الفهرس 
Colorectal carcinoma (CRC)Only 14 pages are availabe for public view
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Abstract
Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy and the third most common cancer globally. In Egypt, CRC represents 6.48% of total malignancies. Despite advances in molecular based cancer therapy, there are resistant cases for therapy. Cancer biology researches have helped to elucidate some of the genetic mechanisms leading to colorectal carcinogenesis and may be a cause of resistance to conventional chemotherapy. However, accumulating evidence suggests that tumor progression is governed not only by genetic changes intrinsic to cancer cells but also by tumor microenvironment (TME). Increased understanding of the TME and correlate it with cancer cells has revealed novel biomarkers that helped in the development of new agents for blockage of all tumor stromal interconnected pathways that promote carcinogenesis.
Among the most promising molecules are silent information regulator 2 homologue1 (SIRT1), signal transducer and activator of transcription 3 (STAT3) and yes-associated protein (YAP). SIRT1 in CRC studies showed a wide controversy between being protective or oncogenic. STAT3 and YAP shared the same proliferative role. STAT3 had been linked to mechanisms of CRC therapy resistance. YAP has an unclarified role on tumor behavior affecting stromal stiffness and creating suitable TME that enables the tumor cells to proliferate continuously.
To date, no drugs are approved by FDA as SIRT1 or STAT3 modulators. However, verteporfin was approved by FDA as YAP antagonist.
However, a clear consensus has not been reached on the triple relationship of SIRT1, STAT3 and YAP.in CRC. This study aimed to evaluate the role of silent information regulator 2 homologue1 (SIRT1), signal transducer and activator of transcription 3 (STAT3) and Yes-associated protein (YAP) in pathogenesis of CRC and to assess their prognostic impact on CRC patients.
This retrospective case control study involved 173 cases, divided into 20 control specimens, 15 cases of ulcerative colitis (UC), 25 adenoma specimens and 113 CRC specimens retrieved from the archival material of Pathology Departments of Faculty of Medicine and National liver Institute, Menoufia University during the period between 2015 and 2020. Hematoxylin and eosin (H&E) stained slides of the selected cases’ blocks were examined carefully to identify viable and representative areas of each sample. Tissue microarray technique was performed through sampling of three cores of representative areas of the tumor and stroma from each specimen.