Biomedical subjects

U Stendahl

Publications and source records attributed to U Stendahl.

At least 19 recordsLinked to original sources

PubMed2004

Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to vesicular level.

The local immune privilege of the fetus is created by the placenta. Fas ligand (FasL) expression in trophoblast has been implied as one of the mechanisms of fetal tolerance. However, the expression of membranal FasL by trophoblast has failed to explain this role of FasL. Two objections can be raised: (1) there have been contradictions considering which trophoblast cells, syncytiotrophoblast (ST) or cytotrophoblast, express FasL; (2) in vivo and in vitro studies have shown that the membranal form of FasL evokes inflammatory response and thus may promote fetal rejection. Using different assays and the FasL-specific antibody G247-4 we demonstrate beyond doubt that in vivo, (1) FasL is produced by and stored in the first trimester human ST only and (2) the human ST lacks surface membranal FasL. Instead, FasL, loaded in microvesicles, is stored in cytoplasmic granules. These results complement the recent in vitro studies of the microvesicular form of FasL secretion by cultured trophoblast cells, and suggest that placental FasL is synthesized by villous ST, stored in microvesicular form and secreted as exosomes. Secretion of the exosome-associated form of FasL may be one mechanism by which the placenta promotes a state of immune privilege. Additionally, FasL expression in Hofbauer cells is also demonstrated.

Antibodies↗

PubMed1999

Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer.

BACKGROUND: Infection with the human papillomavirus (HPV) has been established as a cause of cervical cancer, but the association between a positive test for HPV DNA and the risk of the subsequent development of invasive cervical cancer is unknown. METHODS: In a study of women who participated in a population-based screening program for cancer of the cervix in Sweden from 1969 to 1995, we compared the proportion of normal cervical smears (Pap smears) that were positive for HPV DNA among 118 women in whom invasive cervical cancer developed an average of 5.6 years later (range, 0.5 month to 26.2 years) with the proportion of HPV DNA-positive smears from 118 women who remained healthy during a similar length of follow-up (controls). The control women were matched for age to the women with cancer, and they had had two normal Pap smears obtained at time points that were similar to the times of the baseline smear and the diagnosis of cancer confirmed by biopsy in the women with cancer. RESULTS: At baseline, 35 of the women with cancer (30 percent) and 3 of the control women (3 percent) were positive for HPV DNA (odds ratio, 16.4; 95 percent confidence interval, 4.4 to 75.1). At the time of diagnosis, 80 of the 104 women with cancer for whom tissue samples were available (77 percent) and 4 of the 104 matched control women (4 percent) were positive for HPV DNA. The HPV DNA type was the same in the base-line smear and the biopsy specimen in all of the women with cancer in whom HPV DNA was detected at base line. None of the control women had the same type of HPV in both smears. CONCLUSIONS: A single positive finding of HPV DNA in a Pap smear confers an increased risk of future invasive cervical cancer that is positive for the same type of virus as identified earlier.

Adenocarcinoma↗

PubMed1996

Iohexol clearance for renal function measurement in gynaecologic cancer patients.

PURPOSE: To determine a valid and practical routine for glomerular filtration rate measurement in gynaecologic cancer patients. MATERIAL AND METHODS: The established method, endogenous creatinine clearance, was compared to 51Cr-EDTA clearance and contrast medium clearance in 68 women with various gynaecologic carcinomas. Contrast medium clearance was determined in association with conventional urography (iohexal 300 mg I/ml, 40 ml) for evaluation of urinary tract involvement by the tumour. Automated X-ray fluorescence analysis equipment was used for the plasma analysis of iohexol and clearance calculations. Endogenous creatinine clearance and 51Cr-EDTA clearance were determined according to standard routine procedures. Simultaneous determinations of contrast medium clearance and 51Cr-EDTA clearance (n = 33), contrast medium clearance and endogenous creatinine clearance (n = 50), as well as 51Cr-EDTA clearance and endogenous creatinine clearance (n = 30) were compared. RESULTS AND CONCLUSION: The mean differences were -2.8 (SD 6.6), -1.8 (SD 22.3), and 2.7 (SD 18.3) ml/min/1.73 m2, respectively. It is concluded that contrast medium clearance is as adequate as 51Cr-EDTA clearance for glomerular filtration rate measurement. We suggest that contrast medium clearance should replace endogenous creatinine clearance, especially in patients referred for urography.

Adult↗

PubMed1996

Doxorubicin-melphalan with and without cisplatin in advanced ovarian cancer--ten-year survival results from a prospective randomized study by the Swedish Cooperative Ovarian Cancer Study Group.

In a controlled prospective randomized study the regimen doxorubicin (A) 40 mg/m2 + melphalan (M) 0.4 mg/kg was compared with A + M + cisplatin (C) 50 mg/m2 given every four weeks in advanced ovarian cancer, FIGO stage III or IV and with serous or anaplastic histology. From 1981 to 1983, 300 patients entered the study and 295 patients were evaluable for response, toxicity and long-term survival. All patients were followed for at least 10 years. The majority of patients had large residual tumours >2 cm. Patients treated with MAC had a higher response rate compared with patients treated with MA (76% vs. 50%, p < 0.01) and treatment with MAC resulted in significantly more pathological complete responders than MA. There was a significant difference in median duration of response (19 months vs. 13 months, p < 0.006) and in median survival time (26 months vs. 19 months, p = 0.05). After 5- and 10 years a significant difference in progression-free and overall survival was found. The independent prognostic factors in this study were residual tumour after primary surgery, treatment with MAC, tumour grade, ascites, and stage. Objective and subjective side effects were significantly worse with MAC, although tolerable. In conclusion, this study shows that incorporating C into MA improves the duration of progression-free survival and overall survival in women with incompletely resected Stage III or Stage IV ovarian epithelial cancer. A 5- and 10-year survival of 25% and 18%, respectively, is impressive.

Adolescent↗

PubMed1995

Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer.

In a seroepidemiological study of incident cervical cancer, 94 cases and 188 population-based controls were used to evaluate the disease-association of IgG and IgA antibody responses against 6 human papillomavirus (HPV) type-16 antigens. Nine of the tested antibody responses were positively associated with cervical cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses most strongly associated with cervical cancer were IgA against E6:10, an epitope derived from the carboxyterminal part of the HPV16 E6 [OR = 15.0, confidence intervals (CI) = 5.9-48.6], IgG against HPV16 virus-like particles (OR = 9.5, CI = 3.9-28.0) and IgG against the E1:19 epitope in the middle part of the E1 protein of HPV16 (OR = 7.7, C1 = 3.9-16.5). When the 3 serological assays that showed the strongest association with cervical cancer were combined, positivity for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that antibody responses to several linear and conformational HPV epitopes are independently associated with cervical cancer and that combined analysis of several HPV antibody responses can result in better predictive values for HPV-associated cancer.

Age Factors↗

PubMed1995

Serum antibody responses against human papillomavirus in relation to tumor characteristics, response to treatment, and survival in carcinoma of the uterine cervix.

To investigate whether the serum antibody responses to human papillomavirus (HPV) in cervical carcinoma were related to the clinical and histopathological features of the tumors and how the antibody responses were affected by treatment, pretreatment serum samples from 66 patients with carcinoma of the cervix were studied for the presence of IgA or IgG responses against six defined HPV epitopes. Posttreatment serum samples were drawn from the same patients 2-24 months after initiation of treatment. There was no significant correlation between pretreatment level of any of the investigated antibodies and clinical stage or differentiation of tumor. For the IgA responses to the epitopes 245:16 and 245:18 in the E2 protein there was a significant correlation between an increased pretreatment antibody level and a shortened survival. A high pretreatment value of IgA against 245:16 was also associated with the absence of any complete response after therapy. The antibody levels declined dramatically after therapy for most of the antigens studied. However, this decline was seen both among the 53 patients with complete remission and among the 13 patients with remaining or progressive disease. Thus, the investigated serological responses were not useful as tumor markers, since patients with progressive, late-stage disease may fail to mount an antibody response to these proteins. However, pretreatment levels of the serological responses to the HPV epitopes 245:16 and 245:18 were associated with prognosis in cervical cancer.

Adolescent↗

PubMed1995

Experiences of the male partner in cervical and endometrial cancer--a prospective interview study.

This article focuses on social, psychological and sexual experiences of 47 men before their partner was treated for cervical or endometrial cancer and 1 year later. As a complement to the interviews the men completed a symptom check-list. Before initiation of treatment, a great majority of the men were in psychological crisis. The number of psychological symptoms decreased from the first to the last interview. Symptoms with psychosomatic character increased, however, considerably. In the endometrial group, several had intrapsychic problems, while interpersonal problems were more common in the cervical group. Both groups found it difficult to know how to behave and how to communicate with their partner, friends and acquaintances. A majority had nobody to whom they could speak honestly, and most did not obtain basic information about their partner's disease. The experiences of intercourse were much more negative after completed treatment and a majority described impaired sexual desire. Provided that the woman herself desires it, the coping and rehabilitation of the woman, the man and the couple would improve if the male were integrated in the care program from the moment the diagnosis of cancer is made.

Adaptation, Psychological↗

PubMed1995

Synergistic interaction between ORM1 and C3 types in disease associations.

In previous studies of orosomucoid (ORM) types and disease the ORM1 1 type has been found to be associated with sarcoidosis and other immunogenetic diseases, and the ORM 1 2 type with different types of carcinomas. We report significant associations between ORM1 and C3 types in sarcoidosis and breast cancer, but not in healthy individuals. The ORM1 1 and C3S variants in combination increased the risk of sarcoidosis, and the ORM1 2 and C3F variants together gave an increased risk of breast cancer. A probable mechanism may be that the ORM1 and C3 molecules modify the immune response by interacting with the lymphoid cell surface.

Alleles↗

PubMed1994

A population-based seroepidemiological study of cervical cancer.

The epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of HPV and cervical cancer in the counties of Västerbotten and Norrbotten in Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood bank. IgG and IgA antibodies were measured against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis, cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and 2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR = 3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or bovine papillomavirus were, on their own, not significantly associated with cervical cancer, but seropositivity against multiple infections was associated with a successively increased relative risk. An increased risk was also found for IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The results indicate that several HPV antibodies are strongly associated with cervical cancer, providing further seroepidemiological support for an etiological role of HPV in cervical cancer.

Adult↗

PubMed1993

The influence of progesterone and androgens on the growth of endometrial carcinoma.

BACKGROUND: The prognosis for endometrial cancer is correlated to the proliferative activity, expressed as the fraction of cells in the synthesis phase (S-phase fraction [SPF]). Progesterone has an antiproliferative effect on the normal endometrium. Its effect in endometrial adenocarcinoma has not been investigated in such detail. METHODS: The SPF in tumor tissue and serum levels of progesterone, androstenedione, and testosterone were measured in 78 postmenopausal women with the diagnosis of endometrial adenocarcinoma. RESULTS: No correlations were found between the SPF and androstenedione or testosterone level. No linear correlation between the progesterone concentration and the SPF was revealed when all the patients were analyzed. The material was then divided into subgroups according to the tumor grade and ploidy level. A stepwise analysis based on the progesterone concentration showed that, in well-differentiated and moderately differentiated tumors, the growth rate, expressed as the SPF, fell when progesterone reached a serum level above 0.8 nM. CONCLUSIONS: Endogenous progesterone plays a role in the control of the tumor's proliferation activity and, consequently, might be significant in the prognosis.

Adenocarcinoma↗

PubMed1993

Steroid production in different parts of malignant and benign ovarian tumors in vitro.

Pieces of ovaries and tumors from 45 patients (19 with malignant epithelial tumors, 14 with benign epithelial tumors, and 12 with normal postmenopausal ovaries) were incubated, and the release of steroid hormones from different parts of the tumors and from the contralateral ovaries was measured. Tumor tissue (mainly tumor cells with a small number of stromal cells), tumor base tissue (more stromal cells than tumor cells), and control ovaries were preincubated in oxygenated 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-minimum essential medium buffer at 37 degrees C for 30 min followed by a 3-h incubation in fresh, oxygenated medium. Progesterone, androstenedione, testosterone, and estradiol were measured in the medium by radioimmunoassay at the end of the incubation period. Malignant tumors released more progesterone and androstenedione than benign tumors or postmenopausal control ovaries. In contrast, benign tumors released more testosterone than malignant tumors or control ovaries. Release of estradiol was low and not significantly different among control ovaries and malignant and benign tumor tissue. Different parts of the tumors differed in steroid hormone release. Tissue samples containing more tumor cells than stromal cells released more progesterone than those with predominantly stromal cells. Thus, malignant tumors had an active steroid secretion. Progesterone was the main steroid released.

Adult↗

PubMed1993

Prognostic significance of S-phase fraction as measured by DNA flow cytometry in gynecologic malignancies.

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Adenocarcinoma↗

PubMed1993

Radioimmunodetection of ovarian cancer.

Radioimmunoscintigraphy (RIS) is a potentially valuable method for the detection of primary, secondary and recurrent malignant tumours. Antigens that have been used for monitoring as well as for RIS of ovarian carcinomas include CA 125, PLAP, HMFG, and CA 19-9. Between 70 and 100% of the tumours have been detected at RIS when these antigens have been used. Conventional methods, e.g., computerized tomography (CT) and ultrasonography (US), demonstrate similar or lower detection rate than RIS for tumour diagnosis. RIS gives additional information to conventional radiological methods (CT and US) for the detection of occult ovarian carcinomas. A review of earlier investigations is given and our own recent results using PLAP as a target antigen are presented. The future potential of the technology is discussed.

Adult↗

PubMed1993

Alternative technologies to generate monoclonal antibodies.

Several new technologies to generate and modify established hybridomas that produce monoclonal antibodies have recently been presented and further development should make them more suitable for diagnostic and therapeutic techniques. Different proteolytic procedures have been used for the fragmentation of intact antibodies to Fab2' and Fab fragments and recombinant DNA techniques have made it possible to obtain chimeric, humanized, Fv fragments and single-chain Fvs. A review of the new approaches is presented and the future implications are discussed.

Animals↗

PubMed1993

Management of recurrent cervical cancer: the place of ultra-radical surgery.

Although mortality from cervical cancer has decreased substantially the incidence of recurrent disease, at 35-50%, remains unaltered. Many more young patients are seen with recurrent cervical cancer today. This paper reviews this problem--its diagnosis and available modes of treatment. The place of re-irradiation, chemotherapy and ultra-radical surgery are discussed and their limitations highlighted. Better patient selection and individualised treatment planning are emphasised. Newer, more objective prognostic indicators based on molecular understanding of cancer cells are mentioned as hopeful means through which patient selection and treatment could be improved in the future. In the developing world where persistent or recurrent disease is more common, the situation is unlikely to improve soon.

Antineoplastic Agents↗

PubMed1992

Immunohistochemical study of the human 17 beta-hydroxysteroid dehydrogenase and steroid receptors in endometrial adenocarcinoma.

17 beta-Hydroxysteroid dehydrogenase (17HSD) and estrogen (ER) and progestin (PR) receptors were analyzed immunohistochemically in tissue specimens of 66 patients with endometrial adenocarcinoma. Plasma steroid concentrations were correlated to immunohistochemical data. 17HSD was detected in 48% of the specimens and was stained in the cytoplasm of epithelial cells. The tissues were characterized by a heterogeneous staining pattern for 17HSD. In some patients, intensively stained epithelial cell clusters were seen, indicating that local factors were responsible for the expression of the protein. Poorly differentiated adenocarcinoma specimens tended to have no 17HSD more frequently than did well or moderately differentiated tissues. ER and PR were detectable in 24% and 28% of patients, respectively, and were localized in the nuclei of epithelial and stromal cells. There was a significant correlation between 17HSD and PR staining and an inverse correlation between plasma progesterone concentrations and 17HSD staining. This is contrary to the data obtained with normal endometrium. The main reason for this inverse relation between endometrial 17HSD staining and plasma progesterone concentrations was that, in some postmenopausal patients with low plasma progesterone concentrations, intense staining for 17HSD was detectable in the endometrial carcinoma specimens. This indicates a major difference in the regulation of 17HSD expression in endometrial adenocarcinomas, compared with normal tissues of premenopausal women.

17-Hydroxysteroid Dehydrogenases↗

PubMed1992

Surgical management of intestinal complications of radiotherapy for gynecological malignancies.

Sixty patients treated for gynecological malignancies with radiation therapy and operated upon because of late intestinal complications of the treatment were studied. Among patients irradiated for cervical carcinoma an incidence of 3.2% of operated intestinal lesions was encountered. Fifty-nine per cent of the women had a history of previous pelvic inflammatory disease on pelvic surgery. The most common symptoms leading to surgery were mechanical subileus/ileus, pain and fistulas. The majority of patients (53%) were operated upon within 2 years after irradiation, but an interval up to 20 years was recorded. 50% were operated upon within 2 years after irradiation, but an interval up to 20 years was recorded. 50% were reoperated during follow-up. Intestinal resections (38%) and by-passes (15%) were the most frequent surgical procedures at first operation. 57% of the patients were operated upon due to acute conditions and 31% were due to chronic problems, 12% due to tumour suspicion. An operation mortality rate of 5% was found. No obvious correlation could be seen between accumulated irradiation dose and severity of complications. The results of surgical intervention and complications are analysed and different strategies in handling these patients discussed.

Adult↗

PubMed1991

Prognostic flow cytometric information in cervical squamous cell carcinoma: a multivariate analysis of 307 patients.

In a prospective study of 307 patients with invasive squamous cell carcinoma of the uterine cervix, the prognostic impact of flow cytometric parameters (ploidy level and the fraction of S-phase cells) and clinical variables was evaluated using univariate and multivariate analyses (Cox model). Mean follow-up time as 39 (4-84) months. A total of 93 patients died from their disease during the follow-up. The S-phase fraction was evaluable in 242 cases. By means of univariate models, lethality rate was found to increase significantly with increasing age, postmenopausal status, advancing stage, and increasing S-phase fraction. In a multivariate analysis of the clinical variables of age, stage, and grade, only clinical stage was prognostic. The inclusion of ploidy level in the analysis gave no additive prognostic information. In a multivariate analysis including all variables mentioned above, stage was the strongest predictor of survival. S-phase fraction was significantly related to survival both when studied as a continuous variable (P = 0.006) and when studied as a categorized variable (10, 15, 20% as cutoff points), and in this special analysis ploidy level was of prognostic interest with a poorer survival for near-diploid cases. The outcome was poorer with increasing age. The prognostic impact of the S-phase fraction remained highly significant in separate analyses of the clinically interesting stages Ib-IIb (P less than 0.001). We conclude that measurement of the S-phase fraction is of prognostic interest and may be used for the identification of high-risk patients within a given stage, whereas ploidy level yields little information.

Adult↗