Alterations in p53 and pRb pathways and their prognostic significance in oesophageal cancer

Mathew, Robin; Arora, Saurabh; Khanna, R.; Mathur, Meera; Shukla, Nootan Kumar; Ralhan, Ranju

doi:10.1016/s0959-8049(02)00007-2

Cited by 47 publications

(37 citation statements)

References 21 publications

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“…Although there are many encouraging evidences of cyclin D1 to radio response 27,28 and subsequent outcome, 29,30 some debate its association to radiotherapy and involvement in local control and survival. 31,32 In oral cancer, very few reports associate cyclin D1 with radiotherapy. 33 The results of the above referred study showed that the expression of cyclin D1 correlated with radiosensitivity of the tumors.…”

Section: Adenoviral P16mentioning

confidence: 99%

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

Jayasurya

Francis

Kannan

et al. 2004

Intl Journal of Cancer

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Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression.

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Section: Adenoviral P16mentioning

confidence: 99%

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

Jayasurya

Francis

Kannan

et al. 2004

Intl Journal of Cancer

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“…MDM2 overexpression is associated with metastatic and recurrent cancers (14,15), is a significant risk factor for distant metastasis (16), and is associated with poor patient prognosis (17). In addition, a growing body of evidence indicates that MDM2 has many p53-independent activities, which can also play important roles in cancer etiology and progression (18).…”

Section: Introductionmentioning

confidence: 99%

Parthenolide promotes the ubiquitination of MDM2 and activates p53 cellular functions

Gopal

Chanchorn

Dyke

2009

Molecular Cancer Therapeutics

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MDM2 belongs to a class of ring-finger domain -containing ubiquitin ligases that mediate the proteasomal degradation of numerous proteins, including themselves. Arguably, the most important substrate of MDM2 is p53, which controls cell cycle progression and apoptosis. MDM2 and p53 are parts of a feedback regulatory loop whose perturbations are often present in cancer and are targets for anticancer drug development. We found that the natural product, small-molecule anti-inflammatory agent parthenolide (PN), which is actively being investigated as a potential therapeutic for many human cancers, induces ubiquitination of MDM2 in treated cells, resulting in the activation of p53 and other MDM2-regulated tumorsuppressor proteins. Using cells with functional gene deletions and small interfering RNA knockdown studies, we found that these effects required the DNA damage transducer ataxia telangiectasia mutated. The effects of PN on tumor suppressor activation were comparable with that of nutlin-3a, a recently developed small molecule that was designed to interfere with the interaction between MDM2 and p53 but does not promote MDM2 ubiquitination. Our study illustrates an alternative approach for controlling MDM2 and p53 activities and identifies an additional critically important cancer pathway affected by PN. [Mol Cancer Ther 2009; 8(3):552 -62]

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“…MDM2 is a RING fingercontaining E3 enzyme involved in eukaryotic protein degradation via the ubiquitin proteasome system. Overexpression of the human homologue of MDM2, referred to as HDM2, occurs in diverse human malignancies (13,14). Thus, MDM2 expression appears to correlate with an increased risk of distant metastases, which may contribute to an overall poorer prognosis for patients with tumors that overexpress MDM2 (15).…”

mentioning

confidence: 99%

Inhibition of Epithelial to Mesenchymal Transition by E-cadherin Up-regulation via Repression of Slug Transcription and Inhibition of E-cadherin Degradation

Adhikary

Chakraborty

Mazumdar

et al. 2014

Journal of Biological Chemistry

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Background: Epithelial-mesenchymal transition (EMT) is an important program in tumor metastasis. Results: SMAR1 inhibits EMT by up-regulating E-cadherin in a dual manner via repression of Slug transcription and inhibition of E-cadherin degradation. Conclusion: SMAR1 functions as a critical protein in regulating EMT. Significance: This study provides a potential mechanism for the contribution of SMAR1 in inhibiting breast cancer metastasis.

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Alterations in p53 and pRb pathways and their prognostic significance in oesophageal cancer

Cited by 47 publications

References 21 publications

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

Parthenolide promotes the ubiquitination of MDM2 and activates p53 cellular functions

Inhibition of Epithelial to Mesenchymal Transition by E-cadherin Up-regulation via Repression of Slug Transcription and Inhibition of E-cadherin Degradation

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