| 1. |
- Acuña, Ulyana Muñoz, et al.
(författare)
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Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells.
- 2017
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:4, s. 1617-1623
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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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| 2. |
- Ansari, Daniel, et al.
(författare)
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Centrosomal Abnormalities in Pancreatic Cancer : Molecular Mechanisms and Clinical Implications
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1241-1245
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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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| 3. |
- Ansari, Daniel, et al.
(författare)
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The hippo signaling pathway in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3317-3321
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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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| 4. |
- Ansari, Daniel, et al.
(författare)
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The role of PEDF in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3311-3315
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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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| 5. |
- Asciutto, Katrin Christine, et al.
(författare)
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Prevalence of high-risk HPV in postmenopausal women with benign cervical cytology - A population-based cohort study
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:7, s. 4221-4228
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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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| 6. |
- Asciutto, Katrin Christine, et al.
(författare)
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Vaginal and urine self-sampling compared to cervical sampling for HPV-testing with the cobas 4800 HPV test
- 2017
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:8, s. 4183-4187
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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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| 7. |
- Backman, Samuel, et al.
(författare)
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Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:2, s. 705-712
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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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| 8. |
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| 9. |
- Blomberg, Carl, et al.
(författare)
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Randomized Trials of Systemic Medically-treated Malignant Mesothelioma : A Systematic Review
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2493-2501
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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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| 10. |
- Dimberg, Jan, et al.
(författare)
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Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:9, s. 4933-4940
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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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| 11. |
- dos Santos Matias, Lucílio, et al.
(författare)
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Dosimetric and radiobiological evaluation of hybrid inverse planning and optimization for cervical cancer brachytherapy
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:11, s. 6091-6096
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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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| 12. |
- Ernstson, Avalon, et al.
(författare)
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Detection of HPV mRNA in Self-collected Vaginal Samples Among Women at 69-70 Years of Age
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 39:1, s. 381-386
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Cervical cancer is associated with poorer diagnosis among the elderly and pap-smear screening has a lower sensitivity. Self-sampling for detection of high-risk human papillomavirus (hr-HPV) may be an alternative screening method. The aim of this study was to analyze the response rate to vaginal HPV self-sampling and the HPV mRNA prevalence among women 69-70 years. MATERIALS AND METHODS: An HPV self-sampling kit was sent to 1,000 women 69-70 years whom had not taken a cervical smear in ≥5 years. The samples were analyzed by the Aptima HPV mRNA assay. HPV-positive women were recalled for a follow-up examination. RESULTS: The self-sample response rate was 43.3%. The HPV mRNA prevalence was 6.2%. All HPV-positive women attended follow-up. CONCLUSION: HPV self-sampling was accepted among older women. Although the HPV mRNA prevalence was 6.2%, no high-grade cytological abnormalities were found. Larger studies are needed to elucidate hr-HPV self-sampling as a tool to identify older women at risk of cervical cancer.
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| 13. |
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| 14. |
- Falk Delgado, Alberto, et al.
(författare)
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Complete Lymph Node Dissection in Melanoma : A Systematic Review and Meta-Analysis
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:12, s. 6825-6829
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Forskningsöversikt (refereegranskat)abstract
- Background: The aim of this meta-analysis was to estimate the survival after immediate complete lymph node dissection (CLND) compared to observation only (OO) or delayed CLND in patients with melanoma and lymph node metastasis.Materials and Methods: A systematic search was performed in: PubMed, Web of Science, Cochrane Library, CINAHL, Clinical trials and Embase. Eligible studies were randomized controlled trials (RCTs) comparing: CLND with OO, or immediate CLND with delayed CLND.Results: Four RCTs were included. There was no difference in melanoma-specific survival (MSS) (HR=0.91, 95% CI=0.77-1.08, p=0.29). In a sensitivity analysis, MSS was higher after immediate CLND compared to delayed CLND in patients with nodal metastasis (HR=0.63, 95% CI=0.35-0.74, p=0.0004) without evidence of heterogeneity.Conclusion: CLND appears to have no additional survival benefit after SNB compared to OO. However, subgroup analysis suggests a time-dependent benefit for early surgical lymph node removal compared to delayed or none.
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| 15. |
- Falk Delgado, Alberto, et al.
(författare)
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Inconsistent Reporting Between Meta-analysis Protocol and Publication – A Cross-Sectional Study
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:9, s. 5101-5107
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inconsistent reporting in published meta-analyses compared to registered protocol are poorly understood. The aim of the study was to assess inconsistencies between registered protocols and published reports among oncology drug meta-analyses.Materials and Methods: A cross-sectional study was performed including oncology drug meta-analyses published between January 1st and November 14th 2016 with a published protocol. Two investigators extracted data on: selection criteria, outcome(s) and statistical plan in protocol and manuscript, plus self-acknowledgement of inconsistent reporting between protocol and publication.Results: Protocol registration was present in 19% (23/119) of all oncology drug meta-analyses. In meta-analyses with protocol (n= 23), 70% (16/23) had issues with inconsistent reporting between protocol and published report concerning; inclusion criteria, comparator group, intervention, outcome (PICO) or statistical analysis. Self-acknowledgement of changes between protocol and publication was found in 50% (8/16).Conclusion: In meta-analyses with protocol, discrepancies between registered protocols and publications are frequent.
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| 16. |
- Fang, Qi, et al.
(författare)
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Increased CXCL8 expression is negatively correlated with the overall survival of patients with ER-negative breast cancer
- 2017
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:9, s. 4845-4852
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Tidskriftsartikel (refereegranskat)abstract
- Background: C-X-C motif chemokine ligand 8 (CXCL8) is a multi-functional chemokine and has important roles during tumor formation and development. It was previously reported that increased CXCL8 protein levels occurred in certain patients. Materials and Methods: In the present study, we examined levels of CXCL8 mRNA in breast cancer tissues and analyzed its levels in correlation to patients' clinical data and 10-year overall survival (OS). Results: Our results clearly demonstrated that the level of CXCL8 mRNA was significantly higher in patients without estrogen receptor expression. The receiver operating characteristic curve indicated that the best cut-off value for CXCL8 expression was 3.095 for predicting patient's OS. Conclusion: The present study demonstrated that higher CXCL8 mRNA levels in breast cancer tissues together with estrogen receptor negativity was associated with significantly shorter OS, and could be applied as a negative risk factor for 10-year OS.
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| 17. |
- Flejmer, Anna M., et al.
(författare)
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Analytical Anisotropic Algorithm versus Pencil Beam Convolution for treatment planning of breast cancer: implications for target coverage and radiation burden of normal tissue
- 2015
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2841-2848
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The present study aimed to investigate the implications of using the analytical anisotropic algorithm (AAA) for calculation of target coverage and radiation burden of normal tissues. Most model parameters, recommendations and planning guidelines associated with a certain outcome are from the era of pencil beam convolution (PBC) calculations on relatively simple assumptions of energy transport in media. Their relevance for AAA calculations that predict more realistic dose distributions needs to be evaluated. Patients and Methods: Forty patients with left-sided breast cancer receiving 3D conformal radiation therapy were planned using PBC with a standard protocol with 50 Gy in 25 fractions according to existing re-commendations. The plans were subsequently recalculated with the AAA and relevant dose parameters were determined and compared to their PBC equivalents. Results: The majority of the AAA-based plans had a significantly worse coverage of the planning target volume and also a higher maximum dose in hotspots near sensitive structures, suggesting that these criteria could be relaxed for AAA-calculated plans. Furthermore, the AAA predicts higher volumes of the ipsilateral lung will receive doses below 25 Gy and smaller volume doses above 25 Gy. These results indicate that lung tolerance criteria might also have to be relaxed for AAA planning in order to maintain the level of normal tissue toxicity. The AAA also predicts lower doses to the heart, thus indicating that this organ might be more sensitive to radiation than thought from PBC-based calculations. Conclusion: The AAA should be preferred over the PBC algorithm for breast cancer radiotherapy as it gives more realistic dose distributions. Guidelines for plan acceptance might have to be re-evaluated to account for differences in dose predictions in order to maintain the current levels of control and complication rates. The results also suggest an increased radiosensitivity of the heart, thus indicating that a revision of the current models for cardiovascular complications may be needed.
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| 18. |
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| 19. |
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| 20. |
- Frobom, Robin, et al.
(författare)
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Biochemical Inhibition of DOG1/TMEM16A Achieves Antitumoral Effects in Human Gastrointestinal Stromal Tumor Cells In Vitro
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:7, s. 3433-3442
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST. Materials and Methods: Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle. Results: CaCCinh-A01 decreased chloride currents. CaCCinh-A01 and T16(inh)-A01 reduced GIST cell viability and CaCCinh-A01 affected cell cycle distribution leading to G(1) cell-cycle arrest. CaCCinh-A01 also increased the sub-G(1) phase population, indicative of apoptosis, in GIST882. CaCCinh-A01 strongly reduced the colony forming ability of the cells, whereas T16(inh)-A01 did not. Conclusion: DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy.
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| 21. |
- Förnvik, Karolina, et al.
(författare)
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ITPP treatment of RG2 glioblastoma in a rat model
- 2016
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 36:11, s. 5751-5755
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inositol trispyrophosphate (ITPP) has been shown to reduce tumour growth in different animal cancer models, as well as of human U87 glioma cells grafted onto chick chorioallantoic membrane (CAM). The aim of this study was to establish whether ITPP crosses the blood-brain barrier and whether it halts the growth of RG2 glioblastoma tumour. Materials and Methods: A model comprising of Fischer 344 rats was chosen and RG2 cells were implanted either intracranially, or subcutaneously on the left hind leg, and the animals were treated with ITPP either intraperitoneally, intravenously or both routes combined. Overall survival was then calculated. Results: No prolonged survival was seen in animals treated with ITPP. The route of ITPP administration did not affect outcome. Conclusion: ITPP had no favourable effect upon survival in our animal model with RG2 glioblastoma tumours in Fischer 344 rats.
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| 22. |
- Ganesh, Divya, et al.
(författare)
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Potentially Malignant Oral Disorders and Cancer Transformation
- 2018
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:6, s. 3223-3229
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Forskningsöversikt (refereegranskat)abstract
- Cancer in the oral cavity is often preceded by precursor lesions. Nine oral mucosal disorders are known to have an increased risk of malignant transformation. The etiology varies from disorders caused by exogenous factors such as tobacco and autoimmune inflammation to idiopathic or inherited genetic aberrations. In this review, these potentially malignant disorders (PMDs) are described regarding clinical presentation and histopathological architecture. Special attention is paid to the underlying etiologies of PMDs and the potential pathways leading to cancer. The clinical perspective focuses on the importance of accurate and timely diagnosis.
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| 23. |
- Gkekas, Ioannis, et al.
(författare)
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Microsatellite instability as a prognostic factor in stage II colon cancer patients : a meta-analysis of published literature
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:12, s. 6563-6574
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND/AIM: The prognostic role of microsatellite instability (MSI) in stage II colon cancer patients remains controversial despite the fact that it has been investigated in a number of studies. Hazard ratios differ considerably among these studies. We performed a meta-analysis to define the significance of MSI in this group of patients.MATERIALS AND METHODS: Studies indexed in PubMed presenting separate data on MSI status and survival outcomes for stage II colon cancer patients have been analyzed using fixed-effect meta-analysis of hazard ratio (HR) according to the method of Peto.RESULTS: Analysis was performed on 19 studies including 5,998 patients. A 47.3% of patients received postoperative chemotherapy and included 52.8% males and 47.2% females. Eight studies included some rectal cancer patients although this cohort was not clearly defined in 3 of these. MSI observed in 20.8% (mean) of patients (median 19.9%). HR for overall survival (OS) of MSI vs. microsatellite stable (MSS) tumors for the entire population: 0.73 (95% confidence interval (CI)=0.33-1.65); HR for disease-free survival (DFS):0.60 (95%CI=0.27-1.32). No statistical significant difference was found when studies analyzing MSI with genotyping (MG) and immunohistochemistry (IHC) were compared separately (MG vs. IHC: HR OS 0.45, 95%CI=0.10-2.05 vs. 0.95, 95%CI=0.57-1.58; HR DFS 0.51, 95%CI=0.14-1.85 vs. 0.67, 95%CI=0.26-1.70). However, numerically MSI determination with genotyping shows significantly lower hazard ratios for both DFS and OS. Separate analysis of studies describing colon cancer patients only showed HR OS 0.72 (95%CI=0.31-1.71); HR DFS 0.60 (95%CI=0.27-1.31).CONCLUSION: No significant relation was found between MSI status and OS or DFS. Routine determination of MSI status to guide postoperative management of stage II colon cancer patients cannot be recommended. New large scale high quality studies are needed to answer this question definitively, since currently analyzed studies vary considerably.
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| 24. |
- Guo, Jinan, et al.
(författare)
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A panel of biomarkers for diagnosis of prostate cancer using urine samples
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1471-1477
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Prostate cancer (PCa) diagnosis using patient urine samples represents a non-invasive and more convenient method than the conventional biopsy and prostate-specific antigen (PSA) test. This study intended to identify a biomarker panel to distinguish PCa from benign prostate using urine samples. Materials and Methods: We identified six biomarkers with differential gene expression in 154 PCa and benign prostate specimens. We then determined mRNA expression signature and the diagnostic performance of the 6-biomarker panel in 156 urine samples from patients with PCa and benign disease. Results: The 6-biomarker panel distinguished PCa from benign prostate cases with sensitivity of 80.6%, specificity of 62.9% and area under the curve (AUC) of 0.803 (p<0.0001), whereas serum PSA at 4 ng/ml cutoff had sensitivity of 95.5%, specificity of 20.2% and AUC of 0.521 (p<0.0001). Conclusion: The 6-biomarker panel for use in urine samples was able to distinguish PCa from benign prostate with higher specificity and accuracy than PSA and may be useful in clinical settings.
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| 25. |
- Hakelius, Malin, 1965-, et al.
(författare)
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Normal oral keratinocytes and head and neck squamous carcinoma cells induce an innate response in fibroblasts
- 2016
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 36:5, s. 2131-2137
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Tumor stroma is similar to the connective tissue of chronic inflammation. The extracellular matrix of tumors is formed by cancer-associated fibroblasts that also modulate the inflammatory response. Materials and Methods: We studied the ability of oral keratinocytes (NOK) and oral squamous cell carcinoma cells (SCC) to induce an innate immune response in fibroblasts. Co-cultures with fibroblasts in collagen gels and keratinocytes in inserts were used. Pentraxin 3 (PTX3) was used as an indicator of an innate immune response. Results: SCC and NOK up-regulated fibroblast mRNA expression and protein release of PTX3. mRNA levels were more pronounced in cultures with malignant cells. The induction of PTX3 was abrogated by an interleukin-1 receptor antagonist Conclusion: Keratinocytes have the capacity to induce an interleukin-1-dependent innate immune response by fibroblasts in vitro. This could be important for subsequent fibroblast modulation of the inflammatory reaction in non-malignant and malignant disease processes.
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| 26. |
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| 27. |
- Hernroth, Bodil, et al.
(författare)
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Manganese inhibits viability of prostate cancer cells
- 2018
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:1, s. 137-145
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Androgen deprivation therapy is usually in the initial phase a successful treatment for prostate cancer but eventually most patients develop androgen-independent metastatic disease. This study investigated if manganese (Mn) reduces viability of prostate cancer via induction of apoptosis. Materials and Methods: The prostate cancer cell lines PC3, DU145 and LNCaP underwent dose- and time-dependent screening of viability, analyzed by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Flow cytometry was used for the cell-cycle and apoptosis analyses. Intracellular Mn concentration was measured using inductively coupled plasma-mass spectrometry. Results: At Mn concentrations of 200-1000 µM, the effect on viability was most pronounced in PC3 followed by LNCaP cells. These cell lines also showed higher intracellular concentration of Mn compared to DU145. In all cell lines, Mn increased the proportion of cells arrested in the G0/G1 phase and induced apoptosis. Conclusion: To our knowledge, this is the first report demonstrating Mn as a potential agent in prostate cancer therapy.
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| 28. |
- Holgersson, Georg, et al.
(författare)
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Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:10, s. 5491-5497
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC).Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000.Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17).Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.
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| 29. |
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| 30. |
- Hu, Dingyuan, et al.
(författare)
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The Emerging Role of Calcium-activated Chloride Channel Regulator 1 in Cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 39:4, s. 1661-1666
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Forskningsöversikt (refereegranskat)abstract
- Calcium-activated chloride channel regulator 1 (CLCA1) belongs to a group of secreted self-cleaving proteins, which activate calcium-dependent chloride channels. CLCA1 has been shown to participate in the pathogenesis of inflammatory airway diseases such as asthma. Recently, additional functions of CLCA1 have been unveiled, including its metalloprotease property and involvement in mucus homeostasis and immune modulation. Emerging evidence suggests that CLCA1 may also be involved in the pathophysiology of colorectal, pancreatic and ovarian cancer. There is growing interest in utilizing CLCA1 as a diagnostic, prognostic and predictive biomarker, as well as a potential therapeutic target. In this review, the functional role of CLCA1, with a particular focus on cancer, is described.
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| 31. |
- Johansson, Andreas K., et al.
(författare)
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Neurovascular Bundle Infiltration Can Explain Local Relapses Using Conformal Radiotherapy of Prostate Cancer.
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:4, s. 1825-1830
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To quantify the impact of decreased margins for two treatment techniques, three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT), on local control in curative treatment of prostate cancer.MATERIALS AND METHODS: The planning target volume (PTV) margins were decreased in steps of 1 mm from 10 to 1 mm. Treatment plans using 3D-CRT and VMAT technique were produced for all margin sizes and the dose to the neuro vascular bundles (NVB), that was not included in the PTV, was investigated.RESULTS: Due to the more conformal dose delivery using VMAT, the dose to the NVB decreased more rapidly by VMAT compared to the 3D-CRT plans. The dose difference was significant for margins from 1-7 mm.CONCLUSION: One should be very cautious before clinical routines are changed, bearing in mind whether the change means more conformal treatment technique, smaller margins or target segmentation in different imaging modalities.
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| 32. |
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| 33. |
- Kindler, Csaba, et al.
(författare)
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Detection of Free Cancer Cells in Pelvic Lavage with Double Immunocytochemistry at Rectal Cancer Surgery
- 2017
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:4, s. 1563-1568
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The aim of the present study was to describe a double immunocytochemical staining method for detecting free cancer cells after rectal cancer surgery and to evaluate their extent and prognostic role. Materials and Methods: Immunocytochemistry was performed using antibodies against cytokeratin 20/caudal-typehomeobox transcription factor 2 (CDX2) and mucin glycoprotein-2 (MUC2)/p53 protein. The study included 29 patients with infraperitoneal rectal cancer who underwent bowel resection and four controls. The pelvic lavage was retrieved at the start of laparotomy, after total mesorectal excision and after abdominal lavage with sterile water. Results: Free cancer cells were detected with the double immunocytochemical method in the two controls with carcinomatosis and one control with sigmoidal cancer. None of the patients with rectal tumours had presence of free cancer cells. Conclusion: Immunocytochemical analysis of peritoneal lavage was feasible and negative in patients with infraperitoneal rectal cancer. Further studies are encouraged to investigate the clinical relevance in cases with free cancer cells after incomplete total mesorectal excision.
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| 34. |
- Kjellsson Lindblom, Emely, et al.
(författare)
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Hypoxia Induced by Vascular Damage at High Doses Could Compromise the Outcome of Radiotherapy
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:5, s. 2337-2340
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: This study investigated the impact of temporary vascular collapse on tumour control probability (TCP) in stereotactic body radiotherapy (SBRT), taking into account different radiosensitivities of chronically and acutely hypoxic cells. Materials and Methods: Three-dimensional tumours with heterogeneous oxygenation were simulated assuming different fractions of collapsed vessels at every treatment fraction. The modelled tumours contained a chronically hypoxic subvolume of 30-60% of the tumour diameter, and a hypoxic fraction ≤5 mm Hg of 30-50%. The rest of the tumours were well-oxygenated at the start of the simulated treatment. Results: For all simulated cases, the largest reduction in TCP from 97% to 2% was found in a tumour with a small chronically hypoxic core treated with 60 Gy in eight fractions and assuming a treatment-induced vascular collapse of 35% in the well-oxygenated region. Conclusion: The timing of SBRT fractions should be considered together with the tumour oxygenation to avoid loss of TCP in SBRT.
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| 35. |
- Kjellsson Lindblom, Emely, et al.
(författare)
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Radiation-induced vascular damage and the impact on the treatment outcome of stereotactic body radiotherapy
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:6, s. 2721-2727
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The aim of this study was to investigate radiation-induced tumour vascular damage and its impact thereof on the outcome of stereotactic body radiotherapy (SBRT). Materials and Methods: Vessel densities in animal tumours before and after a single dose of 20 Gy were quantified and used as input for simulations of three-dimensional tumours with heterogeneous oxygenation. SBRT treatments of the modelled tumours in 1-8 fractions were simulated. The impact of vessel collapse on the outcome of SBRT was investigated by calculating tumour control probability (TCP) and the dose required to obtain a TCP of 50% (D50). Results: A radiation-induced increase of acute hypoxia in tumours during SBRT treatment could be simulated based on the experimental data. The D50 values for these tumours were higher than for the simulated tumours without vessel collapse. Conclusion: The vascular changes after high doses of radiation could compromise the outcome of SBRT by increasing tumour hypoxia.
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| 36. |
- Koyi, Hirsh, et al.
(författare)
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Co-localisation of Glandular and Squamous Cell Markers in Non-small Cell Lung Cancer
- 2018
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:6, s. 3341-3346
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Accurate classification of lung carcinomas is crucial for selecting appropriate and adequate chemotherapy treatment. In this study, glandular (adenocarcinoma), and squamous cell differentiation were examined in non-small cell lung carcinoma (NSCLC) without obvious light-microscopic signs of squamous and glandular differentiation. Materials and Methods: All lung tumours diagnosed as NSCLC (n=61), without obvious squamous or glandular features, were obtained by bronchial biopsy or core biopsy supported by computed tomography. They were diagnosed during 1996-2009, at the Department of Pathology, Gavle Hospital, Sweden. The tumours were examined immunohistochemically with antibodies against CK5/6, p63 (squamous cell markers) and carcinoembryonic antigen (CEA) (adenocarcinoma cell marker). Double immunostaining (p63/CEA) was also performed on individual tumours. Results: The tumours originated from 36 males and 25 females, aged 54-83 years. Pure squamous cell differentiation (CK5/6 positive only) occurred in 34.4% (n=21) tumours and pure adenocarcinoma cell differentiation (CEA positive only) was present in 14.9% (n=9). Tumours with both squamous and adenocarcinoma features (CK5/6 and CEA positive) were most prevalent (47.5%, n=29). Two tumours (3.3%) were negative with both stains (and also synaptophysin negative). Double immunostaining (p63/CEA) revealed that squamous and adenocarcinoma markers were co-localised in cells in certain tumours. Conclusion: Co-localisation of squamous and adenocarcinoma markers in the same tumour cell suggests that additional analyses for novel biomarkers of specific lung cancer types may subsequently lead to a refined treatment choice for patients with the goal of improving clinical outcomes.
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| 37. |
- Koyi, Hirsh, et al.
(författare)
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Non-small Cell Lung Cancer (NSCLC) in Octogenarians in Clinical Practice
- 2016
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 36:10, s. 5397-5402
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Globally, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice. Patients and Methods: This was a retrospective observational study of all elderly (>= 80 years) patients with NSCLC referred to the Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010, and followed until June, 2016. Results: In total, 452 patients, 216 (47.8%) men and 236 (52.2%) women, were included. The mean and median age was 83 years; 28 (6.2%) were aged 90 years or more. Current or former smokers constituted 91.1%, with men having smoked more (p<0.001). There was no difference in performance status (PS) between genders with PS 0-1 in 45.4%, PS 2 in 25.6% and PS3-4 in 29%. About a third each was diagnosed in stages 1-II, III and IV. Adenocarcinoma was most common (45.6%), 18.1% had squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. Best supportive care (BSC) was given only to 209 patients (46.2%). Potentially curative therapy was administered to 16.5% of men and 20.3% of the women with surgery performed in 35 patients (7.8%) and stereotactic body radiation therapy (SBRT) in 48 patients (10.6%). Chemotherapy was given to 51 patients (11.2%) and palliative radiotherapy to 77 (17.0%). Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth-line. Male patients who received chemotherapy survived a mean of 281 days and for female patients it was 332 days (not significant). Median overall survival (OS) was 115 days in patients receiving BSC and 362 days in patients given any therapy. Patients who underwent surgery for stage I-II had a median OS of 5.6 years compared to 3.5 years for patients given SBRT. Conclusion: Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.
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| 38. |
- Landström, Fredrik, 1966-, et al.
(författare)
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Electrochemotherapy : Evidence for Cell-type Selectivity In Vitro
- 2015
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:11, s. 5813-5820
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Electrochemotherapy (ECT) is a new cancer treatment modality that uses electroporation to potentiate chemotherapeutic agents, especially bleomycin. ECT causes both a direct toxic effect and an anti-vascular effect. The aim of the present study was to investigate a possible selective effect of ECT on the survival of fibroblasts, endothelial cells (HUVEC) and two squamous cell carcinoma cell lines (CAL-27 and SCC-4).Materials and Methods: Cells were electroporated using two bleomycin concentrations. The survival rate was assessed 1, 2, 3 and 4 days after treatment, by two different assays.Results: The survival rate of the fibroblasts was statistically significantly higher than the other cell lines at day 4. The HUVEC survival rate was statistically significantly lower than the other cell types at day 1 after electroporation-alone.Conclusion: A selective survival effect after ECT was observed in vitro, supporting the anti-vascular effect seen in vivo.
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| 39. |
- Lazzeroni, Marta, et al.
(författare)
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Impact of Tumour Cell Infiltration on Treatment Outcome in Gamma Knife Radiosurgery : A Modelling Study
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:4, s. 1675-1687
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-grade gliomas with a widespread infiltration beyond the lesion detectable on diagnostic images are increasingly treated with Gamma Knife (TM) Radiosurgery (GKRS). The aim of this study was to assess the cell infiltration impact on the GKRS outcome for invasive gliomas. Materials and Methods: Tumor cell distribution was predicted using a novel algorithm whose computations are iterated until they reach an agreement with histopathology results. Treatment plans with different combinations of dose prescription (20 Gy at 50%-20% isodose) and targets [Gross Tumour Volume (GTV), zone 1 with 100%-60% of the GTV cell density and zone 2 with 60%-0% of the GTV cell density] were evaluated using standard conformity indexes (CI) and radiobiological parameters. Results: Considerable differences in terms of tumor control probability were found between plans having similar CI but different targets. Conclusion: To account for tumor cell infiltration outside the target is of key importance in GKRS and a radiobiological evaluation should accompany well-established CI.
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| 40. |
- Leandersson, Pia, et al.
(författare)
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A Biomarker Panel Increases the Diagnostic Performance for Epithelial Ovarian Cancer Type I and II in Young Women
- 2016
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 36:3, s. 957-965
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: To assess preoperative blood levels of a biomarker panel in relation to the new classification system of epithelial ovarian cancer (EOC) type I and II. Patients and Methods: Preoperative plasma levels of B7-family protein homolog 4 (B7-H4), intact and cleaved soluble urokinase plasminogen activator receptor (suPAR), human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) were analyzed in 350 patients with adnexal lesions. Results: The levels of suPAR(II-III), HE4, CA125 were all higher in EOC II than in EOC I, borderline and benign ovarian tumors. B7-H4 was increased in EOC II compared with benign ovarian tumors. The combination of suPAR(II-III), HE4, CA125 and age in premenopausal women discriminates EOC and borderline tumors from benign tumors to higher accuracy compared to the Risk of Ovarian Malignancy Algorithm (p=0.007). Conclusion: The biomarker panel suPAR(II-III), HE4, CA125 and age in premenopausal women improved discrimination of malignant and benign ovarian tumors. The plasma levels of B7-H4 were increased in patients with EOC II compared to those with benign ovarian tumors.
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| 41. |
- Leandersson, Pia, et al.
(författare)
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Ovarian Cancer Surgery : a Population-based Registry Study
- 2017
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 37:4, s. 1837-1845
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: To evaluate ovarian cancer surgery in tertiary centers (TC) and regional hospitals (RH). Patients and Methods: Data from the GynOp registry on patients undergoing surgery for ovarian cancer or borderline tumor from 2013 to 2015 were analyzed. Results: Four TC and 21 RH reported 1,108 cases of surgery with curative intent, 770 cases (69.5%) in TC and 338 cases (30.5%) in RH. Out of 458 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV disease 396 (86.5%) had surgery in TC. We found differences in selection for primary debulking surgery (PDS) (45% to 93%, p<0.001) and PDS achieving no residual tumor (36% to 70%, p<0.001) between the four TC. Major complications, re-admissions and re-operation rates did not differ between TC and RH. Conclusion: Tertiary centers perform more extensive surgery compared to regional hospitals without increased frequency of major complications. Tertiary centers display significant differences among patient selection for PDS, as well as achieving no residual tumor.
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| 42. |
- Lewin, Nongnit, et al.
(författare)
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The Influence of Adjuvant Radiotherapy and Single Nucleotide Polymorphisms on Circulating Immune Response Cell Numbers and Phenotypes of Patients With Breast Cancer
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:9, s. 4957-4963
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. Materials and Methods: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. Results: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. Conclusion: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.
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| 43. |
- Lewin, Nongnit, et al.
(författare)
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The Influence of Single Nucleotide Polymorphisms and Adjuvant Radiotherapy on Systemic Inflammatory Proteins, Chemokines and Cytokines of Patients With Breast Cancer
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:3, s. 1287-1292
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Tidskriftsartikel (refereegranskat)abstract
- Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. Materials and Methods: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. Results: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. Conclusion: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.
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| 44. |
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| 45. |
- Lundberg, Ida, et al.
(författare)
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MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers
- 2018
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:2, s. 677-683
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS-and BRAF-mutated CRCs.Materials and Methods: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.Results: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.Conclusion: Our results suggest that KRAS and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS-and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.
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| 46. |
- Lundin, Erik, 1970-, et al.
(författare)
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Validation of a Clinical Cancer Register at the Head and Neck Oncology Center in Orebro
- 2019
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 39:1, s. 285-289
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Tidskriftsartikel (refereegranskat)abstract
- Background: This was a validation study of a regional register of oral cancer in Örebro, Sweden. The purpose was to assess the rate of errors in baseline, and treatment, and the completeness and accuracy of data on recurrences.Materials and Methods: A total of 653 cases with squamous cell cancer in the oral cavity were identified from the register. A randomized sample of 73 (11%) was selected, and a set of relevant data was compared to medical records.Results: Data on patient and tumour characteristics showed high accuracy, with 98% correct data and more than 99% of treatment data were correct. Follow-up data had a higher rate of errors, with 23% of recurrences not recorded, 13.6% misclassified, and 9.1% of cases showing errors in timing of the recurrence.Conclusion: data concerning patients, tumour status, and treatment in the Regional Head and Neck Register in Örebro are highly accurate. However, the follow-up data contain a higher rate of errors, that must be taken into consideration when evaluating outcome after treatment.
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| 47. |
- Marikkannu, Rajeshwari, et al.
(författare)
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Whole-genome Linkage Analysis and Sequence Analysis of Candidate Loci in Familial Breast Cancer
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:6, s. 3155-3165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Known breast cancer-predisposing genes account for fewer than 25% of all familial breast cancer cases and further studies are required to find the remaining high-and moderate-risk genes. We set-out to couple linkage analysis using microsatellite marker data and sequence analysis of linked regions in 13 non-BRCA1/2 families in order to find novel susceptibility loci and high-penetrant genes. Materials and Methods: Genotyping with 540 fluorescently-labeled microsatellite markers located on the 23 chromosomes at 7.25 cM resolution was used for primary linkage analysis and an additional 40 markers were used for fine-mapping of loci with a logarithm of odds (LOD) or heterogeneity LOD (HLOD) score greater than one. Whole-exome sequencing data of 28 members from all 13 families were used for the bioinformatics sequence analysis on the linked regions of these families. Results: Linkage analysis identified three loci on chromosome 18q as a putative region of interest (overall LOD=1, HLOD=1.2). Sequencing analysis of the three linked regions on 18q and mutation prediction algorithms did reveal three probable damaging variants. Conclusion: Overall, our study identified three weakly linked loci on 18q and three probable damaging variants of interest in the 13 families with breast cancer.
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| 48. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Estimation of Risk of Normal-tissue Toxicity Following Gastric Cancer Radiotherapy with Photon- or Scanned Proton-beams
- 2018
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:5, s. 2619-2625
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Gastric cancer (GC) radiotherapy involves irradiation of large tumour volumes located in the proximities of critical structures. The advantageous dose distributions produced by scanned-proton beams could reduce the irradiated volumes of the organs at risk (OARs). However, treatment-induced side-effects may still appear. The aim of this study was to estimate the normal tissue complication probability (NTCP) following proton therapy of GC, compared to photon radiotherapy. Patients and Methods: Eight GC patients, previously treated with volumetric-modulated arc therapy (VMAT), were retrospectively planned with scanned proton beams carried out with the single-field uniform-dose (SFUD) method. A beam-specific planning target volume was used for spot positioning and a clinical target volume (CTV) based robust optimisation was performed considering setup- and range-uncertainties. The dosimetric and NTCP values obtained with the VMAT and SFUD plans were compared. Results: With SFUD, lower or similar dose-volume values were obtained for OARs, compared to VMAT. NTCP values of 0% were determined with the VMAT and SFUD plans for all OARs (p>0.05), except for the left kidney (p<0.05), for which lower toxicity was estimated with SFUD. Conclusion: The NTCP reduction, determined for the left kidney with SFUD, can be of clinical relevance for preserving renal function after radiotherapy of GC.
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| 49. |
- Månsson, Christopher, Läkarexamen, 1977-, et al.
(författare)
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Percutaneous Irreversible Electroporation as First Line Treatment of Locally Advanced Pancreatic Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:5, s. 2509-2512
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim:Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy. The secondary aim was to examine the complication rates.Patients and Methods:Twenty-four patients with LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison.Results:The median survival after diagnosis was 13.3 months in the IRE group compared to 9.9 months in the registry group (p=0.511). Six patients had a severe complication after IRE treatment.Conclusion:No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting.
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| 50. |
- Månsson, Christopher, Läkarexamen, 1977-, et al.
(författare)
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The Value of CA19-9 After Irreversible Electroporation for Pancreatic Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:11, s. 6193-6196
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim:Carbohydrate antigen 19-9 (CA19-9) is a tumor marker for pancreatic cancer. Irreversible electroporation (IRE) is an experimental treatment modality for pancreatic cancer. The aim of this study was to evaluate whether percutaneous IRE lowers the CA19-9 level in pancreatic cancer and whether this correlates with improved overall survival.Patients and Methods:Seventy-one patients with locally advanced pancreatic cancer or local recurrence after resection were treated. Patients with missing data, metastatic disease and normal serum CA19-9 before IRE were excluded. This left 35 cases for analysis.Results:The median CA19-9 did not decrease in the cohort after IRE treatment (282 U/ml before versus 315 U/ml after; p=0.80). The 25th percentile of patients with the best CA19-9 response had improved overall survival compared to the 25th percentile with the worst response (mean 13.1 versus 8.1 months, respectively; p=0.01).Conclusion:IRE did not lower the level of CA19-9 in pancreatic cancer cases. However, a response in CA19-9 was correlated with improved survival.
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