71 research outputs found

    Cardiotocography pattern: not always a true friend

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    : Fetal well-being in labor could be assessed trough cardiotocography (CTG). Some doubts have been raised about its unequivocal applicability. Pathological CTG is in most cases connected to fetal acidosis at birth, but other potential causes must be considered in the differential diagnosis. A 31-years-old G2P1 patient referred to our Department of Obstetrics and Gynecology for her scheduled post-term CTG at 40 weeks and 3 days of gestation. The pregnancy was uneventful. CTG was classified as suspicious, and after pharmacological induction, it switched as pathological: an emergency cesarean section was performed. Venous and arterial blood sample taken from the umbilical cord were normal. The next assessments revealed that Atrial Flutter (AFL) occurred at birth. Suspicious CTG is not always associated to neonatal asphyxia. Cardiotocography can help not only in the evaluation of fetal distress, but also in the assessment of global fetal cardiac activity. The presence of a fetal heart defect should be considered when CTG is suspicious

    MMR vaccine in the postpartum does not expose seronegative women to untoward effects.

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    Contesto : Lo scopo di questo studio è stato quello di valutare se la vaccinazione rosolia immediatamente dopo il parto potrebbe esporre le donne sieronegative per effetti indesiderati specifici.Metodi : 163 donne rosolia-sieronegativi hanno ricevuto il vaccino MMR nel periodo post-partum; sono stati valutati a 1 mese a 3 mesi successivi attraverso interviste telefoniche. Come controlli, abbiamo confrontato 163 donne rosolia-sieropositivi, che potrebbe avere sintomi simili per qualsiasi motivo, nello stesso arco di tempo.Risultati : A un mese di follow-up, 161 donne nel gruppo dei casi e 162 controlli hanno risposto alla nostra intervista telefonica; alle tre mesi di follow-up, 154 casi e 159 controlli. Eruzione cutanea, faringite, artralgia, linfoadenopatia cervicale, mialgia e parestesia sono state le lamentele più frequentemente riportati in entrambi i gruppi. Una differenza statisticamente significativa nella frequenza di linfoadenopatia cervicale e rash cutaneo a un mese (p = 0.028 ep = 0.005, rispettivamente) è stata osservata tra i casi ei controlli; Tuttavia, nessuna differenza significativa è stata ancora osservata nella frequenza delle manifestazioni muscoloscheletriche acute e croniche a tre mesi.Conclusioni : Non sono sostanziali differenze sono stati segnalati tra casi e controlli per quanto riguarda la frequenza di artralgia e conseguente mialgia al MMR vaccinazione in post-partum . Postpartum rosolia la vaccinazione è sicura e consigliabile in caso di necessità per evitare la circolazione del virus e la sindrome da rosolia congenita

    Tra genere e generi. Tradurre e pubblicare testi per ragazze e ragazzi

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    Il volume nasce nell'ambito di un progetto AlmaIdea sulla traduzione di testi per l'infanzia in una prospettiva di genere, e propone una serie di contributi interdisciplinari, al crocevia fra studi traduttologici, letterari e di genere, focalizzati su svariate tipologie di testi per l'infanzia, letterari e non, tradotti dal francese, dall'inglese e dallo spagnolo, un ambito di ricerca ad oggi poco approfondito a livello internazionale e ancor più nel contesto accademico italiano. Nel testo viene proposto, infine, un documento ispirato al Codice Polite e volto a fornire alle case editrici così come a traduttrici e traduttori alcuni suggerimenti al fine di tradurre e pubblicare testi in una prospettiva di inclusione e sensibilità per gli aspetti di genere e delle diversità tutte

    Long-term complete response in a patient with liver metastases from breast cancer treated with metronomic chemotherapy

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    Background. Preclinical studies have shown that several chemotherapeutic agents at low doses may affect the vascular system. Here we report the case of a patient with long-term cancer control by metronomic chemotherapy. Case presentation. A 62-year-old woman with breast cancer underwent a left mastectomy in July 2007. For a liver metastasis she was given first-line chemotherapy with doxorubicin plus paclitaxel every 21 days. A CT scan after the sixth cycle showed a partial response. It was decided to stop the treatment with doxorubicin and paclitaxel, and start metronomic therapy with cyclophosphamide 50 mg daily orally and methotrexate 2.5 mg twice daily, 2 days a week. After 6 months of this maintenance treatment, CT scan showed a complete response. We examined the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in histological sections of the primary tumor of our patient, finding evidence of overexpression of the receptor. The metronomic treatment is still ongoing, and after 60 months the patient maintains a complete response. Conclusion. This clinical case highlights how suitable metronomic chemotherapy can be used as maintenance therapy, allowing long-term treatment with no significant toxicity. This case suggests that the level of VEGFR2 is predictive of best response to antiangiogenic therapy

    Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines

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    INTRODUCTION: The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells. METHODS: The study was performed on MCF-7 and BRC-230 cell lines. The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle. Cell cycle perturbation and apoptosis were evaluated by flow cytometry, and apoptosis-related marker (p53, bcl-2, bax, p21), caspase and thymidylate synthase (TS) expression were assessed by western blot. RESULTS: 5-FU, used as a single agent, exerted a low cytotoxic activity in both cell lines. The Dox→Pacl sequence produced a synergistic cytocidal effect and enhanced the efficacy of subsequent exposure to 5-FU in both cell lines. Specifically, the Dox→Pacl sequence blocked cells in the G2-M phase, and the addition of 5-FU forced the cells to progress through the cell cycle or killed them. Furthermore, Dox→Pacl pretreatment produced a significant reduction in basal TS expression in both cell lines, probably favoring the increase in 5-FU activity. The sequence Dox→Pacl→48-h washout→5-FU produced a synergistic and highly schedule-dependent interaction (combination index < 1), resulting in an induction of apoptosis in both experimental models regardless of hormonal, p53, bcl-2 or bax status. Apoptosis in MCF-7 cells was induced through caspase-9 activation and anti-apoptosis-inducing factor hyperexpression. In the BRC-230 cell line, the apoptotic process was triggered only by a caspase-dependent mechanism. In particular, at the end of the three-drug treatment, caspase-8 activation triggered downstream executioner caspase-3 and, to a lesser degree, caspase-7. CONCLUSION: In our experimental models, characterized by different biomolecular profiles representing the different biology of human breast cancers, the schedule Dox→Pacl→48-h washout→5-FU was highly active and schedule-dependent and has recently been used to plan a phase I/II clinical protocol

    Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer

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    Background:The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity.Patients and methods:This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m(2) intravenously (i.v.) on day 1, docetaxel, 30 mg/m(2) i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle.Results:Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5-53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06-1.30, p = 0.11). Toxicity included grade 3-4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1-2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1-2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase.Conclusions:The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens

    Phase II study of gemcitabine, doxorubicin and paclitaxel (GAT) as first-line chemotherapy for metastatic breast cancer: a translational research experience

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    BACKGROUND: Patients with metastatic breast cancer are frequently treated with anthracyclines and taxanes, which are among the most active agents in this disease. Gemcitabine is an interesting candidate for a three-drug combination because of its different mechanism of action and non-overlapping toxicity with respect to the other two drugs. We aimed to evaluate the activity and toxicity of the GAT (gemcitabine, doxorubicin and paclitaxel) regimen, derived from experimental preclinical studies, as first-line chemotherapy in patients with stage IIIB-IV breast cancer. METHODS: Patients with locally advanced or metastatic breast cancer and at least one bidimensionally measurable lesion were included in the present study. Adequate bone marrow reserve, normal cardiac, hepatic and renal function, and an ECOG performance status of 0 to 2 were required. Only prior adjuvant non anthracycline-based chemotherapy was permitted. Treatment consisted of doxorubicin 50 mg/m(2 )on day 1, paclitaxel 160 mg/m(2 )on day 2 and gemcitabine 800 mg/m(2 )on day 6, repeated every 21–28 days. RESULTS: Thirty-three consecutive breast cancer patients were enrolled onto the trial (7 stage IIIB and 26 stage IV). All patients were evaluable for toxicity and 29 were assessable for response. A total of 169 cycles were administered, with a median of 6 cycles per patient (range 1–8 cycles). Complete and partial responses were observed in 6.9% and 48.3% of patients, respectively, for an overall response rate of 55.2%. A response was reported in all metastatic sites, with a median duration of 16.4 months. Median time to progression and overall survival were 10.2 and 36.4 months, respectively. The most important toxicity was hematological, with grade III-IV neutropenia observed in 69% of patients, sometimes requiring the use of granulocyte colony-stimulating factor (27%). Non hematological toxicity was rare and mild. One patient died from sepsis during the first treatment cycle before the administration of gemcitabine. CONCLUSION: The strong synergism among the three drugs found in the preclinical setting was confirmed in terms of both clinical activity and hematological toxicity. Our results seem to indicate that the GAT regimen is effective in anthracycline-naïve metastatic breast cancer and provides a feasible chemotherapeutic option in this clinical setting
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