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C Botti

Publications and source records attributed to C Botti.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas.

AIMS AND BACKGROUND: Many normal and human cancer tissues express fatty acid synthase (FAS), the major enzyme required for endogenous fatty acid biosynthesis. Strong expression of FAS seems to be associated with a poor prognosis. This study examines the strength of FAS and other common markers of relapse in poorly differentiated breast carcinoma. MATERIALS AND METHODS: Fifty-one patients with poorly differentiated ductal infiltrating breast carcinomas were followed up for more than 10 years. Immunohistochemical detection of FAS was associated with morphological features of the tumors, with immunohistochemical expression of c-erbB-2, cathepsin D, estrogen and progesterone receptor status and with DNA ploidy in order to detect a statistical correlation. RESULTS: The chi-square test revealed a correlation between FAS and peritumoral lymphatic vessel invasion (PLVI) (P = 0.001). Univariate analysis showed that FAS was correlated with disease-free survival (DFS) (P = 0.0001). Other prognosticators associated with DFS were PLVI (P = 0.002), estrogen (P = 0.008) and progesterone receptor status (P = 0.007). Bivariate analysis showed that FAS was a further prognostic discriminant of DFS within the ER, PgR and PLVI subsets. DISCUSSION: FAS is a reliable prognosticator of recurrence in poorly differentiated early breast carcinomas. Association of FAS with PLVI may be useful to plan a correct follow-up in patients with breast neoplasms.

Adult↗
PubMedDate not supplied

Two novel monoclonal antibodies against the MUC4 tandem repeat reacting with an antigen overexpressed by lung cancer.

In this study we investigated the immunochemical and cytochemical reactivity of two monoclonal antibodies against the 16-amino acid tandem repeat of MUC4 to demonstrate a possible variation of the mucin core peptide expression related to lung cancer. The immunocytochemical anti-MUC4 reactivity was analyzed in four lung cancer cell lines (Calu-1, Calu-3, H460, SKMES) and in other tumor cell lines, as well as in frozen materials from 21 lung adenocarcinomas (ACs), including five bronchioloalveolar carcinomas (BACs), and 11 squamous cell lung carcinomas (SqCCs). A weak fluorescence anti-MUC4 positivity (range: 10.3-16.2) was observed only in acetone-fixed lung cancer cell lines Calu-1, Calu-3 and H460. These three lung cancer cell lines also showed a cytoplasmic immunoperoxidase reactivity. The immunostaining in lung cancer tissues showed a granular cytoplasmic reactivity: 15/21 (71%) and 17/21 (80%) ACs were positive with BC-LuC18.2 and BC-LuCF12, respectively. All BACs were positive. Moderate to strong reactivity was present in well-differentiated ACs. In the normal lung parenchyma counterparts weak reactivity was found only in bronchiolar cells. All SqCCs were negative. Anti-MUC4 reactivity was also observed in the alveolar mucus. In conclusion, our anti-MUC4 MAbs detect a secretion product present in mucus and this product is elaborated by lung cancer cells and overexpressed in well-differentiated lung ACs.

Adenocarcinoma↗
PubMedDate not supplied

Mucin-like carcinoma-associated antigen (MCA) in breast cancer: clinical experience at the National Cancer Institute of Milan.

Mucin-like Carcinoma-associated Antigen (MCA) is a glycoprotein belonging to the mucin family; it is defined by the monoclonal antibody b-12. Mucins represent an interesting group of tumor markers and are widely utilized in the clinical monitoring of neoplastic patients. These molecules show a certain degree of tissue specificity and MCA is preferentially associated with breast tissue. Several studies have demonstrated that patients with breast cancer usually have high MCA serum levels. In this paper the experience of the National Cancer Institute of Milan with the clinical use of MCA in breast cancer patients is reported. The observed sensitivity of the MCA test was poor in patients with early-stage disease, while it was acceptable in patients with advanced breast cancer. MCA concentrations appeared to be directly related to disease spread. A clear relationship was seen between MCA levels and lymph-nodal status. The highest MCA plasma levels were observed in patients with metastatic disease. In this group of patients the sensitivity of the test on the basis of a cut-off of 11 U/mL was 52%.

Adenofibroma↗
PubMedDate not supplied

Anti-malignin antibody evaluation: a possible challenge for cancer management.

The major problem in the management of cancer is the difficulty of an early diagnosis. Clinical signs and symptoms generally appear late in the course of the disease. The availability of a non-invasive test which detects a blood molecule closely associated with the malignant transformation of the cells could be of help in the early detection of cancer. Malignin is a 10 kDa polypeptide located in the cytoplasmic and outer membranes of all malignant cells. Anti-malignin antibodies (AMAs) are IgM immunoglobulins spontaneously produced by the host against the oncoprotein malignin when neoplastic transformation occurs; since AMAs are IgM, they can represent an "early" transformation indicator useful for the early detection of cancer. Elevated AMA serum concentrations, measured by means of TARGET@ reagent, have been demonstrated in patients with a wide spectrum of non-terminal active cancers, regardless of the anatomical site and histotype of the tumor. The AMA test showed a sensitivity and specificity of 95% on first determination and > 99% on repeated determinations, and has been reported to be a promising diagnostic tool for the early detection of cancer, as well as for monitoring of the response to treatment and possibly for screening of an asymptomatic population.

Adult↗
PubMedDate not supplied

Bladder cancer monitoring using two novel urinary markers.

Bladder cancer shows extreme variability in its behavior. Even the superficial forms, when surgically treated, are characterized by a high recurrence rate and therefore regular and intensive post-treatment monitoring is an important aspect of the management of this tumor. The standard follow-up of patients with a bladder cancer history is based on cystoscopic examination of the internal bladder, which is an invasive procedure causing discomfort to the patient. In this context, the availability of a non-invasive laboratory test which measures circulating markers associated with bladder cancer could facilitate with monitoring of patients and could be of help in understanding the metastatic potential of bladder tumors, especially the superficial forms.

Antigens, Neoplasm↗
PubMedDate not supplied

Chromogranin A measurement in neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare neoplasms characterized by a low proliferative index and, in some cases, a favorable prognosis. These tumors often overproduce and release biologically active substances that are responsible for severe syndromes. Tumor marker measurement provides the clinician with useful information for the management of NET patients. The substances released by overproducing tumors are currently used as biomarkers, but there is a need for sensitive markers also for the "biochemically silent" NETs. The most effective and reliable blood marker available today is chromogranin A (CgA). Because of its high sensitivity and specificity, this glycoprotein can be used for the diagnosis, prognosis and followup of NETs. Furthermore, CgA measurement can be used for monitoring those tumors not over-producing or releasing any hormones or biological amines. This paper is a synthetic review on the value of CgA in NET management and reports our experiences with CgA measurement in NET patients.

Adenoma, Islet Cell↗
PubMedDate not supplied

Immunosuppressive factors: role in cancer development and progression.

The concept of the immunological surveillance against neoplastic cells was initially proposed by Erlich in 1909 and later elaborated by Burnet. This hypothesis states that the normal function of the immune system, in particular the cell-mediated immunity, is to recognize and destroy the transformed and proliferating tumor cells. The role of cell-mediated immunity during the first steps of tumorigenesis remains controversial. However, there is certain evidence about its importance in the progression and dissemination of cancer. The frequent immunosuppressed condition of cancer patients at tumor relapse or recurrence of secondary tumors is a clinical sign supporting this hypothesis, and many studies have demonstrated a defective immune response in patients diagnosed with advanced cancer. Several mechanisms of escape from the immune surveillance have been described, including the immunoselection of tumor antigen-negative variants, the downregulation of MHC class I expression, suppressive T cells, and the elaboration of immunosuppressive cytokines and other factors. Because of the technical difficulty of isolating the very small amounts from culture supernatants or body fluids, only a few of these substances have been characterized and studied with respect to their biological activity: transforming growth factor-beta (TGF-beta), the protein p15E, interleukin 10 (IL-10), prostaglandin E2 (PGE2), mucins, suppressive E-receptor (SER), immunosuppressive acidic protein (IAP), and adhesion molecules. The possibility of monitoring cancer patients by testing biochemical factors related to cancer growth led to a proposal to measure a number of these factors as tumor markers. Some of them, e.g. mucins, enjoy the consensus of the oncologic community, as for some indications they can help the clinician in the management of cancer patients. Except for the class of mucins, the other above-mentioned immunosuppressive factors have not found any clinical application in the laboratory routine because the information deriving from their measurement, although of speculative and scientific interest, has limited clinical value at present. Nevertheless, even if they have no impact on patient management, these substances do have a potential role to play in the study of cancer patients, and should be taken into account when developing new therapeutic strategies.

Animals↗
PubMedDate not supplied

Hormonal regulation of MUC1 expression.

Several circulating mucinous markers, including CA 15.3, MCA, CA 459, CASA, and Truquant BR, are secreted products of the polymorphic MUC1 gene, and are used as diagnostic tools in patients with breast cancer. In clinical practice the measurement of the levels of these markers in the blood can give important information on the tumor's response to treatment and its biological behavior during disease monitoring. Since the marker levels reflect the activity of the tumor, it is important to know all factors influencing the production/secretion and the blood concentrations of MUC1 mucin. Recent findings suggest that MUC1 gene expression is regulated by steroid hormones and other substances present in the serum. Such observations are very important not only because of their biological significance but also for their clinical implications, as one approach to breast cancer therapy is based on chemical hormone manipulation. Nevertheless, we have preliminarily demonstrated that endocrine treatment in breast cancer patients does not influence the circulating CA 15.3 serum levels, so changes in marker levels are related only to the clinical evolution of the tumor.

Biomarkers, Tumor↗
PubMedDate not supplied

Immunohistochemical study of fatty acid synthase in ovarian neoplasms.

In order to evaluate the prognostic significance of fatty acid synthase (FAS), the key enzyme in fatty acid biosynthesis, in ovarian benign and malignant tumors 98 patients with ovarian masses were immunohistochemically evaluated. Histologic features of the lesions and expression for FAS were statistically associated with clinical data and disease-free survival over a 5-year follow-up period. The mean age of patients was 65 years. TNM surgical stages were I in 31.8%, II in 28.2% and III in 40% of cases. The 5-year disease-free survival of the 85 malignant common epithelial ovarian tumors was 47.1% while 35.3 of patients died with active disease. Seventy-eight (79.6%) out of 98 cases expressed FAS in the neoplastic epithelial cells and 42 (42.9%) in the non-neoplastic stromal cells. Statistical analysis revealed FAS expression and stage of the disease to be significantly correlated to recurrence and survival rates only in the malignant common epithelial tumors. Moreover, multivariate analysis showed FAS expression (p=0.05) and tumor stage (p=0.03) to be independent prognostic predictors. FAS is a reliable predictor of recurrence and disease-free survival in common epithelial ovarian tumors along with neoplastic stage. Clinical data, other histologic subtypes and grading were not statistically significant.

Adult↗
PubMedDate not supplied

The breast cancer cell line MCF7 as a model of 99mTc-SestaMIBI, 99mTc-tetrofosmin and 99mTc-Medronate incorporation.

Hexakis-2-methoxyisobutylisonitrile (SestaMIBI) and 1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) are 99mtechnetium compounds widely used in oncologic imaging. We investigated the uptake and release of SestaMIBI and tetrofosmin together with 99mTc-medronate in the MCF7 breast carcinoma cell line. All the tracers showed similar uptake kinetics, with a rapid increase in the first 30 minutes and a slower trend up to 120 minutes. Cell-associated activity was the same for SestaMIBI and tetrofosmin (4% of administered activity) and considerably lower for medronate (0.8%). For all tracers, almost all the accumulated activity was released within 1 hour. Furthermore, to verify an association between cell proliferation and tracer uptake, we performed growth-curve uptake experiments. Tetrofosmin uptake was lower in the logarithmic phase and higher in the plateau phase, whilst SestaMIBI showed the opposite trend. The differences between the tracers could be due to a relationship between proliferation and SestaMIBI uptake, or even to the influence of medium pH on membrane potential.

Breast Neoplasms↗
PubMedDate not supplied

[Causality in epidemiology: populations, individuals, and alternative explanations].

The purpose of the present paper is to review issues concerning causal reasoning in epidemiology, with special emphasis on the relationship between observation at the individual and population level. The sequence of the three sections of the paper, causality in epidemiology, individual and population, alternative explanations, reflects the need to deal with issues of research methodology mainly derived from discussions in the frame of risk assessment, decision making, regulation and legal setting. In discussing the aforementioned topics, special attention is given to the attribution of causality to a single exposure in the presence of a plurality of potential causes. As a case study, data concerning the occurrence of hepatic and pulmonary tumors among subjects exposed to vinyl chloride are considered making reference to hearings on this topic which took place in Court.

Causality↗
PubMedDate not supplied

[Setting priorities for environmental protection from asbestos: ethical aspects].

The allocation of resources destined for environmental rehabilitation of areas contaminated by asbestos requires scientific, political, economical and ethical evaluation. Ethically relevant issues reviewed in this paper include: identification of the populations most expected to benefit from the intervention, risk assessment, effectiveness of different technical approaches, as well as a comparison between populations of current socio-economic standards, level of legal assistance and access to both information and participation in the decision making process. A relevant ethical criterion is minimizing inequalities within and between communities.

Asbestosis↗
PubMedDate not supplied

BTA-TRAK combined with urinary cytology is a reliable urinary indicator of recurrent transitional cell carcinoma (TCC) of the bladder.

This study evaluated the diagnostic accuracy of BTA-TRAK in combination with urinary cytology (UC) in the follow-up of patients with a history of transitional cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2% (48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and for invasive recurrences (100% (15/15)); when the two tests were used in combination, the sensitivity for superficial lesions increased to 88% (37/42). BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7% (11/16)), and when the two tests were combined the sensitivity increased to 87.5% (14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The differences in urinary BTA-TRAK levels between patients with recurrences and those without evidence of disease were statistically significant (Wilcoxon's test, p<0.05); among patients with recurrences BTA levels were significantly higher in the invasive and poorly differentiated subtypes. In the series of patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive, accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK combined with urinary cytology seems to provide additional information for the monitoring of patients treated for TCC; however, due to the presence of false positive and false negative results, this test cannot replace cystoscopy. In a selected group of patients it could, if combined with cytology and ultrasonography and if correctly used and interpreted, orient the timing and indication for cystoscopy.

Adult↗
PubMedDate not supplied

[Sentinel lymph-node assessment in breast carcinoma. Current status and future perspectives].

The sentinel-node technique was first introduced by Morton in high-risk melanoma of the skin. Recently, this technique has also been used in patients with T1 breast cancer. Lymphoscintigraphy and the gamma probe are currently used in sentinel lymph-node detection. Many investigators have used this technique in clinical practice and there is no standard procedure in terms of the timing of lymphoscintigraphy, type of vital stain, radiolabelled tracer, etc. This heterogeneity might account for the broad range of false-negatives reported in the literature. The aim of our study was to carefully review and analyse the literature in order to identify the most reliable technique for use in sentinel node detection. The results of the review seem to indicate that the simultaneous use of preoperative lymphoscintigraphy, intraoperative gamma probe and vital staining is capable of ensuring the best results. These data have been confirmed in our experience of 15 patients. The sentinel node search was successful in 100% of the cases, and the percentage of false negative was 0%. The use of the best technique available might prove extremely important, particularly in randomised clinical trials, comparing sentinel node biopsy with axillary dissection. In the patient group undergoing sentinel node biopsy, the axillary pathological staging is based exclusively on this technique and therefore its reliability must be assured if it is to serve as a precise guide in the planning of adjuvant treatments.

Breast Neoplasms↗