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Biomedical subjects

G Baroni

Publications and source records attributed to G Baroni.

At least 19 recordsLinked to original sources

A neural network based method for optical patient set-up registration in breast radiotherapy.

Patient set-up optimization is required in breast-cancer radiotherapy to fill the accuracy gap between personalized treatment planning and uncertainties in the irradiation set-up. Opto-electronic systems allow implementing automatic procedures to minimize the positional mismatches of light-reflecting markers located on the patient surface with respect to a corresponding reference configuration. The same systems are used to detect the position of the irradiated body surface by means of laser spots; patient set-up is then corrected by matching the control points onto a CT based reference model through surface registration algorithms. In this paper, a non-deterministic approach based on Artificial Neural Networks is proposed for the automatic, real-time verification of geometrical set-up of breast irradiation. Unlike iterative surface registration methods, no passive fiducials are used and true real-time performance is obtained. Moreover, the non-deterministic modeling performed by the neural algorithm minimizes sensitivity to intra-fractional and inter-fractional non-rigid motion of the breast. The technique was validated through simulated activities by using reference CT data acquired on four subjects. Results show that the procedure is able to detect and reduce simulated set-up errors and revealed high reliability in patient position correction, even when the surface deformation is included in testing conditions.

Breast Neoplasms↗

Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study.

BACKGROUND: Cutaneous melanoma spreads preferentially through the lymphatic route and sentinel lymph node (SLN) status is regarded as the most important predictor of survival. AIMS: To evaluate whether tumour lymphangiogenesis and the expression of vascular endothelial growth factor C (VEGF-C) is related to the risk of SLN metastasis and to clinical outcome in a case-control series of patients with melanoma. METHODS: Forty five invasive melanoma specimens (15 cases and 30 matched controls) were investigated by immunostaining for the lymphatic endothelial marker D2-40 and for VEGF-C. Lymphangiogenesis was measured using computer assisted morphometric analysis. RESULTS: Peritumorous lymphatic vessels were more numerous, had larger average size, and greater relative area than intratumorous lymphatics. The number and area of peritumorous and intratumorous lymphatics was significantly higher in melanomas associated with SLN metastasis than in non-metastatic melanomas. No significant difference in VEGF-C expression by neoplastic cells was shown between metastatic and non-metastatic melanomas. Using logistic regression analysis, intratumorous lymphatic vessel (LV) area was the most significant predictor of SLN metastasis (p = 0.04). Using multivariate analysis, peritumorous LV density was an independent variable affecting overall survival, whereas the intratumorous LV area approached significance (p = 0.07). CONCLUSIONS: This study provides evidence that the presence of high peritumorous and intratumorous lymphatic microvessel density is associated with SLN metastasis and shorter survival. The intratumorous lymphatic vessel area is the most significant factor predicting SLN metastasis. The tumour associated lymphatic network constitutes a potential criterion in the selection of high risk patients for complementary treatment and a new target for antimelanoma therapeutic strategies.

Adult↗

Behavioral outcomes following below-knee amputation in the coordination between balance and leg movement.

Lateral leg movement is accompanied by opposite movements of the supporting leg and trunk segments. This kinematic synergy shifts the center of mass (CM) towards the supporting foot and stabilizes its final position, while the leg movement is being performed. The aim of the present study was to provide insight in the behavioral substitution process responsible for the performance of this kinematic synergy. The kinematic synergy was assessed by the principal component analysis (PCA) applied to both hip joints and supporting ankle joint. Patients after unilateral below-knee amputation and control subjects were asked to perform a lateral leg raising. The first principal component (PC(1)) accounted for more than 99% of the total angular variance for all subjects (amputees and controls). PC(1) thus well represents the possibility to describe this complex multi-joint movement as a one degree of freedom movement with fixed ratios between joint angular time course. In control subjects, the time covariation between joints changes holds during all phases of the leg movement (postural phase, ascending and braking phases). In amputees, PC(1) score decreased during the ascending phase of the movement (i.e. when the body weight transfer is completed, while the movement is initiated). We conclude that a feedback mechanism is involved and discuss the hypothesis that this inter-joint coordination in amputees results from a failure in the pre-setting of the inter-joint coupling.

Adult↗

Tumour-infiltrating gamma/delta T-lymphocytes are correlated with a brief disease-free interval in advanced ovarian serous carcinoma.

BACKGROUND: Significant progress has been made in understanding the molecular biology of ovarian carcinoma. Along with the molecular characteristics of cancer, the patient's response to the tumour may also contribute to survival; in particular, the effect of the immune system may play an important role on survival of cancer patients. PATIENTS AND METHODS: We analysed the CD3 positive tumour-infiltrating T cells and direct molecular assessment of T cell receptors (TCRs) gamma and beta in 95 advanced ovarian carcinomas. RESULTS: Gamma/delta T cells are statistically correlated with a brief disease-free interval (P=0.036). CD3 positive tumour-infiltrating T cells are correlated with a brief disease-free interval and with survival (P=0.004 and P=0.0001, respectively). CD3 positive tumour-infiltrating T cells are associated with clinical responsiveness to chemotherapy (P=0.003). CONCLUSIONS: Further studies are required to better understand the role of gamma/delta T cells in ovarian carcinoma, yet these data underline the importance of host immune response to cancer and the need to better study immune mechanisms to modulate the therapeutic treatment of cancer.

Adult↗

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome.

OBJECTIVES: Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play a critical role in cancer development. We investigated iNOS and COX-2 expression in relation to clinical outcome in 78 International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian serous carcinoma with a low grade of differentiation (G3). METHODS: Disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. A multivariate analysis (Cox-proportional hazards models) was used to determine the independent effect of each variable on prognosis. Fisher's exact test was used to analyze the distribution of iNOS and COX-2 expression according to clinical complete response to chemotherapy and to the presence of a brief disease-free interval (< or =12 months). RESULTS: Overall 60 and 125 months cause-specific survival rates were 32% and 11%, respectively. In univariate analysis, iNOS (P=0.005 and P=0.003, respectively), COX-2 (P=0.002 and P=0.007, respectively), residual disease after surgery (P=0.017 and P=0.032, respectively), and FIGO stage (P=0.008 and P=0.025, respectively) were associated with survival and a disease-free interval. In multivariate analysis (Cox proportional hazards models), the factors that were found to be significantly independent predictors of disease relapse as well as survival were iNOS (P=0.014 and P=0.001, respectively), COX-2 expression (P=0.007 and P=0.029, respectively), and FIGO stage (P=0.026 and P=0.05, respectively). iNOS and COX-2 expressions were correlated with a brief disease-free interval (P=0.001) and clinical complete response to first-line chemotherapy (P=0.038 and P=0.033, respectively). CONCLUSIONS: The evaluation of iNOS and COX-2 expression may give additional prognostic information concerning the clinical outcome of patients with ovarian carcinoma and may encourage them to select more tailored therapies.

Adult↗

ELITE-S2: the multifactorial movement analysis facility for the International Space Station.

Experimental observations of adaptation processes of the motor control system to altered gravity conditions can provide useful elements to the investigations on the mechanisms underlying motor control of human subject. The microgravity environment obtained on orbital flights represents a unique experimental condition for the monitoring of motor adaptation. The research in motor control exploits the changes caused by microgravity on the overall sensorimotor process, due to the impairment of the sensory systems whose function depends upon the presence of the gravity vector. Motor control in microgravity has been investigated during parabolic flights and short-term space missions, in particular for analysis of movement-posture co-ordination when equilibrium is no longer a constraint. Analysis of long-term adaptation would also be very interesting, calling for long-term body motion observations during the process of complete motor adaptation to the weightlessness environment. ELITE-S2 is an innovative facility for quantitative human movement analysis in weightless conditions onboard the International Space Station (ISS). ELITE-S2 is being developed by the Italian Space Agency, ASI is to be delivering the flight models to NASA to be included in an expressed rack in US Lab Module in February 2004. First mission is currently planned for summer 2004 (increment 10 ULF 2 ISS).

Adaptation, Physiological↗

c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study.

BACKGROUND: Recent studies have shown that several tumours express c-KIT, a growth factor receptor with tyrosine kinase activity; moreover, clinical results have shown the efficacy of the tyrosine kinase inhibitor, STI571, in c-KIT-positive tumours. The aim of this study was to determine the incidence and correlation with chemotherapy resistance of c-KIT expression in advanced serous, low grade of differentiation, ovarian carcinoma. PATIENTS AND METHODS: We performed an immunohistochemistry analysis of 56 patients with advanced serous ovarian carcinomas using archival paraffin-embedded specimens. RESULTS: Intense c-KIT immunostaining was observed in 51.7% of cases. c-KIT expression was statistically correlated with progression of disease after first-line chemotherapy (P = 0.029). CONCLUSIONS: c-KIT is also expressed in ovarian carcinoma and it is statistically correlated with chemotherapy resistance. This study suggests the necessity for clinical trials confirming the utility of the tyrosine kinase inhibitor, STI571, in ovarian advanced cancer patients with c-KIT overexpression when these patients have shown no clinical response to conventional chemotherapy.

Drug Resistance, Neoplasm↗

Enhanced surface registration techniques for patient positioning control in breast cancer radiotherapy.

Experimental data, describing patient inter-fractional set-up errors in the clinical practice of breast radiotherapy, were exploited to simulate the performance in errors detection and correction of a constrained surface registration procedure, based on a hybrid configuration of control points (passive and laser). During 47 treatment sessions in three patients undergoing post-quadrantectomy radiotherapy, an opto-electronic localizer was used to acquire the three-dimensional coordinates of the hybrid control points, being two passive markers placed on selected skin landmarks on the sternum. Laser scanning technique was also applied for the acquisition of the 3-D surface model of the irradiated body area, which was used as reference for the automatic position correction procedure. A constrained surface registration algorithm was applied to estimate the rigid spatial transformation, describing the local errors affecting the control points. The improvement of the irradiation geometrical set-up, by correcting the patient position according to the estimated spatial transformation parameters, was simulated. Results showed that the proposed surface registration method allowed us to detect and significantly (Wilcoxon signed rank analysis) reduce the initial misalignments, which exhibited overall median and 75th percentile values equal to 4.26 mm and 5.76 mm. Simulated residual errors dropped down to median and 75th percentile values measuring 2.95 mm and 3.87 mm, respectively. These results confirmed the high potentiality of surface registration techniques for the opto-electronic automatic patient positioning control in breast cancer radiotherapy.

Algorithms↗

[Bcl-2 in ovarian carcinoma: a clinicopathologic, immunohistochemical and molecular study].

We investigated the immunohistochemical espression of bcl-2 and the genetic assessment of the bcl-2 gene in relation to responsiveness to first line chemotherapy and to the clinical outcome in advanced ovarian carcinoma patients. We have compared 17 patients, with FIGO stage III C, ovarian serous carcinomas, G3, living with no evident disease five years after primary surgical treatment; to 19 patients who had died of progression of disease no later than two years after primary surgical treatment. The correlation of bcl-2 expression with the survival and the clinical responsiveness to chemotherapy, were analysed with the logistic regression. We observed a bcl-2 expression in tumor cells in 25% of the cases. Molecular genetic analysis of the bcl-2 gene was performed for all the bcl-2 immunohistochimical positive cases. No traslocation t(14;18)(q32;q21) of the gene bcl-2 were found. The bcl-2 over-expression was found to be a significant independent predictor of responsiveness to chemotherapy (p = 0.04), but it was not correlated with the overall survival of the ovarian cancer patients. The prognostic value of bcl-2 espression may help in the management of ovarian cancer patients permitting the selection of more aggressive first line chemotherapy. In addition, the knowledge of the molecular mechanism, which is responsible of the over-expression of bcl-2, may help in the understanding of mechanisms responsible for chemoresistance. Further studies in this area will help clarify this therapeutic possibility.

Appendectomy↗

Evaluation of methods for opto-electronic body surface sensing applied to patient position control in breast radiation therapy.

The accuracy gap between the high levels of accuracy in radiotherapy planning and the uncertain set-up of each therapy fraction represents a crucial factor in the optimisation of radiation treatment. This occurs because the conventional means of patient alignment and immobilisation do not guarantee accurate implementation of the therapy plan in the actual irradiation treatment. A patient repositioning technique is proposed, based on opto-electronic motion capture and on methods of registration of body surfaces described by a limited dataset. The validation of the method was related to breast cancer radiotherapy and was based on simulated and experimental repositioning procedures involving a phantom and two subjects. With respect to previous work, the surface registration procedure was, in this case, implemented as a constrained non-linear least-square problem (constraints were given by the position of a couple of passive markers placed on the sternum), and three different algorithms were compared in terms of accuracy in misalignment detection and of computational cost. The simulation and experimental activities identified the best performing algorithm, which systematically limited the repositioning errors to below clinically acceptable thresholds (5 mm), with residual surface mismatches lower than 2 mm.

Algorithms↗

Prognostic value of P-glycoprotein and proliferative index in advanced low grade serous ovarian carcinomas.

The aim of this study was to test the prognostic value of p-glycoprotein expression and the proliferative index of tumor cells on the clinical response to chemotherapy, on the brief disease-free interval (< 12 months) and on cause-specific survival in advanced ovarian carcinoma. We evaluated 83 ovarian carcinoma patients homogeneous for stage, type and grade histological. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. Multivariate analysis (Cox proportional hazards models) was used to determine the independent effect of each variable on prognosis. In the univariate analysis, P-glycoprotein expression (P < 0.0005) and proliferative index (P = 0.0003 and P = 0.0006) were independent predictors of survival and brief disease-free interval; residual disease was associated with survival (P = 0.021). In multivariate analysis (Cox proportional hazards models), P-glycoprotein expression (P = 0.001 and P = < 0.0005) and proliferative index (P = 0.081 and P = 0.041) were independent predictors of brief disease-free interval and survival. P-glycoprotein expression (P < 0.0005) and proliferative index (P = 0.008) were associated with clinical response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Self-marking of anatomical landmarks for on-orbit experimental motion analysis compared to expert direct-marking.

The on-orbit application of movement analysis methodology, on-board space stations, for studying the gravity role in motor functions, requires a careful adaptation of the currently adopted techniques in order to obtain reliable data. In those operative conditions, differently from common on-ground experimental activities, a non-specialist operator, an astronaut of the space station crew, is expected to self-administer the experimental protocol, particularly self-marking specific anatomical landmarks. The present paper proposes a movement analysis methodology, which fits the specific constraints of space activity and matches the objective of maximising reliability and minimising on-orbit time, and reports normative data about accuracy and precision of the self-marking of an extended set of anatomical landmarks. The same set of landmarks has been considered also for direct-marking performed by experts in motion analysis and their results have been compared to self-marking ones. The paper contents will support the design of future space experimental campaigns and is, in general, applicable to any on-ground scientific investigation, possibly increasing data reliability.

Adult↗

Multidrug resistance in ovarian cancer: comparing an immunocytochemical study and ATP-tumor chemosensitivity assay.

The aim of our study was to evaluate the possible prognostic and predictive significance of the expression of P-glycoprotein, a transmembrane transport protein related to multidrug resistance, in previously untreated patients with FIGO stage III ovarian cancer; to compare the results of immunocytochemical analysis of tissue sections of tumors to the in vitro chemosensitivity to cytotoxic drug of fresh samples of the same tumors; and to evaluate survival in women who underwent the same surgical treatment and the same adjuvant chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Euromir 95 T4 experiment 'Human Posture in microgravity': global results and future perspectives.

After 7 years of studies on Euromir 95 T4 experiment 'Human Posture in microgravity' dataset, some important remarks can be proposed for best exploiting future experimental campaigns as well as for neurophysiological investigations on-ground. The main focus of such experiments was to monitor the process of learning and adapting to the new environment in performing complex voluntary movements. Euromir 95 was the first quantitative investigation with high technology instrumentation (ELITE-S) involving two subjects starting from 15 days after the launch until 5 months of mission. Results confirm the excellent capability of mutation of motor planning by the central nervous system (CNS) in order to best exploit environmental constraints and advantages. Under this view, the results offer a unique cue for improving the design of rehabilitation processes in motor pathologies.

Journal Article↗

Optimisation of shape kernel and threshold in image-processing motion analysers.

The aim of the work is to optimise the image processing of a motion analyser. This is to improve accuracy, which is crucial for neurophysiological and rehabilitation applications. A new motion analyser, ELITE-S2, for installation on the International Space Station is described, with the focus on image processing. Important improvements are expected in the hardware of ELITE-S2 compared with ELITE and previous versions (ELITE-S and Kinelite). The core algorithm for marker recognition was based on the current ELITE version, using the cross-correlation technique. This technique was based on the matching of the expected marker shape, the so-called kernel, with image features. Optimisation of the kernel parameters was achieved using a genetic algorithm, taking into account noise rejection and accuracy. Optimisation was achieved by performing tests on six highly precise grids (with marker diameters ranging from 1.5 to 4 mm), representing all allowed marker image sizes, and on a noise image. The results of comparing the optimised kernels and the current ELITE version showed a great improvement in marker recognition accuracy, while noise rejection characteristics were preserved. An average increase in marker co-ordinate accuracy of +22% was achieved, corresponding to a mean accuracy of 0.11 pixel in comparison with 0.14 pixel, measured over all grids. An improvement of +37%, corresponding to an improvement from 0.22 pixel to 0.14 pixel, was observed over the grid with the biggest markers.

Algorithms↗

Voluntary head stabilisation in space during oscillatory trunk movements in the frontal plane performed before, during and after a prolonged period of weightlessness.

The ability to voluntarily stabilise the head in space exhibited by two subjects during lateral rhythmic oscillations of the trunk has been investigated before, during and after a prolonged period of microgravity (microG) exposure. In flight acquisitions were performed onboard the Core Module of the Russian Space Station MIR as part of the T4 "Human Posture in Microgravity" experiment of the 179-days ESA-RKA mission EUROMIR-95. Data collection and kinematic analysis were performed by means of a space-qualified version of the automatic motion analyser ELITE. Head stabilisation in space strategy was estimated by means of the head anchoring index and cross-correlation analysis. Results show that head orientation may be well stabilised about the roll axis both with and without the presence of visual information. This was true despite the expected reduction in vestibular efficiency and muscular proprioception occurring in-flight. In one subject, however, vision was found to improve head stabilisation in space post-flight, presumably to recover from the postural deficiency induced by the long-term microG exposure. Head stability during trunk movements was achieved with either over-compensatory (out-of-phase), under-compensatory (in-phase) or mixed movement strategies, as was attested by the analysis of cross-correlation functions between head and shoulder movements. In weightlessness, vision occlusion seemed to influence the choice of the strategies to be used as well as the reduction of movement variability. The feedforward nature of compensatory head movements suggests that head stabilisation could be based in weightlessness on the internal postural body scheme, supposed to be adapted to the weightless environment within 5 months of microG exposure.

Adaptation, Biological↗

Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer.

BACKGROUND & AIMS: Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer. METHODS: Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay. RESULTS: The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03). CONCLUSIONS: COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.

Adenocarcinoma↗