Biomedical subjects

Giovanni Scambia

Publications and source records attributed to Giovanni Scambia.

At least 73 records · Page 4Linked to original sources

PubMed2004

High concentrations of activin A in the peritoneal fluid of women with epithelial ovarian cancer.

OBJECTIVE: The aim of the present study was to evaluate the concentrations of activin A in the peritoneal fluid of women with epithelial (serous) ovarian cancer. METHODS: A group of 160 women was studied and divided in four subgroups as follows: 1) serous ovarian carcinoma (n = 32); 2) serous ovarian cystadenoma (n = 20); 3) endometriosis (n = 53); and 4) healthy controls (n = 55), including both fertile (n = 32) and postmenopausal women (n = 23). Specimens of peritoneal fluid were collected during surgical interventions, and activin A was quantified using a specific two-site enzyme immunoassay. RESULTS: Peritoneal fluid activin A concentrations in women with ovarian carcinoma were about five-fold higher than those found in the control group (median [interquartile range] = 7.60 [2.85-10.15] and 1.50 [1.00-2.50] ng/mL, respectively, P <.001). In contrast, the women with benign serous cystadenoma had peritoneal fluid activin A concentrations (1.50 [1.0-2.70] ng/mL) similar to those of the control group. High peritoneal fluid activin A levels (>2 multiples of the mean) distinguished carcinoma from cystadenoma with a sensitivity of 72% and a specificity of 80%. The follow-up of nine patients with stage IIIc ovarian cancer showed no apparent relationship between the peritoneal fluid activin A levels and overall survival. No significant difference in peritoneal fluid activin A concentrations between patients with endometriosis and control women was observed. CONCLUSION: Most women with serous ovarian carcinoma had high concentrations of activin A in the peritoneal fluid, supporting a possible role of this growth factor in ovarian cancer.

Activins↗

PubMed2004

The unsolved enigma of CDH1 down-regulation in hereditary diffuse gastric cancer.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is a disease mediated by down-regulation of the tumor suppressor E-cadherin (CDH1). This disease is particularly dangerous because of the youth of the patients, and for clinical management, hampered by the submucosal spread of tumor invisible at endoscopy. Two mechanisms of CDH1 down-regulation have been described in HDGC: missense mutations in the CDH1 gene and gene silencing through promoter methylation. MATERIALS AND METHODS: Seven patients affected by HDGC were enrolled. Tumor tissues were checked for CDH1 expression by immunohistochemistry (IHC). CDH1 DNA sequencing was performed for all its 16 exons from tumor and normal tissues of the same patients to detect somatic and germ-line mutations. Methylation promoter study was performed using specific primers and PCR. RESULTS: IHC analysis confirmed CDH1 down-regulation in all patients. DNA sequencing revealed the presence of six missense mutations in five patients. Four mutations were at the EC-3 domain of CDH1, whereas the other two were found in the cytoplasmic region interacting with catenins. All six mutations were absent in normal tissue, thereby excluding its presence in germ-line cells. Four patients exhibited both DNA missense mutations and gene silencing through promoter methylation. In two patients we did not notice either DNA missense mutations or promoter methylation. CONCLUSION: CDH1 somatic mutations and promoter methylation synergistically induce CDH1 down-regulation in HDGC patients, whereas germ-line mutations are relatively rare. However, other unknown mechanisms of CDH1 suppression are involved to explain CDH1 down-regulation in HDGC patients without CDH1 mutations and promoter methylation.

Cadherins↗

PubMed2004

Lymphocyte composition of tumor draining lymph nodes from cervical and endometrial cancer patients.

OBJECTIVE: In the present study we compared the lymphocyte composition of tumor draining lymph nodes (TDLN) in 13 cervical (CC) and 26 endometrial cancer (EC) patients with special emphasis on the suppressive CD4(+) T cell subset constitutively expressing CD25 (T regulatory, Treg, cells). METHODS: Microscopically uninvolved TDLNs (n = 122) collected at different distances from the primary tumor site were used. Proximal TDLN included obturator, and internal and external iliac nodes. Distal TDLN included common iliac, presacral, and aortic nodes. Sixteen relevant lymphocyte subsets were assessed. The proliferative response to PHA and TCR crosslinking, the suppressive activity of Treg cells, and IFN-gamma and IL-4 production were also assessed. RESULTS: Compared to EC patients, TDLN from CC patients contained a higher proportion of naive CD4(+) and CD8(+) cells (P < 0.01), a lower proportion of CD4(+) pre-effector cells (P < 0.05), and a higher proportion of the most potent Treg cell subset identified by coexpression of a high level of CD25 and CD152 (P < 0.05). Functionally, Treg cells were anergic and efficiently inhibited other T cell proliferation, thereby fulfilling the requirements of genuine Treg cells. The proliferative response of TDLN to both PHA and TCR crosslinking tended to be lower in CC than EC patients and was inversely related to the Treg cell content in both type of tumors. No differences were noticed between CC and EC patients in terms of IFN-gamma and IL-4 production. Using pairs of TDLN from individual patients, we showed that proximal TDLN in CC and EC patients displayed a higher CD4/CD8 ratio (P < 0.05 and 0.001, respectively) compared to distal TDLN of the same individual. By contrast, only in EC patients did proximal TDLN contained a proportion of Treg cells higher than distal TDLN (P < 0.02). CONCLUSIONS: The present data highlight differences in immune competency of TDLN in CC and EC patients, suggesting that the former is in a relative immunosuppressive status, and also underlines the importance of the proximity to the primary tumor site.

CD4-Positive T-Lymphocytes↗

PubMed2004

Expression of cyclooxygenase-2 (COX-2) in non-neoplastic and neoplastic vulvar epithelial lesions.

OBJECTIVE: Cyclooxygenase-2 (COX-2) overexpression has been associated with parameters of tumor aggressiveness and unfavourable clinical outcome in several solid tumors. We investigated by immunohistochemistry the expression of COX-2 in normal vulvar tissue, non-neoplastic vulvar epithelial lesions, vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer (IVC). METHODS: The expression pattern of COX-2 was studied in normal vulvar tissue, in six cases of lichen sclerosus (LS), seven cases of squamous cell hyperplasia (SCH), 20 VIN, 2 Paget's disease and 36 IVC. The relationship between COX-2 expression and clinicopathologic parameters in IVC patients has been also addressed. Sections were incubated with normal rabbit serum for 15 min, then with rabbit polyclonal antiserum against human COX-2 (Cayman, Ann Arbor, MI, USA). The results were reported as mean +/- standard error (SE) of COX-2 integrated density values (IDV). RESULTS: Higher levels of tumor/stroma COX-2 IDV ratio were found in stages III-IV (mean +/- SE = 3.5 +/- 0.8) than stages I-II disease (mean +/- SE = 1.4 +/- 0.3) (P value = 0.04). In the subgroup of stage I cases, tumor/stroma COX-2 IDV values were higher in cases with > 1 mm stromal invasion (T1b) than cases with <== 1 mm stromal invasion (T1a) (mean +/- SE = 1.6 +/- 0.3 vs. mean +/- SE = 0.6 +/- 0.1) (P = 0.033). Moreover, we observed higher tumor/stroma COX-2 IDV in cases with metastatic lymph node involvement than cases without lymph node involvement (mean +/- SE = 3.5 +/- 0.8 vs. mean +/- SE = 1.3+/-0.4) (P = 0.037). CONCLUSION: This study suggests that COX-2 overexpression may contribute to vulvar tumorigenesis and progression. Moreover, the correlation of tumor/stroma COX-2 IDV ratio with tumor extension and metastatic lymph node involvement, which represent the major prognostic parameters in this neoplasia, implies that tumor/stroma COX-2 IDV ratio could have a prognostic role in vulvar cancer.

Adult↗

PubMed2004

Pelvic relapses of uterine neoplasms: transvaginal sonographic and Doppler features.

OBJECTIVE: To describe the sonographic and power Doppler features of pelvic relapses in endometrial and cervical cancer. METHODS: We retrospectively analyzed the preoperative transvaginal sonographic reports of 45 women with a histological diagnosis of pelvic relapse. The three diameters of the lesion were recorded; then the shape, margins, content (solid or cystic), and location were analyzed. A subjective assessment of the vascularization (vascular score) was obtained with power Doppler. RESULTS: Twenty-six patients had pelvic recurrence from endometrial cancer and 19 from cervical cancer. In 36 (80%) patients, the recurrence was a central pelvic mass located on the vaginal apex, while in six cases (13%), it was diagnosed as a pelvic side-wall recurrence, and in three (7%), the recurrence occupied the whole pelvis. The recurrences had diameters ranging from 1.0 to 6.8 cm (mean diameter: 3.0 cm, standard deviation: 1.5). In 44/45 cases (98%), the recurrence appeared as a solid nodular mass, while in one case (2%), it was defined as a cystic mass. In 32 (71%) women, the mass showed a hypoechoic content with respect to the surrounding bowel, while in 13 (29%), it manifested a nonhomogeneous content. Vascularization of the mass was assessed in all patients before surgery; in all cases, it was possible to visualize randomly dispersed blood vessels in the context of the relapse. The vascular score revealed scarce blood vessels in 19 relapses, moderate flow in 23, and abundant flow in three cases. CONCLUSIONS: Knowledge of the spectrum of ultrasonographic findings of pelvic relapses will help the physician in diagnosing a recurrent malignant disease at an early stage, when cure rates are high. The widespread availability and low cost of transvaginal sonography (TVS) support its use in routine surveillance of patients operated for uterine neoplasms.

Adult↗

PubMed2004

Pseudo-Meigs' syndrome associated with malignant struma ovarii: a case report.

BACKGROUND: Malignant struma ovarii is a rare tumor, consisting of a struma ovarii with malignant transformation. The association of a malignant struma ovarii with pseudo-Meigs' syndrome and elevated Ca-125 levels has been never reported. CASE: A 66-year-old woman presented with monolateral ovarian mass, ascites, hydrothorax, and elevated Ca-125 levels. Optimal medical staging was performed. Definitive histological examination revealed a malignant struma ovarii. The immediate and complete resolution of symptoms and rapid decline of both Ca-125 and thyroglobulin levels to normal value were achieved post-operatively. After counseling, strict follow-up was planned, and no adjuvant therapy was administered. CONCLUSION: We report the first case of pseudo-Meigs' syndrome associated with malignant struma ovarii and elevated Ca-125 levels. The choice of not performing adjuvant therapy is feasible after optimal surgery and adequate staging procedure given to the usually clinical benign course and the low incidence of metastases in malignant struma ovarii. Careful patient counseling is required.

Aged↗

PubMed2004

Frozen section examination of pelvic lymph nodes in endometrial and cervical cancer: accuracy in patients submitted to neoadjuvant treatments.

OBJECTIVE: The aim of the study was to analyze the accuracy, the positive and negative predictive values, the specificity, and the sensitivity of the pelvic node frozen section examination in endometrial (EC) and cervical cancer (CC) patients. An accurate evaluation of the results of the frozen section examination in patients submitted to neoadjuvant treatments (chemotherapy and radiochemotherapy), and a comparison between specialist and general pathologist results were performed. METHODS: A total of 186 consecutive patients with endometrial [52 cases (27.9%)] and cervical [134 cases (72.1%)] cancer underwent surgery at our Department between January 2000 and September 2003. All patients underwent a systematic pelvic lymphadenectomy. While all definitive diagnosis were primarily performed or secondarily revised by the specialist pathologist, the frozen section examination was performed in 65 (35%) cases by the specialist pathologist and in 121 (65%) cases by a general pathologist. RESULTS: Two thousand seven hundred eighteen out of a total of 6710 pelvic lymph nodes, which underwent a definitive histological analysis, were also analyzed at intraoperative frozen section examination. In our series, we observed 10 false negative and five false positive cases. Six out of the 10 (60%) false negative cases and two out of the five (40%) false positive were found in the neoadjuvant treated cervical cancer patients. In this subgroup, five out the six (83.3%) false negative and the two false positive diagnoses were made by the general pathologist, while the specialist pathologist registered only one false negative diagnosis. CONCLUSION: Intraoperative examination of pelvic lymph nodes during surgery for endometrial and cervical cancer can be considered a safe procedure in the presence of an expert gynecologic oncological team, and can be safely performed in patients submitted to neoadjuvant treatments.

Adult↗

PubMed2004

Cyclooxygenase-2 expression in borderline ovarian tumors.

OBJECTIVES: The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors. METHODS: Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive. RESULTS: Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22). CONCLUSIONS: COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis.

Adolescent↗

PubMed2004

Analysis of cyclooxygenase-2 (COX-2) expression in different sites of endometriosis and correlation with clinico-pathological parameters.

BACKGROUND: Recent studies have demonstrated the overexpression of cyclooxygenase-2 (COX-2) in endometriosis. The aim of this study was to investigate the expression of COX-2 in different anatomical sites of endometriosis and its association with clinico-pathological parameters in a single institutional series of patients undergoing operative treatment. METHODS: COX-2 expression was analysed by immunohistochemistry in 136 samples of endometriotic tissue from 103 patients affected by endometriosis. RESULTS: COX-2 immunoreaction was observed in 78.5% of ovarian endometriotic cysts, in 11.1% of peritoneal implants and 13.3% of recto-vaginal nodules. COX-2 positivity was not distributed differently according to age, pre-operative serum levels of CA125 and AFS score. Moreover, COX-2 positivity did not show any significant variation according to the subjective intensity of pain, as dysmenorrhoea, chronic pelvic pain, lower urinary tract or gastrointestinal symptoms, or according to infertility. CONCLUSIONS: Increased COX-2 expression in the endometriotic ovarian cyst wall was observed with respect to other extraovarian localizations. No relevant correlations between COX-2 positivity and clinico-pathological characteristics and symptoms of patients were observed.

Adult↗

PubMed2004

Clinical isolation and functional characterization of cord blood CD133+ hematopoietic progenitor cells.

BACKGROUND: Human cord blood is a relevant source of CD133+ HPCs. Clinical-scale isolation of human umbilical cord blood (UCB) CD133+ HPCs using immunomagnetic microbeads and the CliniMACS clinical cell isolator is reported. CD133+ HPCs isolated after large-scale processing were functionally characterized. STUDY DESIGN AND METHODS: Closed disposable sets were used to process nine different samples of RBC-reduced UCB nucleated cells. In-vitro hematopoietic assays and human xenografts in NOD/SCID mice were performed to assess the functional properties of isolated CD133+ cells. Different mixtures of human cytokines were tested for the ability to expand nascent CD133+ HPCs. Furthermore, freshly isolated CD133+ cells were conditioned in culture medium specifically tested to support in-vitro myogenesis or osteogenesis. RESULTS: Isolation procedures yielded the recovery of an average of 2.53 x 10(6) CD133+ HPCs with a mean recovery of 96 percent (referred to as RBC-reduced samples) and a final sample purity of 82 percent. Purified CD133+ cells had high cloning efficiency, had relevant long-term activity, and were capable of repopulating irradiated NOD/SCID mice. In 10-day stroma-free cultures, a 2-fold and 8.3-fold expansion of colony-forming cells (CFCs) and extended long-term culture-initiating cells, respectively, was obtained. Freshly isolated CD133+ cells differentiated into large nucleated cells expressing either myosin D or osteopontin (as revealed by RT-PCR and immuno-cytochemistry), with a protein/mRNA expression comparable to or even higher than that observed in UCB CD133- nucleated cells in identical culture conditions. CONCLUSION: Collectively, clinical-scale isolation of UCB CD133+ cells provides a relevant amount of primitive HPCs with high hematopoietic activity and in-vitro mesenchymal potential.

AC133 Antigen↗

PubMed2004

Concomitant radiochemotherapy plus surgery in locally advanced cervical cancer: update of clinical outcome and cyclooxygenase-2 as predictor of treatment susceptibility.

OBJECTIVE: We have updated our findings on the efficacy of concomitant radiochemotherapy plus radical surgery in a larger series of patients (n = 54) with locally advanced cervical cancer (LACC). We also investigated the role of cyclooxygenase-2 (COX-2) in this clinical setting. METHODS: Radiotherapy was administered to the whole pelvic region (1.8 Gy/day, totaling 39.6 Gy) in combination with cisplatin (20 mg/m2) and 5-fluorouracil (1,000 mg/m2) (both on days 1-4 and 27-30). Radical surgery was performed 5-6 weeks after the end of treatment. RESULTS: A clinical complete or partial response was observed in all 53 evaluable patients (75.5 and 24.5%, respectively). At pathological examination, 23 of 51 patients (45.1%) undergoing radical surgery showed complete response to treatment, 18 patients (35.3%) only had microscopic residual disease, 6 patients (11.7%) had a partial response and 4 (7.8%) had no change in their disease. When logistic regression was applied, the FIGO stage (chi2 = 5.28, p = 0.021) and tumor to stroma COX-2 ratio (chi2 = 4.72, p = 0.029) retained an independent role in the prediction of the pathologic response to treatment. The 3-year disease-free survival (DFS) was 75.2%, with local relapse-free survival of 86.2% and metastasis-free interval of 89.9% at 3 years. Cases with a high COX-2 ratio showed a shorter DFS than cases with a low COX-2 ratio (p = 0.016). A direct association was shown between COX-2 ratio values and risk of recurrence, as assessed by Cox analysis using COX-2 ratio values as a continuous covariate (chi2 = 3.94, p = 0.047). CONCLUSION: This study confirms the possibility of achieving a very high rate of pathological responses in LACC patients administered chemoradiation plus surgery (3-year DFS 75.2%). Moreover, COX-2 status may play a role in the prognostic characterization and prediction of tumor response.

Adult↗

PubMed2004

Perioperative morbidity and mortality in elderly gynecological oncological patients (>/= 70 Years) by the American Society of Anesthesiologists physical status classes.

BACKGROUND: We evaluated the morbidity and mortality associated with American Society of Anesthesiologists (ASA) classes III and IV versus ASA classes I and II in elderly women (>/= 70 years) undergoing gynecological oncological surgery. METHODS: From 1986 to 2000, we retrospectively collected patients >/= 70 years of age undergoing oncological gynecological surgery. The study population consisted of 121 ASA class III and IV patients. The control group consisted of the same number of patients with ASA classes I and II, and these were matched to study patients (1:1) by clinical and surgical data. The morbidity and mortality of patients with ASA status III and IV were analyzed before and after 1992. RESULTS: In ASA class III and IV patients, compared with ASA class I and II, a higher rate of severe morbidity (P =.000) occurred, whereas the median postoperative stay was similar (8 days). No differences between patients with ASA class III and IV and ASA class I and II for median operative time, transfusion rate, or median blood loss were found. Mortality was 3% in ASA classes III and IV. CONCLUSIONS: Our study suggests that surgery in elderly gynecological oncological patients aged >/= 70 years with ASA class III or IV results in an acceptable perioperative morbidity and mortality rate.

Aged↗

PubMed2004

The cellular response to PPARgamma ligands is related to the phenotype of neuroblastoma cell lines.

Neuroblastoma (NB) is a phenotypically heterogeneous tumor, displaying cells of neuronal, melanocytic, or glial/schwannian lineage. This cellular heterogeneity is also present in vitro, where cells of neuroblastic (N)- or stromal (S)-type may be identified. Ligands of peroxisome proliferator-activated receptor gamma (PPARgamma) have been shown to inhibit growth in different tumor cell lines. The purpose of this study was to determine PPARgamma expression and the response to its ligands in NB cell lines with different phenotypes. We used eight NB cell lines with N-, mixed, and S-phenotype. PPARgamma expression was found in all NB cell lines, regardless of their phenotype. Mutational analysis and transactivation assays showed that PPARgamma is not mutated and remains functional in NB cells. Two PPARgamma ligands, 15-deoxy-delta12,14-prostaglandin J2 (PGJ2) and rosiglitazone, inhibited growth of all cell lines, with PGJ, being the most potent agent. PGJ2, but not rosiglitazone, induced arrest of the cells in the G2/M phase as well as apoptosis. The sensitivity to the two ligands appeared to be more related to the phenotype than PPARgamma expression, with the S-type cells being less sensitive than the N-type, partly because of their lower capability of undergoing apoptosis. No synergistic effect on growth inhibition was observed when all cell lines were co-treated with 9-cis retinoic acid (9-cis RA) and rosiglitazone. Our data indicate that PPARgamma expression and function are maintained in phenotipically different NB cell lines. Activation of PPARgamma by its synthetic ligands might have a therapeutic role in advanced NB.

Antineoplastic Agents↗

PubMed2004

Angiographic power 3-dimensional quantitative analysis in gynecologic solid tumors: feasibility and reproducibility.

OBJECTIVE: To determine the reproducibility of a simplified method of power Doppler 3-dimensional (3D) sonographic examination. METHODS: Twenty-nine patients with solid pelvic masses underwent transvaginal 3D power Doppler evaluation. The volume of interest was obtained by drawing the margins of the largest section of the mass in the 3 orthogonal planes. The 3D vascular parameters ("relative color," "average color," and "flow measure") obtained by our method were compared with those calculated by a manufacturer-suggested model based on several parallel section planes drawn on the longitudinal frames. The intraobserver variability was quantified on 5 different 3D images acquired by the same operator at 5-minute intervals for each patient. The intraobserver variability was also assayed in 10 patients at 24-hour intervals. Ten patients were scanned by a second sonographer for interobserver variability. RESULTS: There was high agreement between the 3D parameters obtained with the 2 methods. The 3D indices were similar in repeated observations at 5-minute intervals (median coefficients of variation for relative color, average color, and flow measure, 10.9, 4.5, and 13.0, respectively) and at 24-hour intervals (intraclass correlation coefficients for relative color, average color, and flow measure, 0.920, 0.978, and 0.978) and by the second sonographer (interclass correlation coefficients for relative color, average color, and flow measure, 0.978, 0.966, and 0.997). CONCLUSIONS: The acceptable rates of intraobserver and interobserver variability make this approach potentially suitable for research protocols.

Adult↗

PubMed2003

Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1) in estrogen-related Endometrial adenocarcinomas.

PURPOSE: p27(Kip1) 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 gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P </= 0.001). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 193 (91%) of 217 specimens examined. When the clinical outcome of the patients was evaluated in relation to p27 status, we found no significant correlation between the presence of p27 staining and clinicopathological parameters or survival. CONCLUSIONS: These data indicate that p27 expression could progressively decrease from normal endometrium through hyperplastic endometrium to invasive endometrial carcinomas, suggesting that loss of this tumor suppressor may represent a novel and distinct molecular alteration involved in estrogen-related endometrial adenocarcinomas (type I). Despite the suggested role of the p27 protein in determining the prognosis of several human tumors, it was not found to be a predictor of clinical outcome in this large group of patients with endometrial cancer.

Adenocarcinoma↗

PubMed2003

Celecoxib modulates the expression of cyclooxygenase-2, ki67, apoptosis-related marker, and microvessel density in human cervical cancer: a pilot study.

PURPOSE: We investigated whether a short treatment with the cyclooxygenase-2 (COX-2) inhibitor celecoxib could modulate Ki67 antigen and the caspase cleavage product of keratin 18, recognized as a marker of early apoptosis. The activity of celecoxib on microvessel density (MVD) and angio-power Doppler sonography-derived indices of tumor vascularization was also assessed. Serum levels of squamous cell carcinoma antigen and the proliferative potential and subsets of peripheral T cells before and after celecoxib treatment were also analyzed. EXPERIMENTAL DESIGN: Tumor biopsy specimens from 14 patients with cervical cancer were obtained at baseline and after 10 days of celecoxib treatment (400 mg twice daily). Tumor and stroma COX-2 expression, Ki67, apoptosis, and MVD were assessed by immunohistochemistry, whereas prostaglandin E(2) levels were measured by RIA. RESULTS: At baseline, COX-2 integrated density values in tumor compartment ranged from 10.7 to 60.1 (median, 26.5) and were significantly higher than tumor COX-2 integrated density values after celecoxib treatment (range, 0.6-42.3; median, 12.6; P = 0.0043). The percentages of Ki67-positive tumor cells in pre-celecoxib cases ranged from 39.3 to 87.4 (median, 50.8) and were significantly higher than the percentage in the corresponding posttreatment samples (range, 27.7-83.8; median, 43.1; P = 0.0092). MVD values in pre-celecoxib biopsies ranged from 28.0 to 55.0 (median, 38.5) and were significantly higher than the corresponding values in posttreatment samples (range, 16.0-49.5; median; 27.6; P = 0.012). Also, prostaglandin E(2) levels showed a trend to be reduced after celecoxib treatment (range: 4.7-386.6 pg/mg wet tissue in pretreated cases versus 4.8-91.9 pg/mg wet tissue in posttreated cases (P = 0.092). CONCLUSIONS: In cervical cancer, celecoxib treatment decreases tumor COX-2 expression and markers of proliferation and neoangiogenesis, while being uneffective on stroma COX-2 levels, thus suggesting that selective COX-2 inhibitors may be a promising strategy not only for chemopreventive approaches but also for therapeutic approaches in this neoplasia.

Adenocarcinoma↗

PubMed2003

Doppler velocimetry and cytofluorimetric analysis in uterine myomas.

BACKGROUND: To correlate resistance indices (RI) of vessels detected by transvaginal Doppler velocimetry to the proliferative fraction (PF) calculated by flow cytometry in uterine myomas. A prospective study was carried out on patients scheduled for surgery because of symptomatic uterine myomas. A group of 26 myomas characterized by the presence of detectable vessels at Doppler analysis in the inner part of the mass were included in the study. METHODS: The day before surgery patients were studied with both conventional and color Doppler ultrasonography. The volume of the myoma was recorded. The lowest value of RI obtained by Doppler analysis of the vessels within the myoma was considered for the study. Samples from myomas were processed and analyzed by flow cytometry. A PF, representing the cumulative frequency of cells in the S and G2/M phases of the cell cycle, was considered for the analysis. RESULTS: No statistically significant correlation was observed between RI and PF (r = 0.06, p = 0.74). Regression analysis of the intratumoral RI values on the volume of the myoma showed a significant negative correlation (r = -0.46, p = 0.012). CONCLUSIONS: Preoperative Doppler evaluation of uterine myomas did not provide predictive information of the proliferative status of the neoplasm. A significant correlation was found between the volume of the myoma and RI.

Cell Cycle↗

PubMed2003

Identification of a novel subpopulation of human cord blood CD34-CD133-CD7-CD45+lineage- cells capable of lymphoid/NK cell differentiation after in vitro exposure to IL-15.

The hemopoietic stem cell (HSC) compartment encompasses cell subsets with heterogeneous proliferative and developmental potential. Numerous CD34(-) cell subsets that might reside at an earlier stage of differentiation than CD34(+) HSCs have been described and characterized within human umbilical cord blood (UCB). We identified a novel subpopulation of CD34(-)CD133(-)CD7(-)CD45(dim)lineage (lin)(-) HSCs contained within human UCB that were endowed with low but measurable extended long-term culture-initiating cell activity. Exposure of CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs to stem cell factor preserved cell viability and was associated with the following: 1) concordant expression of the stem cell-associated Ags CD34 and CD133, 2) generation of CFU-granulocyte-macrophage, burst-forming unit erythroid, and megakaryocytic aggregates, 3) significant extended long-term culture-initiating cell activity, and 4) up-regulation of mRNA signals for myeloperoxidase. At variance with CD34(+)lin(-) cells, CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs maintained with IL-15, but not with IL-2 or IL-7, proliferated vigorously and differentiated into a homogeneous population of CD7(+)CD45(bright)CD25(+)CD44(+) lymphoid progenitors with high expression of the T cell-associated transcription factor GATA-3. Although they harbored nonclonally rearranged TCRgamma genes, IL-15-primed CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs failed to achieve full maturation, as manifested in their CD3(-)TCRalphabeta(-)gammadelta(-) phenotype. Conversely, culture on stromal cells supplemented with IL-15 was associated with the acquisition of phenotypic and functional features of NK cells. Collectively, CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs from human UCB displayed an exquisite sensitivity to IL-15 and differentiated into lymphoid/NK cells. Whether the transplantation of CD34(-)lin(-) HSCs possessing T/NK cell differentiation potential may impact on immunological reconstitution and control of minimal residual disease after HSC transplantation for autoimmune or malignant diseases remains to be determined.

AC133 Antigen↗