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| 2. |
- Bergqvist, Michael, et al.
(författare)
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Role of non-taxane-containing chemotherapy in advanced non-small cell lung cancer
- 2006
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Ingår i: American Journal of Cancer. - : Springer Science and Business Media LLC. - 1175-6357 .- 2230-6064. ; 5:4, s. 223-244
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Tidskriftsartikel (refereegranskat)abstract
- Treatment for advanced-stage NSCLC generally includes the use of systemic chemotherapy as well as biologic therapies (targeted therapy) at later stages of the disease. However, in general, NSCLC is moderately sensitive to the currently available cytotoxic drugs, so the intention of chemotherapeutic treatment in the advanced setting is mainly palliative. Several treatment regimens are available, but in the first-line setting, treatment traditions differ both within countries and between various parts of the world. The role of taxaneplatinum chemotherapeutic combinations (mainly used in North America) has been questioned in the palliative setting since these combinations are known to cause neutropenia, skin and nail problems, as well as neurological toxicity. This review aims to summarize the current knowledge about the role of non-taxane therapy for patients with advanced NSCLC, with a focus on gemcitabine, vinorelbine, etoposide, pemetrexed, irinotecan, epidermal growth factor receptor (EGFR)-inhibiting agents, angiogenesis inhibitors, and small molecules. The compilation of literature in the present review indicates that the use of non-taxane treatment for patients with advanced NSCLC has an anti-tumor effect that is not different from that which can be seen with various taxane combinations. Furthermore, the combination of cisplatin with gemcitabine or vinorelbine seems to be a most compelling regimen in the first-line setting because of its modest toxicity (when administered by experienced staff), favorable clinical response, and relatively low drug cost. It is also clear that the novel therapies (EGFR inhibitors and inhibitors of angiogenesis) that have been approved so far will be of great clinical value, however, their use will be restricted to small, well defined, subpopulations of patients. The great challenge now is to define the populations benefiting from these novel therapies. © 2006 Adis Data Information BV. All rights reserved.
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| 3. |
- Bolander, Åsa, 1977-
(författare)
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Prognostic Factors in Malignant Melanoma
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.None of the investigated markers in study III and IV correlated with disease free survival or overall survival.In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
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| 4. |
- Bolander, Åsa, et al.
(författare)
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Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients
- 2008
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 18:6, s. 412-419
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan-Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level
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| 5. |
- Bolander, Å., et al.
(författare)
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The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas
- 2008
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Ingår i: Cancer Genomics & Proteomics. - 1109-6535 .- 1790-6245. ; 5:6, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. Patients and Methods: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. Results: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). Conclusion: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.
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| 6. |
- Bolander, Åsa, et al.
(författare)
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The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:5A, s. 3211-3217
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.
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| 7. |
- Cohen, Alexander T., et al.
(författare)
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Venous thromboembolism (VTE) in Europe : The number of VTE events and associated morbidity and mortality
- 2007
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 98:4, s. 756-764
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations.These factors are thought to result in marked underestimates ofVTE incidence.The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of non-fatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries.The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE.Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE.VTE is a major health problem in the EU,with over one millionVTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented.These results have important implications for the allocation of healthcare resources.
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| 8. |
- Dreilich, M., et al.
(författare)
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HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival
- 2006
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Ingår i: Dis Esophagus. - : Oxford University Press (OUP). ; 19:4, s. 224-231
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.
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| 9. |
- Dreilich, Martin, 1970-
(författare)
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Predictive Factors in Esophageal Carcinoma
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Esophageal carcinoma is a malignancy with a poor prognosis and is the sixth cause of cancer related death worldwide. In Sweden approximately 400 new cases are diagnosed every year. The aim of this present thesis was to investigate predictive factors for esophageal carcinoma patients.126 esophageal carcinoma patients admitted to the department of Oncology at the University Hospital in Uppsala between 1990-2000 were investigated with focus on known and potential prognostic factors. Performance status and stage of the disease were the only independent prognostic factors (p-values <0.001). Angiogenic factors VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p=0.04) whereas bFGF was not (p=0.08) in pre-treatment serum samples from 42 esophageal carcinoma patients. The use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, according to the results from the present study, seems limited. HER-2 overexpression was seen in 17% of 97 investigated esophageal tumor samples. In squamous cell carcinoma patients, HER-2 overexpression correlated with poorer survival (p=0.035), whereas in adenocarcinoma patients, HER-2 status did not. HER-2 overexpression seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma. Telomerase activity was detected in all esophageal cell lines, with a broad range of activity levels. No correlation was found between telomerase activity levels and sensitivity to investigated cytotoxic drugs. We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines. The virus HPV-16 was detected in 16 % of the patients; no other type HPV was detected. HPV-16 infection had no significant effect on survival (p=0.72). Our results did not show that HPV-16 increases survival or improve therapy response in patients with esophageal carcinoma.
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| 10. |
- Dreilich, Martin, et al.
(författare)
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Telomerase activity is not a key determinant of sensitivity to standard cytotoxic drugs in human esophageal carcinoma cell lines
- 2006
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Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 17:5, s. 503-509
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate if basal telomerase activity levels may predict sensitivity to cytotoxic drugs in a panel of human esophageal carcinoma cell lines. The TRAPeze telomerase detection assay was used to investigate telomerase activity in the cell lines. Cytotoxic drug sensitivity for 20 standard cytotoxic agents was assessed using the fluorometric microculture cytotoxicity assay (FMCA). Telomerase activity was detected in all cell lines with a broad range of activity levels. Drug sensitivity also varied considerably between the cell lines. Except for a P value towards a correlation between mitoxantrone and telomerase activity (P=0.054), no statistically significant correlation was found between telomerase activity levels and sensitivity to investigated drugs, including key drugs such as cisplatin (P=0.9), 5-fluorouracil (P=0.8) and doxorubicin (P=0.54). We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines.
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