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Sökning: WFRF:(Nygren Peter) > (2010-2014)

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  • Hansson, Johan, 1964-, et al. (författare)
  • Quality of life in peritoneal carcinomatosis after cytoreductive surgery and intraperitoneal chemotherapy
  • 2012
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background:</strong></p><p>Cytoreductive surgery (CRS) plus intraperitoneal chemotherapy (IPC) is considered the most optimal treatment for peritoneal carcinomatosis (PC). Health-related quality of life (HRQL) after treatment is largely unknown. The aims were to assess HRQL in patients with PC treated with CRS and IPC and to analyse the influence of clinical variables on HRQL.</p><p><strong>Methods:</strong></p><p>HRQL was assessed prospectively between November 2001 and March 2005 in 64 consecutive patients with PC through two different self-administered instruments, EORTC QLQ-C30 v3.0 (QLQ-C30) and the SF-36 Health Survey (SF-36), preoperatively, and after 3 and 8 months.<em> </em></p><p><strong>Results:</strong></p><p>For QLQ-C30, 44 (69%) and for SF-36, 42 (66%) out of 64 patients had a complete follow-up. Most scales were worsened at baseline compared to reference in both instruments. HRQL was reduced at 3-months in QLQ-C30 (physical, role and emotional functioning) and in SF-36 (physical summary score). At 8-months, all scales returned to baseline in QLQ-C30, except physical functioning which was still reduced and dyspnoea that was worsened. In SF-36, all values returned to baseline levels. At 8-months, presence of a stoma worsened social functioning and a high peritoneal cancer index decreased social functioning and global QoL, the use of hyperthermic intraperitoneal chemotherapy and 30-days postoperative morbidity had no impact on HRQL.<em> </em></p><p><strong>Conclusion:<em> </em></strong></p><p>CRS with IPC results in reasonable short-term HRQL despite high initial morbidity and an initial decrease in HRQL parameters. The study adds to the notion that this treatment appears beneficial in light of probable life prolongation, despite considerable toxicity.<em> </em></p>
  • Hassan, Saadia Bashir, et al. (författare)
  • The Nanoparticulate Quillaja Saponin BBE Is Selectively Active Towards Renal Cell Carcinoma
  • 2013
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:1, s. 143-151
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Aim: To characterize the cytotoxic effect of BBE, the particulate of desacyl-saponin, in model systems of solid tumours. Materials and Methods: Cytotoxic activity of BBE was investigated in solid human tumour cell lines, in tumour cells from patients with renal cell carcinoma, in normal human renal cells and in peripheral blood mononuclear cells. The BBE mode of cell death was assessed in vitro. In vivo effect of BBE was evaluated in xenograft-bearing mice. Results: BBE was selectively active against renal cell carcinoma, with no or little effect on normal cells. BBE induced caspase activity and apoptosis. An inhibitory activity of BBE on xenograft tumour growth, with no apparent signs of haematological toxicity was shown. In the non-proliferative model of patient tumour cells, BBE was active on only 1/5 patient samples, suggesting association of BBE effect with cell proliferation. Conclusion: BBE has interesting activities against renal cell carcinoma and should be further explored as a drug against this resistant tumour type.</p>
  • Hassan, Saadia, et al. (författare)
  • Novel activity of acriflavine against colorectal cancer tumor cells
  • 2011
  • Ingår i: Cancer Science. - 1347-9032 .- 1349-7006. ; 102:12, s. 2206-2213
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs.</p>
  • Hu, Kefei, et al. (författare)
  • Nanoparticulate Quillaja saponin induces apoptosis in human leukemia cell lines with a high therapeutic index
  • 2010
  • Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 5:1, s. 51-62
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Saponin fractions of Quillaja saponaria Molina (QS) have cytotoxic activity against cancer cells in vitro, but are too toxic to be useful in the clinic. The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol. Two fractions of QS were selected for particle formation, one with an acyl-chain (ASAP) was used to form killing and growth-inhibiting (KGI) particles, and the other without the acyl-chain (DSAP) was used to formulate blocking and balancing effect (BBE) particles. KGI showed significant growth inhibiting and cancer cell-killing activities in nine of 10 cell lines while BBE showed that on one cell line. The monoblastoid lymphoma cell line U937 was selected for analyzing the mode of action. Low concentrations of KGI (0.5 and 2 microg/mL) induced irreversible exit from the cell cycle, differentiation measured by cytokine production, and eventually programmed cell death (apoptosis). Compared to normal human monocytes, the U937 cells were 30-fold more sensitive to KGI. The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner. In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.</p>
  • Hultman, Bo, 1964-, et al. (författare)
  • Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy
  • 2014
  • Ingår i: Journal of Experimental & Clinical Cancer Research. - 1756-9966 .- 1756-9966. ; 33
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background   </strong></p><p>The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC.</p><p><strong>Methods </strong><em>  </em></p><p>Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mito­mycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison.</p><p><strong>Results </strong><em>   </em></p><p>The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs.</p><p><strong>Conclusion  </strong><em>  </em></p><p>Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy.</p>
  • Hultman, Bo, et al. (författare)
  • Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer
  • 2012
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:1, s. 112-121
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong></p><p>The costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer.</p><p><strong>Material and methods</strong></p><p>Ten patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost.</p><p><strong>Results</strong></p><p>The mean overall cost in the loco-regional group was $145 700 (range $49 900-$487 800) and $59 300 (range $23 000-$94 800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1-24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life-year and quality-adjusted life-years gained of $166 716 and $175 164, for loco-regional group compared to systemic chemotherapy.</p><p><strong>Discussion</strong></p><p>Treatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high.</p>
  • Hultman, Bo, et al. (författare)
  • Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy
  • 2013
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:4, s. 824-830
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong></p><p>The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer.</p><p><strong>Material and methods</strong></p><p>Eighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC.</p><p><strong>Results</strong></p><p>At the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%.</p><p><strong>Discussion</strong></p><p>Neoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.</p>
  • Häggblad Sahlberg, Sara, et al. (författare)
  • The effect of a dimeric Affibody molecule (ZEGFR:1907)2 targeting EGFR in combination with radiation in colon cancer cell lines
  • 2012
  • Ingår i: International Journal of Oncology. - 1019-6439. ; 40:1, s. 176-184
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The epidermal growth factor receptor (EGFR) is frequently overexpressed in colorectal cancer and is therefore an attractive target for treatment. (ZEGFR:1907)2 is a newly developed dimeric affibody molecule with high affinity to the extracellular part of EGFR. In this study, we evaluated the cytotoxic effects of (ZEGFR:1907)2 in combination with external radiation and the possible inhibitory effects in the EGFR signalling pathways in the colon cancer cell lines HT-29 and HCT116. The effects were compared with an EGFR antibody (cetuximab) and the tyrosine kinase inhibitors (erlotinib and sunitinib). These cell lines are genotypically different with respect to e.g. KRAS and BRAF mutational status, recently shown to be of clinical significance for therapeutic effects. Both cell lines express approximately 100,000-150,000 EGFRs per cell but differ in the radiation response (HCT116, SF2=0.28 and HT-29, SF2=0.70). Exposure to (ZEGFR:1907)2 produced a small, but significant, reduction in survival in HCT116 but did not affect HT-29 cells. Similar results were obtained after exposure to EGF and the EGFR antibody cetuximab. The EGFR tyrosine kinase targeting inhibitor erlotinib and the multi-tyrosine kinase inhibitor sunitinib reduced survival in both cell lines. However, none of the drugs had any significant radiosensitizing effects in combination with radiation. Akt and Erk are central proteins in the EGFR downstream signalling and in the cellular response to ionizing radiation. The activation of Akt (Ser 473) and Erk (Thr202/Tyr204) by radiation was both dose- and time-dependent. However the activation of EGFR was not clearly affected by radiation. Neither (ZEGFR:1907)2 nor any of the other drugs were able to completely inactivate Akt or Erk. On the contrary, erlotinib stimulated Akt phosphorylation in both cell lines and in HCT116 cells Erk was activated. Overall the results illustrate the complexity in response to radiation and drugs in cells with differential phenotypic status.</p>
  • Händel, Peter, et al. (författare)
  • Smartphone-Based Measurement Systems for Road Vehicle Traffic Monitoring and Usage-Based Insurance
  • 2014
  • Ingår i: IEEE Systems Journal. - IEEE Press. - 1932-8184 .- 1937-9234. ; 8:4, s. 1238-1248
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>A framework is presented to deploy a smartphone-based measurement system for road vehicle traffic monitoring and usage-based insurance (UBI). Through the aid of a hierarchical model to modularize the description, the functionality is described as spanning from sensor-level functionality and technical specification to the topmost business model. The designer of a complex measurement system has to consider the full picture from low-level sensing, actuating, and wireless data transfer to the topmost level, including enticements for the individual smartphone owners, i.e., the end users who are the actual measurement probes. The measurement system provides two data streams: a primary stream to support road vehicle traffic monitoring and a secondary stream to support the UBI program. The former activity has a clear value for a society and its inhabitants, as it may reduce congestion and environmental impacts. The latter data stream drives the business model and parts of the revenue streams, which ensure the funding of the total measurement system and create value for the end users, the service provider, and the insurance company. In addition to the presented framework, outcome from a measurement campaign is presented, including road vehicle traffic monitoring (primary data stream) and a commercial pilot of UBI based on the driver profiles (secondary data stream). The measurement system is believed to be sustainable due to the incitements offered to the individual end users, in terms of favorable pricing for the insurance premium. The measurement campaign itself is believed to have an interest in its own right, as it includes smartphone probing of road traffic with a number of probes in the vicinity of the current state of the art, given by the Berkeley Mobile Millennium Project. During the ten-month run of the project, some 4500 driving h/250 000 km of road vehicle traffic data were collected.</p>
  • Jarvius, Malin, et al. (författare)
  • Piperlongumine induces inhibition of the ubiquitin-proteasome system in cancer cells
  • 2013
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 431:2, s. 117-123
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Piperlongumine, a natural product from the plant Piper longum, has demonstrated selective cytotoxicity to tumor cells and to show anti-tumor activity in animal models [1]. Cytotoxicity of piperlongumine has been attributed to increase in reactive oxygen species (ROS) in cancer cells. We here report that piperlongumine is an inhibitor of the ubiquitin-proteasome system (UPS). Exposure of tumor cells to piperlongumine resulted in accumulation of a reporter substrate known to be rapidly degraded by the proteasome, and of accumulation of ubiquitin conjugated proteins. However, no inhibition of 20S proteolytic activity or 19S deubiquitinating activity was observed at concentrations inducing cytotoxicity. Consistent with previous reports, piperlongumine induced strong ROS activation which correlated closely with UPS inhibition and cytotoxicity. Proteasomal blocking could not be mimicked by agents that induce oxidative stress. Our results suggest that the anti-cancer activity of piperlongumine involves inhibition of the UPS at a pre-proteasomal step, prior to deubiquitination of malfolded protein substrates at the proteasome, and that the previously reported induction of ROS is a consequence of this inhibition. </p>
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