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PubMed2001

Altered mRNA expression of sialyltransferase in squamous cell carcinomas of the cervix.

OBJECTIVE: Increased sialylation has been reported in various kinds of cancers, but to date, sialylation of cervical carcinoma has never been evaluated. This study of the changes in messenger ribonucleic acid (mRNA) expression of the four sialyltransferases (ST3Gal I, ST3Gal III, ST3Gal IV, and ST6Gal I) in a normal cervix and that with FIGO stage IB1 squamous cell carcinoma was undertaken to assess the extent of sialylation associated with establishment of the carcinoma. METHODS: Alterations in ST mRNA expression in FIGO IB1 cervical cancer (n = 30) and normal cervixes (n = 30) were examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: ST6Gal I expression was enhanced in squamous cell carcinoma of the cervix (P = 0.026, Mann-Whitney U test), but mRNA expression from the other three STs (ST3Gal I, ST3Gal III, and ST3Gal IV) was significantly down-expressed in squamous cell carcinoma of the cervix compared to the normal cervix (P = 0.003, P < 0.001, and P = 0.001, respectively). High ST6Gal I expression was associated with more invasive properties of cervical cancer, such as deep stromal invasion, lymph or vascular space involvement, and poor differentiation (P = 0.010, P < 0.001, P < 0.001, respectively). CONCLUSIONS: A combination of enhanced ST6Gal I mRNA expression and decreased mRNA expression from ST3Gal I, ST3Gal III, and ST3Gal IV might be important in cervical cancer. Future studies will investigate whether RT-PCR detection of the expression of these enzymes can be helpful for prognostic purposes.

Carcinoma, Squamous Cell↗
PubMed2006

MR imaging of the uterus and cervix in healthy women: determination of normal values.

The purpose of this study was to establish normal values for the volume of the uterus and cervix in MRI based on age and the menstrual cycle phase. We performed MRI of the pelvis in 100 healthy women. For the uterus, they were further divided into two groups: one with myomas and/or adenomyosis and one without either. The volume of the uterus and cervix and thickness of the uterine wall layers were analysed by age and the menstrual cycle phase. The mean volume of the uterus in both groups and the cervix significantly increased with age to reach its peak at 41-50 years, and then dropped. Likewise, the thickness of the endometrium and the junctional zone, but not the myometrium, significantly increased until 41-50 years, and then decreased. When we compared the volume of the uterus and cervix and the thickness of the uterine wall layers between the two phases of the menstrual cycle, we found no significant differences. The volume of the uterus and cervix and the thickness of the endometrium and junctional zone differ significantly with age, but not between the two phases of the menstrual cycle. Knowledge of MRI-related normal values can be expected to aid the early identification of uterine pathologies.

Adult↗
PubMed2005

P2X receptors in the rat uterine cervix, lumbosacral dorsal root ganglia, and spinal cord during pregnancy.

ATP, an intracellular energy source, is released from cells during tissue stress, damage, or inflammation. The P2X subtype of the ATP receptor is expressed in rat dorsal root ganglion (DRG) cells, spinal cord dorsal horn, and axons in peripheral tissues. ATP binding to P2X receptors on nociceptors generates signals that can be interpreted as pain from damaged tissue. We have hypothesized that tissue stress or damage in the uterine cervix during late pregnancy and parturition can lead to ATP release and sensory signaling via P2X receptors. Consequently, we have examined sensory pathways from the cervix in nonpregnant and pregnant rats for the presence of purinoceptors. Antiserum against the P2X3-receptor subtype showed P2X3- receptor immunoreactivity in axon-like structures of the cervix, in small and medium-sized neurons in the L6/S1 DRG, and in lamina II of the L6/S1 spinal cord segments. Retrograde tracing confirmed the projections of axons of P2X3-receptor-immunoreactive DRG neurons to the cervix. Some P2X3-receptor-positive DRG neurons also expressed estrogen receptor-alpha immunoreactivity and expressed the phosphorylated form of cyclic AMP response-element-binding protein at parturition. Western blots showed a trend toward increases of P2X3-receptor protein between pregnancy (day 10) and parturition (day 22-23) in the cervix, but no significant changes in the DRG or spinal cord. Since serum estrogen rises over pregnancy, estrogen may influence purinoceptors in these DRG neurons. We suggest that receptors responsive to ATP are expressed in uterine cervical afferent nerves that transmit sensory information to the spinal cord at parturition.

Animals↗
PubMed1985

Increase in cervical extensibility during labor induced after isolation of the cervix from the uterus in pregnant ewes.

Surgical transection of the cervix was done on eight ewes in late pregnancy. This procedure resulted in most of the length of the cervix being mechanically disconnected from the uterus. Labor was induced by injection of dexamethasone phosphate into a fetal hind limb during operation in four of the eight ewes. The success of the induction of labor was confirmed by observation of increased uterine activity and by measurement of the concentrations of progesterone and 17 beta-estradiol in peripheral plasma. Ewes were put to death approximately 48 hours after injection of dexamethasone and the extensibility of the isolated portion of the cervix was determined. Cervices taken from ewes in which labor had been induced were found to have softened considerably compared to control cervices taken from ewes in which the cervix had been transected without induction of labor. The results suggest that cervical softening can still occur during labor in the absence of any direct mechanical or local vascular connection between the cervix and uterus.

Animals↗
PubMed1986

Localization of an estrogen-responsive protein in the human cervix during menstrual cycle, pregnancy, and menopause and in abnormal cervical epithelia without atypia.

The presence and distribution of an estrogen-responsive protein with a molecular weight of 28,000 were investigated in the human cervix with use of a monoclonal antibody. This biochemical marker protein was localized with a light microscope and by immunocytochemical studies of the different cell types and cell layers of the cervix. The study involved 60 patients, 48 of whom were sexually active, eight pregnant, and four in menopause; strips of endometrial tissue were analyzed in 22 patients. In cycling women the estrogen-responsive protein was identified in the subcolumnar cells of the endocervix, whereas in the ectocervix the protein was detected mainly in the parabasal and intermediate cell layers but alternating with unstained areas. There were no significant variations in the presence of the protein in the ectocervical and endocervical epithelium during the different phases of the menstrual cycle. During pregnancy a more intense and homogeneous immunostaining of the protein was seen in the ectocervix, endocervical areas with squamous metaplasia showed strong estrogen-responsive immunostaining, and predecidual and decidual cells were positive for the protein. There were no prominent changes in the presence and distribution of the protein in the abnormal ectocervical samples without atypia. However, in the endocervix the protein detection was useful to follow the evolution of the subcolumnar cells to simple squamous metaplasia. These samples displayed intense estrogen-responsive immunostaining. No immunoreaction was observed in the cervix of menopausal women. The results of the present study have shown that the response of the normal uterine cervix to estrogenic influence is heterogeneous in different cervical cell types and in different sites within the same cell layer; during the normal menstrual cycle the capability of response of the cervical cells to variations of estrogen levels is limited when compared with the endometrium; and during pregnancy and in the process of indirect squamous metaplasia some of the cervical cells seem to be very reactive to estrogenic stimulation. This study defines the normal baseline for further analysis of the estrogen-regulated protein in the uterine cervix during abnormal growth.

Acanthosis Nigricans↗
PubMed1989

Invasive carcinoma of the uterine cervix following diagnosis and treatment of in situ carcinoma. Record linkage study within a National Cancer Registry.

56117 women registered in the Swedish National Cancer Registry with the diagnosis carcinoma in situ of the uterine cervix were followed up and the risk for developing an invasive carcinoma of the uterine cervix was studied. The studied cohort provided 453 362 women years at risk. The primary treatment for carcinoma in situ in Sweden is generally conization. Hysterectomy is carried out in relatively few cases and intracavitary radium treatment was given to a limited number during the period studied. Cryosurgery and laser conization were of less quantitative importance during this period. The incidence rates of invasive carcinoma of the uterine cervix were compared with expected rates calculated from the National Cancer Registry. The ratio between observed and expected number of cases of invasive carcinomas of the uterine cervix is roughly 2.5 from the first year of observation after treatment of the in situ carcinoma until 20 years. There seems to be a distinct difference in risk for development of an invasive carcinoma of the uterine cervix for different age groups. In age group 50 years and older at time for treatment of the in situ lesion, 66 cases of invasive cancer were observed against 10.7 expected - O/E = 6.2. In ages 49 years or less, 145 cases were observed compared with 77.4 expected - O/E = 1.9. The conclusion from this study is that women treated for an in situ lesion are at a higher risk for an invasive carcinoma than the common female population and should be carefully followed up for a long time after treatment of the in situ lesion.

Adult↗
PubMed1992

Distribution of NADPH-diaphorase-positive nerves in the uterine cervix and neurons in dorsal root and paracervical ganglia of the female rat.

Nitric oxide synthase (NOS) was selectively stained in nerve fibers of the uterine cervix and neurons of the paracervical (PG) and dorsal root ganglia (DRG) by NADPH diaphorase histochemistry. In the cervix, numerous NADPH-diaphorase-positive nerve fibers were observed in the myometrium, endometrium and around arteries. In addition, a subpopulation of neurons within ganglia that innervate the cervix, i.e., the PG and DRG, were NADPH-diaphorase positive; thus the fibers in the cervix could be sensory and/or autonomic. NADPH-diaphorase/NOS localization identifies sites where nitric oxide (NO) can be synthesized. Since NO relaxes vascular and nonvascular smooth muscle, the prevalence and anatomical localization of NADPH-diaphorase-positive fibers suggest that they could influence functions of the uterine cervix.

Amino Acid Oxidoreductases↗
PubMed2004

Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial.

OBJECTIVE: The purpose of this study was to determine the efficacy of cerclage and bed rest versus bed rest-only for the prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination. STUDY DESIGN: Women with > or =1 of high-risk factors for preterm birth (> or =1 preterm birth at < 35 weeks of gestation, > or =2 curettages, diethylstilbestrol exposure, cone biopsy, Mullerian anomaly, or twin gestation) were screened with transvaginal ultrasonography of the cervix every 2 weeks from 14 weeks of gestation to 23 weeks 6 days of gestation. Enrollment was offered to both asymptomatic women who were at high risk and who were identified to have short cervix (< 25 mm) or significant funneling (>25%) and nonscreened women who were at low risk and who were identified incidentally. The women who gave written consent were assigned randomly to receive either McDonald cerclage or bed rest-only. Both groups received similar counseling and treatment. Primary outcome was preterm birth at < 35 weeks of gestation. RESULTS: Sixty-one women were assigned randomly. Forty-seven pregnancies (77%) were high-risk singleton gestations. Thirty-one women (51%) were allocated to cerclage, and 30 women (49%) were allocated to bed rest. There were no differences between the groups in demographic characteristics, risk factors, and cervical variables. Preterm birth at < 35 weeks of gestation occurred in 14 women (45%) in the cerclage group and in 14 women (47%) in the bed rest group (relative risk, 0.94; 95% CI, 0.34-2.58). There was no difference in any obstetric or neonatal outcomes. A subanalysis of singleton pregnancies with previous preterm birth at < 35 weeks of gestation and a short cervix of < 25 mm (n = 31 women) also revealed no significant difference in recurrent preterm birth at < 35 weeks of gestation (40% vs 56%; relative risk, 0.52; 95% CI, 0.12-2.17). CONCLUSION: Cerclage did not prevent preterm birth in women with a short cervix. These results should be confirmed by larger trials.

Bed Rest↗
PubMed2005

Does the presence of a funnel increase the risk of adverse perinatal outcome in a patient with a short cervix?

OBJECTIVE: This study was undertaken to determine whether the presence of a dilated internal os (funneling or beaking) alters the outcome of patients with a short cervix documented by transvaginal ultrasound in the second trimester. STUDY DESIGN: Between January 1998 and May 2004, all singleton pregnancies with a short cervix (< or =2.5 cm) and no funnel between 16 and 24 weeks' gestational age were identified by query and review of the Lehigh Valley Perinatal Ultrasound Database. These no funnel patients were compared with patients with a short cervix and funnel matched in accordance with cervical length and risk factors. Multiple variables of perinatal outcome were identified and compared between the Funnel and No Funnel groups. Correlations between cervical measurements and gestational age at birth were analyzed. RESULTS: Of the 279 patients with a short cervix identified, 82 were singleton with a T-shaped cervix and no funnel and 82 patients matched with a typical Y-shaped funnel. There was no difference between groups with respect to maternal demographics, previous preterm birth (28.1% No Funnel group vs 36.5% Funnel group, P = .3), prior cervical surgery (24.3% vs 22.0 %, P = .8), gestational age at entry (20.5 +/- 2.1 vs 21.1 +/- 2.4 weeks, P = .1), and cervical length (1.9 +/- 0.4 vs 1.8 +/- 0.5 cm , P = .1). The No Funnel group had significantly less readmissions for preterm labor (43.2% vs 67.1 %, P = .004), chorioamnionitis (2.4% vs 23.2 %, P = .0002), abruption (1.2% vs 13.4 %, P = .007), preterm rupture of membranes (6.1% vs 23.4%, P = .002), and cerclage placement (23.2% vs 43 %, P = .008). The neonates in the no funnel group delivered later (36.2% +/- 4.6 vs 33.8 +/- 5.4 weeks , P = .003), and had less morbidity and mortality (17.1% vs 37.8 %, P = .02) compared with the Funnel group. The width and depth of the funnel did not correlate with perinatal outcome. Cervical length ( R(2) = 0.07, P = .02) and cervical funneling as a categorical variable ( r = 0.3, P = .0002) did correlate with earlier delivery. CONCLUSION: The disruption of the internal os, as documented by funneling, is a significant risk factor for adverse perinatal outcome (ie, preterm labor, chorioamnionitis, abruption, rupture of the membranes, and serious neonatal morbidity and mortality). Cervical funneling is best measured as a categorical variable (present or absent).

Adult↗
PubMed2006

Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix.

OBJECTIVES: (1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence. STUDY DESIGN: This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (IB and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson's chi(2)-test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan-Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. RESULTS: There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p<0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p=0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p<0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p=0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p=0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors. CONCLUSION: The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted.

Adenocarcinoma↗
PubMed2006

Langerhans' cells and smoking in intraepithelial neoplasia of the cervix.

OBJECTIVE: To compare the intraepithelial population of Langerhans' cells (LC) in normal cervix epithelium adjacent to cervical intraepithelial neoplasia grade 3 (CIN 3) and correlate to smoking habit. METHODS: Cases in this study included conization specimens from 48 women affected by CIN 3. The LC count was performed in areas without histopathologic alteration adjacent to CIN 3. The control group is compound by normal cervix from 46 hysterectomy specimens. The identification of LC was done by immunohistochemical study demonstrating immunoreactivity to S-100 protein. The number of intraepithelial LC was determined using 400x magnification light microscope in 10 high-power fields, and results were expressed in number of cells per square millimeter (LC/mm(2)). RESULTS: In the control group, there was lower number of Langerhans' cells in smokers than in non-smokers (P = 0.045). There was lower number of Langerhans' cells in normal areas adjacent to CIN 3 than in normal cervix control group (P = 0.004). There was no significant difference in the number of Langerhans' cells in normal areas of the cervix with CIN 3 between smokers and non-smokers (P = 0.991). The number of cigarettes consumed daily, time of consume, total number of cigarettes consumed showed a reduced LC count, yet was not statistically significant. CONCLUSIONS: It was revealed that smoking reduces the number of intraepithelial Langerhans' cells in the uterine cervix. In women with CIN 3, the LC count was lower, despite the habit of smoking.

Adult↗
PubMed2001

Effect of ovarian steroids on nitric oxide synthase in the rat uterus, cervix and vagina.

The effects of estrogen (E2), progesterone (P) and E2 and P (E2 + P) were examined on nitric oxide synthase (NOS) activity in both cytosolic and particulate fractions isolated from the rat uterus, vagina, cervix and cerebral cortex. Additionally plasma nitrate + nitrite (NO3 + NO2) levels were measured in control and hormone treated rats. Cytosolic NOS was the predominant form being approximately 80% of the total in all four tissues. NOS activity in both fractions from all tissues was highly Ca-dependent (> 90%). Among the reproductive tract tissues, the highest activity was found in the cervix, which was nearly 5- and 2-fold higher than the uterus and vagina, respectively. NOS activity in the cerebral cortex was by far the highest being 5-fold higher than in the cervix. In contrast to the cortex, E2 treatment downregulated cytosolic NOS in all reproductive tract tissue, but this was statistically significant in only uterus. When compared with E2 treated rats, P increased cytosolic NOS in uterus, vagina, and particulate NOS in the cervix. The data do not give any indication whatsoever of differential effects of P in the uterus and cervix.

Animals↗
PubMed2000

Anemia, hypoxia and transfusion in patients with cervix cancer: a review.

BACKGROUND AND PURPOSE: With the recent development of hemopoietic growth factors and alternatives to transfusion, there has been a renewed interest in the relationships between anemia, tumor hypoxia and treatment outcome in a number of human malignancies. This review is intended to provoke a reconsideration of these issues and their effect on clinical trials, aimed at improving treatment outcome in patients with cervix cancer. MATERIALS AND METHODS: Using data from the literature and from our own prospective series of tumor oxygenation in cervix cancer, we modeled the impact of anemia on tumor blood flow and hypoxia in animal models and human tumors, examined the relationship between anemia and hypoxia and treatment outcome in patients, and reviewed the impact of transfusion on tumor hypoxia and treatment outcome in cervix cancer. RESULTS: Anemia may result in a significant reduction in oxygen delivery to tumors, but compensatory mechanisms reduce the impact on tumor oxygenation. Anemia is associated with inferior treatment outcome in cervix cancer, but hemoglobin levels prior to and during treatment are strongly correlated with tumor size, and this may explain the prognostic impact of anemia in older studies. Transfusion and erythropoietin ameliorate hypoxia in only a proportion of anemic patients. Critical analysis of the published data from the Princess Margaret Hospital randomized trial of transfusion in cervix cancer reveals that, when analyzed by intention-to-treat, transfusion did not result in a benefit to patients. CONCLUSIONS: This review suggests that the relationships among anemia, hypoxia, transfusion and treatment outcome are complex. Further study of anemia as an independent prognostic factor is required and randomized studies of transfusion alternatives, such as erythropoietin, must be of sufficient size to detect small treatment effects.

Anemia↗
PubMed2002

Calcitonin gene-related peptide-receptor component protein expression in the uterine cervix, lumbosacral spinal cord, and dorsal root ganglia.

The neuropeptide calcitonin gene-related peptide (CGRP) may play a role in neurogenic inflammation, tissue remodeling of the uterine cervix, promoting vasodilation, parturition, and processing of sensory information in the spinal cord. CGRP-immunoreactive nerves of the cervix and spinal cord have been studied but cellular identification of the CGRP receptor has received little attention. CGRP-receptor component protein (CGRP-RCP) is a small protein associated with the CGRP receptor; thus, immunostaining for the CGRP-RCP can be used to identify sites of the CGRP receptor. We determined sites of CGRP-RCP immunoreactivity relative to the presence of CGRP-ir nerve fibers in the female rat uterine cervix, spinal cord, and dorsal root ganglia. CGRP-RCP immunoreactivity was expressed in the dorsal horn of the spinal cord, venules of the uterine cervix, and perikarya of sensory neurons in dorsal root ganglia. CGRP-immunoreactive fibers were adjacent to CGRP-RCP-immunoreactive vessels in the cervix and among CGRP-RCP-immunoreactive structures in the dorsal horn of the spinal cord. This suggests CGRP-RCP is associated with structures innervated by CGRP nerves and these interactions may be changed in tissues in response to an appropriate stimulus.

Animals↗
PubMed2002

Assessment of the cervix in the third trimester of pregnancy using transvaginal ultrasound scanning.

OBJECTIVES: To evaluate the inter- and intra-observer reproducibility of a technique for examining physical characteristics of the uterine cervix in the third trimester of pregnancy using transvaginal ultrasound scanning (TVS). STUDY DESIGN: Forty-six women of over 27-week-gestation underwent TVS of the cervix using a Toshiba 140 scanner with a 6 MHz probe. Twenty were scanned once and 14 women twice by the same operator, and another 12 women by two different operators. Measurements of cervical length, including length and width and opening of the internal os were taken from hardcopy images. Of the 26 women scanned twice, sets of images were analysed by a blinded single observer. Of the 20 women scanned once, measurements from the hardcopy images were taken by two blinded observers. RESULTS: The mean difference in measurement of the distance from the tip of the cervix to foetal head was 2.3mm for two hardcopy image observers,-1.96mm for two scans by the same operator and -1.52 mm for two scanners. Corresponding differences in width of opening of the internal os were 1.8, 0.44 and 0.32 mm, respectively. Interpretation of two images taken on each occasion gave similar results to those taken from three or more images. CONCLUSIONS: This method of obtaining TVS measurements from the cervix from hardcopy images that has satisfactory intra- and inter-observer error. It remains to be established whether this method will be better than Bishop score in predicting the outcome of induced or spontaneous labour. The technique appears to be suited for use in multicentre trials of TVS of the cervix at term.

Adolescent↗
PubMed1998

Sonographic assessment of the cervix in pregnancy.

Recent studies using transvaginal and transperineal sonography to monitor the cervix have dramatically increased our knowledge of morphological changes of the cervix throughout pregnancy. Knowledge of the normal and abnormal appearance of the cervix gives insight into the processes of premature labor and cervical incompetence. The finding of a short cervix can be used to identify (and possibly treat) patients at risk for premature delivery. This article reviews the use of cervical sonography in obstetric care, including the diagnosis of incompetent cervix, the detection and monitoring of premature labor, and the evaluation of placenta previa.

Cervix Uteri↗
PubMed2000

Volume assessment of the normal female cervix with MR imaging: comparison of the segmentation technique and two geometric formula.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the volume of the normal female cervix and to determine the geometric formula that yields the best estimate. MATERIALS AND METHODS: Magnetic resonance images of the pelvis in 30 young women were reviewed retrospectively. The volume of the cervix was estimated by using the formulas for an ellipse and a cylinder. Manual labeling and segmentation of the cervix were also performed, and the volume was calculated on the basis of the number and size of the voxels. Comparison of these methods was then performed by using a two-tailed Student t test. RESULTS: No statistically significant difference was found (P = .7) between the volume calculated with the segmentation technique (25.3 mL) and that estimated with the formula for a cylinder (24.8 mL). A statistically significant difference (P < .05) was found between the volume calculated with the segmentation technique and that estimated with the formula for an ellipse (16.4 mL). CONCLUSION: The normal volume of the cervix in this population of young women was approximately 25 mL. The volume of the cervix should be estimated with the formula for a cylinder.

Adult↗
PubMedDate not supplied

Evaluation of cellular immune responses in rhesus monkeys subjected to adenovirus-mediated gene transfer into the cervix.

We reported previously that direct injection of a recombinant adenovirus (rAd), Ad5CMV-beta-gal, into the cervix of the rhesus monkey resulted in efficient beta-galactosidase expression in the cervix within 3 days. In these studies, we also observed the induction of anti-adenovirus (Ad)-specific immunoglobulin G responses after 22 days. In the continuation of evaluating the anti-Ad-specific immune responses resulting from this approach of gene targeting to the cervix, we measured the cellular immune responses. The introduction of Ad5CMV-beta-gal into the cervix by direct injection, but not by the abrasion technique, resulted in the induction of strong proliferative responses against extracts of cells infected with Ad5CMV-beta-gal but not against control uninfected cells. These responses were initially detected at 22 days postinjection and coincided with the abrogation of transgene expression. Significant levels of proliferative responses were maintained for < or =83 days. Multiple injections of rAds had no significant enhancing effect on either the level or longevity of the proliferative responses. At 3 days after the injection of Ad5CMV-beta-gal, when the transgene expression in the cervix was clearly evident, proliferative responses against the rAd were not detectable. However, the production of low but significant amounts of interleukin-10, a cytokine characteristic of T helper type 2 responses that promote humoral immune responses, was observed at the 3-day point in these animals. These results suggest that significant differences exist between the kinetics of transgene expression and the priming of specific host immune responses, and that these differences may be important for devising alternate strategies to improve techniques for Ad-mediated gene therapy of cervical cancer.

Adenoviridae↗