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Biomedical subjects

G Scambia

Publications and source records attributed to G Scambia.

At least 235 records · Page 13Linked to original sources
PubMed1993

Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor.

OBJECTIVE: The aim of the study was to investigate the biologic significance of p21 expression in normal and neoplastic ovarian tissues. STUDY DESIGN: Western blotting analysis of p21/ras oncoprotein was conducted in a group of 14 normal and cystic ovaries, six benign tumors, 42 primary ovarian cancers, and 15 omental metastases. RESULTS: Levels of p21 were similar in normal and cystic ovaries and in benign tumors, whereas they were significantly higher in malignant tumors than in control tissues (median 1.91, range 0.12 to 5.00 vs median 1.03, range 0.32 to 2.20; p = 0.023) and in omental metastases than in primary ovarian carcinomas (median 3.05, range 0.55 to 5.72 vs median 1.97, range 0.12 to 5.00; p = 0.14). We found no correlation between p21 expression and histopathologic or clinical characteristics. Estrogen receptor-positive and progesterone receptor-positive tumors expressed higher p21 levels than did estrogen receptor-negative and progesterone receptor-negative tumors (p < 0.05), but no correlation with epidermal growth factor receptor status was found. In the univariate analysis of survival p21 positivity showed a negative prognostic value. CONCLUSION: The enhancement of p21 protein is associated in the ovarian tissue with the malignant phenotype and the acquisition of metastatic potential.

Adult↗
PubMed1993

Evaluation of a novel automated protocol for the collection of peripheral blood stem cells mobilized with chemotherapy or chemotherapy plus G-CSF using the Fresenius AS104 cell separator.

Forty-seven peripheral blood stem cell (PBSC) collections were carried out on patients mobilized with chemotherapy and 63 on patients mobilized with chemotherapy plus G-CSF (Filgrastim), using the Fresenius AS104 cell separator and a novel automated PBSC collection protocol. As expected, cell yields were significantly higher in the series mobilized using chemotherapy plus G-CSF. The low platelet and red blood cell contamination permitted freezing of the apheresis product without further manipulation, other than plasma removal in both series. In patients mobilized with chemotherapy we obtained a MNC and a hemopoietic progenitor (CFU-GM, BFU-e, and CD34+ cells) collection efficiency comparable or superior to those reported by Bender (1992) with the Baxter CS3000 Plus after mobilization with cyclophosphamide. A significant decrease in MNC, BFU-e, and CD34+ cell collection efficiency was found in patients mobilized with chemotherapy plus G-CSF compared to those obtained in patients mobilized with chemotherapy alone. Ten patients achieved a prompt and stable engraftment after high dose chemotherapy and the infusion of cryopreserved PBSC collected using this protocol. Studies are in progress in order to improve MNC and hemopoietic progenitor collection efficiency in patients mobilized with G-CSF to obtain a graft in no more than one or two procedures.

Adolescent↗
PubMed1993

Five-year experience in PBSC collection: results of the Catholic University of Rome.

Several authors have reported a faster immunological and hemopoietic post-transplant reconstitution using autologous peripheral blood stem cell (PBSC) than using autologous bone marrow stem cells. A large number of PBSC can be collected by leukapheresis during the hematological recovery after induction or salvage chemotherapy. In our experience we demonstrated that several separators, even if they have different results in mononuclear cell (MNC) yields, red blood cell and platelet contaminations, are able to collect PBSC for autotransplantation in patients with several malignant diseases and different status of disease. Eighty three patients were submitted to 590 leukapheresis procedures using 4 different blood cell separators: the results showed that all employed protocols are efficient in the collection of peripheral MNC even if after the widespread use of granulocytecolony stimulating factor (G-CSF) in the harvesting phase, the blood cell separator efficiency in terms of MNC is reduced. The use of GCSF in combination with other growth factors, during chemotherapy mobilization could simplify, in the future, this therapeutical program even if improvements in the efficiency of PBSC collection protocols are required.

Adolescent↗
PubMed1992

Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.

Adult↗
PubMed1992

EGF receptor expression in primary laryngeal cancer: correlation with clinico-pathological features and prognostic significance.

Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease-free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub-set of laryngeal-cancer patients with a particularly unfavorable prognosis.

Adult↗
PubMed1992

Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors.

We studied the effect of quercetin (Q) on the proliferation of HT-29, WiDr, COLO 201, and LS-174T human colon cancer cell lines. Q, between 10 nM and 10 microM, exerted a dose-dependent, reversible inhibition of cell proliferation. Cell-cycle analysis revealed that the growth-inhibitory effect of Q was due to a blocking action in the G0/G1 phase. Using a whole-cell assay with 17 beta-[3H]-estradiol as tracer, we demonstrated that all these cell lines contain type-II estrogen-binding sites (type-II EBS). By using Q and other chemically related flavonols (3,7-4'-trimethoxyquercetin, 3,7,3',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-II EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type-II EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-II EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-II EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers.

Adenocarcinoma↗
PubMed1992

The combination of quercetin and cytosine arabinoside synergistically inhibits leukemic cell growth.

It has been demonstrated that quercetin (3,3',4',5,7-pentahydroxyflavone) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is probably mediated through a binding interaction with type II estrogen binding sites (type II EBS). The effect of quercetin and cytosine arabinoside (Ara-C) alone or in combination, was tested on HL-60 cell growth. Quercetin significantly synergized the inhibitory activity of Ara-C on HL-60 cell growth while rutin, the 3-rhamnosylglucoside of quercetin, neither competed with [3H]estradiol for type II EBS nor was effective alone or in combination with Ara-C. Based on these results, we studied by a clonogenic assay the effect of quercetin and Ara-C alone and in combination on colony formation by human leukemic cells (CFU-L). In all cases both drugs exhibited a dose-related inhibition of CFU-L in a range of concentrations between 10 nM and 10 microM and 0.01 nM and 10 microM for quercetin and Ara-C, respectively. The combination of the two drugs resulted in a synergistic inhibitory activity on CFU-L. Considering that plasma concentrations of quercetin effective in vitro were obtained in vivo without any apparent side effects, we conclude that this report represents further experimental evidence that quercetin could be used in the treatment of acute leukemias.

Acute Disease↗
PubMed1992

Effects of dexamethasone on the growth and epidermal growth factor receptor expression of the OVCA 433 ovarian cancer cells.

We studied the correlation between dexamethasone (Dex) induced growth effects and modulation of epidermal growth factor receptor (EGFR) expression in OVCA 433 ovarian cancer cells. These cells express specific high and low affinity 125I-EGF binding sites and are growth stimulated by EGF. Dex exhibits mitoinhibitory effects by recruiting OVCA 433 cells in the G0-G1 phase of the cycle, but increases the number of both the high and the low affinity EGFR in a dose dependent manner. The maximal EGFR expression increase occurs after 24 h of Dex treatment consistently with Northern blot studies. The mitogenic activity of EGF in OVCA 433 cells is not affected by the presence of Dex. Moreover Dex growth inhibition occurs in JA1 cells, an ovarian cancer cell line which expresses unfunctional EGFR and which is unresponsive to EGF. Our results indicate that the Dex induced growth effects occur independently of EGFR expression.

Antibodies, Monoclonal↗
PubMed1992

Synergistic antiproliferative activity of tamoxifen and cisplatin on primary ovarian tumours.

We looked for the presence of the so-called type II oestrogen binding sites (EBS), in four oestrogen (ER) and progesterone (PR) receptor negative primary ovarian tumours. Moreover, the colony-forming assay was used to evaluate the response of ovarian cancer cells from these primary tumours to tamoxifen and cisplatin used alone or in combination. All tumours contained type II EBS, and tamoxifen was able to compete for [3H] oestradiol binding to these sites. Cisplatin and tamoxifen exhibited a dose-dependent inhibition of colony formation in a range of concentrations between 10 and 1000 micrograms/l and 37 and 3710 micrograms/l, respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity, with a potentiation up to and beyond 50-fold. Our results show that in ovarian cancer tamoxifen interacts with type II EBS with an affinity consistent with the concentration effective both in inhibition of colony formation and in synergising cisplatin activity. Based on the experiments performed the action of tamoxifen on cell growth is independent of ER expression, and could be mediated by type II EBS. The possibility that the association of tamoxifen and cisplatin may result in an improved clinical response in ovarian cancer should be investigated.

Binding Sites↗
PubMed1992

Oral condyloma lesions in patients with extensive genital human papillomavirus infection.

OBJECTIVES: The incidence, location, and morphologic appearances of human papillomavirus oral lesions in patients with genital condylomatosis were investigated with clinical, colposcopic, and histologic examination as diagnostic procedures. The human papillomavirus types were also evaluated with filter in situ hybridization. STUDY DESIGN: One hundred one patients, 66 female and 35 male, with genital condyloma underwent an oral cavity examination. Ninety-nine (99%) practiced orogenital sex, and all were asymptomatic for oral lesions. RESULTS: Ninety-one underwent biopsy; histologic studies gave a diagnosis of condyloma in 48% of 101 specimens collected. In 8 of 91 (9%) oral lesions were suspected by naked-eye examination; they were confirmed histologically in all eight. Of 83 patients suspected of having oral condyloma on colposcopic examination, 38 (46%) were confirmed histologically. Thus 38 of 46 patients (83%) had oral condyloma not visible to the naked eye. Colposcopically, oral lesions appeared filiform (50%), moruloid (26%), and mixed (24%). Twenty cytologic oral samples were also collected for deoxyribonucleic filter in situ hybridization analysis. Human papillomavirus deoxyribonucleic genital types were observed in 45% (9/20) of all oral scrapings collected, and all were histologically confirmed. CONCLUSION: Our data indicate that genital human papillomavirus types are capable of establishing a local infection in the oral cavity and demonstrate a high incidence of human papillomavirus oral lesions in patients with genital condyloma.

Adult↗
PubMed1992

Densitometric and morphometric study of immunocytochemical estrogen receptors detection in breast carcinomas.

Immunohistochemical quantitative evaluation of estrogen receptors (ER) detected in tissue sections from 30 breast tumors by monoclonal antibody was performed using a densitometric method. In particular, ER concentration was calculated by nuclear mean optical density (nMOD), while heterogeneity in ER content was calculated by the coefficient of variation (CV) of the nuclear optical density histogram. Tumors which showed more than 60% of positive cells had a mean value of ER-nMOD of 0.116 +/- 0.002 a.u. and of ER-CV of 33.74 +/- 0.68. Tumors which showed 30% to 60% of positive cells had a mean value of ER-nMOD of 0.082 +/- 0.006 a.u. (arbitrary units) and of ER-CV of 36.25 +/- 3.44. Tumors showing less than 30% of positive cells had ER-nMOD of 0.052 +/- 0.009 a.u. and ER-CV of 48.49 +/- 5.61. These results indicate that the greater the concentration the lower the ER heterogeneity within the tumor sample. No significant differences between ER-ICA results, nuclear size and form factors were found.

Breast Neoplasms↗
PubMed1992

Mitomycin C and 5-fluorouracil salvage chemotherapy in platinum-resistant ovarian carcinoma.

Twenty-four patients with progressing or recurrent ovarian carcinoma, all pretreated with cisplatin, were evaluated for response and toxicity to mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy. Eligible patients had histologically proven intra-abdominal disease (67% clinically measurable; 33% nonmeasurable), and 67% of them had progressed on prior platinum-based chemotherapy. WHO response criteria were adopted in patients with measurable disease while those with nonmeasurable lesions were considered as responding in case of nonevident disease and CA-125 values less than 35 U/dl for at least 6 months. All patients received at least 2 treatment courses (median 6, range 2-10), and 5 patients (21%) could be considered as responding: 4/8 (50%) with nonmeasurable and 1/16 (6%) with measurable disease. The overall median survival was 12 months, range 7-30+ (median follow-up: 29.5 months, range 28-30). Progression-free survival was significantly different in responders (15 months) versus nonresponders (3 months) (p = 0.0001). Toxicity was mainly represented by myelosuppression (grade I 29%; II 8% and III 4%). MMC and 5-FU did not show significant activity against large tumor burden, while a relatively good activity was detected in patients with minimal disease. The limited toxicity and possible schedule modifications have to be taken into account for further investigation on selected patients.

Adult↗
PubMed1992

Significance of epidermal growth factor receptor in advanced ovarian cancer.

PURPOSE: The purpose of this study was to investigate the significance of epidermal growth factor receptor (EGF-R) expression in a group of advanced ovarian carcinomas. PATIENTS AND METHODS: The study was conducted on 72 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV disease. The median follow-up was 24 months (range, 4 to 75 months). EGF-R was measured by a radioreceptorial assay. A cutoff of 1.5 fmol per milligram of protein was chosen to define EGF-R positivity. Medians and life tables obtained with the Kaplan and Meier method were analyzed by the log-rank test. The risk of progression was estimated by Cox's proportional hazards model. RESULTS: EGF-R was detected in 54% of primary tumors. When EGF-R was analyzed in different tissue specimens of the same tumor, consistent findings were noted in 88% (seven of eight) of cases. A lower concordance rate (nine of 15; 60%) was found between primary tumors and omental metastases, with a tendency toward higher EGF-R levels in the latter. The EGF-R expression did not significantly correlate with age, stage, grading, and residual tumor after primary surgery. In the univariate analysis, stage IV disease, postoperative residual tumor diameter greater than 2 cm, presence of ascites, and EGF-R positivity were found to be significantly associated with a greater risk of disease progression. In the multivariate analysis, only the postoperative residual tumor and the EGF-R expression remained significantly associated with a high risk of progression. CONCLUSION: Data reported here suggest that the presence of EGF-R in advanced ovarian tumor at the time of the primary surgery identifies a subset of patients with a particularly poor prognosis.

Analysis of Variance↗
PubMed1992

Anatomical study of para-aortic and pelvic lymph nodes in gynecologic malignancies.

Between January 1986 and June 1990, systematic para-aortic and pelvic lymphadenectomy was performed in 208 women with untreated ovarian, endometrial, and cervical cancers. This study aimed to evaluate the median number of nodes collected from each pelvic and para-aortic group and to verify a new detailed nomenclature for the various lymph node groups. The para-aortic nodes were distinguished as paracaval, precaval, and retrocaval, depending on their relationship with the vena cava. Para-aortic, pre-aortic, and retro-aortic nodes were located close to the aorta. The nodes situated between the vena cava and aorta were designated intercavo-aortic. A median of 26 (range 15-48) para-aortic nodes were collected during ovarian or endometrial cancer operations. The lymphatic system of the pelvis was divided into six groups, depending on the relationship with the pelvic blood vessels. The pelvic nodes were distinguished as common, internal and external iliac, presacral, obturator, and parametrial. In cases of cervical cancer, the median number of pelvic nodes collected was 38 (range 20-88). Such anatomical study of the lymphatic system shows that a higher number of nodes than expected can be found in the retroperitoneum.

Aorta, Abdominal↗
PubMed1991

Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report.

The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.

Adult↗
PubMed1991

Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors.

The authors investigated the presence of epidermal growth factor (EGF-R), estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were expressed in all tumor specimens analyzed, with significantly higher levels in tumor samples compared with normal mucosa (P less than 0.05). The immunohistochemical study demonstrated the presence of EGF-R in basal and parabasal cells of normal mucosa and in most of the cancer cells. There was no correlation between EGF-R and tumor localization or T classification. On the other hand, the authors did find an interesting correlation between EGF-R levels and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors. Moreover, the three patients whose tumors expressed the highest EGF-R levels had disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5% expressed very low but detectable ER, PR, and AR levels, respectively. No statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens, and neither was there any correlation of ER, PR, and AR with the pathologic findings. The authors' results suggest that the EGF-R system may play a role in regulating the growth of laryngeal cancer. Additional studies should demonstrate whether, as in other tumor types, EGF-R expression may have prognostic significance in human laryngeal cancer.

Adult↗
PubMed1991

Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival.

Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved 3-year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3-year, disease-free survival of 89%, 73%, and 43% for Stage IB-IIA, IIB, and III, respectively, was found. Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB-IIA, IIB, and III, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress.

Adenocarcinoma↗