| 1. |
- Andreasson, Håkan, et al.
(author)
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Histopathological classification of pseudomyxoma peritonei and the prognostic importance of PINCH protein
- 2012
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In: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
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Journal article (peer-reviewed)abstract
- AIM: The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.MATERIALS AND METHODS: Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.RESULTS: The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).CONCLUSION: The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.
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| 2. |
- Asklund, Thomas, et al.
(author)
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Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.
- 2012
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In: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:7, s. 2407-2413
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Journal article (peer-reviewed)abstract
- Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.
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| 3. |
- Bohr Mordhorst, Louise, 1958-, et al.
(author)
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A study of serum biomarkers associated with relapse of cervical cancer
- 2012
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:11, s. 4913-22
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Journal article (peer-reviewed)abstract
- BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients with cervical cancer that differentiate between patients with relapse from those who are tumor-free after primary treatment with (platinum-based chemo-) radiation.PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from patients with advanced cervical cancer, primarily treated with (platinum-based chemo-) radiation.RESULTS: Ten candidate biomarkers were identified in the serum of 34 patients. Six candidate markers were elevated in patients with no relapse and four were elevated in patients with relapse [p=0.007-0.11; area under the curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to 116,165 Da.CONCLUSION: Patients with relapse from primary advanced cervical cancer exhibit different serum protein expression profiles from those with no relapse.
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| 4. |
- Hirsch, Jan-Michael, et al.
(author)
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Oral Cancer in Swedish Snuff Dippers
- 2012
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3327-3330
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Journal article (peer-reviewed)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.
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| 5. |
- Holgersson, Georg, et al.
(author)
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The value of induction chemotherapy for survival in patients with non-small cell lung cancer treated with radiotherapy.
- 2012
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In: Anticancer research. - : The International Institute of Anticancer Research. - 1791-7530 .- 0250-7005. ; 32:4, s. 1339-46
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Journal article (peer-reviewed)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.
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| 6. |
- Jalouli, Jamshid, et al.
(author)
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Human Papilloma Virus, Herpes Simplex Virus and Epstein Barr Virus in Oral Squamous Cell Carcinoma from Eight Different Countries
- 2012
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:2, s. 571-580
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Journal article (peer-reviewed)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.
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| 7. |
- Lindahl, Bengt, et al.
(author)
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Relapse of Endometrial Carcinoma : Follow-up of 272 Patients with Relapse
- 2012
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3391-3395
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Journal article (peer-reviewed)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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| 8. |
- Lindquist, David, et al.
(author)
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Intense CD44 expression is a negative prognostic factor in tonsillar and base of tongue cancer
- 2012
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In: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:1, s. 153-161
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Journal article (peer-reviewed)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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| 9. |
- Miftakhova, Regina, et al.
(author)
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DNA Methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome translocation
- 2012
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In: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:11, s. 4715-4722
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Journal article (peer-reviewed)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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| 10. |
- Norberg, Maria, et al.
(author)
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Screening for Cytotoxic Compounds in Poor-prognostic Chronic Lymphocytic Leukemia
- 2012
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3125-3136
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Journal article (peer-reviewed)abstract
- Background/Aim: For chronic lymphocytic leukemia (CLL) patients with poor-prognostic genomic aberrations the therapeutic options are limited. We used the Spectrum Collection library to identify compounds with anti-leukemia activity in high-risk CLL.Materials and Methods: We identified substances with equal high cytotoxic activity in vitro in samples from poor-prognostic CLL (11q-/17p-, n=3) as compared to those from favourable-prognostic CLL (13q-, n=3). Cell survival was measured by fluorometric microculture cytotoxicity assay.Results: Out of 2,000 compounds, 65 had a similar effect in both prognostic groups. Fifteen compounds were selected for dose-response experiments in 16 additional CLL samples. Of these compounds, 12 continued to have similar cytotoxicity between prognostic subgroups. Additional experiments demonstrated that in CLL cells with 11q or 17p deletion, 5-azacytidine induced apoptosis in a dose-dependent manner and lipoprotein lipase expression was reduced following orlistat treatment.Conclusion: Using primary cultures of cells from high-risk CLL patients for compound screening is a feasible approach and that 5-azacytidine and orlistat exemplify substances that exhibit cytotoxicity in poor-risk CLL.
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