Papers by franco oreste ranelletti
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Hepatology, Oct 1, 1991
Cytosolic receptors for estrogen and progesterone were assayed in 50 gallbladders from 29 women a... more Cytosolic receptors for estrogen and progesterone were assayed in 50 gallbladders from 29 women and 21 men who had cholecystectomies because of cholelithiasis. High-affinity (equilibrium dissociation constant, KD = 0.46 +/- 0.23 nmol/L of 24 cases) estrogen receptors were detected in 20 of 29 gallbladders from women (range = 1.6 to 32 fmol/mg protein; mean +/- S.D. = 10.9 +/- 8.1), whereas in men only 4 of 21 specimens contained detectable estrogen receptors. High-affinity (KD = 0.45 +/- 0.17 nmol/L; mean +/- S.D. of 41 cases) progesterone receptors were found in 25 of 29 gallbladders of women (range = 2 to 62 fmol/mg protein; mean +/- S.D. = 19.2 +/- 14.4) and in 16 of 21 gallbladders of men (range = 4 to 36 fmol/mg protein; mean +/- S.D. = 12.5 +/- 8.5). There is a statistically significant difference between men and women in the proportion of estrogen receptor-positive gallbladders, 19% and 69% for men and women, respectively. Progesterone receptors are present in similar proportion in the gallbladders of men (72.2%) and women (86.2%). In women a positive correlation between estrogen and progesterone receptors was found. Even in the absence of estrogen receptors, the gallbladders of men express progesterone receptors at levels similar to those observed in women. At least in cholelithiasic gallbladders, this suggests that a sex difference exists in the coexpression of estrogen and progesterone receptors. Such a difference could be related with the higher gallstone incidence in women than in men.
Epithelial Tumors of the Thymus, 1997
Interleukin-6 (IL-6) is a multifunctional cytokine, which regulates the immune response by polycl... more Interleukin-6 (IL-6) is a multifunctional cytokine, which regulates the immune response by polyclonal B cell activation and differentiation; it enhances peripheral T lymphocyte responses, thymocyte growth and induction of cytotoxic T cell differentiation [1]. Many clinical and experimental observations suggest that IL-6 could be involved in pathogenetic processes; in fact, elevated levels of IL-6 have been detected during autoimmune diseases, infections, and tissue injury. It has been shown that cultured human thymic epithelial cells (TECs) are able to secrete IL-6 both constitutively and after stimulation with interleukin-1s (IL-1s) and/or LPS [2]. Some authors have suggested that TEC IL-6 production may be related to the thymic abnormalities found with a high frequency in Myasthenia Gravis (MG) [3]. Thymoma is found in about 10% of the MG patients, while hyperplastic thymus is often observed in MG female patients with young-age at onset. The thymus has estrogen receptors [4]; these steroids modulate IL-6 production in different tissues, such as bone marrow-derived stromal cells, osteoblasts and blood mononuclear cells in vitro [5, 6, 7] and are able to increase secretion of thymic hormones by TECs in vitro [8].
PubMed, Jul 1, 1997
We have studied 25 thymomas by both immunohistochemistry and in situ hybridization for the presen... more We have studied 25 thymomas by both immunohistochemistry and in situ hybridization for the presence of growth hormone (GH)-producing cells. Our results indicate that 1) GH-immunoreactive cells were present in 13 of 17 thymomas of cortical and predominantly cortical type but not in medullary (spindled) thymomas (n = 3) or low- to high-grade thymic carcinomas (n = 5), 2) GH-positive cells were mainly located at the periphery of the neoplastic lobules, at the periphery of the perivascular spaces and in the areas of medullary differentiation, 3) cells containing GH mRNA appeared at locations similar to those of GH-immunoreactive cells, and 4) GH-immunoreactive material was present only in the epithelial cell component as revealed by immunoelectron microscopy. In conclusion, this paper demonstrates the occurrence of GH-producing cells in noncarcinoid thymic tumors. The relevance of GH in thymoma cell biology requires additional investigations.
Journal of Oral Pathology & Medicine, Apr 1, 2002
The human DNA mismatch repair (hMMR) system plays an important role in reducing mutation and main... more The human DNA mismatch repair (hMMR) system plays an important role in reducing mutation and maintaining genomic stability. The MMR system in human cells is composed of at least six genes (hMSH2, hMLH1, hMSH3, hPMS1, hPMS2 and GTBP/hMSH6). In particular, hMSH2 and hMLH1 are expressed in human cells that are undergoing rapid renewal; their reduced expresion has been reported in several tumors. We examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in 25 ameloblastomas. All ameloblastomas expressed hMSH2 and hMLH1 proteins in the outer layer of epithelial cells. The localization of the staining was exclusively nuclear. These data suggest that the development and progression of these tumors do not depend on a defect in the hMMR system.
Gynecologic Oncology, May 1, 2002
Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. ... more Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. Abnormalities of epidermal growth factor receptor (EGFR) and Her-2/neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB family pathways has been proposed. We investigated by immunohistochemistry the expression of COX-2, EGFR, and Her-2/neu in a series of advanced primary ovarian cancers. The study included 76 consecutive stage IIIC-IV ovarian cancer patients with measurable disease after first surgery. Immunohistochemistry was performed on paraffin-embedded sections with rabbit antiserum against COX-2, murine monoclonal antibody (MoAb) 300G9 against Her-2/neu, and monoclonal antibody 108 against EGFR. No association among COX-2, EGFR, and HER-2/neu was found. COX-2 positivity was found in a statistically significant higher percentage of unresponsive cases (80.0%) than in patients responding to chemotherapy (35.7%) (P = 0.0008). The association between COX-2 positivity and poor chance of response to treatment was retained in multivariate analysis. In the subgroup of patients who underwent explorative laparotomy COX-2-positive cases showed a shorter overall survival (P = 0.049). COX-2 could represent a possible new marker of sensitivity to platin-based chemotherapy in ovarian cancer. The lack of association of COX-2 with EGFR or Her-2/neu suggests that the ability of COX-2 to predict tumor sensitivity to chemotherapy is not dependent on EGFR or Her-2/neu status and could be independently associated with prognosis. In this context, the availability of agents able to specifically interfere with COX-2, Her-2/neu, or EGFR tyrosine kinase is of potential interest.
Cancer, Jul 31, 2002
Cyclooxygenase-2 (COX-2) is overexpressed in endometrial hyperplasia and carcinoma, but no data h... more Cyclooxygenase-2 (COX-2) is overexpressed in endometrial hyperplasia and carcinoma, but no data have been reported until now about the expression of COX-2 and its possible clinical significance in endometrial carcinoma. We investigated by immunohistochemistry the expression of COX-2 in a single institutional series of primary untreated endometrial carcinoma patients. The relationship between COX-2 expression and microsatellite instability (MI) status was also analyzed. The study was conducted on 69 primary untreated endometrial carcinoma patients who were admitted to the Department of Obstetrics and Gynecology, Catholic University of Rome. Immunohistochemistry was performed by using rabbit polyclonal antiserum against human COX-2. Analysis of MI was performed for 47 patients with endometrial carcinomas. Twenty-seven patients (39.1%) were scored as COX-2 positive. COX-2 positivity was higher (60.8%) in endometrial carcinoma with cervical or extrauterine involvement than in tumors limited to the corpus (28.3%; P = 0.0174). COX-2 positivity increased from Grade 1 (13.6%) to Grade 2 (41.7%) to Grade 3 (60.9%) endometrial carcinoma (P = 0.0049). Interestingly, considering early International Federation of Gynecology and Obstetrics stage patients (n = 53), the percentage of COX-2 positivity was higher in patients with deep myometrial invasion (66.7%) than in patients without or less than 50% myometrial invasion (15.6%) (P = 0.0003). No association between COX-2 and MI status was found. COX-2-positive patients showed a trend to a shorter disease-free survival than COX-2-negative patients (P = 0.09). COX-2 is expressed in a high percentage of a large series of primary endometrial tumors and its expression may be associated closely with parameters of tumor aggressiveness The possible prognostic role of COX-2 in endometrial carcinoma deserves further study.
Journal of Cardiac Surgery, Aug 23, 2019
Background: Cardiac synovial sarcoma (CSS) is an extremely rare malignant tumor with a severe pro... more Background: Cardiac synovial sarcoma (CSS) is an extremely rare malignant tumor with a severe prognosis, due to frequent relapses and metastases. To obtain useful information for treatment protocols, we analyzed survival and therapy data from the cases reported in the literature. Methods: A search of MEDLINE was performed throughout December 2018. Using key words relating to primary CSS, we collected from the literature a total of 97 cases, mainly consisting of single case reports. To identify predictors of overall survival, statistical analyses were performed on a selected cohort of 55 patients for whom relevant clinicopathological data were available, including surgery and adjuvant therapy. Results: The univariable analysis revealed that patients in their first three decades of life have better overall survival. The univariable analysis also showed that patients not receiving adjuvant chemotherapy are at increased risk of death. In the multivariable analysis, tumor resection and chemotherapy are factors significantly improving overall survival. Conclusion: The survival of patients with CSS is positively influenced by a young patient's age and greatly improved by the administration of chemotherapy, even in the absence of tumor resection.
Carcinogenesis, Aug 18, 2006
Results from some intervention trials indicated that supplemental b-carotene enhanced lung cancer... more Results from some intervention trials indicated that supplemental b-carotene enhanced lung cancer incidence and mortality in chronic smokers. The aim of this study was to verify the hypothesis that high concentrations of the carotenoid, under the pO 2 present in lung (100-150 mmHg), may exert deleterious effects through a prooxidant mechanism. To test this hypothesis, we examined the interactions of b-carotene and cigarette smoke condensate (tar) on the formation of lipid peroxidation products in rat lung microsomal membranes enriched in vitro with varying b-carotene concentrations (from 1 to 10 nmol/ mg prot) and then incubated with tar (6-25 mg/ml) under different pO 2. As markers of lipid peroxidation, we evaluated the levels of conjugated dienes and malondialdehyde, possessing mutagenic and pro-carcinogenic activity. The exposure of microsomal membranes to tar induced a dose-dependent enhancement of lipid peroxidation, which progressively increased as a function of pO 2. Under a low pO 2 (15 mmHg), b-carotene acted clearly as an antioxidant, inhibiting tar-induced lipid peroxidation. However, the carotenoid progressively lost its antioxidant efficiency by increasing pO 2 (50-100 mmHg) and acted as a prooxidant at pO 2 ranging from 100 to 760 mmHg in a dose-dependent manner. Consistent with this finding, the addition of a-tocopherol (25 mM) prevented the prooxidant effects of the carotenoid. b-Carotene auto-oxidation, measured as formation of 5,6-epoxy-b,b-carotene, was faster at high than at low pO 2 and the carotenoid was more rapidly consumed in the presence of tar. These data point out that the carotenoid may enhance cigarette smoke-induced oxidative stress and exert potential deleterious effects at the pO 2 normally present in lung tissue.
Gynecologic Oncology, Oct 1, 2004
The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-... more The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors. Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive. Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22). COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis.
International Journal of Radiation Oncology Biology Physics, 2003
Purpose: To investigate whether cyclooxygenase-2 (COX-2) could be a marker of clinical outcome in... more Purpose: To investigate whether cyclooxygenase-2 (COX-2) could be a marker of clinical outcome in cervical cancer patients undergoing concomitant chemoradiation plus surgery. Methods and Materials: The study included 33 locally advanced cervical cancer patients; all underwent neoadjuvant chemoradiation, and responsive patients underwent radical surgery. Immunohistochemistry was performed with rabbit antiserum against COX-2. Results: COX-2 integrated density values (IDVs) in the tumor component ranged from 1.4 to 72.3 (median 15.0); in stromal inflammatory cells, COX-2 IDVs ranged from 1.4 to 96.0 (median 16.0). A statistically significant inverse relation was found between the COX-2 IDVs of the tumor vs. the stromal inflammatory component (r ؍ ؊0.52, p ؍ 0.0017). When the ratio between COX-2 IDV in the tumor vs. the stromal compartment was <1, it was considered to indicate cervical tumor with COX-2 expression in the tumor component lower or equivalent to COX-2 expression in the stroma. According to the chosen cutoff value, 17 (51.5%) of 33 were scored as having a high (>1) tumor/stroma COX-2 IDV ratio. Patients with a high tumor/stroma COX-2 IDV ratio had a shorter disease-free survival than did those with a low tumor/stroma COX-2 IDV ratio (p ؍ 0.030). Similarly, those with a high tumor/stroma COX-2 IDV ratio had a shorter overall survival (p ؍ 0.033). Conclusion: The assessment of COX-2 status in both the tumor and the stromal compartment could provide additional information in the prognostic characterization of cervical cancer patients administered concomitant chemoradiation plus surgery.
International Journal of Cancer, Feb 1, 1992
We studied the effect of quercetin (0) on the proliferation of HT-29, WiDr, COLO 20 I, and LS-I 7... more We studied the effect of quercetin (0) on the proliferation of HT-29, WiDr, COLO 20 I, and LS-I 7 4 1 human colon cancer cell lines. Q, between I0 nM and I0 pM, exerted a dose-dependent, reversible inhibition of cell proliferation. Cell-cycle analysis revealed that the growth-inhibitory effect of Q was due to a blocking action in the G,/G, phase. Using a whole-cell assay with I7~-F'H]-estradiol as tracer, we demonstrated that all these cell lines contain type-ll estrogen-binding sites (type-ll EBS). By using Q and other chemically related flavonols (3,74'-trimethoxyquercetin, 3,7,3 ',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-ll EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type4 EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-ll EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-ll EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers.
Carcinogenesis, Feb 1, 1998
To investigate the possibility that canthaxanthin inhibits cancer cell growth by inducing apoptos... more To investigate the possibility that canthaxanthin inhibits cancer cell growth by inducing apoptosis, human WiDr colon adenocarcinoma and SK-MEL-2 melanoma cells were treated with two different doses of the carotenoid for 48 h. Canthaxanthin was incorporated and/or associated to cells. The treatment with the carotenoid caused growth inhibition in both cell types. Concomitantly, apoptosis was induced. Increasing time of exposure and carotenoid concentration, this effect was more pronounced. At 48 h, the percentages of apoptotic cells were 13 and 15, using 1 µM canthaxanthin, and 18 and 20, using 10 µM canthaxanthin in WiDr and SK-MEL-2 cells, respectively. This study represents the first demonstration that canthaxanthin is able to induce apoptosis in tumour cells.
International Journal of Gynecologic Cancer, Sep 1, 2004
International Journal of Gynecological Cancer, Mar 1, 2003
COX-2 overexpression has been associated with parameters of tumor aggressiveness and unfavourable... more COX-2 overexpression has been associated with parameters of tumor aggressiveness and unfavourable clinical outcome in solid tumors. We investigated by immunohistochemistry the expression of COX-2 in normal vulvar tissue (n1⁄4 18), NNED lichen sclerosus (LS, n1⁄4 6) and squamous cell hyperplasia (SCH, n1⁄4 7), vulvar intraepithelial neoplasia (VIN, n1⁄4 20) and invasive vulvar cancer (IVC, n1⁄4 36). Sections were incubated with rabbit polyclonal antiserum against human COX-2. The results were reported as mean þ/ standard error (SE). Kruskal-Wallis non parametric test was used to analyze the distribution of COX-2 staining values in IVC according to clinico-pathological parameters. In normal vulvar skin COX-2 is expressed in a few basal cells. On the other hand, we found strong COX-2 immunoreaction spread over the entire epithelium of high grade VIN with respect to low grade VIN, where only the basal layers show COX-2 immunostaining. NNED, such as SCH and LS, exhibited intense cytoplasmic COX-2 immunoreaction. In IVC, higher levels of tumor/stroma COX-2 IDV ratio were found in stage III-IV (mean þ/ SE1⁄4 3.5þ/ 0.8) than stage I-II disease (mean þ/ SE1⁄4 1.4þ/ 0.3) (p value1⁄4 0.040). In stage I, tumor/ stroma COX-2 IDV values were higher in T1b than T1a cases (mean þ/ SE1⁄4 1.6þ/ 0.3 vs mean þ/ SE1⁄4 0.6þ/ 0.1) (p1⁄4 0.033). Moreover, we observed higher tumor/stroma COX-2 IDV in cases with metastatic lymph node than cases ithout node involvement (mean þ/ SE1⁄4 3.5þ/ 0.8 vs mean þ/ SE1⁄4 1.3þ/ 0.4) (p1⁄4 0.037).This study suggests that COX-2 expression may contribute to vulvar tumorigenesis and progression. The correlation of tumor/stroma COX-2 IDV ratio with tumor extension and metastatic lymph node involvement implies that this biological marker could have a prognostic role in IVC.
BMC Cancer, Jun 27, 2022
Background: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome h... more Background: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. Methods: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. Results: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029). Conclusions: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.
Oncology Reports, Nov 1, 2003
Overexpression of cyclooxygenase-2 (COX-2), characterizes tumors with high potential for local in... more Overexpression of cyclooxygenase-2 (COX-2), characterizes tumors with high potential for local invasion and lymph node involvement. We investigated the expression of COX-2 in primary tumors and metastatic regional lymph nodes (TDL) from untreated and chemotherapy treated cervical cancer, as well as vulvar cancer. Immunostaining of COX-2, expressed as values of COX-2 intensity density (COX-2 IDV) was performed on 57 metastatic TDL and 24 corresponding primary rumors from 14 cervical and 9 vulvar cancer patients admitted to the Department of Obstetrics and Gynecology, Catholic University of Rome. In 6 locally advanced cervical cancer tissue samples, from both primary tumor and TDL, were obtained after chemotherapy treatment. In untreated cervical cancer, COX-2 IDV in tumor cells from positive TDL were significantly lower (median 0.69, range 0.22-0.92) than those from primary tumors (median = 3.84, range 0.19-7.67) (p=0.011). In cervical cancer exposed to chemotherapy, COX-2 IDV in tumor cells from positive TDL were significantly lower (median = 2.06, range 1.48-6.52) than those from primary tumors (median = 6.4, range 4.5-13.7) (p=0.037). In vulvar cancer COX-2 IDV in tumor cells from positive TDL were lower (median = 0.39, range 0.02-6.09) than those from primary tumors (median = 2.49, range 0.71-8.10) (p=0.04). In conclusion, we showed that COX-2 expression is down-regulated in cervical and vulvar tumor cells invading the regional lymph nodes with respect to primary tumors, thus emphasizing the need for deeper insight into the tissue specific relation between tumor cells and node microenvironment.
The Journal of Urology, Sep 1, 1994
We studied the effect of quercetin (0) on the proliferation of HT-29, WiDr, COLO 20 I, and LS-I 7... more We studied the effect of quercetin (0) on the proliferation of HT-29, WiDr, COLO 20 I, and LS-I 7 4 1 human colon cancer cell lines. Q, between I0 nM and I0 pM, exerted a dose-dependent, reversible inhibition of cell proliferation. Cell-cycle analysis revealed that the growth-inhibitory effect of Q was due to a blocking action in the G,/G, phase. Using a whole-cell assay with I7~-F'H]-estradiol as tracer, we demonstrated that all these cell lines contain type-ll estrogen-binding sites (type-ll EBS). By using Q and other chemically related flavonols (3,74'-trimethoxyquercetin, 3,7,3 ',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-ll EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type4 EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-ll EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-ll EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers.
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Papers by franco oreste ranelletti