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[Protease-antiprotease balance in patients with invasive carcinoma of the cervix and uterus before and after radiotherapy].

Malignant cells have the ability to invade and metastasize in great part because they secrete proteolytic enzymes. In order to investigate if the abnormal proteinase/antiproteinase balance of cancer bearing patients changes when the malignant tumor is destroyed, we studied 50 patients with invasive carcinoma of the cervix and 33 healthy women as a control group. Patients with cancer were treated with radiation according to the protocols of our hospital. The following serum determinations were performed: plasminogen activators (PA), cathepsin B (CB), antiproteinase alpha-1-antitrypsin (A1AT), trypsin inhibitory capacity (TIC) and antiproteolitic activity ratio (AAR), all of them before and after treatment. Serum proteolytic activity was elevated manyfold in all patients with invasive tumor as well A1AT. The antiproteolytic activity however, was significantly reduced to about 50% of its normal value in the same group of patients. In patients with good response to radiotherapy (tumor necrosis) a great reduction of proteinase activity as well as a recovery to normal of the AAR was observed. Contrary, in those with a poor response after radiation, proteolytic activity remained elevated and AAR diminished. It is concluded that serum PA, CB, A1AT and AAR values can be precise indicators of the presence of malignancy. These tests might be also of help for improving follow-up studies and for better prognostic estimates.

Adult↗

Molecular cloning and hormone-dependent expression of rabbit Muc1 in the cervix and uterus.

The microenvironment of the endocervix is regulated by secretory (> 10-15 x 10(6) Da) and cell-surface (< or = 1 x 10(6) Da) mucins. A survey with antisense and sense (control) oligonucleotides for eight epithelial mucin genes revealed that only MUC1, an anti-adhesive protein believed to modulate immune function and the only transmembrane mucin for which molecular probes exist, is expressed in the rabbit cervix. pMUC7, a 500-base pair cDNA probe to the tandem repeat domain of human MUC1, was used to clone the cDNA for the rabbit homologue. Although the GC-rich tandem repeat of rabbit Muc1 had only 40% sequence identity with its human counterpart, its transmembrane domain and cytoplasmic tail maintained 93% sequence identity with the same regions of human MUC1. Detection of restriction length polymorphisms confirmed the Lagomorpha Muc1 gene, like the human, is polymorphic. Temporal expression of Muc1 transcripts (2.4 kilobases) correlated closely with epithelial differentiation in the cervix. However, compared with the adult cervix, uterine endometrium expressed the highest levels of Muc1. In the endometrium, Muc1 was increased (p < 0.0004) by progesterone and returned to estrous levels by treatment with estrogen. Muc1 levels in the cervix were unaffected by ovarian steroids, confirming tissue-specific regulation of Muc1 in the lower reproductive tract.

Amino Acid Sequence↗

The effects of nifedipine on pregnancy outcome and morphology of the placenta, uterus, and cervix during late pregnancy in the rat.

OBJECTIVE: Although the calcium antagonist nifedipine has been reported to suppress preterm labor, little is known of the effects of long-term nifedipine use in late pregnancy. In this study the effects of nifedipine on pregnancy outcome and the morphologic features of the reproductive tract in the late-pregnant rat were investigated. STUDY DESIGN: From days 14 to 21 of gestation pregnant rats were administered three or 30 times the maximum human dose of nifedipine reported to suppress preterm labor. Analysis was performed on day 21. RESULTS: Blood vessel dilatation, increased vascularization of the uterus and placenta, and trophoblast hypertrophy were seen in both nifedipine-treated groups. Placental weight was increased in the higher-dose group, but neither dose of nifedipine resulted in any change of fetal survival or malformations. Pup weight was not different from that of controls in the lower-dose group but was significantly reduced (p less than 0.001) with the higher dose. Histologic changes in uterine musculature and cervical collagen were consistent with the inhibitory effects of nifedipine on uterine contractions. CONCLUSION: The results suggest that, in addition to tocolysis, nifedipine can cause vascular dilatation in both the uterus and the placenta. The use of nifedipine within the normal dose range does not appear to adversely affect fetal outcome and may potentially improve fetal outcome in some disorders of pregnancy.

Animals↗

Dynamics of the Incidence Rates for Separate Forms of Cancer in the Female Population of Kyrgyzstan.

The purpose of the present research was to estimate trends of change in cancer morbidity for the breast, uterine corpus, cervix uterus, and ovaries of the female population of Kyrgyzstan as a whole and in separate regions over a 10 year period (1989-1998). This retrospective study, applying descriptive and analytical methods of modern oncoepidemiology, established that breast cancer occupies the first place, neoplasia of the cervix uterus the second, of the ovaries the third and the uterine corpus the fourth, within the range of malignant neoplasms of the female reproductive system. On the whole the indicated cancer incidence rates tend to growth in dynamics and different regional specificities.

Journal Article↗

Can medroxyprogesterone acetate alter Toll-like receptor expression in a mouse model of intrauterine inflammation?

OBJECTIVE: Activation of the innate immune receptors, Toll-like receptors 2 and 4, are critical for a host inflammatory response to both Gram-positive and Gram-negative organisms. These receptors can initiate and modulate the inflammatory response. Differential regulation of Toll-like receptors may be one of the mechanisms by which intrauterine inflammation signals parturition. Likewise, progestational agents may have the ability to modify this effect. These studies were performed to elucidate the effect of intrauterine inflammation and medroxyprogesterone acetate on Toll-like receptor expression in the uterus, cervix, and placenta in a mouse model of intrauterine inflammation. STUDY DESIGN: On day 15 of gestation, CD-1 mice were randomized to pretreatment with medroxyprogesterone acetate or vehicle before intrauterine infusion with lipopolysaccharide or sterile saline solution. Six hours after intrauterine infusion, uterine, cervical, and placental tissues were harvested. RNA and protein were extracted. Quantitative polymerase chain reaction was performed for Toll-like receptor 2 and 4 messenger RNA. Western blot analysis was performed with Toll-like receptor 4-specific antibodies. RESULTS: Intrauterine inflammation up-regulated Toll-like receptor 2 and 4 messenger RNA in uterus, cervix, and placenta. Pretreatment with medroxyprogesterone acetate decreased the lipopolysaccharide-induced up-regulation of Toll-like receptor 2 and 4 messenger RNA in the cervix and placenta. Medroxyprogesterone acetate treatment, in the presence of lipopolysaccharide, was unable to prevent the lipopolysaccharide-induced increase in Toll-like receptor 4 messenger RNA and protein in the uterus. Medroxyprogesterone acetate treatment alone in pregnant mice significantly increased Toll-like receptor 4 messenger RNA expression in the uterus. CONCLUSION: Intrauterine inflammation has a differential effect on Toll-like receptor 2 and 4 expression. The observed up-regulation of Toll-like receptor 2 in the uterus in response to intrauterine lipopolysaccharide may be a mechanism to augment the inflammatory response and may serve to promote parturition in the setting of inflammation. Consequently, the ability of medroxyprogesterone acetate to suppress lipopolysaccharide-induced up-regulation of Toll-like receptor 2 messenger RNA may be one of the mechanisms by which progestins are able to decrease preterm birth.

Animals↗

Effect of folate deficiency on the reproductive organs of female rhesus monkeys: a cytomorphological and cytokinetic study.

The effect of folate deficiency was studied on the cytomorphology and the kinetics of proliferation of ovarian granulosa cells, and the epithelial cells lining the uterus, cervix and vagina of six sexually mature female rhesus monkeys. The cellular kinetics were study by in vivo labeling with [3H]thymidine, followed by autoradiography of the histological sections of tissue biopsies taken at various time intervals and labeled mitosis curves. The folate-deficient monkeys showed an increased number of atresic and cystic ovarian follicles with depletion of granulosa cells. There was also a significant impairment of the proliferation kinetics of granulosa cells as indicated by decreased [3H]thymidine labeling index (L.I.), and marked prolongation of the pre- DNA-synthetic time (G1 phase); the DNA-synthetic (S phase) and postsynthetic (G2 phase) periods were only mildly prolonged. These changes may have impaired the ovarian synthesis of the steroidal hormones, estrogen and progesterone. The cervico-vaginal epithelium showed megaloblastosis, multinucleation and impairment of orderly proliferation and maturation. Less pronounced changes were also seen in the uterus. The cytomorphological and functional disturbances in the uterus, cervix and vagina may be partly secondary to those in the ovaries, and partly due to the depletion of their essential folate coenzymes.

Animals↗

In vitro response of prostaglandin E2 receptor (EP3) in the term pregnant rat uterus and cervix to misoprostol.

We examined and compared the in vitro effects of misoprostol (synthetic prostaglandin E1 (PGE1) analogue) on prostaglandin E2 (PGE2) secretion and EP3 receptor mRNA expression in the pregnant rat myometrium and cervix at 19 days gestation. Myometrial and cervical tissue samples were exposed to media with or without misoprostol (50 or 100 pg/ml) and incubated for 15 and 30 min, and 1, 3, 6, 12, and 24 h. Media and tissue samples were collected for quantification of PGE2 and mRNA expression of rEP3alpha and rEP3beta receptor, respectively. PGE2 secretion increased (P < or = 0.05) in the myometrium exposed to 50 and 100 pg/ml misoprostol. Cervical PGE2 secretion increased following exposure to the 100 pg/ml dose only. In the myometrium, 50 and 100 pg/ml misoprostol induced elevations in rEP3alpha and rEP3beta receptor mRNA expression. rEP3alpha and rEP3beta receptor mRNA expression in the cervix was not different from controls. These data demonstrate that the EP3 receptor is differentially expressed in the myometrium and cervix in response to misoprostol. This may account for the ability of misoprostol to stimulate the myometrium when administered for cervical ripening.

Animals↗

Primary chemotherapy with or without radiation therapy and/or surgery for children with localized sarcoma of the bladder, prostate, vagina, uterus, and cervix. A comparison of the results in Intergroup Rhabdomyosarcoma Studies I and II.

A major objective of the second Intergroup Rhabdomyosarcoma Study (IRS-II) (1978 to 1984) was to preserve the bladder without compromising the survival of children with localized genitourinary sarcomas arising in or near the bladder. After incisional biopsy, 109 patients with localized, gross residual sarcoma of the prostate (43 patients), bladder (43 patients), vagina (20 patients), or cervix/uterine corpus (3 patients) were treated with vincristine, dactinomycin, and cyclophosphamide (VAC). After two to four drug courses, radiation therapy and/or surgery were used to treat patients with residual or recurrent tumor. The 3-year survival rate of patients treated on this primary chemotherapy regimen (70%) was similar to that of the primary surgery regimens of IRS-I (78%; P = 0.46), but the 3-year disease-free survival rate was significantly inferior (52% versus 70%; P = 0.02). Since the IRS-II encouraged bladder preservation at the onset of therapy, the percentage of patients with bladder and prostate tumors who retained the bladder was initially substantially higher in IRS-II (97%) than in IRS-I (58%). However, the percentages of 95 patients with bladder-prostate (BP) tumors in IRS-II who retained the bladder and were alive at 2 and 3 years after starting treatment were only 33% and 22%, respectively, compared with 26% and 23%, respectively, in the 66 patients with BP tumors in IRS-I. Thus, sequential treatment with primary chemotherapy, followed by radiation therapy and/or surgery as given in IRS-II, failed to improve the eventual bladder salvage rate.

Adolescent↗

Effects of unilateral ovariectomization on the numbers of sperm in the oviducts, uterus and cervix of rabbits.

The experiment was designed to determine the effect of removing one of the rabbits' ovaries on the numbers of sperm in the oviducts, uterine horns and cervices. The possible relationship between the anatomical asymmetry of the two sides of the reproductive tract and the distribution of sperm within different segments of the tract was also studied. Fifteen female rabbits were used; five were kept intact as the control group, five were right ovariectomized and five were left ovariectomized. All rabbits were injected with 50 IU HCG to induce ovulation and then inseminated with 60x10(6) sperm in 0.25 ml semen. Does were inseminated one month after unilateral ovariectomy. Animals were sacrificed 10 hrs later and sperm was recovered from the right and left oviducts, uterine horns and cervices. Unilateral ovariectomy significantly reduced the total numbers of sperm recovered as compared with intact does. The total numbers of sperm recovered from each of the two sides of the tract were not affected by the site of the removed ovary. Sperm numbers were high in the cervices of all groups and then decreased gradually in the upper segments of the tract. Sperm numbers that reached the oviduct of the intact rabbits were greater than those of both unilateral ovariectomized groups of rabbits. Differences between the length of the left and right cervices and uterine horns were not significant, but the right oviduct was significantly longer than the left oviduct.

Journal Article↗

Intracavitary irradiation of carcinomas of the uterus and cervix: the Créteil method.

The Créteil method is a logical and simple system for intracavitary therapy of cervical and uterine cancer. The system is based on the use of a plastic cervico-vaginal moulage loaded with 0.5 mm diameter iridium 192 wire sources. The dimensions of both the moulage and the sources correspond to the size of the cervix being treated according to precisely defined relationships. The dose is specified on a reference isodose of a "fixed" value enclosing the pear-shaped target volume whose dimensions depend on the geometry of the sources. Source geometry in turn, depends on the size of the cervix. Thus, the dimensions of the target volume can be accurately predicted at the time of the application. Furthermore, treatment can be performed in a single application, with all sources having the same linear reference air kerma rate (or activity). Radioprotective measures are simple but effective and the patient is not subjected to the restrictions imposed by attachment to an after-loading apparatus. Our clinical results for early Stage T1 and T2a cervical tumors show excellent local control without major treatment complications or long term sequelae.

Brachytherapy↗

The temperature, pH, and partial pressure of oxygen in the cervix and uterus of women and uterus of rats during the cycle.

Changes in the temperature, pH, and partial pressure of oxygen (PO2) in the cervical canal and cavum uteri were measured in women with or without an intrauterine device and in the uteri of rats throughout the cycle. Only the PO2 exhibited significant variations, rising during the ovulatory phase in both cervices of women and uteri in rats. It is speculated that the rise in PO2 is related to the function of these organs as reservoirs for spermatozoa.

Adult↗

Extensive psammomatous calcification of the uterus and cervix associated with a uterine serous carcinoma.

This report describes a uterine serous carcinoma with bilateral ovarian metastasis, which was associated with widespread extensive psammomatous calcification of the uterine leiomyomata, the myometrium, and the cervical stroma. These psammoma bodies were not associated with tumour or epithelial elements. This psammomatous calcification is rare, with no previous reports of similar cases. The presence of psammoma bodies is probably related to the serous carcinoma, raising the possibility that psammoma body formation in serous carcinomas is the result of a factor secreted locally by the tumour, rather than the widely held theory that their formation is secondary to necrosis, with subsequent dystrophic calcification within a papillary neoplasm.

Calcinosis↗