| 61. |
- deWeert, Michael J., et al.
(author)
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Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo
- 2003
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In: Proceedings of SPIE. - : SPIE. ; 4959, s. 67-76
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Journal article (peer-reviewed)abstract
- The use of fluorescence and reflectance spectroscopy in the analysis of cervical histopathology is a growing field of research. The majority of this research is performed with point-like probes. Typically, clinicians select probe sites visually, collecting a handful of spectral samples. An exception to this methodology is the Hyperspectral Diagnostic Imaging (HSDI®) instrument developed by Science and Technology International. This non-invasive device collects contiguous hyperspectral images across the entire cervical portio. The high spatial and spectral resolution of the HSDI instruments make them uniquely well suited for addressing the issues of coupled spatial and spectral variability of tissues in vivo. Analysis of HSDI data indicates that tissue spectra vary from point to point, even within histopathologically homogeneous regions. This spectral variability exhibits both random and patterned components, implying that point monitoring may be susceptible to significant sources of noise and clutter inherent in the tissue. We have analyzed HSDI images from clinical CIN (cervical intraepithelial neoplasia) patients to quantify the spatial variability of fluorescence and reflectance spectra. This analysis shows the spatial structure of images to be fractal in nature, in both intensity and spectrum. These fractal tissue textures will limit the performance of any point-monitoring technology.
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| 62. |
- Dib, Karim, et al.
(author)
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Down-regulation of Rac activity during beta 2 integrin-mediated adhesion of human neutrophils
- 2003
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 278:26, s. 24181-24188
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Journal article (peer-reviewed)abstract
- In human neutrophils, beta2 integrin engagement mediated a decrease in GTP-bound Rac1 and Rac2. Pretreatment of neutrophils with LY294002 or PP1 (inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) and Src kinases, respectively) partly reversed the beta2 integrin-induced down-regulation of Rac activities. In contrast, beta2 integrins induced stimulation of Cdc42 that was independent of Src family members. The PI 3-kinase dependence of the beta2 integrin-mediated decrease in GTP-bound Rac could be explained by an enhanced Rac-GAP activity, since this activity was blocked by LY204002, whereas PP1 only had a minor effect. The fact that only Rac1 but not Rac2 (the dominating Rac) redistributed to the detergent-insoluble fraction and that it was independent of GTP loading excludes the possibility that down-regulation of Rac activities was due to depletion of GTP-bound Rac from the detergent-soluble fraction. The beta2 integrin-triggered relocalization of Rac1 to the cytoskeleton was enabled by a PI 3-kinase-induced dissociation of Rac1 from LyGDI. The dissociations of Rac1 and Rac2 from LyGDI also explained the PI 3-kinase-dependent translocations of Rac GTPases to the plasma membrane. However, these accumulations of Rac in the membrane, as well as that of p47phox and p67phox, were also regulated by Src tyrosine kinases. Inasmuch as Rac GTPases are part of the NADPH oxidase and the respiratory burst is elicited in neutrophils adherent by beta2 integrins, our results indicate that activation of the NADPH oxidase does not depend on the levels of Rac-GTP but instead requires a beta2 integrin-induced targeting of the Rac GTPases as well as p47phox and p67phox to the plasma membrane.
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| 63. |
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| 64. |
- Dong, Ying, et al.
(author)
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Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers
- 2003
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In: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 9:5, s. 1710-20
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Journal article (peer-reviewed)abstract
- PURPOSE: The wild-type or variant mRNAs of several kallikrein (KLK) genes, such as KLK4, are highly expressed in ovarian carcinomas and may have potential as tumor markers. Two of these KLK genes (KLK5 and KLK7) and their proteins (hK5 and hK7) were first identified in the skin epidermis, where hK5 may be the physiological activator of hK7. The purpose of this study was to reexamine the expression of KLK5/hK5 and KLK7/hK7 and their association and to determine whether cancer-related variant transcripts were expressed.EXPERIMENTAL DESIGN: The expression of KLK5/hK5 and KLK7/hK7 was analyzed in the same cohort (n = 37) of benign (n = 4) and malignant ovarian tissue (n = 23) samples and primary cultured cells (n = 21) and in 8 ovarian cancer cell lines using semiquantitative RT-PCR; Southern, Northern, and Western blot analyses; and immunohistochemistry techniques.RESULTS: We showed the concordant higher expression of both KLK5/hK5 and KLK7/hK7 in ovarian carcinomas, especially late-stage serous carcinomas, compared with normal ovaries and benign adenomas. We also found that one novel KLK5 transcript with a short 5'-untranslated region and a novel KLK7 transcript with a long 3'-untranslated region were highly expressed in the ovarian cancer cell lines OVCAR-3 and PEO1, respectively, but were expressed at very low levels in normal ovarian epithelial cells. Both Western blot and immunohistochemistry analyses showed that these two enzymes are secreted from ovarian carcinoma cells.CONCLUSIONS: Our study demonstrated that hK5 and hK7, or more specifically, the short KLK5 and long KLK7 transcripts, may be useful as tumor markers for epithelial-derived serous carcinomas. However, additional clinical studies assessing serum levels of these putative biomarkers are required to confirm their usefulness in the diagnosis and/or monitoring of these tumors.
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| 65. |
- Dryver, ET, et al.
(author)
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Follow-up of patients with Hodgkin's disease following curative treatment: the routine CT scan is of little value
- 2003
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 89:3, s. 482-486
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Journal article (peer-reviewed)abstract
- A total of 10-40% of patients with Hodgkin's disease relapse following initial curative therapy. Intensive follow-up is resource intensive and may identify false relapses. We performed a retrospective review of all patients with Hodgkin's disease treated at our centre between 1990 and 1999 to evaluate the utility of the components of follow-up. A total of 107 patients met the inclusion and exclusion criteria. The median age was 33 years and the median duration of follow-up 38 months. The total number of follow-up visits was 1209 and total number of CT scans 283. There were 109 suspected relapses of which 22 proved to be true relapses. Of the latter, 14 were identified clinically, six radiologically and two via lab testing. The routine CT scan detected only two relapses (9%), yet accounted for 29% of the total follow-up costs. Based on data from our centre, the cost per true relapse was $6000 US, 49% incurred by radiological tests. The majority of the cost of follow-up was incurred by routine follow-up (84%) as opposed to the investigation of suspected relapses (16%). We conclude that most true relapses are clinically symptomatic and that the routine CT is an expensive and inefficient mode of routine follow-up.
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| 66. |
- Ebbesson, Lars, et al.
(author)
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Neural circuits and their structural and chemical reorganization in the light-brain-pituitary axis during parr-smolt transformation in salmon
- 2003
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In: Aquaculture. - 0044-8486. ; 222:1-4, s. 59-70
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Journal article (peer-reviewed)abstract
- Salmonid parr-smolt transformation (smoltification) is a transitional stage between freshwater and seawater life when the salmon imprint on their natal stream, change from a territorial feeding behavior to downstream migration, increase their hypoosmoregulatory competence, and change body shape and coloration. Photoperiod is recognized as the most potent initiator and regulator of the smoltification processes. Environmental light signals giving information about photoperiod are conveyed through a light-brain-pituitary axis that encompasses the neural pathways between photoreceptor organs, the brain and the pituitary, and the diurnal rhythm in melatonin secretion by the photosensory pineal organ. In addition, changes in photoperiod may elicit changes in this axis. Employing retinal neural tract tracing and growth associated protein-43 (GAP-43) immunocytochemistry, we provide here new evidence of a structural reorganization in the light-brain-pituitary axis during smoltification. Retinal tract tracing revealed that projections in smolts expand into new territories of the ipsilateral nucleus preopticus parvocellularis pars anterior (PPa) and additional fibers invade deeper into the contralateral PPa and the nucleus preopticus magnocellularis (PM). At this time, GAP-43-immunoreactive cells appear transiently in specific cell groups throughout the brain, but mainly in the olfactory bulb, telencephalon, and hypothalamus. These structural changes in the light-brain-pituitary axis and hypophysiotropic systems are followed by sequential surges of brain neurotransmitters and receptors, and occur prior to the major surges of circulating thyroid hormone and growth hormone levels that are central to smoltification-related processes. Our data point to a specific period of structural reorganization in certain brain circuits, and we hypothesize that these are involved in triggering the subsequent behavioral, endocrine, and physiological changes associated with smoltification. (C) 2003 Published by Elsevier Science B.V.
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| 67. |
- Edsjö, Anders, et al.
(author)
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Expression of trkB in Human Neuroblastoma in Relation to MYCN Expression and Retinoic Acid Treatment.
- 2003
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In: Laboratory Investigation. - 1530-0307. ; 83:6, s. 813-823
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Journal article (peer-reviewed)abstract
- Expression of full-length trkB can be found in some highly malignant neuroblastoma tumors with an amplified MYCN gene. This contrasts sympathetic neuroblasts, from which neuroblastomas are thought to arise, which neither express trkB nor are dependent on the p145trkB ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5, for their normal development. In this study we show that trkB was expressed in two out of five neuroblastoma tumors with amplified MYCN, while no trkB expression was observed when the MYCN gene was overexpressed in a non–MYCN-amplified neuroblastoma cell line. This shows that MYCN overexpression per se is not sufficient to induce trkB expression. trkB expression and BDNF responsiveness in neuroblastoma cells can be induced by all-trans-retinoic acid (RA). When SH-SY5Y cells were stimulated with a combination of RA and BDNF, norepinephrine and tyrosine hydroxylase levels were unaltered, showing that the cells did not change toward a more catecholaminergic sympathetic phenotype. However, expression of growth-associated protein 43, indicative of a neuronal phenotype, was elevated. Vesicular acetylcholine transporter, choline acetyl transferase, and neuropeptide tyrosine mRNA levels also increased in RA-BDNF–treated cells, which could suggest that these cells develop into a sympathetic cholinergic phenotype. In addition, treatment with RA-induced expression of the platelet-derived growth factor receptor-alpha. As previously shown for BDNF, platelet-derived growth factor stimulated growth of the RA-treated cells, findings that could have clinical relevance. If these receptors mediate a mitogenic signal in vivo also, this might limit the effect of RA treatment on neuroblastoma patients.
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| 68. |
- Einhorn, N, et al.
(author)
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A systematic overview of radiation therapy effects in cervical cancer (cervix uteri)
- 2003
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 546-556
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Journal article (peer-reviewed)abstract
- A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for cervical cancer is based on data from 1 meta-analysis and 34 randomized trials. In total, 35 scientific articles are included, involving 7952 patients. The results were compared with those of a similar overview from 1996 including 34 024 patients. The conclusions reached can be summarized in these points: There are limited scientific data supporting that postoperative pelvic radiotherapy improves disease-free survival in early cervical cancer. No firm conclusion can be drawn. There is moderate scientific evidence that external beam radiotherapy combined with brachytherapy gives a similar disease-free and overall survival rate as radical hysterectomy in early cervical cancer. There is strong scientific evidence that concomitant radiochemotherapy improves disease-free and overall survival compared to radiotherapy alone in early cervical cancer. The NCI has recently published an announcement stating that cisplatin-based chemotherapy should be used concomitantly with radiotherapy in cervical cancer. No solid documentation for this statement can be found concerning locally advanced stages ( >IIB). There is a strong scientific evidence that cisplatin-based chemotherapy given concomitantly with radiotherapy is superior to concomitant chemotherapy with hydroxyurea. There is no scientific evidence to show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free or overall survival compared to radiotherapy alone in patients with localized cervical cancer. There is moderate scientific evidence that high-dose-rate brachytherapy gives the same local control rate as low-dose-rate brachytherapy but with fewer rectal complications.
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| 69. |
- Einhorn, N, et al.
(author)
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A systematic overview of radiation therapy effects in ovarian cancer
- 2003
-
In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 562-566
-
Journal article (peer-reviewed)abstract
- A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for ovarian cancer is based on data from six randomized trials. Moreover, data from one prospective study and three retrospective studies were used. In total, 10 scientific articles are included, involving 1282 patients. The results were compared with those of a similar overview from 1996 including 15042 patients. The conclusions reached can be summarized in the following points: There is no scientific documentation supporting adjuvant radiotherapy for early-stage, low-risk patients. No studies have been reported where adjuvant radiotherapy has been compared with no adjuvant therapy in early-stage, high-risk patients. Adjuvant radiotherapy, either whole abdominal irradiation or intraperitoneal p(32), has been compared with adjuvant chemotherapy in early-stage, high-risk patients. There is no scientific evidence to show that there is a difference in efficacy. There is some evidence to suggest that adjuvant radiotherapy after radical surgery leads to an increase in disease-free survival rate for patients with advanced-stage ovarian cancer. There is little documentation on long-term side effects (second malignancy) after adjuvant radiotherapy and no conclusions can be drawn.
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| 70. |
- Einhorn, N, et al.
(author)
-
A systematic overview of radiation therapy effects in uterine cancer (corpus uteri)
- 2003
-
In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 557-561
-
Journal article (peer-reviewed)abstract
- A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for uterine cancer is based on data from one randomized study Moreover, data from two prospective studies and seven retrospective studies were used. In total, 10 scientific articles are included, involving 3446 patients. The results were compared with those of a similar overview from 1996 including 13597 patients. The conclusions reached can be summarized as: There is fairly good evidence that there is no need for adjuvant radiotherapy in patients with good risk uterine cancer. There is fairly good evidence that adjuvant radiotherapy reduces the relapse rate in high-risk patients but has no impact on survival. There is substantial documentation showing that medically inoperable patients and patients with locally recurrent uterine cancer can be treated with radiotherapy alone with curative effect.
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