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1.	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.
2.	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.
3.	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.
4.	Boren, Thomas (författare) HELICOBACTER PYLORI; MULTITALENTED ADAPTATION OF BINDING PROPERTIES 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:10, s. 5840-5841 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	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.
6.	Carlsson, Jorgen (författare) Imaging ff HER2-Expression in Breast Cancer Metastases (Review) 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:10, s. 5855-5855 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
7.	Dasu, Alexandru, et al. (författare) The Potential Benefit of Scanned Proton Beam Versus Intensity Modulated Photon Therapy as Adjuvant Radiation Therapy in Breast Cancer 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:10, s. 5873-5874 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
8.	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.
9.	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.
10.	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.
11.	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.
12.	Engström, Wilhelm, et al. (författare) Epigenic regulation of the IGF2/H19 locus 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 5895-5895 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
13.	Engström, Wilhelm, et al. (författare) The Halifax Project - An attempt to Assess the Carcinogenic Potential of Low Dose Exposures to Chemical Mixtures in the Environment 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 5894-5895 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
14.	Engström, Wilhelm (författare) The RECK Gene and Biological Malignancy-Its Significance in Angiogenesis and Inhibition of Matrix Metalloproteinases 2014 Ingår i: Anticancer Research. - 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.
15.	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.
16.	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.
17.	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.
18.	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. - 0250-7005 .- 1791-7530. ; 34:7, s. 3563-3568 Tidskriftsartikel (refereegranskat)
19.	Fowler, Jack F., et al. (författare) Is the α/β ratio for prostate tumours really low and does it vary with the level of risk at diagnosis? 2013 Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 33:3, s. 1009-1011 Tidskriftsartikel (refereegranskat)abstract Aim: To answer the questions: Is the α/β ratio (radiosensitivity to size of dose-per-fraction) really low enough to justify using a few large dose fractions instead of the traditional many small doses? Does this parameter vary with prognostic risk factors? Methods and Materials: Three large statistical overviews are critiqued, with results for 5,000, 6,000 and 14,000 patients with prostate carcinoma, respectively. Results: These major analyses agree in finding the average α/β ratio to be less than 2 Gy: 1.55, (95% confidence interval=0.46-4.52), 1.4 (0.9-2.2), and the third analysis 1.7 (1.4-2.2) by ASTRO and 1.6 (1.2-2.2) by Phoenix criteria. All agree that α/β values do not vary significantly with the low, intermediate, high and “all included” risk factors. Conclusion: The high sensitivity to dose-per-fraction is an intrinsic property of prostate carcinomas and this supports the use of hypofractionation to increase the therapeutic gain for these tumours with dose-volume modelling to reduce the risk of late complications in rectum and bladder.
20.	Fowler, JF, et al. (författare) Is the α/β ratio for prostate tumours really low and does it vary with the level of risk at diagnosis? 2013 Ingår i: Anticancer research. - 1791-7530 .- 0250-7005. ; 33:3, s. 1009-1011 Tidskriftsartikel (refereegranskat)
21.	Gonterol, P., et al. (författare) Prognostic Factors And Risk Groups In T1g3 Patients Initially Treated With Bcg : Results Of A Multicenter Retrospective Series In 1743 Patients 2013 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:5, s. 2260-2261 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
22.	Hakelius, Malin, et al. (författare) Keratinocytes and Head and Neck Squamous Cell Carcinoma Cells Regulate Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Fibroblasts 2013 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:8, s. 3113-3118 Tidskriftsartikel (refereegranskat)abstract Background: To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover. Materials and Methods: Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR). Results: The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1 alpha) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3. Conclusion: SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.
23.	Hassan, Saadia Bashir, et al. (författare) Alpha Terpineol : A Potential Anticancer Agent which Acts through Suppressing NF-kappa B Signalling 2010 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:6, s. 1911-1919 Tidskriftsartikel (refereegranskat)abstract Background: Alpha terpineol is a bioactive component of Salvia libanotica essential oil extract and has shown antitumour activity. Materials and Methods: The cytotoxicity of alpha terpineol towards different tumour cell lines was evaluated in vitro. Mechanistic characterization was performed using analysis of drug activity in a cell line panel and drug-induced gene expression perturbation using the connectivity map approach. Results: The small cell lung carcinoma was the cell line most sensitive to alpha terpineol. The results proposed alpha terpineol as an NF-kappa B inhibitor, which was confirmed by the observed dose-dependent inhibition of NF-kappa B translocation and activity using two NF-kappa B assays, and by the down-regulation of the expression of several NE-kappa B-related genes such as IL-1 beta and IL1R1. Conclusion: The results suggest that alpha terpineol inhibits the growth of tumour cells through a mechanism that involves inhibition of the NF-kappa B pathway.
24.	Hassan, Saadia Bashir, et al. (författare) The Nanoparticulate Quillaja Saponin BBE Is Selectively Active Towards Renal Cell Carcinoma 2013 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:1, s. 143-151 Tidskriftsartikel (refereegranskat)abstract Aim: To characterize the cytotoxic effect of BBE, the particulate of desacyl-saponin, in model systems of solid tumours. Materials and Methods: Cytotoxic activity of BBE was investigated in solid human tumour cell lines, in tumour cells from patients with renal cell carcinoma, in normal human renal cells and in peripheral blood mononuclear cells. The BBE mode of cell death was assessed in vitro. In vivo effect of BBE was evaluated in xenograft-bearing mice. Results: BBE was selectively active against renal cell carcinoma, with no or little effect on normal cells. BBE induced caspase activity and apoptosis. An inhibitory activity of BBE on xenograft tumour growth, with no apparent signs of haematological toxicity was shown. In the non-proliferative model of patient tumour cells, BBE was active on only 1/5 patient samples, suggesting association of BBE effect with cell proliferation. Conclusion: BBE has interesting activities against renal cell carcinoma and should be further explored as a drug against this resistant tumour type.
25.	Hedman, Mattias, et al. (författare) Fractionated Irradiation of Five Human Lung Cancer Cell Lines and Prediction of Survival According to a Radiobiology Model 2011 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:4, s. 1125-1130 Tidskriftsartikel (refereegranskat)abstract Background: This study evaluates a predictive radiobiology model by measurements of surviving fraction (SF) by the clonogenic assay or the extrapolation method and the proliferation rate in vitro. It is hypothesized that incorporating proliferation to intrinsic radiosensitivity, measured by SF, to predict radiation responsiveness after fractionated irradiation adds to the model's accuracy. Materials and Methods. Five lung cancer cell lines with known SF after 1 Gy (SF1), and also SF2 and SF5, were irradiated with three different fractionation regimes; 10x1 Gy, 5x2 Gy or 2x5 Gy during the same total time to achieve empirical SF. In addition, the SF1, SF2 and SF5 after fractionated irradiation was calculated for each cell line based on the already known single fraction SF and with or without a proliferation factor. The results were compared to the empirical data. Results and Discussion: By using the clonogenic assay to measure radiosensitivity, prediction of radiosensitivity was improved after fractionated radiotherapy when proliferation was used in the radiobiology model. However, this was not the case in the cell lines where the extrapolation method was used to calculate SF. Thus, a radiobiology model including intrinsic radiosensitivity, measured by the clonogenic assay, as well as proliferation, is better at predicting survival after fractionated radiotherapy, compared to the use of intrinsic radiosensitivity alone.
26.	Hellberg, Dan (författare) Sex Steroids and Cervical Cancer 2012 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3045-3054 Forskningsöversikt (refereegranskat)abstract During the 19th century, studies indicated that reproductive events were involved in cervical cancer. Human papillomavirus (HPV) infection is a prerequisite for development of cancer, but co-factors, among them the action of sexual steroid hormones, are necessary. Childbirth has been an important risk factor but now probably plays a minor role in the industrialized world, where parity is low. Longterm oral contraceptive use has been thoroughly studied epidemiologically, and correlates to cervical cancer in most studies. In vitro studies on cervical cell lines transfected with HPV and animal studies indicate that sex steroid hormones are capable to induce cancer. In in vivo cervical cancer tissue studies there have been observations that endogenous progesterone in serum correlates to a negative pattern of expression of cellular and extracellular proteins, tumor markers. Immune response could be another mechanism. Estradiol might be associated with a positive pattern and high estradiol and low progesterone levels increase duration of survival in cervical cancer. Studies where treatment of compounds that influence sex steroid hormones have been given are rare and have been disappointing.
27.	Hellberg, Dan, et al. (författare) Tumor Marker Score for Prognostication of Early-stage Squamous Cell Cervical Cancer 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:2, s. 887-892 Tidskriftsartikel (refereegranskat)abstract Background/Aim: Histopathological and clinical scores to predict prognosis in cervical cancer have been of limited value. In the present study a tumor marker expression score was evaluated for prognostication in early-stage cervical cancer. Materials and Methods: The entire study population included 128 women with invasive squamous cell cervical cancer followed-up for at least 10 years. Results: Expression of 12 tumor markers (epidermal growth factor receptor (EGFR), Ki-67, c-MYC, p53, p27, E-cadherin, CD44, vascular endothelial growth factor receptor (VEGF), cyclooxygenase-2 (COX2), CD4, and leucine-rich immunoglobulin-like repeats-1 (LRIG1) and LRIG2, considered relevant for cervical cancer prognostication was evaluated by immunohistochemistry. Expression of five markers, LRIG1, LRIG2, p53, COX2 and c-MYC were useful to make a prognostication score, ranging from 0 to 5. Score 0-1 correlated to less than 5% 10-year mortality, while the mortality rate of those with score 4-5 approached 70%; those with score 2 formed an intermediate group. Using different models, a high sensitivity, specificity, positive predictive value and negative predictive value was attained. Conclusion: Tumor marker scoring could be an adjunct to histopathological and clinical parameters in prognostication of early-stage cervical cancer.
28.	Hillbertz, Nicolette Salmon, et al. (författare) Viral and Molecular Aspects of Oral Cancer 2012 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:10, s. 4201-4212 Forskningsöversikt (refereegranskat)abstract Squamous cell carcinoma (SCC) is the most common epithelial malignancy in the oral cavity. SCCs and their variants constitute over 90% of oral malignancies, and the disease is associated with poor prognosis. OSCC is a complex malignancy where environmental factors, virus infections, and genetic alterations most likely interact, and thus give rise to the malignant condition. Herein, we review the available literature regarding high-risk factors such as alcohol and tobacco usage; discuss the roles of human papillomaviruses (HPV), the Epstein-Barr virus, and the human herpes simplex virus (HSV); and evaluate several candidate genes associated with the condition: p53, p16(INK4) and p21(WAF1/CIP1) survivin, B-cell lymphoma-2 (BCL-2), keratins, Fibroblast growth factor 3 (FGF3), FGF4, FGF19, Oral cancer overexpressed gene 1 (ORAOV1), and Cyclin D1 (CCND1).
29.	Hirsch, Jan-Michael, et al. (författare) Oral Cancer in Swedish Snuff Dippers 2012 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3327-3330 Tidskriftsartikel (refereegranskat)abstract Over recent decades there has been debate over whether or not Swedish snuff is carcinogenic in humans. Animal studies and molecular biological and experimental studies have shown the carcinogenic potential of Swedish snuff, but this has not been proved in prospective randomized studies. We present a case series of patients with oral squamous cell carcinomas diagnosed at the sites where the patients had used Swedish snuff for several years. Sixteen male patients were referred to and treated at Oral and Maxillofacial Surgery Departments and Ear, Nose and Throat clinics at seven different hospitals in Sweden. The mean age of the patients at the time of diagnosis was 72.9 years and the mean time of snuff use prior to cancer diagnosis was 42.9 years. This case series shows that Swedish snuff may not be a harmless alternative to smoking.
30.	Holgersson, Georg, et al. (författare) The value of induction chemotherapy for survival in patients with non-small cell lung cancer treated with radiotherapy. 2012 Ingår i: Anticancer research. - : The International Institute of Anticancer Research. - 1791-7530 .- 0250-7005. ; 32:4, s. 1339-46 Tidskriftsartikel (refereegranskat)abstract AIM: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (≥50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. RESULTS: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). CONCLUSION: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.
31.	Jagarlamudi, Kiran Kumar, et al. (författare) The new TK 201 ELISA provides prognostic information in patients with breast cancer 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 6808-6809 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
32.	Jalouli, Jamshid, et al. (författare) Human Papilloma Virus, Herpes Simplex Virus and Epstein Barr Virus in Oral Squamous Cell Carcinoma from Eight Different Countries 2012 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:2, s. 571-580 Tidskriftsartikel (refereegranskat)abstract Oral squamous cell carcinoma (OSCC) is a major health problem in many parts of the world, and the major causative agents are thought to he the use of alcohol and tobacco. Oncogenic viruses have also been suggested to be involved in OSCC development. This study investigated the prevalence of human papillomaviruses (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in 155 OSCC from eight different countries from different ethnic groups, continents and with different socioeconomic backgrounds. 41 A total of OSCCs were diagnosed in the tongue (26%) and 23 in the floor of the mouth (15%); the other 91 OSCCs were diagnosed in other locations (59%). The patients were also investigated regarding the use of alcohol and smoking and smokeless tobacco habits. Tissue samples were obtained from formalin-fixed, paraffin-embedded samples of the OSCC. DNA was extracted and the viral genome was examined by single, nested and seminested PCR assays. Sequencing of double-stranded DNA from the PCR product was carried out. Following sequencing of the HPV-, HSV- and EBV-positive PCR products, 100% homology between the sampels was found. Of all the 155 OSCCs examined, 85 (55%) were positive for EBV, 54 (35%) for HPV and 24 (15%) for HSV. The highest prevalence of HPV was seen in Sudan (65%), while HSV (55%) and EBV (80%) were most prevalent in the UK. In 34% (52/155) of all the samples examined, co-infection by two (46/155=30%) or three (6/155=4%) virus specimens was detected. The most frequent double infection was HPV with EBV in 21% (32/155) of all OSCCs. There was a statistically significant higher proportion of samples with HSV (p=0.026) and EBV (p=0.015) in industrialized countries (Sweden, Norway, UK and USA) as compared to developing countries (Sudan, India, Sri Lanka and Yemen). Furthermore, there was a statistically significant higher co-infection of HSV and EBV in samples from industrialized countries (p=0.00031). No firm conclusions could be drawn regarding the relationship between alcohol, tobacco and virus infections. The significance of our findings must be put in relation to other risk factors and these observations warrant further studies to determine the possible role of viral infections and co-infections with HPV, EBV and HSV as risk markers for the development of OSCC.
33.	Jalouli, Miranda M., et al. (författare) Differential Expression of Apoptosis, Cell Cycle Regulation and Intermediate Filament Genes in Oral Squamous Cell Carcinomas Associated with Toombak Use in Sudan 2011 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:10, s. 3345-3351 Tidskriftsartikel (refereegranskat)abstract Previously we used microarray genomic hybridization technology to explore genome-wide profiles of chromosomal aberrations in samples of oral squamous cell carcinomas (OSCCs) and paired normal controls. Based on these findings, 9 genes related to apoptosis, cell cycle regulation and intermediate filament proteins were selected and their differential expression status was examined by real-time quantitative RT-PCR in 26 samples of Sudanese OSCCs and their matched normal controls. The findings were correlated with the habit of toombak use. The mRNA levels of Bcl2, keratin 1, keratin 13 and p53 were significantly lower and the level of survivin was significantly higher in the OSCC samples of the toombak users compared to their paired control samples. A significant down-regulation in keratin I and keratin 13 expression levels was found in the OSCC samples of the non-toombak users compared to their normal control samples. The differential expression of genes related to apoptosis, cell cycle regulation and types I and II keratin could be useful diagnostic markers and provide valuable information for the understanding of oral malignancy in relation to toombak use.
34.	Johansson, Fredrik, et al. (författare) A Review of Dose-dense Temozolomide Alone and in Combination with Bevacizumab in Patients with First Relapse of Glioblastoma 2012 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:9, s. 4001-4006 Forskningsöversikt (refereegranskat)abstract Treatment of patients with glioblastoma improved dramatically when concomitant and adjuvant temozolomide was added to external radiation therapy. The addition of this new treatment schedule as well as the improvements in individually-tailored radiation treatment, has resulted in a larger proportion of patients being fit for further treatment after first relapse. One of the most interesting combinations that have started to become part of the therapeutic arsenal in the daily clinic is dose-dense temozolomide in combination with bevacizumab. We reviewed and compiled the literature concerning the present topic based on a search of the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) for the years between 1995 and 2011. The clinical studies that have been performed are small and divergent, making it difficult to grade the scientific evidence for the combinatorial treatment of dose-dense temozolomide and bevacizumab. However, the available studies and the experience we have at our departments suggest that this combination is of interest for glioblastoma patients experiencing first relapse. More randomized clinical trials are needed in order to establish the standard of treatment at first relapse in patients with glioblastoma.
35.	Jäwert, Fredrik, et al. (författare) Loss of 5-Hydroxymethylcytosine and TET2 in Oral Squamous Cell Carcinoma. 2013 Ingår i: Anticancer research. - 1791-7530 .- 0250-7005. ; 33:10, s. 4325-8 Tidskriftsartikel (refereegranskat)abstract Aim: Epigenetic modifications, such as DNA methylation, are considered important in the regulation of target genes in cancer development. 5-Hydroxymethylcytosine (5hmC) was recently discovered to be related to the process of malignant transformation. The influence of DNA methylation in oral squamous cell carcinomas (OSCC) is not fully-understood. Therefore, the aim of the present study was to investigate the DNA methylation pattern in OSCC compared to healthy oral epithelium.
36.	Kopparapu, Pradeep, et al. (författare) Expression of cyclin d1 and its association with disease characteristics in bladder cancer 2013 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:12, s. 5235-4252 Tidskriftsartikel (refereegranskat)abstract AIM: Invasive urothelial carcinoma of the bladder (UCB) is characterized by alterations in cell-cycle regulatory pathways. Defects in the expression of cyclin D1, a key cell-cycle regulator, have been implicated in progression of various types of cancer. In the present study, we investigated whether cyclin D1 expression is associated with clinicopathological parameters and whether it has any potential prognostic value in determining risk of UCB recurrence.PATIENTS AND METHODS: Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder tissues (n=131) were immunostained using an antibody against cyclin D1. The association between cyclin D1 and clinicopathological parameters including stage, lymph node metastasis, and disease-free survival, were evaluated. Cyclin D1 mRNA expression data from human normal bladder (n=14) and cancer specimens (n=28) were extracted from the public Oncomine database.RESULTS: Cyclin D1 mRNA and protein expression were significantly higher in UCB compared to adjacent non-malignant bladder tissue (for mRNA p=0.003, for protein p=0.001). Cyclin D1 protein expression was significantly higher in non-invasive tumors than in muscle-invasive UCB (p=0.016). Among patients with muscle-invasive UCB, increased cyclin D1 expression in tumor cells significantly correlated with lymph node metastasis (p<0.001), and there was a trend of cyclin D1 together with lymph node positivity to be associated with disease recurrence (p=0.678). Loss of nuclear cyclin D1 expression in tumor cells was likewise significantly associated with the presence of lymph node metastasis (p<0.001).CONCLUSION: Altered expression of cyclin D1 is associated with lymph node metastasis and risk of UCB recurrence. Cyclin D1 expression may therefore have clinical value as a prognostic marker and potential therapeutic target.
37.	Kopparapu, Pradeep Kumar, et al. (författare) Expression and localization of serotonin receptors in human breast cancer 2013 Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:2, s. 363-370 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to examine the expression of serotonin receptors in patients with breast cancer and to explore their utility as diagnostic and prognostic markers. Immunohistochemical analysis was performed to examine the expression of serotonin (5-HT) receptor subtypes 1A, 1B, 2B and 4 in a tissue microarray containing tumor specimens from 102 patients. Statistical analysis was performed to correlate the expression of these proteins with regard to clinical parameters. We found that all four serotonin receptors (5-HTRs) exhibited different expression patterns in breast cancer specimens. In general strong staining for 5-HTR1A was observed on the membrane of cancer cells but it was detected only in the cytoplasm of non-malignant cells. 5-HTR1B and 5-HTR2B were predominantly expressed in the cytoplasm of breast cancer cells, while 5-HTR4 was exclusively found in the nucleus of malignant and non-malignant cells. Correlation analysis revealed a significant correlation of 5-HTR2B with estrogen receptor-α (ER-α) and 5-HTR4 with ER-α and progesterone (PR). In conclusion, the different expression patterns and subcellular localization of 5-HTRs in breast cancer may reflect their role in breast cancer progression.
38.	Kopparapu, Pradeep Kumar, et al. (författare) Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer 2013 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:6, s. 2381-2390 Tidskriftsartikel (refereegranskat)abstract AIM: Vascular endothelial growth factor (VEGF) signaling is frequently altered in invasive tumor cells and is associated with patient outcome. In the present study, we examined VEGF, VEGFR1, and VEGFR2 expression in non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), and evaluated the association between VEGF and its receptors with disease characteristics and bladder cancer recurrence.MATERIALS AND METHODS: Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder mucosa (n=131) were immunostained using antibodies against VEGF, VEGFR1, and VEGFR2. The association between the expression of these proteins and clinical parameters including stage, lymph node metastasis, and recurrence-free survival were statistically evaluated. VEGF mRNA expression data were extracted from the public Oncomine database.RESULTS: VEGF and VEGFR1 mRNA levels were significantly higher in bladder cancer specimens than that of normal mucosa (for VEGF, p<0.001; for VEGFR1, p=0.02). Analysis of their expression at protein levels showed that levels of VEGF and VEGFR1 were significantly higher in NMIBC than in MIBC (p<0.001), while that of VEGFR2 was significantly higher in all cancer specimens compared to benign urothelial mucosa (p=0.001). Further-more, the expression of VEGFR2 was significantly higher in MIBC, as compared to NMIBC (p<0.001). Patients with higher levels of VEGF, VEGFR1, and VEGFR2 tended to have poorer recurrence-free survival than those with lower levels, but this was not statistically significant.CONCLUSION: Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.
39.	Larsson, Dhana E., et al. (författare) The Cytotoxic Agents NSC-95397, Brefeldin A, Bortezomib and Sanguinarine Induce Apoptosis in Neuroendocrine Tumors In Vitro 2010 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:1, s. 149-156 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate the apoptosis resulting from NSC 95397, brefeldin A, bortezomib and sanguinarine in neuroendocrine tumor cell lines. Materials and Methods: A multiparametric high-content screening assay for measurement of apoptosis was used. The human pancreatic carcinoid cell line, BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were tested. After incubation with cytotoxic drugs, the DNA-binding dye Hoechst 33342, fluorescein-tagged probes that covalently bind active caspase-3 and chloromethyl-X-rosamine to detect mitochondrial membrane potential were added. Image acquisition and quantitative measurement of fluorescence was performed using automated image capture and analysis instrument ArrayScan. In addition, nuclear morphology was examined on microscopic slides stained with May-Grunewald-Giemsa. Results: A time- and dose-dependent activation of caspase-3 and increase in nuclear fragmentation and condensation were observed for the drugs using a multiparametric apoptosis assay. These results were confirmed with nuclear morphological examination on microscopic slides. Conclusion: NSC 95397, brefeldin A, bortezomib and sanguinarine induced caspase-3 activation with modest changes in nuclear morphology.
40.	Larsson, Lena, 1969, et al. (författare) Expression of High Mobility Group A proteins in oral leukoplakia 2013 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:10, s. 4261-4266 Tidskriftsartikel (refereegranskat)abstract Background: Oral leukoplakia (LPL) is considered a potentially malignant disorder in the oral cavity and the gastric tract. The high mobility group A (HMGA) proteins are important in the transformation of normal cells into cancer cells, but there is a lack of knowledge about their importance in development of oral cancer. The aim of the current project was to investigate HMGA expression in LPLs with different levels of dysplasia. Materials and Methods: Biopsies were histologically processed to visualize the expression of HMGA1 and HMGA2 using immunohistochemistry. Results: An increase of HMGA1-positive cells correlating to the degree of dysplasia was registered in the epithelium and in the connective tissue. HMGA2 expression was seen in the epithelium and in the connective tissue but with no obvious correlation to the level of dysplasia. Conclusion: This is, to our knowledge, the first study showing the expression of HMGA proteins in healthy and non-healthy oral mucosa.
41.	Laytragoon-Lewin, Nongnit, et al. (författare) Direct Effects of Pure Nicotine, Cigarette Smoke Extract, Swedish-type Smokeless Tobacco (Snus) Extract and Ethanol on Human Normal Endothelial Cells and Fibroblasts 2011 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:5, s. 1527-1534 Tidskriftsartikel (refereegranskat)abstract The adverse health effects of cigarette smoking are well established including the increased risk of various types of cancer. In this study, the direct effects of ethanol, pure nicotine, cigarette smoke extract and Swedish type smokeless tobacco (Snus) extract on normal cells were investigated. Materials and Methods: Primary normal adult human endothelial cells and fibroblasts at early passage were used. Upon exposure to pure nicotine, cigarette smoke extract, Snus extract and ethanol, these cells were assessed for DNA synthesis, gene expression profile and cellular morphology. Results: Normal human fibroblasts and endothelial cells have unique gene expression profiles. The effects of treatment with ethanol and nicotine from different sources was more prominent in endothelial cells than fibroblasts. The combination of alterated gene expressions and strongly inhibited DNA synthesis was only detected in cells exposed to smoke extract. In the presence and absence of ethanol, pure nicotine and Snus extract induced abnormalities in the cytoplasm without any significant degree of cell death. With similar doses of nicotine and ethanol, the additional components in smoke extract had a dominant effect. The smoke extract induced vast cellular abnormalities and massive cell death. Conclusion: Cigarette smoke induced massive cell death and various abnormalities at cellular and molecular levels in surviving endothelial cells and fibroblasts. The combination of genomic alterations and the chronic inflammatory microenvironment induced from massive cell death, will potentially promote tumourigenesis and various diseases in cigarette smokers.
42.	Laytragoon-Lewin, Nongnit, et al. (författare) DNA Content and Methylation of p16, DAPK and RASSF1A Gene in Tumour and Distant, Normal Mucosal Tissue of Head and Neck Squamous Cell Carcinoma Patients 2010 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:11, s. 4643-4648 Tidskriftsartikel (refereegranskat)abstract Long-term survival of head and neck squamous cell carcinoma (HNSCC) patients has not improved significantly during the last 20 years and recurrent disease is frequently observed. In this study, the potential presence of pre-malignant cells or rare malignant cells at the time of diagnosis in HNSCC was investigated. Patients and Methods: Fifty-nine biopsies obtained from 41 HNSCC patients were analysed. Eighteen of these biopsies were normal mucosal tissue, located at least 5 cm from the tumour margin. DNA content and DNA methylation of p16, DAPK and RASSF1A was examined. Results: Thirty-nine out of 41 (95%) tumour biopsies showed p16 methylation and 21 (51%) of them displayed aneuploidy. Of 18 distant normal mucosal biopsies, 6 (33%) of these showed evidence of aneuploidy and 15(83%) of them showed methylated p16 genes. Among paired samples, the highest frequencies of DNA methylation were found in tumours with aneuploidy. Regardless of DNA content, methylation at DAPK, RASSF1A or p16 were found in the corresponding distant mucosal biopsies. Conclusion: The cells with abnormal DNA content or DNA methylation in mucosal tissue were not detected clinically or by pathological macroscopic and microscopic examination. Thus, distant mucosal tissue DNA content and DNA methylation analyses in combination with histopathology will provide a better prognostic base for the evaluation and treatment of HNSCC patients.
43.	Lindahl, Bengt, et al. (författare) Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma 2010 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:9, s. 3727-3730 Tidskriftsartikel (refereegranskat)abstract Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously.
44.	Lindahl, Bengt, et al. (författare) Relapse of Endometrial Carcinoma : Follow-up of 272 Patients with Relapse 2012 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3391-3395 Tidskriftsartikel (refereegranskat)abstract A total of 2090 patients with endometrial carcinoma were followed-up for at least five years. The treatment modalities, as well as the results of treatment, regarding 272 patients with disease relapse are presented. The results are not encouraging. We found no statistically significant difference regarding overall survival, when the patients were divided according to initial stage or ploidy status. There was also no significant difference between overall survival and the mode of treatment. 108 out of 272 patients with relapse died of their disease. Regarding patients in stage I-II we present the survival for every studied year, where we compared those with more than one site of metastasis (n=108), more than one metastasis (n=59), or no relapse at all (n=1289) with an age-corrected Swedish female population. We found that the vast majority of patients did not die from their cancer-related illnesses, and also found an increased death-rate among those with cancer without relapse, compared to those without cancer (20% compared to 14%, 5 year follow-up). We conclude that the majority of patients would benefit from an increased effort to cure other illnesses rather than concentrating on cancer treatment alone.
45.	Lindgren, Theres, et al. (författare) Alterations in Gene Expression During Radiation-Induced Mitotic Catastrophe in He La Hep2 Cells 2014 Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 34:8, s. 3875-3880 Tidskriftsartikel (refereegranskat)abstract Aim: To explore kinetic changes in the gene expression profile during radiation-induced mitotic catastrophes. Materials and Methods: Gene expression changes were measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of ionizing radiation (Co-60). Signaling pathways were explored and correlated to the biological responses linked to mitotic catastrophe. Results: Following irradiation a transient G(2)-arrest was induced. Anaphase bridge formation and centrosome hyperamplification was observed. These phenotypical changes correlated well with the observed gene expression changes. Genes with altered expression were found to be involved in mitotic processes as well as G(2)- and spindle assembly checkpoints. Also centrosome-associated genes displayed an increased expression. Conclusion: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be correlated to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies modulating these alterations might potentiate future therapy and enhance tumor cell killing.
46.	Lindquist, David, et al. (författare) Intense CD44 expression is a negative prognostic factor in tonsillar and base of tongue cancer 2012 Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:1, s. 153-161 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Patients with tonsillar and base of tongue cancer, which are human papillomavirus (HPV) positive, have a better clinical outcome than those with HPV-negative tumors. The identification of additional predictive markers for response to therapy could still be of great use.MATERIALS AND METHODS: Tumor markers CD44, p16, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, cyclooxygenase-2 (COX 2), Ki-67, and p27 were analyzed by immunochemistry, and HPV status was tested by polymerase chain reaction (PCR) in tumors from 73 patients and correlated to survival.RESULTS: High intensity CD44 staining (p=0.006) and high EGFR expression (p=0.026) were indicators of poor prognosis, while high p16 expression (p=0.021) and younger age (p=0.002) were positive prognostic markers for disease-specific survival. Furthermore, staining of CD44 (p=0.026) and age (p=0.002) were shown to be strong prognostic markers in multivariate analysis, which should be evaluated further for possible use in clinical practice.
47.	Lunde, Mai Lill Suhr, et al. (författare) Gene expression analysis by cDNA microarray in oral cancers from two Western populations 2010 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:4, s. 1083-1091 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In this work, gene expression profile was examined in 19 cases of oral cancer (OC) obtained from patients from Sweden (n=8) and UK (n=11) and the findings were tested for correlation to patient's clinicopathological data. MATERIALS AND METHODS: Following total RNA extraction, cDNA synthesis, labeling with fluorescent dyes and hybridization to the 21 k human oligonucleotide microarrays, slides were scanned and images were subjected to Genepix and J-Express analysis. Results for selected genes were validated by quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). RESULTS: 42 genes were identified as being differentially expressed. These included 39 genes of known functions (such as fatty acid synthase (FASN), 5' nucleotidase, ecto (NT5E), high mobility group AT-hook (HMGA1), and v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS)) and 3 novel genes; 26 (67%) of the 39 genes with known functions were previously reported in oral/head and neck tumors examined from other populations. Hierarchical clustering of the samples using the 42 genes demonstrated that samples mainly clustered in the same population. CONCLUSION: These results illustrate that microarrays can be used to identify distinct patterns of gene expression in different populations, but with no direct association to clinicopathological parameters. The fact that 67% of the 39 genes with known functions found in this work were previously reported in oral/head and neck tumors from other populations provides clear evidence that development of these tumors follows the same biological pathways irrespective of the source of the samples used.
48.	Miftakhova, Regina, et al. (författare) DNA Methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome translocation 2012 Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:11, s. 4715-4722 Tidskriftsartikel (refereegranskat)abstract Abstract A deficient retinoic acid signaling has been suggested to be an important cause of the clinical inefficacy of all-trans retinoic acid (ATRA) therapy in non-promyelocytic (non-PML) forms of acute myeloid leukemia (AML). The general aim of the present work was to explore novel ways to take advantage of the anti-leukemic potential of ATRA, and, specifically, to search for a synergism between ATRA and epigenetic drugs. Because previous reports have found no major influence of ATRA on DNA methylation, we investigated whether ATRA-mediated differentiation of the U937 and HL-60 AML cell lines, both lacking a PML-retinoic acid receptor (RAR) fusion product, is accompanied by early-appearing and weak changes in CpG methylation. We report that in HL-60 cells, by using a highly quantitative analysis of a set of genes found to be abnormally expressed in AML, polymerase chain reaction (PCR)-amplified p16 gene promoter molecules (each with 15 CpG sites), exhibited a CpG methylation level of 0-4% in untreated cells, which increased to 4-21% after treatment with ATRA for seven days. In contrast to HL-60 cells, U937 cells exhibited a very high CpG methylation level in p16, and ATRA did not influence the promoter methylation of this gene. In the total CCGG sites of the genome, analysed using a methylation-sensitive restriction enzyme, CpG methylation was significantly lower in ATRA-treated HL-60 (p<0.01) and U937 cells (p<0.05) than in controls. Taken together, our findings show that ATRA can influence DNA methylation, and suggest that future research should investigate whether epigenetic modulation may evoke a clinical effect of ATRA in leukemia.
49.	Mohanty, Chitralekha, et al. (författare) Predicting the sensitivity to ion therapy based on the response to photon irradiation - experimental evidence and mathematical modelling 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:6, s. 2801-2806 Tidskriftsartikel (refereegranskat)abstract Background/Aim: The use of ion radiation therapy is growing due to the continuously increasing positive clinical experience obtained. Therefore, there is a high interest in radio-biological experiments comparing the relative efficiency in cell killing of ions and photons as the photons are currently the main radiation modality used for cancer treatment. This comparison is particularly important since the treatment planning systems (TPSs) used at the main ion therapy centres make use of parameters describing the cellular response to photons, respectively ions, determined in vitro. It was therefore the aim of this paper to compare the effects of high LET ion radiation with low LET photons and determine whether the cellular response to low LET could predict the response to high LET irradiation. Materials and Methods: Clonogenic cell survival data of five tumor cell lines irradiated with different ion beams of similar, clinically-relevant, LET were studied in relation to the response to low LET photons. Two mathematical models were used to fit the data, the repairable-conditionally repairable damage (RCR) model and the linear quadratic (LQ) model. Results: The results indicate that the relative biological efficiency of the high LET radiation assessed with the RCR model could be predicted based only on the response to the low LET irradiation. Conclusion: The particular features of the RCR model indicate thus that tumor cells showing a large capacity for repairing the damage will have the larger benefit from radiation therapy with ions beams.
50.	Månsson, Christopher, et al. (författare) Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer 2014 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:1A, s. 289-293 Tidskriftsartikel (refereegranskat)abstract Background:Irreversible electroporation (IRE) is a local tumor treatment. Thin needles are placed percutaneously around the tumor under ultrasound guidance. Short pulses of direct current sent through the tissue irreversibly increase cell membrane permeability leading to cell death. We report a phase I study assessing the safety of ultrasound guided percutaneous IRE in patients with localized pancreatic cancer (LPC).Patients and Methods:Five patients (three males) with LPC, judged unsuitable for surgery, chemotherapy, or non-resectable after standard oncological treatment, were treated with IRE. The treatment was given under general anesthesia with muscle relaxation.Results:No serious treatment-related adverse events were observed. There was no 30-day mortality. One patient went on to laparotomy and had a R0 pancreaticoduodenectomy with portal vein resection. Six months after the treatment, two patients had no signs of recurrence on computed tomography or contrast-enhanced ultrasound.Conclusion: IRE for LPC can be safely performed percutaneously under ultrasound guidance, with promising initial results regarding efficacy.

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