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Biomedical subjects

G Scambia

Publications and source records attributed to G Scambia.

At least 109 records · Page 6Linked to original sources
PubMed2000

Antagonistic effect of the combination gemcitabine/topotecan in ovarian cancer cells.

The in vitro interaction between the new antimetabolite gemcitabine (GEM) and topotecan (TPT) was analyzed in A2780 ovarian cancer cells. The growth inhibitory effect was assessed after 3 days of drug exposure. GEM and TPT obtained in vitro IC50 values of 2.1 +/- 0.9 and 33.7 +/- 10.2 nM, respectively. The interaction between GEM and TPT was evaluated by exposing cancer cells at increasing doses of GEM (0.1, 1, and 10 nM) and TPT (1, 10, 100, and 1000 nM). Analysis of data about the interaction between GEM and TPT was performed by applying the isobole method. An antagonistic effect was noticed when GEM was combined with TPT in the tested concentration range. DNA analysis was also performed and showed an augmentation of cells blocked in the G2/M phase during TPT exposure, while an increase of blocked cells in the G0/1, phase was observed after GEM treatment. This latter effect was predominant when the two drugs were used in combination. We also investigated the effect of sequential exposure to drugs, pretreating A2780 cells for 24 h with TPT and then for 48 h with GEM, and, conversely, pretreating A2780 cells with GEM for 24 h and thereafter with TPT for 48 h. Both these combined sequential treatments showed an antagonist effect of the drugs' combination. Long-term growth inhibition effect was established by clonogenic assay performed after 10 days of culture after drug treatment. Also these data confirmed the antagonistic effect between GEM and TPT in A2780 ovarian cancer cells.

Antimetabolites, Antineoplastic↗
PubMed2000

Growth inhibitory effects and radiosensitization induced by fatty aromatic acids on human cervical cancer cells.

Evidences have been reported that phenylacetic (PA) and phenylbutyric (PB) fatty aromatic acids can exert tumor growth inhibition in vitro and in vivo. Moreover, clinical trials also showed some activity for these drugs to modulate the expression of genes implicated in tumor growth, metastasis, immunogenicity, and to potentiate the efficacy of cytotoxic agents. The aim of the study was to examine the effects of PA and PB on the growth as well as sensitization to cisplatin and radiation in human cervical cancer cells. The effects of PA and PB on the proliferative activity and apoptosis induction in cervical tumor tissue was investigated. Both PA and PB exhibited a time- and dose-dependent antiproliferative activity in SW756 and ME180 cell lines: after 72-h treatment, the IC50 (concentration able to inhibit 50% of cell growth) of PB was 1.9 +/- 0.2 mM and 1.5 +/- 0.2 mM in SW756 and ME180 cells, respectively, while the IC50 of PA was 13.0 +/- 1.7 mM and 10.0 +/- 1.2 mM in SW756 and ME180 cells, respectively. In tumor tissue biopsies obtained from patients affected by squamous cervical cancer, both drugs resulted in a marked reduction of the percentage of bromodeoxyuridine-labeled cells compared with untreated samples [19.0 +/- 1.63% in untreated tissues with respect to 1.30 +/- 0.54% and 4.20 +/- 2.50% of stained cells after treatment with PA (30 mM) (P < 0.0001) and PB (5 mM) (P < 0.0001), respectively]. Moreover, analysis of the staining with M30 monoclonal antibody revealed that PA (30 mM) and PB (5 mM) were able to produce a marked increase in the number of stained apoptotic nuclei with respect to untreated samples. Finally, PB and PA were shown to enhance the sensitivity of SW756 to radiation and to exert an additive effect when combined with cisplatin. A significant reduction of the processed form of p21ras and rhoB proteins in the membrane fraction of cells exposed to PA and PB was observed. When farnesol, which is able to circumvent the enzymatic step inhibited by PA and PB, was added to the medium only a partial reversal of the growth inhibition and potentiation of sensitivity to radiation induced by PA and PB were found. In conclusion, the growth inhibitory properties of fatty aromatic acids suggest that these molecules could represent the prototype of a new class of compounds with some therapeutic potential in cervical cancer.

Antimetabolites, Antineoplastic↗
PubMed2000

p21WAF1/CIP1 protein expression in primary ovarian cancer.

p21WAF1/CIP1 protein is a cyclin-dependent kinase inhibitor, able to prevent the CDK2/cyclin E induced retinoblastoma protein (pRB) phosphorylation, thus inhibiting cell cycle progression at G1 phase. p21WAF1/CIP1 protein levels were examined in a series of 102 ovarian tissue samples including normal ovary, primary ovarian tumors, omental metastasis, recurrent disease and residual tumor after chemotherapy exposure, by Western blot analysis. The association of p21WAF1/CIP1 status with clinicopathological parameters and clinical outcome was also investigated. p21WAF1/CIP1 protein was detectable in 76 out of 102 (74%) ovarian tissue samples. We observed a significant trend of p21 levels to gradually increase from normal ovarian tissues (median 0 a.u.) through primary ovarian cancers (median 0.19 a.u.), omental metastases (median 0.33 a.u.) and recurrence of disease (median 0.44 a.u.) (p=0.015). In the group of stage III-IV ovarian cancer patients, p21-positive cases showed a more favourable prognosis with respect to p21-negative cases: the 3-year time to progression (TTP) rate was 58% for p21-positive compared with 33% of p21-negative cases (p=0.036). In conclusion, p21WAF1/CIP1 expression levels seem to be correlated with tumor status at the time of diagnosis and can predict TTP in a selected group of patients.

Adult↗
PubMed2000

p27Kip1 expression is associated with clinical outcome in advanced epithelial ovarian cancer: multivariate analysis.

Few biological parameters have been shown to have a prognostic role in patients with advanced ovarian cancer. p27Kip1 is a cyclin-dependent kinase inhibitor, and its loss may contribute to tumor progression. We determined whether p27Kip1 protein expression in advanced ovarian cancer could be associated with prognosis. p27Kip1 status was assessed by immunohistochemical analysis of tissue sections from primary tumors of 99 patients with stages III-IV ovarian carcinoma and was analyzed in relation to clinicopathological variables, time to progression (TTP), and overall survival (OS). p27Kip1 expression was detected in 47 (47%) of the 99 patients. p27 expression did not correlate with any of the classical clinicopathological parameters. Loss of p27 protein was significantly associated with a short TTP (P = 0.0004) and decreased OS (P = 0.0302). The 5-year TTP rate in p27-positive patients was 50% versus 11% in p27-negative patients. p27-positive cases showed a 5-year OS rate of 53% compared with 43% of p27-negative cases. In multivariate analysis, p27 expression was an independent predictor of progression of disease (P = 0.0009) and survival (P = 0.0032) when considered together with stage of disease, presence of ascites, and residual tumor at surgery. Loss of p27Kip1 conferred poor prognosis independently of proliferative index, as assessed by proliferating cell nuclear antigen immunostaining. p27 immunoreactivity can be used to predict progression of disease and survival in patients with advanced epithelial ovarian cancer and therefore may represent a new prognostic marker.

Age Factors↗
PubMed2000

[The use of erythropoietin alpha in programs of high-dose chemotherapy].

Epoetin (Epo) is physiologically present in the human body, stimulating erythropoiesis from bone marrow. Anemia is observed in cancer patients submitted to high-dose chemotherapy (HDCT), mainly caused by myelosuppression. Epoetin alfa has been widely used to treat the anemia that develops in the HDCT setting. Controlled studies in patients with hematologic malignancies or solid tumors who received Epo following HDCT have shown a decreased red blood cell transfusion requirement at least in patients receiving allogeneic bone marrow transplantation (BMT), while results in patients receiving autologous BMT have been disappointing. The administration of Epo before HDCT, in a period when bone marrow is still responsive to growth factors, may represent a new strategy aimed at decreasing the degree of anemia in these patients. A combination of granulocyte-colony stimulating factor and Epo has proved to be effective in mobilizing stem cell and committed myeloid/erythroid precursors.

Anemia↗
PubMed2000

Expression of bcl-2, bax-xL, and bcl-xS in endometrial and cervical tissues.

We assessed the protein expression levels of bcl-2, bax, bcl-xL, and bcl-xS in a group of 51 endometrial cancers and 8 normal samples as well as in 59 cervical neoplasms and in 15 normal cervical tissues. Neoplastic endometria (median, 1.30 absorbance units [AU]; range, 0.13-7.26 AU) had slightly higher bcl-2 levels than did normal tissue (median, 0.83 AU; range, 0.29-1.90 AU; P < .068), whereas bcl-2 was lower in neoplastic (median, 3.59 AU; range, 0.13-19.86 AU) than in normal cervical samples (median, 8.45 AU; range, 2.09-15.04 AU; P < .010). Bcl-xL levels were higher in endometrial carcinoma (median, 1.23 AU; range, 0.03(4.29 AU) than in normal tissues (median, 0.56 AU; range, 0.46-1.48 AU; P < .048), whereas no significant difference was observed in cervical tissues. Bax levels did not show any variation in either system. The protein bcl-xS was marginally detectable in only a few samples. In endometrial carcinoma, bcl-2 and bcl-xL levels were correlated inversely (r = -0.27; P < .054), whereas in cervical cancer, they were correlated directly (r = +0.40; P < .002). The different expression patterns of bcl-2 family members in endometrial and cervical tissues confirm the hypothesis of a strictly tissue-specific regulation of these proteins.

Adult↗
PubMed2000

[Quaternary ammonium salts in gynecology and obstetrics].

We have summarized chemical, physical, and microbiological characteristics of Quaternary Ammonium Salts: particularly, benzalchromium chloride and didecyl-dimethyl-ammonium chloride characteristics were analyzed. These compounds may act as antimicrobial agents in different way: 1) they are surface-active agents and will denature protein or cause dissociation of an enzyme from its prosthetic group; 2) they may alter the cell permeability of bacteria and yeasts; 3) they may stimulate the glycolysis reaction and 4) may inhibit oxidation of lactate. These latest activities may play a role in maintenance of physiologic microbial ecology of vagina or in the re-establishment of the vaginal ecosystem after vaginitis or vaginosis. We have also summarized the physiologic variation of vaginal ecosystem during the different phases of women's life and the microbiology of vagina during vaginitis and vaginosis. The results of more recent studies about the therapeutic role of quaternary ammonium compounds in vulvo-vaginal infections an in vaginosis are synthetically reported. We concluded that quarternary ammonium compounds are efficacious, handy and safe, in obstetrics and gynecology. A very good compliance and low costs of these compounds suggest that they may be used alone as well in association with specific antimicrobial agents in the treatment of most of gynecological infections, and particularly in bacterial vaginosis.

Anti-Infective Agents, Local↗
PubMed1999

N-deacetyl-N-aminoacylthiocolchicine derivatives: synthesis and biological evaluation on MDR-positive and MDR-negative human cancer cell lines.

A new series of N-deacetyl-N-(N-trifluoroacetylaminoacyl)thiocolchicine derivatives 9-15 have been synthesized starting from the corresponding N-deacetylthiocolchicine (3) and the N-trifluoroacetylamino acids 5-8 which were used as a racemic mixture. The trifluoroacetyl protecting group has been removed easily, giving the corresponding N-deacetyl-N-aminoacylthiocolchicines 16-22. Optical pure compounds 9-22 were isolated from the diastereoisomeric mixture or were prepared starting from compound 3 and an optical pure amino acid derivative; the configuration of each compound was assigned unequivocally. The diastereoisomeric couples of amino acids synthesized were tested, and their antiproliferative activity on MDR-positive and MDR-negative human cancer cell lines was evaluated.

Antineoplastic Agents↗
PubMed1999

Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer.

p27Kip1 is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of tumors, including breast, colon, prostate, and lung carcinomas. In the present study, p27 protein expression was investigated by immunohistochemistry and Western blot analysis in a series of 82 epithelial ovarian tumors [16 classified as low malignant potential (LMP) and 66 classified as primary ovarian adenocarcinomas]. Immunohistochemical analysis revealed frequent loss of p27 expression in primary ovarian adenocarcinomas (33%), with respect to LMP tumors (6%; P = 0.0009). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 45 (55%) of 82 cases. p27 levels inversely correlated with cdk2 kinase activity in a representative subset of tumors. When the clinical outcome of the patients was evaluated in relationship to p27 status, we observed a significant correlation between presence of p27 staining and a longer time to progression (P = 0.032 by log-rank test). These data indicate that loss of p27 is a frequent event in ovarian carcinomas as compared with LMP tumors, suggesting that these tumor types may have different pathogenesis. p27 levels may also represent a useful prognostic marker for predicting disease recurrence in primary ovarian carcinomas.

Adenocarcinoma↗
PubMed1999

Epidermal growth factor receptor expression in primary laryngeal cancer: an independent prognostic factor of neck node relapse.

Specimens of laryngeal squamous cell carcinoma (LSCC) were examined for epidermal growth factor receptor (EGFR) content using a radioreceptor method; 140 untreated consecutive patients with primary LSCC undergoing initial surgical resection were followed up for a median of 49 months (range 2-84 months) after surgery. Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels were directly associated with the risk of lymph node metastasis. A significant relationship between EGFR status and cervical node metastasis was observed. The cutoff value of 20 fmol/mg protein was the best prognostic discriminator. The 5-year metastasis-free survival (MFS) was 66% for patients with EGFR- tumors compared with 15% for patients with EGFR+ tumors. By multivariate analysis, the EGFR status appeared to be a significant independent prognostic factor for MFS. Our results suggest that the assessment of EGFR status at the time of diagnosis may identify a subset of LSCC patients highly susceptible to neck node metastases thus defining therapy accordingly.

Analysis of Variance↗
PubMed1999

Sequence of metabolic changes during X-ray-induced apoptosis.

A cell population undergoing apoptosis usually contains varying proportions of cells in the diverse stages of the process, from very early continuously through to secondary necrosis. This heterogeneity acts as a confounding factor in metabolic studies if a general population is investigated. Using fluorescent probes and multiparameter flow cytometry, we report on metabolic changes occurring during X-ray-induced apoptosis in human peripheral blood lymphocytes and relate the observed alterations to cells at various phases of the process assessed by monitoring the progressive loss of selective plasma membrane permeability. Data show that alterations of mitochondria cardiolipin and a reduction of plasma membrane potential are rather early events as they commence in cells which still possess an impermeable plasma membrane. Conversely, mitochondrial transmembrane potential is impaired only when plasma membrane permeability starts to be altered, that is, in relatively later apoptotic cells, thereby reflecting the complexity of mitochondria demise during apoptosis. The prooxidant/antioxidant balance is altered in cells in early apoptosis with a correlated increase of prooxidants and depletion of thiols, the latter indicative for the progressive impairment of this detoxifying mechanism. The imbalance in prooxidant/antioxidant remained evident through apoptosis suggesting that oxidative damage starts early and then continues, eventually leading to cellular disruption. Assessing cell transit through the apoptotic process and coupling the observed metabolic changes to selected stages of the process enables one to improve the understanding of the temporary sequence of biochemical phenomena occurring in a given model.

Antioxidants↗
PubMed1999

Gynecologic oncologic surgery in the elderly: A retrospective analysis of 213 patients.

OBJECTIVES: The aims of the study were (1) to analyze morbidity and mortality for elderly women (>/=70 years) operated on for gynecological malignancies at our department between 1985 and 1996; and (2) to compare two periods of time (years 1985-1990 versus years 1991-1996) to investigate whether new expedience in the surgical technique as well as in the perioperative management introduced by 1991 influenced the feasibility and tolerability of surgery in elderly patients. METHODS: In a retrospective analysis, we evaluated tumor site, comorbidities, surgical features, morbidity, and mortality. By 1991, several modifications in management were introduced, including: (1) early postoperative mobilization; (2) self-donation with autologous blood transfusion; (3) intraoperative antibiotic prophylaxis; (4) the retroperitoneum was left open and drains were not used after pelvic and aortic lymphadenectomy; (5) use of coagulator forceps and hemoclips for meticolous hemostasis. RESULTS: In 213 patients, tumor site distribution was uterine corpus n = 93, ovary n = 51, vulva n = 29, cervix n = 23, breast n = 15, and vagina n = 2. There were advanced stage diseases in 47%, comorbid illnesses in 76%, and high surgical risk in 48%. Sixty-nine patients (group A) and 144 patients (group B) were treated in the first and second study periods, respectively. Overall, severe postoperative morbidity and mortality were 17 and 2.8%, respectively. Group B compared to group A showed more frequent use of major surgical procedures (P < 0.01) and lymphadenectomy (P < 0.04), lower transfusion rate (P < 0.001), reduced severe morbidity (P < 0.002), lower mortality (P = 0.3), and shorter hospital stay (P < 0.001). CONCLUSIONS: Our study suggests that surgery, including very radical procedures, is reasonably feasible and well tolerated by elderly patients. The introduction of technical and medical advances in the later years of the study resulted in a significant improvement of surgical rates.

Aged↗
PubMed1999

Isolation of MUC1-primed B lymphocytes from tumour-draining lymph nodes by immunomagnetic beads.

The humoral immune response against a tumour-associated antigen, polymorphic epithelial mucin (PEM, MUC1) in cancer patients was studied by isolating specific B cells primed for the antigen. Human B lymphocytes from tumour-draining lymph nodes, obtained from 12 patients with epithelial cancers, were immunoselected with magnetic beads coated with a 60mer synthetic peptide corresponding to three tandem repeats of the protein core of the MUC1 antigen. Short-term cultures of B cells were established utilizing interleukin-10 (IL-10), IL-4 and monoclonal antibody anti-CD40, and were maintained for a maximum of 3 weeks. B cell culture supernatants contained human anti-MUC1 antibodies, as detected by enzyme-linked immunosorbent assay, in 6/12 of the patients tested. Five of these patients, all with early-stage cancer, also had high levels of circulating anti-MUC1 IgM antibodies in the serum. A significant correlation was found (two-tailed P = 0.041) between the presence of circulating anti-MUC1 antibodies and the ability to isolate PEM-specific B cells from tumour-draining lymph nodes. The technique proposed provides a useful method for the analysis of natural immunity against defined tumour antigens.

Adult↗
PubMed1999

Early feeding compared with nasogastric decompression after major oncologic gynecologic surgery: a randomized study.

OBJECTIVE: To evaluate the feasibility, safety, and tolerance of early feeding in patients undergoing surgery for gynecologic malignancies. METHODS: Patients were stratified according to operative time and type of tumor and were randomized into two arms: A) early oral feeding and B) nasogastric decompression followed by feeding at the first passage of flatus. Variables assessed included nausea, vomiting, time to first passage of flatus and stool, time elapsed before adequate tolerance of a regular diet, postoperative stay, and complications. RESULTS: Sixty-one patients were randomized into each arm. The types of tumor, the surgical procedures performed, and the operative times were similar in both groups. Early oral feeding in patients in arm A was associated with a significantly faster resolution of postoperative ileus (P < .01), with a more rapid return to a regular diet (P < .01), with an earlier first passage of stool (P < .01), and with a shorter postoperative stay (P < .05) than patients in arm B. Rates of nausea and vomiting were similar in both arms. Hindered deglutition and nasal soreness caused by the nasogastric tube were observed in 88% of patients in arm B. Insertion of a nasogastric tube was necessary in six patients in arm A (10%), and three of these had postoperative complications. Thus, early feeding was feasible in 95% of patients and did not seem to be related to preoperative chemotherapy, tumor type, or lymphadenectomy. CONCLUSION: Early feeding is feasible and well tolerated and is associated with reduced postoperative discomfort and a more rapid recovery in patients undergoing major surgery for gynecologic malignancies.

Adult↗
PubMed1999

Reproductive effects of dietary soy in female Wistar rats.

This study was designed to assess the effects of administration of dietary soy on reproductive function and fertility of female Wistar rats. Four groups, each of 20 females, were used. Control animals were fed a standard cereal-based diet for rats. Treated animals were fed a standard diet supplemented with 0.7%, 1.2% or 2.4% of a soy extract. Treatment started at weaning and continued until day 7 post-partum (day of sacrifice). Growth depression was seen in the 2.4% soy group. Vaginal opening occurred earlier in females receiving soy supplemented feed when compared with controls. Analysis of vaginal smears revealed that all animals were cycling, although an increase in the mean duration of each cycle was seen in the 2.4% soy group. Uterine effects were observed in high-dose females and included increases in weight, oedema, endothelial hyperplasia and leucocytic infiltration. Vaginal modifications (i.e. inflammation, hyperkeratosis and dyskeratosis) and alterations in the distribution of follicular size in the ovaries were also observed among treated animals. These data suggest that long-term exposure to high doses of phytoestrogens can produce significant agonistic actions in several oestrogen-dependent tissues and parameters, even though in this model no clear influence on reproductive processes was observed.

Animals↗
PubMed1999

Expansion of granulocyte colony-stimulating factor/chemotherapy-mobilized CD34+ hematopoietic progenitors: role of granulocyte-macrophage colony-stimulating factor/erythropoietin hybrid protein (MEN11303) and interleukin-15.

Ex vivo stroma-free static liquid cultures of granulocyte colony-stimulating factor (G-CSF)/chemotherapy-mobilized CD34+ cells were established from patients with epithelial solid tumors. Different culture conditions were generated by adding G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), Flt3 ligand (Flt3), megakaryocyte growth and development factor (Peg-rHuMGDF), GM-CSF/erythropoietin (EPO) hybrid protein (MEN11303), and interleukin-15 (IL-15) to the basic stem cell factor (SCF) + interleukin-3 (IL-3) + EPO combination. This study showed that, among the nine different combinations tested in our 5% autologous plasma-containing cultures, only those containing IL-3/SCF/Flt3/MEN11303 and IL-3/SCF/Flt3/MEN11303/IL-15 significantly expanded colony-forming unit granulocyte-macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), long-term culture-initiating cells (LTC-IC), CD34+, and CD34+/CD38- cells after 14 days of culture. Particularly, the addition of IL-15 to IL-3/SCF/Flt3/MEN11303 combination produced a significant increase of LTC-IC, with an average 26-fold amplification as compared to input cells, without any detrimental effect on CFU-GM and BFU-E expansion. This combination also produced a statistically significant 3.6-fold expansion of primitive CD34+/CD38- cells. Moreover, this study confirms the previously described erythropoietic effect of MEN11303, which, in our experience, was the only factor capable of expanding BFU-E. Compared to equimolar concentrations of GM-CSF and EPO, MEN11303 hybrid protein showed a significantly higher capacity of expanding CFU-GM, BFU-E, LTC-IC, CD34+, and CD34+/CD38- cells when these cytokines were tested in combination with IL-3/SCF/Flt3. These cultures indicated that Peg-rHuMGDF addition to IL-3/SCF/EPO/Flt3 does not affect CFU-GM and BFU-E expansion but, unlike G-CSF or GM-CSF, it does not decrease the ability of Flt3 to expand primitive LTC-IC. These studies indicate that, starting from G-CSF/chemotherapy-mobilized CD34+ cells, concomitant expansion of primitive LTC-IC, CFU-GM, BFU-E, CD34+, and CD34+/CD38- cells is feasible in simple stroma-free static liquid cultures, provided IL-3/SCF/Flt3/MEN11303/IL-15 combination is used as expanding cocktail in the presence of 5% autologous plasma.

Adolescent↗
PubMed1999

Antitumour activity of oxaliplatin in neuroblastoma cell lines.

Oxaliplatin appears non cross-resistant with cisplatin and has a comparable antitumour effect both in preclinical and clinical studies. We compared the antitumour effect of oxaliplatin with that of cisplatin in human neuroblastoma cell lines SK-N-DZ, LAN-1 and BE(2)M17 following 24 h exposure at concentrations ranging from 0.5 to 5 microM. Oxaliplatin was less potent with IC50 values 1.08-3.4-fold higher than cisplatin. Like cisplatin, oxaliplatin induced a cell cycle block in the G2/M phase although to a lesser extent than that caused by cisplatin. The concomitant increase of DNA fragmentation and decrease of G2/G1 ratio at 72 h indicated that a fraction of blocked cells underwent apoptosis. Morphological analysis confirmed these data, although oxaliplatin appeared to be 2-3 times less potent than cisplatin in inducing apoptosis. Our results indicate that oxaliplatin is active in neuroblastoma in vitro and this finding warrants in vivo preclinical studies.

Antineoplastic Agents↗