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Biomedical subjects

S Di Lollo

Publications and source records attributed to S Di Lollo.

At least 19 recordsLinked to original sources

Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086.

WEB-2086 -- an antagonist of platelet-activating factor receptor (PAFR) with known anti-inflammatory, antiangiogenic and antileukaemic properties -- also proved to inhibit the proliferation in human solid tumour cell lines of different histology, and with much higher efficacy than in normal fibroblasts. A detailed analysis of WEB-2086 anticancer activity was then performed focusing on breast adenocarcinoma MCF-7 and MDA-MB-231 cells. WEB-2086-treated cells, either expressing (MCF-7) or unexpressing (MDA-MB-231) the oestrogen receptor (ER)alpha, underwent a dose-dependent growth arrest (IC(50)=0.65+/-0.09 and 0.41+/-0.07 mM, respectively) and accumulation in G(0)-G(1) phase. WEB-2086 also induced morphological and functional changes typical of mature mammary phenotype including (i) cell enlargement and massive neutral lipid deposition (best accomplished in MCF-7 cells); (ii) decrease in motility and active cathepsin D levels (mainly observed in highly invasive MDA-MB-231 cells). The expression of ERalpha was neither increased nor reactivated in treated MCF-7 or MDA-MB-231 cells, respectively. WEB-2086-induced differentiation in breast cancer cells involved the upregulation of PTEN, a key tumour suppressor protein opposing tumorigenesis, and was apparently independent of p53, PAFR, peripheral benzodiazepine receptor and ERalpha status. Overall, WEB-2086 can be proposed as an effective antiproliferative and differentiative agent with interesting translational opportunities to treat breast cancers in support to conventional chemotherapy.

Azepines↗

[The Haemolymphopathology Italian Group (H.I.G.): an essential resource for the new technical and organization problems troubling modern haemolymphopathology diagnostics].

Recently, many progresses have been recorded in the molecular and histogenetic characterization of the haematopoietic and lymphoid tumours, resulting in important classifying changes. As a consequence, the exact definition of lymphoma subtype requires an integration between traditional morphologic "expertise" and several bio-functional data obtained from advanced and complex ancillary techniques (immunohistochemistry, molecular biology and cytogenetics). At the same time, the data provided by gene expression profiling studies are going to deeply modify the therapies in haematological cancers. These studies are expected to allow the achievement of single-patient-tailored genic therapy; for this reason it is necessary to get biological samples of good quality. Indeed, while these progresses contribute to highlight the pathologist's diagnostic role, they should make us reflect on the state of the art of the Italian haemolymphopathology diagnostics and on its ability to cope up with the new challanges. The aim of this article is to outline a realistic picture of the present condition, and to explain the reasons for setting up, inside SIAPEC-IAP, the Haemolymphopathology Italian Group (H.I.G.). The purpose of H.I.G. will be twofold: first of all, scheduling of a series of projects so as to the haemolymphopathological diagnostic standardization; secondly, building a national network among all the pathologists involved in this exciting and complex field of the anatomic pathology.

Europe↗

Consistency of prostate cancer grading results in screened populations across Europe.

OBJECTIVE: To assess the consistency of grading outcome among seven of eight participating centres of the European Randomised Screening Program of Prostate Cancer (ERSPC), a multicentre randomized trial intended to detect a difference in prostate cancer-related mortality between screened participants and a control group. Currently, tumour stage and grade in prostatectomy specimens represent the most predictive variables for biological behaviour. In prostate needle biopsies the tumour grade is a strong factor for deciding therapy. PATIENTS AND METHODS: Within the ERSPC all prostate cancers detected in needle biopsies were graded according to the Gleason score system. Gleason scores were compressed in three categories of < or = 6, 7 and 8-10. Data for grading outcome were obtained from the databases from seven individual centres; in one centre the slide sets with cancer were separately reviewed. RESULTS: Combining the data of seven ERSPC centres 66% of cancers detected in the screening arm were Gleason score < or = 6 and 92% were < or = 7. Gleason score 8-10 cancers varied from 2 to 11%. This variation in Gleason scores may be attributed to differences in the population characteristics and biopsy indications. CONCLUSIONS: These data indicate that in the seven ERSPC centres most screen-detected cancers have favourable characteristics on biopsy. Men with these cancers are amenable for treatment with curative intent. The observed differences in Gleason score distribution in different centres may partly be attributed to geographical differences and differences in the age range of the screened populations.

Biopsy, Needle↗

Guidelines for processing and reporting of prostatic needle biopsies.

The reported detection rate of prostate cancer, lesions suspicious for cancer, and prostatic intraepithelial neoplasia (PIN) in needle biopsies is highly variable. In part, technical factors, including the quality of the biopsies, the tissue processing, and histopathological reporting, may account for these differences. It has been thought that standardisation of tissue processing might reduce the observed variations in detection rate. Consensus among the members of the pathology committee of the European Randomised study of Screening for Prostate Cancer (ERSPC) concerning the optimal methodology of tissue embedding resulting in guidelines for prostatic needle biopsy processing was reached. The adoption of an unequivocal and uniform way of reporting lesions encountered in prostatic needle biopsies is considered helpful for decision taking by the clinician. The definition of parameters for quality control of prostatic needle biopsy diagnostics will further facilitate clinical epidemiological multicentre studies of prostate cancer.

Biopsy, Needle↗

Transperineal sonography guided biopsy of the prostate: critical review of 1107 cases.

PURPOSE: To assess the predictive value for a positive biopsy of different indicators (rectal examination, transrectal ultrasonography, total PSA, PSA density). MATERIAL AND METHODS: Positive predictive value was assessed on 1107 consecutive US-guided transperineal biopsies performed from 1991 to 2001 (cancer=344, dysplasia (PIN)=64, atypical hyperplasia=4, benign hyperplasia=686, inadequate=9) with univariate and multivariate analysis. RESULTS: Increasing age (chi square for trend 52.2, p <0.001), positive rectal examination (chi square 233, df=1, p<0.001) or ultrasonography (chi square 191, df=1, p<0.001), total PSA (chi square for trend 68.9, p<0.001) and PSA density (cutoff 0.15, chi square 104, df=1, p<0.001; cutoff 0.20, chi square 104, df=1, p<0,001) were all significantly associated to the likelihood of a positive biopsy outcome. Multivariate analysis stresses the independent role of Psa density over total PSA. If the parameters studied had determined the biopsy, spared benign biopsies [positive rectal examination=505 (66%), positive ultrasonography=467 (61%), PSA>4=124 (16%), PSA>10=159 (74%), PSA density >0,15=426 (62%), PSA density >0.20=517 (75%)] would not have justified the amount of delayed cancer biopsies [positive rectal examination=103 (29%), positive ultrasonography=55 (15%), PSA>4=42 (12%), PSA>10=569 (46%), PSA density >0,15=73 (25%), PSA density >0,20=107 (37%)]. CONCLUSIONS: The parameters currently available prior to biopsy, if used alone, allow no reliable prediction of biopsy outcome. Positive predictive value, particularly for PSA density, allows a better evaluation of biopsy indication, particularly for random sextant biopsies in the 4-10 ng/ml PSA range, which are frequently negative.

Adult↗

Epstein-Barr virus infection and P53 expression in HIV-related oral large B cell lymphoma.

BACKGROUND: Head and neck non-Hodgkin's lymphomas in HIV positive patients are highly related with Epstein-Barr virus (EBV) infection. In general, viral agents can alter p53 protein levels by enhancing degradation of cellular p53 or by increasing its half-life by viral protein-p53 interaction. Moreover, it has been reported that modifications of p53 gene can modulate tumor cells' response to radio- and chemotherapy. METHODS: To assess a possible role of EBV infection, p53 protein deregulation, and p53 gene alterations in exons 5 to 8, we have studied six cases of HIV-related primary oral large B-cell lymphoma. We used in situ hybridization (ISH) for EBV-DNA and EBV-encoded nuclear RNA-1 (EBER-1), immunohistochemistry (IHC) for EBV latent membrane protein -1 (LMP-1) and p53 proteins expression, and single strand conformational polymorphism (SSCP) analysis to screen p53 gene mutations in exons 5 to 8. RESULTS: The EBV-DNA was present in all specimens, according to conventional DNA-ISH. No evidence for EBER-1 was found by ISH. The presence of EBV-DNA was correlated with the LMP-1 expression in all but one case. Moreover, p53 protein expression was negative in three cases and strongly positive in the others. However, mutational analysis of p53 gene in exons 5-8 showed no alteration. CONCLUSIONS: Our data may suggest that both EBV infection and LMP-1 expression may cause p53 loss of function even in the absence of p53 gene mutations, as assessed by SSCP. We speculate that the presence of EBV-infection and p53 protein deregulation may be responsible for radio- and chemotherapy resistance, by influencing apoptosis of cancer cells.

Adult↗

Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers.

Excessive consumption of alcoholic beverages may be associated with gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear whether or not chronic alcohol ingestion damages the mucosa of the small intestine. We investigated the effect of chronic alcohol abuse on the duodenal mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal biopsy specimens were obtained during upper gastrointestinal endoscopy from 50 chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological studies were performed by routine histology, immunohistochemistry and electron microscopy. Morphometry of duodenal tissues was performed with a computerized image analyser. No significant duodenal epithelial changes were found in alcoholics, despite an evident reduction in the enterocyte turnover. Myofibroblast-like cells were significantly increased in the villus stroma of alcoholics in comparison to controls. These cells stained positively for desmin, alpha-smooth muscle actin and for several ECM components. In alcohol abusers the thickness of the mucosal basement membrane was greater and the staining for collagen I and III was enhanced both in the basement membrane and in the villus stroma. A higher expression of tenascin was also seen at the base of villi of alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is associated with a transformation of villus juxta-parenchymal cells into active subepithelial myofibroblast-like cells able to produce different ECM components.

Adult↗

Persistent damage to Enterocytozoon bieneusi, with persistent symptomatic relief, after combined furazolidone and albendazole in AIDS patients.

AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients.

AIDS-Related Opportunistic Infections↗

Chronic cryptosporidiosis in patients with AIDS: stable remission and possible eradication after long-term, low dose azithromycin.

AIMS: To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS. METHODS: Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency. RESULTS: Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side effects occurred with the 1500 mg daily dose. CONCLUSIONS: Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.

AIDS-Related Opportunistic Infections↗

[Percutaneous biopsy in the definition of breast lesions: fine needle vs. 14-gauge].

INTRODUCTION: Any breast lesion/abnormality detected at mammography must be characterized as (non)-neoplastic before surgery. Fine needle aspiration cytology (FNAC) permits a precise diagnosis in over 70% of cases but exhibits many inadequate, false negatives or questionable findings. This makes surgical biopsy mandatory in many cases. An alternative is offered by fine needle biopsy (FNB: 16-18 G needles) or by large core biopsy (LCB: 14 G needles), which procedures can reduce the number of questionable diagnoses with no major discomfort or side-effects for the patient. MATERIAL AND METHODS: January, 1996, to October, 1997, we performed 422 microhistologic biopsies on breast lesions at the Unità Integrata di Senologia, Azienda Ospedaliera Careggi, Florence, Italy. 383 of these lesions were nonpalpable. FNB was performed in 221 cases and LCB in 201. Most biopsies (65%) were carried out under US guidance and some others (25%) under stereotactic guidance. RESULTS: Microhistologic biopsy allowed accurate lesion characterization in most cases, even though LCB obviously performed much better. Samples were inadequate in 5.88% of cases with FNB and only in 2.98% of cases with LCB. The false negative rate was 1.92% for FNB and 0.99% for LCB. Surgical biopsy was needed for an unquestionable diagnosis only in 9.5% of FNB and 3.9% of LCB cases. CONCLUSIONS: Our results confirm the literature data on how LCB can be considered a valid alternative to surgical biopsy (and, to some extent, to FNAC); in particular, its advantages are: moderate invasiveness, little patient discomfort and high diagnostic accuracy. Moreover, the procedure is short (5-10 minutes) and costs much less than surgical biopsies (1/2 to 1/4).

Adult↗

The morphology of the prostatic capsule with particular regard to the posterosuperior region: an anatomical and clinical problem.

The composition of the prostatic capsule is important from a clinical point of view, since it is considered to be a barrier against the spread of prostatic tumours. Clinical follow-up demonstrates that apparently intracapsular tumours, particularly in the posterosuperior region of the gland, are frequently understaged at clinical diagnosis. The morphology of the prostatic capsule was studied in 6 cadavers. In each case the prostate was obtained in one block together with the basal portion of the bladder, the seminal vesicles, the anterior wall of the rectum and the periprostatic connective tissue. Part of the material was plastinated, while the remainder was studied using histological and immunohistochemical methods. The prostate was found to be surrounded by connective tissue abundant with smooth muscle cells, and continuous with the stromal septa which subdivide the glandular tissue. A rich network of blood vessels was identifiable. In some regions, particularly in the posterosuperior region, a real capsule was not identifiable. The connective tissue seemed to constitute a continuum between the prostate gland and neighbouring organs, in particular, a connective tissue barrier between the prostate and the seminal vesicles was completely absent. Therefore, due to the absence of a capsular barrier and to the presence of a rich vascular network a prostatic tumour which begins in the posterior region of the gland should be considered as potentially extracapsular.

Adult↗

Enterocytozoon bieneusi in AIDS: symptomatic relief and parasite changes after furazolidone.

AIMS: To investigate changes in morphology of the developmental stages of Enterocytozoon bieneusi and symptomatic relief observed in AIDS patients after treatment with furazolidone. METHODS: Six AIDS patients with symptomatic E bieneusi infection of the small intestine were treated with a course of furazolidone. All patients had a weekly monitoring of parasite shedding in stool by light microscopy during and after treatment. At the end of the treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists who were unaware of the patients' treatment. RESULTS: All patients showed both clinical and parasitological response with transient clearance or decrease of spore shedding in stool. After treatment, alterations in faecal spores were observed in all patients by light microscopy, and ultrastructural changes in E bieneusi at all stages of the life cycle were demonstrated in biopsy specimens of the three patients who underwent post-treatment endoscopy. CONCLUSIONS: The clinical benefit seen after treatment with furazolidone in six AIDS patients with E bieneusi intestinal infection may be due to damage to the developmental stages causing a partial inhibition to reproduction of the parasite.

AIDS-Related Opportunistic Infections↗

Chronic intestinal infection due to subgenus F type 40 adenovirus in a patient with AIDS.

A case of chronic intestinal infection due to adenovirus type 40 lasting for 13 months in a patient with AIDS is described. Adenovirus particles were detected by electron microscopy in biopsy samples taken from the duodenum 3 months after the onset of diarrhoea. The virus was identified as adenovirus type 40 in stool samples by ELISA monoclonal antibodies to adenovirus group antigen (MAd-g2) and types 40 and 41 (MA 40-1 and MA 41-1). No other enteropathogens were found. These data support a causal relationship between adenovirus 40 and the gastrointestinal symptoms of the patient. This is the first reported case of intestinal infection caused by adenovirus type 40 in a patient with AIDS.

AIDS-Related Opportunistic Infections↗

Morphological injury of the intestinal mucosa and infection in patients with AIDS. The role of combined tissue and stool examination.

AIMS: To define the relationship between morphological injury of the intestinal mucosa and infections in AIDS patients. METHODS: Forty-nine AIDS patients were examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum, were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool examination for microorganisms was routinely performed in all patients. RESULTS: Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue and stool examination. The histological study revealed villous atrophy, inter- and intra-enterocyte oedema and epithelial degenerative changes in most of the patients whether or not they had detectable microorganisms. CONCLUSIONS: Combined methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological study of stool samples) may be used to improve the documentation of infections and morphological injury of the intestinal mucosa in AIDS patients.

AIDS-Related Opportunistic Infections↗

Incidence rates of leukemias, lymphomas and myelomas in Italy: geographic distribution and NHL histotypes.

The annual incidence of non-Hodgkin's lymphomas is increasing by 3 to 4% in different parts of the developed world, while rates for Hodgkin's disease, myelomas and leukemias are more stable. In the case of this group of malignancies, hypothesis generation on risk factors has been limited by the use of the ICD classification in mortality and incidence statistics. We have computed incidence rates in different Italian areas after careful re-classification of diagnoses, and considering specific histotypes (Working Formulation for NHL, Rye's classification for HD). While no particularly interesting pattern is suggested for Hodgkin's disease (even after considering specific Rye subgroups), multiple myeloma and leukemias, for non-Hodgkin's lymphomas the high rate in one agricultural area (Forli) was mainly due to the A sub-group in the Working Formulation (low-grade). In a heavily industrialized area (Varese), the high incidence rate was at least partly explained by a higher proportion of cases classified in the G sub-group (intermediate grade). Excesses of non-Hodgkin's lymphomas have been observed in populations exposed to phenoxy-acetic-acid herbicides, to insecticides and to organic solvents. One can hypothesize that different risk factors act on different stem cells and induce lymphoid malignancies belonging to different histologic sub-types.

Adult↗