Biomedical subjects

F Marzullo

Publications and source records attributed to F Marzullo.

At least 19 recordsLinked to original sources

PubMed2001

Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer.

PURPOSE: The prospective applicability of new biologic tumor information to personalize adjuvant treatment of women with operable breast cancer remains to be demonstrated. The aim of the present study was to investigate whether patients with fast-proliferating, node-negative breast cancer could benefit from adjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC). PATIENTS AND METHODS: Beginning in November 1989, we analyzed the proliferative activity of primary tumors in a consecutive series of women with node-negative breast cancer to identify subgroups of patients with a worse prognosis and who were therefore suitable candidates for adjuvant systemic therapy. Proliferative activity was determined by means of the [3H]-thymidine incorporation assay using an autoradiographic technique. Women with fast-proliferating breast cancer ([3H]-thymidine labeling index, > 2.3%) were randomized to receive either six cycles of adjuvant FEC or no adjuvant therapy until disease progression. RESULTS: One-hundred twenty-five and 123 patients treated with radical surgery for pT1 to T2, N0, M0 breast cancer were randomized to the FEC and control arms, respectively. After a median follow-up of 70 months, 27 events (21.6%) were observed in the FEC arm and 39 (32.2%) in the control arm, with a significantly lower number of locoregional relapses in the FEC group. Five-year disease-free survival (DFS) was 81% in the FEC group and 69% in the control group (P <.02 by log-rank test). Cox multivariate analysis described the impact of adjuvant therapy with FEC on DFS as independent of the patients' main clinical-pathologic characteristics. CONCLUSION: FEC adjuvant polychemotherapy seems able to significantly improve the clinical outcome of patients with fast-proliferating, node-negative breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Mutations spanning P53 exons 5-9 detected by non-isotopic RNAse cleavage assay and protein expression in human colon cancer.

The non-isotopic assay (NIRCA), based on the observation that RNAse is able to specifically cleave a single mismatch in RNA/RNA duplexes, has been recently proposed to detect p53 mutations. To verify the use of this method as a valid screening for P53 mutations in a routinely collected cancer series, we used this assay on 3 cases with normal and 5 cases with abnormal P53 expression detected by Western blots. In all cases, P53 exons 5-6, 7 and 8-9 regions were analyzed. There were mutations only in the five overexpressed cases: two cases showed mutations in exon 5, one between intron 6 and exon 6 and two in the region spanning exons 8 and 9. Our experience showed NIRCA to be fast, reliable and providing the ability to study long target regions in a single step, thus making this assay useful for genetic screenings.

Colonic Neoplasms↗

PubMed2001

Primary tumours neoangiogenesis and P53 expression in oral carcinoma patients.

Paraffin embebbed tumour tissues from 47 T1-2 N0-1 M0 primary oral squamous carcinoma have been utilized for immunohistochemical analysis of p53 expression (moab DO-7) and microvessel density (MVD) analysis (moab CD34). Fifty percent of cases showed p53 immunostaining with an average of 21% of p53 positive cells. A strong trend for a longer survival in patients with tumor p53- versus p53+ was evidenced (median survival: 12 months versus not reached, respectively; p=0.08 by log-rank test). A mean value of 27 MVD was found. The probability of overall survival did not result significantly different in the subgroups of tumours with high and low MVD (median survival: 6 months versus 6 months, respectively; p=0.24). Cox multivariate analysis confirmed that the only prognostic factor significantly related to the overall survival was clinical nodal status (O.R.=2.7; 95% C.I. 1.09-6.9), while p53 status only approached the statistical significance (O.R.=2.5; 95% C.I. 0.96-6.5; p=0.06).

Antigens, CD34↗

PubMed2001

[Biological-clinical significance of angiogenesis and mast cell infiltration in squamous cell carcinoma of the oral cavity].

There are little data on the biological and prognostic role of neoangiogenesis in squamous cell carcinoma of the oral cavity (SCCOC). In particular, the role mast cells--reservoirs of angiogenetic peptides--play in neovascularization is not clear. In this work 50 cases of SCCOC T1-3 N0-1 M0 were studied, examining the microvasal density (MVD), mast cell density (MCD), relationship between these two parameters and their relationship with the pathological clinical features. Microvessels were identified with an immunohistochemical method using pan-endothelial anti-CD34 antibody while a histochemical method was used to label the mast cells with toluidine blue on adjacent sections for each tumor sample. MVD and MCD were characterized using an image analyzer. The mean MVD was 30 +/- 17 s.d. per sample while the average MCD was 8 +/- 6 s.d. per sample. Statistical analysis comparing MVD and MCD using the Pearson method showed a direct, significant correlation between the two variables (correlation coefficient = 0.496; p = 0.000). When the carcinomas were divided into subgroups with high and low MVD and MCD--using the median counts (27 and 7 respectively) as cutoff point--no association was found with the main clinical pathological features (age, sex, tumor diameter, lymph node status, cytopathological grading). As regards the correlation with prognosis, after an median 020 months of follow-up, the subgroup of patients with tumors with high MVD presented a better overall survival at 18 months from diagnosis than did the subgroup with tumors with a lower degree of vascularization (70% vs. 45%; p = 0.049 log rank test). The data obtained suggest that mast cells play an active role in angiogenetic processes in SCCOC and indicate that MVD is a favorable prognostic factor for SCCOC patients.

Carcinoma, Squamous Cell↗

PubMed2000

The expression pattern of the AML1 gene in non-Hodgkin's B-cell lymphomas and normal B lymphocytes.

We have studied the expression of the three human acute myeloid leukemia (AML) genes in primary samples of non-Hodgkin's B-cell lymphomas in which translocations involving these loci were not present. We found a widespread expression of the three AML genes in all the lymphoma samples as well as in the purified normal B-lymphocytes. Thus, the presence of the three mRNAs "per se" does not allow the identification of the pathological status. However, AML1 showed a different transcription pattern in the neoplastic tissues with respect to the normal B-cells. The AML1b isoform proved to be peculiar to this lymphoma. Our data support the idea that qualitative and quantitative alterations of AML1 gene expression deriving from deregulating mechanisms other than translocations may be involved in this malignancy. The usage of two differently regulated promoters driving the expression of the transcripts AML1b and AML1c may be one of these mechanisms. Finally, we report the presence of a new alternatively spliced transcript in normal B-cells.

B-Lymphocytes↗

PubMed2000

GnRH receptors in human breast cancer and its contiguous not-involved breast tissue.

The present study was undertaken to evaluate the presence of GnRH receptors (GnRH-R) in breast cancer and not-involved breast tissue, and the relationships between GnRH-R and receptors for estrogen (ER) and progesterone (PgR) in the same tissues. Utilizing a tritiated natural GnRH in order to assay the native receptor binding we analyzed the level of binding sites for GnRH in membranes derived from 90 breast tumors and in 40 cases from neighboring, not-involved breast tissue. GnRH-R was found both in cancer and normal tissues. The prevalence for GnRH-R was higher in tumor than in not-tumor tissue (45% vs 39%, respectively), but the overall levels were not significantly different (15.9+/-24 fmol/mg protein vs 18.2+/-39 fmol/mg protein, respectively). The only statistically different content of GnRH-R we found concerned PgR negative vs PgR positive tumor tissues (mean content: 23 vs 11 fmol/mg protein, respectively in PgR- and PgR+ tumors, p=0.03 by t test); furthermore the proportion of GnRH-R positive cases in the tumor resulted significantly higher in premenopausal patients vs postmenopausal (56% vs 32%, by Chi square test, p<0.05). The GnRH receptors status of primary tumor and contiguous not-involved breast tissue resulted associated (overall agreement: 63%, p<0.05) but no specific steroid patterns for GnRH-R positivity was observed.

Binding Sites↗

PubMed2000

CEOP-B/VIMB vs. promace-CytaBOM in the treatment of intermediate or high grade non-Hodgkin's lymphoma: A randomised multicenter study of Southern Italy Cooperative Group.

From January 1992 to December 1995, 129 patients with previously untreated non-Hodgkin's lymphoma were randomised in a phase III multicenter trial to receive CEOP-B/VIMB or ProMACE-CytaBOM. Eligibility criteria included intermediate or high grade lymphoma (follicular large cell, diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic) with an Ann Arbor stage II bulky, III or IV. All patients entered into the study were considered evaluable according to intent to treat analysis. At a median follow-up of 60 months there were no significant differences between the treatment response rates [82% (60%CR) for CEOP-B/VIMB vs. 81% (69% CR) for ProMACE-CytaBOM]. Conversely, with regard to disease-free survival, a significant difference was observed between the two treatment arms (42% for CEOP-B/VIMB vs. 24% for ProMACE-CytaBOM at 5 years; p=0.046). However, this difference did not translate in a significant difference in overall survival (45% vs. 39% at 5 years). Moreover, when response rates and outcome were analysed for different prognostic subgroups according to International Prognostic Index, no significant differences were observed between the treatment groups. It is important to note that neither regimen was able to improve outcome of poor risk patients who fared badly with both treatments (median survival 9 and 8 months respectively). Toxicity was also similar in both treatments with grade 3-4 leukopenia observed in 39% and 47% of cases and grade 3-4 thrombocytopenia in 24% and 27% of cases respectively. In conclusion, in this study CEOP-B/VIMB was not superior to ProMACE-CytaBOM in aggressive lymphomas and the alternating strategy failed to improve outcome of poor risk patients in which newer more aggressive treatments are needed.

Adolescent↗

PubMed1998

nm23 expression in human breast cancer: correlation with cell proliferation (S-phase) as observed with a double-labeling immunocytochemical-autoradiographic technique.

In 51 unselected breast cancer samples, a double-labeling immunocytochemical technique was utilized to observe the phenotypic expression of the nm23 gene during S-phase. The feasibility of the method was confirmed by comparison with routine evaluations for both thymidine-labeling index and nm23 (p<0.001). No correlation was found between the two parameters in the overall series or when subgroups regarding menopausal status, nodal involvement, tumor size, hormone receptor content were considered. Tumors with a higher nuclear grade showed a significant correlation only with TLI (p=0. 02). A trend for an inverse relationship between the two parameters was noted but was not statistically significant. A significant association between TLI and nm23 expression was found by Chi-square test using median values as cut-off. Our data based on morphological and in situ observations do not confirm a correlation between nm23 and cell proliferation, even if this correlation cannot be completely excluded. Multicentric trials of high power with these same techniques are still necessary to definitely establish the prognostic role of nm23 in breast cancer.

Adult↗

PubMed1998

Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study.

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.

Adult↗

PubMed1998

Timing of breast cancer surgery within the menstrual cycle: tumor proliferative activity, receptor status and short-term clinical outcome.

We verified the variations of primary tumour steroid receptor status and proliferative activity at different times and phases (follicular vs luteal) of the menstrual cycle and their relationship with short clinical outcome in a cohort of 248 N- breast cancer patients. Steroid receptor content (ER and PgR) was evaluated by DCC assay and proliferative activity by 3H-Thymidine autoradiographic assay (TLI). Median age was 44 years, 60% of tumors were T1, and cytohistological grade was G1-2 in 54% of cases. At surgery, 57% were in the luteal phase while 43% were in the follicular phase. No significant variations were found in mean TLI or ER and PgR characteristics of the primary tumors surgically treated in different periods of the menstrual cycle; however, the ER level resulted significantly higher in 4th with respect to the 3rd week of menstrual cycle, while PgR level was higher in PgR+ cases treated during the 3rd week. The number of relapses and disease-free survival curves after 36 months median follow-up did not differ significantly for patients treated in different periods of the menstrual cycle (12% and 9% of disease relapses in luteal and follicular phases; p=n.s.). We can conclude, therefore, that TLI, ER and PgR expressions could vary significantly during menstrual cycle only in certain specific tumor subgroups.

Adult↗

PubMed1997

1H NMR ganglioside ceramide resonance region on the differential diagnosis of low and high malignancy of brain gliomas.

1. The high-resolution 1H NMR (MRS) spectra of human brain tumor homogenates revealed a broad resonance at 5.3-5.4 ppm in glioblastoma multiforme (N = 16) and brain metastases (N = 3). The broad resonance was identified as ceramide, a sphingosine-fatty acid combination portion of ganglioside, indicating an elevated abundance of monounsaturated fatty acids. GLC analysis of gangliosides in the highly malignant glioblastoma multiforme revealed that the elevated monounsaturated fatty acid is oleic acid (C18:1). The resonance at 5.3-5.4 ppm region was not detectable in normal human brain (N = 2), in meningiomas (N = 2), or in low-grade astrocytomas (N = 12). In normal human brain the abundance of monounsaturated fatty acid is minimal. 2. This investigation was made possible because the method of producing homogenate resulted in (i) no loss of lipids during the process and (ii) a well-homogenised sample, with (iii) no loss in chemical integrity. 3. The properties of tumor gangliosides include antigenic specificity and immunosuppressive activity and the ceramide, a sphingosine-fatty acid combination, noticeably influences the ganglioside immunosuppressive activity. 4. The observation of 1H NMR ceramide resonance in high-malignant brain tumors emphasizes the dramatic role of aberant gangliosides and ceramide precursors on the grade of malignancy and invasiveness. 5. Further insight into the specific nature of the ceramide portion of gangliosides in grading the malignancy of brain tumors should be investigated further.

Astrocytoma↗

PubMed1997

The effect of fixation type on DNA extracted from paraffin-embedded tissue for PCR studies in dermatopathology.

BACKGROUND: Amplification of nucleic acids from paraffin-embedded material by the polymerase chain reaction (PCR) is widely used to detect viral genomes, clonal gene rearrangements and oncogene mutations in skin specimens. Fixation with embedding of skin tissue is a procedure that has a profound effect on its molecular arrangement. OBJECTIVE: The aim of this study was to determine the effect of different fixatives on the PCR amplification of DNA. METHODS: We fixed randomly chosen fresh pathologic skin specimens in formalin, ethanol and Histochoice for 24 and 72 h and then embedded the tissue in paraffin. DNA was extracted from the paraffin-embedded tissues and used as template for amplification, producing 530- and 760-bp fragments of the phosphoglycerokinase gene. RESULTS: Our results indicate that PCR can be performed with excellent results on ethanol- and Histochoice-fixed, paraffin-embedded skin tissue with a rate of success comparable to that using fresh tissues; formalin-fixed tissue gave slightly less satisfactory results. CONCLUSION: This investigation corroborates previous reports investigating the effect of ethanol and formalin fixation on DNA amplification by PCR. Moreover, this is the first study showing that DNA extracted from tissue fixed with Histochoice is suitable for PCR gene amplification.

Base Sequence↗

PubMed1997

Comparison of formalin, ethanol, and Histochoice fixation on the PCR amplification from paraffin-embedded breast cancer tissue.

The polymerase chain reaction (PCR) has been successfully employed for the laboratory analyses of genetic and infectious disorders using DNA extracted from paraffin-embedded tissues. However, fixative type and fixation time influenced PCR reactions and in some circumstances amplification fragments could not be efficiently generated. In this study, we determined the effects of three commonly used fixatives including ethanol, formalin and Histochoice, on the PCR amplification of DNA from paraffin-embedded breast cancer tissue. The effect of fixatives and fixation times was measured by the ability of the extracted DNA to serve as a template for the amplification of 280 and 530 base pair DNA fragments. On amplifying DNA, positive reactions were uniformly seen in the ethanol specimens. The next best fixative was Histochoice with positive results almost constantly observed in the PCR reactions performed. Formalin fixation sometimes compromised DNA amplification. Our results are consistent with previous reports investigating the effect of ethanol and formalin fixation on DNA amplification by PCR. Moreover, this is the first study showing that paraffin-embedded tissues fixed with Histochoice can be efficiently used for PCR gene amplification.

Breast Neoplasms↗

PubMed1996

Infiltrating cribriform carcinoma of the breast. A clinico-pathologic and immunohistochemical study of 5 cases.

Clinical and pathological features of five cases of infiltrating cribriform carcinoma (ICC) of the breast observed between 1990 and 1994 are reported. Using histological criteria by Page et al., three cases of pure ICC and two cases of mixed ICC were identified. In the mixed forms, the cribriform component made up about 80% of the neoplasm. After clinical follow-up, from one to five years long, no relapses, axillary lymph nodes or distant metastases were found, even in two cases with very large neoplasms (20 cm and 10 cm, respectively). This report confirms that this type of carcinoma has a very favorable prognosis, especially pure and mixed forms with a predominant cribriform component. Clinical and histological features make ICC a peculiar form of breast carcinoma.

Adenocarcinoma↗

PubMed1996

[Dna synthesis and expression of steroid receptors in cells of human breast carcinoma].

In order to observe receptor expression (ER and PgR) in human breast cancer cells during the S-phase of the cellular cycle, we evaluated 21 tumoral samples using a double labeling immunocytochemical-autoradiographic assay. In 16 of these we have verified that expression of ER and PgR is not influenced by incubation with 3H-Thymidine for 60 minutes. The results also demonstrated that receptor expression during the S-phase is more common in postmenopausal tumors and is principally dependent on percentages of ER+ (p < 0.01) and PgR+ (p < 0.01) cells; moreover, proliferative activity occurs almost exclusively in ER- (p = 0.003) and Pgr- (p = 0.001) cellular sub populations and the presence of PgR, but not of ER, is related to arrest of DNA synthesis (p = 0.02).

Adult↗

PubMed1995

Heterogeneity of intratumour proliferative activity in primary breast cancer: biological and clinical aspects.

The present retrospective study was undertaken to verify whether the extent of intratumour proliferative activity variation or the method of quantifying tumour proliferative activity is related to biological characteristics and clinical outcome in a series of operable node-negative breast cancer patients. For tumour proliferative activity evaluation, the 3H-thymidine autoradiographic assay was used. After incubation of 3-8 samples from different areas of the equatorial section of each tumour for 1 h at 37 degrees C with 3H-thymidine, the following methods were used for evaluation of tumour cell labelling: mean tumour labelling index (LI), the highest labelling value from a specific area (LI-max), and the extent of intratumour labelling variation from several samples (LI-CV). LI-max was related to ER and PgR status, and linearly correlated with LI (c.c. = 0.92, P < 10(-6)) whereas LI-CV was independent of tumour size, grade ER and PgR status, but dependent on the number of tumour samples analysed for each tumour. After 5 years of median follow-up, disease-free survival was only related to tumour size (T1 versus T2: 84 versus 64%, P < 0.04 by log rank analysis) and different LI values (low versus high 3H-Tdr-LI:86 versus 61%, P < 0.03 by log rank analysis). LI-max and LI-CV values were not significantly related to clinical outcome. Cox multivariate analysis confirmed the independent prognostic value of LI and tumour size on disease-free survival.

Breast Neoplasms↗

PubMed1995

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study.

PURPOSE: To improve response and toxicity in treatment of non-Hodgkin's lymphomas (NHLs), a prospective single-arm trial was initiated using cyclophosphamide, epirubicin, vincristine, prednisone, and bleomycin (CEOP-B) alternated with etoposide (VP-16), ifosfamide, mitoxantrone, and bleomycin (VIMB). PATIENTS AND METHODS: From December 1988 to April 1992, 60 consecutive previously untreated patients with intermediate- or high-grade NHL were admitted to the study and were assessable. Patient characteristics were as follows: 32% greater than 60 years of age, 63% with stage III to IV disease, 42% with a performance status (PS) of 2 or 3, 23% with high lactate dehydrogenase (LDH) levels, and 22% with two or more extranodal disease sites. Stage I and II patients received three cycles of CEOP-B/VIMB plus radiotherapy (RT) to involved fields; stage III and IV patients received four cycles of chemotherapy alone. RESULTS: The complete remission (CR) rate was 77%; actuarial 48-month overall survival (OS) and time to treatment failure (TTF) rates were 70% and 59%, respectively. With univariate analysis, CR, OS, and TTF rates were significantly influenced by serum LDH levels (P = .0485, P = .0017, and P = .0064, respectively) and performance status (P = .0005, P < .00005, and P = .0001, respectively). The actuarial 48-month disease-free survival (DFS) rate was 83% and was negatively influenced only by high-grade histology (P < .004). Toxicity was mild. A lower epirubicin dose-intensity (DI) was found in patients older than 60 years of age, with a borderline P value. Patients were divided into four groups according to the International Prognostic Factor Project; low-risk and low-intermediate-risk groups had similar OS and TTF rates; when considered together, they showed superior, but not statistically significant, OS and TTF rates as compared with the high-intermediate-risk group, which in turn had significantly superior OS and TTF rates when compared with the high-risk group. CONCLUSION: CEOP-B/VIMB compares favorably with third-generation regimens and results in lower toxicity.

Actuarial Analysis↗

PubMed1994

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different nosological entities?

BACKGROUND: The relationship between solitary plasmacytoma and multiple myeloma is still unclear, but they can be distinguished by their different clinical course. Indicators of disease activity and extension, and of a possible evolution to multiple myeloma, have not been identified as yet. METHODS: Two cases of solitary plasmacytoma are described: one of the mandible and one extramedullary plasmacytoma (EMP) of the rhinopharynx. Pathologic data included immunohistochemical staining for heavy and light Ig chains, and for the proliferating cell nuclear antigen (PCNA). Analysis of the peripheral immunological status and serum parameters (beta 2 microglobulin, thymidine kinase, IL-2, IL-6 and soluble IL-2 receptor) was performed and correlation was made with the clinical status. Flow cytometry analysis of nuclear DNA content and S-phase cell fraction were also studied in both neoplasms. RESULTS: Solitary plasmacytoma of bone (SPB) showed important basal immunologic alterations and a marked increase in all serum parameters considered with respect to EMP. Ploidy analysis demonstrated an almost complete aneuploidy cell population for the SPB patient (80%), whereas in the EMP patient only 2% of the cells were aneuploid. The S-phase cells were 16% and 4%, respectively. PCNA index was 60% in SPB and 10% in EMP. CONCLUSIONS: Solitary plasmacytoma of the bone appeared to be a more aggressive form of plasmacellular neoplasia, distinct from EMP and similar to multiple myeloma. The study of serum parameters, together with analysis of PCNA, ploidy and S-phase fraction, can aid in better understanding disease activity, and in the choice of more adequate treatment. Moreover, serial analysis of some serum factors might be useful markers for monitoring the disease.

Aged↗