Sigma 2 receptor expression levels in blood and bladder from healthy and bladder cancer cattle.

The expression of sigma-2 receptor (S2R) was assayed in blood and bladder samples from healthy cattle and in blood and bladder of cattle with deltapapillomavirus-associated urothelial tumors. Samples of bladder from cattle with neoplasia had significantly higher S2R than samples of bladder from healthy cattle (95% CI 0.31-0.82, P < 0.05). In addition, significantly higher S2R was detected in the blood of cattle with bladder cancer than blood from healthy cattle (95% CI 0.22-0.41, P < 0.05). The results provide evidence that increased expression of SR2 in blood could be useful as circulating biomarker for bladder cancer in cattle. PGRMC1 protein levels were also found to be increased in blood and bladder from cattle with cancer and increased expression of PGRMC1 transcripts was detected by quantitative real time PCR in samples from cattle neoplasia. Furthermore, electron microscopy revealed phagophores and numerous autophagosomes, ultrastructural hallmark of autophagy.

A structure-affinity relationship study on derivatives of N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a high-affinity and selective D(4) receptor ligand.

N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1), a high-affinity and selective dopamine D(4) receptor ligand, was chosen as a lead, and structural modifications were done on its amide bond and on its alkyl chain linking the benzamide moiety to the piperazine ring and by preparing some semirigid analogues. The binding profile at dopamine D(4) and dopamine D(2), serotonin 5-HT(1A), and adrenergic alpha(1) receptors of 16 new compounds was determined. From the results emerged that the modification of the amide bond and the elongation of the intermediate alkyl chain caused a decrease in dopamine D(4) receptor affinity. All prepared semirigid analogues displayed D(4) receptor affinity values in the same range of the opened counterparts.

N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide: a potent and selective dopamine D4 ligand.

A series of new 1-aryl-4-alkylpiperazines containing a terminal benzamide fragment or a tetralin-1-yl nucleus on the alkyl chain were synthesized and tested for binding at cloned human dopamine D4 and D2 receptor subtypes. A SAFIR (structure-affinity relationship) study on this series is herein discussed. The most relevant D4 receptor affinities were displayed by N-[omega-[4-arylpiperazin-1-yl]alkyl]-methoxybenzamides (compounds 5, 16-20), their IC50 values ranging between 0.057 and 7.8 nM. Among these, N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (17) emerged since it exhibited very high affinity for dopamine D4 receptor (IC50 = 0.057 nM) with selectivity of >10 000 for the D4 versus the D2 receptor; compound 17 was also selective versus serotonin 5-HT1A and adrenergic alpha1 receptors.

1-aryl-4-[(5-methoxy-1,2,3, 4-tetrahydronaphthalen-1-yl)alkyl]piperazines and their analogues: influence of the stereochemistry of the tetrahydronaphthalen-1-yl nucleus on 5-HT1A receptor affinity and selectivity versus alpha1 and D2 receptors. 5.

Some 1-aryl-4-[(5-methoxy-1,2,3, 4-tetrahydronaphthalen-1-yl)-n-propyl]piperazines and their alkylamino and alkylamido analogues, previously studied as 5-HT1A ligands, were prepared in enantiomerically pure form, and their absolute configuration was determined by chemical correlation or by chiroptical properties. They were evaluated for in vitro 5-HT1A, D2, and alpha1 receptor affinity by radioligand binding assays, to study the influence of the chiral carbon atom of the tetrahydronaphthalene nucleus on the 5-HT1A affinity and selectivity. Results indicated that, as regarding the 5-HT1A receptor affinity, there was no difference in affinity between (-)- and (+)-enantiomers as well as the racemate of each compound. The stereochemistry, instead, influenced the selectivity: all (-)-enantiomers displayed affinity values higher than those of (+)-isomers at D2 receptors, and conversely, all (+)-enantiomers displayed affinity values higher than those of (-)-isomers at alpha1 receptors. As a result of this trend, it is not possible to predict the isomer with a better selectivity profile. However, compounds (S)-(+)-2, (S)-(+)-4, and (R)-(+)-6 displayed high affinity for the 5-HT1A receptor (IC50 values ranging between 7.0 and 2.3 nM) and good selectivity (>/=250-fold) versus both D2 and alpha1 receptors. Furthermore, compounds (S)-(+)-4 and (R)-(-)-4 were submitted to the [35S]GTPgammaS binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT1A receptor.

Oxygen isosteric derivatives of 3-(3-hydroxyphenyl)-N-n-propylpiperidine.

Some substituted 3-phenylmorpholines (10a-e,j,k) and 3-thienylmorpholines (10f,g), isosteres of 3-(3-hydroxy-phenyl)-N-n-propylpiperidine (3-PPP), were prepared and submitted to binding assays on D-2 dopaminergic and 5-HT1 and 5-HT2 serotonergic receptors, in comparison with 3-PPP and its analogue 3a,b. The results show the loss of D-2 affinity for all morpholines, while a certain activity was still observable for piperidine derivatives. Regarding the serotonergic affinity, only chloro and methoxy derivatives (10a-d) were moderately active on the 5-HT1A receptor, either when the substituent was in the C-2 or C-3 position, whereas no tested compounds showed affinity toward the 5-HT2 receptor.

Novel potent sigma 1 ligands: N-[omega-(tetralin-1-yl)alkyl]piperidine derivatives.

A series of substituted N-[(tetralin-1-yl)alkyl]piperidines and a number of related N-di-n-propyl-[(tetralin-1-yl)alkyl]amines were prepared. Structural modifications such as piperidine substitutions, intermediate chain lengthening, and the nature of the aromatic ring were explored in order to identify structural requirements for selective sigma 1 affinity. They were tested in radioligand binding assays on sigma 1, 5-HT1A and 5-HT2 serotonergic, PCP (phencyclidine), and D-2 dopaminergic receptors. Almost all the compounds reported here showed a high to superpotent sigma 1 affinity, and some compounds also demonstrated a widespread selectivity over the other receptors. In [3H]-(+)-pentazocine binding, 3,3-dimethyl-1-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n- propyl] piperidine (24) and 3,3-dimethyl-1-[4-(1,2,3,4-tetrahydronaphthalen-1-yl)-n- butyl]piperidine (26) reached the lowest Ki values (0.4 and 0.8 nM, respectively); compound 24 also demonstrated a considerable PCP affinity (Ki = 34.2 nM), whereas compound 26 was suitably selective. Furthermore the presence of a 4-benzyl substituent on the piperidine ring (compound 16, Ki = 3.9 nM on sigma 1 sites) caused an increase in 5-HT1A affinity (Ki < 0.14 nM).

New sigma and 5-HT1A receptor ligands: omega-(tetralin-1-yl)-n-alkylamine derivatives.

Two series of compounds that are structurally related to benzomorphans, derived by structural modification of arylpiperazines with high 5-HT1A affinity and moderate sigma affinity, were prepared in order to increase sigma affinity and selectivity. All new compounds are N-substituted-omega-(1,2,3,4-tetrahydronaphthalen-1-yl)- or -omega-(1,2-dihydronaphthalen-4-yl)-n-alkylamines with, in some cases, a methoxy group on the tetralin moiety. They were tested in radioligand binding assays on sigma ([3H]DTG and [3H]-(+)-pentazocine), D-2 dopaminergic, 5-HT1A and 5-HT2 serotonergic, and PCP (phencyclidine) receptors. A first set of compounds bearing a 4-(1-substituted)piperazine moiety as terminal fragment on the alkyl chain showed moderate to high sigma affinity (Ki = 5.3-139 nM), the most active and selective being 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n- propyl ]piperazine (14), with probable pronounced sigma 2 affinity (Ki = 5.3 nM on [3H]DTG and Ki = 71 nM on [3H]-(+)-pentazocine). Moreover, compound 13, a 1-benzylpiperazine analogue of 14, preserved a dual high 5-HT1A and sigma affinity (Ki = 3.6 nM on [3H]-5-HT and Ki = 7.0 nM on [3H]DTG). The second set of compounds includes some N-phenylalkyl derivatives of 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)- n-propylamine that can be considered to be open-chain derivatives of 4-substituted-1-arylpiperazines. Among these compounds that had a lower activity toward sigma binding sites, a high 5-HT1A affinity was found for the N-(3-phenylpropyl) derivative 21 (Ki = 4.4 nM) which demonstrated very good selectivity.

N-[omega-(Tetralin-1-yl)alkyl] derivatives of 3,3-dimethylpiperidine are highly potent and selective sigma1 or sigma2 ligands.

Several 3, 3-dimethyl-N-[omega-(tetrahydronaphthalen-1-yl)alkyl]piperidine derivatives and some related compounds were prepared. Their affinities and sigma-subtype selectivities were investigated by radioligand binding assays, labeling sigma1 receptors with [3H]-SKF 10047 and sigma2 receptors with [3H]-DTG. Many tested compounds bound sigma1 and/or sigma2 receptors with nanomolar or subnanomolar IC50 values. Compound (+)-22, (+)-3,3-dimethyl-1-[3-(5-methoxy-1,2,3, 4-tetrahydronaphthalen-1-yl)-n-propyl]piperidine, was the most potent (IC50 = 0.089 nM) and selective sigma1 ligand (1340-fold), showing a 10-fold enantioselectivity. Compounds 29 (3, 3-dimethyl-1-[4-(6-methoxy-1,2,3, 4-tetrahydronaphthalen-1-yl)-n-butyl]piperidine) and 31 (3, 3-dimethyl-1-[5-(1,2,3, 4-tetrahydronaphthalen-1-yl)-n-pentyl]piperidine) were highly potent (IC50 = 0.016 nM and IC50 = 0.008 nM, respectively) and highly selective sigma2 ligands (more than 100000-fold).

1-aryl-4-[(1-tetralinyl)alkyl]piperazines: alkylamido and alkylamino derivatives. Synthesis, 5-HT1A receptor affinity, and selectivity. 3.

The synthesis and binding profile on 5-HT1A, 5-HT2, D-1, D-2, alpha 1, and alpha 2 receptors of the N-4 long-chain arylpiperazines 22-40 are reported, where an amino or amido function is inserted into the intermediate chain linked to the alpha position of the tetralin nucleus. Unlike the buspirone analogues, for the amido derivatives studied in this paper, the terminal amide function of long-chain piperazines is not important for 5-HT1A receptor affinity binding, and its removal yields high-affinity 5-HT1A receptor agents.

trans-4-[4-(Methoxyphenyl)cyclohexyl]-1-arylpiperazines: a new class of potent and selective 5-HT(1A) receptor ligands as conformationally constrained analogues of 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-arylpiperazines.

The present paper concerns the influence of conformational parameters on the recognition by rat 5-HT1A receptors of derivatives 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-(2-pyridinyl)piperazine (1a) and 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-N-[2-(2-pyridyloxy)ethyl]propanamine (3b), two highly potent and selective 5-HT1A receptor ligands. Fifteen corresponding flexible and rigid analogues were prepared following several synthetic routes and were tested in binding assays with radioligands at 5-HT1A, D2, and alpha1 receptors from rat brain membranes. Among the new derivatives emerged trans-4-[4-(3-methoxyphenyl)cyclohexyl]-1-(2-pyridinyl)piperazine (trans-8a) and trans-N-[4-(3-methoxyphenyl)cyclohexyl]-2-(2-pyridyloxy)ethylamine (trans-8b). These compounds can be considered as conformationally constrained analogues of compounds 1a and 3a, respectively. In fact, compounds trans-8a and trans-8b showed a marked enhancement in 5-HT1A receptor affinity when compared to the corresponding cis isomers. Because compound trans-8a was a potent and selective 5-HT1A ligand (K(i), nM: 5-HT1A = 0.028, D2 = 2194, alpha1 = 767), it was chosen as a lead to prepare other analogues that were tested at 5-HT1A, D2, and alpha1 receptors from rat brain membranes, showing high affinity at the 5-HT1A and selectivity vs D2 and alpha1 receptors. Selected compounds were tested for their affinity at the human cloned 5-HT1A, alpha1a, alpha1b, alpha1d receptor subtypes. They were also submitted to the [35S]GTPgammaS binding assay stimulating the 5-HT1A receptor-mediated G-protein activation, therefore behaving as full or as partial agonists. Finally, the ability of iv administration of trans-8a to induce fore-paw treading in rats was evaluated in comparison with 8-OH-DPAT. Although the affinity (K(i)) and in vitro activity (pD'2) of trans-8a at the 5-HT1A receptor were higher than those of 8-OH-DPAT, the compound was less potent than the reference standard in inducing the symptom.

Structure-activity relationship studies on the 5-HT(1A) receptor affinity of 1-phenyl-4-[omega-(alpha- or beta-tetralinyl)alkyl]piperazines. 4.

The synthesis of 1-phenylpiperazines, linked in the alpha or beta position of the tetralin moiety on the terminal part of the N-4 alkyl chain, and their radioligand binding affinities for 5-HT(1A), 5-HT(2A), D-1, D-2, alpha1, and alpha2 receptors along with SAR studies on the 5-HT(1A) receptor are reported. Several changes have been carried out on previous structures of type 2, by inserting the alkyl chain with variable length in the alpha or beta position of the tetralin moiety and by changing the position of the methoxy group on the aromatic ring of the tetralin nucleus. The highest affinity (IC50 = 0.50 nM) and selectivity for the 5-HT(1A) receptor were showed by 1-phenylpiperazine 2a with a three-membered alkyl chain bearing a 5-methoxytetralin-1-yl ring in the omega position.

Mixed 5-HT1A/D-2 activity of a new model of arylpiperazines: 1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines. 1. Synthesis and structure-activity relationships.

A new model of 4-alkyl-1-arylpiperazines containing a terminal dihydronaphthalene fragment on the alkyl chain was synthesized in order to have mixed serotonergic and dopaminergic activity and to pursue the recent alternative approaches to the discovery of novel antipsychotic and anxiolytic agents. Title compounds were evaluated for in vitro activity on dopamine D-2 and serotonin 5-HT1A and 5-HT2 receptors by radioreceptor binding assays. They show high nanomolar affinity for 5-HT1A, moderate affinity for D-2, and low affinity for 5-HT2 receptors, and in particular, two compounds, 4-[3-(1,2-dihydro-6-methoxynaphthalen-4-yl)-n-propyl]-1-(2- methoxyphenyl)piperazine (8) and 4-[3-(1,2-dihydro-8-methoxynaphthalen-4-yl)-n-propyl]-1-(2- pyridyl)piperazine (15), show values (nM) of IC50 = 2.0 and 1.4 for 5-HT1A and IC50 = 90.6 and 119.3 for D-2, respectively. Some in vivo behavioral studies show compound 8 to be an antagonist on 5-HT1A receptors. These first findings place the new arylpiperazines on the same level as that of the azaspirone class, e.g., 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-n-butyl]piperazine (NAN-190) and buspirone.

High affinity and selectivity on 5-HT1A receptor of 1-aryl-4-[1-tetralin)alkyl]piperazines. 2.

Several 4-alkyl-1-arylpiperazines that present a tetralin moiety on the terminal part of the side chain were synthesized in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines). Several synthetic procedures were followed to obtain the final products, depending on the presence or absence of a double bond, as well as of a heteroatom on the side chain. In the first case versatile use of Grignard reaction was made, whereas in the second one usual synthetic ways were applied. Final compounds were evaluated for in vitro activity on dopamine D-1 and D-2, serotonin 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2, alpha 1 adrenergic, and sigma receptors by radioreceptor binding assay. For the 2-MeO-Ph, 2-pyridyl, and unsubstituted phenyl N-piperazine derivatives, low IC50 values (0.3 nM) on 5-HT1A receptors and high selectivity values were observed.

Fec (Fluorouracil, epirubicin, cyclophosphamide) plus granulocyte macrophage-colony-stimulating factor (gm-csf) in advanced or inflammatory breast-cancer - a dose-finding study.

Seven patients with inflammatory and 11 with metastatic breast cancer were treated with high dose FEC chemotherapy plus GM-CSF; 5-fluorouracil and cyclophosphamide were administered at 500 mg/m2/iv/day 1, epirubicin at three dose levels: 100 mg, 120 mg and 140 mg/m2/iv/day 1 every three weeks (six patients per level). GM-CSF was administered at a dosage of 5 mg/kg/sc from day 5 to 12 of each cycle. The overall response rate was 83% (95% CI: 66%-100%) with 22% complete response. The median response duration for patients with metastatic disease was 7 months (range: 4-10). The hematological toxicity was moderate but reversible due to GM-CSF rescue; mucositis represented the dose limiting toxicity. In conclusion, the increase of dose intensity resulted in a higher response rate but not longer response duration, which must be taken into account when administering high-dose chemotherapy with growth factor rescue.

Determination of dopamine D(4) receptor density in rat striatum using PB12 as a probe.

N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB12), a potent and selective dopamine D(4) receptor ligand, was used as a probe for the direct determination of the dopamine D(4) receptor density in rat striatum as an alternative to the subtraction method. The experiment was performed using [(3)H]spiroperidol to label D(2), D(3) and D(4) receptors and PB12 to determine directly dopamine D(4) receptor specific binding. The determined B(max) value was 82 fmol/mg protein. The contribution of the dopamine D(4) receptor to the overall population of D(2)-like receptors was 63%; however, this value cannot be considered reliable because of the observed difference in the kinetic profiles of D(2), D(3) and D(4) receptors.

Carbon-11 pb-12: an attempt to visualize the dopamine d(4) receptor in the primate brain with positron emission tomography.

The dopamine D(4) receptor (D(4)R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but no selective positron emission tomography (PET) ligand is available to date to study the distribution in vivo. The arylpiperazine derivative N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB-12) is a novel, high-affinity ( K(i)=0.040 nM) and selective D(4)R ligand. We radiolabeled PB-12 with carbon-11 (t(1/2) 20.4 min) by O-methylation of the corresponding desmethyl analogue N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-hydroxybenzamide (LM-190) with [(11)C]methyl triflate. Derivative LM-190 was prepared by condensing 3-hydroxybenzoic acid with the appropriate amine. For the radiolabeling, the incorporation yield was >90% and the total synthesis time including high performance liquid chromatography (HPLC) purification was about 35 min. The specific radioactivity of [(11)C]PB-12 at time of injection was 67-118 GBq x micromol(-1). PET studies in a cynomolgus monkey showed a high uptake and widespread distribution of radioactivity in the brain, including the neocortex and thalamus. About 40% of total radioactivity in plasma represented unchanged radioligand at 60 min after injection as determined by HPLC. Pretreatment with the D(4)R ligand 3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrollo[2,3-b]pyridine (L-745,870) prior to radioligand injection failed to demonstrate receptor-specific binding in the monkey brain. Furthermore, the brain radioactivity distribution was left unaffected by pretreating with unlabeled PB-12. This failure to detect a D(4)R-specific signal may be related to a very low density of the D(4)R in primate brain, insufficient binding affinity of the radioligand, and a high background of nonspecific binding. It can be concluded from these findings that [(11)C]PB-12 is not suitable to visualize the D(4)R in the primate brain with PET.

Accelerated chemotherapy with mitoxantrone plus g-csf in heavily pretreated patients with metastatic breast-cancer.

Twenty-two women with metastatic breast cancer, previously submitted to one or more lines of chemotherapy, were treated with mitoxantrone as single agent delivered at full dosage (14 mg/m(2)) every other week (accelerated chemotherapy). This dose was possible with concomitant subcutaneous administration of granulocyte colony stimulating factor (G-CSF) on days 5 to 12 of each 14 day cycle. Although grade III-IV leukopenia, anemia and thrombocytopenia were observed in 50%, 13%, and 27% of cases, respectively, a complete recovery of neutrophils, due to G-CSF administration, permitted on time cycle delivery in the majority of cases. Partial response was observed in 6/22 patients (27%). In conclusion, accelerated chemotherapy with mithoxantrone plus G-CSF is both feasible and effective for patients with previously treated breast cancer.

Ifosfamide plus mitoxantrone as salvage treatment in non-Hodgkin's lymphomas.

Twenty-two patients affected by relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a combination of ifosfamide (IFO) at the dose of 1.2 g/m2 intravenous (i.v.) (1 h infusion) for 5 consecutive days with mesna as uroprotector plus mitoxantrone (NOV) at the dose of 12 mg/m2 i.v. on day 1; both drugs were recycled every 3-4 weeks. Of 21 evaluable patients, overall response observed was 57% (38% complete response and 19% partial response with a median duration of response of 7 months (5-23+). Dose-limiting toxicity was represented by leukopenia (grade III-IV in 43% of cases); severe thrombocytopenia was observed less frequently (grade III-IV in 19% of cases). This hematologic toxicity prevented administration of therapy every 3 weeks as initially planned. However, the complete hematological recovery, usually observed at the fourth week, permitted therapy administration to all patients without dose reduction. Low-grade lymphomas responded to treatment as well as intermediate or high grade lymphomas. Moreover, patients treated with third- or fourth-line chemotherapy also responded. However, response was observed in 11/13 (85%) relapsed patients as compared to 2/8 (25%) refractory cases. The combination of IFO plus NOV is active in heavily pretreated patients with NHL. Nevertheless, the study of a larger number of patients is necessary to better define the exact role of this combination as "salvage" therapy for NHL.

M-VECA (methotrexate, vinblastine, epidoxorubicin and carboplatin) in the treatment of advanced urothelial carcinoma.

AIMS AND BACKGROUND: Urothelial cancer is a chemosensitive disease. However, cisplatin or anthracycline-containing regimens still provoke severe toxicity mainly due to reduced renal function and poor performance status (PS) of patients. The aim of this study was to verify the possibility of substituting carboplatin for cisplatin and epirubicin for doxorubicin in the M-VAC regimen in order to reduce toxicity and improve patient tolerance. METHODS: Twenty patients with advanced urothelial tract tumors were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/mq iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epidoxorubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every four weeks (M-VECA). All patients had bidimensionally measurable disease. RESULTS: Of the 18 evaluable patients, 3 (17%) obtained complete response and 7 (33%) obtained partial response (50% overall response). The median duration of response was 50 weeks (range, 28-88+). Grade III-IV toxicity (leukothrombocytopenia and mucositis) was observed in 20% of cases. Nevertheless, recovery was prompt in all but 2 patients with poor PS who died of nadir sepsis. CONCLUSIONS: M-VECA was an effective regimen for the treatment of patients with metastatic urothelial tumors and was safely employed in patients with a good PS. However, the possibility of substituting carboplatin for cisplatin as neoadjuvant therapy for less advanced stages needs further investigation in randomized studies.

Metastatic involvement of the stomach secondary to breast carcinoma. A case report.

The Authors describe a case of gastric metastases from breast cancer. The staging procedures in breast cancer do not usually include the endoscopic examination of the gastroenteric tract; nevertheless the complaint of persistent gastric disorders in patients affected by metastatic breast cancers must not be underestimated. In this case the finding of gastric neoplastic involvement led to effective treatment of the above mentioned disorders and consequently to an improvement in the patient's quality of life. Moreover, the evaluation of this clinical case shows that chemotherapeutic treatment of this metastatic localisation does not differ from that of metastases in other sites.