| 31. |
- Burek, C. J., et al.
(författare)
-
The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells
- 2001
-
Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 20:45, s. 6493-6502
-
Tidskriftsartikel (refereegranskat)abstract
- The activation of sphingomyelinases leading to the generation of ceramide has been implicated in various apoptotic pathways. However, the role of ceramide as an essential death mediator remains highly controversial. In the present study, we investigated the functional relevance of ceramide in a genetic model by using primary cells from a Farber disease patient. These cells accumulate ceramide as the result of an inherited deficiency of acidic ceramidase. We demonstrate that Farber disease lymphocytes and fibroblasts underwent apoptosis induced by various stress stimuli, including staurosporine, anticancer drugs and gamma -irradiation, equally as normal control cells. In addition, caspase activation by these proapoptotic agents occurred rather similarly in Farber disease and control fibroblasts. Interestingly, Farber disease lymphoid cells underwent apoptosis induced by the CD95 death receptor more rapidly than control cells. Our data therefore suggest that ceramide does not play an essential role as a second messenger in stress-induced apoptosis. However, in accordance with a role in lipid-rich microdomains, ceramide by altering membrane composition may function as an amplifier in CD95-mediated apoptosis.
|
|
| 32. |
- Carlsson, C., et al.
(författare)
-
Voluntary associations for cancer patients in Sweden: supportive activities
- 2001
-
Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 9:8, s. 581-590
-
Tidskriftsartikel (refereegranskat)abstract
- Our aim was to describe voluntary associations for patients with cancer in Sweden (n=108) and their activities, type and extent of member support, and the associations' collaboration with the health care system. A specially constructed questionnaire with structured and open questions was used for the investigation. The frequency of answers was 89%. The results show in the broadest sense that the associations have two missions. The direct patient-related mission concerns providing patients with support in the form of close proximity, approachability and through distribution of knowledge together with financial and practical support; the indirect patient-related mission deals with activities aimed at improving conditions for patients in general within the health care system and by influencing authorities as well as supporting family members and significant others and providing financing. The associations collaborate with the health care system, although they face difficulties in becoming 'sanctioned' and in establishing positive relationships with the health care community. The associations display a positive attitude towards their cause and the personal gratification that the voluntary work brings. In general, the findings indicate that the associations have a potential to help patients live and cope with their cancer disease.
|
|
| 33. |
- Çiray, Ipek
(författare)
-
Diagnosis and evaluation of therapeutic response of bone metastases.
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to investigate different aspects of different imaging modalities in the diagnosis of bone metastases and in the assessment of their response to therapy. The role of CT, with and without clinical information, was investigated as compared to CT-guided bone biopsy in the evaluation of suspected bone metastases. The diagnostic accuracy of CT alone (44%) increased to 82% when clinical information was taken into account, especially for the lesions diagnosed histopathologically as benign. In most cases, CT in combination with clinical information gave enough information about the nature (malignant or benign) of a bone lesion. In uncertain cases the diagnostic accuracy could be improved by means of CT-guided bone biopsy. Possible misinterpretation of new sclerotic lesions when judged according to the WHO criteria during treatment was studied. One hundred and thirty-nine breast cancer patients with bone metastases, who participated a the clinical trial of clodronate therapy, were studied retrospectively. In 8 of the 24 patients considered at conventional radiography to have progressive disease according to WHO criteria, 17 of 52 apparently new sclerotic lesions (33%) were detected on previous bone scintigraphy. WHO criteria may give rice to misinterpretations in patients with new sclerotic lesions. For better assessment more sensitive techniques, e.g. bone scintigraphy, can be used as a complement to conventional radiography. Eighteen breast cancer patients with known bone metastases were studied prospectively regarding evaluation of therapy response. T1-weighted spin echo (SE) and fat-suppressed long echo time inversion recovery turbo spin echo (long TE IR-TSE) MR sequences, conventional radiography, bone scintigraphy and CT-guided bone biopsy were performed before and during systemic chemotherapy. T1-weighted sequences and long TE IR-TSE sequences were compared regarding evaluation of early response of breast cancer bone metastases to chemotherapy, using a combination of clinical, radiographic and scintigraphic examinations as a reference. Therapeutic response evaluation with MR imaging was based on change in tumor size assessed quantitatively by measuring all focal metastases, and on change in pattern and signal intensity (SI) of the metastases, assessed visually. The long TE IR-TSE sequence demonstrated partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence (58% vs. 17%). The effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on MR images of normal red bone marrow was investigated. A diffuse, homogeneous SI increase was observed visually and quantitatively in initially normal bone marrow during G-CSF therapy, obscuring some focal lesions. No such SI change was visible after G-CSF therapy or in patients not receiving G-CSF. We concluded that G-CSF-supported chemotherapy might induce diffuse SI changes in normal red bone marrow on MRI, and that this might lead to misinterpretations in the evaluation of response of bone metastases. Early response of bone metastases to therapy was assessed in targeted metastatic lesions in breast cancer patients with T1-weighted and long TE IR-TSE MR sequences and CT compared with histopathological findings. The results indicated that the SI increase in the metastatic lesions following therapy on long TE IR-TSE images might be useful in indicating an early response. T1-weighted images are of limited value in assessing alterations in the amount of tumor cells. An increase in electron density on CT can be seen in both responding and progressing lesions.
|
|
| 34. |
- Fadl-Elmula, Imad, et al.
(författare)
-
Characterization of chromosomal abnormalities in uroepithelial carcinomas by G-banding, spectral karyotyping and fish analysis
- 2001
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:6, s. 824-831
-
Tidskriftsartikel (refereegranskat)abstract
- Chromosome analysis by G-banding, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) was per formed on 24 short-term cultured transitional cell bladder carcinomas and 5 cell lines established from bladder carcinomas. Except for one tumor with an apparently normal chromosomal constitution, clonal chromosome abnormalities were detected in all examined cases by the combined approach. The application of SKY and FISH techniques improved the karyotypic descriptions, originally based on C-banding only, by identifying 32 additional numerical changes, by establishing the chromosomal origin of 27 markers and 2 ring chromosomes, by redefining 53 aberrations and by detecting 15 hidden chromosomal rearrangements. No recurrent translocation, however, was detected. The most prominent: karyotypic feature was thus the occurrence of deletions and losses of whole chromosome copies indicating the importance of tumor suppressor genes in transitional cell carcinoma pathogenesis. Invasive carcinomas were karyotypically more complex than were low grade superficial tumors. Specific leases of material from chromosome 9 and from chromosome arms I Ip and 8p, and gains of 8q and Iq seem to be early changes appearing in superficial tumors, whereas losses from 4p and 17p and the formation of an isochromosome for 5p were associated with more aggressive tumor phenotypes.
|
|
| 35. |
- Frisk, Peter
(författare)
-
Expressions of mercury-selenium interaction in vitro
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Interaction between mercury and selenium has previously been observed both in man and in animals. The aim of this work was to study expressions of interaction between mercury and selenium in human K-562 cells. Inorganic and organic forms of mercury and selenium were used and cells were either pre-treated with selenium or simultaneously exposed to selenium and mercury. Concentrations of selenium and mercury chosen were indicated by a study of growth inhibition in the individual compounds: a low concentration of selenium and selenomethionine induced slight cell growth inhibition, while a high concentration resulted in a notable growth inhibition. Two mercury concentrations were chosen: one with minimal toxicity and another with high cell toxicity. In addition, uptake and retention patterns of selenomethionine and selenite differed in both selenocompounds.All simultaneous treatments with 3.5 μM methylmercury produced a reduction in cellular mercury with increased selenium concentration. This was particularly obvious in selenite treatments. Growth curves from the simultaneous 3.5 μM methylmercury and selenite treatments indicated protection with increased selenite concentrations. In both exposure protocols, the 5 μM methylmercury treatments were toxic to the cells. In both study protocols, cells exposed to selenite and mercuric chloride manifested increased cellular mercury uptake with increased selenium concentration. In all selenite and 35 μM mercuric chloride treatments, no inhibition of growth was observed, while the 50 μM mercuric chloride treatments were toxic to the cells. Selenite-dependent protection was achieved in both exposure protocols when considering the cellular uptake of mercury. With few exceptions, selenomethionine produced similar effects as selenite on mercuric chloride uptake and growth inhibition.
|
|
| 36. |
- Gelig Thurfjell, Mercidyl
(författare)
-
Aspects in mammographic screening : Detection, prediction, recurrence and prognosis
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Screening mammograms comprising of 32 first round, 10 interval and 32 second round detected cancers and 46 normal were examined by an expert screener, a screening radiologist, a clinical radiologist and a computer-assisted diagnosis (CAD) system. The expert screener, screening radiologist, clinical radiologist and the CAD detected 44, 41, 34 and 37 cancers, respectively, while their respective specificities were 80%, 83%, 100% and 22%. Later, with CAD prompting, the screening and the clinical radiologist detected 1 and 3 additional cancers each with unchanged specificities.Screening mammograms comprising 35 first round, 12 interval and 14 second round detected cancers and 89 normal findings were examined without and with previous mammograms by experienced screeners. Without previous mammograms, the screeners detected 40.3 cancers with a specificity of 87%. With previous mammograms, 37.7 cancers were detected with a 96% specificity. The decrease in sensitivity was not significant but the screeners showed significant increase in specificity.Local recurrences in 303 nonpalpable breast cancers with preoperative localizations and breast conservation therapy were evaluated for needle-caused implant metastasis. A total of 214 percutaneous biopsies were performed. There were 33 local recurrences. Needle-caused seeding or implantation as based on the location of the recurrence in comparison to the needle path in the mammograms was suspected in 3/44 (7%) invasive cancers without radiotherapy.The mammographic characteristics of 317 nonpalpable breast cancers were categorized. Logistic regression showed that the risk ratios for a spiculated mass without calcifications and calcifications alone were 12 and 19 for invasive cancer and ductal cancer in situ (DCIS), respectively. Invasive ductal grade 1, ductal grade 2, lobular and ductal grade 3, had a risk ratio (RR) of 28, 17, 11 and 4.6, respectively, for a spiculated mass without calcifications. DCIS nuclear grade 3 and invasive ductal grade 3 had an RR of 17 and 9.7, respectively, for sole casting calcifications.The eight-year survival of 96 1-9 mm invasive breast cancers were investigated in relation to their mammographic appearance, node status and histologic grade. After a median follow-up of 7 years, 6/96 died from breast cancer: 3/14 had calcifications alone, 2/56 had spiculated masses, 1/12 had rounded mass, 5/78 were node-negative and 1/4 was node-positive. The survival rate was 93%: 77% for the calcifications alone, 95% for spiculated masses, 91% for rounded masses, 92% for node-negative and 75% for node-positive. Calcifications alone and node positivity, each, carried a significantly higher risk of death.
|
|
| 37. |
- Jordhoy, M S, et al.
(författare)
-
Quality of life in advanced cancer patients: the impact of sociodemographic and medical characteristics
- 2001
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 85:10, s. 1478-1485
-
Tidskriftsartikel (refereegranskat)abstract
- Population-based surveys have shown that health-related quality of life (HRQL) is influenced by patients' characteristics such as age, gender, living situation and diagnoses. The present study explores the impact of such factors on the HRQL of severely ill cancer patients. The study sample included 395 cancer patients who participated in a cluster randomised trial of palliative care. Median survival was 13 weeks. HRQL assessments (using the EORTC QLQ-C30 questionnaire) were compared among subgroups of relevant patients' characteristics (ANOVA), and the significance of individual covariates was explored by multivariate linear regression. Most EORTC QLQ-C30 scores showed minor differences between genders. Higher age was associated with less sleeping disturbance, less pain and better emotional functioning. No positive impact of living with a partner was found. Performance status and/or time from assessment to death were significantly associated with most functioning and symptom scores. We concluded that although the overall impact of sociodemographic characteristics may seem less important to HRQL scores among advanced cancer patients than in general populations, age and gender should be allowed for. Performance status and closeness to death also need to be reported.
|
|
| 38. |
- Krüger Hagen, Else
(författare)
-
Contrast enhanced transrectal ultrasound of the prostate : An experimental and clinical study
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to evaluate the diagnostic potential of a new ultrasound contrast agent,SonazoidTM, intended for use in patients with suspicion of prostate cancer.The sonographic appearance of normal prostatic vascularity in dogs was evaluated before and after injection of Sonazoid,using different Doppler flow detection modes.The use of Sonazoid significantly improved the visibility of the vascular pattern in normal dog prostate,both with colour and power Doppler imaging.There was a significant difference in the depiction of blood flow in the prostate between the two imaging modalities,showing the power Doppler superior to colour Doppler imaging.The contrast revealed a radial,spoke-like intraprostatic pattern,not seen prior to contrast injection.Different ultrasound imaging modalities were tested in a small group of young healthy male volunteers to evaluate the visibility of the normal prostate blood flow with and without Sonazoid.The ultrasound contrast agent improved the visibility of the normal human prostate vascular anatomy for both colour and power Doppler imaging.Again,the improvement was significantly better for power Doppler than for colour Doppler imaging.Using fundamental B-mode,there was no major difference in the ultrasound appearance of the prost ate vascular it y before and after i njection of Sonazoid.Cont rast dynamic st udies of blood flow wit hi n t he normal gland showed a filling from the periphery towards the centre in all subjects,demonstrating a symmetric, radial vascular pattern.A canine prostate model was used to investigate if Sonazoid,could improve the visualisation of prostatic vessels to better delineate areas on normal and decreased blood flow.Both 2D and 3D power Doppler imaging was performed in this study.The visibility of the prostate blood flow improved significantly following injection of Sonazoid for both 2D and 3D power Doppler imaging.There was,however,no major difference in depicting the vascularity using 2D and 3D imaging.After injection of Sonazoid,a disturbance of the radial vascular pattern and a lack of blood flow symmetry between the two prostate lobes were possible to identify.The added information gained by injection of Sonazoid made it possible to identify areas of decreased blood flow not seen prior to contrast injection.The vascular pattern of lesions,identified with B-mode imaging in patients with suspicion of prostate cancer,was studied,using Sonazoid.Contrast dynamic inflow in the lesions,compared to the adjacent tissue was investigated in the same study.Prostate cancer lesions appeared hypervasuclar prior to ultrasound contrast agent.Three of six cancer lesions changed from hypervascular to marked hypervascular following injection of Sonazoid,a finding that might be interpreted as a higher level of confidence.None of the non-cancer lesions were assessed as hypervascular after Sonazoid injection,a possible increased value of a negative finding.Four of the cancer lesions enhanced earlier compared to the surrounding prostate tissue,following ultrasound contrast injection.The results indicate that changes in vascular architecture,e.g.induction of angiogenesis by tumour cells,can be observed by ultrasonographically determining the inflow pattern of an intravenously injected ultrasound contrast agent.
|
|
| 39. |
- Lindholm, Lars H, et al.
(författare)
-
Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial
- 2001
-
Ingår i: The Lancet. - 1474-547X. ; 358, s. 539-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Is cancer related to hypertension and blood pressure? Do antihypertensive drugs promote cancer? Do antihypertensive drugs protect against cancer? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency of cancer in these patients. METHODS: We randomly assigned 6614 elderly patients with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one of three treatment strategies: conventional drugs (diuretics or b-blockers), calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age, sex, and calendar-year-specific reference frequencies for the general Swedish population. We also compared the number of cancers between the three treatment groups. FINDINGS: At baseline, 607 (9%) patients had previous malignant disease. Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients. During follow-up, there were 625 new cases of cancer in 590 patients. The frequency of cancer did not differ significantly between the treatment strategies, including all cancers and those at individual sites. The standardised incidence ratios (SIRs) for all cancers were also close to unity: 0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. INTERPRETATIONS: No difference in cancer risk was seen between patients randomly assigned to conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer.
|
|
| 40. |
- Lubberink, Mark
(författare)
-
Quantitative imaging with PET : performance and applications of 76Br, 52Fe, 110mIn and 134La
- 2001
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of positron emission tomography (PET) has so far mainly been limited to a few nuclides with short half-lives such as 11C and 18F. Certain applications require nuclides with longer half-lives, such as 76Br and 52Fe. In radionuclide therapy positron emitting analogues of therapeutic nuclides, such as 110mIn, or daughter nuclides, such as 134La, can enable improved dosimetry with the use of PET. A challenge associated with the use of these positron emitters is that they emit gamma radiation in cascade with positrons, which complicates quantitative PET imaging. Other possible problems are the high energies of the emitted positrons, and the decay of 52Fe to the short-lived positron emitter 52mMn.Performance measurements were made to investigate the effects of these decay characteristics on the quantitative accuracy, spatial resolution, and other parameters of PET. The distribution of gamma radiation coincidences in PET data was studied and correction methods were implemented and evaluated. PET resolution degrades with 1-2 mm for the studied nuclides in comparison with 18F. The implemented sinogram tail fit and delayed coincidence based gamma radiation coincidence correction methods lead to a quantitative accuracy similar as for 18F and to improved image contrast. Standard dead time corrections are not adequate for gamma-emitting nuclides. Noise equivalent count rates are considerably lower for 76Br than for 18F at clinically relevant radioactivity concentrations.A method to correct 52Fe patient data for the contribution of 52mMn is discussed. The use of 110mIn is evaluated in a patient study and compared to SPECT imaging with 111In. A dosimetric and PET evaluation of the use of 134Ce/134La for radionuclide therapy and dosimetry is presented. Dosimetry of 76Br-labelled antibodies is studied in a pig model. Finally, the possibility to use PET for dosimetry during radionuclide therapy is studied and a nonuniform dose calculation program is presented.
|
|
