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Biomedical subjects

S Leo

Publications and source records attributed to S Leo.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial dynamics and Ca2+ signaling.

Recent data shed light on two novel aspects of the mitochondria-Ca2+ liaison. First, it was extensively investigated how Ca2+ handling is controlled by mitochondrial shape, and positioning; a playground also of cell death and survival regulation. On the other hand, significant progress has been made to explore how intra- and near-mitochondrial Ca2+ signals modify mitochondrial morphology and cellular distribution. Here, we shortly summarize these advances and provide a model of Ca2+-mitochondria interactions.

Animals↗
PubMed2005

Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial.

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.

Adult↗
PubMed1999

5-fluorouracil and levofolinic acid with or without recombinant interferon-2b in patients with advanced colorectal carcinoma: a randomized multicenter study with stratification for tumor burden and liver involvement by the Southern Italy Oncology Group.

BACKGROUND: The objectives of the current study were: 1) to verify whether the addition of modulating low doses of interferon-2b (IFN) to 5-fluorouracil (5-FU) and levofolinic acid (1-FA) could improve clinical results in patients with advanced colorectal carcinoma; and 2) to evaluate the role of tumor burden and liver involvement as prognostic factors. METHODS: A total of 204 untreated patients were randomized to receive 1-FA at 100 mg/m2 and 5-FU at 375 mg/m2 for 5 consecutive days with or without IFN every 3 weeks. IFN was given subcutaneously at 3 MU/day for 7 days starting 2 days before chemotherapy administration. Patients were stratified according to the presence or absence of hepatic disease (H+ or H-) and to total tumor burden defined as "low" or "high" using an area of 10 cm2 as the cutoff value. Thus, four patient categories were obtained: Group 1: H+ > or = 10 cm2; Group 2: H+ < 10 cm2; Group 3: H- > or = 10 cm2; and Group 4: H- < 10 cm2. RESULTS: No differences were observed in the objective response rate (23% for the combination of 1-FA and 5-FU vs. 24% for the 1-FA, 5-FU, and IFN regimen), median duration of response (11 months vs. 10 months), time to progression (5 months in both arms), and median survival (11 months vs. 12 months). A statistically significant improvement in response rate was observed in patients with limited liver involvement versus those with massive involvement independent of the chemotherapy arm (44% vs. 22%; P = 0.02). Overall survival also was improved in patients with limited liver disease (P = 0.0001) and in those without liver involvement (P = 0.004). Multivariate analysis confirmed these data and identified response and female gender as positive prognostic factors. Toxic side effects (mainly diarrhea, mucositis, and fever) were statistically more frequent in the IFN arm. CONCLUSIONS: The addition of low modulating doses of IFN to the regimen of 5-FU and I-FA failed to increase the response rate and survival of patients with advanced colorectal adenocarcinoma and significantly worsened toxicity. High tumor burden and the presence of liver involvement were confirmed prospectively as poor prognostic factors and should be taken in account in designing future Phase II or comparative trials.

Adenocarcinoma↗
PubMed1998

Impairment of phagocytic and T-cell-mediated antibacterial activity and plasma endotoxins in patients with untreated gastrointestinal cancer.

BACKGROUND: Cancer patients have multiple immune deficits, and mediators, such as prostaglandins, transforming growth factor-beta, and interleukin (IL)-10, may play a role in the pathogenesis of these immune dysfunctions. METHODS: Fifty-six patients with gastrointestinal cancer (11 gastric cancer, 7 papilla of Vater cancer, and 38 colorectal cancer) were enrolled for this study, before starting conventional treatments. Phagocytosis and killing exerted by polymorphonuclear cells and monocytes, peripheral blood mononuclear cell absolute numbers, T-cell-mediated antibacterial activity, serum levels of IL-10 and interferon (IFN)-gamma, and plasma bacterial endotoxin concentration were evaluated. RESULTS: Data show an impaired phagocytic and T-cell-mediated antibacterial activity in all cancer patients, whereas only in subjects with gastric cancer were IFN-gamma serum levels reduced. Circulating endotoxins were detected in 17 patients. CONCLUSIONS: In untreated gastrointestinal cancer patients the capacity of phagocytes and T-cells to clear pathogens is reduced. This dysfunction may increase the risk of becoming infected and may account for the presence of endotoxin in 30% of patients.

Adult↗
PubMed1995

Efficacy of the association of folinic acid and 5-fluorouracil alone versus folinic acid and 5-fluorouracil plus 4-epidoxorubicin in the treatment of advanced gastric carcinoma.

A total of 71 patients with advanced gastric carcinoma were randomized to receive either folinic acid + fluorouracil (arm A) or the same combination with the addition of 4-epidoxorubicin (arm B). Of the 62 evaluable patients (31 in both arms), six patients achieved a CR (10%) and 16 a PR (25.5%) with an overall response rate of 35.5% (29% in arm A and 42% in arm B; p = .28). Median duration of response was 6 and 7 months for arm A and B, respectively (p = .6). Responder patients showed a significantly better median survival duration than nonresponders (p = .01); in arm B the median survival duration was 16 months for responder patients in contrast to 7 months for nonresponders (p = .004). Toxicity was mild without significant differences between the two groups. There was one death due to hematological toxicity (arm A). The EPI-FA-FU combination appears effective and well tolerated with the additional advantage of being able to be administered in the outpatient clinic.

Adult↗
PubMed1994

Prognostic value of cytosolic estrogen receptors in human colorectal carcinoma and surrounding mucosa. Preliminary results.

Estrogen receptors have been found in normal and neoplastic gastrointestinal mucosa. The aim of our study was to verify whether the content of cytosolic estrogen receptor in normal and neoplastic tissue has a prognostic value in patients with colorectal adenocarcinoma. Eighty consecutive patients entered the study, and their follow-up was complete because none were lost to follow-up. Estrogen receptors were evaluated by an enzymatic immunoassay. Fifty-four percent of neoplastic samples and 84% of samples from surrounding mucosa showed an estrogen receptor content higher than 1.0 fmol/mg of cytosolic proteins (cut point for positive/negative hormone receptor status). Estrogen receptor levels were lower in neoplastic tissue than surrounding mucosa (1.2 +/- 1.05 fmol/mg protein vs 2.07 +/- 1.36 fmol/mg protein, respectively, t test P = 0.001). The survival of patients with estrogen receptor expression in uninvolved surrounding mucosa was longer than that of patients without estrogen receptor in the same type of mucosa (log rank test, P < 0.01). In the neoplastic tissue, receptor status had no prognostic value (log rank, P = 0.8). After taking into account the most important potential confounders by using the Cox proportional hazard model, the estrogen receptor status in normal mucosa samples maintained an independent prognostic value. These results support an association between the estrogen receptor status in normal mucosa and survival of patients with colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1994

Sequential treatment with high-dose methotrexate and fluorouracil in advanced colorectal cancer. Experience of the Southern Italian Oncology Group (GOIM).

A total of 101 patients with advanced colorectal cancer in two consecutive Southern Italian Oncology Groups (GOIM) studies (8501 and 8801--arm A) were treated with a sequential combination of high dose methotrexate (HDMTX) and fluorouracil (FU). Of the 92 eligible patients, 2 achieved complete response (2%) and 27 partial response (30%), with a median duration of 7 months. When classified according to the time interval between administration of the two drugs, retrospective analysis showed significant improvement (p = 0.04) in overall survival in the shorter time interval group (6 hours). The observed toxicities were generally mild and transient. Our data confirm the efficacy of the synergism between the two chemotherapeutic agents, in particular when administered with a 6-hour interval. Further studies are necessary to establish the possibility of enhancing the efficacy of sequential treatment with the modulation of FU with high-dose folinic acid.

Adult↗
PubMed1994

Dermatological toxicity from chemotherapy containing 5-fluorouracil.

5-Fluorouracil (5-FU) is an antimetabolite frequently used in the treatment of cancer. The most common adverse reactions are acute gastrointestinal effects and bone marrow suppression while neurological, ocular and dermatological toxicities are unusual. Several cutaneous manifestations can be found. They are hyperpigmentation, maculo-papular eruption and palmar-plantar erythrodysesthesia (PPES) promptly reversed with discontinuation of 5-FU. The etiopathogenesis of such manifestations is still unknown particularly as regards PPES, but it has been postulated that the local drug accumulation secondary to different scheduling (continuous infusion instead of bolus infusion), the total amount of drug, alcoholism, local trauma, increased blood flow could be responsible for them. In this study we have reported 10 cases of dermatological toxicity (1 of these had PPES) observed from January '91 to December '93 in 81 patients treated with bolus injection of 5-FU containing combination chemotherapy.

Adult↗
PubMed1994

[The clinical aspects of 49 cases of early gastric cancer].

Forty-nine consecutive patients with early gastric cancer (EGC), observed from January 1978 to December 1992 in the Surgery Department of our Institute, were included in a retrospective study. The EGC prevalence in the overall cases of gastric cancer was 11%. This frequency was 8% in the period 1978-1985 and 15% in the period 1986-1992. All patients underwent gastroscopy with gastric biopsy, but only in 35 cases (72%) was a preoperative diagnosis of gastric cancer possible. In the remaining 14 cases only the histological examination of surgical specimens made possible a definitive diagnosis. A subtotal gastrectomy was carried out in 36 cases (73%), a total gastrectomy in 12 cases (25%) while only in one case (2%) was a superior polar resection carried out. The postoperative morbidity was 5% and mortality was 2%. The median survival was 61 months and, at the moment, 41 patients are alive and free from disease. Our data confirm the favourable prognosis of EGC compared to the advanced gastric cancer. We think it useful to carry out a routine gastroscopy when there are symptoms related to the upper abdomen in order to make an early diagnosis of gastric cancer.

Adult↗
PubMed1990

Cholelithiasis in inflammatory bowel disease. A case-control study.

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.

Adult↗
PubMed1989

[Diagnostic value of CEA in neoplasms fo the colon and rectum. Review of cases].

A personal series of colo-rectal tumours from 1979 to 1987 has been examined so as to check the validity of CEA as a marker in the diagnosis of these tumours. The data confirmed what has already been reported, namely its poor diagnostic sensitivity even though its utility for prognosis and in the follow-up of these patients remains confirmed, as is shown by the literature.

Adolescent↗
PubMed1989

Ulcerative colitis in remission: it is possible to predict the risk of relapse?

A series of anamnestic, clinical, endoscopic and histologic parameters was evaluated in 64 patients with ulcerative colitis in remission to assess whether any of these had predictive value of relapse. All patients with quiescent disease were followed for at least 6 months. The statistical analysis was carried out by means of likelihood chi 2 test, receiver operating characteristic curve, Youden index and stepwise logistic regression. Eighteen patients out of 64 (28%) had a relapse, in a mean period of 9 months after the beginning of the study. The findings of our study suggest that only three factors were useful in selecting a subpopulation with a higher risk of recurrence: (a) a fiber-poor diet; (b) a number of previous episodes of relapse higher than 10, and (c) the presence of extraintestinal manifestations.

Adolescent↗
PubMed1989

Cigarette smoking and ulcerative colitis. A case control study.

In order to examine the relationship between cigarette smoking and ulcerative colitis (UC), we carried out a case-control study of smoking habits in 84 patients with UC and in two different types of controls: 84 taken from a hospital population and 84 from the general population, matched to the cases for age, sex, school education and social class. Non-smokers were found to have a greater UC risk than smokers in both internal controls (Odds ratio = 4.6, 95% CL = 1.8-11.7) and external controls (OR = 10, 95% CL = 3.6-26.9). There was a larger number of ex-smokers among patients with UC than among the controls. Evaluations at the time of disease onset also demonstrated that ex-smokers had a greater relative risk. Furthermore, 84% of the ex-smoker patients had stopped smoking before the onset of symptoms. Conditional multiple logistic regression with the introduction of alcohol (wine) and coffee as additional variable factors to age, sex, education and social class confirmed the independent protective effect of smoking on UC (OR for internal controls = 4.2, 95% CL = 1.7-10.2, OR for external controls = 5.7, 95% CL = 2.3-14.1). These results indicate that non-smokers and especially ex-smokers of cigarettes have a greater risk of UC, and thus confirm the results of other studies.

Adolescent↗
PubMedDate not supplied

Prognostic value of low density lipoprotein receptor expression in colorectal carcinoma.

Cancer cells require more cholesterol than normal cells. This requirement seems to be satisfied by a higher HMG-CoA reductase activity or a higher activity of low density lipoprotein receptor (LDLR). We investigated the prognostic value of LDLR in colorectal carcinoma (CRC) patients. The LDLR was evaluated in 90 patients with CRC by ELISA. The survival time and the relative risk of prognostic factors were analyzed by Kaplan-Meier estimates and Cox proportional hazard model. Thirty three cases were LDLR positive (+), while 57 LDLR negative (-). The survival of LDLR(-) patients was shorter than that of LDLR(+). By Cox model, the absence of LDLR and time until metastasis resulted significantly associated with the CRC-related survival. The absence of LDLR in CRC predicts a shorter survival.

Aged↗
PubMedDate not supplied

Erythrocyte polyamines and prognosis in colorectal cancer patients.

BACKGROUND: Polyamines play a role in cell proliferation and in cancer development: they are mainly carried by red blood cells (RBCs). Abnormally high polyamine levels in RBCs have been demonstrated in patients with various types of cancer and the prognostic value of RBC polyamine levels has also been underlined. Our aims were to compare polyamine levels in RBCs from colorectal adenocarcinoma (CRA) patients with those from non neoplastic patients and to evaluate the prognostic value of pre-treatment polyamine erythrocyte levels. PATIENTS AND METHODS: Sixty-one patients with colorectal cancer and 28 surgical patients affected by non neoplastic diseases were included in this study. RBCs polyamine levels were evaluated by HPLC. RESULTS: Significantly higher spermidine, spermine and total polyamine levels were found in RBCs from CRA patients compared to those from control patients. However, there was no significant difference in the survival of patients with different polyamine levels. CONCLUSION: Our findings show that RBC polyamine levels are not a biologic parameter that may help to discriminate between good and poor prognosis in colorectal cancer patients.

Adenocarcinoma↗
PubMedDate not supplied

[Smoking trials with mercury contaminated cigarettes. Studies of attempted poisoning].

In the context with an attempted poisoning it was investigated, to which extent an intoxication can be caused by smoking cigarettes, which contain elementary mercury. With a smoking apparatus the effect of the amount (9 mg to 1.4 g) and of the distribution of the Hg within the cigarette on its concentration in the mainstream and sidestream smoke as well as in the ash and the filter was analytically determined. It follows from these experiments, that at a good distribution almost independently of the amount involved only up to 2 mg Hg per cigarette are inhalated with the mainstream smoke, whereas up to 97% are found in the sidestream smoke. In the ash and the filter only small amounts are detected. By comparison with cases described in literature it is shown, that a poisoning by such cigarettes is possible only after frequent smoking or by passive smoking via the sidestream smoke in small and badly aerated rooms.

Humans↗