| 1. |
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| 2. |
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| 3. |
- Andersson, Ken G, et al.
(författare)
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Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
- 2015
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 34:2, s. 1042-8
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Tidskriftsartikel (refereegranskat)abstract
- Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium‑111 (111In) and assessed invitro and invivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with 111In provided stable conjugates. Invitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT‑474 breast carcinoma cells. In mice bearing BT‑474 xenografts, the tumor uptake of the two conjugates was receptor‑specific. Direct invivo comparison of 111In-HEHEHE-Z08698-NOTA and 111In-HEHEHE-Z08699‑NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for 111In-HEHEHE-Z08698-NOTA [12±3 vs. 8±1, 4h post injection (p.i.)] due to more efficient blood clearance. 111In-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.
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| 4. |
- Andreasen, S., et al.
(författare)
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Genomic profiling of a combined large cell neuroendocrine carcinoma of the submandibular gland
- 2016
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 35:4, s. 2177-2182
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Tidskriftsartikel (refereegranskat)abstract
- A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small-cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection and selective neck dissection was performed and histopathologic examination revealed a combined large-cell neuroendocrine carcinoma (LCNEC) with a squamous component and without lymph node metastases. Resection of the lung tumor revealed a papillary adenocarcinoma that was morphologically distinctly different from the LCNEC. The patient died of her lung cancer after 19 months without evidence of recurrence of the LCNEC. Genomic profiling of the salivary gland LCNEC revealed a hypodiploid genome predominated by losses of whole chromosomes or chromosome arms involving chromosomes 3p, 4, 7q, 10, 11, 13, 16q and gains of 3q and 16p. In addition, there was a segmental gain of 9p23-p22.3 including the NFIB oncogene. Continued studies of salivary gland LCNEC may provide new knowledge concerning potential diagnostic biomarkers and may ultimately also lead to the identification of new treatment targets for patients with these aggressive carcinomas.
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| 5. |
- Argyropoulos, C., et al.
(författare)
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Operational criteria for selecting a cDNA microarray data normalization algorithm
- 2006
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 15:4, s. 983-996
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Tidskriftsartikel (refereegranskat)abstract
- Microarray technology allows gene expression profiling at a global level. Many algorithms for the normalization of raw microarray data have been proposed, but no attempt has yet been made to propose operationally verifiable criteria for their comparative evaluation, which is necessary for the selection of the most appropriate method for a given dataset. This study develops a set of operational criteria for assessing the impact of various normalization algorithms in terms of accuracy (bias), precision (variance) and over-fitting (information reduction). The use of these criteria is illustrated by applying the three most widely used algorithms (global median normalization, spiked-in based normalization and lowess) on a specifically designed, multiply-controlled dataset.
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| 6. |
- Arlehag, L, et al.
(författare)
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ATM expression in rectal cancers with or without preoperative radiotherapy
- 2005
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 14:2, s. 313-317
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Tidskriftsartikel (refereegranskat)abstract
- Patients with ATM (Ataxia-Telangiectasia mutated) mutation show increased sensitivity to radiation and have a higher risk of developing malignancies. The present study aimed to investigate whether ATM expression was related to radiotherapy, and clinicopathological and biological variables in rectal cancers. ATM expression was immunohistochemically examined in 78 rectal cancers from patients who participated in a Swedish rectal cancer trial of preoperative radiotherapy. Of 78 patients, 44 underwent surgery alone, and 34 underwent both preoperative radiotherapy and surgery. Fifty-eight cases had normal rectal mucosa adjacent to the tumour. The results showed that, compared to normal mucosa, tumours had less nuclear (p=0.03) but more cytoplasmic expression of ATM (p=0.004). In tumours, less expression of ATM, either in the nucleus (p=0.07) or in the cytoplasm (p=0.02 for staining intensity, and p=0.07 for staining percentage), tended to be correlated with male patients. Also, ATM expression was not related to radiotherapy or other clinicopathological and biological variables (p > 0.05). In conclusion, the pattern of ATM expression was changed from normal mucosa to tumour. Less expression of ATM may be related to males.
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| 7. |
- Armakolas, Athanasios, et al.
(författare)
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Subdivision of molecularly-classified groups by new gene signatures in breast cancer patients
- 2012
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 28:6, s. 2255-2263
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Babaei, Mohammad Hossein, et al.
(författare)
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[99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo : preparation and pre-clinical evaluation
- 2005
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 13:6, s. 1169-75
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Tidskriftsartikel (refereegranskat)abstract
- Expression of epidermal growth factor receptors (EGFR) has prognostic and predictive value in many kinds of tumors. Imaging of expression of EGFR in vivo may give valuable diagnostic information. The epidermal growth factor (EGF), a natural ligand, is a possible candidate for the targeting of EGFR. The present study describes a method for preparation of (99m)Tc-EGF via the hydrazinopyridine-3-carboxylic acid (HYNIC) conjugation using tricine and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands. Both conjugates bound EGFR expressing cells with nanomolar affinity, and demonstrated good intracellular retention. The complex with EDDA demonstrated much higher stability in blood serum and during cysteine challenge. Biodistribution of (99m)Tc-EDDA-HYNIC-EGF in normal mice demonstrated fast blood clearance of conjugate, and its ability to bind EGFR in vivo. (99m)Tc-EDDA-HYNIC-EGF is a promising candidate for visualization of EGFR expression in vivo.
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| 9. |
- Bartuma, Katarina, et al.
(författare)
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Genetic profiles distinguish different types of hereditary ovarian cancer.
- 2010
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 24:4, s. 885-895
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Tidskriftsartikel (refereegranskat)abstract
- Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles, with an average 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17 and 19 characterized the HNPCC tumors, but target genes herein are unknown. The results indicate that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.
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| 10. |
- Berglund, Mattias, et al.
(författare)
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High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma
- 2013
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 29:2, s. 720-724
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas. A new and important tool for understanding the biology and clinical course of DLBCL is microRNA expression. This study presents microRNA-200c expression data from 61 DLBCL patients treated with CHOP or R-CHOP. Patients with high microRNA-200c expression had a median survival of 20.3 months and a significantly shorter overall survival (P=0.019) compared to patients with low microRNA-200c expression, who had a median survival of 35.8 months. We also found that patients treated with R-CHOP only and displaying high microRNA-200c expression had a significantly shorter overall survival compared to patients with low microRNA-200c expression, where all patients were still alive at the time of the last follow-up (P=0.0036). Lastly, we found that patients with high microRNA-200c expression had a significantly shorter time from initial diagnosis to the first relapse compared to patients with low microRNA-200c expression (P=0.0001). To our knowledge, this is the first study showing that the expression of microRNA-200c affects the clinical outcome of DLBCL patients, and that microRNA-200c is involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-200c in DLBCL.
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| 11. |
- Bu, H, et al.
(författare)
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Significance of glutathione S-transferases M1, T1 and P1 polymorphisms in Swedish melanoma patients.
- 2007
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 17:4, s. 859-864
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.
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| 12. |
- Burgos, Jonathan R, et al.
(författare)
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MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.
- 2016
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Ingår i: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 35:4, s. 2425-2430
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor perse. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid Pcomponent (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.
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| 13. |
- Byström, P., et al.
(författare)
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An explorative study on the clinical utility of baseline and serial serum tumour marker measurements in advanced upper gastrointestinal cancer
- 2010
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 24:6, s. 1645-1652
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Tidskriftsartikel (refereegranskat)abstract
- The value of early tumour marker changes during palliative chemotherapy in patients with upper gastrointestinal adenocarcinoma (UGIA) is unclear. Seventy-three patients with advanced UGIA were randomised to receive 45 mg/m2 docetaxel or 180 mg/m2 irinotecan with 5-FU/leucovorin. After every 2nd course the patients were crossed over to the other regimen. Serum was sampled before start of chemotherapy and every 2nd week during 8 weeks for CEA, TPA, TPS, CA72-4, CA19-9 and CA242 measurements. Eighteen patients (25%) had partial response (PR) and 21 patients had stable disease for at least 4 months (SD4). All baseline marker levels, except CA72-4, correlated with time to progression and survival. Patients with normal levels, except CA72-4, also had more clinical responses (PR+SD4) than patients with elevated values. Tumour marker changes early during treatment provided modest predictive information for tumour response and survival. A model combining baseline level, the change and the interaction between them gave the best prediction of outcome, however, insignificantly better than baseline level for all markers except CA242. Baseline tumour marker levels provide prognostic information for patients with UGIA on palliative chemotherapy. Early changes generally failed to provide accurate information for tumour response and survival.
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| 14. |
- Campa, Daniele, et al.
(författare)
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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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Ingår i: Oncology Reports. - Athen : National Hellenic Research Foundation. - 1021-335X .- 1791-2431. ; 26:4, s. 979-986
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Carlberg, Michael, et al.
(författare)
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Pooled analysis of Swedish case-control studies during 1997-2003 and 2007-2009 on meningioma risk associated with the use of mobile and cordless phones
- 2015
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Ingår i: Oncology Reports. - : Spandidos. - 1021-335X .- 1791-2431. ; 33:6, s. 3093-3098
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Tidskriftsartikel (refereegranskat)abstract
- A pooled analysis of two case-control studies on meningioma with patients diagnosed during 1997-2003 and 2007-2009 was conducted. Both genders were included, aged 20-80 and 18-75 years, respectively, at the time of diagnosis. Population-based controls, matched according to age and gender, were enrolled. Exposure was assessed by questionnaire. In the entire study, cases with all brain tumor types were included. The whole reference group was used in the unconditional logistic regression analysis on meningioma, with adjustments for gender, age, year of diagnosis and socioeconomic index (SEI). In total, 1,625 meningioma cases and 3,530 controls were analyzed. Overall no association with use of mobile or cordless phones was found. In the fourth quartile of use (>1,436 h) somewhat increased risk was found for mobile phones yielding an odds ratio (OR)=1.2, 95% confidence intervals (CI)=0.9-1.6 and cordless phones OR=1.7, 95% CI=1.3-2.2. Higher risk was calculated in the highest decile (>3,358 h), OR=1.5, 95% CI=0.99-2.1 and OR=2.0, 95% CI=1.4-2.8, respectively. In addition, the longest latency time gave somewhat increased risk for both phone types although the result was not statistically significant. There was no association for ipsilateral use or anatomical tumor location. The present study showed a somewhat increased risk among heavy users of mobile and cordless phones. Since meningioma is generally a slow-growing tumor, longer latency period is necessary for definitive conclusions.
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| 16. |
- Dalmo, Johanna, et al.
(författare)
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Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2.
- 2012
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Ingår i: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 27:1, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177Lu-octreotate and 111In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177Lu-octreotate or 111In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111In-MG0. Animals were sacrificed 1-7 days after injection in the 177Lu-octreotate study and 1h after injection of 111In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177Lu were calculated. There was a specific tumor uptake of either 177Lu-octreotate or 111In-MG0. 177Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- El-Salhy, Magdy, 1951-
(författare)
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Comparison between triple therapy with octreotide, galanin and serotonin, 5-fluorouracil/leucovorin, and sequential treatment with both, on human colon cancer.
- 2004
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 11:6, s. 1161-1168
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Tidskriftsartikel (refereegranskat)abstract
- Human colon cancer cells were implanted s.c. in nude mice. After 6 days, the mice were divided into four groups, 10 in each. During the first 5 days, the first and second groups were injected i.p. with leucovorin (LV)/5-fluorouracil (FU), and the third and fourth groups with sterile saline solution. During the subsequent 14 days, groups 1 and 4 received continuous i.p. infusion with sterile saline solution, while groups 2 and 3 received octreotide, galanin and serotonin via an implanted osmotic pump. Tumour volumes diminished significantly in mice treated with both LV/FU and LV/FU-triple therapy, as compared with controls. Both volume and weight of the tumours in mice given LV/FU-triple therapy were less than in those received LV/FU. The volume and weight of the tumours in animals treated with triple therapy was reduced as compared with controls, though not statistically significantly. The proliferation index, and the number of tumour blood vessels were both reduced, while the apoptotic index was increased in the mice treated with both LV/FU-triple therapy, and with triple therapy only as compared with LV/FU-treated mice. The present study has shown that the anti-tumour efficacy and therapeutic efficacy of triple therapy with octreotide, galanin and serotonin is equivalent to LV/FU and that sequential treatment with both could be beneficial.
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| 22. |
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| 23. |
- El-Salhy, Magdy, 1951-
(författare)
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Effects of octreotide, galanin and serotonin on a human gastric cancer cell line.
- 2005
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 13:5, s. 787-791
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Tidskriftsartikel (refereegranskat)abstract
- Human gastric cancer cell line was exposed in vitro to octreotide, galanin and serotonin alone, or in double or triple combination, and the number of viable cells and proliferation index were measured after 3, 6 and 12 h. The tumour cells were also implanted subcutaneously in nude mice. After 8 days, the animals were randomly allocated to either of two groups, with 8 in each. The first group received a bolus intraperitoneal injection, twice daily with 100 microl sterile saline solution for 10 days, while the second group was given sterile saline solution containing 100 microg/kg body weight of octreotide, galanin and serotonin. In vitro exposure to octreotide, galanin and serotonin alone or in double or triple combination reduced the number of viable cells and proliferation index. Both the volume and weight of tumours in mice given triple therapy were less than in controls. There was no statistical difference between treated and control tumours regarding proliferation and apoptotic indices or the labelling index of epidermal growth factor (EGF). It was concluded that the reduction in tumour volume and weight following triple treatment in vivo experiments could be not explained by inhibition of proliferation, induction of apoptosis or decreased expression of EGF of the tumour cells, and that other mechanisms must be involved. The reduction of proliferation in vitro but not in vivo could not be explained by the difference in concentrations of octreotide, galanin and serotonin used in vitro and in vivo.
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| 24. |
- El-Salhy, Magdy, 1951-
(författare)
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Effects of triple therapy with octreotide, galanin and serotonin on a human colon cancer cell line.
- 2005
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 13:1, s. 45-49
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Tidskriftsartikel (refereegranskat)abstract
- Human colon cancer cells were implanted subcutaneously into nude mice. After 12 days, the animals were divided into two groups. The first group received 40 microg/kg body weight of octreotide, galanin and serotonin via an intraperitoneally implanted pump. The second group received sterile saline only. Treatment lasted for 14 days. The volume and weight of the tumours in treated mice tended to decrease, though not with statistical significance. The proliferation index and the number of tumour blood vessels was significantly reduced in the mice given triple therapy. The apoptotic index, as detected by TUNEL method and monoclonal anti-poly (ADP-ribose) polymerase, was significantly higher in the treated mice. Though the results of this investigation are promising, it is uncertain as to what use the present findings may imply for the treatment of patients with colorectal cancer.
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| 25. |
- El-Salhy, Magdy, 1951-, et al.
(författare)
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Effects of triple therapy with octreotide, galanin and serotonin on liver metastasis of human colon cancer in xenografts.
- 2004
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 11:6, s. 1177-1182
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Tidskriftsartikel (refereegranskat)abstract
- Human colon cancer cells (SW 620) were implanted under the capsule of the left liver lobe of female nude (C57BL/6JBom-nu) mice. After 7 days, relaparatomy was performed and an ALZET osmotic pump was implanted intraperitoneally and left in situ for 14 days. The mice were divided into 2 groups, 10 in each. The first group received 40 micro g/kg body weight of octreotide, galanin and serotonin, and the second group received sterile saline. The number of metastases in the liver, and to the intra-abdominal lymph nodes was significantly greater in the controls. The incidence of metastases to the peritoneal cavity was lower in the treated animals (though not statistically significantly). Tumour volume, wet weight, proliferation index and number of tumour blood vessels decreased significantly in the treated animals. The apoptotic index was significantly higher in the treated mice. The decrease in the volume and weight of tumours following the triple therapy seemed to be caused by low proliferation, and increased apoptosis, and reduced vascularization of the tumours. The low invasion of cancer cells observed following this treatment could have been due to the low tumour burden, and to the reduced number of the blood and lymph vessels.
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| 26. |
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| 27. |
- Farnebo, Lovisa, et al.
(författare)
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Number of negative points : a novel method for predicting radiosensitivity in head and neck tumor cell lines.
- 2008
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 20:2, s. 453-461
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Tidskriftsartikel (refereegranskat)abstract
- The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.
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| 28. |
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| 29. |
- Gabrielson, Marike, et al.
(författare)
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The mitochondrial transport protein SLC25A43 affects drug efficacy and drug-induced cell cycle arrest in breast cancer cell lines
- 2013
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 29:4, s. 1268-
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Tidskriftsartikel (refereegranskat)abstract
- The mitochondria have been identified as key players of apoptosis, cell proliferation and cell cycle regulation. However, the role of mitochondria in breast cancer and treatment failure remains unclear. We have previously shown a common deletion of the gene SLC25A43 in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This gene is coding for a mitochondrial inner membrane transporter and, to date, little is known about the function of this protein. We have also found that low protein expression of SLC25A43 significantly correlates with a lower S phase fraction in HER2-positive breast cancer. The aim of this study was to investigate whether knockdown (KD) of SLC25A43 could have an effect on the cytotoxicity of different cytostatic drugs using MCF10A, MCF7 and BT-474 cells. Following siRNA-mediated KD of SLC25A43, one non-malignant and two breast cancer cell lines were exposed to the anthracycline epirubicin or the taxane paclitaxel. The HER2-positive breast cancer cells were also exposed to the targeted therapy trastuzumab and dual exposure to trastuzumab and paclitaxel. We found that KD of SLC25A43 resulted in a decreased cytotoxic effect of paclitaxel in the two cancer cell lines (P<0.05). Further analysis of cell cycle phase distribution showed that KD increased the paclitaxel-induced G2/M block in these two cell lines (P<0.05). KD of SLC25A43 also reduced the inhibitory effect of trastuzumab on cell proliferation in the HER2-positive cancer cell line BT-474 (P<0.05), and the drug-induced G0/G1 block (P<0.05). Moreover, SLC25A43 influenced the percentage of Ki-67-positive cells. Our findings demonstrate that the mitochondrial protein SLC25A43 affects drug efficacy and cell cycle regulation following drug exposure in breast cancer cell lines.
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| 30. |
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| 31. |
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| 32. |
- Graflund, M., et al.
(författare)
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Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma : correlation with clinical outcome
- 2004
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Ingår i: Oncology Reports. - Athens, Greece : Spandidos Publications. - 1021-335X .- 1791-2431. ; 12:1, s. 169-176
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.
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| 33. |
- Gunnarsson, Cecilia, 1970-, et al.
(författare)
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Expression of COX-2 and steroid converting enzymes in breast cancer
- 2006
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 16:2, s. 219-224
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Tidskriftsartikel (refereegranskat)abstract
- COX-2 is upregulated in many breast tumors, and one of the products of COX-2 is PGE2 that is suggested to upregulate aromatase through cAMP signaling in breast cancer. Although aromatase can increase the estrogen levels in tumors, 17β-hydroxysteroid dehydrogenase (17HSD) activity is finally needed for the estrone/estradiol regulation. The aim of this study was to investigate if the protein expression of enzymes involved in estrogen synthesis shows covariation with the expression of COX-2. We also wanted to correlate these results with prognosis. We analyzed the expression of COX-2, aromatase, 17HSD1 and 17HSD2 with immunohistochemistry using tissue microarrays composed of 356 primary breast tumors. In the present study COX-2 was correlated to aromatase (P<0.00001), 17HSD1 (P=0.0073), and 17HSD2 (P<0.00001). Patients with ER positive tumors expressing low amounts of 17HSD2 had decreased breast cancer survival (P=0.013). Elevated expression of COX-2 and aromatase was more frequent among larger tumors (P=0.017 and P=0.013). COX-2 expression correlates with the levels of the examined steroid converting enzymes and may contribute to increased estrogen levels in the tumor. In breast cancer cells, the regulatory function of 17HSD2 could be lost, and in the present study patients with low or non-detectable levels of 17HSD2 had worse prognosis than had breast cancer patients with higher levels of the enzyme.
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| 34. |
- Göstring, L., et al.
(författare)
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17AAG-induced internalisation of HER2-specific Affibody molecules
- 2016
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082 .- 1021-335X .- 1791-2431. ; 12:4, s. 2574-2580
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Tidskriftsartikel (refereegranskat)abstract
- The geldanamycin derivative 17-allylamino- 17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled211At-ABY-025 and radiometal-labelled111In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells. © 2016, Spandidos Publications. All rights reserved.
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| 35. |
- Göthlin Eremo, Anna, 1980-, et al.
(författare)
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Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients
- 2013
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Ingår i: Oncology Reports. - Athens, Greece : Spandidos Publications. - 1021-335X .- 1791-2431. ; 29:4, s. 1467-1474
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Tidskriftsartikel (refereegranskat)abstract
- Reduced or absent Wwox expression has recently been associated with tamoxifen resistance in breast cancer and has also been proposed as a candidate predictive marker for treatment. We aimed to investigate the correlation of Wwox expression with the outcome of tamoxifen treatment by examining tissues from 912 randomized breast cancer patients. Paraffin-embedded tissues from patient tumors were arranged on tissue microarray, and Wwox protein was stained using immunohistochemistry. After microscopic examination, the results were analyzed with Cox regression, Kaplan-Meier survival curves and the log-rank test. In the group of cases having a tumor absent for Wwox expression, there was no difference in recurrence-free survival between treated and untreated patients (P=0.81). For treated cases with a tumor expressing moderate or strong Wwox protein, recurrence-free survival was improved (P=0.001 and P=0.003, respectively). The test for interaction between Wwox and treatment response demonstrated a decreased risk of recurrence for treated patients with a moderate or strong Wwox expression (HR=0.31, 95% CI 0.10-0.98 and HR=0.28, 95% CI 0.08-0.97, respectively). Our results indicate that patients with high expression of Wwox may gain more benefit from treatment with tamoxifen.
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| 36. |
- Hardell, Karin, 1975-, et al.
(författare)
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Concentrations of organohalogen compounds and titres of antibodies to Epstein-Barr virus antigens and the risk for non-Hodgkin lymphoma
- 2009
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Ingår i: Oncology Reports. - Athens, Greece : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 21:6, s. 1567-1576
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to some pesticides and persistent organic pollutants (POPs) has been indicated to be a risk factor for non-Hodgkin's lymphoma (NHL). Epstein-Barr virus (EBV) has been associated with some subgroups of NHL. In a previous study we found an interaction between high concentrations of some POPs and titres of antibodies to EBV early antigen (EA IgG) in relation to NHL. In the present study we measured lipid adjusted plasma concentrations of 35 congeners of polychlorinated biphenyls (PCB). p,p'-dichlorodiphenyldichloroethyelene (p,p'-DDE), hexachlorobenzene (HCB), seven subgroups of chlordanes (cis-heptachlorepoxide, cis-chlordane, trans-chlordane, oxychlordane, MC6, trans-nonachlordane, cis-nonachlordane) and one polybrominated diphenylether (PBDE) congener (no. 47) in 99 cases with NHL and 99 population based controls. Odds ratios (OR) for NHL were estimated. Sum of PCBs > median in the controls gave odds ratio (OR) 2.0, 95% confidence interval (CI) 0.99-3.9. High sum of chlordanes yielded OR 2.3, 95% CI 1.2-4.5. An interaction with EBV EA IgG was found. High sum of PCB gave OR 5.2, 95% CI 1.9-14 in the group with EA IgG > 40. Similarly HCB yielded OR 5.3, 95% CI 1.9-15, pp'-DDE gave OR 3.3, 95% CI 1.4-7.7 and sum of chlordanes yielded OR 6.8, 95% CI 2.3-20, whereas no association was found with PBDE. In summary this study confirmed an association between certain POPs and NHL with all interaction with titre of IgG antibody to EBV EA.
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| 37. |
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| 38. |
- Hemmingsson, Oskar, 1975-, et al.
(författare)
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Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1
- 2009
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 22:4, s. 869-875
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Tidskriftsartikel (refereegranskat)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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| 39. |
- Holmqvist (Knutsen), Annica, et al.
(författare)
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PINCH expression in relation to radiation response in co-cultured colon cancer cells and in rectal cancer patients
- 2013
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 30:5, s. 2097-2104
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Tidskriftsartikel (refereegranskat)abstract
- Particularly interesting new cysteine-histidine rich protein (PINCH), involved in cell spreading, motility and proliferation, has been shown to enhance radioresistance in colon cancer cell lines. The expression of PINCH in relation to radiation was studied in co-cultured colon cancer cells. Furthermore, the clinical significance between PINCH and radiotherapy (RT) was analyzed in rectal cancer patients with or without RT. The relative PINCH expression in colon cancer (KM12C) cells cultured separately and in co-culture was examined by western blotting and real-time PCR, and was analyzed over a period of 8 and 24 h after radiation. PINCH expression was immunohistochemically examined in 137 primary rectal tumors for which 65 cases did not receive RT and 72 cases received RT. PINCH expression tended to decrease from that in the separately cultured KM12C cells without radiation to that in cells with radiation at 8 h (P=0.060); while in the co-cultured cells, no significant difference was found (P=0.446). In patients with RT, strong PINCH expression was related to worse survival, when compared to patients with weak expression, independent of TNM stage, degree of differentiation, age and p53 status (P=0.029, RR 4.03, 95% CI 1.34-12.1). No survival relationship for the patients without RT was observed (P=0.287). A statistical interaction analysis between PINCH, RT and survival showed a trend towards significance (P=0.057). In conclusion, PINCH predicts survival in rectal cancer patients with RT, but not in patients without RT. The expression of PINCH may be regulated by radiation and by environmental factors surrounding the cells.
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| 40. |
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| 41. |
- Höglund, Johanna, et al.
(författare)
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Cellular processing in the SW1222 cell line of mAb A33 directly and indirectly radiohalogenated
- 2006
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 16:1, s. 159-63
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Tidskriftsartikel (refereegranskat)abstract
- Investigations into the cellular processing of radiolabeled monoclonal antibodies (mAbs) for their further use in radioimmunodiagnosis and cancer therapy are needed in order to understand the fate of internalized and catabolized mAbs. The anti-colorectal cancer mAb, A33, was labelled with 76Br and 125I using the direct Chloramine-T method, or by labelling N-succinimidyl para-(tri-methylstannyl) benzoate and its further conjugation to the mAb. The cellular processing of the four conjugates was investigated in SW1222 cells in vitro. Uptake of mAb was rapid, peaking after 14-16 h. Intracellular degradation was slow and the early loss of radioactivity was due to dissociation of cell-surface bound mAb. The indirect labelling resulted in stronger binding of the mAb as well as prolonged intracellular retention of the radiolabel. Direct and indirect halogen radiolabelling results in different cell-processing patterns of radiolabels, and radioactive catabolic products follow different routes of cellular excretion. The results of this cellular study indicate that indirect labelling is preferable to the direct Chloramine-T method.
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| 42. |
- Isaksson, Helena S., 1978-, et al.
(författare)
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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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Ingår i: Oncology Reports. - Athens, Greece : Spandidos Publications Ltd.. - 1021-335X .- 1791-2431. ; 27:5, s. 1331-1335
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Tidskriftsartikel (refereegranskat)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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| 43. |
- Jansson, Agneta, 1973-, et al.
(författare)
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mRNA and protein expression of PUMA in sporadic colorectal cancer.
- 2004
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 12:6, s. 1245-1249
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Tidskriftsartikel (refereegranskat)abstract
- PUMA is a BH3-only member of the Bcl-2 family, up-regulated by p53 as a response to DNA damage. We have investigated the mRNA expression of PUMA with real-time PCR in 94 colorectal adenocarcinomas and the corresponding normal mucosa. Among them PUMA protein expression was investigated with immunohistochemistry in 23 tumours and 17 corresponding normal mucosa samples. The mRNA expression of PUMA decreased in 4% and increased in 4% of the tumours compared with the normal mucosa. The protein expression of PUMA decreased in 6% and increased in 29% of the tumours compared with the normal mucosa. Decreased PUMA expression in the tumour compared with the corresponding mucosa was correlated with the distal colon and rectum (P=0.02). We did not find any other relationship to clinical or pathological features. We suggest that the changes in PUMA expression may be of minor importance in the development of colorectal cancer.
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| 44. |
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| 45. |
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| 46. |
- Kertat, Khadija, et al.
(författare)
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The Gln/Gln genotype of XPD codon 751 as a genetic marker for melanoma risk and Lys/Gln as an important predictor for melanoma progression : A case control study in the Swedish population
- 2008
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 20:1, s. 179-183
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Tidskriftsartikel (refereegranskat)abstract
- The Xeroderma pigmentosum complementation group D (XPD) is a critical protein in the nucleotide excision repair system for DNA damage. Genetic variations in XPD exert an important effect on the capacity of DNA repair. In this study, we examined Lys751Gln polymorphism at the XPD gene in 244 melanoma patients and 251 healthy individuals (as controls) from the south-eastern region of Sweden. The associations of polymorphism with melanoma risk, as well as with melanoma features and pigment phenotypes of the melanoma patients were analysed. DNA was extracted from the mononuclear cells of venous blood of the melanoma patients and controls. XPD codon 751 was genotyped by the PCR restriction fragment length polymorphism technique. Results showed that there was no difference in the distribution of the XPD codon 751 genotypes between the melanoma patients and healthy controls. However, the Gln/Gln genotype was found to be associated with melanoma risk in the male population. Furthermore, the frequency of the Gln/Gln genotype was significantly higher in the early stages of melanomas, whereas Lys/Gln was more frequent in the later stages and in the patients with melanoma located on intermittently UV-exposed areas. No correlations between the polymorphisms and phenotypes of the patients were found. In conclusion, Gln/Gln was a useful genetic marker for melanoma risk in the males, while Lys/Gln was an important predictor for melanoma progression.
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| 47. |
- Khan, Maria, et al.
(författare)
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Reduced tumor growth in EP2 knockout mice is related to signaling pathways favoring an increase local anti-tumor immunity in the tumor stroma
- 2022
-
Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 47:6
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well‑established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor‑stroma, at conditions of reduced disease progression due to decreased host inflammation. In the present study, wild‑type tumor cells, producing high levels of prostaglandin E2 (MCG 101 cells, EP2+/+), were inoculated into EP2 knockout (EP2‑/‑) and EP2 wild‑type (EP2+/+) mice. Solid tumors were dissected into tumor‑ and tumor‑stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. Immunohistochemistry was used to confirm adequate dissections of tissue compartments, and to assess cell proliferation (Ki‑67), prostaglandin enzymes (cyclooxygenase 2) and immunity biomarkers (CD4 and CD8) at the protein level. Microarray analyses revealed statistically significant alterations in gene expression in the tumor‑stroma compartment, while significantly less pathway alterations occurred in the tumor tissue compartment. The host knockout of EP2 receptors led to a significant downregulation of cell cycle regulatory factors in the tumor‑stroma compartment, while interferon γ‑related pathways, chemokine signaling pathways and anti‑tumor chemokines [chemokine (C‑X‑C motif) ligand 9 and 10] were upregulated in the tumor compartment. Thus, such gene alterations were likely related to reduced tumor growth in EP2‑deficient hosts. On the whole, pathway analyses of both tumor‑ and tumor‑stroma compartments suggested that absence of host EP2 receptor signaling reduces ‘remodeling’ of tumor microenvironments and increase local immunity, probably by decreased productions of stimulating growth factors, perhaps similar to well‑recognized physiological observations in wound healing.
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| 48. |
- Knutsen Holmqvist, Annica, 1974-, et al.
(författare)
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Inflammatory infiltration, fibrosis, necrosis and mucinous content in relation to clinicopathological and molecular factors in rectal cancers with or without preoperative radiotherapy.
- 2006
-
Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 16:2, s. 321-327
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Tidskriftsartikel (refereegranskat)abstract
- The association between inflammatory infiltration, fibrosis, necrosis and mucinous content in rectal cancers, and their relationship to preoperative radiotherapy (RT) clinicopathological and biological factors (p53, apoptosis and Cox-2) is not fully characterised. We analysed these histopathological parameters and their relationships in rectal cancer patients who participated in a clinical trial of preoperative RT. One hundred and forty-eight preoperative biopsies and 153 surgically resected tumours were examined. Of the surgical specimens, 81 had surgery alone and 72 received RT before surgery. A higher grade of inflammatory infiltration was related to favourable survival in the whole group of patients (p=0.004, for multivariate analysis p=0.01) as well as in the subgroups of patients with (p=0.04) or without RT (p=0.01). After RT, tumours showed a decreased infiltration (p=0.0003) and increased necrosis (p=0.006), strong necrosis was related to favourable survival (p=0.046). Necrosis (p=0.054) and fibrosis (p=0.06) tended to be increased in p53-negative tumours after RT. Inflammatory infiltration was a strong prognostic factor in rectal cancer patients, regardless of RT. RT tended to induce necrosis and fibrosis in p53-negative tumours.
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| 49. |
- Krona, Annika, 1973, et al.
(författare)
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Oncostatin M signaling in human glioma cell lines.
- 2005
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Ingår i: Oncology reports. - 1021-335X .- 1791-2431. ; 13:5, s. 807-11
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Tidskriftsartikel (refereegranskat)abstract
- We have recently found that oncostatin M (OSM) is overexpressed in most human brain tumors. The effects of OSM are unclear with conflicting reports of growth stimulatory or inhibitory effects in various cell types. The aim of this study was to investigate the effects of OSM in 5 glioma cell lines and 7 short-term cultures of human gliomas and in normal cultured human astrocytes. None of the cell lines and short-term cultured tumor cells expressed OSM in vitro. OSM signals through a gp130 containing receptor complex over the JAK/STAT pathway. Immunofluorescence and RT-PCR analysis showed that the tumor cells express gp130 and the other receptor components, LIFRbeta and OSMRbeta. OSM treatment induced phosphorylation of STAT3 and STAT1 indicating presence of a functional JAK/STAT pathway. No OSM effect on proliferation was observed. OSM gave no protective effects against tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced cytotoxicity.
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| 50. |
- Lagerstedt-Robinson, K., et al.
(författare)
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Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population
- 2016
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 36:5, s. 2823-2835
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Tidskriftsartikel (refereegranskat)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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