Biomedical subjects

G Scambia

Publications and source records attributed to G Scambia.

At least 217 records · Page 12Linked to original sources

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

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

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

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↗

PubMed1994

Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer.

PURPOSE: The aim of the study was to investigate the role of squamous cell carcinoma antigen (SCC) in the management of patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery. PATIENTS AND METHODS: SCC assay was performed with a radioimmunoassay kit in a series of 102 patients with locally advanced cervical cancer. The values of 2.5, 5, and 7 ng/mL were used to define SCC antigen positivity. The chi 2 and Fisher's exact test and the stepwise logistic regression were used to evaluate the distribution of marker values. Analysis of survival was performed using the Kaplan and Meier test and Cox multivariate regression analysis. RESULTS: SCC levels were elevated in 65%, 45%, and 32% of patients with primary tumors for cutoff values of 2.5, 5, and 7 ng/mL, respectively. SCC pretreatment levels correlated with stage, tumor volume and lymph node status. In the multivariate analysis, SCC expression proved to be an independent predictor of response to neoadjuvant chemotherapy. SCC posttreatment levels were strongly related to chemotherapy response. Moreover, the overall correlation between the clinical course of the disease and the variation of SCC levels was 83%. In patients with squamous cell tumors, survival was significantly longer in SCC-negative cases compared with SCC-positive cases (P = .04). Moreover, in patients undergoing surgery after response to neoadjuvant chemotherapy, low SCC values were associated with better prognosis (P = .02). In the multivariate analysis, parametrial involvement and SCC status proved to retain an independent prognostic value. CONCLUSION: Our data show that SCC assay may provide useful information to improve the prognostic characterization and disease monitoring of patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.

Adenocarcinoma↗

PubMed1994

In vitro and in vivo effects of recombinant human erythropoietin plus recombinant human G-CSF on human haemopoietic progenitor cells.

We tested in vitro the effect of recombinant human erythropoietin (rhEPO) plus recombinant human G-CSF (rhG-CSF) on purified human CD34+ haemopoietic progenitors (HP) and in vivo in patients who had undergone anti-cancer chemotherapy for advanced ovarian cancer. In this preliminary experience we found that, in vitro, rhEPO potentiates the effect of rhG-CSF on HP growth and differentiation toward the granulocyte-macrophage lineage. rhEPO plus rhG-CSF produced in vitro a proliferative stimulus of HP which represents 26% of the maximum stimulation obtained using IL-1, IL-3, IL-6, G-CSF, GM-CSF and stem cell factor in combination. In the patients treated with rhEPO plus rhG-CSF after chemotherapy, we observed a favourable trend for platelet and neutrophil recoveries compared with a control group treated with rhG-CSF alone and a significantly higher haematocrit nadir was observed in the rhEPO plus rhG-CSF series. In the patients treated with rhEPO plus rhG-CSF we observed a significant increase of circulating colony-forming unit granulocyte-macrophage (CFU-GM) and burst forming unit-erythroid (BFU-e) compared with the rhG-CSF series. Our results, in vitro and in vivo, encourage the in vivo use of rhEPO plus rhG-CSF to improve blood cell recoveries of patients who have undergone conventional or high-dose chemotherapy. Moreover, rhEPO plus rhG-CSF was demonstrated to be a good HP mobilising treatment for blood stem cell collection after chemotherapy.

Adult↗

PubMed1994

Low-dose cyclophosphamide in combination with cisplatin or epirubicin plus rhG-CSF allows adequate collection of PBSC for autotransplantation during adjuvant therapy for high-risk cancer.

Six patients with advanced ovarian carcinoma (OvCa), and six patients with stage II or III resectable breast cancer (BrCa) were treated with low-dose CY (LD-CY, 1500 mg/m2) and cisplatin (CDDP) 100 mg/m2 (OvCa) or epirubicin (EPR) 120 mg/m2 (BrCa) plus recombinant human G-CSF (rhG-CSF). Twelve days after chemotherapy, all patients underwent PBSC collection on an outpatient basis. Following the completion of the induction programme, all patients underwent high-dose chemotherapy (HDC) with carboplatin 1200 mg/m2, etoposide 900 mg/m2 and melphalan 100 mg/m2 with the reinfusion of PBSC. LD-CY plus rhG-CSF in combination with CDDP or EPR mobilised a very large number of PBSC. After a median of 13 days from chemotherapy, the concentration of PBSC in the peripheral blood was 40-fold higher than the same patient's baseline value. Each collection yielded a median of 10.8 x 10(4)/kg colony-forming unit granulocyte-macrophage. Severe myelosuppression occurred in all patients following HDC, but the infusion of PBSC produced a rapid and sustained haemopoietic recovery. After a median of 11 days from reinfusion, haemopoietic engraftment was complete and 80% of the patients had platelets > 100 x 10(9)/l and PMN > 1 x 10(9)/l within 14 days after reinfusion. We can conclude that the present therapeutic approach is an excellent option for mobilisation, collection and transplantation of PBSC during intensive dose adjuvant polychemotherapy of high-risk cancer.

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 and antiproliferative activity of quercetin in human meningiomas.

Eleven cases of meningiomas were investigated for the presence of estrogen and progesterone receptors. These tumors specifically bound estradiol. This binding activity almost exclusively resulted from the presence of high numbers of type II estrogen binding sites (EBS). Estrogen receptors were absent or present at low concentrations. Competition analysis showed that the flavonoid, quercetin, competed for tritiated estradiol binding to type II EBS; both rutin and hesperidin did not. In addition, 10 microM quercetin, unlike rutin or hesperidin, was effective in inhibiting in vitro bromodeoxyuridine incorporation by meningioma cells. Although the mechanism of the antiproliferative activity of quercetin remains to be clarified, it is possible that this flavonoid may regulate cell growth through a ligand interaction with type II EBS.

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↗

PubMed1993

Anatomical and pathological study of retroperitoneal nodes in epithelial ovarian cancer.

The pattern of lymphatic spread was evaluated in 81 previously untreated ovarian cancer patients (Stage I, 35; Stage II, 2; Stage III, 44) undergoing systematic aortic and pelvic lymphadenectomy. Positive nodes were found in 14% Stage I and 68% Stage III patients. Either pre- and paraaortic, or pre- and paracaval nodes were the only aortic node metastasis in 14% of patients. Common iliac nodes were the sole metastasis in pelvic area in 11%, external iliac in 14%, and obturator in 6% of patients. Therefore, the above node groups, which overall were the most frequently involved, may be considered those primarily invaded by the tumor. When data were analyzed according to stage, aortic nodes were the site of metastasis in 6% Stage I and 14% Stage III patients and pelvic nodes in 8% Stage I and 11% Stage III patients. Both aortic and pelvic areas were positive in 43% Stage III patients. The median number of positive nodes/patient was 2 (range, 1-3) and 4 (range 2-46) in Stages I and III, respectively. Lymphatic spread was ipsilateral to the tumor in all Stage I and in 40% Stage III patients. In Stage III metastases were also observed in intercavoaortic, retrocaval, retroaortic, internal iliac, and presacral nodes. In apparent Stage I, lymphatic metastasis seemed to be limited to one ipsilateral group, and the removal of the primary nodes ipsilateral to the tumor may be considered an adequate procedure. In Stage III, the presence of metastasis beyond the primary nodes and the frequent bilateral involvement suggest that all lymphatic tissue surround the aorta, the cava, and the pelvic vessels should be removed if a cytoreductive intent is pursued.

Adult↗

PubMed1993

Immunological reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation for advanced ovarian cancer.

We evaluated the immunological reconstitution of patients who underwent high-dose chemotherapy and autologous blood stem cell transplantation (ABSCT) for advanced ovarian cancer. Sixty days after transplantation a complete reconstitution of lymphocytes and of the CD3, CD4, CD8, CD19, and CD16/56 subsets was observed in this series. A significant increase in the count of interleukin-2 receptor expressing lymphocyte (CD25) was found on day +60 after transplantation compared to that obtained at diagnosis and before transplantation. A significantly higher lymphokine-activated killer (LAK) precursor activity was seen on day +60 compared to the values obtained at diagnosis and before transplantation while natural killer activity did not show any significant variation. We conclude that ABSCT gives prompt and complete immunohaematopoietic reconstitution after high-dose treatment. Moreover, our data support the feasibility of interleukin-2/LAK therapy as consolidative therapy after ABSCT.

Antineoplastic Combined Chemotherapy Protocols↗