| 41. |
- Rubio, Carlos A., et al.
(författare)
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Assessing the Size of Polyp Phantoms in Tandem Colonoscopies
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:5, s. 1539-1545
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Tidskriftsartikel (refereegranskat)abstract
- Background: The size of colorectal neoplastic polyps is important for their clinical management. Materials and Methods: The size of 12 polyp phantoms was assessed in tandem colonoscopies carried out by 7 endoscopists differing in years of clinical endoscopical experience. The endoscopists measured, with (n=5) or without (n=2) the aid of open forceps, the largest diameter of 12 polyp phantoms. Measurements in two independent trials were compared with the gold standard-size assessed at The Department Of Production Engineering, The Royal Institute of Technology. Results: In tandem trials, 99.4% (167/168) of the measurements underscored the gold standard size. In the 1st trial, the size in all 84 measurements was underestimated by -40% (range -34% to -45%) and in the 2nd trial the size in 83 of the 84 measurements was underestimated by -34% (range -24% to -42%). Neither the age of the participant, nor the years of experience with clinical endoscopy improved the results obtained. The participants significantly underestimated larger devices (>= 20 mm) whereas the smallest "polyps" were also underestimated, but with a lower degree of inaccuracy. The absolute difference between the golden standard size and the mean of all measurements performed on each polyp in 167 out of 168 measurements followed a regular downward trend. The volume of the devices was one of the confounding factors in size assessment. When compared to the gold standard size, the larger the "polyp" size, the higher the degree of underestimation. This may be crucial considering that the risk for colorectal adenomas to shelter an invasive growth is 46%, for adenomas measuring >= 2 cm, a limit accepted as a guideline worldwide for the management of patients with large colorectal polyps. Conclusion: Considering the clinical implications of the results obtained, the possibility of developing a method that would allow the assessment of the true size of polyps in clinical colonoscopy, is being explored.
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| 42. |
- Rubio, Carlos A., et al.
(författare)
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Reliability of the reported size of removed colorectal polyps
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4895-4899
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Tidskriftsartikel (refereegranskat)abstract
- Background: The size of colorectal polyps is important in the clinical management of these lesions. Aim: To audit the accuracy in calculating the size of polyps by various specialists. Materials and Methods: Eighteen pathologists and four surgeons measured, with a conventional millimetre ruler, the largest diameter of 12 polyp phantoms. The results of two independent measurements (two weeks apart) were compared with the gold standard-size assessed at The Royal Institute of Technology, Sweden. Results: Thirty-one percent (83/264-trial 1) and 33% (88/264-trial 2) of the measurements underestimated or overestimated the gold standard size by > 1 mm. Of the 22 experienced participants, 95% (21/22-trial 1) and 91% (20/22-trial 2) misjudged by > 1 mm the size of one or more polyps. Values given by 13 participants (4.9%) in trial I and by 15 participants (5.7%) in trial 2, differed by ! 4 mm from the gold standard size. In addition, a big difference between the highest and the lowest values was recorded in some polyps (up to 11.4 mm). Those disparate values were regarded as a human error in reading the scale on the ruler. Conclusion: Using a conventional ruler (the tool of pathologists worldwide) unacceptably high intra-observer and inter-observer variations in assessing the size of polyp-phantoms was found. The volume and the shape of devices, as well as human error in reading the scale of the ruler were confounding factors in size assessment. In praxis, the size is crucial in the management of colorectal polyps. Considering the clinical implications of the results obtained, the possibility of developing a method that will allow assessment of the true size of removed clinical polyps is being explored.
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| 43. |
- Schultz, Iman J., et al.
(författare)
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Simultaneous proteomic and genomic analysis of primary Ta urothelial cell carcinomas for the prediction of tumor recurrence
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 1051-1058
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prediction of tumor recurrence in patients with Ta urothelial cell carcinoma is inaccurate and new prognostic markers are desirable. Materials and Methods: Surface-enhanced laser-desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on 33 primary Ta tumors (16 and 17 tumors were from patients with long and short recurrence-free periods, respectively) and data were compared to previously obtained mRNA expression profiles of 49 genes. Results: The intensities of a protein peak at m/z 33331 varied most significantly between the two patient groups (p=0.0048). This was comparable to survivin, whose mRNA expression differed most significantly (p=0.0042) of the 49 genes. ROC analysis revealed an area under the curve for protein peak 33331 and survivin of 0.78 (95% CI, 0.62-0.94) and 0.79 (95% CI, 0.63-0.94), respectively. Protein peak 33331 and survivin identified 3 (17%) and 8 (47%) patients with a recurrence-free period of at least 4 years, respectively, without generating false-negatives. Conclusion: These findings indicate that SELDI-TOF MS and real-time Q-PCR analysis on the same tissue can result in the identification of markers with comparable differential expression. Such combined analyses may yield combinations of several markers that might improve disease prognosis.
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| 44. |
- Schultz, Iman J., et al.
(författare)
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The Prognostic Role of the STK15 T91A Polymorphism and of STK15 mRNA Expression in Patients with Urothelial Cell Carcinoma
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 1025-1030
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic role of the STK15 T91A polymorphism and of STK15 mRNA expression was investigated in patients with urothelial cell carcinoma (UCC). Materials and Methods: The STK15 genotype with respect to the T91A polymorphism was assessed by restriction fragment length polymorphism in 135 patients. STK15 mRNA expression was measured in tumor tissues of 103 patients, using real-time quantitative PCR. Results: The T91A polymorphism lacked any prognostic information in our patient cohort. Interestingly though, STK15 mRNA expression was increased in invasive and high-grade tumors (p-values of 0.009 and 0.0001, respectively). Additionally, patients with superficial UCC (n=82) who had a tumor recurrence in the first year after surgery displayed elevated STK15 mRNA expression levels (p=0.009). Kaplan-Meier survival analysis revealed an increased risk of tumor progression for patients with Ta tumors (n=62) and high STK15 expression (log-rank p=0.04). Furthermore, a decreased overall (log-rank p=0.006) and UCC-specific survival (log-rank p=0.001) were shown for patients with elevated STK15 mRNA levels. Conclusion: Patients with UCC and elevated levels of STK15 mRNA generally showed a more adverse disease course than patients with low levels. This may help in identifying patients in need of more aggressive treatment.
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| 45. |
- Sjödin, Anna, et al.
(författare)
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Mammaglobin and lipophilin B expression in breast tumors and their lack of effect on breast cancer cell proliferation.
- 2008
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:3A, s. 1493-1498
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Tidskriftsartikel (refereegranskat)abstract
- Mammaglobin (SCGB2A2) and lipophilin B (SCGB1D2) are members of the secretoglobin polypeptide family. Mammaglobin has been shown to be overexpressed in breast tumor tissue, indicating that mammaglobin might confer a growth advantage to mammaglobin-expressing tumor cells. Materials and Methods: The mammaglobin and lipophilin B mRNA expression levels were investigated in seven breast tumors and matched non-neoplastic tissues from the same patients using quantitative real-time RT-PCR. The effect of mammaglobin and lipophilin B expression on breast cancer cell proliferation rates was investigated by analyzing retrovirally transduced Hs578T cell clones. Cell proliferation rates were determined during the exponential growth phase by analyzing the change in lactate dehydrogenase activity over time. Results: All analyzed breast cancer tumors had lower expression levels of mammaglobin and lipophilin B than the respective mean level of the non-neoplastic breast tissues; no prominent overexpression was evident. There was high variability in the expression of mammaglobin and lipophilin B among the non-neoplastic samples, showing that caution should be taken when evaluating their over- and underexpression in tumors. The expression levels of mammaglobin and lipophilin B correlated with each other in the analyzed samples (p=0.001). Ectopic overexpression of mammaglobin and lipophilin B did not affect the cell proliferation rate of Hs578T breast carcinoma cells in vitro. Conclusion: Our findings suggest that the overexpression of mammaglobin observed in certain breast tumors is an epiphenomenon not causally involved in breast carcinogenesis.
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| 46. |
- Sköldenberg, Erik G., et al.
(författare)
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The angiogenic growth factors HGF and VEGF in serum and plasma from neuroblastoma patients
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:8, s. 3311-3319
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To determine whether concentrations of the angiogenic growth factors hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A) correlate with clinical and genetic markers in samples taken at diagnosis in children with neuroblastoma (NB). PATIENTS AND METHODS: Heparin plasma (P-) and serum (S-) samples of healthy controls (n=73, mean age +/- SD 3.5+/-2.1; females/males: 23/50) and patients with NB (n=62; 2.2+/-1.8; 26/36) were collected between 1988 and 1999. Clinical data included age at diagnosis, gender, stage, outcome, amplification of the oncogene MYCN, loss of heterozygosity at the short arm of chromosome 1 (1p LOH) and ploidy. RESULTS: HGF and S-VEGF-A were elevated in NB as compared to controls (38/62 patients, p<0.0001 and p<0.05, Mann-Whitney U test). HGF concentrations were higher in high-stage (stage 3-4) as compared to low-stage (stage 1-2) disease (p<0.01). P-HGF was elevated in patients with 1p LOH (p<0.01), MYCN amplification (p<0.001) and di- or tetraploidy (p<0.001). S-HGF concentration was elevated in patients MYCN-amplified tumors only. Plasma and S-HGF concentrations were higher in the deceased group (p<0.05), but not P or S-VEGF-A. CONCLUSION: This study showed that concentrations of HGF and S-VEGF-A are elevated in patients with NB. Furthermore, HGF and S-VEGF-A concentrations correlate to higher stage disease and HGF correlates to genetic markers known to indicate a poor outcome. These observations imply that HGF and VEGF-A have biological roles in NB and suggest the possibility of interference with HGF or VEGF-A signaling as a therapeutic strategy.
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| 47. |
- Suzuki, Chikako, et al.
(författare)
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Assessing polyp size by improved digitalized computed tomography (CT)
- 2008
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:3B, s. 1911-1915
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Tidskriftsartikel (refereegranskat)abstract
- Background: The size of colorectal polyps is important in the clinical management of these lesions. When using a conventional ruler (the tool of pathologists worldwide), we have previously found unacceptably high intra- and inter-observer variations in assessing the size of phantom polyps. The aim of this study was to assess the size of 12 phantom polyps by computed tomography (CT). Materials and Methods: The size of phantom polyps as assessed by CT was compared to the gold standard size (GSS) measured at The Royal Institute of Technology, Stockholm, Sweden. Results: In 33.3% (n=4) of the 12 polyps and in 41.7% (n=25) of the 60 measurements, the mean CT size under- or overestimated the GSS by more than 1 mm. In 15%, or in 9 of the 60 measurements, the CT size was under- or overestimated by more than 2 mm. In polyp #5 the GSS size was 8.41 mm where the expected cancer-risk in adenomas is 1%. But 3 out of 5 CT measurements were >10 mm, where the expected cancer-risk in adenomas is 10%. In polyp #10 the GSS size was 10.20 mm where the expected cancer-risk is 10%. But 2 out of 5 CT measurements were <10 mm where the expected risk is only 1%. Conclusion: The size assessed by CT was more reliable than that obtained with a millimetre ruler using the same devices, inasmuch as the disparate individual deviation-values found with the latter method were avoided. The volume and the shape of the devices influenced size assessment of phantom polyps by CT.
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| 48. |
- Suzuki, F., et al.
(författare)
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Tumor-specificity and type of cell death induced by phenoxazines
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:6B, s. 4233-4238
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Tidskriftsartikel (refereegranskat)abstract
- Phenoxazines have shown diverse biological activities, but tumor-specific cytotoxic activity has not been investigated. A total of 24 phenoxazine derivatives (WM1-24) was investigated for their relative cytotoxicity against human tumor cell lines vs. normal cells. WM7 and WM8 showed the highest tumor-specificity index of 4.3 and 4.8, respectively. Considerable difference in drug-sensitivity was found among these tumor cell lines. Human promyelocytic leukemia HL-60 cells showed the highest sensitivity to both WM7 and WM8, followed by human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), and human gingival fibroblast (HGF), pulp cell (HPC) and periodontal ligament fibroblast (HPLF) were the most resistant. WM7 and WM8 induced little or no internucleosomal DNA fragmentation, and activated caspase-3 in HSC-2, HSC-4 and human glioblastoma T98G cells. These compounds failed to induce autophagic cell death, as judged by acridine orange and microtubule-associated protein I light chain 3 (LC3)-GFP assays. These results suggested that the higher cytotoxicity of WM7 and WM8 are derived from the positively-charged quaternary nitrogen substituents on the phenoxazine ring and the electron density of nitrogen at N12, and that inhibition of autophagy is not always coupled with apoplosis induction.
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| 49. |
- Svensson, Åsa, et al.
(författare)
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Angiogenesis can be reduced without significant reduction of tumor growth
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:6B, s. 3883-3889
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Tidskriftsartikel (refereegranskat)abstract
- Background: High risk neuroblastoma (NB) patients have an overall five-year survival of similar to 50%, indicating the need for new treatment strategies, such as angiogenesis inhibition. Materials and Methods: The angiogenesis inhibitor TNP-470 (30 mg/kg, every other day, subcutaneously) was given to nude mice with subcutaneous human neuroblastoma xenografts. The plasma concentrations of the angiogenesis stimulators, i.e. vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and hepatocyte growth factor (HGF), were assayed longitudinally. Angiogenesis, proliferation and apoptosis were quantified on tumor tissue slides. Results: Upon treatment with TNP-470, angiogenesis was significantly inhibited by the reduction of length and surface area of vessels per tumor volume, without having significant effect on tumor growth, tumor cell proliferation or apoptosis. Plasma concentrations of VEGF-A per tumor volume were significantly increased upon treatment. Conclusion: Angiogenesis inhibition must reach a threshold before significant tumor cell apoptosis and a reduction of the tumor growth rate occur.
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| 50. |
- Tell, Roger, et al.
(författare)
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Multicentre Phase II Trial of Paclitaxel and Carboplatin with Concurrent Radiotherapy in Locally Advanced Non-small Cell Lung Cancer
- 2008
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:5B, s. 2851-2857
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate weekly, induction chemotherapy followed by weekly concomitant chemoradiotherapy in a multicentre phase II study of patients with wiresectable stage III non-small cell lung cancer (NSCLC; stage wet IIIB excluded). Patients (aid Methods: Eligible patients received three weekly cycles of paclitaxel 100 mg/m(2) and carboplatin AUC2 followed by six weekly cycles of paclitaxel 60 mg/m(2) and carboplatin AUC2 in combination with thoracic radiotherapy (2 Gy per fraction and day to a total (lose of 60 Gy), Results: Sixty-four patients (40 males and 24 females) with a median age of 63 Years (range, 43-79 years) entered the study. T and N stage were distributed as follows: T1 2 patients (3.2%). T2 10 patients (15.6%), T3 15 patients (23.4%). T4 37 patients (57.8%), N0 10 patients (15.6%). N1 1 patient (1.6%), N2 26 patients (40.6%), N3 26 patients (40.6%), and N missing I patient (1.6%). Seven patients (10.9%) suffered from grade 314 oesophagitis. Grade 112 oesophagitis occurred in 36 patients (56.3%) and pneumonitis grade 112 occurred in 10 patients (15.6%). Sixty-three patients were evaluated on an intent-to-treat basis. The overall response rate was 74.6%. The median time to progression was 247 days and median overall survival was 461 days. According to subgroup analyses, no statistically signicant differences were noted according to gender, age (<65 vs. >= 65 years), perfromance status, histology, or study centre. Conclusion: Induction chemotherapy followed by concurrent chemoradiotherapy with weekly cycles of paclitaxel and carboplatin is feasible and generates moderate toxicity. Efficacy is comparable to other recently published regimens. However, prognosis remains, ill general, poor for this group of patients and further work to develop better therapy is required.
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