| 1. |
- Afram, Gabriel, et al.
(författare)
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Reduced intensity conditioning increases risk of severe cGVHD : identification of risk factors for cGVHD in a multicenter setting
- 2018
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:6
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Tidskriftsartikel (refereegranskat)abstract
- Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.
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| 2. |
- Ali, Abir Salwa, et al.
(författare)
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Intravenous versus oral etoposide : efficacy and correlation to clinical outcome in patients with high-grade metastatic gastroenteropancreatic neuroendocrine neoplasms (WHO G3)
- 2018
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Ingår i: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 35:4
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Tidskriftsartikel (refereegranskat)abstract
- High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.
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| 3. |
- Amptoulach, Sousana, et al.
(författare)
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Expression of caspase-3 predicts prognosis in advanced noncardia gastric cancer
- 2015
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 32:1, s. 416-416
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Tidskriftsartikel (refereegranskat)abstract
- There is strong evidence that tumor growth is not only a result of uncontrolled cell proliferation but also of decreased apoptosis. Caspase-3 is a member of interleukin-1 beta-converting enzyme which is involved in the induction of apoptosis. Data on the expression of caspase-3 in patients with gastric cancer and its association with patient outcome are somewhat contradictory. We aimed to investigate the potential relation of the expression of caspase-3 protein with response to therapy and overall survival in patients with advanced noncardia gastric cancer. Tumor tissue samples collected from 359 consecutive patients with gastric cancer stage IV were retrospectively analyzed for the expression of caspase-3 in the primary tumor. The DNA apoptotic index assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method. All patients were followed up until death. Caspase-3 was expressed in 43.5 % of tumors. Caspase-3 expression compared to no expression was related with a higher DNA apoptotic index (p < 0.05). In multivariate analysis, tumor expression of caspase-3 was found to be an independent predictor of poor treatment response and survival (p < 0.05). Expression of caspase-3 in advanced gastric cancer is a predictor of poor response to treatment and survival. Further studies are needed to fully elucidate the prognostic value of caspase-3 expression in these patients.
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| 4. |
- Bergfelt, Emma, et al.
(författare)
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Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia : a Swedish registry-based study
- 2015
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.
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| 5. |
- Falk, Peter, 1962, et al.
(författare)
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Role of matrix metalloproteinases in tumour invasion: immunohistochemistry of peritoneum from peritoneal carcinomatosis
- 2018
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:5
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer is one of the most common forms of cancer. Spread of tumour to the peritoneal cavity may lead to seeding of cancer cells that adhere to and invade the peritoneal membrane causing peritoneal carcinomatosis. Matrix metalloproteinases (MMPs) play an essential role in cancer cell invasion and dissemination. The aim of this study was to evaluate the morphology and presence of matrix metalloproteinases in peritoneal carcinomatosis. Biopsy samples of the parietal peritoneum were taken from patients undergoing cytoreductive surgery for peritoneal carcinomatosis. The samples were fixed in formalin, dehydrated and embedded in paraffin prior to cutting into 4-mu m slices. Staining with haematoxylin/eosin was used for morphology studies, and MMP-1, MMP-2 and TIMP-1 levels were evaluated using immunohistochemistry and light microscopy. The microscopically tumour-free areas of the peritoneal membrane were thin compared to the peripheral invasion zone and the areas invaded by tumour. Peritoneum invaded by tumour was richly vascularised and contained inflammatory cells. MMP-1 was expressed in tumour-free peritoneum and in the invasion zone between tumour and peritoneal tissue, but not in tumour-invaded areas. MMP-2 and TIMP-1 were mostly expressed in the proximity of blood vessels and inflammatory cells in tumour-invaded areas, but was not seen in tumour-free areas. MMPs play an important role in the process of cancer cell invasion of the peritoneum in peritoneal carcinomatosis. The peripheral zone of the tumour appears to be of importance for tumour invasion.
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| 6. |
- Holgersson, Georg, et al.
(författare)
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A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer
- 2015
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects. The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC). Patients with previously untreated, locally advanced, or metastatic NSCLC (squamous cell cancer or adenocarcinoma) in good performance status and with preserved major organ functions were enrolled in the study. The study was an open-label phase I study with planned cohorts of three patients per dose level of AXL1717 (215, 290, and 390 mg BID). In total, 12 patients were enrolled in the study, and of these, two were prematurely excluded. AXL1717 was administered at one dose level, 215 mg BID. A total number of 81 unique adverse events were reported. Bone marrow toxicity was reported in 10 out of 12 patients, and this organ class showed the largest number of related events. AXL1717 in combination with gemcitabine HCl and carboplatin is a possible treatment approach in previously untreated, locally advanced, or metastatic non-small cell lung cancer. However, due to the bone marrow toxicity profile shown in the present study, further dose increases of AXL1717 above 215 mg BID will probably not be feasible. Therefore, 215 mg BID constitutes maximum tolerated dose and RPTD.
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| 7. |
- Jonsson, Andreas, 1984, et al.
(författare)
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Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer.
- 2018
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Ingår i: Medical oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 35:4
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at -80°C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9years of cryopreservation (median values 9.9 and 9.7ng/mL, respectively; p>0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1ng/mL, respectively; p<0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5ng/mL, respectively; p<0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at -80°C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.
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| 8. |
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| 9. |
- Lagunas-Rangel, Francisco Alejandro, et al.
(författare)
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FLT3–ITD and its current role in acute myeloid leukaemia
- 2017
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Ingår i: Medical Oncology. - : Springer Nature. - 1357-0560 .- 1559-131X. ; 34:6
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Forskningsöversikt (refereegranskat)abstract
- FMS-like tyrosine kinase 3 (FLT3) is a proto-oncogene involved in crucial steps of haematopoiesis such as proliferation, differentiation and survival. In recent years, FLT3 has been an important marker in different haematological malignancies, highlighting in acute myeloid leukaemia, where FLT3 mutations have been associated with the clinical prognosis, treatment and survival of patients. The most common form of FLT3 mutation is an internal tandem duplication (ITD) that promotes ligand-independent auto-phosphorylation and constitutive activation of the receptor. FLT3–ITD has been strongly associated with a bad prognosis, leukocytosis, high blast counts, increased risk of relapse and shorter overall survival. In order to improve the clinical condition of FLT3–ITD-positive patients, several FLT3 inhibitors have been developed showing variable results. Currently, the main challenges to be overcome are the different forms of resistance to FLT3 inhibitors. Thus, the purpose of this review is to present, in a general way, the current role that FLT3–ITD mutation plays in patients with AML, with a particular emphasis on the molecular mechanisms associated with clinical prognosis, treatment, and survival of patients.
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| 10. |
- Lewin, Nongnit, et al.
(författare)
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The use of rapid and cost-effective blood-based biomarkers in combination with tumour TNM stage for individual head and neck cancer patient treatment selection
- 2017
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Ingår i: Medical Oncology. - : HUMANA PRESS INC. - 1357-0560 .- 1559-131X. ; 34:4
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Forskningsöversikt (refereegranskat)abstract
- Head and neck (Hamp;N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analysis, high cost, time consumption and requirement of special laboratory facilities have been investigated. However, none of these biomarkers have been shown to be suitable to use for individual Hamp;N cancer patient treatment selection in the clinic. For practical use in clinical settings, the given biomarkers must be simple to analyse, rapid, cost effective and available in routine laboratories. With this intension, we suggested the combination of standard TNM staging and biomarkers associated with inflammation such as neutrophils, neutrophil to lymphocyte ratio, plasma C-reactive protein or plasma tumour necrosis factor alpha (TNFa) and single-nucleotide polymorphism in TNFa rs1800629 using blood-based analysis. The optimal treatment outcome of Hamp;N cancer by using combination of TNM stage and these blood-based biomarkers for individual patient selection need further investigation.
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| 11. |
- Nilsson, Jonas, et al.
(författare)
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The role of income in brain tumor patients : a descriptive register-based study
- 2018
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Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 35:4
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic status (SES) and its association with cancer in general have been thoroughly studied in the last decades. Several studies have shown associations between SES and many types of cancer such as lung cancer, breast cancer, and prostate cancer. For gliomas, no clear occupational or exposure risk factors have been identified, although some possible risk factors such as use of cellular telephone are still controversial. The aim in the present study is to analyze whether there is an association between SES and development of brain cancer. Data from 1999 through 2013 were collected from the Swedish Cancer Registry and from the National Statistics of Sweden. Age-standardized incidence rates for people with different income were calculated using linear regression model. A total of 11,892 patients were included, of which 5675 were meningiomas, 1216 low-grade gliomas, and 5001 high-grade gliomas. No clear trend between increasing incidence rates and higher income was seen in neither of the investigated brain tumor histologies. In conclusion, the results should be interpreted with caution, but there does not seem to be a correlation in this material between increased income and development of brain cancer.
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| 12. |
- Pędziwiatr, Michał, et al.
(författare)
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Is ERAS in laparoscopic surgery for colorectal cancer changing risk factors for delayed recovery?
- 2016
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Ingår i: Medical Oncology. - Heidelberg, Germany : Springer. - 1357-0560 .- 1559-131X. ; 33:3
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that implementation of enhanced recovery after surgery (ERAS) protocols into colorectal surgery reduces complication rate and improves postoperative recovery. However, most published papers on ERAS outcomes and length of stay in hospital (LOS) include patients undergoing open resections. The aim of this pilot study was to determine the factors affecting recovery and LOS in patients after laparoscopic colorectal surgery for cancer combined with ERAS protocol. One hundred and forty-three consecutive patients undergoing elective laparoscopic resection were prospectively evaluated. They were divided into two subgroups depending on their reaching the targeted length of stay-LOS (75 patients in group 1-≤4 days, 68 patients in group 2->4 days). A univariate and multivariate logistic regression analysis was performed to assess for factors (demographics, perioperative parameters, complications and compliance with the ERAS protocol) independently associated with LOS of 4 days or longer. The median LOS in the entire group was 4 days. The postoperative complication rate was higher (18.7 vs. 36.7 %), and the compliance with ERAS protocol was lower (91.2 vs. 76.7 %) in group 2. There was an association between the pre- and postoperative compliance and the subsequent complications. In uni- and multivariate analysis, the lack of balanced fluid therapy (OR 3.87), lack of early mobilization (OR 20.74), prolonged urinary catheterization (OR 4.58) and use of drainage (OR 2.86) were significantly associated with prolonged LOS. Neither traditional patient risk factors nor the stage of the cancer was predictive of the duration of hospital stay. Instead, compliance with the ERAS protocol seems to influence recovery and LOS when applied to laparoscopic colorectal cancer surgery.
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| 13. |
- Qvick, Alvida, 1990-, et al.
(författare)
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Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?
- 2017
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Ingår i: Medical Oncology. - Heidelberg, Germany : Springer. - 1357-0560 .- 1559-131X. ; 34:3
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Tidskriftsartikel (refereegranskat)abstract
- Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in susceptibility to cancer induced by this virus, but with contradicting results. In this study, we have investigated the prognostic value of the codon 72 polymorphism by real-time PCR (qPCR) in two cohorts of vaginal (n = 66) and vulvar (n = 123) carcinomas. In vaginal carcinoma, arginine homozygous patients were significantly associated with a higher primary cure rate (p = 0.023) but also associated with a higher recurrence rate (p = 0.073), significant at distant locations (p = 0.009). No significant differences were found in overall survival rate (p = 0.499) or cancer-specific survival rate (p = 0.222). A higher frequency of arginine homozygosity was noted in HPV-positive tumors (p = 0.190) in comparison with HPV-negative tumors. In vulvar carcinoma, the genotype homozygous for arginine was significantly associated with a larger tumor size at diagnosis in the entire cohort (p = 0.015) and a lower cancer-specific survival rate (p = 0.024) compared with heterozygous (arginine/proline) in HPV-negative tumors. Our results indicate that the relation between HPV and the p53 codon 72 polymorphism is complex and the significance and mechanisms responsible for this relationship need to be further elucidated.
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| 14. |
- Strömberg, Thomas, et al.
(författare)
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Picropodophyllin inhibits proliferation and survival of diffuse large B-cell lymphoma cells
- 2015
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:7
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. Although chemotherapy in combination with anti-CD20 antibodies results in a cure rate of 60-70 %, novel treatment approaches are warranted for the remaining patients. The insulin-like growth factor-1 receptor (IGF-1R) and its principal ligands IGF-1 and IGF-2 have been suggested to play pivotal roles in different cancers. However, in DLBCL the importance of this system is less well understood. To assess whether interference with IGF-1R-mediated signaling may represent a therapeutic option for this malignancy, we used a panel of eight DLBCL cell lines together with primary tumor cells derived from lymph nodes in four DLBCL patients. The cells were treated with the cyclolignan picropodophyllin (PPP), a small molecule compound initially described to selectively inhibit the IGF-1R. PPP dose-dependently inhibited proliferation/survival in all cell lines and primary cell preparations. In parallel experiments, the IGF-1R inhibitor NVP-AEW541 and the microtubule-destabilizing compounds podophyllotoxin (PPT) and colchicine were demonstrated to also inhibit growth of the cell lines. Linear regression analysis showed that the responses of the cell lines to PPP correlated with their responses to the microtubule inhibitors PPT and colchicine, but not with the response to NVP-AEW541 or the expression level of surface IGF-1R. Analysis of cell cycle phase distribution revealed that treatment with PPP for only 1 h induced a clear accumulation of cells in the G2/M-phase with a corresponding depletion of the G0/G1-phase. Interestingly, these cell cycle effects could be closely mimicked by using PPT or colchicine. Treatment with PPP led to increased apoptotic cell death in the SU-DHL-6 and U-2932 cell lines, whereas the DB and U-2940 did not undergo apoptosis. However, the DB cells were still killed by PPP, suggesting another mode of cell death for this cell line. The U-2940 cells responded to PPP mainly by inhibition of proliferation. Pretreatment of U-2932 or U-2940 cell lines with PPP at biologically active concentrations did not prevent ligand-induced phosphorylation of IGF-1R at Tyr1131/1136 or its downstream targets AKT and ERK1/2. In contrast, the IGF-1R inhibitor NVP-AEW541 clearly inhibited phosphorylation of IGF-1R and AKT, while ERK1/2 phosphorylation was less affected. Taken together, the inhibitory effects of PPP in DLBCL cells together with its low toxicity in vivo makes it a promising drug candidate in the treatment of this disease. However, we suggest that the primary target of PPP in these cells is not related to inhibition of IGF-1R phosphorylation.
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| 15. |
- Stäubert, Claudia, et al.
(författare)
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Increased lanosterol turnover : a metabolic burden for daunorubicin-resistant leukemia cells
- 2016
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Ingår i: Medical Oncology. - : Springer-Verlag New York. - 1357-0560 .- 1559-131X. ; 33:1
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Tidskriftsartikel (refereegranskat)abstract
- The cholesterol metabolism is essential for cancer cell proliferation. We found the expression of genes involved in the cholesterol biosynthesis pathway up-regulated in the daunorubicin-resistant leukemia cell line CEM/R2, which is a daughter cell line to the leukemia cell line CCRF-CEM (CEM). Cellular (H2O)-H-2 labelling, mass spectrometry, and isotopomer analysis revealed an increase in lanosterol synthesis which was not accompanied by an increase in cholesterol flux or pool size in CEM/R2 cells. Exogenous addition of lanosterol had a negative effect on CEM/R2 and a positive effect on sensitive CEM cell viability. Treatment of CEM and CEM/R2 cells with cholesterol biosynthesis inhibitors acting on the enzymes squalene epoxidase and lanosterol synthase, both also involved in the 24,25-epoxycholesterol shunt pathway, revealed a connection of this pathway to lanosterol turnover. Our data highlight that an increased lanosterol flux poses a metabolic weakness of resistant cells that potentially could be therapeutically exploited.
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