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  • Engström, Wilhelm (författare)
  • The RECK Gene and Biological Malignancy-Its Significance in Angiogenesis and Inhibition of Matrix Metalloproteinases
  • 2014
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 34, s. 3867-3873
  • Forskningsöversikt (refereegranskat)abstract
    • The RECK (reversion-inducing cysteine-rich protein with Kazal motifs) gene is a relatively newly discovered gene with important implications in cancer biology. RECK is normally expressed in all cells of the body and has an important role in the balance between destructive and constructive features of the extracellular matrix (ECM). The RECK protein is a membrane-bound glycoprotein that inhibits matrix metalloproteinases with the function of breaking-down the ECM. There is a significant correlation between RECK gene expression and the formation of new vessels, presumably via the mediation of vascular endothelial growth factor (VEGF), which is an important and powerful inducer of angiogenesis.. Research has shown that down-regulation of RECK is caused by the rat sarcoma oncogene (RAS), which is also a common cause of tumor development in the early stages. For a tumor to progress and gain characteristics that classifies it as malignant, the degradation of the ECM and mobilization of new blood vessels are essential functions. If the tumor is inhibited with respect to these functions, it will cease to grow. RECK is, therefore, a potential tumor inhibitor but also a prognostic marker available at early clinical stages.
  • Eriksson, David, et al. (författare)
  • Apoptotic signalling in HeLa Hep2 cells following 5 Gy of cobalt-60 gamma radiation
  • 2009
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:11, s. 4361-4366
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The apoptotic signalling pathways involved in the delayed type of apoptosis occurring in HeLa Hep2 cells following radiation were investigated. MATERIALS AND METHODS: HeLa Hep2 cells were exposed to 5 Gy of cobalt-60 radiation. The activation of caspase-2, caspase-8, caspase-9 and effector caspase-3 was investigated by caspase assay plates and Western blots. Cleavage of poly (ADP-ribose) polymerase (PARP) was analysed on Western blots. HeLa Hep2 cells were irradiated with or without preincubation with inhibitors of protein synthesis (cycloheximide, CHX) and caspases, followed by TUNEL staining and caspase assay plate evaluation. RESULTS: Initiator caspases-2, -8, -9, and effector caspase-3, were found to be activated and PARP cleaved following irradiation. CHX completely inhibited the caspase activation and the associated apoptosis. Pretreatment with caspase-2 inhibitor indicated that caspase-2 was involved in the execution of the apoptosis. CONCLUSION: Activation of the apoptotic signalling pathways following irradiation of HeLa Hep2 cells includes components from the intrinsic as well as the extrinsic pathways and seems to require de novo protein synthesis.
  • Eriksson, Mathilda, et al. (författare)
  • Utilization of a right-handed coiled-coil protein from archaebacterium Staphylothermus marinus as a carrier for cisplatin
  • 2009
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:1, s. 11-18
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The nano-sized right-handed coiled-coil (RHCC) protein, originating from the archaebacterium Staphylothermus marinus, is stable at high salt concentrations, high temperatures, high pressures and extremes of pH. Its crystal structure reveals four hydrophobic cavities which can incorporate heavy metals. Nano-sized compounds have been used to carry cytotoxic drugs to tumours, avoiding delivery to healthy tissue, in part due to enhanced permeability in tumour blood vessels (enhanced permeability and retention effect). MATERIALS AND METHODS: The ability of RHCC to carry the platinum-containing chemotherapeutic drug cisplatin to cells, while retaining the cytotoxic potential was tested both in vitro and in vivo. RESULTS: RHCC was able to bind and enter cells in vitro and was not severely toxic or immunogenic in mice. Moreover, RHCC incorporated cisplatin, without inhibiting the cytotoxic potential of the drug against tumour cell lines in vitro or in vivo. CONCLUSION: RHCC can be used as a carrier of cisplatin without abrogating the effect of the drug.
  • Evertsson, Sofia, 1972-, et al. (författare)
  • Microsatellite instability and MBD4 mutation in unselected colorectal cancer
  • 2003
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 23:4, s. 3569-3574
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We investigated the prognostic significance of microsatellite instability (MSI) and the association with clinicopathological factors in colorectal cancer, and further identified MBD4 mutations and their clinicopathological significance.PATIENTS AND METHODS: MSI was analyzed in 201 colorectal cancers. Sequencing analysis of MBD4 was performed in 26 MSI and 28 microsatellite stable (MSS) tumors.RESULTS: Twenty-seven tumors (13.4%) were MSI but did not correlate with improved survival. MSI was significantly correlated with proximal colon tumors (p < 0.001), poor differentiation or mucinous type (p = 0.005) and multiple tumors (p = 0.04). MBD4 mutations were found in 15% MSI but not in MSS tumors. The mutated cases showed female overrepresentation, proximal site and poorly-differentiated/mucinous type.CONCLUSION: MSI was not correlated with survival, but shared other features associated with MSI in colorectal cancer as demonstrated by others. The clinicopathological variables associated with the MBD4 mutations were probably the reflection of MSI features.
  • Falk Delgado, Alberto, et al. (författare)
  • Complete Lymph Node Dissection in Melanoma : A Systematic Review and Meta-Analysis
  • 2017
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:12, s. 6825-6829
  • 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.
  • Falk Delgado, Alberto, et al. (författare)
  • Inconsistent Reporting Between Meta-analysis Protocol and Publication – A Cross-Sectional Study
  • 2017
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:9, s. 5101-5107
  • 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.
  • Falk, Magnus (författare)
  • Self-estimation or Phototest Measurement of Skin UV Sensitivity and its Association with Peoples Attitudes Towards Sun Exposure
  • 2014
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 34:2, s. 797-803
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Fitzpatrick's classification is the most common way of assessing skin UV sensitivity. The study aim was to investigate how self-estimated and actual UV sensitivity, as measured by phototest, are associated with attitudes towards sunbathing and the propensity to increase sun protection, as well as the correlation between self-estimated and actual UV sensitivity.PATIENTS AND METHODS:A total of 166 primary healthcare patients filled-out a questionnaire investigating attitudes towards sunbathing and the propensity to increase sun protection. They reported their skin type according to Fitzpatrick, and a UV sensitivity phototest was performed.RESULTS:Self-rated low UV sensitivity (skin type III-VI) was associated with a more positive attitude towards sunbathing and a lower propensity to increase sun protection, compared to high UV sensitivity. The correlation between the two methods was weak.CONCLUSION:The findings might indicate that individuals with a perceived low but in reality high UV sensitivity do not seek adequate sun protection with regard to skin cancer risk. Furthermore, the poor correlation between self-reported and actual UV sensitivity, measured by phototest, makes the clinical use of Fitzpatrick's classification questionable.
  • Falk, Magnus, et al. (författare)
  • Sun Exposure Habits and Health Risk-related Behaviours Among Individuals with Previous History of Skin Cancer
  • 2013
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 33:2, s. 631-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The aim of the present study was to investigate possible associations between UV exposure and other health risk behaviours in different social environments and in regard to previous history of skin cancer. Patients and Methods: In two closely-located, equally-sized cities in Sweden, representing different social environments (blue collar and white collar), patients aged 55-69 years, diagnosed with skin cancer (study group, n=489) or seborrhoeic keratosis (control group, n=664), were identified through a regional Health Care Register, and were given a questionnaire mapping for sun habits, tobacco smoking, alcohol use, and physical activity. Results: A previous history of skin cancer was associated with reduced UV exposure (pandlt;0.01) and increased UV protection (pandlt;0.00.1), higher alcohol consumption (pandlt;0.05), and higher level of physical activity (pandlt;0.05). Smoking was more common among subjects frequently sunbathing and rarely using sunscreen, but frequent sunbathing was positively associated with physical activity (pandlt;0.05). Daily smoking and risky drinking habits were more common in the blue collar social environment, while no differences were seen for sun habits in this respect. Conclusion: A previous history of skin cancer appears to promote increased UV protection. In contrast to alcohol/smoking habits, no association between social environment and sun habits was found.
  • Flejmer, Anna M., et al. (författare)
  • Analytical Anisotropic Algorithm versus Pencil Beam Convolution for treatment planning of breast cancer: implications for target coverage and radiation burden of normal tissue
  • 2015
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2841-2848
  • 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.
  • Flejmer, Anna M., et al. (författare)
  • Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations
  • 2014
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:7, s. 3563-3568
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The project studied the implications of using the irregular surface compensator (ISC) technique in comparison to three-dimensional conformal radiation therapy (3D-CRT) for breast cancer treatment. ISC is an electronic compensation algorithm that modulates the fluence across the radiation fields to compensate for irregularly shaped surfaces and deliver a homogeneous dose to a compensation plane. Methods: Ten breast cancer patients (five left- and five right-sided) were planned with both techniques. The planning was done for 50 Gy in 25 fractions with 2 Gy per fraction in all patients. Physical parameters such as doses to the clinical target volume (CTV-T) and the planned target volume (PTV), heterogeneity index and doses to lung and heart were determined and compared for the treatment plans. Results: The ISC technique led to significantly better coverage of the CTV-T and PTV in almost all patients with statistically significant better homogeneity of the dose distribution. The contralateral lung and the heart receive the same doses with both ISC and 3D-CRT plans. However, ISC showed a trend towards decreasing the volumes of the ipsilateral lung irradiated with high doses. Consequently this led to better compliance with the national recommendations for breast radiotherapy. Conclusion: The ISC technique leads to an improvement of the target coverage and the radiation burden of the ipsilateral lung thus allowing better compliance with the national recommendations and increasing the potential for improved quality of life for breast cancer patients. It should therefore be preferred over 3D-CRT for breast cases with difficult dose homogeneity to the PTV or CTV-T.
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