| 1. |
- Armakolas, Athanasios, et al.
(author)
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Subdivision of molecularly-classified groups by new gene signatures in breast cancer patients
- 2012
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In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 28:6, s. 2255-2263
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Journal article (peer-reviewed)abstract
- Gene expression patterns as well as gene interactions are under investigation for their involvement in tumour heterogeneity. The molecular classification of breast cancer based on hormone receptor expression, grade and HER2 receptor levels, is indicative but not adequate enough to complete the prognostic data. The objectives of this study were to validate the prognostic value of 19 genes, solely, and as parts of classifiers (sets of genes), in breast cancer patients and to determine whether the expression of these genes and classifiers is correlated with breast cancer molecular classification. Gene expression was examined in the blood of 88 breast cancer patients and 50 healthy controls using multiplex quantitative real-time PCR. Patients with a second primary malignancy showed a statistically significant difference when compared with: i) patients with a single breast cancer, for an 8-gene classifier (p<0.02); and ii) healthy individuals (classifier FBX033, FLJ339115) (p<0.01), with respect to gene expression. The classifier ENY2, USP38 was associated with the development of primary breast cancer. A newly established classifier (ENY2, USP38, RPS7, Osbpl-1 and ETF1) indicated a statistically significant association with HER2 subtype patients, compared to patients with a different molecular classification (p<0.04). The gene FLJ33915 was differentially expressed in a subgroup of HER2-positive patients with infiltrated axillary lymph nodes (p<0.028). We validated the prognostic value of 4 classifiers for primary and second primary malignancy. Evidence of a classifier predicting the HER2 subtype and the gene FLJ33915 which subdivides HER2 subtype patients is also presented.
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| 2. |
- Campa, Daniele, et al.
(author)
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Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer
- 2011
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In: Oncology Reports. - Athen : National Hellenic Research Foundation. - 1021-335X .- 1791-2431. ; 26:4, s. 979-986
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Journal article (peer-reviewed)abstract
- Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men.
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| 3. |
- Hemmingsson, Oskar, 1975-, et al.
(author)
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Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1
- 2009
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In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 22:4, s. 869-875
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Journal article (peer-reviewed)abstract
- Platinating agents constitute the first line treatment for ovarian cancer but treatment failure is common because of intrinsic and acquired resistance. Cancer cells develop the RASP-phenotype (cross resistance against arsenite, antimonite and platinum) associated with decreased accumulation of cisplatin and arsenite. ASNA1 is a possible subunit of a transport system for cisplatin and arsenite due to homology to arsA, an ATPase in the E. coli ars-complex responsible for efflux of arsenite and antimonite. Eukaryotic ASNA1 is a targeting factor for membrane insertion of tail-anchored proteins involved in the secretory pathway and cellular stress responses. The purpose with this study was to evaluate if ASNA1 expression influenced cisplatin, carboplatin, oxaliplatin or arsenite sensitivity in ovarian cancer. Human ovarian cancer cell line 2008 was transfected with a sense or an antisense ASNA1 construct. ASNA1 downregulated and overexpressing clones were identified by Western blots. Cell growth and chemosensitivity was determined by the MTT assay. Down-regulated ASNA1 expression was associated with retarded growth and increased sensitivity to cisplatin, carboplatin, oxaliplatin and arsenite whereas the cisplatin resistant 2008/A overexpresses ASNA1. These observations support the hypothesis that ASNA1 is a target to overcome platinum resistance in ovarian cancer.
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| 4. |
- Isaksson, Helena S., 1978-, et al.
(author)
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Whole blood RNA expression profiles in ovarian cancer patients with or without residual tumors after primary cytoreductive surgery
- 2012
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In: Oncology Reports. - Athens, Greece : Spandidos Publications Ltd.. - 1021-335X .- 1791-2431. ; 27:5, s. 1331-1335
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Journal article (peer-reviewed)abstract
- Significant improvements in the treatment results of ovarian cancer have been achieved during the last decades, but further improvements require additional methods identifying signs of the disease and its biological behavior, preferably by a simple blood test. We hypothesized that peripheral blood leukocytes may express genes that carry such clinical information. Therefore, we studied the relative gene expressions of 168 cancer- and metastasis-specific genes in blood samples from ovarian cancer patients with different prognoses after primary cytoreductive surgery. Total RNA was extracted from whole blood and the relative gene expression profile of 168 genes were analyzed using real-time qPCR assays. Two groups of patients were analyzed; one group with residual tumor mass after primary surgery, and one group where the tumor was macroscopically radically resected, resulting in no visible tumor mass left behind. The group with the remaining tumor mass after surgery showed significantly different gene expression profiles compared to the group with no remaining tumor mass. Differences were noted for the metastasis associated 1 family, member 2 gene (MTA2), the TNF, alpha-catenin, interleukin 1 beta, the KiSS-1 metastasis suppressor and the matrix metalloproteinase 10 genes. All genes were downregulated with a fold-change between 1.15 to 1.57; there were no upregulated genes. Thus, a signature of genes involved in metastasis, invasion and inflammation was found to be significantly downregulated in native unstimulated blood leukocytes from ovarian cancer patients with a poor prognosis. Preoperatively it may serve as a guide to the biology of the tumor and postoperatively in the optimization of adjuvant treatment of ovarian cancer patients.
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| 5. |
- Lagerstedt-Robinson, K., et al.
(author)
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Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population
- 2016
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In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 36:5, s. 2823-2835
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Journal article (peer-reviewed)abstract
- Lynch syndrome caused by constitutional mismatch-repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2. After 20 years of genetic counseling and genetic testing for Lynch syndrome, we have compiled the mutation spectrum in Sweden with the aim to provide a population-based perspective on the contribution from the different MMR genes, the various types of mutations and the influence from founder mutations. Mutation data were collected on a national basis from all laboratories involved in genetic testing. Mutation analyses were performed using mainly Sanger sequencing and multiplex ligation-dependent probe amplification. A total of 201 unique disease-predisposing MMR gene mutations were identified in 369 Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder mutation that accounted for 15% of the families with mutations in MLH1. In conclusion, the Swedish Lynch syndrome mutation spectrum is diverse with private MMR gene mutations in two-thirds of the families, has a significant contribution from internationally recognized mutations and a limited effect from founder mutations.
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| 6. |
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| 7. |
- Stattin, Pär, et al.
(author)
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Plasma leptin and colorectal cancer risk : a prospective study in Northern Sweden.
- 2003
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In: Oncology Reports. - 1021-335X .- 1791-2431. ; 10:6, s. 2015-2021
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Journal article (peer-reviewed)abstract
- Obesity is associated with an increased risk of colorectal cancer. Circulating levels of leptin are high in obesity and strongly correlated to levels of insulin. Leptin stimulates growth of colon cancer cells. In a nested case-control study, we measured leptin levels in prediagnostic plasma from 75 men and 93 women who were diagnosed with colorectal cancer mean time 3.4 years (SD 2.4) after recruitment and among 327 control subjects. Logistic regression analyses showed increases in colorectal cancer risk in men with increasing levels of leptin, odds ratios (OR) were 1.00 (ref), 0.85 (95% C.I.=0.33-2.23), 1.04 (0.43-2.53), and 2.15 (0.89-5.22), (pfor trend=0.08). There was a distinct threshold between the third and fourth quartile of leptin, and the odds ratio for top quartile vs. three bottom quartiles was 2.28 (1.09-4.76). Adjustment for body mass index and insulin did not affect risk estimates. In separate analysis, odds ratio for top vs. bottom tertile of colon cancer was 1.96 (95% C.I.=0.72-5.29), whereas no increase was seen for rectal cancer. In women, no association between leptin and risk was seen. These data support the hypothesis that leptin is a risk marker for colorectal cancer in men, but not in women.
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| 8. |
- Stefansson, Kristina, et al.
(author)
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LRIG1‑2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma : association with prognosis in relation to HPV‑DNA and p16INK4a status
- 2019
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In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 42:1, s. 142-150
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Journal article (peer-reviewed)abstract
- The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1‑2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)‑ and p16INK4a‑status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990‑2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV‑PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV‑positive, 27% were p16INK4a‑positive and 23% were positive for both HPV and p16INK4a (considered HPV‑driven). HPV‑positivity and p16INK4a‑positivity were associated with prolonged disease‑free survival (DFS) in Kaplan‑Meier survival analysis. Leucine‑rich repeats and immunoglobulin‑like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine‑rich repeats and immunoglobulin‑like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV‑negative cases only, it was determined that high LRIG2 immunoreactivity was associated with both favorable OS (P=0.008) and DFS (P=0.031). LRIG2 immunoreactivity was also an independent prognostic factor in multivariate analysis of OS (P=0.002, HR=0.41; 95% CI, 0.24‑0.71). High immunoreactivity with LMO7‑1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV‑negative and not HPV‑driven tumors (P=0.038 and 0.042, respectively). The present study indicated that LRIG2 and LMO7 may be useful prognostic markers in VSCC, particularly for patients without HPV‑driven tumors or with advanced tumors at diagnosis. In contrast to earlier observations regarding other types of squamous cell carcinoma, LRIG1 was not a significant prognostic factor in VSCC.
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| 9. |
- Zovko, Ana, et al.
(author)
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Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis
- 2018
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In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 40:2, s. 902-908
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Journal article (peer-reviewed)abstract
- The clinical outcome for patients with chronic myeloid leukemia (CML) has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). However, their curative potential appears limited, probably as a consequence of TKI-resistant leukemic stem cells (LSCs) that persist as a result of aberrant pathways independent of the well-established oncoprotein Bcr-Abl. One such pathway involves signaling through leukotrienes (LTs), bioactive compounds that have been suggested to play a role in several other malignancies. Cysteinyl LT1 receptor (CysLT1R) has been reported to be overexpressed in a number of solid cancers, and blocking of this receptor with the antagonist montelukast (treatment approved for bronchial asthma) has resulted in the killing of cancer cells. We recently demonstrated that montelukast, alone or in combination with imatinib, can effectively reduce the growth of CML cells, while normal bone marrow cells were left unaffected. Herein, we further investigated the importance of CysLT1R for the survival of CML cells and the mechanisms by which montelukast induces cell death. Knockdown of the CysLT1R of K562 cells with siRNA reduced their growth by 25%. Montelukast had no effect on these cells, while it killed more than 50% of CysLT1R-expressing cells. Growth inhibition exerted by imatinib was unaffected by CysLT1R status. Montelukast-induced killing of K562/JURL-MK1 CML cells was paralleled by Bax overexpression, cytochrome c release, PARP-1 cleavage, and caspase-3 activation, an event further increased in a setting where montelukast was added to imatinib. Wnt/-catenin signaling was activated by CysLT1R and we observed that montelukast could induce proteins in this pathway, a finding of relevance for LSC survival. Thus, montelukast, employed at in vivo-like concentrations, induces the killing of CML cells through apoptotic pathways and may provide an additional, novel therapeutic possibility in CML.
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