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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the antitumor effect of oral antitumor agents on gynecological malignant tumors, experimental studies were carried out using nude mice which had received implants of human endometrial carcinoma. The agents used for the study were tegafur (T) and UFT, and their effects on inhibiting tumor growth, and on preventing tumors from implanting or recurring were investigated in mice in continuous long-term administrations. The results were as follows: As to the inhibitory effect on the tumor growth, while both T and UFT had no inhibitory effect on large to medium tumors, both were mildly effective on small tumors having a diameter of 2-3 mm (Inhibition Rate (IR): T-60.0%, UFT-71.0%), however, the no effect great enough to reduce the tumor size was recognized with either agent. The implantation rates of tumor under the administration of T and UFT were 80.0% and 70.0% respectively, indicating no significant differences from the control (90.0%) and either agent, however, UFT was judged to have the effect of preventing tumors from implanting to a certain extent. The recurrence rates for tumor under the administration of T and UFT were 30.0% (6/20) in both cases, which was significantly lower than the control (70.0%) (p less than 0.05). Both agents were evaluated as useful for preventing tumors from recurring. These findings, indicated that while the maintenance therapy of an oral antitumor agent has no effect on macroscopic tumors, a fairly good effect is expected on microscopic tumors, especially on the prevention of tumor recurrence.
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PMID:[Experimental studies on the antitumor effect of oral antitumor agents on gynecological malignant tumors]. 310 48

This paper reviews epidemiologic evidence regarding the association between exposure to oral contraceptives (OCs) and the development of 4 cancers involving the reproductive system: breast, ovarian, endometrial, and cervical. Most knowledge in this area has been derived from cohort or case-control studies. Currently available evidence suggests that OC use does not influence breast cancer risk either adversely or favorably, although there may be a favorable influence on tumor growth. In view of the long latency of effect seen with known risk factors such as radiation exposure, age at menarche, and age at 1st full-term pregnancy, further studies are needed in this area. The epidemiologic evidence consistently supports the prediction that OC use makes the ovaries less susceptible to malignant change, perhaps by a mechanism similar to the protective effect of pregnancies. The magnitude of the effect is considerable, and should have a significant impact on the future incidence of ovarian cancer. In terms of endometrial cancer, there is evidence that sustained estrogenic stimulation unopposed or inadequately opposed by progestogen leads to endometrial hyperplasia and an increased longterm risk of malignancy. In currently used OC formulations, however, the progestogenic component has the predominant effect on the endometrium, and this effect is protective. It remains unknown whether OCs increase cervical cancer risk directly, or whether the association is an indirect one linked to some aspect of sexual behavior that is not being controlled. On the other hand, it seems reasonable to conclude that longterm OC users have an above average risk of cervical cancer and should have regular screening by cervical cytology. It should be kept in mind that recent changes in OC formulations and use patterns render epidemiologic data now available obsolete. It will be many years before sound data will be available on the low-dose estrogen OCs now in almost universal use.
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PMID:Oral contraception and cancer of the female reproductive system. 389 28

From July 1975 to April 1983, 237 patients had primary treatment for endometrial cancer at the Long Island Jewish-Hillside Medical Center. Included in this study were 74 of these patients with Stage I and 20 with Stage II endometrial carcinoma who underwent laparotomy without preoperative radiation. The purpose of the study was to determine the prevalence of extrauterine spread in endometrial carcinoma clinically confined to the uterus and to correlate risk variables with this spread. The parameters assessed were retroperitoneal nodal metastases, adnexal involvement, peritoneal implants and peritoneal cytology. The overall prevalence of extrauterine spread was 23.4% (Stage I, 18.9%; Stage II, 40.0%). The rate of nodal metastasis, adnexal involvement, peritoneal implant, and positive peritoneal cytology were 18.7, 7.4, 4.3, and 8.5%, respectively. No positive relationship was demonstrated between surface spread and risk variables. There was positive correlation between surface spread and peritoneal cytology (87.5%). Direct correlations were found between positive nodes and tumor growth over more than one-third of the endometrial surface (P less than 0.001), gross cervical involvement (P less than 0.001), deep myometrial invasion (p less than 0.001), length of uterine cavity, grade 3 tumor, papillary adenocarcinoma (40%), and stage of disease. Five-year survival rate of Stage I and Stage II in this small series was 77.8 and 55.6%. Complications of 16 radical hysterectomies in Stage II were minimal and transient. Because of frequent extrauterine spread in endometrial carcinoma clinically confined to the uterus, and exploratory laparotomy and peritoneal cytology may be desirable in Stage I and II disease before definitive treatment.
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PMID:Extrauterine spread in endometrial carcinoma clinically confined to the uterus. 398 26

The present study was undertaken in patients with Stage I carcinoma of the endometrium to correlate risk factors and the prevalence of retroperitoneal lymph node metastases. From January 1975 to April 1983, 202 patients with Stage I disease had initial therapy at the Long Island Jewish-Hillside Medical Center, New Hyde Park, New York. Among these patients, 74 who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and selective lymph node biopsy without preoperative radiation were included in the study. Results indicate that risk factors associated with nodal metastasis were Grade 3 tumor (42.1%), papillary adenocarcinoma (28.6%), deep myometrial invasion (42.9%), surface extent of tumor growth greater than 1/3 of the endometrial cavity (31.8%), and a diffuse pattern of tumor growth (17.2%). In Stage 1 endometrial cancer with any of the above 5 risk factors, it is urged that a selective biopsy of para-aortic and pelvic nodes during hysterectomy should be performed.
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PMID:Retroperitoneal lymph node metastases in Stage I carcinoma of the endometrium: correlation with risk factors. 665 76

A study aimed at the enhancement of endometrial carcinoma tissue-sensitivity to progesterone by estrogen priming involved the serial transplantation of human moderately-differentiated endometrial carcinoma into nude mice in which estradiol receptors were detectable but progesterone receptors undetectable. Quantitative induction of cytosol progesterone receptors occurred in the groups receiving a small dose of estradiol concomitantly with progesterone but not in the groups receiving estradiol alone and progesterone alone. Ultrastructurally, the effects of progesterone tended to be more conspicuous in these concomitantly treated groups than in the progesterone-treated group in respect of an increase in the number of lysosomes and lipid droplets and appearance of secretory granules and other vesicles. Suppression of tumor growth was evident in the progesterone-treated group and in the concomitantly treated groups as compared with the control group, and the effect was somewhat more pronounced in the latter groups. The present data suggest that the administration of a small dose of estradiol concomitantly with progesterone is more effective than that of progesterone alone in gestagen therapy for endometrial carcinoma, when it is assumed that the progesterone effects on endometrial carcinoma are mediated primarily by progesterone receptors.
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PMID:Effects of sex steroid hormones on the human endometrial carcinoma transplanted endometrial carcinoma transplanted into nude mice. Estrogen priming aimed at the enhancement of tumor tissue-sensitivity to progesterone. 666 32

Recent experimental results from our laboratories revealed the following facts: Addition of GMP to homogenates or cytosol prepared from endometrial tissue or cultured endometrial adenocarcinoma cells during the assay for specific estrogen binders markedly increases specific binding levels. The effect is completed in about 15 min at 4 C (Fleming et al, 1983). Cyclic AMP has the opposite effect and in many cases lowers the number of binding sites to undetectable levels. ATP, a nucleotide that stimulates a particulate form of guanylate cyclase, Na2MoO4, a compound that can elevate cGMP levels (Fleming and Blumenthal, unpublished) and GTP, a metabolic precursor of cGMP, increase specific estradiol binding in the presence of plasma membranes and soluble factors. Cyclic AMP reduces the levels of estrogen binding when added to cell homogenates or to cytosol and counteracts the effects of cGMP, MoO4, ATP and GTP. ATP is required for the expression of cGMP and cAMP effects on estradiol binding. It is therefore likely that phosphorylations are involved in the generation and inactivation of estrogen binding sites. Divalent cation requirements for these effects also suggest participation of protein kinases in these processes. The reported effects of nucleotides and molybdate have been observed in specimens of histologically normal endometrium, in specimens of endometrial carcinoma, in two endometrial adenocarcinoma cell lines, HEC-1 and HEC-50 (Suzuki et al, 1980), and in two breast cancer cell lines, CG-5, a variant of MCF-7 obtained in Iacobelli's laboratory (Natoli et al, 1983), and in T47D) (Fleming et al, in press) Rapid changes in the levels of estrogen binding capacity observed in endometrial cells in culture can be associated with changes in cGMP/cAMP ratios shown, to vary during the cell cycle. Although it has not yet been demonstrated that cGMP-induced increases in specific estrogen binding can enhance responses to available estrogens, such possibility is of potential importance. Reduction of estrogen receptor levels in patients with cancers of estrogen sensitive tissues may inhibit tumor growth promoted by endogenous estrogen. Cho-Chung et al have recently reported that cholera toxin causes a reduction in estrogen receptor levels and arrests hormone dependent growth of DMBA-induced mammary carcinoma in rats (Cho-Chung et al, 1983). They postulated that the effect of cholera toxin is mediated by a cAMP effect on the estrogen receptor, an hypothesis supported by the observation that only tumors containing receptor responded to treatment. Conversely, cGMP-induced increases in specific estrogen binders may be useful in promoting a response of tumors to estr
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PMID:Regulation of estrogen receptor levels in endometrial cancer cells. 670 55

The effect of tamoxifen (TAM) on human endometrial carcinoma was investigated in nude mice bearing an estrogen receptor-positive or estrogen receptor-negative tumor. The receptor-negative tumor grew rapidly, and the rates of tumor growth of 17 beta-estradiol or TAM-treated animals were identical to the rate of controls. The estradiol receptor and progesterone receptor (PR) concentrations in the tumor cytosol remained undetectable under all experimental conditions. In contrast, the rate of growth of steroid receptor positive tumor was significantly accelerated in the presence of TAM compared to controls (p less than 0.02). The increased tumor growth rate was, however, significantly lower (p less than 0.01) than that observed in animals receiving 17 beta-estradiol. The PR concentration in these tumors was elevated in response to TAM treatment. That the TAM-induced PR was indeed functional was evident from (a) increased activities of the progestin-sensitive enzyme, 17 beta-estradiol hydroxysteroid dehydrogenase and (b) histological appearance of subnuclear vacuolization in these tumors after progestin administration. These studies indicate that continuous, short-term administration of TAM to nude mice results in an estrogen-like effect on endometrial carcinoma. Based on the finding that TAM induces functional PR, we predict that steroid receptor-positive endometrial carcinoma may show a greater response rate to combined, long-term treatment with TAM and progestin.
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PMID:Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice. 674 16

Endometrial intraepithelial carcinoma (EIC) is a recently described lesion characterized by replacement of endometrial surface epithelium or glands by malignant cells resembling high-grade invasive endometrial carcinoma. EIC has been identified in a high proportion of uteri containing serous carcinoma, but its association with other endometrial tumors is unknown. To determine the strength and specificity of the association of EIC with tumors displaying serous differentiation, the appearance of the endometrium in 38 uteri with serous carcinoma, 113 with endometrioid carcinoma, and 34 with malignant mixed mesodermal tumor (MMMT) were compared. EIC was present in 34 (98%) uteri with serous carcinoma compared with 7 (6%) uteri removed for endometrioid carcinoma (P = .0001). Hyperplasia without atypia was found in only 2 (5%) of 38 serous carcinomas compared with 38 (34%) of 113 endometrioid carcinomas. Similarly, atypical hyperplasia was not found in any uterus with serous carcinoma, but was present in 14 (12%) uteri with endometrioid carcinoma (P = .02). The endometrium was inactive or atrophic in 29 (76%) patients with serous carcinoma compared with 33 (29%) with endometrioid carcinoma (P = .0001). EIC was found in five (56%) of nine MMMTs with a serous epithelial component (serous-MMMT) compared with one (4%) of 25 MMMTs woth an endometrioid epithelial component (endometrioid-MMMT). As with endometrioid and serous carcinomas, hyperplasia with and without atypia was more common with endometrioid-MMMTs as compared with serous-MMMTs. Hyperplasia was found in 25 (100%) and atypical hyperplasia in 8 (32%) of 25 endometrioid-MMMTs, but in none of the nine serous-MMMTs. This study shows that EIC is frequently and specifically associated with uterine tumors displaying serous differentiation. The findings suggest that EIC represents a form of intraepithelial tumor growth characteristic of serous carcinoma and serous MMMT and that EIC is the likely precursor of these neoplasms. In addition, the findings provide further evidence supporting the view that MMMTs represent variants of carcinoma not sarcoma.
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PMID:Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation. 759 Jul 2

The expression of P450 aromatase and other steroidogenic enzymes were evaluated in 42 endometrioid endometrial carcinomas, 23 endometrial hyperplasias, and 7 normal endometrial specimens. These findings were correlated with clinicopathological findings to elucidate the possible biological significance of in situ estrogen production in the development of human endometrial carcinoma. Only weak aromatase immunoreactivity was observed in vascular walls and myometrial cells. In contrast, strong aromatase stromal immunoreactivity was observed in 28 of 42 (66.7%) endometrial carcinomas. However, no stromal immunoreactivity was seen in normal or hyperplastic endometrial specimens. Immunoreactivity in the carcinoma stromal cells was significantly increased at sites of invasion. These aromatase-positive cells were immunohistochemically negative for other steroidogenic enzymes involved in estrogen biosynthesis. In situ hybridization studies revealed aromatase mRNA hybridization signals in stromal cells but not in carcinoma cells. The distribution of aromatase mRNA correlated well with the immunohistochemical localization of aromatase enzyme. Quantitation of aromatase activity demonstrated 8.75 +/- 2.75 pmol/hour/mg of protein for endometrial carcinomas (22 specimens) and 0.98 +/- 1.95 pmol/hour/mg of protein for normal endometrial specimens (4 specimens). Aromatase activity was found in both estrogen receptor-positive and -negative endometrial carcinomas. Aromatase did not vary with respect to the menopausal status of patients with endometrial carcinoma. These results suggest that estrogen is produced in situ in endometrial carcinoma but not in benign endometrial lesions. Such locally synthesized estrogen may act on carcinoma cells in a paracrine fashion to promote tumor growth. Additional investigations are necessary, but increased aromatase expression in the stromal cells of endometrial carcinoma may therefore play an important role in the development of human endometrioid endometrial carcinoma.
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PMID:Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studies. 785 58

For patients with disseminated endometrial cancer the prognosis is poor. Radiotherapy, chemotherapy or high-dose progestins have been of limited value in the clinic, with low response rates and a usually short duration. Because of the role of estrogen in the etiology of this disease, a rationale exists for therapies using estrogen antagonists. In order to test this strategy, we used the EnDA endometrial carcinoma of the rat recently described by us. The nonsteroidal antiestrogen ZK 119.010 inhibited the primary-tumor growth of the s.c. implanted EnDA endometrial carcinoma by 50%, being superior to high-dose progestin and tamoxifen (TAM). Moreover, in intact as well as in castrated estrogen (E2)-substituted rats, ZK 119.010 substantially reduced metastatic-tumor growth in the lymph nodes and lungs. With TAM, however, the number of lung metastases in intact and in castrated E2-substituted rats either rose or remained stable and the weight of lymph nodes in intact rats increased. After TAM treatment, almost no low-salt-extractable (cytosolic) estrogen receptor (ER) was measurable in the tumor, whereas ZK 119.010 did not alter ER concentrations. The stimulation of metastatic tumor growth, as well as the loss of cytosolic ER under TAM therapy, may reflect the well-known agonist activity of this compound in uterine tissues. ZK 119.010, however, not only lacks this agonist activity, but it exerts a strong antagonistic one. In conclusion, pure antiestrogens may help to improve treatment of endometrial cancer.
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PMID:Effect of the nonsteroidal antiestrogen ZK 119.010 on growth and metastasis of the EnDA endometrial carcinoma. 805 Aug 24


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