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Sökning: WFRF:(Mahteme Haile)

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  • Föregående 1234[5]67Nästa
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41.
  • Mahteme, Haile, et al. (författare)
  • Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of experimental colonic carcinoma liver metastases
  • 1998
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 18:2A, s. 843-848
  • Tidskriftsartikel (refereegranskat)abstract
    • Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a nude rat model of experimental liver metastases. Thirty-three rats were injected intraportally through a mesenteric vein with 5 x 10(6) cells from the human colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n = 5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA) monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas control groups received either i.v. saline injections (n = 12) or 150 MBq of the irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed that more than 80% of the initially MAb-bound radioiodine was excreted during the first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I-79C were essentially similar. At sacrifice 5-7 weeks after administration, neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of liver metastases. By contrast, with 150 MBq, no metastases formed in the animals treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the haematopoietic system was found in the 150MBq dosage groups. It is concluded that the inhibition of tumour induction was not strictly dependent on a radiation dose delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a smaller group of animals, proved equally efficacious in preventing tumour growth, the total body 131I dose was probably the major contributing factor.
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42.
  • Mahteme, Haile, et al. (författare)
  • Good colorectal cancer surgery.
  • 2005
  • Ingår i: Tech Coloproctol. - 1123-6337. ; 9:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)
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43.
  • Mahteme, Haile (författare)
  • Hepatic and Peritoneal Colorectal Metastases Aspects of Prognosis and Treatment
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Although two-thirds of colorectal cancer patients are cured by surgery, approximately 50% of the patients with this disease develop locally recurrent or distant metastases during the course of their illness. The aim of this study was to identify metastatic sites associated with poor prognosis in rectal cancer and then to investigate methods that can prevent the development and growth of metastases and optimise uptake of drugs at these sites in animal models.In a defined population, 151 patients with irresectable metastatic or local rectal cancer were identified. Bilateral liver involvement, abnormal liver function tests, paritoneal growth or abdominal lymph node metastases implied a poor prognosis.In a study on Wistar rats with liver metastases from colorectal cancer, blocking of hyaluronan uptake and elimination by the liver enhanced the hyaluronan uptake in liver metastases. Hyaluronan may thus be used to promote uptake of drugs in specific hyaluronan receptor-positive turnout sites.Adjuvant intravenous radioimmunotherapy delivered as a specific or unspecific monoclonal antibody prevented human colonic cancer calls inoculated into the portal vein of nude rats from developing into liver metastases. Furthermore, intraperitoneally administered radioimmunotherapy inhibited the growth of peritoneal metastases.Blocking of 5-FU absorption with a vasoconstrictive agent enhanced the uptake of 5-FU in peritoneal metastases. In addition, the uptake of 5-FU in peritoneal metastases could be improved when these turnouts were mechanically disintegrated by surgical turnout reduction and the drug was given intraperitoneally.
44.
  • Mahteme, Haile, et al. (författare)
  • Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis
  • 2008
  • Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 34:5, s. 547-552
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS:To investigate if the pattern of cytotoxic drug sensitivity in vitro in patient samples of peritoneal carcinomatosis (PC) is supportive to the current standardized approach for drug selection for perioperative intraperitoneal chemotherapy (IPC).METHODS:The cytotoxic effect of cisplatin, oxaliplatin, irinotecan, 5-fluorouracil, mitomycin-C, doxorubicin and melphalan was investigated in vitro on tumour cells from 223 patient tumour samples of different PC origins.RESULTS:Considerable differences in cytotoxic drug sensitivity between tumour types of the PC entity and within each tumour type were observed. Cisplatin showed high cross-resistance with oxaliplatin but low cross-resistance with doxorubicin and irinotecan. No cross-resistance was found between irinotecan and doxorubicin. The dose-response relationships for melphalan and irinotecan in individual samples showed great variability.CONCLUSIONS:The activity in vitro of cytotoxic drugs commonly used in IPC for PC is very heterogeneous. Efforts for individualizing drug selection for PC patients undergoing IPC seem justified.
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45.
  • Mahteme, Haile, et al. (författare)
  • Systemic exposure of the parent drug oxaliplatin during hyperthermic intraperitoneal perfusion
  • 2008
  • Ingår i: European Journal of Clinical Pharmacology. - 0031-6970 .- 1432-1041. ; 64:9, s. 907-911
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate the perfusate and systemic kinetics of oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) using a selective analytical technique. Methods HIPEC was carried out in eight patients by the open abdomen coliseum technique for 30 min at 41.5-43 degrees C with an average of 427 mg/m(2) of oxaliplatin in 5% dextrose solution. Blood and perfusate samples were collected during the perfusion. Additional blood samples were taken up to 2 h after the end of perfusion. The analysis was performed by liquid chromatography and post-column derivatization with N,N-diethyldithiocarbamate using microwave heating. Results The mean elimination half-life of oxaliplatin in the perfusate was 29.5 min (range 21.1-41.2 min) and in the peripheral circulation 24.7 min (range 21.7-27.7 min). The ratio of the areas under the time concentration curve in perfusate and blood was 12.8 +/- 2.9. Conclusion The systemic exposure of oxaliplatin measured after HIPEC using a selective analytical technique is considerably lower than previously reported results obtained by atomic absorption spectroscopy.
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46.
  • Mahteme, Haile, et al. (författare)
  • Uptake of 5-fluorouracil (5-FU) in peritoneal metastases in relation to the route of drug administration and tumour debulking surgery : an autoradiographic study in the rat
  • 2004
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 40:1, s. 142-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with peritoneal metastases from colorectal cancer have a poor prognosis. Aggressive treatment by debulking surgery and intraperitoneal (i.p.) chemotherapy has been suggested as an alternative therapy. However, the drug penetrance into the tumour in relation to the administration route and surgical reduction of the tumour is not well known. We compared locoregional administration with intravenous (i.v.) injection. Thirty-four in-bred rats with peritoneal metastases were randomly allocated into eight groups and injected with 14C-labelled 5-fluorouracil (5-FU) either through the i.v. or i.p. route, with or without a preceding tumour debulking, and were sacrificed after 2 or 8 h. Tumour radioactivity was visualised by autoradiography and quantified by a computer-based image analysis. After 8 h, 19 debulked and i.p.-injected tumours had a higher drug uptake, 63.2+/-28 (mean+/-standard deviation (SD)) kBq/g than 62 native i.p.-injected tumours (32.8+/-14) or 22 debulked and i.v.-injected tumours (18.5+/-18, P=0.002). After 8 h, 9 small tumours (<median 571 pixels) which underwent i.p. injection and tumour reduction had a higher drug uptake (77.4+/-26) than 29 non-debulked and i.p.-injected (35.1+/-17) or eight debulked and i.v. injected tumours (23.0+/-16, P=0.004). For larger tumours (>/=median 571 pixels), 16 debulked and i.p.-injected tumours had a higher radioactivity (drug uptake) (150.7+/-63) at 2 h than 49 i.p.-injected native tumours (48.5+/-59) or 11 reduced and i.v.-injected tumours (19.9+/-13, P=0.03). At 8 h, 10 debulked and i.p.-injected tumours had a higher drug uptake (50.3+/-24) than 33 native and i.p.-injected (30.8+/-10) or 14 debulked and i.v.-injected tumours (16.0+/-19, P=0.001). These results indicate that a debulking procedure and locoregional treatment of peritoneal metastases is associated with an increased level of 5-FU in the tumours.
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47.
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48.
  • Näslund Andréasson, Sara, et al. (författare)
  • Is Platinum Present in Blood and Urine from Treatment Givers during Hyperthermic Intraperitoneal Chemotherapy?
  • 2010
  • Ingår i: Journal of oncology. - 1687-8469. ; 2010, s. 649719
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. In selected patients with peritoneal carcinomatosis (PC) originating from colorectal cancer (CRC) the high dosage of oxaliplatin (460 mg/m(2)) is recommended for hyperthermic intraperitoneal chemotherapy (HIPEC), which may be a health risk to those administering the drug. The aim of this study was to determine the risk of platinum (Pt) exposure for the two main people handling and administering the cytotoxic agent during HIPEC. Methods. Samples of blood and urine were collected from one male surgeon and one female perfusionist during oxaliplatin-based HIPEC treatment with open abdomen coliseum technique on six consecutive patients with PC from CRC. Results. All blood samples analysed were below the detection limit of <0.05 nmol/L Pt, and the urine samples were all below the detection limit of <0.03 nmol/L Pt. Conclusions. There appears to be little or no risk of Pt exposure during HIPEC when the recommended protective garment is used and the safety considerations are followed.
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49.
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50.
  • Segelman, J., et al. (författare)
  • Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer
  • 2012
  • Ingår i: British Journal of Surgery. - 0007-1323 .- 1365-2168. ; 99:5, s. 699-705
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This was a population-based cohort study to determine the incidence, prevalence and risk factors for peritoneal carcinomatosis (PC) from colorectal cancer.Methods: Prospectively collected data were obtained from the Regional Quality Registry. The Cox proportional hazards regression model was used for multivariable analysis of clinicopathological factors to determine independent predictors of PC.Results: All 11 124 patients with colorectal cancer in Stockholm County during 1995-2007 were included and followed until 2010. In total, 924 patients (8.3 per cent) had synchronous or metachronous PC. PC was the first and only localization of metastases in 535 patients (4.8 per cent). The prevalence of synchronous PC was 4.3 per cent (477 of 11 124). The cumulative incidence of metachronous PC was 4.2 per cent (447 of 10 646). Independent predictors for metachronous PC were colonic cancer (hazard ratio (HR) 1.77, 95 per cent confidence interval 1.31 to 2.39; P = 0.002 for right-sided colonic cancer), advanced tumour (T) status (HR 9.98, 3.10 to 32.11; P < 0.001 for T4), advanced node (N) status (HR 7.41, 4.78 to 11.51; P < 0.001 for N2 with fewer than 12 lymph nodes examined), emergency surgery (HR 2.11, 1.66 to 2.69; P < 0.001) and non-radical resection of the primary tumour (HR 2.75, 2.10 to 3.61; P < 0.001 for R2 resection). Patients aged > 70 years had a decreased risk of metachronous PC (HR 0.69, 0.55 to 0.87; P = 0.003).Conclusion: PC is common in patients with colorectal cancer and is associated with identifiable risk factors.
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