Search PubMed⌕ Search

Biomedical subjects

F Pettersson

Publications and source records attributed to F Pettersson.

At least 19 recordsLinked to original sources
PubMed2006

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment.

Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation - time of flight - mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches.

Animals↗
PubMed2002

Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax.

All-trans-retinoic acid and 9-cis-retinoic acid have been reported to have inhibitory effects on pancreatic adenocarcinoma cells and we have shown that this is partly due to induction of apoptosis. In this study, the mechanisms whereby 9-cis-retinoic acid induces apoptosis in these cells were investigated. An involvement of the Bcl-2 family of proteins was shown, such that 9-cis-retinoic acid causes a decrease in the Bcl-2/Bax ratio. Overexpression of Bcl-2 also resulted in inhibition of apoptosis induced by 9-cis-retinoic acid. Furthermore, two broad-range caspase inhibitors blocked DNA fragmentation induced by 9-cis-retinoic acid, but had no effect on viability defined by mitochondrial activity. Using synthetic retinoids, which bind selectively to specific retinoic acid receptor subtypes, we further established that activation of retinoic acid receptor-gamma is essential for induction of apoptosis. Only pan-retinoic acid receptor and retinoic acid receptor-gamma selective agonists reduced viability and a cell line expressing very low levels of retinoic acid receptor-gamma is resistant to the effects of 9-cis-retinoic acid. A retinoic acid receptor-beta/gamma selective antagonist also suppressed the cytotoxic effects of 9-cis-retinoic acid in a dose-dependent manner. This study provides important insight into the mechanisms involved in suppression of pancreatic tumour cell growth by retinoids. Our results encourage further work evaluating the clinical use of receptor subtype selective retinoids in pancreatic carcinoma.

Adenocarcinoma↗
PubMed2001

Retinoic acid enhances the cytotoxic effects of gemcitabine and cisplatin in pancreatic adenocarcinoma cells.

INTRODUCTION: Retinoids, which are derivatives of vitamin A, are important factors involved in the control of biologic functions such as cell growth and differentiation, development, and carcinogenesis. We have shown previously that the naturally occurring retinoids all-trans-retinoic acid (ATRA) and 9-cisretinoic acid (9cRA) induce growth inhibition followed by apoptosis in pancreatic adenocarcinoma cells in vitro. AIM: To evaluate the efficacy of retinoids in combination with the chemotherapeutic drugs gemcitabine and cisplatin. METHODOLOGY: In vitro growth inhibition and induction of apoptosis by different combinations of retinoids and cytotoxic drugs were studied by using the T3M-4 and BxPc-3 cell lines. For in vivo studies, T3M-4 cells were injected subcutaneously in nude mice. RESULTS: Pre-treatment of pancreatic adenocarcinoma cells with ATRA or 9cRA before the addition of the drugs resulted in significant reduction in cell number compared with treatment with the drugs alone. Pre-treatment with 9cRA followed by gemcitabine or cisplatin alone also resulted in a strong increase in the percentage of cells undergoing programmed cell death, or apoptosis. Furthermore, there was an indication that the combination of ATRA and gemcitabine caused increased apoptosis in vivo. CONCLUSION: Our results clearly suggest the need for additional studies exploring the potential role of the combination of retinoids and gemcitabine in the management of pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors.

The sequestration of Plasmodium falciparum-infected erythrocytes (pRBC) away from the peripheral circulation is a property of all field isolates. Here we have examined the pRBC of 111 fresh clinical isolates from children with malaria for a number of adhesive features in order to study their possible coexpression and association with severity of disease. A large number of adhesion assays were performed studying rosetting, giant rosetting, and binding to CD36, intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, thrombospondin, heparin, blood group A, and immunoglobulins. Suspension assays were performed at the actual parasitemia of the isolate, while all the static adhesion assays were carried out at an equal adjusted parasitemia. The ability to bind to multiple receptors, as well as the ability to form rosettes and giant rosettes, was found to be more frequent among isolates from children with severe versus mild malaria (P = 0.0015). Rosettes and giant rosettes were more frequent for children with severe malaria, and the cell aggregates were larger and tighter, than for those with mild disease (P = 0.0023). Binding of immunoglobulins (97% of isolates) and of heparin (81% of isolates) to infected erythrocytes was common, and binding to heparin and blood group A was associated with severity of disease (P = 0.011 and P = 0.031, respectively). These results support the idea that isolates that bind to multiple receptors are involved in the causation of severe malaria and that several receptor-ligand interactions work synergistically in bringing about severe disease.

Animals↗
PubMed2001

Carcinoma of the cervical stump. The radiumhemmet series 1959-1987. Treatment and prognosis.

BACKGROUND: The purpose of this retrospective study is to evaluate the longterm prognosis for cervical stump cancer compared to matched controls with cancer in an intact uterus. METHODS: From 1959 to 1987, 145 patients were treated for an infiltrating carcinoma of the cervical stump at Radiumhemmet representing 2.2% of all cervical cancers. Three control cases to each case were selected from the cohort of cervical carcinoma cases - matched to year of treatment, stage, histology and age (plus, minus 2 years). Actuarial survival was calculated for cases and controls. Survival differences were analyzed with the Kaplan-Meier technique. The age distribution for cases ranged between 36 and 84 years with a mean age of 60.6 years. The mean age for the control series is 9 years of age (range 35-86 years). Among the cases 87.6% were squamous cell carcinoma and 12.4% were adenocarcinomas. Treatment of carcinoma of the uterine stump at Radiumhemmet followed the same modality as was practised for ordinary cervical cancer cases i.e. two brachyradium applications with 3 weeks interval followed by external irradiation. The dose of irradiation from the intracavitary application given to the stump cancers was lower than that given to comparable cases of the common cervical cases. RESULTS: No evidence was found of poorer longterm prognosis for radiologically treated squamous cell carcinoma of the uterine stump compared to that of the ordinary cervical carcinomas. Stump cancers of the adenocarcinoma type had a worse prognosis than adenocarcinomas in an intact uterus (p<0.07) and also compared with stump cancers of the squamous epithelial type (p=0.05). The complication rate was higher for the stump cancer cases compared with that for cervical cancers in intact uterus. The mean time interval from subtotal hysterectomy to the stump cancer diagnosis was 17.6 years with a range from 1 to 46 years. CONCLUSIONS: Recent discussions argue for a better sexual function after subtotal hysterectomy. Our study gave no convincing argument in terms of poorer prognosis for radiologically treated carcinoma of the uterine stump compared to that of the total cervical cancer series. It is thus necessary to weigh the possible gains with subtotal hysterectomy against the relatively low risk to fall victim of a stump cancer. Complications following surgery, as well as possible physiologic and sexual functions of the cervix, should be taken into account.

Adenocarcinoma↗
PubMed2000

Differential and antagonistic effects of 9-cis-retinoic acid and vitamin D analogues on pancreatic cancer cells in vitro.

Retinoids and vitamin D are known to exert important anti-tumour effects in a variety of cell types. In this study the effects of 9-cis-retinoic acid (9cRA) the vitamin D analogues EB1089 and CB1093 on three pancreatic adenocarcinoma cell lines were investigated. All compounds caused inhibition of in vitro growth but the vitamin D analogues were generally the more potent growth inhibitors. They were also more effective on their own than in combination with 9cRA. Growth arrest correlated with an increased proportion of cells in the G0/G1 phase. Apoptosis was induced in the three cell lines by 9cRA, whereas neither EB1089 nor CB1093 had this effect. Furthermore, addition of EB1089 or CB1093 together with 9cRA resulted in significantly reduced apoptosis. Our results show that retinoic acids as well as vitamin D analogues have inhibitory effects on pancreatic tumour cells but different and antagonistic mechanisms seem to be employed.

Alitretinoin↗
PubMed1996

Delay in diagnosis of epithelial ovarian cancer.

OBJECTIVES: To investigate and analyze the process from first recognition of symptom(s) to final diagnosis at operation in patients with ovarian epithelial cancer. METHOD: The medical records of 160 women with ovarian cancer were studied and traced back to the doctor first consulted, in order to obtain information on patient- and doctor-related delay. RESULTS: Symptom duration was 12 weeks in patients with serous tumors and 7 weeks in patients with other histopathological classes; 56% were diagnosed within 4 weeks. Women in stages I and II were diagnosed faster than those in stages III and IV; 4% were diagnosed within 3 days because of an emergency operation; 30% were not diagnosed within 8 weeks. CONCLUSION: Diagnosis of ovarian cancer is difficult due to the vagueness of the symptoms which mislead both patients and doctors. Methods to enable earlier diagnosis must be sought.

Adult↗
PubMed1995

Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study.

A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

Aged↗
PubMed1993

Symptoms and diagnostic difficulties in ovarian epithelial cancer.

OBJECTIVE: To investigate and analyze symptoms in patients with different types of ovarian cancer. METHOD: Records of 160 women with ovarian cancer were studied in detail following the patients from first consultation to operation and diagnosis at Sodersjukhuset, Stockholm. RESULT: No specific group of symptoms could be linked to type or stage of ovarian cancer. Gastrointestinal symptoms were more common in patients with class 1C tumors. Only 21% complained of gynecological symptoms. Women with class 1C cancer had significantly more advanced disease than those with 2C-5C cancer as 77% had a stage III-IV tumor compared with 40% of class 2C-5C patients. CONCLUSION: Diagnosis of ovarian cancer is difficult due to the multitude of symptoms often appearing late in the disease. The majority of women did not experience symptoms in the genital organs. Methods to encourage early consultation should be investigated.

Adult↗
PubMed1991

Medical induction prior to surgical evacuation of hydatidiform mole: is there a greater risk of persistent trophoblastic disease?

A retrospective study was undertaken to assess whether stimulation of uterine contractility prior to surgical evacuation of a molar pregnancy will lead to an increased frequency of persistent trophoblastic disease. Forty-seven patients treated with chemotherapy for persistent trophoblastic disease after a hydatidiform mole between 1971 and 1988 were evaluated. The use of medical methods in this study group was compared to a control group of 219 patients with hydatidiform mole not requiring further treatment. A medical method, mainly treatment with prostaglandins, was used in 61.7% in the study group compared to 35.2% in the control group. This difference was, however, due to different stage distribution in the groups. Persistent disease was significantly correlated to uterine size and medical methods were mainly used in patients where uterine size corresponded to 15 weeks gestation or more. In this subset of patients, a medical method was used in the same frequency in both groups. Thus, large uterine size seems to be an independent risk factor. We conclude that stimulation of uterine contractility, which in Sweden is frequently used before surgical evacuation of the uterus in patients with hydatidiform mole and large uteri, carries no additional risk.

Adolescent↗
PubMed1991

Efficacy of cervical cancer screening.

The earlier optimistic predictions that invasive carcinoma of the uterine cervix could be totally eradicated by means of Pap screening have failed. Experiences from different countries give evidence, however, that a considerable reduction of incidence and mortality can be gained with this type of secondary prevention. Improved knowledge of the epidemiology of carcinoma of the uterine cervix and of its natural history could be anticipated to give a better basis for the planning of preventive measures. Maintenance of a high laboratory standard, a good technique for taking of smears, and improved communications between laboratories and the doctor or nurse taking the smear and the doctor or clinic performing the treatment and an adequate reaction to the report from the laboratory with adequate treatment of the precancerous stages is supposed to improve the effect of the screening programmes.

Female↗
PubMed1990

Leukemia following chemotherapy for ovarian cancer.

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.

Antineoplastic Agents↗
PubMed1990

Mixed müllerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases.

One hundred and forty-seven women with uterine mixed Müllerian tumours (UMMT) treated at Radiumhemmet from 1936 through 1981 were reviewed. The prognostic value of clinical and histopathologic data was analysed with bivariate and multivariate techniques. Stage, age and abdominal pain were found to be significant predictors of survival. Surgery and combined radiotherapy (intracavitary + external irradiation) gave in stage I, a lower local failure rate (p = 0.006) and better overall survival (p = 0.001) than surgery in combination with either intracavitary or external irradiation.

Adult↗
PubMed1990

Cardiovascular death after radiotherapy for benign bleeding disorders. The Radiumhemmet metropathia cohort 1912-1977.

Of 788 women treated with ionizing irradiation for benign bleeding disorders (metropathia) 308 (39%) died of cardiovascular disease. In a control group, consisting of 1219 women with metropathia who were not irradiated, 257 (21%) cardiovascular deaths occurred. Although the risk of cardiovascular death in the two studied cohorts compared with national death rates was only 0.92 (lower limit 0.82; upper limit 1.03) and 0.88 (lower limit 0.78; upper limit 0.99) respectively, it was found that women irradiated before the menopause (age 50 years) run a higher risk of cardiovascular death than the controls in the same age group and those irradiated after the menopause.

Adult↗
PubMed1990

Second primary cancer after treatment of invasive carcinoma of the uterine cervix, compared with those arising after treatment for in situ carcinomas. An effect of irradiation? A cancer registry study.

A cancer registry cohort of 16,704 cases of invasive carcinoma of the uterine cervix and 56,116 cases of in situ carcinomas of the uterine cervix was followed up and second new primary cancers were recorded. The invasive carcinomas contributed 127,118 woman-years at risk and the in situ carcinomas contributed 453,362 woman-years at risk. The main treatment for the invasive carcinomas had been radiotherapy and for the in situ carcinomas, conization and other types of surgical intervention. 767 new primaries occurred after treatment of invasive carcinoma of the uterine cervix, compared with 644.5 expected. O/E is 1.19. After the in situ carcinomas, 1,421 malignant tumors were observed, vs. 1,188.0 expected (O/E 1.19). If, however, cases of invasive carcinoma of the uterine cervix after in situ carcinomas are excluded, the ratio observed/expected is 1.10. For some sites the increased observed/expected ratios were found after both invasive and in situ carcinomas, which speaks for some common carcinogenic effect other than irradiation (for instance, in bronchus and trachea, pharynx, nose, sinus and larynx, but also in rectum, urinary bladder, other female genital organs, pancreas, lymphosarcoma, as well as acute and non-lymphatic leukemia). A lower risk than expected--after both in situ and invasive carcinoma of the uterine cervix--is observed for breast cancer, cancer of the corpus uteri and for multiple myeloma. However, analyses based on time since treatment provide evidence of a carcinogenic effect of irradiation, especially in intensively irradiated organs such as bladder, rectum, corpus uteri and ovary, and also for acute and non-lymphatic leukemia.

Adult↗
PubMed1990

Malignant disease after radiation treatment of benign gynaecological disorders. A study of a cohort of metropathia patients.

One hundred and seven cases of malignant tumours occurred among 788 women irradiated 1912 to 1977 for metropathia. One hundred and seventy-three women out of 1,219 referred for the same diagnosis and not irradiated developed a malignant tumour. The tumours were diagnosed between 1958 and 1982. The relative risk of malignant tumours among the irradiated women was 1.22 and among the non-irradiated 1.09 compared to cancer registry data. A statistically non-significant increase of the relative risk was found in the irradiated patients for tumours of the rectum (1.58), colon (1.46), and the nervous system (1.67). A decreased overall relative risk was seen for cancer of the breast (0.92) after irradiation, but women treated at the age of 50 or more had an increased risk (2.08). The relative cancer risk of the heavily irradiated sites was not increased during the first 20 years after irradiation, but a statistically significant increase of the risk was seen after 30 years.

Brachytherapy↗