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Sökning: L773:1791 7530 OR L773:0250 7005

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1.
  • Acuña, Ulyana Muñoz, et al. (författare)
  • Activity in MCF-7 Estrogen-sensitive Breast Cancer Cells of Capsicodendrin from Cinnamosma fragrans
  • 2021
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 41:12, s. 5935-5944
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Effect of capsicodendrin on the NF-KB pathway was studied in MCF-7 cancer cells. Materials and Methods: The transcription factor assay was used to screen for NF-KB activity. The effect on IKK beta, ICAM-1, and caspase-7 were studied using western blot. Caspase-1 was studied using Promega Caspase-Glo (R) assay. Reactive oxygen species (ROS) were detected using the fluorescent probe DCFH-DA. The potentiometric dye JC-1 was used to assess mitochondrial membrane potential (Delta psi m) and the cell cycle was examined using a fluorescence-activated cell sorter. Results: NF-kappa B p65 inhibitory effect was IC50=8.6 mu M and cytotoxic activity was IC50=7.5 mu M. The upstream IKK and the downstream ICAM-1 were down-regulated. Sub G1-phase population increased to 81% after 12 h of treatment with capsicodendrin (10 mu M) and there was no loss of Delta psi M. Conclusion: Increased levels of intracellular ROS promoted activity of caspase-1 and induced cell death in MCF-7 cells. Capsicodendrin may be a future anticancer agent that prevents the progression of metastatic breast cancer.
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2.
  • Acuña, Ulyana Muñoz, et al. (författare)
  • Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells.
  • 2017
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:4, s. 1617-1623
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIM: The survival rate of women diagnosed with triple-negative breast-cancer (TNBC) remains low. Hence, this study aimed at the chemical and biological optimization of furanosteroid derivatives for the treatment of this type of malignancy using TNBC cells.MATERIALS AND METHODS: Semi-synthetic analogs of wortmannolone (1-6) that negatively affected the aberrant pathways in tumor cells were evaluated in hormone-independent breast cancer cells using western blot and cell-cycle analysis.RESULTS: Wortmannolone derivatization generated NF-ĸB inhibitors as new lead structures for further development. Compound (3) was found to be the most significantly active lead.CONCLUSION: Structure-activity analysis in the present study showed that acetylation of the hydroxyl groups and substitution on C3 and C17 of wortmannolone enhanced biological activity. Alpha-substitution of the acetyl group in C3 on ring A (compound 3) resulted in ROS inducing effect; however, presence of an acetyl group in β-position of C3 displayed the highest NF-ĸB p65 inhibitory activity (0.60 μM).
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3.
  • Alanazi, Sultan, et al. (författare)
  • Histone Methyltransferase Inhibition Has a Cytotoxic Impact on Transformed Mast Cells : Implications for Mastocytosis
  • 2020
  • Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 40:5, s. 2525-2536
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Mast cell transformation, as manifested in mastocytosis, can be a serious condition for which there are limited therapeutic options. Mastocytosis cells can be sensitive to histone deacetylase (HDAC) inhibitors, but their sensitivity to other histone-modifying enzymes has not been assessed. Here we addressed this issue.Materials and Methods: Inhibitors of histone methyl transferases, histone demethylases, histone acetyl transferases and HDACs were tested for their effects on growth, viability, caspase-3 activation and annexin V/DRAQ7 staining in transformed mast cells.Results: Transformed mast cells underwent cell death in response to histone methyl transferase and HDAC inhibition, but were not sensitive to histone demethylase or histone acetyl transferase inhibition. Histone methyl transferase inhibition led to cell death with characteristics of apoptosis, as judged by caspase-3 activation. However, DNA fragmentation was not apparent and Annexin V+/DRAQ7(-) cells were not predominant, suggesting a type of cell death differing from classical apoptosis.Conclusion: Histone methyl transferase inhibition could be developed as a novel regimen for targeting mastocytosis.
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4.
  • Almlöv, Karin, et al. (författare)
  • MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer
  • 2020
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 40:5, s. 2757-2763
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.
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6.
  • Andreasson, Håkan, et al. (författare)
  • Histopathological classification of pseudomyxoma peritonei and the prognostic importance of PINCH protein
  • 2012
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.MATERIALS AND METHODS: Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.RESULTS: The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).CONCLUSION: The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.
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7.
  • Ansari, Daniel, et al. (författare)
  • Centrosomal Abnormalities in Pancreatic Cancer : Molecular Mechanisms and Clinical Implications
  • 2018
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1241-1245
  • Forskningsöversikt (refereegranskat)abstract
    • The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes. In this review, we summarize recent advances in the understanding of centrosomal aberrations in pancreatic cancer, focusing on regulatory mechanisms and prospects for future anticancer treatment.
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8.
  • Ansari, Daniel, et al. (författare)
  • The hippo signaling pathway in pancreatic cancer
  • 2019
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3317-3321
  • Forskningsöversikt (refereegranskat)abstract
    • Hippo signaling is a key regulator of organ size, tissue hemostasis and regeneration. Dysregulation of the Hippo pathway has been recognized in a variety of human cancers, including pancreatic cancer. YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the two major downstream effectors of the Hippo pathway. YAP and TAZ have been found to promote pancreatic tumor development and progression, even in the absence of mutant Kirsten RAS (KRAS). Pancreatic cancer is associated with an abundant stromal reaction leading to tumor growth and immune escape. It has been found that YAP and TAZ modulate behavior of pancreatic stellate cells and recruitment of tumor-associated macrophages and myeloid-derived suppressor cells. Moreover, YAP and TAZ are associated with chemoresistance and poor prognosis in pancreatic cancer. This review dissects the role of Hippo signaling in pancreatic cancer, focusing on molecular mechanisms and prospects for future intervention.
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9.
  • Ansari, Daniel, et al. (författare)
  • The role of PEDF in pancreatic cancer
  • 2019
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3311-3315
  • Forskningsöversikt (refereegranskat)abstract
    • Pigment epithelium-derived factor (PEDF) is an important antiangiogenic and antitumorigenic factor in a variety of cancer forms, including pancreatic cancer. PEDF is mainly secreted as a soluble monomeric glycoprotein. In human pancreatic cancer PEDF levels are decreased, both in the tissue and serum. The decrease is associated with increased tumor angiogenesis, fibrosis, inflammation, autophagy, occurrence of liver metastasis and worse prognosis. In murine models, loss of PEDF is sufficient to induce invasive carcinoma and this phenotype is associated with large lesions characterized by poor differentiation. Lentiviral gene transfer of PEDF has resulted in decreased microvessel density and has inhibited tumor growth. Herein we review the multifunctional role of PEDF in pancreatic cancer and its therapeutic potential.
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10.
  • Antonsson, Andreas, et al. (författare)
  • Induction of apoptosis by staurosporine involves the inhibition of expression of the major cell cycle proteins at the G(2)/m checkpoint accompanied by alterations in Erk and Akt kinase activities
  • 2009
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:8, s. 2893-2898
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Staurosporine is a therapeutic agent that inhibits tumor cell growth by inducing cell death via intrinsic apoptotic pathways. Our previous studies in clinical settings have suggested that certain subpopulations of patients with acute myeloid leukemia (AML) had poor response to chemotherapy.MATERIALS AND METHODS: The effect of staurosporine on apoptosis and cell cycle distribution in human leukemic cell line U-937 cells was determined. U-937 cells were treated with staurosporine at 0.5 microM for 18 hours or 1 microM for 24 hours. Analyses of cell cycle distribution and apoptosis were performed using flow cytometric analysis. The effects of staurosporine on the targeted proteins were assessed by immunoblot analysis.RESULTS: A blockade of the cell cycle at the G(2)/M phase was observed in U-937 cells treated with staurosporine. A concomitant induction of apoptosis and activation of caspase-3 in U-937 cells was also achieved. Treatment of U-937 cells with staurosporine at 1 microM for 24 hours, compared with 0.5 microM for 18 hours, appeared to kill the leukemic more efficiently cells and this dose and duration may specifically target p27, Erk and Akt pathways that are important for cancer cell survival and resistance to treatment. We also show that the effects of stauroporine on cell cycle progression and apoptosis in U-937 cells are closely linked.CONCLUSION: Our results suggest that induction of apoptosis and inhibitory proliferation and survival pathways are important events induced by staurosporine. Understanding the conditions under which staurosporine shows high specificity and low toxicity in treatment of leukemic cells is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to chemotherapeutic agents.
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11.
  • Asciutto, Katrin Christine, et al. (författare)
  • Prevalence of high-risk HPV in postmenopausal women with benign cervical cytology - A population-based cohort study
  • 2018
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:7, s. 4221-4228
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To compare the clinical performance of human papillomavirus (HPV) mRNA and DNA assays in postmenopausal women. Materials and Methods: A total of 5,925 postmenopausal women were tested with cytology and the Luminex HPV DNA assay. High risk-HPV-positive women with benign cytology underwent a complimentary HPV mRNA assay (APTIMA). Both assays and the cytological testing were repeated after 12 months. Results: A total of 334 women were found to be high-risk HPV-positive; 272 out of these women met the inclusion criteria. At follow-up, 25 (9.2%) out of the 272 included women had cytological abnormalities. HPV mRNA assay at follow-up had a sensitivity of 84% (95% confidence interval=63.9-95.4%) and a specificity of 60.2% (95% confidence interval=53.7-66.3%; p=0.0003) to detect these lesions. Corresponding values for the HPV DNA assay were 88% (95% confidence interval=68.8-97.4%) and 43.5% (95% confidence interval=37.2-49.4%). Conclusion: The HPV mRNA assay offers a comparable sensitivity but a higher specificity than the HPV DNA assay in detecting precancerous cervical lesions.
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12.
  • Asciutto, Katrin Christine, et al. (författare)
  • Vaginal and urine self-sampling compared to cervical sampling for HPV-testing with the cobas 4800 HPV test
  • 2017
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:8, s. 4183-4187
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: To compare human papillomavirus (HPV) DNA detection in self-collected vaginal and urine samples with clinician-taken cervical samples in relation to histology. Materials and Methods: Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 218 women with the Cobas 4800 HPV test (Roche Molecular Diagnostics). Results: The sensitivity for detection of HPV in the vaginal self-sampling test was 96.4% and in urine was 83.9% relative to detection by clinician-taken cervical sample. The vaginal self-sampling and the clinician-taken HPV tests had the same sensitivity of 92.8% (95% confidence interval=86.3-96.8%) and specificity for detection of high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Detection in urine samples had a sensitivity of 76.3% (95% confidence interval=67.9-84.2%) for HSIL/AIS. Conclusion: The Cobas 4800 HPV test detects high-grade pre-cancerous cervical lesions in self-collected vaginal samples with the same high sensitivity as in clinician-taken cervical samples.
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13.
  • Asklund, Thomas, et al. (författare)
  • Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.
  • 2012
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:7, s. 2407-2413
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.
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14.
  • Asp, Mihaela, et al. (författare)
  • Prognostic Value of Peritoneal Cancer Index After Complete Cytoreductive Surgery in Advanced Ovarian Cancer
  • 2022
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:5, s. 2541-2551
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/aim: Residual disease (RD) after primary debulking surgery (PDS) is a prognostic factor for survival in advanced ovarian cancer (AOC). This study aimed to examine whether the tumor extent affects overall survival (OS) and progression-free survival (PFS) in AOC patients treated with PDS.Patients and methods: A total of 118 patients treated with PDS were included. Age, ECOG score, AOC International Federation of Gynecology and Obstetrics (FIGO) stage, CA-125, RD, peritoneal cancer index (PCI), preoperative imaging (CT-PCI) and macroscopic visualization at the surgery start (S-PCI) were analyzed. Tumor extent was quantified using the PCI, and by CT-PCI and S-PCI. Cox regression, Kaplan-Meier and receiver operating curves (ROC) were performed for survival analyses.Results: S-PCI correlated with both OS (1.067, 95%CI=1.018-1.119, p<0.007) and PFS. Patients exhibiting S-PCI≥18.5, adjusted to age, performance status, and RD, had a two-fold risk of dying (HR=2.070, 95%CI=1.061-4.038, p=0.033) compared those with PCI<18.5. CT-PCI correlated with OS in crude data (1.037, 95%CI=1.005-1.071, p=0.025), but this was not sustained in multivariate analyses. RD of any size doubled the risk of dying (2.177, 95%CI=1.235-3.838, p=0.007).Conclusion: The tumor extent at the beginning of surgery seemed to affect OS in patients with AOC, regardless of the extent of RD at the end of the surgery. PCI above 18.5 doubled the risk of dying of the disease. No difference in major complications was noted in the two groups of patients. CT-PCI seemed to play a prognostic role for PFS; however, it is still to be investigated as a prognostic factor for OS.
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15.
  • Backlin, Carin, et al. (författare)
  • Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex
  • 1995
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 15:6B, s. 2453-2459
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion.MATERIAL AND METHODS:Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation.RESULTS:Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody.CONCLUSION:IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.
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16.
  • Backman, Samuel, et al. (författare)
  • Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing
  • 2017
  • Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:2, s. 705-712
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.
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19.
  • Blomberg, Carl, et al. (författare)
  • Randomized Trials of Systemic Medically-treated Malignant Mesothelioma : A Systematic Review
  • 2015
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2493-2501
  • Forskningsöversikt (refereegranskat)abstract
    • Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.
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20.
  • Bohr Mordhorst, Louise, 1958-, et al. (författare)
  • A study of serum biomarkers associated with relapse of cervical cancer
  • 2012
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:11, s. 4913-22
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients with cervical cancer that differentiate between patients with relapse from those who are tumor-free after primary treatment with (platinum-based chemo-) radiation.PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from patients with advanced cervical cancer, primarily treated with (platinum-based chemo-) radiation.RESULTS: Ten candidate biomarkers were identified in the serum of 34 patients. Six candidate markers were elevated in patients with no relapse and four were elevated in patients with relapse [p=0.007-0.11; area under the curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to 116,165 Da.CONCLUSION: Patients with relapse from primary advanced cervical cancer exhibit different serum protein expression profiles from those with no relapse.
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21.
  • Bolander, Åsa, et al. (författare)
  • The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
  • 2007
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:5A, s. 3211-3217
  • Tidskriftsartikel (refereegranskat)abstract
    • Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.
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23.
  • Bäckman, Ulrika, et al. (författare)
  • The Bisphosphonate Zoledronic Acid Reduces Experimental Neuroblastoma Growth by Interference with Tumor Angiogenesis
  • 2008
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:3A, s. 1551-1557
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Zoledronic acid is a new member of the bisphosphonate (BP) class of compounds, a family of closely related synthetic molecules originally derived from the naturally occurring pyrophosphate. These compounds that are potent inhibitors of bone resorption, have been shown to reduce the growth of several cancer cell lines in vitro, and can act as inhibitors of angiogenesis. The angiogenesis inhibitor TNP-470, a synthetic analogue of the fungal antibiotic fumagillin, has been shown to inhibit the growth of multiple tumors in vivo, and is currently in Phase H clinical trials for cancer. Materials and Methods: The effects of daily subcutaneous (s.c.) administration of zoledronic acid (0.1 mg/kg) were compared with those of TNP-470 (15 mg/kg/day and 30 mg/kg every other day, s.c.) in a nude mouse xenograft model for the childhood cancer, neuroblastoma (NB). Results: Zoledronic acid reduced the tumor growth by 33% whereas TNP-470 was less effective and reduced the tumor growth by 26% and 11% for animals treated with 15 mg/kg/day and 30 mg/kg every other day, respectively. Analysis of angiogenesis showed a significant reduction of the number of vessels per grid and in vessel length in all the treatment groups. Conclusion: Zoledronic acid shows tumoristatic and angiostatic properties that might be beneficial in the treatment of solid tumors such as neuroblastoma.
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24.
  • Cai, Feng Feng, et al. (författare)
  • Mutations of mitochondrial DNA as potential biomarkers in breast cancer
  • 2011
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:12, s. 4267-4271
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alterations of mitochondrial DNA (mtDNA) have been found in cancer patients, therefore informative mtDNA mutations could serve as biomarkers for the disease. Materials and Methods: The two hypervariable regions HVR1 and HVR2 in the D-Loop region were sequenced in ten paired tissue and plasma samples from breast cancer patients. Results: MtDNA mutations were found in all patients' samples, suggesting a 100% detection rate. Examining germline mtDNA mutations, a total of 85 mutations in the D-loop region were found; 31 of these mutations were detected in both tissues and matched plasma samples, the other 54 germline mtDNA mutations were found only in the plasma samples. Regarding somatic mtDNA mutations, a total of 42 mutations in the D-loop region were found in breast cancer tissues. Conclusion: Somatic mtDNA mutations in the D-loop region were detected in breast cancer tissues but not in the matched plasma samples, suggesting that more sensitive methods will be needed for such detection to be of clinical utility.
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25.
  • Carlsson, Adam, et al. (författare)
  • Melanoma Risk Estimation Based on Objective Measures as a Complement to Self-Assessment
  • 2020
  • Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 40:6, s. 3325-3331
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: A variety of self-tests addressing individual skin cancer risk are available online. These are generally based on self-estimated measures, such as self-rated skin sensitivity to sun exposure, affecting its reliability. The aim of this study was to investigate whether the addition of objective variables, by means of ultraviolet (UV) sensitivity phototesting and nevi count, could be of contributory value for the composition of a comprehensive risk score for skin cancer, and whether the use of such a score could contribute to change of behavior in the sun after assessment of individual risk. Patients and Methods: A sample of 70 voluntary participants, all university students, were recruited for the study. The participants rated their sun exposure habits by filling out the Sun Exposure and Protection Index (SEPI) questionnaire, and their skin UV-sensitivity was decided both by self-estimation, using Fitzpatrickss skin type scale, and objectively, by the performance of a UV-sensitivity phototest. Finally, the number of pigmented nevi on the lower arm was counted both by the participants themselves and by a trained observer. A cumulated skin cancer risk score was calculated on the basis on these three variables (sun habits, UV-sensitivity and nevi count), and the outcome compared whether based on the participants self-assessments or on the objective assessment. The individual risk score, based on objective measures, along with a tailored sun protection advice, was communicated to the participants, and after three weeks they once again filled-out the SEPI part addressing propensity to increase sun protection. Results: The results showed good correlation between the self-assessed and trained observer performed nevi count, but poor agreement between self-estimated and objectively measured skin UV-sensitivity. For the cumulative risk score, the self-performed score was on average slightly lower than its reference, but no systematic difference could be observed. At follow-up, high-risk individuals showed a significant decrease in total SEPI score (p<0.05). Conclusion: Objective assessment of nevi count and skin UV-sensitivity might be of significant value when estimating individual skin cancer risk, in order to communicate tailored sun protection advice.
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27.
  • Carlsson, Maria, 1958-, et al. (författare)
  • Treatment modality affects long-term quality of life in gynaecological cancer.
  • 2000
  • Ingår i: Anticancer Research. - : The International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 20:1B, s. 563-568
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to survey the side effects after cancer treatment, quality of life data were collected from females in clinical remission. MATERIALS AND METHODS The study was cross-sectional; every patient that visited the outpatient clinic during a period of three months was asked to anonymously complete the EORTC QLQ-C30 questionnaire and five additional specific questions related to gynaecological cancer. RESULTS In total, 235 patients (90%) returned the questionnaire. In general, both the levels of functioning and symptomatology were time-dependent. Patients with short treatment-free intervals reported more problems than the others. When using treatment modality as an independent variable in the statistical calculations, a treatment-related effect on functioning and symptomatology was demonstrated (p < 0.05 to p < 0.001). Patients previously treated with chemotherapy had poorer role- and cognitive functioning and more problems with fatigue, nausea, vomiting, dyspnoea, constipation and financial problems, compared with those not treated with chemotherapy (p < 0.05 to p < 0.01). Those patients who had been treated with external radiotherapy and/or brachytherapy had significantly more problems with flatulence and diarrhoea (p < 0.05 to p < 0.001). In conclusion, patients who underwent treatment for gynaecological cancer reported long-term side effects also many years after finishing treatment. The problems where related to treatment modality which should be considered, especially when planning adjuvant treatment.
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28.
  • Clausen, S., et al. (författare)
  • Outcome of Ordinary Polymorphous Adenocarcinomas of the Salivary Glands in Comparison With Papillary and Cribriform Subtypes
  • 2022
  • Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 42:3, s. 1455-1463
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Polymorphous adenocarcinoma (PAC) is a low-grade salivary gland malignancy in contrast to variants with papillary (PAP) or cribriform (CASG) architecture and confers the second most common malignancy of minor salivary glands. Our study aimed to identify prognostic factors and to evaluate histomorphological and molecular diagnostic criteria of PACs. Patients and Methods: A series of 155 PACs, including 10 PAPs and 12 CASGs from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW) and the Hamburg Salivary Gland Reference Centre (HRC) were analyzed. Results: One fifth of the tumors were located in the major salivary glands and PACS/CASGS invariably lacked p40 expression. Fifty-two percent of PACs showed a PRKD1 E710D mutation. Ordinary PACs had a disease-specific 10-year survival probability of 97% compared to 90% when combining PAPs and CASGs. T-stage at diagnosis was a prognostic factor with 98% for stages T1/T2 versus 75% for T3/T4. Conclusion: Diagnostic algorithms for the PAC/CASG spectrum of tumors need to be improved and should include molecular markers.
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29.
  • Dahlgren, Liselotte, et al. (författare)
  • Differences in human papillomavirus type may influence clinical outcome in early stage cervical cancer.
  • 2006
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:2A, s. 829-32
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The presence of human papillomavirus (HPV), the HPV type and viral load in early stage cervical carcinoma were investigated in order to elucidate whether any of these factors were important for clinical outcome. PATIENTS AND METHODS: Twelve patients who were disease-free 5 years after diagnosis were matched and compared with 12 patients who died within 2 years. The presence of HPV, HPV type and viral load in their tumours was examined by PCR. RESULTS: The distribution and load of HPV was similar in the 2 patient groups. HPV-16 was, however, significantly more common in tumours of the surviving patients than in those of patients who died (88.9% and 18.2%, respectively, p = 0.0152). CONCLUSION: HPV-16 was significantly more common in early stage carcinomas of patients surviving more than 5 years in comparison to early stage carcinomas of patients with a poor prognosis.
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30.
  • Dahlstrand, Hanna, et al. (författare)
  • Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer.
  • 2008
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:2B, s. 1133-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this review is to present the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. An increase in the incidence of tonsillar cancer has been reported and recent data suggest that this increase is due to an increased proportion of HPV in these tumours. Furthermore, patients with HPV positive cancer have been shown to have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. Tailoring individual treatment in tonsillar cancer may be of importance in order to reduce patient suffering as well as to increase patient survival. Finally, the fact that the presence of HPV-type 16 E6 and E7 mRNA has been ascertained in tonsillar cancer suggests that HPV-16 indeed is an aetiological factor associated with the disease and that preventive vaccination for this patient group should be discussed.
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31.
  • Dahlstrand, Hanna, et al. (författare)
  • Presence of human papillomavirus in tonsillar cancer is a favourable prognostic factor for clinical outcome.
  • 2004
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 24:3b, s. 1829-35
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this article is to review the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. Current data in scientific reports and data from the Karolinska Hospital and Karolinska Institute, Sweden, demonstrate that approximately half of all tonsillar cancer is HPV-positive. Moreover, patients with HPV-positive cancer have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. The favourable outcome for patients harbouring HPV-positive tonsillar cancer cannot be attributed to increased radiosensitivity, since there is no significant difference in sensitivity to radiotherapy between HPV-positive and -negative tonsillar cancer. However, HPV-positive cancer exhibits less genetic instability i.e. shows a lower degree of aneuploidy and a tendency to have fewer chromosomal aberrations, when compared to HPV-negative tonsillar cancer.
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32.
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33.
  • Derwinger, Kristoffer, 1969, et al. (författare)
  • Age Aspects of Demography, Pathology and Survival Assessment in Colorectal Cancer
  • 2010
  • Ingår i: ANTICANCER RESEARCH. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:12, s. 5227-5231
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The aim of this study was to assess how age is related to differences in stage, tumour differentiation and treatment in colorectal cancer. Patients and Methods: A retrospective study in a consecutive series of colorectal cancer patients (n=2220) where age was related to demography, stage, tumour characteristics, treatment and outcome (OS/CSS) both as a continuous variable and grouped by high/low 10th percentiles, as young/old groups, with a third median reference group. Results: Young patients had more advanced cancer stages (p=0.012), higher N-status (p=0.011) and more frequent T4/G4 tumours. Old patients had higher postoperative mortality and were less likely to receive chemotherapy. The proportion of cancer-related deaths was stage-dependent and decreased with age. Conclusion: Cancer stage, tumour characteristics, treatment and outcome can vary with age in colorectal cancer. The increasing proportion of non-cancer deaths at a higher age can affect the use of overall survival as an outcome parameter, which may be of importance in evaluating clinical and translational research.
  •  
34.
  • Dimakakos, Evangelos, et al. (författare)
  • Thromboembolic Disease in Patients With Cancer and COVID-19 : Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art
  • 2022
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:7, s. 3261-3274
  • Forskningsöversikt (refereegranskat)abstract
    • Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.
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35.
  • Dimberg, Jan, et al. (författare)
  • Detection of Cytomegalovirus DNA in Colorectal Tissue from Swedish and Vietnamese Patients with Colorectal Cancer
  • 2013
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:11, s. 4947-4950
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human cytomegalovirus (HCMV) has been implicated as a factor, which might be associated with colorectal cancer (CRC) progression. Data from studies with HCMV-infected tumour cell lines have highlighted an oncomodulatory potential of HCMV. In the present study, we aimed to evaluate the prevalence of HCMV DNA in CRC tissue compared to matched normal tissue, and its association with clinical factors.Patients and Methods: We used quantitative real-time polymerase chain reaction assay to detect HCMV DNA in 202 cancerous and paired normal tissue from Swedish (n=119) and Vietnamese (n=83) CRC patients.Results: Overall, the HCMV DNA rate was significantly higher in cancerous in relation to paired normal tissue. Furthermore, a significantly higher frequency (39.8%) of HCMV DNA was observed in cancer tissues from the Vietnamese patients compared to the Swedish patients (15.1%). The prevalence of HCMV DNA in CRC tissue of 50% of those with disseminated disease tended to be higher compared to those with localized disease, with a prevalence of 33.3% in Vietnamese patients.Conclusion: Our observations indicate that the prevalence of HCMV DNA differs significantly between cancer and matched normal tissues. Thus, these data support a possible role of CMV in CRC. Moreover, we noted differences between Swedish and Vietnamese patients, indicating a role of ethnicity.
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36.
  •  
37.
  • Dimberg, Jan, et al. (författare)
  • Enhanced expression of cyclooxygenase-2 and nuclear beta-catenin are related to mutations in the APC gene in human colorectal cancer
  • 2001
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 21:2A, s. 911-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutational inactivation of the human tumour suppressor gene adenomatous polyposis coli (APC) results in constitutive activation of beta -catenin/T cell factor-4 (Tcf-4) mediated transcription of target genes. Up-regulation of cyclooxygenase-2 (COX-2) protein is frequently found in human colorectal cancer (CRC). We analysed 38 CRC for mutations in APC and beta -catenin and found an association between APC mutations and elevated COX-2 levels. Furthermore, APC mutations were predominantly observed in tumour tissues from the rectum compared to tumours of colonic origin. Western blot analysis revealed that nuclear beta -catenin levels were generally higher in tumours with APC mutations compared to tumours with wild type APC. However, there was also a higher level of nuclear beta -catenin in tumour compared to normal tissue, hut nuclear Tcf-4 protein was constitutively expressed in tumour and normal tissue and showed no differences. An identified putative Tcf-4 binding element in the COX-2 promoter may partly explain the enhanced level of COX-2 and support the idea that COX-2 may be a downstream target of the APC/beta -catenin/Tcf-4 pathway.
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38.
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39.
  • Dimberg, Jan, et al. (författare)
  • Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer
  • 2019
  • Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:9, s. 4933-4940
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.
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40.
  • Dimberg, Jan, et al. (författare)
  • Novel and Differential Accumulation of Mitochondrial DNA Deletions in Swedish and Vietnamese Patients with Colorectal Cancer
  • 2014
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:1, s. 147-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and aging. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in colorectal cancer (CRC). In the present study, we aimed to evaluate the frequency of mtDNA 4977 bp deletion in CRC tissues and its association with clinical factors. Patients and Methods: We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 105 Swedish and 88 Vietnamese patients with CRC using polymerase chain reaction (PCR) assays. Results: The mtDNA 4977 bp deletion was shown to be significantly more frequent in normal tissues in comparison with paired cancer tissues in both Swedish and Vietnamese patients. The 4977 bp common deletion was significantly more frequent in cancer tissues of the Vietnamese patients compared to the Swedish patients, and in Vietnamese cancer tissues, the 4977 bp deletion was significantly over represented in those with localized disease compared to those with disseminated disease. Moreover, we detected nine novel mtDNA deletions and found a significantly higher rate of these in CRC tissues in Swedish in comparison to Vietnamese patients. Conclusion: The mtDNA 4977 bp deletion seems to have an impact on the clinical outcome of CRC in Vietnamese patients, that the Swedish patients accumulate more of the detected novel deletions in CRC tissue compared to Vietnamese patients probably indicates divergent mechanisms in colorectal carcinogenesis.
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41.
  • Djureinovic, Tatjana, et al. (författare)
  • The CHEK2 1100delC variant in Swedish colorectal cancer
  • 2006
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4885-4888
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.
  •  
42.
  • Dobilas, Arturas, et al. (författare)
  • Circulating Markers of Neutrophil Extracellular Traps (NETs) in Patients With Ovarian Tumors
  • 2022
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:2, s. 965-971
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIM: Inflammation is a hallmark of cancer, and the role of neutrophils and neutrophil extracellular traps (NETs) in cancer and cancer-associated thrombosis has attracted a lot of interest. The NET-specific marker H3Cit has been found to be elevated in the plasma of patients with malignancies, suggesting NETs markers as novel cancer biomarkers. This study aimed to determine the levels of NETs markers (H3Cit and dsDNA) in the plasma of women with adnexal masses. PATIENTS AND METHODS: Peripheral blood samples were obtained from 199 patients admitted for primary surgery of adnexal masses. Patients were grouped according to tumor type and stage. Plasma levels of H3Cit-DNA, dsDNA, and CA125 were quantified. RESULTS: Plasma levels of H3Cit-DNA and dsDNA were not elevated in women with borderline or malignant ovarian tumors compared with those of the benign group. Increased levels of CA125 were found in the borderline and ovarian cancer group (ptrend<0.001). In Cox regression analysis, CA125 levels dichotomized at 326 IU/ml (median) were associated with worse overall survival (HR=1.9; 95%CI=1.03-3.36; p=0.038). No differences were found in the survival analyses of malignant ovarian tumors by analyzing the dsDNA and H3Cit-DNA levels. CONCLUSION: There is no association between NETs markers and ovarian tumors.
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43.
  • dos Santos Matias, Lucílio, et al. (författare)
  • Dosimetric and radiobiological evaluation of hybrid inverse planning and optimization for cervical cancer brachytherapy
  • 2015
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:11, s. 6091-6096
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To compare manual graphical optimization (GrO) with hybrid inverse planning optimization (HIPO) of cervical cancer brachytherapy treatment plans using physical and radiobiological tools. Patients and Methods: Ten patients suffering from cervical cancer, treated with pulsed brachytherapy using GrO plans, were included in the study. For each patient, four different HIPO class solutions with different dose objectives to the target and constraints to the organs at risk (OAR) produced four optimized plans, that were each compared to the corresponding GrO plan. Class solution in HIPO is a set of parameters consisting of dose constraints and penalty weights, which are used for optimization. The comparison was based on the following dosimetric parameters: conformity index (COIN), minimum dose received by 98% and 90% of the high-risk clinical target volume (represented by D98 and D90, respectively), and the minimum dose imparted to 2 cm3 (D2cm3) of the most exposed OAR i.e. bladder, sigmoid colon or rectum. The HIPO class solution which produced plans with overall better dosimetric parameters was selected and its plans were compared with manual GrO plans from a radiobiological viewpoint based on the calculated complication-free tumour control probability, P+. Results: The average COIN for the GrO and the selected HIPO plans were 0.22 and 0.30, respectively. The median COIN of the GrO and the HIPO plans were not statistically different (p>0.05, Wilcoxon test). The relative percentage difference of the averaged P+ values between the HIPO and GrO plans evaluated together with the external beam radiation therapy plans was 0.01%, 0.37% and 0.98% for the bladder, sigmoid colon and rectum, respectively. The lowest P+ value for all the plans was 98.44% for sigmoid colon. Conclusion: HIPO presented comparable results in relation to manual planning with respect to dosimetric and radiobiological parameters.
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44.
  • Edgren, M, et al. (författare)
  • Biological characteristics of adrenocortical carcinoma : A study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas
  • 1997
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 17:2B, s. 1303-1310
  • Tidskriftsartikel (refereegranskat)abstract
    • Adrenocortical carcinoma (ACC) is a rare neoplasm with a poor prognosis. Prognostic factors are needed to identify patients who should be treated aggressively and those for which a less aggressive approach is warranted. As a result of advances within the field of immunohistochemistry, investigations of Ki-67, PCNA, IGF, EGF-r and p53 were performed in 17 ACC. The aim of this study was to clarify the role of Ki-67, PCNA, EGF-r, IGF and p53 in correlation to tumour behaviour and outcome. This retrospective study includes 16 patients, 10 women and 6 men, with a median age of 46 years. Nine tumours were hormonally functioning and 7 were non-functioning. The results obtained revealed that all tumours expressed PCNA and Ki-67 with median values of 59% and 14%, respectively, while p53 was negative in 88%, IGF negative in 82% and EGF-r positive in 94% of the tumours. No correlation was found between p53, IGF, EGF-r and survival rate. There was no interdependence between PCNA and Ki-67, or between PCNA, Ki-67 and the survival rate.
  •  
45.
  • Edgren, M, et al. (författare)
  • Serum concentrations of VEGF and b-FGF in renal cell, prostate and urinary bladder carcinomas.
  • 1999
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 19:1B, s. 869-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Sixty nine patients with urogenital cancers (renal, bladder and prostate cancer) were studied to determine whether the serum concentrations of Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (b-FGF) reflected the status of the patients and/or the prognosis of the disease. Of the patients included in this study, renal cell carcinoma patients expressed the highest levels of VEGF indicating that these tumours are more VEGF dependent. The values of b-FGF could be considered normal in all three malignancies. No correlation was observed between the expression of VEGF and b-FGF, nor between VEGF and b-FGF and patients survival.
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46.
  • Ekman, Simon, et al. (författare)
  • Clinical value of using serological cytokeratins as therapeutic markers in thoracic malignancies
  • 2007
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:5B, s. 3545-3553
  • Forskningsöversikt (refereegranskat)abstract
    • In recent years, there has been an increasing awareness among physicians of the value of therapeutic interventions in patients suffering from lung cancer and mesothelioma. A search for an optimal approach using surgery, irradiation and chemotherapy in different settings of the tumour disease, including curatively aimed adjuvant chemotherapy after locoregional surgery or radiotherapy, has resulted in gradually improved survival rates. Still, early detection is crucial if there is to be a possibility of curing patients or prolonging life in cases of relapsed disease. Several studies have been initiated in which surrogate markers are evaluated in comparison to chest X-rays and computer tomography. The present review focuses on the predictive and prognostic value of using serological cytokeratins as tumour markers for patients suffering from thoracic malignancies.
  •  
47.
  • Elander, Nils, 1980-, et al. (författare)
  • Matrix metalloproteinase (MMP) -1, -2, -3 and -9 promoter polymorphisms in colorectal cancer
  • 2006
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:1B, s. 791-795
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Matrix metalloproteinases (MMPs) are a group of matrix-degrading proteins implicated in several pathological processes, e.g., invasion and metastasis in malignant diseases such as colorectal cancer (CRC). Materials and methods: One hundred and twenty-seven CRC patients and 208 controls were genotyped for MMP-1, -2, -3 and -9 promoter polymorphisms. The genotyping was performed with PCR/primer-extension/DHPLC or PCR/RFLP. Results: The MMP-1 2G allele was significantly associated with CRC (p=0.037). No significant association between CRC and MMP-2, -3 or -9 polymorphisms was evident. The analysis of polymorphisms in the clinicopathological subgroups displayed no significant associations. Conclusion: The MMP-1 promoter polymorphism seems to affect the susceptibility to CRC, while MMP-2, -3 and -9 polymorphisms appear less likely to have any impact on CRC.
  •  
48.
  • Elliot, Anders H., et al. (författare)
  • Pretreatment MRI in Primary Rectal Cancer as a Predictor for Oncological Outcomes After Surgery for Local Recurrence
  • 2021
  • Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 41:5, s. 2459-2465
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: For patients with locally recurrent rectal cancer (LRRC) extensive surgery is often the only curative option and patient selection is crucial. This study aimed to investigate whether magnetic resonance imaging (MRI) characteristics of the primary tumour can predict oncological outcome after surgery for locally recurrent rectal cancer (LRRC). Patients andMethods: All patients undergoing surgery for LRRC with a curative intent at the Karolinska University Hospital 2003-2013 were included. MRI examinations of the primary tumour were re-evaluated.Results: In total, 54 patients were included. A tumour volume decrease of <70% after preoperative radiotherapy or chemoradiotherapy (C)RT for the primary tumour was correlated with a lower proportion of R0 resection of the LRRC (OR=0.07, 95% CI=0.01-0.84). No association between MRI characteristics of the primary tumour and prognosis after LRRC surgery was found.Conclusion: Long-term outcomes after surgery for LRRC were not significantly associated with MRI characteristics of the index tumour. However, factors associated with increased risk of R1 resection of LRRC were identified.
  •  
49.
  • Elmroth, Kerstin, 1970, et al. (författare)
  • Radiation and hypothermia: changes in DNA supercoiling in human diploid fibroblasts
  • 1999
  • Ingår i: Anticancer Res. - 0250-7005 .- 1791-7530. ; 19:6B, s. 5307-11
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of hypothermia (2 degrees, 15 degrees and 28 degrees C) upon the effect of X-irradiation on chromatin from human diploid fibroblast cells (AG1518) was studied using the fluorescent halo assay. Rewinding of supercoils was inhibited in a dose-dependent manner when cells were irradiated with 4, 8 or 16 Gy. This inhibition of rewinding was reduced when cells were irradiated at subnormal temperatures compared with cells irradiated at 37 degrees C. One hour's preincubation at low temperature did not influence rewinding. When AG1518 cells were irradiated at 37 degrees C in the presence of the radical scavenger DMSO (0.5 M), the radiation-induced damage was reduced. No additional protection of DMSO in hypothermic cells (2 degrees C) was found, possibly indicating that OH-radical-mediated effects are more temperature dependent. These results are similar to those recently found for the malignant MCF-7 cell line.
  •  
50.
  • Engström, Wilhelm (författare)
  • Effects of Insulin-like Growth Factor Binding Protein 7 on Apoptosis in Human Teratocarcinoma Cells In Vitro
  • 2010
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30, s. 911-914
  • Tidskriftsartikel (refereegranskat)abstract
    • Human teratocarcinoma cells (Tera-2) deprived of serum undergo programmed cell death which can be counteracted by simultaneous addition of IGF-II. This protective effect of IGF-II was specific in the sense that addition of IGF-binding protein 7 (IGFBP-7) resulted in an increased apoptotic rate almost comparable to that of the classical IGFBPs. Autoradiographic analysis of incorporated tritiated thymidine indicated that the proportion of S-phase cells was comparable, irrespective of total cell numbers. This further suggests that IGF-II rescues cells from apoptosis and that IGFBP-7 is a specific antagonist.
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