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Biomedical subjects

R Cherubini

Publications and source records attributed to R Cherubini.

49 records · Page 3Linked to original sources
PubMed1997

Mutant frequency at the Hprt locus and in minisatellite sequences in Chinese hamster V79 cells irradiated with low-energy protons (31 keV/microm) and ultraviolet light (254 nm).

Ionizing radiations induce mutations which can be detected both in coding sequences (Hprt locus) by measuring the frequency of 6-thioguanine-resistant cells and in minisatellite sequences by DNA fingerprint analysis. We analyzed the effects of irradiation with low-energy protons (31 keV/pm) and, for comparison, with ultraviolet light (254 nm), for which DNA damage and repair mechanisms are better understood, on cultures of Chinese hamster V79 cells with the two methods mentioned above. The results indicate that the frequency of 6-thioguanine-resistant cells was increased significantly, although very differently, by both treatments. The analyses carried out by DNA fingerprinting with a multilocus DNA probe show that the level of induction in minisatellite sequences was higher compared to those measured at the Hprt locus after proton irradiation, but lower after treatment with ultraviolet light.

Animals↗
PubMed1996

Effects of recombinant growth hormone (GH) treatment on bone mineral density and body composition in adults with childhood onset growth hormone deficiency.

Lumbar spine, whole proximal femur and total body bone mineral density (BMD, g/cm2) and the regional soft tissue composition were measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) in eight adults with childhood onset GHD, before and after 6 months of recombinant GH treatment (0.5 IU/kg/week). Data obtained from patients were compared with those recorded in an age and sex matched control group. Before treatment, lumbar (L2-L4) spine BMD (mean +/- SD: 0.811 +/- 0.159 g/cm2), whole proximal femur BMD (0.739 +/- 0.094 g/cm2) and total body BMD (0.946 +/- 0.087 g/cm2) of patients were significantly (p < 0.001, 0.01 and 0.001, respectively) lower than those recorded in an age- and sex-matched control group (1.077 +/- 0.155 g/cm2, 0.968 +/- 0.166 g/cm2 and 1.168 +/- 0.058 g/cm2, respectively), although three patients showed BMD values at the lower limit of the normal range. Mean lumbar spine BMD, whole proximal femur BMD and total body BMD did not significantly change alter 6 months' GH treatment (-1.4 +/- 3.7%, +2.7 +/- 3.7% and -1.1 +/- 5.0% vs basal values, respectively). On the other hand, trochanteric subregion showed a significant 4.8 +/- 5.3% increase (vs basal, p < 0.05), while other hip subregions did not show significant changes. GH therapy caused marked effects on body composition; in fact, a significant decrease (p < 0.01) of trunk fat (-25.2 +/- 15.0%) and a marked increase (p < 0.01) of limbs lean mass (+10.0 +/- 5.3%), resulting in a significant (p < 0.02) reduction (-16.5 +/- 13.5%) of the axial to peripheral fat ratio (APFR), were clearly evident after six months of therapy. In conclusion, our study shows that six months of GH treatment do not exert relevant effects on the BMD of adults with childhood onset GHD. On the contrary, the effects of GH therapy on body composition are more marked, being clearly appreciable after six months of treatment.

Adult↗
PubMed1996

DNA double strand break production and rejoining in V79 cells irradiated with light ions.

Low energy protons and other densely ionizing light ions are known to have RBE>1 for cellular end points relevant for stochastic and deterministic effects. The occurrence of a close relationship between them and induction of DNA dsb is still a matter of debate. We studied the production of DNA dsb in V79 cells irradiated with low energy protons having LET values ranging from 11 to 31 keV/micrometer, i.e. in the energy range characteristic of the Bragg peak, using the sedimentation technique. We found that the initial yield of dsb is quite insensitive to proton LET and not significantly higher than that observed with X-rays, in agreement with recent data on V79 cells irradiated with alpha particles of various LET up to 120 keV/micrometer. By contrast, RBE for cell inactivation and for mutation induction rises with the proton LET. In experiments aimed at evaluating the rejoining of dsb after proton irradiation we found that the amount of dsb left unrepaired after 120 min incubation is higher for protons than for sparsely ionizing radiation. These results indicate that dsb are not homogeneous with respect to repair and give support to the hypothesis that increasing LET leads to an increase in the complexity of DNA lesions with a consequent decrease in their repairability.

Alpha Particles↗
PubMed1995

Effects on bone mineral density of 12-month goserelin treatment in over 40-year-old women with uterine myomas.

We evaluated the effects on bone mineral density (BMD) of a 12-month treatment with goserelin depot, a gonadotropin-releasing hormone agonist, in a group of women with symptomatic uterine myomas requiring hysterectomy. Sixteen women, mean age 45.6 +/- 5.0, reporting menorrhagia associated with uterine myomas, candidates for hysterectomy, were scheduled to be treated with goserelin depot for 12 months. BMD was measured at the vertebral (L2-L4) and proximal femur level (femoral neck and trochanter) at the start of therapy and 6, 12, and 18 months later using dual energy X-ray absorptiometry (Hologic QDR 1000/W). The patients were followed for a minimum of 6 months after the end of treatment. Thirteen of the 16 women enrolled completed the treatment and three suspended it after 5, 6, and 7 months, respectively, because of side effects (hot flashes, insomnia, depression). Of the 13 women who completed the treatment, three underwent hysterectomy because of myoma regrowth and the recurrence of symptoms 3-18 months later; four reached the menopause 5-16 months later, and six were all menstruating normally with a follow-up varying from 6 to 18 months. After 12 months of therapy we observed a bone loss at vertebral, femoral neck, and trochanter of 4.4% (P < 0.05 versus baseline; P = not significant versus 6 months), 7.5% (P < 0.01 versus baseline, P < 0.01 versus 6 months), and 7.6% (P < 0.001 versus baseline, P < 0.05 versus 6 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

DNA double-strand breaks induced by low energy protons in V79 cells.

The initial production of DNA double-strand breaks (dsb) was determined in V79 Chinese hamster cells irradiated with proton beams of 3.24, 1.50 and 0.88 MeV, corresponding to values of unrestricted LET evaluated at the cell midplane of 10.9, 20.0 and 30.5 keV/micron, respectively. X-rays were used for comparison. Dsb were measured with the low speed sedimentation technique in neutral sucrose gradients. The initial yield of dsb rose linearly with the dose and did not significantly depend on the proton LET, in contrast with the results obtained in previous studies for cell inactivation and mutation induction. Also, no significant differences for dsb induction were found between protons and X-rays. Two possible explanations, not necessarily mutually exclusive, are proposed: (1) dsb are not the only lesions involved in cellular effects; and (2) the initial number of dsb is not the only important parameter since a fundamental role is played by the degree of clustering, i.e. the association of dsb with other dsb or other types of damage.

Animals↗
PubMed1993

Dual X-ray absorptiometry for the evaluation of bone density from the proximal femur after total hip arthroplasty: analysis protocols and reproducibility.

Dual X-ray absorptiometry (DXA) instruments are now able to evaluate bone mineral density (BMD) of bone surrounding metal implants. The assessment of BMD around prosthetic components could provide additional information for the follow-up of total hip arthroplasty (THA). In this study, we evaluated the potential application of DXA in the field of THA. BMD was measured in the proximal femur of both THA and THA-free sides in 14 postmenopausal women 6-18 months after THA. The explored segment was divided into seven zones as proposed by Gruen et al. [18]. The precision error of BMD measurements ranged from 1.8 to 6.8% on the THA side and from 1.1 to 2% to the THA-free side. The reduction of BMD of the THA versus the THA-free side was significant in all seven zones (P < 0.01, t-test for paired data). These results showed significant differences in BMD around femoral components of THA with respect to contralateral healthy side, and demonstrate the sensitivity of DXA for detecting these changes.

Absorptiometry, Photon↗
PubMed1993

Use of track detectors in biomedical sciences.

The CR-39 track detectors have been applied to irradiate the Chinese hamster V79-753B cells for survival studies. The survival curves have given satisfactory results. Energies of the incoming as well as outgoing proton beams evaluated from the track diameters are found to be close to the values found separately by surface barrier detector (SSBD).

Animals↗
PubMed1993

Inactivation and mutation induction in V79 cells by low energy protons: re-evaluation of the results at the LNL facility.

During the upgrading of the radiobiological facility at the Laboratori Nazionali di Legnaro (LNL) we found that uncorrected values of the proton energy were used in the past. This circumstance prompted us to perform the re-evaluation of the physical parameters for all the proton beams used in our previous radiobiological investigations (Belli et al. 1987) and, subsequently, the re-evaluation of all our previous dose-response curves for inactivation and mutation induction (Belli et al. 1989, 1991). This re-evaluation leads to significant changes in the dose-response curves and in the RBE-LET relationships only at the two lowest energies (highest LET) used. These two points are not reliable for the identification of a peak in RBE-LET relationship for cell inactivation. In spite of that, the extent of the changes is not such as to modify the general conclusion previously drawn, pointing out that there is a LET range where protons are more effective than alpha-particles.

Animals↗
PubMed1991

Mutation induction and RBE-LET relationship of low-energy protons in V79 cells.

The mutation induction at the HGPRT locus has been studied in V79-753B Chinese hamster cells irradiated with proton beams with energies of 3.36, 1.70 and 1.16 MeV, corresponding to average LET values of 10.6, 17.8 and 23.9 keV/microns, respectively. The mutation curve obtained with 200 kV X-rays was used for comparison. The mutation frequency induced by all the proton beams is considerably higher than that induced at the same dose by X-rays and it is linearly related to the dose. Moreover, the proton effectiveness increases with the LET. The RBEs (evaluated as the initial slope ratios) are 5.0 +/- 0.8, 5.4 +/- 0.8 and 7.7 +/- 1.2 for protons with average LETs of 10.6, 17.8 and 23.9 keV/microns, respectively. These values are higher than those reported in the literature for other ions of comparable LET. This finding parallels what we have already found for cell inactivation (for which RBEs of 3.0, 4.6 and 7.3 were obtained at the same LETs), and indicates that for mutation induction, also, the RBE-LET relationship may depend on the type of radiation.

Animals↗
PubMed1989

RBE-LET relationship for the survival of V79 cells irradiated with low energy protons.

The survival of V79 Chinese hamster cells irradiated with proton beams with energies of 0.73, 0.84, 1.16, 1.70 and 3.36 MeV, corresponding to LET values, evaluated at the cell midplane, of 34.5, 30.4, 23.9, 17.8 and 10.6 keV/micron respectively, have been studied in the dose range 0.5-6.0 Gy. As a reference, the survival curve obtained with 200 kV X-rays was used. The initial shoulder, typical of survival curves obtained with sparsely ionizing radiation, decreases as the LET increases and completely disappears at 23.9 keV/micron. This value corresponds to the maximum of the RBE, expressed as the initial slope ratio. In the energy range we have considered, the RBEs for protons are higher than those reported for other ions of comparable LET and the RBE-LET relationship results shifted to lower LET values. Our data seem to indicate that the RBE-LET curve depends on the type of radiation and this could imply that LET is not a good reference for the dose-effectiveness relationship.

Animals↗
PubMedDate not supplied

Results of a prospective study with high-dose etoposide, thiotepa and carboplatin and peripheral blood stem cell rescue for high-risk stage II-IIIA and selected stage IV breast cancer patients.

AIMS AND BACKGROUND: To investigate the safety and efficacy of a high-dose chemotherapy regimen with etoposide, carboplatin and thiotepa in high-risk stage II-IIIA breast cancer and in responsive metastatic patients. STUDY DESIGN: From April 1992 to December 1998, 24 patients with high-risk stage II-IIIA breast cancer (> or = 9 positive nodes) and 9 responsive metastatic patients were enrolled in the trial. After induction chemotherapy with an anthracycline-based regimen, peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (5-16 microg/kg/s.c./day). The high-dose chemotherapy regimen consisted of etoposide (1000 mg/m2), carboplatin (800 mg/m2) and thiotepa (500 mg/m2). At the end of the high-dose chemotherapy, all stage II-IIIA patients received radiotherapy to the breast or chest wall and draining nodes; stage IV patients were irradiated to sites of disease, if feasible. All ER+ and/or PgR+ patients were treated with hormone therapy. RESULTS: For stage II-IIIA high-risk patients, the median follow-up was 4.36 years (range, 1.93-6.94), and the Kaplan-Meier estimate at 5 years of disease-free survival and overall survival was 54.8 +/- 11% SE and 76.73 +/- 9.4% SE, respectively. For metastatic patients, the median follow-up was 4.93 years (range, 4.15-7.95), and the Kaplan-Meier estimate at 5 years of progression-free survival and overall survival was 22.2 +/- 13.9% SE and 76.2 +/- 14.8% SE, respectively. No treatment-related deaths were observed. CONCLUSIONS: Our results are comparable to those obtained in other high-dose chemotherapy trials but do not seem to be superior to conventional-dose therapy given to similar patients.

Adult↗