Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 253 records · Page 14Linked to original sources

PubMed1994

Growth hormone induces in vitro maturation of follicle- and cumulus-enclosed rat oocytes.

The aim of this study was to assess the possible role of growth hormone (GH) on rat oocyte maturation. This effect was analyzed in follicle-enclosed, cumulus-enclosed and denuded oocytes obtained from immature pregnant mare's serum gonadotropin (PMSG)-treated rats. The addition of GH to the cultures significantly accelerated maturation in both follicle- and cumulus-enclosed oocytes while no effect was seen on denuded oocytes maturation. Also, GH accelerated meiotic maturation in follicle-enclosed oocytes from immature untreated rats. The GH action was not mediated by lactogenic receptors since prolactin (Prl) did not affect the maturation process while it was mediated by insulin growth factor-I (IGF-I) as suggested by the block of GH action observed in the presence of antibodies anti-IGF-I. Finally, no GH effect was found when dbcAMP was added to the cultures. Our results demonstrate that GH is capable of inducing maturation in oocytes from both primed and unprimed rats. Since the presence of physiological levels of GH in the ovary is now well established, the present data strongly suggest a potential relevance of GH in the reproductive biology.

Animals↗

PubMed1994

Clinical significance of cathepsin D in primary ovarian cancer.

Cathepsin D (Cath D) levels were assayed in a prospective series of 72 patients with primary ovarian carcinoma, by using an immunoradiometric assay. Cath D levels ranged from 2.00 to 45.60 pmol/mg protein with a median value of 15.80 pmol/mg protein. Cath D levels were higher in metastatic deposits than in primary tumors (median 24.12, range 9.33-98.33 pmol/mg protein versus median 12.76, range 2.00-45.20 pmol/mg protein; P = 0.04). The cut-off levels of the lower, median and upper quartiles of the distribution of Cath D were identified to distinguish patients with low, intermediate, and high Cath D content. Cases with low Cath D content showed a lower percentage of complete response to chemotherapy than cases with intermediate and high Cath D content (22% versus 65% and 47%, respectively) (P = 0.003). Moreover cases with high Cath D content showed a worse prognosis with respect to patients with intermediate Cath D levels (P = 0.09). Interestingly, cases with low Cath D content had a shorter progression-free survival with respect to cases with intermediate Cath D content (P = 0.04). Cath D status retained an independent prognostic value when assessed in the multivariate analysis.

Adult↗

PubMed1994

Anatomic abnormalities of the retroperitoneum encountered during aortic and pelvic lymphadenectomy.

OBJECTIVE: Our purpose was to describe retroperitoneal abnormalities and related surgical problems encountered during lymphadenectomy. STUDY DESIGN: A prospective study was carried out on 309 consecutive patients with cervical, endometrial, and ovarian cancer treated with systematic aortic and pelvic lymphadenectomy at the Department of Gynecological Oncology of the Catholic University, Rome. RESULTS: Urinary and vascular anomalies were observed in five (1.6%) and 42 (13.6%) cases, respectively. Preoperative diagnosis was made by intravenous pyelography and computed tomographic scan in 14.9% (seven of 47) of patients with malformations. In three cases abnormal vessels were accidentally injured during lymphadenectomy with no postoperative sequelae. CONCLUSIONS: Preoperative diagnosis of retroperitoneal abnormalities is rarely made during routine preoperative workup. Thus during surgery an accurate surgical technique including adequate exposure of retroperitoneal organs and careful blunt dissection together with a knowledge of both normal and abnormal anatomy are necessary to avoid accidental injury to abnormal retroperitoneal organs.

Adult↗

PubMed1994

Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin as a trigger of ovulation in polycystic ovarian disease gonadotropin hyperstimulated cycles.

OBJECTIVE: To compare the use of GnRH agonist (GnRH-a) versus hCG in triggering the follicular rupture in patients with polycystic ovarian disease (PCOD) in whom ovulation was induced by gonadotropins. DESIGN: Polycystic ovarian disease gonadotropin hyperstimulated cycles outcome was investigated in a prospective study. PATIENTS AND INTERVENTIONS: Thirty-three PCOD patients (40 cycles) with gonadotropin-induced mild to moderate degree of ovarian hyperstimulation received 5,000 IU IM hCG or 200 microg [corrected] SC GnRH-a. A subgroup of GnRH-a-treated patients received P for luteal support. Five GnRH-a-treated patients underwent a GnRH test during luteal phase. MAIN OUTCOME MEASURES: Echographic and endocrine characteristics both during the therapy and the luteal phase. RESULTS: There was a similar percentage of ovulation and pregnancy rate in both groups of patients. The ovarian enlargement during the luteal phase in the GnRH-a-treated patients was lower than in the hCG group. Progesterone plasma levels (at midluteal phase) and the length of luteal phase was significantly lower in GnRH-a-treated patients with respect to the hCG-treated group. These differences disappeared in patients receiving luteal support. After GnRH injection, LH secretion decreased in GnRH-a-treated patients with respect to controls; however, corpus luteum was able to respond with a normal increase of P production. CONCLUSION: The GnRH-a appears to be an effective alternative to hCG for inducing the follicular rupture in stimulated cycles in women who are at risk for developing ovarian hyperstimulation syndrome. However, GnRH-a administration can induce short luteal phase. This defect may be ascribed to the pituitary desensitization rather than to a direct effect on corpus luteum. Luteal phase support is needed to prevent luteal phase deficiency.

Adult↗

PubMed1994

Effect of activin-A on progesterone synthesis in human luteal cells.

OBJECTIVE: To examine the effect of activin-A on basal and hCG-stimulated P production by human luteal cells. DESIGN: Mixed luteal cell cultures and distinct cultures of two luteal cell types: small and large luteal cells from early and midluteal phase. SETTING: Corpora lutea (CL) were obtained from the Obstetrics and Gynecology Department of the Catholic University, Rome, Italy. PATIENTS: Fifteen nonpregnant women between 30 and 45 years of age underwent surgery for nonendocrine gynecological diseases. INTERVENTIONS: Corpora lutea were obtained at the time of hysterectomy. The luteal cells were dispersed in Ham's F-12 medium containing collagenase at 37 degrees C in shaking water bath for 2 hours, filtered, centrifuged, and resuspended in fresh medium. MAIN OUTCOME MEASURES: The cells diluted to a final concentration of 60,000 to 100,000 cells/mL of medium. After 24 hours, the cells attached to the wells and were incubated with or without hCG and/or activin-A at different concentrations. RESULTS: Activin-A starting from 25 micrograms/L significantly decreased basal and hCG (250 mIU/mL [conversion to SI unit, 1.00])-induced P production by mixed luteal cells. The small luteal cells responded to hCG (250 mIU/mL), and the treatment with activin-A (from 25 to 100 micrograms/L) reduced their basal and hCG-induced P production. Activin-A addition did not change the amount of P release by large luteal cells at any concentration. CONCLUSIONS: These results imply that activin-A plays a role in the local regulation of human CL.

Activins↗

PubMed1994

Correlation Between AFS Classification Systems of Adnexal Adhesions and Distal Tubal Occlusion, Tubal Mucosa at Salpingoscopy and Reproductive Outcome of the Patient

From November 1988 to December 1991, 45 infertile patients underwent salpingo-ovariolysis and/or salpingoneostomy during laparotomy or laparoscopy. Findings at surgery were scored according to the AFS classification. Salpingoscopy was performed to evaluate the status of the ampullary mucosa. The mean age of the patients was 29.5 years and the mean length of infertility prior to surgery was 4.4 years. All patients were contacted by phone to obtain information on reproductive outcome with a minimum period of 18 months of follow-up. Statistical analysis of data was performed using the Fisher's exact test. AFS scores were not correlated with reproductive outcome, while the status of the tubal mucosa at salpingoscopy was significantly correlated with reproductive outcome.

Journal Article↗

PubMed1994

Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors.

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer.

Adult↗

PubMed1994

Differential androgen response to adrenocorticotrophin hormone stimulation and effect of opioid antagonist on insulin secretion in polycystic ovarian syndrome.

To investigate the effect of a chronic anti-opioid treatment on the adrenal steroid production in polycystic ovarian syndrome (PCOS), 20 women affected by PCOS were studied before and after 6 weeks of treatment with an opioid antagonist. All women had an oral glucose tolerance test (OGTT) (75 g) on day 5 of the cycle. At 11.00 p.m. 2 mg of dexamethasone was orally administered and blood samples collected the following day at 7.00 a.m. Then 250 micrograms of adrenocorticotrophin hormone (ACTH) was injected i.v. and samples collected 60 min later. At this time a 6 week course of naltrexone treatment (50 mg/day orally) was started, following which the protocol was repeated on day 6-7 of the menstrual cycle. According to OGTT responses, 10 patients were classified as hyperinsulinaemic and 10 as normoinsulinaemic. No difference in baseline hormone concentrations was found, except for sex hormone-binding globulin, which was significantly greater in normoinsulinaemic patients (P < 0.02). The plasma concentration of all steroids after dexamethasone and ACTH administration was similar in both groups, except for androstenedione (P < 0.02) and 17 alpha-hydroxyprogesterone (17-OHP) (P < 0.05), which were significantly greater after ACTH injection in hyperinsulinaemic compared with normoinsulinaemic PCOS patients. Naltrexone treatment significantly (P < 0.001) reduced insulin response to OGTT in the hyperinsulinaemic group, while it did not affect the response in the normoinsulinaemic group; thus at the end of the treatment the two groups had the same insulin concentrations. Similarly, naltrexone abolished the difference between normoinsulinaemic and hyperinsulinaemic patients regarding androstenedione and 17-OHP response to ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

A new transabdominal approach to the left retroperitoneum for systematic removal of lymph nodes left of the aorta in gynecologic malignancies.

To improve the exposure of the left retroperitoneum, a peritoneal incision is made in the left paracolic gutter up to the splenic flexure. By elevating and medially displacing the left colon, the avascular plane between this and the prerenal fascia is entered and developed caudally to the aorta bifurcation, and cranially 3-4 cm beyond the left renal pedicle. Thus, the left kidney, its pedicle, the ureter, the ovarian vessels, and the aorta are adequately exposed. In 81 patients with gynecologic tumors who underwent the modified lymphadenectomy, the median number of aortic nodes removed was 29 (range 21-56). The median duration of left dissection was 35 minutes (range 25-50) and of the entire aortic lymphadenectomy 70 minutes (range 50-120). No major intraoperative injuries occurred. The frequency and type of postoperative complications were not affected by this modification. This new approach provides better exposure of the left retroperitoneum, thus permitting safe and complete dissection of the nodes left of the aorta without increased morbidity. If aortic dissection can be limited to the left side, this technique makes it possible to avoid opening the right retroperitoneum.

Adult↗

PubMed1994

Insulin secretion in patients with gestational diabetes: relationship with pregnancy outcome.

The authors observed that there is wide variability in insulin response to an oral glucose tolerance test in women developing carbohydrate intolerance during pregnancy. This variability ranges from a reduction of pancreatic islet function to a normal or exaggerated secretory pattern of insulin. Moreover the results also suggest that exaggerated insulin secretion and/or high insulin resistance may play a role in the regulation of gestational blood pressure and that a higher glucose/insulin ratio may be positively related to birth weight. Clearly, further studies are needed to investigate the impact of this metabolic situation on the optimization of the clinical control of glucose metabolism and fetal homeostasis.

Adult↗

PubMed1994

Preoperative ultrasound assessment of omental spread in ovarian cancer.

The accuracy of high-resolution ultrasound in the detection of macroscopic omental metastases was evaluated in 50 consecutive patients undergoing surgery for ovarian cancer. Ultrasound provided an overall diagnostic accuracy of 83.7%, with a sensitivity of 76.6% and a specificity of 100%. The sensitivity in the diagnosis of diffuse omental involvement was 93.3%. Moreover, the overall diagnostic accuracy, sensitivity and positive predictive value of the method increased as the study progressed. In the last 25 cases examined, in fact, these values were 94.7, 90, and 90%, respectively.

Adult↗

PubMed1993

Human B-cell immune response to the polymorphic epithelial mucin.

Human antibodies generated by Epstein-Barr virus immortalized B-cells from tumor-draining lymph nodes of an ovarian cancer patient were screened for reactivity in enzyme-linked immunosorbent assay with a synthetic peptide corresponding to the protein core of the polymorphic epithelial mucin. Epitopes within this region are in fact considered tumor specific since they are selectively exposed in tumor cells due to aberrant glycosylation. Human antibody BB5, thus selected, reacts in enzyme-linked immunosorbent assay and immunohistochemistry with polymorphic epithelial mucin-expressing tumor cells. This is the first demonstration of the existence of a B-cell immune response to selected epitopes of polymorphic epithelial mucin and, together with the cytotoxic T-cell response already demonstrated, constitutes the basis for the use of synthetic peptides as a vaccine in cancer patients.

Adult↗

PubMed1993

Quercetin induces type-II estrogen-binding sites in estrogen-receptor-negative (MDA-MB231) and estrogen-receptor-positive (MCF-7) human breast-cancer cell lines.

We show that flavonoids positively regulate type-II estrogen-binding site (type-II EBS) levels both in MCF-7 (ER-positive) and in MDA-MB231 (ER-negative) breast-cancer cells. Type-II EBS were measured by a whole-cell assay at 4 degrees C for 2.5 hr using [3H]-estradiol as tracer. In both cell lines the effect of quercetin (Q) was dose-related and already evident after 12 hr of Q treatment. The increase of type-II EBS levels after Q exposure requires both RNA and protein synthesis, since actinomycin D and cycloheximide completely abolished the stimulatory effect. The ability of flavonoids in inducing type-II EBS is well correlated with their relative binding affinity for type-II EBS. The flavonoid-induced enhancement of type-II EBS levels is accompanied by increased sensitivity of cancer cells to the inhibitory effect of low Q concentrations. Our data suggest that type-II EBS are ligand-regulated receptors.

Binding Sites↗

PubMed1993

Autologous stem cell transplantation: sequential production of hematopoietic cytokines underlying granulocyte recovery.

We investigated the serum concentrations of a variety of cytokines [granulocyte-macrophage-colony-stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin (IL) 1 alpha, IL-3, IL-6, IL-8, erythropoietin, tumor necrosis factor alpha, gamma-interferon in 10 patients with advanced ovarian cancer undergoing autologous peripheral blood stem cell (PBSC) harvesting followed by treatment with high-dose cisplatin, etoposide, and carboplatin and PBSC transplantation (chemotherapy was administered on days 1 through 3, PBSCT on day 6). Preliminary observations on cytokine serum levels were performed for 4 patients; on this basis, the kinetics of cytokines was then investigated in greater detail at closely sequential times in 6 further patients. We observed a consistent pattern of sequential GM-CSF, G-CSF, and IL-8 release after chemotherapy/PBSCT in all 10 cases, including the 6 patients monitored in detail: (a) at days 5-10 a GM-CSF peak; (b) at days 12-14 a pronounced release of both G-CSF and IL-8, which always preceded granulocyte recovery by approximately 7 days. At days 17-23, a second GM-CSF peak was monitored in 5 of the 6 patients analyzed in detail, as well as in the other 4 cases. Particularly relevant are the observations that: (a) the peak of G-CSF serum concentration and neutrophil number in the recovery phase are strikingly and directly correlated, thus indicating a key role for G-CSF in granulocyte rescue; (b) the time courses of G-CSF and IL-8 levels are strictly parallel, thereby suggesting a coordinate stimulus for production of granulocytes, mediated by G-CSF, and their activation/migration capacity, mediated by IL-8. Results were essentially negative for IL-3, tumor necrosis factor alpha, and gamma-interferon concentrations (except in one case for each cytokine). An early peak of IL-1 alpha was observed in all 3 analyzed patients, while an IL-6 peak was monitored at days 13-15 in all 4 patients analyzed in detail. The present results indicate a sequential coordinate pattern of cytokine release after ablative therapy and PBSCT and shed light on the mechanisms mediating the recovery of granulocytes, and more generally of hematopoiesis, after stem cell transplantation. Furthermore, these studies may contribute to the design of improved protocols for cytokine administration following myelosuppressive anticancer therapy, as well as to the prediction of granulocytic response.

Adult↗

PubMed1993

Type II estrogen-binding sites in human ovarian cancer: correlation with estrogen, progesterone, and epidermal growth factor receptor.

Type II estrogen-binding sites (Type II EBS) and the recently identified bioflavonoid-like ligand methyl-p-hydroxyphenyllactate may be regarded as a growth regulatory system active on both normal and neoplastic tissues. It has been reported that, in addition to estrogen and progesterone receptors, primary ovarian cancers also express Type II estrogen binding sites. These sites are able to bind estrogenic compounds and also some naturally occurring flavonoids such as quercetin. In this study we report the presence of cytosolic Type II EBS in a series of 10 normal ovaries, 42 primary ovarian tumors, and 14 metastatic deposits. Scattered levels of Type II EBS were found in normal ovarian tissues (median, 1603 fM/mg protein, range, 271-4943). In primary ovarian tumors and in omental metastases median levels of Type II EBS were 835 fM/mg protein (range, 134-4875) and 758 fM/mg protein (range, 204-2007), respectively. Although Type II EBS tend to be higher in normal than in malignant tissues the difference was not statistically significant. No correlation was found between Type II EBS levels and the common clinicopathological characteristics of the tumors. Moreover there was no relation between Type II EBS and estrogen and epidermal growth factor receptors. A significative inverse correlation with progesterone receptor levels was observed. The presence of Type II EBS in ovarian cancer could be of clinical importance since it has been demonstrated that bioflavonoids, through the interaction with Type II EBS, may exert a growth inhibitory activity both alone or in combination with chemotherapeutic agents on ovarian cancer cell lines and primary tumors.

Aged↗

PubMed1993

Cisplatin (P), bleomycin (B), and methotrexate (M) preoperative chemotherapy in locally advanced vulvar carcinoma.

Based on the encouraging results of neoadjuvant chemotherapy (NACT) and radical surgery (RS) observed in locally advanced cervical cancer, 21 patients with advanced squamous cell carcinoma of the vulva (FIGO stages, IVa, 21; TNM stages, T2N2M0, 6, T3N2M0, 11, T4N2M0, 4) were submitted to two to three cycles of cisplatin (P, 100 mg/m2, Day 1), bleomycin (B, 15 mg, Days 1, 8), and methotrexate (M, 300 mg/m2 + cfr, Day 8) NACT followed by RS in operable patients. Two patients (10%) had a partial response in the primary tumor (T) and 14 (67% CR+PR) in the inguinal nodes (N). The operability rate following NACT was 90% (pathological downstaging rate, 33%) but surgery was really radical in 79% of cases. Pathological N response was significantly related to the pathological T downstaging, and a persistently high N positivity rate was detected (inguinal, 81%; pelvic, 47%). NACT+RS had an acceptable morbidity but the therapeutic results were less encouraging than expected with a 3-year survival of 24% and stage, pathological T downstaging, and N status all significantly affected survival. Sixty-eight percent of the operated patients recurred 3-17 months from the end of treatment and 50% of them had a distant relapse. PBM NACT did not seem to add any substantial benefit to the surgery alone in this subset of patients with extremely advanced disease. Studies on a chemoradiotherapeutic approach are currently in progress in order to confirm the promising preliminary results.

Adult↗

PubMed1993

Radical hysterectomy: a randomized study comparing two techniques for resection of the cardinal ligament.

To compare two different surgical techniques for the resection of the cardinal ligaments during radical operation for cervical cancer, 84 patients with locally advanced cervical cancer (FIGO stages IB-IIA > or = 4 cm, IIB-III) primarily treated with chemotherapy and then eligible for radical surgery underwent radical hysterectomy. Lateral parametria were resected by using the Meigs technique or a modified Magara technique. The procedure to be performed on the right hand side was randomly chosen, consequently the left cardinal ligament was resected with the other technique. Evaluation of the first 35 cases showed that the median size of the parametria resected with the modified Magara technique (52 mm) was significantly greater than that removed with the Meigs technique (34 mm) (P < 0.05). Therefore hemoclips were routinely adopted in the following 49 cases. In 11% of cases hemoclips could not be used due to a deep and narrow pelvis or varicosities of the hypogastric plexus, therefore clamps were necessary. Bleeding complicating parametrial dissection occurred independently of the adopted technique. Five-years DFS is 100, 80, and 52% for stage IB-IIA > 4 cm, IIB and III, respectively. The study showed that the modified Magara technique is feasible and safe and allows for a more radical resection of the parametrial tissue. Furthermore, this approach seems to improve the local control of disease.

Adenocarcinoma↗

PubMed1993

Expression of ras p21 oncoprotein in normal and neoplastic human endometrium.

The ras-encoded p21 protein expression was investigated in 18 normal endometrial tissues and in 37 human primary endometrial carcinomas by Western blotting analysis. Scattered p21 levels were found in normal specimens (mean = 1.29 OD; median = 1.10 OD; range = 0.33-2.65). The p21 levels were significantly higher in secretory (mean = 1.99 OD; median = 2.16 OD; range = 0.71-2.65) than in proliferative (mean = 0.97 OD; median = 1.07 OD; range 0.38-1.73) endometrium (P = 0.009) and higher in primary endometrial carcinomas (mean = 2.05 OD; median = 2.04 OD; range 0.21-4.36) than in normal proliferative tissues (P = 0.004). Immunohistochemical analysis showed that most of the tumor cells expressed p21 oncoprotein while the stromal component was unreactive. No correlation between p21 expression and histopathological characteristics of the tumors was observed. Moreover, estrogen receptor (ER)-positive tumors expressed higher p21 levels than did ER-negative tumors (77% vs 33%; P = 0.009). A similar trend, although not statistically significant, was found between p21 values and progesterone receptor expression (74% vs 44%; P = 0.060). On the other side, p21 levels were unrelated to epidermal growth factor receptor levels. Further studies should verify the possible significance of p21 expression in the prognostic characterization of patients with endometrial cancer.

Adult↗