PubMed Health⌕ Search

Biomedical subjects

R Mortel

Publications and source records attributed to R Mortel.

At least 73 records · Page 4Linked to original sources

An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma.

Preoperative serum CA 125 levels were determined for 36 patients with Stage I and II ovarian carcinoma. Levels ranged from 9 to 1962 U/ml with a mean of 216 U/ml. In Stage I patients, CA 125 levels averaged 133 U/ml and in Stage II patients 382 U/ml. Nine of 24 Stage I (38%) and 9 of 12 Stage II patients (75%) had CA 125 levels in excess of 65 U/ml in a population somewhat overrepresented in mucinous tumors. Patients with non-mucinous neoplasms had CA 125 elevations more often--in 75% of the cases--than those with mucinous tumors. A larger study will be required to more precisely estimate the fraction of early stage patients with elevated preoperative serum CA 125 levels; however, this investigation demonstrates an assay sensitivity minimally adequate to initiate a pilot evaluation of serum CA 125 levels in a population at risk for ovarian carcinoma.

Antigens, Neoplasm↗

Bladder and rectal complications following radiotherapy for cervix cancer.

One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.

Analysis of Variance↗

Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease.

CA 125 levels were measured in 158 patients with palpable pelvic masses who were about to undergo diagnostic laparotomy. When the 68 patients found to have cancer were compared with the 90 patients with benign disease, those with malignancies were significantly older, were more frequently postmenopausal, and had significantly higher values of serum CA 125. Patients with benign pelvic masses had CA 125 levels greater than 65 U/ml in 8% of cases, whereas those with malignancies had CA 125 levels greater than 65 U/ml in 75% of cases. If only those patients who had frankly malignant, primary, nonmucinous epithelial ovarian carcinomas were considered, CA 125 levels greater than 65 U/ml predicted malignancy with a sensitivity of 91% for all patients. Greater sensitivity and specificity were observed in the postmenopausal subgroup than in the premenopausal subgroup. In the postmenopausal group with a 63% prevalence of ovarian cancer the predictive positive value was 98% and the predictive value negative was 72%. In a premenopausal population with a 15% prevalence of ovarian cancer the predictive value for a positive test was 49%, while the predictive value for a negative test was 93%.

Adolescent↗

Effect of alpha-difluoromethylornithine (DFMO) on the growth of human ovarian carcinoma.

The antiproliferative effect of alpha-difluoromethylornithine (DFMO) was investigated in a human ovarian cancer cell line (NIH:OVCAR3) both in vitro and in vivo. DFMO at 5 X 10(-5) M, 5 X 10(-4) M and 1 X 10(-3) M concentrations showed growth inhibition of NIH:OVCAR3 cells in culture. Parallel determination of CA 125 in the culture media of these cells show significant decrease in the presence of DFMO compared to controls. Oral administration of DFMO (2% aqueous solution) to nude mice bearing intraperitoneal tumors resulted in a mean survival of 45 days (38-60) versus 25 days (20-35) for control. Both in vitro and in vivo results suggest that DFMO has potential value in the treatment of ovarian carcinoma and should be considered for clinical trials in appropriate cancer patients.

Animals↗

Steroid receptors and human endometrial carcinoma: studies in a nude mouse model.

An experimental nude mouse system where human endometrial carcinomas of different histologic grade and steroid receptor characteristics can be grown and maintained under defined hormonal milieu by serial transplantation has been developed. Biologically and clinically important information on the role of steroid receptors in eliciting hormonal responses in these tumors has been obtained using this model. These results form the basis for designing and testing various treatment strategies for endometrial carcinomas of different histologic grade and receptor content.

Animals↗

Nude mouse system in the study of tumor biology, treatment strategies and progesterone receptor physiology in human endometrial carcinoma.

A nude mouse system where the biological, morphological and biochemical characteristics of human endometrial carcinoma are maintained during serial transplantation has been previously described. Applications of this system to the study of (a) hormonal sensitivity (b) treatment strategies and (c) progesterone receptor physiology of human endometrial carcinomas are presented here.

Animals↗

Radioimaging of human ovarian carcinoma xenograft in nude mice.

Human ovarian carcinomas in nude mice were radioimaged using a well-characterized antibody against a tumor-associated antigen (CA 125) and three transplantable human ovarian carcinoma tumor lines: NIH:OVCAR 3, NIH:OVCAR 5, and NIH:OVCAR 9. Radioiodinated monoclonal antibody OC125 was used in these studies. In order to establish the optimal conditions for imaging, tumor/blood ratios were determined. Gamma scintigraphy of nude mice bearing subcutaneous transplants of human ovarian carcinomas 3-4 days after 131I-OC125 administration demonstrated selective localization of the radiolabeled monoclonal antibody by these tumors without need for any background subtraction techniques.

Animals↗

Use of second-look laparotomy in the management of patients with ovarian epithelial malignancies.

Between June 1976 and January 1986, 94 evaluable patients with stage I-IV disease underwent second-look laparotomy as part of their treatment for ovarian epithelial carcinomas. Stage and residual tumor size after initial debulking surgery demonstrated a significant association with absence of disease at reexploration. Forty-nine patients (52%) had no evidence of disease at second-look laparotomy. Thirty patients (32%) had macroscopic residual tumor, and 15 patients (16%) had microscopic disease at reexploration. Patients with a negative second-look laparotomy had an excellent prognosis; uncorrected 2- and 5-year survival rates exceed 90%. None of the patients with stage I or II disease developed recurrent tumor after a negative second-look laparotomy. However, 7 of the 25 (28%) patients with stage III disease and a negative second-look have demonstrated recurrent carcinomas. Recurrences were documented from 15.4 to 51.7 months after second-look laparotomy and were located within the abdominal cavity. Life table methods demonstrated improved survival for patients with microscopic disease as compared to those with gross tumor at second-look survey. Both groups had similar mean patient ages and tumor stage distributions. Patients with microscopic residual disease had uncorrected 2- and 5-year survival rates of 76 and 64%. The 2-year uncorrected survival rate for patients with gross tumor at second-look laparotomy was 25%. Thirty patients with macroscopic disease at second-look laparotomy underwent a repeat attempt at tumor debulking. Seventeen patients completed second-look surgery with residual disease less than 1 cm in maximum dimensions. Life table methods demonstrated improved survival when residual disease was less than 1 cm. Regardless of residual tumor size after reexploration, patients with gross tumor had a worse survival than those with microscopic disease.

Adult↗

Aminothiadiazole (NSC #4728) in patients with advanced cervical carcinoma. A phase II study of the Gynecologic Oncology Group.

Twenty-one evaluable patients with advanced squamous-cell cervical cancer were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Nineteen had prior chemotherapy. One patient had a partial response; six had stable disease; 14 had increasing disease; and two were unevaluable for response. There was a single life-threatening toxic episode. Aminothiadiazole used in this dosage and schedule has minimal activity in previously treated cervical carcinoma patients.

Antineoplastic Agents↗

The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer.

Serum CA 125 levels were obtained from 55 women with epithelial ovarian cancer before a second-look surgical procedure and serially thereafter. All patients were clinically and radiographically free of tumor at the time of the second-look operation and were followed to clinical recurrence. Median follow-up was 12 months. CA 125 levels obtained at the second-look operation had a sensitivity and specificity for predicting clinical recurrence of 94% and 88%, respectively. Patients with an elevated CA 125 level (greater than or equal to 35 U/ml) had a 60% chance of clinical recurrence within 4 months, while patients with levels less than 35 U/ml had a 5% chance of clinical recurrence over the same time period. Serial CA 125 levels obtained after second-look operations were strong predictors of clinical outcome, and distinctly different monitoring profiles were observed among those patients remaining clinically free of tumor and those suffering clinical recurrence. The CA 125 assay became elevated (greater than or equal to 35 U/ml) before clinical recurrence in 94% of 35 cases with a median lead time of 3 months. The CA 125 assay identifies patients destined to suffer a clinical recurrence and provides a warning measurable in months. This may have important implications for therapy.

Adult↗

Absence of bile acid malabsorption as a late effect of pelvic irradiation.

The pathophysiology of chronic radiation-induced diarrhea was evaluated in 28 patients who had undergone pelvic irradiation for gynecologic neoplasms 2 to 7 years previously. Twenty-seven patients undergoing radiotherapy with techniques that did not require abdominal or pelvic irradiation served as controls. The glycine conjugates of cholic acid (GC) were measured in serum by radioimmunoassay. Fasting and 2 hr. pp GC levels for the pelvic irradiated patients were 11.0 +/- 11.1 (mean +/- SD) and 24.8 +/- 17.3 micrograms/dl. Fasting and 2 hr. pp GC levels for controls were 12.6 +/- 7.4 and 28.0 +/- 14.7. There were no significant differences in the post-prandial increases in serum GC between pelvic irradiated patients and controls (p = .23, Type II error probability = .13). There was also no significant difference in the 2 hr. pp and fasting GC ratio (p = .39). There was significant difference between the stool frequency (p less than .01) and the prevalence of diarrhea (p less than .02) between pelvic irradiated patients and controls. The data suggest that bile acid malabsorption due to ileal dysfunction is not an inevitable late complication of pelvic irradiation and is not the major determinant in the pathophysiology of chronic radiation-induced diarrhea.

Aged↗

In vivo transformation of human skin with human papillomavirus type 11 from condylomata acuminata.

Human papillomaviruses (HPVs) have been implicated in the development of a number of human malignancies, but direct tests of their involvement have not been possible. We describe a system in which human skin from various sites was infected with HPV type 11 (HPV-11) extracted from vulvar condylomata and was grafted beneath the renal capsule of athymic mice. Most of the skin grafts so treated underwent morphological transformation, resulting in the development of condylomata identical to those which occur spontaneously in patients. Foreskins responded with the most vigorous proliferative response to HPV-11. The lesions produced the characteristic intranuclear group-specific antigen of papillomaviruses. Both dot blot and Southern blot analysis of DNA from the lesions revealed the presence of HPV-11 DNA in the transformed grafts. These results demonstrate the first laboratory system for the study of the interaction of human skin with an HPV. The method may be useful in understanding the mechanisms of HPV transformation and replication and is free of the ethical restraints which have impeded study. This system will allow the direct study of factors which permit neoplastic progression of HPV-induced cutaneous lesions in human tissues.

Animals↗

Former cancer patients as counselors of newly diagnosed cancer patients.

This study tested the hypothesis that counseling of newly diagnosed cancer patients by former cancer patients will increase the use of coping strategies and reduce psychological stress beyond what can be accomplished by just counseling from professional staff. Thirty-two newly diagnosed patients in a gynecologic oncology service were subjects in this study. All subjects received supportive services from professionals assigned to the service. Control group patients received just the professional support program, while the experimental group patients received professional support plus additional counseling by former cancer patients that emphasized four coping strategies characteristic of patients who have adapted well to cancer. Results 6 and 12 weeks after entering the study showed no statistically significant differences in emotional status between experimental and control groups and only one significant difference in coping behaviors that was opposite to what was predicted. The findings do not support the hypothesis.

Adaptation, Psychological↗

Sex steroid receptors in normal and malignant endometrium.

Estradiol and progesterone receptor concentrations have been measured and their hormonal regulation extensively studied in normal human endometrium. However, in endometrial cancer, the biochemical assays presently used face the complex problem of tumor and tissue heterogeneity. This problem may be circumvented by immunocytochemistry on tissue sections proven to be histologically malignant. The in vivo experimental model developed in our laboratory is an ideal source of tissue necessary for purification of the progesterone receptor and antibody production. Hopefully, the physiology of the receptor may be studied under ideal conditions in this experimental system.

Affinity Labels↗

Plasminogen activator activity in human endometrial carcinoma.

Plasminogen activator activity (PAA) has been proposed as an indicator of aggressiveness of tumors and has been shown to be hormonally modulated. To test this hypotheses in human endometrial carcinoma, tumor explants were assayed for PAA secretion and the results correlated with histopathologic criteria of aggressiveness. The effect of medroxyprogesterone acetate (MPA) on PAA secretion was also investigated. Lower levels of PAA were found to be associated with tumors displaying aggressive tendencies. MPA generally decreased PAA secretion. No apparent correlation was found between estrogen or progesterone receptor concentrations and PAA levels.

Female↗

Histologic response of normal human endometrium to steroid hormones in athymic mice.

Despite the widespread use of hormonal therapy for menopausal symptoms, oral contraception, and treatment of metastatic breast carcinoma, information concerning the histologic and biologic effects of individual sex steroids on the human endometrium remains incomplete. Repetitive endometrial biopsy is impractical, and ethical constraints limit the dosage and duration of administration for some steroids. The ovariectomized athymic mouse was investigated as a host for human endometrium in which the hormonal milieu may be manipulated and the histologic response determined. Minced proliferative-phase endometrium from hysterectomy specimens of normally cycling women was inserted into the subcutis of 4- to 6-week-old mice. Proliferation of endometrial gland cells occurred in the transplanted endometrium of estradiol-treated mice, while the complete sequence of secretory-phase events, including subnuclear vacuolization, luminal secretion, and decidualization of stroma, was observed during a 14-day period of treatment with estradiol and progestin (medroxyprogesterone acetate). Progestin treatment alone also caused secretory-phase changes, but the response was delayed and appeared weaker. The transplanted endometrium in control mice appeared to be inactive. These observations provide support for the use of this model to study the histologic response of human endometrium to sex steroids.

Animals↗

Hormonal therapy of human endometrial adenocarcinoma in a nude mouse model.

The hypothesis that 17 beta-estradiol or tamoxifen (TAM) can potentiate clinical response of endometrial cancer treated with progestin was tested in an ovariectomized nude mouse system, using a sex steroid receptor-positive and a receptor-negative human endometrial carcinoma. Animals were divided into three groups: control; 17 beta-estradiol-treated; and TAM-treated. When tumors of a group reached about 1 cm in diameter, subgroups were given either 0.9% NaCl solution (saline) or medroxyprogesterone acetate (MPA). The receptor-negative tumor grew rapidly in all three groups, and several animals were dead before or during progestin treatment. The growth rate of receptor-containing carcinoma was significantly increased in TAM-treated mice compared to controls (p less than 0.02) but significantly less than that in 17 beta-estradiol-treated animals (p less than 0.01). Endometrial carcinoma in 17 beta-estradiol-saline-treated animals continued to grow rapidly, and all animals were dead by 11 weeks. The growth of tumors in the 17 beta-estradiol-progestin group was suppressed at 11 weeks, and some of these animals lived 20 weeks. Administration of progestin to TAM-exposed animals resulted in a remarkable regression of the tumor compared to TAM-saline-treated group. The growth rate of tumors in control animals (no implants) was unaffected by progestin treatment. We conclude that, in this nude mouse model, treatment with TAM and MPA is superior to MPA alone, or 17 beta-estradiol plus MPA for sex steroid receptor-positive endometrial carcinoma.

Adenocarcinoma↗