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Biomedical subjects

N Ragni

Publications and source records attributed to N Ragni.

At least 37 records · Page 2Linked to original sources
PubMed2001

Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: results of two phase I studies.

UNLABELLED: STUDY PURPOSES: To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 72-hour continuous infusion followed by bolus intravenous ifosfamide on days 4 and 5 or epirubicin on day 4, every 21 days. To assess the toxicity and preliminary activity in patients with advanced refractory solid tumors. PATIENTS AND METHODS: Sixteen patients with progressive disease after standard chemotherapy for advanced disease were treated with the combination paclitaxel-ifosfamide and 10 patients with the combination paclitaxel-epirubicin. RESULTS: In the first phase I study the MTDs were: paclitaxel 135 mg/m2 and ifosfamide 2.5 mg/m2/day; hematologic toxicity was the dose-limiting toxicity (DLT) during the first cycle of therapy at dose level 4. Paclitaxel administered at 135 mg/m2 and epirubicin 50 mg/m2 were the MTDs in the second phase I study; grade 4 stomatitis was the DLT of this combination. CONCLUSIONS: Paclitaxel by 72-hour continuous infusion followed by bolus ifosfamide was a manageable regimen with an acceptable hematologic toxicity in the absence of neurotoxicity. Preliminary activity of this combination was encouraging in a group of patients with ovarian cancer. The optimal way to combine paclitaxel and epirubicin and the best schedule relative to such a long paclitaxel infusion time in this combination regimen remain to be determined.

Adult↗
PubMed2001

[Luteal phase support in assisted reproductive cycles using either vaginal (Crinone 8) or intramuscular (Prontogest) progesterone: results of a prospective randomized study].

BACKGROUND: To compare local tolerance and patients compliance to intravaginal and intramuscular progesterone administration. METHODS: Ninety-nine patients have been randomised to receive either intravaginal Crinone, 90 mg/day (n=51) or intramuscular Prontogest 50 mg/day (n=48) for luteal supplementation in IVF/ICSI cycles. Local and systemic side effects as well as pattern of menstrual bleeding were reported on a self administered questionnaire. Progesterone levels were evaluated pre-treatment, in the mid-luteal phase and the day of pregnancy test. RESULTS: Patients age, BMI, duration and causes of infertility were comparable in the two treatment groups. All parameters of ovarian response as well as pregnancy rates did not show significative difference in the two groups. A significative larger number of patients assigned to intravaginal support were free from side effects. Furthermore side effects, when reported, resulted significantly more severe in the intramuscular group. In the non pregnant patients menstrual flow appeared significantly earlier in those treated with vaginal progesterone (p<0.001). CONCLUSIONS: Crinone 8 is a good alternative to parental progesterone for luteal support in ART cycles. It is well tolerated but it is linked to an earlier appearance of menstrual flow in non conceptional cycles.

Administration, Intravaginal↗
PubMed2000

Growth hormone response to clonidine in anovulatory infertile women resistant to clomiphene citrate stimulation.

OBJECTIVE: To evaluate the GH response to the clonidine test in a group of infertile women and to determine their ovulatory response to clomiphene citrate (CC) stimulation. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit. PATIENT(S): Thirty-three anovulatory infertile women (age range, 25-36 years) and 9 healthy controls with normal ovulation. INTERVENTION(S): In the early follicular phase, 0.3 mg of clonidine was administered between 8:30 and 9:00 A.M. and blood samples were collected for 120 minutes thereafter for measurement of serum GH levels. Plasma levels of insulin and glucose were measured after a 75-g glucose load, and CC was given at a dosage of 50-250 mg/d for ovulation-induction. MAIN OUTCOME MEASURE(S): Serum concentrations of GH, insulin-like growth factor I, insulin, and insulin-like growth factor binding protein-1. RESULT(S): On the basis of their ovulatory response to CC, 15 patients were considered nonresponsive (group 1) and 18 patients were considered responsive (group 2). Baseline levels of GH, insulin-like growth factor I, and insulin-like growth factor binding protein-1 were similar in the two groups of patients and the controls. The GH response to clonidine was significantly greater in group 2 and in the controls than in group 1. Concentrations of insulin and glucose after the glucose load were not different among the three groups. CONCLUSION(S): Women who were resistant to CC had a reduced GH response to clonidine. These data suggest that adequate GH secretory capacity is important for CC action.

Adult↗
PubMed2000

Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients.

The hypothesis that sperm aneuploidy and diploidy increase as a function of spermatogenesis impairment was addressed. Ejaculated semen samples from a series of men (n = 22) with very low total normal motile count (1 x 10(6)) was analysed in terms of sperm aneuploidy and diploidy by in-situ hybridization and compared with controls (n = 10). Germ cell aneuploidy was also analysed in an additional series of infertile patients presenting unexplained infertility (n = 3), congenital absence of the vas deferens (CAVD) (n = 6) and non-obstructive azoospermia (n = 3) undergoing IVF, microsurgical epididymal sperm aspiration (MESA)/ICSI and testicular sperm extraction (TESE)/ICSI cycles respectively. In-situ hybridization for chromosomes 1, 17, X and Y was performed on ejaculate, epididymal and testicular spermatozoa. Significantly higher sperm aneuploidy and diploidy rates where found (for the four chromosomes analysed) in spermatozoa from oligoasthenoteratozoospermia (OAT) over controls (18 versus 2.28% and 2.8 versus 0.13% respectively; P < 0.001). Testicular germ cells had even higher rates of sperm aneuploidy and diploidy. However, in this group it was difficult to determine whether the cells analysed were dysmorphic spermatozoa or spermatids. The data warrant further investigation on the cytogenetic abnormalities found in most germ cells identified in testicular tissue biopsies of azoospermic patients.

Adult↗
PubMed1999

Use of hysterosonography in women with abnormal postmenopausal bleeding.

PURPOSE OF INVESTIGATION: Hysterosonography (HS) allows evaluation of the endometrial cavity by endouterine administration of sterile physiologic solution. We aimed to identify the role of HS and transvaginal ultrasonography (TU) in postmenopausal women with unexplained bleeding in order to avoid further invasive investigation for patients with atrophic endometrium, and to obtain significant information on intracavitary focal lesions. METHODS: Eighty postmenopausal women with unexplained metrorrhage underwent both TU and HS. They were subsequently referred for hysteroscopy or dilatation and curettage, and histology was obtained. RESULTS: The sensibility of TU was comparable with that of HS (90% vs 93%). However, the specificity of TU was only 30%. Combined use of TU and HS raised sensibility and specificity to 95.9% and 96.7%, respectively. CONCLUSION: HS is superior to TU in the diagnosis of focal lesions because the uterine cavity, lesion volume and margins, and associated diffuse endometrial alterations are adequately depicted. HS is particularly valuable with benign focal lesions associated with atrophic endometrium, as in patients under tamoxifen in whom TU fails to detect the uterine cavity.

Adult↗
PubMed1999

Increased cyclin D1 expression is associated with features of malignancy and disease recurrence in ovarian tumors.

Alterations in the expression of cyclin D1 have been reported frequently in several human cancers, but their significance in the multistep model of carcinogenesis has been scantly described. To define the pattern of cyclin D1 expression in the development of ovarian cancer and clinical outcome, 55 cases of benign ovarian tumors, 12 borderline cases, and 37 ovarian carcinomas (32 primary and 5 recurrent carcinomas) were studied. Analyses were carried out on fresh tumor specimens by Western blotting and reverse transcription-PCR and provided significant superimposable results (P = 0.00001). Cyclin D1 abundance was classed according to the densitometric values as undetectable, detectable, well detectable, and highly detectable. A significant increase (P < 0.000001) in median cyclin D1 values was observed from benign (0.038; range, 0.001-0.705) to borderline (0.226; range, 0.001-0.623) to malignant (0.347; range, 0.027-2.330) to recurrent (0.887; range, 0.309-2.2260) tumors. In addition, higher median cyclin D1 values were reported in serous carcinomas (P = 0.058) and advanced-stage diseases (P = 0.003). Survival analyses carried out in the 32 primary carcinomas showed no significant difference in overall survival between detectable versus well/highly detectable cyclin D1 neoplasms. Conversely, a significant relationship between cyclin D1 expression and progression-free survival was found (P = 0.031). These results may elucidate the function of altered cyclin D1 expression in ovarian tumorigenesis and provide a basis for additional studies on its prognostic role.

Biomarkers, Tumor↗
PubMed1997

Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.

From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin 400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1-72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.

Adult↗
PubMed1997

Expression of cyclin D1 correlates with malignancy in human ovarian tumours.

Cyclin D1 is a cell cycle regulator of G1 progression that has been suggested to play a relevant role in the pathogenesis of several human cancer types. In the current study, the expression of cyclin D1 has been investigated in a series of 33 patients, with benign (10 patients), borderline (five patients) and malignant (18 patients) ovarian disease. Cyclin D1 protein and mRNA content were analysed by Western blotting and reverse transcriptase polymerase chain reaction respectively. The levels of cyclin D1 protein were undetectable in patients with benign disease, detectable in the majority of patients with borderline disease and elevated in those with ovarian carcinomas, being significantly related to the degree of malignancy (carcinoma vs benign, P = 0.0001; benign vs borderline, P = 0.0238). A significant relationship between cyclin D1 expression and tumour proliferative activity was also found (P = 0.000001). Moreover, eight benign lesions, two borderline tumours and 11 carcinomas proved to be suitable for the analysis of cyclin D1 transcript, and emerging data demonstrated significant agreement between protein abundance and mRNA expression. Results from the current study suggest that cyclin D1 expression is associated with the degree of transformation and most probably plays a role in the early development of ovarian malignancy.

Adolescent↗
PubMed1996

Establishment and characterization of three new cell lines derived from the ascites of human ovarian carcinomas.

Three human cancer cell lines (OC 314, OC 315, and OC 316) were newly established in permanent culture from the ascites of patients with serous adenocarcinoma of the ovary. OC 314 was derived from an untreated tumor presenting with ascites at diagnosis; OC 315 was isolated from a neoplasm progressing after cisplatin-containing regimen; and OC 316 was collected from a patient with pleural metastasis at diagnosis, resistant to different chemotherapeutic treatments including Taxol. These cell lines were repetitively subcultured once to twice a week through 75-80 passage generations. Tumor cells grew as monolayers and displayed epithelial-like morphology, consistent with a feature of adenocarcinoma, which was then confirmed by the expressions of cytokeratins and vimentin. The cell lines proved highly tumorigenic when transplanted into nude mice, both subcutaneously and intraperitoneally. In addition, the mice inoculated with subcutaneous OC 316 developed extremely aggressive tumor, also invading the peritoneum, which correlated with the malignant behavior of the original tumor. Drug sensitivity, evaluated by the MTT assay, showed that the three cell lines expressed similar sensitivity to doxorubicin. Responses to cisplatin essentially reported low sensitivity of OC 314 and OC 315 and resistance of OC 316, thus reflecting the original sensitivity at the clinical level.

Animals↗
PubMed1996

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

Adult↗
PubMed1995

Role of major histocompatibility complex class I expression and natural killer-like T cells in the genetic control of endometriosis.

OBJECTIVE: To evaluate whether the expression of human leukocyte antigen (HLA) class I on eutopic and ectopic endometrial cells modify the susceptibility to lysis mediated by lymphocytes. DESIGN: Evaluation of T lymphocyte cytotoxic activity and HLA class I expression on endometrial cells. SETTING: Subjects were recruited at laparoscopy. PATIENTS: Patients with endometriosis (n = 7). Healthy women as controls (n = 10). MAIN OUTCOME MEASURES: Human leukocyte antigen class I molecule analysis of endometrial cells was carried out by immunofluorescence and flow cytometry. Phenotyping of T lymphocytes was performed to analyze T-cell subsets. Cytotoxicity was performed to determine cytolytic activity against endometrial cells. RESULTS: In vitro culture of endometrial cells down-regulates the expression of HLA class I molecules and enhances the susceptibility to lysis mediated by natural killer (NK)-like T lymphocytes. Cytolytic T-cell clones, expressing the CD94 antigen, are inhibited by the HLA-B7 allele on endometrial cells. Ectopic endometrial cells modulate the expression of HLA class I molecules. CONCLUSIONS: The resistance to lysis of endometrial cells is related to expression of surface HLA class I molecules, which send a negative signal for lysis mediated by NK-like T lymphocytes. The HLA-B7 allele inhibits the cytotoxic activity, suggesting that the growth of ectopic endometrial cells might be under a genetic control.

Alleles↗
PubMed1994

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Therapeutic experience of the North-West Oncology Group (GONO) on ovarian carcinoma.

The North West Oncology Group is a cooperative group that has carried out several clinical trials on the treatment of ovarian carcinoma in the last 10 years. In a randomized study of advanced ovarian carcinoma patients, the combination of cisplatin plus cyclophosphamide (PC) came out as superior to cisplatin plus cyclophosphamide plus doxorubicin in terms of complete clinical and pathological response rates and 8-years progression free survival (PFS). A randomized trial showed that PAC and cyclophosphamide plus doxorubicin plus carboplatin (CAC) were equivalent in terms of objective response (OR) rates, pathologic complete response (pCR) rates, median survival (S) and median PFS. After PAC or CAC therapy, patients with pCR or minimal residual disease were included in a randomized trial comparing abdominopelvic radiotherapy (RT) versus 3 more courses of the chemotherapy they had received before. This study was stopped early because of a clear advantage in S and PFS for chemotherapy arm. Patients with macroscopic residual disease at second-look surgery and patients with progressing or relapsing disease after first line chemotherapy crossed to an alternative analogue: from PAC to carboplatin and from CAC to cisplatin. An OR was obtained in 25% of the patients of the cisplatin arm and in only 9% of the patients of carboplatin arm. Randomized clinical trials analyzing the role of intraperitoneal administration of chemotherapy and the role of biological response modifiers such as interferons in the treatment of patients with advanced epithelial ovarian carcinoma are currently ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Treatment of FIGO stage Ib cervical carcinoma with nodal involvement.

One hundred and eighty one patients with stage Ib cervical cancer underwent hysterectomy with pelvic lymphadenectomy. The overall incidence of lymph node metastases was 20%. Twenty seven (71%) patients with nodal involvement were treated by external radiotherapy (TCT) and 11 (29%) by both chemotherapy and radiotherapy (Lin. Acc.). The overall survival at 5 years was 80%; it was 43% for patients with positive nodes and 89% for patients without metastatic nodal disease. The 3 year survival of patients with positive nodes who underwent radiation therapy by TCT was 58%, while it was 72% for those treated by chemotherapy plus radiotherapy. We observed a recurrence in 23% of the cases, 52% in patients with positive nodes and 15% in those with negative nodes. The association chemo-radiotherapy in patients with metastatic lymph nodes seems to improve the survival and reduce the recurrence rate.

Adenocarcinoma↗
PubMed1993

Lymphocytes isolated from the peritoneal fluid of women with advanced ovarian carcinoma differ significantly from autologous peripheral blood lymphocytes.

The phenotypic and functional analysis of ovarian carcinoma-associated lymphocytes (OCAL), obtained from a group of patients with neoplastic carcinosis, reveals major differences between OCAL and peripheral blood lymphocytes (PBL). Virtually all of the OCAL belong to the T cell lineage, whereas both B and natural killer (NK) cells are virtually absent. NK activity is also significantly lower than that exerted by PBL. Following treatment with rIL-2, lymphokine-activated killer cell activity is poorly inducible in OCAL. In addition, in vitro stimulated OCAL produce low amounts of lymphokines. Clonal analyses reveal a low clonal efficiency, which indicates a severe proliferative defect. T cell clones obtained show peculiar features: the percentage of CD4 and CD8 clones varies greatly in the different samples. Both CD8 and a significant proportion of proliferating CD4+ clones are cytotoxic in a lectin-dependent cytolytic assay. These findings, together with the results obtained from comparative analyses of the peripheral blood of the same group of patients, demonstrate the unique characteristics of OCAL and should be considered in the preparation of protocols for the locoregional immunotherapy of ovarian carcinoma.

Adenocarcinoma↗
PubMed1993

Recombinant interleukin-2 corrects in vitro the immunological defect of endometriosis.

PROBLEM: It has been shown recently that women with endometriosis have several immunological defects. In particular, these patients have a defect in peripheral blood natural killer cell activity and have lost their capacity of recognizing and lysing autologous endometrial cells. METHOD: We evaluated the effect of recombinant interleukin-2 (rIL-2) on peripheral blood lymphocytes obtained from both healthy donors and endometriosis patients. The generation of a strong cytolytic activity against autologous endometrial cells was obtained from both normal donors and endometriosis patients. RESULTS: Interestingly, these cytolytic cells belong to the T-cell lineage and do not recognize both autologous keratinocytes and allogeneic endometrial cells, thus suggesting a mechanism of specific recognition of autologous cells. CONCLUSION: The capability of restoring cytolytic activity using rIL-2 suggests a new immunotherapeutic approach for the treatment of severe endometriosis.

Antigens, Differentiation, T-Lymphocyte↗