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Träfflista för sökning "AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) srt2:(1995-1999)"

Sökning: AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) > (1995-1999)

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  • Eriksson, Björn, et al. (författare)
  • Establishment and characterization of a mouse strain (TLL) that spontaneously develops T-cell lymphomas/leukemia
  • 1999
  • Ingår i: Experimental Hematology. - 0301-472X .- 1873-2399. ; 27:4, s. 682-688
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In this study, a mouse strain (TLL) that spontaneously develops T-cell lymphomas/leukemia with an early onset and high incidence was established and characterized. All tumors analyzed were found to express the alpha,beta T-cell receptor, and the majority of them had a mature, CD3+CD4+CD8- immunophenotype. In a few cases, tumors with a more immature CD3+CD4+CD8+ phenotype were isolated. Expanded phenotyping using a broad panel of lymphocyte differentiation markers confirmed the mature T-cell phenotype of the tumors. Histologic and cell cycle analysis of the tumors revealed an aggressive lymphoblastic malignancy with a very high proliferation rate and widespread engagement of bone marrow and lymphoid as well as nonlymphoid organs. Thus, the TLL mouse strain represents a unique model for the analysis of the oncogenesis and progression of mature T-cell tumors and for the development of therapeutic measures to combat such tumors.</p>
  • Hartman, Torbjörn (författare)
  • Tumour targeting with stable and radioactive nuclides : Dosimetric aspects at the cellular level
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Targeting with radioactive nuclides or nuclides that can be activated by neutrons may be a powerful tool for treatment of invasive tumours and disseminated tumour cells. The targeting agents are designed to find tumour cells and deliver the nuclides. The aim of the thesis was to investigate the dosimetry at the cellular level for three forms of radiation of interest for targeted radiotherapy: neutron activated emission of <sup>4</sup>He- and <sup>7</sup>Li- ions from <sup>10</sup>B; high energy β-particles from <sup>131</sup>I and α- particles from <sup>211</sup>At. Computer models of cells and groups of cellswere developed for Monte Carlo simulations and point dose kernel calculations of the energy depositions in the cell nuclei.</p><p>Simulations of boron neutron capture therapy (BNCT), mostly with a thermal neutron fluence of 5x10<sup>12</sup> cm<sup>-2</sup>, showed that 10<sup>8</sup> atoms of <sup>10</sup>B per cell always gave too low doses. Located in the nucleus, 10<sup>9</sup> atoms of <sup>10</sup>B gave therapeutically interesting doses while location elsewhere in the cell gave insufficient dose to the nucleus. Boron dependent enhancement of tumour doses in fast neutron therapy demand at least 100 ppm of <sup>10</sup>B in the tumour cells, a concentration at which BNCT, compared to fast neutron therapy, showed to give higher tumour doses and lower doses to normal tissue.</p><p>With 10<sup>5</sup> atoms of <sup>131</sup>I per cell and an effective half-life of 24 h the <sup>131</sup>I had to be located in the nucleus to give therapeutically interesting doses in single cells. However, in tumour cell clusters with a diameter larger than 40 µm therapeutic doses were reached due to crossfire irradiation.</p><p><sup>211</sup>At is a most promising radionuclide for targeting of single cells or microscopic metastases. Between 30 and 1000 atoms of <sup>211</sup>At per cell, depending on cell size and position of <sup>211</sup>At, suffice to deliver, on the average, 10 Gy in the nucleus of a single cell, a dose relevant for therapy.</p>
  • Hugosson, Claes (författare)
  • Diagnosis of solid abdomino-pelvic tumours in children : A retrospective radiological study
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><i>Problems and Aims</i>: Solid abdomino-pelvic tumours (APTs) in children constitute a heterogeneous group of masses which may originate from the retroperitoneum, the abdominal or pelvic cavities or any adjacent structure. They have different histological features, growth patterns and prognoses.</p><p>The aim of the present investigation was to study the potential of modern imaging to assess the location, size and type of tumour, the extent of the disease and, if possible, the tumour stage in order to provide information to guide therapy.</p><p><i>Materials and Methods</i>: Imaging was performed in 92 children and adolescents with a primary APT using conventional radiography, radionuclide scintigraphy, US, CT and MR imaging for pre-treatment assessment, US-guided biopsies were performed in 61 children: the results were analysed retrospectively for yield and complications.</p><p><i>Results</i>: In pelvic bone tumours, all imaging modalities contributed to the evaluation of the primary tumour. Conventional radiography and bone scintigraphy were necessary for an initial diagnosis and CT for further evaluation. MR imaging and/or dynamic contrast-enhanced CT were mandatory prior to surgical resection.</p><p>In primary kidney tumours contrast-enhanced CT and non-enhanced MR imaging were equally accurate in determining the size and origin of the tumours but were inadequate in assessment of tumour staging. MR imaging findings varied somewhat between Wilms' tumours and non-Wilms' tumours.</p><p>In solid pelvic tumours compartmental localization was equally assessed with CT and MR and, together with gender, was found to correlate with the type of tumour.</p><p>In abdominal neuroplastoma, evaluation of the local disease was equally accurate with CT and MR imaging, while assessment of invasion and lymphadenopathy was not possible regardless of imaging modality. Metastatic disease needed imaging with CT, MR, scintigraphy and bone marrow aspiration for assessment. Staging accuracy improved if an increased number of imaging methods were used.</p><p>Needle core biopsy provided significantly better results than fine needle aspiration biopsy without an increase in complications.</p><p><i>Conclusions</i>: Assessment of APT in children requires the use of several different yet complementary imaging modalities in defining location, extent and tissue characteristics of the tumour. The choice of imaging modality depends on history, clinical findings, presumed location and available techniques. Pre-treatment assessment with imaging constitutes the basis for presentation of a staging protocol.</p>
  • Knutson, Folke (författare)
  • The quality of red blood cells and platelets intended for transfusion : Opportunities for improvements
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>A new, automated technique for collection and instant preparation of blood components has been developed. The device enables the combined collection of red cells (250 mL) and plasma (475 mL). No adverse effects were seen in the donors. The blood components were of good quality. The impact of the pre-separation temperature on whole blood was studied in two studies. In the first study blood was collected and put into stoppered test tubes. The test tubes were then put into water bath at 15,20,25 and 30 °C. Samples were taken at intervals during 24 hours. The lactate concentration increased and 2,3-DPG concentrations decreased during storage and at a higher rate with higher temperature. In the second study blood was collected and dived into half units. One half unit was actively cooled to 20 °C the other half kept at 28 °C. Blood component preparation was done after 6 hours. There were a significant change in 2,3-DPG, pH and lactate already after two hours hold of the whole blood. The differences were maintained for one week and for 2,3-DPG throughout 28 days storage. Myeloperoxidase levels in plasma were lower in the cooled units. The leucocytes reduction properties of BAT procedure were improved by addition of mannitol in the anticoagulant. The contents of leucocytes in RBC units were in the test group 32x10<sup>6</sup> and in the control group 573x10<sup>6</sup>. In vitro storage data showed no significant difference between the two groups during 42 days of storage of the red cells. A photochemical treatment (PCT) process has been used in decontamination of buffy-coat derived platelets (BC-PCs). Different strains of bacteria known to be associated with bacterial contamination's of blood components were added to two pooled ABO matched BC-PCs. After mixing the BC-PCs were divided. One BC-PC underwent PCT and the other did not. All bacterial experiments were made in duplicates. In all experiments, the bacteria were killed except in one with <em>Bacillus cereus</em>, a known spore former. PCT conditions similar to those used in the bacterial inactivation experiment were efficacious to inactivate HIV-1. In a second study a number of in vitro parameters known to be related to viability or function of stored platelets were tested. No physiologically relevant differences were found between the test and the control BC-PCs during 7 days of storage.</p>
  • Larsson, Gunnel, et al. (författare)
  • Health-related quality of life in patients with endocrine tumours of the gastrointestinal tract
  • 1999
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:4, s. 481-490
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Health-related quality of life (HRQOL) (EORTC QLQ-C30) and levels of anxiety and depression (HADS) were investigated in patients with endocrine tumours of the gastrointestinal tract treated with interferon and/or a somatostatin analogue. In addition, patient perceptions of the importance of and satisfaction with some HRQOL aspects were studied. QOL was perceived as quite good, but more than half of the patients reported diarrhoea. The levels of anxiety and depression were low. Patients perceived physical HRQOL aspects as most important for a good QOL and stated the highest satisfaction with some social aspects. Patients who reported high levels of anxiety or depression were less satisfied with several HRQOL aspects, had more health problems, and a lower level of functioning on several of the EORTC QLQ-C30 scales and single items. Neither demographic nor medical background variables seemed to have an influence on the results. The relatively high QOL could be explained by the fact that most patients had had their treatment for a long period and thus had time to adjust to the situation.</p>
  • Rodriguez, Miriam (författare)
  • Computed tomography, magnetic resonance imaging and positron emission tomography in non-Hodgkin's lymphoma
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>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.</p><p>Subjective evaluation of the tumor pattern on CT images, and quantification of tracer uptake using <sup>11</sup>C methionine (<sup>11</sup>C Met) and [<sup>18</sup>F] fluorodeoxyglucose (<sup>18</sup>FDG) PET in patients with NHL, were performed to determine their relations to malignancy grade.</p><p>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.</p><p>All tumors were clearly visualized with both <sup>11</sup>C Met and <sup>18</sup>FDG PET. The uptake values for <sup>18</sup>FDG were significantly higher in high- than in low-grade tumors, while no significant differences between the prognostic groups were found for <sup>11</sup>C Met.</p><p>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.</p><p>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 ( &gt;2.56) on MRI and 9 out of 11 patients with severe inhomogeneities on CT images died.</p><p>All patients with gastric NHL except for one patient with low-grade NHL of the MALT type displayed high <sup>18</sup>FDG uptake at PET corresponding to the pathological findings at endoscopy and /or CT. <sup>18</sup>FDG 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 <sup>18</sup>FDG PET may demonstrate the extension of NHL in the gastric wall more accurately than CT and endoscopy.</p><p>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.</p>
  • Tolmachev, Vladimir (författare)
  • Production and biomedical use of non-conventional positron emitters
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>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 <sup>11</sup>C and <sup>18</sup>F. 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.</p><p>A new production method for the halogen <sup>76</sup>Br (T<sub>1/2</sub> = 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.</p><p>A new method (etching technique) was developed to produce a positron-emitting isotope of indium, <sup>110</sup>In (T<sub>1/2</sub> = 69 min) and gallium, <sup>68</sup>Ga (T<sub>1/2</sub> = 68 min) and <sup>66</sup>Ga (T<sub>1/2</sub> = 9.4 h). A somatostatin analog, DTPA-octreotide, was labelled with <sup>110</sup>In and used in a PET study. The use of PET enabled at efficient visualization of tumor metastases as well as dosimetric calculations.</p><p>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.</p>
  • Wang, Chen (författare)
  • Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p>
  • Zhao, Qinghai (författare)
  • Targeting to EGF receptors : Preparation and experimental analysis of end-end coupled mEGF-dextran conjugates
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Targeted tumor therapy is to deliver cytotoxic agents selectively to tumor cells. By such delivery, normal tissues receive minimal damage while a therapeutical effect is achieved in tumor. A targetingsystem can be constructed by conjugating a tumor-seeking molecule and toxic agents via a carrier. In this thesis, mouse epidermal growth factor, mEGF, was the tumor-seeking molecule for targeting against malignancies that overexpress EGF receptors. Dextran was attached to mEGF by different methods and used as a carrier. Preparation of different mEGF-dextran conjugates, effects of different conjugation methods on cellular intenalization and the biodistribution of the conjugates in vivo were studied in the planning for future clinic trials.</p><p>Two end-end coupling methods have been developed in this thesis. One is direct reductive amination by which the terminal amino group of mEGF reacts with the aldehyde group on rhe reducting end of dextran. The other end-end coupling methods is glutaraldehyde mediated cross-linking, in which a few glutaraldehyde molecules act as a linker between the amino terminus of mEGF and the end-aminated dextran.</p><p>The end-end coupled mEGF-dextran conjugates were investigated together with a randomly coupled mEGF-dextran conjugate, for cellular binding ptterns using cultured glioma cells. The time for maximal binding and the intracellular retention of the conjugates were analysed. The intracellular radioactivity associated with free mEGF had a fast turnover whereas all three conjugates gave long half-lives for the intracellular retention.</p><p>The end-end coupled mEGF-dextran, type A prepared by reductive amination, had a dissociation constant of 7.1 x 10<sup>-9</sup> M and free mEGF had a value of 6.6 x 10<sup>-10</sup> M. The end-end coupled intermediate was further activated by the cyanopyridinium agent CDAP and tyrosines were introduced to the dextran part of the conjugate. The iodinated conjugate could to a large extent be internalized in test cells and the radioactivity was retained intracellularly better than when the radioactivity only was on the mEGF part of the conjugate.</p><p>Dextranated mEGF had a slower clearance in blood and liver than mEGF as seen in positron emission tomography on rats. Dextranated mEGF also had a lower uptake in kidney than free mEGF. There was an "unknown mEGF complex" in the blood circulation which was formed after mEGF was injected but this complex did not appear in urine samples.</p>
  • Andersson, P, et al. (författare)
  • Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide.
  • 1996
  • Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:12, s. 2002-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells.
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