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Sökning: L773:0007 0920 OR L773:1532 1827 > (2000-2004)

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11.
  • Dalen, Helge, et al. (författare)
  • a-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-?B activation
  • 2003
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 88:1, s. 153-158
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Activation of nuclear factor-?B (NF-?B) can interfere with induction of apoptosis triggered by the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L). Therefore, agents that suppress NF-?B activation may sensitise cells to TRAIL-dependent apoptosis. Exposure of Jurkat cells to TRAIL resulted in massive and saturable apoptosis induction, following an initial lag time. This lag was abolished by pretreatment of the cells with subapoptotic doses of a-tocopheryl succinate (a-TOS) or the proteasome inhibitor MGI32. Exposure of the cells to TRAIL led to a rapid, transient activation of NF-?B, a process that was suppressed by cell pretreatment with a-TOS or MGI32. Activation of NF-?B by TNF-a prior to TRAIL exposure increased resistance of the cells to TRAIL-mediated apoptosis. We conclude that a-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-?B activation. This further supports the possibility that this semisynthetic analogue of vitamin E is a potential adjuvant in cancer treatment, such as in the case of TRAIL-mediated inhibition of cancer.</p>
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12.
  • Hultdin, M, et al. (författare)
  • Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia : clinical and biological implications.
  • 2003
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 88:4, s. 593-8
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (&gt;6%) had long telomeres ( approximately 8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.</p>
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13.
  • Hultdin, Magnus, et al. (författare)
  • Association between telomere length and V-H gene mutation status in chronic lymphocytic leukaemia : clinical and biological implications
  • 2003
  • Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 88:4, s. 593-598
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The immunoglobulin V-H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V-H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated VH genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and VH gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between VH gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 63 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months), Furthermore, the I-g gene sequence data revealed that samples with high mutations frequency (&gt; 6%) had long telomeres (similar to 8 kbp). Thus, both the telomere and VH gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. (C) 2003 Cancer Research UK.</p>
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14.
  • Håkansson, Annika, 1962-, et al. (författare)
  • Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes
  • 2001
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 85:12, s. 1871-1877
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The therapeutic efficacy of biochemotherapy in metastatic malignant melanoma still carries a low remission rate, but with some durable responses. It would therefore be of considerable importance if patients with a high probability of responding could be identified using predictive tests. The response to interferon-alpha (IFN-a) correlates with the occurrence of CD4+ lymphocytes identified by fine-needle aspirates from melanoma metastases (Hσkansson et al, 1996). The present investigation studies a possible correlation between tumour-infiltrating CD4+ lymphocytes in malignant melanoma metastases and the therapeutic effect of biochemotherapy. A total of 25 patients with systemic and 16 with regional metastatic melanoma were analysed before initiation of biochemotherapy (cis-platinum 30 mg/m2 d.1-3, DTIC 250 mg/m2 d.1-3 i.v. and IFN-a2b 10 million IU s.c. 3 days a week, q. 28d.). A monoclonal antibody, anti-CD4, was used to identify tumour-infiltrating lymphocytes in fine-needle aspirates before start of treatment. The presence of these lymphocytes was correlated to response, time to progression and overall survival. A statistically significant correlation (P = 0.01) was found between the occurrence of CD4+ lymphocytes and tumour regression during biochemotherapy in patients with systemic disease. Out of 14 patients with moderate to high numbers of infiltrating CD4+ lymphocytes, 12 achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, 8 out of 11 had progressive disease. We also found a significantly longer time to progression (P &lt; 0.003) and overall survival (P &lt; 0.01) among patients with moderate to high numbers of these cells compared to patients with low numbers of these cells before initiation of biochemotherapy. Furthermore, in patients with regional disease, we found a significantly longer time to progression (P = 0.01) and a trend toward a longer overall survival time (P = 0.09). Based on these results and as previously shown with IFN-a therapy alone, there seems to be a need for CD4+ lymphocytes infiltrating the tumours before the start of biochemotherapy to make the treatment successful. Determination of these cells in fine-needle aspirates seems to be a method to predict responders to biochemotherapy, thus increasing the cost-benefit of this treatment strategy considerably, both in terms of patient adverse reactions and health care costs. ⌐ 2001 Cancer Research Campaign.</p>
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15.
  • Johansson, M., et al. (författare)
  • Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma
  • 2000
  • Ingår i: British Journal of Cancer. - Cancer Research Campaign. - 0007-0920 .- 1532-1827. ; 83:6, s. 826-832
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg(-1)s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma.</p>
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16.
  • Jordhøy, Marit 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. - Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 85:10, s. 1478-1485
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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17.
  • Kjellberg, L, et al. (författare)
  • Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.
  • 2000
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 82:7, s. 1332-8
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P &lt; 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.</p>
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18.
  • Larsson, Susanna C., et al. (författare)
  • Fruit and vegetable consumption in relation to ovarian cancer incidence : the Swedish Mammography Cohort
  • 2004
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 90:11, s. 2167-70
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We prospectively examined the incidence of epithelial ovarian cancer and its subtypes in relation to baseline fruit and vegetable consumption in the Swedish Mammography Cohort, a population-based cohort study of 61 084 women aged 38-76 years in 1987-1990. During an average follow-up of 13.5 years, 266 incident cases of invasive epithelial ovarian cancer were diagnosed. After adjustment for potential confounders, we observed a statistically significant inverse association between consumption of vegetables and ovarian cancer risk (P-value for trend=0.01); the multivariate rate ratio (RR) for the comparison of three or more servings of vegetables per day with one or fewer servings per day was 0.61 (95% confidence interval (CI), 0.38-0.97). For fruit consumption a modest, not statistically significant, positive association was found (P-value for trend=0.07); the multivariate RR for the highest compared with the lowest category of consumption being 1.37 (95% CI, 0.90-2.06). The associations with fruit and vegetable consumption did not vary by subtype of ovarian cancer. These findings suggest that high consumption of vegetables, but not of fruits, may reduce the risk of ovarian cancer.</p>
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19.
  • Mucci, L A, et al. (författare)
  • Dietary acrylamide and cancer of the large bowel, kidney, and bladder : Absence of an association in a population-based study in Sweden
  • 2003
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 88:1, s. 84-89
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Recently, disturbingly high levels of acrylamide were unexpectedly detected in widely consumed food items, notably French fries, potato crisps, and bread. Much international public concern arose since acrylamide has been classified as a probable carcinogen, although based chiefly on laboratory evidence; informative human data are largely lacking. We reanalysed a population-based Swedish case-control study encompassing cases with cancer of the large bowel (N = 591), bladder (N = 263) and kidney (N = 133), and 538 healthy controls, assessing dietary acrylamide by linking extensive food frequency data with acrylamide levels in certain food items recorded by the Swedish National Food Administration. Unconditional logistic regression was used to estimate odds ratios, adjusting for potential confounders. We found consistently a lack of an excess risk, or any convincing trend, of cancer of the bowel, bladder, or kidney in high consumers of 14 different food items with a high (range 300-1200 mug kg(-1)) or moderate (range 30-299 mug kg(-1)) acrylamide content. Likewise, when we analysed quartiles of known dietary acrylamide intake, no association was found with cancer of the bladder or kidney. Unexpectedly, an inverse trend was found for large bowel cancer (P for trend 0.01) with a 40% reduced risk in the highest compared to lowest quartile. We found reassuring evidence that dietary exposure to acrylamide in amounts typically ingested by Swedish adults in certain foods has no measurable impact on risk of three major types of cancer. It should be noted, however, that relation of risk to the acrylamide content of all foods could not be studied. </p>
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20.
  • Neuzil, Jiri, 1958- (författare)
  • Vitamin E succinate and cancer treatment : A vitamin E prototype for selective antitumour activity
  • 2003
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 89:10, s. 1822-1826
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Great hope has been given to micronutrients as anticancer agents, since they present natural compounds with beneficial effects for normal cells and tissues. One of these is vitamin E (VE), an antioxidant and an essential component of biological membranes and circulating lipoproteins. In spite of a number of epidemiological and intervention studies, little or no correlation between VE intake and incidence of cancer has been found. Recent reports have identified a redox-silent analogue of VE, a-tocopheryl succinate (a-TOS), as a potent anticancer agent with a unique structure and pharmacokinetics in vivo. a-TOS is highly selective for malignant cells, inducing them into apoptotic death largely via the mitochondrial route. The molecule of a-TOS may be modified so that analogues with higher activity are generated. Finally, a-TOS and similar agents are metabolised to VE, thereby yielding a compound with a secondary beneficial activity. Thus, a-TOS epitomises a group of novel compounds that hold substantial promise as future anticancer drugs. The reasons for this optimistic notion are discussed in the following paragraphs. ⌐ 2003 Cancer Research UK.</p>
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