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Sökning: WFRF:(Horvath György)

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1.
  • Horvath, György, 1942-, et al. (författare)
  • Human ovarian carcinomas detected by specific odor.
  • 2008
  • Ingår i: Integrative cancer therapies. - 1534-7354. ; 7:2, s. 76-80
  • Tidskriftsartikel (refereegranskat)abstract
    • The high mortality rate associated with ovarian carcinoma is mainly owing to late diagnosis. It is thus essential to develop inexpensive and simple methods for early diagnosis. Papers on canine scent detection of malignancies such as melanoma and bladder, lung, and breast cancer have recently been published in peer-reviewed journals, indicating a new diagnostic tool for malignancies. However, in these studies the dogs may have responded to odors associated with cancer, such as inflammation or metabolic products, rather than specifically to cancer itself. Therefore, it is important to ascertain whether or not human cancers are characterized by specific odors. We hypothesized that if ovarian carcinoma emits a specific odor, dogs may be trained to detect it. Using our training method, we taught a dog to distinguish different histopathological types and grades of ovarian carcinomas, including borderline tumors, from healthy control samples. Double-blind tests showed 100% sensitivity and 97.5% specificity. Moreover, the odor of ovarian carcinomas seems to differ from those of other gynecological malignances such cervical, endometrial, and vulvar carcinomas. Our study strongly suggests that the most common ovarian carcinomas are characterized by a single specific odor.
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2.
  • Andersson, Håkan, 1944-, et al. (författare)
  • Astatine-211-labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model
  • 2003
  • Ingår i: Clin Cancer Res. - 1078-0432 (Print). ; 9:10 Pt 2, s. 3914S-21S
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The aim of the study was to establish and refine a preclinical model to alpha-immunoradiotherapy of ovarian cancer. EXPERIMENTAL DESIGN: At-211 was produced by cyclotron irradiation of a bismuth-209 target and isolated using a novel dry distillation procedure. Monoclonal antibodies were radiohalogenated with the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate and characterized in terms of radiochemical yield and in vitro binding properties. In vitro OVCAR-3 cells were irradiated using an external Cobalt-60 beam, as reference, or At-211-albumin and labeled antibody. Growth assays were used to establish cell survival. A Monte Carlo program was developed to simulate the energy imparted and the track length distribution. Nude mice were used for studies of WBC depression, with various activities of Tc-99m antibodies, as reference, and At-211 antibodies. In efficacy studies, OVCAR-3 cells were inoculated i.p., and animals were treated 2 weeks later. The animals were either dissected 6 weeks later or followed-up for long-term survival. RESULTS: A rapid distillation procedure, as well as a rapid and high-yield, single-pot labeling procedure, was achieved. From growth inhibition data, the relative biological effectiveness of the alpha-emission for OVCAR-3 cells was estimated to be approximately 5, which is in the same range as found in vivo for hematological toxicity. At-211 MOv18 was found to effectively inhibit the development of tumors and ascites, also resulting in long-term survival without significant toxic effect. CONCLUSIONS: Use of the short-range, high-linear energy transfer alpha-emitter At-211 conjugated to a surface epitope-recognizing monoclonal antibody appears to be highly efficient without significant toxicity in a mouse peritoneal tumor model, urging a Phase I clinical trial.
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3.
  • Andersson, Håkan, 1944-, et al. (författare)
  • Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer.
  • 2001
  • Ingår i: Anticancer research. - 0250-7005. ; 21:1A, s. 409-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to compare the therapeutic efficacy of the alpha-emitter Astatine-211 with the beta-emitter Iodine-131 bound to the specific monoclonal antibody MOv18. The measurements were performed in an ovarian cancer cell line (NIH:OVCAR 3) growing intraperitoneally in nude mice. Two weeks after the intraperitoneal inoculation of 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR-3 twenty mice were treated intraperitoneally with the specific monoclonal antibody MOv-18 labelled with either 211At (310-400 kBq) or 131I (5100-6200 kBq). The pharmacokinetics and biodistribution of labelled antibody in tumour-free animals were studied and the resulting bone marrow dose was estimated. When the mice were treated with 211At-labelled antibody 9 out of 10 mice were free of macro- and microscopic tumour compared to 3 out of 10 when Iodine-131 was used. The equivalent dose to the bone marrow was 2.4-3.1 Sv from 211At- and 3.4-4.1 Sv from 131I-irradiation. The therapeutic efficacy of 211At-labelled specific antibody is very good and, at approximately equivalent bone marrow doses, better than that of 131I.
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4.
  • Andersson, Håkan, 1944-, et al. (författare)
  • Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study.
  • 2009
  • Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 50:7, s. 1153-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The alpha-emitter (211)At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. METHODS: Nine patients underwent laparoscopy 2-5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. (211)At was labeled to MX35 F(ab')(2) using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with (211)At-MX35 F(ab')(2) (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. gamma-Camera scans were acquired on 3-5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1-48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. RESULTS: Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% +/- 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 +/- 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 +/- 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 +/- 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 +/- 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 +/- 1.6 mGy/(MBq/L) (mean +/- SD). No adverse effects were observed either subjectively or in laboratory parameters. CONCLUSION: This study indicates that by intraperitoneal administration of (211)At-MX35 F(ab')(2) it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity.
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5.
  • Betancourt, Lazaro Hiram, et al. (författare)
  • The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes
  • 2019
  • Ingår i: Cancers. - Multidisciplinary Digital Publishing Institute (MDPI). - 2072-6694. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
6.
  • Browall, Maria, et al. (författare)
  • Information needs of women with recently diagnosed ovarian cancer : a longitudinal study.
  • 2004
  • Ingår i: European Journal of Oncology Nursing. - 1462-3889 .- 1532-2122. ; 8:3, s. 200-207
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The aim of this study was to investigate the information needs among patients with ovarian cancer and whether these information needs change over time. The information needs were evaluated three times, through structured interviews, and were based on the paired comparison approach developed by Degner and colleagues. A consecutive sample of patients (n = 82) with recently diagnosed ovarian cancer was asked to participate. Sixty-four patients (78%) chose to participate. The three different measurements of participants' information needs revealed only small changes in these needs. The three most important information needs, in all measurements, were information about the likelihood of cure, information about the stage and spreading of the disease, and information about different treatment options. Information regarding sexual attractiveness was the lowest ranked item in all measurements. Regarding subgroups (age, education) the only significant difference throughout all measurements was that younger patients rated issues of sexual attractiveness higher than older patients (p = 0.005). In this longitudinal study patients with ovarian cancer ranked information about the disease and its treatment (i.e. likelihood of cure, stage of disease, and treatment options) highest, and information about psychosocial aspects and self-care lowest. These findings are in accordance with the results from studies of women diagnosed with other types of cancer, which used the same methodology.</p> <p></p>
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7.
  • Browall, Maria, 1963-, et al. (författare)
  • Information needs of women with recently diagnosed ovarian cancer--a longitudinal study.
  • 2004
  • Ingår i: European journal of oncology nursing : the official journal of European Oncology Nursing Society. - 1462-3889. ; 8:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the information needs among patients with ovarian cancer and whether these information needs change over time. The information needs were evaluated three times, through structured interviews, and were based on the paired comparison approach developed by Degner and colleagues. A consecutive sample of patients (n = 82) with recently diagnosed ovarian cancer was asked to participate. Sixty-four patients (78%) chose to participate. The three different measurements of participants' information needs revealed only small changes in these needs. The three most important information needs, in all measurements, were information about the likelihood of cure, information about the stage and spreading of the disease, and information about different treatment options. Information regarding sexual attractiveness was the lowest ranked item in all measurements. Regarding subgroups (age, education) the only significant difference throughout all measurements was that younger patients rated issues of sexual attractiveness higher than older patients (p = 0.005). In this longitudinal study patients with ovarian cancer ranked information about the disease and its treatment (i.e. likelihood of cure, stage of disease, and treatment options) highest, and information about psychosocial aspects and self-care lowest. These findings are in accordance with the results from studies of women diagnosed with other types of cancer, which used the same methodology.
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8.
  • Browall, Maria, et al. (författare)
  • Information needs of women with recently diagnosed ovarian cancer - A longitudinal study
  • 2004
  • Ingår i: European Journal of Oncology Nursing. - Elsevier. - 1462-3889 .- 1532-2122. ; 8:3, s. 200-207
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The aim of this study was to investigate the information needs among patients with ovarian cancer and whether these information needs change over time. The information needs were evaluated three times, through structured interviews, and were based on the paired comparison approach developed by Degner and colleagues. A consecutive sample of patients (n=82) with recently diagnosed ovarian cancer was asked to participate.Sixty-four patients (78%) chose to participate. The three different measurements of participants' information needs revealed only small changes in these needs. The three most important information needs, in all measurements, were information about the likelihood of cure, information about the stage and spreading of the disease, and information about different treatment options. Information regarding sexual attractiveness was the lowest ranked item in all measurements. Regarding subgroups (age, education) the only significant difference throughout all measurements was that younger patients rated issues of sexual attractiveness higher than older patients (p=0.005).In this longitudinal study patients with ovarian cancer ranked information about the disease and its treatment (i.e. likelihood of cure, stage of disease, and treatment options) highest, and information about psychosocial aspects and self-care lowest. These findings are in accordance with the results from studies of women diagnosed with other types of cancer, which used the same methodology. © 2004 Elsevier Ltd. All rights reserved.</p>
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9.
  • Browall, Maria, et al. (författare)
  • Information needs of women with recently diagnosed ovarian cancer - A longitudinal study
  • 2004
  • Ingår i: European Journal of Oncology Nursing. - Elsevier. - 1462-3889 .- 1532-2122. ; 8:3, s. 200-207
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The aim of this study was to investigate the information needs among patients with ovarian cancer and whether these information needs change over time. The information needs were evaluated three times, through structured interviews, and were based on the paired comparison approach developed by Degner and colleagues. A consecutive sample of patients (n=82) with recently diagnosed ovarian cancer was asked to participate.Sixty-four patients (78%) chose to participate. The three different measurements of participants' information needs revealed only small changes in these needs. The three most important information needs, in all measurements, were information about the likelihood of cure, information about the stage and spreading of the disease, and information about different treatment options. Information regarding sexual attractiveness was the lowest ranked item in all measurements. Regarding subgroups (age, education) the only significant difference throughout all measurements was that younger patients rated issues of sexual attractiveness higher than older patients (p=0.005).In this longitudinal study patients with ovarian cancer ranked information about the disease and its treatment (i.e. likelihood of cure, stage of disease, and treatment options) highest, and information about psychosocial aspects and self-care lowest. These findings are in accordance with the results from studies of women diagnosed with other types of cancer, which used the same methodology. © 2004 Elsevier Ltd. All rights reserved.</p>
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10.
  • Chilo, José, 1960-, et al. (författare)
  • A Flexible Electronic Nose for Odor Discrimination Using Different Methods of Classification
  • 2009
  • Ingår i: IEEE NPSS Real Time Conference 2009. - New York : IEEE. - 978-1-4244-5796-0 ; s. 317-320
  • Konferensbidrag (refereegranskat)abstract
    • <p>Ovarian cancer is one of the leading causes of death front cancer in women. The lifetime risk is around 1.5%, which makes it the second most common gynecologic malignancy (the first one being breast cancer). To have a definitive diagnose, a surgical procedure is generally required and suspicious areas (samples) will be removed and sent for microscopic and other analysis. This paper describes the result of a pilot study in which an electronic nose is used to "smell" the aforementioned samples, analyze the multi-sensor signals and have a close to real-time answer on the detection of cancer. Besides being, fast. the detection method is inexpensive and simple. Experimental analysis using real ovarian carcinoma samples shows that the use of proper algorithms for analysis of the multi-sensor data front the electronic nose yielded surprisingly good results with more than 77% classification rate. The electronic nose used in this pilot study was originally developed to be used as a "bomb dog" and can distinguish between e.g. TNT. Dynamex. Prillit. However, it was constructed to be a flexible multi-sensor device and the individual (16) sensors call easily be replaced/exchanged. This is suggestive for further investigations to obtain even better results with new, specific sensors. In another pilot experiment, headspace of an ovarian carcinoma sample and a control sample were analyzed using gas chromatography-mass spectrometry. Significant differences in chemical composition and compound levels were recorded, which would explain the different response obtained with the electronic nose.</p>
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