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Biomedical subjects

M Piantelli

Publications and source records attributed to M Piantelli.

At least 37 records · Page 2Linked to original sources
PubMed1996

nm23 in ovarian cancer: correlation with clinical outcome and other clinicopathologic and biochemical prognostic parameters.

PURPOSE: The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients. PATIENTS AND METHODS: Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody. RESULTS: Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles. CONCLUSION: The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.

Blotting, Northern↗
PubMed1996

Quercetin and the growth of leukemic progenitors.

The bioflavonoid quercetin (3, 3', 4', 5-7-pentahydroxyflavone) inhibits in a dose-dependent manner the in vitro growth of acute leukemias and enhances the anti-proliferative activity of cytosine arabinoside. Quercetin exerts a blocking action of cell transition from the G0/G1 to the S phase of the cell cycle. Acute myeloid leukemias (AML)-M3,-M4 and -M5, and acute lymphoid leukemias (ALL) were more sensitive to quercetin than AML-M1 and -M2 subtypes. The sensitivity of leukemic progenitors to the growth inhibitory effect of quercetin significantly correlated with their clonogenic efficiency. We postulate that quercetin exerts its growth inhibitory action by interaction with type II estrogen binding sites and subsequent induction of Transforming Growth Factor-beta 1 expression and secretion. Finally quercetin is synergistic with hyperthermia in inducing apoptosis of leukemic cells sparing normal stem cell progenitors. Taken together these results stress the potential role of quercetin in the treatment of acute leukemias and its in vitro use in purging procedures for autologous bone marrow transplantation.

Animals↗
PubMed1995

Spontaneous and glucocorticoid-induced apoptosis in human mature T lymphocytes.

Glucocorticoid (GC)-induced apoptosis is a well-recognized physiologic regulator of murine T-cell number and function. We have analyzed its mechanisms in human mature T cells, which have been thought to be insensitive until recently. Peripheral blood T cells showed sensitivity to GC-induced apoptosis soon after the proliferative response to a mitogenic stimulation, and were also sensitive to spontaneous (ie, growth factor deprivation-dependent) apoptosis. CD8+ T cells were more sensitive to both forms than CD4+ T cells. Acquisition of sensitivity to GC-induced apoptosis was not associated with any change in number or affinity of GC receptors. Both spontaneous and GC-induced apoptosis were increased by the macromolecular synthesis inhibitors, cycloheximide (CHX) and puromycin. A positive correlation between the degree of protein synthesis inhibition and the extent of apoptosis was observed. Interleukin-2 (IL-2) IL-4, and IL-10 protected (IL-2 > IL-10 > IL-4) T cells from both forms of apoptosis in a dose-dependent manner. Our data suggest that spontaneous and GC-induced apoptosis regulate the human mature T-cell repertoire by acting early after the immune response and differentially affecting T-cell subsets.

Apoptosis↗
PubMed1995

Methyl-p-hydroxyphenyllactate-esterase activity and type-II estrogen-binding sites in ovarian cancer: correlation with biological and clinico-pathological parameters.

We examined the levels of activity of methyl-p-hydroxyphenyllactate esterase (MeHPLA-ase) and cytosolic Type-II-estrogen-binding sites (Type-II EBS) in 61 and 71 cases, respectively, of primary ovarian cancer. MeHPLA-ase activity and Type-II EBS were seen to by asymmetrically distributed, in that levels were skewed towards the lower values. A statistically significant direct correlation was found between MeHPLA-ase activity and Type-II EBS. MeHPLA-ase activity and Type-II EBS were inversely correlated with ER and PR levels and showed a trend towards inverse correlation with the percentage of cells in S-phase of the cell cycle. MeHPLA-ase activity and Type-II EBS did not correlate with clinico-pathological parameters. The median MeHPLA-ase activity tended to be higher in responders than in unresponsive patients, but statistical significance was not reached. Higher Type-II-EBS levels were found in cases showing complete and partial response to chemotherapy than in cases which did not respond. A statistically significant relationship was found between high MeHPLA-ase activity and longer overall survival.

Carboxylic Ester Hydrolases↗
PubMed1995

Interaction of tamoxifen with cytosolic and nuclear type II estrogen binding sites (type II EBS).

The aim of this study was to investigate the interaction of tamoxifen (TAM) with the so-called Type II estrogen binding sites (Type II EBS) in both the cytosolic and the nuclear fraction of the ER-negative A 2780 human ovarian cancer cell line and in an ER-negative ovarian cancer tissue. Although cytosolic and nuclear Type II EBS in A 2780 cells showed substantially similar binding characteristics in terms of ligand affinity and specificity, TAM, while exhibiting the ability to displace [3H]estradiol from cytosolic Type II EBS failed to interact with nuclear Type II EBS. The ability of TAM to interact only with cytosolic Type II EBS seems also to be a characteristic of ovarian cancer tissue and to be shared by several TAM metabolites. The hypothesis that the interaction of TAM with cytosolic Type II EBS could mobilize the true endogenous ligand of Type II EBS which would become available for binding to nuclear Type II EBS was tested by incubating the nuclear fraction with the cytosolic fraction. In the presence of cytosol, TAM acquires the ability to displace the tracer from nuclear Type II EBS but when the cytosolic fraction was DCC, stripped in order to remove the endogenous ligand, the competing activity of TAM for nuclear Type II EBS was abolished. Our results suggest that TAM does not interact with nuclear Type II EBS, but can favor the nuclear binding of endogenous ligand by displacing it from cytosolic Type II EBS.

Binding Sites↗
PubMed1995

Quercetin inhibits the growth of leukemic progenitors and induces the expression of transforming growth factor-beta 1 in these cells.

We previously showed that quercetin (3,3',4',5,7 pentahydroxyflavone) inhibits in a dose-dependent manner the growth of acute leukemias and is able to enhance the antiproliferative activity of cytosine arabinoside. We show here that quercetin inhibits the clonogenic activity of 20 of 22 acute leukemias (AL; 4 M1-AML, 3 M2-AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL). In the present report, we show that the induction of transforming growth factor-beta 1 (TGF-beta 1) in leukemic blasts is one of the growth-inhibitory mechanisms of quercetin in these cells. This observation was supported by the following data. (1) Quercetin-sensitive leukemic blasts, when treated with quercetin, secrete large amounts of TGF-beta 1 in the medium and show positivity for TGF-beta 1-immunoreactive material in the cytoplasm. (2) At a concentration of 8 mumol/L, antisense TGF-beta 1 oligonucleotides prevent the growth-inhibitory action of quercetin. (3) Anti-TGF-beta 1 neutralizing monoclonal antibodies can prevent almost completely the growth-inhibitory activity of quercetin. The analysis of quercetin-resistant cases confirmed as well the central role of TGF-beta 1 in the growth-inhibitory activity of quercetin. In conclusion, quercetin can act as a cytostatic agent for leukemic cells by modulating the production of TGF-beta 1.

Bone Marrow↗
PubMed1995

Tamoxifen and quercetin interact with type II estrogen binding sites and inhibit the growth of human melanoma cells.

The mechanism of the antiproliferative activity of tamoxifen on melanoma cells in vitro and in vivo is poorly understood, as it is not mediated by the antiestrogenic properties of tamoxifen. Using a whole-cell assay and nuclear and cytosolic radio-binding experiments with [3H]-estradiol as tracer, we found that MNT1, M10, and M14 melanoma cell lines as well as primary tumors expressed type II estrogen binding sites that bind tamoxifen and the flavonoid quercetin with similar affinity (KD 10-25 nM). Cell count and clonogenic assay showed both compounds to inhibit melanoma cell growth in a concentration-dependent manner in the range of concentrations between 1 nM and 1 microM. Neither the pure antiestrogen ICI-182780 nor the 3-rhamnosylglucoside of quercetin, rutin, bound to type II estrogen binding sites or inhibited cell growth. Our results suggesting that tamoxifen and quercetin can inhibit melanoma cell growth by interacting with type II estrogen binding sites help explain the reported effectiveness of tamoxifen, particularly in estrogen-receptor-negative tumors, and stress the potential role of quercetin in the treatment of melanoma.

Binding Sites↗
PubMed1995

Effect of synthetic and naturally occurring chalcones on ovarian cancer cell growth: structure-activity relationships.

This study was carried out to determine the effect of 15 different natural and synthetic chalcones on the proliferation of both established and primary ovarian cancer cells expressing type II oestrogen binding sites (type II EBS). The binding affinity of chalcones for type II EBS was also tested. At concentrations from 0.1 to 10 microM, chalcones inhibited ovarian cancer cell proliferation and [3H]oestradiol ([3H]E2) binding to type II EBS. Considering the structure-related variation in IC50 (concentration resulting in a 50% inhibition of cell growth) and Di50 (concentration resulting in a 50% displacement of [3H]E2 bound to type II EBS), it appeared that the presence of an alpha-beta double bond, the hydroxylation in 3 or 2 of ring B and the absence of a prenyl group were important to both the antiproliferative and binding activity. Structure-related variations in IC50 and Di50 were significantly concordant (Fisher's exact test: P = 0.0291), suggesting that there may be a type II EBS-mediated mechanism for chalcone antiproliferative activity. Our data indicate that chalcones could be considered as potential new anticancer drugs.

Binding Sites↗
PubMed1994

Quercetin enhances transforming growth factor beta 1 secretion by human ovarian cancer cells.

Our study demonstrates that quercetin (Q)-induced growth-inhibitory activity in ovarian cancer cells may be mediated by modulation of transforming growth factor beta 1 (TGF beta 1) production. We used the OVCA 433 cell line which is very sensitive to the anti-proliferative effect of Q and expresses high-affinity, low-capacity TGF beta 1 receptors. Conditioned medium (CM) from Q-treated cells is able to displace 125I-TGF beta 1 from binding to its receptor; moreover Q (10 microM) increases TGF beta 1 activity in CM in a time-dependent fashion starting after 4 hr and reaching a maximum by 24 hr of Q treatment. Q-induced growth inhibition is reversed by a neutralizing anti-TGF beta 1 MAb both in OVCA 433 and in a clonogenic assay of cells from a primary ovarian tumor. Q-induced increase of TGF beta 1 activity in CM is specific since other anti-proliferative compounds, such as Dexamethasone, which is as active on the cell cycle as Q, had no effect on TGF beta 1 secretion. Northern-blot analysis of TGF beta 1 mRNA levels at various times of Q (10 microM) exposure revealed that there was no increase, suggesting that regulation of TGF beta 1 occurs at posttranscriptional levels.

Cell Division↗
PubMed1994

Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target.

This study demonstrates that the flavonoid quercetin (Q), a plant-derived compound with low toxicity in vivo, greatly potentiates the growth-inhibitory activity of Adriamycin (ADR) on MCF-7 ADR-resistant human breast cancer cells. The effect of Q was dose-dependent at concentrations ranging between 1 and 10 microM. Since ADR resistance in these cells is associated with the expression of high levels of P-glycoprotein (Pgp), we evaluated the effect of Q and related flavonoids of Pgp activity in cytofluorographic efflux experiments with the fluorescent dye rhodamine 123 (Rh 123). Our results indicate that Q and 3-OMe Q (3',4',7-trimethoxyquercetin) but not the 3-rhamnosylglucoside of Q (rutin) inhibit the Pgp pump-efflux activity in a dose-related manner. Moreover, 10 microM Q reduces the expression of the immunoreactive Pgp in MCF-7 ADR-resistant cells as evaluated by cytofluorimetric assay. In conclusion, these findings provide a further biological basis for the potential therapeutic application of Q as an anti-cancer drug either alone or in combination with ADR in multidrug-resistant breast tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Growth-inhibitory effect of quercetin and presence of type II estrogen binding sites in primary human transitional cell carcinomas.

Eight cases of transitional cell carcinoma (TCC) of the bladder were investigated for the presence of estrogen receptors (ER) and Type II estrogen binding sites (Type II EBS). All these tumors specifically expressed type II EBS, while only 3 of 8 cases contained low amounts of ER. All the cases assayed for the presence of both nuclear and cytoplasmic type II EBS revealed the presence of these binding sites in the two compartments. Both cytoplasmic and nuclear receptors were similar to type II EBS described in other tissues relative to their binding specificity for estrogens and quercetin and their sensitivity to reducing agents. Quercetin, 10 microM., was effective in inhibiting in vitro bromodeoxyuridine (BrdUdR) incorporation by TCC cells. Rutin, which bound little if any to type II EBS, did not show any inhibitory effect on in vitro BrdUdR incorporation by tumor cells, suggesting a type II EBS mediated effect of flavonoids. Although the mechanism of the antiproliferative activity of quercetin remains to be fully clarified, the possible therapeutic potential of quercetin and related flavonoids should be considered.

Aged↗
PubMed1994

Detection of growth hormone-producing cells in human thymus by immunohistochemistry and non-radioactive in situ hybridization.

It is well recognized that growth hormone (GH) may act as a growth and differentiation factor for the thymus gland. Recently, it has been reported that Pit-1/GHF-1 transcription factor, which controls the expression of both GH and prolactin, is expressed in stromal (not lymphoid) cells of human thymus. Here, we demonstrated by immunohistochemistry and in situ hybridization the presence of distinct GH-producing epithelial cell subsets in human thymus. The cells positive for GH mRNA and GH-immunoreactive substance are both located in the same thymus compartments, i.e., along the thymus capsule, in the subcapsular cortex, and within the septa. Local concentration of GH higher than systemic ones, in combination with other factors, may be important in regulating the thymic microenvironment necessary for T-lymphocyte differentiation.

Child, Preschool↗
PubMed1994

[Primary carcinoid of the umbilicus. Description of the 1st case].

A 78-year old male came to our observation presenting and enlargement of bilateral inguinal lymph nodes and a tumor of the mesogastric abdominal wall. Three years before the patient had been operated on for a primary tumor of the umbilicus with concomitant longstanding diarrhea. No histological examination was performed at that time. We performed a lymph node biopsy which demonstrated carcinoid metastasis. We went on to perform radical resection of the abdominal wall, regional lymphadenectomy and right hemicolectomy for malignant villous adenoma of the right colon. The abdominal defect was repaired by using Goretex mesh. Cyclic adjuvant alpha-interferon therapy was continued for more than 1 year, followed by long term therapy with longastatin. Twenty months after the operation the patient is in good clinical conditions and disease-free. On the basis of literature review our case appears to be the first primary carcinoid of the umbilicus.

Abdominal Muscles↗
PubMed1993

Quercetin induces type-II estrogen-binding sites in estrogen-receptor-negative (MDA-MB231) and estrogen-receptor-positive (MCF-7) human breast-cancer cell lines.

We show that flavonoids positively regulate type-II estrogen-binding site (type-II EBS) levels both in MCF-7 (ER-positive) and in MDA-MB231 (ER-negative) breast-cancer cells. Type-II EBS were measured by a whole-cell assay at 4 degrees C for 2.5 hr using [3H]-estradiol as tracer. In both cell lines the effect of quercetin (Q) was dose-related and already evident after 12 hr of Q treatment. The increase of type-II EBS levels after Q exposure requires both RNA and protein synthesis, since actinomycin D and cycloheximide completely abolished the stimulatory effect. The ability of flavonoids in inducing type-II EBS is well correlated with their relative binding affinity for type-II EBS. The flavonoid-induced enhancement of type-II EBS levels is accompanied by increased sensitivity of cancer cells to the inhibitory effect of low Q concentrations. Our data suggest that type-II EBS are ligand-regulated receptors.

Binding Sites↗
PubMed1993

Type II estrogen binding sites and antiproliferative activity of quercetin in human meningiomas.

Eleven cases of meningiomas were investigated for the presence of estrogen and progesterone receptors. These tumors specifically bound estradiol. This binding activity almost exclusively resulted from the presence of high numbers of type II estrogen binding sites (EBS). Estrogen receptors were absent or present at low concentrations. Competition analysis showed that the flavonoid, quercetin, competed for tritiated estradiol binding to type II EBS; both rutin and hesperidin did not. In addition, 10 microM quercetin, unlike rutin or hesperidin, was effective in inhibiting in vitro bromodeoxyuridine incorporation by meningioma cells. Although the mechanism of the antiproliferative activity of quercetin remains to be clarified, it is possible that this flavonoid may regulate cell growth through a ligand interaction with type II EBS.

Adult↗
PubMed1993

Type II estrogen-binding sites in human ovarian cancer: correlation with estrogen, progesterone, and epidermal growth factor receptor.

Type II estrogen-binding sites (Type II EBS) and the recently identified bioflavonoid-like ligand methyl-p-hydroxyphenyllactate may be regarded as a growth regulatory system active on both normal and neoplastic tissues. It has been reported that, in addition to estrogen and progesterone receptors, primary ovarian cancers also express Type II estrogen binding sites. These sites are able to bind estrogenic compounds and also some naturally occurring flavonoids such as quercetin. In this study we report the presence of cytosolic Type II EBS in a series of 10 normal ovaries, 42 primary ovarian tumors, and 14 metastatic deposits. Scattered levels of Type II EBS were found in normal ovarian tissues (median, 1603 fM/mg protein, range, 271-4943). In primary ovarian tumors and in omental metastases median levels of Type II EBS were 835 fM/mg protein (range, 134-4875) and 758 fM/mg protein (range, 204-2007), respectively. Although Type II EBS tend to be higher in normal than in malignant tissues the difference was not statistically significant. No correlation was found between Type II EBS levels and the common clinicopathological characteristics of the tumors. Moreover there was no relation between Type II EBS and estrogen and epidermal growth factor receptors. A significative inverse correlation with progesterone receptor levels was observed. The presence of Type II EBS in ovarian cancer could be of clinical importance since it has been demonstrated that bioflavonoids, through the interaction with Type II EBS, may exert a growth inhibitory activity both alone or in combination with chemotherapeutic agents on ovarian cancer cell lines and primary tumors.

Aged↗
PubMed1992

Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors.

We studied the effect of quercetin (Q) on the proliferation of HT-29, WiDr, COLO 201, and LS-174T human colon cancer cell lines. Q, between 10 nM and 10 microM, 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 G0/G1 phase. Using a whole-cell assay with 17 beta-[3H]-estradiol as tracer, we demonstrated that all these cell lines contain type-II estrogen-binding sites (type-II EBS). By using Q and other chemically related flavonols (3,7-4'-trimethoxyquercetin, 3,7,3',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-II EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type-II EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-II EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-II 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.

Adenocarcinoma↗