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[Salivary LH as an ovulation indicator: on the value of autopalpation of the cervix uteri for the detection of fertile and infertile days of the cycle].

The validity of autopalpation of the cervix as an indicator of fertility has been studied in 115 cycles of 13 nulliparous and 13 parous women, aged 22 to 35 years and experienced in self-observation methods (SOM) of family planning. For this purpose, the reported cyclic changes of the cervix uteri (hard, closed and low positioned; soft, open and higher positioned or intermediate stages) have been compared with the salivary LH-peak as indicator of ovulation, the BBT-readings and cervical mucus quality. The study has confirmed that in principle it is possible to collect sufficiently reliable self observation data for family planning purposes by autopalpation of the cervix. Parous women detect the first preovulatory changes of the cervix earlier and more frequently than nulliparous. Nevertheless it is not possible for either group to determine the beginning of the fertile days in this way. The beginning of the postovulatory infertile phase, however, can be detected: if, in accordance with rising BBT, the cervix has returned to a hard and closed appearance for 4 days, this symptom signals infertility with the same high degree of accuracy as the third measurement of elevated BBT (BBT3). Thus a "rule of thumb" can be established, linking the beginning of postovulatory infertility to either the fourth day of the hard and closed cervix or to the evening of the day of BBT3, "whatever comes first". In this way, the beginning of the infertile phase could be recognized one to three days earlier by referring to the cervix in about 20% of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regional differences in water content, collagen content, and collagen degradation in the cervix of nonpregnant cows.

The cow could be a suitable model for studies concerning functional changes of the cervix. However, as in many species, the bovine cervix becomes softer in texture during the follicular phase of the estrous cycle compared to the luteal phase. In the present study, we explored if changes in the collagen network take place that could be responsible for this phenomenon and if regional differences in water content, collagen content, and collagen degradation along the cross-sectional and longitudinal axes of the cervix were present. Two groups of nonpregnant animals with different progesterone status were studied. One group (n = 11) was under high progesterone influence, and the other group (n = 12) was under low progesterone influence. The water content was derived from the weight of the samples before and after lyophilization. The collagen content and the ratio of collagenous to noncollagenous proteins (hydroxyproline:proline ratio) were determined by performing amino acid analysis on hydrolyzed samples using high-performance liquid chromatography. Collagen denaturation was quantified with a colorimetric assay by determining the amount of hydroxyproline released from samples treated with alpha-chymotrypsine. The water content of the superficial layer of the submucosa was always significantly (P < 0.01) higher than the water content of the deep layer in the vaginal, mid, and uterine segments, but this was unrelated to the progesterone status of the animals. No effect of the tissue layers or of the progesterone status of the animals on the collagen content was observed, but an effect of segment was noted. The collagen content (mug/mg dry wt) in the vaginal segment of the cervix was significantly higher than in the mid (P < 0.05) and the uterine (P < 0.01) segments. The hydroxyproline:proline ratio showed the same pattern as the collagen content. The percentage of collagen denaturation in the superficial layer was always significantly (P < 0.01) higher than that in the deep layer, but no effect of the progesterone status or of the segment along the longitudinal axis was seen. It is concluded that regional differences in collagen biochemistry are present in the cervix of nonpregnant cows, which may account for the difference in firmness of different parts along the circular or the longitudinal axis of the cervix. However, differences in texture of the cervix between the two groups of cows could not be explained by differences in the collagen content, percentage of collagen denaturation, or water content.

Animals↗

Follicle-stimulating hormone receptor and its messenger ribonucleic acid are present in the bovine cervix and can regulate cervical prostanoid synthesis.

The hypothesis that FSH regulates the bovine cervical prostaglandin E(2) (PGE(2)) synthesis that is known to be associated with cervical relaxation and opening at the time of estrus was investigated. Cervical tissue from pre-estrous/estrous, luteal, and postovulatory cows were examined for 1) the presence of bovine (b) FSH receptor (R) and its corresponding mRNA and 2) the effect of FSH on the PGE(2) regulatory pathway in vitro. The presence of bFSHR mRNA in the cervix (maximal during pre-estrus/estrus) was demonstrated by the expression of a reverse transcription (RT) polymerase chain reaction (PCR) product (384 base pairs) specific for bFSHR mRNA and sequencing. Northern blotting revealed three transcripts (2.5, 3.3, and 3.8 kilobases [kb]) in cervix from pre-estrous/estrous cows. The level of FSHR (75 kDa) was significantly higher (p < 0.01) in Western blots of pre-estrous/estrous cervix than in other cervical tissues. There was a good correlation between the 75-kDa protein expression and its corresponding transcript of 2.55 kb throughout the estrous cycle as described by Northern blot analysis as well as RT-PCR. Incubation of FSH (10 ng/ml) with pre-estrous/estrous cervix resulted in a 3-fold increase in the expression of FSHR and a 2-fold increase in both G protein (alpha(s)) and cyclooxygenase II. FSH (5-20 ng/ml) significantly increased (p < 0.01) cAMP, inositol phosphate (p < 0.01), and PGE(2) (p < 0.01) production by pre-estrous/estrous cervix but not by cervix at the other stages. We conclude that bovine cervix at the time of the peripheral plasma FSH peak (pre-estrus/estrus) contains high levels of FSHR and responds to FSH by increasing the PGE(2) production responsible for cervical relaxation at estrus.

Adenylyl Cyclases↗

Distribution of cervical intraepithelial neoplasia 2, 3 and cancer on the uterine cervix.

OBJECTIVE: To determine the distribution of cervical intraepithelial neoplasia 2 or 3 on the uterine cervix. MATERIALS AND METHODS: During two screening studies, 5,060 women underwent colposcopy with biopsy. If a cervical quadrant had no lesion, a random biopsy at the squamocolumnar junction was obtained. RESULTS: Cervical intraepithelial neoplasia 2 or worse was more common on the posterior (426/806; 52.9%) than on the anterior (380/806; 47.2%) cervix (p < .05) and was equally likely on the right (411/806; 51.0%) and left (395/806; 49.0%) sides of the cervix. More quadrants with colposcopically detected lesions of human papillomavirus or worse came from the anterior (1,338; 57.5%) than posterior (991; 42.6%) cervix (p < .05), whereas similar numbers of these lesions were found on the left (1,163) and right (1,166) sides of the cervix. CONCLUSIONS: Cervical intraepithelial neoplasia 2 or worse is slightly more common on the posterior cervix. Using colposcopically detected lesions as a surrogate for cervical intraepithelial neoplasia 2 or worse inflates the prevalence of cervical intraepithelial neoplasia on the anterior cervix.

Adult↗

Ripening and dilatation of the unfavourable cervix for induction of labour by a double balloon device: experience with 250 cases.

OBJECTIVE: To determine the efficacy of the double balloon device (the Atad Ripener Device) in ripening and dilatation of the unfavourable cervix for induction of labour. METHODS: Two hundred and fifty women with unfavourable cervices (Bishop score < or = 4) underwent induction of labour with the Atad Ripener Device. Indications were pregnancy induced hypertension (n = 118), post-dates (n = 69), elective inductions (n = 23), other reasons including nonreassuring nonstress test, intrauterine growth retardation, previous caesarean section and diabetes mellitus (n = 40). The Atad Ripener Device was inserted into the cervix, the uterine balloon inflated in the internal os, and the cervico-vaginal balloon in the external os of the cervix (100 mL of normal saline to each balloon). Pressure produced by the inflated balloons caused gradual dilatation and effacement of the cervix. The Atad Ripener Device was removed 12 h after insertion, the cervix assessed again, and labour managed according to obstetrical criteria. RESULTS: The Atad Ripener Device caused an increase in the Bishop score in all subgroups with a mean change of 4.6 (from 2.0 prior to induction to 6.6 upon removal of the Atad Ripener Device; P < 0.05). The mean time interval from insertion of the Atad Ripener Device to delivery was 18.9 h, and from removal to delivery was 6.9 h. Caesarean section was performed in 39/250 patients (16%), and the others had a normal vaginal delivery. CONCLUSIONS: 1. The double balloon device induces significant ripening and dilatation of the unfavourable cervix. 2. Induction of labour was successfully achieved following removal of the Atad Ripener Device. 3. Our caesarean section rate was low compared with rates reported for women with an unfavourable cervix induced by other methods.

Adult↗

Characterization of vascular endothelial growth factor (VEGF) in the uterine cervix over pregnancy: effects of denervation and implications for cervical ripening.

Bilateral neurectomy of the pelvic nerve (BLPN) that carries uterine cervix-related sensory nerves induces dystocia, and administration of its vasoactive neuropeptides induces changes in the cervical microvasculature, resembling those that occur in the ripening cervix. This study was designed to test the hypothesis that (a) the cervix of pregnant rats expresses vascular endothelial growth factor (VEGF) and components of the angiogenic signaling pathway [VEGF receptors (Flt-1, KDR), activity of protein kinase B, Akt (phosphorylated Akt), and endothelial nitric oxide synthase (eNOS)] and von Willebrand Factor (vWF) and that these molecules undergo changes with pregnancy, and (b) bilateral pelvic neurectomy (BLPN) alters levels of VEGF concentration in the cervix. Using RT-PCR and sequencing, two VEGF isoforms, 120 and 164, were identified in the rat cervix. VEGF, VEGF receptor-1 (Flt-1), eNOS, and vWF immunoreactivities (ir) were localized in the microvasculature of cervical stroma. Their protein levels increased during pregnancy but decreased to control levels by 2 days postpartum. VEGF receptor-2 (KDR)-ir was confined to the epithelium of the endocervix. BLPN downregulated levels of VEGF by a third. Therefore, the components of the angiogenic signaling pathway are expressed in the cervix and change over pregnancy. Furthermore, angiogenic and sensory neuronal factors may be important in regulating the dynamic microvasculature in the ripening cervix and may subsequently play a role in cervical ripening and the birth process.

Animals↗

[Analysis of physiologic and abnormal pictures of uterine cervix by means of infrared thermography].

RATIONALE FOR THE STUDY: Diagnosis of the uterine cervix lesions remains a key element of the women's health care especially in the context of the cervical carcinoma prophylaxis. The infrared mapping constitutes a new generation biophysical diagnostic method of potential application in medicine. OBJECTIVE: The study was planned to analyze uterine cervix thermograms in both physiology and pathology of this organ. An attempt was made to establish the standard thermographic pattern of the portion. MATERIAL AND METHODS: The study population consisted of 51 women aged from 20 do 70 years. In total, 109 thermographic patterns were analyzed by the computer processing of the thermovision data. In order to establish a physiologic standard, 14 thermograms of the normal cervix were analyzed in detail. Furthermore, thermograms of such cervical lesions as endocervical polyp (3 patients), erosion (PAP II) (11 cases), CIN I-III (9 patients) and invasive cancer (6 patients) were studied. The diagnosis was based on clinical, cytologic and colposcopic criteria as well as on the pathology report. The infrared camera AGEMA AGA-880 and the specialized software was used. The measurements were done in a standardized climatic environment. RESULTS: Comparisons between the studied groups revealed significant differences between invasive cervical cancer and benign lesions or healthy cervix. Significant were also differences in mean temperature and highest temperature for all the studied groups. The difference in mean whole portion temperature between the normal cervix and invasive planoepithelial cancer amounted to 1.4 degrees C while in comparison to other lesions it did not exceed 0.5 degree C. Statistical analysis of the averaged profiles of cervical temperatures has also shown significant differences between invasive cancer and the remaining groups--by 1.5 degrees C in average. Strong interrelationships (p < 0.001) were found among the single results of thermography measurements within all the groups. The thermographic profiles of all 14 thermograms of normal portion did not exceed the two standard deviations range of the established standard with the mean temperature of 36.56 degrees +/- 0.56 degree C. CONCLUSIONS: 1. The established thermographic mapping patterns of the normal cervix may form a basis for the future evaluation of the diagnostic application of computer thermography in gynecology. 2. Statistically significant differences were found in thermographic profiles of the portion between the normal cervix and such cervical lesions as endocervical polyp, erosion (PAP II), CIN and invasive cancer. 3. Invasive cervical cancer reveals thermographic pattern of relatively high specificity within the analyzed cervical lesions.

Adult↗

The significance of documenting clinical appearance of the uterine cervix in the cervical cytology form.

OBJECTIVE: To determine whether or not the Pap smear taker is reporting the clinical appearance of the cervix on the cytology request form, and if cytologist / smear taker are giving any importance to this information prior to issuing advice on subsequent follow-up. Finally, to evaluate the clinicians' response to normal Pap smear report in the absence of the clinical comment on the cervix. METHODS: A retrospective study, for a total of 1196 random smear results performed between 1999 and 2000 at King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with its relevant charts were evaluated. The samples were divided into 2 main groups. Group I, the Pap smears sent with the absence of clinical description of the cervix, and group II, was sent with the clinical description of the cervix. Cytologist follow up recommendations and the clinicians' response were evaluated. RESULTS: A total of 1196 Pap smears were reviewed. Of the total 510 (42.6%) smears represented group I. Vast majority 506/510 (99.2%) were reported to be normal. A 12 months follow up was given for 505/506 (99.8%) smears. Only 4/510 (0.8%) Pap smears were abnormal and relevant cytologist's recommendations were given. Clinicians reassessed the uterine cervix for only 7.7% of the patients in the group. A total of 686/1196 (57.4%) smears represented group II. The vast majority 630 (91.8%) were with normal cervical appearance, 627/630 (99.5%) had normal cytology and only 3/630 (0.5%) had significant intraepithelial lesion. Relevant recommendations were given by the cytologist and were accepted by clinicians. A total of 56/686 (8.2%) had abnormal cervical appearance and 45/56 (80.4%) had normal cytology. A 12 months follow up was recommended for all except 7/45 (15.6%). Clinicians have followed these recommendations for all except 5/45 (11.1%). Eleven out of 56 (19.6%) smears were abnormal, relevant recommendations were given by the cytologist and all were followed by the clinicians. CONCLUSION: High proportion of cervical smears request did not report clinical appearance of uterine cervix (42.6%). In patients whose cervical smear was reported abnormal (8.2%), 19.6% of them were found with significant intra-epithelial lesion. The clinical appearance of the cervix should be documented on the Pap smear request. Follow up recommendation for Pap smears carried out without clinical appearance description should be left to the clinician.

Cervix Uteri↗

Primary adenocarcinoma of the uterine cervix. A clinical study.

In a retrospective clinical study, 67 matched cases of primary adenocarcinoma and squamous cell carcinoma of the cervix were compared. The mean age, weight, and menopausal age of women with adenocarcinoma of the cervix were in excess of the corresponding figures for squamous cell carcinoma. There was a significantly (P less than 0.05) larger number of diabetics and nulliparous women amongst the patients with adenocarcinoma of the cervix. Blood group A was significantly (P less than 0.05) more frequent in patients with cervix cancer. Treatment choice was independent of the tumors histological type. The five-year survival rates for adenocarcinoma of the cervix were 83.3% (Stage IB), 60.0% (Stage IIA), and 45.5% (Stage IIB). The corresponding five-year survival rates for squamous cell carcinoma were 90.0%, 73.3%, and 40.9%. There were indications that adenocarcinoma of the cervix was less radiosensitive than squamous cell carcinoma. Estrogen substitution following treatment of adenocarcinoma of the cervix did not adversely affect the outcome.

Adenocarcinoma↗

Human papillomavirus DNA sequences in adenocarcinoma of the uterine cervix in Indian women.

BACKGROUND: Infection with human papillomavirus (HPV) is considered to be the principal causal agent in the development of squamous cell carcinoma of the uterine cervix. Although adenocarcinoma of the cervix originates adjacent to the squamous epithelial neoplastic lesions, the etiopathogenesis of adenocarcinoma is not yet clearly understood. Recent studies have raised more controversy, rather than answering the question of whether specific HPV infection also plays a role in the development of adenocarcinoma of the cervix. Molecular DNA hybridization techniques were used to detect HPV types prevalent in both adenocarcinoma and squamous cell carcinoma of the uterine cervix, which is the most common cancer in Indian women. METHODS: Histologically confirmed, formaldehyde-fixed, paraffin-embedded tissue sections from 12 cases of adenocarcinoma and 30 cases of squamous cell carcinoma of the uterine cervix were analyzed retrospectively for the presence of HPV DNA types 6b, 11, 16, and 18 by both Southern blot hybridization and in situ hybridization. RESULTS: Of 12 adenocarcinomas, 5 (41.67%) tumors were positive for HPV DNA: All five cases were positive for HPV 16, and two (16.6%) of these were hybridized again to the HPV 18-specific DNA probe. All tumors were negative for HPV 6b and 11. In addition, no biopsy specimens were positive after hybridization with a mixed probe of HPV 31, 33, 35, 39, and 45. These results were compared to those obtained for 30 squamous cell carcinomas of the cervix. Although 20 (66%) were exclusively positive for HPV 16 and 6 (20%), more tumors were of HPV 16 related types as detected under nonstringent conditions of hybridization, only one (3%) was positive for HPV 18. The results of in situ hybridization were found to be in good agreement with those of Southern blotting. CONCLUSIONS: HPV 16 is the type present almost exclusively in squamous cell carcinoma of Indian women. A higher frequency of HPV 16 in adenocarcinoma of Indian women, in contrast to HPV 18, as reported from other regions, may be attributed to geographic variation rather than to histologic differences only, and both HPV 16 and 18 may be present in adenocarcinoma of the uterine cervix.

Adenocarcinoma↗

Foci of stromal melanocytes (so-called blue naevus) of the uterine cervix in Japanese women.

Foci of stromal melanocytes (FSM) of the uterine cervix have been known as extra-cutaneous "blue naevus". However macroscopic and histological findings suggest that FSM of the cervix are analogous to dermal melanocytosis, rather than to cutaneous blue naevus and the lesions are more appropriately called stromal melanocytosis. FSM of the cervix have been considered rare, but our study showed that they are not uncommon in Japanese women occurring in 8.6% (42/486). The lesions were initially observed in the third decade of life and became most prevalent in the fifth decade (15/86 cases, 17.4%). In stroma of the cervix, stromal melanocytes (SM) were present where many peripheral nerve fibres were seen. SM of the cervix were positive for S-100 protein in immunohistochemical studies and were sometimes observed close to peripheral nerve fibres. Melanocytes were never observed in the ectocervical and endocervical epithelium, but only in the stroma of the cervix. We suggest that malignant melanoma of the uterine cervix may originate from SM.

Adolescent↗

The results of isotope renography and intravenous pyelography in 420 patients with carcinoma of the uterine cervix.

A group of women with carcinoma of the cervix was studied by renography and i.v. pyelography. The incidence of renal and urinary tract disorders detected by these tests increased as did the stage of the disease, being 17.1% with Stage I carcinoma of the cervix, 27.8% with Stage II carcinoma of the cervix, 47% with Stage III carcinoma of the cervix, and 83.3% in Stage IV carcinoma of the cervix. In patients with Stage I and Stage II carcinoma of the cervix, those selected for radiotherapy had twice the incidence of abnormal renograms as those selected for surgery. This difference probably reflected a higher incidence of medical disorders affecting renal and urinary tract function in those considered unfit for surgery. We believe that renograms should be used routinely as a screening test in patients with carcinoma of the cervix.

Female↗

Radiation therapy alone or combined with surgery in the treatment of barrel-shaped carcinoma of the uterine cervix (stages IB, IIA, IIB).

This retrospective analysis reports the results of therapy in 128 patients with carcinoma of the uterine cervix classified as barrel-shaped or expanded cervix (over 5 cm in diameter). Seventy-five percent of the patients were treated with irradiation alone and 25% with combinations of irradiation and surgery. The results of therapy are compared with those observed in 714 patients with non-barrel-shaped carcinoma of the uterine cervix treated with similar techniques during the same period of time. The distribution of histological type of tumor was similar in both groups (90% epidermoid carcinoma, 8% adenocarcinoma, and 2% adenosquamous carcinoma). Approximately 15% of the patients in both groups with Stage IB and 25% with Stage IIA and IIB had positive endometrial curettings (stromal invasion or replacement by tumor only). Thus, the aggressive behavior observed in the barrel-shaped tumors is not a result of endometrial involvement, but to the large volume of tumor present. The actuarial 5-year tumor free survival in Stage IB barrel-shaped cervix was 76% compared to 92% in the non-barrel-shaped lesions. In Stage IIA the 5-year NED survival for patients with barrel-shaped cervix was 60 compared to 80% for the patients with non-barrel-shaped cervix. In Stage IIB the survival rates were 58 and 70%, respectively. A noteworthy finding in this analysis is the high incidence of distant metastases in the patients with barrel-shaped cervix (32% in Stage IB, 40% in Stage IIA, and 32% in Stage IIB) in comparison with patients with non-barrel-shaped tumors (10% in Stage IB, 16% in Stage IIA, and 25% in Stage IIB). The incidence of pelvic failures was comparable in both groups. Higher doses of irradiation resulted in better tumor control, which was comparable to that observed with a combination of irradiation and surgery (conservative hysterectomy). The 5-year survival rate in Stage IB was similar in both the barrel-shaped and non-barrel-shaped tumors treated with irradiation alone or combination irradiation and surgery. In Stage IIA the non-barrel-shaped lesions had the same survival with either treatment technique. In the barrel-shape group, eight patients treated with irradiation alone or survival of 70%, compared to 45% in 24 patients treated with irradiation alone. However, these differences are not statistically significant (p = .50). In eight patients treated with definitive irradiation and a lymphadenectomy and four patients irradiated after an exploratory laparotomy, two major and three minor (grade 2) complications were noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma↗

Oncofoetal antigens in cancer of the cervix and ovary.

The incidence of oncofoetal antigens has been reported to be increased in patients with gynaecological cancers. In this study the incidence of CEA, AFP, and hCG (beta subunit) were studied in patients with adenocarcinoma of the ovary, adenocarcinoma of the cervix, and squamous-cell carcinoma of the cervix. Using a low cut-off point (CEA 2.5 microgram/l, AFP 5 microgram/l, and hCG 3 i.u./l) there is an unacceptably high proportion of control patients having one or more positive tests (42-54%) compared to cancer-bearing patients (67%). The specificity of the tests can be increased to over 95% by increasing the cut-off point to CEA 10 microgram/l, AFP 10 microgram/l, and hCG 10 i.u./l). Although this reduces the sensitivity considerably, the incidence of false positives in the control population is reduced to nil in non-cancer patients and to 2% in cancer patients tested when free of tumour, compared to 17% of patients with cancer of the ovary, 33% with adenocarcinoma of the cervix, and 6% with squamous-cell carcinoma of the cervix. Patients with adenocarcinoma of the cervix were clearly distinguishable from those with squamous-cell carcinoma of the cervix by these tests. There was also a significant correlation between AFP and hCG levels in adenocarcinoma of the cervix (r = 0.53, P less than 0.05).

Adenocarcinoma↗

Pessaries for the treatment of incompetent cervix and premature delivery.

The purpose of this study was to review published articles about using pessaries in women with an incompetent cervix or who are at risk for preterm delivery. A MEDLINE search was performed from 1966 to 2000, with articles published before 1966 being extracted from the reference lists of articles obtained. Foreign articles were translated into English. Key words included pessary, incompetent cervix, and preterm labor. All studies that included patient data were included. A variety of studies suggest that pessaries can increase the percentage of full-term deliveries when used in women with an incompetent cervix or at risk for preterm delivery. When looking at women thought to have an incompetent cervix, the studies are mostly old case series. One prospective, randomized trial demonstrated no difference between women treated with a pessary and a cerclage. However, 27 weeks was the average gestational age at which therapy was started. In women at risk for preterm delivery, retrospective studies show an increase in full-term pregnancy rates with pessary use. One prospective, nonrandomized study also shows an increase in full-term pregnancy rate. However, in this study, lower risk patients received the pessary. Because of the poor nature of most of the studies, pessaries should not replace cerclage use at this time in women with an incompetent cervix. However, pessary use should be considered as adjuncts to cerclage or in women who are not candidates for cerclage. Also, pessary use may be considered in some women at risk for preterm delivery. Randomized perspective controlled trials are in progress to address the use of pessaries in these situations. Vaginal pessaries have been reported to be useful in women at risk for preterm delivery since 1959. Bedrest and cervical cerclage has become standard therapy in the United States for women with an incompetent cervix. However, cerclage is not without risk. Furthermore, advances in ultrasound have allowed us to identify women potentially at risk for preterm delivery by detecting cervical shortening before dilatation. This ability has raised questions concerning how to manage patients with subtle ultrasound changes. This article reviews the published literature concerning the use of pessaries in women with an incompetent cervix or at risk for early delivery.

Female↗

The RASSF1A tumor suppressor gene is commonly inactivated in adenocarcinoma of the uterine cervix.

PURPOSE: Development of adenocarcinoma (AC) of the uterine cervix, as well as squamous cell carcinoma (SCC), is strongly linked to infection by high-risk human papillomavirus (HPV) types. Human HPV E6 and E7 proteins inactivate the tumor suppressor genes p53 and retinoblastoma, respectively. However, additional genetic alterations may be required to maintain a malignant phenotype. Allelic loss at the short arm of chromosome 3 is one of the most frequent genetic changes found in cervical cancer and various other types of human cancer, including lung, breast, and ovarian cancer. This implies that a resident tumor-suppressor gene in this region is involved in the genesis of these tumors. RASSF1A, which is located at 3p21.3, is rarely inactivated by mutations but has been suggested as a target tumor suppressor gene on the basis of its frequent inactivation through promoter hypermethylation and loss of heterozygosity in a variety of primary human cancers. In the present study, we sought to determine whether epigenetic silencing of RASSF1A caused by hypermethylation of the promoter region plays a role in the development of uterine cervical cancer. EXPERIMENTAL DESIGN: We studied 51 uterine cervical carcinoma samples. These 51 cases were comprised of 31 SCCs and 20 ACs. Real-time methylation-specific PCR system was used for the detection and quantitation of the bisulfite-converted methylated version of the RASSF1A promoter region. The 20 cases of cervical AC were also analyzed for the presence of oncogenic HPV 16 DNA using a PCR-based method. RESULTS: We found complete methylation of the RASSF1A promoter in 45% (9 of 20 samples) of AC cases. There was no promoter methylation observed in any of the 31 cases of SCC. We also correlated RASSF1A promoter hypermethylation to oncogenic HPV 16 infection. HPV 16 DNA was found in 3 of 9 (33%) AC tumors with RASSF1A promoter hypermethylation and 5 of 11 (45%) AC tumors without RASSF1A promoter hypermethylation. We could not demonstrate an inverse correlation between RASSF1A methylation and HPV 16 infection in AC of the uterine cervix. CONCLUSIONS: Hypermethylation of the RASSF1A promoter region is common in AC of the uterine cervix and rare in squamous carcinoma of uterine cervix. HPV infection does not correlate with RASSF1A methylation status in AC of the uterine cervix, but the absence of RASSF1A methylation in SCC of the uterine cervix coupled with the high incidence of HPV 16 infection in this subtype is in accord with previous reports. Our results suggest that epigenetic silencing of RASSF1A may play a role in the development of AC of the uterine cervix.

Adenocarcinoma↗

N-acetyltransferase is involved in gypenosides-induced N-acetylation of 2-aminofluorene and DNA adduct formation in human cervix epidermoid carcinoma cells (Ca Ski).

The effects of gypenosides on the inhibition of N-acetyltransferase (NAT) activity, AF-DNA adduct formation and NAT gene expression in a human cervix cancer cell line (Ca Ski) were studied. Various concentrations of gypenosides were added to the cytosols or individually to the culture medium of human cervix cancer cells. The NAT activity was determined by high performance liquid chromatography, assaying for the amounts of acetylated 2-aminofluorene (AAF) and non-acetylated 2-aminofluorene (AF). The NAT activity in the human cervix intact cancer cells and cytosols was suppressed by gypenosides in a dose-dependent manner. The results also demonstrated that gene expression (NAT1 mRNA) in human cervix cancer cells was decreased by gypenosides in a dose-dependent manner. The apparent values of Km and Vmax of NAT of human cervix cancer cells were also decreased by gypenosides in cytosols. Gypenosides may act as noncompetitive inhibitors. After the incubation of human cervix cancer cells with 30 or 60 microM AF and with or without 350 micrograms/ml gypenosides co-treatment, the cells were recovered, DNA was prepared and hydrolyzed to nucleotides; adducted nucleotides were extracted in butanol and AF-DNA adducts were analyzed by HPLC. The results demonstrated that gypenosides decreased the levels of AF-DNA adduct formation in these cells. The NAT PCR and cDNA microarray also demonstrated that gypenosides inhibited NAT mRNA expression in human cervix cancer cells.

Acetylation↗

Cancers of the uterine cervix in Port Harcourt, Rivers State--a 13-year clinico-pathological review.

BACKGROUND: Carcinoma of the uterine cervix is still the commonest gynaecological malignancy among women in the developing world. This study aims at assessing the prevalence of carcinoma of the cervix, the most common presenting complaints and histological types as seen in Port Harcourt, Rivers State. METHODS: All the tissue slides of specimen (cervix and hysterectomy) diagnosed as cervical carcinoma over a period of 13 years were retrieved and re-evaluated for confirmation of diagnosis and tumour typing in the Anatomical Pathology Department of the University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State. Clinical data were obtained from histopathology registers, request forms as well as case notes of patients from the records department. RESULTS: There were 2,236 malignancies diagnosed; 302 (13.5%) were malignancies of the genital tract while 188 (8.4%) were carcinoma of the cervix constituting 62.3% of female genital malignancies. Cervical cancer was commonest between the ages of 50-69 years. There was no patient with carcinoma of the cervix below the age of 20 years. Abnormal vaginal bleeding (84.1%) in pre and post-menopausal periods was the commonest presenting complaint while squamous cell carcinoma (70.2%) and adenocarcinoma (14.9%) of the uterine cervix were the main histological types. CONCLUSION: Post menopausal women are mostly affected by cancers of the uterine cervix while abnormal vaginal bleeding is the most common presenting complaint. Squamous cell and adenocarcinoma are the most frequent histological types.

Adult↗