Dr. Fulvia Farabegoli has been mainly involved in studies
concerning the relationship betweenstructure and function of
ribosomal genes in situ at ultrastructural level, performing and
improvingmany histochemical and immunocytochemical methods. By
means of these techniques Dr. FulviaFarabegoli investigated the
role of ribosomal gene structural modifications in transcriptional
control; the relationship between histone absence and the extended
structure of ribosomal chromatin and the nucleolar components
involved in ribosomal gene transcription (2,3,5,10,12,14,17,18).
Other ultrastructural studies were conducted in collaboration with
various research teams (7,8,13,15).
Dr. Fulvia Farabegoli also studied the relationship between
ribosomal gene distribution, nucleic acid synthesis, nucleolar
morphology and the cell cycle in order to demonstrate the utility
of cytochemical AgNOR staining for acidic proteins associated with
ribosomal genes in diagnosis and prognosis of human tumours
(1,4,6,9,11,16).
Since June 1991 Dr. Fulvia Farabegoli has performed non
radioactive in situ hybridization techniques in order to
investigate chromosome aberrations in human neuroblastoma and
paediatricALL. October 1992: Dr. Fulvia Farabegoli started a
research project concerning breast cancer in order to investigate
chromosome 1 aberrations in this neoplasm by dual targetFISH
techniques. The results demonstrated that chromosome 1 aberrations
with 1p36 underrepresentation was correlated with the DNA index
value, histologic grade, high cerbB2 expression and low bcl2
expression (19,20). FISH analysis was also used to investigate the
biopathologiccharacteristics of a group ofbreast carcinoma samples,
previously screened for cerbB2 overexpression by
immunohistochemistry. The results indicated that only amplified
samples overexpressing cerbB2 were correlated to poor prognostic
factors. In contrast, samples overexpressing cerbB2 without
amplification had biologic characteristics similar to
immunonegative samples (22). Dr. Fulvia Farabegoli has investigated
the genetic evolution of breast carcinoma by two different
approaches. The first project has been aimed at investigating
several chromosome alterations (1, 8, 12,16, 17 and 18) in breast
carcinoma progression in diploid and aneuploid samples by means of
FISH techniques (23). The second study concerned Ductal Carcinoma
In Situ (DCIS) alterations as detected by a LOHPCR techniques using
microsatellite DNA sequences. This study has been conducted in
collaboration with the Laboratoire d'Oncogénétique, Centre René
Huguenin, SaintCloud, France, directed by Dr. Rosette Lidereau
(24). Fourty seven breast carcinoma samples have also been
investigated by Comparative Genomic Hybridization, in order to
study the relation between genomic imbalance and biopathologic
parameters currently used in breast cancer pathology. This study
has been conducted in the Department of Pathology of the Free
University Hospital, Amsterdam, The Netherlands (26). CGH
investigated samples were also studied with respect to polymorphism
of codon 72 of p53 protein and found to be related to poor
prognosis (25).
Recent investigations concern SOCS2 protein in breast carcinoma.
SOCS-2 expression was found to be correlated with low proliferation
indicators in a group of 50 reast carcinoma samples (27). The
relation between SOCS-2, proliferation and oestrogen receptor
expression is currently under investigation in breast carcinoma
cells in vitro (30).
A second research project concern the effects of EGCG, the most
active principle present in green tea, on breast carcinma cells in
vitro (28, 29) and the mechanisms by which EGCG is citotoxic to
breast carcinoma cells resistant to tamoxifen (31, 32).
Synergism between EGCG and molecules obtained from edible plants
(34) or synthetic drugs are currently investigated in collaboration
with different research groups.
Green tea and EGCG, the most active principle present in green
tea, are subject of extensive investigations, because of their
activity as anti-inflammatory, antioxidant and chemopreventive
agents. The chemopreventive avtivity of green tea has been
demonstrated by epidemiologic studies and the cytotoxic,
antiangiogenic and anti metastatic activity demonstrated in animals
and in vitro studies. We found that EGCG was cytotoxic to breast
carcinoma cells having the oestrogen receptors and EGCG was able to
downregulate the oestrogen receptor signalling pathway. We also
found that EGCG could circumvent drug-resistence in cells resistant
to tamoxifen (the first line treatment in breast carcinoma patients
showing oestrogen receptors) by modulating the proteins involved in
drug-resistance.
EGCG can decrease multidrug resistance either by down-regulation
or inactivation of proteins belonging to the MRP subfamily,
physiologically involved in molecule transport. Furthermore EGCG
can down-regulate EGFR signalling pathway, a very important
signalling pathway highly activated in tamoxifen resistant
cells.
