RESUMO
We have demonstrated that interferon-alpha 2 recombinant (IFN alpha) inhibits the growth and modulates the expression of the receptor for transferrin (TRF-R) in human epidermoid carcinoma KB cells. Receptor upregulation results in the reconstitution of intracellular iron levels in the IFN alpha-treated cells. Several anti-TRF-R murine monoclonal antibodies (MAbs) have been generated which induce tumor cell growth inhibition through blockade of receptor function. We have evaluated by MTT assay the effect of anti-TRF-R 42/6, E2.3, A27.15 and D65.30 MAbs given in combination with IFN alpha on the growth of human epidermoid carcinoma KB cells. We found that IFN alpha and A27.15 MAb induced a synergistic antiproliferative effect on these cells. These results suggest that IFN alpha may potentiate the antitumor efficacy of TRF-R-targeted therapy.
RESUMO
Paraffin-embedded tissues are used in retrospective studies to evaluate the prognostic significance of DNA-flow cytometry (DNA-FCM) in human breast cancer. Although paraffin-embedded samples yield information on disease-free survival (DFS) and overall survival (GAS) of homogeneously selected patients, the resulting DNA-histograms have a lower resolution of aneuploid subpopulations and higher debris levels than those of fresh tumor samples. The aim of this study was to evaluate, retrospectively, the prognostic value of ploidy and the S-phase fraction (SPF) using 515 samples of paraffin-embedded consecutive primary breast cancer tissue (median follow-up: 75.4 months). Ploidy was detectable in 89% cases (34% diploid and 66% aneuploid) and SPF in 77%. The optimal cut-off for SPF was 6%. High SPF values were significantly correlated with shorter DFS (p=0.028) and OAS (p=0.018); aneuploidy was significantly correlated only with a shorter OAS (p=0.0058). Using the Cox proportional hazards regression model to evaluate the independence of DNA-FCM derived parameters, only high SPF was able to predict both a shorter DFS (p=0.02) and OAS (p=0.002). Furthermore, high SPF values were found correlated to aneuploidy (p<0.00001), tumor necrosis (p<0.015) and high histopathological grade (p<0.03). The data reported confirm that SPF is a valuable single independent prognostic factor in human breast, cancer and strongly support the use of archival tumor specimens to study the prognostic role of DNA-FCM in human cancer.
RESUMO
The antitumor activity and toxicity profile of a new therapeutic combination was investigated for patients with non-Hodgkin's lymphoma (NHL). The regimen consisted of mitoxantrone (10 mg/m(2)/day by intravenous (i.v.) bolus injection on day 1), etoposide (100 mg by 24 hours continuous i.v. infusion on days 1, 2, 3) and bleomycin (4 mg by i.v. bolus injection on day 1 followed by 24 hours continuous i.v. infusion at 4 mg/m2/day dose on days 1, 2, 3) (MEB). MEB chemotherapy was administered to 22 patients affected by intermediate/high grade or clinically symptomatic low grade NHL who were considered non-elegible for standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. Major responses were achieved in 11/22 (50%) patients with 5 (23%) complete responses. Grade 3-4 neutropenia occurred in 59% of patients. The results of this study demonstrate that MEB chemotherapy possesses good antitumor activity and a manageable toxicity in a prognostically unfavourable subset of lymphoma patients.
RESUMO
The impact of multicentricity in primary breast cancer on relapse or death after radical or modified radical mastectomy was evaluated in 1336 consecutive patients. Multiple tumor foci were found in 11.7% of breast cancers: in 8.4% multicentricity was infiltrating, while in 3.3% of cases an in situ growth pattern was observed. There was a statistically significant association between multicentric primaries and lobular infiltrating carcinoma, age less than or equal to 50 years, large tumors and metastatic axillary nodes, while no relationship was observed with histological grade. Both 5-year disease-free survival and overall survival were shorter in patients with infiltrating multicentric primary tumors. Multivariate analysis confirmed the prognostic role of infiltrating multicentric tumors after adjusting for nodal status, tumor size, age and adjuvant therapy.
RESUMO
The effect of cimetropium bromide, a new anticholinergic agent, in patients with primary achalasia was studied. Twenty such patients (12 females and 8 males, mean age 38 years, range 15-56) were studied. Diagnosis was performed by radiology, endoscopy, and manometry. Lower esophageal sphincter pressure and body wave amplitude were measured by means of a five-channel catheter constantly perfused by a low-compliance pneumohydraulic pump. Patient received cimetropium bromide 10 mg intravenously over 3 min or placebo in a double-blind manner. In five patients esophageal transit evaluated by scintiscanning was studied on separate occasions after cimetropium bromide or placebo. Baseline mean lower esophageal sphincter pressure was 46 +/- 5 mm Hg and mean amplitude of body waves was 30 +/- 8 mm Hg. Cimetropium bromide induced a significant decrease in sphincter pressure and body wave amplitude that measured 13 +/- 3 mm Hg and 8 +/- 4 mm Hg, respectively, 15 min after the end of infusion. The decrease was maintained for 45 +/- 5 min. A marked reduction in repetitive body waves was also noted. Esophageal transit was also accelerated with cimetropium bromide. Maximal stomach radioactivity was observed after 8 +/- 1.8 sec while with placebo this was reached after 65 +/- 1.5 sec (P < 0.01). It is concluded with cimetropium bromide reduces LES pressure and shortens transit in primary esophageal achalasia. It may be useful in the treatment of this esophageal motility disorder.