| 1. |
- Batra, Satish, et al.
(författare)
-
Release of intracellular calcium and stimulation of cell growth by ATP and histamine in human ovarian cancer cells (SKOV-3)
- 1994
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 77:1, s. 57-63
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of ATP and histamine on cell proliferation and intracellular calcium concentrations ([Ca2+]i) were examined in the human ovarian cancer cell line SKOV-3. Micromolar concentrations of ATP induced a biphasic increase in [Ca2+]i representing a rapid rise to a peak level followed by a smaller but more sustained phase. When influx of extracellular calcium was blocked by calcium chelation to EGTA, the ATP-stimulated rise in [Ca2+]i was rapid and only monophasic. Histamine, in contrast to ATP, caused only a monophasic rise in [Ca2+]i both in the presence and absence of external calcium. The histaminergic H1 receptor antagonist pyrilamine, but not the H2 receptor antagonist cimetidine, totally blocked rises in [Ca2+]i caused by histamine. Fetal calf serum (FCS) induced a slow and monophasic increase in [Ca2+]i in these cells, distinctly different from rises in [Ca2+]i caused by ATP and histamine. Inclusion of low micromolar concentrations of ATP in the growth medium stimulated proliferation of these cells, while higher concentrations (100 microM-1 mM) significantly decreased cellular proliferation. Histamine, in micromolar concentrations, also stimulated cell proliferation. From these results it was concluded that the release of intracellularly bound Ca2+ following receptor stimulation is sufficient to induce cellular proliferation in SKOV-3 cells.
|
|
| 2. |
- Borg, Åke, et al.
(författare)
-
ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
- 1994
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
-
Tidskriftsartikel (refereegranskat)abstract
- Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.
|
|
| 3. |
- Gisselsson, D, et al.
(författare)
-
A case of dermatofibrosarcoma protuberans with a ring chromosome 5 and a rearranged chromosome 22 containing amplified COL1A1 and PDGFB sequences
- 1998
-
Ingår i: Cancer Letters. - 0304-3835 .- 1872-7980. ; 133:2, s. 34-129
-
Tidskriftsartikel (refereegranskat)abstract
- Dermatofibrosarcoma protuberans (DFSP) is a cutaneous tumour of borderline malignancy, the cytogenetic features of which include the translocation t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing material from 17q22 and 22q13. These rearrangements result in the COL1A1/PDGFB fusion gene. Here, we describe a case of DFSP displaying a ring chromosome 5 together with a large marker chromosome composed of chromosome 22 alphoid DNA, material from distal 12q and amplified COL1A1 and PDGFB sequences. This is the first case of DFSP with multiple copies of COL1A1 and PDGFB not confined to ring chromosomes, showing that DFSP is similar to other borderline malignant mesenchymal tumours, where rings and giant markers are alternative vehicles for amplified material.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Karlsson, Mats G., 1960-, et al.
(författare)
-
No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation
- 1997
-
Ingår i: Cancer Letters. - Clare, Ireland : Elsevier. - 0304-3835 .- 1872-7980. ; 120:2, s. 173-177
-
Tidskriftsartikel (refereegranskat)abstract
- An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Lotfi, Kourosh, 1966-, et al.
(författare)
-
Comparison of idarubicin and daunorubicin regarding intracellular uptake, induction of apoptosis, and resistance
- 2002
-
Ingår i: Cancer Letters. - 0304-3835 .- 1872-7980. ; 178:2, s. 141-149
-
Tidskriftsartikel (refereegranskat)abstract
- Anthracycline antibiotics are widely used as anticancer agents. Idarubicin (4-demethoxydaunorubicin; Ida), a semisynthetic derivative of daunorubicin (Dnr) is more potent than the parent compound in vitro and in vivo. The equitoxic dose of Ida in patients is about one-fourth of that of Dnr. We compared these drugs regarding cytotoxicity, apoptosis induction, and resistance mechanisms in human leukaemic cell lines. Cytotoxicity was studied by means of the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and drug-induced apoptosis by means of the Annexin V–fluorescein isothiocyanate method at similar intracellular concentrations (extracellular concentrations of 0.35 μM for Ida and 1 μM for Dnr). Ida was at least twice as potent as Dnr in MOLT-4, HL60, CEM, and K562 cell lines. It took 8 h for Ida to induce approximately 20% apoptosis, but at least 22 h for Dnr to reach 20% apoptosis at identical intracellular concentration. Ida induces a faster and higher apoptosis rate compared with Dnr. The human chronic myelogenous leukaemia cell line (K562) was selected for resistance to Dnr and Ida with and without verapamil (Ver). Continuous incubation with Dnr, but not with Ida, led to an increased mdr1 gene expression as assessed by real-time PCR. The development of mdr1 gene expression in Dnr-resistant cells could be reversed by the presence of Ver. Ver also reversed the cytotoxicity to Dnr, but not to Ida, in K562/Dnr cells. The results show that Ida is more effective than Dnr in inducing apoptosis and that there are differences in resistance mechanisms between the drugs.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Nannmark, Ulf, 1958, et al.
(författare)
-
Inhibition of leukocyte phagocytosis by serotonin and its possible role in tumor cell destruction.
- 1992
-
Ingår i: Cancer letters. - : Elsevier BV. - 0304-3835. ; 62:1, s. 83-6
-
Tidskriftsartikel (refereegranskat)abstract
- Intraportal tumour cell (TC) injection activates platelets which release serotonin (5-HT). Thrombocytopenia or 5-HT blockade decrease the hepatic lodgement of the injected TCs. A hypothetical explanation of this is 5-HT inhibition of TC killing by phagocytes (e.g. leukocytes and Kupffer cells). In this study, leukocyte phagocytosis was analysed by a chemiluminescence technique at different 5-HT concentrations. Significant inhibition of phagocytosis occurred at 5-HT concentrations of 10(-4) M to 10(-8) M, with maximum inhibition at 10(-4) M. Comparable concentrations of 5-HT may be found locally in the liver during TC infusion, supporting the hypothesis that 5-HT has an inhibitory effect on phagocyte-mediated TC killing.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Ullen, H, et al.
(författare)
-
Supplementary iron intake and risk of cancer : Reversed causality?
- 1997
-
Ingår i: Cancer Letters. - 0304-3835 .- 1872-7980. ; 114:1-2, s. 215-216
-
Tidskriftsartikel (refereegranskat)abstract
- Dietary iron intake and body iron stores have been suggested to increase cancer risk, especially colorectal cancer. Within a population-based case-control study in Stockholm county 1993-94, information on dietary and supplementary iron intake were collected through a food frequency questionnaire. An initially noted positive association between intake of supplementary iron and colorectal cancer risk was reversed when intake 5 years prior to cancer diagnosis was subtracted. Reversed causality due to early disease giving symptoms of iron shortage, resulting in iron supplementation, is an issue to consider when a possible association between intake of iron and cancer risk is investigated.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Yang, K., et al.
(författare)
-
Novel somatic mutations in the VHL gene in Swedish archived sporadic renal cell carcinomas
- 1999
-
Ingår i: Cancer Letters. - Clare, Ireland : Elsevier. - 0304-3835 .- 1872-7980. ; 141:1-2, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Frequent loss-of-function somatic mutations of the VHL gene have been detected in sporadic renal cell carcinoma (RCC), indicating that inactivation of the VHL gene plays a critical role in RCC. In this study, we collected 35 archived Swedish sporadic RCCs identified from an epidemiological study on occupational exposure and kidney cancer to test how well stored pathological specimens could be retrieved and analyzed for VHL mutations. Thirty specimens were successfully analyzed with PCR-SSCP and sequencing. Aberrant SSCP bands were detected in 16 out of the 30 samples (53%). Sequencing analysis of the aberrant bands revealed seven deletions, one insertion, one base substitution on a splicing site, six missense mutations, one silent mutation and several base substitutions in the 5' non-coding region and intron 1. Most were novel somatic mutations that have not been reported in sporadic RCC. The mutations were found in three types of non-papillary RCC cases, i.e. 14 clear cells, one granular chromophilic and one sarcomatoid RCC. Interesting multiple mutations were found in three cases (5, 3, 2 mutations, respectively).
|
|
| 31. |
|
|
| 32. |
- Zhang, Zhi-Jia, et al.
(författare)
-
Synergistic inhibitory effects of interferon-alpha and 5-fluorouracil on human meningeoma cells in vitro
- 1996
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 100:1-2, s. 99-105
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated the effects of interferon-α (IFN-α) and 5-fluorouracil (5-FU) on meningioma cells in two different culture systems, evaluated by the uptake of radiolabelled methionine. With both IFN-α and 5-FU an inhibitory effect on the uptake of radiolabelled methionine by the meningioma cells was demonstrated, and we found a synergistic inhibitory effect with a combination of IFN-α and 5-FU. To obtain a maximal inhibition of cell metabolism without causing cell toxicity, we were able to decrease the dose of 5-FU by simultaneously adding IFN-α. Our results suggest that a combined treatment of IFN-α and 5-FU may be a successful alternative for patients with inoperable meningiomas. A novel in vitro positron emission tomography technique was used for the study of metabolic changes in tumour cells caused by drug treatment, which is complementary to conventional cell culture techniques.
|
|
| 33. |
- Zhuang, Shi-Mei, 1965-, et al.
(författare)
-
Mutation analysis of the pRb pathway in 2',3'-dideoxycytidine- and 1,3-butadiene-induced mouse lymphomas
- 2000
-
Ingår i: Cancer Letters. - 0304-3835 .- 1872-7980. ; 152:2, s. 129-134
-
Tidskriftsartikel (refereegranskat)abstract
- The pRb pathway plays a key role in controlling the G1/S transition in cell cycle progression. Aberrations of various components of the pRb pathway, such as retinoblastoma protein and its upstream actors including cyclin D1, cyclin dependence kinase-4 and p16/p15 cyclin dependent kinase inhibitors, have been reported in a variety of human tumors. Furthermore, the alterations of retinoblastoma protein and its upstream components often occur in a reciprocal manner. Previously, we have reported frequent inactivation of the Cdkn2a/Cdkn2b loci encoding p16/p15 cyclin dependent kinase inhibitors in a subset of 2',3'-dideoxycytidine- and 1,3-butadiene-induced mouse lymphomas (S.-M. Zhuang, A. Schippert, A. Haugen-Strano, R.W. Wiseman, P. Soderkvist, Inactivation of p16(INK4a)-a, p16(INK4a)-▀ and p15(INK4b) genes in 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas, Oncogene 16 (1998) 803-808), indicating the involvement of pRb pathway in lymphomagenesis. To investigate whether alteration of other components in pRb pathway is an alternative mechanism underlying the development of these chemically induced lymphomas, we have examined the genetic status of Rb1, Ccnd1 and Cdk4 genes that encode retinoblastoma protein, cyclin D1 and cyclin dependence kinase-4, respectively. Gross alterations of the Rb1, Ccnd1, and Cdk4 genes were not detected by Southern analysis in any of the tumors examined. In addition, single-strand conformation analysis failed to reveal point mutations in the Cdk4 amino terminal domain that is important for its association with Cdkn2a gene products. These results indicate that the mechanisms underlying the development of 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas involve inactivation of p16/p15 cyclin-dependent kinase inhibitors but not genomic alterations of the Rb1, Ccnd1 and Cdk4 genes. Copyright (C) 2000 Elsevier Science Ireland Ltd.
|
|
| 34. |
- Österström, Anna, et al.
(författare)
-
Expression of cytosolic and group X secretory phospholipase A2 genes in human colorectal adenocarcinomas
- 2002
-
Ingår i: Cancer Letters. - 0304-3835 .- 1872-7980. ; 182:2, s. 175-182
-
Tidskriftsartikel (refereegranskat)abstract
- Gene expression of cytosolic phospholipase A2 (cPLA2) and protein level of secretory PLA2 group X (sPLA2-X) are upregulated in human colorectal cancer and provide cyclooxygenase-2 (COX-2) with arachidonic acid, resulting in increased levels of PGE2. Mutated ras-genes are suggested to be involved in the regulatory pathway of cPLA2 in lung cancer cells. We analysed the gene expression of cPLA2 and sPLA2-X in 42 and 38 primary colorectal tumours, respectively, with and without K-ras mutations. We found an up-regulation of cPLA2 mRNA but the induction in tumour tissues does not correlate with Ras-gene mutations. Moreover, our results cannot consistently reflect an overexpression of sPLA2-X gene in colorectal cancer tissues.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Al-Haidari, Amr, et al.
(författare)
-
MiR-155-5p controls colon cancer cell migration via post-transcriptional regulation of Human Antigen R (HuR)
- 2018
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 421, s. 145-151
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR. Bioinformatics analysis predicted two putative binding sites in the AU-rich elements (AREs) at the 3′-UTR of HuR mRNA. MiR-155-5p binding to HuR was verified using specific target site blockers and functionally validated by use of RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of HuR expression is mediated by AREs. Targeting AREs with a specific blocker inhibited colon cancer cell migration. Taken together, these novel findings demonstrate that AREs mediate miR-155-5p positive regulation of HuR mRNA levels and translation as well as migration in colon cancer cells, suggesting that targeting miR-155-5p and/or Hur might be useful therapeutic strategies against colon cancer metastasis.
|
|
| 38. |
|
|
| 39. |
- Andreasson, Ulrika, et al.
(författare)
-
B cell lymphomas express CX(3)CR1 a non-B cell lineage adhesion molecule
- 2008
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 259:2, s. 138-145
-
Tidskriftsartikel (refereegranskat)abstract
- To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Balassiano, Karen, et al.
(författare)
-
Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
- 2011
-
Ingår i: Cancer Letters. - Amsterdam : Elsevier BV. - 1872-7980 .- 0304-3835. ; 311:1, s. 85-95
-
Tidskriftsartikel (refereegranskat)abstract
- Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological subtype and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
|
|
| 43. |
- Bellamkonda, Kishan, et al.
(författare)
-
Montelukast, a CysLT1 receptor antagonist, reduces colon cancer stemness and tumor burden in a mouse xenograft model of human colon cancer
- 2018
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 437, s. 13-24
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation is implicated in the etiology of sporadic colon cancer (CC), which is one of the leading causes of cancer-related deaths worldwide. Here, we report that inhibition of the inflammatory receptor CysLT1 through its antagonist, montelukast, is beneficial in minimizing stemness in CC and thereby minimizing tumor growth in a mouse xenograft model of human colon cancer. Upon treatment with montelukast, colonospheres derived from HT-29 and SW-480 human colon cancer cells exhibited a significant phenotypic change coupled with the downregulation of mRNA and protein expression of cancer stem cell (CSC) markers ALDH1 and DCLK1. Moreover, montelukast reduced the size of HT-29 cell-derived tumors in mice. The reduction in tumor size was associated with decreased levels of ALDH1A1, DCLK1, BCL2 mRNA and macrophage infiltration into the tumor tissue. Interestingly, this treatment elevated levels of the tumor suppressor 15-PGDH while reducing COX-2 expression. Our data highlight the association of CysLT1R with CSCs and demonstrate that inhibition of CysLT1R could prove beneficial in minimizing CSC-induced tumor growth. This work advances the notion that targeting CSCs is a promising approach to improve outcomes in those afflicted with colon cancer.
|
|
| 44. |
- Bendrik, Christina, et al.
(författare)
-
Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer
- 2010
-
Ingår i: CANCER LETTERS. - : Elsevier Science B.V., Amsterdam.. - 0304-3835. ; 292:1, s. 32-40
-
Tidskriftsartikel (refereegranskat)abstract
- There are several similarities between breast and ovarian cancer but anti-estrogen treatment is rarely used in ovarian cancer. We have previously shown that the most widely used anti-estrogen tamoxifen increased MMP-9 activity and endostatin generation in breast cancer. Here, we show that tamoxifen exposure of highly hormone responsive ovarian cancer cells decreased proliferation, and increased MMP-9 activity leading to increased levels of endostatin both in cell culture in vitro and in solid tumors of nude mice. Tamoxifen exposed tumors also exhibited significantly decreased tumor growth and vascularisation. Moreover, in ascites from ovarian cancer patients, MMP-9 was undetectable in majority of cases but a significant correlation of MMP-2 and endostatin was found. The effects on MMPs and endostatin generation are previously unknown mechanisms of estradiol and tamoxifen in ovarian cancer, which may have therapeutic implications in future anti-cancer options of hormone dependent ovarian cancer.
|
|
| 45. |
|
|
| 46. |
- Berndt, Carsten, et al.
(författare)
-
Ascorbate and endocytosed Motexafin gadolinium induce lysosomal rupture.
- 2011
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 307:2, s. 119-23
-
Tidskriftsartikel (refereegranskat)abstract
- Motexafin gadolinium (MGd) sensitizes malignant cells to ionizing radiation, although the underlying mechanisms for uptake and sensitization are both unclear. Here we show that MGd is endocytosed by the clathrin-dependent pathway with ensuing lysosomal membrane permeabilization, most likely via formation of reactive oxygen species involving redox-active metabolites, such as ascorbate. We propose that subsequent apoptosis is a synergistic effect of irradiation and high MGd concentrations in malignant cells due to their pronounced endocytic activity. The results provide novel insights into the mode of action of this promising anti-cancer drug, which is currently under clinical trials.
|
|
| 47. |
- Bethke, Lara, et al.
(författare)
-
CASP8 D302H and meningioma risk : an analysis of five case-control series
- 2009
-
Ingår i: Cancer Letters. - Clare : Elsevier. - 0304-3835 .- 1872-7980. ; 273:2, s. 312-315
-
Tidskriftsartikel (refereegranskat)abstract
- Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.
|
|
| 48. |
- Braekeveldt, Noémie, et al.
(författare)
-
Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours
- 2016
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 375:2, s. 384-389
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment of high-risk childhood neuroblastoma is a clinical challenge hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing.
|
|
| 49. |
- Broberg Palmgren, Karin, et al.
(författare)
-
Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma.
- 2007
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 258:1, s. 38-44
-
Tidskriftsartikel (refereegranskat)abstract
- The newly identified protein BLAP75/RMI1 associates with the helicase BLM and is critical for the function of the homologous recombination complex. Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom's syndrome). We have analyzed the common polymorphism Ser455Asn in RMI1 and its association with cancer risk in acute myeloid leukemia (AML, N=93), myelodysplatic syndromes (MDS, N=74), and malignant melanoma (MM, N=166). Two control groups were used: one population-based (N=119) and one recruited from spouses of cancer patients (N=189). The results showed a consistent pattern, where carriers of the Asn variant had a significantly increased risk of AML/MDS. The risk of AML/MDS for SerAsn+AsnAsn subjects was odds ratio (OR)=1.7, 95% confidence interval (CI) 1.1-2.5 or MM was OR=1.5, 95% CI 1.0-2.2. Age might modify the effect of RMI1 on cancer risk. This was most evident for MM: AsnAsn homozygotes > or =64 years showed OR=2.7, 95% CI 1.1-6.0, whereas individuals <64 years showed OR=0.87, 95% CI 0.31-2.5. These results indicate a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.
|
|
| 50. |
- Catela Ivkovic, Tina, et al.
(författare)
-
MicroRNAs as cancer therapeutics : A step closer to clinical application
- 2017
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 407, s. 113-122
-
Forskningsöversikt (refereegranskat)abstract
- During the last decades, basic and translational research has enabled great improvements in the clinical management of cancer. However, scarcity of complete remission and many drug-induced toxicities are still a major problem in the clinics. Recently, microRNAs (miRNAs) have emerged as promising therapeutic targets due to their involvement in cancer development and progression. Their extraordinary regulatory potential, which enables regulation of entire signalling networks within the cells, makes them an interesting tool for the development of cancer therapeutics. In this review we will focus on miRNAs with experimentally proven therapeutic potential, and discuss recent advances in the technical development and clinical evaluation of miRNA-based therapeutic agents.
|
|
