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1.
Br J Cancer ; 104(6): 899-902, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21343938

ABSTRACT

BACKGROUND: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease. METHODS: Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P=0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke. CONCLUSION: In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.


Subject(s)
Breast Neoplasms/drug therapy , Carcinoma/drug therapy , Cerebrovascular Disorders/epidemiology , Randomized Controlled Trials as Topic/statistics & numerical data , Tamoxifen/therapeutic use , Adult , Aged , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/complications , Breast Neoplasms/epidemiology , Carcinoma/complications , Carcinoma/epidemiology , Cerebrovascular Disorders/etiology , Chemotherapy, Adjuvant , Comorbidity , Female , Follow-Up Studies , Humans , Middle Aged , Risk Factors , Sweden/epidemiology , Tamoxifen/pharmacology , Time Factors
2.
Eur J Cancer ; 43(2): 291-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17118648

ABSTRACT

AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Case-Control Studies , Cohort Studies , Female , Humans , Mastectomy, Segmental , Radiotherapy, Adjuvant , Risk Factors
3.
Scand J Immunol ; 63(2): 90-6, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16476007

ABSTRACT

Transfusions of high-dose (> or =10,000 Joule/m(2)) ultraviolet-B (UVB)-irradiated allogeneic leukocytes in rodent models have been shown to induce immunologic tolerance that is mediated by allospecific regulatory CD4(+) T cells. Whether these regulatory T cells recognize alloantigens through the direct or indirect pathway of allorecognition is controversial. Here, we demonstrate that the proliferative response obtained in standard primary mixed leukocyte reactions (MLRs) with human peripheral blood mononuclear cells (PBMCs) reflected a CD4(+) T-cell-dependent direct pathway of allorecognition and that high-dose UVB irradiation of PBMCs totally inhibited their capacity to induce a proliferative alloresponse. Re-stimulation with gamma-irradiated PBMCs from the same allogeneic donor (secondary MLR) elicited a proliferative and Th1-deviated response that was similar to the response induced in unprimed PBMCs. Finally, high-dose UVB was found to induce a rapid and massive apoptosis of irradiated PBMCs. Collectively, these data indicate that leukocytes irradiated with high-dose UVB are unable to prime for unresponsiveness or immune deviation in T cells directly recognizing allogeneic major histocompatibility complex molecules. Because it is well-established that antigens within transfused apoptotic cells are captured by resident tolerogenic spleen dendritic cells, we propose that tolerance induced by transfusions of high-dose UVB-irradiated leukocytes primarily involve T cells indirectly recognizing alloantigens.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/radiation effects , Immune Tolerance/radiation effects , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/radiation effects , Apoptosis , Blood Transfusion , CD4-Positive T-Lymphocytes/cytology , Cells, Cultured , Humans , Immune Tolerance/immunology , Interferon-gamma/immunology , Leukocytes, Mononuclear/cytology , Lymphocyte Activation/radiation effects , Lymphocyte Culture Test, Mixed , Ultraviolet Rays
4.
Scand J Immunol ; 62(3): 234-42, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16179010

ABSTRACT

T-cell sensitization to indirectly presented alloantigens (indirect pathway of allorecognition) plays a critical role in chronic rejection. The usual very efficient priming of such self-restricted, T helper type 1 (Th1)-deviated CD4+ T cells obviously conflicts with the fact that allogeneic MHC molecules are poorly immunogenic per se. The aim of the present study is to elucidate whether direct allosensitization induces production of inflammatory mediators that may affect recruitment and activation of immature bystander (host) dendritic cells (DC). These potential mechanisms were studied in vitro by conducting primary allogeneic mixed leucocyte reactions (MLR), mimicking the priming phase in secondary lymphoid organs, and secondary MLR, mimicking the effector phase within the graft. Primary, and particularly secondary, MLR supernatants were found to contain high levels of monocyte/immature DC-recruiting CC chemokines and pro-inflammatory cytokines. Exposure of immature DC to primary or secondary MLR supernatants was found to upregulate CD40 expression and further enhanced lipopolysaccharide-induced interleukin-12 (IL-12) p70 production. Secondary MLR supernatants additionally induced upregulation of CD86 and deviated allogeneic T-cell responses towards Th1 (enhanced interferon-gamma production without concomitant induction of detectable IL-4 or IL-10 production). These findings indicate that direct allorecognition may act as a Th1-deviating adjuvant for indirect allosensitization.


Subject(s)
Antigen Presentation/immunology , Chemokines/metabolism , Dendritic Cells/immunology , Isoantigens/immunology , Th1 Cells/immunology , Antigens, CD/analysis , Cell Differentiation/immunology , Chemokines/analysis , Chemokines/pharmacology , Dendritic Cells/drug effects , Humans , Interleukin-12/metabolism , Lymphocyte Culture Test, Mixed , Protein Subunits/metabolism , Receptors, CCR7 , Receptors, Chemokine/analysis , Th1 Cells/drug effects , Up-Regulation
5.
Eur J Cancer ; 39(12): 1690-7, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12888363

ABSTRACT

The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.


Subject(s)
Breast Neoplasms/surgery , Mammography/methods , Mass Screening/methods , Mastectomy, Segmental/methods , Adult , Aged , Axilla , Breast Neoplasms/radiotherapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymph Node Excision , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local/etiology , Postoperative Care , Treatment Outcome
6.
J Clin Oncol ; 21(7): 1205-13, 2003 Apr 01.
Article in English | MEDLINE | ID: mdl-12663706

ABSTRACT

PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.


Subject(s)
Breast Neoplasms/pathology , Neoplasm Recurrence, Local/etiology , Breast Neoplasms/therapy , Chemotherapy, Adjuvant , Female , Humans , Lymph Nodes/pathology , Mastectomy , Menopause , Middle Aged , Risk Factors
7.
Eur J Cancer ; 37(15): 1904-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11576847

ABSTRACT

The aim of this study was to describe and characterise a founder mutation of the BRCA1 gene in western Sweden. Of 62 families screened for BRCA mutations, 24 had BRCA1 mutations and two had BRCA2 mutations. Tumours that occurred in family members were histologically reviewed and mutational status was analysed using archival paraffin-embedded tissues. The same BRCA1 mutation, 3171ins5, was found in 16 families who were clustered along the western coast of Sweden. Mutation analysis revealed a maternal linkage in 13 families and a paternal linkage in 3. There was complete agreement between mutation analysis results obtained from blood and archival tissues. The penetrance of breast or ovarian cancer by age 70 years was estimated to be between 59 and 93%. There were no differences in survivals between breast or ovarian cancer patients with the mutation and age-matched controls. Thus, a predominant BRCA1 gene founder mutation associated with a high risk of breast and ovarian cancer has been identified and found to occur in a restricted geographical area, thereby allowing timely and cost-effective mutation screening using blood samples or archival histological material.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1/genetics , Mutation , Neoplastic Syndromes, Hereditary/genetics , Ovarian Neoplasms/genetics , Adult , Aged , Breast Neoplasms/epidemiology , DNA Mutational Analysis/methods , Female , Founder Effect , Humans , Incidence , Middle Aged , Multivariate Analysis , Neoplastic Syndromes, Hereditary/epidemiology , Ovarian Neoplasms/epidemiology , Polymerase Chain Reaction/methods , Risk Assessment , Survival Rate , Sweden/epidemiology
8.
Br J Cancer ; 85(3): 362-6, 2001 Aug 03.
Article in English | MEDLINE | ID: mdl-11487266

ABSTRACT

Exposure to ionizing radiation is a known risk factor for breast cancer and the fertility pattern is a recognized modifier of breast cancer risk. The aim of this study was to elucidate the interaction between these 2 factors. This study is based on a Swedish cohort of 17 202 women who had been irradiated for skin haemangiomas in infancy between 1920 and 1965. The mean age at treatment was 6 months and the median breast dose was 0.05 Gy (range 0-35.8 Gy). Follow-up information on vital status, parity, age at first childbirth and breast cancer incidence was retrieved through record linkage with national population registers for the period 1958-1995. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. In this cohort, the fertility pattern differed from that in the Swedish population, with significantly fewer childbirths overall and before 25 years of age but more childbirth after that age. There were 307 breast cancers in the cohort and the standardized incidence ratio (SIR) was 1.22 (95% CI 1.09-1.36). A linear dose-response model with stratification for fertility pattern and menopausal status resulted in the best fit of the data. ERR/Gy was 0.33 (95% CI 0.17-0.53). In absolute terms this means an excess of 2.1 and 5.4 cases per Gy per 10(4) breast-years in the age groups 40-49 and 50-59 years respectively. The fertility pattern influenced the breast cancer risk in this irradiated population in a similar way to that observed in other studies. SIR at dose = 0 was highest, 2.31, among postmenopausal nulliparous women (95% CI 1.48-3.40, n = 62). SIR at dose = 0 was lowest in pre- or postmenopausal women with a first childbirth before 25 years of age; 0.89 (0.71-1.09) and 0.88 (0.58-1.25) respectively. Thus, in addition to the dose-effect response in the cohort, part of the breast cancer excess could be explained by a different fertility pattern. The estimates of ERR/Gy for the various categories of age at first childbirth, number of children, menopausal status and ovarian dose were very similar, contradicting any interaction effects on the scale of relative risk.


Subject(s)
Breast Neoplasms/etiology , Maternal Age , Neoplasms, Radiation-Induced/etiology , Parity , Adult , Age of Onset , Aged , Birth Rate , Breast Neoplasms/epidemiology , Cohort Studies , Female , Hemangioma/radiotherapy , Humans , Infant , Infant, Newborn , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Radiation Dosage , Registries , Risk Factors , Skin Neoplasms/radiotherapy , Sweden/epidemiology
9.
Br J Cancer ; 84(9): 1193-8, 2001 May 04.
Article in English | MEDLINE | ID: mdl-11336470

ABSTRACT

The relationship between fetal growth as indicated by weight and length at birth, and cancer risk in 1080 adult Swedish women was examined. Birth factors were retrieved from original midwife records for the years 1914, 1918, 1922 and 1930, and primary cancer cases were identified by matching with national and regional cancer registries through the year 1998. A positive and statistically significant increased risk for cancer was found with increasing birth weight or birth length for all site cancer and non-hormone related cancer, defined as all cancer sites excluding breast, uterus and ovary. Addition of factors suspected to influence cancer risk, maternal proteinuria, birth order, own parity and age at menarche, did not attenuate this relation. Previously only breast cancer has been reported to be related to size at birth in adult women and this is the first study to report that cancer sites other than the major hormone-related sites may be influenced by size at birth, as measured by either weight or length at birth; these findings warrant further investigation.


Subject(s)
Birth Weight , Neoplasms/etiology , Prenatal Exposure Delayed Effects , Age Factors , Aged , Epidemiologic Studies , Female , Humans , Incidence , Infant, Newborn , Menarche , Middle Aged , Neoplasms/epidemiology , Parity , Pregnancy , Risk Factors , Sweden/epidemiology
10.
Eur J Hum Genet ; 9(10): 787-93, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11781691

ABSTRACT

The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cM. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cM was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the P(excess) and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.


Subject(s)
BRCA1 Protein/genetics , Conserved Sequence/genetics , Founder Effect , Haplotypes/genetics , Mutation/genetics , Breast Neoplasms/genetics , DNA Mutational Analysis , Female , Geography , Humans , Male , Microsatellite Repeats , Mutagenesis, Insertional/genetics , Pedigree , Sweden , Time Factors
11.
Scand J Immunol ; 51(6): 612-7, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10849373

ABSTRACT

The aim of this study was to investigate the frequency and possible clinical relevance of SSA/Ro antibodies, as determined by enzyme-linked immunosorbent assay (ELISA), in patient sera not exhibiting a concomitant positive reaction by the standard immunofluorescence (IF) test using HEP-2 cells as substrate. SSA/Ro reactivity, as shown by ELISA, was found in 285 (7%) of 4025 serum samples consecutively remitted for antinuclear antibody (ANA) screening. Seventy-five of these serum samples (26%), derived from 64 patients, were negative by the IF-ANA screening test. Serum samples from all 64 patients exhibiting SSA/Ro reactivity by ELISA without concomitant positivity by IF-ANA were further investigated by IF using transfected HEP-2 cells hyperexpressing the 60,000 MW SSA/Ro antigen (HEP-2000(R)) and by immunodiffusion (ID) and Western blot. In 55 of these 64 patients, SSA/Ro reactivity could be verified by one or more of the other techniques investigated. Twelve of these patients fulfilled four or more American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) and another five patients exhibited a histologically confirmed cutaneous lupus erythematosus (LE). In four of the 12 IF-ANA-negative patients with a diagnosis of SLE, the SSA/Ro reactivity was only detectable by ELISA and Western blot. In conclusion, the use of a sensitive ELISA assay could provide a clinically important supplement to the routine ANA screening by IF, which does not detect certain anti-SSA/Ro-containing sera among patients with relevant autoimmune diagnoses. Detection of anti-SSA/Ro antibodies, however, does not alone signify cutaneous LE or SLE but adds weight to these diagnoses that should rely heavily on other clinical information.


Subject(s)
Antibodies, Antinuclear/isolation & purification , Autoantigens/immunology , RNA, Small Cytoplasmic , Ribonucleoproteins/immunology , Adult , Animals , Blotting, Western , Cell Line , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique, Indirect , Humans , Immune Sera/chemistry , Immunodiffusion , Male , Middle Aged
14.
Eur J Cancer Care (Engl) ; 8(4): 224-32, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10889620

ABSTRACT

Fatigue--which is a complex, multicausal, and multidimensional subjective experience--is today the most frequently reported symptom from patients with cancer. The aim of this study was to explore the experience of fatigue in cancer patients and to describe the categories and dimensions of the symptoms. A qualitative method--grounded theory--was used. Unstructured, tape-recorded interviews with 15 cancer patients were used for data collection. The categories found in this study illustrate fatigue as a process. Three major categories were found: (1) experiences (of loss, need, malaise, psychological stress, emotional affection, abnormal weakness, difficulties in taking the initiative); (2) consequences (social limitation, affected self-esteem, affected quality of life); and (3) actions (coping). The categories were constructed on the basis of dimensions with subordinated qualities. Knowledge concerning the different expressions of fatigue is important in caring for patients with cancer. The results from this study may contribute to a better understanding of how a cancer patient can experience and express fatigue and how the symptoms may affect the patient.


Subject(s)
Adaptation, Psychological , Attitude to Health , Fatigue/etiology , Fatigue/psychology , Neoplasms/complications , Self Care/methods , Self Care/psychology , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Fatigue/prevention & control , Female , Humans , Male , Middle Aged , Models, Nursing , Models, Psychological , Nursing Methodology Research , Quality of Life , Self Concept , Surveys and Questionnaires
15.
Xenotransplantation ; 6(4): 271-80, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10704070

ABSTRACT

The process of islet xenograft rejection is still poorly understood. To elucidate further possible mechanism(s) involved in xenograft rejection, the effect of different immunization protocols was investigated. Fetal porcine islet-like cell clusters (ICCs) were transplanted under the kidney capsule in otherwise untreated rats, rats pre-immunized by s.c. injections of ICCs and in rats passively immunized with immune serum. The rejection process was evaluated with regard to antibody and complement deposition in the graft, as well as to morphology and phenotype of the infiltrating cells. In otherwise untreated animals, a moderate perigraft mononuclear cell infiltrate was seen after 3 days. Graft destruction became evident on day 6 with marked intragraft infiltration by macrophages (ED1 positive), whereas T cells were in the minority and mainly located in the perigraft area. In contrast to the findings in non-immunized rats, the rejection process in pre-immunized rats was characterized by marked intragraft infiltration by macrophages 3 days after transplantation. Moreover, both T cells and macrophages heavily infiltrated the adjacent kidney parenchyma, and major histocompatibility complex (MHC) class II expression in surrounding kidney tubular cells was concomitantly enhanced. Syngeneic rat islets mixed with porcine ICCs escaped the rejection process in non-immunized rats but were affected in pre-immunized animals. Thus, the specificity of the rejection process in non-immunized animals seems to be lost in pre-immunized animals. The early macrophage infiltration was also accelerated in rats passively immunized with immune serum, but no early switch from perigraft to intragraft infiltration or subsequent cellular infiltration in the adjacent kidney parenchyma was seen. Circulating xenoreactive antibodies of the IgG isotype increased after transplantation in normal and otherwise untreated rats. No distinct IgG deposition in the ICC xenografts was observed until day 12 after transplantation in untreated rats, whereas perigraft deposition of IgG was found 1 day after transplantation in pre-immunized rats and in rats given immune serum. No deposition of complement was observed within the ICC xenograft in any of the groups during the observation period. The dependence on T cells, the massive infiltration of macrophages with a unique phenotype, the cellular distribution, and the loss of specificity (bystander killing) of the rejection process in immunized rats suggest that ICC xenograft rejection shares some of its main characteristics with a delayed type hypersensitivity-like (DTH) immune response.


Subject(s)
Fetal Tissue Transplantation/immunology , Graft Rejection/immunology , Immunization, Passive , Immunization , Islets of Langerhans Transplantation/immunology , Transplantation, Heterologous/immunology , Animals , Fetal Tissue Transplantation/pathology , Graft Rejection/pathology , Graft Rejection/prevention & control , Histocompatibility Antigens Class II/analysis , Immune Sera , Islets of Langerhans Transplantation/pathology , Male , Rats , Rats, Inbred WF , Swine , Transplantation, Heterologous/pathology , Transplantation, Isogeneic
17.
Radiat Res ; 150(3): 357-64, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9728664

ABSTRACT

The risk of intracranial tumors after exposure to ionizing radiation during infancy has been studied in a pooled analysis of two Swedish hemangioma cohorts (n = 28,008). The mean absorbed intracranial dose was low (7 cGy, range 0-11.5 Gy). The cohorts were followed up in the Swedish Cancer Register for incident intracranial tumors during the period 1958-1993. Eighty-eight tumors were found in 86 individuals compared to 60.72 expected [standardized incidence ratio (SIR) 1.42, 95% confidence interval (CI) 1.13-1.75]. The SIR increased significantly in ascending dose categories (P = 0.02). Dose-response analyses were performed with Poisson regression methods. There was a significant effect of dose, and the dose-effect relationship was negatively modified by age at first treatment. This indicates a higher risk for those exposed earlier in life. A linear dose-response model modified by age at first treatment resulted in the best fit. The excess relative risk (ERR) was 2.7/Gy (95% CI 1.0-5.6). The ERR/Gy was 4.5 if the treatment was given before 5 months of age, 1.5 if it was given at 5-7 months and 0.4 if it was given later. The study thus strongly indicates that there exists a dose-response relationship between absorbed dose in the brain and the subsequent risk of developing an intracranial tumor and that the risk is higher among infants exposed at younger ages.


Subject(s)
Brain Neoplasms/epidemiology , Hemangioma/radiotherapy , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Second Primary/epidemiology , Skin Neoplasms/radiotherapy , Adult , Brain Neoplasms/etiology , Cohort Studies , Dose-Response Relationship, Radiation , Humans , Infant , Infant, Newborn , Middle Aged , Neoplasms, Radiation-Induced/etiology , Neoplasms, Second Primary/etiology , Sweden/epidemiology
18.
Cancer Res ; 58(7): 1372-5, 1998 Apr 01.
Article in English | MEDLINE | ID: mdl-9537232

ABSTRACT

We describe the identification of a large deletion in the BRCA2 gene as the disease-causing mutation in a Swedish breast/ovarian cancer family. The 5068-bp deletion encompassed the 3' region of exon 3, including the 3' splice site and most of intron 3, and it resulted on the mRNA level in an inframe exon 3 skipping. The junction site also included an insertion of 4 bp (CCAT). The mutation (nt504del5068insCCAT) resulted in a genotype absent of the two transcription activation regions localized to exon 3. The breast cancer phenotype associated with the described mutation resembled the phenotype of breast cancer found in both BRCA1 and BRCA2 mutation carriers. This is the first report of a large deletion as the disease-causing mutation in the BRCA2 gene.


Subject(s)
Breast Neoplasms/genetics , Exons , Gene Deletion , Neoplasm Proteins/genetics , Ovarian Neoplasms/genetics , Transcription Factors/genetics , Transcriptional Activation , Adult , Aged , BRCA2 Protein , Base Sequence , DNA, Neoplasm/genetics , Family Health , Female , Germ-Line Mutation , Humans , Male , Molecular Sequence Data , Pedigree
19.
Radiat Res ; 149(2): 202-8, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9457901

ABSTRACT

The possible impact of early gonadal irradiation on the results of future pregnancies is unclear. This study is based on the progeny of 17,393 women who were treated with irradiation for skin hemangiomas at the age of 18 months or less. The mean ovarian dose was 6 cGy, and the maximum was 8.55 Gy. Using Swedish central health registers, the outcome of delivery was studied in these women; 19,494 infants born were identified. The treated women deviated from the general population by having a longer education and by smoking less. This may explain a reduced risk for low birth weight and preterm birth (not related to radiation dose). Women with ovarian doses greater than 1 cGy had fewer infants than women with a lower ovarian dose. An excess of perinatal deaths was evident as well as a slight excess in the rate of malformation, but neither was related to dose. There was a statistically significant trend of an increasing rate of neural tube defects with ovarian dose, possibly a chance result of multiple statistical testing. Cleft lip/palate occurred at levels significantly below expectation. No increase in the rate of infants with Down syndrome or in childhood malignancies was detected. No major adverse results in outcome of delivery were seen after ovarian irradiation in childhood with the possible exception of neural tube defects.


Subject(s)
Hemangioma/radiotherapy , Reproduction/radiation effects , Skin Neoplasms/radiotherapy , Congenital Abnormalities/epidemiology , Dose-Response Relationship, Radiation , Female , Humans , Infant , Male , Neoplasms, Radiation-Induced/etiology , Ovary/radiation effects , Parity , Pregnancy , Radiation Injuries , Sweden
20.
Eur J Cancer ; 34(13): 2068-75, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10070313

ABSTRACT

The aim was to quantify the risk of post-treatment sarcoma in breast cancer patients. All 122,991 women with a breast cancer from 1958 to 1992 in the Swedish Cancer Register were followed up for soft tissue sarcomas and 116 were found, giving a standardised incidence ratio of 1.9 (95% CI 1.5-2.2). The absolute risk was 1.3 per 10(4) person-years. The sarcomas were located in the breast region or on the ipsilateral arm in 63% (67/106). There were 40 angiosarcomas and 76 sarcomas of other types. In a case-control study, angiosarcoma correlated significantly with lymphoedema of the arm, odds ratio (OR) 9.5 (95% CI 3.2-28.0), but no correlation with radiotherapy was observed. For other types of sarcoma there was a correlation with the integral dose. The dose-response relationship indicated that the risk increased linearly with the integral dose to 150-200 J and stabilised at higher energies. The OR was 2.4 (95% CI 1.4-4.2) for an energy of 50 J, approximately corresponding to the radiation of the breast after breast-conserving surgery. Thus, only oedema of the arm correlated with angiosarcoma, but for other types of sarcoma the integral dose of radiotherapy was a predictor of the risk.


Subject(s)
Breast Neoplasms/radiotherapy , Neoplasms, Radiation-Induced/etiology , Sarcoma/etiology , Adult , Age Distribution , Aged , Aged, 80 and over , Breast Neoplasms/epidemiology , Case-Control Studies , Dose-Response Relationship, Radiation , Female , Hemangiosarcoma/radiotherapy , Humans , Incidence , Lymphedema/radiotherapy , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Registries , Risk Factors , Sarcoma/epidemiology
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