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Biomedical subjects

R Mortel

Publications and source records attributed to R Mortel.

At least 91 records · Page 5Linked to original sources
PubMed1984

Heterogeneity and progesterone-receptor distribution in endometrial adenocarcinoma.

Objective response to progestin therapy occurs in 30% to 35% of patients with recurrent or metastatic endometrial carcinoma. Measurement of progesterone receptor (PR) in these tumors has been suggested as a method for distinguishing between responders and nonresponders. However, studies on steroid receptor measurements in endometrial carcinoma may be subject to complexities of tumor, tissue, and cellular heterogeneity. The authors provide evidence for the existence of various types of heterogeneity and address the problem of cellular heterogeneity by determination of PR concentrations in the glandular and stromal cells of the endometrium. It is concluded that until the problem of tumor and tissue heterogeneity is resolved, PR concentrations in endometrial carcinoma must be interpreted with caution.

Adenocarcinoma↗
PubMed1984

Residual carcinoma in the surgical specimen of patients with endometrial adenocarcinoma undergoing preoperative radiation therapy. A study of 80 patients and a literature review.

Controversy continues to surround the significance of residual endometrial adenocarcinoma in the uterus following radiation therapy. Eighty patients with FIGO stage IA, IB, and II endometrial adenocarcinoma treated by preoperative radiotherapy were studied. No correlation was noted between the histologic grade of the lesion and the stage of disease. The frequency and the site of residual carcinoma were not related to the stage of disease but less-differentiated tumors persisted more frequently than grade I lesions. The modality of preoperative radiotherapy did not affect the frequency of residual tumor. Residual carcinoma within the uterus had no effect on the site or frequency of recurrence nor on patient survival.

Adenocarcinoma↗
PubMed1984

The preservation of ovarian function in young women undergoing pelvic radiation therapy.

Because cervical carcinoma rarely metastasizes to the ovaries, it became logical to preserve ovarian function by the method of lateral ovarian transposition as part of the management of young women with this disease. This technique prevents castration should subsequent radiation therapy be planned or become necessary. Forty patients with carcinoma of the cervix or vagina underwent unilateral or bilateral ovarian transposition. Eighteen patients received radiation therapy. Of these, 16 had gonadotropin measurements and only 6 (37%) had levels elevated to the postmenopausal range. If patients whose ovaries were not shielded or who received paraaortic radiotherapy are excluded, then only two (17%) had elevated gonadotropin values. It is concluded that, if properly performed, lateral ovarian transposition and ovarian shielding will protect ovarian function in patients receiving pelvic radiotherapy.

Adenocarcinoma↗
PubMed1984

Morphology of human uterine cancer in nude mice. Effects of hormone and antihormone treatment.

We have recently described an experimental model for studying the hormonal modulation of growth and receptor content of human endometrial adenocarcinoma in ovariectomized athymic mice. The morphologic features of endometrial carcinomas can be maintained during serial transplantation in control animals. Further, administration of estradiol, tamoxifen citrate, and medroxyprogesterone acetate to animals with tumors containing estradiol and progesterone receptors resulted in histologic and ultrastructural changes in most foci resembling the response of normal human endometrium to these agents. No morphologic change was detected in the steroid-receptor-negative tumors of hormone-treated mice. These results demonstrate that histologic changes parallel the changes in the growth rate and hormone receptor content of tumors in this model system, and they provide support for the concept of receptor-mediated alteration in the morphologic features of endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed1984

Spontaneous occurrence of synergistic bacterial gangrene following external pelvic irradiation.

A case of spontaneous synergistic bacterial gangrene occurring after external pelvic irradiation is presented in a 25-year-old woman with invasive cervical cancer. Treatment consisted of aggressive antibiotic therapy and extensive excision and debridement followed by split-thickness skin grafting. Both recovery and cosmetic results were satisfactory. The pathophysiology, predisposing factors, and treatment modalities are presented.

Anti-Bacterial Agents↗
PubMed1984

Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice.

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.

Animals↗
PubMed1983

Creatine kinase activity in human endometrium: relative distribution in isolated glands and stroma.

Creatine kinase (CK) activity was measured in human endometrium as a function of the normal menstrual cycle. The specific activity of CK was consistently higher in the secretory endometrium than in the proliferative tissue (proliferative, 0.9 U/mg of protein; secretory, 3.3 U/mg of protein). The relative distribution of CK activity in isolated glands and stromal cells was determined following collagenase digestion of the endometrial specimen according to our previously described procedure. These studies show an enrichment of CK activity in the glands that is greater than fivefold that present in the stromal cells. Electrophoretic mobility of CK activity on cellulose acetate further indicates that the endometrial enzyme is a BB (brain type) isoenzyme. In the rat uterus, CK has been shown to be an estrogen-induced protein. In contrast, the activity of this enzyme may be modulated by progesterone in human endometrium.

Adult↗
PubMed1983

Human endometrial adenocarcinoma transplanted into nude mice: growth regulation by estradiol.

A model for studying the growth of primary tumors of human endometrium and its regulation by 17 beta-estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17 beta-dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

Adenocarcinoma↗
PubMed1983

Treatment outcome of recurrent cervical cancer.

A total of 85 patients with recurrent cervical cancer were reviewed: 17 patients with recurrences were treated by radical surgery, 18 by radiotherapy, 29 by chemotherapy, and 21 cases received no further treatment. Survival was presented according to the site of recurrence and the mode of therapy. All patients were followed for a minimum of 24 months after recurrence. Of the total group, 14% are living without evidence of disease, 29% died of metastatic disease with no involvement in the pelvis, and 45% died of pelvic cancer. Overall, 22% were living more than 2 years, and only 2% lived over 5 years after recurrence. The NED (no evidence of disease) rate for radical surgery group was 47 and 44% for the radiotherapy group. There were no significant differences in median survival between the chemotherapy group and the no-treatment group (6.8 versus 4.8 months). New chemotherapy agents and adjuvant systemic therapy are discussed.

Adult↗
PubMed1983

The significance of histologic findings in predicting nodal metastases in invasive squamous cell carcinoma of the vulva.

The significance of tumor differentiation, depth of stromal penetration, and vascular channel involvement in predicting nodal metastases was studied in 62 patients with invasive squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinal and femoral lymphadenectomy. The pattern of arrangement of vulvar neoplastic cells at the interface with stroma was used as a criterion for histologic grading. Patients with less differentiated tumors had a higher incidence of nodal metastasis within each stage of disease. No nodal metastases were noted in patients with Grade III tumors who had Stage I disease. No well-differentiated tumor with less than 5 mm of stromal penetration was associated with nodal metastases. In this study, the degree of tumor differentiation and the depth of stromal penetration were important predictors of nodal metastases. It was concluded that a subgroup of patients with Stage I well-differentiated vulvar carcinoma invading less than 5 mm into the underlying stroma may benefit by less radical surgery without compromising cure.

Carcinoma, Squamous Cell↗
PubMed1983

The prognostic significance of vascular channel involvement and deep stromal penetration in early cervical carcinoma.

Eighty-eight patients with FIGO Stage Ib and IIa squamous cell carcinoma of the cervix underwent radical hysterectomy with pelvic and paraaortic lymphadenectomy. The records and histopathologic material were reviewed to determine the prognostic significance of vascular channel involvement and deep stromal penetration by tumor. Seventy-four patients (84%) were alive and free of disease for more than 2 years and 14 (16%) developed recurrent carcinoma within that time. A positive correlation was found between depth of stromal penetration by tumor and the degree of vascular channel involvement (p less than 0.05). Vascular involvement in itself did not significantly affect nodal status, survival or the rate of recurrence. Depth of penetration was associated with a higher incidence of positive nodes (p less than 0.05). There was a trend towards a lower survival rate and a higher recurrence rate in patients with deep stromal penetration as compared to those with superficial tumors. Microscopic nodal disease increased the rate of recurrence and had an adverse effect on survival. The combination of deep tumor penetration and positive nodes in the same patient was associated with the highest recurrence rate and the lowest survival (p less than 0.05). Nodal status was a more significant prognostic indicator than depth of tumor penetration because patients with deeply penetrating tumors and positive nodes had more than twice the recurrence rate than did patients with deep tumors and negative nodes. Postoperative radiation therapy was beneficial to patients whose tumors demonstrated deep stromal penetration and microscopic metastases to pelvic lymph nodes.

Carcinoma, Squamous Cell↗
PubMed1982

Analysis of residual disease following preoperative radiotherapy versus initial surgery in endometrial carcinoma.

A clinicopathologic study of residual disease following pre-operative radiotherapy (RT) in 67 patients and initial surgery in 40 patients with early invasive endometrial carcinoma is presented. In 10%, extrauterine spread was found at operation. In 10% of patients, the histologic type, and in 19% the grade of tumor, differed between the curettage and hysterectomy specimens. Pre-op RT altered the depth of myometrial invasion and frequency of vascular invasion, but there was no evidence that irradiation itself affected the histologic type or grade of tumor. The patients with residual tumor after pre-op RT had significantly more cancer-related deaths than those without residual disease. The high risk factors were deep myometrial invasion and residual disease outside the uterus. Vascular invasion did not affect the prognosis in this series. The importance of surgical-pathologic staging by initial surgery is discussed.

Adenocarcinoma↗
PubMed1982

Epithelial alterations in proximity to invasive squamous carcinoma of the vulva.

The histologic changes within epithelium adjacent to invasive carcinomas theoretically may include the specific lesions that precede the development of the invasive neoplasm, or may reflect the response of host epithelium to the carcinoma or to nonspecific inflammatory stimuli related to ulceration and tissue necrosis. We have studied the vulvar epithelium surrounding squamous carcinomas of 60 women undergoing vulvectomy to determine the frequency and type of potential precursor lesions and their relationship to various biologic parameters. Using modified criteria and nomenclature of the International Society for the Study of Vulvar Disease, we identified some degree of nuclear atypia (either atypical hyperplastic dystrophy or carcinoma in situ) in 72% of patients; in only 3% was there a direct transition from normal epithelium to invasive carcinoma. There was no apparent relationship between the presence of atypia and histologic grade, depth of invasion, size or stage of tumor, or frequency of nodal metastasis. Although direct evidence is lacking, these atypical lesions may serve to identify a population at increased risk for subsequent development of invasive carcinoma.

Carcinoma in Situ↗
PubMed1982

Distribution of progesterone receptor, estradiol dehydrogenase, and 20 alpha-dihydroprogesterone dehydrogenase activities in human endometrial glands and stroma: progestin induction of steroid dehydrogenase activities in vitro is restricted to the glandular epithelium.

Endometrial glands were separated from stromal cells by collagenase digestion of human endometrium, and the distribution of progesterone (P) receptor and the activities of P-regulated enzymes, 17 beta-estradiol dehydrogenase (E2DH) and 20 alpha-dihydroprogesterone dehydrogenase (20 alpha DH), were determined in these preparations. Concentrations of cytosolic P receptor were estimated by Scatchard plot analysis of specific [3H]P binding in intact proliferative endometrium and in glands and stromal cells isolated from this tissue. Epithelial cells were more than 10-fold enriched in high affinity, P-specific binding sites compared to stromal cells. The binding constants (Kd) for [3H]P binding were essentially similar in undissociated endometrium, glandular epithelium, and stroma, ranging from 1--5 nM. The activities of E2DH and 20 alpha DH were also 3-fold higher in the glandular epithelium than in whole tissue or stroma during both proliferative and secretory stages of the menstrual cycle. In addition, the induction of these enzyme activities by progestin in vitro in cultured explants of proliferative endometrium was restricted to the glandular epithelium. Thus, the effects of P on E2DH and 20 alpha DH are expressed in the same cells that contain receptors for P.

17-Hydroxysteroid Dehydrogenases↗
PubMed1982

Glassy cell carcinoma of the uterine cervix. An ultrastructural study and review.

Glassy cell carcinoma is an unusual neoplasm of the uterine cervix that accounts for 1% to 2% of all cervical malignant neoplasms. Although it seems to have a distinct histologic appearance, it has generally not been recognized, as indicated by the extremely small number of cases reported in the literature. Previous studies have indicated an aggressive behavior, a poor response to irradiation and surgery, and a tendency to widespread metastases. It occurs in a younger age group (mean age, 41 years) than other cervical neoplasms and often has been associated with pregnancy. The histogenesis is not known, but electron microscopic examination of one case we studied, and review of one previously described case, demonstrate that it is an adenosquamous carcinoma. The need to define this neoplasm better will be satisfied only by additional, thorough histologic and clinical studies.

Adenocarcinoma↗
PubMed1982

Failure of progestins to induce estradiol dehydrogenase activity in endometrial carcinoma, in vitro.

Estradiol dehydrogenase (E2DH) is a well-known progesterone-dependent enzyme in human endometrium, and its induction has been proposed as a means to test hormonal sensitivity of endometrial carcinoma. While administration of progestins to some patients with endometrial carcinoma resulted in increased endometrial E2DH activity, efforts to induce this enzyme, in vitro, in these tumors have been unsuccessful. The reasons for such failure were investigated in the present study. Progesterone receptor (PR) concentrations and E2DH activities were simultaneously measured in proliferative and malignant endometria under organ culture conditions. Cytoplasmic PR concentrations were determined by Scatchard plot analysis of [3H]progesterone binding in fresh samples and in tissue explants incubated in nutrient medium at 37 degrees in a humidified 5% CO2 atmosphere for various periods of time. Parallel incubations of explants with and without 500 ng medroxyprogesterone acetate per ml were carried out for monitoring E2DH induction. In proliferative endometrium, the progesterone-specific binding sites remained stable during the culture periods, and the E2DH activities were stimulated severalfold by medroxyprogesterone acetate. In contrast, the PR concentrations in carcinoma explants were undetectable after a 24-hr period, and this was associated with a lack of increase in E2DH activity. These findings provide evidence that progestin-induced endometrial E2DH activity is a receptor-mediated phenomenon. In addition, these results demonstrate clearly that the ineffectiveness of progestin to induce E2DH in endometrial cancer specimens, in vitro, is related to the instability of PR under culture conditions. It is suggested that any experiment designed to follow effects of steroids on target tissues must take into account the stability of steroid receptors under in vitro conditions.

17-Hydroxysteroid Dehydrogenases↗
PubMed1981

Endometrial carcinoma: an aberration of endometrial cell differentiation.

A model endometrial cell differentiation is being proposed. It is in agreement with the available information on the concentrations of female sex steroid receptors in the human endometrium and the effects of estradiol and progesterone during the normal menstrual cycle. The scheme is extended to include endometrial carcinoma as a derangement of normal cell differentiation. Evidence is cited, from various studied on estradiol and progesterone receptor measurements and hormone responses of human endometrial carcinoma, in support of this hypothesis. This concept provides a rational basis for the selection of patients for hormonal (progestin) therapy.

Carcinoma↗