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Biomedical subjects

F Perrone

Publications and source records attributed to F Perrone.

At least 55 records · Page 3Linked to original sources

Chemotherapy with mitomycin C and vinblastine in pretreated metastatic breast cancer.

AIMS: In February 1986 we began a study to test the activity of mitomycin C (12 mg/m2) plus vinblastine (6 mg/m2) on day 1 of a 28-day cycle (MV) as second or third-line chemotherapy for metastatic breast cancer patients. METHODS: As of February 1988 the study was stopped after 26 patients had been enrolled. The median age of the patients was 54 years (range 35-78); all patients were progressive from chemotherapy; 15 (57.7%) patients were treated as second and 11 (42.3%) as third line; 19 (73.1%) patients had received anthracyclines as first (13 patients) or second-line (6 patients) chemotherapy; 18 (69.2%) patients had visceral involvement; 7 (26.9%) had one metastatic site, 11 (42.3%) two sites, 6 (23.1%) three sites and 2 (7.7%) four sites. RESULTS: Overall, 86 cycles were administered, with a median number of 3 cycles per patient. Toxicity was mild; hematologic side effects required discontinuation of treatment in 3 cases. Vomiting occurred in 3 (11.5%) patients, nausea in 5 (19.2%). Moderate neurologic toxicity was recorded in 6 (23%) patients. No complete and 3 partial responses were observed. The objective response rate was 11.5% (exact 95% confidence interval, 2.4-30.1). Responses occurred independently of disease-free interval, dominant metastatic site, response to previous chemotherapy, previous anthracycline and line of treatment; all responses were recorded in patients under 50 years of age. Kaplan-Meier estimated median time to progression and overall survival were 13 and 40 weeks, respectively. CONCLUSION: The MV regimen was well tolerated but showed little activity in pretreated metastatic breast cancer.

Adult

Prognostic significance of the CaMBr1 antigen on breast carcinoma: relevance of the type of recognised glycoconjugate.

An extensive study of the expression of the blood group-related antigen CaMBr1 has been performed by immunohistochemistry, immunoblotting and high performance thin layer chromatography both on frozen and paraffin-embedded (paraffin) samples from normal and neoplastic breast tissues. The glycolipid antigenic fraction (from frozen samples) was preferentially expressed on functioning breast epithelium. In a prospective series of 143 breast cancer cases CaMBr1 expression was associate, on frozen sections, with the transferrin receptor (P = 0.01), the positivity with oestrogen receptor immunochemical assay (P = 0.06), premenopausal status (P = 0.06) and node negativity (P = 0.07). Non-significant correlation with longer disease-free survival (DFS) was observed. In a retrospective series of 862 cases on paraffin sections the glycoproteic antigenic fraction was significantly associated with premenopausal status (P < 0.05) and lobular histotype (P < 0.01), but failed to predict survival, although a trend for longer DFS was observed for positive cases.

Antigens, Neoplasm

Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma.

We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours.

Adult

Salvage chemotherapy with CCNU and methotrexate for small cell lung cancer resistant to CAV/PE alternating chemotherapy.

CCNU and methotrexate were employed as salvage treatment in 34 small cell lung cancer patients resistant to CAV/PE alternating induction chemotherapy. In the 33 evaluable patients we observed an objective response rate of 21.2% and 3% complete response; median survival was 4 months with 2 patients alive 18 months from starting salvages chemotherapy. The treatment was well tolerated. CCNU and methotrexate has shown to be a moderately active and tolerable salvage treatment for small cell lung cancer after CAV/PE alternating first-line chemotherapy.

Adult

[Perioperative total parenteral nutrition. Our experience].

The Authors analyze the results of 83 cases of TPN in a surgical department after a revision of the literature from which it comes out how such a method has been proposed to reduce the catabolism by surgical trauma of fasting, especially after greater surgical operations.

Evaluation Studies as Topic

Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer.

The prognostic role of drug-induced amenorrhea (DIA) was restrospectively evaluated in 221 out of 254 consecutive premenopausal patients treated with adjuvant CMF or a CMF-containing regimen; 33 patients were eliminated because of lack of menstrual data. All patients had metastatic axillary nodes; drug regimens were: CMF x 9 courses +/- Tamoxifen (TM) and CMF x 6 courses; median age was 43 (range 26-54). Premenopausal status was defined as last normal menses within the 6 weeks preceding initiation of chemotherapy: DIA as cessation of menses for at least 3 months not later than 3 months from the end of chemotherapy. DIA occurred in 166,221 (75.1%) patients and was strictly related to the age of the patients; also, the older the patients the shorter the time required to develop DIA. At median follow up of 69 months, Mantel-Byar analysis showed a longer disease free survival (DFS) for patients who developed DIA as compared with non amenorrheic women (P less than 0.001). DIA prognostic value was independent of age, number of involved nodes, tumour size and number of CMF cycles, as assessed by the Cox model (RH 0.43, 95% C.I. 0.24-0.77), in which DIA was entered as a time dependent covariate.

Adult

LH-RH analogue Zoladex in the treatment of pre- and perimenopausal women with metastatic breast cancer (results of the Italian Cooperative Study).

From May 1987 to May 1989 sixty one pre- and perimenopausal women with advanced or recurrent breast cancer entered in an open non comparative study. They were treated, as a first-line therapy, with goserelin (Zoladex ICI-118630) a long acting gonadotropin-releasing hormone (LH-RH)-analogue in a depot formulation. Fifty three patients were evaluable for response; median age at entry was 41 years (range 28-56). Serum concentrations of 17 beta estradiol, LH and FSH were significantly suppressed within the first four weeks of therapy and remained suppressed for the whole duration of treatment. Subjective responses were observed, such as pain reduction and/or performance status improvement in 58% of patients. Overall objective response (CR + PR) occurred in 16 (30.2%) patients in all major sites of disease with a median time to response of 12 weeks (range 8 to 48 weeks) and a lifetable median duration of response of 36 weeks (range 16 to 76 weeks). The lifetable median time to progression was 17 weeks (range 5 to 76 weeks). Goserelin depot was well tolerated with no withdrawal due to possible adverse reactions. The observed subjective and objective response rates are comparable to those induced by surgical oophorectomy. Goserelin provides a well tolerated medical alternative to ovarian ablation, without the morbidity associated to surgery. In conclusion the present paper suggests that this innovative chemical estrogen deprivation, in premenopausal breast cancer patients, might be favorably investigated as an adjuvant therapy in future clinical trials.

Adult

Expression of two antigens defined by monoclonal antibodies in normal, benign and malignant human mammary tissues.

We examined the reactivity of two monoclonal antibodies (MAbs), MBrI and MBr8, on sections from normal breast tissues, benign lesions, primary infiltrating carcinomas and distant breast cancer metastases and compared the expression of the recognized antigens (CaMBr1 and CaMBr8 respectively) in these different normal and pathologic conditions. The expression of both antigens was found to significantly decrease in the neoplastic tissues, in comparison to normal breast tissue (34% vs 61% for MBr1 and 52% vs 86% for MBr8; p less than 0.001 for both). Atypical epithelial hyperplasia was found to be reactive on the same level (31%) of the tumors when tested with MBr1, whereas its reactivity was similar to that of normal tissues (78%) when MBr8 was used. Nonatypical epithelial hyperplasia showed the same reactivity with both MAbs (positive staining on about 50% of the cells). 65% of the "in situ" ductal carcinoma cases was MBr1-positive, whereas 50% was MBr8-positive; these values, when compared with the reactivity on normal glands, were significantly lower for MBr8, but not for MBr1. When testing sections from premenopausal women who had biopsies performed on different days during their menstrual cycle a correlation was found between the expression of CaMBr1 in normal breast epithelial cells and the stimulatory phase of the cycle. These findings suggest that both antigens are typical of normal breast and their expression could possibly decrease in pathologic tissues.

Antibodies, Monoclonal

Steroid hormone receptor levels and adjuvant tamoxifen in early breast cancer. Ten year results of the Naples (GUN) Study.

Ten year disease-free survival (DFS) results of the Naples randomized trial of adjuvant tamoxifen (TM), 30 mg per day for 2 years versus no therapy according to receptor levels, are reported. From Feb. 1, 1978, through Dec. 31, 1983, 308 pre- and postmenopausal patients with early breast cancer entered the trial. Estrogen receptor (ER) data were available on 239 (77.6%) patients, progesterone receptor (PgR) data on 194 (63.0%), and both receptor data on 181 (58.8%). ER and PgR were assayed by dextran-coated charcoal technique in a single laboratory. The effect of adjuvant TM was significantly related to ER and PgR concentration of the primary tumor. The greatest TM benefit on DFS was evident in patients with the highest levels of receptors. The interaction between the treatment effect and receptor concentration was found whether ER and PgR were considered separately or together.

Adult

Prolactin receptor does not correlate with oestrogen and progesterone receptors in primary breast cancer and lacks prognostic significance. Ten year results of the Naples adjuvant (GUN) study.

The correlation between prolactin (PRLR) and oestrogen (ER) or progesterone receptors (PgR) in breast cancer and a possible prognostic significance of PRLR at 10 year follow-up have been investigated in the Naples (GUN) adjuvant trial. A total of 308 pre- and post-menopausal patients with early breast cancer, who entered the trial from 1 February 1978 to 31 December 1983, received randomly Tamoxifen (TM), 30 mg per die for 2 years, or no therapy. PRLR status was known in 229 (74.3%) patients. Values of specific binding less than 1% were considered negative. PRLR was positive in 75/229 (32.8%). ER was assayed in 210/229 (91.7%) patients and PgR in 188/229 (82.1%). No significant correlation, by the Spearman test, was found between PRLR and ER or PgR, while ER status was highly interrelated with PgR status. By the Cox model no evidence of an independent prognostic role of PRLR on disease-free survival (DFS) was observed, nor an interaction between PRLR and adjuvant treatment with TM was found.

Adult

Relationship between thyroid hormones and nutrition in chronic renal failure.

A cross-sectional study was performed in 19 patients on haemodialysis and in 11 on continuous ambulatory peritoneal dialysis (CAPD) in order to investigate the relationship between thyroid hormones and nutritional status. T4, T3 resin uptake, T3, rT3 and TSH were measured by radio-immunoassay and compared with controls. Nutritional status was assessed by measurements of blood proteins, albumin, gamma-globulin, transferrin, arm muscle circumference and triceps skinfold thickness. In haemodialysis, T4, FTI, T3 and rT3 were significantly decreased. TSH was normal. In CAPD, thyroid hormones were normal. In both groups, proteins, albumin, gamma-globulin and transferrin were normal. Triceps skinfold thickness was normal in males and females, whereas arm muscle area was dramatically reduced in males and normal in females. In haemodialysis, a negative correlation was found between T3 and proteins (p less than 0.01), rT3 versus proteins (p less than 0.01) and versus gamma-globulin (p less than 0.01). In CAPD, a positive correlation was found between T3 and triceps skinfold thickness (p less than 0.05). We suggest that the overload of carbohydrate might normalize the thyroid hormones in patients on CAPD. The relationship between thyroid hormones and nutritional status in patients treated by dialysis suggests a putative protective effect of low T3 levels against protein breakdown.

Adult

Biopharmacokinetic evaluation of peptichemio (PTC) by reversed-phase high-performance liquid chromatography (HPLC): preliminary in vitro studies.

The Authors describe a reversed-phase HPLC method for the separation of the six peptides which constitute the antitumoral drug Peptichemio (PTC). They also present some preliminary investigations concerning the in vitro biopharmacokinetics of this drug. Differences in selectivity and kinetics of peptides uptake have been investigated using human peripheral blood lymphocytes (PBL) and a human neuroblastoma derived cell line (SK-N-SH). Results will be discussed along with their clinical and pharmacological research implications.

Cell Line

Oxalate depuration during biofiltration with AN69 and in conventional hemodialysis in chronic renal failure (CRF) patients.

Oxalate (Ox), an end product of amino acid metabolism, accumulates in CRF patients as calcium crystal deposits in many soft tissues such as myocardium, kidney interstitium, etc. Since BF employs AN69, a high efficiency membrane, we tested its depurative efficacy for Ox against a hollow-fiber cuprophan dialyzer. Five CRF patients previously in HD and after six months of BF were studied. End-dialysis and pre-dialysis Ox values and dialyzer clearance were obtained. Predialysis Ox values were: 0.44 +/- 0.15 mg/dl in HD and 0.42 +/- 0.09 mg/dl in BF (NS). End-dialysis Ox values were: 0.30 +/- 0.09 mg/dl in HD and 0.22 +/- 0.04 mg/dl in BF (p less than 0.001). Pre and post dialysis values differed by 31% in HD and 47% in BF (p less than 0.001). Ox clearance was 98.8 +/- 10.3 ml/min in HD and 143 +/- 20.5 ml/min in BF. There was a rebound in Ox values at 48 hours (0.41 +/- 0.08 mg/dl in HD and 0.32 +/- 0.12 mg/dl in BF, (NS). These results indicate that Ox is depurated better during BF than during HD.

Acrylic Resins

[Decrease in triiodothyronine and its reverse form under the effect of extrarenal dialysis. Role of carbohydrate intake].

Thyroid hormone levels were measured in 12 patients on continuous ambulatory peritoneal dialysis and in 18 patients on haemodialysis, all in stable clinical status. Values in patients on peritoneal dialysis were not different from those found in controls, whereas a highly significant decrease in T3 and r T3 was observed in patients on haemodialysis. These results are in contrast with the low T3 syndrome and the high r T3 levels of systemic diseases and malnutrition. The difference between the two groups of patients on dialysis suggests that thyroid abnormalities do not result from renal failure alone, nor from malnutrition, but from a disturbance in the calorie/carbohydrate ratio of the ingesta.

Adult

Hemoglobin Pontoise alpha63 Ala replaced by Asp(E12). A new fast moving variant.

The present report describes structural and functional studies of a new hemoglobin variant, Hb J Pontoise. This abnormal hemoglobin was discovered in a 36 year old Spanish man. The substitution of alpha63 (E12) Ala replaced by Asp is situated at an external site and appears to have no influence on the function of the hemoglobin. Nevertheless, it presents some instability in vitro, as demonstrated by the isopropanol test. This instability could partially explain the low percentage of the abnormal hemoglobin in the hemolysate (12%), since its rate of synthesis was normal.

Adult

Prognostic significance of necrosis, elastosis, fibrosis and inflammatory cell reaction in operable breast cancer.

We analyzed retrospectively the relationships and the prognostic significance of four anatomopathological features (elastosis, fibrosis, necrosis, inflammatory cell reaction) of the primary tumor in a series of 1,457 cases of infiltrating ductal carcinoma observed at our institution from January 1978 to December 1991. Necrosis, elastosis, fibrosis and inflammatory cell reaction were strongly associated among themselves (all p < 0.0001), the only exception being necrosis and elastosis. Necrosis was significantly related to tumor size (odds ratio [OR] = 5.40, p < 0.0001) and tumor grade (OR = 2.22, p < 0.0001). Univariate analysis showed that the presence of necrosis and cell reaction were significantly related to worse survival (p < 0.0001 and p = 0.03, respectively). Multivariate analysis, including the four variables plus nodal status, tumor size, grading, adjuvant therapy, age and first order interactions, revealed that greater tumor size (p < 0.0001), positive nodal status (p < 0.0001), higher histologic grade (p < 0.0001) and presence of inflammatory cell reaction (p = 0.0007) independently worsened survival. On the other hand, adjuvant therapy had a significant independent role in preventing deaths (p = 0.03). The only first-order interaction retained in the model was that between grading and cell reaction (p = 0.002). Cell reaction had a different prognostic behaviour in the groups G1-G2 and G3: in the former group, survival was worse (p = 0.0001) when the inflammatory cell reaction was present. In conclusion, we demonstrate that cell reaction is an independent prognostic factor in the G1-G2 subgroup of patients, and propose a hypothesis as to the role of cell reaction in primary breast cancer.

Adolescent