| 41. |
- Laytragoon-Lewin, Nongnit, et al.
(författare)
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Direct Effects of Pure Nicotine, Cigarette Smoke Extract, Swedish-type Smokeless Tobacco (Snus) Extract and Ethanol on Human Normal Endothelial Cells and Fibroblasts
- 2011
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:5, s. 1527-1534
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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.
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| 42. |
- Laytragoon-Lewin, Nongnit, et al.
(författare)
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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
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:11, s. 4643-4648
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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.
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| 43. |
- Lindahl, Bengt, et al.
(författare)
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Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma
- 2010
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:9, s. 3727-3730
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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.
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| 44. |
- Lindahl, Bengt, et al.
(författare)
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Relapse of Endometrial Carcinoma : Follow-up of 272 Patients with Relapse
- 2012
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3391-3395
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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.
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| 45. |
- Lindgren, Theres, et al.
(författare)
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Alterations in Gene Expression During Radiation-Induced Mitotic Catastrophe in He La Hep2 Cells
- 2014
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 34:8, s. 3875-3880
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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.
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| 46. |
- Lindquist, David, et al.
(författare)
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Intense CD44 expression is a negative prognostic factor in tonsillar and base of tongue cancer
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:1, s. 153-161
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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.
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| 47. |
- Lunde, Mai Lill Suhr, et al.
(författare)
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Gene expression analysis by cDNA microarray in oral cancers from two Western populations
- 2010
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:4, s. 1083-1091
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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.
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| 48. |
- Miftakhova, Regina, et al.
(författare)
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DNA Methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome translocation
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:11, s. 4715-4722
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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.
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| 49. |
- Mohanty, Chitralekha, et al.
(författare)
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Predicting the sensitivity to ion therapy based on the response to photon irradiation - experimental evidence and mathematical modelling
- 2014
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:6, s. 2801-2806
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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.
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| 50. |
- Månsson, Christopher, et al.
(författare)
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Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer
- 2014
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:1A, s. 289-293
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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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