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- Bongcam Rudloff, Erik
(författare)
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Recommendations for biomarker identification and qualification in clinical proteomics
- 2010
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Clinical proteomics has yielded some early positive results-the identification of potential disease biomarkers-indicating the promise for this analytical approach to improve the current state of the art in clinical practice. However, the inability to verify some candidate molecules in subsequent studies has led to skepticism among many clinicians and regulatory bodies, and it has become evident that commonly encountered shortcomings in fundamental aspects of experimental design mainly during biomarker discovery must be addressed in order to provide robust data. In this Perspective, we assert that successful studies generally use suitable statistical approaches for biomarker definition and confirm results in independent test sets; in addition, we describe a brief set of practical and feasible recommendations that we have developed for investigators to properly identify and qualify proteomic biomarkers, which could also be used as reporting requirements. Such recommendations should help put proteomic biomarker discovery on the solid ground needed for turning the old promise into a new reality.
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| 2. |
- Eriksson, Staffan
(författare)
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High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma
- 2012
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 33, s. 475-483
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explore the association of thymidine kinase 1 (TK1) expression in tumour tissues with clinical pathological parameters and prognosis in patients with pathological T1 (pT1) lung adenocarcinoma. The expression of TK1 was studied by immunohistochemistry techniques in 80 patients with surgically resected pT1 lung adenocarcinoma, retrospectively and at > 10-year follow-up. Compared to patients with low TK1 expression [labelling index (LI) < 25.0%], patients with high TK1 expression (LI a parts per thousand yen25.0%) showed significantly increased lymphatic/vascular permeation and lymph node involvement and higher stromal invasion grade and pathological stage, and a greater number of patients had a tumour size of 2.1 to 3.0 cm. The 5-year survival and the mortality during follow-up for patients with high TK1 expression were significantly worse than that of patients with low TK1 expression. The prognoses of the cases with grade 0, grade 1 and grade 2 stromal invasions were similar and were better than those of cases with grade 3. In patients with stromal invasion grade 3, the 5-year survival and the mortality during follow-up were significantly worse for patients with high TK1 compared to patients with low TK1 expression. Univariate analyses showed that stromal invasion and TK1 expression were significant prognostic factors, while in the multivariate analysis, TK1 expression and tumour stage were found to be independent prognostic factors, but not stromal invasion. This is the first study showing that TK1 expression in combination with stromal invasion is a more reliable prognostic factor than stromal invasion classification itself in patients with pT1 lung adenocarcinoma. TK1 expression enables a further classification of the patients and opens opportunities for improved treatment outcome.
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| 4. |
- Jensen Waern, Marianne, et al.
(författare)
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Oral immunosuppressive medication for growing pigs in transplantation studies
- 2012
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Ingår i: Laboratory Animals. - Thousand Oaks, USA : Sage Publications. - 0023-6772 .- 1758-1117. ; 46:2, s. 148-151
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Tidskriftsartikel (refereegranskat)abstract
- Immunosuppressive (IS) medication is needed to avoid graft rejection in porcine transplantation models. An ideal IS therapy should have no side-effects, but increased susceptibility to infections, disturbed intestinal microflora and toxic effects on organs and tissues are commonly reported. The aim of the present study was to design an IS protocol with tacrolimus and mycophenolic acid to be used for maintenance therapy in the post-transplant period. An eligible whole blood trough value for tacrolimus was 5-15 mu g/L. Conventional specific pathogen-free pigs were fitted with an indwelling catheter under general anaesthesia, and after the acclimatization period three groups were formed: group A (n = 4) received 0.15 mg/kg body weight (BW) twice daily tacrolimus and 500 mg twice daily mycophenolic acid; group B (n = 4) received 0.3 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid; group C (n = 2) did not receive any medication. Daily clinical examinations and analyses of blood concentrations of tacrolimus and glucose were performed. Total and differential white blood cell counts, enzyme activities, bilirubin and electrolyte concentrations were measured every fourth day. At the end of the experiment, the pigs were killed with an overdose of pentobarbital intravenously and a necropsy was performed immediately. All animals seemed to tolerate the IS treatment well. No alterations in their clinical state of health were observed throughout the study and daily weight gain was similar for the three groups. The necropsy did not reveal any pathological findings related to medication. The study showed that 0.25 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid would be an appropriate maintenance dosage for conventional pigs.
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| 5. |
- Tvedten, Harold
(författare)
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Cytology in small mammals and exotic animals
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Department of Clinical Sciences Swedish University of Agricultural Sciences Uppsala Sweden CYTOLOGY OF SMALL MAMMALS AND EXOTIC ANIMALS H W Tvedten Abstract Cytologic diagnosis of samples from small mammals and exotic species is based on the same principles used for cytologic diagnosis of the common domestic species. The cytologist should use the same approach for samples from all species. Unusual species may have unique cell types which should be recognized. Most cytologic diagnoses are general such as septic exudate, granulomatous inflammation, fungal infection, reactive lymph node, carcinoma, etc. Diagnosis begins with correct identification and systematic description of pathologic changes in the sample. Many diagnoses are not more than a proper summary of cytologic changes as a morphologic diagnosis. Each species of small mammal has a short list of diseases which are expected and common in various situations. These diagnoses are recognized quickly. Unexpected or rare diagnoses usually require a search of references. Each species under certain conditions have infections unique for that, but then specific techniques such as PCR are usually required for diagnosis. Good references describing cytologic changes of most common diseases of an unusual species may be difficult to find. Pathology textbooks give gross and histologic diagnoses which may be sufficient to interpret cytologic changes. Using key words from your cytologic description plus the name of the species in an internet search engine such as Internet Explorer or Google Scholar is often successful in finding a useful reference. A PDF file of photographic illustrations presented in the lecture will be available from the author at tvedten@msu.edu. References 1. Al-Rukibat RK, Irizarry AR, Lacey JK, Kazacos KR, Storandt ST, DeNicola DB. (2001): Impression smear of liver tissue from a rabbit. Vet Clin Path 30:57-61. 2. Zimmerman KL, Moore DM, Smith SA. (2010): Hematology of the Guinea Pig. In Schalm's Veterinary Hematology 6th ed, Weiss and Wardrop eds. Wiley-Blackwell Ames Iowa: 893-898. 3. Percy DH, Barthold RW. (2007): Pathology of Laboratory Rodents and Rabbits, 3 ed. Blackwell Publishing Ames Iowa. Corresponding Author Harold Tvedten DVM, PhD, DACVP, DECVCP Department of Clinical Sciences Swedish University of Agricultural Sciences Box 7054 SE-750-07Uppsala Sweden Phone 46 18 671614 Fax 46 18 672883 E-Mail Harold.tvedten@kv.slu.se or Tvedten@msu.edu
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| 6. |
- Tvedten, Harold, et al.
(författare)
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Validation of Advia plateletcrit for assessing platelet mass in dogs, including Cavalier King Charles Spaniels
- 2012
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Ingår i: Veterinary Clinical Pathology. - 0275-6382 .- 1939-165X. ; 41, s. 336-343
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Tidskriftsartikel (refereegranskat)abstract
- Background Determination of the plateletcrit (PCT) is the most effective way to evaluate platelet mass in dogs, such as Cavalier King Charles spaniel (CKCS) dogs, with macrothrombocytopenia. The IDEXX VetAutoread hematology analyzer, which performs quantitative buffy coat (QBC) analysis, has been validated to determine platelet mass in CKCS dogs. The Advia 2120 reports a PCT, but the validity of this value has not been evaluated for dogs with macrothrombocytopenia. Objectives The goal of this study was to validate MPV and PCT determined by the Advia 2120 in dogs, including CKCS dogs, comparing values with those obtained from QBC analysis. Methods Advia PCT was compared with QBC results from 43 CKCS dogs and 15 dogs of other breeds in one study. Advia PCT, platelet count, and MPV were evaluated to identify biologic patterns in 31 clinically healthy CKCS dogs and 66 dogs of 3 other breeds and to generate values used for comparisons. Results Advia PCT agreed well with QBC results in general, but had a negative bias and appeared to underestimate PCT in CKCS dogs with the lowest PCTs. Advia PCT and MPV results followed expected biologic patterns in CKCS dogs and dogs of other breeds with MPVs being highest in dogs with the lowest platelet counts. Conclusions Advia 2120 PCT and MPV satisfactorily identified changes in platelet mass and size in CKCS dogs, but PCTs were lower than expected, especially in CKCS dogs with the lowest PCTs, when compared with QBC results.
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