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Biomedical subjects

G Ambrosini

Publications and source records attributed to G Ambrosini.

At least 55 records · Page 3Linked to original sources
PubMed1997

Activation-dependent exposure of the inter-EGF sequence Leu83-Leu88 in factor Xa mediates ligand binding to effector cell protease receptor-1.

Binding of factor Xa to human umbilical vein endothelial cells (HUVEC) is contributed by effector cell protease receptor-1 (EPR-1). The structural requirements of this recognition were investigated. Factor Xa or catalytically inactive 5-dimethylaminonaphthalene-1sulfonyl (dansyl) Glu-Gly-Arg-(DEGR)-chloromethylketone-factor Xa bound indistinguishably to HUVEC and EPR-1 transfectants, and inhibited equally well the binding of 125I-factor Xa to these cells. Similarly, factor Xa active site inhibitors TAP or NAP5 did not reduce ligand binding to EPR-1. A factor X peptide duplicating the inter-EGF sequence Leu83-Phe84-Thr85-Arg86-Lys87-Leu88- (Gly) inhibited factor V/Va-independent prothrombin activation by HUVEC and blocked binding of 125I-factor Xa to these cells in a dose-dependent manner (IC50 approximately 20-40 microM). In contrast, none of the other factor X peptides tested or a control peptide with the inter-EGF sequence in scrambled order was effective. A recombinant chimeric molecule expressing the factor X sequence Leu83-Leu88 within a factor IX backbone inhibited binding of 125I-factor Xa to HUVEC and EPR-1 transfectants in a dose-dependent fashion, while recombinant factor IX or plasma IXa had no effect. An antibody generated against the factor X peptide 83-88, and designated JC15, inhibited 125I-factor Xa binding to HUVEC. The JC15 antibody bound to factor Xa and the recombinant IX/X83-88 chimera in a concentration dependent manner, while no specific reactivity with factors X or IXa was observed. Furthermore, binding of 125I-factor Xa to immobilized JC15 was inhibited by molar excess of unlabeled factor Xa, but not by comparable concentrations of factors X or IXa. These findings identify the inter-EGF sequence Leu83-Leu88 in factor Xa as a novel recognition site for EPR-1, and suggest its potential role as a protease activation-dependent neo-epitope. This interacting motif may help elucidate the contribution of factor Xa to cellular assembly of coagulation and vascular injury.

Binding Sites↗
PubMed1997

A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.

Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.

Adult↗
PubMed1997

Combined chemotherapy and radiation with selective organ preservation for muscle-invasive bladder carcinoma. A single-institution phase II study.

OBJECTIVE: To assess in a phase II trial the effectiveness and toxicity of combined chemotherapy and radiation with selective bladder preservation by response in the treatment of muscle-invasive bladder carcinoma. PATIENTS AND METHODS: Fifty-six eligible patients with T2-4 M0 transitional cell bladder cancer suitable for radical surgery and multi-agent chemotherapy received two courses of methotrexate, cisplatin and vinblastine, followed by 40 Gy of pelvic radiotherapy in 1.8 Gy fractions with concomitant cisplatin. Tumour response was evaluated by cystoscopy and biopsy. Those responding completely were given a 24 Gy bladder boost plus cisplatin; patients with residual tumour were assigned to immediate cystectomy. RESULTS: After induction therapy, 28 patients (50%) responded completely; 22 operable patients with residual tumour underwent immediate cystectomy, while 34 patients were consolidated with cisplatin and radiation. Bladder relapses developed in 16 patients; seven had successful endovesical therapy for superficial disease and salvage cystectomy was possible in four of nine cases with invasive recurrence. Distant metastases occurred in 22 cases (39%). After a median follow-up of 46 months, the 5-year actuarial disease-specific survival was 59%, disease-free survival 54% and local control without cystectomy (bladder preservation) 41%. There were no treatment-related deaths; grade 3 late complications occurred in two patients. CONCLUSION: This combined chemotherapy-radiotherapy regimen with selective organ preservation should be considered as an option for muscle-invasive bladder carcinoma. The initial results suggest the possibility of retaining a functioning bladder in many patients, without compromising survival, compared with elective cystectomy approaches. A longer follow-up and quality-of-life assessment remain essential for a better definition of selection criteria and long-term results of this combined modality.

Adult↗
PubMed1996

Protease receptors in Hodgkin's disease: expression of the factor Xa receptor, effector cell protease receptor-1, in Reed-Sternberg cells.

The expression of a cellular receptor for the blood-clotting protease factor Xa, designated effector cell protease receptor-1 (EPR-1), was investigated in lymphoma. Immunohistochemical analysis demonstrated prominent reactivity of monoclonal antibodies to EPR-1 with Reed-Sternberg cells in 30 of 35 cases of nodular-sclerosis, lymphocyte-depletion, and mixed-cellularity Hodgkin's disease (HD). In contrast, several non-Hodgkin's lymphomas, or the nonneoplastic cellular components of HD, did not react with anti-EPR-1 monoclonal antibodies. A single molecular species of approximately 62 kD, consistent with the size and structural organization of EPR-1, was immunoblotted by an anti-EPR-1 monoclonal antibody from tissue samples of HD, but not from normal lymph nodes. Expression of EPR-1 transcripts in Reed-Sternberg cells was demonstrated by in situ hybridization with an antisense EPR-1 riboprobe, and by amplification of reverse-transcribed HD RNA with EPR-1-specific primers. These findings identify the factor Xa receptor, EPR-1, as a novel marker of Reed-Sternberg cells, and suggest its potential role in the histopathogenesis of HD.

Antibodies, Monoclonal↗
PubMed1996

Molecular dissection of effector cell protease receptor-1 recognition of factor Xa. Assignment of critical residues involved in antibody reactivity and ligand binding.

Receptor-mediated assembly of blood proteases on vascular cells maintains the hemostatic balance and initiates intracellular signal transduction. Effector cell protease receptor-1 (EPR-1) is an approximately 62-kDa vascular cell membrane receptor for the clotting protease factor Xa, participating in thrombin formation and lymphocyte activation. Here, recombinant EPR-1 fragments were engineered in the frame of intercellular adhesion molecule-1, transfected in mammalian cells, and analyzed for antibody recognition and ligand binding. Chimeric transfectants containing the EPR-1 sequence Met1-Arg60 bound the immunosuppressive anti-EPR-1 monoclonal antibody (mAb) 2E1. In contrast, transfected cells expressing the EPR-1 sequence Pro120-Ala154 were recognized by the functionally inhibitory anti-EPR-1 mAbs 9D4 and B6, bound 125I-factor Xa in a reaction quantitatively indistinguishable from that of wild-type EPR-1 transfectants, and promoted factor Xa concentration-dependent prothrombin activation in the absence of exogenous factor V/Va. Chimeric transfectants expressing the COOH terminus end of the EPR-1 extracellular domain (Ala157-Glu221) did not bind anti-EPR-1 mAbs and did not associate with factor Xa. Mutagenesis of Asn131 or Lys133 in the EPR-1 ligand recognition domain abolished factor Xa binding by 80 +/- 5.5 and 96 +/- 4%, respectively, while mutation of Lys126, Gly128, Asn129, and Asn134 was without effect. A synthetic peptide duplicating the EPR-1 sequence S123PGKPGNQNSKNEPP137 dose dependently inhibited factor V/Va-independent thrombin generation of resting endothelium (IC50 approximately 1 microM), while the adjacent EPR-1 sequence P136PKK-RERERSSHCYP150 was ineffective. These findings demonstrate that EPR-1 contains two spatially distinct functional domains implicated in lymphocyte activation (Met1-Arg60) or factor Xa binding and prothrombin activation (Pro120-Ala154). These interacting sequences may provide a novel potential target for inhibition of factor Xa-dependent vascular cell responses.

Amino Acid Sequence↗
PubMed1996

Oligomenorrhea treatment by purified FSH using a fixed protocol.

This study is designed to evaluate the effectiveness, safety and tolerability of a low dose of purified FSH administration using a fixed protocol in oligomenorrheic patients not desiring pregnancy. We used a low dose (75 IU/day for 5 days) of purified FSH (Metrodin) in 10 oligomenorrheic patients (aged 18-30) for 25 cycles. The onset of menstruation occurred in 7 patients (70%) and in 19 treatment cycles (76%), the ovulation was verified in 5 of these patients (50%) for 13 cycles (52%). One patient had spotting after the treatment, 2 patients did not have any response. The treatment did not cause side effects and it showed a good tolerability.

Adult↗
PubMed1994

Effects of exogenous ATP and related analogues on the proliferation rate of dissociated primary cultures of rat astrocytes.

The effects of ATP (5-500 microM) were evaluated on the proliferation rate of cultured astrocytes by measuring 3H-thymidine incorporation and by flow cytometric analysis of the cell cycle. Determinations after 16 hours showed that ATP present in the culture medium for the whole period caused a dose-dependent reduction of cell proliferation, while if the exposure to ATP was limited to the first 8 hours, the proliferation was increased (always in a dose-dependent manner). A time course study of 3H-thymidine incorporation showed that, in the presence of ATP, 3H-thymidine was incorporated at a slower rate than in controls; the replacement of the culture medium with an ATP-free fresh medium, at the 8th hour, was followed by a 3H-thymidine incorporation occurring at such a fast rate to overshoot the control values. High performance liquid chromatography (HPLC) analysis, carried out to identify purine compounds present in the culture medium during cell exposure to ATP, indicated that more than 95% of the added ATP was metabolized within 1 hr. Conversely, an increase of purine metabolites was measured, this accumulation being greater at the highest concentrations of added ATP. The presence of high levels of extracellular ATP catabolites suggested that these compounds may act on the regulation of cell replication via the different purine receptors. This hypothesis was tested and confirmed by using agonists and antagonists selective for the P1 and the P2 sites. One hundred microM 2methylthio-ATP (2MeSATP), a P2Y agonist metabolized as fast as ATP, reproduced effects very similar to the ATP-induced ones. On the other hand, the nonhydrolisable ATP analogue, adenosine 5'-(beta, gamma-imido)-triphosphate (AMP-PNP) at 100 microM, induced a mitogenic effect as well as the A2 site stimulation. On the contrary, the activation of A1 receptors by 5 microM R-phenyl-isopropyladenosine (R-PIA) inhibited astrocyte proliferation; moreover, 100 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1 site antagonist, reversed the ATP-induced inhibition of cell proliferation. These results indicate that exogenous ATP, as a consequence of its rapid extracellular breakdown, exerts a dual influence on astrocyte proliferation by the involvement of both P1 and P2Y receptors. These findings might be relevant to such pathological conditions of the central nervous system (CNS), as seizures, hypoxia or ischemia, in which great amounts of purines released in the brain can influence a reactive astrocyte proliferative response to injury.

Adenosine Triphosphate↗
PubMed1994

Double modulation of 5-fluorouracil in advanced colorectal cancer with low-dose interferon-alpha 2b and folinic acid. The "GISCAD" experience. Italian Group for the Study of Digestive Tract Cancer.

In advanced colorectal cancer the addition of folinic acid (FA) has been shown to lead to increased activity, at least in terms of response rate, in comparison with 5-fluorouracil (5FU) alone. Similarly, interferon-alpha (IFN) is able to potentiate 5FU, although high doses cause heavy toxicity. Given the different mechanisms of action of the two agents, the double modulation of 5FU deserves clinical evaluation. In a multicenter study (involving both primary care and referral institutions) 63 patients with advanced colorectal cancer, previously untreated with chemotherapy, received, in an outpatient setting, FA (200 mg/m2 i.v. bolus) + 5FU (400 mg/m2 i.v. in 15 min) for 5 consecutive days every 4 weeks + IFN 3 x 10(6) U on alternate days, starting 1 week before chemotherapy. During the 5 days of 5FU + FA, IFN was administered daily. The antitumour activity, the impact on response duration and survival and toxicity of the combination were evaluated according to WHO criteria. Of the 63 enrolled patients, 56 were evaluable: there were 2 complete responses (3%) and 13 partial responses (21%), giving an objective response rate of 24% (95% confidence interval 13-35%); no change was observed in 17 cases and progressive disease in 24. Median duration of response was 9 months and median survival (all patients) 13 months. Toxicity was acceptable, even though 4 patients presented reversible grade 4 side-effects (2 mucositis and 2 diarrhoea). With this schedule and these doses, addition of IFN did not lead to any increase in the activity of 5FU + FA. In colorectal cancer, further clinical studies with these drugs should be based on a deeper experimental knowledge of their mechanisms of interaction.

Adult↗
PubMed1994

Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study.

PURPOSE: To evaluate the efficacy and toxicity of single-agent vinorelbine (VNB), a semisynthetic vinca alkaloid, in patients with breast cancer previously treated with other chemotherapeutic regimens for metastatic disease. PATIENTS AND METHODS: Sixty-seven of 70 patients with assessable disease entered onto the study were assessable. The main characteristics were as follows: median age, 60 years (range, 41 to 77); median performance status (PS; Karnofsky score), 90 (range, 60 to 100); and number of previous chemotherapeutic regimens given--one in 17, two in 27, three in eight, four in two, and five in one patient. The dominant sites of metastasis were viscera in 40, bone in 16, and soft tissues in 11 patients. VNB was administered beginning with the dose of 20 mg/m2 by 60-minute intravenous (iv) infusion weekly, with a dose escalation up to 25 mg/m2 if the first four courses were well tolerated. The treatment was continued until disease progression. RESULTS: Overall, 845 courses of VNB were given (median, 10; range, eight to 33). Objective responses were as follows: complete response (CR) in three (4.5%), partial response (PR) in 21 (31.2%), stable disease (SD) in 20 (30%), and progressive disease (PD) in 23 patients (34.3%). Twenty-four of 67 assessable patients obtained a major objective response (CR or PR, 36%; 95% confidence interval [Cl], 24% to 47%). Thirty-three percent of patients had a > or = 33% reduction of dose-intensity (DI). The median time to progression was 18 weeks. The drug was active in patients pretreated with either cyclophosphamide, methotrexate, and fluorouracil (CMF) or anthracyclines. The most relevant toxicity observed was myelosuppression: 17 (25%) and 19 patients (28%) had World Health Organization grade III, and six (9%) and six patients (9%) had grade IV leukopenia and granulocytopenia, respectively; two (3%) and two patients (3%) had grade III and IV anemia, respectively. Nonhematologic toxicities were phlebitis (grade II or III in 15 patients), alopecia (grade I or II in 16), nausea and vomiting (grade II or III in 15), diarrhea (grade II in two), constipation (grade II or III in 16), stomatitis (grade II or III in 13), peripheral neuropathy (grade II in seven), and asthenia (grade II in five). CONCLUSION: This study shows that VNB is an effective and well-tolerated agent in pretreated patients with advanced breast cancer. This drug does not seem to present cross-resistance with previous CMF or anthracycline regimens. Future clinical trials should be designed to prove whether the inclusion of VNB in combination chemotherapy regimens, or whether an enhancement of its dose-intensity using bone marrow growth factors, is able to improve further the efficacy of this drug in breast carcinoma.

Adult↗
PubMed1994

[Echographic monitoring of follicular growth].

The sonographic monitoring of the ovarian follicular growth has been widely adopted, being a non invasive method, easily repeatable, well tolerated by the patient and low cost. A further impulse has been obtained by the endovaginal sonography. During a natural menstrual cycle the sonography can highlight the alterations that occur to the follicle and to the endometrium, supplying useful information on ovulatory timing. In pharmacologically induced menstrual cycles, the sonography enables us to evaluate the ovarian response to the therapy in tennis of number, size, site, and the type of growth of the recruited follicles, enabling us therefore to modulate the stimulation according to the individual response. Fluximetric studies are among the new applications the most promising, since they allow us not only to identify quickly the vascular structures, but also to supply a predictive value for the embryo implantation and the pregnancy evolution. The sonography at present proves to be irreplaceable in assisted reproduction programmes.

Endometrium↗
PubMed1993

Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing.

The cDNA for human beta-arrestin-1 was cloned by polymerase chain reaction (PCR) and identified based on its remarkably high amino acid identity (98.6%) with the bovine sequence. Two alternatively spliced isoforms of human beta-arrestin-1, differing only in the presence or absence of 24 base pairs/8 amino acids within the sequence, were identified and called beta-arrestin-1A and beta-arrestin-1B, respectively. Both isoforms were found in all tissues tested. Southern blot analysis revealed the existence of a single gene for beta-arrestin-1, suggesting that the two isoforms are generated by alternative mRNA splicing. The possible presence of similar isoforms was investigated for the other members of the arrestin/beta-arrestin gene family by PCR. Two isoforms of arrestin were revealed in bovine peripheral blood leukocytes. The expression of beta-arrestin-1 was studied in several human tissues and cell types. High levels of beta-arrestin-1 mRNA and immunoreactivity were found in peripheral blood leukocytes. The possible regulation of the expression of beta-arrestin-1 was also investigated. Our work documents for the first time that the expression of beta-arrestin-1 is modulated by intracellular cAMP. Using two cell types, human endothelial cells and smooth muscle cells, we found that 6-8-h treatments with the cAMP-inducing agents cholera toxin, forskolin, iloprost, and isoproterenol raised beta-arrestin-1 mRNA by 2-4-fold. Forskolin preferentially increased beta-arrestin-1A expression in smooth muscle cells, as assessed by PCR. beta-Arrestin-1 immunoreactivity was 2-3-fold higher in smooth muscle cells exposed to forskolin for 8 h, compared with untreated controls. We conclude that (i) the finding of alternatively spliced isoforms of beta-arrestin-1 and arrestin documents a novel mechanism to generate diversity within the arrestin/beta-arrestin gene family; (ii) the abundant expression of beta-arrestin-1 in peripheral blood leukocytes further supports our previous suggestion of a major role for the beta ARK/beta-arrestin system in regulating receptor-mediated immune functions; (iii) the increased expression of beta-arrestin-1 by cAMP suggests a new mechanism for the regulation of receptor-mediated responses.

Alternative Splicing↗
PubMed1993

Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2.

In the present study the cDNA of human beta ARK2 was cloned using both PCR and cDNA library screening, subcloned into an expression vector and transiently expressed in COS7 cells. The expressed kinase activity was approximately 40% as efficient as human beta ARK1 in phosphorylating bovine rod outer segments in vitro. Northern blot analysis of human and bovine mRNA revealed a species-specific pattern of multiple hybridization bands, with two major transcripts in human rather than one in bovine. High levels of mRNA expression were found in peripheral blood leukocytes.

Amino Acid Sequence↗
PubMed1993

Comparative analysis of beta-adrenergic receptor kinase and beta-arrestin mRNA expression in human cells.

Receptor phosphorylation is a key step in the process of rapid desensitization. beta-Adrenergic receptor kinase is a specific receptor kinase that is known to phosphorylate and induce desensitization of several G-coupled synaptic receptors only when they are occupied by their agonists. We recently cloned human beta ARK cDNA and reported high levels of beta ARK expression in human peripheral blood leukocytes, also providing the first evidence for its possible functional role in these cells. Complete homologous receptor desensitization by beta ARK requires an additional cytosolic factor, called beta-arrestin. In the present study, we have cloned a 212 bp fragment of the human beta-arrestin cDNA to perform a comparative analysis of beta ARK and beta-arrestin mRNA expression in various human cell types. We found that also beta-arrestin mRNA is abundant in non-innervated tissues and cells. The fact that the entire machinery for G-coupled receptor desensitization is highly expressed in these cells further supports the idea that beta ARK may regulate nonsynaptic as well as synaptic receptors.

Antigens↗
PubMed1993

Is magnesium content in erythrocytes suitable for evaluating cation retention after oral physiological supplementation in marginally magnesium-deficient subjects?

In this study, the effects of oral magnesium supplementation were evaluated on plasma, erythrocyte, and urinary cation levels. The study was carried out with an open, cross-over and randomized design. Healthy subjects received two sachets per day of magnesium (366 mg Mg2+/d) for two 28 d cycles, separated by a 3-week washout interval. Magnesium concentrations were measured before the supplementation and at weekly intervals during the treatment. Urinary excretion of Mg was significantly increased during supplementation, with no differences among the weeks examined. Only small increases in plasma magnesium occurred, and values returned to the prestudy levels before the end of supplementation. The increase in erythrocyte magnesium, however, was statistically significant; this trend suggests the existence of a saturable mechanisms, which prevents any possible magnesium overload during oral supplementation. We conclude that erythrocytes might be considered a suitable index for evaluating the bioavailability of magnesium salts in marginally magnesium-deficient subjects.

Administration, Oral↗
PubMed1993

Endovaginal ultrasound in patients at risk for repeated abortion.

Transvaginal echography was used to examine 78 asymptomatic patients at their first ultrasound examination, at risk for repeated abortion in the first trimester of pregnancy. The purpose of this study was to evidentiate, in the initial stages of pregnancy, reliable echographical evidence that can be used as a prognostic value on the future course of pregnancy. The normal sequential appearance of the yolk sac of the embryo and of the fetal heart activity have proved to be reassuring criteria on the course of pregnancy in 87% of the cases. Non-echographic visualization of the yolk sac has been associated in 48% of the cases to short-term abortion, whereas an abnormally low embryonic growth rate represents a risk-factor for medium-term abortion in this group of patients.

Abortion, Habitual↗
PubMed1992

High expression of beta-adrenergic receptor kinase in human peripheral blood leukocytes. Isoproterenol and platelet activating factor can induce kinase translocation.

Receptor phosphorylation is a key step in the process of desensitization of the beta-adrenergic and other related receptors. A selective kinase (called beta-adrenergic receptor kinase, beta ARK) has been identified which phosphorylates the agonist-occupied form of the receptor. Recently the bovine beta ARK cDNA has been cloned and the highest levels of specific mRNA were found in highly innervated tissues. It was proposed that beta ARK may be primarily active on synaptic receptors. In the present study, the cDNA of human beta ARK was cloned and sequenced. The sequence was very similar to that of the bovine beta ARK (the overall amino acid homology was 98%). Very high levels of beta ARK mRNA and kinase activity were found in peripheral blood leukocytes and in several myeloid and lymphoid leukemia cell lines. Since agonist-induced beta ARK translocation is considered the first step involved in beta ARK-mediated homologous desensitization, we screened a number of G-protein-coupled receptor agonists for their ability to induce beta ARK translocation. In human mononuclear leukocytes, beta-AR agonist isoproterenol and platelet-activating factor were able to induce translocation of beta ARK from cytosol to membrane. After 20 min of exposure to isoproterenol (10 microM), the cytosolic beta ARK activity decreased to 61% of control, while membrane-associated beta ARK activity increased to 170%. 20-min exposure to platelet-activating factor (1 microM) reduced the cytosolic beta ARK activity to 42% of control with concomitant increase in membrane beta ARK activity to 214% of control. The high levels of beta ARK expression in human peripheral blood leukocytes together with the ability of isoproterenol and platelet-activating factor to induce beta ARK translocation, suggest a role for beta ARK in modulating some receptor-mediated immune functions.

Amino Acid Sequence↗
PubMed1991

[Radiotherapy, radiotherapy combined with surgery, radiotherapy combined with chemotherapy in the treatment of carcinoma of the pyriform sinus. A retrospective study].

A rectrospective analysis was performed of the results of 104 consecutive patients with carcinoma of the pyriform sinus, who underwent radiation therapy. Thirty-four patients underwent radical surgery and postoperative radiation therapy (group 1); 36 patients received radical radiation therapy alone (group 2); neoadjuvant chemotherapy was administered prior to full-dose radiation to 20 patients (group 3); 14 patients received palliative radiation therapy (group 4). Loco-regional control and survival rates at 5 years were 60.4% and 34.3% in group 1, 23.8% and 23.8% in group 2, 17.5% and 23.8% in group 3; no patients in group 4 survived at 5 years. Patients in group 1 experienced significantly better survival and local control than those in groups 2 and 3. No differences were observed between groups 2 and 3. Loco-regional recurrence was the main cause of failure in group 2 (69.4%) and 3 (70.0%). In group 1, 20.3% of cases developed distant metastases. Overall 5-year survival rate was 23.7%, confirming the poor prognosis of this disease. These results provide further support to the need of improving prevention and early diagnosis to improve both results and outcome in patients with carcinoma of the pyriform sinus.

Adult↗