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S Grenman

Publications and source records attributed to S Grenman.

32 records · Page 2Linked to original sources

Immunohistochemical localization of syndecan-1 in normal and pathological human uterine cervix.

Expression of syndecan-1, a cell surface proteoglycan that binds growth factors and extracellular matrix components, was studied in normal and pathological human uterine cervix using immunohistochemical methods. Normal cervical squamous epithelium showed positive staining for syndecan-1 in all cell layers, except the basal cell layer, whereas endocervical columnar epithelium stained weakly. In non-neoplastic reactive lesions, metaplastic squamous cells were positive for syndecan-1, whereas columnar cells showed weak or negative staining. In cervical condylomas, cells showing koilocytotic atypia were positive for syndecan-1. The progression of cervical intraepithelial neoplasia (CIN) grade I to grade III was associated with reduced syndecan-1 expression and localization of syndecan-1 to more superficial cell layers. In squamous cell carcinomas (SCCs), syndecan-1 expression correlated with histological differentiation, being absent from most poorly differentiated tumours. The results suggest that loss of syndecan-1 from atypical cells is an early event during cervical carcinogenesis and show a close association of syndecan-1 expression with preserved epithelial morphology and differentiation.

Carcinoma, Squamous Cell↗

Imaging of uterine carcinoma by carbon-11-methionine and PET.

UNLABELLED: L-[methyl-11C]methionine ([11C]methionine) is probably one of the most useful positron-emitting tracers for metabolic imaging of human cancer. In this study, we investigated whether human uterine cancer can be imaged with [11C]methionine and PET. METHODS: Fourteen patients with primary uterine malignancy participated in the study. Eight patients had endometrial carcinoma and six had cervical carcinoma. The normal endometrium was analyzed in four additional patients with no uterine malignancy and in one patient with cervical cancer. Tracer uptake was quantitated by calculating both the standardized uptake values (SUVs) and the kinetic influx constants (Ki values) for the tracer. RESULTS: All patients with either cervical or endometrial carcinoma had increased uptake of [11C]methionine in the PET image. The mean SUV of the carcinomas was 8.4 (n = 13; s.d., 1.5) and the mean Ki was 0.15 min-1 (n = 12; s.d., 0.08 min-1), whereas the mean SUV of the normal endometrium was only 4.6 (n = 5; s.d., 0.8). Histologically poorly (Grade III) or moderately (Grade II) differentiated endometrial carcinomas accumulated more [11C]methionine than the well-differentiated (Grade I) ones (p = 0.04 for the SUVs, and p = 0.05 for the Ki values). There were also variable physiological accumulations of [11C]methionine in the pelvis. CONCLUSIONS: Uterine carcinoma accumulated [11C]methionine more than the normal endometrium. However, the physiological accumulations of [11C]methionine in the pelvis may confuse the interpreter of the PET image; thus, morphological imaging also needs to be performed as a reference to localize the tumor accurately. We conclude that human uterine carcinoma can be effectively imaged with [11C]methionine and PET.

Adenocarcinoma↗

Maternal weight, weight gain during pregnancy and pregnancy outcome.

OBJECTIVE: To evaluate the effects of abnormal maternal weight or weight gain on pregnancy outcome. METHOD: Records for 191 mothers with abnormal prepregnancy weight (> or = 20%) above, or under, ideal body weight for height) or weight gain > or = 20 kg, or < or = 5 kg during pregnancy were reviewed. The control group consisted of 166 mothers with normal prepregnancy weight and normal weight gain during pregnancy. Data on mothers and their infants were analyzed by one-way analysis of variance. RESULTS: Obese women and mothers with excessive weight gain during pregnancy had an increased incidence of induced labor (P < or = 0.05) and tendency for emergency cesarean sections during the delivery. Obese women had more large-for-date babies than controls (P < or = 0.05). Weight gain < or = 5 kg during pregnancy was most common in slightly obese women and did not carry any special obstetric or neonatal risk. Underweight women had a significant risk for delivering a small-for-data baby. CONCLUSION: Obese women and women with excessive weight gain during pregnancy need special follow-up and counseling during pregnancy and delivery. Underweight women may need prepregnancy nutritional counseling to guarantee normal fetal growth. In developed countries suboptimal weight gain (< or = 5 kg) during pregnancy seems not to need any medical intervention.

Adult↗

Effects of the antiestrogen toremifene on growth of the human mammary carcinoma cell line MCF-7.

The effects of toremifene, a new antiestrogenic drug, were investigated in vitro on the exponentially growing human mammary carcinoma cell line MCF-7. The drug effects were monitored by serial cell counts and DNA flow cytometry. The inhibitory effect of toremifene on MCF-7 became greater as the drug concentration was increased from 1 microM to 10 microM. At 5 microM toremifene induced a large decrease in the relative percentages of S- and G2/M-phase cells, and an increase in the amount of cell debris, indicating increased cell death. After withdrawal of the drug the mammary cancer cells resumed logarithmic growth similar to that of control cells. The effects caused by toremifene were similar to those caused by tamoxifen both in quality and quantity.

Antineoplastic Agents↗

Radiation response of vulvar squamous cell carcinoma (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and A-431) cells in vitro.

Standard therapy for squamous cell carcinoma (SCC) of the vulva consists of radical surgery and inguinal node dissection. Radiation therapy has been used for preoperative treatment in advanced cases to reduce the size of the tumor, and also as the only treatment in inoperable or recurrent disease. To study the inherent radiation sensitivity of vulvar carcinoma, we tested three new vulvar carcinoma cell lines and the long-established cell line A-431 by using a 96-well plate clonogenic assay, earlier shown by us to be suitable for survival studies of SCC. SCC and adenocarcinoma cell lines derived from other sites were used as a reference. Cells were irradiated with a 4-MeV linear accelerator at a dose rate of 2.0 Gy/min. The vulvar cell lines were found to be highly resistant to radiation with the average mean inactivation dose of 3.44 +/- 0.34 Gy as calculated from the area under the curve. The results were consistent in repeated experiments and for all cell lines. The average value for area under the curve was 1.79 +/- 0.30 for the other SCC lines tested. The values for area under the curve differed significantly (P less than 0.0001) between the vulvar lines and reference SCC lines. These results indicate that vulvar SCC cells in vitro express exceptional inherent radioresistance, and thus development of other forms of additional treatment would be more advantageous in advanced cases.

Carcinoma, Squamous Cell↗

In vitro response of cervical cancer cell lines CaSki, HeLa, and ME-180 to the antiestrogen tamoxifen.

The effect of tamoxifen, a nonsteroidal antiestrogenic drug, on the in vitro growth of three cell lines derived from carcinoma of the uterine cervix (HeLa, CaSki, ME-180) was studied using the breast cancer cell line MCF-7 as a tamoxifen-sensitive control. Logarithmically growing cells were fed daily with medium containing 5% dextran-charcoal-treated fetal bovine serum (D5) and 0, 1, 2.5, 5, 7.5, or 10 microM tamoxifen. The cell number in replicate cultures was assessed every other day by cell counts. Growth inhibition was expressed as the percentage of the cell number in control cultures fed with D5. At a concentration of 5 microM tamoxifen, a clear decrease in cell proliferation, resulting in 66-74% inhibition of growth, was observed with MCF-7, HeLa, and ME-180 after 6 days of exposure to tamoxifen. Doses greater than 5 microM resulted in cytotoxicity and progressive cell loss. With the CaSki cell line, 2.5 microM tamoxifen induced more than 60% growth inhibition and 5 microM tamoxifen was cytotoxic. Tamoxifen-induced growth inhibition was reversed by removing tamoxifen from the cell cultures, and the cells resumed logarithmic growth after a lag period of 24-48 hr. MCF-7, but not the cervical carcinoma, lines required estradiol for complete and rapid recovery of logarithmic growth. Our results indicate that tamoxifen inhibits cell growth of these cervical carcinoma cell lines by a mechanism different from that in MCF-7.

Breast Neoplasms↗

The effect of a short-term ritodrine treatment on the concentration of beta-adrenergic receptors in human myometrium.

The concentration of beta-adrenoceptors in human myometrium has been studied of women giving birth by elective cesarean section at term. Eight of the woman were treated with intravenous ritodrine two hours prior to the operation. In the control group seven women received physiological saline with the same infusion rate as ritodrine in the study group. The concentration of beta-receptors in the myometrium of the lower uterine segment was determined with radioligand binding assay. Ritodrine treatment decreased the available beta-receptors significantly.

Female↗

Steroid receptors and response of endometrial cancer to hormones in vitro.

The sensitivity to medroxyprogesterone acetate (MPA) and tamoxifen (T) and their combination was assayed in 13 patients with untreated endometrial cancer by an in vitro ATP-bioluminescence method. The method measures the levels of adenosinetriphosphate (ATP), the basic energy source of living cells. A tumor was considered to respond to the drug, if the proportion of living cells after manipulation was 50% or less from unmanipulated control culture. Estrogen (ER) and progesterone (PR) receptors were assayed by the DCC-method and the results calculated by Scatchard-analysis. ER (greater than or equal to 3 fmol/kg cytosol protein) was present in all tumors and PR (greater than or equal to 10 fmol/kg cytosol protein) in 85% of the tumors. The response rate in vitro to MPA was 67% (8 out of 12 tumors), to T 18% (2 out of 11) and to their combination 69% (9 out of 13). The G1 tumors responded statistically significantly better to MPA (p less than 0.01) and MPA + T (p less than 0.02) as compared to T. MPA produced higher cell kill of G1 than G2 tumors (p less than 0.05). The ER content correlated with the effect of MPA in vitro in 67%, with the effect of T in 18% and with that of their combination in 69% of the tumors. The PR content correlated with the effects of MPA in vitro in 83%, with the effect of T in 36% and with that of their combination in 54% of the tumors. It was concluded that the in vitro ATP-bioluminescence method provides valuable information besides steroid receptor determinations for sensitivity testing of endometrial cancer to hormones.

Adenocarcinoma↗

Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction.

To examine hormonal status in obese, gynecologically normal women we studied 25 regularly menstruating, massively obese (mean weight, 120 kg) women participating in a weight reduction program and 25 age-matched normal weight (mean weight, 60 kg) women. Serum 17 beta-estradiol (E2), estrone (E1), androstenedione (A), dehydroepiandrosterone sulfate, testosterone, LH, FSH, PRL, and cortisol concentrations were measured during the follicular phase of the menstrual cycle. Waist to hip ratio and abdominal fat cell size were measured at the beginning of the study. The serum levels of E2 (P less than 0.04) as well as those of A, SHBG, and LH (P less than 0.002) were lower in the obese group. Consequently, the testosterone to SHBG ratio and the E1 to A ratio were higher and the LH to FSH ratio was lower in this group. Waist to hip ratio did not correlate with the levels of circulating hormones or SHBG, but an inverse correlation was found between abdominal fat cell size and A as well as the LH to FSH ratio in the nonhirsute women of the obese group. Subsequent to moderate weight reduction (13.2 kg), serum A and E1 levels (P less than 0.01) increased, and serum cortisol levels decreased (P less than 0.001). Thus, massive obesity is associated with abnormalities in hormonal balance in gynecologically symptomless women, there being an association between E1, E2, A, LH, cortisol, and relative weight and/or abdominal fat cell size.

Adipose Tissue↗

Diagnostic aspects of primary tubal malignancy.

Eleven cases of primary tubal malignancy are reported to characterize clinical symptoms and diagnostic procedures. The importance of a yellow vaginal discharge is emphasized as being a diagnostic sign.

Adenocarcinoma, Papillary↗

Epidural and paracervical blockades in obstetrics. Catecholamines, arginine vasopressin and analgesic effect.

A comparative study of analgesic and endocrinologic effects of obstetrical epidural anesthesia (EA, n = 23) and paracervical block (PCB, n = 39) was performed. Pain intensity was assessed on a horizontal linear scale. Simultaneously, blood samples for the determination of concentrations of norepinephrine (NE), epinephrine (E) and arginine vasopressin (AVP) were obtained. NE and AVP levels did not bear any relationship to pain scores. Instead, the average plasma E profile during labor was practically identical with the profile of pain scores. Plasma levels of E decreased significantly after EA. A similar but short-lived effect was observed also after PCB. When comparable doses of bupivacaine were used (30 mg in the EA group and 25 mg in the PCB group); initial pain relief after EA and PCB was similar, though after 30 min the pain score increased for patients who received the PCB, while patients who received EA had continued pain relief. Faster absorption of bupivacaine was observed after paracervical than epidural injection. Decreased variability was seen in the fetal cardiograms in 25% after EA and in 33% after PCB. Transient bradycardia was observed in 2 cases after paracervical injection.

Adult↗

Ovarian cancer and gonadotropins in vitro: new evidence in favor of independence.

BACKGROUND: The aim of this study was to investigate whether newly established epithelial ovarian carcinoma cell lines secrete inhibins, and whether their proliferative and secretory activity can be regulated by gonadotropins. MATERIALS AND METHODS: Three recently characterized human epithelial ovarian carcinoma cell lines were exposed to human choriongonadotropin hCG and follicle stimulating hormone FSH. Cell proliferation was determined by counting. Secretory activity of the cell lines was studied by analyzing inhibin A, inhibin B, inhibin pro-aC, estradiol, progesterone, testosterone, and CA 125 concentrations from the medium. The expression of gonadotropin receptors was studied by RT-PCR. RESULTS: None of the cell lines were found to secrete any of the inhibins, progesterone or testosterone. Only UT-OC-4 cells secreted low levels of estradiol. Gonadotropin receptors were not expressed by any of the cell lines, and accordingly neither FSH nor hCG stimulated the growth of these cells. However, hCG had some dose dependent growth inhibitory effect on UT-OC-3. Passage 42 cells of UT-OC-3 secreted significantly more CA 125 than passages 8 cells (P = 0.000). CONCLUSIONS: The present results suggest that the carcinomatous epithelial cells of the ovary do not secrete inhibins. The serum inhibin levels previously detected in patients with epithelial ovarian carcinoma may therefore reflect an ovarian stromal response to carcinoma. The findings are also in favor of an independence of ovarian cancer of gonadotropins.

CA-125 Antigen↗

Taxane sensitivity of ovarian carcinoma in vitro.

Paclitaxel, the first clinically available taxane, has proven to be effective in the treatment of ovarian carcinoma. Docetaxel is the second taxoid derivative which has also shown activity in ovarian carcinoma. These two compounds have clear differences in pharmacokinetics and side-effects. In the present study we have tested the cytotoxic effect of docetaxel in seven ovarian carcinoma cell lines using the 96-well plate clonogenic assay. These results have been compared with data obtained from our recent study on cisplatin and paclitaxel sensitivities of the same cell lines. Chemosensitivity has been expressed as IC50 value, the drug concentration causing 50% inhibition of clonogenic survival. The IC50 values for docetaxel were 0.23-2.30 nM showing a 10-fold difference between individual cell lines. On a molar basis, docetaxel was 1.2 to 2.6 times more active than paclitaxel in six out of seven cell lines. This may be explained by differences in the mechanism of action or by differences in other pharmacological properties.

Adenocarcinoma↗