Biomedical subjects

J Ranstam

Publications and source records attributed to J Ranstam.

140 records · Page 8Linked to original sources

PubMedDate not supplied

Progression of human endometrial adenocarcinoma heterotransplanted into nude mice from hormone-sensitive to hormone resistant growth.

We have used a human tumor nude mouse model involving heterotransplantation and serial passage of an estrogen receptor (ER) positive, progesterone receptor (PgR) negative human endometrial adenocarcinoma. The effects of estradiol treatment on tumor growth, ER activation and PgR induction were investigated two and four years after heterotransplantation. In Experiment I, two years after initial heterotransplantation, tumor growth and proliferative rate showed a dose-related decrease, ER was activated by estradiol treatment (measured through an increased amount of ER bound with high affinity to nuclear element(s) (ERhs) and PgR was induced. Two years later (Experiment II), the amount of ER1s (ER measured in cytosolic fraction) as well as of ERhs was lower than at the beginning of Experiment I. ER could again be activated by estradiol treatment and PgR was also induced. However, in this experiment no effect either of tumor growth or of proliferative rate was observed during the estradiol treatment. Our study therefore indicates that an estrogen non-sensitive growth can develop during serial passages in intact, non-treated female nude mice, although the capacity for ER activation and PgR induction is maintained.

Adenocarcinoma↗

PubMedDate not supplied

Survival in breast cancer and age at start of oral contraceptive usage.

In general, findings in studies on oral contraceptives (OCs) and breast cancer have not indicated prognosis to be worse among users of OCs. In few studies, however, has age at the start of OC usage been considered as a prognostic factor. In the present study, prognosis in breast cancer is compared with OC usage, particularly with age at the start of OC usage, among 193 consecutive patients at the Department of Oncology, University Hospital, Lund. An earlier series of 193 breast cancer patients at Malmö General Hospital is included for comparisons. In the Lund series, five-year survival was 62% among women who started to use OCs before the age of 20.78% among those who started to use OCs between the ages of 20 and 25, and 86% among non-users and those who started to use OCs after the age of 25 (p = 0.009, test for homogeneity). Although age was found to be a prognostic factor in the Lund series (RR = 0.90, p = 0.001), this was not so in the earlier (older) Malmö series. The relationship with age differed significantly between the two series (p = 0.003), suggesting the apparent effect of age at diagnosis to be a cohort effect due to the introduction of OCs during the 'sixties. The age-specific relationship between survival and OC usage would seem to indicate the presence of a biological mechanism in which OCs may participate during precancerous and early stages of breast cancer.

Adult↗

PubMedDate not supplied

Estradiol induced changes in tumor growth and steroid receptor content in a heterotransplanted human endometrial adenocarcinoma.

To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.

Adenocarcinoma↗

PubMedDate not supplied

Increased plasma prolactin levels in a group of men with breast cancer--a preliminary study.

Gonadal and hypophyseal hormones were investigated in 15 males with breast cancer and 15 tumour referents, on average 1 month postoperatively. Plasma prolactin was found to be significantly more often elevated in men with breast cancer compared with referents (p less than 0.005). Another group of men with breast cancer disclosed a tendency for lower S-FSH levels compared with the referents (p less than 0.01). No significant difference was seen between cases and referents regarding S-LH, p-estradiol or p-testosterone. The size of the primary breast tumour was correlated with a higher prolactin level. The findings lend support to a theory implicating prolactin and possibly prolactinomas as a risk factor for the disease in males.

Aged↗

PubMedDate not supplied

Estrogen receptor activation in relation to previous estrogen treatment in carcinoma corporis uteri heterotransplanted into nude mice.

The interaction between estradiol and its receptor in human endometrial adenocarcinoma was investigated in a human tumor-nude mice model. Estradiol treatment was found to activate estrogen receptor (ER), estimated through the measurement of ER in the nuclear fraction. The receptor activation in the tumors was significantly higher in tumors previously treated with estradiol than in previously non-treated tumors. The activation seems also to be dependent on the estrogen dose. We concluded, that previous influence of estradiol may change the sensitivity of estrogen receptor positive tumors for its hormone, and therefore the measurement of the receptor content alone does not seem to be a sufficient marker for the prediction of the receptor activation process.

Adenocarcinoma↗

PubMedDate not supplied

Prediction of survival in gastric carcinoma and a new histopathologic approach.

During six years 188 consecutive patients with gastric carcinoma admitted to the Department of Surgery, University Hospital, Lund, were followed up to evaluate clinical as well as histopathologic factors which might be important to predict postoperative survival. We also introduced a new histopathologic scoring system based on nine different parameters. Radicality estimated by the surgeon, resection line margin, score at histologic grading and TNM were factors which in a multivariate analysis strongly correlated to survival.

Carcinoma↗

PubMedDate not supplied

Early oral contraceptive use as a prognostic factor in breast cancer.

The survival of 193 premenopausal breast cancer patients was investigated in relation to their history of early use of oral contraceptives. The women were born in 1939 or later and diagnosed in the southern health care region of Sweden. Women, who had started their oral contraceptive use (OC-use) before 20 years of age had a significantly lower survival rate as compared with those who had never used OC and late users (p = 0.02 and = 0.04 respectively, generalized Wilcoxon test). For women who started OC-use between 20 to 25 years of age, a tendency for a shorter survival was seen in comparison with women who had never used OC (p = 0.18). For all patients simultaneously, the relative risk adjusted for age at diagnosis increased for earlier OC-start. When only stages II and III were considered in a stratified multivariate model, a significantly elevated risk was seen for early users of OC irrespective of age or of adjuvant treatment given. The estrogen and progesterone receptor concentrations of the primary tumor were significantly lower among early users (p = 0.001 and p = 0.05 respectively).

Age Factors↗

PubMedDate not supplied

Prospective malignancy grading and flow cytometry DNA distribution in biopsy specimens from invasive squamous cell carcinoma of the uterine cervix.

Flow cytometry was used for the investigation of the DNA distribution in biopsy specimens from 72 patients with squamous cell carcinoma of the uterine cervix. A prospective grading score system using tumor cell parameters and tumor host parameters was also applied. 50% of the tumors were aneuploid with up to 4 different tumor populations. The definition of DI +/- 8% was applied. The median age of the patients was 61 years with FIGO median value of 2B. Significant correlations were observed between ploidy and MGS-scores and stage stadium according to FIGO. Increasing MGS score was noted with increasingly distorted ploidy. No significant difference was found between DI below and above 1.5 for MGS, FIGO stage stadium, histology according to Ackerman, tumor parameters and tumor host parameters for the total material. However, for aneuploid tumors MGS and tumor cell parameters were related with DI below and above 1.5 (P = 0.05 and P = 0.02, respectively). No correlation between clinical stage according to FIGO and S-phase % was noted. It remains to be settled to what extent DNA flow cytometry and MGS-scoring in our ongoing prospective series of invasive squamous cell carcinoma of the uterine cervix can take their place in the multifactorial prognostic index suggested by Jacobsen et al (Am. J. Clin. Oncol. 8: 39, 1985).

Adult↗

PubMedDate not supplied

Permanent alterations induced in plasma prolactin and estrogen receptor concentration in benign and malignant tissue of women who started oral contraceptive use at an early age.

In 65 young women undergoing curettage for benign uterine disorders a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p less than 0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.

Adult↗

PubMedDate not supplied

Identification of high-risk groups in endometrial carcinoma stage I-II. A combination of DNA- and steroid receptor-measurements identifies early deaths from the disease.

BACKGROUND: Treatment of endometrial carcinoma has not improved during the last decades, due to the already good results. Such therapy has been a compromise, strong enough to cure some of those in need of harder treatment, but weak enough not to cause too severe side-effects. One way of solving the problem of overtreatment is to identify those in real need of a harder regimen. Generally, the histopathologic picture and the depth of myometrial invasion of the tumour have been used. However, this often means a too large high-risk group, often exceeding 50% of the patients. METHODS: Steroid receptor concentrations and later DNA-measurements have been increasingly used to identify high-risk groups not, however, in combination. In 156 patients with endometrial carcinoma, both estradiol receptor concentration and flow cytometrically estimated DNA content were measured on all patients and the patients were followed-up for over five years. RESULTS: By using the number of DNA-populations (ploidy) we could identify a small high-risk group (28%) with a death frequency of 35%. This small group could be further divided, by using the estradiol receptor concentration, into an extremely small high-high-risk group (11%) consisting of 17 patients of whom 9 died from the disease within 5 years, almost all of the deaths occurring within 2 years. CONCLUSION: Thus histopathology was reduced to merely identifying cancer but DNA- and estradiol receptor measurements in combination could identify an extremely small high-risk group, with almost all deaths occurring within 2 years.

Adult↗

PubMedDate not supplied

Prospective malignancy grading, flow cytometry DNA-measurements and adjuvant chemotherapy for invasive squamous cell carcinoma of the uterine cervix.

In a prospective study comprising 310 consecutive patients with carcinoma of the cervix, FIGO stages I-IV, the prognostic significance of clinical and flow cytometric variable was evaluated in a univariate and multivariate analysis. The parameters studied included stage according to FIGO, age, histopathologic grade according to Ackerman and MGS scores, DNA ploidy, S-phase fraction as well as treatment with radiation only, surgery only or a combination thereof as well as adjuvant chemotherapy. Univariate analysis showed that patients in FIGO stages IA-IIA with MGS up to 14 points survived significantly better than other groups. MGS parameter mitosis, vascular invasion and type of invasion predicted survival as did clinical stage. Diploid cases with SPF > 15% survived less than remaining other cases. Multivariate analysis not including treatment indicated that FIGO stage and diploid cases with SPF > 15% predicted survival but not total MGS score and age. When treatment for FIGO stages IA-IIA was included, elderly women had a worse prognosis. Adjuvant chemotherapy, surgical alone or radiation alone did not demonstrate any differences within groups. In Figo stages IIB-IV, cases with radiotherapy only survived significantly better than patients with other treatment schedules. The frequency of low malignancy patients (< MGS 16) in relation to year of initial diagnosis was found to have decreased between years 1967 and 1988, probably as a result of screening activities.

Adult↗

PubMedDate not supplied

Endometrial carcinoma: results of primary surgery on FIGO stages Ia-Ic and predictive value of histopathological parameters.

The aim of the present investigation was to see if alternative histopathological parameters could identify a smaller high risk group than commonly seen using routine histopathological parameters. The material consisted of 150 primary resected patients of FIGO Ia-Ic diagnosed as endometrial carcinoma and 12 cases of atypical hyperplasias which were suspected to contain small areas of carcinoma. The patients were treated from December 1979 to April 1993 at the Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. Those with deep myometrial invasion (> 50%) were given external radiotherapy (20-30 Gy) postoperatively. The follow-up period ranged from 2.5 to 5 years with 116 patients followed-up for more than 5 years. As no therapy was given before surgery we could investigate histopathologic variables such as degree of differentiation and cytology, number of mitoses per high power field (x 40), nuclear polymorphism, mode of invasion, the extension of myometrial invasion, vessel invasion as well as grade of lymphocyte reaction around the tumour cells. We found the degree of differentiation, vessel invasion, number of mitoses, mode of invasion and cytologic abberation to be significant prognostic parameters. The frequency of deep myometrial invasion (> 50%) was extremly high (51/150 = 33%). However, this usually strong parameter was only significant when comparing stage Ia with Ic. Thus the prognostic capacity of myometrial invasion is diminished in primary hysterectomized patients. In the regression analyses only vascular invasion remained significant. By combining vascular invasion with the degree of differentiation we diminished the high-risk group consisting of candidates for further investigation and treatment. Thus a high risk group consisting of poorly differentiated carcinomas with vascular invasion was constructed comprising 24 of 139 patients with a mortality rate of 60%.

Endometrial Neoplasms↗

PubMedDate not supplied

Endometrial thickness and ovarian cysts as measured by ultrasound in asymptomatic postmenopausal breast cancer patients on various adjuvant treatments including tamoxifen.

Endometrial thickness as measured by ultrasound during tamoxifen treatment has previously been reported. However, there has not been any study investigating endometrial thickness before treatment and following it at regular intervals during treatment. 90 patients with breast cancer without any gynecological symptoms were followed (aged more than 50 years at the operation of their breast cancer). They were investigated by vaginal ultrasound and a common clinical investigation at our out-care patient department. Adjuvant breast cancer therapy consisted of tamoxifen, tamoxifen after radiotherapy and/or in a few cases cytostatics, cytostatics with or without the addition of radiotherapy, radiotherapy or no further therapy. Patients with receptor positive tumours were given tamoxifen. Their endometrium was already thicker before the start of adjuvant treatment as measured by ultrasound. After 3 months and 12 months we found the endometrium to be significantly thicker in those treated with tamoxifen compared to other treatment groups. After 12 months of tamoxifen treatment 22/32 women had an endometrial thickness of 5 mm or more. The frequency of ovarian cysts also seemed to be affected by therapy. In patients treated with tamoxifen alone or in combination, the frequency of cysts was 5/35 before treatment, 6/37 after 3 months, and 0/32 after one year. The corresponding frequencies for those not treated with tamoxifen were 2/20, 3/11 and 3/23 respectively.

Antineoplastic Agents, Hormonal↗

PubMedDate not supplied

Histopathologic findings in thickened endometria, as measured by ultrasound in asymptomatic, postmenopausal breast cancer patients on various adjuvant treatment including tamoxifen.

Pallents with breast cancer exhibit an increased risk of developing cancer from other organs, a risk that might increase due to tamoxifen treatment. This drug has been found to cause activation of oestrogen receptors, leading to oestrogenic effects on the postmenopausal endometrium. We report follow-up of 94 patients with breast cancer without initial symptoms aged more than 50 years at the time of operation. They were followed-up with vaginal ultrasound at regular intervals and endometrial sampling was performed according to treatment after surgery: tamoxifen, tamoxifen in combination with other regimes and without tamoxifen treatment. A large proportion were investigated prior to treatment. We identified endometrial carcinoma, metastasis of breast carcinoma and histopathological changes in 17/67 (25%) of the patients treated with tamoxifen compared to 1/32 in those not treated with tamoxifen.

Breast Neoplasms↗