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References 1. Kashiwabara K, Tetsunari O, Takaaki S, Toshio F, Takashi N: Correlation between methylation status of the p16/CDKN2 gene and the expression of p16 and Rb proteins in primary non small cell lung cancers. Int J Cancer 1998, 79: 215-220 2. Pérez-Sayáns M, Suárez-Peñaranda JM, Gayoso-Diz P, Barros- Angueira F, Gándara-Rey JM, García-García A: p16(INK4a)/ CDKN2 expression and its relationship with oral squamous cell carcinoma is our current knowledge enough. Cancer Lett 2011, 306:134-141 3. Koh VM, Shi YX, Tang QH: P16 and retinoblastoma protein

-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366:704-707. 5. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70. 6. Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994;264:436-440. 7. Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, De-Pinho RA. Role of the INK4a locus in tumor suppression and cell mortality. Cell. 1996;85:27-37. 8. Liggett WH Jr, Sidransky D. Role of the p16 tumor suppressor gene in cancer. J Clin Oncol. 1998;16:1197-1206. 9

References 1. Agoff S.N., Lin P., Morihara J., Mao C., Kiviat N.B., Koutsky L.A.: p16INK4a expression correlates with degree of cervical neoplasia: A comparison with Ki-67 expression and detection of high-risk HPV types. Mod Pathol 2003, 16 , 665-673. 2. Barnard N.J., Hall P.A., Lemoine N.R., Kadar N.: Proliferative index in breast carcinoma determined in situ by Ki67 immunostaining and its relationship to clinical and pathological variables. J Pathol 1987, 152 , 287-295. 3. Beaumont P.R., O’Brien J.B., Allen H.L., Tucker J.A.: Mast cell sarcoma of the larynx

Abstract

Background: The proteins p16, p53, Bcl-2, and Bax are important cell cycle and apoptotic regulators involved in carcinogenesis and found to have prognostic significance in various cancers. However, the data for squamous cell carcinoma of oral cavity (OSCC) and of oropharynx (OPSCC) are conflicting.

Objective: We sought to determine if expression of p16, p53, Bcl-2, and Bax expression are associated with 5-year overall survival (OS) of patients with OSCC and OPSCC.

Methods: One-hundred thirty-seven cases of OSCC and 140 cases of OPSCC diagnosed from January 2002 to December 2004 at Songklanagrind Hospital, Songkhla, Thailand, were analyzed using a Cox proportional hazards model for 5-year OS in relation to immunohistochemical detection of Bcl-2, Bax, p53, and p16 proteins.

Results: The frequencies of p16, p53, Bcl-2, and Bax expression in OSCC were 13%, 45%, 4%, and 66%, and in OPSCC were 18%, 53%, 22%, and 75%, respectively. In univariate analysis, clinical variables including T stage, N stage and treatment were significantly associated with survival. In multivariate Cox regression, Bax overexpression was significantly associated with poor survival both in OSCC (HR 1.77, 95% CI 1.04-3.01) and in OPSCC (HR 2.21, 95% CI 1.00-4.85). We found no significant association of p16, Bcl-2, and p53 expression with survival.

Conclusion: The expression pattern of p16, p53, Bcl-2, and Bax are similar in OSCC and OPSCC. Only Bax expression has prognostic significance for both tumor sites.

Introduction p16/Ki-67 dual immunocytochemical staining (DS) is considered easy to interpret if evaluators are properly trained. However, there is no consensus on what constitutes proper training. Authors have used different training approaches in studies investigating inter-observer reproducibility and accuracy of DS. 1 , 2 , 3 , 4 , 5 , 6 Most training protocols described in these studies consisted of initial and additional training. The initial training was provided by the manufacturer, however, it was not exactly the same in all cases except that it was

, rheumatoid and other disease. Nat Med 1995; 1: 27-31. 24. Debniak T, Gorski B, Huzarski T, Byrski T, Cybulski C, Mackiewicz A et al. A common variant of CDKN2A (p16) predisposes to breast cancer. J Med Genet 2005; 42: 763–765. 25. Diehl JA, Zindy F, and Sherr CJ. Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway. Genes Dev 1997; 11: 957-972. 26. Cudejko C, Wouters K, Fuentes L, et al. p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. Blood

Expression and characterisation of the ryegrass mottle virus non-structural proteins

The Ryegrass mottle virus (RGMoV) single-stranded RNA genome is organised into four open reading frames (ORF) which encode several proteins: ORF1 encodes protein P1, ORF2a contains the membrane-associated 3C-like serine protease, genome-linked protein VPg and a P16 protein gene. ORF2b encodes replicase RdRP and the only structural protein, coat protein, is synthesised from ORF3. To obtain the non-structural proteins in preparative quantities and to characterise them, the corresponding RGMoV gene cDNAs were cloned in pET- and pColdI-derived expression vectors and overexpressed in several E. coli host cells. For protease and RdRP, the best expression system containing pColdI vector and E. coli WK6 strain was determined. VPg and P16 proteins were obtained from the pET- or pACYC- vectors and E. coli BL21 (DE3) host cells and purified using Ni-Sepharose affinity chromatography. Attempts to crystallize VPg and P16 were unsuccessful, possibly due to non-structured amino acid sequences in both protein structures. Methods based on bioinformatic analysis indicated that the entire VPg domain and the C-terminal part of the P16 contain unstructured amino acid stretches, which possibly prevented the formation of crystals.

, Gomez MA, Dulout FN. C-myc gene amplification detected in preinvasive intraephitelial neoplasia. Int J Gynecol Cancer. 2001; 11(6):462-5 25. Klaes R, Friedrich T, Spitkovsy D, Ridder R., Rudy U, Petry G et al. Overexpression of p16ink4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer. 2001; 92:276-84 26. Sahebali S, Depuydt CE, Segers K, Moeneclay AJ, Vereecken AJ, Van Marck E, et al. P16INK4A as an adjunct marker inliquid-based cervical cytology. Int J Cancer. 2004; 108:871-6 27. Tringler B, Gup CJ, Singh M

References Fombonne J, Devouassoux-Shisheboran M, Bouvier R, Droz J-P, Benahmed M, Krantic S. Analysis of p16INK4A gene promoter in male germ-cell tumors: identification of a new point mutation. Cancer Detect Prev 2005; 29 : 1-7. Kachanov DY, Dobrenkov KV, Shamanskaya TV, Abdullaev RT, Inushkina EV, Savkova RF. Solid tumors in young children in Moscow Region of Russian Federation. Radiol Oncol 2008; 42 : 39-44. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Tumours of the testis and paratesticular tissue. In: Kleihues P, Sobin LH, editors. World Health

liberal market model. Hall and Soskice [2001, p. 16] claimed that “two institutions can be said to be complementary if the presence (or efficiency) of one increases the returns from (or efficiency of) the other.” Firms and governments can utilize the institutional complementarities which are already present in the economy in order to reach the efficiency gains ensured by such complementarities. Moreover, if the actors recognize these complementarities, they may try to preserve institutional arrangements in one sphere so as to ensure the efficiency gains they provide