| 351. |
- Romiani, Arman, 1991, et al.
(författare)
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Neuroblastoma xenograft models demonstrate the therapeutic potential of Lu-177-octreotate
- 2021
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40-50%, indicating the need for novel and improved treatment options. Lu-177-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of Lu-177-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of Lu-177-octreotate for treatment of NB. Methods BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts (n = 5-7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq Lu-177-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1-5, and Ki67 were carried out for tumor xenografts from the three cell lines. Results High Lu-177 concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq Lu-177-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq Lu-177-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32. Conclusion T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of Lu-177-octreotate as a therapeutic alternative for metastatic NB.
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| 352. |
- Russnes, Kjell M., et al.
(författare)
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Total antioxidant intake and prostate cancer in the Cancer of the Prostate in Sweden (CAPS) study. A case control study
- 2016
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Ingår i: BMC Cancer. - : BIOMED CENTRAL LTD. - 1471-2407 .- 1471-2407. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The total intake of dietary antioxidants may reduce prostate cancer risk but available data are sparse and the possible role of supplements unclear. We investigated the potential association between total and dietary antioxidant intake and prostate cancer in a Swedish population. Methods: We used FFQ data from 1499 cases and 1112 controls in the population based case-control study Cancer of the Prostate in Sweden (CAPS). The ferric reducing antioxidant potential (FRAP) assay was used to assess the total antioxidant capacity (TAC) of diet and supplements. We calculated odds ratios (ORs) for the risk of prostate cancer across quintiles of antioxidant intake from all foods, from fruit and vegetables only, and from dietary supplements using unconditional logistic regression. Results: Coffee comprised 62 % of the dietary antioxidant intake, tea 4 %, berries 4 %, chocolate 2 %, and boiled potatoes 2 %. In total 19 % and 13 % of the population took multivitamins and supplemental Vitamin C respectively, on a regular basis. Antioxidant intake from all foods and from fruits and vegetables separately measured by the FRAP assay was not associated with prostate cancer risk. For antioxidant intake from supplements we found a positive association with total, advanced, localized, high grade and low grade prostate cancer in those above median supplemental TAC intake of users compared to non-users (Adjusted ORs for total prostate cancer: 1. 37, 95 % CI 1.08-1.73, advanced: 1.51, 95 % CI 1.11-2.06, localized: 1.36. 95 % CI 1.06-1.76, high grade 1.60, 95 % CI 1.06-2.40, low grade 1.36, 95 % CI 1.03-1.81). A high intake of coffee (>= 6 cups/day) was associated with a possible risk reduction of fatal and significantly with reduced risk for high grade prostate cancer, adjusted OR: 0.45 (95 % CI: 0.22-0.90), whereas a high intake of chocolate was positively associated with risk of total, advanced, localized and low grade disease (adjusted OR for total: 1.43, 95 % CI 1.12-1.82, advanced: 1.40, 95 % CI 1.01-1.96, localized: 1.43, 95 % CI 1.08-1.88, low-grade: 1.41, 95 % CI 1.03-1.93). Conclusions: Total antioxidant intake from diet was not associated with prostate cancer risk. Supplement use may be associated with greater risk of disease.
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| 353. |
- Rydén, Isabelle, et al.
(författare)
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Psychotropic and anti-epileptic drug use, before and after surgery, among patients with low-grade glioma: a nationwide matched cohort study
- 2021
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-grade glioma (LGG) is a relatively rare type of brain tumour. The use of antidepressant, sedative and anti-epileptic drugs can reflect the burden of the disease. While epilepsy is well-described in patients with LGG, less is known about depression and anxiety.Methods: We used nationwide registers to study the use (dispense) of antidepressants, sedatives, and anti-epileptic drugs (AEDs) before and after histopathological LGG diagnosis (WHO grade II). A total of 485 adult patients with a first-time diagnosis and a matched control cohort (n = 2412) were included. Patterns of use were analysed from one year prior to until one year following index date (date of surgery). Logistic regression analysis identified predictors for postoperative use.Results: At one year before index date, patients were dispensed AEDs 4 times more than controls, while antidepressants and sedatives were similar. Sedatives and AED peaked shortly after index date at 25 and 69%, respectively. AEDs then stabilized while sedatives decreased rapidly. For antidepressants, a delayed increase was seen after index date, stabilizing at 12%. At one year after index date, the use of antidepressants, sedatives, and AEDs among patients was 2, 3, and 26 times higher, respectively, compared to controls. Predictor for use of AEDs and sedatives at one year following index was previous use and/or a related diagnosis. Female sex and later index year were additional predictors for antidepressants.Conclusions: Use of antidepressants, sedatives and AEDs is elevated following diagnosis of LGG. Antidepressants were more commonly dispensed to female patients and in recent years.
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| 354. |
- Saamarthy, Karunakar, et al.
(författare)
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Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells
- 2024
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Ingår i: BMC Cancer. - 1471-2407. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular targeted therapy using a drug that suppresses the growth and spread of cancer cells via inhibition of a specific protein is a foundation of precision medicine and treatment. High expression of the proto-oncogene Bcl-3 promotes the proliferation and metastasis of cancer cells originating from tissues such as the colon, prostate, breast, and skin. The development of novel drugs targeting Bcl-3 alone or in combination with other therapies can cure these patients or prolong their survival. As a proof of concept, in the present study, we focused on metastatic melanoma as a model system. High-throughput screening and in vitro experiments identified BCL3ANT as a lead molecule that could interfere with Bcl-3-mediated cyclin D1 expression and cell proliferation and migration in melanoma. In experimental animal models of melanoma, it was demonstrated that the use of a Bcl-3 inhibitor can influence the survival of melanoma cells. Since there are no other inhibitors against Bcl-3 in the clinical pipeline for cancer treatment, this presents a unique opportunity to develop a highly specific drug against malignant melanoma to meet an urgent clinical need.
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| 355. |
- Saamarthy, Karunakar, et al.
(författare)
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Early diagnostic value of Bcl-3 localization in colorectal cancer
- 2015
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 15:341
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Tidskriftsartikel (refereegranskat)abstract
- Background: B-cell leukemia 3 (Bcl-3) is a member of the inhibitor of kappa B family, which regulates a wide range of biological processes by functioning as a transcriptional activator or as a repressor of target genes. Elevated expression, sustained nuclear accumulation, and uncontrolled activation of Bcl-3 causes increased cellular proliferation or survival, dependent on the tissue and type of stimuli. Methods: We retrospectively reviewed patients who were diagnosed with colorectal cancer at Skane University Hospital in Malmo between 1st of January 1990 and 31st of December 1991. Bcl-3 localization in colorectal cancer was assessed by immunohistochemistry on tissue microarray and freshly isolated colon from patients. Correlation between Bcl-3 localization and clinicopathological parameters of the cohort were evaluated using the Spearman rank-order correlation coefficient. In addition, Bcl-3 expression and localization in colon adenocarcinoma cells were analysed by western blot, immunohistochemistry and subcellular fractionation separately. Results: We found that Bcl-3 was mainly localized in the cytoplasm in the tumour tissue isolated from colon cancer patients. Normal colon samples from the same patients showed Bcl-3 localization in the nucleus. In three out of six colon cancer cell lines, we detected elevated levels of Bcl-3. In these cell lines Bcl-3 was accumulated in the cytosol. We confirmed these findings by analysing Bcl-3 localization in a colon tissue micro array consisting of 270 cases. In these samples Bcl-3 localization correlated with the proliferation marker Ki-67, but not with the apoptotic marker Caspase 3. Conclusion: These findings indicate that analysis of the subcellular localization of Bcl-3 could be a potential-early diagnostic marker in colon cancer.
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| 356. |
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| 357. |
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| 358. |
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| 359. |
- Salimzadeh, Hamideh, 1975, et al.
(författare)
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Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival
- 2020
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSingle nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.MethodsSNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS.ResultsThe CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p=0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p=0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p=0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p=0.006 and p=0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p=0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p=0.02). However, there was no significant association between the SNPs and 5-year RFS.ConclusionsBoth SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.
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