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G Simone

Publications and source records attributed to G Simone.

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

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients.

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy.

Adult↗
PubMed2000

Inactivation of human normal and tumour cells irradiated with low energy protons.

PURPOSE: To analyse the cell inactivation frequencies induced by low energy protons in human cells with different sensitivity to photon radiation. MATERIALS AND METHODS: Four human cell lines with various sensitivities to photon irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours of the tongue and larynx, respectively, and the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were irradiated with y-rays and proton beams with linear energy transfer (LET) from 7 to 33 keV/microm. Clonogenic survival was assessed. RESULTS: Survival curves are reported for each cell line following irradiation with gamma-rays and with various proton LETs. The surviving fraction after 2 Gy of gamma-rays was 0.72 for SQ20B cells, and 0.28-0.35 for the other cell lines. The maximum LET proton effectiveness was generally greater than that of gamma-rays. In particular there was a marked increase in beam effectiveness with increasing LET for the most resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with gamma-radiation down to 0.37 with 30 keV/microm protons. The relative biological effectiveness (RBE(2 Gy gamma)) with the 30 keV/microm beam, evaluated as the ratio of 2 Gy to the proton dose producing the same inactivation level as that given by 2 Gy of gamma-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively. CONCLUSIONS: RBE for inactivation with high-LET protons increased with the cellular radioresistance to gamma-rays. The cell line with the greatest resistance to gamma-rays was the most responsive to the highest LET proton beam. A similar trend has also been found in studies reported in the literature with He, C, N ions with LET in the range 20-125 keV/microm on human tumour cell lines.

Cell Line↗
PubMed2000

DNA DSB induction and rejoining in V79 cells irradiated with light ions: a constant field gel electrophoresis study.

PURPOSE: To study the induction and the time-course of rejoining of DNA double strand breaks (DSB) in V79 cells irradiated with light ions with different linear energy transfer (LET). MATERIALS AND METHODS: V79 cells were irradiated in monolayer with monoenergetic proton, deuteron, helium-3 or helium-4 ion beams, each at two different energy values. Gamma rays were used as reference radiation. DSB have been measured by constant field gel electrophoresis (CFGE). RESULTS: The initial yield depended little on the particle type and LET. The amount of DSB left unrejoined for up to 2 h incubation time could be roughly described by a decreasing exponential function with a final plateau, although more complex functions cannot be excluded. Radiation quality had little effect on the rejoining rate but affected the plateau. The amount of residual DSB after 2 h was higher for densely than for sparsely ionizing radiation, and for the same particle was dependent on LET. The corresponding RBE ranged from 1.8 to 6.0. CONCLUSIONS: The results support the hypothesis that complex, less reparable DSB are induced in higher proportion by light ions with respect to gamma-rays and that, for the same ion, increasing LET leads to an increase in this proportion.

Animals↗
PubMed2000

Fewer women than men have positive SPECT and PET cardiac findings among patients with no history of heart disease.

UNLABELLED: A lower detection rate of coronary artery disease (CAD) has been reported for SPECT imaging in women, despite the fact that similar numbers of women and men die each year of heart disease. Ruling out instrumentation as a possible source of this low detection rate for CAD in women could be important in determining the root cause of this difference. METHODS: Patients were referred by cardiologists and randomized to PET or SPECT by the imaging center. A total of 210 patients (106 women, 104 men) were enrolled in this study, with 105 imaged by dual-isotope SPECT and 105 imaged by 82Rb PET. Rest/stress scanning was performed using dipyridamole. The effects of sex, prior history of CAD, and instrumentation on the detection of positive scans were determined using multiple logistic regression analysis with positive scans as the endpoint. RESULTS: For the total study population, sex and prior history of CAD are significantly associated with positive scans, whereas imaging modality and age are not. There was no significant interaction between sex and prior history of CAD. Men have 4.1-fold greater odds of having a positive nuclear scan than women, and patients with prior history of CAD have 5.2-fold greater odds of a positive scan after controlling for the confounding effects of age and imaging modality. In the subgroup of patients with no prior history of heart disease, men have 3.9-fold greater odds of a positive scan than women, and the odds ratio of a positive scan is 2.5-fold greater for PET than for SPECT. There was no statistical difference in the number of positive scans by SPECT or PET, or positive scans by sex in patients with documented history of CAD. CONCLUSION: Fewer women than men have positive nuclear cardiology scans by both PET and SPECT, despite similar symptoms. Instrumentation characteristics alone do not account for this sex-based difference and suggest the possibility that early CAD may present differently in women than in men.

Aged↗
PubMed1998

RBE-LET relationships for cell inactivation and mutation induced by low energy protons in V79 cells: further results at the LNL facility.

PURPOSE: RBE-LET relationships for cell inactivation and hprt mutation in V79 cells have been studied with mono-energetic low-energy proton beams at the radiobiological facility of the INFN-Laboratori Nazionali di Legnaro (LNL), Padova, Italy. MATERIALS AND METHODS: V79 cells were irradiated in mono-layer on mylar coated stainless steel petri dishes, in air. Inactivation data were obtained at 7.7, 34.6 and 37.8 keV/microm and hprt mutation was studied at 7 7 and 37.8 keV/microm. Additional data were also collected for both the end points with the proton LET already considered in our previous publications, namely 11.0, 20.0 and 30.5 keV/microm. RESULTS: A maximum in the RBE-LET relationship for cell inactivation was found at around 31 keV/microm, while the RBE for mutation induction increased continuously with LET. CONCLUSIONS: The proton RBE-LET relationship for cell inactivation is shifted to lower LET values compared with that for heavier ions. For mutation induction, protons of LET equal to 7.7keV/microm gave an RBE value comparable with that obtained by helium ions of about 20 keV/microm. Mutagenicity and lethality caused by protons at low doses in the LET range 7.7-31 keV/microm were proportional, while the data at 37.8 keV/microm suggest that this may not hold at higher LET values.

Animals↗
PubMed1998

A review of dsb induction data for varying quality radiations.

PURPOSE: This short review summarizes the data obtained with various techniques for measuring the yields of double strand breaks (dsb) produced by particle radiations of differing linear energy transfer (LET) in order to obtain relative biological effectiveness (RBE) values. RESULTS AND CONCLUSIONS: Studies aimed at understanding the interactions of different types of radiation with cellular DNA have monitored the yields of DNA dsb versus radiation quality. Several techniques have been used to measure dsb yields in mammalian cells, and these include: neutral sedimentation gradients, filter elution and more recently pulsed field gel electrophoresis techniques (PFGE). Recent developments in PFGE have allowed the measurement of both the yields and the distribution of breaks within the genome, which go part of the way to explaining the RBE values close to 1.0 previously measured using other approaches with various radiation qualities. It is clear that future studies to determine the effectiveness of radiations of differing LET must use techniques that determine both yields and distributions of dsb, and assays need to be developed to allow these measurements at biologically relevant doses.

Alkalies↗
PubMed1998

nm23 expression in human breast cancer: correlation with cell proliferation (S-phase) as observed with a double-labeling immunocytochemical-autoradiographic technique.

In 51 unselected breast cancer samples, a double-labeling immunocytochemical technique was utilized to observe the phenotypic expression of the nm23 gene during S-phase. The feasibility of the method was confirmed by comparison with routine evaluations for both thymidine-labeling index and nm23 (p<0.001). No correlation was found between the two parameters in the overall series or when subgroups regarding menopausal status, nodal involvement, tumor size, hormone receptor content were considered. Tumors with a higher nuclear grade showed a significant correlation only with TLI (p=0. 02). A trend for an inverse relationship between the two parameters was noted but was not statistically significant. A significant association between TLI and nm23 expression was found by Chi-square test using median values as cut-off. Our data based on morphological and in situ observations do not confirm a correlation between nm23 and cell proliferation, even if this correlation cannot be completely excluded. Multicentric trials of high power with these same techniques are still necessary to definitely establish the prognostic role of nm23 in breast cancer.

Adult↗
PubMed1998

Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study.

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.

Adult↗
PubMed1997

Alexithymia, immunity and cervical intraepithelial neoplasia: replication.

BACKGROUND: In a previous study [Psychother Psychosom 1994;61:199-204] we investigated the relationship between alexithymia, carcinogenesis and immunity in a group of women who were unconscious sufferers from precancerous lesions of the cervix (CIN). The results of this study showed a high level of association between alexithymia and CIN and, an even more interesting fact, between alexithymia and reduced levels of immunity. METHODS: The aim of the present study is to check the results of the previous one by testing a larger group (43 women affected by cervical dysplasia and 67 healthy women) and by the use of a self-administered test for detection of alexithymia, the well-validated Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: The results confirm that women suffering from CIN have higher average TAS-20 ratings (55) than normal women (47.32) and that the level of alexithymia detected in the group of women suffering from dysplasia (42.5%) is higher than that of normal women (12.85%). Moreover, the present study confirms that alexithymic women have lower rates of a number of lymphocyte subsets than non-alexithymic women. CONCLUSIONS: This study fully confirms the results of our previous work and those of a number of other studies: (1) personality might be one of the factors jointly responsible for the outbreak of cancer; (2) the immune system appears to play an important part as a mediator between personality and cancer.

Adult↗
PubMed1996

p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

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↗
PubMed1996

[Dna synthesis and expression of steroid receptors in cells of human breast carcinoma].

In order to observe receptor expression (ER and PgR) in human breast cancer cells during the S-phase of the cellular cycle, we evaluated 21 tumoral samples using a double labeling immunocytochemical-autoradiographic assay. In 16 of these we have verified that expression of ER and PgR is not influenced by incubation with 3H-Thymidine for 60 minutes. The results also demonstrated that receptor expression during the S-phase is more common in postmenopausal tumors and is principally dependent on percentages of ER+ (p < 0.01) and PgR+ (p < 0.01) cells; moreover, proliferative activity occurs almost exclusively in ER- (p = 0.003) and Pgr- (p = 0.001) cellular sub populations and the presence of PgR, but not of ER, is related to arrest of DNA synthesis (p = 0.02).

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

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↗
PubMed1992

Induction of myogenic differentiation in human rhabdomyosarcoma cells by ionising radiation, N,N-dimethylformamide and their combination.

Differentiation-inducing ability of gamma-radiation, N,N-dimethylformamide and their combination has been tested on human rhabdomyosarcoma RMZ-RC2 clone cells. Ionising radiation at 2-5 Gy doses induced a more differentiated morphology, with the appearance of an increased proportion of multinuclear myotube-like cells, and a significant increase in myosin-positive and multinuclear cells. Radiation appeared to act by inducing de novo differentiated elements. N,N-dimethylformamide was able to induce an increased myosin expression, but did not affect multinuclear cell proportion. The combined treatment (ionising radiation and N,N-dimethylformamide) resulted in an additive increase in the proportion of myosin-positive cells, approaching 25-35%, but de novo differentiated elements were not increased above the levels obtained with irradiation alone.

Cell Differentiation↗
PubMed1992

Direct comparison between protons and alpha-particles of the same LET: I. Irradiation methods and inactivation of asynchronous V79, HeLa and C3H 10T1/2 cells.

A direct comparison was carried out of the biological effectiveness of protons and alpha-particles of the same linear energy transfer (LET) under identical conditions with a variety of in vitro biological systems. Monolayers of mammalian cells were irradiated with accelerated beams of protons (1.2 and 1.4 MeV) and alpha-particles (30 and 35 MeV) corresponding to LETs of 23 and 20 keV microns-1 for each particle type. For V79-4 cells it was observed that the linear term of the dose-response for cell inactivation by protons was significantly greater than that for alpha-particles of the same LET. For HeLa and HeLa S3 cells, also, the linear term appeared to be greater for protons, but this was not observed with more limited data for C3H 10T1/2 cells. The result for V79 cells is in agreement with the report of Belli et al. (1989) who observed that the biological effectiveness of protons rose sharply between 17 and 30 keV microns-1 in strong contrast to alpha-particles which reached a peak effectiveness at greater than 100 keV microns-1. These results place new constraints on the biologically relevant features of the microscopic structure of radiation tracks, and have implications for the mechanistic and practical comparison between radiations.

Alpha Particles↗
PubMed1992

Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. II. Mutation induction at the HPRT locus in V79 cells.

Mutation induction at the hprt locus has been studied in V79-4 Chinese hamster cells irradiated with mono-energetic protons and alpha-particles with LET of 20.3 and 23 keV microns-1. The mutation frequency increased linearly with the dose for all the four radiation qualities investigated, so that effectiveness for mutation induction could be expressed by the slope of the relevant curve. This effectiveness did not significantly change with the small change in LET of each kind of particle, while sizeable differences were found between particles. Protons were more effective in mutation induction than alpha-particles with the same LET by a factor of about 2. This finding is similar to, although slightly larger than, the factors 1.5-1.8 found for inactivation of the same cells in the same series of experiments.

Alpha Particles↗