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Biomedical subjects

G Modica

Publications and source records attributed to G Modica.

At least 19 recordsLinked to original sources

60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis.

The aim of the present study was to evaluate the expression of the heat shock protein 60 (HSP60), a mitochondrial matrix-associated protein belonging to the chaperonin family, in colorectal adenomas and cancers, comparing them to normal colonic tissues and hyperplastic polyps. We performed both immunohistochemistry and Western blot analysis for HSP60. Immunohistochemistry resulted positive in all tubular adenomas and infiltrating adenocarcinomas. By contrast, normal tissues and hyperplastic polyps were negative. Quantitative analysis showed that tubular adenomas with different levels of dysplasia did not present statistical differences concerning HSP60 positivity. In addition, carcinomas always showed the highest expression. Western blot analysis confirmed these observations. These data suggest that HSP60 over-expression is an early event in carcinogenesis. We suspect that HSP60 plays a different role in colorectal carcinogenesis with respect to that in normal cells, which foresees its possible use as diagnostic and prognostic tools.

Adenocarcinoma↗

High levels of exogenous C2-ceramide promote morphological and biochemical evidences of necrotic features in thyroid follicular cells.

CD95 and ceramide are known to be involved in the apoptotic mechanism. The triggering of CD95 induces a cascade of metabolic events that progressively and dramatically modifies the cell shape by intense membrane blebbing, leading to apoptotic bodies production. Although the CD95 pathway has been abundantly described in normal thyrocytes, the effects of cell permeable synthetic ceramide at morphological and biochemical levels are not fully known. In the present study, we show that thyroid follicular cells (TFC) exposed to 20 microM of C(2)-ceramide for 4 h are characterized by morphological features of necrosis, such as electron-lucent cytoplasm, mitochondrial swelling, and loss of plasma membrane integrity without drastic morphological changes in the nuclei. By contrast, TFC treated with 2 microM of C(2)-ceramide for 4 h are able to accumulate GD3, activate caspases cascade, and induce apoptosis. Furthermore, we provide evidence that 20 microM of C(2)-ceramide determine the destruction of mitochondria and are not able to induce PARP cleavage and internucleosomal DNA fragmentation, suggesting that the apoptotic program is not activated during the death process and nuclear DNA is randomly cleaved as the consequence of cellular degeneration. Pretreatment with 30 microM of zVAD-fmk rescued TFC from 2 microM of C(2)-ceramide-induced apoptosis, whereas, 20 microM of C(2)-ceramide exposure induced necrotic features. Deltapsi(m) was obviously altered in cells treated with 20 microM of C(2)-ceramide for 4 h (75% +/- 3.5%) compared with the low percentage (12.5% +/- 0.4%) of cells with altered Deltapsi(m) exposed to 2 microM of C(2)-ceramide. Whereas, only 20% +/- 1.1% of cells treated with anti-CD95 for 1 h showed altered Deltapsi(m). Additionally, Bax and Bak, two pro-apoptotic members, seem to be not oligomerized in the mitochondrial membrane following ceramide exposure. These results imply that high levels of exogenous ceramide contribute to the necrotic process in TFC, and may provide key molecular basis to the understanding of thyroid signaling pathways that might promote the apoptotic mechanism in thyroid tumoral cells.

Apoptosis↗

Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study.

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age <or=75 years; evaluable or measurable progressive lesions; PS (ECOG) 0-2; adequate haematology and biochemistry parameters; no serious concurrent diseases; no symptomatic brain lesions; and informed consent. The end points were assessment of overall response rate, toxicity and quality of life (QoL). Patients were re-evaluated at the end of every cycle. An interim analysis of 18 patients (16 M) was performed. Weekly courses were 132; 16 of 18 patients were evaluable for response and 17 of 18 for toxicity. Two of the 16 patients (12.5%) had a partial response (95% CI: 10.5-14.7%). Haematological toxicity was very mild: grade 1-2 neutropenia occurred in four patients, grade 3 neutropenia in two patients; grade 1-2 anaemia in four patients; and grade 1-2 thrombocytopenia in two patients. Non-haematological toxicity was also very mild, with the exclusion of asthenia (grade 1-2 in ten patients and grade 3 in five patients) and alopecia (grade 1-2 in seven patients and grade 3 in eight patients). No cases of grade 4 toxicity were observed. No QoL evaluations were reported in this interim analysis. In conclusion, these preliminary data confirm that weekly D results in tolerable toxicity in pre-treated NSCLC. Myelo-suppression, the dose-limiting toxicity of every 3 week schedules, is not a clinically relevant problem when D is administered weekly. G-CSF was used only sporadically in four patients, and no febrile neutropenia was reported. Patients were pre-treated with dexamethasone and no allergic reactions were seen. Although the therapeutic activity appears to be comparable to that of every 3 week schedules, more data are necessary before definite conclusions can be drawn. Accrual of patients is still ongoing.

Adult↗

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma.

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.

Adenocarcinoma↗

[Ventral hernia surgery].

BACKGROUND: A personal technique for polypropilene mesh implantation in the treatment of massive, boundary and recurrent incisional hernias is described. METHODS. DESIGN: retrospective evaluation of cases observed over the last 3 years. SETTING: division of General, Oncological and Thoracic Surgery, Department of Surgical and Anatomical Sciences, University of Palermo. SUBJECTS: twenty-four patients with massive, boundary and recurrent ventral hernia were selected and treated with this technique. INTERVENTIONS: the patients were submitted to implantation of a polypropilene prosthesis by using a part of the well vascularised hernial sac in order to close completely the peritoneal layer under the prosthesis (so as to avoid the contact between prosthesis and viscera) and to close the layer over the prosthesis (avoiding a contact between prosthesis and subcutis). MAIN OUTCOME MEASURES: morbidity and mortality have been evaluated. RESULTS: Patients were discharged from the 7th and 15th postoperative day. No mortality was recorded. In four out of 24 patients the following complications were observed: 1 case of high postoperative fever; 2 cases of superficial infection of the surgical wound; 1 case of wide cutaneous suppuration without prosthesis involvement. No recurrences were observed during the follow-up (6 months-3 year). CONCLUSIONS: Even if a scientific evaluation of the results is not possible due to the poor number of cases, short-term follow-up and unavailable randomized studies, this technique may be useful since it permits to avoid the contact between prosthesis and viscera, with lower postoperative adherences and the isolation of prosthesis from the subcutaneous tissue, sometimes involved in suppuration.

Adult↗

[Double-chamber right ventricle: a case report].

The double-chamber right ventricle is a congenital cardiac malformation usually associated with other cardiac defects, seldom isolated and in adult subject. It is characterized by the presence of an anomalous bundle that divides the right ventricle into two chambers. The clinical and electrocardiographic signs of isolated double-chamber right ventricle are few and not specific. An echocardiographic diagnosis of isolated double-chamber right ventricle is reported. In a 18-year-old asymptomatic male with systolic murmur 2/6 at third space over the left sternal border, right ventricular hypertrophy and intraventricular conduction delay at ECG, two-dimensional echo showed an anomalous transversal muscle bundle that divided the right ventricle into two chambers, superior and inferior. Color Doppler showed a diastolic tricuspidal-like flow through a paraseptal discontinuity of the bundle and a systolic jet that reached the right atrium, with a pressure gradient of 30.9 mmHg. The absence of symptoms and other cardiopathy, without significant right outflow tract obstruction, was considered as an index of a good prognosis; therefore cardiac catheterization was not advised.

Adult↗

[Cross-over study on the effects of ketanserin vs enalapril in the treatment of hypertension].

The aim of the study was to compare antihypertensive efficacy and safety of ketanserin with those of enalapril in the treatment of hypertension. The study design was controlled, cross-over, with randomized sequences. The efficacy was evaluated from data of 19 (9 males, 10 females) mean age 59.5 +/- 10.1 years, weight kg 68 +/- 12.1 with hypertension lasting over 5 years. Posology was ketanserin 20-40 mg bid, and enalapril 10-20 mg bid; both for three weeks. The efficacy was good with both treatments and the effects similar. In fact, at the end of the treatment with ketanserin, supine SBP was decreased 10 +/- 20 and DBP 5 +/- 10 mmHg, standing SBP was reduced 15 +/- 19 and DBP 7 +/- 15 mmHg. With enalapril supine SBP decreased 25 +/- 16 and DBP 10 +/- 13 mmHg, standing SBP was reduced 16 +/- 19 and DBP 8 +/- 18 mmHg. Changes of heart rate by either treatment were of no clinical importance. The safety of treatment with ketanserin was excellent, while 14.3% of the patients treated with enalapril had undesirable effects.

Aged↗

[Diastolic flow in the left ventricle of healthy subjects: a study using processing of intracardiac color-Doppler maps].

UNLABELLED: Aim of the study was to evaluate the left ventricular (LV) diastolic flow propagation. Ten healthy subjects (28 +/- 6 years) were examined. Two-dimensional echocardiography and color-Doppler at mitral valve were performed. A cine-loop was transferred on-line to a color image processor. Selected digitized images were stored on microdisk. LV end-diastolic, end-systolic and early filling (EF) volumes were measured. Doppler measurements across the mitral valve were obtained: peak E, peak A, E/A, the integral (VTI) of E and A, acceleration and filling time. Extension of color and time base to apex, time of EF and atrial filling (AF) were obtained by M-color, along the base-apex axis. On frames of EF and AF of 2D-color, diastolic maps were processed: surface area and pixel velocity, mean (mv) and peak (pv), were obtained of the entire color area and of 4 selected areas, 2 mm wide: 1 along the annulus-apex axis (LAx), and 3 transverse, planes, at the annulus, at papillary (1/3) and at the apex (2/3 of LAx). Three-dimensional plot and velocity distribution were obtained. Values of pixel of the entire color area were stored on microdisk and processed using a Macintosh PC. For each transverse section, 1 pixel wide, mv and pv were obtained, and data were referred to normalized axis and the mean was calculated. RESULTS: end-diastolic volume index (EDVI): 66 +/- 7, end-systolic volume index (ESVI): 26 +/- 5 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of BICAP in a case of colon angiodysplasia.

This paper reports on a case of colonic bleeding from an angiodysplastic lesion of the ascending colon in a 71-year-old diabetic woman, resulting in severe anemia in the patient, who was treated using the BICAP electrocoagulation system. The present report includes a description of this technique, which involves the use of a 7-F hemostatic probe connected to a 25-W BICAP source.

Aged↗

[Pathophysiologic classification of heart failure: contribution of echocardiography].

Aim of the study was to examine the role of echocardiography to classify patients with heart failure. Fifty-seven subjects (32 dilated cardiomyopathy (DCM), 9 aortic regurgitation (AR), 16 hypertensives (HT)--4 in Class (CI) NYHA I, 24 II, 15 III, 14 IV--were studied by M-2D echo. Eighty-seven normals (N) were the control group; 11 were controlled after clinical improvement (3.4 +/- 3.8 months); 11 after worsening (12 +/- 17). We have evaluated: left ventricular diastolic dimension (LVIDd), wall thickness/radius ratio (H/R), diastolic (D) and systolic volume (S Vol), ejection fraction (EF), systolic arterial pressure/end-systolic volume ratio (P/V), and stress. LVIDd and stress were increased in all groups; H/R reduced, except in HT and in Cl I; EF and P/V reduced except in Cl I. Between I and II LVIDd was different; between II and III all parameters were different, between III and IV only EF and P/V. According to regression S-D Vol, EF-P/V and EF-stress we identify the reduction of EF and the related mechanisms, ie reduced contractility or increased afterload. Thus, according to P/V and stress, we classify the patients in 4 pathopysiologic classes: 1 and 2 with P/V within 2 SD N: 1 with stress within 2SD N, EF and H/R normal; 2 with stress greater than +2SD, H/R normal and EF reduced; 3 and 4 with P/C less than -2 SD N: 3 with normal, 4 with stress greater than +2 SD. In the 1 and 2, 1 out 14 is in III Cl NYHA, none in IV; in 3,6 out 8 are in II, in 4, 9 out 35 are in Cl less than III. In the follow-up, in 8 of the improved patients, EF and P/V were increased and stress reduced; in 3, EF was reduced. In 8 of the worsened, EF and P/V were reduced, LVIDd and stress increased; in 3 EF and LVIDd were increased, P/V reduced. This study demonstrates discordance between Cl NYHA and echo, and how classification of NYHA does not give information about the several components of heart failure. However LVID and EF are not sufficient. By a correlation of echo-parameters of contractility, afterload and pump performance, we may suggest a classification of heart failure in pathophysiologic classes.

Adolescent↗

[Screening for liver metastases of colorectal carcinoma by the routine use of intraoperative echography].

The detection and distribution of liver metastases from colorectal carcinoma is an important problem for the therapeutic approach and prognosis. In this study we evaluated the diagnostic accuracy and technical utility of intraoperative ultrasonography (I.O.U.) in the treatment for liver metastases from colorectal carcinoma. I.O.U. has been routine performed in 70 patients. 13 metastatic lesions have been diagnosed in 10/70 patients with colorectal carcinoma (14.3%). Only 6 of 13 lesions (sensitivity of 46.1%) have been diagnosed preoperatively and/or by surgical exploration. Instead 7 small intrahepatic metastatic lesions (53.9%) have been diagnosed exclusively by I.O.U. It has not been possible to detect this lesions by surgical exploration; the size of these metastatic tumor ranged from 0.4 x 0.6 to 1.2 x 1.6 cm. I.O.U. has been useful for its high sensitivity, for the study of anatomic relation between metastatic lesions and vascular and biliary hepatic structure (good guidance for surgical hepatic resection) and for the possibility of performing deep ultrasound guided biopsies of hepatic lesions.

Carcinoma↗