Piero Tosi - Academia.edu (original) (raw)
Papers by Piero Tosi
The American Journal of Surgical Pathology, 1982
Journal of General …, 1999
The complete ORF54 of the Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpes-virus... more The complete ORF54 of the Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpes-virus-8; HHV-8) was cloned and expressed in E. coli. The results show that KSHV/HHV-8 ORF54 encodes a functional dUTPase which specifically hydrolyses dUTP ...
…, 2005
The normal counterpart of the neoplastic B cells in Burkitt lymphoma (BL) is still unclear. Based... more The normal counterpart of the neoplastic B cells in Burkitt lymphoma (BL) is still unclear. Based on immunoglobulin gene rearrangement studies, some authors suggest an origin from germinal center cells and others from memory B cells. However, most of these studies rely on cell lines or on a small series of cases. To help clarify the cell of origin of BL, seminested polymerase chain reaction (PCR) was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (V H) genes, and the resultant amplificates were sequenced for comparison with known germline V H segments. The results of this approach revealed that all cases (15 endemic BL [eBL], 10 sporadic BL [sBL], and 6 AIDS-related BL) harbor mutated V H genes, with different mutation ranges among the 3 types of BL. The eBL and AIDS-related forms showed considerably higher mutation rates than the sBL form (5.1%, 5.4%, and 1.5%, respectively). The mutations in eBL and AIDS-related BL also showed signs of antigen selection, whereas no signs of antigen selection were found in sBL. Finally, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations in any of the cases analyzed. Given that one of the main differences between eBL and AIDS-related BL on the one hand and sBL on the other hand is the association with Epstein-Barr virus (EBV), we compared EBVpositive and EBV-negative BLs independently of their geographic origin and HIV status. The differences in the number of somatic mutations and antigen selection were even more evident when this approach was used. According to our molecular results, it appears that EBV-positive and EBV-negative BL may originate from 2 distinct subsets of B cells, pointing to a particular role for the germinalcenter reaction in the pathogenesis of these tumors. The different types of C-MYC translocation reported in BL may also be related to the different stages of B-cell maturation. (Blood. 2005
International Journal of Oncology, Dec 1, 2003
Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telom... more Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.
Experimental Cell Research, Dec 31, 1995
International Journal of Cancer, Feb 1, 2001
International Journal of Oncology, 2003
Leukemia and Lymphoma, Nov 1, 2007
Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth f... more Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that activate the Vascular Endothelial Growth Factor Receptor (VEGFR)-2 and VEGFR-3, which are mainly expressed in blood and lymphatic vessels. Here we have analyzed by using monoclonal antibodies, the expression of VEGF-D and its cognate receptor VEGFR-3 in normal and pathologic bone marrow and lymph node biopsies. This analysis revealed that VEGF-D is expressed in B cells of the germinal centers, scattered B and T blasts, myeloid progenitors, acute leukemia, several types of non Hodgkin lymphoma, and classical Hodgkin's lymphoma. In normal tissues VEGFR-3 was only expressed in fenestrated capillaries of bone marrow and in lymphatic vessels of lymph nodes, while in VEGF-D expressing tumors newly formed vessels, but not malignant cells, showed high VEGFR-3 expression. These data suggest that VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues.
Sexually Transmitted Diseases, Sep 1, 2003
On a global scale, the New Independent States (NIS) of the former Soviet Union have an intermedia... more On a global scale, the New Independent States (NIS) of the former Soviet Union have an intermediate incidence of cervical cancer, the main etiologic factor of which is human papillomavirus (HPV), a major sexually transmitted disease (STD). Recently, the prevalence of all STDs has exploded in these countries. The goal of this study was to examine the sexual habits and HPV prevalence among females in three NIS countries. In this multinational (European Community-funded) trial, a series of 3,175 consecutive female patients were examined for HPV status (by Hybrid Capture II) at six clinics in Russia, Belarus, and Latvia. A meticulous survey of their sexual habits and other potential risk factors of HPV infections was made by structured questionnaire. Three categories of patients were examined: those attending STD clinics (n=722), gynecological patients (n=761), and those who participated in cervical cancer screening (n=1,692). These three categories were significantly differentiated by a large number of key variables, including the HPV detection rate (44.9% of STD patients, 39.8% of gynecological patients, and 24.5% of those who were screened). A wide variety sexual habits of these subjects were predictors of the HPV status in univariate analysis. Binary logistic regression analysis found that six different variables remained as independent predictors of HPV status. Patient category (STD) and (young) age were two highly significant predictors of increased risk (P<0.0001), whereas having a nonsmoking partner and having zero or one partner during the past 2 years were significant protective factors (P=0.004 and P=0.007, respectively). The results of this study indicate that women and girls in these NIS countries are conservative in many key characteristics of "high-risk" sexual behavior, such as age at onset of sexual activity, number of partners, and casual sex partners. HPV-positive and HPV-negative groups are clearly distinguished by the same variables identified as the key risk factors of HPV infection and cervical intraepithelial neoplasia in Western countries.
Eur J Endocrinology, 2003
Background: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of t... more Background: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of transforming growth factor-b (TGF-b), inhibin and activin activities into cells. TGF-b and inhibin-related proteins are growth factors that are expressed by several tissues and in pregnancy. They have a function in modulating the growth, differentiation and invasion of the placental trophoblast. Objective: To evaluate whether betaglycan is expressed by intrauterine tissues throughout gestation. Design and methods: Expression of betaglycan mRNA and protein was evaluated (by RT-PCR and immunohistochemistry, respectively) in trophoblast, decidua and fetal membranes collected during the first (n ¼ 6 elective terminations of pregnancy, between 8 and 12 gestational weeks) and third (n ¼ 6 elective caesarean sections, between 39 and 40 weeks) trimesters of pregnancy. Results: Betaglycan mRNA was expressed by all gestational tissues, independently of gestational age. Immunoreactive protein was found in decidual cells and in some chorionic, but not epithelial, amniotic cells. With respect to the placental localization, syncytiotrophoblast, but not cytotrophoblast, cells were intensively stained both in the placental bed and in the villous trophoblast, and in some cells within the stroma of terminal villi, of the first and third trimesters of pregnancy. Immunoreactive betaglycan was demonstrated in the endothelial cells of decidual vessels in both the first and third trimesters of pregnancy, whereas endothelial cells of fetal blood vessels in the villous were clearly represented only in first trimester samples, not in those of term placenta. Conclusions: Betaglycan mRNA and peptide are expressed by the trophoblast, the decidua and the fetal membranes, but the localization of the peptide in vessel walls is dependent on gestational age.
Clinical Cancer Research, Dec 1, 1999
pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cel... more pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cellular growth and differentiation. Because recent functional studies have indicated that the expression of the RB-related proteins p107 and pRb2/p130 are tightly cell cycle regulated, we were interested in investigating their expression along with cellular kinetic characteristics and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pRb2/ p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients with NHLs of various histiotypes. The expression of these two RB-related proteins was correlated with the mitotic index, apoptotic index, and percentages of Ki-67(؉), cyclin A(؉), p34(؉), and cyclin B(؉) cells. The overall survival rate was evalu-ated according to the Kaplan-Meier method and the logrank test. We found a positive correlation between the percentages of cells positive for p107 and proliferative features such as mitotic index and percentage of Ki-67(؉) and cyclin A(؉) cells, whereas such correlation could not be demonstrated for the percentages of pRb2/p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected in untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and proliferation-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells. Interestingly, such cases showed the highest survival percentage (82.5%) after the observation period of 10 years. Thus, down-regulation of the RB-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation and why they respond so well to therapy.
Anticancer Research, 2006
Background: Oral contraception (OC) has been proclaimed by the IARC as a risk factor of cervical ... more Background: Oral contraception (OC) has been proclaimed by the IARC as a risk factor of cervical cancer (CC), on prolonged use by high-risk human papillomavirus (HPV) positive women. However, the available data are far from complete, and more evidence is necessary on the potential confounding effects of sexual behavior and HPV infection. The aim of the present was study to analyse the risk estimates for OC users in order to develop several intermediate end-point markers in cervical carcinogenesis. Patients and Methods: A cohort of 3,187 women, enrolled in a multi-center screening trial in three New Independent States (NIS) of the former Soviet Union (the NIS Cohort Study), was stratified into three groups according to their contraception modes: i) non-users of contraception, ii) non-OC users and iii) OC users. These groups were analysed for predictors of three outcome measures: a) exposure to HR-HPV; b) progression to high-grade cervical intraepithelial neoplasia (CIN2/3 and HSIL); and c) persistence/clearance of HR-HPV and cytological abnormalities during a prospective follow-up. Results: All three groups had an identical prevalence of HR-HPV (HCII and PCR), Pap smear abnormalities and CIN histology, but differed significantly (p=0.0001) with regard to all key variables of sexual behaviour, known as risk factors for CC. Predictors of HR-HPV, CIN2/3 and HSIL were different in the three groups, reflecting these different sexual preferences. Use of OC was not a significant predictor of CIN2/3 or HSIL in HPV-positive or HPVnegative women. Outcomes of cervical disease and HR-HPV infection were unrelated to contraception. In a multivariate regression model, mode of contraception was of no predictive value for either HR-HPV or high-grade CIN. Conclusion: Sexual behaviour is different among OC users, non-OC users and in nonusers of contraception; these risk factors predispose women to HR-HPV, high-grade CIN, and determine the outcome of their cervical disease/HR-HPV infection. The use of OC is not an independent risk factor for any of these intermediate end-point markers of cervical carcinogenesis. Failure to record these epidemiological data inevitably leads to erroneous conclusions about the role of OC as an independent risk factor of cervical cancer.
Bollettino della Società italiana di biologia sperimentale
The effects of hypophysectomy on the lymphoid organs were evaluated in Wistar rats by morphometri... more The effects of hypophysectomy on the lymphoid organs were evaluated in Wistar rats by morphometrical analysis: after 30 days the percentage of thymus cortical area and lymph node paracortical areas were reduced. In the thymus cortex, signs of orthological involution (e.c.: nodular cortex) appeared. A significant enlargement of lymph node cortical areas, containing a high number of germinal centers with degenerative changes, could be seen. These findings suggest a significant trophic action of hypophysis on thymus and, perhaps, an impaired lymph node antibody mediated response due to the loss of T-B cooperation.
Bollettino della Società italiana di biologia sperimentale
Morphometrical analysis of lymphoid organs has been performed 30 days after bilateral orchidectom... more Morphometrical analysis of lymphoid organs has been performed 30 days after bilateral orchidectomy in Wistar rats. The percentage of thymus cortical area and of lymph node paracortical areas (filled with large lymphoid cells) has been found increased. These morphological changes seem to indicate that orchidectomy enhance lymph node cell-mediated immune response in the rat.
American Journal Of Pathology
A comparison between neoplastic and nonneoplastic lymphoid cell nuclei within germinal centers of... more A comparison between neoplastic and nonneoplastic lymphoid cell nuclei within germinal centers of nodular lymphomas and of reactive follicular hyperplasias has been carried out with the help of a semiautomated image analyzer by measuring nuclear area, by assessing the presence or absence of invaginations, and by defining the form of the invagination. Nuclear areas are larger in lymphomas, where the invagination, if present, decreases in depth and increases in angle as the value of nuclear area becomes greater. Nuclei with such a large area and shallow invaginations are not present within the nonneoplastic germinal centers. Moreover, no correspondence has been found between neoplastic and nonneoplastic nuclei with regard to the form of the invagination, that is, its symmetry and angle. Therefore, it is possible to argue that the neoplastic nuclei in nodular lymphomas are different from the nuclei found in the sequential pathway of reactive germinal centers.
European journal of respiratory diseases
The report deals with a series of peribronchial and mediastinal lymph node silicotic lesions, whi... more The report deals with a series of peribronchial and mediastinal lymph node silicotic lesions, which were histologically and histochemically typical, in patients with bronchogenic cancer without any form of occupational dust exposure. The presence of a significant quantity of quartz was confirmed in the lesions by the use of backscatter electron imaging analysis, X-ray mapping and X-ray spectrometry. The lymph node lesions observed were actually silicotic in nature and had possible epidemiologic implications. There is a need for further investigations on larger series of cases to evaluate the incidence of the phenomenon and correlations between lung changes and lymph node lesions.
Archiv für Geschwulstforschung
To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mas... more To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the lymph nodes with the functional assays measuring cytotoxic and tumor cell membrane-bound antibodies in mouse sera. Regional and non-regional (RLN, NRLN) lymph nodes, were subjected to stereological analysis to determine the volume fractions (Vv) of the cortex (C), the paracortex (PCA), the germinal centers (GC), and the medulla (M), using a computerized analysis system (IBAS I, Kontron). In both RLN:s and NRLN:s, lymphocyte subsets were identified and their ratios determined using the ABC (avidin-biotin peroxidase complex) technique and following monoclonal antibodies; Anti-Thy 1.2, Anti-Lyt 1, Anti-Lyt 2, and Anti-I-Ad. The 51Cr release assay was used to test the mouse sera for cytotoxic antibodies, and an indirect immunofluorescence (IF) technique to assess the sera for tumor cell membrane-bound antibodies. There was a marked enlargement of the RLN:s reaching the peak on day 12, due to increase of the Vv of the B-zone as well as of the T-zone. Evidence of distinct B-cell stimulation by the growing of P815X2 was provided by an early decrease of Thy1.2+/I-Ad+ cell ratio both in the RLN:s and in NRLN:s. This activation of B-cells seems to be parallel to the elevation of Lyt1+/Lyt2+ ratio in T-cell region on day 6. The IF-tests for or the presence of tumor cell membrane-bound antibodies were almost invariably negative. With exception of two sera, the 51Cr-release assay for cytotoxic antibodies against P815X2 targets was negative. The present study confirms the previous observations on failure to find circulating cytotoxic or cell membrane-bound antibodies in DBA/2 mice bearing P815X2 mastocytoma, despite the morphologically well definable activation in RLN:s and in NRLN:s of the B-cell areas. This is in alignment with the findings in the majority of human tumors, where B-cell predominance in RLN:s does not represent a favourable prognostic sign.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology
The areas and shapes of cell nuclei were morphometrically analyzed in peripheral T-zone lymphomas... more The areas and shapes of cell nuclei were morphometrically analyzed in peripheral T-zone lymphomas, which have a characteristic nuclear pleomorphism, as well as in paracortical areas of normal and reactive lymph nodes; the aim of the study was to compare the neoplastic and nonneoplastic lymphoid cell populations. Although the means and standard deviations (SDs) of nuclear area and shape features differed significantly between the T-zone lymphomas, reactive nodes and normal nodes, there was considerable overlap between the lymphomas and the reactive lymph nodes in all of the features investigated. Therefore, the composition of populations of nuclei was studied. In lymphomas, the frequencies of regular and irregular nuclei were about the same in all nuclear area classes, whereas increasingly larger nuclei had an increasingly regular shape in reactive lymph nodes. An attempt to classify the cells, divided into those with small nuclei (less than 25 sq microns) and those with large nuclei (greater than 25 sq microns), on the basis of their morphometric shape features showed the usefulness of form factors in the class of nuclei with a large area. The results show that, while means and SDs of nuclear area and shape are not very accurate descriptors of the differences between the T-zone lymphomas and nonneoplastic lymph nodes, analysis of the percentage of regularly shaped nuclei in a certain nuclear area class can describe the differences much more accurately. The compositional differences in nuclear shape are in agreement with subjective impressions and can objectively support the pathologist's qualitative impression of pleomorphism in malignant T-zone lymphomas.
The American Journal of Surgical Pathology, 1982
Journal of General …, 1999
The complete ORF54 of the Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpes-virus... more The complete ORF54 of the Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpes-virus-8; HHV-8) was cloned and expressed in E. coli. The results show that KSHV/HHV-8 ORF54 encodes a functional dUTPase which specifically hydrolyses dUTP ...
…, 2005
The normal counterpart of the neoplastic B cells in Burkitt lymphoma (BL) is still unclear. Based... more The normal counterpart of the neoplastic B cells in Burkitt lymphoma (BL) is still unclear. Based on immunoglobulin gene rearrangement studies, some authors suggest an origin from germinal center cells and others from memory B cells. However, most of these studies rely on cell lines or on a small series of cases. To help clarify the cell of origin of BL, seminested polymerase chain reaction (PCR) was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (V H) genes, and the resultant amplificates were sequenced for comparison with known germline V H segments. The results of this approach revealed that all cases (15 endemic BL [eBL], 10 sporadic BL [sBL], and 6 AIDS-related BL) harbor mutated V H genes, with different mutation ranges among the 3 types of BL. The eBL and AIDS-related forms showed considerably higher mutation rates than the sBL form (5.1%, 5.4%, and 1.5%, respectively). The mutations in eBL and AIDS-related BL also showed signs of antigen selection, whereas no signs of antigen selection were found in sBL. Finally, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations in any of the cases analyzed. Given that one of the main differences between eBL and AIDS-related BL on the one hand and sBL on the other hand is the association with Epstein-Barr virus (EBV), we compared EBVpositive and EBV-negative BLs independently of their geographic origin and HIV status. The differences in the number of somatic mutations and antigen selection were even more evident when this approach was used. According to our molecular results, it appears that EBV-positive and EBV-negative BL may originate from 2 distinct subsets of B cells, pointing to a particular role for the germinalcenter reaction in the pathogenesis of these tumors. The different types of C-MYC translocation reported in BL may also be related to the different stages of B-cell maturation. (Blood. 2005
International Journal of Oncology, Dec 1, 2003
Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telom... more Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.
Experimental Cell Research, Dec 31, 1995
International Journal of Cancer, Feb 1, 2001
International Journal of Oncology, 2003
Leukemia and Lymphoma, Nov 1, 2007
Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth f... more Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that activate the Vascular Endothelial Growth Factor Receptor (VEGFR)-2 and VEGFR-3, which are mainly expressed in blood and lymphatic vessels. Here we have analyzed by using monoclonal antibodies, the expression of VEGF-D and its cognate receptor VEGFR-3 in normal and pathologic bone marrow and lymph node biopsies. This analysis revealed that VEGF-D is expressed in B cells of the germinal centers, scattered B and T blasts, myeloid progenitors, acute leukemia, several types of non Hodgkin lymphoma, and classical Hodgkin's lymphoma. In normal tissues VEGFR-3 was only expressed in fenestrated capillaries of bone marrow and in lymphatic vessels of lymph nodes, while in VEGF-D expressing tumors newly formed vessels, but not malignant cells, showed high VEGFR-3 expression. These data suggest that VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues.
Sexually Transmitted Diseases, Sep 1, 2003
On a global scale, the New Independent States (NIS) of the former Soviet Union have an intermedia... more On a global scale, the New Independent States (NIS) of the former Soviet Union have an intermediate incidence of cervical cancer, the main etiologic factor of which is human papillomavirus (HPV), a major sexually transmitted disease (STD). Recently, the prevalence of all STDs has exploded in these countries. The goal of this study was to examine the sexual habits and HPV prevalence among females in three NIS countries. In this multinational (European Community-funded) trial, a series of 3,175 consecutive female patients were examined for HPV status (by Hybrid Capture II) at six clinics in Russia, Belarus, and Latvia. A meticulous survey of their sexual habits and other potential risk factors of HPV infections was made by structured questionnaire. Three categories of patients were examined: those attending STD clinics (n=722), gynecological patients (n=761), and those who participated in cervical cancer screening (n=1,692). These three categories were significantly differentiated by a large number of key variables, including the HPV detection rate (44.9% of STD patients, 39.8% of gynecological patients, and 24.5% of those who were screened). A wide variety sexual habits of these subjects were predictors of the HPV status in univariate analysis. Binary logistic regression analysis found that six different variables remained as independent predictors of HPV status. Patient category (STD) and (young) age were two highly significant predictors of increased risk (P<0.0001), whereas having a nonsmoking partner and having zero or one partner during the past 2 years were significant protective factors (P=0.004 and P=0.007, respectively). The results of this study indicate that women and girls in these NIS countries are conservative in many key characteristics of "high-risk" sexual behavior, such as age at onset of sexual activity, number of partners, and casual sex partners. HPV-positive and HPV-negative groups are clearly distinguished by the same variables identified as the key risk factors of HPV infection and cervical intraepithelial neoplasia in Western countries.
Eur J Endocrinology, 2003
Background: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of t... more Background: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of transforming growth factor-b (TGF-b), inhibin and activin activities into cells. TGF-b and inhibin-related proteins are growth factors that are expressed by several tissues and in pregnancy. They have a function in modulating the growth, differentiation and invasion of the placental trophoblast. Objective: To evaluate whether betaglycan is expressed by intrauterine tissues throughout gestation. Design and methods: Expression of betaglycan mRNA and protein was evaluated (by RT-PCR and immunohistochemistry, respectively) in trophoblast, decidua and fetal membranes collected during the first (n ¼ 6 elective terminations of pregnancy, between 8 and 12 gestational weeks) and third (n ¼ 6 elective caesarean sections, between 39 and 40 weeks) trimesters of pregnancy. Results: Betaglycan mRNA was expressed by all gestational tissues, independently of gestational age. Immunoreactive protein was found in decidual cells and in some chorionic, but not epithelial, amniotic cells. With respect to the placental localization, syncytiotrophoblast, but not cytotrophoblast, cells were intensively stained both in the placental bed and in the villous trophoblast, and in some cells within the stroma of terminal villi, of the first and third trimesters of pregnancy. Immunoreactive betaglycan was demonstrated in the endothelial cells of decidual vessels in both the first and third trimesters of pregnancy, whereas endothelial cells of fetal blood vessels in the villous were clearly represented only in first trimester samples, not in those of term placenta. Conclusions: Betaglycan mRNA and peptide are expressed by the trophoblast, the decidua and the fetal membranes, but the localization of the peptide in vessel walls is dependent on gestational age.
Clinical Cancer Research, Dec 1, 1999
pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cel... more pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cellular growth and differentiation. Because recent functional studies have indicated that the expression of the RB-related proteins p107 and pRb2/p130 are tightly cell cycle regulated, we were interested in investigating their expression along with cellular kinetic characteristics and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pRb2/ p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients with NHLs of various histiotypes. The expression of these two RB-related proteins was correlated with the mitotic index, apoptotic index, and percentages of Ki-67(؉), cyclin A(؉), p34(؉), and cyclin B(؉) cells. The overall survival rate was evalu-ated according to the Kaplan-Meier method and the logrank test. We found a positive correlation between the percentages of cells positive for p107 and proliferative features such as mitotic index and percentage of Ki-67(؉) and cyclin A(؉) cells, whereas such correlation could not be demonstrated for the percentages of pRb2/p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected in untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and proliferation-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells. Interestingly, such cases showed the highest survival percentage (82.5%) after the observation period of 10 years. Thus, down-regulation of the RB-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation and why they respond so well to therapy.
Anticancer Research, 2006
Background: Oral contraception (OC) has been proclaimed by the IARC as a risk factor of cervical ... more Background: Oral contraception (OC) has been proclaimed by the IARC as a risk factor of cervical cancer (CC), on prolonged use by high-risk human papillomavirus (HPV) positive women. However, the available data are far from complete, and more evidence is necessary on the potential confounding effects of sexual behavior and HPV infection. The aim of the present was study to analyse the risk estimates for OC users in order to develop several intermediate end-point markers in cervical carcinogenesis. Patients and Methods: A cohort of 3,187 women, enrolled in a multi-center screening trial in three New Independent States (NIS) of the former Soviet Union (the NIS Cohort Study), was stratified into three groups according to their contraception modes: i) non-users of contraception, ii) non-OC users and iii) OC users. These groups were analysed for predictors of three outcome measures: a) exposure to HR-HPV; b) progression to high-grade cervical intraepithelial neoplasia (CIN2/3 and HSIL); and c) persistence/clearance of HR-HPV and cytological abnormalities during a prospective follow-up. Results: All three groups had an identical prevalence of HR-HPV (HCII and PCR), Pap smear abnormalities and CIN histology, but differed significantly (p=0.0001) with regard to all key variables of sexual behaviour, known as risk factors for CC. Predictors of HR-HPV, CIN2/3 and HSIL were different in the three groups, reflecting these different sexual preferences. Use of OC was not a significant predictor of CIN2/3 or HSIL in HPV-positive or HPVnegative women. Outcomes of cervical disease and HR-HPV infection were unrelated to contraception. In a multivariate regression model, mode of contraception was of no predictive value for either HR-HPV or high-grade CIN. Conclusion: Sexual behaviour is different among OC users, non-OC users and in nonusers of contraception; these risk factors predispose women to HR-HPV, high-grade CIN, and determine the outcome of their cervical disease/HR-HPV infection. The use of OC is not an independent risk factor for any of these intermediate end-point markers of cervical carcinogenesis. Failure to record these epidemiological data inevitably leads to erroneous conclusions about the role of OC as an independent risk factor of cervical cancer.
Bollettino della Società italiana di biologia sperimentale
The effects of hypophysectomy on the lymphoid organs were evaluated in Wistar rats by morphometri... more The effects of hypophysectomy on the lymphoid organs were evaluated in Wistar rats by morphometrical analysis: after 30 days the percentage of thymus cortical area and lymph node paracortical areas were reduced. In the thymus cortex, signs of orthological involution (e.c.: nodular cortex) appeared. A significant enlargement of lymph node cortical areas, containing a high number of germinal centers with degenerative changes, could be seen. These findings suggest a significant trophic action of hypophysis on thymus and, perhaps, an impaired lymph node antibody mediated response due to the loss of T-B cooperation.
Bollettino della Società italiana di biologia sperimentale
Morphometrical analysis of lymphoid organs has been performed 30 days after bilateral orchidectom... more Morphometrical analysis of lymphoid organs has been performed 30 days after bilateral orchidectomy in Wistar rats. The percentage of thymus cortical area and of lymph node paracortical areas (filled with large lymphoid cells) has been found increased. These morphological changes seem to indicate that orchidectomy enhance lymph node cell-mediated immune response in the rat.
American Journal Of Pathology
A comparison between neoplastic and nonneoplastic lymphoid cell nuclei within germinal centers of... more A comparison between neoplastic and nonneoplastic lymphoid cell nuclei within germinal centers of nodular lymphomas and of reactive follicular hyperplasias has been carried out with the help of a semiautomated image analyzer by measuring nuclear area, by assessing the presence or absence of invaginations, and by defining the form of the invagination. Nuclear areas are larger in lymphomas, where the invagination, if present, decreases in depth and increases in angle as the value of nuclear area becomes greater. Nuclei with such a large area and shallow invaginations are not present within the nonneoplastic germinal centers. Moreover, no correspondence has been found between neoplastic and nonneoplastic nuclei with regard to the form of the invagination, that is, its symmetry and angle. Therefore, it is possible to argue that the neoplastic nuclei in nodular lymphomas are different from the nuclei found in the sequential pathway of reactive germinal centers.
European journal of respiratory diseases
The report deals with a series of peribronchial and mediastinal lymph node silicotic lesions, whi... more The report deals with a series of peribronchial and mediastinal lymph node silicotic lesions, which were histologically and histochemically typical, in patients with bronchogenic cancer without any form of occupational dust exposure. The presence of a significant quantity of quartz was confirmed in the lesions by the use of backscatter electron imaging analysis, X-ray mapping and X-ray spectrometry. The lymph node lesions observed were actually silicotic in nature and had possible epidemiologic implications. There is a need for further investigations on larger series of cases to evaluate the incidence of the phenomenon and correlations between lung changes and lymph node lesions.
Archiv für Geschwulstforschung
To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mas... more To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the lymph nodes with the functional assays measuring cytotoxic and tumor cell membrane-bound antibodies in mouse sera. Regional and non-regional (RLN, NRLN) lymph nodes, were subjected to stereological analysis to determine the volume fractions (Vv) of the cortex (C), the paracortex (PCA), the germinal centers (GC), and the medulla (M), using a computerized analysis system (IBAS I, Kontron). In both RLN:s and NRLN:s, lymphocyte subsets were identified and their ratios determined using the ABC (avidin-biotin peroxidase complex) technique and following monoclonal antibodies; Anti-Thy 1.2, Anti-Lyt 1, Anti-Lyt 2, and Anti-I-Ad. The 51Cr release assay was used to test the mouse sera for cytotoxic antibodies, and an indirect immunofluorescence (IF) technique to assess the sera for tumor cell membrane-bound antibodies. There was a marked enlargement of the RLN:s reaching the peak on day 12, due to increase of the Vv of the B-zone as well as of the T-zone. Evidence of distinct B-cell stimulation by the growing of P815X2 was provided by an early decrease of Thy1.2+/I-Ad+ cell ratio both in the RLN:s and in NRLN:s. This activation of B-cells seems to be parallel to the elevation of Lyt1+/Lyt2+ ratio in T-cell region on day 6. The IF-tests for or the presence of tumor cell membrane-bound antibodies were almost invariably negative. With exception of two sera, the 51Cr-release assay for cytotoxic antibodies against P815X2 targets was negative. The present study confirms the previous observations on failure to find circulating cytotoxic or cell membrane-bound antibodies in DBA/2 mice bearing P815X2 mastocytoma, despite the morphologically well definable activation in RLN:s and in NRLN:s of the B-cell areas. This is in alignment with the findings in the majority of human tumors, where B-cell predominance in RLN:s does not represent a favourable prognostic sign.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology
The areas and shapes of cell nuclei were morphometrically analyzed in peripheral T-zone lymphomas... more The areas and shapes of cell nuclei were morphometrically analyzed in peripheral T-zone lymphomas, which have a characteristic nuclear pleomorphism, as well as in paracortical areas of normal and reactive lymph nodes; the aim of the study was to compare the neoplastic and nonneoplastic lymphoid cell populations. Although the means and standard deviations (SDs) of nuclear area and shape features differed significantly between the T-zone lymphomas, reactive nodes and normal nodes, there was considerable overlap between the lymphomas and the reactive lymph nodes in all of the features investigated. Therefore, the composition of populations of nuclei was studied. In lymphomas, the frequencies of regular and irregular nuclei were about the same in all nuclear area classes, whereas increasingly larger nuclei had an increasingly regular shape in reactive lymph nodes. An attempt to classify the cells, divided into those with small nuclei (less than 25 sq microns) and those with large nuclei (greater than 25 sq microns), on the basis of their morphometric shape features showed the usefulness of form factors in the class of nuclei with a large area. The results show that, while means and SDs of nuclear area and shape are not very accurate descriptors of the differences between the T-zone lymphomas and nonneoplastic lymph nodes, analysis of the percentage of regularly shaped nuclei in a certain nuclear area class can describe the differences much more accurately. The compositional differences in nuclear shape are in agreement with subjective impressions and can objectively support the pathologist's qualitative impression of pleomorphism in malignant T-zone lymphomas.