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Biomedical subjects

O Nanni

Publications and source records attributed to O Nanni.

68 records · Page 4Linked to original sources

In vitro potentiation by lonidamine of the cytotoxic effect of adriamycin on primary and established breast cancer cell lines.

Lonidamine is a new potential chemotherapeutic agent, relatively non-toxic, that can positively modulate the efficacy of several antineoplastic drugs. We evaluated the response of two established human breast cancer cell lines (MCF-7 and BRC-230) and of 20 primary breast cancer cell lines to lonidamine, either alone or in combination with adriamycin, the drug most widely used in the management of breast cancer. Different schedules were tested by varying either concentration of the drugs (LND: 10-150 micrograms/ml; ADM: 0.10-0.15 micrograms/ml), or time of exposure (1-96 hours), or sequence of administration (ADM-->LND; LND-->ADM; ADM+LND). Our results indicate slight sensitivity of the cell lines to lonidamine when used alone, whereas an increase of efficacy was noted when lonidamine was added for at least 24 hours after a 4 hour exposure to adriamycin. Such efficacy was significantly greater than that expected from an additive effect between the two drugs. We conclude that lonidamine, when given according to an appropriate schedule, enhances, in vitro, the efficacy of adriamycin. A correct employment of lonidamine in the management of breast cancer might therefore potentiate the therapeutic effect of adriamycin.

Antineoplastic Agents↗

Clinical and laboratory evaluation of the myeloprotective effect of medroxyprogesterone acetate in head and neck cancer.

The action of high-dose medroxyprogesterone acetate (MPA) was studied by analysing the behaviour of colony-forming-unit granulocyte-macrophage (CFU-GM) during chemotherapy. 21 non-pretreated men with locally advanced carcinoma of the head and neck were randomised into two arms: A (11 patients) received three alternating cycles of cisplatin, 5-fluorouracil (CF)/cisplatin, methotrexate, bleomycin, vincristine and then CF every 4 weeks and B (10 patients) were treated with the same schedule plus 1000 mg per day of MPA. MPA was administered 14 days before the start of chemotherapy (day 0) and continued daily up to the 90th day. Bone marrow was harvested in arm A on days 0, +14 and +90, and in B, also on day -14. There was diverse CFU-GM behaviour in the two arms on the 14th day. These data support the hypothesis that the myeloprotective effect of MPA is due to induction of a mitotic rest in the stem cells, which protects them from drug action.

Antineoplastic Agents↗

Hepatocellular carcinoma. Prognostic factors and survival analysis in 135 Italian patients.

This is a retrospective study to evaluate the history of hepatocellular carcinoma and find the relationship between clinical, biochemical and ultrasonographic features and survival in Italian patients. In 135 consecutive patients median follow-up was 16 months (range 1-66 months) and median survival from the time of diagnosis was 12 months. Univariate analysis showed that individual variables associated with significantly decreased survival included: absence of therapy, Okuda's Stage III, Child-Pugh's Class C, alpha-fetoprotein greater than 400 ng/ml, presence of symptoms, moderate or severe ascites, tumor involving both lobes, mixed internal echo pattern, and multinodular or massive type. Multiple regression analysis (Cox model) revealed that the mixed internal echo pattern of hepatocellular carcinoma, the presence of moderate or severe ascites and Okuda's Stage III were independent predictors of high risk of death. These data can help in selecting patients whose probability of survival is considered high enough to undergo treatment and may be useful for stratifying patients in randomized controlled trials.

Adult↗

Cell kinetics and hormonal features in relation to pathological stage in breast cancer.

Proliferative activity (expressed as 3H-thymidine labeling index, 3H-TdR LI) was evaluated on a series of 281 primary tumors recruited in two years in 6 different institutions from central Italy. 3H-TdR LI proved to be low in intraductal, or well and moderately differentiated, or hormone receptor positive tumors. Conversely, no relation was observed between 3H-TdR LI and menopause, tumor size, or lymph node involvement. An inverse relation was observed between 3H-TdR LI and hormone receptor content. Specific patterns of 3H-TdR LI value and ER content association were observed as a function of menopause, lymph nodal status, and degree of lymph nodal involvement.

Breast Neoplasms↗

Prognostic value of persistent thallium-201 defects that become reversible after reinjection in patients with chronic myocardial infarction.

BACKGROUND: The presence of defects at stress-redistribution thallium-201 scintigraphy is related to a higher risk of cardiac events. However, the prognostic value of defects that become reversible after reinjection is not known. In this study we evaluated the prognostic contribution of stress-redistribution-reinjection with special regard to 3-hour fixed defects that become reversible after reinjection. METHODS AND RESULTS: We studied 122 patients with chronic myocardial infarction (>2 months) and suspected or known residual ischemia, with stress-redistribution-reinjection planar scintigraphy. Thallium scans were analyzed by three observers (three segments per view, 5-point score) and classified as normal, fixed, and reversible. The lung/heart ratio was also calculated. At a median follow-up of 47 months, 10 patients had hard events (four deaths and six myocardial infarctions) (group I), 12 patients had unstable angina (group II), 12 patients underwent planned coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (group III), and 86 patients had no events (group IV). The presence of fixed defects that became reversible after reinjection did not identify patients at higher risk. The number of reversible defects at 3 hours was significantly higher only in patients who underwent revascularization. Unstable angina was not predicted by any scintigraphic pattern. The variables that were statistically related to hard events by univariate analysis were increased lung uptake, reversible cavity dilation, and the number of fixed defects that remained fixed after reinjection. By Cox multivariate analysis, the strongest predictor of hard events was the presence of more than three fixed defects that remained fixed after reinjection as a marker of irreversible myocardial damage. CONCLUSIONS: (201)Tl reinjection is a useful approach for not only detecting viable myocardium but also risk stratification in patients with chronic myocardial infarction.

Angina, Unstable↗

Telomerase activity detected by quantitative assay in bladder carcinoma and exfoliated cells in urine.

Early diagnosis is one of the most determining factors for patient survival. The detection of telomerase activity is a potentially promising tool in the diagnosis of bladder and other types of cancer due to the high expression of this enzyme in tumor cells. We carried out a quantitative evaluation of telomerase activity in urine samples in an attempt to determine a cut-off capable of identifying cancer patients. Telomerase activity was quantified by fluorescence TRAP assay in urine from 50 healthy volunteers and in urine and bioptic tumor samples from 56 previously untreated bladder cancer patients and expressed in arbitrary enzymatic units (AEU). Telomerase activity in urine ranged from 0 to 106 AEU (median 0) in healthy donors and from 0 to 282 AEU (median 87) in patients with cancer. A telomerase expression higher than the cut off value determined by receiver operating characteristic (ROC) analysis was observed in 78% of cases, regardless of tumor grade and in 71% (15/21) of cases of nonassessable or negative cytology. The quantitative analysis of telomerase activity in urine enabled us to define cut-off values characterized by different sensitivity and specificity. Cytologic and telomerase determination, used sequentially, enabled us to detect about 90% of tumors.

Humans↗

Feasibility of a cell kinetic-based adjuvant chemotherapy trial in axillary node-negative breast cancer.

AIMS AND BACKGROUND: Accumulated information on biologic prognostic indicators and predictors of response to different types of treatment in patients with different tumor characteristics has made it possible to design clinical protocols on biologic bases. Among cell proliferation indices, the thymidine labelling index (TLI) has proved to be an independent and consistent prognostic indicator over time. Moreover, experimental and retrospective analyses of clinical studies have revealed a direct relation between TLI and response to chemotherapy. On the basis of the results, a prospective clinical protocol on axillary node-negative breast cancer was activated in Italy in 1989. METHODS: Patients with low TLI tumors were treated with local-regional therapy alone, whereas patients with high TLI tumors were randomized to receive local-regional therapy followed or not by adjuvant chemotherapy consisting of 6 cycles of CMF. RESULTS AND CONCLUSIONS: The present paper reports on the feasibility of a prospective clinical protocol based on a subgroup of patients with specific pathologic (node negative) and biologic (rapidly proliferating) breast cancers. However, patient eligibility was only 11%.

Adult↗

Early gastric cancer in the province of Forlì: follow-up of 337 patients in a high risk region for gastric cancer.

Long-term clinical outcome was analysed in a series of 337 patients with early gastric cancer (EGC) at a median follow-up of 8 years. Tumours were classified according to the macroscopic and microscopic criteria proposed by the Japanese society of gastroenterological endoscopy (JSGE) and Lauren, respectively. Type of penetration (PEN) was classified according to Kodama. Overall survival rate was 92% at 5 years and 88% at 8 years and was significantly related to depth, type of penetration, lymph node status and tumour size. A significantly lower 5-year survival (p<0.05) was observed for patients with lymph node metastases and PEN A type EGC (55%) or for those with node-positive tumours and submucosal wall penetration (58%) than for the other pathologic subgroups. Therefore, these two subgroups should be considered as advanced gastric cancer patients from the prognostic point of view. Moreover, multivariate analysis by Cox regression model showed the degree of lymph node involvement and Kodama's type PEN A as the only independent prognostic factors.

Adult↗

[Value of the in situ hybridization technique in the diagnosis of human papilloma virus infections of the uterine cervix. Correlations between the human papilloma virus type and the morphological features].

Clinico-pathologic, epidemiologic and molecular analytic studies have shown that: i) the squamous cancer of the uterine cervix derives from intraepithelial lesions with different degrees of atypia; ii) human papillomavirus (HPV) can play a fundamental role in the progression of these lesions. We have examined 219 uterine cervix biopsies by means of the in situ hybridization technique (ISH) using biotinylated probes for 6/11, 16/18 and 31/35/51 HPV strains. The histologic lesions were as follows: 104 (49.7%) focal koilocytotic lesions 26 (11.8%) low grade intraepithelial lesions (SIL) 45 (20.5%) high grade intraepithelial lesions (SIL) 18 (8.2%) condylomata acuminata 21 (9.8%) invasive cancers. The percentage of the positivity found in the whole material examined is 14.1%. In particular, none of the 109 cases of focal koilocytotic lesions was positive, whereas the 28.1% of the remaining 110 biopsies turned out to contain HPV. We hypothesize that our small percentage of positivity in preinvasive and invasive lesions of the uterine cervix can be due to the fact that the HPV is not the only cancerogenic factor involved, although the possibility of a low sensitivity of the technique cannot completely be excluded.

Carcinoma in Situ↗

Do Italian small cell lung cancer (SCLC) specialists share a common language? An analysis based on 549 questionnaires.

Different specialists are involved in the treatment of SCLC: medical oncologists, pneumologists, radiotherapists, and thoracic surgeons; only in large institutions the therapeutic policy is the result of a multidisciplinary approach. In order to investigate the opinions of the Italian physicians about the state of the art in the diagnosis and treatment of SCLC, 2369 questionnaires have been sent to an equal number of specialists. Each questionnaire contained 16 topics addressing what we consider major open questions. The analysis is based on 549 interpretable questionnaires received back (23.1%). The general attitude of responding physicians is quite pessimistic on the present state of the art; the large majority considering insufficient the current knowledge of both clinical and basic research. Some differences have been registered, among different specialists, regarding the role of surgery and radiation therapy in prolonging the expected survival; while a nearly unanimous consensus has been reached on the role of radiation therapy for local control. Optimism merges about the possibilities of ameliorating the survival in the next decades: 48% have confidence in new drugs, 45% in the development of integrated modalities, and 41% in the application of basic research.

Adult↗

A randomized trial on breast self-examination in Faenza (northern-Italy).

AIMS AND BACKGROUND: The aim of this randomized controlled trial was to compare two methods for teaching breast self-examination: theoretical and practical session versus mailed material. METHODS: A random sample of women aged 20-64 years was drawn from the demographic file of the city of Faenza (Northern-Italy). Of 825 sampled eligible women, 168 declined participation, 657 were randomly assigned, after completing a pretest questionnaire aimed at evaluating practice and quality of breast self-examination. Individualised instruction was administered to the treatment group invited to be taught breast self-examination in a medical practice setting. The control group received mailed information about breast self-examination. One year later, 443 women completed the posttest questionnaire. RESULTS: As far as concerns the first outcome of the trial (change in practice of breast-self examination) our study showed, after adjusting for lost-to-follow-up, no difference between the treatment and the control group. The analysis performed to evaluate the second outcome (change in quality of breast self-examination practice) showed that women of the treatment group improved the quality of breast self-examination practice more than the control group (Wilcoxon test, z = 2.4, P < 0.01). The same results have been confirmed by multiple regression analyses taking into account all potential confounders. No selection bias affected these results. CONCLUSION: Theoretical and practical sessions resulted in an improved quality of examination technique than did mailed material.

Adult↗

Gastric cancer: epidemiologic and biological aspects.

Although temporal trends and regional-racial variations in gastric cancer incidence have led to the formulation of different hypotheses, no definite association has been seen between this disease and any behavioural or genetic determinant. In fact, several aetiological factors have been associated with risk of gastric cancer, but not without controversy. Various studies have suggested that genetic factors might be of importance in the pathogenesis of gastric tumours. In fact, stomach carcinoma occurs more frequently among close relatives of affected individuals than in the general population and some of the most common pre-cancerous lesions seem to be genetically determined. In the light of this circumstantial evidence, we decided to investigate the role of various genetic alterations in gastric cancer in order to study their relationship with aetiopathogenesis and disease progression and their value as indicators of risk and prognosis. Our main areas of interest were: i. c-Ha-ras locus polymorphism; ii, truncated c-myc gene variant; iii. loss of heterozygosity, iv. p53 gene mutations; v. oncogene amplification; vi. oncogene amplification proliferative activity and their relation to prognosis in gastric cancer.

Carcinoma↗