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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 163 records · Page 9Linked to original sources
PubMed1997

Growth factor administration following autologous peripheral blood progenitor cell transplantation.

Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia. Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia. However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production. Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone. The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery. Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT. A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect. Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT. Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.

Erythropoietin↗
PubMed1997

Cytology, histology, and colposcopy in the diagnosis of neoplastic non-invasive epithelial lesions of the cervix.

The purpose of our study was to examine the concordance among colposcopy, cytology, and histology in the diagnoses of intraepithelial lesions of the uterine cervix. We compared the results of Pap tests, biopsies, and colposcopy in 190 patients, who had histologically proven CIN and/or HPV infection, using histology as "the gold standard". The chi 2 (chi square) test was used for the statistics analysis. The sensitivity of cytology for the detection of CIN was 70%, and was lower for LGL (low grade lesions) than for HGL (high grade lesions): 61.2% versus 88.5%, respectively (p < 0.0001). We obtained a high rate of false negative smears (30%), with a relatively high rate of inadequate samples (59.6%). The sensitivity of colposcopy was 92%. Our results suggest that the Pap test alone is no longer sufficient for the screening of precancerous lesions of the cervix, and colposcopy is compulsory each time the smear is inadequate or altered.

Adolescent↗
PubMed1996

Modified type IV-V radical hysterectomy with systematic pelvic and aortic lymphadenectomy in the treatment of patients with stage III cervical carcinoma. Feasibility, technique, and clinical results.

BACKGROUND: Due to the high prevalence of perioperative major morbidity and the difficulties in achieving surgical disease free margins, surgery has had no role in the treatment of patients with Stage III cervical carcinoma. METHODS: Forty-two women with International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical carcinoma responding to platinum-based neoadjuvant chemotherapy underwent the maximum surgical effort, comprised of a modified type IV-V radical hysterectomy (37 patients) or anterior pelvectomy (5 patients) with systematic pelvic and aortic lymphadenectomy. Feasibility, modifications of surgical technique, and pathologic and clinical data were analyzed. RESULTS: Surgery was feasible in all 42 patients intraoperatively selected. Disease free margins were achieved in all but one patient. The median operating time was 390 minutes, and the median estimated blood loss was 800 mL. In the last series of patients, these figures declined to 320 minutes and 600 mL, respectively. Major morbidity consisted of severe intraoperative hemorrhage in two patients, pulmonary embolism in four, ureteral fistula in three, and laparocele in three. The number of lymph nodes removed ranged from 30 to 117 with a median of 56. The mean lengths of vagina and lateral parametrium resected were 55 and 48 mm, respectively. Despite perioperative chemotherapy, lymph node metastasis was present in 36% of patients, parametrial disease in 38%, and vaginal disease in 45%. After a median follow-up of 53 months, the 5-year overall and disease-free survival rates of radically operated patients were 70% and 58%, respectively. CONCLUSIONS: Thanks to improved surgical technique and perioperative care, extended radical surgery appears to be feasible with acceptable morbidity in chemosensitive women with Stage III cervical carcinoma and may constitute a valid alternative to radiotherapy in these patients.

Adenocarcinoma↗
PubMed1996

Tamoxifen synergizes the antiproliferative effect of cisplatin in human ovarian cancer cells: enhancement of DNA platination as a possible mechanism.

We investigated the chemosensitizing activity of tamoxifen (TAM) on estrogen receptor negative ovarian cancer cell lines sensitive (A2780 WT) and resistant to cisplatin (CP) (A2780 CP3). Our results showed that the treatment of both cell lines with the association TAM + CP (concentration range 0.01-1 microN and 0.1-1 microgram/ml, respectively) results in a synergistic antiproliferative activity and a complete reversal of the acquired CP-resistant phenotype. We demonstrated that in A2780 cells the addition of TAM to CP treatment is able to significantly enhance at every tested CP dose (P < 0.001) the amount of platinum (Pt) bound to the DNA. Since Pt-DNA levels in the genome are clearly related to the growth inhibitory effect of CP (correlation value = 0.97, P < 0.001) in our experimental model, we hypothesized that TAM could act synergistically with CP and overcome the acquired CP-resistance by enhancing Pt binding to the DNA. We suggest that, from a clinical point of view, TAM may be usefully included in CP-based chemotherapy regimens for ovarian cancer patients since plasma concentrations of the drug capable of in vitro CP resistance modulation are achievable in vivo. A prospective clinical trial to verify the clinical usefulness of combined TAM + CP treatment in ovarian cancer patients refractory to prior Pt-based chemotherapy is now underway in our department.

Antineoplastic Agents↗
PubMed1996

Modulatory effect of tamoxifen and ICI 182,780 on adriamycin resistance in MCF-7 human breast-cancer cells.

In this study the ability of the new pure anti-estrogen ICI 182,780 to modulate the cytotoxic action of adriamycin (ADR) on parental and ADR-resistant MCF-7 (MCF-7 ADRr) human breast-cancer cells was investigated and compared with that of tamoxifen (TAM). TAM enhanced ADR cytotoxicity in MCF-7 ADRr cells in a dose-related manner, but this effect was slight or absent in MCF-7 WT. In contrast, ICI 182,780 was able to enhance ADR toxicity both in MCF-7 ADRr and in the parental cell line. ICI 182,780 was up to 2.5-fold more effective than TAM in reducing the IC50 of ADR in MCF-7 ADRr cells. Analysis of the data by the isobole method showed that the combination ADR/TAM and ADR/ICI 182,780 produced synergistic anti-proliferative activity in MCF-7 ADRr cells. Because ADR resistance in these cells is associated with the expression of high levels of P-glycoprotein (Pgp), we evaluated the effect of anti-estrogens on Pgp expression and activity. Both ICI 182,780 and TAM failed to modulate Pgp expression as assessed by flow cytometry and Western-blot analysis, performed using the monoclonal antibodies MM4.17 and C 219, which are specific for an external or an internal determinant respectively. Pgp activity was investigated by flow cytometry measuring the extrusion of ADR and the cationic dye Rhodamine 123 (Rh 123). ICI 182,780, but not TAM, reduced the activity of Pgp in MCF-7 ADRr cells. Flow cytometry was also used to investigate cell-cycle modifications induced by ADR in MCF-7 ADRr cells, both in the presence and in the absence of anti-estrogens. After 72 hr, higher doses induced an arrest of cells at the G2/M phase. The same effect was visible when lower doses of ADR were combined with ICI 182,780 or TAM. In terms of cell-cycle-blocking activity ICI 182,780 was largely more effective than TAM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Cathepsin D concentration in primary laryngeal cancer: correlation with clinico-pathological parameters, EGFR status and prognosis.

Sixty-three patients with primary laryngeal squamous-cell carcinoma were followed up for a median of 33 months after surgery. Cathepsin D (Cath D) concentration was assayed using a solid phase 2-site immunoradiometric assay in which the first monoclonal antibody (MAb) was coated on the ELISA solid phase and the second one, MIG8 radiolabeled with 1125-EGF, was used as the tracer. The median value of Cath D (13.8 pM/mg protein) was chosen as cut-off. Cath D > or = median value was closely related to neck lymph node involvement at presentation and to a short metastasis-free survival (MFS) and actual overall survival (OS). The 5-year MFS was 71% for patients with Cath D < median value tumors as compared with 0% for patients with Cath D > or = median value tumors. Lymph node status at presentation was not related to a short MFS and OS. Cox's univariate regression analysis using Cath D as a continuous variable showed that Cath D levels are correlated with neck lymph node metastasis. On multivariate analysis, Cath D status proved to be an independent factor for predicting a short MFS. Cath D assay may prove to be particularly useful in identifying laryngeal cancer patients who, with or without neck lymph node involvement at presentation, are at high risk of metastatic disease and poor outcome.

Carcinoma, Squamous Cell↗
PubMed1996

Growth hormone stimulates androsterone synthesis by rat theca-interstitial cells.

The aim of this study was to assess the possible role of growth hormone (GH) on androsterone synthesis. This effect was analyzed in theca-interstitial cells obtained from immature female rats. The addition of GH to the cultures significantly stimulated androsterone (A) synthesis in a dose- and time-dependent way and this effect was not due to a cellular number increase. When added to the hCG cultures, GH significantly enhanced androgen production even though it did not synergyze with the chorionic gonadotropin. The addition of antibodies anti-IGF-I to the GH cultures did not modify the growth hormone effect suggesting that GH probably does not require IGF-I to achieve its effect on A production. Finally, no effect of GH on cAMP levels were observed in the cultures at the end of the treatment. Our results demonstrate that GH is able to significantly induce A synthesis by rat theca-interstitial cells. Since the presence of GH and its receptors in the ovary is now well established the present data strongly suggest a potential relevance of GH in reproductive biology.

Androsterone↗
PubMed1996

Locally advanced cervical adenocarcinoma: is there a place for chemo-surgical treatment?

The increased frequency and poor prognosis of cervical adenocarcinoma call for new therapeutic strategies, especially in locally advanced disease. Combined neoadjuvant chemotherapy (NACT)-radical surgery (RS) has been investigated to assess its feasibility and the possible impact on disease outcome. Data were pooled from three consecutive trials on a total of 42 patients with FIGO Stage IB-IIA >4 cm (9), IIB (19), and IIIB (14) cervical adenocarcinomas. NACT regimens consisted of cisplatin (P), bleomycin (B) and methotrexate, high-dose PB, and P and doxorubicin combinations for one to three cycles. Responding patients underwent RS while those still ineligible for RS underwent radiotherapy. Fisher and chi squared tests were used to detect significant factors affecting response to NACT. Cox multivariate regression analysis was used to evaluate parameters affecting response and survival. Medians and life tables were computed by the method of Kaplan and Meier. Median follow-up times were 56 (17-95) and 54 months (15-92) from enrollment and RS, respectively. NACT-induced toxicity was generally mild and did not compromise RS when indicated. The 33 (79%) responders underwent laparotomy, while the 9 nonresponders received radiotherapy. RS was feasible in 29 (69%) patients. Macroscopic intraperitoneal tumor (IPT) excluded abandoning RS in 4 cases. Mild to moderate RS-related complications were seen in 41% of cases with the same pattern as in the absence of any prior treatment. In patients undergoing RS, node metastasis and microscopic IPT were detected in 2 (7%) and 3 (10%) patients, respectively. The 5-year overall and disease-free survivals were 71% (100% IB-IIA and 84% IIB vs 36% IIIB; P = 0.001) and 88%, respectively. None of the nonresponders survived (median 10 months, 6-25), compared with an 84% 5-year survival of responders (P < 0.001). FIGO stage and parametrial involvement significantly predicted response to NACT which was the only independent variable affecting survival (P = 0.006). This retrospective study provided evidence of the chemosensitivity of locally advanced cervical adenocarcinoma and that chemoresponsiveness is the most potent predictor of cure, as demonstrated in squamous cell cervical cancer. Combined NACT and RS is a feasible treatment which seems to be able to improve the outcome of Stage IB-IIB cervical adenocarcinoma. Randomized trials comparing this new strategy with conventional treatments seem to be warranted.

Adult↗
PubMed1996

Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy.

To assess the patterns of lymphatic spread in cervical carcinoma, radical hysterectomy with systematic lymphadenectomy was performed in 66 patients FIGO stage IB-IIA <4 cm, and 159 patients stage IB-IIA >4 cm to stage IV. The latter patients were treated with neoadjuvant chemotherapy (NACT). Parametria were evaluated by the giant section technique in 109 patients. In 40 of these, the superficial and deep layers of the vesicouterine ligament, the sacrouterine ligament, and the distal part of the cardinal ligament were separately evaluated. The median number of nodes removed was 48 pelvic (range 20-107) and 22 aortic (range 7-64). Positive nodes were found in 14 (21%) stage IB-IIA <4 cm and in 38 (23%) NACT-treated patients, all having pelvic node metastasis. Aortic nodes were involved in 2 (3%) and 5 (3%) patients, respectively. Solitary metastases were found in the superficial obturator (21% of stage IB-IIA <4 cm and 31% of NACT-treated positive node patients, respectively), external iliac (7 and 3%, respectively), and common iliac nodes (7 and 3%, respectively). Parametrial nodes were found in 59% of giant sections (8% metastatic). The superficial and deep layers of the vesicouterine ligament, the uterosacral ligament, and the distal part of the lateral parametrium revealed the presence of nodes in 33% (no metastatic nodes), 26% (3% metastatic), 5% (no metastatic nodes), and 70% (5% metastatic) of patients, respectively. Overall, parametrial nodes were positive in 12% of stage IB-IIA <4 cm and 7% of NACT-treated patients. The diameter of node metastasis was <10 mm in more than 80% of positive nodes. In conclusion, parametrial nodes were mainly located in the cardinal and vesicouterine ligaments, both being a potential site of metastasis. The superficial obturator, external iliac, common iliac, paracaval, intercavoaortic, and paraaortic nodes were the groups more frequently involved. These data may be useful for tailoring radical hysterectomy and lymphadenectomy according to the primary tumor and the surgeon's intent.

Adult↗
PubMed1996

Transvaginal color Doppler ultrasonography in the presurgical characterization of adnexal masses.

The aim of our study was to evaluate flow-velocity waveforms from ovarian tumors with color Doppler, in order to test the predictivity of malignancy and to compare the Doppler technique with some morphological scoring systems. Color Doppler examination of ovarian neoplasms was performed in 122 patients within 2-3 days from surgery and, based on vascular characteristics and on Doppler resistance index, a "vascular" score was calculated. One hundred one women had benign and 21 had malignant tumors on histopathology. In all of the malignant lesions color Doppler was able to detect vascular patterns, whereas only 43% of the benign tumors showed recognizable vessels (P < 0.001). Malignant masses showed significantly greater vascular scores than those of benign tumors (P < 0.001). Doppler ultrasonography achieved better specificity and PPV when compared to morphological scores (96% vs 61-75% and 82% vs 35-48%). Color Doppler ultrasonography of ovarian tumors seems to be a reliable method in the presurgical characterization of ovarian neoplasms.

Adnexal Diseases↗