was observed between the amount of vascular endothelial growth factor (VEGF) produced in vitro by cultured cells and the efficiency of tumor engraftment (r = 0.808; P = 0.001), and an inverse correlation was found between VEGF production and the time of tumor engraftment (r = -0.792; P = 0.006) and between VEGF production and the frequency of apoptotic/dead cells in solid tumors (r = -0.892; P = 0.007). Moreover, VEGF production correlated with the frequency of endothelial (CD31+/CD34+) cells in solid tumors (r = 0.897; P = 0.001). Taken together with in vitro data presented here and indicating that the VEGF antagonist Flt-1/Fc chimera inhibits leukemia and lymphoma cell proliferation, our findings support a role for tumor-derived VEGF in leukemia and lymphoma progression. Furthermore, the present study confirms previous observations indicating that VEGF expression may play a crucial role in xenotransplantability of human solid malignancies in SCID mice. The NOD/SCID model is promising for future evaluations of antiangiogenic drugs, alone or in combination with established chemo- or immunotherapy regimens.

Acute Disease↗
PubMed2000

The thin red line: angiogenesis in normal and malignant hematopoiesis.

This review describes the current knowledge about cell subsets involved in vasculogenesis (i.e., differentiation of endothelial cells from mesodermal precursors) and angiogenesis (i.e., blood vessel generation from pre-existing vessels), together with recent findings about angiogenesis and antiangiogenic therapies in hematopoietic malignancies such as leukemia, lymphoma, myeloma, and myelodysplastic syndromes.

Animals↗
PubMed2000

Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis by green tea in animal models of human high-grade non-Hodgkin's lymphoma.

Recent reports suggest that green tea consumption may prevent or delay the growth of human cancer, possibly by impairing tumor invasion and/or by an anti-angiogenic effect. In NOD/SCID mice transplanted intraperitoneally with human non-Hodgkin's lymphoma (NHL) cell lines, Namalwa, RAP1-EIO and HS-Sultan, green tea prevented 50% of Namalwa tumors (P = 0.0017 by log-rank) and significantly inhibited RAP1-EIO and HS-Sultan tumor growth. Notably, treatment with the chemotherapy drug cyclophosphamide at the maximum tolerable dose was unable to prevent Namalwa tumor occurrence. In the three models evaluated, the frequency of apoptotic endothelial and tumor cells was significantly increased in mice given green tea compared to controls. These results support further trials in NHL to evaluate whether green tea, alone or in combination with chemotherapy, may delay or prevent disease progression.

Animals↗
PubMed2000

[Conservative therapy in dentigerous cysts. A case report].

Dentigerous cysts are one of the most common embryological anomalies of the maxilla and mandible. They are connected with one or more permanent tooth germs. For this reason, therapy is very important to preserve the vitality of the permanent germs and to allow them a complete growth and a functional migration in the alveolar arch. In the present paper, the clinical features and the surgical conservative treatment of a case personally observed, are described.

Child↗
PubMed2000

Pre- and postsurgical psycho-emotional aspects of the orthognathic surgery patient.

The current study represents an attempt to examine psychologic changes, emotional impact, expectations, and satisfaction in patients before and after orthognathic surgery. Levels of presurgical anxiety, postsurgical depression, body concept, and all the important changes in physiologic functions were measured by 4 questionnaires, which were self-administered before and after surgery. The results of this study suggest that surgery does, in fact, produce improvements in self-esteem and body image (patient's evaluation of his or her facial attractiveness) and in mastication and speech, and therefore in their lifestyle. All patients experienced a medium to high level of presurgical anxiety, but no major problems after surgery.

Adaptation, Psychological↗
PubMed2000

Skeletal relapse of maxillary osteotomies in unilateral cleft lip and palate patients.

The outcomes of a consecutive series of 10 adults who had unilateral cleft lip and palate and who had undergone Le Fort I advancement fixed with miniplates were investigated. The amount and timing of horizontal and vertical relapse, the correlation between advancement and relapse, and the effectiveness of various methods of internal fixation were analyzed with respect to the authors' clinical experience and the data from the international literature. Tracings of the preoperative and serial postoperative lateral cephalograms--taken immediately and during the 1 1/2 to 2 postoperative years--were analyzed to calculate horizontal and vertical maxillary change. We found that the use of rigid fixation is associated with a significantly more stable postoperative result, as described by other authors. Our study suggests that this useful technique does not eliminate but reduces and controls the problem of relapse in a series of unilateral cleft lip and palate adult patients undergoing Le Fort I osteotomy.

Adult↗
PubMed1999

Angiogenesis in myelodysplastic syndromes.

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 +/- 9 vs 6 +/- 2 and 10 +/- 8 respectively) but lower than AML (30 +/- 12) and MPD (40 +/- 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P= 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.

Antigens, CD34↗
PubMed1999

Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma.

A number of clinical studies have demonstrated the prognostic significance of angiogenesis and angiogenic growth factors in solid tumours; however, very little is known about the relevance of these parameters in haematological malignancies. We evaluated circulating levels of angiogenic growth factors and endostatin in 36 non-Hodgkin's lymphoma (NHL) patients. Baseline vascular endothelial growth factor (VEGF) levels of patients in complete remission (CR) after a median follow-up of 21 months were significantly lower than those of patients with progressive disease (P = 0.016). Event-free survival (EFS) rate was significantly higher in patients who had baseline VEGF and basic-fibroblast growth factor (b.FGF) levels below the median values of 147 and 19.5 pg/ml (P = 0.018 and 0.039 by log-rank test, respectively). Conversely, the levels of endostatin, angiogenin and leptin were not different in CR patients compared to relapsed patients and did not correlate with EFS. Our data suggest that b-FGF and, particularly, VEGF might be considered prognostic factors in NHL staging and management.

Adult↗
PubMed1999

Active mandibular protrusion in the rational treatment of skeletal Class II malocclusions.

BACKGROUND: Aim of the present study is to assess the ideal mandibular protrusion exercises, which should always be associated with functional treatment of skeletal Class II malocclusions, characterized by mandibular hypoplasia. METHODS: The study was carried out on a sample including 8 growing subjects (mean age 10.6 years +/- 0.6), similar in age and biotypology (mandibular hypoplasia; normodivergent growth pattern). The electromyography (EMG) activity of the superficial bundle of the masseter (considered as an accessory protrusive muscle) was bilaterally recorded at rest and, during voluntary contraction, at different degrees of protrusion (minimum, medium, maximum), condition dynamically analyzed at various times of contraction (initial, 5, 10, 30 seconds). The mean values of the recruitment pattern during the whole contraction, the number of turns/sec and the ratio turns/mean amplitude were evaluated. RESULTS: The data obtained by means of a precise electromyographic analysis suggest that the ideal exercise for an active mandibular protrusion should be a medium degree contraction lasting 10 seconds. These results are consistent with the linear relationship between muscle force and EMG amplitude, correlation effective only up to 60% of the exerted force, because of the muscular fatigue appearing beyond this threshold. During such a muscular fatigue, due to maximum contraction, it is possible to observe a progressive decrease in the EMG activity, owing in particular to the motor-neuron reduced discharge-frequency. CONCLUSIONS: This result suggests a small benefit of long-lasting muscular contractions, both in maximum and in medium protrusion movements, for re-educational purposes. Only during the medium-degree, 10 sec-lasting contraction it's possible to point out a turns-number variation significant of an active and constant contraction, which decreases if long-lasting (30 sec).

Child↗
PubMed1998

Hematopoietic progenitor cell collection and neoplastic cell contamination in breast cancer patients receiving chemotherapy plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization.

BACKGROUND: We compared hematopoietic progenitor cell (HPC) collection and neoplastic cell contamination in breast cancer patients given cyclophosphamide (CTX) plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone for mobilization. PATIENTS AND METHODS: In 57 stage II-III breast cancer patients, CD34+ cells, colony-forming units-granulocyte macrophage (CFU-GM), early HPC and breast cancer cells were counted in HPC collections obtained after CTX plus G-CSF (n = 27) or G-CSF-alone mobilization (n = 30). RESULTS: The CD34+ cell collection was about two-fold greater after CTX plus G-CSF mobilization (11.0 +/- 7.9 vs. 5.8 +/- 3.5 x 10(6)/kg, P < 0.001). Similarly, the total number of CFU-GM, CD34+CD38- cells and of week-5 cobblestone area forming cells (CAFC) collected was significantly higher in patients mobilized with CTX plus G-CSF. Breast cancer cells were found in the apheresis products of 22% of patients mobilized with CTX plus G-CSF and in 10% of patients mobilized with G-CSF alone (P = 0.36). Of seven patients who failed G-CSF-alone mobilization and eventually underwent chemotherapy plus G-CSF mobilization, none had cytokeratin-positive cells after G-CSF mobilization, whereas four out of seven had cytokeratin-positive cells after chemotherapy plus G-CSF (P = 0.07 by chi 2 test). CONCLUSION: The CTX plus G-CSF mobilization protocol was associated with a significantly higher HPC collection. However, this benefit was not accompanied by a reduction in the incidence of tumor-contaminated HPC graft.

Adult↗
PubMed1998

Epithelial tumour cell detection and the unsolved problems of nested RT-PCR: a new sensitive one step method without false positive results.

Sensitive detection of circulating epithelial cancer cells might have important therapeutic and prognostic implications in patients with breast cancer (BC) receiving high-dose chemotherapy and PBSC support. We have compared the specificity and sensitivity of the recently developed 'one tube' reverse transcriptase PCR (RT-PCR) assay with the more widely used nested RT-PCR method for detection of cytokeratin 19 (CK19)-positive cells. The analysis of 30 control samples provides evidence that one tube RT-PCR is highly specific in contrast to the nested method which showed 23% false positive results. The sensitivity of both techniques to detect tumour contamination was 10(-6). PBSC harvests from 45 BC patients were tested with both RT-PCR methods and the results were compared with immunocytochemistry (ICC). The five samples found positive by ICC were also positive by one tube RT-PCR; in addition, 11 more samples were positive by one tube RT-PCR analysis. The greater number of PBSC found positive by one tube RT-PCR might be due to the larger number of cells analysed. We conclude that one tube RT-PCR is sensitive and reveals no false positive results. This method is less time consuming than the nested one, technically simpler and should be considered for tumour cell detection.

Biomarkers, Tumor↗
PubMed1998

Hematopoietic stem cells from different sources: biological and technical aspects.

Hematopoietic stem cell (HSC) enumeration is crucial to predict the engraftment potential of a given HSC collection, and currently involves the surrogate count of nucleated cells, CFU or CD34+ cells. However, there is raising evidence that CFU are HSC involved in short-term but not in long-term reconstitution, and that only a small fraction of all CD34+ cells have long term multilineage engraftment potential. In this regard, there is evidence that cord blood (CB), bone marrow (BM) and peripheral blood (PB) derived HSC are highly heterogeneous for a number of antigens useful for HSC enumeration by flow cytometry. Moreover, there is a raising evidence that a CD34 human HSC might exist. The CD34 HSC has been already described in animals and in human Hoechst 33342 negative HSC. This notwithstanding, clinical data have clearly demonstrated that purified allogeneic CD34+ cells can reconstitute the myeloid and the lymphoid lineages in myeloablated recipients. In the lack of a suitable marker for CD34 HSC enumeration, it is hard to predict the role of CD34 HSC in hematopoietic reconstitution after transplantation. On the other hand, these cells might be a better target for HSC expansion and gene transfer.

Antigens, CD34↗
PubMed1998

Control of stem cell proliferation and differentiation to achieve stable gene transfer and expression.

Although the hematopoietic stem cell (HSC) seems to be a convenient target for gene therapy, data from human clinical trials have so far shown low levels of gene transduction. The new model of human stem cells, immunodeficient mice repopulating cells (SRC), has similarly demonstrated that SRC were rarely transduced by protocols used in past studies. Cytokines such as stem cell factor and interleukin-3, used so far to obtain cell proliferation in transduction protocols, might induce HSC to differentiate and impair their repopulating potential. In this scenario, there is a need for new gene transfer protocols associated with minimal cell differentiation and stable expression of the transduced gene in the majority of mature cells generated from transduced HSC.

Animals↗
PubMed1998

Stem cell enumeration in cord blood vs bone marrow and peripheral blood.

Recent reports have suggested that the total number of autologous or allogeneic hematopoietic stem cell (HSC) infused after high-dose chemotherapy might predict survival, post-transplant morbidity and rate of hematopoietic engraftment. However, HSC capable of long-term multilineage potential are still poorly defined, and tools for accurate and reproducible HSC enumeration are highly warranted.

ADP-ribosyl Cyclase↗
PubMed1998

Ex vivo expansion of hematopoietic cells and their clinical use.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cells are being increasingly used for treatment of malignant and nonmalignant disorders. Various attempts have been made in recent years to expand and manipulate these cells in order to increase their therapeutic potential. A Working Group on Hematopoietic Cells has analyzed the most recent advances in this field. EVIDENCE AND INFORMATION SOURCES: The method used for preparing this review was an informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to achieve an agreement on different judgments, and eventually approved the final manuscript. Some authors of the present review have been working in the field of stem cell biology, processing and transplantation, and have contributed original papers in peer-reviewed Journals. In addition, the material examined in the present review includes articles and abstracts published in Journals covered by the Science Citation Index and Medline. STATE OF ART: Over the last decade, recombinant DNA technology has allowed the large scale production of cytokines controlling the proliferation and differentiation of hemo-lymphopoietic cells. Thus, in principle, ex vivo manipulation of hemopoiesis has become feasible. The present review covers three major area of interest in experimental and clinical hematology: manipulation of hematopoietic stem/progenitor cells, cytotoxic effector cells and antigen presenting dendritic cells. Preliminary data demonstrate the possibility of using, in a clinical setting, ex vivo expanded hematopoietic cells with the aim of reducting, and perhaps abrogating, the myelosuppression after high-dose chemotherapy. Concurrently, other important potential applications for ex vivo manipulation of hematopoietic cells have recently been investigated such as the generation and expansion of cytotoxic cells for cancer immunotherapy, and the large scale production of professional antigen presenting cells capable of initiating the process of immune response. CONCLUSIONS AND PERSPECTIVES: Present and future challenges in this field are represented by the expansion of true human stem cells without maturation, to extend this strategy to allogeneic stem cell transplantation as well as the manipulation of cycling of primitive progenitors for gene therapy programs. The selective outgrowth of normal progenitor cells over neoplastic cells to achieve tumor-free autografts may ameliorate the results of autologous transplantation. The selective production of cellular subsets to manipulate the graft versus-host and graft versus-tumor effects and anti-tumor vaccination strategies may be important to improve cellular adoptive immunotherapy.

Animals↗