| 61. |
- Hellquist, H. B., et al.
(författare)
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Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12
- 1996
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Ingår i: Virchows Archiv. - New York, USA : Springer. - 0945-6317 .- 1432-2307. ; 429:2-3, s. 149-158
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Tidskriftsartikel (refereegranskat)abstract
- Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity for the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot pla a major role as protective agent in the specific apoptotic pathway induced by NK cells.
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| 62. |
- Isacsson, Ulf
(författare)
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Comparative treatment planning in external radiotherapy of malignant tumours : Potential gains using protons
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is well known that protons have physical characteristics superior to conventional radiation qualities in external beam radiotherapy. The primary aim of this work is to determine if the physical advantages also may lead to clinical advantages. A second aim is to evaluate the treatment planning algorithms incorporated into a 3D treatment planning system, used in the prediction, Helax-TMSTM. The potential benefits of using protons instead of conventional radiation qualities is evaluated by comparing treatment plans. Dose-response models of tumour control probability (TCP) and normal tissue complication probability (NTCP) were used to predict the treatment outcome for the different plans. Uncertainties in the results were studied in sensitivity analyses.Comparative studies were performed in four different tumour types, locally advanced rectal cancer, a paraspinal tumour, oesophageal cancer and left-sided node-positive breast cancer. Advantages with protons were seen in all cases, but the advantages were of different size.Proton therapy in patients with oesophageal carcinoma increases the TCP from 6 to 49% if a risk of 1% in the spinal cord and a total NTCP for the two lungs equivalent to a one-sided pulmectomy is allowed. This gain is relatively insensitive to variations, within reasonable limits, in the dose-response parameters.Proton therapy reduces the risk for cardiac mortality and radiation pneumonitis to almost zero when treating node-positive left-sided breast cancer after breast-conserving surgery.The evaluation of the treatment planning algorithms shows that pencil kernel algorithms are required in order to accurately calculate dose distributions in heterogeneous patient volumes. The scattering phenomenon in the vicinity of interfaces between different materials is modelled. The magnitude of the effect is underestimated (less than 1%) due to the inherent approximations.
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| 63. |
- Jahnson, S., et al.
(författare)
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p53 and Rb immunostaining in locally advanced bladder cancer : relation to prognostic variables and predictive value for the local response to radical radiotherapy
- 1995
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Ingår i: European Urology. - Basel, Switzerland : S. Karger. - 0302-2838 .- 1873-7560. ; 28:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- The association between known prognostic variables and altered immunostaining for the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous series of locally advanced bladder cancer. The predictive value of this immunostaining for the local response to intended radical radiotherapy was investigated. Among 262 patients treated with intended radical radiotherapy between 1967 and 1986, a total of 154 patients were evaluable with respect to local response to treatment. The paraffin-embedded specimen from the tumour prior to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at 650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the tumours, respectively. p53 overexpression was associated with higher tumour grade. However, the results of the p53 and Rb immunostaining procedures had no predictive value for tumor response to radiation treatment, local control or cancer-specific mortality.
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| 64. |
- Jahnson, Staffan, et al.
(författare)
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Predictive value of p53 and pRb immunostaining in locally advanced bladder cancer treated with cystectomy
- 1998
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Ingår i: Journal of Urology. - Philadelphia, USA : Elsevier. - 0022-5347 .- 1527-3792. ; 160:4, s. 1291-1296
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer.Materials and Methods: The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression.Results: An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined.Conclusions: An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.
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| 65. |
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| 66. |
- Nilsson, Henrik, et al.
(författare)
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Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice
- 1997
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 76:3, s. 355-364
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Tidskriftsartikel (refereegranskat)abstract
- The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.
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| 67. |
- Nordén, T, et al.
(författare)
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Mammographic screening for breast cancer : What cancers do we find?
- 1997
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 33:4, s. 624-628
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare lymph node involvement of breast cancer cases detected at mammography screening with clinically-detected cases. During a 3-year period, 273 primary breast cancers were detected in a population-based screening programme, and 149 primary breast cancers were diagnosed clinically. Lymph node involvement was evaluated in univariate and multivariate logistic regression models correcting for tumour size, histological grade, steroid receptor status and DNA-ploidy. Patients with screen-detected cancers had a low relative risk of having lymph node metastases (univariate, OR = 0.31; 95% confidence interval = 0.19-0.52). In the multivariate logistic regression model, the relative risk was halved (OR = 0.47; 0.28-0.78). The reduced risk was more pronounced for women younger than 50 years of age compared to older women. The risk for screen-detected cases of having lymph node metastases at diagnosis was statistically significantly lower than for clinically-detected cases. The marked reduction, even when correcting for tumour size, makes it less likely that factors such as detection of clinically innocent tumours, length bias sampling or clinical symptoms related to axillary metastases can explain the whole difference. The results indicate at least part of the effect may be explained by tumour progression in the late preclinical detectable phase.
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| 68. |
- Rodriguez, Miriam
(författare)
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Computed tomography, magnetic resonance imaging and positron emission tomography in non-Hodgkin's lymphoma
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Certain aspects of the use of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) were evaluated in patients with non-Hodgkin'slymphoma (NHL) with the aim of improving the management of these patients.Subjective evaluation of the tumor pattern on CT images, and quantification of tracer uptake using 11C methionine (11C Met) and [18F] fluorodeoxyglucose (18FDG) PET in patients with NHL, were performed to determine their relations to malignancy grade.An inhomogeneous tumor pattern was found in 75% of high-grade tumors, whereas 68% of low-grade tumors were homogeneous. Sixteen (94%) of the 17 tumors with a severely inhomogeneous pattern on CT were high-grade NHL, while 22 (72 %) of the 29 homogeneous tumors were low-grade.All tumors were clearly visualized with both 11C Met and 18FDG PET. The uptake values for 18FDG were significantly higher in high- than in low-grade tumors, while no significant differences between the prognostic groups were found for 11C Met.A subjective evaluation of the tumor pattern on CT and on MR images was performed. An inhomogeneity index (IH8) was also used in MR images to make a quantitative assessment of the degree of inhomogeneity.Patients with localized NHL, treated with radiotherapy, had an excellent prognosis irrespective of the degree of inhomogeneity, while patients with generalized disease, treated with chemotherapy, had a poor prognosis if the tumors were heterogeneous. Among chemotherapy-treated patients, all 9 patients with high IH8 values ( >2.56) on MRI and 9 out of 11 patients with severe inhomogeneities on CT images died.All patients with gastric NHL except for one patient with low-grade NHL of the MALT type displayed high 18FDG uptake at PET corresponding to the pathological findings at endoscopy and /or CT. 18FDG correctly excluded gastric NHL in a patient with benign gastric ulcer, but was unable to discriminate between gastric NHL and gastric carcinoma. The results suggest that 18FDG PET may demonstrate the extension of NHL in the gastric wall more accurately than CT and endoscopy.The prognostic importance of the size of a residual mass after completion of chemotherapy, and of tumor regression rates during chemotherapy, was evaluated in patients with high-grade NHL. Neither a large tumor size before treatment nor a large residual tumor after treatment correlated with relapse, It appears, however, as if the response rate halfway through thetherapy may predict the recurrence rate, although statistical significance was not reached.
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| 69. |
- Tolmachev, Vladimir
(författare)
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Production and biomedical use of non-conventional positron emitters
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Positron Emission Tomography (PET) is a powerful diagnostic tool. So far, it has mainly been associated with the use of short-lived positron emitters with half-lives shorter than 2 h, like 11C and 18F. However, many biochemical processes in vivo have to be monitored for several hours or longer and thus positron emitters with longer half-lives are of interest. Sometimes, the replacement of single-photon emitting nuclides by positron emitting counterparts in established radiopharmaceuticals enable to use PET, which has better resolution and enables easier quantification.A new production method for the halogen 76Br (T1/2 = 16 h) is presented in paper I. An efficient dry distillation method is used for separation of this isotope from an isotopically enriched copper selenide target. This production method provides a nuclide with high chemial quality, which enabled simple labeling of monoclonal antibodies using Chloramine-T in mild neutral conditions. This nuclide was successfully used in a PET pharmacokinetic study on the effect of dextranation of peptides.A new method (etching technique) was developed to produce a positron-emitting isotope of indium, 110In (T1/2 = 69 min) and gallium, 68Ga (T1/2 = 68 min) and 66Ga (T1/2 = 9.4 h). A somatostatin analog, DTPA-octreotide, was labelled with 110In and used in a PET study. The use of PET enabled at efficient visualization of tumor metastases as well as dosimetric calculations.Dry distillation technique was used to produce zinc isotopes, which are of interest for investigation of trace element metabolism in vivo. At the same time, dyy distillation of group IIB elements from target material belonging to group IB of Periodic Table was examined. It has been shown that diffusion in solid state is the rate-determining process in such separations.
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| 70. |
- Wang, Chen
(författare)
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Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Contrast-enhanced magnetic resonance imaging (MRI) of the liver and pancreas is frequently performed to improve the sensitivity and specificity of lesion detection in these organs. The concept of using tissue-specific contrast media is to selectively enhance the normal parenchyma, but not lesions, so that the contrast between tumorous and normal tissue is increased, and lesion detectability improved. Mangafodipir trisodium (MnDPDP) has been developed as a hepatocellular-specific contrast agent, but uptake has also been found in pancreatic tissue. In this study the safety and diagnostic efficacy of MnDPDP were investigated in both healthy volunteers and patients with liver and pancreatic tumors.In healthy volunteers (n=8), dose-dependent enhancement in T1-weighted images was observed in the normal liver and pancreatic parenchyma after infusion of MnDPDP at doses of 5 and 10 μmol/kg. The maximal enhancement in the two dose groups was 77 and 110% in the liver, and 57 and 84% in the pancreas, respectively. The enhancement-over-time profiles demonstrated that the effective imaging window was about 2 h for the liver, and over 4 h for the pancreas. There was no measurable enhancement in brain structures protected by intact blood-brain barrier, and no changes of clinical importance were found in vital signs or in blood and urinary chemistry variables.Compared with unenhanced images (including T2-weighted images), significantly more lesions were detected, on MnDPDP-enhanced T1 images in 82 patients with liver tumors (mostly metastases). Features such as rim enhancement and the enhancement in hepatocellular carcinomas can provide information for differential diagnosis.In a study on patients with pancreatic tumors, mainly adenocarcinomas (n=21) and islet cell tumors (n=19), two additional lesions were found in the MnDPDP-enhanced images. The contrast enhancement in the pancreatic parenchyma can vary greatly, depending on the site of the enhancingpart of the organ in relation to a large tumor. The tumors of both origins were also enhanced post-contrast, but to a lesser degree than the normal pancreatic tissue.MnDPDP enhancement was investigated in 30 liver metastases from endocrine tumors in 13 patients. These lesions showed a signal increase of about 49% post-contrast, which lasted longer than that in the normal liver tissue. The findings may help to distinguish these tumors from other metastatic tumors.T1-weighted sequences of four types, including a spin-echo and three variants of fast gradient-echo sequences, and various parameter combinations, were investigated in healthy volunteers (n=6), with the aim of finding the optimal sequence for MnDPDP-enhanced MRI of the liver andpancreas. The fat-and-water out-of-phase, fast field (gradient)-echo sequence was the best for imaging of both the liver and pancreas.The studies have shown that MnDPDP is safe when given as an infusion and is effective as a liver- and pancreas-specific contrast medium, with improved lesion detection in MRI of these organs. It is also useful for the characterization of liver tumors.
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