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At least 19 recordsLinked to original sources
PubMed2006

Pre-invasive cervical disease and uterine cervical cancer in Brazilian adolescents: prevalence and related factors.

The objective was to describe the prevalence and factors associated with uterine cervical cancer (CA) and high-grade squamous intraepithelial lesions (HSIL) in adolescents. A cross-sectional study was carried out with 702 sexually active adolescents treated at a general hospital in Rio de Janeiro, Brazil, from 1993 to 2002. Screening was performed by cytopathology and colposcopy and confirmation by biopsy. Exposure variables were socio-demographic characteristics and those related to reproductive health, habits, and sexual behavior. Adjusted odds ratios were estimated using multivariate logistic regression analysis. Based on histopathology, the prevalence of HSIL/CA was 3% (95%CI: 1.8-4.6). There was one case of invasive cancer. With each additional pregnancy, the odds of HSIL/CA increased by 2.2 (95%CI: 1.1-4.4). Age was also associated with this outcome, doubling the odds of acquiring this degree of disease with each year of age (OR = 2.0; 95%CI: 1.2-3.4). The prevalence of lesions suggests the importance of including sexually active adolescent females in cervical cancer screening programs aimed at early detection and treatment of these lesions.

Adolescent↗
PubMed2001

[The detection of human papillomavirus 16, 18, 35 and 58 in cervical-uterine cancer and advanced degree of squamous intraepithelial lesions in Western Mexico: clinical-molecular correlation].

The purposes of this study were to estimate the infection frequency of Human Papilomavirus (HPV) and to identify the viral types in patients with diagnosis of uterine cervical cancer (UCC) and High Grade Squamous Intraepitelial lesions (HGSILs), and to correlate the molecular findings versus HPV infection suggestive clinical findings. Biopsies from 50 patients (37 HGSILs and 13 UCC) histopathologically diagnosed were studied. The presence of HPV were detected by means of the polymerase chain reaction (PCR) using consensus primers for types 6, 11, 16, 18, 31, 33, 35, and 58 among others, as well as specific primers for some of them. The frequencies for HPV 16, 18, 33, 35, and 58 in HGSIL samples were 24.3, 2.7, 0, 5.4 and 16.2% respectively. In UCC samples were 61.5, 7.7, 0, 0 and 15.4% with significative differences only for HPV 16. Clinical findings (histologic, colposcopic and histopathologic), showed deficient diagnostic accuracy in the identification of HPV 16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV. These results are similar to those previously described in our country and the other populations, with the exception of HPV16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV 58 in our region. When analyzing clinical features with the presence of HPV DNA, we conclude that these are insufficient to discard or establish the possibility of HPV infection in patients with HGSIL's and UUC.

Adult↗
PubMedDate not supplied

[Global expression analysis in uterine cervical cancer: metabolic pathways and altered genes].

High risk human papillomavirus (HPV) infection is considered to be the most important etiological factor of Cervical Uterine Cancer. In order to determine the global expression pattern and to identify possible molecular markers of cervical cancer, cDNA arrays with probe sets complementary to 8,000 human genes were used to examine the expression profiles among 5 cell lines derived from human cervical cancer, three HPV16(+) tumor samples and three normal cervical tissues HPV(-). The levels of expression of different cellular processes were identified. Hierarchical clustering was performed and the gene expression using RT-PCR was confirmed. Two genes were found to be consistently overexpressed in invasive cervical cancer biopsies; one of them, IL-6 was previously reported to be overexpressed in cervical cancer and one novel gene, MMP10, previously not known to be related to cervical cancer. Hierarchical clustering of the expression data revealed that samples with common HPV type infection grouped together, maybe this could mean that differences between HPV types could be indirectly determined by expression profiles.

Adult↗
PubMed1998

[Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].

We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.

Adjuvants, Immunologic↗
PubMed1992

Immunohistochemical detection of the multi-drug-resistance marker P-glycoprotein in uterine cervical carcinomas and normal cervical tissue.

Uterine cervical carcinomas and normal cervical tissue (controls) were investigated for the presence of the multi-drug-resistance gene product P-glycoprotein by means of immunohistochemistry, with the C219 monoclonal antibody and the streptavidin-biotin-peroxidase technique. Ten of 11 cervical carcinomas, 2 of which were previously treated with chemotherapeutic agents of the multi-drug-resistance group, showed a positive reaction of tumor cells. All normal controls showed a positive reaction of the ectocervical and endocervical epithelial cells. P-glycoprotein seems to be implicated at least in part in resistance to chemotherapy of cervical carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Expression of tumor necrosis factor-alpha stimulated gene-6 mRNA in cultured human uterine cervical fibroblasts.

BACKGROUND: Uterine cervical ripening process is an active biochemical process similar in part to inflammatory reaction. In this process, hyaluronan plays important roles including facilitation of tissue hydration, release of matrix metalloproteinases and migration of inflammatory cells. The activities of hyaluronan are mediated by the hyaluronan binding proteins, hyaladherins. In the present study, we investigated the mRNA expression of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a member of the hyaladherin family, in cultured human uterine fibroblasts and uterine cervical tissues. METHODS: We developed one-step RT-PCR method for the quantification of TSG-6 mRNA and quantified the expression of TSG-6 mRNA in cultured human uterine fibroblasts, treated with or not proinflammatory cytokines, and TSG-6 mRNA in uterine cervical tissues. RESULTS: We clarified that [1] TSG-6 mRNA was expressed constitutively in cultured human uterine cervical fibroblasts, [2] expression of TSG-6 mRNA was upregulated in a dose dependent manner by proinflammatory cytokines, such as IL-1beta and TNF-alpha, which were key mediators in the cervical ripening process, [3] expression of TSG-6 mRNA in uterine cervices during parturition was significantly (P < 0.05) higher than that in a non-pregnant state. CONCLUSIONS: Our results suggest that TSG-6 might participate in the cervical ripening process.

Base Sequence↗
PubMed2002

Micronuclei in cervical smears and peripheral blood lymphocytes from women with and without cervical uterine cancer.

Cervical cancer represents the second most common malignant neoplasia in women world-wide. In Mexico, cervical cancer is the most common female malignancy. It has been recently seen an increased frequencies of micronuclei (MN) lymphocytes and cervical epithelial cells of cervical cancer patients. The aim of this hospital-based unmatched case-control study was to investigate the association between progressive stages in development of cervical cancer and frequency of micronucleated cells in the cervical epithelium and peripheral lymphocytes of 40 women, grouped by disease stage. Women at the Obstetrics and Gynecology Hospital of the Instituto Mexicano del Seguro Social (IMSS) in Monterrey, Mexico were diagnosed and classified on the bases of the Papanicolaou (PAP) smear and colposcopy/biopsy into control, low-grade squamous intraepithelial lesions (LGSIL), high-grade squamous intraepithelial lesions (HGSIL), and invasive groups. Analysis of the MN data in both cell types revealed (a) homogeneity among women within each of the four groups with regard to MN frequency, (b) in general, a correlation between MN frequency and grade of cervical lesion, and (c) a positive linear trend between the MN frequency and increased cervical cancer risk. In conclusion, we suggest that MN are a useful biomarker of cancer risk. Nonetheless, these results should be validated by other researchers.

Adult↗
PubMed2002

Prostaglandin F(2alpha), cytokines and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibroblast cells.

Human uterine cervical tissue is composed mainly of fibroblast cells and the extracellular matrix in which collagen types I and III predominate. It is hypothesized that these collagens are degraded by matrix metalloproteinases (MMPs) in the initial step of uterine cervical ripening during parturition. Among the MMPs, MMP-1, -8 and -13 have substrate selectivity for collagen types I and III. In the present study, we examined the regulation of MMP-1 secretion from the human uterine cervix. Immunohistochemistry detected strong staining of MMP-1, but not of MMP-8 or -13, in stromal cells of the pregnant uterine cervix. The MMP-1 expression in the pregnant uterine cervix was further confirmed by Western blot analysis and RT-PCR. To clarify the regulation of MMP-1 production, we subsequently investigated the effects of prostaglandins, inflammatory cytokines and cyclic mechanical stretch on the secretion of MMP-1 from cultured human uterine cervical fibroblast cells. Treatment with prostaglandin (PG)F(2alpha) (10(-7) to 10(-5) mol/l) or interleukin (IL)-1alpha (0.01-1.0 ng/ml) or stimulation with cyclic mechanical stretch increased MMP-1 secretion from cultured human uterine cervical fibroblast cells, with maximal increases of 3.4-, 4.5- and 1.9-fold respectively (24 h of treatment, P < 0.05 for all comparisons). These data suggest that MMP-1 may play a significant role in the degradation of extracellular collagen types I and III in the pregnant uterine cervix during the process of cervical ripening, in response to various stimulations such as PGF(2alpha), IL-1alpha and mechanical stretch.

Cells, Cultured↗
PubMed1996

Purification and characterization of hexosaminidase from human uterine cervical carcinoma.

Normal human uterine cervical tissue and uterine cervical carcinoma tissue were collected and subjected to fractionation of hexosaminidase isoenzymes Hex A, Hex B, and Hex I using DEAE-cellulose anion-exchange chromatography. Hex A was found to be the major isoenzyme in control tissues, whereas Hex B was the major isoenzyme in carcinoma tissues. These two major isoenzyme fractions were first purified using heparin-Sepharose 4B affinity chromatography and then subjected to further purification on epsilon-ACMA-Sepharose 4B. The purified isoenzymes were found to be homogeneous by polyacrylamide gel electrophoresis. The Hex A and Hex B isoenzymes obtained from control and carcinoma patients were characterized. Hex A from control and carcinoma patients exhibited more or less similar properties. However, the Hex B isoenzyme from carcinoma patients exhibited some characteristic variations in pH, temperature, substrate concentration optima, and isoelectric point compared with the control. From these observations it may be inferred that altered properties of the Hex B isoenzyme fraction from carcinoma patients may be the reason for the elevated activity of hexosaminidase in carcinoma of the uterine cervix.

Chemical Fractionation↗
PubMed2001

Nitric oxide increases matrix metalloproteinase-1 production in human uterine cervical fibroblast cells.

Since uterine cervical ripening is an active biochemical process similar in part to an inflammatory reaction, nitric oxide (NO) has been proposed as a key mediator of this event. However, the mechanism by which NO modulates human cervical ripening has not been fully elucidated. In the present study we investigated the presence of NO synthases in human uterine cervix by immunohistochemistry and reverse transcriptase-polymerase chain reaction analysis. Furthermore, we examined the presence of NO-mediated regulation of matrix metalloproteinase-1 (MMP-1) production in cultured human uterine cervical fibroblast cells using enzyme-linked immunosorbent assay and Northern blot analysis. Endothelial and inducible NO synthases were detected in the form of mRNA and protein expression in pregnant uterine cervix. Interleukin-1alpha (IL-1alpha) increased the expression of inducible NO synthase mRNA in cultured human uterine cervical fibroblast cells. IL-1alpha also increased MMP-1 secretion from the cultured cervical fibroblast cells. This IL-1alpha-augmented MMP-1 secretion was partially but significantly blocked by an NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester. On the other hand, NO donors increased MMP-1 production in the cultured cervical fibroblast cells. These findings together suggest that NO contributes to the process of cervical ripening via enhancement of MMP-1 production, and that IL-1alpha increases MMP-1 secretion from cervical fibroblasts at least in part via NO synthesis.

Basic Helix-Loop-Helix Proteins↗
PubMed2004

Loss of heterozygosity analysis in uterine cervical adenocarcinoma.

OBJECTIVE: Uterine cervical adenocarcinoma (CAC) is a rare form of cervical cancer, constituting only 5-8% of all cervical epithelial malignancies. Loss of heterozygosity (LOH) analysis of CAC was undertaken to identify alterations of chromosomal loci that may play important roles in the development of this tumor type. METHODS: We analyzed loss of heterozygosity (LOH) using a total of 50 markers on 20 chromosomal arms in 37 cases of microdissected CAC DNA. RESULTS: LOH of >40% was observed on 2p (50%), 3p (45%), 9p (45%), 11q (46%), 17p (57%), 17q (44%), 18q (57%), and 19p (44%). LOH of 30-40% was observed on 6p (38%), 6q (40%), and 10q (31%). Overall, mean LOH was 34% and fractional allelic loss (FAL) was 0.34. High-level and low-level microsatellite instability (MSI) was shown in four cases (11%) and six cases (16%), respectively. Frequency of LOH on10q was significantly higher in endometrioid-type than endocervical-type adenocarcinoma (71% versus 20%; P < 0.05). Conversely, 6q LOH was higher in endocervical type than endometrioid type (0% versus 60%; P < 0.05). 19p13.3 has been reported to be frequently deleted in adenoma malignum, a histological subtype of CAC. To define the critical regions of LOH in CAC in general, we further performed deletion mapping of 19p using 13 markers. Unlike adenoma malignum, multiple regions on 19p appeared to be important loci of LOH for CAC. CONCLUSION: CACs develop with frequent LOH of multiple chromosomal arms, which may be related to its aggressive clinical behavior and poor prognosis. LOH of 10q may be unique to endometrioid-type CAC.

Adenocarcinoma↗
PubMed1997

Hormonal regulation of matrix metalloproteinase 9/gelatinase B gene expression in rabbit uterine cervical fibroblasts.

Since the degradation of uterine cervical extracellular matrix is an essential process in cervical ripening and dilatation at term, we examined the effect of pregnancy on the level of pro-matrix metalloproteinase 9 (proMMP-9)/progelatinase B in the rabbit uterine cervix and its regulation in uterine cervical fibroblasts. Uterine cervices shortly before term parturition contained high levels of proMMP-9 compared with those of nonpregnant rabbits. Uterine cervical fibroblasts prepared from rabbits at 23 days of gestation did not produce proMMP-9; in contrast, interleukin (IL)-1 alpha, IL-1 beta, or phorbol 12-myristate 13-acetate (PMA) induced proMMP-9 production along with an increase of proMMP-9 mRNA, and the IL-1-mediated induction of proMMP-9 was synergistically enhanced by PMA. On the other hand, physiological concentrations of progesterone suppressed IL-1-and/or PMA-mediated production of proMMP-9 in a dose-dependent manner. This suppressive effect of progesterone on proMMP-9 production was accompanied by a decrease in matrix metalloproteinase 9 (MMP-9) mRNA, indicating that progesterone down-regulates the production of proMMP-9 at the transcriptional level. These results indicate that in the rabbit uterine cervix, IL-1 alpha and IL-1 beta are effective inducers of the proMMP-9 production, and progesterone is a physiological suppressor. Thus, MMP-9 and progesterone are very likely to play essential roles in cervical ripening and dilatation in the rabbit, and the production of MMP-9 in the cervix is finely regulated during pregnancy.

Animals↗
PubMed1975

Different agglutinability of fibroblasts underlying various precursor lesions of human uterine cervical carcinoma.

Fibroblasts underlying human uterine cervical dysplasia, carcinoma in situ, and invasive carcinoma are agglutinable by concanavalin A (Con A) but not by wheat germ agglutinin, except at very high concentration. Studies with low levels of Con A show that maximal agglutination is obtained with fibroblasts from invasive carcinoma, while the fibroblasts underlying dysplasia give minimal agglutination reactions. Fibroblasts underlying carcinoma in situ give agglutination reactions halfway between those obtained with fibroblasts underlying dysplasia and invasive carcinoma. An epithelial-like cell line obtained from a case of dysplasia shows agglutinability by Con A very similar to that obtained with fibroblasts underlying dysplasia. These epithelial-like cells are also not agglutinable by wheat germ agglutinin. Treatment of the cervical cells, both epithelial and fibroblasts, with neuraminidase leads to slight increase in agglutination by both Con A and wheat germ agglutinin. Marked increase in agglutination is not obtained even after treatment with high concentration of neuraminidase (10 units/10(6) cells). Marked agglutinability, however, is observed after trypsin treatment. The results suggest that, while the fibroblasts obtained from normal cervix are not agglutinable by Con A, surface alterations necessary for Con A-specific agglutination exist in fibroblasts during the early stage of development of uterine cervical epithelial neoplasia (dysplasia) and increase with the progression through carcinoma in situ to invasive carcinoma. Loss of cell surface sialic acids may result in a slight increase in agglutinability, but some other mechanism(s) is likely to be involved in alteration of surface properties that lead to marked agglutinability of the human uterine cervical cells obtained from cancer precursor lesions.

Agglutination↗
PubMed1994

Progesterone increases the production of tissue inhibitor of metalloproteinases-2 in rabbit uterine cervical fibroblasts.

Rabbit uterine cervical fibroblasts in culture produces tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. When cells were treated with physiological concentrations of progesterone, the production of two TIMPs increased, and essentially all TIMP-2 was found to be complexed with promatrix metalloproteinase 2 (proMMP-2)/progelatinase A. Progesterone did not modulate the production of proMMP-2 and resulted in the increased total amount of proMMP-2-TIMP-2 complex. These observations provide the first evidence that progesterone participates in maintaining the homeostasis of connective tissue matrix in uterine cervix by augmenting both TIMP-1 and TIMP-2 production along with the known suppressive effects on the proMMP-1 and proMMP-3 production.

Animals↗
PubMed2003

Uterine cervical distension induces cFos expression in deep dorsal horn neurons of the rat spinal cord.

BACKGROUND: Uterine cervical distension underlies labor pain, yet its neurophysiology and pharmacology of inhibition remain unexplored. The authors examined uterine cervical distension-evoked cFos immunoreactivity in rat spinal cords, and the inhibitory effect of spinal cyclo-oxygenase inhibition on cFos expression. METHODS: Female rats were anesthetized with halothane, and pairs of metal rods were inserted in each cervical os through a mid-line laparotomy. A submaximal distension force (75 g) was applied for either 30 or 60 min, or, in control animals, no force was applied. Other animals received cervical lidocaine infiltration prior to uterine cervical distension. At the end of the experiments, the spinal cord at T12 to L2 levels was harvested and immunostained for cFos protein. Other animals received intrathecal ketorolac (0, 5, 25, and 50 microg; n = 5-6 for each group) prior to uterine cervical distension. RESULTS: Uterine cervical distension significantly increased cFos immunoreactivity in the spinal cord from T12 to L2, with most cFos expression in the deep dorsal and central canal regions. Surgical preparation alone without uterine cervical distension resulted in minimal cFos expression, primarily in the superficial dorsal horn. Uterine cervical distension-evoked cFos expression was prevented by prior infiltration of lidocaine into the cervix. Intrathecal ketorolac produced a dose-dependent inhibition of uterine cervical distension-induced cFos expression. CONCLUSION: The present study demonstrates that uterine cervical distension results in a similar pattern of spinal cord neuronal activation as seen with other noxious visceral stimuli. The inhibition of cFos expression by intrathecal ketorolac suggests that spinal cyclo-oxygenase plays a role in uterine cervical distension-induced nociception.

Animals↗